Postthrombotic Syndrome and Chronic Pulmonary Embolism after Obstetric Venous Thromboembolism.

OBJECTIVE: While the majority of venous thromboembolism (VTE) during pregnancy events resolve with anticoagulation, long-term complications may occur including (1) postthrombotic syndrome and (2) chronic pulmonary embolism. The objective of this study was to determine risk of these two complications. STUDY DESIGN: A retrospective cohort study using the MarketScan databases was performed on deliveries from 2008 to 2014. We identified women aged 15 to 54 years diagnosed with acute VTE during pregnancy, the delivery hospitalization, or ≤60 days postpartum who received at least one prescription postpartum for anticoagulants. Risks of (1) chronic PE and (2) postthrombotic syndrome were evaluated for women at 6, 12, 24, and 60 months after delivery hospitalization through 2017 via the International Classification of Diseases, 9th/10th Revision, Clinical Modification codes. RESULTS: Of 4,267 of 4,128,900 pregnancies complicated by VTE, the majority had DVT alone (61.8%, n = 2,637), while 25.8% had PE alone (n = 1,103) and 12.4% (n = 527) had both DVT and PE. Of the entire cohort, 3,328 retained insurance coverage at 6 months, 2,823 at 12 months, 2,161 at 24 months, and 831 at 60 months. Restricted to DVT, risk of postthrombotic syndrome was 0.7% at 6 months (n = 17), 1.1% at 12 months (n = 22), 1.7% at 24 months (n = 26), and 2.7% at 60 months (n = 16). Among women with PE diagnoses, the risk of chronic PE was 2.4% at 6 months (n = 30), 3.3% at 12 months (n = 36), 4.2% at 24 months (n = 36), and 7.2% at 60 months (n = 24). CONCLUSION: In comparison to the general population, the risk of postthrombotic syndrome was lower. In comparison, the risk of chronic PE was similar to the estimates in the general population at comparable time points after PE events. For women with obstetric PE, it may be appropriate to be vigilant for findings and symptoms associated with chronic PE. KEY POINTS: · Risk of postthrombotic syndrome after obstetric deep vein thrombosis is low.. · Risk of chronic pulmonary embolism may approximate that in the general population.. · Overall risk of chronic complications after obstetric VTE was relatively low..

Prophylactic endovascular internal iliac balloon placement during cesarean hysterectomy for placenta accreta spectrum.

BACKGROUND: The utility of prophylactic endovascular internal iliac balloon placement in the surgical management of placenta accreta spectrum is debated. OBJECTIVE: In this study, we review outcomes of surgical management of placenta accreta spectrum with and without prophylactic endovascular internal iliac balloon catheter use at a single institution. STUDY DESIGN: This is a retrospective cohort study of consecutive viable singleton pregnancies with a confirmed pathologic diagnosis of placenta accreta spectrum undergoing scheduled delivery from October 2018 through November 2020. In the T1 period (October 2018-August 2019), prophylactic endovascular internal iliac balloon catheters were placed in the operating room before the start of surgery. Balloons were inflated after neonatal delivery and deflated after hysterectomy completion. In the T2 period (September 2019-November 2020), endovascular catheters were not used. In both time periods, all surgeries were performed by a dedicated multidisciplinary team using a standardized surgical approach. The outcomes compared included the estimated blood loss, anesthesia duration, operating room time, surgical duration, and a composite of surgical complications. Comparisons were made using the Wilcoxon rank-sum test and the Fisher exact test. RESULTS: A total of 30 patients were included in the study (T1=10; T2=20). The proportion of patients with placenta increta or percreta was 80% in both groups, as defined by surgical pathology. The median estimated blood loss was 875 mL in T1 and 1000 mL in T2 (P=.84). The proportion of patients requiring any packed red blood cell transfusion was 60% in T1 and 40% in T2 (P=.44). The proportion of patients requiring >4 units of packed red blood cells was 20% in T1 and 5% in T2 (P=.25). Surgical complications were observed in 1 patient in each group. Median operative anesthesia duration was 497 minutes in T1 and 296 minutes in T2 (P<.001). Median duration of operating room time was 498 minutes in T1 and 205 minutes in T2 (P<.001). Median surgical duration was 227 minutes in T1 and 182 minutes in T2 (P<.05). The median duration of time for prophylactic balloon catheter placement was 74 minutes (range, 46-109 minutes). The median postoperative length of stay was similar in both groups (6 days in T1 and 5.5 days in T2; P=.36). CONCLUSION: The use of prophylactic endovascular internal iliac balloon catheters was not associated with decreased blood loss, packed red blood cell transfusion, or surgical complications. Catheter use was associated with increased duration of anesthesia, operating room time, and surgical time.

