While upfront autologous transplantation has bested bortezomib-based intensification therapy in a large, randomized multiple myeloma (MM) trial, investigators and observers say more research will be needed to determine the optimal treatment strategy in the era of novel agents.

Nephron/Wikimedia Commons

Autologous hematopoietic stem cell transplantation (HSCT) extended progression-free survival by almost 15 months compared with bortezomib, melphalan, and prednisone (VMP) intensification therapy for the treatment of newly diagnosed multiple myeloma, according to results of the randomized, phase 3 trial of 1,503 patients enrolled at 172 centers in the European Myeloma Network.

That finding could provide more fodder for the ongoing debate over the role of upfront autologous HSCT as a gold-standard intensification treatment for patients who can tolerate myeloablative doses of chemotherapy in light of the proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies that are now available.

However, the study is not without limitations, including the use of bortezomib, cyclophosphamide, and dexamethasone (VCD) as induction therapy, according to the investigators, led by Michele Cavo, MD, with the Seràgnoli Institute of Hematology at Bologna (Italy) University.

The VCD regimen was one of the most frequently used induction regimens back when the trial was designed, but now it’s considered “less optimal” versus regimens such as bortezomib, lenalidomide, and dexamethasone (VRD), according to Dr. Cavo and coinvestigators.

Besides, the field is moving forward based on clinical trials of “highly active” daratumumab-based four-drug regimens, which appear to enhance rates of response and minimal residual disease (MRD) negativity when given as induction before autologous HSCT and as consolidation afterward, they said.

“Final results from these studies should be awaited before a shift from routine use of upfront autologous HSCT to delayed HSCT or alternative treatment strategies driven by MRD status can be offered to patients with newly diagnosed multiple myeloma who are fit for high-dose chemotherapy,” Dr. Cavo and colleagues noted in their report, available in The Lancet Hematology.

The multicenter, randomized, open-label, phase 3 study by Dr. Cavo and coinvestigators, known as EMN02/HO95, included patients up to 65 years of age with symptomatic multiple myeloma, measurable disease, and WHO performance of 0 to 2. Patients were treated with VCD induction therapy, followed by randomization to either VMP or autologous HSCT after high-dose melphalan. In a second randomization, patients were assigned to either VRD consolidation therapy or no consolidation. All patients then received lenalidomide maintenance therapy until progression.

Median progression-free survival was 56.7 months in patients initially randomized to HSCT, compared with 41.9 months for MP (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P = .0001), according to the investigators, who said that finding supports the value of HSCT “even in the era of highly active novel agents.”

Turning to results of the second randomization, Dr. Cavo and colleagues said the VRD consolidation strategy resulted in median progression-free survival that was significantly improved versus no consolidation, at 58.9 months and 45.5 months, respectively (P = .014).

While this is an important study, the added benefit of HSCT intensification therapy is in question given the high rates of MRD being reported for potent, daratumumab-based four-drug combination regimens, according to a related commentary by Omar Nadeem, MD, and Irene M. Ghobrial, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“We are entering an era in which novel combinations have shown unprecedented efficacy and future studies with or without HSCT will be needed to answer these key questions,” wrote Dr. Nadeem and Dr. Ghobrial.

Dr. Cavo and colleagues said the estimated 5-year rate of overall survival in EMN02/HO95 was “comparable” between arms, at 75% for the HSCT strategy and 72% for VMP.

“Although this suggests that delaying HSCT to a later time is not harmful, a substantial proportion of patients may become ineligible for high-dose melphalan at first relapse,” they said, noting that 63% of VMP-treated patients went on to receive salvage HSCT.

Further follow-up could demonstrate a survival advantage, as seen in other studies, they added.

Dr. Cavo reported that he has received honoraria from multiple pharmaceutical companies, and is a member of speakers bureaus for Janssen and Celgene. Dr. Nadeem and Dr. Ghobrial reported serving on the advisory boards of multiple pharmaceutical companies.

SOURCE: Cavo M et al. Lancet Haematol. 2020 Apr 30. doi: 10.1016/S2352-3026(20)30099-5.

While upfront autologous transplantation has bested bortezomib-based intensification therapy in a large, randomized multiple myeloma (MM) trial, investigators and observers say more research will be needed to determine the optimal treatment strategy in the era of novel agents.

Nephron/Wikimedia Commons

Autologous hematopoietic stem cell transplantation (HSCT) extended progression-free survival by almost 15 months compared with bortezomib, melphalan, and prednisone (VMP) intensification therapy for the treatment of newly diagnosed multiple myeloma, according to results of the randomized, phase 3 trial of 1,503 patients enrolled at 172 centers in the European Myeloma Network.

That finding could provide more fodder for the ongoing debate over the role of upfront autologous HSCT as a gold-standard intensification treatment for patients who can tolerate myeloablative doses of chemotherapy in light of the proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies that are now available.

However, the study is not without limitations, including the use of bortezomib, cyclophosphamide, and dexamethasone (VCD) as induction therapy, according to the investigators, led by Michele Cavo, MD, with the Seràgnoli Institute of Hematology at Bologna (Italy) University.

The VCD regimen was one of the most frequently used induction regimens back when the trial was designed, but now it’s considered “less optimal” versus regimens such as bortezomib, lenalidomide, and dexamethasone (VRD), according to Dr. Cavo and coinvestigators.

Besides, the field is moving forward based on clinical trials of “highly active” daratumumab-based four-drug regimens, which appear to enhance rates of response and minimal residual disease (MRD) negativity when given as induction before autologous HSCT and as consolidation afterward, they said.

“Final results from these studies should be awaited before a shift from routine use of upfront autologous HSCT to delayed HSCT or alternative treatment strategies driven by MRD status can be offered to patients with newly diagnosed multiple myeloma who are fit for high-dose chemotherapy,” Dr. Cavo and colleagues noted in their report, available in The Lancet Hematology.

The multicenter, randomized, open-label, phase 3 study by Dr. Cavo and coinvestigators, known as EMN02/HO95, included patients up to 65 years of age with symptomatic multiple myeloma, measurable disease, and WHO performance of 0 to 2. Patients were treated with VCD induction therapy, followed by randomization to either VMP or autologous HSCT after high-dose melphalan. In a second randomization, patients were assigned to either VRD consolidation therapy or no consolidation. All patients then received lenalidomide maintenance therapy until progression.

Median progression-free survival was 56.7 months in patients initially randomized to HSCT, compared with 41.9 months for MP (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P = .0001), according to the investigators, who said that finding supports the value of HSCT “even in the era of highly active novel agents.”

Turning to results of the second randomization, Dr. Cavo and colleagues said the VRD consolidation strategy resulted in median progression-free survival that was significantly improved versus no consolidation, at 58.9 months and 45.5 months, respectively (P = .014).

While this is an important study, the added benefit of HSCT intensification therapy is in question given the high rates of MRD being reported for potent, daratumumab-based four-drug combination regimens, according to a related commentary by Omar Nadeem, MD, and Irene M. Ghobrial, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“We are entering an era in which novel combinations have shown unprecedented efficacy and future studies with or without HSCT will be needed to answer these key questions,” wrote Dr. Nadeem and Dr. Ghobrial.

Dr. Cavo and colleagues said the estimated 5-year rate of overall survival in EMN02/HO95 was “comparable” between arms, at 75% for the HSCT strategy and 72% for VMP.

“Although this suggests that delaying HSCT to a later time is not harmful, a substantial proportion of patients may become ineligible for high-dose melphalan at first relapse,” they said, noting that 63% of VMP-treated patients went on to receive salvage HSCT.

Further follow-up could demonstrate a survival advantage, as seen in other studies, they added.

Dr. Cavo reported that he has received honoraria from multiple pharmaceutical companies, and is a member of speakers bureaus for Janssen and Celgene. Dr. Nadeem and Dr. Ghobrial reported serving on the advisory boards of multiple pharmaceutical companies.

SOURCE: Cavo M et al. Lancet Haematol. 2020 Apr 30. doi: 10.1016/S2352-3026(20)30099-5.

While upfront autologous transplantation has bested bortezomib-based intensification therapy in a large, randomized multiple myeloma (MM) trial, investigators and observers say more research will be needed to determine the optimal treatment strategy in the era of novel agents.

Nephron/Wikimedia Commons

Autologous hematopoietic stem cell transplantation (HSCT) extended progression-free survival by almost 15 months compared with bortezomib, melphalan, and prednisone (VMP) intensification therapy for the treatment of newly diagnosed multiple myeloma, according to results of the randomized, phase 3 trial of 1,503 patients enrolled at 172 centers in the European Myeloma Network.

That finding could provide more fodder for the ongoing debate over the role of upfront autologous HSCT as a gold-standard intensification treatment for patients who can tolerate myeloablative doses of chemotherapy in light of the proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies that are now available.

However, the study is not without limitations, including the use of bortezomib, cyclophosphamide, and dexamethasone (VCD) as induction therapy, according to the investigators, led by Michele Cavo, MD, with the Seràgnoli Institute of Hematology at Bologna (Italy) University.

The VCD regimen was one of the most frequently used induction regimens back when the trial was designed, but now it’s considered “less optimal” versus regimens such as bortezomib, lenalidomide, and dexamethasone (VRD), according to Dr. Cavo and coinvestigators.

Besides, the field is moving forward based on clinical trials of “highly active” daratumumab-based four-drug regimens, which appear to enhance rates of response and minimal residual disease (MRD) negativity when given as induction before autologous HSCT and as consolidation afterward, they said.

“Final results from these studies should be awaited before a shift from routine use of upfront autologous HSCT to delayed HSCT or alternative treatment strategies driven by MRD status can be offered to patients with newly diagnosed multiple myeloma who are fit for high-dose chemotherapy,” Dr. Cavo and colleagues noted in their report, available in The Lancet Hematology.

The multicenter, randomized, open-label, phase 3 study by Dr. Cavo and coinvestigators, known as EMN02/HO95, included patients up to 65 years of age with symptomatic multiple myeloma, measurable disease, and WHO performance of 0 to 2. Patients were treated with VCD induction therapy, followed by randomization to either VMP or autologous HSCT after high-dose melphalan. In a second randomization, patients were assigned to either VRD consolidation therapy or no consolidation. All patients then received lenalidomide maintenance therapy until progression.

Median progression-free survival was 56.7 months in patients initially randomized to HSCT, compared with 41.9 months for MP (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P = .0001), according to the investigators, who said that finding supports the value of HSCT “even in the era of highly active novel agents.”

Turning to results of the second randomization, Dr. Cavo and colleagues said the VRD consolidation strategy resulted in median progression-free survival that was significantly improved versus no consolidation, at 58.9 months and 45.5 months, respectively (P = .014).

While this is an important study, the added benefit of HSCT intensification therapy is in question given the high rates of MRD being reported for potent, daratumumab-based four-drug combination regimens, according to a related commentary by Omar Nadeem, MD, and Irene M. Ghobrial, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“We are entering an era in which novel combinations have shown unprecedented efficacy and future studies with or without HSCT will be needed to answer these key questions,” wrote Dr. Nadeem and Dr. Ghobrial.

Dr. Cavo and colleagues said the estimated 5-year rate of overall survival in EMN02/HO95 was “comparable” between arms, at 75% for the HSCT strategy and 72% for VMP.

“Although this suggests that delaying HSCT to a later time is not harmful, a substantial proportion of patients may become ineligible for high-dose melphalan at first relapse,” they said, noting that 63% of VMP-treated patients went on to receive salvage HSCT.

Further follow-up could demonstrate a survival advantage, as seen in other studies, they added.

Dr. Cavo reported that he has received honoraria from multiple pharmaceutical companies, and is a member of speakers bureaus for Janssen and Celgene. Dr. Nadeem and Dr. Ghobrial reported serving on the advisory boards of multiple pharmaceutical companies.

SOURCE: Cavo M et al. Lancet Haematol. 2020 Apr 30. doi: 10.1016/S2352-3026(20)30099-5.

Delaying high school start times by about an hour increased the amount adolescents slept on school nights, and also reduced their catch-up sleep on weekends, according to results from a cohort study.

For their research published in JAMA Pediatrics, Rachel Widome, PhD, of the University of Minnesota, Minneapolis, and colleagues followed a cohort of students at five public high schools in suburban and rural Minneapolis, randomly selecting 455 (225 girls; mean age, 15 years) for wrist actigraphy to track sleep and activity.

The students were followed up over 2 years, from 2016 to 2018. Sleep and activity were monitored at baseline, at year 1, and at year 2. Baseline monitoring lasted a month, and each follow-up monitoring period lasted over 2 months.

Although all the high schools in the study had early start times when the study began, two moved within the first year to delay their starting times to after 8:30 a.m., after a decision by the local school district. The other three schools retained start times of 7:30 a.m. This allowed investigators to compare students’ sleep patterns between start times for an extended period.

Dr. Widome and colleagues found significant improvements in sleep at 1 year that did not attenuate in the second year. At the end of year 2, students in the delayed-start schools slept 43 minutes more on weeknights than their early-starting peers (95% confidence interval, 25-61, P < .001.) The investigators did not see significant between-group differences in weeknight bedtimes. On weekends, students in the delayed-start group slept a mean 34 minutes less at year 2 (95% CI, –65 to –3, P = .03) than their peers in the early groups.

