Red blood cells

Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.

The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.

The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.

The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.

Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.

With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.

With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.

The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.

Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.

Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a^-b^-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.

To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.

The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rh_null), Kell (K₀), Duffy (Duffy_null), and GPB (S^-s^-U^-).

RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.

“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”

Red blood cells

Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.

The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.

The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.

The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.

Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.

With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.

With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.

The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.

Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.

Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a^-b^-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.

To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.

The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rh_null), Kell (K₀), Duffy (Duffy_null), and GPB (S^-s^-U^-).

RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.

“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”

Red blood cells

Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.

The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.

The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.

The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.

Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.

With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.

With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.

The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.

Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.

Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a^-b^-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.

To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.

The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rh_null), Kell (K₀), Duffy (Duffy_null), and GPB (S^-s^-U^-).

RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.

“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”

Cancer Research Center

Overexpression of HOXA9 and activated JAK/STAT signaling cooperate to drive the development of T-cell acute lymphoblastic leukemia (ALL), according to researchers.

The team found that JAK3 mutations are significantly associated with elevated HOXA9 expression in T-ALL, and co-expression of HOXA9 and JAK3 mutations prompt “rapid” leukemia development in mice.

In addition, STAT5 and HOXA9 occupy similar genetic loci, which results in increased JAK-STAT signaling in leukemia cells.

These discoveries, and results of subsequent experiments, suggested that PIM1 and JAK1 are potential therapeutic targets for T-ALL.

Jan Cools, PhD, of VIB-KU Leuven Center for Cancer Biology in Leuven, Belgium, and his colleagues described this research in Cancer Discovery.

“JAK3/STAT5 mutations are important in ALL since they stimulate the growth of the cells,” Dr Cools said. “[W]e found that JAK3/STAT5 mutations frequently occur together with HOXA9 mutations.”

In analyzing data from 2 cohorts of T-ALL patients, the researchers found that IL7R/JAK/STAT5 mutations were more frequent in HOXA+ cases, and HOXA9 was “the most important upregulated gene of the HOXA cluster.” (HOXA9 expression levels were significantly higher than HOXA10 or HOXA11 levels.)

“We examined the cooperation between JAK3/STAT5 mutation and HOXA9, [and] we observed that HOXA9 boosts the effects of other genes, leading to tumor development,” said study author Charles de Bock, PhD, of VIB-KU Leuven.

“As a result, when JAK3/STAT5 mutations and HOXA9 are both present, leukemia develops more rapidly and aggressively.”

The researchers found that co-expression of HOXA9 and the JAK3 M511I mutation led to rapid leukemia development in mice. Animals with co-expression of HOXA9 and JAK3 (M511I) developed leukemia that was characterized by an increase in peripheral white blood cell counts that exceeded 10,000 cells/mm³ within 30 days.

In addition, these mice had a significant decrease in disease-free survival compared to mice with JAK3 (M511I) alone. The median disease-free survival was 25 days and 126.5 days, respectively (P<0.0001).

Further analysis revealed co-localization of HOXA9 and STAT5. The researchers also found that HOXA9 enhances transcriptional activity of STAT5 in leukemia cells.

The team said this reconfirms STAT5 as “a major central player” in T-ALL, and it suggests that STAT5 target genes such as PIM1 could be therapeutic targets for T-ALL.

To test this theory, the researchers inhibited both PIM1 and JAK1 in JAK/STAT mutant T-ALL. The PIM1 inhibitor AZD1208 and the JAK1/2 inhibitor ruxolitinib demonstrated synergy and significantly reduced leukemia burden in vivo.

Cancer Research Center

Overexpression of HOXA9 and activated JAK/STAT signaling cooperate to drive the development of T-cell acute lymphoblastic leukemia (ALL), according to researchers.

The team found that JAK3 mutations are significantly associated with elevated HOXA9 expression in T-ALL, and co-expression of HOXA9 and JAK3 mutations prompt “rapid” leukemia development in mice.

In addition, STAT5 and HOXA9 occupy similar genetic loci, which results in increased JAK-STAT signaling in leukemia cells.

These discoveries, and results of subsequent experiments, suggested that PIM1 and JAK1 are potential therapeutic targets for T-ALL.

Jan Cools, PhD, of VIB-KU Leuven Center for Cancer Biology in Leuven, Belgium, and his colleagues described this research in Cancer Discovery.

“JAK3/STAT5 mutations are important in ALL since they stimulate the growth of the cells,” Dr Cools said. “[W]e found that JAK3/STAT5 mutations frequently occur together with HOXA9 mutations.”

In analyzing data from 2 cohorts of T-ALL patients, the researchers found that IL7R/JAK/STAT5 mutations were more frequent in HOXA+ cases, and HOXA9 was “the most important upregulated gene of the HOXA cluster.” (HOXA9 expression levels were significantly higher than HOXA10 or HOXA11 levels.)

“We examined the cooperation between JAK3/STAT5 mutation and HOXA9, [and] we observed that HOXA9 boosts the effects of other genes, leading to tumor development,” said study author Charles de Bock, PhD, of VIB-KU Leuven.

“As a result, when JAK3/STAT5 mutations and HOXA9 are both present, leukemia develops more rapidly and aggressively.”

The researchers found that co-expression of HOXA9 and the JAK3 M511I mutation led to rapid leukemia development in mice. Animals with co-expression of HOXA9 and JAK3 (M511I) developed leukemia that was characterized by an increase in peripheral white blood cell counts that exceeded 10,000 cells/mm³ within 30 days.

In addition, these mice had a significant decrease in disease-free survival compared to mice with JAK3 (M511I) alone. The median disease-free survival was 25 days and 126.5 days, respectively (P<0.0001).

Further analysis revealed co-localization of HOXA9 and STAT5. The researchers also found that HOXA9 enhances transcriptional activity of STAT5 in leukemia cells.

The team said this reconfirms STAT5 as “a major central player” in T-ALL, and it suggests that STAT5 target genes such as PIM1 could be therapeutic targets for T-ALL.

To test this theory, the researchers inhibited both PIM1 and JAK1 in JAK/STAT mutant T-ALL. The PIM1 inhibitor AZD1208 and the JAK1/2 inhibitor ruxolitinib demonstrated synergy and significantly reduced leukemia burden in vivo.

Cancer Research Center

Overexpression of HOXA9 and activated JAK/STAT signaling cooperate to drive the development of T-cell acute lymphoblastic leukemia (ALL), according to researchers.

The team found that JAK3 mutations are significantly associated with elevated HOXA9 expression in T-ALL, and co-expression of HOXA9 and JAK3 mutations prompt “rapid” leukemia development in mice.

In addition, STAT5 and HOXA9 occupy similar genetic loci, which results in increased JAK-STAT signaling in leukemia cells.

These discoveries, and results of subsequent experiments, suggested that PIM1 and JAK1 are potential therapeutic targets for T-ALL.

Jan Cools, PhD, of VIB-KU Leuven Center for Cancer Biology in Leuven, Belgium, and his colleagues described this research in Cancer Discovery.

“JAK3/STAT5 mutations are important in ALL since they stimulate the growth of the cells,” Dr Cools said. “[W]e found that JAK3/STAT5 mutations frequently occur together with HOXA9 mutations.”

In analyzing data from 2 cohorts of T-ALL patients, the researchers found that IL7R/JAK/STAT5 mutations were more frequent in HOXA+ cases, and HOXA9 was “the most important upregulated gene of the HOXA cluster.” (HOXA9 expression levels were significantly higher than HOXA10 or HOXA11 levels.)

“We examined the cooperation between JAK3/STAT5 mutation and HOXA9, [and] we observed that HOXA9 boosts the effects of other genes, leading to tumor development,” said study author Charles de Bock, PhD, of VIB-KU Leuven.

“As a result, when JAK3/STAT5 mutations and HOXA9 are both present, leukemia develops more rapidly and aggressively.”