Postpartum cardiac readmissions among women without a cardiac diagnosis at delivery.

OBJECTIVE: To determine risk for cardiac readmissions among women without cardiac diagnoses present at delivery up to 9 months after delivery hospitalization discharge. METHODS: Delivery hospitalizations without cardiac diagnoses were identified from the 2010-2014 Nationwide Readmissions Database and linked with subsequent cardiac hospitalizations over the following 9 months. The temporality of new-onset cardiac hospitalizations was calculated for each 30-day interval from delivery discharge up to 9 months postpartum. Multivariable log-linear regression models were fit to identify risk factors for cardiac readmissions adjusting for patient, medical, and obstetrical factors with adjusted risk ratios as measures of effect (aRR). RESULTS: Among 4.4 million delivery hospitalizations without a cardiac diagnosis, readmission for a cardiac condition within 9 months occurred in 26.8 per 10,000 women. Almost half of readmissions (45.9%) occurred within the first 30 days after delivery discharge with subsequent hospitalizations broadly distributed over the remaining 8 months. Factors such as hypertensive diseases of pregnancy (aRR 2.19, 95% CI 2.09, 2.30), severe maternal morbidity at delivery (aRR 2.06, 95% CI 1.79, 2.37), chronic hypertension (aRR 2.52, 95% CI 2.31, 2.74), lupus (aRR 4.62, 95% CI 3.82, 5.60), and venous thromboembolism during delivery (aRR 3.72, 95% CI 2.75, 5.02) were all associated with increased risk for 9-month postpartum cardiac admissions as were Medicaid (aRR 1.57, 95% CI 1.51, 1.64) and Medicare insurance (aRR 3.06, 95% CI 2.70, 3.46) compared to commercial insurance and maternal ages 35-39 and 40-54 years (aRR 1.24, 95% CI 1.17, 1.32, aRR 1.74, 95% CI 1.60, 1.90, respectively) compared to maternal age 25-29 years. CONCLUSIONS: Among women without a cardiac diagnosis at delivery, multiple medical factors and obstetrical complications are associated with development of new cardiac disease requiring readmission in the postpartum period. Given that pregnancy complications and comorbidities may be associated with intermediate-term health outcomes, these findings support the importance of continued health care access after six weeks postpartum.

Receipt of anticoagulation after venous thromboembolism diagnoses during delivery hospitalizations.

INTRODUCTION: Obstetric venous thromboembolism (VTE) is a leading cause of maternal mortality. While hospital discharge data provide a readily accessible means of studying this relatively rare outcome, diagnosis codes are of limited validity. Prior studies have demonstrated that VTE billing codes may be subject to misclassification and false positives and overestimate obstetric VTE risk. Given the public health significance of accurately estimating obstetric VTE, the purpose of this study was to determine to what degree patients received anticoagulants after discharge from a delivery hospitalization associated with an acute VTE diagnosis as pharmacy claims may more accurately assess the incidence of obstetric VTE. STUDY DESIGN: A retrospective cohort study using the MarketScan database was performed using 2008-2014 claims data. We identified women 15-54 years of age diagnosed with acute VTE during a delivery hospitalization. We determined the proportion of women with VTE that received anticoagulants within 60 days of delivery discharge. Only women with ≥60 days of pharmacy benefits after discharge were included. Receipt of low molecular weight and unfractionated heparin, warfarin, and Xa inhibitors was ascertained. Receipt of anticoagulants was analyzed individually based on diagnoses for deep vein thrombosis (DVT), pulmonary embolism (PE), or both. The Chi-square test was performed for categorical comparisons. RESULTS: Of 2,664,951 delivery hospitalizations, 2112 women had a diagnosis of VTE (0.08%) including 236 women with PE alone, 1760 women with DVT alone, and 116 women with both DVT and PE. Of these women, 51.3% (95% CI 49.2-53.4%) received an anticoagulant including 49.5% of women with DVT (95% CI 47.2-51.8%), 50.0% of women with PE (95% CI 43.7-56.3%), and 81.9% of women with both DVT and PE (95% CI 73.9-87.9%). CONCLUSION: This analysis of pharmacy claims found that estimates for the proportion of deliveries with acute VTE diagnoses that subsequently received anticoagulants was similar to chart-confirmed VTE, albeit in a large population. In addition to previous studies comparing database claims to chart review that showed that the prevalence of VTE was grossly overestimated, these findings support that the proportion of cases with VTE during delivery hospitalization may be approximately half that ascertained with billing codes.