The researchers described the study’s design, a natural experiment with long follow-up and objectively measured sleep data, as its key strength. “No previous studies have been performed of sufficient quality to conclude that later start times cause students to get more sleep and that this effect can be sustained,” they concluded.

In an editorial comment, Erika R. Cheng, PhD, and Aaron E. Carroll, MD, of Indiana University, Indianapolis, wrote that the study provides strong evidence that delaying early school start times “would help adolescents get the sleep they need to thrive,” and belies the commonly held argument that delayed school times would merely lead to them staying awake later on school nights.

Adolescents “experience natural circadian and physiological brain changes that shift their sleep preference to go to bed and wake up later than adults or younger children,” Dr. Cheng and Dr. Carroll noted, with 12th graders’ bedtimes typically after 11 p.m. on weekdays. Regardless, “more than 40% of high schools in the United States start before 8 a.m., and more than 20% of middle schools start at 7:45 a.m. or earlier.”

Dr. Cheng and Dr. Carroll cautioned that the population in this study comprised “relatively affluent students and schools,” and that there were “socioeconomic and racial differences in student characteristics between schools that did and did not adopt the later start times.” For instance, they noted, nearly 90% of students in the delayed-start schools reported having at least one college-educated parent, while in the comparison schools fewer than 75% did. Unmeasured characteristics associated with parent education may have “influenced the school district’s decision to delay schools’ start times and had an effect on student sleep duration.”

Dr. Widome and colleagues’ study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the authors received support from a grant from the Minnesota Population Center. One coauthor acknowledged receiving a consulting fee from Jazz Pharmaceuticals. Dr. Cheng and Dr. Carroll disclosed no relevant conflicts of interest.

SOURCES: Widome R et al. JAMA Pedatr. 2020 Apr 27. doi: 10.1001/jamapediatrics.2020.0344; Cheng ER, Carroll AE. JAMA Pediatr. 2020 Apr 27. oi: 10.1001/jamapediatrics.2020.0351.

Delaying high school start times by about an hour increased the amount adolescents slept on school nights, and also reduced their catch-up sleep on weekends, according to results from a cohort study.

For their research published in JAMA Pediatrics, Rachel Widome, PhD, of the University of Minnesota, Minneapolis, and colleagues followed a cohort of students at five public high schools in suburban and rural Minneapolis, randomly selecting 455 (225 girls; mean age, 15 years) for wrist actigraphy to track sleep and activity.

The students were followed up over 2 years, from 2016 to 2018. Sleep and activity were monitored at baseline, at year 1, and at year 2. Baseline monitoring lasted a month, and each follow-up monitoring period lasted over 2 months.

Although all the high schools in the study had early start times when the study began, two moved within the first year to delay their starting times to after 8:30 a.m., after a decision by the local school district. The other three schools retained start times of 7:30 a.m. This allowed investigators to compare students’ sleep patterns between start times for an extended period.

Dr. Widome and colleagues found significant improvements in sleep at 1 year that did not attenuate in the second year. At the end of year 2, students in the delayed-start schools slept 43 minutes more on weeknights than their early-starting peers (95% confidence interval, 25-61, P < .001.) The investigators did not see significant between-group differences in weeknight bedtimes. On weekends, students in the delayed-start group slept a mean 34 minutes less at year 2 (95% CI, –65 to –3, P = .03) than their peers in the early groups.

The researchers described the study’s design, a natural experiment with long follow-up and objectively measured sleep data, as its key strength. “No previous studies have been performed of sufficient quality to conclude that later start times cause students to get more sleep and that this effect can be sustained,” they concluded.

In an editorial comment, Erika R. Cheng, PhD, and Aaron E. Carroll, MD, of Indiana University, Indianapolis, wrote that the study provides strong evidence that delaying early school start times “would help adolescents get the sleep they need to thrive,” and belies the commonly held argument that delayed school times would merely lead to them staying awake later on school nights.

Adolescents “experience natural circadian and physiological brain changes that shift their sleep preference to go to bed and wake up later than adults or younger children,” Dr. Cheng and Dr. Carroll noted, with 12th graders’ bedtimes typically after 11 p.m. on weekdays. Regardless, “more than 40% of high schools in the United States start before 8 a.m., and more than 20% of middle schools start at 7:45 a.m. or earlier.”

Dr. Cheng and Dr. Carroll cautioned that the population in this study comprised “relatively affluent students and schools,” and that there were “socioeconomic and racial differences in student characteristics between schools that did and did not adopt the later start times.” For instance, they noted, nearly 90% of students in the delayed-start schools reported having at least one college-educated parent, while in the comparison schools fewer than 75% did. Unmeasured characteristics associated with parent education may have “influenced the school district’s decision to delay schools’ start times and had an effect on student sleep duration.”

Dr. Widome and colleagues’ study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the authors received support from a grant from the Minnesota Population Center. One coauthor acknowledged receiving a consulting fee from Jazz Pharmaceuticals. Dr. Cheng and Dr. Carroll disclosed no relevant conflicts of interest.

SOURCES: Widome R et al. JAMA Pedatr. 2020 Apr 27. doi: 10.1001/jamapediatrics.2020.0344; Cheng ER, Carroll AE. JAMA Pediatr. 2020 Apr 27. oi: 10.1001/jamapediatrics.2020.0351.

Delaying high school start times by about an hour increased the amount adolescents slept on school nights, and also reduced their catch-up sleep on weekends, according to results from a cohort study.

For their research published in JAMA Pediatrics, Rachel Widome, PhD, of the University of Minnesota, Minneapolis, and colleagues followed a cohort of students at five public high schools in suburban and rural Minneapolis, randomly selecting 455 (225 girls; mean age, 15 years) for wrist actigraphy to track sleep and activity.

The students were followed up over 2 years, from 2016 to 2018. Sleep and activity were monitored at baseline, at year 1, and at year 2. Baseline monitoring lasted a month, and each follow-up monitoring period lasted over 2 months.

Although all the high schools in the study had early start times when the study began, two moved within the first year to delay their starting times to after 8:30 a.m., after a decision by the local school district. The other three schools retained start times of 7:30 a.m. This allowed investigators to compare students’ sleep patterns between start times for an extended period.

Dr. Widome and colleagues found significant improvements in sleep at 1 year that did not attenuate in the second year. At the end of year 2, students in the delayed-start schools slept 43 minutes more on weeknights than their early-starting peers (95% confidence interval, 25-61, P < .001.) The investigators did not see significant between-group differences in weeknight bedtimes. On weekends, students in the delayed-start group slept a mean 34 minutes less at year 2 (95% CI, –65 to –3, P = .03) than their peers in the early groups.

The researchers described the study’s design, a natural experiment with long follow-up and objectively measured sleep data, as its key strength. “No previous studies have been performed of sufficient quality to conclude that later start times cause students to get more sleep and that this effect can be sustained,” they concluded.

In an editorial comment, Erika R. Cheng, PhD, and Aaron E. Carroll, MD, of Indiana University, Indianapolis, wrote that the study provides strong evidence that delaying early school start times “would help adolescents get the sleep they need to thrive,” and belies the commonly held argument that delayed school times would merely lead to them staying awake later on school nights.

Adolescents “experience natural circadian and physiological brain changes that shift their sleep preference to go to bed and wake up later than adults or younger children,” Dr. Cheng and Dr. Carroll noted, with 12th graders’ bedtimes typically after 11 p.m. on weekdays. Regardless, “more than 40% of high schools in the United States start before 8 a.m., and more than 20% of middle schools start at 7:45 a.m. or earlier.”

Dr. Cheng and Dr. Carroll cautioned that the population in this study comprised “relatively affluent students and schools,” and that there were “socioeconomic and racial differences in student characteristics between schools that did and did not adopt the later start times.” For instance, they noted, nearly 90% of students in the delayed-start schools reported having at least one college-educated parent, while in the comparison schools fewer than 75% did. Unmeasured characteristics associated with parent education may have “influenced the school district’s decision to delay schools’ start times and had an effect on student sleep duration.”

Dr. Widome and colleagues’ study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the authors received support from a grant from the Minnesota Population Center. One coauthor acknowledged receiving a consulting fee from Jazz Pharmaceuticals. Dr. Cheng and Dr. Carroll disclosed no relevant conflicts of interest.

SOURCES: Widome R et al. JAMA Pedatr. 2020 Apr 27. doi: 10.1001/jamapediatrics.2020.0344; Cheng ER, Carroll AE. JAMA Pediatr. 2020 Apr 27. oi: 10.1001/jamapediatrics.2020.0351.

Patients with epilepsy may report less than half of their seizures to clinicians, according to survey results presented online as part of the 2020 American Academy of Neurology Science Highlights.

Clinicians, for their part, may underestimate the number of seizures that go unreported. This disconnect may contribute to complacency about epilepsy treatment regimens among patients, caregivers, and health care professionals (HCPs), despite continuations in seizures. “Improved reporting of all seizure occurrences and more frequent discussion of potential treatment changes, initiated by all groups, may be needed to optimize treatment outcomes,” said Patricia E. Penovich, MD, a neurologist at Minnesota Epilepsy Group in St. Paul, and colleagues.

jremaly@mdedge.com

SOURCE: Penovich PE et al. AAN 2020, Abstract S59.007.

Patients with epilepsy may report less than half of their seizures to clinicians, according to survey results presented online as part of the 2020 American Academy of Neurology Science Highlights.

Clinicians, for their part, may underestimate the number of seizures that go unreported. This disconnect may contribute to complacency about epilepsy treatment regimens among patients, caregivers, and health care professionals (HCPs), despite continuations in seizures. “Improved reporting of all seizure occurrences and more frequent discussion of potential treatment changes, initiated by all groups, may be needed to optimize treatment outcomes,” said Patricia E. Penovich, MD, a neurologist at Minnesota Epilepsy Group in St. Paul, and colleagues.

jremaly@mdedge.com

SOURCE: Penovich PE et al. AAN 2020, Abstract S59.007.

Patients with epilepsy may report less than half of their seizures to clinicians, according to survey results presented online as part of the 2020 American Academy of Neurology Science Highlights.

Clinicians, for their part, may underestimate the number of seizures that go unreported. This disconnect may contribute to complacency about epilepsy treatment regimens among patients, caregivers, and health care professionals (HCPs), despite continuations in seizures. “Improved reporting of all seizure occurrences and more frequent discussion of potential treatment changes, initiated by all groups, may be needed to optimize treatment outcomes,” said Patricia E. Penovich, MD, a neurologist at Minnesota Epilepsy Group in St. Paul, and colleagues.

jremaly@mdedge.com

SOURCE: Penovich PE et al. AAN 2020, Abstract S59.007.

Based on the clinical appearance of hyperpigmented and hypopigmented scaly plaques in sun-exposed facial areas (with associated scarring and follicular plugging in affected lesions), the patient was given a diagnosis of discoid lupus erythematosus. The diagnosis was confirmed with a punch biopsy that showed characteristic interface dermatitis with superficial and deep perivascular and peri-adnexal lymphocytes. Direct immunofluorescence showed a band of C3 at the dermo-epidermal junction, consistent with various forms of cutaneous lupus.

A review of systems was negative for signs of systemic disease, including a lack of weakness, joint pain/swelling, fever, or known blood clots. An antinuclear antibody panel was also negative, largely excluding systemic disease.

Discoid lupus erythematosus is a form of cutaneous lupus. Patients often are genetically predisposed to autoimmune disease, and disease may be triggered by sun exposure. Up to 80% of patients develop lesions that are limited to the head and neck. Up to 25% of patients develop systemic lupus erythematosus that may occur months—or even decades—after the initial diagnosis. Lesions may lead to longstanding scars; this cannot always be prevented.

Two- to 3-week trials of topical potent or superpotent steroids applied to affected plaques may lead to clearance. Additionally, lesions may be treated with intralesional triamcinolone 3 mg/mL to 10 mg/mL and repeated every 3 to 4 weeks. Systemic therapies include hydroxychloroquine, chloroquine, retinoids, steroid sparing immunomodulators, and rarely prednisone.

This patient tolerated topical therapy well and though some scars remained, he was able to control flares with 2- to 3-week courses of clobetasol 0.05% twice daily. He is followed 2 to 3 times annually and has not developed signs or serologic findings of systemic disease over several years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Based on the clinical appearance of hyperpigmented and hypopigmented scaly plaques in sun-exposed facial areas (with associated scarring and follicular plugging in affected lesions), the patient was given a diagnosis of discoid lupus erythematosus. The diagnosis was confirmed with a punch biopsy that showed characteristic interface dermatitis with superficial and deep perivascular and peri-adnexal lymphocytes. Direct immunofluorescence showed a band of C3 at the dermo-epidermal junction, consistent with various forms of cutaneous lupus.

A review of systems was negative for signs of systemic disease, including a lack of weakness, joint pain/swelling, fever, or known blood clots. An antinuclear antibody panel was also negative, largely excluding systemic disease.

Discoid lupus erythematosus is a form of cutaneous lupus. Patients often are genetically predisposed to autoimmune disease, and disease may be triggered by sun exposure. Up to 80% of patients develop lesions that are limited to the head and neck. Up to 25% of patients develop systemic lupus erythematosus that may occur months—or even decades—after the initial diagnosis. Lesions may lead to longstanding scars; this cannot always be prevented.