The researchers found that co-expression of HOXA9 and the JAK3 M511I mutation led to rapid leukemia development in mice. Animals with co-expression of HOXA9 and JAK3 (M511I) developed leukemia that was characterized by an increase in peripheral white blood cell counts that exceeded 10,000 cells/mm³ within 30 days.

In addition, these mice had a significant decrease in disease-free survival compared to mice with JAK3 (M511I) alone. The median disease-free survival was 25 days and 126.5 days, respectively (P<0.0001).

Further analysis revealed co-localization of HOXA9 and STAT5. The researchers also found that HOXA9 enhances transcriptional activity of STAT5 in leukemia cells.

The team said this reconfirms STAT5 as “a major central player” in T-ALL, and it suggests that STAT5 target genes such as PIM1 could be therapeutic targets for T-ALL.

To test this theory, the researchers inhibited both PIM1 and JAK1 in JAK/STAT mutant T-ALL. The PIM1 inhibitor AZD1208 and the JAK1/2 inhibitor ruxolitinib demonstrated synergy and significantly reduced leukemia burden in vivo.

Emotional regulation (ER) skills training lowers the likelihood that young adolescents with mental health symptoms will have vaginal sex.

“The inclusion of ER training in a small-group behavioral intervention reduced sexual risk behaviors among seventh-graders with suspected mental health symptoms over a 2.5-year follow-up beyond that achieved with more traditional health education,” wrote Chistopher Houck, PhD, and his colleagues at Bradley Hasbro Children’s Research Center, Providence, R.I., in Pediatrics. “This was true across a range of behaviors, such as engaging in fewer condom-less sex acts, being less likely to have multiple partners, and being less likely to use substances before sex.”

Valeriy_G/iStock/Getty Images

ilacy@mdedge.com

SOURCE: Houck C et al. Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-2525.

Emotional regulation (ER) skills training lowers the likelihood that young adolescents with mental health symptoms will have vaginal sex.

“The inclusion of ER training in a small-group behavioral intervention reduced sexual risk behaviors among seventh-graders with suspected mental health symptoms over a 2.5-year follow-up beyond that achieved with more traditional health education,” wrote Chistopher Houck, PhD, and his colleagues at Bradley Hasbro Children’s Research Center, Providence, R.I., in Pediatrics. “This was true across a range of behaviors, such as engaging in fewer condom-less sex acts, being less likely to have multiple partners, and being less likely to use substances before sex.”

Valeriy_G/iStock/Getty Images

ilacy@mdedge.com

SOURCE: Houck C et al. Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-2525.

Emotional regulation (ER) skills training lowers the likelihood that young adolescents with mental health symptoms will have vaginal sex.

“The inclusion of ER training in a small-group behavioral intervention reduced sexual risk behaviors among seventh-graders with suspected mental health symptoms over a 2.5-year follow-up beyond that achieved with more traditional health education,” wrote Chistopher Houck, PhD, and his colleagues at Bradley Hasbro Children’s Research Center, Providence, R.I., in Pediatrics. “This was true across a range of behaviors, such as engaging in fewer condom-less sex acts, being less likely to have multiple partners, and being less likely to use substances before sex.”

Valeriy_G/iStock/Getty Images

ilacy@mdedge.com

SOURCE: Houck C et al. Pediatrics. 2018 May 10. doi: 10.1542/peds.2017-2525.

The FP recognized this lesion as a congenital nevus.

He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.

The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized this lesion as a congenital nevus.

He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.

The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized this lesion as a congenital nevus.

He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.

The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Testing donated blood for Zika virus in the United States confirmed just 8 authentic cases and cost nearly $42 million over a period of 15 months, investigators reported online May 10 in the New England Journal of Medicine.

That price did not reflect a commercial price hike, said Paula Saá, PhD, of the American Red Cross in Gaithersburg, MD, and her associates. Furthermore, more than half of the Zika cases had a low viral level that might not be infectious.

Vlad/Fotolia

SOURCE: Saá P et al. New Engl J Med. 2018;378:1778-88.

Testing donated blood for Zika virus in the United States confirmed just 8 authentic cases and cost nearly $42 million over a period of 15 months, investigators reported online May 10 in the New England Journal of Medicine.

That price did not reflect a commercial price hike, said Paula Saá, PhD, of the American Red Cross in Gaithersburg, MD, and her associates. Furthermore, more than half of the Zika cases had a low viral level that might not be infectious.

Vlad/Fotolia

SOURCE: Saá P et al. New Engl J Med. 2018;378:1778-88.

Testing donated blood for Zika virus in the United States confirmed just 8 authentic cases and cost nearly $42 million over a period of 15 months, investigators reported online May 10 in the New England Journal of Medicine.

That price did not reflect a commercial price hike, said Paula Saá, PhD, of the American Red Cross in Gaithersburg, MD, and her associates. Furthermore, more than half of the Zika cases had a low viral level that might not be infectious.

Vlad/Fotolia

SOURCE: Saá P et al. New Engl J Med. 2018;378:1778-88.

Case Report

A 56-year-old woman with well-controlled hypertension, hyperlipidemia, and gastroesophageal reflux disease initially presented with itching and a rash in the perianal region of 1 year’s duration. She had been treated intermittently by her primary care physician over the past year for presumed hemorrhoids and a perianal fungal infection without improvement. Physical examination at the time of intitial presentation revealed a single, well-demarcated, scaly, pink plaque on the perianal area on the right buttock extending toward the anal canal (Figure 1). Histologic sections of a punch biopsy of the lesion showed a proliferation of cells with atypical nuclei and clear cytoplasm located throughout the epidermis (Figure 2A). Immunohistochemistry was positive for cytokeratin 7 (Figure 2B) and cytokeratin 20 (Figure 2C) and negative for melanoma antigen and human melanoma black 45. Following a negative workup for internal malignancy, which included basic laboratory testing (including serum carcinoembryonic antigen and cancer antigen 125 levels), computed tomography of the abdomen and pelvis, positron-emission tomography, Papanicolaou test, mammography, and colonoscopy, a diagnosis of primary extramammary Paget disease (EMPD) was made. The patient underwent wide local excision (Figure 3A) of the lesion with Mohs micrographic surgery tissue processing of marginal tissue (Figure 3B) with clear margins and reconstruction of the perianal region.

Four years later, the patient returned with new symptoms of bleeding when wiping the perianal region, pruritus, and fecal urgency of 3 to 4 months’ duration. Physical examination revealed scaly patches on the anus that were suspicious for recurrence of EMPD. Biopsies from the anal margin and anal canal confirmed recurrent EMPD involving the anal canal. Repeat evaluation for internal malignancy was negative.

Given the involvement of the anal canal, repeat wide local excision would have required anal resection and would therefore have been functionally impairing. The patient refused further surgical intervention as well as radiotherapy. Rather, a novel 16-week immunomodulatory regimen involving imiquimod cream 5% cream and low-dose oral cimetidine was started. To address the anal involvement, the patient was instructed to lubricate glycerin suppositories with the imiquimod cream and insert intra-anally once weekly. Dosing was adjusted based on the patient’s inflammatory response and tolerability, as she did initially report some flulike symptoms with the first few weeks of treatment. For most of the 16-week course, she applied 250 mg of imiquimod cream 5% to the perianal area 3 times weekly and 250 mg into the anal canal once weekly. Oral cimetidine initially was dosed at 800 mg twice daily as tolerated, but due to stomach irritation, the patient self-reduced her intake to 800 mg 3 times weekly.

To determine treatment response, scouting biopsies of the anal margin and anal canal were obtained 4 weeks after treatment cessation and demonstrated no evidence of residual disease. The patient resumed topical imiquimod applied once weekly into the anal canal and around the anus for a planned prolonged course of at least 1 year. To reduce the risk of recurrence, the patient continued taking oral cimetidine 800 mg 3 times weekly. Recommended follow-up included annual anoscopy or colonoscopy, serum carcinoembryonic antigen evaluation, and regular clinical monitoring by the dermatology and colorectal surgery teams.

