Federal Practitioner

Throughout the COVID-19 pandemic, health care professionals (HCPs), including emergency medicine physicians and hospitalists, have been continuously challenged to maintain an up-to-date clinical practice on COVID-19 therapeutics as new evidence emerged.^1,2 In the early part of the pandemic, these included not only appropriate and time-sensitive prescriptions of COVID-19 therapeutics, such as remdesivir and dexamethasone, but also judicious use of empiric antibiotics given the low prevalence for bacterial coinfection in early disease.^3-6 Alongside this, curbing the excessive laboratory testing of these patients during the pandemic was important not only to minimize costs but also to reduce potential iatrogenic harm and extended length of stay (LOS).⁷

At the beginning of the pandemic in March 2020 at the US Department of Veterans Affairs (VA) North Texas Health Care System (VANTHCS) Dallas VA Medical Center (DVAMC), we attempted to provide therapeutic guidance for physicians primarily through direct infectious disease (ID) consultation (in-person or electronic).⁸ This was secondarily supported by a pharmacist and ID physician–curated “living guidance” document on COVID-19 care accessible to all physicians through the DVAMC electronic health record (EHR) and intranet.

As the alpha variant (lineage B.1.1.7) of COVID-19 began spreading throughout North Texas in the winter of 2020, we implemented a targeted educational intervention toward the hospitalist group taking care of patients with COVID-19 with the primary goal of improving the accuracy of COVID-19 therapeutics while minimizing the consultative burden on ID clinical and pharmacy staff. This initiative consisted of (1) proactive guideline dissemination through email and text messages; (2) virtual didactics; and (3) physician reminders during the consultation process. Our ultimate aims were to improve hospitalist-led appropriate prescriptions of remdesivir and dexamethasone, reducing empiric antibiotic days of therapy in patients with COVID-19 at low risk of bacterial coinfection, and reducing laboratory orders that were not indicated for the management of these patients. Following this intervention and the resolution of the second wave, we retrospectively assessed the temporal trends of COVID-19 practices by hospitalists and associated patterns of ID consultation in the DVAMC from October 1, 2020, to March 31, 2021.

METHODS

The educational intervention was carried out at the DVAMC, a 1A high complex facility with more than 200 inpatient beds and part of the VANTHCS. During the study period, patients admitted with COVID-19 were located either on a closed floor (managed by the hospitalist team) or in a closed intensive care unit (ICU) (managed by the pulmonary/critical care team) contingent on the level of care or oxygen supplementation required. ID and other subspecialties provided consultation services as requested by hospitalists or ICU teams either electronically or in person. During the study period, 66 hospitalists were involved in the care of the patients: 59 (89.5%) permanent staff, 4 (6.0%) fee-basis physicians, and 3 (4.5%) moonlighting fellows.

Educational Initiative

We delivered educational sessions to the hospitalists, using collaboration software with video meeting capability every 1 to 2 months beginning in December 2020. An additional session focused on reducing empiric antibiotic prescriptions was also delivered to the emergency medicine department, based on feedback from the hospitalist group. The content for the educational sessions came from informal surveys of both ID trainees assigned to the consultation service and hospitalists, covering the following topics: understanding the stages of COVID-19 illness (virologic replication vs inflammatory) and rationales for therapy; assessing disease severity; indications and use of remdesivir; indications and use of dexamethasone; assessing for bacterial coinfections; when an ID consultation is required; management algorithm for COVID-19; and locating guidelines on the intranet. About 15 to 20 physicians participated in each session. In addition, slides of these didactics and updated institutional COVID-19 guidelines were disseminated to the hospitalist group via email and text messaging. We also linked the intranet institution guidelines in our communication, including a revised user-friendly flowchart (eAppendix).

Laboratory Stewardship Initiative

Laboratory stewardship initiatives were implemented by modifying suggested orders on the admission of patients with COVID-19 and directly educating hospitalist and emergency medicine physicians on evidence-based laboratory orders. At the beginning of the pandemic, a broad admission order set was established at DVAMC, based on the then limited knowledge of the course of infection with COVID-19. This order set allowed the admitting physicians to efficiently order laboratory tests for patients, especially during the demanding increase in patient volume experienced by DVAMC.

As new evidence emerged during the pandemic, many of the laboratory orders were reviewed for clinical utility during care for the patient with COVID-19 per the latest guidance. In December 2020, the admission orders for patients with COVID-19 were revised to reflect better laboratory stewardship to reduce cost and harm. The ID section revised the laboratory orders and disseminated the new order set to admitting physicians. Specifically, the admission order set removed the following laboratory tests available for selection: routine blood cultures, interleukin 6 (IL-6) level, and Legionella sputum culture. These laboratory orders were removed based on the lack of supporting evidence in persons admitted with COVID-19.⁹ In addition to modification of the admission order set, educational sessions were held with hospitalists to disseminate knowledge of the new changes and address any concerns.

Observations of Care

This study was approved by the VANTHCS Institutional Review Board (protocol code 20-047). Records were retrospectively reviewed for patients admitted to DVAMC for COVID-19 under hospitalist care (patients admitted directly to the ICU were excluded) from October 1, 2020, to March 31, 2021. Age, sex, race and ethnicity, and comorbidities were collected from the EHR. In addition clinical measures such as maximum oxygen requirement during admission (none, nasal cannula of 2-4 L/min, high flow/bilevel positive airway pressure [BiPAP] or mechanical ventilation), proven presence of coinfection (defined as the isolation of a probable pathogen in pure culture and/or clinically determined by ID specialist evaluation), and the average LOS also were collected. For laboratory stewardship data, a retrospective chart review was conducted to determine the total number of blood cultures obtained within 24 hours of admission per month during the study period. Both IL-6 levels and Legionella sputum culture data were collected as the total number of laboratory orders per month, as it was assumed that most of these orders were obtained for patients admitted with COVID-19.

Individual patient-level data were extracted to calculate monthly percentages of ID consultations for COVID-19 by the hospitalist team, adherence to institutional guidelines for dexamethasone and remdesivir prescriptions, and empiric antibiotic prescriptions for patients with COVID-19, including use of a priori adjudication criteria to determine justified vs unjustified empiric use. These criteria included asymmetric chest X-ray infiltrates concerning for bacterial pneumonia; peripheral white blood cell count > 11 K/μL; critical respiratory failure in the emergency department (ED) and being transferred to the ICU; and ID consultation recommended. Because the total number of antibiotics was not being analyzed but rather just the use of antibiotics for the justified and unjustified groups, antibiotic days were reported as the length of therapy (LOT).¹⁰ A subset analysis was performed on antibiotic prescriptions by the hospitalist group focusing on those with mild-to-moderate oxygen requirements (no high flow, noninvasive or invasive ventilatory methods) and excluding infections with a proven microbiologic entity.

Differences in demographic and clinical characteristics of patients with COVID-19 admitted from October 1, 2020, to March 31, 2021, were assessed using ANOVA, χ², and Kruskal-Wallis test. χ² was used to compare the difference in total laboratory orders for routine blood cultures, IL-6 levels, and Legionella sputum cultures between pre-intervention (October to December 2020) and postintervention (January to March 2021). These pre- and postintervention periods were determined based on the timing of revised admission orders in the EHR and initiation of focused educational sessions starting in late December 2020 and early January 2021. Linear regressions were used to examine the possible 6-month trend of the percentage of patients receiving ID consultation for appropriate dexamethasone prescriptions, appropriate remdesivir prescriptions, appropriate antibiotic coadministration, and mean number of antibiotic days per patient. Linear and logistic regression were also used to assess the trend in LOS over the 6 months while adjusting for age, race and ethnicity, sex, and coinfections. All analyses were performed using SAS 9.4. Statistical significance was defined as P < .05.

RESULTS

From October 1, 2020, to March 31, 2021, there were 565 admissions for COVID-19, which peaked in January 2021 with 163. Analysis of the patient characteristics showed no statistically significant difference for age, sex, oxygen requirements during admission, or proven presence of coinfection between the months of interest (Table 1).

The number of blood cultures obtained in the first 24 hours of admission significantly decreased from 58.1% of admissions in October 2020 to 34.8% of admissions in March 2021 (P < .01) (Table 2).

DISCUSSION

As the COVID-19 pandemic has evolved, the ability to enact up-to-date guidance is crucial to streamlining patient care, improving time to COVID-19–specific therapies, and minimizing the burden on subspecialty consultation services. At DVAMC, we initiated a targeted and deliberate educational effort directed toward hospitalist and ED groups combined with a laboratory stewardship effort over 6 months to improve the implementation of COVID-19 therapeutics, reduce empiric antibiotic use without reliance on ID consultation services, and reduce the number of unnecessary laboratory orders for admitted patients with COVID-19. During this time, we observed modest but statistically significant improvements in the accuracy of dexamethasone and remdesivir prescribing. In addition, we observed statistically significant improvement in the average LOT per patient regarding antibiotic use and overall decreased LOS. These improvements were seen in parallel with decreasing requests for ID consultation, suggesting that they were attributable in part to increasing self-confidence and efficacy in COVID-19 practices by the hospitalist group. Modification of the COVID-19 admission order set for our facility resulted in substantial decreases in orders for blood cultures, IL-6 levels, and sputum cultures for Legionella.

ID consultation, either in person or remotely, has been instrumental in assisting physicians in COVID-19 management and has been shown to reduce morbidity, mortality, and patient LOS in other infections.^11,12 However, in scenarios where ID consultation is not available or in limited supply, accessibility, familiarity, and confidence of primary practitioners to use therapeutic guidance material are integral. Frequent and accessible guidance for the management of COVID-19 has been provided by the National Institutes of Health and the Infectious Diseases Society of America.^13,14 Other mechanisms of assisting physicians in both test ordering and therapeutics include clinical decision support tools built into the EHR and the use of a smartphone digital application.¹⁵ Guidance needs to be adapted to the context of the facility, including available resources and specific restrictions and/or prohibitions on therapeutics (eg, mandatory ID consultation or approval). In our facility, while COVID-19 therapeutic living guidance documents were maintained and accessible through the intranet, proactive dissemination and redirection were important steps in enabling the use of these documents.

Limitations

We acknowledge several limitations to this study. Most important, the correlations we observed do not represent causation. Our analysis was not designed to ascertain the direct impact of any single or combined educational and laboratory stewardship intervention from this study, and we acknowledge that the improvements in part could be related to increased experience and confidence with COVID-19 management that occurred over time independent of our programs. Furthermore, we acknowledge that several areas of COVID-19 management did not improve over time (such as overall empiric antibiotic use from the ED) or had very modest improvements (hospitalist-initiated remdesivir use). These results underscore the complex dynamics and contextual barriers to rapidly implementing guideline-based care at VANTHCS. Potential factors include insufficient reach to all physicians, variable learner motivation, and therapeutic momentum of antibiotic use carried forward from the ED.^16,17 These factors should be considered as grounds for further study. Another limitation was the inability to track viewership and engagement of our COVID-19 guidance document. Without the use metrics, it is difficult to know the individual impact of the document regarding the changing trends in COVID-19 management we observed during the study period.

Conclusions

We report improvements in COVID-19 therapeutic prescriptions and the use of antibiotics and laboratory testing over 6 months at the DVAMC. This was correlated with a deliberate COVID-19 educational initiative that included antibiotic and laboratory stewardship interventions with simultaneous decreased reliance on ID consultation. These efforts lend support to the proof of the principle of combined educational and laboratory stewardship interventions to improve the care of COVID-19 patients, especially where ID support may not be available or is accessed remotely.

