SAGES guidelines for the use of laparoscopy during pregnancy.

BACKGROUND: When pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD). METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Expert opinion was utilized when the available evidence was deemed insufficient. RESULTS: The expert panel agreed on ten recommendations addressing the management of appendicitis, biliary disease, and IBD during pregnancy. CONCLUSIONS: Conditional recommendations were made in favor of appendectomy over nonoperative treatment of appendicitis, laparoscopic appendectomy over open appendectomy, and laparoscopic cholecystectomy over nonoperative treatment of biliary disease and acute cholecystitis specifically. Based on expert opinion, the panel also suggested either operative or nonoperative treatment of biliary diseases other than acute cholecystitis in the third trimester, endoscopic retrograde cholangiopancreatography rather than common bile duct exploration for symptomatic choledocholithiasis, applying the same criteria for emergent surgical intervention in pregnant and non-pregnant IBD patients, utilizing an open rather than minimally invasive approach for pregnant patients requiring emergent surgical treatment of IBD, and managing pregnant patients with active IBD flares in a multidisciplinary fashion at centers with IBD expertise.

The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC): International consensus statement and user guide.

Effective physical activity messaging plays an important role in the pathway towards changing physical activity behaviour at a population level. The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC) are outputs from a recent modified Delphi study. This sought consensus from an international expert panel on how to aid the creation and evaluation of physical activity messages. In this paper, we (1) present an overview of the various concepts within the PAMF and PAMC, (2) discuss in detail how the PAMF and PAMC can be used to create physical activity messages, plan evaluation of messages, and aid understanding and categorisation of existing messages, and (3) highlight areas for future development and research. If adopted, we propose that the PAMF and PAMC could improve physical activity messaging practice by encouraging evidence-based and target population-focused messages with clearly stated aims and consideration of potential working pathways. They could also enhance the physical activity messaging research base by harmonising key messaging terminologies, improving quality of reporting, and aiding collation and synthesis of the evidence.

The compliance with a patient-safety bundle for management of placenta accreta spectrum†.

OBJECTIVE: Our objective was to evaluate the compliance with a patient-safety bundle for placenta accreta spectrum (PAS) by comparing the implementation of the components of the patient-safety bundle in the pre- and post-protocol time periods as a quality improvement project. STUDY DESIGN: This is a before and after retrospective cohort study as a quality improvement report examining compliance with a multidisciplinary delivery approach for patients with suspected PAS between 2007 and 2018. This bundle involved a multidisciplinary approach with maternal-fetal medicine, gynecologic oncology, intervention radiology, obstetric anesthesia, neonatology, and blood bank. The primary outcome was incorporation of all six of the components of the bundle into a PAS procedure: (1) betamethasone, (2) gynecologic oncology intraoperative consult, (3) preoperative balloon catheters, (4) cell salvage technology in the operating room, (5) vertical skin incision, and (6) fundal or high transverse hysterotomy. Demographic, delivery, and patient outcome data were also collected. RESULTS: There were 39 patients included in the study, 17 were pre-protocol and 22 were post-protocol. Patients were more likely to have a PAS suspected in the antenatal period during post protocol period (23.5 versus 90.9%, p < .0001), as well as having a placenta previa (35.3 versus 81.8%, p = .003), and receive betamethasone prior to delivery (23.5 versus 86.3%, p < .0001). Patients were delivered at an earlier gestational age in post protocol period (36.8 ± 2.52 versus 33.87 ± 2.4, p = .001). The primary outcome, adherence to all components of the patient-safety bundle, was more likely to occur in the post protocol period (0 versus 40.9%, p < .0001). Maternal and postoperative outcomes were not significantly different between groups. CONCLUSIONS: We have successfully implemented a patient-safety bundle for PAS and have standardized the execution of multidisciplinary management for PAS at our institution.

Cannabinoid Receptor Interacting Protein 1a (CRIP1a) in Health and Disease.

Endocannabinoid signaling depends upon the CB1 and CB2 cannabinoid receptors, their endogenous ligands anandamide and 2-arachidonoylglycerol, and intracellular proteins that mediate responses via the C-terminal and other intracellular receptor domains. The CB1 receptor regulates and is regulated by associated G proteins predominantly of the Gi/o subtypes, ß-arrestins 1 and 2, and the cannabinoid receptor-interacting protein 1a (CRIP1a). Evidence for a physiological role for CRIP1a is emerging as data regarding the cellular localization and function of CRIP1a are generated. Here we summarize the neuronal distribution and role of CRIP1a in endocannabinoid signaling, as well as discuss investigations linking CRIP1a to development, vision and hearing sensory systems, hippocampus and seizure regulation, and psychiatric disorders including schizophrenia. We also examine the genetic and epigenetic association of CRIP1a within a variety of cancer subtypes. This review provides evidence upon which to base future investigations on the function of CRIP1a in health and disease.