Receipt of Proton-Pump Inhibitors during Pregnancy and Risk for Preeclampsia.

OBJECTIVE: This study aimed to determine whether receiving a proton-pump inhibitor (PPI) prescription during pregnancy was associated with decreased risk for preeclampsia. STUDY DESIGN: The Truven Health MarketScan database was used to determine whether receiving a PPI prescription was associated with risk for preeclampsia. Risk for preeclampsia was evaluated based on the presence or absence of receiving a PPI prescription (1) any time during pregnancy, and 2) individually during the 1st, 2nd, and 3rd trimesters. In addition to evaluating risk for all preeclampsia, severe preeclampsia and preterm severe preeclampsia were evaluated. Adjusted models including risk factors such as chronic hypertension, maternal age, multiple gestation, and diabetes were performed with adjusted risk ratios (aRR) with 95% confidence intervals [CIs] as measures of effect. RESULTS: A total of 2,755,885 women were included in the analysis of whom 69,249 were prescribed a PPI during pregnancy (2.5%). In adjusted models, receiving a PPI prescription anytime during pregnancy (aRR 1.28, 95% CI 1.24-1.32), the 1st trimester (aRR 1.12, 95% CI 1.04-1.22), the 2nd trimester (aRR 1.20, 95% CI 1.15-1.26), and the 3rd trimester (aRR 1.41, 95% CI 1.35-1.47) were all associated with increased risk for preeclampsia. Risk for severe preeclampsia was also significantly increased with receiving a PPI prescription anytime during pregnancy (aRR 1.21, 95% CI 1.15-1.27), during the 2nd trimester (aRR 1.14, 95% CI 1.06-1.23), and during the 3rd trimester (aRR 1.33, 95% CI 1.24-1.43), but not the first trimester (aRR 1.04, 95% CI 0.92-1.19). Evaluating the risk for preterm severe preeclampsia, adjusted risk was significantly increased with receiving a PPI prescription in the second trimester (aRR 1.35, 95% CI 1.21-1.52) but not the first trimester (aRR 1.06, 95% CI 0.86-1.32). CONCLUSION: In this analysis of payer data, receiving a PPI prescription during pregnancy was not associated with decreased risk for preeclampsia. Further empiric research is required to determine whether an effect may be present. KEY POINTS: · Proton pump inhibitors were not associated with decreased risk for preeclampsia.. · Proton pump inhibitors were not associated with decreased risk for severe preterm preeclampsia.. · Proton pump inhibitors are commonly prescribed during pregnancy..

Preparation and redeployment of house staff during a pandemic.

The COVID-19 pandemic created unique issues for house staff physicians. Gaps in surgical experience due to canceled cases, a focus on obstetrics over gynecology during the spring months when many senior residents and fellows are completing their case requirements and the stress of working with patients infected with a highly communicable disease all contributed to an unprecedented challenge facing residency and fellowship programs. Our objective is to describe how the Obstetrics and Gynecology residency and fellowship programs at Columbia University Irving Medical Center adapted to their changing landscape, redeployed their residents and fellows while assuring ongoing trainee education, wellness and scholarship during the peak of the pandemic.

