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

Avaliação do extrato hidroalcoólico de Aroeira (Schinus terebinthifolius Raddi) no processo de cicatrização de feridas em pele de ratos Evaluation of hydroalcoholic extract of Aroeira (Shinus Terebinthifolius Raddi) in the healing process of wound skin in rats

OBJETIVO: Avaliar o efeito cicatrizante da administração tópica do extrato hidroalcoólico de aroeira em feridas abertas na região dorsocostal de ratos. MÉTODOS: Utilizou-se 60 ratos Wistar, machos, que tiveram retirado fragmentos de pele com dois centímetros de diâmetro, sob anestesia inalatória com éter etílico. Foram divididos em dois grupos de 30 animais: o grupo aroeira, que recebeu aplicação do extrato hidroalcoólico da planta, e o grupo controle, que recebeu aplicação de solução salina a 0,9%. Cada grupo foi subdividido em 3 com 10 animais cada para serem observados aos sete, 14 ou 21 dias. As áreas das lesões foram analisadas pelo aspecto macroscópico e por planimetria digital. Os espécimes ressecados das feridas foram analisados por microscopia ótica em colorações de hematoxilina-eosina e tricrômio de Masson. RESULTADOS: Os achados macroscópicos demonstraram reepitelização completa mais precoce no grupo controle aos 14 dias. Pela planimetria digital as áreas médias das feridas dos ratos do grupo controle (0,5278 cm²) foram menores que as das feridas dos ratos do grupo aroeira (0,6897 cm²), com significância estatística aos 14 dias de pós-operatório (p=0,036). O estudo histológico demonstrou diferença estatística (p=0,023) em relação às células mononucleares no 14º dia de avaliação, com maior número no grupo aroeira, não havendo diferenças significantes em relação aos outros parâmetros em nenhum dos dias estudados. CONCLUSÃO: O extrato hidroalcoólico de aroeira retardou a reepitelização das feridas da pele dos ratos.<br>PURPOSE: To evaluate the healing effect of the topic administration of the hydroalcoholic extract of aroeira in open wounds in the dorsocostal region of rats. METHODS: Sixty Wistar rats, males, were used. In all animals one skin fragment was removed, with two centimeters in diameter. Inhalatory anesthesia with ethyl ether was done, The rats were divided in two groups of 30 animals: aroeira group, submitted to an topic application of the hydralcoholic extract of the plant, and control group, with the same process but with 0.9% saline solution. Each group was divided in three sub-groups of 10 animals according to the period of observation: 7, 14 and 21 days. The areas of the injuries were analyzed by the macrocospic aspect and digital planimetry, and the resected segments of the wounds were studied by optic microscopy stainned with hematoxilin-eosine and trichromium of Masson. RESULTS: The macrocospic findings showed early complete reepitelization in the control group by the 14th day. According to the digital planimetry the average wound areas of the rats from the control group (0.5278 cm²) had been smaller than those from the wounds of the rats of the aroeira group (0.6897 cm²), with statistical significance to the 14th day (p=0.036). The hystologic study showed statistical difference (p=0.023) regarding the mononuclear cells in 14th day of evaluation, with larger number in the aroeira group, without significant differences regarding other parameters in all the remaining days. CONCLUSION: The topic use of the hydralcoholic extract of aroeira delayed the reepitelization of the skin wounds in rats