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

Crotapotin induced modification of T lymphocyte proliferative response through interference with PGE(2) synthesis

The immunosuppressive property has been demonstrated for the venom of the Crotalus durissus terrificus. Using a simple, novel method for obtaining crotapotin and phospholipase A(2) isoforms from venom, it was possible to demonstrate that the addition of crotapotin to cultures of isolated lymphocytes resulted in a significant inhibition of the cellular proliferative response to Concanavalin A. This reduction in blastogenic response of lymphocytes is accompanied by a significant increase in the production of PGE(2) by macrophages. This effect on the innate immune response suggests that this compound may modify the subsequent adaptative immune response. (C) 2003 Elsevier Ltd. All rights reserved.42443343

Interferon beta-modulates experimental autoimmune encephalomyelitis by altering the pattern of cytokine secretion

The mechanism of action underlying the beneficial effect of IFN beta in Multiple Sclerosis is poorly understood. Experimental Autoimmune Encephalomyelitis (EAE) is the experimental model for Multiple Sclerosis; therefore, we investigated the effects of recombinant mouse IFN beta on the severity of EAE induced in SJL mice and on cytokine production by Th1 and Th2 lymphocytes. The results indicated that rmIFN beta reduced the disease activity with an I.P, dosage of 10,000 U/day every other day, and successfully treated EAE mice revealed reduced amounts of IFN gamma; no changes in the levels of IL4 were observed, although thera was a significant increase in IL10 and TGF beta production. Beneficial effects on EAE are associated with inhibition of inflammatory cytokines and stimulation of anti-inflammatory cytokines.284170011512

Evidence for cross-reactivity between antigen derived from Trypanosoma cruzi and myelin basic protein in experimental Chagas disease

Evidence for crossreactivity between antigen derived from Trypanosoma cruzi and myelin basic protein in experimental Chagas disease. Experimental Parasitology 89, 304-311. Some autoimmune diseases are thought to arise after an infection. Infectious agents can initiate a chronic inflammatory response associated with autoimmune reactions. Chagas disease, caused by the intracellular parasite Trypanosoma cruzi, is an excellent model for autoimmune disease induced by an infection. The chronic disease is characterized by rich inflammatory infiltrate in myocardial and nervous tissues, with virtually no demonstrable parasites. We were able to demonstrate the presence of antibody to myelin basic protein (MBP) in the serum from T. cruzi chronically infected mice. Lymphocytes from mice immunized with T. cruzi-derived soluble extract antigen (TCSE) proliferate in response to MBP in vitro. Lymphocytes from animals immunized with MBP also were activated by TCSE in vitro. By studying the overlapping peptides from the MBP molecule, we were able to identify two regions responsible for the cross-reactivity. (C) 1998 Academic Press.89330431

Abnormal production of transforming growth factor beta and interferon gamma by peripheral blood cells of patients with multidrug-resistant pulmonary tuberculosis in Brazil

Objectives. The aim of the present study was to determine the immune response profile that differentiates patients with newly diagnosed (non-treated) pulmonary tuberculosis from multidrug-resistant (MDR) ones, as well as from healthy, tuberculin positive individuals. Methods. Lymphocytes proliferative response to non-specific mitogen (PHA) and PPD were evaluated by H-3 thymidine incorporation and cytokines were quantified using an ELISA assay. Results. Patients with active disease showed a diminished proliferative response to PHA and PPD, white multidrug-resistant patients showed a diminished proliferative response to PHA, but a normal response to PPD. The cytokine production of newly diagnosed patients was characterized by a diminished production of IFN gamma and normal production of transforming growth factor (TGF beta), while MDR patients revealed a normal production of IFN gamma accompanied by an increase in TGF beta. Conclusions. The production of significant amounts of TGF beta in MDR patients leads to a poor immune response and may contribute to the resistance of tuberculosis patients to drugs. (C) 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.51431832