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Systematic review of radiofrequency microneedling studies unveiled
Of the according to results from a new systematic review.
“Most devices for aesthetic purposes induce denaturation and remodeling of collagen, elastin, and other dermal structures through tissue injury and stimulating the body’s wound-healing response,” lead study author Marcus G. Tan, MD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “Radiofrequency microneedling is no exception in this regard. RFMN creates perforations in the skin and delivers radiofrequency-generated thermal energy into the underlying tissue. However, RFMN is unique in that thermal energy is delivered in a fashion that produces a reverse temperature gradient to most ablative lasers.”
When using ablative lasers, which target water as its chromophore through selective photothermolysis, the temperature gradient is highest at the epidermis and papillary dermis, and decreases as it penetrates the deeper structures of the skin. In RFMN, radiofrequency energy is delivered directly to the target depth through the microneedle electrodes, thus creating a temperature gradient that is highest in the deep, target structures and cooler at the superficial structures. “This results in less unwanted epidermal heating and reduces the risk of postinflammatory hyperpigmentation,” explained Dr. Tan, a resident in the division of dermatology at the University of Ottawa.
“Because RFMN is unaffected by skin chromophores, it is essentially a ‘color-blind’ technology and safe for use in patients of all skin phototypes. In comparison to lasers, radiofrequency energy can also be delivered to deeper structures of the skin by increasing the length of microneedle electrodes. Despite these advantages of RFMN, this technology remains utilized less frequently compared to ablative lasers for its skin rejuvenating effects.”
To review high-quality medical literature related to RFMN, Dr. Tan and colleagues searched EMBASE and MEDLINE from inception to May 13, 2020, by using the terms “radiofrequency microneedling,” “fractional radiofrequency,” “radiofrequency needling,” or “radiofrequency percutaneous collagen induction.” They limited the analysis to dermatology-related randomized, split-body, or blinded studies with original data in humans. Of the 42 studies included in the final analysis, there were 14 studies of skin rejuvenation, 7 of acne scars, 6 of acne vulgaris, 5 each of striae and axillary hyperhidrosis, 2 of melasma, and 1 each of rosacea, cellulite, and androgenetic alopecia.
After reviewing the 42 studies, the study authors proposed that a strong recommendation for RFMN be made for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, and a weak recommendation for the technology to be used for papulopustular rosacea, striae, and male-pattern androgenetic alopecia when used in conjunction with topical 5% minoxidil. There was insufficient evidence to make recommendations for its use in cellulite and melasma.
One finding that Dr. Tan described as “interesting” was the observation that RFMN was superior to Er:YAG fractional ablative lasers for treatment of rhytides on the lower face (i.e., the nasolabial, perioral, jawline and neck regions). “Secondly, we observed that one session of RFMN was able to achieve 37% efficacy of a surgical face-lift, but without any adverse effects,” Dr. Tan said. “Two-thirds of the patients who received surgical face-lift developed hypertrophic scarring requiring further scar management, compared to none of the patients receiving RFMN.”
Based on their review, Dr. Tan and colleagues recommend that RFMN be offered as one of the therapeutic options for patients seeking treatment for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis. “It is usually tolerable with just topical anesthesia applied 30-60 minutes before treatment, and its side effects are transient and usually resolve after 5 days,” he said. “Patients should be counseled that the benefits of RFMN may have a slower onset, compared to other treatments, but it is progressive, durable, and can be used repeatedly and safely in all skin types including darker-skin phenotypes with minimal risk of adverse events.”
One of the abstract section chairs, Fernanda H. Sakamoto, MD, PhD, said that RFMN devices have become increasingly popular in recent years. “The paper presented by Tan et al. is very relevant, as it compares clinical indications, parameters, and results in search for evidence of efficacy and appropriate settings,” said Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, told this news organization. “The paper provides long-needed guidelines to clinicians and helps manage patients’ expectations.”
Dr. Tan acknowledged certain limitations of the study, including the lack of head-to-head studies comparing specific RFMN devices. “There are many RFMN devices available commercially, each with different capabilities and degrees of effectiveness,” he said. “With more research and technological advancements since the first radiofrequency device was approved in 2002, RFMN has made significant improvements. In general, the newer generation devices produce markedly better results.”
Dr. Tan reported having no financial disclosures. Dr. Sakamoto disclosed that she holds intellectual property rights with Accure Acne, Massachusetts General Hospital, and Lightwater Biosciences.
Of the according to results from a new systematic review.
“Most devices for aesthetic purposes induce denaturation and remodeling of collagen, elastin, and other dermal structures through tissue injury and stimulating the body’s wound-healing response,” lead study author Marcus G. Tan, MD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “Radiofrequency microneedling is no exception in this regard. RFMN creates perforations in the skin and delivers radiofrequency-generated thermal energy into the underlying tissue. However, RFMN is unique in that thermal energy is delivered in a fashion that produces a reverse temperature gradient to most ablative lasers.”
When using ablative lasers, which target water as its chromophore through selective photothermolysis, the temperature gradient is highest at the epidermis and papillary dermis, and decreases as it penetrates the deeper structures of the skin. In RFMN, radiofrequency energy is delivered directly to the target depth through the microneedle electrodes, thus creating a temperature gradient that is highest in the deep, target structures and cooler at the superficial structures. “This results in less unwanted epidermal heating and reduces the risk of postinflammatory hyperpigmentation,” explained Dr. Tan, a resident in the division of dermatology at the University of Ottawa.
“Because RFMN is unaffected by skin chromophores, it is essentially a ‘color-blind’ technology and safe for use in patients of all skin phototypes. In comparison to lasers, radiofrequency energy can also be delivered to deeper structures of the skin by increasing the length of microneedle electrodes. Despite these advantages of RFMN, this technology remains utilized less frequently compared to ablative lasers for its skin rejuvenating effects.”
To review high-quality medical literature related to RFMN, Dr. Tan and colleagues searched EMBASE and MEDLINE from inception to May 13, 2020, by using the terms “radiofrequency microneedling,” “fractional radiofrequency,” “radiofrequency needling,” or “radiofrequency percutaneous collagen induction.” They limited the analysis to dermatology-related randomized, split-body, or blinded studies with original data in humans. Of the 42 studies included in the final analysis, there were 14 studies of skin rejuvenation, 7 of acne scars, 6 of acne vulgaris, 5 each of striae and axillary hyperhidrosis, 2 of melasma, and 1 each of rosacea, cellulite, and androgenetic alopecia.
After reviewing the 42 studies, the study authors proposed that a strong recommendation for RFMN be made for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, and a weak recommendation for the technology to be used for papulopustular rosacea, striae, and male-pattern androgenetic alopecia when used in conjunction with topical 5% minoxidil. There was insufficient evidence to make recommendations for its use in cellulite and melasma.
One finding that Dr. Tan described as “interesting” was the observation that RFMN was superior to Er:YAG fractional ablative lasers for treatment of rhytides on the lower face (i.e., the nasolabial, perioral, jawline and neck regions). “Secondly, we observed that one session of RFMN was able to achieve 37% efficacy of a surgical face-lift, but without any adverse effects,” Dr. Tan said. “Two-thirds of the patients who received surgical face-lift developed hypertrophic scarring requiring further scar management, compared to none of the patients receiving RFMN.”
Based on their review, Dr. Tan and colleagues recommend that RFMN be offered as one of the therapeutic options for patients seeking treatment for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis. “It is usually tolerable with just topical anesthesia applied 30-60 minutes before treatment, and its side effects are transient and usually resolve after 5 days,” he said. “Patients should be counseled that the benefits of RFMN may have a slower onset, compared to other treatments, but it is progressive, durable, and can be used repeatedly and safely in all skin types including darker-skin phenotypes with minimal risk of adverse events.”
One of the abstract section chairs, Fernanda H. Sakamoto, MD, PhD, said that RFMN devices have become increasingly popular in recent years. “The paper presented by Tan et al. is very relevant, as it compares clinical indications, parameters, and results in search for evidence of efficacy and appropriate settings,” said Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, told this news organization. “The paper provides long-needed guidelines to clinicians and helps manage patients’ expectations.”
Dr. Tan acknowledged certain limitations of the study, including the lack of head-to-head studies comparing specific RFMN devices. “There are many RFMN devices available commercially, each with different capabilities and degrees of effectiveness,” he said. “With more research and technological advancements since the first radiofrequency device was approved in 2002, RFMN has made significant improvements. In general, the newer generation devices produce markedly better results.”
Dr. Tan reported having no financial disclosures. Dr. Sakamoto disclosed that she holds intellectual property rights with Accure Acne, Massachusetts General Hospital, and Lightwater Biosciences.
Of the according to results from a new systematic review.
“Most devices for aesthetic purposes induce denaturation and remodeling of collagen, elastin, and other dermal structures through tissue injury and stimulating the body’s wound-healing response,” lead study author Marcus G. Tan, MD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “Radiofrequency microneedling is no exception in this regard. RFMN creates perforations in the skin and delivers radiofrequency-generated thermal energy into the underlying tissue. However, RFMN is unique in that thermal energy is delivered in a fashion that produces a reverse temperature gradient to most ablative lasers.”
When using ablative lasers, which target water as its chromophore through selective photothermolysis, the temperature gradient is highest at the epidermis and papillary dermis, and decreases as it penetrates the deeper structures of the skin. In RFMN, radiofrequency energy is delivered directly to the target depth through the microneedle electrodes, thus creating a temperature gradient that is highest in the deep, target structures and cooler at the superficial structures. “This results in less unwanted epidermal heating and reduces the risk of postinflammatory hyperpigmentation,” explained Dr. Tan, a resident in the division of dermatology at the University of Ottawa.
“Because RFMN is unaffected by skin chromophores, it is essentially a ‘color-blind’ technology and safe for use in patients of all skin phototypes. In comparison to lasers, radiofrequency energy can also be delivered to deeper structures of the skin by increasing the length of microneedle electrodes. Despite these advantages of RFMN, this technology remains utilized less frequently compared to ablative lasers for its skin rejuvenating effects.”
To review high-quality medical literature related to RFMN, Dr. Tan and colleagues searched EMBASE and MEDLINE from inception to May 13, 2020, by using the terms “radiofrequency microneedling,” “fractional radiofrequency,” “radiofrequency needling,” or “radiofrequency percutaneous collagen induction.” They limited the analysis to dermatology-related randomized, split-body, or blinded studies with original data in humans. Of the 42 studies included in the final analysis, there were 14 studies of skin rejuvenation, 7 of acne scars, 6 of acne vulgaris, 5 each of striae and axillary hyperhidrosis, 2 of melasma, and 1 each of rosacea, cellulite, and androgenetic alopecia.
After reviewing the 42 studies, the study authors proposed that a strong recommendation for RFMN be made for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, and a weak recommendation for the technology to be used for papulopustular rosacea, striae, and male-pattern androgenetic alopecia when used in conjunction with topical 5% minoxidil. There was insufficient evidence to make recommendations for its use in cellulite and melasma.
One finding that Dr. Tan described as “interesting” was the observation that RFMN was superior to Er:YAG fractional ablative lasers for treatment of rhytides on the lower face (i.e., the nasolabial, perioral, jawline and neck regions). “Secondly, we observed that one session of RFMN was able to achieve 37% efficacy of a surgical face-lift, but without any adverse effects,” Dr. Tan said. “Two-thirds of the patients who received surgical face-lift developed hypertrophic scarring requiring further scar management, compared to none of the patients receiving RFMN.”
Based on their review, Dr. Tan and colleagues recommend that RFMN be offered as one of the therapeutic options for patients seeking treatment for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis. “It is usually tolerable with just topical anesthesia applied 30-60 minutes before treatment, and its side effects are transient and usually resolve after 5 days,” he said. “Patients should be counseled that the benefits of RFMN may have a slower onset, compared to other treatments, but it is progressive, durable, and can be used repeatedly and safely in all skin types including darker-skin phenotypes with minimal risk of adverse events.”
One of the abstract section chairs, Fernanda H. Sakamoto, MD, PhD, said that RFMN devices have become increasingly popular in recent years. “The paper presented by Tan et al. is very relevant, as it compares clinical indications, parameters, and results in search for evidence of efficacy and appropriate settings,” said Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, told this news organization. “The paper provides long-needed guidelines to clinicians and helps manage patients’ expectations.”
Dr. Tan acknowledged certain limitations of the study, including the lack of head-to-head studies comparing specific RFMN devices. “There are many RFMN devices available commercially, each with different capabilities and degrees of effectiveness,” he said. “With more research and technological advancements since the first radiofrequency device was approved in 2002, RFMN has made significant improvements. In general, the newer generation devices produce markedly better results.”
Dr. Tan reported having no financial disclosures. Dr. Sakamoto disclosed that she holds intellectual property rights with Accure Acne, Massachusetts General Hospital, and Lightwater Biosciences.
FROM ASLMS 2021
Photobiomodulation reduced acute radiodermatitis severity in head and neck cancer patients
The delivery of , according to results from the first randomized study of its kind.
“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.
Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.
For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.
As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm2 based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.
After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).
“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”
The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.
“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”
Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”
This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”
Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”
This work won a “best of clinical applications” abstract award from the ASLMS.
The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.
The delivery of , according to results from the first randomized study of its kind.
“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.
Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.
For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.
As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm2 based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.
After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).
“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”
The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.
“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”
Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”
This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”
Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”
This work won a “best of clinical applications” abstract award from the ASLMS.
The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.
The delivery of , according to results from the first randomized study of its kind.
“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.
Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.
For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.
As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm2 based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.
After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).
“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”
The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.
“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”
Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”
This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”
Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”
This work won a “best of clinical applications” abstract award from the ASLMS.
The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.
FROM ASLMS 2021
Sex differences in COPD symptoms predict cardiac comorbidity
Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.
Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.
In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.
(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)
“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
GOLD standard
The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.
They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.
The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.
They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.
and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).
In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.
In women, however, only age was significantly predictive for cardiac disease.
“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
Reassuring data
David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.
“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”
Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.
“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.
The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.
A version of the article first appeared on Medscape.com.
Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.
Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.
In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.
(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)
“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
GOLD standard
The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.
They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.
The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.
They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.
and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).
In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.
In women, however, only age was significantly predictive for cardiac disease.
“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
Reassuring data
David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.
“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”
Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.
“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.
The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.
A version of the article first appeared on Medscape.com.
Sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) may point to different criteria for diagnosing cardiac comorbidities in women and men, a retrospective analysis suggests.
Among 2,046 patients in the German COSYCONET (COPD and Systemic Consequences–Comorbidities Net) cohort, most functional parameters and comorbidities and several items on the COPD Assessment Test (CAT) differed significantly between men and women.
In addition, there were sex-specific differences in the association between symptoms and cardiac disease, Franziska C. Trudzinski, MD, from the University of Heidelberg (Germany), and colleagues reported.
(Note: Although the authors used the term “gender” to distinguish male from female, this news organization has used the term “sex” in this article to refer to biological attributes of individual patients rather than personal identity.)
“[Sex]-specific differences in COPD comprised not only differences in the level of symptoms, comorbidities, and functional alterations but also differences in their mutual relationships. This was reflected in different sets of predictors for cardiac disease,” they wrote in a thematic poster presented at the American Thoracic Society’s virtual international conference.
GOLD standard
The investigators conducted an analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease from the COSYCONET COPD cohort.
They looked at the patients’ clinical history, comorbidities, lung function, CAT scores, and modified Medical Research Council (mMRC) dyspnea score.
The authors used multivariate regression analysis to model potential sex-related differences in the relationship between symptoms in general and CAT items in particular, and the pattern of comorbidities and functional alterations.
They also performed logistic regression analyses to identify predictors for cardiac disease, defined as myocardial infarction, heart failure, or coronary artery disease. The analyses were controlled for age, body mass index (BMI), smoking status, mMRC, CAT items, and z scores of forced expiratory volume in 1 second/forced vital capacity ratio.
and for CAT items of cough (item 1), phlegm (item 2), and energy (item 8; P < .05 for all comparisons).
In logistic regression analysis, predictors for cardiac disease in men were energy (CAT item 8), mMRC score, smoking status, BMI, age, and spirometric lung function.
In women, however, only age was significantly predictive for cardiac disease.
“Our findings give hints how diagnostic information might be used differently in men and women,” Dr. Trudzinski and colleagues wrote.
Reassuring data
David Mannino, MD, medical director of the COPD Foundation, who was not involved in the study, said in an interview that sex differences in COPD presentation and severity are common.
“In general, men and women report symptoms differently. For example, women don’t report a whole lot of chronic bronchitis and phlegm, although they may have it,” he said, “whereas men may report less dyspnea. It varies, but in general we know that men and women, even with the same type of disease, report symptoms differently.”
Comorbidities also differ between the sexes, he noted. Women more frequently have osteoporosis, and men more frequently have heart disease, as borne out in the study. The prevalence of heart disease among patients in the study was approximately 2.5 times higher in men than women.
“It’s reassuring, because what we’re seeing is similar to what we’ve seen in other [studies] with regards to comorbidities,” he said.
The study was sponsored by Philipps University Marburg Medical Center, Germany. The authors and Dr. Mannino have reported no relevant financial relationships.
A version of the article first appeared on Medscape.com.
Weighing the pros and cons of disposable duodenoscopes
Disposable duodenoscopes have one irrefutable advantage over their reusable counterparts: They definitively solve the problem of scope-related multidrug-resistant organism (MDRO) infections. Yet they also come with trade-offs, such as increased cost and medical waste, which has triggered pushback from skeptical endoscopists. How endoscopists weigh their differing concerns will ultimately determine the uptake of these devices going forward, according to Andrew S. Ross, MD, medical director for strategic growth at Virginia Mason Medical Center, Seattle.
“What would you pay to not have to deal with the scope infection issue at all?” Dr. Ross asked during a virtual presentation at the 2021 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology. “I think that x-factor is going to depend [on] who you’re talking to and how much they really believe in [duodenoscope-related infection] as an issue.”
Dr. Ross explained that some endoscopists doubt the clinical relevance of duodenoscope-related MDRO infections, possibly because of a lack of direct experience.
“There still is a prevailing sentiment among some endoscopists that duodenoscope infection is really not a problem,” Dr. Ross said. “Or [they may say,]: ‘We haven’t had that issue here in our medical center, so therefore it is not a problem.’ ”
In fact, the exact magnitude of the problem remains unknown.
“In the end, we have an unquantifiable risk to patients wherever [reusable duodenoscopes] are used,” Dr. Ross said.
Just how common are scope-related MDRO infections?
According to V. Raman Muthusamy, MD, AGAF, immediate former chair of the AGA Center for GI Innovation and Technology, and director of endoscopy at the University of California, Los Angeles Health System, scope-related MDRO infections are “relatively uncommon,” but they do occur.
MDRO infections are generally linked with contaminated endoscopes, but duodenoscopes are the most common culprit because they pose a unique risk.
“Traditionally, when outbreaks have occurred [with nonduodenoscopes], it has usually been due to a breach in the reprocessing protocol,” Dr. Muthusamy said in an interview. “But with duodenoscopes, we’ve found that that does not appear to be necessary, and that in many cases there are no identified breaches, and yet there are still outbreaks.”
Dr. Muthusamy, the first endoscopist to test a disposable duodenoscope in a human patient, noted that it’s challenging to definitively prove infection from a reusable scope. Citing an Executive Summary from the Food and Drug Administration, he said, “We know it’s happened 300-400 times over the past decade or so,” with infection rates peaking in 2014-2016 and steadily declining since then.
Approximately 5% of reprocessed duodenoscopes harbor pathogenic bacteria, according to Dr. Muthusamy, but the rate of infection is significantly lower.
“[The use of a contaminated duodenoscope] doesn’t mean a patient will actually get sick ... but it does mean the potential exists, obviously,” he said. “It just shows that these devices are hard to clean and a fraction of people have the potential of becoming ill. It’s our goal to improve on those numbers, and really try to eliminate the risk of this problem, as best we can.”
Infection isn’t the only concern
There are several potential ways to tackle the issue of scope-related infections, Dr. Ross said during his presentation, including designing devices that are easier to clean and optimizing the cleaning process; however, the only definitive solution is to eliminate cleaning altogether.
This is where disposable duodenoscopes come in.
At present, there are two such FDA-approved devices, the Ascope Duodeno from Ambu and the Exalt Model D from Boston Scientific, both of which Dr. Ross characterized as being “in their infancy.”
Studies testing the Exalt Model D suggest that performance compares favorably with reusable duodenoscopes.
