Outcomes of stab wounds presenting to Kamuzu Central Hospital in Malawi

IntroductionInjuries are a leading cause of morbidity and mortality worldwide, necessitating that we understand the local burden of injury to improve injury-related trauma care and patient outcomes. The characteristics, outcomes, and risk factors for mortality following stab wounds in Malawi are poorly delineated.MethodsThis is a retrospective, descriptive analysis of patients presenting to Kamuzu Central Hospital in Lilongwe, Malawi, with stab wounds from February 2008 to May 2018. Univariate and bivariate analyses were performed to compare patient and injury characteristics based on mortality. We performed Poisson multivariate regression to predict the factors that increase the relative risk of mortality. Results During the study, 32,297 patients presented with assault. Of those patients, 2,352 (7.3%) presented with stab wounds resulting in a 3.2% (n=74) overall mortality. The majority of wounds were to the head or cervical spine (n=1,043, 44.6%), while injuries to the chest (n=319, 13.7%) were less frequent. We found an increased relative risk of mortality in patients who presented with an injury to the chest (RR 3.95, 95% CI 1.79-8.72, p=0.001) and who were brought in by the police (RR 33.24, 95% CI 11.23–98.35, p<0.001). ConclusionIn this study, stab wounds accounted for 7.3% of all assault cases, with a 3.2% mortality. Though the commonest site of stab was the head, wounds to the chest conferred the highest relative risk of mortality. A multifaceted approach to reducing mortality is needed. Incorporating training of first responders in basic life support, including the police, may reduce stab-related mortality

Difference in Postoperative Outcomes and Perioperative Resource Utilization Between General Surgeons and Pediatric Surgeons: A Systematic Review

Background: Both general surgeons (GS) and pediatric surgeons (PS) perform a high volume of appendectomies in pediatric patients, but there is a paucity of data on these outcomes based on surgeon training. We performed a systematic review and meta-analysis to compare postoperative outcomes and perioperative resource utilization for pediatric appendectomies.Methods: We searched PubMed to identify articles examining the association between surgeon specialization and outcomes for pediatric patients undergoing appendectomies. Study selection, data extraction, risk of bias assessment, and quality assessment were performed by one reviewer, with another reviewer to resolve discrepancies.Results: We identified 4799 articles, with 98.4% (4724/2799) concordance after initial review. Following resolution of discrepancies, 16 studies met inclusion criteria. Of the studies that reported each outcome, GS and PS demonstrated similar rates of readmission within 30 days (pooled RR 1.61 95% CI 0.66, 2.55) wound infections (pooled RR 1.07, 95% CI .55, 1.60), use of laparoscopic surgery (pooled RR 1.87, 95% CI .21, 3.53), postoperative complications (pooled RR 1.40, 95% CI .83, 1.97), use of preoperative imaging (pooled RR .98,95% CI .90, 1.05), and intra-abdominal abscesses (pooled RR .80, 95% CI .03, 1.58). Patients treated by GS did have a significantly higher risk of negative appendectomies (pooled RR 1.47, 95% CI 1.10, 1.84) when compared to PS.Discussion: This is the first meta-analysis to compare outcomes for pediatric appendectomies performed by GS compared to PS. Patient outcomes and resource utilization were similar among PS and GS, except for negative appendectomies were significantly more likely with GS

Injury Patterns, Imaging Usage, and Disparities Associated With Car Restraint Use in Children

Background Motor vehicle collision (MVC) is a leading cause of accidental death in children. Despite effective forms of child safety restraint (eg, car seat and booster seat), studies demonstrate poor compliance with guidelines. The goal of this study was to delineate injury patterns, imaging usage, and potential demographic disparities associated with child restraint use following MVC. Methods A retrospective review of the North Carolina Trauma Registry was performed to determine demographic factors and outcomes associated with improper restraint of children (0-8 years) involved in MVC from 2013 to 2018. Bivariate analysis was performed by the appropriateness of restraint. Multivariable Poisson regression identified demographic factors for the relative risk of inappropriate restraint. Results Inappropriately restrained patients were older (5.1 years v. 3.6 yrs, P < .001) and weighed more (44.1 lbs v. 35.3 lbs, P < .001). A higher proportion of African American (56.9% v. 39.3%, P < .001) and Medicaid (52.2% v. 39.0%, P < .001) patients were inappropriately restrained. Multivariable Poisson regression showed that African American patients (RR 1.43), Asian patients (RR 1.51), and Medicaid payor status (RR 1.25) were associated with a higher risk of inappropriate restraint. Inappropriately restrained patients had a longer length of stay, but injury severity score and mortality were no different. Discussion African American children, Asian children, and Medicaid insurance payor status patients had an increased risk of inappropriate restraint use in MVC. This study describes unequal restraint patterns in children, which suggests opportunity for targeted patient education and necessitates research to further delineate the underlying etiology of these differences

The Effect of an Enhanced Recovery Protocol on Pediatric Colorectal Surgical Patient Outcomes at a Single Institution

Introduction Enhanced recovery protocols (ERP) have been associated with fewer postoperative complications in adult colorectal surgery patients, but there is a paucity of data on pediatric patients. Our aim is to describe the effect of an ERP, compared to conventional care, on pediatric colorectal surgical complications. Materials and Methods We performed a single institution, retrospective cohort study (2014-2020) on pediatric (≤18 years old) colorectal surgery patients pre- and post-implementation of an ERP. Bivariate analysis and logistic regression were used to assess the effect of an ERP on return visits to the emergency room, reoperation, and readmission within 30-days. Results There were 194 patients included in this study, with 54 in the control cohort and 140 in the ERP cohort. There was no significant difference in the age, BMI, primary diagnosis, or use of laparoscopic technique between the cohorts. The ERP cohort had a significantly shorter foley duration, postoperative stay, and had nerve blocks performed. After controlling for pertinent covariates, the ERP cohort experienced higher odds of reoperation within 30 days (OR 5.83, P = .04). There was no significant difference in the other outcomes analyzed. Conclusion In this study, there was no difference in the odds of overall complications, readmission or return to the ER within 30-days of surgery. However, although infrequent, there were higher odds of returns to the OR within 30 days. Future studies are needed to analyze how adherence to individual components may influence patient outcomes to ensure patient safety during ERP implementation

