bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut epithelial impairment, microbial translocation and immune system activation in inflammatory bowel disease–associated spondyloarthritis
Authors: Luchetti Michele Maria , Ciccia Francesco , Avellini Chiara , Benfaremo Devis , Rizzo Aroldo , Spadoni Tatiana , Svegliati Silvia , Marzioni Daniela , Santinelli Alfredo , Costantini Andrea , Viola Nadia , Berretta Antonella , Ciferri Monia , Mattioli Belmonte Cima Monica , Mosca Piergiorgio , Benedetti Antonio , Gabrielli Armando 
Published: March 2020

Abstract

Objectives
Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients.

Methods
Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line.

Results
Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells.

Conclusion
SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients.
Preparing for the MD: How Long, at What Cost, and With What Outcomes?
Authors: Gonnella Joseph S. , Callahan Clara A. , Erdmann James B. , Veloski J. Jon , Jafari Niusha , Markle Ronald A. , Hojat Mohammadreza 
Published: March 2020

Purpose
To assess educational and professional outcomes of an accelerated combined bachelor of science–doctor of medicine (BS–MD) program using data collected from 1968 through 2018.

Method
Participants of this longitudinal study included 2,235 students who entered medical school between 1968 and 2014: 1,134 in the accelerated program and 1,101 in the regular curriculum (control group)—matched by year of entrance to medical school, gender, and Medical College Admission Test (MCAT) scores. Outcome measures included performance on medical licensing examinations, academic progress, satisfaction with medical school, educational debt, first-year residency program directors’ ratings on clinical competence, specialty choice, board certification, and faculty appointments.

Results
The authors found no practically important differences between students in the accelerated program and those in the control group on licensing examination performance, academic progress, specialty choice, board certification, and faculty appointments. Accelerated students had lower mean educational debt (P < .01, effect sizes = 0.81 and 0.45 for, respectively, their baccalaureate debt and medical school debt), lower satisfaction with their second year of medical school (P < .01, effect size = 0.21), and lower global satisfaction with their medical school education (P < .01, effect size = 0.35). Residency program directors’ ratings in 6 postgraduate competency areas showed no practically important differences between the students in the accelerated program and those in the control group. The proportion of Asian students was higher among program participants (P < .01, effect size = 0.43).

Conclusions
Students in the accelerated program earned BS and MD degrees at a faster pace and pursued careers that were comparable to students in a matched control who were in a regular MD program. Findings indicate that shortening the length of medical education does not compromise educational and professional outcomes.
Effect of Thyroxine Therapy on Depressive Symptoms Among Women With Subclinical Hypothyroidism
Authors: Costantine Maged M. , Smith Karen , Thom Elizabeth A. , Casey Brian M. , Peaceman Alan M. , Varner Michael W. , Sorokin Yoram , Reddy Uma M. , Wapner Ronald J. , Boggess Kim , Tita Alan T.N. , Rouse Dwight J. , Sibai Baha , Iams Jay D. , Mercer Brian M. , Tolosa Jorge E. , Caritis Steve N. , VanDorsten J. Peter ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, Bethesda, MD
Published: March 2020

OBJECTIVE:
To estimate the effect of antenatal treatment of subclinical hypothyroidism on maternal depressive symptoms.

METHODS:
We conducted an ancillary study to a multicenter trial in women with singleton pregnancies diagnosed with subclinical hypothyroidism randomized to antenatal thyroxine therapy or placebo. Treatment was discontinued at the end of pregnancy. Women with overt thyroid disease, diabetes, autoimmune disease, and those diagnosed with depression were excluded. Participants were assessed for depressive symptoms using the Center for Epidemiological Studies-Depression scale (CES-D) before starting the study drug (between 11 and 20 weeks of gestation), between 32 and 38 weeks of gestation, and at 1 year postpartum. The primary outcome was maternal depressive symptoms score as assessed using the CES-D. Secondary outcome was the percentage of women who scored 16 or higher on the CES-D, as such a score is considered screen-positive for depression.

RESULTS:
Two hundred forty-five (36.2% of parent trial) women with subclinical hypothyroidism were allocated to thyroxine (n=124) or placebo (n=121). Median CES-D scores and the proportion of participants with positive scores were similar at baseline between the two groups. Treatment with thyroxine was not associated with differences in CES-D scores (10 [5–15] vs 10 [5–17]; P=.46) or in odds of screening positive in the third trimester compared with placebo, even after adjusting for baseline scores (24.3% vs 30.1%, adjusted odds ratio 0.63, 95% CI 0.31–1.28, P=.20). At 1 year postpartum, CES-D scores were not different (6 [3–11] vs 6 [3–12]; P=.79), nor was the frequency of screen-positive CES-D scores in the treated compared with the placebo group (9.7% vs 15.8%; P=.19). Treatment with thyroxine during pregnancy was also not associated with differences in odds of screening positive at the postpartum visit compared with placebo even after adjusting for baseline scores. Sensitivity analysis including women who were diagnosed with depression by the postpartum visit did not change the results.