Primed for a pandemic: Implementation of telehealth outpatient monitoring for women with mild COVID-19.

Close observation and rapid escalation of care is essential for obstetric patients with COVID-19. The pandemic forced widespread conversion of in-person to virtual care delivery and telehealth was primed to enable outpatient surveillance of infected patients. We describe the experience and lessons learned while designing and implementing a virtual telemonitoring COVID-19 clinic for obstetric patients. All patients with suspected for confirmed COVID-19 were referred and enrolled. Telehealth visits were conducted every 24 to 72 hours based on the severity of symptoms and care was escalated to in person when necessary. The outcome of the majority (96.1%) of telehealth visits was to continue outpatient management. With regard to escalation of care, 25 patients (26.6%) presented for in person evaluation and five patients (5.3%) required inpatient admission. A virtual telemonitoring clinic for obstetric patients with mild COVID-19 offers an effective surveillance strategy as it allows for close monitoring, direct connection to in person evaluation, minimization of patient and provider exposure, and scalability.

Building an obstetric intensive care unit during the COVID-19 pandemic at a tertiary hospital and selected maternal-fetal and delivery considerations.

During the novel Coronavirus Disease 2019 pandemic, New York City became an international epicenter for this highly infectious respiratory virus. In anticipation of the unfortunate reality of community spread and high disease burden, the Anesthesia and Obstetrics and Gynecology departments at NewYork-Presbyterian / Columbia University Irving Medical Center, an academic hospital system in Manhattan, created an Obstetric Intensive Care Unit on Labor and Delivery to defray volume from the hospital's preexisting intensive care units. Its purpose was threefold: (1) to accommodate the anticipated influx of critically ill pregnant and postpartum patients due to novel coronavirus, (2) to care for critically ill obstetric patients who would previously have been transferred to a non-obstetric intensive care unit, and (3) to continue caring for our usual census of pregnant and postpartum patients, who are novel Coronavirus negative and require a higher level of care. In this chapter, we share key operational details for the conversion of a non-intensive care space into an obstetric intensive care unit, with an emphasis on the infrastructure, personnel and workflow, as well as the goals for maternal and fetal monitoring.

The clinical course of COVID in pregnancy.

The 2019 novel coronavirus disease (COVID-19) pandemic poses unique challenges to the medical community as the optimal treatment has not been determined and is often at the discretion of institutional guidelines. Pregnancy has previously been described as a high-risk state in the context of infectious diseases, given a particular susceptibility to pathogens and adverse outcomes. Although ongoing studies have provided insight on the course of this disease in the adult population, the implications of COVID-19 on pregnancy remains an understudied area. The objective of this study is to review the literature and describe clinical presentations among pregnant women afflicted with COVID-19.

Trends in venous thromboembolism prophylaxis in gynecologic surgery for benign and malignant indications.

PURPOSE: Venous thromboembolism (VTE) is a leading cause of perioperative morbidity and mortality. We analyzed the trends in use of VTE prophylaxis over time in women undergoing hysterectomy for both benign and malignant indications. METHODS: The Premier Database was used to identify women who underwent hysterectomy from 2011 to 2017. Women were stratified by indication for surgery (benign or malignant) and route of hysterectomy. VTE prophylaxis was classified as none, mechanical, pharmacologic, or combination (mechanical and pharmacologic). Trends in use of prophylaxis over time were analyzed. Multivariate models were developed to examine predictors of use of prophylaxis. RESULTS: Among 920,477 patients identified, 579,824 (63.0%) received VTE prophylaxis, including 15.4% who received pharmacologic, 34.5% who received mechanical, and 13.1% who received combination prophylaxis. Overall use of prophylaxis declined annually from 68.1% in 2011 to 56.7% in 2017 (P < 0.001). Among patients with cancer, the use of prophylaxis declined from 84.5% in 2011 to 78.6% in 2017 (P < 0.001). A similar trend was noted among women with benign conditions, with rates of prophylaxis declining from 66.2 to 53.3% (P < 0.001). Additionally, use of prophylaxis declined for patients undergoing MIS hysterectomy from 65.4% in 2011 to 53.3% in 2017, and from 73.1 to 66.7% in patients who underwent abdominal hysterectomy. Among patients with cancer, rates of pharmacologic and combined prophylaxis was 70.9% in 2011 and 69.7% in 2017. However, among women with benign conditions, the rates of pharmacologic and combined prophylaxis rose from 19.4% in 2011 to 25.6% in 2017 (P < 0.001). Despite these changes in prophylaxis rates and methods, there was no significant change in the rate of VTE between 2011 and 2017 (P = 0.06). CONCLUSION: Despite the lack of change in guidelines for VTE prophylaxis in gynecologic surgery, the overall rates of prophylaxis decreased over time independent of the indication or route of surgery. The rates of thromboembolic events did not significantly increase in response to the decreased use of VTE prophylaxis.