Throughout the COVID-19 pandemic, health care professionals (HCPs), including emergency medicine physicians and hospitalists, have been continuously challenged to maintain an up-to-date clinical practice on COVID-19 therapeutics as new evidence emerged.^1,2 In the early part of the pandemic, these included not only appropriate and time-sensitive prescriptions of COVID-19 therapeutics, such as remdesivir and dexamethasone, but also judicious use of empiric antibiotics given the low prevalence for bacterial coinfection in early disease.^3-6 Alongside this, curbing the excessive laboratory testing of these patients during the pandemic was important not only to minimize costs but also to reduce potential iatrogenic harm and extended length of stay (LOS).⁷

At the beginning of the pandemic in March 2020 at the US Department of Veterans Affairs (VA) North Texas Health Care System (VANTHCS) Dallas VA Medical Center (DVAMC), we attempted to provide therapeutic guidance for physicians primarily through direct infectious disease (ID) consultation (in-person or electronic).⁸ This was secondarily supported by a pharmacist and ID physician–curated “living guidance” document on COVID-19 care accessible to all physicians through the DVAMC electronic health record (EHR) and intranet.

As the alpha variant (lineage B.1.1.7) of COVID-19 began spreading throughout North Texas in the winter of 2020, we implemented a targeted educational intervention toward the hospitalist group taking care of patients with COVID-19 with the primary goal of improving the accuracy of COVID-19 therapeutics while minimizing the consultative burden on ID clinical and pharmacy staff. This initiative consisted of (1) proactive guideline dissemination through email and text messages; (2) virtual didactics; and (3) physician reminders during the consultation process. Our ultimate aims were to improve hospitalist-led appropriate prescriptions of remdesivir and dexamethasone, reducing empiric antibiotic days of therapy in patients with COVID-19 at low risk of bacterial coinfection, and reducing laboratory orders that were not indicated for the management of these patients. Following this intervention and the resolution of the second wave, we retrospectively assessed the temporal trends of COVID-19 practices by hospitalists and associated patterns of ID consultation in the DVAMC from October 1, 2020, to March 31, 2021.

METHODS

The educational intervention was carried out at the DVAMC, a 1A high complex facility with more than 200 inpatient beds and part of the VANTHCS. During the study period, patients admitted with COVID-19 were located either on a closed floor (managed by the hospitalist team) or in a closed intensive care unit (ICU) (managed by the pulmonary/critical care team) contingent on the level of care or oxygen supplementation required. ID and other subspecialties provided consultation services as requested by hospitalists or ICU teams either electronically or in person. During the study period, 66 hospitalists were involved in the care of the patients: 59 (89.5%) permanent staff, 4 (6.0%) fee-basis physicians, and 3 (4.5%) moonlighting fellows.

Educational Initiative

We delivered educational sessions to the hospitalists, using collaboration software with video meeting capability every 1 to 2 months beginning in December 2020. An additional session focused on reducing empiric antibiotic prescriptions was also delivered to the emergency medicine department, based on feedback from the hospitalist group. The content for the educational sessions came from informal surveys of both ID trainees assigned to the consultation service and hospitalists, covering the following topics: understanding the stages of COVID-19 illness (virologic replication vs inflammatory) and rationales for therapy; assessing disease severity; indications and use of remdesivir; indications and use of dexamethasone; assessing for bacterial coinfections; when an ID consultation is required; management algorithm for COVID-19; and locating guidelines on the intranet. About 15 to 20 physicians participated in each session. In addition, slides of these didactics and updated institutional COVID-19 guidelines were disseminated to the hospitalist group via email and text messaging. We also linked the intranet institution guidelines in our communication, including a revised user-friendly flowchart (eAppendix).

Laboratory Stewardship Initiative

Laboratory stewardship initiatives were implemented by modifying suggested orders on the admission of patients with COVID-19 and directly educating hospitalist and emergency medicine physicians on evidence-based laboratory orders. At the beginning of the pandemic, a broad admission order set was established at DVAMC, based on the then limited knowledge of the course of infection with COVID-19. This order set allowed the admitting physicians to efficiently order laboratory tests for patients, especially during the demanding increase in patient volume experienced by DVAMC.

As new evidence emerged during the pandemic, many of the laboratory orders were reviewed for clinical utility during care for the patient with COVID-19 per the latest guidance. In December 2020, the admission orders for patients with COVID-19 were revised to reflect better laboratory stewardship to reduce cost and harm. The ID section revised the laboratory orders and disseminated the new order set to admitting physicians. Specifically, the admission order set removed the following laboratory tests available for selection: routine blood cultures, interleukin 6 (IL-6) level, and Legionella sputum culture. These laboratory orders were removed based on the lack of supporting evidence in persons admitted with COVID-19.⁹ In addition to modification of the admission order set, educational sessions were held with hospitalists to disseminate knowledge of the new changes and address any concerns.

Observations of Care

This study was approved by the VANTHCS Institutional Review Board (protocol code 20-047). Records were retrospectively reviewed for patients admitted to DVAMC for COVID-19 under hospitalist care (patients admitted directly to the ICU were excluded) from October 1, 2020, to March 31, 2021. Age, sex, race and ethnicity, and comorbidities were collected from the EHR. In addition clinical measures such as maximum oxygen requirement during admission (none, nasal cannula of 2-4 L/min, high flow/bilevel positive airway pressure [BiPAP] or mechanical ventilation), proven presence of coinfection (defined as the isolation of a probable pathogen in pure culture and/or clinically determined by ID specialist evaluation), and the average LOS also were collected. For laboratory stewardship data, a retrospective chart review was conducted to determine the total number of blood cultures obtained within 24 hours of admission per month during the study period. Both IL-6 levels and Legionella sputum culture data were collected as the total number of laboratory orders per month, as it was assumed that most of these orders were obtained for patients admitted with COVID-19.

Individual patient-level data were extracted to calculate monthly percentages of ID consultations for COVID-19 by the hospitalist team, adherence to institutional guidelines for dexamethasone and remdesivir prescriptions, and empiric antibiotic prescriptions for patients with COVID-19, including use of a priori adjudication criteria to determine justified vs unjustified empiric use. These criteria included asymmetric chest X-ray infiltrates concerning for bacterial pneumonia; peripheral white blood cell count > 11 K/μL; critical respiratory failure in the emergency department (ED) and being transferred to the ICU; and ID consultation recommended. Because the total number of antibiotics was not being analyzed but rather just the use of antibiotics for the justified and unjustified groups, antibiotic days were reported as the length of therapy (LOT).¹⁰ A subset analysis was performed on antibiotic prescriptions by the hospitalist group focusing on those with mild-to-moderate oxygen requirements (no high flow, noninvasive or invasive ventilatory methods) and excluding infections with a proven microbiologic entity.

Differences in demographic and clinical characteristics of patients with COVID-19 admitted from October 1, 2020, to March 31, 2021, were assessed using ANOVA, χ², and Kruskal-Wallis test. χ² was used to compare the difference in total laboratory orders for routine blood cultures, IL-6 levels, and Legionella sputum cultures between pre-intervention (October to December 2020) and postintervention (January to March 2021). These pre- and postintervention periods were determined based on the timing of revised admission orders in the EHR and initiation of focused educational sessions starting in late December 2020 and early January 2021. Linear regressions were used to examine the possible 6-month trend of the percentage of patients receiving ID consultation for appropriate dexamethasone prescriptions, appropriate remdesivir prescriptions, appropriate antibiotic coadministration, and mean number of antibiotic days per patient. Linear and logistic regression were also used to assess the trend in LOS over the 6 months while adjusting for age, race and ethnicity, sex, and coinfections. All analyses were performed using SAS 9.4. Statistical significance was defined as P < .05.

RESULTS

From October 1, 2020, to March 31, 2021, there were 565 admissions for COVID-19, which peaked in January 2021 with 163. Analysis of the patient characteristics showed no statistically significant difference for age, sex, oxygen requirements during admission, or proven presence of coinfection between the months of interest (Table 1).

The number of blood cultures obtained in the first 24 hours of admission significantly decreased from 58.1% of admissions in October 2020 to 34.8% of admissions in March 2021 (P < .01) (Table 2).

DISCUSSION

As the COVID-19 pandemic has evolved, the ability to enact up-to-date guidance is crucial to streamlining patient care, improving time to COVID-19–specific therapies, and minimizing the burden on subspecialty consultation services. At DVAMC, we initiated a targeted and deliberate educational effort directed toward hospitalist and ED groups combined with a laboratory stewardship effort over 6 months to improve the implementation of COVID-19 therapeutics, reduce empiric antibiotic use without reliance on ID consultation services, and reduce the number of unnecessary laboratory orders for admitted patients with COVID-19. During this time, we observed modest but statistically significant improvements in the accuracy of dexamethasone and remdesivir prescribing. In addition, we observed statistically significant improvement in the average LOT per patient regarding antibiotic use and overall decreased LOS. These improvements were seen in parallel with decreasing requests for ID consultation, suggesting that they were attributable in part to increasing self-confidence and efficacy in COVID-19 practices by the hospitalist group. Modification of the COVID-19 admission order set for our facility resulted in substantial decreases in orders for blood cultures, IL-6 levels, and sputum cultures for Legionella.

ID consultation, either in person or remotely, has been instrumental in assisting physicians in COVID-19 management and has been shown to reduce morbidity, mortality, and patient LOS in other infections.^11,12 However, in scenarios where ID consultation is not available or in limited supply, accessibility, familiarity, and confidence of primary practitioners to use therapeutic guidance material are integral. Frequent and accessible guidance for the management of COVID-19 has been provided by the National Institutes of Health and the Infectious Diseases Society of America.^13,14 Other mechanisms of assisting physicians in both test ordering and therapeutics include clinical decision support tools built into the EHR and the use of a smartphone digital application.¹⁵ Guidance needs to be adapted to the context of the facility, including available resources and specific restrictions and/or prohibitions on therapeutics (eg, mandatory ID consultation or approval). In our facility, while COVID-19 therapeutic living guidance documents were maintained and accessible through the intranet, proactive dissemination and redirection were important steps in enabling the use of these documents.

Limitations

We acknowledge several limitations to this study. Most important, the correlations we observed do not represent causation. Our analysis was not designed to ascertain the direct impact of any single or combined educational and laboratory stewardship intervention from this study, and we acknowledge that the improvements in part could be related to increased experience and confidence with COVID-19 management that occurred over time independent of our programs. Furthermore, we acknowledge that several areas of COVID-19 management did not improve over time (such as overall empiric antibiotic use from the ED) or had very modest improvements (hospitalist-initiated remdesivir use). These results underscore the complex dynamics and contextual barriers to rapidly implementing guideline-based care at VANTHCS. Potential factors include insufficient reach to all physicians, variable learner motivation, and therapeutic momentum of antibiotic use carried forward from the ED.^16,17 These factors should be considered as grounds for further study. Another limitation was the inability to track viewership and engagement of our COVID-19 guidance document. Without the use metrics, it is difficult to know the individual impact of the document regarding the changing trends in COVID-19 management we observed during the study period.

Conclusions

We report improvements in COVID-19 therapeutic prescriptions and the use of antibiotics and laboratory testing over 6 months at the DVAMC. This was correlated with a deliberate COVID-19 educational initiative that included antibiotic and laboratory stewardship interventions with simultaneous decreased reliance on ID consultation. These efforts lend support to the proof of the principle of combined educational and laboratory stewardship interventions to improve the care of COVID-19 patients, especially where ID support may not be available or is accessed remotely.