CONCLUSIONS:
This study did not achieve its planned sample size, thus our conclusions may be limited, but in this cohort of pregnant women with subclinical hypothyroidism, antenatal thyroxine replacement did not improve maternal depressive symptoms.
Psychosocial Factors Associated With Postpartum Contraceptive Method Use After an Unintended Birth
Authors: Steinberg Julia R. , Harrison Eowna Young , Boudreaux Michel 
Published: March 2020

OBJECTIVE:
To examine whether depression, intimate partner violence, and other psychosocial stressors were independently associated with effectiveness level of postpartum contraception among women who recently had an unintended birth.

METHODS:
We analyzed cross-sectional data from PRAMS (the Pregnancy Risk Assessment Monitoring System) to identify women who had an unintended birth between 2012 and 2015. The effectiveness level of the contraceptive method was coded into one of five categories based on the postpartum contraceptive method that women were using: none, less effective (withdrawal, rhythm, condoms, or other barrier), moderately effective (pill, patch, ring, or shot), long-acting reversible contraception (LARC; intrauterine devices or implants), and sterilization (female or male sterilization). Multinomial logistic regression was used to examine whether prepregnancy depression or elevated postpartum depressive symptoms, intimate partner violence before or during pregnancy, and number of psychosocial stressors before birth were associated with effectiveness level of method (compared with no method), in models adjusted for sociodemographics, pregnancy context, and postpartum context.

RESULTS:
Complete data were available for 56,445 (88.2%) of the 64,030 eligible women: 24.2% experienced depression; 5.3% experienced intimate partner violence; and 16.8% experienced five or more psychosocial stressors around the time of pregnancy or birth. In adjusted models, experiencing intimate partner violence and more stressors lowered women's relative risk of using sterilization, LARC, moderately effective methods, and less-effective contraceptive methods relative to no method use. Only prepregnancy depression was associated with using sterilization compared with no method use.

CONCLUSIONS:
Experiencing intimate partner violence and having more psychosocial stressors were each independently associated with not using a postpartum contraceptive method. Standardized screening for psychosocial factors during prenatal and postpartum care should be integrated, and practices that encourage the discussion of patients' psychosocial experiences and postpartum contraception use together are warranted.
Hepatitis C Virus Antibody Screening in a Cohort of Pregnant Women
Authors: Prasad Mona , Saade George R. , Sandoval Grecio , Hughes Brenna L. , Reddy Uma M. , Mele Lisa , Salazar Ashley , Varner Michael W. , Gyamfi-Bannerman Cynthia , Thorp John M. , Tita Alan T. N. , Swamy Geeta K. , Chien Edward K. , Casey Brian M. , Peaceman Alan M. , El-Sayed Yasser Y. , Iams Jay D. , Gibbs Ronald S. , Sibai Baha , Wiese Nicholas , Kamili Saleem , Macones George A. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: March 2020

OBJECTIVE:
To describe the prevalence of hepatitis C virus (HCV) antibody, evaluate current risk factors associated with HCV antibody positivity, and identify novel composite risk factors for identification of groups most likely to demonstrate HCV antibody seropositivity in an obstetric population from 2012 to 2015.

METHODS:
The Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network initiated an observational study of mother-to-child transmission of HCV in 2012 that included offering HCV antibody screening to their entire obstetric population. Women presenting for prenatal care before 23 weeks of gestation without a known multifetal gestation were eligible. For each woman who was HCV antibody–positive, two women at similar gestational age who were HCV antibody–negative were identified and included for comparison. Risk factors were evaluated by patient interview and chart review. Women in the case group were identified to have a signal-to-cutoff value of at least 5 on the Abbott ARCHITECT platform. RNA status was evaluated for women in the case group.

RESULTS:
Of 106,842 women screened for the HCV antibody, 254 had positive results. The HCV antibody seroprevalence rate was 2.4 cases per 1,000 women (95% CI 2.1–2.7). One hundred thirty-one women in the case group and 251 women in the control group were included in the case–control analysis. Factors associated with HCV antibody positivity included injection drug use (adjusted odds ratio [aOR] 22.9, 95% CI 8.2–64.0), blood transfusion (aOR 3.7, 95% CI 1.3–10.4), having a partner with HCV (aOR 6.3, 95% CI 1.8–22.6), more than three lifetime sexual partners (aOR 5.3, 95% CI 1.4–19.8), and smoking (aOR 2.4, 95% CI 1.2–4.6). A composite of any of these potential risk factors provided the highest sensitivity for detecting HCV antibody (75/82 cases, 91%).