Chemotherapy, Radiation, or Combination Therapy for Stage III Uterine Cancer.

OBJECTIVE: To compare the outcomes of women with stage III uterine cancer treated with chemotherapy alone, external beam radiation alone, and combination chemotherapy and radiation. METHODS: The National Cancer Database was used to identify women with stage III endometrioid, serous, and clear cell uterine cancer treated with either chemotherapy (with or without vaginal brachytherapy) alone, external beam radiation (with or without brachytherapy), or combination chemotherapy and external beam radiation (with or without vaginal brachytherapy) from 2004 to 2015. Survival was estimated using Cox proportional hazards models and adjusted survival curves after propensity score analysis using inverse probability of treatment weighting to balance the clinical and demographic characteristics between the cohorts. RESULTS: Of the 20,873 patients identified, 9,456 (45.3%) received chemotherapy alone, 2,417 (11.6%) were treated with radiation alone, and 9,000 (43.1%) received chemotherapy in combination with external beam radiation. Use of combination therapy was 33.0% in 2004, and then rose to 50.5% in 2015. The mortality of the cohort was 33.1% and median survival was 115 months. Within the cohort, combination therapy was associated with a 23% reduction in mortality (hazard ratio [HR]=0.77; 95% CI 0.73-0.80) compared with chemotherapy alone. Similar findings of decreased mortality were noted in subgroup analyses for both stage IIIA (HR=0.81; 95% CI 0.68-0.98) and stage IIIC (HR=0.79; 95% CI 0.75-0.84) tumors. Similarly, when compared with radiation alone, combination therapy was accompanied by a 19% decrease in mortality (HR=0.81; 95% CI 0.73-0.89). Combination chemoradiation was associated with decreased mortality across all of the histologic subtypes. CONCLUSION: Among women with stage III uterine cancer, combination chemotherapy and external beam radiation is associated with decreased mortality compared with chemotherapy or radiation alone.

The Effect of Smoking Status on Successful Arthrodesis After Lumbar Instrumentation Supplemented with rhBMP-2.

OBJECTIVE: The primary objective of this study is to examine the effects smoking status on rhBMP-2 supplementation in spinal fusion constructs. METHODS: Patient records were reviewed retrospectively for a consecutive set of patients who underwent first-time posterolateral, instrumented fusion of the lumbar spine for degenerative spinal disease. All operations included arthrodesis supplementation with rhBMP-2. All patients were followed for at least 2 years. The primary endpoint of this study was reoperation for pseudarthrosis, instrumentation failure, or adjacent segment disease. After a rigorous sensitivity analysis, the measure of association was calculated with a multivariable logistic regression controlling for smoking, age, and number of spinal levels fused. RESULTS: Of the 110 patients in the study population, 82 (74.6%) were nonsmokers and 28 (25.5%) were smokers. Among perioperative predictors, smokers were younger in age (53.9 ± 9.6 vs. 61.1 ± 13.1 years; P = 0.008) and had shorter length of inpatient hospital stay (4.1 ± 1.8 vs. 5.3 ± 3.0; P = 0.039). After a mean follow-up of 59 months, the 32% incidence of reoperation for pseudarthrosis, instrumentation failure, or adjacent segment among smokers was statistically significantly higher than the 13.4% incidence in nonsmokers (P = 0.027). Following multivariable logistic regression, the odds of reoperation among smokers was 4.75-fold higher than for nonsmokers (P = 0.009; 95% confidence interval, 1.48-15.24). CONCLUSIONS: While rhBMP-2 supplements arthrodesis of instrumented lumbar fusion constructs, smoking status ascertains the strongest predictor of reoperation for pseudarthrosis, instrumentation failure, and adjacent segment.

rhBMP-2 protects against reoperation for pseudoarthrosis and/or instrumentation failure: A matched case-control study of 448 patients.