Throughout the COVID-19 pandemic, health care professionals (HCPs), including emergency medicine physicians and hospitalists, have been continuously challenged to maintain an up-to-date clinical practice on COVID-19 therapeutics as new evidence emerged.^1,2 In the early part of the pandemic, these included not only appropriate and time-sensitive prescriptions of COVID-19 therapeutics, such as remdesivir and dexamethasone, but also judicious use of empiric antibiotics given the low prevalence for bacterial coinfection in early disease.^3-6 Alongside this, curbing the excessive laboratory testing of these patients during the pandemic was important not only to minimize costs but also to reduce potential iatrogenic harm and extended length of stay (LOS).⁷

At the beginning of the pandemic in March 2020 at the US Department of Veterans Affairs (VA) North Texas Health Care System (VANTHCS) Dallas VA Medical Center (DVAMC), we attempted to provide therapeutic guidance for physicians primarily through direct infectious disease (ID) consultation (in-person or electronic).⁸ This was secondarily supported by a pharmacist and ID physician–curated “living guidance” document on COVID-19 care accessible to all physicians through the DVAMC electronic health record (EHR) and intranet.

As the alpha variant (lineage B.1.1.7) of COVID-19 began spreading throughout North Texas in the winter of 2020, we implemented a targeted educational intervention toward the hospitalist group taking care of patients with COVID-19 with the primary goal of improving the accuracy of COVID-19 therapeutics while minimizing the consultative burden on ID clinical and pharmacy staff. This initiative consisted of (1) proactive guideline dissemination through email and text messages; (2) virtual didactics; and (3) physician reminders during the consultation process. Our ultimate aims were to improve hospitalist-led appropriate prescriptions of remdesivir and dexamethasone, reducing empiric antibiotic days of therapy in patients with COVID-19 at low risk of bacterial coinfection, and reducing laboratory orders that were not indicated for the management of these patients. Following this intervention and the resolution of the second wave, we retrospectively assessed the temporal trends of COVID-19 practices by hospitalists and associated patterns of ID consultation in the DVAMC from October 1, 2020, to March 31, 2021.

METHODS

The educational intervention was carried out at the DVAMC, a 1A high complex facility with more than 200 inpatient beds and part of the VANTHCS. During the study period, patients admitted with COVID-19 were located either on a closed floor (managed by the hospitalist team) or in a closed intensive care unit (ICU) (managed by the pulmonary/critical care team) contingent on the level of care or oxygen supplementation required. ID and other subspecialties provided consultation services as requested by hospitalists or ICU teams either electronically or in person. During the study period, 66 hospitalists were involved in the care of the patients: 59 (89.5%) permanent staff, 4 (6.0%) fee-basis physicians, and 3 (4.5%) moonlighting fellows.

Educational Initiative

We delivered educational sessions to the hospitalists, using collaboration software with video meeting capability every 1 to 2 months beginning in December 2020. An additional session focused on reducing empiric antibiotic prescriptions was also delivered to the emergency medicine department, based on feedback from the hospitalist group. The content for the educational sessions came from informal surveys of both ID trainees assigned to the consultation service and hospitalists, covering the following topics: understanding the stages of COVID-19 illness (virologic replication vs inflammatory) and rationales for therapy; assessing disease severity; indications and use of remdesivir; indications and use of dexamethasone; assessing for bacterial coinfections; when an ID consultation is required; management algorithm for COVID-19; and locating guidelines on the intranet. About 15 to 20 physicians participated in each session. In addition, slides of these didactics and updated institutional COVID-19 guidelines were disseminated to the hospitalist group via email and text messaging. We also linked the intranet institution guidelines in our communication, including a revised user-friendly flowchart (eAppendix).

Laboratory Stewardship Initiative

Laboratory stewardship initiatives were implemented by modifying suggested orders on the admission of patients with COVID-19 and directly educating hospitalist and emergency medicine physicians on evidence-based laboratory orders. At the beginning of the pandemic, a broad admission order set was established at DVAMC, based on the then limited knowledge of the course of infection with COVID-19. This order set allowed the admitting physicians to efficiently order laboratory tests for patients, especially during the demanding increase in patient volume experienced by DVAMC.

As new evidence emerged during the pandemic, many of the laboratory orders were reviewed for clinical utility during care for the patient with COVID-19 per the latest guidance. In December 2020, the admission orders for patients with COVID-19 were revised to reflect better laboratory stewardship to reduce cost and harm. The ID section revised the laboratory orders and disseminated the new order set to admitting physicians. Specifically, the admission order set removed the following laboratory tests available for selection: routine blood cultures, interleukin 6 (IL-6) level, and Legionella sputum culture. These laboratory orders were removed based on the lack of supporting evidence in persons admitted with COVID-19.⁹ In addition to modification of the admission order set, educational sessions were held with hospitalists to disseminate knowledge of the new changes and address any concerns.

Observations of Care

This study was approved by the VANTHCS Institutional Review Board (protocol code 20-047). Records were retrospectively reviewed for patients admitted to DVAMC for COVID-19 under hospitalist care (patients admitted directly to the ICU were excluded) from October 1, 2020, to March 31, 2021. Age, sex, race and ethnicity, and comorbidities were collected from the EHR. In addition clinical measures such as maximum oxygen requirement during admission (none, nasal cannula of 2-4 L/min, high flow/bilevel positive airway pressure [BiPAP] or mechanical ventilation), proven presence of coinfection (defined as the isolation of a probable pathogen in pure culture and/or clinically determined by ID specialist evaluation), and the average LOS also were collected. For laboratory stewardship data, a retrospective chart review was conducted to determine the total number of blood cultures obtained within 24 hours of admission per month during the study period. Both IL-6 levels and Legionella sputum culture data were collected as the total number of laboratory orders per month, as it was assumed that most of these orders were obtained for patients admitted with COVID-19.

Individual patient-level data were extracted to calculate monthly percentages of ID consultations for COVID-19 by the hospitalist team, adherence to institutional guidelines for dexamethasone and remdesivir prescriptions, and empiric antibiotic prescriptions for patients with COVID-19, including use of a priori adjudication criteria to determine justified vs unjustified empiric use. These criteria included asymmetric chest X-ray infiltrates concerning for bacterial pneumonia; peripheral white blood cell count > 11 K/μL; critical respiratory failure in the emergency department (ED) and being transferred to the ICU; and ID consultation recommended. Because the total number of antibiotics was not being analyzed but rather just the use of antibiotics for the justified and unjustified groups, antibiotic days were reported as the length of therapy (LOT).¹⁰ A subset analysis was performed on antibiotic prescriptions by the hospitalist group focusing on those with mild-to-moderate oxygen requirements (no high flow, noninvasive or invasive ventilatory methods) and excluding infections with a proven microbiologic entity.

Differences in demographic and clinical characteristics of patients with COVID-19 admitted from October 1, 2020, to March 31, 2021, were assessed using ANOVA, χ², and Kruskal-Wallis test. χ² was used to compare the difference in total laboratory orders for routine blood cultures, IL-6 levels, and Legionella sputum cultures between pre-intervention (October to December 2020) and postintervention (January to March 2021). These pre- and postintervention periods were determined based on the timing of revised admission orders in the EHR and initiation of focused educational sessions starting in late December 2020 and early January 2021. Linear regressions were used to examine the possible 6-month trend of the percentage of patients receiving ID consultation for appropriate dexamethasone prescriptions, appropriate remdesivir prescriptions, appropriate antibiotic coadministration, and mean number of antibiotic days per patient. Linear and logistic regression were also used to assess the trend in LOS over the 6 months while adjusting for age, race and ethnicity, sex, and coinfections. All analyses were performed using SAS 9.4. Statistical significance was defined as P < .05.

RESULTS

From October 1, 2020, to March 31, 2021, there were 565 admissions for COVID-19, which peaked in January 2021 with 163. Analysis of the patient characteristics showed no statistically significant difference for age, sex, oxygen requirements during admission, or proven presence of coinfection between the months of interest (Table 1).

The number of blood cultures obtained in the first 24 hours of admission significantly decreased from 58.1% of admissions in October 2020 to 34.8% of admissions in March 2021 (P < .01) (Table 2).

DISCUSSION

As the COVID-19 pandemic has evolved, the ability to enact up-to-date guidance is crucial to streamlining patient care, improving time to COVID-19–specific therapies, and minimizing the burden on subspecialty consultation services. At DVAMC, we initiated a targeted and deliberate educational effort directed toward hospitalist and ED groups combined with a laboratory stewardship effort over 6 months to improve the implementation of COVID-19 therapeutics, reduce empiric antibiotic use without reliance on ID consultation services, and reduce the number of unnecessary laboratory orders for admitted patients with COVID-19. During this time, we observed modest but statistically significant improvements in the accuracy of dexamethasone and remdesivir prescribing. In addition, we observed statistically significant improvement in the average LOT per patient regarding antibiotic use and overall decreased LOS. These improvements were seen in parallel with decreasing requests for ID consultation, suggesting that they were attributable in part to increasing self-confidence and efficacy in COVID-19 practices by the hospitalist group. Modification of the COVID-19 admission order set for our facility resulted in substantial decreases in orders for blood cultures, IL-6 levels, and sputum cultures for Legionella.

ID consultation, either in person or remotely, has been instrumental in assisting physicians in COVID-19 management and has been shown to reduce morbidity, mortality, and patient LOS in other infections.^11,12 However, in scenarios where ID consultation is not available or in limited supply, accessibility, familiarity, and confidence of primary practitioners to use therapeutic guidance material are integral. Frequent and accessible guidance for the management of COVID-19 has been provided by the National Institutes of Health and the Infectious Diseases Society of America.^13,14 Other mechanisms of assisting physicians in both test ordering and therapeutics include clinical decision support tools built into the EHR and the use of a smartphone digital application.¹⁵ Guidance needs to be adapted to the context of the facility, including available resources and specific restrictions and/or prohibitions on therapeutics (eg, mandatory ID consultation or approval). In our facility, while COVID-19 therapeutic living guidance documents were maintained and accessible through the intranet, proactive dissemination and redirection were important steps in enabling the use of these documents.

Limitations

We acknowledge several limitations to this study. Most important, the correlations we observed do not represent causation. Our analysis was not designed to ascertain the direct impact of any single or combined educational and laboratory stewardship intervention from this study, and we acknowledge that the improvements in part could be related to increased experience and confidence with COVID-19 management that occurred over time independent of our programs. Furthermore, we acknowledge that several areas of COVID-19 management did not improve over time (such as overall empiric antibiotic use from the ED) or had very modest improvements (hospitalist-initiated remdesivir use). These results underscore the complex dynamics and contextual barriers to rapidly implementing guideline-based care at VANTHCS. Potential factors include insufficient reach to all physicians, variable learner motivation, and therapeutic momentum of antibiotic use carried forward from the ED.^16,17 These factors should be considered as grounds for further study. Another limitation was the inability to track viewership and engagement of our COVID-19 guidance document. Without the use metrics, it is difficult to know the individual impact of the document regarding the changing trends in COVID-19 management we observed during the study period.

Conclusions

We report improvements in COVID-19 therapeutic prescriptions and the use of antibiotics and laboratory testing over 6 months at the DVAMC. This was correlated with a deliberate COVID-19 educational initiative that included antibiotic and laboratory stewardship interventions with simultaneous decreased reliance on ID consultation. These efforts lend support to the proof of the principle of combined educational and laboratory stewardship interventions to improve the care of COVID-19 patients, especially where ID support may not be available or is accessed remotely.