CONCLUSION:
In this cohort, the seroprevalence of HCV antibody was low, and the current risk factors for HCV screening were not identified. These findings may be useful in defining new strategies for identifying mothers with the HCV antibody and the neonates susceptible to maternal transmission of HCV.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01959321.
Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device
Authors: Turok David K. , Nelson Anita L. , Dart Clint , Schreiber Courtney A. , Peters Kevin , Schreifels Mary Jo , Katz Bob ,   on behalf of the VeraCept Phase 2 Clinical Investigator Group
Published: March 2020

OBJECTIVE:
To assess in parous and nulliparous women, the efficacy, safety, and tolerability of a new, low-dose copper (175 mm2) intrauterine contraceptive with a flexible nitinol frame provided in a preloaded applicator.

METHODS:
Institutional review boards at 12 U.S. sites approved this commercially funded project. Patients met standard inclusion and exclusion criteria for a copper-based intrauterine device (IUD), generally consistent with the Centers for Disease Control and Prevention's U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. Intrauterine device placement occurred at any day in the eligible patient's menstrual cycle after assuring she was not pregnant. The primary outcome measure assessed efficacy (measured by the Pearl Index) in this 1-year study with a 2-year extension. Secondary outcomes included placement success, ease of placement, safety as measured by adverse events, and tolerability assessed by discontinuation rate and bleeding and spotting patterns.

RESULTS:
A total of 286 women provided 5,640 cycles evaluable for pregnancy. Patients averaged 27.1 years of age. Nulliparous women represented 60.8% of the patients. Over 36 months of observation, we identified two pregnancies (Pearl Index 0.46 [95% CI 0.06–1.67]) and 10 serious adverse events; none were study-related. Successful placement occurred in 283 participants (99.0%). Median (range) continuation times were 2.7 years (0–3.4). We identified five expulsions (1.8%), zero uterine perforations, and one report of pelvic inflammatory disease. Adverse events prompted 30 women (10.6%) to discontinue early in the first year of use with 23 (8.1%) discontinuing for issues of bleeding, pain, or both. Altogether, 107 (37.8%) completed 36 months of device use. Mean bleeding days per cycle decreased from 7.6 in cycle 1 to 5.2 in cycle 13.

CONCLUSION:
The novel, low-dose copper and nitinol IUD demonstrated high efficacy and safety in this phase 2 U.S. Food and Drug Administration trial and warrants further expanded study in a phase 3 clinical trial.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02446821.

FUNDING SOURCE:
Sebela Pharmaceuticals, Inc.
Machine Learning and Statistical Models to Predict Postpartum Hemorrhage
Authors: Venkatesh Kartik K. , Strauss Robert A. , Grotegut Chad A. , Heine R. Philip , Chescheir Nancy C. , Stringer Jeffrey S. A. , Stamilio David M. , Menard Katherine M. , Jelovsek J. Eric 
Published: March 2020

OBJECTIVE:To predict a woman's risk of postpartum hemorrhage at labor admission using machine learning and statistical models.METHODS:Predictive models were constructed and compared using data from 10 of 12 sites in the U.S. Consortium for Safe Labor Study (2002–2008) that consistently reported estimated blood loss at delivery. The outcome was postpartum hemorrhage, defined as an estimated blood loss at least 1,000 mL. Fifty-five candidate risk factors routinely available on labor admission were considered. We used logistic regression with and without lasso regularization (lasso regression) as the two statistical models, and random forest and extreme gradient boosting as the two machine learning models to predict postpartum hemorrhage. Model performance was measured by C statistics (ie, concordance index), calibration, and decision curves. Models were constructed from the first phase (2002–2006) and externally validated (ie, temporally) in the second phase (2007–2008). Further validation was performed combining both temporal and site-specific validation.RESULTS:Of the 152,279 assessed births, 7,279 (4.8%, 95% CI 4.7–4.9) had postpartum hemorrhage. All models had good-to-excellent discrimination. The extreme gradient boosting model had the best discriminative ability to predict postpartum hemorrhage (C statistic: 0.93; 95% CI 0.92–0.93), followed by random forest (C statistic: 0.92; 95% CI 0.91–0.92). The lasso regression model (C statistic: 0.87; 95% CI 0.86–0.88) and logistic regression (C statistic: 0.87; 95% CI 0.86–0.87) had lower-but-good discriminative ability. The above results held with validation across both time and sites. Decision curve analysis demonstrated that, although all models provided superior net benefit when clinical decision thresholds were between 0% and 80% predicted risk, the extreme gradient boosting model provided the greatest net benefit.CONCLUSION:Postpartum hemorrhage on labor admission can be predicted with excellent discriminative ability using machine learning and statistical models. Further clinical application is needed, which may assist health care providers to be prepared and triage at-risk women.
Cochrane Review Summaries—April 2020
Authors: Kumar Nimisha , Jahanfar Shayesteh , Haas David M. 
Published: March 2020