A unified framework for multi-locus association analysis of both common and rare variants

<p>Abstract</p> <p>Background</p> <p>Common, complex diseases are hypothesized to result from a combination of common and rare genetic variants. We developed a unified framework for the joint association testing of both types of variants. Within the framework, we developed a union-intersection test suitable for genome-wide analysis of single nucleotide polymorphisms (SNPs), candidate gene data, as well as medical sequencing data. The union-intersection test is a composite test of association of genotype frequencies and differential correlation among markers.</p> <p>Results</p> <p>We demonstrated by computer simulation that the false positive error rate was controlled at the expected level. We also demonstrated scenarios in which the multi-locus test was more powerful than traditional single marker analysis. To illustrate use of the union-intersection test with real data, we analyzed a publically available data set of 319,813 autosomal SNPs genotyped for 938 cases of Parkinson disease and 863 neurologically normal controls for which no genome-wide significant results were found by traditional single marker analysis. We also analyzed an independent follow-up sample of 183 cases and 248 controls for replication.</p> <p>Conclusions</p> <p>We identified a single risk haplotype with a directionally consistent effect in both samples in the gene <it>GAK</it>, which is involved in clathrin-mediated membrane trafficking. We also found suggestive evidence that directionally inconsistent marginal effects from single marker analysis appeared to result from risk being driven by different haplotypes in the two samples for the genes <it>SYN3 </it>and <it>NGLY1</it>, which are involved in neurotransmitter release and proteasomal degradation, respectively. These results illustrate the utility of our unified framework for genome-wide association analysis of common, complex diseases.</p

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

A LOV Protein Modulates the Physiological Attributes of Xanthomonas axonopodis pv. citri Relevant for Host Plant Colonization

Recent studies have demonstrated that an appropriate light environment is required for the establishment of efficient vegetal resistance responses in several plant-pathogen interactions. The photoreceptors implicated in such responses are mainly those belonging to the phytochrome family. Data obtained from bacterial genome sequences revealed the presence of photosensory proteins of the BLUF (Blue Light sensing Using FAD), LOV (Light, Oxygen, Voltage) and phytochrome families with no known functions. Xanthomonas axonopodis pv. citri is a Gram-negative bacterium responsible for citrus canker. The in silico analysis of the X. axonopodis pv. citri genome sequence revealed the presence of a gene encoding a putative LOV photoreceptor, in addition to two genes encoding BLUF proteins. This suggests that blue light sensing could play a role in X. axonopodis pv. citri physiology. We obtained the recombinant Xac-LOV protein by expression in Escherichia coli and performed a spectroscopic analysis of the purified protein, which demonstrated that it has a canonical LOV photochemistry. We also constructed a mutant strain of X. axonopodis pv. citri lacking the LOV protein and found that the loss of this protein altered bacterial motility, exopolysaccharide production and biofilm formation. Moreover, we observed that the adhesion of the mutant strain to abiotic and biotic surfaces was significantly diminished compared to the wild-type. Finally, inoculation of orange (Citrus sinensis) leaves with the mutant strain of X. axonopodis pv. citri resulted in marked differences in the development of symptoms in plant tissues relative to the wild-type, suggesting a role for the Xac-LOV protein in the pathogenic process. Altogether, these results suggest the novel involvement of a photosensory system in the regulation of physiological attributes of a phytopathogenic bacterium. A functional blue light receptor in Xanthomonas spp. has been described for the first time, showing an important role in virulence during citrus canker disease

Genomic Ancestry of North Africans Supports Back-to-Africa Migrations

North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from “back-to-Africa” gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa

Quantitative trait locus analysis identifies Gabra3 as a regulator of behavioral despair in mice

The Tail Suspension Test (TST), which measures behavioral despair, is widely used as an animal model of human depressive disorders and antidepressant efficacy. In order to identify novel genes involved in the regulation of TST performance, we crossed an inbred strain exhibiting low immobility in the TST (RIIIS/J) with two high-immobility strains (C57BL/6J and NZB/BlNJ) to create two distinct F2 hybrid populations. All F2 offspring (n = 655) were genotyped at high density with a panel of SNP markers. Whole-genome interval mapping of the F2 populations identified statistically significant quantitative trait loci (QTLs) on mouse chromosomes (MMU) 4, 6, and X. Microarray analysis of hippocampal gene expression in the three parental strains was used to identify potential candidate genes within the MMUX QTLs identified in the NZB/BlNJ × RIIIS/J cross. Expression of Gabra3, which encodes the GABAA receptor α3 subunit, was robust in the hippocampus of B6 and RIIIS mice but absent from NZB hippocampal tissue. To verify the role of Gabra3 in regulating TST behavior in vivo, mice were treated with SB-205384, a positive modulator of the α3 subunit. SB-205384 significantly reduced TST immobility in B6 mice without affecting general activity, but it had no effect on behavior in NZB mice. This work suggests that GABRA3 regulates a behavioral endophenotype of depression and establishes this gene as a viable new target for the study and treatment of human depression