A modified Delphi study to gain consensus for a taxonomy to report and classify physical activity referral schemes (PARS).

BACKGROUND: Physical Activity Referral Schemes (PARS), including exercise referral schemes, are a popular approach to health improvement, but understanding of effectiveness is limited by considerable heterogeneity in reporting and evaluation. We aimed to gain consensus for a PARS taxonomy as a comprehensive method for reporting and recording of such schemes. METHODS: We invited 62 experts from PARS policy, research and practice to complete a modified Delphi study. In round one, participants rated the need for a PARS taxonomy, the suitability of three proposed classification levels and commented on proposed elements. In round two, participants rated proposed taxonomy elements on an 11-point Likert scale. Elements scoring a median of ≥7, indicating high agreement, were included in the final taxonomy. RESULTS: Of those invited, 47 (75.8%) participated in round one, with high retention in round two (n = 43; 91.5%). 42 were UK-based, meaning the resultant taxonomy has been scrutinised for fit to the UK context only. The study gained consensus for a three-level taxonomy: Level 1: PARS classification (primary classification, provider, setting, conditions accepted [have or at risk of], activity type and funding). Level 2: scheme characteristics (staff structure, staff qualifications, behaviour change theories, behaviour change techniques, referral source, referrers, referral process, scheme duration, session frequency, session length, session times, session type, exit routes, action in case of non-attendance, baseline assessment, exit assessment, feedback to referrer and exclusion criteria) and Level 3: participant measures (demographics, monitoring and evaluation, and measures of change). CONCLUSION: Using a modified Delphi method, this study developed UK-based consensus on a PARS classification taxonomy. We encourage PARS practitioners and public health colleagues, especially those working with similar service models internationally, to test, refine and use this taxonomy to inform policy and practice.

Labor and delivery guidance for COVID-19.

This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation; and provide specific guidance for management of L&D of the COVID-19-positive woman, as well as the critically ill COVID-19-positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19-positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19-positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities.

Is It Safe to Manage Acute Cholecystitis Nonoperatively During Pregnancy?: A Nationwide Analysis of Morbidity According to Management Strategy.

OBJECTIVES: To compare cholecystectomy (CCY) and nonoperative treatment (no-CCY) for acute cholecystitis in pregnancy. SUMMARY OF BACKGROUND DATA: Current Society of Gastrointestinal and Endoscopic Surgery guidelines recommend CCY over nonoperative management of acute cholecystitis during pregnancy, and the American College of Obstetricians and Gynecologists recommend medically necessary surgery regardless of trimester. This approach has been recently questioned. METHODS: Pregnant women admitted with acute cholecystitis were identified using the Nationwide Readmission Database 2010-2015. Propensity-score adjusted logistic regression models were used to compare CCY and no-CCY. The primary outcome was a composite measure of adverse maternal-fetal outcomes (intrauterine death/stillbirth, poor fetal growth, abortion, preterm delivery, C-section, obstetric bleeding, infection of the amniotic fluid, venous thromboembolism). RESULTS: There were 6390 pregnant women with acute cholecystitis: 38.2% underwent CCY, of which 5.1% were open. Patients were more likely to be managed operatively in their second trimester (First 43.9%, Second 59.1%, Third 34.2%; P < 0.01). Patients managed with CCY did not differ in age, insurance, income, Charlson Comorbidity Index, diabetes or obesity when compared to no-CCY (all P > 0.05), but were less likely to have a previous C-section, gestational diabetes, preeclampsia/eclampsia or be in the third trimester (P ≤ 0.01). Risk-adjusted analyses showed that no-CCY was associated with significantly increased maternal-fetal complications during the index admission [odds ratio 3.0 (95% confidence interval 2.08-4.34), P < 0.01] and 30-day readmissions [odds ratio 1.61 (confidence interval % CI 1.12-2.32), P < 0.01]. CONCLUSIONS: Contrary to current guidelines, most pregnant women admitted in the US with acute cholecystitis are managed nonoperatively. This is associated with over twice the odds of maternal-fetal complications in addition to increased readmissions.

Preterm Birth and Gestational Length in Four Race-Nativity Groups, Including Somali Americans.

OBJECTIVE: To compare preterm birth rates and gestational length in four race-nativity groups including Somali Americans. METHODS: Using a retrospective cohort study design of Ohio birth certificates, we analyzed all singleton births between 2000 and 2015 from four groups of women categorized as U.S.-born, non-Hispanic white (USBW), U.S.-born, non-Hispanic black (USBB), African-born black (ABB, primarily of West African birth country), and Somalia-born (SB). An algorithm trained on maternal names was used to confirm Somali ethnicity. Gestational length was analyzed as completed weeks or aggregated by clinically relevant periods. Risk of spontaneous and health care provider-initiated preterm birth was calculated in a competing risk model. RESULTS: Births to women in the designated groups accounted for 1,960,693 births (USBW n=1,638,219; USBB n=303,028; ABB n=10,966, and SB n=8,480). Women in the SB group had a lower preterm birth rate (5.9%) compared with women in the USBB (13.0%), ABB (8.4%), and USBW (7.9%) groups (P<.001). Women in the SB group had a higher frequency of postterm pregnancy (5.8% vs less than 1%, P<.001 for all groups). The lower rate of preterm birth in the SB group was unrelated to differences in parity or smoking or whether preterm birth was spontaneous or health care provider-initiated. The lower rate of preterm birth and tendency for prolonged gestation was attenuated in ethnic Somali women born outside Somalia. CONCLUSION: We report a positive disparity in preterm birth and a tendency for prolonged gestation for ethnic Somali women in Ohio. Etiologic studies in multiethnic cohorts aimed to uncover the sociobiological determinants of gestational length may lead to practical approaches to reduce prematurity in the general population.

High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth, and the source may be the damaged fetal membranes.

BACKGROUND: High Mobility Group Box-1 (HMGB1) is considered a prototype alarmin molecule. Upon its extracellular release, HMGB1 engages pattern recognition receptors and the Receptor for Advanced Glycation End-products (RAGE) followed by an outpouring of inflammatory cytokines, including interleukin (IL)-6. METHODS: We assayed the amniotic fluid (AF) levels of HMGB1 and IL-6 in 255 women that either had a normal pregnancy outcome or delivered preterm. Immunohistochemistry on fetal membranes was used for cellular localization and validation of immunoassay findings. HMGB1 also was analyzed in amniochorion tissue explants subjected to endotoxin. RESULTS: AF HMGB1 levels are not gestational age regulated but are increased in women with intra-amniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments. CONCLUSIONS: Our research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure to elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth.

Strengthening Health Systems of Developing Countries: Inclusion of Surgery in Universal Health Coverage.

INTRODUCTION: Universal health coverage (UHC) has its roots in the Universal Declaration of Human Rights and has recently gained momentum. Out-of-pocket payments (OPP) remain a significant barrier to care. There is an increasing global prevalence of non-communicable diseases, many of which are surgically treatable. We sought to provide a comparative analysis of the inclusion of surgical care in operating plans for UHC in low- and middle-income countries (LMIC). METHODS: We systematically searched PubMed and Google Scholar using pre-defined criteria for articles published in English, Spanish, or French between January 1991 and November 2013. Keywords included "insurance," "OPP," "surgery," "trauma," "cancer," and "congenital anomalies." World Health Organization (WHO), World Bank, and Joint Learning Network for UHC websites were searched for supporting documents. Ministries of Health were contacted to provide further information on the inclusion of surgery. RESULTS: We found 696 articles and selected 265 for full-text review based on our criteria. Some countries enumerated surgical conditions in detail (India, 947 conditions). Other countries mentioned surgery broadly. Obstetric care was most commonly covered (19 countries). Solid organ transplantation was least covered. Cancer care was mentioned broadly, often without specifying the therapeutic modality. No countries were identified where hospitals are required to provide emergency care regardless of insurance coverage. OPP varied greatly between countries. Eighty percent of countries had OPP of 60% or more, making these services, even if partially covered, largely inaccessible. CONCLUSION: While OPP, delivery, and utilization continue to represent challenges to health care access in many LMICs, the inclusion of surgery in many UHC policies sets an important precedent in addressing a growing global prevalence of surgically treatable conditions. Barriers to access, including inequalities in financial protection in the form of high OPP, remain a fundamental challenge to providing surgical care in LMICs.