Two- to 3-week trials of topical potent or superpotent steroids applied to affected plaques may lead to clearance. Additionally, lesions may be treated with intralesional triamcinolone 3 mg/mL to 10 mg/mL and repeated every 3 to 4 weeks. Systemic therapies include hydroxychloroquine, chloroquine, retinoids, steroid sparing immunomodulators, and rarely prednisone.

This patient tolerated topical therapy well and though some scars remained, he was able to control flares with 2- to 3-week courses of clobetasol 0.05% twice daily. He is followed 2 to 3 times annually and has not developed signs or serologic findings of systemic disease over several years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Based on the clinical appearance of hyperpigmented and hypopigmented scaly plaques in sun-exposed facial areas (with associated scarring and follicular plugging in affected lesions), the patient was given a diagnosis of discoid lupus erythematosus. The diagnosis was confirmed with a punch biopsy that showed characteristic interface dermatitis with superficial and deep perivascular and peri-adnexal lymphocytes. Direct immunofluorescence showed a band of C3 at the dermo-epidermal junction, consistent with various forms of cutaneous lupus.

A review of systems was negative for signs of systemic disease, including a lack of weakness, joint pain/swelling, fever, or known blood clots. An antinuclear antibody panel was also negative, largely excluding systemic disease.

Discoid lupus erythematosus is a form of cutaneous lupus. Patients often are genetically predisposed to autoimmune disease, and disease may be triggered by sun exposure. Up to 80% of patients develop lesions that are limited to the head and neck. Up to 25% of patients develop systemic lupus erythematosus that may occur months—or even decades—after the initial diagnosis. Lesions may lead to longstanding scars; this cannot always be prevented.

Two- to 3-week trials of topical potent or superpotent steroids applied to affected plaques may lead to clearance. Additionally, lesions may be treated with intralesional triamcinolone 3 mg/mL to 10 mg/mL and repeated every 3 to 4 weeks. Systemic therapies include hydroxychloroquine, chloroquine, retinoids, steroid sparing immunomodulators, and rarely prednisone.

This patient tolerated topical therapy well and though some scars remained, he was able to control flares with 2- to 3-week courses of clobetasol 0.05% twice daily. He is followed 2 to 3 times annually and has not developed signs or serologic findings of systemic disease over several years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The Food and Drug Administration has approved capmatinib (Tabrecta) to treat adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, as detected by an FDA-approved test.

The FDA also approved the FoundationOne CDx assay (F1CDx) as a companion diagnostic for capmatinib. F1CDx is a next-generation sequencing-based, in vitro diagnostic device that detects several mutations, including MET exon 14 skipping mutations.

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and the first treatment FDA-approved for NSCLC with MET exon 14 skipping mutations.

Capmatinib was granted accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, the FDA said. Results from this trial were recently presented at the AACR Virtual Annual Meeting I.

The phase 2 trial enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping mutations, 69 of whom were previously treated and 28 of whom were treatment naive. The patients received capmatinib at 400 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months, respectively, according to the FDA.

The most common adverse events (occurring in at least 20% of patients) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

The full prescribing information for capmatinib is available for download from the FDA website.

The FDA granted the approval of capmatinib to Novartis Pharmaceuticals Corporation and the approval of the F1CDx companion diagnostic to Foundation Medicine.

jensmith@mdedge.com

The Food and Drug Administration has approved capmatinib (Tabrecta) to treat adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, as detected by an FDA-approved test.

The FDA also approved the FoundationOne CDx assay (F1CDx) as a companion diagnostic for capmatinib. F1CDx is a next-generation sequencing-based, in vitro diagnostic device that detects several mutations, including MET exon 14 skipping mutations.

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and the first treatment FDA-approved for NSCLC with MET exon 14 skipping mutations.

Capmatinib was granted accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, the FDA said. Results from this trial were recently presented at the AACR Virtual Annual Meeting I.

The phase 2 trial enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping mutations, 69 of whom were previously treated and 28 of whom were treatment naive. The patients received capmatinib at 400 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months, respectively, according to the FDA.

The most common adverse events (occurring in at least 20% of patients) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

The full prescribing information for capmatinib is available for download from the FDA website.

The FDA granted the approval of capmatinib to Novartis Pharmaceuticals Corporation and the approval of the F1CDx companion diagnostic to Foundation Medicine.

jensmith@mdedge.com

The Food and Drug Administration has approved capmatinib (Tabrecta) to treat adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, as detected by an FDA-approved test.

The FDA also approved the FoundationOne CDx assay (F1CDx) as a companion diagnostic for capmatinib. F1CDx is a next-generation sequencing-based, in vitro diagnostic device that detects several mutations, including MET exon 14 skipping mutations.

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and the first treatment FDA-approved for NSCLC with MET exon 14 skipping mutations.

Capmatinib was granted accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, the FDA said. Results from this trial were recently presented at the AACR Virtual Annual Meeting I.

The phase 2 trial enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping mutations, 69 of whom were previously treated and 28 of whom were treatment naive. The patients received capmatinib at 400 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months, respectively, according to the FDA.

The most common adverse events (occurring in at least 20% of patients) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

The full prescribing information for capmatinib is available for download from the FDA website.

The FDA granted the approval of capmatinib to Novartis Pharmaceuticals Corporation and the approval of the F1CDx companion diagnostic to Foundation Medicine.

jensmith@mdedge.com

Capmatinib produced rapid, deep responses in patients with advanced non–small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations, according to a presentation at the AACR virtual meeting I.

The duration of response was impressive in both treatment-naive and previously treated patients, according to presenter Edward B. Garon, MD, of the University of California, Los Angeles.

In view of these responses, Dr. Garon urged early molecular testing in NSCLC.

He also noted that capmatinib produced responses in patients with brain metastases. However, because of small patient numbers, additional study is needed to validate the intracranial efficacy of capmatinib and ascertain mechanisms of resistance.

Study rationale and details

METex14 mutations are reported in up to 4% of patients with NSCLC and portend poor outcomes with chemotherapy and immune checkpoint inhibitors (PLoS One 2014; 9:e107677; Ann Oncol 2018;29:2085-91).

Capmatinib is a highly selective, reversible, and potent inhibitor of MET tyrosine kinase that crosses the blood-brain barrier.

In the phase 2 GEOMETRY mono-1 study, Dr. Garon and colleagues tested capmatinib, given at 400 mg orally twice a day, in patients with METex14-mutated, ALK and EGFR wild-type, stage IIIB/IV NSCLC. Patients with neurologically stable or asymptomatic brain metastases were eligible.

Dr. Garon presented safety data for all patients enrolled in this study and efficacy data for patients in cohorts 4 and 5b. Cohort 4 enrolled patients who received prior systemic therapy for advanced disease, and cohort 5b enrolled treatment-naive patients. Both cohorts had METex14 gene mutations but not amplification.

Efficacy

There were 97 patients evaluable for efficacy – 69 previously treated and 28 treatment naive. The median age in both cohorts was 71 years, most patients were female (58% of previously treated and 64.3% of treatment-naive patients), and most were never-smokers (58% and 64.3%, respectively). Adenocarcinoma was the predominant histology.

The overall response rate, per an independent review committee, was 40.6% in previously treated patients and 67.9% in treatment-naive patients.

Waterfall plots showed deep responses, with only four cases of disease progression in the previously treated cohort and none in the treatment-naive cohort.

Responses occurred rapidly. Many responses exceeded 1 year and were ongoing at the data cut-off. The median response duration was 9.72 months in previously treated patients and 11.14 months in treatment-naive patients.

There were 13 patients with evaluable baseline brain metastases (3.3 brain lesions per patient [range, 1-8]). Twelve patients had intracranial disease control, and seven patients (54%) had intracranial response. Four patients had complete resolution of all brain lesions.

Intracranial responses were generally seen by the first radiologic evaluation and occurred as rapidly as systemic responses.

Safety

With safety data on all 334 patients in the trial, the GEOMETRY mono-1 study is the largest reported experience with capmatinib in NSCLC patients. The median treatment exposure time was 14.9 weeks.

Overall, 35.6% of patients experienced a grade 3/4 adverse event (AE). Grade 4 AEs were observed in 4.5% of patients, and there were no treatment-related deaths.

Peripheral edema (41.6%), nausea (33.2%), increased blood creatinine (19.5%), and vomiting (18.9%) were the most frequent AEs of any grade.

In all, 21.9% of patients required dose adjustments due to treatment-related AEs, and 11.1% of patients stopped treatment because of an AE.

This study was sponsored by Novartis. Dr. Garon disclosed relationships with Novartis, AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Eli Lilly, EMD Serono, Genentech, GSK, Iovance, Merck, Mirati, and Neon.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Garon EB et al. AACR 2020, Abstract CT082.

Capmatinib produced rapid, deep responses in patients with advanced non–small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations, according to a presentation at the AACR virtual meeting I.

The duration of response was impressive in both treatment-naive and previously treated patients, according to presenter Edward B. Garon, MD, of the University of California, Los Angeles.

In view of these responses, Dr. Garon urged early molecular testing in NSCLC.

He also noted that capmatinib produced responses in patients with brain metastases. However, because of small patient numbers, additional study is needed to validate the intracranial efficacy of capmatinib and ascertain mechanisms of resistance.

Study rationale and details

METex14 mutations are reported in up to 4% of patients with NSCLC and portend poor outcomes with chemotherapy and immune checkpoint inhibitors (PLoS One 2014; 9:e107677; Ann Oncol 2018;29:2085-91).

Capmatinib is a highly selective, reversible, and potent inhibitor of MET tyrosine kinase that crosses the blood-brain barrier.

In the phase 2 GEOMETRY mono-1 study, Dr. Garon and colleagues tested capmatinib, given at 400 mg orally twice a day, in patients with METex14-mutated, ALK and EGFR wild-type, stage IIIB/IV NSCLC. Patients with neurologically stable or asymptomatic brain metastases were eligible.

Dr. Garon presented safety data for all patients enrolled in this study and efficacy data for patients in cohorts 4 and 5b. Cohort 4 enrolled patients who received prior systemic therapy for advanced disease, and cohort 5b enrolled treatment-naive patients. Both cohorts had METex14 gene mutations but not amplification.

Efficacy

There were 97 patients evaluable for efficacy – 69 previously treated and 28 treatment naive. The median age in both cohorts was 71 years, most patients were female (58% of previously treated and 64.3% of treatment-naive patients), and most were never-smokers (58% and 64.3%, respectively). Adenocarcinoma was the predominant histology.

The overall response rate, per an independent review committee, was 40.6% in previously treated patients and 67.9% in treatment-naive patients.

Waterfall plots showed deep responses, with only four cases of disease progression in the previously treated cohort and none in the treatment-naive cohort.

Responses occurred rapidly. Many responses exceeded 1 year and were ongoing at the data cut-off. The median response duration was 9.72 months in previously treated patients and 11.14 months in treatment-naive patients.

There were 13 patients with evaluable baseline brain metastases (3.3 brain lesions per patient [range, 1-8]). Twelve patients had intracranial disease control, and seven patients (54%) had intracranial response. Four patients had complete resolution of all brain lesions.

Intracranial responses were generally seen by the first radiologic evaluation and occurred as rapidly as systemic responses.

Safety

With safety data on all 334 patients in the trial, the GEOMETRY mono-1 study is the largest reported experience with capmatinib in NSCLC patients. The median treatment exposure time was 14.9 weeks.

Overall, 35.6% of patients experienced a grade 3/4 adverse event (AE). Grade 4 AEs were observed in 4.5% of patients, and there were no treatment-related deaths.

Peripheral edema (41.6%), nausea (33.2%), increased blood creatinine (19.5%), and vomiting (18.9%) were the most frequent AEs of any grade.

In all, 21.9% of patients required dose adjustments due to treatment-related AEs, and 11.1% of patients stopped treatment because of an AE.

This study was sponsored by Novartis. Dr. Garon disclosed relationships with Novartis, AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Eli Lilly, EMD Serono, Genentech, GSK, Iovance, Merck, Mirati, and Neon.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Garon EB et al. AACR 2020, Abstract CT082.

Capmatinib produced rapid, deep responses in patients with advanced non–small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations, according to a presentation at the AACR virtual meeting I.

The duration of response was impressive in both treatment-naive and previously treated patients, according to presenter Edward B. Garon, MD, of the University of California, Los Angeles.

In view of these responses, Dr. Garon urged early molecular testing in NSCLC.

He also noted that capmatinib produced responses in patients with brain metastases. However, because of small patient numbers, additional study is needed to validate the intracranial efficacy of capmatinib and ascertain mechanisms of resistance.

Study rationale and details

METex14 mutations are reported in up to 4% of patients with NSCLC and portend poor outcomes with chemotherapy and immune checkpoint inhibitors (PLoS One 2014; 9:e107677; Ann Oncol 2018;29:2085-91).

Capmatinib is a highly selective, reversible, and potent inhibitor of MET tyrosine kinase that crosses the blood-brain barrier.