BY ALICIA AULT

The Centers for Disease Control and Prevention is alerting clinicians to be on the lookout for a severe antifungal-resistant form of tinea, as it was recently detected in two patients in New York.

Tinea, or ringworm, one of the most common fungal infections, is responsible for almost 5 million outpatient visits and 690 hospitalizations annually, according to the CDC.

Over the past 10 years, severe, antifungal-resistant tinea has spread in South Asia, in part because of the rise of a new dermatophyte species known as Trichophyton indotineae, wrote the authors of a report on the two patients with the drug-resistant strain. This epidemic “has likely been driven by misuse and overuse of topical antifungals and corticosteroids,” added the authors, in Morbidity and Mortality Weekly Report.

The cases were detected by a New York City dermatologist. In the first case, a 28-year-old woman developed a widespread pruritic eruption in the summer of 2021. She did not consult a dermatologist until December, when she was in the third trimester of pregnancy. She had large, annular, scaly, pruritic plaques on her neck, abdomen, pubic region, and buttocks, but had no underlying medical conditions, no known exposures to someone with a similar rash, and no recent international travel history.

After she gave birth in January, she started oral terbinafine therapy but had no improvement after 2 weeks. Clinicians administered a 4-week course of itraconazole, which resolved the infection.

The second patient, a 47-year-old woman with no medical conditions, developed a rash while in Bangladesh in the summer of 2022. Other family members had a similar rash. She was treated with topical antifungal and steroid combination creams but had no resolution. Back in the United States, she was prescribed hydrocortisone 2.5% ointment and diphenhydramine, clotrimazole cream, and terbinafine cream in three successive emergency department visits. In December 2022, dermatologists, observing widespread, discrete, scaly, annular, pruritic plaques on the thighs and buttocks, prescribed a 4-week course of oral terbinafine. When the rash did not resolve, she was given 4 weeks of griseofulvin. The rash persisted, although there was 80% improvement. Clinicians are now considering itraconazole. The woman’s son and husband are also being evaluated, as they have similar rashes.

In both cases, skin culture isolates were initially identified as Trichophyton mentagrophytes. Further analysis at the New York State Department of Health’s lab, using Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis, identified the isolates as T. indotineae.

The authors note that culture-based techniques used by most clinical laboratories typically misidentify T. indotineae as T. mentagrophytes or T. interdigitale. Genomic sequencing must be used to properly identify T. indotineae, they wrote.

Clinicians should consider T. indotineae in patients with widespread ringworm, especially if they do not improve with topical antifungals or oral terbinafine, said the authors. If T. indotineae is suspected, state or local public health departments can direct clinicians to testing.

The authors report no relevant financial relationships.

BY ALICIA AULT

The Centers for Disease Control and Prevention is alerting clinicians to be on the lookout for a severe antifungal-resistant form of tinea, as it was recently detected in two patients in New York.

Tinea, or ringworm, one of the most common fungal infections, is responsible for almost 5 million outpatient visits and 690 hospitalizations annually, according to the CDC.

Over the past 10 years, severe, antifungal-resistant tinea has spread in South Asia, in part because of the rise of a new dermatophyte species known as Trichophyton indotineae, wrote the authors of a report on the two patients with the drug-resistant strain. This epidemic “has likely been driven by misuse and overuse of topical antifungals and corticosteroids,” added the authors, in Morbidity and Mortality Weekly Report.

The cases were detected by a New York City dermatologist. In the first case, a 28-year-old woman developed a widespread pruritic eruption in the summer of 2021. She did not consult a dermatologist until December, when she was in the third trimester of pregnancy. She had large, annular, scaly, pruritic plaques on her neck, abdomen, pubic region, and buttocks, but had no underlying medical conditions, no known exposures to someone with a similar rash, and no recent international travel history.

After she gave birth in January, she started oral terbinafine therapy but had no improvement after 2 weeks. Clinicians administered a 4-week course of itraconazole, which resolved the infection.

The second patient, a 47-year-old woman with no medical conditions, developed a rash while in Bangladesh in the summer of 2022. Other family members had a similar rash. She was treated with topical antifungal and steroid combination creams but had no resolution. Back in the United States, she was prescribed hydrocortisone 2.5% ointment and diphenhydramine, clotrimazole cream, and terbinafine cream in three successive emergency department visits. In December 2022, dermatologists, observing widespread, discrete, scaly, annular, pruritic plaques on the thighs and buttocks, prescribed a 4-week course of oral terbinafine. When the rash did not resolve, she was given 4 weeks of griseofulvin. The rash persisted, although there was 80% improvement. Clinicians are now considering itraconazole. The woman’s son and husband are also being evaluated, as they have similar rashes.

In both cases, skin culture isolates were initially identified as Trichophyton mentagrophytes. Further analysis at the New York State Department of Health’s lab, using Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis, identified the isolates as T. indotineae.

The authors note that culture-based techniques used by most clinical laboratories typically misidentify T. indotineae as T. mentagrophytes or T. interdigitale. Genomic sequencing must be used to properly identify T. indotineae, they wrote.

Clinicians should consider T. indotineae in patients with widespread ringworm, especially if they do not improve with topical antifungals or oral terbinafine, said the authors. If T. indotineae is suspected, state or local public health departments can direct clinicians to testing.

The authors report no relevant financial relationships.

BY ALICIA AULT

The Centers for Disease Control and Prevention is alerting clinicians to be on the lookout for a severe antifungal-resistant form of tinea, as it was recently detected in two patients in New York.

Tinea, or ringworm, one of the most common fungal infections, is responsible for almost 5 million outpatient visits and 690 hospitalizations annually, according to the CDC.

Over the past 10 years, severe, antifungal-resistant tinea has spread in South Asia, in part because of the rise of a new dermatophyte species known as Trichophyton indotineae, wrote the authors of a report on the two patients with the drug-resistant strain. This epidemic “has likely been driven by misuse and overuse of topical antifungals and corticosteroids,” added the authors, in Morbidity and Mortality Weekly Report.

The cases were detected by a New York City dermatologist. In the first case, a 28-year-old woman developed a widespread pruritic eruption in the summer of 2021. She did not consult a dermatologist until December, when she was in the third trimester of pregnancy. She had large, annular, scaly, pruritic plaques on her neck, abdomen, pubic region, and buttocks, but had no underlying medical conditions, no known exposures to someone with a similar rash, and no recent international travel history.

After she gave birth in January, she started oral terbinafine therapy but had no improvement after 2 weeks. Clinicians administered a 4-week course of itraconazole, which resolved the infection.

The second patient, a 47-year-old woman with no medical conditions, developed a rash while in Bangladesh in the summer of 2022. Other family members had a similar rash. She was treated with topical antifungal and steroid combination creams but had no resolution. Back in the United States, she was prescribed hydrocortisone 2.5% ointment and diphenhydramine, clotrimazole cream, and terbinafine cream in three successive emergency department visits. In December 2022, dermatologists, observing widespread, discrete, scaly, annular, pruritic plaques on the thighs and buttocks, prescribed a 4-week course of oral terbinafine. When the rash did not resolve, she was given 4 weeks of griseofulvin. The rash persisted, although there was 80% improvement. Clinicians are now considering itraconazole. The woman’s son and husband are also being evaluated, as they have similar rashes.

In both cases, skin culture isolates were initially identified as Trichophyton mentagrophytes. Further analysis at the New York State Department of Health’s lab, using Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis, identified the isolates as T. indotineae.

The authors note that culture-based techniques used by most clinical laboratories typically misidentify T. indotineae as T. mentagrophytes or T. interdigitale. Genomic sequencing must be used to properly identify T. indotineae, they wrote.

Clinicians should consider T. indotineae in patients with widespread ringworm, especially if they do not improve with topical antifungals or oral terbinafine, said the authors. If T. indotineae is suspected, state or local public health departments can direct clinicians to testing.

The authors report no relevant financial relationships.

It has been a troubling mystery—and yet, is an unsolved one: Last January, at least 9 service members who had worked at Malmstrom Air Force Base (AFB) in Montana were reported to have been diagnosed with non-Hodgkin lymphoma. Then more cancer cases were reported, not only at Malmstrom, but at Francis E. Warren AFB in Wyoming, Minot AFB in North Dakota, and Vandenberg AFB in California. The bases operate the silos that house nuclear warheads carried by Minuteman III intercontinental ballistic missiles (ICBMs).

In all, 36 cancer cases were reported among missileers: 10 developed non-Hodgkin lymphoma, 2 Hodgkin lymphoma, and 24 another form of cancer. Eight of the missileers, the majority of whom served at Malmstrom between 1997 and 2007, have died.

So far, though, the US Air Force (USAF) reports that it has found no current risk factors that could explain the unusual number of cases.

In February, Gen. Thomas Bussiere, commander of Air Force Global Strike Command, approved a study to conduct a formal assessment related to specific cancer concerns and examine the possibility of cancer clusters at ICBM bases. The Missile Community Cancer Study, conducted by the Air Force School of Aerospace Medicine, will look at all ICBM wings, all missileers, and those who maintain, guard, and support the bases. The review also incorporates active-duty medical data, the US Department of Veterans Affairs cancer registry data, mortality data, and public cancer registries.

Missileers may be exposed to a variety of chemicals and toxins. The potential hazardous materials exposure at the missile silos extends to all 3 missile bases, USAF says. The equipment in the launch control center and equipment buildings were identical. However, each of the ICBM bases has specific environmental and agricultural factors that will be considered as studies continue, according to the USAF. The land surrounding missile alert facilities, launch control centers, and launch facilities is not owned by the government; the study teams noted that locations could contain additional unknown agricultural hazards. Procedures for testing and cleaning the facilities vary across installations, creating inconsistencies, according to the USAF.

The study teams recently presented their initial findings. “[O]verall,” they said, “there were no factors identified that would be considered immediate concerns for acute cancer risks,” according to a report from the USAF 711^th Human Performance Wing, obtained by the Associated Press.

This isn’t the first time that concerns have been raised about possible cancer clusters at Malmstrom. In 2001, after cases of various cancers from missileers were reported—including cervical, thyroid, Hodgkin lymphoma, and non-Hodgkin lymphoma—the Air Force Institute for Operational Health conducted a site evaluation and sampling for possible chemical and biologic contaminants at their facilities. Results of all tests, the 2005 report said, did not demonstrate any levels above acceptable standards according to state and federal regulations. The survey concluded that launch control centers provide a safe and healthy working environment.

In 2005, following the release of the report, the USAF said “There is not sufficient evidence to consider the possibility of a cancer clustering to justify further investigation.” The research report noted, “[S]ometimes illnesses tend to occur by chance alone and it is not uncommon to see clustering or what has been referred to as ‘perceived clustering’ of conditions, especially when they occur in a close group of people or certain communities as in the military.”

On its website, though, the Air Force Medical Service now says that the findings from 2 decades ago may have changed.

The findings from the new study are not final. The USAF is continuing its investigation, including conducting an epidemiological study of cancers within the missile community. In the meantime, Air Force Global Strike Command Public Affairs says that, in response to the review panel’s recommendations, Gen. Bussiere has directed that facilities be deep cleaned regularly, signage denoting the presence of polychlorinated biphenyls be updated, and burning no longer allowed as a means of destroying classified materials inside the facilities.

