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

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 middle-income 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 low-income 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 low-income, 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

Filipino women\u27s use of intra-uterine device and some contextual variables: Knowledge for commercial promotion

In its effort to achieve contraceptive self-reliance as a result of the gradual withdrawal of foreign donations of contraceptive supplies, the Philippines has been instituting \u27e user-pay scheme. This scheme, which requires women to pay for their contraceptives has already been implemented, albeit in differing levels, for condoms, and injectables. The IUD is next to be marketed as a commercial product. To guide the IUDs transition, a synthesis of relevant and existing quantitative and qualitative information in the Philippines was undertaken. Findings suggest that IUD has commercial prospects because it has potential groups of users, and it has unique attributes on which its commercial value can be packaged. To enhance its prospects, IUD’s service provision and marketing and promotion must be improve

Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome

Microcephaly-capillary malformation (MIC-CAP) syndrome is characterized by severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay and multiple small capillary malformations on the skin. We used whole-exome sequencing of five patients with MIC-CAP syndrome and identified recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB) isopeptidase STAMBP (STAM-binding protein, also known as AMSH, associated molecule with the SH3 domain of STAM) that has a key role in cell surface receptor-mediated endocytosis and sorting. Patient cell lines showed reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and PI3K-AKT-mTOR pathways. The latter cellular phenotype is notable considering the established connection between these pathways and their association with vascular and capillary malformations. Furthermore, our findings of a congenital human disorder caused by a defective DUB protein that functions in endocytosis implicates ubiquitin-conjugate aggregation and elevated apoptosis as factors potentially influencing the progressive neuronal loss underlying MIC-CAP syndrome

Identification of Burkholderia cenocepacia Strain H111 virulence factors using nonmammalian infection hosts

Burkholderia cenocepacia H111, a strain isolated from a cystic fibrosis patient, has been shown to effectively kill the nematode Caenorhabditis elegans. We used the C. elegans model of infection to screen a mini-Tn5 mutant library of B. cenocepacia H111 for attenuated virulence. Of the approximately 5,500 B. cenocepacia H111 random mini-Tn5 insertion mutants that were screened, 22 showed attenuated virulence in C. elegans. Except for the quorum-sensing regulator cepR, none of the mutated genes coded for the biosynthesis of classical virulence factors such as extracellular proteases or siderophores. Instead, the mutants contained insertions in metabolic and regulatory genes. Mutants attenuated in virulence in the C. elegans infection model were also tested in the Drosophila melanogaster pricking model, and those also attenuated in this model were further tested in Galleria mellonella. Six of the 22 mutants were attenuated in D. melanogaster, and five of these were less pathogenic in the G. mellonella model. We show that genes encoding enzymes of the purine, pyrimidine, and shikimate biosynthesis pathways are critical for virulence in multiple host models of infection

Patients with Crohn's disease have longer post-operative in-hospital stay than patients with colon cancer but no difference in complications' rate

BACKGROUNDRight hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC).AIMTo investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD.METHODSThis is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission.RESULTSThree hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P &lt; 0.01), had lower American Society of Anesthesiology score (ASA) grade (P &lt; 0.01) and less comorbidity (P &lt; 0.01), but were more likely to be current smokers (P &lt; 0.01). Patients with CD were more frequently operated on by colorectal surgeons (P &lt; 0.01) and frequently underwent ileocecal resection (P &lt; 0.01) with higher rate of de-functioning/primary stoma construction (P &lt; 0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P &lt; 0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers.CONCLUSIONPatients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complication's rate was not different between the two groups