In the phase 2 GEOMETRY mono-1 study, Dr. Garon and colleagues tested capmatinib, given at 400 mg orally twice a day, in patients with METex14-mutated, ALK and EGFR wild-type, stage IIIB/IV NSCLC. Patients with neurologically stable or asymptomatic brain metastases were eligible.

Dr. Garon presented safety data for all patients enrolled in this study and efficacy data for patients in cohorts 4 and 5b. Cohort 4 enrolled patients who received prior systemic therapy for advanced disease, and cohort 5b enrolled treatment-naive patients. Both cohorts had METex14 gene mutations but not amplification.

Efficacy

There were 97 patients evaluable for efficacy – 69 previously treated and 28 treatment naive. The median age in both cohorts was 71 years, most patients were female (58% of previously treated and 64.3% of treatment-naive patients), and most were never-smokers (58% and 64.3%, respectively). Adenocarcinoma was the predominant histology.

The overall response rate, per an independent review committee, was 40.6% in previously treated patients and 67.9% in treatment-naive patients.

Waterfall plots showed deep responses, with only four cases of disease progression in the previously treated cohort and none in the treatment-naive cohort.

Responses occurred rapidly. Many responses exceeded 1 year and were ongoing at the data cut-off. The median response duration was 9.72 months in previously treated patients and 11.14 months in treatment-naive patients.

There were 13 patients with evaluable baseline brain metastases (3.3 brain lesions per patient [range, 1-8]). Twelve patients had intracranial disease control, and seven patients (54%) had intracranial response. Four patients had complete resolution of all brain lesions.

Intracranial responses were generally seen by the first radiologic evaluation and occurred as rapidly as systemic responses.

Safety

With safety data on all 334 patients in the trial, the GEOMETRY mono-1 study is the largest reported experience with capmatinib in NSCLC patients. The median treatment exposure time was 14.9 weeks.

Overall, 35.6% of patients experienced a grade 3/4 adverse event (AE). Grade 4 AEs were observed in 4.5% of patients, and there were no treatment-related deaths.

Peripheral edema (41.6%), nausea (33.2%), increased blood creatinine (19.5%), and vomiting (18.9%) were the most frequent AEs of any grade.

In all, 21.9% of patients required dose adjustments due to treatment-related AEs, and 11.1% of patients stopped treatment because of an AE.

This study was sponsored by Novartis. Dr. Garon disclosed relationships with Novartis, AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Eli Lilly, EMD Serono, Genentech, GSK, Iovance, Merck, Mirati, and Neon.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Garon EB et al. AACR 2020, Abstract CT082.

Since the 1950s, when Shirodkar (1955) and McDonald (1957) published their seminal works detailing a transvaginal method to suture a “weak” cervix, clinicians and researchers have debated the indications for and utility of cerclage for preventing pregnancy loss and preterm birth.^1,2

Originally based on a history of recurrent mid-trimester loss (that is, a clinical diagnosis of cervical insufficiency), cerclage has been expanded to capture both ultrasonography and physical-exam indications. While cerclage has proven useful in select patient populations, an infrequent but vexing problem is what to do when a woman has experienced 1 or more (transvaginal) cerclage “failures.”

With a dearth of well-controlled, randomized data to support the use of cerclage for either history- or physical-exam indications, it is not surprising that we still debate whether the Shirodkar method is superior to the McDonald technique as well as how to best manage a patient when either or both methods previously resulted in an unsatisfactory outcome.

First randomized study to directly compare cerclage techniques

Fortunately, Shennan and colleagues in the United Kingdom have greatly enlarged our knowledge in this area by performing the first well-powered, 3-arm, randomized trial of transabdominal cerclage (TAC) compared with both high and low vaginal cerclage (HVC, LVC).³ They analyzed data for 111 women who were randomly assigned to TAC
(n = 39), HVC (n = 39), or LVC (n = 33).

Interestingly, the investigators chose to not attach conventional eponymous labels to their transvaginal methods, and they do not even provide a reference or detailed description of the surgical methods, telling us instead that, “Techniques used were left to the local clinician’s discretion.” Writing also that HVC cases, like the transabdominal surgeries, were carried out in specialty centers, they implied that additional training was required for the HVC. I inferred that indeed they actually were performing the McDonald and Shirodkar transvaginal methods and with possible by-physician, local modifications.

I am certain that the authors’ results did not surprise proponents of transabdominal cerclage for transvaginal cerclage failures, defined in this trial as prior birth from 14 to 28 weeks’ gestation. Since some clinicians use a more generous definition of cerclage failure (such as birth at less than 34 weeks), this study population was clearly at high risk for poor outcomes; in fact, more than 90% of each group had experienced at least 2 prior mid-trimester losses. As anticipated with randomization, other characteristics were well distributed across the 3 groups.

Continue to: Transabdominal cerclage significantly reduced preterm birth rates...

Transabdominal cerclage significantly reduced preterm birth rates

Using a primary outcome of preterm birth less than 32 weeks, which concentrates neonatal morbidities, the investigators observed an overall 4.5-fold higher rate of preterm birth in the transvaginal cohorts compared with the transabdominal patients (33% and 38% versus 8%, respectively). Comparing the TAC group individually with both LVC and HVC groups, the relative risk of preterm birth was 0.20 compared with the HVC group and 0.23 compared with the LVC group, reflecting an approximate 80% reduction.

Not surprising to me, the investigators observed nearly identical outcomes between the HVC and LVC cohorts, substantiating my bias that the 2 transvaginal methods are similarly effective. Opponents will quickly remind me that the study was not well-powered to detect a clinically significant difference between these 2 groups; touché!

Risks of TAC. We all know that, despite its now-proven benefits, the transabdominal approach is associated with a risk of special complications, including the surgical risks of placement (and removal) of the cerclage, the management of fetal death beyond approximately 14 weeks, and the absolute requisite for hysterotomy/cesarean birth. While serious complications are rare, in the trial by Shennan and colleagues none were recorded in the 39 TAC cases. Nevertheless, for women with no children or only prior early births, the risks seem to be justified; the number needed to treat was less than 4 to prevent 1 birth at less than 32 weeks and was 5.3 to prevent a fetal loss.

TAC is an option for select patients

Given that TAC now can be successfully placed using minimally invasive surgery, either prior to or following conception, this study provides unique level I evidence that should not be discounted and should further be considered in the context of confirming prior cohort studies that suggested a significant benefit. Although specialized training is required and the procedure may involve travel to a specialty center, the weight of clinical data clearly supports the use of TAC.

In summary, based largely on the trial by Shennan and colleagues, women with prior failed vaginal cerclage can and should be counseled regarding the availability of TAC and given the opportunity to weigh the reported risks and benefits. ●

Since the 1950s, when Shirodkar (1955) and McDonald (1957) published their seminal works detailing a transvaginal method to suture a “weak” cervix, clinicians and researchers have debated the indications for and utility of cerclage for preventing pregnancy loss and preterm birth.^1,2

Originally based on a history of recurrent mid-trimester loss (that is, a clinical diagnosis of cervical insufficiency), cerclage has been expanded to capture both ultrasonography and physical-exam indications. While cerclage has proven useful in select patient populations, an infrequent but vexing problem is what to do when a woman has experienced 1 or more (transvaginal) cerclage “failures.”

With a dearth of well-controlled, randomized data to support the use of cerclage for either history- or physical-exam indications, it is not surprising that we still debate whether the Shirodkar method is superior to the McDonald technique as well as how to best manage a patient when either or both methods previously resulted in an unsatisfactory outcome.

First randomized study to directly compare cerclage techniques

Fortunately, Shennan and colleagues in the United Kingdom have greatly enlarged our knowledge in this area by performing the first well-powered, 3-arm, randomized trial of transabdominal cerclage (TAC) compared with both high and low vaginal cerclage (HVC, LVC).³ They analyzed data for 111 women who were randomly assigned to TAC
(n = 39), HVC (n = 39), or LVC (n = 33).

Interestingly, the investigators chose to not attach conventional eponymous labels to their transvaginal methods, and they do not even provide a reference or detailed description of the surgical methods, telling us instead that, “Techniques used were left to the local clinician’s discretion.” Writing also that HVC cases, like the transabdominal surgeries, were carried out in specialty centers, they implied that additional training was required for the HVC. I inferred that indeed they actually were performing the McDonald and Shirodkar transvaginal methods and with possible by-physician, local modifications.

I am certain that the authors’ results did not surprise proponents of transabdominal cerclage for transvaginal cerclage failures, defined in this trial as prior birth from 14 to 28 weeks’ gestation. Since some clinicians use a more generous definition of cerclage failure (such as birth at less than 34 weeks), this study population was clearly at high risk for poor outcomes; in fact, more than 90% of each group had experienced at least 2 prior mid-trimester losses. As anticipated with randomization, other characteristics were well distributed across the 3 groups.

Continue to: Transabdominal cerclage significantly reduced preterm birth rates...

Transabdominal cerclage significantly reduced preterm birth rates

Using a primary outcome of preterm birth less than 32 weeks, which concentrates neonatal morbidities, the investigators observed an overall 4.5-fold higher rate of preterm birth in the transvaginal cohorts compared with the transabdominal patients (33% and 38% versus 8%, respectively). Comparing the TAC group individually with both LVC and HVC groups, the relative risk of preterm birth was 0.20 compared with the HVC group and 0.23 compared with the LVC group, reflecting an approximate 80% reduction.

Not surprising to me, the investigators observed nearly identical outcomes between the HVC and LVC cohorts, substantiating my bias that the 2 transvaginal methods are similarly effective. Opponents will quickly remind me that the study was not well-powered to detect a clinically significant difference between these 2 groups; touché!

Risks of TAC. We all know that, despite its now-proven benefits, the transabdominal approach is associated with a risk of special complications, including the surgical risks of placement (and removal) of the cerclage, the management of fetal death beyond approximately 14 weeks, and the absolute requisite for hysterotomy/cesarean birth. While serious complications are rare, in the trial by Shennan and colleagues none were recorded in the 39 TAC cases. Nevertheless, for women with no children or only prior early births, the risks seem to be justified; the number needed to treat was less than 4 to prevent 1 birth at less than 32 weeks and was 5.3 to prevent a fetal loss.

TAC is an option for select patients

Given that TAC now can be successfully placed using minimally invasive surgery, either prior to or following conception, this study provides unique level I evidence that should not be discounted and should further be considered in the context of confirming prior cohort studies that suggested a significant benefit. Although specialized training is required and the procedure may involve travel to a specialty center, the weight of clinical data clearly supports the use of TAC.

In summary, based largely on the trial by Shennan and colleagues, women with prior failed vaginal cerclage can and should be counseled regarding the availability of TAC and given the opportunity to weigh the reported risks and benefits. ●

Since the 1950s, when Shirodkar (1955) and McDonald (1957) published their seminal works detailing a transvaginal method to suture a “weak” cervix, clinicians and researchers have debated the indications for and utility of cerclage for preventing pregnancy loss and preterm birth.^1,2

Originally based on a history of recurrent mid-trimester loss (that is, a clinical diagnosis of cervical insufficiency), cerclage has been expanded to capture both ultrasonography and physical-exam indications. While cerclage has proven useful in select patient populations, an infrequent but vexing problem is what to do when a woman has experienced 1 or more (transvaginal) cerclage “failures.”

With a dearth of well-controlled, randomized data to support the use of cerclage for either history- or physical-exam indications, it is not surprising that we still debate whether the Shirodkar method is superior to the McDonald technique as well as how to best manage a patient when either or both methods previously resulted in an unsatisfactory outcome.

First randomized study to directly compare cerclage techniques

Fortunately, Shennan and colleagues in the United Kingdom have greatly enlarged our knowledge in this area by performing the first well-powered, 3-arm, randomized trial of transabdominal cerclage (TAC) compared with both high and low vaginal cerclage (HVC, LVC).³ They analyzed data for 111 women who were randomly assigned to TAC
(n = 39), HVC (n = 39), or LVC (n = 33).

Interestingly, the investigators chose to not attach conventional eponymous labels to their transvaginal methods, and they do not even provide a reference or detailed description of the surgical methods, telling us instead that, “Techniques used were left to the local clinician’s discretion.” Writing also that HVC cases, like the transabdominal surgeries, were carried out in specialty centers, they implied that additional training was required for the HVC. I inferred that indeed they actually were performing the McDonald and Shirodkar transvaginal methods and with possible by-physician, local modifications.

I am certain that the authors’ results did not surprise proponents of transabdominal cerclage for transvaginal cerclage failures, defined in this trial as prior birth from 14 to 28 weeks’ gestation. Since some clinicians use a more generous definition of cerclage failure (such as birth at less than 34 weeks), this study population was clearly at high risk for poor outcomes; in fact, more than 90% of each group had experienced at least 2 prior mid-trimester losses. As anticipated with randomization, other characteristics were well distributed across the 3 groups.

Continue to: Transabdominal cerclage significantly reduced preterm birth rates...

Transabdominal cerclage significantly reduced preterm birth rates

Using a primary outcome of preterm birth less than 32 weeks, which concentrates neonatal morbidities, the investigators observed an overall 4.5-fold higher rate of preterm birth in the transvaginal cohorts compared with the transabdominal patients (33% and 38% versus 8%, respectively). Comparing the TAC group individually with both LVC and HVC groups, the relative risk of preterm birth was 0.20 compared with the HVC group and 0.23 compared with the LVC group, reflecting an approximate 80% reduction.