Six months after completing the combination therapy, she was seen by the dermatology department and remained clinically free of disease (Figure 4). Anoscopy examination by the colorectal surgery department 4 months later showed no clinical evidence of malignancy.

Comment

Extramammary Paget disease is a rare intraepithelial adenocarcinoma with a predilection for white females and an average age of onset of 50 to 80 years.^1-3 The vulva, perianal region, scrotum, penis, and perineum are the most commonly affected sites.^1-3 Clinically, EMPD presents as a chronic, well-demarcated, scaly, and often expanding plaque. The incidence of EMPD is unknown, as there are only a few hundred cases reported in the literature.²

Extramammary Paget disease can occur primarily, arising in the epidermis at the sweat-gland level or from primitive epidermal basal cells, or secondarily due to pagetoid spread of malignant cells from an adjacent or contiguous underlying adnexal adenocarcinoma or visceral malignancy.² While primary EMPD is not associated with an underlying adenocarcinoma, it may become invasive, infiltrate the dermis, or metastasize via the lymphatics.² Secondary EMPD is associated with underlying malignancy most often originating in the gastrointestinal or genitourinary tracts.^1,2

Currently, treatment of primary EMPD typically is surgical with wide local excision or Mohs micrographic surgery.^1,2 However, margins often are positive, and the local recurrence rate is high (ie, 33%–66%).^2,3 There are a variety of other therapies that have been reported in the literature, including radiation, topical chemotherapeutics (eg, imiquimod, 5-fluorouracil, bleomycin), photodynamic therapy, and CO₂ laser ablation.^1,3 To our knowledge, there are no randomized controlled trials that compare surgery with other treatment options for EMPD.

Despite recurrence of EMPD with involvement of the anal canal, our patient refused further surgical intervention, as it would have required anal resection and radiotherapy due to the potentially negative impact on sphincter function. While investigating minimally invasive treatment options, we found several citations in the literature highlighting positive response with imiquimod cream 5% in patients with vulvar and periscrotal EMPD.^4,5 A large, systematic review that analyzed 63 cases of vulvar EMPD—nearly half of which were recurrences of a prior malignancy—reported a response rate of 52% to 80% following treatment with imiquimod.⁵ Almost 70% of patients achieved complete clearance while applying imiquimod 3 to 4 times weekly for a median of 4 months; however, little has been written about the effectiveness of topical imiquimod in EMPD. Knight et al⁶ reported the case of a 40-year-old woman with perianal EMPD who was treated with imiquimod 3 times weekly for 16 weeks. At the end of treatment, the patient was completely clear of disease both clinically and histologically on random biopsies of the perianal skin; however, the EMPD later recurred with lymph node metastasis 18 months after stopping treatment.⁶

Given the growing evidence demonstrating disease control of EMPD with topical imiquimod, we elected to utilize this agent in combination with oral cimetidine in our patient. Cimetidine, an H₂ receptor antagonist, has been shown to have antineoplastic properties in a broad range of preclinical and clinical studies for a number of different malignancies.⁷ Four distinct mechanisms of action have been shown. Cimetidine, which blocks the histamine pathway, has been shown to have a direct antiproliferative action on cancer cells.⁷ Histamine has been associated with increased regulatory T-cell activity, decreased antigen-presenting activity of dendritic cells, reduced natural killer cell activity, and increased myeloid-derived suppressor cell activity, which create an immunosuppressive tumor microenvironment in the setting of cancer. By blocking histamine and thus reversing this immunosuppressive environment, cimetidine demonstrates immunomodulatory effects.⁷ Cimetidine also has demonstrated an inhibitory effect on cancer cell adhesion to endothelial cells, which is noted to be independent of histamine-blocking activity.⁷ Finally, an antiangiogenic action is attributed to blocking of the upregulation of vascular endothelial growth factor that is normally induced by histamine.⁷

Cimetidine’s antineoplastic properties, specifically in the setting of colorectal cancer,⁸ were particularly compelling given our patient’s EMPD involvement of the anal canal. The most impressive clinical trial data showed a dramatically increased survival rate for colorectal cancer patients treated with oral cimetidine (800 mg once daily) and oral 5-fluorouracil (200 mg once daily) for 1 year following curative resection. The cimetidine-treated group had a 10-year survival rate of 84.6% versus 49.8% for the 5-fluorouracil–only group.⁸

Conclusion

We present this case of recurrent perianal and anal EMPD treated successfully with imiquimod cream 5% and oral cimetidine to highlight a potential alternative treatment regimen for poor surgical candidates with EMPD.

Case Report

A 56-year-old woman with well-controlled hypertension, hyperlipidemia, and gastroesophageal reflux disease initially presented with itching and a rash in the perianal region of 1 year’s duration. She had been treated intermittently by her primary care physician over the past year for presumed hemorrhoids and a perianal fungal infection without improvement. Physical examination at the time of intitial presentation revealed a single, well-demarcated, scaly, pink plaque on the perianal area on the right buttock extending toward the anal canal (Figure 1). Histologic sections of a punch biopsy of the lesion showed a proliferation of cells with atypical nuclei and clear cytoplasm located throughout the epidermis (Figure 2A). Immunohistochemistry was positive for cytokeratin 7 (Figure 2B) and cytokeratin 20 (Figure 2C) and negative for melanoma antigen and human melanoma black 45. Following a negative workup for internal malignancy, which included basic laboratory testing (including serum carcinoembryonic antigen and cancer antigen 125 levels), computed tomography of the abdomen and pelvis, positron-emission tomography, Papanicolaou test, mammography, and colonoscopy, a diagnosis of primary extramammary Paget disease (EMPD) was made. The patient underwent wide local excision (Figure 3A) of the lesion with Mohs micrographic surgery tissue processing of marginal tissue (Figure 3B) with clear margins and reconstruction of the perianal region.

Four years later, the patient returned with new symptoms of bleeding when wiping the perianal region, pruritus, and fecal urgency of 3 to 4 months’ duration. Physical examination revealed scaly patches on the anus that were suspicious for recurrence of EMPD. Biopsies from the anal margin and anal canal confirmed recurrent EMPD involving the anal canal. Repeat evaluation for internal malignancy was negative.

Given the involvement of the anal canal, repeat wide local excision would have required anal resection and would therefore have been functionally impairing. The patient refused further surgical intervention as well as radiotherapy. Rather, a novel 16-week immunomodulatory regimen involving imiquimod cream 5% cream and low-dose oral cimetidine was started. To address the anal involvement, the patient was instructed to lubricate glycerin suppositories with the imiquimod cream and insert intra-anally once weekly. Dosing was adjusted based on the patient’s inflammatory response and tolerability, as she did initially report some flulike symptoms with the first few weeks of treatment. For most of the 16-week course, she applied 250 mg of imiquimod cream 5% to the perianal area 3 times weekly and 250 mg into the anal canal once weekly. Oral cimetidine initially was dosed at 800 mg twice daily as tolerated, but due to stomach irritation, the patient self-reduced her intake to 800 mg 3 times weekly.

To determine treatment response, scouting biopsies of the anal margin and anal canal were obtained 4 weeks after treatment cessation and demonstrated no evidence of residual disease. The patient resumed topical imiquimod applied once weekly into the anal canal and around the anus for a planned prolonged course of at least 1 year. To reduce the risk of recurrence, the patient continued taking oral cimetidine 800 mg 3 times weekly. Recommended follow-up included annual anoscopy or colonoscopy, serum carcinoembryonic antigen evaluation, and regular clinical monitoring by the dermatology and colorectal surgery teams.

Six months after completing the combination therapy, she was seen by the dermatology department and remained clinically free of disease (Figure 4). Anoscopy examination by the colorectal surgery department 4 months later showed no clinical evidence of malignancy.

