Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Expression of Th-17 related cytokines (IL-17A and F) in severe asthma

Inflammation and airway remodelling are hallmarks of severe asthma pathology. Although severe asthma represents 10% of the asthmatic population, this subset of patients has greater morbidity, mortality and a disproportionate need for health care services. Severe asthma appears to have a different inflammatory pattern compared to mild and moderate asthma. There is an increase in neutrophil infiltration, upregulation of IL-8 and disregulation of Th-2 cytokines. IL-17A and F are two proinflammatory and profibrotic cytokines produced primarily by Th-17 cells. These cytokines can act on a broad range of cell types to induce cytokines, chemokines and metalloproteinases as well as have important roles in neutrophil activity. We hypothesize that IL-17A and F are expressed in asthmatic airways and are increased in severe disease. The objective of our study is to investigate the expression of IL-17A and F in biopsies of severe asthmatics, and compare them with moderate and mild asthmatics as well as control subjects and relate this expression to that of IL-8 and neutrophilia. The expression of IL-17A and F mRNA and protein was evaluated in bronchial biopsies using immunocytochemistry and real-time PCR. The expression of both IL-17A and F were shown to be increased in severe asthmatic airways compared to mild asthmatics and control subjects. IL-17A was mostly expressed in mononuclear cells present in the subepithelial tissue within clusters of inflammatory cells, whereas IL-17F was expressed not only in inflammatory cells but also in epithelial cells. This observation was confirmed using laser capture microdissection. Our results are consistent with the possible role of IL-17 family in steroid hyperresponsive disorders, including rheumatoid arthritis, psoriasis and refractory asthma. We suggest that both IL-17A and F contribute to severe asthma inflammatory and airway remodelling pathology. Our findings further the knowledge on severe asthma disease and open new options toLe processus inflammatoire et le remodelage des voies respiratoires sont typiquement liés à la pathologie de l'asthme réfractaire. Bien que l'asthme réfractaire n'affecte que 10% des asthmatiques, ce sous-groupe de patients est caractérisé par une plus grande morbidité, mortalité ainsi qu'un besoin disproportionné des services des soins de santé. Il semble que l'asthme réfractaire utilise un mécanisme d'inflammation distinct de celui associé à l'asthme léger et modéré. Il y a une augmentation de l'infiltration des neutrophiles, une régulation positive de l'IL-8 ainsi qu'une dérégulation des cytokines Th-2. Les cytokines IL-17A et F sont pro-inflammatoires, pro-fibrotiques et sont principalement produites par les cellules Th-17. Ces cytokines peuvent agir sur plusieurs types de cellules afin d'induire la production de cytokines, chémokines et métalloprotéinases. De plus, ces deux cytokines jouent un rôle prédominant dans l'activité des neutrophiles. Nous faisons l'hypothèse que l'IL-17A et F sont exprimées dans les voies respiratoires des asthmatiques et qu'elles sont augmentées dans l'asthme réfractaire. Cette étude a pour but d'investiguer l'expression de l'IL-17A et F sur biopsies provenant d'asthmatiques réfractaires et d'en faire la comparaison à celles provenant d'asthmatiques légers, modérés ainsi que de sujets sains et de relier cette expression à celle de l'IL-8 et de la neutrophilie. L'expression des ARNm et des protéines de l'IL-17A et F a été évaluée sur biopsies par immunocytochimie et ‘real-time PCR'. Il a été démontré que l'expression de l'IL-17A et F est augmentée dans les voies aériennes des asthmatiques réfractaires en comparaison aux asthmatiques légers et sujets sains. L'IL-17A est principalement exprimée par les cellules mononucléaires des tissus des régions sous-épithéliales parmi les grappes de cellules inflammatoires. L'IL-17F n'est pas uniquement exprimée par les cellules inflammato

Atlantic-dip: excessive gestational weight gain and pregnancy outcomes in women with gestational or pregestational diabetes mellitus

Context: Women who have diabetes mellitus during pregnancy are at higher risk of adverse outcomes. Excessive gestational weight gain (GWG) is also emerging as a risk factor for maternofetal complications, and in 2009, the Institute of Medicine published recommendations for appropriate GWG. It is unclear whether excessive GWG confers additional risk to women with diabetes in pregnancy and whether Institute of Medicine recommendations are applicable to this population. Objective: The objective of this study was to examine whether excessive GWG in pregnancies complicated by diabetes mellitus is associated with higher adverse obstetric outcomes. Design: This was an observational study. Setting: The study was conducted at five antenatal centers along the Irish Atlantic seaboard. Participants: 802 women with diabetes in pregnancy participated in the study. Main Outcome Measure: Maternal outcomes examined included preeclampsia, gestational hypertension, and cesarean delivery. Fetal outcomes included large for gestational age (LGA), macrosomia, and small for gestational age. Results: Excessive GWG was noted in 59% of women. In all women, excessive GWG resulted in higher odds for LGA [adjusted odds ratio (aOR) 2.01, 95% confidence intervals 1.24-3.25 in GDM; aOR 3.97, CI 1.85-8.53 in pregestational diabetes mellitus (PGDM)] and macrosomia (aOR 2.17, CI 1.32-3.55 in GDM; aOR 3.58, CI 1.77-7.24 in PGDM). Excessive GWG was also associated with an increased odds for gestational hypertension (aOR 1.72, CI 1.04-2.85) in women with GDM, and treatment with insulin further increased the odds for LGA (aOR 2.80, CI 1.23-6.38) and macrosomia (aOR 5.63, CI 2.16-14.69) in this group. Conclusion: We show that in the already high-risk settings of both GDM and PGDM, excessive GWG confers an additive risk for LGA birth weight, macrosomia, and gestational hypertension

Atlantic-dip: excessive gestational weight gain and pregnancy outcomes in women with gestational or pregestational diabetes mellitus

Context: Women who have diabetes mellitus during pregnancy are at higher risk of adverse outcomes. Excessive gestational weight gain (GWG) is also emerging as a risk factor for maternofetal complications, and in 2009, the Institute of Medicine published recommendations for appropriate GWG. It is unclear whether excessive GWG confers additional risk to women with diabetes in pregnancy and whether Institute of Medicine recommendations are applicable to this population. Objective: The objective of this study was to examine whether excessive GWG in pregnancies complicated by diabetes mellitus is associated with higher adverse obstetric outcomes. Design: This was an observational study. Setting: The study was conducted at five antenatal centers along the Irish Atlantic seaboard. Participants: 802 women with diabetes in pregnancy participated in the study. Main Outcome Measure: Maternal outcomes examined included preeclampsia, gestational hypertension, and cesarean delivery. Fetal outcomes included large for gestational age (LGA), macrosomia, and small for gestational age. Results: Excessive GWG was noted in 59% of women. In all women, excessive GWG resulted in higher odds for LGA [adjusted odds ratio (aOR) 2.01, 95% confidence intervals 1.24-3.25 in GDM; aOR 3.97, CI 1.85-8.53 in pregestational diabetes mellitus (PGDM)] and macrosomia (aOR 2.17, CI 1.32-3.55 in GDM; aOR 3.58, CI 1.77-7.24 in PGDM). Excessive GWG was also associated with an increased odds for gestational hypertension (aOR 1.72, CI 1.04-2.85) in women with GDM, and treatment with insulin further increased the odds for LGA (aOR 2.80, CI 1.23-6.38) and macrosomia (aOR 5.63, CI 2.16-14.69) in this group. Conclusion: We show that in the already high-risk settings of both GDM and PGDM, excessive GWG confers an additive risk for LGA birth weight, macrosomia, and gestational hypertension

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population