Not surprising to me, the investigators observed nearly identical outcomes between the HVC and LVC cohorts, substantiating my bias that the 2 transvaginal methods are similarly effective. Opponents will quickly remind me that the study was not well-powered to detect a clinically significant difference between these 2 groups; touché!

Risks of TAC. We all know that, despite its now-proven benefits, the transabdominal approach is associated with a risk of special complications, including the surgical risks of placement (and removal) of the cerclage, the management of fetal death beyond approximately 14 weeks, and the absolute requisite for hysterotomy/cesarean birth. While serious complications are rare, in the trial by Shennan and colleagues none were recorded in the 39 TAC cases. Nevertheless, for women with no children or only prior early births, the risks seem to be justified; the number needed to treat was less than 4 to prevent 1 birth at less than 32 weeks and was 5.3 to prevent a fetal loss.

TAC is an option for select patients

Given that TAC now can be successfully placed using minimally invasive surgery, either prior to or following conception, this study provides unique level I evidence that should not be discounted and should further be considered in the context of confirming prior cohort studies that suggested a significant benefit. Although specialized training is required and the procedure may involve travel to a specialty center, the weight of clinical data clearly supports the use of TAC.

In summary, based largely on the trial by Shennan and colleagues, women with prior failed vaginal cerclage can and should be counseled regarding the availability of TAC and given the opportunity to weigh the reported risks and benefits. ●

Wiesenfeld HC, Meyn LA, Darville T, et al. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin Infect Dis. February 13, 2020. doi:10.1093/cid/ciaa101.

EXPERT COMMENTARY

Pelvic inflammatory disease remains prevalent among young women and is commonly diagnosed in emergency departments and sexually transmitted disease (STD) clinics. This tubal infection is associated with significant reproductive sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, these women remain at risk for recurrent PID.

Bacterial vaginosis is present in more than half of women with PID. Not surprisingly, anaerobic microorganisms are more commonly isolated from the upper genital tract of patients with acute PID than either Neisseria gonorrhoeae or Chlamydia trachomatis, yet recommended antimicrobial regimens do not necessarily include antibiotics with an excellent antianaerobic spectrum.

Details of the study

In a randomized, double-blind, placebo-controlled trial, Wiesenfeld and colleagues enrolled women from hospital emergency departments or an STD clinic with symptoms of lower abdominal or pelvic pain associated with pelvic organ tenderness. The 233 study participants were randomly assigned to 2 treatment arms: ceftriaxone, doxycycline, and placebo (n = 117) or ceftriaxone, doxycycline, and metronidazole (n = 116).

Findings. Women treated with metronidazole were less likely to have pelvic organ tenderness a month after enrollment compared with the placebo group (9% vs 20%, respectively). Although the clinical cure rates at 30 days were statistically similar in both arms of the study, those receiving metronidazole had a 97% clinical cure rate while those not treated with metronidazole had a 90% clinical cure rate
(P = .38).

Moreover, the concurrent disorders of bacterial vaginosis and trichomonas vaginitis were more effectively treated in the metronidazole group, and fewer women had positive follow-up endometrial cultures for anaerobic bacteria compared with the placebo group (8% vs 21%, respectively).

The anticipated gastrointestinal adverse effects of a combination doxycycline-and-metronidazole regimen was a significant concern; however, combination therapy was no more likely to cause gastrointestinal adverse effects than doxycycline alone.

Continue to: Study strengths and limitations...

Study strengths and limitations

This well-designed randomized, double-blinded clinical trial was performed by clinical investigators experienced in the clinical diagnosis of PID. The demography of the population and their history of C trachomatis, N gonorrhoeae, plus the concurrent diagnosis of bacterial vaginosis make the diagnosis believable and real world, and these factors contribute to the generalizability of the study results.

However, PID is an imprecise clinical diagnosis (specificity averages 65%) when held to the gold standard of diagnostic laparoscopy to confirm the presence of acute salpingitis. Given the reticence of investigators and clinicians to embark on such an invasive procedure to confirm this diagnosis, endometrial biopsy showing evidence of histologic acute endometritis has been offered as an alternative gold standard. Confirmation of acute endometritis in the trial participants would have enhanced the validity of this study.

This study challenges a long held, but never proven, belief that the combination of doxycycline and metronidazole would be poorly tolerated as a combination antimicrobial regimen. It also further solidifies the role of anaerobic bacteria as major players in the microbial etiology of acute PID. In addition, it appears that treating bacterial vaginosis concurrently may lessen the likelihood of endometrial recolonization with anaerobic bacteria. ●

Wiesenfeld HC, Meyn LA, Darville T, et al. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin Infect Dis. February 13, 2020. doi:10.1093/cid/ciaa101.

EXPERT COMMENTARY

Pelvic inflammatory disease remains prevalent among young women and is commonly diagnosed in emergency departments and sexually transmitted disease (STD) clinics. This tubal infection is associated with significant reproductive sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, these women remain at risk for recurrent PID.

Bacterial vaginosis is present in more than half of women with PID. Not surprisingly, anaerobic microorganisms are more commonly isolated from the upper genital tract of patients with acute PID than either Neisseria gonorrhoeae or Chlamydia trachomatis, yet recommended antimicrobial regimens do not necessarily include antibiotics with an excellent antianaerobic spectrum.

Details of the study

In a randomized, double-blind, placebo-controlled trial, Wiesenfeld and colleagues enrolled women from hospital emergency departments or an STD clinic with symptoms of lower abdominal or pelvic pain associated with pelvic organ tenderness. The 233 study participants were randomly assigned to 2 treatment arms: ceftriaxone, doxycycline, and placebo (n = 117) or ceftriaxone, doxycycline, and metronidazole (n = 116).

Findings. Women treated with metronidazole were less likely to have pelvic organ tenderness a month after enrollment compared with the placebo group (9% vs 20%, respectively). Although the clinical cure rates at 30 days were statistically similar in both arms of the study, those receiving metronidazole had a 97% clinical cure rate while those not treated with metronidazole had a 90% clinical cure rate
(P = .38).

Moreover, the concurrent disorders of bacterial vaginosis and trichomonas vaginitis were more effectively treated in the metronidazole group, and fewer women had positive follow-up endometrial cultures for anaerobic bacteria compared with the placebo group (8% vs 21%, respectively).

The anticipated gastrointestinal adverse effects of a combination doxycycline-and-metronidazole regimen was a significant concern; however, combination therapy was no more likely to cause gastrointestinal adverse effects than doxycycline alone.

Continue to: Study strengths and limitations...

Study strengths and limitations

This well-designed randomized, double-blinded clinical trial was performed by clinical investigators experienced in the clinical diagnosis of PID. The demography of the population and their history of C trachomatis, N gonorrhoeae, plus the concurrent diagnosis of bacterial vaginosis make the diagnosis believable and real world, and these factors contribute to the generalizability of the study results.

However, PID is an imprecise clinical diagnosis (specificity averages 65%) when held to the gold standard of diagnostic laparoscopy to confirm the presence of acute salpingitis. Given the reticence of investigators and clinicians to embark on such an invasive procedure to confirm this diagnosis, endometrial biopsy showing evidence of histologic acute endometritis has been offered as an alternative gold standard. Confirmation of acute endometritis in the trial participants would have enhanced the validity of this study.

This study challenges a long held, but never proven, belief that the combination of doxycycline and metronidazole would be poorly tolerated as a combination antimicrobial regimen. It also further solidifies the role of anaerobic bacteria as major players in the microbial etiology of acute PID. In addition, it appears that treating bacterial vaginosis concurrently may lessen the likelihood of endometrial recolonization with anaerobic bacteria. ●

Wiesenfeld HC, Meyn LA, Darville T, et al. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin Infect Dis. February 13, 2020. doi:10.1093/cid/ciaa101.

EXPERT COMMENTARY

Pelvic inflammatory disease remains prevalent among young women and is commonly diagnosed in emergency departments and sexually transmitted disease (STD) clinics. This tubal infection is associated with significant reproductive sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, these women remain at risk for recurrent PID.

Bacterial vaginosis is present in more than half of women with PID. Not surprisingly, anaerobic microorganisms are more commonly isolated from the upper genital tract of patients with acute PID than either Neisseria gonorrhoeae or Chlamydia trachomatis, yet recommended antimicrobial regimens do not necessarily include antibiotics with an excellent antianaerobic spectrum.

Details of the study

In a randomized, double-blind, placebo-controlled trial, Wiesenfeld and colleagues enrolled women from hospital emergency departments or an STD clinic with symptoms of lower abdominal or pelvic pain associated with pelvic organ tenderness. The 233 study participants were randomly assigned to 2 treatment arms: ceftriaxone, doxycycline, and placebo (n = 117) or ceftriaxone, doxycycline, and metronidazole (n = 116).

Findings. Women treated with metronidazole were less likely to have pelvic organ tenderness a month after enrollment compared with the placebo group (9% vs 20%, respectively). Although the clinical cure rates at 30 days were statistically similar in both arms of the study, those receiving metronidazole had a 97% clinical cure rate while those not treated with metronidazole had a 90% clinical cure rate
(P = .38).

Moreover, the concurrent disorders of bacterial vaginosis and trichomonas vaginitis were more effectively treated in the metronidazole group, and fewer women had positive follow-up endometrial cultures for anaerobic bacteria compared with the placebo group (8% vs 21%, respectively).

The anticipated gastrointestinal adverse effects of a combination doxycycline-and-metronidazole regimen was a significant concern; however, combination therapy was no more likely to cause gastrointestinal adverse effects than doxycycline alone.

Continue to: Study strengths and limitations...

Study strengths and limitations

This well-designed randomized, double-blinded clinical trial was performed by clinical investigators experienced in the clinical diagnosis of PID. The demography of the population and their history of C trachomatis, N gonorrhoeae, plus the concurrent diagnosis of bacterial vaginosis make the diagnosis believable and real world, and these factors contribute to the generalizability of the study results.

However, PID is an imprecise clinical diagnosis (specificity averages 65%) when held to the gold standard of diagnostic laparoscopy to confirm the presence of acute salpingitis. Given the reticence of investigators and clinicians to embark on such an invasive procedure to confirm this diagnosis, endometrial biopsy showing evidence of histologic acute endometritis has been offered as an alternative gold standard. Confirmation of acute endometritis in the trial participants would have enhanced the validity of this study.

This study challenges a long held, but never proven, belief that the combination of doxycycline and metronidazole would be poorly tolerated as a combination antimicrobial regimen. It also further solidifies the role of anaerobic bacteria as major players in the microbial etiology of acute PID. In addition, it appears that treating bacterial vaginosis concurrently may lessen the likelihood of endometrial recolonization with anaerobic bacteria. ●

CASE A woman with recurrent pregnancy loss

A 38-year-old woman (G4P0221) presents to your office for preconception counseling. Her history is significant for the following: a spontaneous pregnancy loss at 15 weeks’ gestation; a pregnancy loss at 17 weeks secondary to preterm premature rupture of membranes (PPROM); a cesarean delivery at 30 weeks and 6 days’ gestation after placement of a transvaginal cerclage at 20 weeks for cervical dilation noted on physical exam (the child now has developmental delays); and most recently a delivery at 24 weeks and 4 days due to preterm labor with subsequent neonatal demise (this followed a transvaginal cerclage placed at 13 weeks and 6 days).

How would you counsel this patient?

Cervical insufficiency describes the inability of the cervix to retain a pregnancy in the absence of the signs and symptoms of clinical contractions, labor, or both in the second trimester.¹ This condition affects an estimated 1% of obstetric patients and 8% of women with recurrent losses who have experienced a second-trimester loss.²

Diagnosis of cervical insufficiency is based on a history of painless cervical dilation after the first trimester with expulsion of the pregnancy in the second trimester before 24 weeks of gestation without contractions and in the absence of other pathology, such as bleeding, infection, or ruptured membranes.¹ Diagnosis also can be made by noting cervical dilation on physical exam during the second trimester; more recently, short cervical length on transvaginal ultrasonography in the second trimester has been used to try to predict when a cervical cerclage may be indicated, although sonographic cervical length is more a marker for risk of preterm birth than for cervical insufficiency specifically.^1,3

Given the considerable emotional and physical distress that patients experience with recurrent second-trimester losses and the significant neonatal morbidity and mortality that can occur with preterm delivery, substantial efforts are made to prevent these outcomes by treating patients with cervical insufficiency and those at risk for preterm delivery.

Transvaginal cerclage: A treatment mainstay

Standard treatment options for cervical insufficiency depend on the patient’s history. One of the treatment mainstays for women with prior second-trimester losses or preterm deliveries is transvaginal cervical cerclage. A transvaginal cerclage can be placed using either a Shirodkar technique, in which the vesicocervical mucosa is dissected and a suture is placed as close to the internal cervical os as possible, or a McDonald technique, in which a purse-string suture is placed around the cervicovaginal junction. No randomized trials have compared the effectiveness of these 2 methods, but most observational studies show no difference, and one suggests that the Shirodkar technique may be more effective in obese women specifically.^4-6

Indications for transvaginal cerclage. The indication for transvaginal cerclage is based on history, physical exam, or ultrasonography.