Notably, the changes will also include improving communication and coordination between medical personnel and missile community members. Bussiere directed his staff to explore specifically assigning medical professionals to ICBM units, to have a better understanding of the environment and missions. He also ordered further engagement with personnel who work with known occupational hazards to collect more data and information. While awaiting the eventual replacement of the Minuteman III ICBM with the LGM-35A Sentinel, preventive maintenance and environmental upgrades will be prioritized and any upgrade or new piece of equipment will be “scrutinized for hazards.”

The USAF has also established a website to address the missileer community’s concerns.

It has been a troubling mystery—and yet, is an unsolved one: Last January, at least 9 service members who had worked at Malmstrom Air Force Base (AFB) in Montana were reported to have been diagnosed with non-Hodgkin lymphoma. Then more cancer cases were reported, not only at Malmstrom, but at Francis E. Warren AFB in Wyoming, Minot AFB in North Dakota, and Vandenberg AFB in California. The bases operate the silos that house nuclear warheads carried by Minuteman III intercontinental ballistic missiles (ICBMs).

In all, 36 cancer cases were reported among missileers: 10 developed non-Hodgkin lymphoma, 2 Hodgkin lymphoma, and 24 another form of cancer. Eight of the missileers, the majority of whom served at Malmstrom between 1997 and 2007, have died.

So far, though, the US Air Force (USAF) reports that it has found no current risk factors that could explain the unusual number of cases.

In February, Gen. Thomas Bussiere, commander of Air Force Global Strike Command, approved a study to conduct a formal assessment related to specific cancer concerns and examine the possibility of cancer clusters at ICBM bases. The Missile Community Cancer Study, conducted by the Air Force School of Aerospace Medicine, will look at all ICBM wings, all missileers, and those who maintain, guard, and support the bases. The review also incorporates active-duty medical data, the US Department of Veterans Affairs cancer registry data, mortality data, and public cancer registries.

Missileers may be exposed to a variety of chemicals and toxins. The potential hazardous materials exposure at the missile silos extends to all 3 missile bases, USAF says. The equipment in the launch control center and equipment buildings were identical. However, each of the ICBM bases has specific environmental and agricultural factors that will be considered as studies continue, according to the USAF. The land surrounding missile alert facilities, launch control centers, and launch facilities is not owned by the government; the study teams noted that locations could contain additional unknown agricultural hazards. Procedures for testing and cleaning the facilities vary across installations, creating inconsistencies, according to the USAF.

The study teams recently presented their initial findings. “[O]verall,” they said, “there were no factors identified that would be considered immediate concerns for acute cancer risks,” according to a report from the USAF 711^th Human Performance Wing, obtained by the Associated Press.

This isn’t the first time that concerns have been raised about possible cancer clusters at Malmstrom. In 2001, after cases of various cancers from missileers were reported—including cervical, thyroid, Hodgkin lymphoma, and non-Hodgkin lymphoma—the Air Force Institute for Operational Health conducted a site evaluation and sampling for possible chemical and biologic contaminants at their facilities. Results of all tests, the 2005 report said, did not demonstrate any levels above acceptable standards according to state and federal regulations. The survey concluded that launch control centers provide a safe and healthy working environment.

In 2005, following the release of the report, the USAF said “There is not sufficient evidence to consider the possibility of a cancer clustering to justify further investigation.” The research report noted, “[S]ometimes illnesses tend to occur by chance alone and it is not uncommon to see clustering or what has been referred to as ‘perceived clustering’ of conditions, especially when they occur in a close group of people or certain communities as in the military.”

On its website, though, the Air Force Medical Service now says that the findings from 2 decades ago may have changed.

The findings from the new study are not final. The USAF is continuing its investigation, including conducting an epidemiological study of cancers within the missile community. In the meantime, Air Force Global Strike Command Public Affairs says that, in response to the review panel’s recommendations, Gen. Bussiere has directed that facilities be deep cleaned regularly, signage denoting the presence of polychlorinated biphenyls be updated, and burning no longer allowed as a means of destroying classified materials inside the facilities.

Notably, the changes will also include improving communication and coordination between medical personnel and missile community members. Bussiere directed his staff to explore specifically assigning medical professionals to ICBM units, to have a better understanding of the environment and missions. He also ordered further engagement with personnel who work with known occupational hazards to collect more data and information. While awaiting the eventual replacement of the Minuteman III ICBM with the LGM-35A Sentinel, preventive maintenance and environmental upgrades will be prioritized and any upgrade or new piece of equipment will be “scrutinized for hazards.”

The USAF has also established a website to address the missileer community’s concerns.

It has been a troubling mystery—and yet, is an unsolved one: Last January, at least 9 service members who had worked at Malmstrom Air Force Base (AFB) in Montana were reported to have been diagnosed with non-Hodgkin lymphoma. Then more cancer cases were reported, not only at Malmstrom, but at Francis E. Warren AFB in Wyoming, Minot AFB in North Dakota, and Vandenberg AFB in California. The bases operate the silos that house nuclear warheads carried by Minuteman III intercontinental ballistic missiles (ICBMs).

In all, 36 cancer cases were reported among missileers: 10 developed non-Hodgkin lymphoma, 2 Hodgkin lymphoma, and 24 another form of cancer. Eight of the missileers, the majority of whom served at Malmstrom between 1997 and 2007, have died.

So far, though, the US Air Force (USAF) reports that it has found no current risk factors that could explain the unusual number of cases.

In February, Gen. Thomas Bussiere, commander of Air Force Global Strike Command, approved a study to conduct a formal assessment related to specific cancer concerns and examine the possibility of cancer clusters at ICBM bases. The Missile Community Cancer Study, conducted by the Air Force School of Aerospace Medicine, will look at all ICBM wings, all missileers, and those who maintain, guard, and support the bases. The review also incorporates active-duty medical data, the US Department of Veterans Affairs cancer registry data, mortality data, and public cancer registries.

Missileers may be exposed to a variety of chemicals and toxins. The potential hazardous materials exposure at the missile silos extends to all 3 missile bases, USAF says. The equipment in the launch control center and equipment buildings were identical. However, each of the ICBM bases has specific environmental and agricultural factors that will be considered as studies continue, according to the USAF. The land surrounding missile alert facilities, launch control centers, and launch facilities is not owned by the government; the study teams noted that locations could contain additional unknown agricultural hazards. Procedures for testing and cleaning the facilities vary across installations, creating inconsistencies, according to the USAF.

The study teams recently presented their initial findings. “[O]verall,” they said, “there were no factors identified that would be considered immediate concerns for acute cancer risks,” according to a report from the USAF 711^th Human Performance Wing, obtained by the Associated Press.

This isn’t the first time that concerns have been raised about possible cancer clusters at Malmstrom. In 2001, after cases of various cancers from missileers were reported—including cervical, thyroid, Hodgkin lymphoma, and non-Hodgkin lymphoma—the Air Force Institute for Operational Health conducted a site evaluation and sampling for possible chemical and biologic contaminants at their facilities. Results of all tests, the 2005 report said, did not demonstrate any levels above acceptable standards according to state and federal regulations. The survey concluded that launch control centers provide a safe and healthy working environment.

In 2005, following the release of the report, the USAF said “There is not sufficient evidence to consider the possibility of a cancer clustering to justify further investigation.” The research report noted, “[S]ometimes illnesses tend to occur by chance alone and it is not uncommon to see clustering or what has been referred to as ‘perceived clustering’ of conditions, especially when they occur in a close group of people or certain communities as in the military.”

On its website, though, the Air Force Medical Service now says that the findings from 2 decades ago may have changed.

The findings from the new study are not final. The USAF is continuing its investigation, including conducting an epidemiological study of cancers within the missile community. In the meantime, Air Force Global Strike Command Public Affairs says that, in response to the review panel’s recommendations, Gen. Bussiere has directed that facilities be deep cleaned regularly, signage denoting the presence of polychlorinated biphenyls be updated, and burning no longer allowed as a means of destroying classified materials inside the facilities.

Notably, the changes will also include improving communication and coordination between medical personnel and missile community members. Bussiere directed his staff to explore specifically assigning medical professionals to ICBM units, to have a better understanding of the environment and missions. He also ordered further engagement with personnel who work with known occupational hazards to collect more data and information. While awaiting the eventual replacement of the Minuteman III ICBM with the LGM-35A Sentinel, preventive maintenance and environmental upgrades will be prioritized and any upgrade or new piece of equipment will be “scrutinized for hazards.”

The USAF has also established a website to address the missileer community’s concerns.

In one of the first studies to examine this phenomenon, metabolically unhealthy obesity is associated with an increased risk, around 1.5-fold higher, of any obesity-related cancer, and an even higher risk, two- to threefold higher, for specific cancers, such as endometrial, liver, and renal cell cancers, compared with metabolically healthy normal weight.

Even in people with so-called “metabolically healthy” obesity, the risk for overall obesity-related cancer is increased, compared with normal-weight, metabolically healthy individuals; however, the associations here are weaker than in people with metabolically unhealthy obesity.

“The type of metabolic obesity phenotype is important when assessing obesity-related cancer risk,” lead researcher Ming Sun, PhD, from Lund University, Malmö, Sweden, said in an interview. “In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.”

“This synergy means that when obesity and metabolic unhealth occur together, that’s particularly bad,” added Tanja Stocks, PhD, senior author, also of Lund University.

“But the data also highlight that even obesity and overweight alone comprise an increased risk of cancer,” Dr. Stocks noted.

Dr. Sun said the findings have important public health implications, suggesting that “a significant number of cancer cases could potentially be prevented by targeting the coexistence of metabolic problems and obesity, in particular for obesity-related cancers among men.”

The results will be presented as a poster by Dr. Sun at the European Congress on Obesity 2023, being held in Dublin, and have been published in the Journal of the National Cancer Institute.
 

Metabolically unhealthy obesity worst for cancer risks

Andrew G. Renehan, PhD, FRCS, professor of cancer studies and surgery, University of Manchester, England, welcomed the new work, saying it addresses the issue with very large study numbers. “[It] nicely demonstrates that there are clear examples where metabolically unhealthy overweight and obese phenotypes have increased cancer risk relative to [metabolically] healthy overweight and obese phenotypes,” he said.

“There is a clear need for clinically based research addressing these hypotheses ... but these studies will additionally need to factor in other dimensions such as the selection of treatment for metabolic aberrations, both medical and surgical, and the consequent metabolic control resulting from these interventions,” Dr. Renehan observed.

Vibhu Chittajallu, MD, a gastroenterologist based at University Hospitals Cleveland Medical Center, said it was beneficial to see another study further validating the association of obesity with the development of obesity-associated cancers.

“This is an interesting study [because it focuses] on the role of metabolic syndrome in obesity and how it affects the risk of development of obesity-associated cancers,” he said in an interview.

“I believe that the results of this study further strengthen the need for improved management of obesity and metabolic syndrome to reduce the risk of obesity-associated cancer formation that plays a role in preventable and premature deaths in adult patients with obesity.”
 

Synergy between metabolic aberrations and obesity, and cancer risk

Dr. Sun and colleagues note that obesity is an established risk factor for several cancers. It is often accompanied by metabolic aberrations, which have been a commonly proposed mechanism to link obesity with cancer. During the last decade, obesity with or without metabolic aberrations – commonly termed “metabolically unhealthy” or “healthy obesity” – has been extensively investigated in the cardiovascular field; however, studies regarding cancer are limited.