“The scope works in a benchtop model, it works in a lab, and it seems to be functional in expert hands,” Dr. Ross said. “With inexperienced users, we also see that this device works, albeit with a rate of crossover that may approach up to 10%. So, a functional, disposable scope has been produced.”
Despite availability, several pain points may slow adoption, Dr. Ross said, including reluctance to use new technology, skepticism about the clinical impact of scope-related infections, environmental concerns of increased medical waste, and increased cost.
On this latter topic, Dr. Ross pointed out that the true cost of a reusable scope goes beyond the purchase or lease price to include repair costs, reprocessing costs, and, potentially, the cost of litigation from scope-related infection.
“If you have an outbreak in your medical center, you can rest assured that you will have some litigation exposure,” Dr. Ross said.
Fitting disposable duodenoscopes into routine practice
Currently, both FDA-approved disposable duodenoscopes are covered by outpatient pass-through reimbursement for Medicare, and in October, both will be covered on an inpatient basis, according to Dr. Ross.
“I think the big question regarding pass-through reimbursement is what happens when the codes get revalued,” he said. “How long will the additional reimbursement stay in place?”
For now, Dr. Ross suggested that endoscopists reach for disposable duodenoscopes in unique scenarios, such as weekend or night procedures, to avoid calling in a scope-reprocessing technician; or in operating room cases when the scope enters a sterile field. Disposable scopes should also be considered for patients with known MDROs, he added, and conversely, for patients who are immunocompromised or critically ill and “can least afford a scope-related infection.”
Ultimately, the role of disposable duodenoscopes may be decided by the patients themselves, Dr. Ross concluded.
“Certainly, patients know about this – they may come in and demand the use of a single-use scope in certain situations,” Dr. Ross said. “We have to remember when we’re bringing any new technology into the marketplace that while it’s important to understand the input and perspectives of multiple stakeholders, the single-most important stakeholder at the end of the day are our patients.”
Dr. Ross disclosed a relationship with Boston Scientific. Dr. Muthusamy disclosed a relationship with Boston Scientific and Medivators.
Disposable duodenoscopes have one irrefutable advantage over their reusable counterparts: They definitively solve the problem of scope-related multidrug-resistant organism (MDRO) infections. Yet they also come with trade-offs, such as increased cost and medical waste, which has triggered pushback from skeptical endoscopists. How endoscopists weigh their differing concerns will ultimately determine the uptake of these devices going forward, according to Andrew S. Ross, MD, medical director for strategic growth at Virginia Mason Medical Center, Seattle.
“What would you pay to not have to deal with the scope infection issue at all?” Dr. Ross asked during a virtual presentation at the 2021 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology. “I think that x-factor is going to depend [on] who you’re talking to and how much they really believe in [duodenoscope-related infection] as an issue.”
Dr. Ross explained that some endoscopists doubt the clinical relevance of duodenoscope-related MDRO infections, possibly because of a lack of direct experience.
“There still is a prevailing sentiment among some endoscopists that duodenoscope infection is really not a problem,” Dr. Ross said. “Or [they may say,]: ‘We haven’t had that issue here in our medical center, so therefore it is not a problem.’ ”
In fact, the exact magnitude of the problem remains unknown.
“In the end, we have an unquantifiable risk to patients wherever [reusable duodenoscopes] are used,” Dr. Ross said.
Just how common are scope-related MDRO infections?
According to V. Raman Muthusamy, MD, AGAF, immediate former chair of the AGA Center for GI Innovation and Technology, and director of endoscopy at the University of California, Los Angeles Health System, scope-related MDRO infections are “relatively uncommon,” but they do occur.
MDRO infections are generally linked with contaminated endoscopes, but duodenoscopes are the most common culprit because they pose a unique risk.
“Traditionally, when outbreaks have occurred [with nonduodenoscopes], it has usually been due to a breach in the reprocessing protocol,” Dr. Muthusamy said in an interview. “But with duodenoscopes, we’ve found that that does not appear to be necessary, and that in many cases there are no identified breaches, and yet there are still outbreaks.”
Dr. Muthusamy, the first endoscopist to test a disposable duodenoscope in a human patient, noted that it’s challenging to definitively prove infection from a reusable scope. Citing an Executive Summary from the Food and Drug Administration, he said, “We know it’s happened 300-400 times over the past decade or so,” with infection rates peaking in 2014-2016 and steadily declining since then.
Approximately 5% of reprocessed duodenoscopes harbor pathogenic bacteria, according to Dr. Muthusamy, but the rate of infection is significantly lower.
“[The use of a contaminated duodenoscope] doesn’t mean a patient will actually get sick ... but it does mean the potential exists, obviously,” he said. “It just shows that these devices are hard to clean and a fraction of people have the potential of becoming ill. It’s our goal to improve on those numbers, and really try to eliminate the risk of this problem, as best we can.”
Infection isn’t the only concern
There are several potential ways to tackle the issue of scope-related infections, Dr. Ross said during his presentation, including designing devices that are easier to clean and optimizing the cleaning process; however, the only definitive solution is to eliminate cleaning altogether.
This is where disposable duodenoscopes come in.
At present, there are two such FDA-approved devices, the Ascope Duodeno from Ambu and the Exalt Model D from Boston Scientific, both of which Dr. Ross characterized as being “in their infancy.”
Studies testing the Exalt Model D suggest that performance compares favorably with reusable duodenoscopes.
“The scope works in a benchtop model, it works in a lab, and it seems to be functional in expert hands,” Dr. Ross said. “With inexperienced users, we also see that this device works, albeit with a rate of crossover that may approach up to 10%. So, a functional, disposable scope has been produced.”
Despite availability, several pain points may slow adoption, Dr. Ross said, including reluctance to use new technology, skepticism about the clinical impact of scope-related infections, environmental concerns of increased medical waste, and increased cost.
On this latter topic, Dr. Ross pointed out that the true cost of a reusable scope goes beyond the purchase or lease price to include repair costs, reprocessing costs, and, potentially, the cost of litigation from scope-related infection.
“If you have an outbreak in your medical center, you can rest assured that you will have some litigation exposure,” Dr. Ross said.
Fitting disposable duodenoscopes into routine practice
Currently, both FDA-approved disposable duodenoscopes are covered by outpatient pass-through reimbursement for Medicare, and in October, both will be covered on an inpatient basis, according to Dr. Ross.
“I think the big question regarding pass-through reimbursement is what happens when the codes get revalued,” he said. “How long will the additional reimbursement stay in place?”
For now, Dr. Ross suggested that endoscopists reach for disposable duodenoscopes in unique scenarios, such as weekend or night procedures, to avoid calling in a scope-reprocessing technician; or in operating room cases when the scope enters a sterile field. Disposable scopes should also be considered for patients with known MDROs, he added, and conversely, for patients who are immunocompromised or critically ill and “can least afford a scope-related infection.”
Ultimately, the role of disposable duodenoscopes may be decided by the patients themselves, Dr. Ross concluded.