A physical-exam indication is the most straightforward of the 3. Transvaginal cerclage placement is indicated if on physical exam in the second trimester a patient has cervical dilation without contractions or infection.^1,7

A history-indicated cerclage (typically placed between 12 and 14 weeks’ gestation) is based on a cerclage having been placed in a prior pregnancy due to painless cervical dilation in the second trimester (either ultrasonography- or physical-exam indicated), and it also can be considered in the case of a history of 1 or more second-trimester pregnancy losses related to painless cervical dilation.¹

More recent evidence suggests that in patients with 1 prior second-trimester loss or preterm delivery, serial sonographic cervical length can be measured safely from 16 to 24 weeks, with a cerclage being placed only if cervical length decreases to less than 25 mm. By using the ultrasonography-based indication, unnecessary history-indicated cerclages for 1 prior second-trimester or preterm birth can be avoided in more than one-half of patients (FIGURE 1).^1,7

Efficacy. The effectiveness of transvaginal cerclage varies by the indication. Authors of a 2017 Cochrane review found an overall reduced risk of giving birth before 34 weeks’ gestation for any indication, with an average relative risk of 0.77.² Other recent studies showed the following^8-10:

• a 63% delivery rate after 28 weeks’ gestation for physical-exam indicated cerclages in the presence of bulging amniotic membranes
• an 86.2% delivery rate after 32 weeks’ gestation for ultrasonography-indicated cerclages
• an 86% delivery rate after 32 weeks’ gestation for a history-indicated cerclage in patients with 2 or more prior second-trimester losses.

Success rates, especially for ultrasonography- and history-indicated cerclage, are thus high. For the 14% who still fail these methods, however, a different management strategy is needed, which is where transabdominal cerclage comes into play.

Continue to: Transabdominal cerclage is an option for certain patients...

Transabdominal cerclage is an option for certain patients

In transabdominal cerclage, an abdominal approach is used to place a stitch at the cervicouterine junction. With this approach, the cerclage can reach a closer proximity to the internal os compared with the vaginal approach, providing better support of the cervical tissue (FIGURE 2).¹¹ Whether performed via laparotomy or laparoscopy, the transabdominal cerclage procedure likely carries higher morbidity than a transvaginal approach, and cesarean delivery is required after placement.

Since transvaginal cerclage often is successful, in most cases the transabdominal approach should not be viewed as the first-line treatment for cervical insufficiency if a history-indicated transvaginal cerclage has not been attempted. For women who fail a history-indicated transvaginal cerclage, however, a transabdominal cerclage has been proven to decrease the rate of preterm delivery and PPROM compared with attempting another history-indicated transvaginal cerclage.^11,12

A recent systematic review of pregnancy outcomes after transabdominal cerclage placement reported neonatal survival of 96.5% and an 83% delivery rate after 34 weeks’ gestation.¹³ Thus, even among a population that failed transvaginal cerclage, a transabdominal cerclage has a high success rate in providing a good pregnancy outcome (TABLE). Transabdominal cerclage also can be considered as first-line treatment in patients who had prior cervical surgery or cervical deformities that might preclude the ability to place a cerclage transvaginally.

CASE Continued: A candidate for transabdominal cerclage

Given the patient’s poor obstetric history, which includes a preterm delivery and neonatal loss despite a history-indicated cerclage, you recommend that the patient have a transabdominal cerclage placed as the procedure has been proven to increase the chances of neonatal survival and delivery after 34 weeks in women with a similar obstetric history. The patient is interested in this option and asks about how this cerclage is placed and when it would need to be placed during her next pregnancy.

Surgical technique for transabdominal cerclage placement

A transabdominal cerclage can be placed via laparotomy, laparoscopy, or robot-assisted laparoscopy. No differences in obstetric outcomes have been shown between the laparotomy and laparoscopic approaches.^14,15 Given the benefits of minimally invasive surgery, a laparoscopic or robot-assisted approach is preferred when feasible.

Additionally, for ease of placement, transabdominal cerclage can be placed prior to conception—known as interval placement—or during pregnancy between 10 and 14 weeks (preferably closer to 10 weeks). Because of the increased difficulty in placing a cerclage in the gravid uterus, interval transabdominal cerclage placement is recommended when possible.^13,16 Authors of one observational study noted that improved obstetric outcomes occurred with interval placement compared with cerclage placement between 9 and 10 weeks’ gestation, with a delivery rate at more than 34 weeks’ gestation in 90% versus 74% of patients, respectively.¹⁶

Continue to: Steps for interval cerclage and during pregnancy...

Steps for interval cerclage and during pregnancy

Our practice is to place transabdominal cerclage via conventional laparoscopy as an interval procedure when possible. We find no benefit in using robotic assistance.

For an interval procedure, the patient is placed in a dorsal lithotomy position, and we place a 10-mm umbilical port, 2 lateral 5-mm ports, 1 suprapubic 5-mm port, and a uterine manipulator. We use a flexible laparoscope to provide optimal visualization of the pelvis from any angle.

The first step of the surgery involves dissecting the vesicouterine peritoneum in order to move the bladder inferiorly (FIGURE 3A). Uterine arteries are then identified lateral to the cervix as part of this dissection, and a window is created in the inferior aspect of the broad ligament just anterior and lateral to the insertion of the uterosacral ligaments onto the uterus, with care taken to avoid the uterine vessels superiorly (FIGURE 3B). Two 5-mm Mersilene tape sutures are then tied together to create 1 suture with a needle at each end. This is then passed into the abdomen, and 1 needle is passed through the parametrial space at the level of the internal os inferior to the uterine vessels on 1 side of the uterus while the other needle is passed through the parametrial space on the opposite side.

Vidyard Video

CASE Continued: Patient pursues transabdominal cerclage

You explain to your patient that ideally the cerclage should be placed now in a laparoscopic fashion before she becomes pregnant. You then refer her to a local gynecologic surgeon who places many laparoscopic transabdominal cerclages. She undergoes the procedure, becomes pregnant, and after presenting in labor at 35 weeks’ gestation has a cesarean delivery. Her baby is born without any neonatal complications, and the patient is overjoyed with the outcome.

Management during and after pregnancy

Pregnant patients with a transabdominal cerclage are precluded from having a vaginal delivery and must deliver via cesarean. During the antepartum period, patients are managed in the same manner as those who have a transvaginal cerclage. Delivery via cesarean at the onset of regular contractions is recommended to reduce the risk of uterine rupture. In the absence of labor, scheduled cesarean is performed at term.

Our practice is to schedule cesarean delivery at 38 weeks’ gestation, although there are no data or consensus to support a specific gestational age between 37 and 39 weeks. Unlike a transvaginal cerclage, a transabdominal cerclage can be left in place for use in subsequent pregnancies. Data are limited on whether the transabdominal cerclage should be removed in women who no longer desire childbearing and whether there are long-term sequelae if the suture is left in situ.¹⁷

Continue to: Complications and risks of abdominal cerclage...

Complications and risks of abdominal cerclage

As the data suggest and our experience confirms, transabdominal cerclage is highly successful in patients who have failed a history-indicated transvaginal cerclage; however, the transabdominal approach carries a higher surgical risk. Risks include intraoperative hemorrhage, conversion to laparotomy, and a range of rare surgical and obstetric complications, such as bladder injury and PPROM.^13,18

If a patient experiences a fetal loss in the first trimester, a dilation and curettage (D&C) can be performed, with good obstetric outcomes in subsequent pregnancies.¹⁹ If the patient experiences an early-to-mid second-trimester loss, some studies suggest that a dilation and evacuation (D&E) of the uterus can be done with sufficient dilation of the cervix to accommodate up to a 15-mm cannula and Sopher forceps.¹⁹ Laminaria also may be used in this process. However, no data exist regarding success of future pregnancies and transabdominal cerclage integrity after a D&E.²⁰ If the cerclage prevents successful dilation of the cervix, the cerclage must be removed laparoscopically prior to performing the D&E.

In late second-trimester and third-trimester loss, the cerclage must be removed to allow passage of the fetus and placenta prior to a D&E or an induction of labor.²⁰

For patients with PPROM or preterm labor, data are limited regarding management recommendations. However, in these complex cases, we strongly recommend an individualized approach and co-management with maternal-fetal medicine specialists.

CASE Resolved

The cerclage is left in place during the patient’s cesarean delivery, and her postpartum course is uneventful. She continued without complications for the next year, at which time she sees you in the office with plans to have another pregnancy later in the year. You counsel her that her abdominal cerclage will still be effective and that she can get pregnant with expectations of similar outcomes as her previous pregnancy. She thanks you for everything and reports that she hopes to return later in the year for her first prenatal visit. ●

CASE A woman with recurrent pregnancy loss

A 38-year-old woman (G4P0221) presents to your office for preconception counseling. Her history is significant for the following: a spontaneous pregnancy loss at 15 weeks’ gestation; a pregnancy loss at 17 weeks secondary to preterm premature rupture of membranes (PPROM); a cesarean delivery at 30 weeks and 6 days’ gestation after placement of a transvaginal cerclage at 20 weeks for cervical dilation noted on physical exam (the child now has developmental delays); and most recently a delivery at 24 weeks and 4 days due to preterm labor with subsequent neonatal demise (this followed a transvaginal cerclage placed at 13 weeks and 6 days).

How would you counsel this patient?

Cervical insufficiency describes the inability of the cervix to retain a pregnancy in the absence of the signs and symptoms of clinical contractions, labor, or both in the second trimester.¹ This condition affects an estimated 1% of obstetric patients and 8% of women with recurrent losses who have experienced a second-trimester loss.²

Diagnosis of cervical insufficiency is based on a history of painless cervical dilation after the first trimester with expulsion of the pregnancy in the second trimester before 24 weeks of gestation without contractions and in the absence of other pathology, such as bleeding, infection, or ruptured membranes.¹ Diagnosis also can be made by noting cervical dilation on physical exam during the second trimester; more recently, short cervical length on transvaginal ultrasonography in the second trimester has been used to try to predict when a cervical cerclage may be indicated, although sonographic cervical length is more a marker for risk of preterm birth than for cervical insufficiency specifically.^1,3

Given the considerable emotional and physical distress that patients experience with recurrent second-trimester losses and the significant neonatal morbidity and mortality that can occur with preterm delivery, substantial efforts are made to prevent these outcomes by treating patients with cervical insufficiency and those at risk for preterm delivery.

Transvaginal cerclage: A treatment mainstay

Standard treatment options for cervical insufficiency depend on the patient’s history. One of the treatment mainstays for women with prior second-trimester losses or preterm deliveries is transvaginal cervical cerclage. A transvaginal cerclage can be placed using either a Shirodkar technique, in which the vesicocervical mucosa is dissected and a suture is placed as close to the internal cervical os as possible, or a McDonald technique, in which a purse-string suture is placed around the cervicovaginal junction. No randomized trials have compared the effectiveness of these 2 methods, but most observational studies show no difference, and one suggests that the Shirodkar technique may be more effective in obese women specifically.^4-6

Indications for transvaginal cerclage. The indication for transvaginal cerclage is based on history, physical exam, or ultrasonography.

A physical-exam indication is the most straightforward of the 3. Transvaginal cerclage placement is indicated if on physical exam in the second trimester a patient has cervical dilation without contractions or infection.^1,7

A history-indicated cerclage (typically placed between 12 and 14 weeks’ gestation) is based on a cerclage having been placed in a prior pregnancy due to painless cervical dilation in the second trimester (either ultrasonography- or physical-exam indicated), and it also can be considered in the case of a history of 1 or more second-trimester pregnancy losses related to painless cervical dilation.¹

More recent evidence suggests that in patients with 1 prior second-trimester loss or preterm delivery, serial sonographic cervical length can be measured safely from 16 to 24 weeks, with a cerclage being placed only if cervical length decreases to less than 25 mm. By using the ultrasonography-based indication, unnecessary history-indicated cerclages for 1 prior second-trimester or preterm birth can be avoided in more than one-half of patients (FIGURE 1).^1,7

Efficacy. The effectiveness of transvaginal cerclage varies by the indication. Authors of a 2017 Cochrane review found an overall reduced risk of giving birth before 34 weeks’ gestation for any indication, with an average relative risk of 0.77.² Other recent studies showed the following^8-10:

• a 63% delivery rate after 28 weeks’ gestation for physical-exam indicated cerclages in the presence of bulging amniotic membranes
• an 86.2% delivery rate after 32 weeks’ gestation for ultrasonography-indicated cerclages
• an 86% delivery rate after 32 weeks’ gestation for a history-indicated cerclage in patients with 2 or more prior second-trimester losses.

Success rates, especially for ultrasonography- and history-indicated cerclage, are thus high. For the 14% who still fail these methods, however, a different management strategy is needed, which is where transabdominal cerclage comes into play.

Continue to: Transabdominal cerclage is an option for certain patients...

Transabdominal cerclage is an option for certain patients

In transabdominal cerclage, an abdominal approach is used to place a stitch at the cervicouterine junction. With this approach, the cerclage can reach a closer proximity to the internal os compared with the vaginal approach, providing better support of the cervical tissue (FIGURE 2).¹¹ Whether performed via laparotomy or laparoscopy, the transabdominal cerclage procedure likely carries higher morbidity than a transvaginal approach, and cesarean delivery is required after placement.