According to Dr. Sun, this new study is the first to look at the synergistic effect of unhealthy metabolism and body mass index – the latter was further categorized as normal weight (BMI < 25 kg/m2), overweight (BMI < 30) and obesity (BMI ≤ 30) – and the association with cancer risk, both overall and in relation to site-specific cancers.

Data were drawn from 797,193 European individuals (in Norway, Sweden, and Austria), of whom 23,630 developed an obesity-related cancer during the follow-up period. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to provide a measure of healthy or unhealthy metabolic status. Relative risks (hazard ratios) for overall and site-specific cancers were determined. Comparisons were made with metabolically healthy people of normal weight (effectively controls).

When different metabolic scores and BMIs were combined, participants fell into six categories: metabolically unhealthy obesity (6.8% of participants); metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically healthy overweight (19.8%), metabolically unhealthy normal weight (12.5%), and metabolically healthy normal weight (42.0%).

Metabolically unhealthy women with obesity had a hazard ratio of 1.43 for overall obesity-related cancers, compared with metabolically healthy women of normal weight. Of particular note were risks of two cancer types in women with metabolically unhealthy obesity: renal cancer, with an HR of 2.43, and endometrial cancer, with an HR of 3.0, compared with controls.

Even in metabolically healthy women with obesity, compared with metabolically healthy women of normal weight, there was an increased risk of endometrial cancer, with an HR of 2.36.

“If you look at individual cancers, in particular endometrial cancer, this seems to be very much driven by obesity and not so much by the metabolic factor,” remarked Dr. Stocks.

In males, compared with metabolically healthy men of normal weight, metabolically unhealthy men with obesity had an overall obesity-related cancer risk HR of 1.91. Specifically, the risk of renal cell cancer was more than doubled, with an HR of 2.59. The HR for colon cancer was 1.85, and that for rectal cancer and pancreatic cancer was similar, both having HRs of 1.32.

Again, risk was lower in metabolically healthy men with obesity, although still higher than for metabolically healthy normal-weight men.

A version of this article first appeared on Medscape.com.

In one of the first studies to examine this phenomenon, metabolically unhealthy obesity is associated with an increased risk, around 1.5-fold higher, of any obesity-related cancer, and an even higher risk, two- to threefold higher, for specific cancers, such as endometrial, liver, and renal cell cancers, compared with metabolically healthy normal weight.

Even in people with so-called “metabolically healthy” obesity, the risk for overall obesity-related cancer is increased, compared with normal-weight, metabolically healthy individuals; however, the associations here are weaker than in people with metabolically unhealthy obesity.

“The type of metabolic obesity phenotype is important when assessing obesity-related cancer risk,” lead researcher Ming Sun, PhD, from Lund University, Malmö, Sweden, said in an interview. “In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.”

“This synergy means that when obesity and metabolic unhealth occur together, that’s particularly bad,” added Tanja Stocks, PhD, senior author, also of Lund University.

“But the data also highlight that even obesity and overweight alone comprise an increased risk of cancer,” Dr. Stocks noted.

Dr. Sun said the findings have important public health implications, suggesting that “a significant number of cancer cases could potentially be prevented by targeting the coexistence of metabolic problems and obesity, in particular for obesity-related cancers among men.”

The results will be presented as a poster by Dr. Sun at the European Congress on Obesity 2023, being held in Dublin, and have been published in the Journal of the National Cancer Institute.
 

Metabolically unhealthy obesity worst for cancer risks

Andrew G. Renehan, PhD, FRCS, professor of cancer studies and surgery, University of Manchester, England, welcomed the new work, saying it addresses the issue with very large study numbers. “[It] nicely demonstrates that there are clear examples where metabolically unhealthy overweight and obese phenotypes have increased cancer risk relative to [metabolically] healthy overweight and obese phenotypes,” he said.

“There is a clear need for clinically based research addressing these hypotheses ... but these studies will additionally need to factor in other dimensions such as the selection of treatment for metabolic aberrations, both medical and surgical, and the consequent metabolic control resulting from these interventions,” Dr. Renehan observed.

Vibhu Chittajallu, MD, a gastroenterologist based at University Hospitals Cleveland Medical Center, said it was beneficial to see another study further validating the association of obesity with the development of obesity-associated cancers.

“This is an interesting study [because it focuses] on the role of metabolic syndrome in obesity and how it affects the risk of development of obesity-associated cancers,” he said in an interview.

“I believe that the results of this study further strengthen the need for improved management of obesity and metabolic syndrome to reduce the risk of obesity-associated cancer formation that plays a role in preventable and premature deaths in adult patients with obesity.”
 

Synergy between metabolic aberrations and obesity, and cancer risk

Dr. Sun and colleagues note that obesity is an established risk factor for several cancers. It is often accompanied by metabolic aberrations, which have been a commonly proposed mechanism to link obesity with cancer. During the last decade, obesity with or without metabolic aberrations – commonly termed “metabolically unhealthy” or “healthy obesity” – has been extensively investigated in the cardiovascular field; however, studies regarding cancer are limited.

According to Dr. Sun, this new study is the first to look at the synergistic effect of unhealthy metabolism and body mass index – the latter was further categorized as normal weight (BMI < 25 kg/m2), overweight (BMI < 30) and obesity (BMI ≤ 30) – and the association with cancer risk, both overall and in relation to site-specific cancers.

Data were drawn from 797,193 European individuals (in Norway, Sweden, and Austria), of whom 23,630 developed an obesity-related cancer during the follow-up period. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to provide a measure of healthy or unhealthy metabolic status. Relative risks (hazard ratios) for overall and site-specific cancers were determined. Comparisons were made with metabolically healthy people of normal weight (effectively controls).

When different metabolic scores and BMIs were combined, participants fell into six categories: metabolically unhealthy obesity (6.8% of participants); metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically healthy overweight (19.8%), metabolically unhealthy normal weight (12.5%), and metabolically healthy normal weight (42.0%).

Metabolically unhealthy women with obesity had a hazard ratio of 1.43 for overall obesity-related cancers, compared with metabolically healthy women of normal weight. Of particular note were risks of two cancer types in women with metabolically unhealthy obesity: renal cancer, with an HR of 2.43, and endometrial cancer, with an HR of 3.0, compared with controls.

Even in metabolically healthy women with obesity, compared with metabolically healthy women of normal weight, there was an increased risk of endometrial cancer, with an HR of 2.36.

“If you look at individual cancers, in particular endometrial cancer, this seems to be very much driven by obesity and not so much by the metabolic factor,” remarked Dr. Stocks.

In males, compared with metabolically healthy men of normal weight, metabolically unhealthy men with obesity had an overall obesity-related cancer risk HR of 1.91. Specifically, the risk of renal cell cancer was more than doubled, with an HR of 2.59. The HR for colon cancer was 1.85, and that for rectal cancer and pancreatic cancer was similar, both having HRs of 1.32.

Again, risk was lower in metabolically healthy men with obesity, although still higher than for metabolically healthy normal-weight men.

A version of this article first appeared on Medscape.com.

In one of the first studies to examine this phenomenon, metabolically unhealthy obesity is associated with an increased risk, around 1.5-fold higher, of any obesity-related cancer, and an even higher risk, two- to threefold higher, for specific cancers, such as endometrial, liver, and renal cell cancers, compared with metabolically healthy normal weight.

Even in people with so-called “metabolically healthy” obesity, the risk for overall obesity-related cancer is increased, compared with normal-weight, metabolically healthy individuals; however, the associations here are weaker than in people with metabolically unhealthy obesity.

“The type of metabolic obesity phenotype is important when assessing obesity-related cancer risk,” lead researcher Ming Sun, PhD, from Lund University, Malmö, Sweden, said in an interview. “In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.”

“This synergy means that when obesity and metabolic unhealth occur together, that’s particularly bad,” added Tanja Stocks, PhD, senior author, also of Lund University.

“But the data also highlight that even obesity and overweight alone comprise an increased risk of cancer,” Dr. Stocks noted.

Dr. Sun said the findings have important public health implications, suggesting that “a significant number of cancer cases could potentially be prevented by targeting the coexistence of metabolic problems and obesity, in particular for obesity-related cancers among men.”

The results will be presented as a poster by Dr. Sun at the European Congress on Obesity 2023, being held in Dublin, and have been published in the Journal of the National Cancer Institute.
 

Metabolically unhealthy obesity worst for cancer risks

Andrew G. Renehan, PhD, FRCS, professor of cancer studies and surgery, University of Manchester, England, welcomed the new work, saying it addresses the issue with very large study numbers. “[It] nicely demonstrates that there are clear examples where metabolically unhealthy overweight and obese phenotypes have increased cancer risk relative to [metabolically] healthy overweight and obese phenotypes,” he said.

“There is a clear need for clinically based research addressing these hypotheses ... but these studies will additionally need to factor in other dimensions such as the selection of treatment for metabolic aberrations, both medical and surgical, and the consequent metabolic control resulting from these interventions,” Dr. Renehan observed.

Vibhu Chittajallu, MD, a gastroenterologist based at University Hospitals Cleveland Medical Center, said it was beneficial to see another study further validating the association of obesity with the development of obesity-associated cancers.

“This is an interesting study [because it focuses] on the role of metabolic syndrome in obesity and how it affects the risk of development of obesity-associated cancers,” he said in an interview.

“I believe that the results of this study further strengthen the need for improved management of obesity and metabolic syndrome to reduce the risk of obesity-associated cancer formation that plays a role in preventable and premature deaths in adult patients with obesity.”
 

Synergy between metabolic aberrations and obesity, and cancer risk

Dr. Sun and colleagues note that obesity is an established risk factor for several cancers. It is often accompanied by metabolic aberrations, which have been a commonly proposed mechanism to link obesity with cancer. During the last decade, obesity with or without metabolic aberrations – commonly termed “metabolically unhealthy” or “healthy obesity” – has been extensively investigated in the cardiovascular field; however, studies regarding cancer are limited.

According to Dr. Sun, this new study is the first to look at the synergistic effect of unhealthy metabolism and body mass index – the latter was further categorized as normal weight (BMI < 25 kg/m2), overweight (BMI < 30) and obesity (BMI ≤ 30) – and the association with cancer risk, both overall and in relation to site-specific cancers.

Data were drawn from 797,193 European individuals (in Norway, Sweden, and Austria), of whom 23,630 developed an obesity-related cancer during the follow-up period. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to provide a measure of healthy or unhealthy metabolic status. Relative risks (hazard ratios) for overall and site-specific cancers were determined. Comparisons were made with metabolically healthy people of normal weight (effectively controls).

When different metabolic scores and BMIs were combined, participants fell into six categories: metabolically unhealthy obesity (6.8% of participants); metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically healthy overweight (19.8%), metabolically unhealthy normal weight (12.5%), and metabolically healthy normal weight (42.0%).

Metabolically unhealthy women with obesity had a hazard ratio of 1.43 for overall obesity-related cancers, compared with metabolically healthy women of normal weight. Of particular note were risks of two cancer types in women with metabolically unhealthy obesity: renal cancer, with an HR of 2.43, and endometrial cancer, with an HR of 3.0, compared with controls.

Even in metabolically healthy women with obesity, compared with metabolically healthy women of normal weight, there was an increased risk of endometrial cancer, with an HR of 2.36.

“If you look at individual cancers, in particular endometrial cancer, this seems to be very much driven by obesity and not so much by the metabolic factor,” remarked Dr. Stocks.

In males, compared with metabolically healthy men of normal weight, metabolically unhealthy men with obesity had an overall obesity-related cancer risk HR of 1.91. Specifically, the risk of renal cell cancer was more than doubled, with an HR of 2.59. The HR for colon cancer was 1.85, and that for rectal cancer and pancreatic cancer was similar, both having HRs of 1.32.

