Glutathione S-transferase M1, T1 and P1 gene polymorphisms and the risk of developing type 2 diabetes mellitus in Egyptian diabetic patients with and without diabetic vascular complications

Background and aim of work: Persistent oxidative stress is one of several factors thatparticipate in the pathogenesis of type 2 diabetes mellitus (T2DM). Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that exert important antioxidant roles in the elimination of reactive oxygen species. We aimed to assess the association of genetic polymorphisms in the GST isoenzymes M1, T1 and P1 with the risk of developing T2DM and its vascular related complications in Egyptian diabetic patients.Subjects and methods: Fifty-four T2DM patients of whom twenty-seven were suffering from vascular complications were compared to fifty-one healthy volunteers. Null genotypes in the GST M1 and T1 genes were screened using polymerase chain reaction (PCR). The A313G single nucleotide polymorphism in the GSTP1 gene was detected using PCR–restriction fragment length polymorphism.Results: No significant differences were noted between diabetic cases and control group regarding frequencies of null genotypes of GSTM1 and GSTT1 genes (χ2p=0.631 and χ2p= 0.832, respectively). Furthermore, both null genotypes were not associated with the risk of developing T2DM or its related vascular complications whether alone or in combination. The frequency of the heterozygous mutation (AG) in the A313G GSTP1 polymorphism among diabetic cases with and diabetic cases without vascular complications was significantly higher compared to the control group (p=0.023). The risk of developing T2DM was significantly higher in cases presenting with combined heterozygous GSTP1 and null GSTM1 genotypes (Odds ratio= 6.285, 95% confidence interval =1.184–33.347, p=0.021).Conclusion: Our results could point out to potential roles of GSTP1 polymorphism alone or combined with GSTM1 gene polymorphism in the pathogenesis of T2DM related oxidative stress. Screening for other functional GST gene polymorphisms is important to understand the impact of interaction of multiple genetic factors in the pathogenesis of T2DM

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone