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

Proteomics of Secretory and Endocytic Organelles in Giardia lamblia

Giardia lamblia is a flagellated protozoan enteroparasite transmitted as an environmentally resistant cyst. Trophozoites attach to the small intestine of vertebrate hosts and proliferate by binary fission. They access nutrients directly via uptake of bulk fluid phase material into specialized endocytic organelles termed peripheral vesicles (PVs), mainly on the exposed dorsal side. When trophozoites reach the G2/M restriction point in the cell cycle they can begin another round of cell division or encyst if they encounter specific environmental cues. They induce neogenesis of Golgi-like organelles, encystation-specific vesicles (ESVs), for regulated secretion of cyst wall material. PVs and ESVs are highly simplified and thus evolutionary diverged endocytic and exocytic organelle systems with key roles in proliferation and transmission to a new host, respectively. Both organelle systems physically and functionally intersect at the endoplasmic reticulum (ER) which has catabolic as well as anabolic functions. However, the unusually high degree of sequence divergence in Giardia rapidly exhausts phylogenomic strategies to identify and characterize the molecular underpinnings of these streamlined organelles. To define the first proteome of ESVs and PVs we used a novel strategy combining flow cytometry-based organelle sorting with in silico filtration of mass spectrometry data. From the limited size datasets we retrieved many hypothetical but also known organelle-specific factors. In contrast to PVs, ESVs appear to maintain a strong physical and functional link to the ER including recruitment of ribosomes to organelle membranes. Overall the data provide further evidence for the formation of a cyst extracellular matrix with minimal complexity. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000694

Mitochondria, hydrogenosomes and mitosomes: products of evolutionary tinkering!

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Epigenetics of Autoimmune Diseases

This chapter provides several examples of epigenetic deregulation in autoimmune diseases, a heterogeneous group of human conditions characterized by a deregulated immune response against the body own organs and tissues. Early studies based on the candidate gene approach have been flanked by genomewide screenings in the last few years, revealing global changes in DNA methylation or histone tail modifications, as well as deregulated methylation and/or expression of hundreds of genes and microRNAs in cells from patients affected by those disorders. This chapter will focus on epigenetic deregulations observed in systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, psoriasis, multiple sclerosis, systemic sclerosis, and autoimmune thyroid diseases, even though epigenetic modifications are increasingly being observed in many other autoimmune diseases. By contrast, only a few environmental factors have been shown or suspected to induce the observed epigenetic changes. Epigenetic drugs and RNA silencing experiments have often reversed autoimmune disease-like phenotypes in rodents or cell cultures, leading researchers to debate on their potential use in the treatment of these human conditions

Understanding differences between summer vs. school obesogenic behaviors of children: the structured days hypothesis

Abstract Background Although the scientific community has acknowledged modest improvements can be made to weight status and obesogenic behaviors (i.e., physical activity, sedentary/screen time, diet, and sleep) during the school year, studies suggests improvements are erased as elementary-age children are released to summer vacation. Emerging evidence shows children return to school after summer vacation displaying accelerated weight gain compared to the weight gained occurring during the school year. Understanding how summer days differ from when children are in school is, therefore, essential. Discussion There is limited evidence on the etiology of accelerated weight gain during summer, with few studies comparing obesogenic behaviors on the same children during school and summer. For many children, summer days may be analogous to weekend days throughout the school year. Weekend days are often limited in consistent and formal structure, and thus differ from school days where segmented, pre-planned, restrictive, and compulsory components exist that shape obesogenic behaviors. The authors hypothesize that obesogenic behaviors are beneficially regulated when children are exposed to a structured day (i.e., school weekday) compared to what commonly occurs during summer. This is referred to as the ‘Structured Days Hypothesis’ (SDH). To illustrate how the SDH operates, this study examines empirical data that compares weekend day (less-structured) versus weekday (structured) obesogenic behaviors in U.S. elementary school-aged children. From 190 studies, 155 (~80%) demonstrate elementary-aged children’s obesogenic behaviors are more unfavorable during weekend days compared to weekdays. Conclusion In light of the SDH, consistent evidence demonstrates the structured environment of weekdays may help to protect children by regulating obesogenic behaviors, most likely through compulsory physical activity opportunities, restricting caloric intake, reducing screen time occasions, and regulating sleep schedules. Summer is emerging as the critical period where childhood obesity prevention efforts need to be focused. The SDH can help researchers understand the drivers of obesogenic behaviors during summer and lead to innovative intervention development