Again, risk was lower in metabolically healthy men with obesity, although still higher than for metabolically healthy normal-weight men.

A version of this article first appeared on Medscape.com.

Bariatric surgery for obesity is associated with a reduced risk of developing breast cancer, new data suggest.

In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.

The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”

The study was published online in JAMA Surgery.
 

Protective association

To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).

Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.

Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).

In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.

Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.

Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.

There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).

In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).

“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.

Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”

There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
 

A universal benefit?

“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.

“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.

“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”

Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”

The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”

At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”

The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Bariatric surgery for obesity is associated with a reduced risk of developing breast cancer, new data suggest.

In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.

The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”

The study was published online in JAMA Surgery.
 

Protective association

To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).

Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.

Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).

In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.

Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.

Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.

There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).

In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).

“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.

Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”

There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
 

A universal benefit?

“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.

“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.

“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”

Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”

The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”

At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”

The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Bariatric surgery for obesity is associated with a reduced risk of developing breast cancer, new data suggest.

In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.

The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”

The study was published online in JAMA Surgery.
 

Protective association

To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).

Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.

Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).

In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.

Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.

Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.

There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).

In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).

“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.

Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”

There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
 

A universal benefit?

“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.

“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.

“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”

Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”

The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”

At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”

The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

A single dose of a new antibody-drug conjugate known as patritumab deruxtecan provoked a response in nearly one-third of patients with HR-positive/HER2-negative or triple-negative breast cancer, according to data presented from Abstract 1240 at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

Heidi Splete/MDedge News

Patritumab deruxtecan (HER3-DXd) has previously demonstrated an acceptable safety profile and antitumor activity in phase I studies involving heavily pretreated patients with metastatic breast cancer and various levels of HER3 protein expression, said Mafalda Oliveira, MD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona.

Antibody-drug conjugates (ADCs) are a combination of a monoclonal antibody chemically linked to a drug, as defined by the National Cancer Institute. ADCs work by binding to receptors or proteins and selectively delivering cytotoxic drugs to the site of a tumor.

Dr. Oliveira presented results from part B the of SOLTI TOT-HER3 trial, a window-of-opportunity trial that evaluated the effect of a single dose of HER3-Dxd in patients with treatment-naive HR+/HER2– early breast cancer.

In such trials, patients receive one or more new compounds between the time of cancer diagnosis and standard treatment. Biological and clinical activity from part A of the SOLTI TOT-HER3 trial were presented at last year’s ESMO Breast Cancer Congress, Dr. Oliveira said.

In the current study, Dr. Oliveira and colleagues recruited 37 women with HR+/HER2– early breast cancer, including 20 who were hormone receptor–positive and 17 who had triple negative breast cancer (TNBC). The age of the participants ranged from 30 to 81 years, with a median age of 51 years; 54% were premenopausal. The mean tumor size was 21 mm, with a range of 10-81 mm.

Distinct from part A of the SOLTI TOT-HER3 trial, part B included a subset of patients with TNBC to assess preliminary efficacy in this subtype, Dr. Oliveira noted.

All patients in part B received a single dose of 5.6 mg/kg of HER3-DXd. The primary outcome was the variation in the tumor cellularity and tumor-infiltrating lymphocyte (CelTIL) score at baseline and after 21 days via breast ultrasound.

At day 21, the total CelTIL score increased by a significant mean difference of 9.4 points after a single dose; the mean differences for TNBC and HR+/HER2– patients, were 17.9 points and 2.2 points, respectively, Dr. Oliveira said. The overall response rate was 32% (35% in TNBC patients and 30% in HR+/HER2– patients) and was significantly associated with the absolute change in CelTIL (area under the curve = 0.693; P = .049). 

In a subtype analysis, a statistically significant change in CelTIL was observed between paired samples overall (P = .046) and in TNBC (P = .016), but not in HR+ (P = .793).

Baseline levels of ERBB3 (also known as human epidermal growth factor receptor type 3, or HER3) were not associated with changes in CelTIL or in overall response rate.

HER3-DXd induced high expression of immune-related genes (such as PD1, CD8, and CD19), and suppressed proliferation-related genes, she said.

A total of 31 patients (84%) reported any adverse events. Of these, the most common were nausea, fatigue, alopecia, diarrhea, constipation, and vomiting, and one patient experienced grade 3 treatment-related nausea. No interstitial lung disease events were reported during the study, and the incidence of hematological and hepatic toxicity was lower with the lower dose in part B, compared with the 6.5 mg/kg dose used in part A, Dr. Oliveira noted.

To further validate the findings of the current study and assess the activity of HER3-DXd in early breast cancer, Dr. Oliveira and colleagues are conducting a neoadjuvant phase II trial known as SOLTI-2103 VALENTINE. In this study, they are testing six cycles of HER3-DXd at a 5.6 mg/kg dose in HR+/HER2– breast cancer patients, she said.

During a question-and-answer session, Dr. Oliveira was asked whether CelTIL is the best endpoint for assessing HER3-DXd. Finding the best endpoint is always a challenge when conducting window-of-opportunity trials, she said. The CelTIL score has been correlated with pathologic complete response (pCR), as well as with disease-free survival and overall survival, she added.
 

ICARUS-BREAST01

In a presentation of Abstract 1890 during the same session, Barbari Pistilli, MD, of Gustave Roussy Cancer Center, Villejuif, France, shared data from a phase II study known as ICARUS-BREAST.

Heidi Splete/MDedge News

The study population included women with unresectable locally advanced breast cancer (ABC) who had undergone a median of two previous systemic therapies. In the current study, the patients underwent a median of eight cycles of HER3-DXd. The dosage was 5.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

The primary outcome was overall response and disease progression after 3 months. Dr. Pistilli, who is also a coauthor of the research, provided data from 56 evaluable patients.

After 3 months, 16 patients (28.6%) showed a partial response, 30 patients showed stable disease (54%), and 10 (18%) showed disease progression. “No patients had a complete response,” Dr. Pistilli noted.

As for the safety profile, all patients reported at least one treatment-emergent event of any grade, but less than half (48.2%) were grade 3 or higher, and 12.5% led to treatment discontinuation. Fatigue and nausea were the most frequently reported adverse events overall, and occurred in 89.3% and 76.8% of patients, respectively. All grade and grade 3 or higher neutropenia occurred in four patients and six patients, respectively; all grade and grade 3 or higher thrombocytopenia occurred in four patients and two patients, respectively, Dr. Pistilli said.

Data on circulating tumor cells (CTCs) were available for 31 patients, and the researchers reviewed CTC counts after the first HER3-DXd cycle.

“We found that the median number of CTCs decreased by one to two cell cycles of HER3-DXd,” said Dr. Pistilli. She and her coauthors found no substantial impact of the treatment on HER3 negative CTC counts, and “more importantly, no increase of HER3 negative CTC counts at disease progression,” Dr. Pistilli continued.

In addition, patients with higher HER+ CTC counts at baseline or a greater decrease in HER3+ CTC counts after one cycle of HER3-DXd were more likely to have an early treatment response, but this association was not statistically significant.

Looking ahead, further analysis will be performed to evaluate the association between HER3+ CTC counts and dynamics and the main outcomes of overall response rate and progression-free survival to determine the potential of HER3+ CTC counts to identify patients who can benefit from HER3-DXd, said Dr. Pistilli. The ICARUS-BREAST01 study is ongoing, and further efficacy and biomarker analysis will be presented, she added.

In the question-and-answer session, Dr. Pistilli was asked why she chose CTC as a measure.

Dr. Pistilli responded that she and her coauthors wanted to understand whether CTC could serve as a biomarker to help in patient selection.

Also, when asked about which genes might be upregulated and downregulated in responders vs. nonresponders, she noted that some genes related to DNA repair were involved in patients who were responders, but more research is needed.
 

Early results merit further exploration

Although patritumab deruxtecan is early in development, “there is a clear signal to expand,” based on preliminary research, said Rebecca A. Dent, MD, who served as discussant for the two studies.

Heidi Splete/MDedge News

“There is no clear role for a specific subtype in both protein and gene expression,” noted Dr. Dent, who is a professor at Duke NUS Medical School, a collaboration between Duke University, Durham, N.C., and the National University of Singapore.

In the SOLTI TOT-HER3 trial, the small numbers make teasing out correlations a challenge, said Dr. Dent. However, changes were observed after just one cycle of the drug, and the upregulation of immune signature genes was reassuring, she said.

“A single dose of HER3-DXd induced an overall response of approximately 30% independently of hormone receptor status,” she emphasized, and the lower incidence of hematological and hepatic toxicity with the lower dose is good news as well. The findings were limited by the small sample size, but the results support moving forward with clinical development of HER3-DXd, she said.

The ICARUS-BREAST01 study researchers tried to show whether they could identify potential markers of early treatment response, and they examined CTCs and gene alterations, said Dr. Dent. “I think it is reassuring that despite these patients being heavily pretreated, HER-DXd seems to be active regardless of most frequent breast cancer genomic alterations,” she noted. Remaining questions include the need for more data on primary resistance.

“We are able to get these patients to respond, but what makes patients resistant to ADCs is just as important,” she said. “We see exciting data across all these subtypes,”

In Dr. Dent’s opinion, future research should focus on triple negative breast cancer, an opinion supported by the stronger response in this subset of patients in the SOLTI TOT-HER3 trial. “I think you need to bring triple negative to the table,” she said.

The SOLTI TOT-HER3 study was funded by Daiichi Sankyo. Dr. Oliveira disclosed relationships with companies including AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, Zenith Epigenetics, Daiichi Sankyo, iTEOS, MSD, Pierre-Fabre, Relay Therapeutics, and Eisai. ICARUS-BREAST01 was sponsored by the Gustave Roussy Cancer Center and supported by Daiichi Sankyo. Dr. Pistilli disclosed relationships with multiple companies including Daiichi-Sankyo, AstraZeneca, Gilead, Seagen, MSD, Novartis, Lilly, and Pierre Fabre. Dr. Dent disclosed financial relationships with companies including AstraZeneca, Roche, Eisai, Lilly, MSD, Novartis, and Pfizer.

Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.

EXPERT COMMENTARY

Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)¹ We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.^2-4

Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.⁵

Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.⁶ When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.⁷

Details of the study

Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.⁸ They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.

The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.

Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.

Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.

Study strengths and limitations

Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.⁹

The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.⁸ And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.⁴ ●

Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.

EXPERT COMMENTARY

Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)¹ We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.^2-4

Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.⁵

Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.⁶ When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.⁷

Details of the study

Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.⁸ They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.

The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.

Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.

Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.

Study strengths and limitations

Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.⁹

The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.⁸ And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.⁴ ●

Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.

EXPERT COMMENTARY

Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)¹ We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.^2-4

Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.⁵

Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.⁶ When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.⁷

Details of the study

Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.⁸ They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.

The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.

Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.

Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.

Study strengths and limitations

Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.⁹

The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.⁸ And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.⁴ ●

It was a quiet day. I got up around 3 o’clock in the afternoon for my shift at 6 p.m. I was shaking off the cobwebs and making coffee at our front window that overlooked Brown Street in North Philadelphia. I looked out the window and saw a man stumbling down the street, grabbing his abdomen and yelling for help. There was nobody else around so I went outside to see what was going on.

He was in his 50s or 60s, bleeding and obviously in distress. I had him sit down. Then I ran back inside and grabbed a dish towel and some exam gloves that I had in the house.