Comment

Extramammary Paget disease is a rare intraepithelial adenocarcinoma with a predilection for white females and an average age of onset of 50 to 80 years.^1-3 The vulva, perianal region, scrotum, penis, and perineum are the most commonly affected sites.^1-3 Clinically, EMPD presents as a chronic, well-demarcated, scaly, and often expanding plaque. The incidence of EMPD is unknown, as there are only a few hundred cases reported in the literature.²

Extramammary Paget disease can occur primarily, arising in the epidermis at the sweat-gland level or from primitive epidermal basal cells, or secondarily due to pagetoid spread of malignant cells from an adjacent or contiguous underlying adnexal adenocarcinoma or visceral malignancy.² While primary EMPD is not associated with an underlying adenocarcinoma, it may become invasive, infiltrate the dermis, or metastasize via the lymphatics.² Secondary EMPD is associated with underlying malignancy most often originating in the gastrointestinal or genitourinary tracts.^1,2

Currently, treatment of primary EMPD typically is surgical with wide local excision or Mohs micrographic surgery.^1,2 However, margins often are positive, and the local recurrence rate is high (ie, 33%–66%).^2,3 There are a variety of other therapies that have been reported in the literature, including radiation, topical chemotherapeutics (eg, imiquimod, 5-fluorouracil, bleomycin), photodynamic therapy, and CO₂ laser ablation.^1,3 To our knowledge, there are no randomized controlled trials that compare surgery with other treatment options for EMPD.

Despite recurrence of EMPD with involvement of the anal canal, our patient refused further surgical intervention, as it would have required anal resection and radiotherapy due to the potentially negative impact on sphincter function. While investigating minimally invasive treatment options, we found several citations in the literature highlighting positive response with imiquimod cream 5% in patients with vulvar and periscrotal EMPD.^4,5 A large, systematic review that analyzed 63 cases of vulvar EMPD—nearly half of which were recurrences of a prior malignancy—reported a response rate of 52% to 80% following treatment with imiquimod.⁵ Almost 70% of patients achieved complete clearance while applying imiquimod 3 to 4 times weekly for a median of 4 months; however, little has been written about the effectiveness of topical imiquimod in EMPD. Knight et al⁶ reported the case of a 40-year-old woman with perianal EMPD who was treated with imiquimod 3 times weekly for 16 weeks. At the end of treatment, the patient was completely clear of disease both clinically and histologically on random biopsies of the perianal skin; however, the EMPD later recurred with lymph node metastasis 18 months after stopping treatment.⁶

Given the growing evidence demonstrating disease control of EMPD with topical imiquimod, we elected to utilize this agent in combination with oral cimetidine in our patient. Cimetidine, an H₂ receptor antagonist, has been shown to have antineoplastic properties in a broad range of preclinical and clinical studies for a number of different malignancies.⁷ Four distinct mechanisms of action have been shown. Cimetidine, which blocks the histamine pathway, has been shown to have a direct antiproliferative action on cancer cells.⁷ Histamine has been associated with increased regulatory T-cell activity, decreased antigen-presenting activity of dendritic cells, reduced natural killer cell activity, and increased myeloid-derived suppressor cell activity, which create an immunosuppressive tumor microenvironment in the setting of cancer. By blocking histamine and thus reversing this immunosuppressive environment, cimetidine demonstrates immunomodulatory effects.⁷ Cimetidine also has demonstrated an inhibitory effect on cancer cell adhesion to endothelial cells, which is noted to be independent of histamine-blocking activity.⁷ Finally, an antiangiogenic action is attributed to blocking of the upregulation of vascular endothelial growth factor that is normally induced by histamine.⁷

Cimetidine’s antineoplastic properties, specifically in the setting of colorectal cancer,⁸ were particularly compelling given our patient’s EMPD involvement of the anal canal. The most impressive clinical trial data showed a dramatically increased survival rate for colorectal cancer patients treated with oral cimetidine (800 mg once daily) and oral 5-fluorouracil (200 mg once daily) for 1 year following curative resection. The cimetidine-treated group had a 10-year survival rate of 84.6% versus 49.8% for the 5-fluorouracil–only group.⁸

Conclusion

We present this case of recurrent perianal and anal EMPD treated successfully with imiquimod cream 5% and oral cimetidine to highlight a potential alternative treatment regimen for poor surgical candidates with EMPD.

Case Report

A 56-year-old woman with well-controlled hypertension, hyperlipidemia, and gastroesophageal reflux disease initially presented with itching and a rash in the perianal region of 1 year’s duration. She had been treated intermittently by her primary care physician over the past year for presumed hemorrhoids and a perianal fungal infection without improvement. Physical examination at the time of intitial presentation revealed a single, well-demarcated, scaly, pink plaque on the perianal area on the right buttock extending toward the anal canal (Figure 1). Histologic sections of a punch biopsy of the lesion showed a proliferation of cells with atypical nuclei and clear cytoplasm located throughout the epidermis (Figure 2A). Immunohistochemistry was positive for cytokeratin 7 (Figure 2B) and cytokeratin 20 (Figure 2C) and negative for melanoma antigen and human melanoma black 45. Following a negative workup for internal malignancy, which included basic laboratory testing (including serum carcinoembryonic antigen and cancer antigen 125 levels), computed tomography of the abdomen and pelvis, positron-emission tomography, Papanicolaou test, mammography, and colonoscopy, a diagnosis of primary extramammary Paget disease (EMPD) was made. The patient underwent wide local excision (Figure 3A) of the lesion with Mohs micrographic surgery tissue processing of marginal tissue (Figure 3B) with clear margins and reconstruction of the perianal region.

Four years later, the patient returned with new symptoms of bleeding when wiping the perianal region, pruritus, and fecal urgency of 3 to 4 months’ duration. Physical examination revealed scaly patches on the anus that were suspicious for recurrence of EMPD. Biopsies from the anal margin and anal canal confirmed recurrent EMPD involving the anal canal. Repeat evaluation for internal malignancy was negative.

Given the involvement of the anal canal, repeat wide local excision would have required anal resection and would therefore have been functionally impairing. The patient refused further surgical intervention as well as radiotherapy. Rather, a novel 16-week immunomodulatory regimen involving imiquimod cream 5% cream and low-dose oral cimetidine was started. To address the anal involvement, the patient was instructed to lubricate glycerin suppositories with the imiquimod cream and insert intra-anally once weekly. Dosing was adjusted based on the patient’s inflammatory response and tolerability, as she did initially report some flulike symptoms with the first few weeks of treatment. For most of the 16-week course, she applied 250 mg of imiquimod cream 5% to the perianal area 3 times weekly and 250 mg into the anal canal once weekly. Oral cimetidine initially was dosed at 800 mg twice daily as tolerated, but due to stomach irritation, the patient self-reduced her intake to 800 mg 3 times weekly.

To determine treatment response, scouting biopsies of the anal margin and anal canal were obtained 4 weeks after treatment cessation and demonstrated no evidence of residual disease. The patient resumed topical imiquimod applied once weekly into the anal canal and around the anus for a planned prolonged course of at least 1 year. To reduce the risk of recurrence, the patient continued taking oral cimetidine 800 mg 3 times weekly. Recommended follow-up included annual anoscopy or colonoscopy, serum carcinoembryonic antigen evaluation, and regular clinical monitoring by the dermatology and colorectal surgery teams.

Six months after completing the combination therapy, she was seen by the dermatology department and remained clinically free of disease (Figure 4). Anoscopy examination by the colorectal surgery department 4 months later showed no clinical evidence of malignancy.

