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

Effectiveness of dexamethasone and hyaluronidase + valerate of bethasone associated with prepucial massage in the treatment of child phimosis

Introduction: The phimosis condition is characterized by the inability to retract the foreskin on the glans, making it impossible to expose them. Surgical treatment, although effective, has been questioned by the risk to which the patient is exposed. Therefore, we have opted for the use of topical corticosteroids to resolve this pathology. Goals: To compare the effectiveness of Dexamethasone and Hyaluronidase + Betamethasone Valerate associated with preputial massage in the treatment of infantile phimosis, the degree of regression of phimosis, the time needed to achieve complete efficacy, possible adverse reactions, long-term outcome and parental adherence to treatment in children attending a specialized service in Blumenau, Santa Catarina. Materials and methods: Controlled clinical trial, quantitative, non-blind, prospective and randomized sample analysis through the analysis of 523 patients. Results: After 1 month of treatment, 435 patients presented some degree of regression and 63 children were referred to surgery. The success rate in this period was 45.8% in boys who were taking Hyaluronidase + Betamethasone Valerate and 49.8% in those who used Dexamethasone. In the late evaluation, 398 children reached grade 0, and 213 used Hyaluronidase + Betamethasone Valerate and 185, Dexamethasone; 39 patients were referred to the postectomy. Adherence to treatment was similar in both groups. The average time for degree 0 to be reached similar in both. Conclusion: Both topical corticosteroids were effective in the resolution of phimosis. However, in the evaluation after the first month and in the regression, Dexamethasone proved to be more effective. The time to resolution of the condition was similar for both. The surgical procedure was taken when there was no clinical improvement. No adverse effects were reported in both groups

Evaluation of an experimental model for anorectal anomalies induced by ethylenethiourea Avaliação de um modelo experimental de anomalia anorretal induzida pela etilenotiouréia

PURPOSE: To evaluate an experimental model for anorectal anomalies and their principal associated malformations induced by ethylene thiourea (ETU). METHODS: Rat fetuses were utilized, divided into two groups: experimental group - fetuses from rats that received ETU on the 11th day of gestation at the dose of 125 mg/kg, diluted in distilled water to 1% concentration (12.5 ml/kg); and control group - fetuses from rats that received distilled water alone, at a volume of 12.5 ml/kg. On the 21st day of gestation, the animals were sacrificed by hypoxia in a carbon dioxide chamber, followed by laparotomy to remove the fetuses. These were initially examined externally to determine the sex and whether anorectal anomalies and malformations of the vertebral column and tail were present. Then, with the aid of microscopy, the fetuses underwent exploratory laparotomy to characterize the type of anorectal anomaly and investigate urological malformations. RESULTS: None of the fetuses in the control group presented anorectal anomaly, vertebral column malformation or urological structural alterations. In the experimental group, 71% presented anorectal anomaly, 80% presented vertebral column alterations and 35% presented urological alterations. CONCLUSION: The model described was shown to be easy to implement and presented results that allow its use in studying anorectal anomalies and associated malformations.<br>OBJETIVO: Avaliar o modelo experimental de AAR, induzido pela Etilenotiouréia (ETU), quanto à ocorrência de anomalia anorretal e das principais malformações associadas. MÉTODOS: Foram utilizados fetos de ratos distribuídos em 2 grupos: Grupo experimental - Fetos provenientes de ratas que receberam ETU no décimo primeiro dia de gestação na dose de 125 mg/Kg, diluída em água destilada na concentração de 1% (12,5 ml/Kg) e Grupo controle - Fetos de ratas que receberam somente água destilada num volume de 12,5 ml/Kg. No 21&deg; dia de gestação, os animais foram submetidos à eutanásia por hipóxia em câmara de gás carbônico e laparotomia para retirada dos fetos. Os fetos foram, inicialmente, examinados externamente para determinação do sexo, presença de AAR, de malformações de coluna vertebral e da cauda. A seguir, com o auxílio de microscopia, os fetos foram submetidos a laparotomia exploradora para caracterização do tipo de AAR e investigação de malformações urológicas. RESULTADOS: Nenhum dos fetos do grupo controle apresentou AAR, malformações de coluna vertebral e alterações urológicas estruturais. No grupo experimental, 71% apresentaram anomalia anorretal, 80% apresentaram alterações de coluna vertebral e 35% apresentaram alterações urológicas. CONCLUSÃO: O modelo descrito se mostrou de fácil execução e apresentou resultados que permite o seu emprego no estudo das anomalias anorretais e das malformações associadas

Pneumonia necrosante em crianças submetidas à toracoscopia por empiema pleural: incidência, tratamento e evolução clínica

OBJETIVO: Analisar a incidência de pneumonia necrosante (PN) em crianças submetidas a toracoscopia e comparar pacientes com e sem PN em relação às diferentes apresentações e evolução clínica. MÉTODOS: Estudo retrospectivo de crianças portadoras de empiema e submetidas a toracoscopia. A toracoscopia foi realizada em pacientes não submetidos a drenagem torácica prévia e evidência de derrame septado ou pneumotórax, assim como naqueles submetidos previamente a drenagem torácica e pneumotórax persistente ou febre e secreção purulenta. Baseado na presença de PN durante a toracoscopia, os pacientes foram divididos em dois grupos: com PN e sem PN. RESULTADOS: Participaram do estudo 52 pacientes. Dos 24 pacientes com PN, 19 (79%) foram submetidos a drenagem torácica anterior à toracoscopia, 11 (46%) apresentaram pneumotórax, e 16 (67%) evoluíram com fístula broncopleural. Neste grupo, as medianas do tempo de drenagem e de hospitalização foram, respectivamente, 18 e 19 dias. Dos 28 pacientes sem PN, 10 (36%) foram submetidos a drenagem torácica anterior à toracoscopia, 9 (32%) apresentaram pneumotórax, e 5 (18%) evoluíram com fístula broncopleural. Neste grupo, as medianas do tempo médio de drenagem e de hospitalização foram, respectivamente, 6 e 10 dias. CONCLUSÕES: A PN deve ser suspeitada na presença de pneumotórax. A toracoscopia precoce pode ser uma opção terapêutica de grande valor na PN da infância, pois acelera a recuperação quando comparada ao tratamento médico isolado e evita ressecções pulmonares extensas da toracotomia tardia

Study of the density of ganglion cells in the terminal bowel of rats with anorectal malformations Estudo da densidade das células ganglionares no intestino terminal de ratos portadores de anomalia anorretal

PURPOSE: To study the ganglion cells (GC) in the terminal bowel of rats with ethylenethiourea (ETU) induced anorectal malformations (ARM). METHODS: The animals were divided into three groups: Group A - normal fetuses from pregnant rats that were not administered ETU; Group B - fetuses without ARM born from pregnant rats that were administered ETU and Group C - fetuses with ARM born from pregnant rats that received ETU. ETU was administered on the 11th day of pregnancy at the dose of 125 mg/kg body weight by gastric gavage. The rats had cesarean section on the 21st day of gestation. The fetuses’ terminal bowel tissue was analyzed by immunohistochemistry to demonstrate ganglion cells. RESULTS: Statistically significant differences were found between groups A, B and C regarding ganglion cell densities. Group A had the highest cell density, followed by Group B and the lowest density was found in Group C. CONCLUSION: Ganglion cell densities are decreased in the terminal bowel of rats with ARM.<br>OBJETIVO: Estudar as células ganglionares (CG) no intestino terminal de ratos portadores de anomalia anorretal (AAR) induzida pela etilenotiouréia (ETU). MÉTODOS: Os animais foram distribuídos em três grupos: Grupo A - fetos normais, obtidos de ratas grávidas às quais não foi administrada ETU; Grupo B - fetos não portadores de AAR obtidos de ratas grávidas às quais foi administrada ETU e Grupo C - fetos portadores de AAR obtidos de ratas grávidas às quais foi administrada ETU. A ETU foi administrada no décimo primeiro dia de gestação na dose de 125 mg/Kg, por gavagem. As ratas foram submetidas à laparotomia e histerotomia para retirada dos fetos no vigésimo primeiro dia de gestação. O intestino terminal dos fetos foi retirado e analisado por imunohistoquímica para pesquisa de CG. RESULTADOS: Foram encontradas diferenças estatisticamente significantes entre os grupos A, B e C quanto à densidade de CG. O grupo A apresentou a maior densidade, seguida pelo grupo B, e a menor densidade foi encontrada no Grupo C. CONCLUSÃO: Existe uma menor densidade de CG no intestino terminal de ratos portadores de AAR

Avaliação de um modelo experimental de enterocolite necrosante neonatal em ratos Evaluation of an experimental model of necrotizing enterocolitis in rats

OBJETIVO: Avaliar um modelo experimental de enterocolite necrosante em ratos proposto por Okur e colaboradores em 1995. MÉTODOS: Utilizou-se 28 ratos da raça EPM-Wistar no primeiro dia de vida, com peso entre 4 a 6 gramas. Os animais foram submetidos a hipóxia (H) colocando os filhotes em uma câmara de gás CO2 para sacrifício de roedores onde receberam um fluxo de ar contendo 100% de CO2 durante 5 minutos. Após a hipóxia os animais foram reanimados (R) com fluxo de ar contendo O2 a 100%, também durante 5 minutos. Os animais divididos em dois grupos: G1: controle (n=12): ratos não submetidos a H-R; G2: (n=16): ratos submetidos a H-R. Segmentos de intestino delgado e cólon foram preparados para análise histológica. O restante do intestino foi utilizado para dosagem de malondialdeído tecidual. RESULTADOS: Dosagem de malondialdeído do G1 foi em média 1,05 (0,44-2,03) e do G2 foi em média 2,60 (0,59- 6,4) nmol MDA/mg proteína. O G2 teve média significativamente maior do que a do grupo controle (p<0,002). Foi encontrada diferença estatisticamente significante entre os grupos de estudo quanto à distribuição do grau de lesão onde o grupo G1 apresentou graus significantemente menores do que o grupo G2. CONCLUSÕES: O modelo mostrou que a hipóxia neonatal em ratos provoca lesões na parede intestinal.. Apesar das lesões histológicas discretas é um bom método para avaliação da liberação de radicais livres teciduais.<br>OBJECTIVE: To evaluate an experimental model of necrotizing enterocolitis in rats proposed by OKUR e col. in 1995. METHODS: On their first day of life, 28 EPM-Wistar rats weighing between 4 and 6 grams were submitted to hypoxia (H) by placing them in a CO2 gas chamber for rodents' sacrifice, where they received a 100% CO2 air flow for 5 minutes. After the hypoxia the animals were reanimated (R) with a 100% O2 air flow, also for 5 minutes. The animals were allocated in two groups: G1: control (n=12): rats not submitted to H-R; G2: (n=16): rats submitted to H-R. Segments of the small intestine and colon were prepared for histological analysis. The remaining intestine was used to measure tissular malondialdehyde. RESULTS: Mean malondialdehyde dosages were 1.05 (0.44-2.03) and 2.60 (0.59- 6.4) nmol MDA/mg protein for G1 and G2, respectively. G2's mean value was significantly higher than in the control group (p<0.002). Significant statistical difference between the studied groups was found in relation the level of injury, with G1 presenting significantly lower levels than G2. CONCLUSIONS: The model showed that neonatal hypoxia may cause intestinal wall injury in rats. Despite the discreet histological injuries found, the method is suitable for evaluation of tissular free radicals