Since transvaginal cerclage often is successful, in most cases the transabdominal approach should not be viewed as the first-line treatment for cervical insufficiency if a history-indicated transvaginal cerclage has not been attempted. For women who fail a history-indicated transvaginal cerclage, however, a transabdominal cerclage has been proven to decrease the rate of preterm delivery and PPROM compared with attempting another history-indicated transvaginal cerclage.^11,12

A recent systematic review of pregnancy outcomes after transabdominal cerclage placement reported neonatal survival of 96.5% and an 83% delivery rate after 34 weeks’ gestation.¹³ Thus, even among a population that failed transvaginal cerclage, a transabdominal cerclage has a high success rate in providing a good pregnancy outcome (TABLE). Transabdominal cerclage also can be considered as first-line treatment in patients who had prior cervical surgery or cervical deformities that might preclude the ability to place a cerclage transvaginally.

CASE Continued: A candidate for transabdominal cerclage

Given the patient’s poor obstetric history, which includes a preterm delivery and neonatal loss despite a history-indicated cerclage, you recommend that the patient have a transabdominal cerclage placed as the procedure has been proven to increase the chances of neonatal survival and delivery after 34 weeks in women with a similar obstetric history. The patient is interested in this option and asks about how this cerclage is placed and when it would need to be placed during her next pregnancy.

Surgical technique for transabdominal cerclage placement

A transabdominal cerclage can be placed via laparotomy, laparoscopy, or robot-assisted laparoscopy. No differences in obstetric outcomes have been shown between the laparotomy and laparoscopic approaches.^14,15 Given the benefits of minimally invasive surgery, a laparoscopic or robot-assisted approach is preferred when feasible.

Additionally, for ease of placement, transabdominal cerclage can be placed prior to conception—known as interval placement—or during pregnancy between 10 and 14 weeks (preferably closer to 10 weeks). Because of the increased difficulty in placing a cerclage in the gravid uterus, interval transabdominal cerclage placement is recommended when possible.^13,16 Authors of one observational study noted that improved obstetric outcomes occurred with interval placement compared with cerclage placement between 9 and 10 weeks’ gestation, with a delivery rate at more than 34 weeks’ gestation in 90% versus 74% of patients, respectively.¹⁶

Continue to: Steps for interval cerclage and during pregnancy...

Steps for interval cerclage and during pregnancy

Our practice is to place transabdominal cerclage via conventional laparoscopy as an interval procedure when possible. We find no benefit in using robotic assistance.

For an interval procedure, the patient is placed in a dorsal lithotomy position, and we place a 10-mm umbilical port, 2 lateral 5-mm ports, 1 suprapubic 5-mm port, and a uterine manipulator. We use a flexible laparoscope to provide optimal visualization of the pelvis from any angle.

The first step of the surgery involves dissecting the vesicouterine peritoneum in order to move the bladder inferiorly (FIGURE 3A). Uterine arteries are then identified lateral to the cervix as part of this dissection, and a window is created in the inferior aspect of the broad ligament just anterior and lateral to the insertion of the uterosacral ligaments onto the uterus, with care taken to avoid the uterine vessels superiorly (FIGURE 3B). Two 5-mm Mersilene tape sutures are then tied together to create 1 suture with a needle at each end. This is then passed into the abdomen, and 1 needle is passed through the parametrial space at the level of the internal os inferior to the uterine vessels on 1 side of the uterus while the other needle is passed through the parametrial space on the opposite side.

Vidyard Video

CASE Continued: Patient pursues transabdominal cerclage

You explain to your patient that ideally the cerclage should be placed now in a laparoscopic fashion before she becomes pregnant. You then refer her to a local gynecologic surgeon who places many laparoscopic transabdominal cerclages. She undergoes the procedure, becomes pregnant, and after presenting in labor at 35 weeks’ gestation has a cesarean delivery. Her baby is born without any neonatal complications, and the patient is overjoyed with the outcome.

Management during and after pregnancy

Pregnant patients with a transabdominal cerclage are precluded from having a vaginal delivery and must deliver via cesarean. During the antepartum period, patients are managed in the same manner as those who have a transvaginal cerclage. Delivery via cesarean at the onset of regular contractions is recommended to reduce the risk of uterine rupture. In the absence of labor, scheduled cesarean is performed at term.

Our practice is to schedule cesarean delivery at 38 weeks’ gestation, although there are no data or consensus to support a specific gestational age between 37 and 39 weeks. Unlike a transvaginal cerclage, a transabdominal cerclage can be left in place for use in subsequent pregnancies. Data are limited on whether the transabdominal cerclage should be removed in women who no longer desire childbearing and whether there are long-term sequelae if the suture is left in situ.¹⁷

Continue to: Complications and risks of abdominal cerclage...

Complications and risks of abdominal cerclage

As the data suggest and our experience confirms, transabdominal cerclage is highly successful in patients who have failed a history-indicated transvaginal cerclage; however, the transabdominal approach carries a higher surgical risk. Risks include intraoperative hemorrhage, conversion to laparotomy, and a range of rare surgical and obstetric complications, such as bladder injury and PPROM.^13,18

If a patient experiences a fetal loss in the first trimester, a dilation and curettage (D&C) can be performed, with good obstetric outcomes in subsequent pregnancies.¹⁹ If the patient experiences an early-to-mid second-trimester loss, some studies suggest that a dilation and evacuation (D&E) of the uterus can be done with sufficient dilation of the cervix to accommodate up to a 15-mm cannula and Sopher forceps.¹⁹ Laminaria also may be used in this process. However, no data exist regarding success of future pregnancies and transabdominal cerclage integrity after a D&E.²⁰ If the cerclage prevents successful dilation of the cervix, the cerclage must be removed laparoscopically prior to performing the D&E.

In late second-trimester and third-trimester loss, the cerclage must be removed to allow passage of the fetus and placenta prior to a D&E or an induction of labor.²⁰

For patients with PPROM or preterm labor, data are limited regarding management recommendations. However, in these complex cases, we strongly recommend an individualized approach and co-management with maternal-fetal medicine specialists.

CASE Resolved

The cerclage is left in place during the patient’s cesarean delivery, and her postpartum course is uneventful. She continued without complications for the next year, at which time she sees you in the office with plans to have another pregnancy later in the year. You counsel her that her abdominal cerclage will still be effective and that she can get pregnant with expectations of similar outcomes as her previous pregnancy. She thanks you for everything and reports that she hopes to return later in the year for her first prenatal visit. ●

CASE A woman with recurrent pregnancy loss

A 38-year-old woman (G4P0221) presents to your office for preconception counseling. Her history is significant for the following: a spontaneous pregnancy loss at 15 weeks’ gestation; a pregnancy loss at 17 weeks secondary to preterm premature rupture of membranes (PPROM); a cesarean delivery at 30 weeks and 6 days’ gestation after placement of a transvaginal cerclage at 20 weeks for cervical dilation noted on physical exam (the child now has developmental delays); and most recently a delivery at 24 weeks and 4 days due to preterm labor with subsequent neonatal demise (this followed a transvaginal cerclage placed at 13 weeks and 6 days).

How would you counsel this patient?

Cervical insufficiency describes the inability of the cervix to retain a pregnancy in the absence of the signs and symptoms of clinical contractions, labor, or both in the second trimester.¹ This condition affects an estimated 1% of obstetric patients and 8% of women with recurrent losses who have experienced a second-trimester loss.²

Diagnosis of cervical insufficiency is based on a history of painless cervical dilation after the first trimester with expulsion of the pregnancy in the second trimester before 24 weeks of gestation without contractions and in the absence of other pathology, such as bleeding, infection, or ruptured membranes.¹ Diagnosis also can be made by noting cervical dilation on physical exam during the second trimester; more recently, short cervical length on transvaginal ultrasonography in the second trimester has been used to try to predict when a cervical cerclage may be indicated, although sonographic cervical length is more a marker for risk of preterm birth than for cervical insufficiency specifically.^1,3

Given the considerable emotional and physical distress that patients experience with recurrent second-trimester losses and the significant neonatal morbidity and mortality that can occur with preterm delivery, substantial efforts are made to prevent these outcomes by treating patients with cervical insufficiency and those at risk for preterm delivery.

Transvaginal cerclage: A treatment mainstay

Standard treatment options for cervical insufficiency depend on the patient’s history. One of the treatment mainstays for women with prior second-trimester losses or preterm deliveries is transvaginal cervical cerclage. A transvaginal cerclage can be placed using either a Shirodkar technique, in which the vesicocervical mucosa is dissected and a suture is placed as close to the internal cervical os as possible, or a McDonald technique, in which a purse-string suture is placed around the cervicovaginal junction. No randomized trials have compared the effectiveness of these 2 methods, but most observational studies show no difference, and one suggests that the Shirodkar technique may be more effective in obese women specifically.^4-6

Indications for transvaginal cerclage. The indication for transvaginal cerclage is based on history, physical exam, or ultrasonography.

A physical-exam indication is the most straightforward of the 3. Transvaginal cerclage placement is indicated if on physical exam in the second trimester a patient has cervical dilation without contractions or infection.^1,7

A history-indicated cerclage (typically placed between 12 and 14 weeks’ gestation) is based on a cerclage having been placed in a prior pregnancy due to painless cervical dilation in the second trimester (either ultrasonography- or physical-exam indicated), and it also can be considered in the case of a history of 1 or more second-trimester pregnancy losses related to painless cervical dilation.¹

More recent evidence suggests that in patients with 1 prior second-trimester loss or preterm delivery, serial sonographic cervical length can be measured safely from 16 to 24 weeks, with a cerclage being placed only if cervical length decreases to less than 25 mm. By using the ultrasonography-based indication, unnecessary history-indicated cerclages for 1 prior second-trimester or preterm birth can be avoided in more than one-half of patients (FIGURE 1).^1,7

Efficacy. The effectiveness of transvaginal cerclage varies by the indication. Authors of a 2017 Cochrane review found an overall reduced risk of giving birth before 34 weeks’ gestation for any indication, with an average relative risk of 0.77.² Other recent studies showed the following^8-10:

• a 63% delivery rate after 28 weeks’ gestation for physical-exam indicated cerclages in the presence of bulging amniotic membranes
• an 86.2% delivery rate after 32 weeks’ gestation for ultrasonography-indicated cerclages
• an 86% delivery rate after 32 weeks’ gestation for a history-indicated cerclage in patients with 2 or more prior second-trimester losses.

Success rates, especially for ultrasonography- and history-indicated cerclage, are thus high. For the 14% who still fail these methods, however, a different management strategy is needed, which is where transabdominal cerclage comes into play.

Continue to: Transabdominal cerclage is an option for certain patients...

Transabdominal cerclage is an option for certain patients

In transabdominal cerclage, an abdominal approach is used to place a stitch at the cervicouterine junction. With this approach, the cerclage can reach a closer proximity to the internal os compared with the vaginal approach, providing better support of the cervical tissue (FIGURE 2).¹¹ Whether performed via laparotomy or laparoscopy, the transabdominal cerclage procedure likely carries higher morbidity than a transvaginal approach, and cesarean delivery is required after placement.

Since transvaginal cerclage often is successful, in most cases the transabdominal approach should not be viewed as the first-line treatment for cervical insufficiency if a history-indicated transvaginal cerclage has not been attempted. For women who fail a history-indicated transvaginal cerclage, however, a transabdominal cerclage has been proven to decrease the rate of preterm delivery and PPROM compared with attempting another history-indicated transvaginal cerclage.^11,12

A recent systematic review of pregnancy outcomes after transabdominal cerclage placement reported neonatal survival of 96.5% and an 83% delivery rate after 34 weeks’ gestation.¹³ Thus, even among a population that failed transvaginal cerclage, a transabdominal cerclage has a high success rate in providing a good pregnancy outcome (TABLE). Transabdominal cerclage also can be considered as first-line treatment in patients who had prior cervical surgery or cervical deformities that might preclude the ability to place a cerclage transvaginally.

CASE Continued: A candidate for transabdominal cerclage

Given the patient’s poor obstetric history, which includes a preterm delivery and neonatal loss despite a history-indicated cerclage, you recommend that the patient have a transabdominal cerclage placed as the procedure has been proven to increase the chances of neonatal survival and delivery after 34 weeks in women with a similar obstetric history. The patient is interested in this option and asks about how this cerclage is placed and when it would need to be placed during her next pregnancy.

Surgical technique for transabdominal cerclage placement

A transabdominal cerclage can be placed via laparotomy, laparoscopy, or robot-assisted laparoscopy. No differences in obstetric outcomes have been shown between the laparotomy and laparoscopic approaches.^14,15 Given the benefits of minimally invasive surgery, a laparoscopic or robot-assisted approach is preferred when feasible.

Additionally, for ease of placement, transabdominal cerclage can be placed prior to conception—known as interval placement—or during pregnancy between 10 and 14 weeks (preferably closer to 10 weeks). Because of the increased difficulty in placing a cerclage in the gravid uterus, interval transabdominal cerclage placement is recommended when possible.^13,16 Authors of one observational study noted that improved obstetric outcomes occurred with interval placement compared with cerclage placement between 9 and 10 weeks’ gestation, with a delivery rate at more than 34 weeks’ gestation in 90% versus 74% of patients, respectively.¹⁶

Continue to: Steps for interval cerclage and during pregnancy...

