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

Evidence of a humoral response to a novel protein WARF4 embedded in the West Nile virus NS4B gene encoded by an alternative open reading frame

West Nile virus (WNV) is a flavivirus that is maintained in a bird-mosquito transmission cycle. Humans, horses and other non-avian vertebrates are usually incidental hosts. However, WNV is a neurotropic virus, which requires an efficient humoral response for the control of a neuroinvasive infection. The WNV genome encodes three structural (capsid, premembrane/membrane and envelope) and seven non-structural proteins. Bioinformatic analysis performed on the WNV genomes detected a conserved alternative open reading frame restricted to the lineage I virus. To quickly verify the existence of this putative protein, entitled West Nile Alternative Reading Frame 4 (WARF4), we produced a prokaryotic recombinant source of WARF4 and verified its immunogenicity in vivo by analyzing 43 horse serum samples, of which 15 were positive for antibodies to WNV premembrane and envelope (prM-E) proteins. Specific antibodies to WARF4 were significantly detected in 5 out of the 15 serum samples testing positive for antibodies to prM-E WNV proteins. Our findings provide evidence of a significant antibody response to the WARF4 protein in the serum of the horse testing positive for antibodies to prM-E proteins, thus indicating that this antigen might be a potential tool for further characterization of the immune response of WNV infections in humans as well

Genetic diversity of Theileria equi and Babesia caballi infecting horses of Central-Southern Italy and preliminary results of its correlation with clinical and serological status.

Babesia caballi and Theileria equi are tick-borne pathogens causing equine piroplasmosis infecting the Equidae family in which they cause significant sanitary and economic losses. Furthermore, equine piroplasmosis is included in the World Animal Health Organization (OIE) notifiable diseases list with possible movement restrictions for positive horses. Thirty-nine EDTA and whole-blood samples collected during 2013 and 2014 from symptomatic and asymptomatic horses of Central-Southern Italy were included in the present study either because of their strongly positive results in Real Time (RT) PCRs targeting the 18S rRNA gene specific for each piroplasm and/or due to their serological ELISA/18S rRNA RT-PCR discordant results. A nested PCR amplifying the hypervariable V4 region of the 18S rRNA gene of both piroplasms was performed on all samples. T. equi positive samples were also analysed with a PCR targeting the equi merozoite antigen 1-gene (EMA-1). The sequences obtained were thirty for T. equi, 25 of which were for the hypervariable V4 region of the 18S rRNA gene and 13 for the EMA-1 gene, with eight samples positive for both targets, while only six 18S rRNA gene sequences were retrieved for B. caballi. The phylogenetic analysis results are as follows: T. equi sequences of the 18S rRNA gene clustered in three different phylogenetic groups, respectively in the A (15), B (9) and C (1) while those of B. caballi in the A (1), B1 (3) and B2 (2) groups. T. equi sequences for EMA-1 gene clustered in A (11) and in B (2). This analysis confirms that both T. equi and B. caballi sequences present a genetic heterogeneity independently of their geographical location, similar to that reported by other authors. Statistical associations were evaluated between phylogenetic groups of T. equi 18S rRNA gene and each of the following variables, using Fisher's exact test: clinical signs, serological ELISA/18S rRNA RT-PCR discordant results and T. equi EMA-1 negativity. The different groups were found to be statistically related to the presence of signs (less present in group B samples), to ELISA negativity/18S rRNA RT-PCR positivity (more seronegative samples in group B). No statistical analysis was performed for the B. caballi as the number of sequences available was insufficient and for the EMA −1 sequences which almost all grouped in the same cluster. The results here obtained provide additional information about T. equi and B. caballi sequences, which could also be used to verify the performance of serological and molecular diagnostic methods

VDAC2 enables BAX to mediate apoptosis and limit tumor development

Intrinsic apoptosis is critical to prevent tumor formation and is engaged by many anti-cancer agents to eliminate tumor cells. BAX and BAK, the two essential mediators of apoptosis, are thought to be regulated through similar mechanisms and act redundantly to drive apoptotic cell death. From an unbiased genome-wide CRISPR/Cas9 screen, we identified VDAC2 (voltage-dependent anion channel 2) as important for BAX, but not BAK, to function. Genetic deletion of VDAC2 abrogated the association of BAX and BAK with mitochondrial complexes containing VDAC1, VDAC2, and VDAC3, but only inhibited BAX apoptotic function. Deleting VDAC2 phenocopied the loss of BAX in impairing both the killing of tumor cells by anti-cancer agents and the ability to suppress tumor formation. Together, our studies show that efficient BAX-mediated apoptosis depends on VDAC2, and reveal a striking difference in how BAX and BAK are functionally impacted by their interactions with VDAC2