“Certainly, patients know about this – they may come in and demand the use of a single-use scope in certain situations,” Dr. Ross said. “We have to remember when we’re bringing any new technology into the marketplace that while it’s important to understand the input and perspectives of multiple stakeholders, the single-most important stakeholder at the end of the day are our patients.”
Dr. Ross disclosed a relationship with Boston Scientific. Dr. Muthusamy disclosed a relationship with Boston Scientific and Medivators.
Disposable duodenoscopes have one irrefutable advantage over their reusable counterparts: They definitively solve the problem of scope-related multidrug-resistant organism (MDRO) infections. Yet they also come with trade-offs, such as increased cost and medical waste, which has triggered pushback from skeptical endoscopists. How endoscopists weigh their differing concerns will ultimately determine the uptake of these devices going forward, according to Andrew S. Ross, MD, medical director for strategic growth at Virginia Mason Medical Center, Seattle.
“What would you pay to not have to deal with the scope infection issue at all?” Dr. Ross asked during a virtual presentation at the 2021 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology. “I think that x-factor is going to depend [on] who you’re talking to and how much they really believe in [duodenoscope-related infection] as an issue.”
Dr. Ross explained that some endoscopists doubt the clinical relevance of duodenoscope-related MDRO infections, possibly because of a lack of direct experience.
“There still is a prevailing sentiment among some endoscopists that duodenoscope infection is really not a problem,” Dr. Ross said. “Or [they may say,]: ‘We haven’t had that issue here in our medical center, so therefore it is not a problem.’ ”
In fact, the exact magnitude of the problem remains unknown.
“In the end, we have an unquantifiable risk to patients wherever [reusable duodenoscopes] are used,” Dr. Ross said.
Just how common are scope-related MDRO infections?
According to V. Raman Muthusamy, MD, AGAF, immediate former chair of the AGA Center for GI Innovation and Technology, and director of endoscopy at the University of California, Los Angeles Health System, scope-related MDRO infections are “relatively uncommon,” but they do occur.
MDRO infections are generally linked with contaminated endoscopes, but duodenoscopes are the most common culprit because they pose a unique risk.
“Traditionally, when outbreaks have occurred [with nonduodenoscopes], it has usually been due to a breach in the reprocessing protocol,” Dr. Muthusamy said in an interview. “But with duodenoscopes, we’ve found that that does not appear to be necessary, and that in many cases there are no identified breaches, and yet there are still outbreaks.”
Dr. Muthusamy, the first endoscopist to test a disposable duodenoscope in a human patient, noted that it’s challenging to definitively prove infection from a reusable scope. Citing an Executive Summary from the Food and Drug Administration, he said, “We know it’s happened 300-400 times over the past decade or so,” with infection rates peaking in 2014-2016 and steadily declining since then.
Approximately 5% of reprocessed duodenoscopes harbor pathogenic bacteria, according to Dr. Muthusamy, but the rate of infection is significantly lower.
“[The use of a contaminated duodenoscope] doesn’t mean a patient will actually get sick ... but it does mean the potential exists, obviously,” he said. “It just shows that these devices are hard to clean and a fraction of people have the potential of becoming ill. It’s our goal to improve on those numbers, and really try to eliminate the risk of this problem, as best we can.”
Infection isn’t the only concern
There are several potential ways to tackle the issue of scope-related infections, Dr. Ross said during his presentation, including designing devices that are easier to clean and optimizing the cleaning process; however, the only definitive solution is to eliminate cleaning altogether.
This is where disposable duodenoscopes come in.
At present, there are two such FDA-approved devices, the Ascope Duodeno from Ambu and the Exalt Model D from Boston Scientific, both of which Dr. Ross characterized as being “in their infancy.”
Studies testing the Exalt Model D suggest that performance compares favorably with reusable duodenoscopes.
“The scope works in a benchtop model, it works in a lab, and it seems to be functional in expert hands,” Dr. Ross said. “With inexperienced users, we also see that this device works, albeit with a rate of crossover that may approach up to 10%. So, a functional, disposable scope has been produced.”
Despite availability, several pain points may slow adoption, Dr. Ross said, including reluctance to use new technology, skepticism about the clinical impact of scope-related infections, environmental concerns of increased medical waste, and increased cost.
On this latter topic, Dr. Ross pointed out that the true cost of a reusable scope goes beyond the purchase or lease price to include repair costs, reprocessing costs, and, potentially, the cost of litigation from scope-related infection.
“If you have an outbreak in your medical center, you can rest assured that you will have some litigation exposure,” Dr. Ross said.
Fitting disposable duodenoscopes into routine practice
Currently, both FDA-approved disposable duodenoscopes are covered by outpatient pass-through reimbursement for Medicare, and in October, both will be covered on an inpatient basis, according to Dr. Ross.
“I think the big question regarding pass-through reimbursement is what happens when the codes get revalued,” he said. “How long will the additional reimbursement stay in place?”
For now, Dr. Ross suggested that endoscopists reach for disposable duodenoscopes in unique scenarios, such as weekend or night procedures, to avoid calling in a scope-reprocessing technician; or in operating room cases when the scope enters a sterile field. Disposable scopes should also be considered for patients with known MDROs, he added, and conversely, for patients who are immunocompromised or critically ill and “can least afford a scope-related infection.”
Ultimately, the role of disposable duodenoscopes may be decided by the patients themselves, Dr. Ross concluded.
“Certainly, patients know about this – they may come in and demand the use of a single-use scope in certain situations,” Dr. Ross said. “We have to remember when we’re bringing any new technology into the marketplace that while it’s important to understand the input and perspectives of multiple stakeholders, the single-most important stakeholder at the end of the day are our patients.”
Dr. Ross disclosed a relationship with Boston Scientific. Dr. Muthusamy disclosed a relationship with Boston Scientific and Medivators.
FROM THE 2021 AGA TECH SUMMIT
Mother-to-infant COVID-19 transmission is unlikely
Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.
“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.
The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.
In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.
During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.
Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.
No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.
The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
Study supports safety of rooming in
The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.
Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.
“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.
The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.
In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.
During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.
Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.
No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.
The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
Study supports safety of rooming in
The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.
Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
Mothers with a history of COVID-19 exposure during pregnancy are not likely to transmit the infection to their newborns, based on data from more than 2,000 women.
“Uncertainty at the onset of the COVID-19 pandemic led to varying postnatal care recommendations for newborns exposed to SARS-CoV-2 in utero,” said Margaret H. Kyle, of Columbia University, New York, and colleagues.
The Columbia University Irving Medical Center, an early epicenter of the pandemic, allowed rooming-in and encouraged direct breastfeeding between infected mothers and their newborns while adopting extensive safety measures, the researchers said.
In a study presented at the virtual meeting of the Pediatric Academic Societies (Poster 141), the researchers conducted a retrospective chart review of all newborns born at the medical center from March 22, 2020, through August 7, 2020. The study was part of Columbia University’s ongoing COVID-19 Mother Baby Outcomes (COMBO) initiative to “describe the health and well-being of mother-infant dyads with and without prenatal SARS-CoV-2 infections,” according to the researchers.