Steps for interval cerclage and during pregnancy

Our practice is to place transabdominal cerclage via conventional laparoscopy as an interval procedure when possible. We find no benefit in using robotic assistance.

For an interval procedure, the patient is placed in a dorsal lithotomy position, and we place a 10-mm umbilical port, 2 lateral 5-mm ports, 1 suprapubic 5-mm port, and a uterine manipulator. We use a flexible laparoscope to provide optimal visualization of the pelvis from any angle.

The first step of the surgery involves dissecting the vesicouterine peritoneum in order to move the bladder inferiorly (FIGURE 3A). Uterine arteries are then identified lateral to the cervix as part of this dissection, and a window is created in the inferior aspect of the broad ligament just anterior and lateral to the insertion of the uterosacral ligaments onto the uterus, with care taken to avoid the uterine vessels superiorly (FIGURE 3B). Two 5-mm Mersilene tape sutures are then tied together to create 1 suture with a needle at each end. This is then passed into the abdomen, and 1 needle is passed through the parametrial space at the level of the internal os inferior to the uterine vessels on 1 side of the uterus while the other needle is passed through the parametrial space on the opposite side.

Vidyard Video

CASE Continued: Patient pursues transabdominal cerclage

You explain to your patient that ideally the cerclage should be placed now in a laparoscopic fashion before she becomes pregnant. You then refer her to a local gynecologic surgeon who places many laparoscopic transabdominal cerclages. She undergoes the procedure, becomes pregnant, and after presenting in labor at 35 weeks’ gestation has a cesarean delivery. Her baby is born without any neonatal complications, and the patient is overjoyed with the outcome.

Management during and after pregnancy

Pregnant patients with a transabdominal cerclage are precluded from having a vaginal delivery and must deliver via cesarean. During the antepartum period, patients are managed in the same manner as those who have a transvaginal cerclage. Delivery via cesarean at the onset of regular contractions is recommended to reduce the risk of uterine rupture. In the absence of labor, scheduled cesarean is performed at term.

Our practice is to schedule cesarean delivery at 38 weeks’ gestation, although there are no data or consensus to support a specific gestational age between 37 and 39 weeks. Unlike a transvaginal cerclage, a transabdominal cerclage can be left in place for use in subsequent pregnancies. Data are limited on whether the transabdominal cerclage should be removed in women who no longer desire childbearing and whether there are long-term sequelae if the suture is left in situ.¹⁷

Continue to: Complications and risks of abdominal cerclage...

Complications and risks of abdominal cerclage

As the data suggest and our experience confirms, transabdominal cerclage is highly successful in patients who have failed a history-indicated transvaginal cerclage; however, the transabdominal approach carries a higher surgical risk. Risks include intraoperative hemorrhage, conversion to laparotomy, and a range of rare surgical and obstetric complications, such as bladder injury and PPROM.^13,18

If a patient experiences a fetal loss in the first trimester, a dilation and curettage (D&C) can be performed, with good obstetric outcomes in subsequent pregnancies.¹⁹ If the patient experiences an early-to-mid second-trimester loss, some studies suggest that a dilation and evacuation (D&E) of the uterus can be done with sufficient dilation of the cervix to accommodate up to a 15-mm cannula and Sopher forceps.¹⁹ Laminaria also may be used in this process. However, no data exist regarding success of future pregnancies and transabdominal cerclage integrity after a D&E.²⁰ If the cerclage prevents successful dilation of the cervix, the cerclage must be removed laparoscopically prior to performing the D&E.

In late second-trimester and third-trimester loss, the cerclage must be removed to allow passage of the fetus and placenta prior to a D&E or an induction of labor.²⁰

For patients with PPROM or preterm labor, data are limited regarding management recommendations. However, in these complex cases, we strongly recommend an individualized approach and co-management with maternal-fetal medicine specialists.

CASE Resolved

The cerclage is left in place during the patient’s cesarean delivery, and her postpartum course is uneventful. She continued without complications for the next year, at which time she sees you in the office with plans to have another pregnancy later in the year. You counsel her that her abdominal cerclage will still be effective and that she can get pregnant with expectations of similar outcomes as her previous pregnancy. She thanks you for everything and reports that she hopes to return later in the year for her first prenatal visit. ●

A new meta-analysis has concluded that the benefit of statin therapy in the prevention of ischemic stroke “greatly exceeds” the risk for intracerebral hemorrhage (ICH). The meta-analysis was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Coauthor Abhi Pandhi, MD, the University of Tennessee Health Science Center, Memphis, explained that some previous studies have suggested that statin therapy may be associated with an increased risk for ICH, especially at higher doses. Other studies, however, have failed to confirm this and have shown an increase in cardiovascular events if statins are stopped.

To look further into this issue, Dr. Pandhi and colleagues conducted a meta-analysis of 19 clinical studies involving patients who had a history of cardiovascular or cerebrovascular events and who had been treated with statins. A total of 35,842 patients were included.

Results showed that statin use was not significantly associated with the risk for combined primary and secondary ICH (relative risk, 1.03; 95% confidence interval, 0.85–1.08). But the risk for cerebral ischemia (stroke and transient ischemic attack) was significantly lower in those who received statins (RR, 0.79; 95% CI, 0.61–0.87).

“Overall, we found no effect of statins on the risk of ICH, and benefits on reducing ischemic events are clear,” Dr. Pandhi said.
 

Increased secondary ICH?

However, a sensitivity analysis showed a trend toward a higher risk for secondary ICH among those who were assigned to statin treatment (odds ratio, 1.87; 95% CI, 0.91–3.86).

“While this may suggest an increased risk of secondary ICH, when we look at the big picture, putting all the data together, and given that ischemic events are far more common than ICH, the risk of stopping statins and losing the protection against ischemic events is probably greater than any harm even in patients with underlying risk factors for ICH,” Dr. Pandhi concluded.

Commenting on the study, Michael Szarek, PhD, who has also conducted research in this field, said: “The results of this meta-analysis appear to be consistent with individual randomized trials of statins in patients with cerebrovascular disease that have shown clear benefit in terms of ischemic stroke or TIA and potential harm in terms of hemorrhagic stroke.”

Dr. Szarek is chair and professor in the Department of Epidemiology and Biostatistics at the SUNY Downstate Health Sciences University, New York City.

“However, the much greater frequency of ischemic events, coupled with benefits in coronary and peripheral vascular territories, suggest the risk/benefit of statin treatment remains favorable in this patient population, with the possible exception of patients with a history of hemorrhagic stroke,” he added.

Also commenting on this latest meta-analysis, Pamela Rist, ScD, associate epidemiologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, Boston, who has also authored studies in this area, said the results of this study seem similar to prior results from meta-analyses of clinical trials.

“It will be interesting to see the full manuscript to learn more about the sensitivity analyses they conducted and why they may have observed a nonsignificant increased risk of secondary ICH among some individuals using statins,” Dr. Rist added.

“Based on prior published meta-analyses of statin use and ICH, any potential increase in risk of hemorrhagic stroke is probably outweighed by the reduction in ischemic stroke and other cardiovascular events,” she concluded.

Dr. Pandhi has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Ishfaq A et al. AAN 2020. Abstract S9.010.

A new meta-analysis has concluded that the benefit of statin therapy in the prevention of ischemic stroke “greatly exceeds” the risk for intracerebral hemorrhage (ICH). The meta-analysis was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Coauthor Abhi Pandhi, MD, the University of Tennessee Health Science Center, Memphis, explained that some previous studies have suggested that statin therapy may be associated with an increased risk for ICH, especially at higher doses. Other studies, however, have failed to confirm this and have shown an increase in cardiovascular events if statins are stopped.

To look further into this issue, Dr. Pandhi and colleagues conducted a meta-analysis of 19 clinical studies involving patients who had a history of cardiovascular or cerebrovascular events and who had been treated with statins. A total of 35,842 patients were included.

Results showed that statin use was not significantly associated with the risk for combined primary and secondary ICH (relative risk, 1.03; 95% confidence interval, 0.85–1.08). But the risk for cerebral ischemia (stroke and transient ischemic attack) was significantly lower in those who received statins (RR, 0.79; 95% CI, 0.61–0.87).

“Overall, we found no effect of statins on the risk of ICH, and benefits on reducing ischemic events are clear,” Dr. Pandhi said.
 

Increased secondary ICH?

However, a sensitivity analysis showed a trend toward a higher risk for secondary ICH among those who were assigned to statin treatment (odds ratio, 1.87; 95% CI, 0.91–3.86).

“While this may suggest an increased risk of secondary ICH, when we look at the big picture, putting all the data together, and given that ischemic events are far more common than ICH, the risk of stopping statins and losing the protection against ischemic events is probably greater than any harm even in patients with underlying risk factors for ICH,” Dr. Pandhi concluded.

Commenting on the study, Michael Szarek, PhD, who has also conducted research in this field, said: “The results of this meta-analysis appear to be consistent with individual randomized trials of statins in patients with cerebrovascular disease that have shown clear benefit in terms of ischemic stroke or TIA and potential harm in terms of hemorrhagic stroke.”

Dr. Szarek is chair and professor in the Department of Epidemiology and Biostatistics at the SUNY Downstate Health Sciences University, New York City.

“However, the much greater frequency of ischemic events, coupled with benefits in coronary and peripheral vascular territories, suggest the risk/benefit of statin treatment remains favorable in this patient population, with the possible exception of patients with a history of hemorrhagic stroke,” he added.

Also commenting on this latest meta-analysis, Pamela Rist, ScD, associate epidemiologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, Boston, who has also authored studies in this area, said the results of this study seem similar to prior results from meta-analyses of clinical trials.

“It will be interesting to see the full manuscript to learn more about the sensitivity analyses they conducted and why they may have observed a nonsignificant increased risk of secondary ICH among some individuals using statins,” Dr. Rist added.

“Based on prior published meta-analyses of statin use and ICH, any potential increase in risk of hemorrhagic stroke is probably outweighed by the reduction in ischemic stroke and other cardiovascular events,” she concluded.

Dr. Pandhi has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Ishfaq A et al. AAN 2020. Abstract S9.010.

A new meta-analysis has concluded that the benefit of statin therapy in the prevention of ischemic stroke “greatly exceeds” the risk for intracerebral hemorrhage (ICH). The meta-analysis was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Coauthor Abhi Pandhi, MD, the University of Tennessee Health Science Center, Memphis, explained that some previous studies have suggested that statin therapy may be associated with an increased risk for ICH, especially at higher doses. Other studies, however, have failed to confirm this and have shown an increase in cardiovascular events if statins are stopped.

To look further into this issue, Dr. Pandhi and colleagues conducted a meta-analysis of 19 clinical studies involving patients who had a history of cardiovascular or cerebrovascular events and who had been treated with statins. A total of 35,842 patients were included.

Results showed that statin use was not significantly associated with the risk for combined primary and secondary ICH (relative risk, 1.03; 95% confidence interval, 0.85–1.08). But the risk for cerebral ischemia (stroke and transient ischemic attack) was significantly lower in those who received statins (RR, 0.79; 95% CI, 0.61–0.87).

“Overall, we found no effect of statins on the risk of ICH, and benefits on reducing ischemic events are clear,” Dr. Pandhi said.
 

Increased secondary ICH?

However, a sensitivity analysis showed a trend toward a higher risk for secondary ICH among those who were assigned to statin treatment (odds ratio, 1.87; 95% CI, 0.91–3.86).

“While this may suggest an increased risk of secondary ICH, when we look at the big picture, putting all the data together, and given that ischemic events are far more common than ICH, the risk of stopping statins and losing the protection against ischemic events is probably greater than any harm even in patients with underlying risk factors for ICH,” Dr. Pandhi concluded.

Commenting on the study, Michael Szarek, PhD, who has also conducted research in this field, said: “The results of this meta-analysis appear to be consistent with individual randomized trials of statins in patients with cerebrovascular disease that have shown clear benefit in terms of ischemic stroke or TIA and potential harm in terms of hemorrhagic stroke.”

Dr. Szarek is chair and professor in the Department of Epidemiology and Biostatistics at the SUNY Downstate Health Sciences University, New York City.

“However, the much greater frequency of ischemic events, coupled with benefits in coronary and peripheral vascular territories, suggest the risk/benefit of statin treatment remains favorable in this patient population, with the possible exception of patients with a history of hemorrhagic stroke,” he added.

Also commenting on this latest meta-analysis, Pamela Rist, ScD, associate epidemiologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, Boston, who has also authored studies in this area, said the results of this study seem similar to prior results from meta-analyses of clinical trials.

“It will be interesting to see the full manuscript to learn more about the sensitivity analyses they conducted and why they may have observed a nonsignificant increased risk of secondary ICH among some individuals using statins,” Dr. Rist added.

“Based on prior published meta-analyses of statin use and ICH, any potential increase in risk of hemorrhagic stroke is probably outweighed by the reduction in ischemic stroke and other cardiovascular events,” she concluded.

Dr. Pandhi has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Ishfaq A et al. AAN 2020. Abstract S9.010.