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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

DOES SLC11A2 GENE MUTATION ASSOCIATE WITH IRON-REFRACTORY IRON-DEFICIENCY ANEMIA AFTER BARIATRIC SURGERY?

ABSTRACT - BACKGROUND: After bariatric surgery, if there is iron-refractory iron-deficiency anemia (IRIDA) and does not respond to supplemental iron therapy, excluding other possible etiologies, genetic changes involved in iron metabolism should be considered. AIM: This study aimed to investigate the association of both mutations 1285G-C and 1246C-T, in the SLC11A2 gene, and the etiopathogenesis of anemia refractory to iron supplementation in patients undergoing bariatric surgery using Roux-en-Y gastric bypass (RYGB). METHODS: A case-control study was conducted, in which 100 patients were evaluated as Cases Group [subdivided into (i) with Anemia and (ii) without Anemia] and 100 individuals as Controls, comprising both sexes. Inherited and acquired causes of IRIDA were excluded. DNA was extracted from leukocytes of peripheral blood, and the regions that cover both mutations have been amplified by the molecular techniques such as polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 1285G-C mutation was not determined in any of the 400 alleles analyzed. Regarding the 1246C-T mutation, the wild CC genotype was found with a higher prevalence in the Control Group (34%) (OR 0.5475; 95%CI 0.2920-1.027; p=0.0827). The mutant TT genotype was found only in the Cases Group I (with Anemia) (13%). CONCLUSION: The results show the association between 1246C-T mutation, in the SLC11A2 gene, and the etiopathogenesis of IRIDA to iron supplementation in the evaluated sample. There are differences, at the molecular level, in patients with and without IRIDA after bariatric surgery using RYGB.</jats:p

DOES SLC11A2 GENE MUTATION ASSOCIATE WITH IRON-REFRACTORY IRON-DEFICIENCY ANEMIA AFTER BARIATRIC SURGERY?

ABSTRACT - BACKGROUND: After bariatric surgery, if there is iron-refractory iron-deficiency anemia (IRIDA) and does not respond to supplemental iron therapy, excluding other possible etiologies, genetic changes involved in iron metabolism should be considered. AIM: This study aimed to investigate the association of both mutations 1285G-C and 1246C-T, in the SLC11A2 gene, and the etiopathogenesis of anemia refractory to iron supplementation in patients undergoing bariatric surgery using Roux-en-Y gastric bypass (RYGB). METHODS: A case-control study was conducted, in which 100 patients were evaluated as Cases Group [subdivided into (i) with Anemia and (ii) without Anemia] and 100 individuals as Controls, comprising both sexes. Inherited and acquired causes of IRIDA were excluded. DNA was extracted from leukocytes of peripheral blood, and the regions that cover both mutations have been amplified by the molecular techniques such as polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 1285G-C mutation was not determined in any of the 400 alleles analyzed. Regarding the 1246C-T mutation, the wild CC genotype was found with a higher prevalence in the Control Group (34%) (OR 0.5475; 95%CI 0.2920-1.027; p=0.0827). The mutant TT genotype was found only in the Cases Group I (with Anemia) (13%). CONCLUSION: The results show the association between 1246C-T mutation, in the SLC11A2 gene, and the etiopathogenesis of IRIDA to iron supplementation in the evaluated sample. There are differences, at the molecular level, in patients with and without IRIDA after bariatric surgery using RYGB.</div

IS -94INS/DELATTG POLYMORPHISM IN THE NUCLEAR FACTOR KAPPA-B1 GENE (NFKB1) ASSOCIATED WITH NECROTIZING ENTEROCOLITIS?

ABSTRACT BACKGROUND: Abnormalities in the different stages of the intestinal maturation process cause metabolic and molecular changes. Among the genetic alterations associated with necrotizing enterocolitis, the -94ins/delATTG polymorphism in NFKB1 gene leads to unregulated activation of the NFKB protein due to an increase in the inherent pro-inflammatory state of the premature intestine. AIMS:To determine the prevalence of the -94ins/delATTG polymorphism in NFKB1 gene in neonates with and without necrotizing enterocolitis. METHODS:This is a case-control study, in which 25 neonates were evaluated as the case group and 50 neonates as the control group, of both genders. DNA was extracted from peripheral blood leukocytes, and the site encompassing the polymorphism was amplified by molecular techniques (polymerase chain reaction/polymorphism in restriction fragment length). RESULTS:Necrotizing enterocolitis was diagnosed in 25 (33%) neonates and, of these, 3 (12%) died. Male gender was more prevalent in both groups (p=0.1613): cases (52%) and controls (62%). Moderate and extreme preterm newborns were predominant in both groups: cases (80%) and controls (88%) (p=0.3036). Low birth weight and extremely low birth weight newborns were the most prevalent in cases (78%), and very low birth weight and extremely low birth weight were the most prevalent in controls (81%) (p=0.1073). Clinical treatment was successful in 72%, and hospital discharge was achieved in 88% of newborns with NEC. The -94ins/delATTG polymorphism in NFKB1 gene was not identified in all the 150 alleles analyzed (100%). CONCLUSIONS:The absence of the -94ins/delATTG polymorphism in NFKB1 gene in newborns with and without necrotizing enterocolitis does not rule out the possibility of alterations in this and/or in other genes in newborns with this condition, which reinforces the need for further research.</jats:p

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p&lt;0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p&lt;0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status