During the study period, the researchers identified newborns of 327 women who tested positive for COVID-19 at any point during pregnancy and compared them to newborns of 2,125 unexposed women. Demographics were similar between the groups.
Overall, the total test positivity was 0.7% for exposed newborns; 1.0% tested positive on an initial test, and 0% were positive on retest. During the newborn hospital stay and a 2-week follow-up, 0% of all newborns showed clinical evidence of infection.
No significant differences were noted between exposed and unexposed newborns in clinical outcomes including gestational age, mode of delivery, 5-minute Apgar score, heart rate, respiratory rate, or temperature. Although more infants of COVID-19–exposed mothers compared with unexposed mothers had an emergency department visit within the first 14 days of life (6% vs. 3%, P = .002), none of the infants was diagnosed with COVID-19 during these visits. Cough, fever, congestion, or bilirubin were more frequent reasons for emergency department visits in the exposed infants compared with unexposed infants, but these differences were not significant.
The study findings were limited by several factors, including the retrospective design and the limited follow-up period to only the first 2 weeks of life, the researchers noted. In addition, perinatal transmission rates were available only for the 202 newborns who were followed up in the hospital system, they said. However, the results suggest that the risk of mother-to-newborn vertical transmission of COVID-19 remains low, even when mothers are breastfeeding and infants are rooming in, they concluded.
Study supports safety of rooming in
The study is important because of the value of mother and infant bonding, Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview. “We know maternal and infant bonding and breastfeeding are extremely important in the first few days of life,” she said. “Initially, COVID-positive moms were separated from their babies during this important time.” Dr. Kinsella said she was not surprised by the study findings, as they reflect other research that newborns have not been getting infected with COVID-19 from their mothers.
Consequently, the take-home message is that newborns can room in with their mothers in the hospital setting, and they are at low risk for COVID-19 regardless of the mother’s exposure history, said Dr. Kinsella. Looking ahead, future areas of research could include examining SARS-CoV-2 antibodies in newborns, she noted.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
FROM PAS 2021
Herbal and dietary weight-loss supplements: No evidence that they work
Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.
“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.
She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.
But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.
“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.
The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
Herbal and dietary supplement industry booming
Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.
In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”
Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.
“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.
“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.
One review for herbal supplements, one for organic compounds
To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.
Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.
Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.
The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.
The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.
Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).
The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.
Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
No clinically significant results
Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”
The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.
For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).
Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).
In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.
Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.
She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”
The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.
Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
A version of this article first appeared on Medscape.com.
Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.
“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.
She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.
But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.
“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.
The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
Herbal and dietary supplement industry booming
Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.
In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”
Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.
“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.
“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.
One review for herbal supplements, one for organic compounds
To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.
Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.
Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.
The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.
The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.
Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).
The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.
Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
No clinically significant results
Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”
The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.
For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).
Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).
In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.
Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.
She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”
The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.
Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
A version of this article first appeared on Medscape.com.
Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.
“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.
She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.
But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.
“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.
The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
Herbal and dietary supplement industry booming
Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.
In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”
Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.
“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.
“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.
One review for herbal supplements, one for organic compounds
To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.
Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.
Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.
The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.
The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.
Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).
The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.
Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
No clinically significant results
Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”
The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.
For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).
Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).
In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.
Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.
She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”
The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.
Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
A version of this article first appeared on Medscape.com.
‘Inflammasomes’ may play a role in obesity-related CRC
Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.
“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.
“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.
The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic. The meeting was presented by the European Association for the Study of Obesity.
Tissue samples
Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.
A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.
Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.
Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.
“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.
Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.
“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.
Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.
The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.
Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.
Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.
“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
A version of this article first appeared on Medscape.com.
Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.
“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.
“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.
The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic. The meeting was presented by the European Association for the Study of Obesity.
Tissue samples
Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.
A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.
Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.
Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.
“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.
Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.
“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.
Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.
The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.
Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.
Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.
“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
A version of this article first appeared on Medscape.com.
Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.
“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.
“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.
The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic. The meeting was presented by the European Association for the Study of Obesity.
Tissue samples
Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.
A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.
Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.
Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.
“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.
Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.
“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.
Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.
The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.
Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.
Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.
“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
A version of this article first appeared on Medscape.com.
Worse outcomes for patients with COPD and COVID-19
A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.
Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.
Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.
A critical care specialist who was not involved in the study said that the results are concerning but not surprising.
“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.
The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
Retrospective analysis
Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.
Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).
In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).
Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
‘Mechanisms unclear’
“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”
They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”
Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.
No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.
Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.
Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.
A critical care specialist who was not involved in the study said that the results are concerning but not surprising.
“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.
The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
Retrospective analysis
Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.
Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).
In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).
Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
‘Mechanisms unclear’
“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”
They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”
Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.
No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.
Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.
Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.
A critical care specialist who was not involved in the study said that the results are concerning but not surprising.
“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.
The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
Retrospective analysis
Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.
Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).
In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).
Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
‘Mechanisms unclear’
“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”
They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”
Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.
No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
GI and liver diseases linked to alcohol spiked during pandemic
It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.
Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.
“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.
“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.
“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.
Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”
“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.
Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.
Suggested questions include: Do you drink alcohol? How much did you drink in the past week?
“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.
After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.
At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.
However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.
Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.
“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.
“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.
Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”
Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”
A version of this article first appeared on Medscape.com.
It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.
Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.
“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.
“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.
“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.
Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”
“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.
Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.
Suggested questions include: Do you drink alcohol? How much did you drink in the past week?
“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.
After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.
At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.
However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.
Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.
“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.
“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.
Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”
Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”
A version of this article first appeared on Medscape.com.
It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.
Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.
“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.
“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.
“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.
Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”
“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.
Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.
Suggested questions include: Do you drink alcohol? How much did you drink in the past week?
“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.
After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.
At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.
However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.
Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.
“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.
“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.
Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”
Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”
A version of this article first appeared on Medscape.com.
GELATO trial: Chemoimmunotherapy may help in metastatic invasive lobular breast cancer
The PD-L1 inhibitor atezolizumab (Tecentriq) combined with carboplatin has shown signs of clinical activity in women with metastatic invasive lobular breast cancer (ILC) according to the first results to come from the ongoing GELATO trial.
The 6-month objective response rate was 19%, based on 4 of 21 patients who could be evaluated exhibiting a partial response to the chemoimmunotherapy. A further two (10%) patients had stable disease, meaning that clinical benefit rate was 29%.
GELATO (AssessinG Efficacy of Carboplatin and ATezOlizumab in Metastatic Lobular Breast Cancer) is a phase 2 trial being conducted at four Dutch centers. The primary premise of the study is that “there’s an immune-related subtype of ILC,” researcher Leonie Voorwerk, BSc, reported at the European Society for Medical Oncology: Breast Cancer virtual meeting (Abstract LBA3).