Comment

Extramammary Paget disease is a rare intraepithelial adenocarcinoma with a predilection for white females and an average age of onset of 50 to 80 years.^1-3 The vulva, perianal region, scrotum, penis, and perineum are the most commonly affected sites.^1-3 Clinically, EMPD presents as a chronic, well-demarcated, scaly, and often expanding plaque. The incidence of EMPD is unknown, as there are only a few hundred cases reported in the literature.²

Extramammary Paget disease can occur primarily, arising in the epidermis at the sweat-gland level or from primitive epidermal basal cells, or secondarily due to pagetoid spread of malignant cells from an adjacent or contiguous underlying adnexal adenocarcinoma or visceral malignancy.² While primary EMPD is not associated with an underlying adenocarcinoma, it may become invasive, infiltrate the dermis, or metastasize via the lymphatics.² Secondary EMPD is associated with underlying malignancy most often originating in the gastrointestinal or genitourinary tracts.^1,2

Currently, treatment of primary EMPD typically is surgical with wide local excision or Mohs micrographic surgery.^1,2 However, margins often are positive, and the local recurrence rate is high (ie, 33%–66%).^2,3 There are a variety of other therapies that have been reported in the literature, including radiation, topical chemotherapeutics (eg, imiquimod, 5-fluorouracil, bleomycin), photodynamic therapy, and CO₂ laser ablation.^1,3 To our knowledge, there are no randomized controlled trials that compare surgery with other treatment options for EMPD.

Despite recurrence of EMPD with involvement of the anal canal, our patient refused further surgical intervention, as it would have required anal resection and radiotherapy due to the potentially negative impact on sphincter function. While investigating minimally invasive treatment options, we found several citations in the literature highlighting positive response with imiquimod cream 5% in patients with vulvar and periscrotal EMPD.^4,5 A large, systematic review that analyzed 63 cases of vulvar EMPD—nearly half of which were recurrences of a prior malignancy—reported a response rate of 52% to 80% following treatment with imiquimod.⁵ Almost 70% of patients achieved complete clearance while applying imiquimod 3 to 4 times weekly for a median of 4 months; however, little has been written about the effectiveness of topical imiquimod in EMPD. Knight et al⁶ reported the case of a 40-year-old woman with perianal EMPD who was treated with imiquimod 3 times weekly for 16 weeks. At the end of treatment, the patient was completely clear of disease both clinically and histologically on random biopsies of the perianal skin; however, the EMPD later recurred with lymph node metastasis 18 months after stopping treatment.⁶

Given the growing evidence demonstrating disease control of EMPD with topical imiquimod, we elected to utilize this agent in combination with oral cimetidine in our patient. Cimetidine, an H₂ receptor antagonist, has been shown to have antineoplastic properties in a broad range of preclinical and clinical studies for a number of different malignancies.⁷ Four distinct mechanisms of action have been shown. Cimetidine, which blocks the histamine pathway, has been shown to have a direct antiproliferative action on cancer cells.⁷ Histamine has been associated with increased regulatory T-cell activity, decreased antigen-presenting activity of dendritic cells, reduced natural killer cell activity, and increased myeloid-derived suppressor cell activity, which create an immunosuppressive tumor microenvironment in the setting of cancer. By blocking histamine and thus reversing this immunosuppressive environment, cimetidine demonstrates immunomodulatory effects.⁷ Cimetidine also has demonstrated an inhibitory effect on cancer cell adhesion to endothelial cells, which is noted to be independent of histamine-blocking activity.⁷ Finally, an antiangiogenic action is attributed to blocking of the upregulation of vascular endothelial growth factor that is normally induced by histamine.⁷

Cimetidine’s antineoplastic properties, specifically in the setting of colorectal cancer,⁸ were particularly compelling given our patient’s EMPD involvement of the anal canal. The most impressive clinical trial data showed a dramatically increased survival rate for colorectal cancer patients treated with oral cimetidine (800 mg once daily) and oral 5-fluorouracil (200 mg once daily) for 1 year following curative resection. The cimetidine-treated group had a 10-year survival rate of 84.6% versus 49.8% for the 5-fluorouracil–only group.⁸

Conclusion

We present this case of recurrent perianal and anal EMPD treated successfully with imiquimod cream 5% and oral cimetidine to highlight a potential alternative treatment regimen for poor surgical candidates with EMPD.

Male physicians make more money than female physicians, and that seems to be a rule with few exceptions. Among the 50 largest metro areas, there were none where women earn as much as men, according to a new survey by the medical social network Doximity.

The metro area that comes the closest is Las Vegas, where female physicians earned 20% less – that works out to $73,654 – than their male counterparts in 2017. Rochester, N.Y., had the smallest gap in terms of dollars ($68,758) and the second-smallest percent difference (21%), Doximity said in its 2018 Physician Compensation Report.

The largest wage gap on both measures can be found in Charleston, S.C., where women earned 37%, or $134,499, less than men in 2017. The other members of the largest-wage-gap club are as follows: Kansas City, Mo., and Nashville, Tenn., both had differences of 32%, and Providence, R.I., and Riverside, Calif., had differences of 31%, Doximity said in the report, which was based on data from “compensation surveys completed in 2016 and 2017 by more than 65,000 full-time, licensed U.S. physicians who practice at least 40 hours per week.”

A quick look at the 2016 data shows that the wage gap between female and male physicians increased from 26.5% to 27.7% in 2017, going from more than $92,000 to $105,000. “Medicine is a highly trained field, and as such, one might expect the gender wage gap to be less prominent here than in other industries. However, the gap endures, despite the level of education required to practice medicine and market forces suggesting that this gap should shrink,” Doximity said.

In a recent issue of AGA Perspectives, Ellen M. Zimmermann, MD, AGAF, chair of the AGA Women’s Committee, wrote about the need for transparent policies at institutions to help close the gender gap. Read more at http://ow.ly/43If30jTlEc.

rfranki@mdedge.com

Male physicians make more money than female physicians, and that seems to be a rule with few exceptions. Among the 50 largest metro areas, there were none where women earn as much as men, according to a new survey by the medical social network Doximity.

The metro area that comes the closest is Las Vegas, where female physicians earned 20% less – that works out to $73,654 – than their male counterparts in 2017. Rochester, N.Y., had the smallest gap in terms of dollars ($68,758) and the second-smallest percent difference (21%), Doximity said in its 2018 Physician Compensation Report.

The largest wage gap on both measures can be found in Charleston, S.C., where women earned 37%, or $134,499, less than men in 2017. The other members of the largest-wage-gap club are as follows: Kansas City, Mo., and Nashville, Tenn., both had differences of 32%, and Providence, R.I., and Riverside, Calif., had differences of 31%, Doximity said in the report, which was based on data from “compensation surveys completed in 2016 and 2017 by more than 65,000 full-time, licensed U.S. physicians who practice at least 40 hours per week.”

A quick look at the 2016 data shows that the wage gap between female and male physicians increased from 26.5% to 27.7% in 2017, going from more than $92,000 to $105,000. “Medicine is a highly trained field, and as such, one might expect the gender wage gap to be less prominent here than in other industries. However, the gap endures, despite the level of education required to practice medicine and market forces suggesting that this gap should shrink,” Doximity said.

In a recent issue of AGA Perspectives, Ellen M. Zimmermann, MD, AGAF, chair of the AGA Women’s Committee, wrote about the need for transparent policies at institutions to help close the gender gap. Read more at http://ow.ly/43If30jTlEc.

rfranki@mdedge.com

Male physicians make more money than female physicians, and that seems to be a rule with few exceptions. Among the 50 largest metro areas, there were none where women earn as much as men, according to a new survey by the medical social network Doximity.

The metro area that comes the closest is Las Vegas, where female physicians earned 20% less – that works out to $73,654 – than their male counterparts in 2017. Rochester, N.Y., had the smallest gap in terms of dollars ($68,758) and the second-smallest percent difference (21%), Doximity said in its 2018 Physician Compensation Report.

The largest wage gap on both measures can be found in Charleston, S.C., where women earned 37%, or $134,499, less than men in 2017. The other members of the largest-wage-gap club are as follows: Kansas City, Mo., and Nashville, Tenn., both had differences of 32%, and Providence, R.I., and Riverside, Calif., had differences of 31%, Doximity said in the report, which was based on data from “compensation surveys completed in 2016 and 2017 by more than 65,000 full-time, licensed U.S. physicians who practice at least 40 hours per week.”

A quick look at the 2016 data shows that the wage gap between female and male physicians increased from 26.5% to 27.7% in 2017, going from more than $92,000 to $105,000. “Medicine is a highly trained field, and as such, one might expect the gender wage gap to be less prominent here than in other industries. However, the gap endures, despite the level of education required to practice medicine and market forces suggesting that this gap should shrink,” Doximity said.