Modulation of amniotic fluid activin-a and inhibin-a in women with preterm premature rupture of the membranes and infection-induced preterm birth.

PROBLEM: Activins and inhibins are important modulators of inflammatory processes. We explored activation of amniotic fluid (AF) activin-A and inhibin-A system in women with intra-amniotic infection and preterm premature rupture of the membranes (PPROM). METHOD OF STUDY: We analyzed 78 AF samples: '2nd trimester-control' (n=12), '3rd trimester-control' (n=14), preterm labor with intact membranes [positive-AF-cultures (n=13), negative-AF-cultures (n=13)], and PPROM [positive-AF-cultures (n=13), negative-AF-cultures (n=13)]. Activin-A levels were evaluated ex-vivo following incubation of amniochorion and placental villous explants with Gram-negative lipopolysaccharide (LPS) or Gram-positive (Pam3Cys) bacterial mimics. Ability of recombinant activin-A and inhibin-A to modulate inflammatory reactions in fetal membranes was explored through explants' IL-8 release. RESULTS: Activin-A and inhibin-A were present in human AF and were gestational age-regulated. Activin-A was significantly upregulated by infection. Lower inhibin-A levels were seen in PPROM. LPS elicited release of activin-A from amniochorion, but not from villous explants. Recombinant activin-A stimulated IL-8 release from amniochorion, an effect that was not reversed by inhibin-A. CONCLUSION: Human AF activin-A and inhibin-A are involved in biological processes linked to intra-amniotic infection/inflammation-induced preterm birth.

Cord blood erythropoietin and interleukin-6 for prediction of intraventricular hemorrhage in the preterm neonate.

OBJECTIVE: To evaluate cord blood erythropoietin (EPO) and interleukin-6 (IL-6) levels to predict preterm infants at risk of developing intraventricular hemorrhage (IVH). METHODS: Levels of umbilical cord EPO, acid-base status and IL-6 were analyzed in 116 consecutive, preterm newborns (GA at delivery: 29 [23-34 ] weeks) born to mothers who had a clinically indicated amniocentesis to rule out infection. Early-onset neonatal sepsis (EONS) was diagnosed using symptoms, hematological criteria and blood cultures. RESULTS: IVH was diagnosed by cranial ultrasounds. The prevalence of IVH in our population was 25% (29/116). There was a direct relationship between cord blood EPO and cord blood IL-6 concentration (r = 0.225, p = 0.014), independent of GA at birth. Elevated cord blood EPO levels (r = 0.182, p = 0.016) and GA at birth (r =  -0.236, p = 0.004) remained significant independent factors associated with the risk of IVH, when evaluated with stepwise logistic regression analyses. Cord blood IL-6, pH, and EONS were not associated with IVH. These relationships remained following correction for GA at birth (p = 0.027). CONCLUSIONS: Our results suggest that elevation in cord blood EPO may predict newborns at risk for IVH, independent of fetal inflammatory status. Further studies are warranted to confirm this association.

Characterization of RAGE, HMGB1, and S100beta in inflammation-induced preterm birth and fetal tissue injury.

Immune activation represents an adaptive reaction triggered by both noxious exogenous (microbes) and endogenous [high mobility group box-1 protein (HMGB1), S100 calcium binding proteins] inducers of inflammation. Cell stress or necrosis lead the release of HMGB1 and S100 proteins in the extracellular compartment where they act as damage-associated molecular pattern molecules (or alarmins) by engaging the receptor for advanced glycation end-products (RAGE). Although the biology of RAGE is dictated by the accumulation of damage-associated molecular pattern molecules at sites of tissue injury, the role of RAGE in mediating antenatal fetal injury remains unknown. First, we studied the relationships at birth between the intensity of human fetal inflammation and sRAGE (an endogenous RAGE antagonist), HMGB1, and S100beta protein. We found significantly lower sRAGE in human fetuses that mounted robust inflammatory responses. HMGB1 levels correlated significantly with levels of interleukin-6 and S100beta in fetal circulation. We then evaluated the levels and areas of tissue expression of RAGE, HMGB1, and S100beta in specific organs of mouse fetuses on E16. Using an animal model of endotoxin-induced fetal damage and preterm birth, we determined that inflammation induces a significant change in expression of RAGE and HMGB1, but not S100beta, at sites of tissue damage. Our findings indicate that RAGE and HMGB1 may be important mediators of cellular injury in fetuses delivered in the setting of inflammation-induced preterm birth.