This ILC subtype is “characterized by high expression of immune-related genes and high levels of TILs [tumor-infiltrating lymphocytes] and PDL-1,” said Ms. Voorwerk, a PhD student working with medical oncologist Marleen Kok, MD, PhD, at the Netherlands Cancer Institute in Amsterdam.
Furthermore, she added, in vitro data suggest sensitivity of immune-related-ILCs to platinum and there is preclinical work showing that there is synergy between platinum-based chemotherapy and checkpoint blockade.
First chemoimmunotherapy trial in lobular cancer setting
GELATO is a significant trial as it is “the first chemoimmunotherapy trial in metastatic lobular breast cancer,” said Sylvia Adams, MD, professor of medicine and director of the Breast Cancer Center at NYU Langone Health in New York City.
“Of note, the further research should include the immune-related genes and TMB [tumor mutational burden],” proposed Dr. Adams, who was not involved in the trial.
“We should look to tumor mutational burden because while it is not typically high in early disease, metastatic lesions can have higher TMB,” she explained. “Also, metastatic ILC is known to have higher tumor mutational burden compared to IDC [invasive ductal carcinoma], so this is an important thing along with the clinical factors as described in looking at outcomes.”
Trial design and patient characteristics
GELATO is a single-arm, nonrandomized trial in which 37 patients with metastatic ILC were screened for inclusion between November 2017 and January 2021. A total of 26 of these patients were registered for the trial, and 23 have so far received at least one cycle of atezolizumab.
Prerequisites for entry into the trial were that patients had to have negative or aberrant E-cadherin, a characteristic feature of ILC. Patients with estrogen receptor (ER)-positive (ER+) disease could be included, but they had to be proven to be resistant to endocrine therapies. No more than two prior lines of palliative chemotherapy were allowed, and all participants had to have lactose dehydrogenase levels of less than 2 times the upper limit of normal.
Patients were then treated with up to 12 cycles of weekly carboplatin (AUC = 1.5 mg/mL/min), with atezolizumab (1,200 mg) added in from cycle 3 onward. Treatment was continued until disease progression or unacceptable toxicity occurred.
“Baseline characteristics were mainly as expected for this patient population,” Ms. Voorwerk stated. Patients were aged 45-89 years, with a median of 60 years. Around half each had a WHO performance status of 0 or 1, and around half each had one to two or three or more metastatic sites; 78% had liver metastases.
“But I want to highlight that we included five patients with the triple-negative ILC,” said Ms. Voorwerk, also highlighting that approximately 50% of patients had received prior palliative chemotherapy. Later in her presentation she noted that four out of the six patients that showed any clinical benefit had triple negative disease.
Key findings and next steps
The primary endpoint was progression-free survival (PFS) at 6 months, with secondary endpoints of the best overall response rate, PFS at 1 year, overall survival, and safety.
While details of the latter three endpoints are yet to be reported, Ms. Voorwerk noted that there was a median duration of response of 12 weeks and the median PFS was 15 weeks. The primary endpoint of PFS was met as four patients were free of progression at 6 months and the statistical method used called for patients to be progression free at this time point.
“We observed that stromal TILs and CD8+ cells were not associated with clinical benefits,” said Ms. Voorwerk. There was, however, “a slight trend” toward higher PD-L1 expression in responding patients.
“Further translational research is needed to provide the rationale for new strategies to improve checkpoint blockade in patients with lobular breast cancer,” she concluded.
Dr. Adams concurred, adding that a future research question was whether either atezolizumab or carboplatin was contributing to the response. This is “difficult to tell as the study was a single arm trial.”
Another question, said Dr. Adams, is are “anti-CDK 4/6 inhibitors helpful in improving response rates and durability?” In the trial, 70% of patients had prior exposure to CDK 4/6 inhibitors.
The GELATO trial was sponsored by the Netherlands Cancer Institute with funding from Roche Pharma AG. Ms. Voorwerk had nothing to disclose. Dr. Adams disclosed uncompensated consulting or advisory roles with Bristol-Myers Squibb, Genentech, and Merck from whom she has received research funding. Dr. Adams also disclosed research funding from Amgen, Celgene, and Novartis.
The PD-L1 inhibitor atezolizumab (Tecentriq) combined with carboplatin has shown signs of clinical activity in women with metastatic invasive lobular breast cancer (ILC) according to the first results to come from the ongoing GELATO trial.
The 6-month objective response rate was 19%, based on 4 of 21 patients who could be evaluated exhibiting a partial response to the chemoimmunotherapy. A further two (10%) patients had stable disease, meaning that clinical benefit rate was 29%.
GELATO (AssessinG Efficacy of Carboplatin and ATezOlizumab in Metastatic Lobular Breast Cancer) is a phase 2 trial being conducted at four Dutch centers. The primary premise of the study is that “there’s an immune-related subtype of ILC,” researcher Leonie Voorwerk, BSc, reported at the European Society for Medical Oncology: Breast Cancer virtual meeting (Abstract LBA3).
This ILC subtype is “characterized by high expression of immune-related genes and high levels of TILs [tumor-infiltrating lymphocytes] and PDL-1,” said Ms. Voorwerk, a PhD student working with medical oncologist Marleen Kok, MD, PhD, at the Netherlands Cancer Institute in Amsterdam.
Furthermore, she added, in vitro data suggest sensitivity of immune-related-ILCs to platinum and there is preclinical work showing that there is synergy between platinum-based chemotherapy and checkpoint blockade.
First chemoimmunotherapy trial in lobular cancer setting
GELATO is a significant trial as it is “the first chemoimmunotherapy trial in metastatic lobular breast cancer,” said Sylvia Adams, MD, professor of medicine and director of the Breast Cancer Center at NYU Langone Health in New York City.
“Of note, the further research should include the immune-related genes and TMB [tumor mutational burden],” proposed Dr. Adams, who was not involved in the trial.
“We should look to tumor mutational burden because while it is not typically high in early disease, metastatic lesions can have higher TMB,” she explained. “Also, metastatic ILC is known to have higher tumor mutational burden compared to IDC [invasive ductal carcinoma], so this is an important thing along with the clinical factors as described in looking at outcomes.”
Trial design and patient characteristics
GELATO is a single-arm, nonrandomized trial in which 37 patients with metastatic ILC were screened for inclusion between November 2017 and January 2021. A total of 26 of these patients were registered for the trial, and 23 have so far received at least one cycle of atezolizumab.
Prerequisites for entry into the trial were that patients had to have negative or aberrant E-cadherin, a characteristic feature of ILC. Patients with estrogen receptor (ER)-positive (ER+) disease could be included, but they had to be proven to be resistant to endocrine therapies. No more than two prior lines of palliative chemotherapy were allowed, and all participants had to have lactose dehydrogenase levels of less than 2 times the upper limit of normal.
Patients were then treated with up to 12 cycles of weekly carboplatin (AUC = 1.5 mg/mL/min), with atezolizumab (1,200 mg) added in from cycle 3 onward. Treatment was continued until disease progression or unacceptable toxicity occurred.