I ran back out and assessed him. A bullet had gone through one of his hands, but he had other wounds. I had to expose him, so I trauma stripped him on the sidewalk. I got his pants and his shirt off and saw a gunshot going through his lower pelvis. He was bleeding out from there.

I got the towel and started applying deep pressure down into the iliac vein in case they hit something, which I found out later, they had. I held it there. The man was just lying there begging not to die.

I’m someone who is very calm, maybe abnormally calm, as people tell me. I try to use that during my resuscitations and traumas. Just keeping everybody calm makes the situation easier. Afterwards, people asked me, “Weren’t you worried that you were going to get shot?” That does happen in North Philadelphia. But it didn’t even cross my mind.

I didn’t have to think at all about what I was doing. We saw so many gunshots, especially at Einstein Medical Center. We saw them daily. I’d sometimes get more than half a dozen gunshots in one shift.

So, I was holding pressure and some people started to come over. I got somebody to call 911 and asked the man about his medical history. I found out he had diabetes. Five or 10 minutes later, EMS showed up. They looked pretty stunned when I was able to give the handoff presentation to them. I told them what happened and his back-story. I wanted to make sure they would check his sugar and take extra precautions.

They got him on the stretcher, and he eventually made it to the hospital where he had surgery. They had to have a vascular surgeon work on him. I called later, and they told me, “Yeah, he’s alive.” But that’s about the extent of the update I got.

After the ambulance left, it was kind of chaos. All the neighbors poured out of their houses. People were panicked, talking and getting excited about it. I didn’t know, but everyone else had actually been home the whole time. They didn’t come out until then.

I went back inside and tried to get ready for work. I wasn’t planning on talking to the media, but my next door neighbor just walked the news camera crew over to my house and knocked on my door. I wasn’t exactly dressed to be on TV, but they talked to me on camera, and it was on the news later that night.

I went to work and didn’t say anything about it. To be honest, I was trying to avoid telling anyone. Our team had a close-knit bond, and we would often tease each other when we received any type of recognition.

Naturally one of my attendings saw it on the local news and told everybody. So, I got a lot of happy harassment for quite some time. Someone baked me a cake that said, “Hero of Fairmount” (the Philly neighborhood in which I live). Someone else printed out a photo of me that said, “Stop the Bleed Hero of Fairmount,” and put it on every single computer screen.

The man came to see me about 2 weeks later (a neighbor told him where I lived). The man was very tearful and gave me a big hug. We just embraced for a while, and he said how thankful he was. He brought me a bottle of wine, which I thought was really nice.

He told me what happened to him: There was a lot of construction on our street and he was the contractor overseeing a couple of home remodels and demolitions. Sometimes he paid workers in cash and carried it with him. Somebody had tipped off somebody else that he was going to be there that day. The contractor walked into one of the houses and a guy in a ski mask waited there with a gun. The guy shot him and took the cash. The bullet went through his hand into his pelvis.

I had never had to deal with something that intense before outside of work. Most of it really comes down to the basics – the ABCs and bleeding control. You do whatever you can with what you have. In this case, it was just a dish towel, gloves, and my hands to put as much pressure as possible.

It really was strange that I happened to be looking out the window at that moment. I don’t know if it was just a coincidence. The man told me he believed God had put somebody there at the right place at the right time to save his life. I just felt very fortunate to have been able to help him. I never saw him again.

I think something like this gives you a little confidence that you can actually do something and make a meaningful impact anywhere when it’s needed. It lets you know that you’re capable of doing it. You always think about it, but you don’t know until it happens.

A version of this article first appeared on Medscape.com.

It was a quiet day. I got up around 3 o’clock in the afternoon for my shift at 6 p.m. I was shaking off the cobwebs and making coffee at our front window that overlooked Brown Street in North Philadelphia. I looked out the window and saw a man stumbling down the street, grabbing his abdomen and yelling for help. There was nobody else around so I went outside to see what was going on.

He was in his 50s or 60s, bleeding and obviously in distress. I had him sit down. Then I ran back inside and grabbed a dish towel and some exam gloves that I had in the house.

I ran back out and assessed him. A bullet had gone through one of his hands, but he had other wounds. I had to expose him, so I trauma stripped him on the sidewalk. I got his pants and his shirt off and saw a gunshot going through his lower pelvis. He was bleeding out from there.

I got the towel and started applying deep pressure down into the iliac vein in case they hit something, which I found out later, they had. I held it there. The man was just lying there begging not to die.

I’m someone who is very calm, maybe abnormally calm, as people tell me. I try to use that during my resuscitations and traumas. Just keeping everybody calm makes the situation easier. Afterwards, people asked me, “Weren’t you worried that you were going to get shot?” That does happen in North Philadelphia. But it didn’t even cross my mind.

I didn’t have to think at all about what I was doing. We saw so many gunshots, especially at Einstein Medical Center. We saw them daily. I’d sometimes get more than half a dozen gunshots in one shift.

So, I was holding pressure and some people started to come over. I got somebody to call 911 and asked the man about his medical history. I found out he had diabetes. Five or 10 minutes later, EMS showed up. They looked pretty stunned when I was able to give the handoff presentation to them. I told them what happened and his back-story. I wanted to make sure they would check his sugar and take extra precautions.

They got him on the stretcher, and he eventually made it to the hospital where he had surgery. They had to have a vascular surgeon work on him. I called later, and they told me, “Yeah, he’s alive.” But that’s about the extent of the update I got.

After the ambulance left, it was kind of chaos. All the neighbors poured out of their houses. People were panicked, talking and getting excited about it. I didn’t know, but everyone else had actually been home the whole time. They didn’t come out until then.

I went back inside and tried to get ready for work. I wasn’t planning on talking to the media, but my next door neighbor just walked the news camera crew over to my house and knocked on my door. I wasn’t exactly dressed to be on TV, but they talked to me on camera, and it was on the news later that night.

I went to work and didn’t say anything about it. To be honest, I was trying to avoid telling anyone. Our team had a close-knit bond, and we would often tease each other when we received any type of recognition.

Naturally one of my attendings saw it on the local news and told everybody. So, I got a lot of happy harassment for quite some time. Someone baked me a cake that said, “Hero of Fairmount” (the Philly neighborhood in which I live). Someone else printed out a photo of me that said, “Stop the Bleed Hero of Fairmount,” and put it on every single computer screen.

The man came to see me about 2 weeks later (a neighbor told him where I lived). The man was very tearful and gave me a big hug. We just embraced for a while, and he said how thankful he was. He brought me a bottle of wine, which I thought was really nice.

He told me what happened to him: There was a lot of construction on our street and he was the contractor overseeing a couple of home remodels and demolitions. Sometimes he paid workers in cash and carried it with him. Somebody had tipped off somebody else that he was going to be there that day. The contractor walked into one of the houses and a guy in a ski mask waited there with a gun. The guy shot him and took the cash. The bullet went through his hand into his pelvis.

I had never had to deal with something that intense before outside of work. Most of it really comes down to the basics – the ABCs and bleeding control. You do whatever you can with what you have. In this case, it was just a dish towel, gloves, and my hands to put as much pressure as possible.

It really was strange that I happened to be looking out the window at that moment. I don’t know if it was just a coincidence. The man told me he believed God had put somebody there at the right place at the right time to save his life. I just felt very fortunate to have been able to help him. I never saw him again.

I think something like this gives you a little confidence that you can actually do something and make a meaningful impact anywhere when it’s needed. It lets you know that you’re capable of doing it. You always think about it, but you don’t know until it happens.

A version of this article first appeared on Medscape.com.

It was a quiet day. I got up around 3 o’clock in the afternoon for my shift at 6 p.m. I was shaking off the cobwebs and making coffee at our front window that overlooked Brown Street in North Philadelphia. I looked out the window and saw a man stumbling down the street, grabbing his abdomen and yelling for help. There was nobody else around so I went outside to see what was going on.

He was in his 50s or 60s, bleeding and obviously in distress. I had him sit down. Then I ran back inside and grabbed a dish towel and some exam gloves that I had in the house.

I ran back out and assessed him. A bullet had gone through one of his hands, but he had other wounds. I had to expose him, so I trauma stripped him on the sidewalk. I got his pants and his shirt off and saw a gunshot going through his lower pelvis. He was bleeding out from there.

I got the towel and started applying deep pressure down into the iliac vein in case they hit something, which I found out later, they had. I held it there. The man was just lying there begging not to die.

I’m someone who is very calm, maybe abnormally calm, as people tell me. I try to use that during my resuscitations and traumas. Just keeping everybody calm makes the situation easier. Afterwards, people asked me, “Weren’t you worried that you were going to get shot?” That does happen in North Philadelphia. But it didn’t even cross my mind.

I didn’t have to think at all about what I was doing. We saw so many gunshots, especially at Einstein Medical Center. We saw them daily. I’d sometimes get more than half a dozen gunshots in one shift.

So, I was holding pressure and some people started to come over. I got somebody to call 911 and asked the man about his medical history. I found out he had diabetes. Five or 10 minutes later, EMS showed up. They looked pretty stunned when I was able to give the handoff presentation to them. I told them what happened and his back-story. I wanted to make sure they would check his sugar and take extra precautions.

They got him on the stretcher, and he eventually made it to the hospital where he had surgery. They had to have a vascular surgeon work on him. I called later, and they told me, “Yeah, he’s alive.” But that’s about the extent of the update I got.

After the ambulance left, it was kind of chaos. All the neighbors poured out of their houses. People were panicked, talking and getting excited about it. I didn’t know, but everyone else had actually been home the whole time. They didn’t come out until then.

I went back inside and tried to get ready for work. I wasn’t planning on talking to the media, but my next door neighbor just walked the news camera crew over to my house and knocked on my door. I wasn’t exactly dressed to be on TV, but they talked to me on camera, and it was on the news later that night.

I went to work and didn’t say anything about it. To be honest, I was trying to avoid telling anyone. Our team had a close-knit bond, and we would often tease each other when we received any type of recognition.

Naturally one of my attendings saw it on the local news and told everybody. So, I got a lot of happy harassment for quite some time. Someone baked me a cake that said, “Hero of Fairmount” (the Philly neighborhood in which I live). Someone else printed out a photo of me that said, “Stop the Bleed Hero of Fairmount,” and put it on every single computer screen.

The man came to see me about 2 weeks later (a neighbor told him where I lived). The man was very tearful and gave me a big hug. We just embraced for a while, and he said how thankful he was. He brought me a bottle of wine, which I thought was really nice.

He told me what happened to him: There was a lot of construction on our street and he was the contractor overseeing a couple of home remodels and demolitions. Sometimes he paid workers in cash and carried it with him. Somebody had tipped off somebody else that he was going to be there that day. The contractor walked into one of the houses and a guy in a ski mask waited there with a gun. The guy shot him and took the cash. The bullet went through his hand into his pelvis.

I had never had to deal with something that intense before outside of work. Most of it really comes down to the basics – the ABCs and bleeding control. You do whatever you can with what you have. In this case, it was just a dish towel, gloves, and my hands to put as much pressure as possible.

It really was strange that I happened to be looking out the window at that moment. I don’t know if it was just a coincidence. The man told me he believed God had put somebody there at the right place at the right time to save his life. I just felt very fortunate to have been able to help him. I never saw him again.

I think something like this gives you a little confidence that you can actually do something and make a meaningful impact anywhere when it’s needed. It lets you know that you’re capable of doing it. You always think about it, but you don’t know until it happens.

A version of this article first appeared on Medscape.com.