This feature highlights recently published Cochrane Reviews of interest to the readers of Obstetrics & Gynecology. This month, we focus on two obstetric reviews on umbilical cord clamping and induction of labor and one gynecology review on epithelial ovarian cancer. The brief summaries are published below and the complete references, along with a hyperlink, are listed in Box 1

Box 1. Abstracts Discussed in This Summary

Rabe H, Gyte GML, Díaz-Rossello JL, Duley L. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. The Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No.: CD003248. Available at: https://doi.org/10.1002/14651858.CD003248.pub4
de Vaan MDT, ten Eikelder MLG, Jozwiak M, Palmer KR, Davies-Tuck M, Bloemenkamp KWM, et al. Mechanical methods for induction of labour. The Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD001233. Available at: https://doi.org/10.1002/14651858.CD001233.pub3.Coleridge SL, Bryant A, Lyons TJ, Goodall RJ, Kehoe S, Morrison J. Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer. The Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD005343. Available at: https://doi.org/10.1002/14651858.CD005343.pub4.
Bariatric Surgery Population at Significantly Increased Risk of Spinal Disorders and Surgical Intervention Compared With Morbidly Obese Patients
Authors: Passias Peter G. , Horn Samantha R. , Ihejirika Yael U. , Vasques-Montes Dennis , Segreto Frank A. , Bortz Cole A. , Brown Avery E. , Pierce Katherine E. , Alas Haddy , Poorman Gregory W. , Jalai Cyrus M. , Wang Charles , Buza John A. , Steinmetz Leah , Varlotta Christopher G. , Vira Shaleen , Diebo Bassel G. , Hassanzadeh Hamid , Lafage Renaud , Lafage Virginie 
Published: March 2020

Introduction:
Obesity is associated with acceleration of musculoskeletal degenerative diseases and functional impairment secondary to spinal disorders. Bariatric surgery (BS) is an increasingly common treatment for severe obesity but can affect bone and mineral metabolism. The effect of BS on degenerative spinal disorders is yet to be fully described. The aim of our study was to analyze changes in bariatric patients’ risk for spinal degenerative diseases and spinal surgery.

Methods:
Retrospective analysis of the prospectively collected New York State Inpatient Database (NYSID) years (2004–2013) using patient linkage codes. The incidence of degenerative spinal diagnoses and spinal surgery was queried using International Classification of Diseases, Ninth Revision (ICD)-9 codes for morbidly obese patients (ICD-9 278.01) with and without a history of BS. The incidence of degenerative spinal diagnoses and spinal surgery was determined using χ2 tests for independence. Logistic testing controlled for age, sex, and comorbidity burden.

Results:
A total of 18,176 patients were identified in the NYSID database with a history of BS and 146,252 patients were identified as morbidly obese without a history of BS. BS patients have a significantly higher rate of spinal diagnoses than morbidly obese patients without BS (19.3% vs. 8.1%, P<0.001). Bariatric patients were more likely to have spinal diagnoses and procedures than nonbariatric obese patients (P<0.001). This was mostly observed in lumbar spinal stenosis (5.0%), cervical disk herniation (3.3%), lumbar disk degeneration (3.4%), lumbar spondylolisthesis (2.9%), lumbar spondylosis (1.9%), and cervical spondylosis with myelopathy (2.0%). Spine procedure rates are higher for bariatric patients than nonbariatric overall (25.6% vs. 2.3, P<0.001) and for fusions and decompressions (P<0.001). When controlling for age, sex, and comorbidities (and diagnosis rate with regards to procedure rates), these results persist, with BS patients having a higher likelihood of spinal diagnoses and procedures. In addition, bariatric patients had a lower comorbidity burden than morbidly obese patients without a history of BS.

Conclusions:
Morbidly obese BS patients have a dramatically higher incidence of spinal diagnoses and procedures, relative to morbidly obese patients without BS. Further study is necessary to determine if there is a pathophysiological mechanism underlying this higher risk of spinal disease and intervention in bariatric patients, and the effect of BS on these rates following treatment.

Level of Evidence:
Level III.