“Baseline characteristics were mainly as expected for this patient population,” Ms. Voorwerk stated. Patients were aged 45-89 years, with a median of 60 years. Around half each had a WHO performance status of 0 or 1, and around half each had one to two or three or more metastatic sites; 78% had liver metastases.
“But I want to highlight that we included five patients with the triple-negative ILC,” said Ms. Voorwerk, also highlighting that approximately 50% of patients had received prior palliative chemotherapy. Later in her presentation she noted that four out of the six patients that showed any clinical benefit had triple negative disease.
Key findings and next steps
The primary endpoint was progression-free survival (PFS) at 6 months, with secondary endpoints of the best overall response rate, PFS at 1 year, overall survival, and safety.
While details of the latter three endpoints are yet to be reported, Ms. Voorwerk noted that there was a median duration of response of 12 weeks and the median PFS was 15 weeks. The primary endpoint of PFS was met as four patients were free of progression at 6 months and the statistical method used called for patients to be progression free at this time point.
“We observed that stromal TILs and CD8+ cells were not associated with clinical benefits,” said Ms. Voorwerk. There was, however, “a slight trend” toward higher PD-L1 expression in responding patients.
“Further translational research is needed to provide the rationale for new strategies to improve checkpoint blockade in patients with lobular breast cancer,” she concluded.
Dr. Adams concurred, adding that a future research question was whether either atezolizumab or carboplatin was contributing to the response. This is “difficult to tell as the study was a single arm trial.”
Another question, said Dr. Adams, is are “anti-CDK 4/6 inhibitors helpful in improving response rates and durability?” In the trial, 70% of patients had prior exposure to CDK 4/6 inhibitors.
The GELATO trial was sponsored by the Netherlands Cancer Institute with funding from Roche Pharma AG. Ms. Voorwerk had nothing to disclose. Dr. Adams disclosed uncompensated consulting or advisory roles with Bristol-Myers Squibb, Genentech, and Merck from whom she has received research funding. Dr. Adams also disclosed research funding from Amgen, Celgene, and Novartis.
The PD-L1 inhibitor atezolizumab (Tecentriq) combined with carboplatin has shown signs of clinical activity in women with metastatic invasive lobular breast cancer (ILC) according to the first results to come from the ongoing GELATO trial.
The 6-month objective response rate was 19%, based on 4 of 21 patients who could be evaluated exhibiting a partial response to the chemoimmunotherapy. A further two (10%) patients had stable disease, meaning that clinical benefit rate was 29%.
GELATO (AssessinG Efficacy of Carboplatin and ATezOlizumab in Metastatic Lobular Breast Cancer) is a phase 2 trial being conducted at four Dutch centers. The primary premise of the study is that “there’s an immune-related subtype of ILC,” researcher Leonie Voorwerk, BSc, reported at the European Society for Medical Oncology: Breast Cancer virtual meeting (Abstract LBA3).
This ILC subtype is “characterized by high expression of immune-related genes and high levels of TILs [tumor-infiltrating lymphocytes] and PDL-1,” said Ms. Voorwerk, a PhD student working with medical oncologist Marleen Kok, MD, PhD, at the Netherlands Cancer Institute in Amsterdam.
Furthermore, she added, in vitro data suggest sensitivity of immune-related-ILCs to platinum and there is preclinical work showing that there is synergy between platinum-based chemotherapy and checkpoint blockade.
First chemoimmunotherapy trial in lobular cancer setting
GELATO is a significant trial as it is “the first chemoimmunotherapy trial in metastatic lobular breast cancer,” said Sylvia Adams, MD, professor of medicine and director of the Breast Cancer Center at NYU Langone Health in New York City.
“Of note, the further research should include the immune-related genes and TMB [tumor mutational burden],” proposed Dr. Adams, who was not involved in the trial.
“We should look to tumor mutational burden because while it is not typically high in early disease, metastatic lesions can have higher TMB,” she explained. “Also, metastatic ILC is known to have higher tumor mutational burden compared to IDC [invasive ductal carcinoma], so this is an important thing along with the clinical factors as described in looking at outcomes.”
Trial design and patient characteristics
GELATO is a single-arm, nonrandomized trial in which 37 patients with metastatic ILC were screened for inclusion between November 2017 and January 2021. A total of 26 of these patients were registered for the trial, and 23 have so far received at least one cycle of atezolizumab.
Prerequisites for entry into the trial were that patients had to have negative or aberrant E-cadherin, a characteristic feature of ILC. Patients with estrogen receptor (ER)-positive (ER+) disease could be included, but they had to be proven to be resistant to endocrine therapies. No more than two prior lines of palliative chemotherapy were allowed, and all participants had to have lactose dehydrogenase levels of less than 2 times the upper limit of normal.
Patients were then treated with up to 12 cycles of weekly carboplatin (AUC = 1.5 mg/mL/min), with atezolizumab (1,200 mg) added in from cycle 3 onward. Treatment was continued until disease progression or unacceptable toxicity occurred.
“Baseline characteristics were mainly as expected for this patient population,” Ms. Voorwerk stated. Patients were aged 45-89 years, with a median of 60 years. Around half each had a WHO performance status of 0 or 1, and around half each had one to two or three or more metastatic sites; 78% had liver metastases.
“But I want to highlight that we included five patients with the triple-negative ILC,” said Ms. Voorwerk, also highlighting that approximately 50% of patients had received prior palliative chemotherapy. Later in her presentation she noted that four out of the six patients that showed any clinical benefit had triple negative disease.
Key findings and next steps
The primary endpoint was progression-free survival (PFS) at 6 months, with secondary endpoints of the best overall response rate, PFS at 1 year, overall survival, and safety.
While details of the latter three endpoints are yet to be reported, Ms. Voorwerk noted that there was a median duration of response of 12 weeks and the median PFS was 15 weeks. The primary endpoint of PFS was met as four patients were free of progression at 6 months and the statistical method used called for patients to be progression free at this time point.
“We observed that stromal TILs and CD8+ cells were not associated with clinical benefits,” said Ms. Voorwerk. There was, however, “a slight trend” toward higher PD-L1 expression in responding patients.
“Further translational research is needed to provide the rationale for new strategies to improve checkpoint blockade in patients with lobular breast cancer,” she concluded.
Dr. Adams concurred, adding that a future research question was whether either atezolizumab or carboplatin was contributing to the response. This is “difficult to tell as the study was a single arm trial.”
Another question, said Dr. Adams, is are “anti-CDK 4/6 inhibitors helpful in improving response rates and durability?” In the trial, 70% of patients had prior exposure to CDK 4/6 inhibitors.
The GELATO trial was sponsored by the Netherlands Cancer Institute with funding from Roche Pharma AG. Ms. Voorwerk had nothing to disclose. Dr. Adams disclosed uncompensated consulting or advisory roles with Bristol-Myers Squibb, Genentech, and Merck from whom she has received research funding. Dr. Adams also disclosed research funding from Amgen, Celgene, and Novartis.
FROM ESMO BREAST CANCER 2021