In a recent issue of AGA Perspectives, Ellen M. Zimmermann, MD, AGAF, chair of the AGA Women’s Committee, wrote about the need for transparent policies at institutions to help close the gender gap. Read more at http://ow.ly/43If30jTlEc.

rfranki@mdedge.com

TORONTO – Teaching parents of newborns to respond to eating and satiety cues in ways that promote self-regulation was associated with improvements in some weight outcomes at 3 years in a randomized clinical trial.

For the primary outcome of body mass index (BMI) z score at 3 years, a significant difference favoring the responsive parenting (RP) intervention was seen (–0.13 vs. 0.15 for controls; absolute difference, –0.28; P = .04). A longitudinal analysis examining the entire intervention period confirmed that the mean BMI group differences across seven study visits confirmed the effect of the RP intervention on BMI (P less than .001).

“We felt that the BMI z score and longitudinal growth analysis are probably the most sustained effects for an early-life intervention that have been recorded to date,” reported Ian M. Paul, MD, MSc, of Penn State University, Hershey. “While the differences between study groups were modest and not all achieved statistical significance, all favored the responsive-parenting intervention.”

Study details

With upwards of one-quarter of U.S. children aged 2-5 years being overweight or obese, interventions to prevent rapid weight gain and reduce risk for overweight status in infancy are needed, noted Dr. Paul. Another reason to consider very early intervention, he added, is that infancy is a time of both “metabolic and behavioral plasticity.” However, most efforts to intervene early have, thus far, had limited success.

“Our responses to a baby crying are to feed that baby,” said Dr. Paul. This urge, along with others (such as “clear your plate”), evolved during times of food scarcity but persist now that we have inexpensive and palatable food, and promote rapid infant weight gain and increased obesity risk.

An alternative to those traditional parenting practices are responsive feeding and responsive parenting, he explained. “Responsive feeding and parenting requires prompt, developmentally appropriate responses to a child’s behaviors including hunger and satiety cues.”

In other studies, RP has been shown to foster cognitive, social, and emotional development. “The question we had was: Can responsive parenting reduce obesity risk?” he said.

TORONTO – Teaching parents of newborns to respond to eating and satiety cues in ways that promote self-regulation was associated with improvements in some weight outcomes at 3 years in a randomized clinical trial.

For the primary outcome of body mass index (BMI) z score at 3 years, a significant difference favoring the responsive parenting (RP) intervention was seen (–0.13 vs. 0.15 for controls; absolute difference, –0.28; P = .04). A longitudinal analysis examining the entire intervention period confirmed that the mean BMI group differences across seven study visits confirmed the effect of the RP intervention on BMI (P less than .001).

“We felt that the BMI z score and longitudinal growth analysis are probably the most sustained effects for an early-life intervention that have been recorded to date,” reported Ian M. Paul, MD, MSc, of Penn State University, Hershey. “While the differences between study groups were modest and not all achieved statistical significance, all favored the responsive-parenting intervention.”

Study details

With upwards of one-quarter of U.S. children aged 2-5 years being overweight or obese, interventions to prevent rapid weight gain and reduce risk for overweight status in infancy are needed, noted Dr. Paul. Another reason to consider very early intervention, he added, is that infancy is a time of both “metabolic and behavioral plasticity.” However, most efforts to intervene early have, thus far, had limited success.

“Our responses to a baby crying are to feed that baby,” said Dr. Paul. This urge, along with others (such as “clear your plate”), evolved during times of food scarcity but persist now that we have inexpensive and palatable food, and promote rapid infant weight gain and increased obesity risk.

An alternative to those traditional parenting practices are responsive feeding and responsive parenting, he explained. “Responsive feeding and parenting requires prompt, developmentally appropriate responses to a child’s behaviors including hunger and satiety cues.”

In other studies, RP has been shown to foster cognitive, social, and emotional development. “The question we had was: Can responsive parenting reduce obesity risk?” he said.

TORONTO – Teaching parents of newborns to respond to eating and satiety cues in ways that promote self-regulation was associated with improvements in some weight outcomes at 3 years in a randomized clinical trial.

For the primary outcome of body mass index (BMI) z score at 3 years, a significant difference favoring the responsive parenting (RP) intervention was seen (–0.13 vs. 0.15 for controls; absolute difference, –0.28; P = .04). A longitudinal analysis examining the entire intervention period confirmed that the mean BMI group differences across seven study visits confirmed the effect of the RP intervention on BMI (P less than .001).

“We felt that the BMI z score and longitudinal growth analysis are probably the most sustained effects for an early-life intervention that have been recorded to date,” reported Ian M. Paul, MD, MSc, of Penn State University, Hershey. “While the differences between study groups were modest and not all achieved statistical significance, all favored the responsive-parenting intervention.”

Study details

With upwards of one-quarter of U.S. children aged 2-5 years being overweight or obese, interventions to prevent rapid weight gain and reduce risk for overweight status in infancy are needed, noted Dr. Paul. Another reason to consider very early intervention, he added, is that infancy is a time of both “metabolic and behavioral plasticity.” However, most efforts to intervene early have, thus far, had limited success.

“Our responses to a baby crying are to feed that baby,” said Dr. Paul. This urge, along with others (such as “clear your plate”), evolved during times of food scarcity but persist now that we have inexpensive and palatable food, and promote rapid infant weight gain and increased obesity risk.

An alternative to those traditional parenting practices are responsive feeding and responsive parenting, he explained. “Responsive feeding and parenting requires prompt, developmentally appropriate responses to a child’s behaviors including hunger and satiety cues.”

In other studies, RP has been shown to foster cognitive, social, and emotional development. “The question we had was: Can responsive parenting reduce obesity risk?” he said.

AUSTIN, TEX. – Utilizing intravenous treatment for iron deficiency in anemic pregnant women was more efficacious than oral iron supplements, according to a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

With 42% of pregnancies worldwide affected by anemia, according to the World Health Organization, improving treatment beyond the standard oral treatment could have a large effect on decreasing pregnancy complications.

“Women with bariatric surgery and inflammatory bowel disease are at higher risk of failure,” said Shravya Govindappagari, MD, a gynecologist affiliated with New York–Presbyterian Hospital. “Intravenous iron overcomes the limited intestinal absorption of oral formulations, and may increase iron stores more quickly.”

Dr. Govindappagari and her colleagues conducted a meta-analysis of 11 randomly controlled trials published between 2002 and 2017 to uncover the possible benefits of intravenous iron over oral treatment.

Studies were conducted in India, Egypt, France, and Turkey, with one additional multicenter study that gathered patients from seven different countries. Participants were given iron sucrose, ferric carboxymaltose, or low molecular weight iron dextran, according to Dr. Govindappagari.

In an overall assessment of subjects who achieved target hemoglobin levels, patients receiving intravenous iron were 2.66 times more likely to reach target levels than those given oral treatment (P less than .001). After 4 weeks of treatment, patients in the intravenous groups had a mean hemoglobin increase of 0.84 g/dl higher than those in the oral group (P less than .001).

Some clinicians may be wary about switching treatment modality from oral to intravenous; however, Dr. Govindappagari and fellow investigators found those taking oral treatment were 35% more likely to experience adverse effects than those receiving intravenous treatment.

While the analysis, according to Dr. Govindappagari, has merit, she and her team did not have access to relevant blinded, randomly controlled trials, which may have affected the findings. Maternal and neonatal outcomes were also not included in any of the studies analyzed, nor was a cost analysis of the financial burden of switching from oral to intravenous treatment.

Despite these limitations, Dr. Govindappagari and her colleagues assert the use of intravenous iron could have a significant effect on this problem.

“Intravenous iron compared to oral iron has a higher number reach target, a greater increase in hemoglobin, and has fewer side effects,” Dr. Govindappagari said to attendees. “This could be particularly useful in women in labor, during the third trimester, and women who are iron deficient and are at risk for postpartum hemorrhage.”

Dr. Govindappagari and her colleagues reported no relevant financial disclosures.

ezimmerman@mdedge.com

SOURCE: Govindappagari S et al. ACOG 2018, Abstract 10OP.

AUSTIN, TEX. – Utilizing intravenous treatment for iron deficiency in anemic pregnant women was more efficacious than oral iron supplements, according to a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

With 42% of pregnancies worldwide affected by anemia, according to the World Health Organization, improving treatment beyond the standard oral treatment could have a large effect on decreasing pregnancy complications.

“Women with bariatric surgery and inflammatory bowel disease are at higher risk of failure,” said Shravya Govindappagari, MD, a gynecologist affiliated with New York–Presbyterian Hospital. “Intravenous iron overcomes the limited intestinal absorption of oral formulations, and may increase iron stores more quickly.”

Dr. Govindappagari and her colleagues conducted a meta-analysis of 11 randomly controlled trials published between 2002 and 2017 to uncover the possible benefits of intravenous iron over oral treatment.

Studies were conducted in India, Egypt, France, and Turkey, with one additional multicenter study that gathered patients from seven different countries. Participants were given iron sucrose, ferric carboxymaltose, or low molecular weight iron dextran, according to Dr. Govindappagari.

In an overall assessment of subjects who achieved target hemoglobin levels, patients receiving intravenous iron were 2.66 times more likely to reach target levels than those given oral treatment (P less than .001). After 4 weeks of treatment, patients in the intravenous groups had a mean hemoglobin increase of 0.84 g/dl higher than those in the oral group (P less than .001).

Some clinicians may be wary about switching treatment modality from oral to intravenous; however, Dr. Govindappagari and fellow investigators found those taking oral treatment were 35% more likely to experience adverse effects than those receiving intravenous treatment.

While the analysis, according to Dr. Govindappagari, has merit, she and her team did not have access to relevant blinded, randomly controlled trials, which may have affected the findings. Maternal and neonatal outcomes were also not included in any of the studies analyzed, nor was a cost analysis of the financial burden of switching from oral to intravenous treatment.

Despite these limitations, Dr. Govindappagari and her colleagues assert the use of intravenous iron could have a significant effect on this problem.

“Intravenous iron compared to oral iron has a higher number reach target, a greater increase in hemoglobin, and has fewer side effects,” Dr. Govindappagari said to attendees. “This could be particularly useful in women in labor, during the third trimester, and women who are iron deficient and are at risk for postpartum hemorrhage.”

Dr. Govindappagari and her colleagues reported no relevant financial disclosures.

ezimmerman@mdedge.com

SOURCE: Govindappagari S et al. ACOG 2018, Abstract 10OP.

AUSTIN, TEX. – Utilizing intravenous treatment for iron deficiency in anemic pregnant women was more efficacious than oral iron supplements, according to a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

With 42% of pregnancies worldwide affected by anemia, according to the World Health Organization, improving treatment beyond the standard oral treatment could have a large effect on decreasing pregnancy complications.

“Women with bariatric surgery and inflammatory bowel disease are at higher risk of failure,” said Shravya Govindappagari, MD, a gynecologist affiliated with New York–Presbyterian Hospital. “Intravenous iron overcomes the limited intestinal absorption of oral formulations, and may increase iron stores more quickly.”

Dr. Govindappagari and her colleagues conducted a meta-analysis of 11 randomly controlled trials published between 2002 and 2017 to uncover the possible benefits of intravenous iron over oral treatment.

Studies were conducted in India, Egypt, France, and Turkey, with one additional multicenter study that gathered patients from seven different countries. Participants were given iron sucrose, ferric carboxymaltose, or low molecular weight iron dextran, according to Dr. Govindappagari.

In an overall assessment of subjects who achieved target hemoglobin levels, patients receiving intravenous iron were 2.66 times more likely to reach target levels than those given oral treatment (P less than .001). After 4 weeks of treatment, patients in the intravenous groups had a mean hemoglobin increase of 0.84 g/dl higher than those in the oral group (P less than .001).

Some clinicians may be wary about switching treatment modality from oral to intravenous; however, Dr. Govindappagari and fellow investigators found those taking oral treatment were 35% more likely to experience adverse effects than those receiving intravenous treatment.

While the analysis, according to Dr. Govindappagari, has merit, she and her team did not have access to relevant blinded, randomly controlled trials, which may have affected the findings. Maternal and neonatal outcomes were also not included in any of the studies analyzed, nor was a cost analysis of the financial burden of switching from oral to intravenous treatment.

Despite these limitations, Dr. Govindappagari and her colleagues assert the use of intravenous iron could have a significant effect on this problem.

“Intravenous iron compared to oral iron has a higher number reach target, a greater increase in hemoglobin, and has fewer side effects,” Dr. Govindappagari said to attendees. “This could be particularly useful in women in labor, during the third trimester, and women who are iron deficient and are at risk for postpartum hemorrhage.”

Dr. Govindappagari and her colleagues reported no relevant financial disclosures.

ezimmerman@mdedge.com

SOURCE: Govindappagari S et al. ACOG 2018, Abstract 10OP.

The Society of Hospital Medicine recently partnered with the Neurohospitalist Society (NHS) to apply the neurology, stroke, and neurohospitalist expertise of NHS to the hospital and mentored implementation expertise of SHM for a uniquely positioned program for hospitals and health care systems: the Optimizing Neurovascular Intervention Care for Stroke Patients Mentored Implementation program.

This program aims to provide the resources and training to equip neurologists and hospitals with the skills to help assure continuous quality in the care of stroke patients with large vessel occlusion. The program will help neurohospitalists and other clinicians identify opportunities to engage multidisciplinary team members to implement evidence-based management practices in their hospital.

Reading Hospital – Tower Health, West Reading, Pa., was one of four hospitals selected to participate in the first wave of this program. Tower Health also recently became SHM’s first health system institutional partner. The Hospitalist spoke with a team from Reading Hospital about their participation in the new program and how they think it could affect their care. Interviewees included Sarah Keller, RN, nurse specialist; Deepam Gokal, MD, an associate director of hospitalist services; and Ruth Bailey, RN, stroke program manager.
 

What led you to partner with SHM for this program?

Dr. Gokal is an associate director of hospitalist services and comedical director of the stroke program, is a member of SHM, and was a former member of NHS; he received an email regarding the mentored implementation program for continuous quality monitoring and improvement in the care of stroke patients with large vessel occlusions. Karen Hoerst, MD, is a vascular neurologist and stroke program comedical director, and Ruth Bailey, RN, is the stroke program manager; together, we reviewed the introductory webinar with Dr. Gokal and felt this program would be beneficial for our organization, in particular because of Reading Hospital’s recent acquisition of five hospitals to form Tower Health – Brandywine Hospital, Coatesville, Pa.; Chestnut Hill Hospital, Philadelphia; Jennersville Hospital, West Grove, Pa.; Phoenixville (Pa.) Hospital; and Pottstown (Pa.) Hospital – and to help fulfill our vision to become the hub facility and a comprehensive stroke center.

Did you have a history with SHM prior to this program and before Tower Health’s new institutional partnership with SHM?

Reading Hospital participated in Project BOOST, SHM’s care transitions mentored implementation program, from 2012 to 2013. The goal was to optimize the hospital discharge process and to mitigate and prevent known complications and errors that occur during transitions. This was championed by hospitalists Walter R. Bohnenblust Jr., MD, SFHM, former Director of Hospitalist Services, and Binu Pappachen, MD, FHM.

The pain management provider team at Reading Hospital also championed an opioid management mentored implementation program in 2016-2017 that sought to improve safety and reduce adverse events for patients receiving opioids.
 

How do you anticipate this program will affect outcomes?

Reading Hospital – Tower Health is committed to advancing health care and transforming lives. The aim is to provide better care for individuals, improve health strategies, and reduce health care costs. This mentorship program should support this commitment to value-based care and population health management. It should prove beneficial to Reading Hospital by optimizing neurovascular interventions, which will help it become the intended hub for the Tower Health Teleneurology Program.