The objective of this independent study is to determine the impact of recombinant human bone morphogenetic protein 2 (rhBMP-2) on reoperation for pseudarthrosis and/or instrumentation failure. A nested case-control study of first-time posterolateral, instrumented fusion of the lumbar spine for degenerative spinal disease was undertaken. Cases of reoperation for pseudoarthrosis and/or instrumentation failure were assigned to controls, who did not experience the primary outcome measure at the time of reoperation. Cases and controls were matched on number of interspaces fused and inclusion of interbody. Predictors of reoperation for pseudoarthrosis and/or instrumentation failure were assessed with a conditional logistical regression controlling for rhBMP-2, age, obesity, and smoking. Of the 448 patients, 155 cases of reoperation for pseudoarthrosis and/or instrumentation were matched with 293 controls. Twenty-six percent of first-time surgeries included rhBMP-2, which was statistically more commonly used in the control cohort (33.11%) versus the case cohort (12.90%) (Unadjusted odds ratio [ORunadj]=0.28) (95% confidence interval [CI]: 0.16-0.49). Following a multivariate analysis controlling for age, obesity, and smoking, the rhBMP-2 recipients incurred a 73% lower odds of reoperation for pseudoarthrosis and/or instrumentation failure (95% CI, 0.15-0.48). Neither sarcomatous nor osseous neoplasm was detected in the study population. Mean follow up did not differ between the cases (81.57±standard deviation [SD] 4.98months) versus controls (74.75±2.49month) (ORunadj=1.01) (95% CI: 1.00-1.01). rhBMP-2 in lumbar fusion constructs protects against reoperation for pseudoarthrosis and/or instrumentation failure. However, the decision to include fusion supplements should be weighted between surgical determinants and clinical outcomes.

Preoperative motor strength and time to surgery are the most important predictors of improvement in foot drop due to degenerative lumbar disease.

OBJECTIVE: Palsy of dorsiflexion, or foot drop, may be due to degenerative lumbar disease and amenable to posterior spinal decompression. The objective of this study is to measure prognostic factors of and time to foot drop improvement after posterior lumbar decompression. METHODS: We retrospectively reviewed 71 patients undergoing first-time, posterior lumbar decompression for foot drop due to degenerative spinal disease. Patient sex, age, comorbidities (Charlson Comorbidity Index), preoperative anterior tibialis strength (manual muscle testing, MMT), and duration of foot drop were ascertained from clinical notes. Prognostic factors affecting foot drop improvement were calculated with a discrete time proportional hazards model, in which follow-up times and outcome measures were binned into six time intervals: 1 week, 6 weeks, 3 months, 6 months, 1 year, and ≥ 1 year. RESULTS: Of the 71 patients, the mean age was 54.6 ± 16.0 years, and 66.2% (n=47) were males. The mean Charlson Comorbidity Index was 2.42. During a mean follow-up of 30.4 months, dorsiflexion function improved postoperatively in 73.2% (n=52) of patients. The median time to surgery from onset of foot drop was within 6 weeks, and the median preoperative MMT strength of patients with foot drop improvement was 3. Following a discrete-time proportional hazards model, duration of anterior tibialis palsy (HR=0.67, P=0.004) and preoperative muscle strength (HR=1.10, P=0.010) were significant predictors of foot drop improvement. Following an adjusted Kaplan-Meier analysis, the median time to foot drop improvement was within 6 weeks of surgical intervention. CONCLUSIONS: Preoperative muscle strength and palsy duration were statistically significant predictors of foot drop improvement. Furthermore, the median time to improvement was 6 weeks.

Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism.

We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder.