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

Long-Term Mortality and Morbidity Related to Congestive Heart Failure with Reduced Ejection Fraction (CHFrEF) in Palestinian Patients Maintained on Submaximal Sacubitril/Valsartan Doses: A Pilot Study

Background. The efficacy of sacubitril/valsartan, a newly introduced combination drug for heart failure with reduced ejection fraction (HFrEF), was demonstrated in the PARADIGM-HF trial conducted in Western countries. However, these findings need to be verified in the Middle Eastern context, where patients may exhibit a different response due to different environmental and racial factors. Objectives. The goal of this study was to evaluate the efficacy of submaximal sacubitril/valsartan doses in terms of improving the disease symptoms, as measured by the New York Heart Association (NYHA) classification and left ventricular ejection fraction (LVEF) percentage, as well as establish long-term morbidity and mortality associated with HFrEF among Palestinian patients administered target doses of an angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs). Material and Methods. This study involved a retrospective review of charts related to patients with HFrEF maintained on sacubitril/valsartan and was conducted in a referral cardiology clinic in Palestine. The inclusion criteria were age 18+, HFrEF diagnosis, sacubitril/valsartan usage for at least six months during the period between January 1, 2016, and June 30, 2019, and LVEF &lt; 40 % . The exclusion criteria included LVEF ≥ 40 % and drug administration duration &lt; 6 months. The collected data included NYHA class, as well as LVEF, serum sodium (Na), potassium (K), serum creatinine (Cr), and blood urea nitrogen (BUN) levels and the mortality rate before and after the minimum treatment duration. IBM SPSS STATISTICS for Windows, version 20.0, Armonk, NY: IBM Corp. IBM Corp., released 2012, was used for data analysis, whereby T score was calculated for comparisons between numerical groups, and p &lt; 0.05 was considered statistically significant. Results. The initial study sample comprised of 205 consecutive patients with HFrEF maintained on sacubitril/valsartan for at least six months from January 1, 2016, to June 30, 2019. Three patients were excluded due to attrition, along with further 12 patients with LVEF ≥ 40 % (based on the PARADIGM-HF trial criteria). Throughout the treatment period, most patients showed escalating improvement in terms of the LVEF and NYHA classification, as LVEF = 29.8 % and NYHA = 3 were obtained on average before initiating sacubitril/valsartan, compared to 41% and 1.7, respectively, after 6-month treatment ( p = 0.0003 and 0.046, respectively). These improvements in LVEF and NYHA class were noted across all sacubitril/valsartan doses (50−400 mg). However, 23 patients (12%) died while undergoing sacubitril/valsartan treatment. Conclusion. A significant long-term reduction in the mortality and morbidity rates was observed in Palestinian patients with HFrEF maintained on submaximal doses of sacubitril/valsartan.</jats:p

H-type anorectal malformation associated with H-type tracheoesophageal fistula

An extremely rare association of H-type anorectal malformation (ARM) and H-type tracheoesophageal fistula case is presented with literature review of the previously reported cases. Characteristics of the most commonly reported male H-type ARM patients are discussed. The proposed embryology and options for repair are discussed as well. Most surgical approaches have satisfactory results leaving approach selection to the surgeon experience and comfortability

Familial Mediterranean Fever Complicated by a Triad of Adrenal Crisis: Amyloid Goiter and Cardiac Amyloidosis

Background. FMF is a common disease in the Mediterranean populations and may be complicated by AA amyloidosis. The coexistence of adrenal and thyroid amyloidosis in AA amyloidosis secondary to familial Mediterranean fever (FMF) is an extremely rare reported condition. We presented a previously unreported triad of adrenal, thyroid, and cardiac amyloidosis secondary to FMF. Presentation of Case. We reported a 23-year-old Palestinian male patient presented with hypotension, vomiting, diarrhea, and abdominal pain. The patient was subsequently diagnosed to have an adrenal crisis with both amyloid goiter and cardiac amyloidosis. Conclusion. It is crucial to recognize the adrenal crisis in patients with AA amyloidosis secondary to FMF who present similarly to acute FMF inflammatory episodes. The adrenal crisis has high morbidity and mortality, especially if not recognized early in the course of the disease

Familial Mediterranean Fever Complicated by a Triad of Adrenal Crisis: Amyloid Goiter and Cardiac Amyloidosis

Background. FMF is a common disease in the Mediterranean populations and may be complicated by AA amyloidosis. The coexistence of adrenal and thyroid amyloidosis in AA amyloidosis secondary to familial Mediterranean fever (FMF) is an extremely rare reported condition. We presented a previously unreported triad of adrenal, thyroid, and cardiac amyloidosis secondary to FMF. Presentation of Case. We reported a 23-year-old Palestinian male patient presented with hypotension, vomiting, diarrhea, and abdominal pain. The patient was subsequently diagnosed to have an adrenal crisis with both amyloid goiter and cardiac amyloidosis. Conclusion. It is crucial to recognize the adrenal crisis in patients with AA amyloidosis secondary to FMF who present similarly to acute FMF inflammatory episodes. The adrenal crisis has high morbidity and mortality, especially if not recognized early in the course of the disease.</jats:p

Intrauterine Limb Ischemia in Patient Heterozygous for the 677C>T) RS1801133 (Polymorphism of Methylenetetrahydrofolate Reductase MTHR Gene

Background. Intrauterine arterial thrombosis is extremely rare. Multiple inherited coagulopathies were found to be associated with thrombophilia and an increased risk of intrauterine arterial thrombosis. Methylenetetrahydrofolate reductase MTHFR (C667T) polymorphism was found to be associated with mild hyper-homocysteinemia, which, in turn, can promote thrombotic complications. Materials and Methods. We reported a case of intrauterine upper limb ischemia in a neonate who was found to be heterozygous for the 677C > T polymorphism of the MTHFR gene despite the dispute regarding its clinical significance as a risk of arterial thrombosis. We also reviewed the literature and summarized the clinical features, treatment, and prognosis of similar cases. Case Presentation. We reported a full-term female, born by normal spontaneous vaginal delivery who was found to have a swollen, blue left upper limb in the delivery room. Left upper limb computed tomography angiography (CTA) revealed left subclavian artery thrombosis. Investigations for the risk revealed heterozygosity for the MTHFR (C667T) polymorphism. Left upper limb amputation was done after the failure of medical management. Conclusion. Despite the conflict about whether heterozygosity for MTHFR (C667T) polymorphism increases the risk of arterial thrombosis or not, there are few cases in the literature presented with intrauterine upper limb ischemia and were found to be heterozygous for the mutation. We recommend investigating neonates and their parents for complete thrombophilia mutations when they present with unusual vascular occlusion sites as newborns