What will success look like to you and to members of the hospitalist team?

Future success for hospitalist services at Reading Hospital will include the fruition of a neurohospitalist subspecialty. Participation in this mentored implementation program should provide valuable resources for the development of this subspecialty that are aligned with the vision of Reading Hospital’s Advanced Primary Stroke Center. This vision is to serve as the comprehensive stroke center of choice for the patients both in our community and the surrounding region and to provide them with 24/7 state-of-the-art complex stroke treatment with demonstrated optimization of quality patient outcomes throughout the continuum of care.

For more information about SHM’s mentored implementation programs, visit hospitalmedicine.org/qi.

The Society of Hospital Medicine recently partnered with the Neurohospitalist Society (NHS) to apply the neurology, stroke, and neurohospitalist expertise of NHS to the hospital and mentored implementation expertise of SHM for a uniquely positioned program for hospitals and health care systems: the Optimizing Neurovascular Intervention Care for Stroke Patients Mentored Implementation program.

This program aims to provide the resources and training to equip neurologists and hospitals with the skills to help assure continuous quality in the care of stroke patients with large vessel occlusion. The program will help neurohospitalists and other clinicians identify opportunities to engage multidisciplinary team members to implement evidence-based management practices in their hospital.

Reading Hospital – Tower Health, West Reading, Pa., was one of four hospitals selected to participate in the first wave of this program. Tower Health also recently became SHM’s first health system institutional partner. The Hospitalist spoke with a team from Reading Hospital about their participation in the new program and how they think it could affect their care. Interviewees included Sarah Keller, RN, nurse specialist; Deepam Gokal, MD, an associate director of hospitalist services; and Ruth Bailey, RN, stroke program manager.
 

What led you to partner with SHM for this program?

Dr. Gokal is an associate director of hospitalist services and comedical director of the stroke program, is a member of SHM, and was a former member of NHS; he received an email regarding the mentored implementation program for continuous quality monitoring and improvement in the care of stroke patients with large vessel occlusions. Karen Hoerst, MD, is a vascular neurologist and stroke program comedical director, and Ruth Bailey, RN, is the stroke program manager; together, we reviewed the introductory webinar with Dr. Gokal and felt this program would be beneficial for our organization, in particular because of Reading Hospital’s recent acquisition of five hospitals to form Tower Health – Brandywine Hospital, Coatesville, Pa.; Chestnut Hill Hospital, Philadelphia; Jennersville Hospital, West Grove, Pa.; Phoenixville (Pa.) Hospital; and Pottstown (Pa.) Hospital – and to help fulfill our vision to become the hub facility and a comprehensive stroke center.

Did you have a history with SHM prior to this program and before Tower Health’s new institutional partnership with SHM?

Reading Hospital participated in Project BOOST, SHM’s care transitions mentored implementation program, from 2012 to 2013. The goal was to optimize the hospital discharge process and to mitigate and prevent known complications and errors that occur during transitions. This was championed by hospitalists Walter R. Bohnenblust Jr., MD, SFHM, former Director of Hospitalist Services, and Binu Pappachen, MD, FHM.

The pain management provider team at Reading Hospital also championed an opioid management mentored implementation program in 2016-2017 that sought to improve safety and reduce adverse events for patients receiving opioids.
 

How do you anticipate this program will affect outcomes?

Reading Hospital – Tower Health is committed to advancing health care and transforming lives. The aim is to provide better care for individuals, improve health strategies, and reduce health care costs. This mentorship program should support this commitment to value-based care and population health management. It should prove beneficial to Reading Hospital by optimizing neurovascular interventions, which will help it become the intended hub for the Tower Health Teleneurology Program.

What will success look like to you and to members of the hospitalist team?

Future success for hospitalist services at Reading Hospital will include the fruition of a neurohospitalist subspecialty. Participation in this mentored implementation program should provide valuable resources for the development of this subspecialty that are aligned with the vision of Reading Hospital’s Advanced Primary Stroke Center. This vision is to serve as the comprehensive stroke center of choice for the patients both in our community and the surrounding region and to provide them with 24/7 state-of-the-art complex stroke treatment with demonstrated optimization of quality patient outcomes throughout the continuum of care.

For more information about SHM’s mentored implementation programs, visit hospitalmedicine.org/qi.

The Society of Hospital Medicine recently partnered with the Neurohospitalist Society (NHS) to apply the neurology, stroke, and neurohospitalist expertise of NHS to the hospital and mentored implementation expertise of SHM for a uniquely positioned program for hospitals and health care systems: the Optimizing Neurovascular Intervention Care for Stroke Patients Mentored Implementation program.

This program aims to provide the resources and training to equip neurologists and hospitals with the skills to help assure continuous quality in the care of stroke patients with large vessel occlusion. The program will help neurohospitalists and other clinicians identify opportunities to engage multidisciplinary team members to implement evidence-based management practices in their hospital.

Reading Hospital – Tower Health, West Reading, Pa., was one of four hospitals selected to participate in the first wave of this program. Tower Health also recently became SHM’s first health system institutional partner. The Hospitalist spoke with a team from Reading Hospital about their participation in the new program and how they think it could affect their care. Interviewees included Sarah Keller, RN, nurse specialist; Deepam Gokal, MD, an associate director of hospitalist services; and Ruth Bailey, RN, stroke program manager.
 

What led you to partner with SHM for this program?

Dr. Gokal is an associate director of hospitalist services and comedical director of the stroke program, is a member of SHM, and was a former member of NHS; he received an email regarding the mentored implementation program for continuous quality monitoring and improvement in the care of stroke patients with large vessel occlusions. Karen Hoerst, MD, is a vascular neurologist and stroke program comedical director, and Ruth Bailey, RN, is the stroke program manager; together, we reviewed the introductory webinar with Dr. Gokal and felt this program would be beneficial for our organization, in particular because of Reading Hospital’s recent acquisition of five hospitals to form Tower Health – Brandywine Hospital, Coatesville, Pa.; Chestnut Hill Hospital, Philadelphia; Jennersville Hospital, West Grove, Pa.; Phoenixville (Pa.) Hospital; and Pottstown (Pa.) Hospital – and to help fulfill our vision to become the hub facility and a comprehensive stroke center.

Did you have a history with SHM prior to this program and before Tower Health’s new institutional partnership with SHM?

Reading Hospital participated in Project BOOST, SHM’s care transitions mentored implementation program, from 2012 to 2013. The goal was to optimize the hospital discharge process and to mitigate and prevent known complications and errors that occur during transitions. This was championed by hospitalists Walter R. Bohnenblust Jr., MD, SFHM, former Director of Hospitalist Services, and Binu Pappachen, MD, FHM.

The pain management provider team at Reading Hospital also championed an opioid management mentored implementation program in 2016-2017 that sought to improve safety and reduce adverse events for patients receiving opioids.
 

How do you anticipate this program will affect outcomes?

Reading Hospital – Tower Health is committed to advancing health care and transforming lives. The aim is to provide better care for individuals, improve health strategies, and reduce health care costs. This mentorship program should support this commitment to value-based care and population health management. It should prove beneficial to Reading Hospital by optimizing neurovascular interventions, which will help it become the intended hub for the Tower Health Teleneurology Program.

What will success look like to you and to members of the hospitalist team?

Future success for hospitalist services at Reading Hospital will include the fruition of a neurohospitalist subspecialty. Participation in this mentored implementation program should provide valuable resources for the development of this subspecialty that are aligned with the vision of Reading Hospital’s Advanced Primary Stroke Center. This vision is to serve as the comprehensive stroke center of choice for the patients both in our community and the surrounding region and to provide them with 24/7 state-of-the-art complex stroke treatment with demonstrated optimization of quality patient outcomes throughout the continuum of care.

For more information about SHM’s mentored implementation programs, visit hospitalmedicine.org/qi.