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

EFFICACY AND SAFETY OF LUSPATERCEPT IN MYELODYSPLASTIC SYNDROME/NEOPLASM WITH VERY LOW/LOW/INTERMEDIATE RISK REQUIRED TRANSFUSION: A SYSTEMATIC REVIEW AND SINGLEARM META-ANALYSIS

Objective: Myelodysplastic syndrome (MDS) and myeloid neoplasms are hematological disorders characterized by abnormal blood cell production. Patients with very low, low, or intermediate-risk MDS/neoplasms often require regular red blood cell (RBC) transfusions to manage anemia. Luspatercept has been evaluated in several retrospective studies and randomized controlled trials as a promising treatment. However, the results of these studies have shown some discrepancies. Therefore, we conducted a systematic review and a single-arm meta-analysis to consolidate the current evidence on the efficacy and safety of luspatercept in the treatment of patients with very low, low, or intermediate-risk MDS/neoplasms who require regular RBC transfusions. Methods: Following PRISMA guidelines, we performed a systematic literature review and a meta-analysis. Our search strategy encompassed PubMed, Embase, and Cochrane Library databases, utilizing the key terms ’luspatercept’, ’myelodysplastic syndrome’. Efficacy outcomes included achieving transfusion independence for at least 8 weeks or longer (TI≥8) and hematological improvement-erythroid (HI-E) response as defined by the IWG 2006 criteria. Safety outcomes comprised adverse events. Data were summarized using pooled mean for continuous outcomes and pooled proportion for dichotomous outcomes, with 95% confidence intervals. I2 was used to assess heterogeneity. Statistical analyses were performed using R software, version 4.3.2. Results: Out of 940 initially identified studies, 11 were included in the final analysis, comprising a total of 1,069 patients. All patients required regular red blood cell transfusions. The follow-up periods were not specified. The mean age and gender distribution of patients were not mentioned in the given text. The pooled proportion for (TI≥8) was 40.5% (95% CI: 25.49-55.5%; I2 = 98%). The pooled proportion for (HI-E) response was 47.27% (95% CI: 35.21-59.33%; I2 = 90%), In the subgroup analysis, the prevalence of TI≥8 in the RCT group was 51.31% (95% CI: 25.14-77.47%; I2 = 96%), while in the real-world group, it was 28.10% (95% CI: 15.81-40.38, I2 = 81%). Most common AEs by pooled proportion were: gastrointestinal disorders, 11.07% (95% CI, 2.0-20.14%; I2 = 95%); fatigue, 8.85% (95% CI: 3.56-14.15%; I2 = 90%); cardiac events, 8.94% (95% CI: 4.57-13.31%; I2 = 88%); and nervous system disorders, 6.84% (95% CI: 1.43-12.24%; I2 = 86%). Discussion: Luspatercept demonstrated significant benefits in achieving transfusion independence and improving erythroid response, especially in patients for whom traditional stimulating agents were ineffective. However, real-world data indicated lower success rates compared to RCTs, likely due to treatment discontinuation and previous multiple drug use. Common adverse events included fatigue and nervous system, gastrointestinal and cardiac disorders. Despite limitations such as high heterogeneity and small sample sizes in some studies, Luspatercept's favorable safety profile and substantial benefits support its use in MDS patient management. Conclusion: This meta-analysis demonstrates Luspatercept's efficacy and safety in treating transfusion-dependent MDS patients with lower-risk disease. However, significant heterogeneity and differences between RCTs and real-world data necessitate cautious interpretation. Further prospective studies are needed to strengthen the evidence and fully assess Luspatercept's efficacy and safety profile

Horizontal and vertical distribution of mosquitoes (Diptera: Culicidae) in the rainforest of Maromizaha, Madagascar: implications for pathogen transmission to humans and animals

International audienceThe horizontal and vertical distribution of mosquito species was studied in Maromizaha rainforest, Madagascar. In November 2014, horizontal distribution was studied using light traps that were placed in four habitat types, ranging from degraded forest to primary rainforest. In November to December 2016, vertical distribution was studied using light traps placed near to the ground and elevated near the canopy. From the horizontal survey, 476 adults were collected: Uranotaenia (52.10%) and Culex (35.2%) were the most abundant genera. The highest numbers of mosquitoes were observed in the rainforest edge habitat, while the highest mosquito diversity was observed within primary rainforest. From the vertical survey, 276 adults were collected: Culex was the most abundant genus and represented 75.70% of adults caught. Mosquitoes were more abundant in traps placed near the ground than those near the canopy. The highest species diversity was observed near the canopy. The higher abundance of mosquitoes at the forest edge agrees with the role of this zone as an ecotone between intact rainforest and the nearest human habitation. Increased mosquito abundance in lower strata might heighten their contact with particular vertebrate hosts. The presence of vectors in different habitats and in varying elevations likely influences the risk of pathogen transmission between animals and humans in this rainforest