COVID-19 and Mortality in the Global Surgical Population: A Systematic Review and Meta-Analysis.

INTRODUCTION: To date, no systematic review or meta-analysis has comprehensively estimated the risk of mortality by surgery type on an international scale. We aim to delineate the risk of mortality in patients with COVID-19 who undergo surgery. METHODS: PubMed (MEDLINE), Scopus, OVID, the World Health Organization Global Literature on Coronavirus Disease, and Corona-Central databases were searched from December 2019 through January 2022. Studies providing data on mortality in patients undergoing surgery were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for abstracting data were followed and performed independently by two reviewers. The main outcome was mortality in patients with COVID-19. RESULTS: Of a total of 4023 studies identified, 46 studies with 80,015 patients met our inclusion criteria. The mean age was 67 y; 57% were male. Surgery types included general (14.9%), orthopedic (23.4%), vascular (6.4%), thoracic (10.6%), and urologic (8.5%). Patients undergoing surgery with COVID-19 elicited a nine-fold increased risk of mortality (relative risk [RR] 8.99, 95% confidence interval [CI] 4.96-16.32) over those without COVID-19. In low-income and middle-income countries (RR: 16.04, 95% CI: 4.59-56.12), the mortality risk was twice as high compared to high-income countries (RR: 7.50, 95% CI: 4.30-13.09). CONCLUSIONS: Mortality risk in surgical patients with COVID-19 compared to those without is increased almost 10-fold. The risk was highest in low-income and middle-income countries compared to high-income countries, suggesting a disproportionate effect of the pandemic on resource-constrained regions.

Association of Long COVID with mental health disorders: a retrospective cohort study using real-world data from the USA.

OBJECTIVES: Mental health disorders (MHD) rank third for US adult hospitalisations. Given the substantial prevalence of 'Long COVID' in SARS-CoV-2 survivors, this study aims to assess its association with increased MHD risk using extensive real-world data. DESIGN: A retrospective cohort study with propensity score matching was conducted. We used the International Classification of Diseases, 10th Revision codes to identify individuals with Long COVID status and COVID-19 histories. Multivariable stratified Cox proportional hazards regression analysis was conducted to determine the association of Long COVID status with MHD. SETTING: Data were sourced from the TriNetX database, spanning records from 1 October 2021 to 16 April 2023. PARTICIPANTS: Two distinct cohorts were established: one comprising individuals diagnosed with Long COVID and another comprising individuals with no history of Long COVID or COVID-19. At the start of the study, none of the participants had a recorded MHD. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcome of interest was a composite diagnosis of MHD. Secondary outcomes were individual mental health conditions. RESULTS: The study included 43 060 control participants without Long COVID and 4306 Long COVID participants, demonstrating well-balanced distribution across all covariates. After adjusting for 4 demographic factors and 10 comorbidities, Long COVID was associated with MHD (adjusted HR, aHR 2.60; 95% CI 2.37 to 2.85). In subgroup analysis, Long COVID was associated with major depression disorder (aHR 3.36; 95% CI 2.82 to 4.00) and generalised anxiety disorder (aHR 3.44; 95% CI 2.99 to 3.96). CONCLUSIONS: In this retrospective large real-world cohort study, Long COVID was associated with an increased risk of incident MHD. The MHD impact is significant considering the vast number of patients with Long COVID. Enhanced MHD screening among COVID-19 survivors should be a priority.

Race and Ethnic Representation in Crohn's Disease Trials of Biologic and Small Molecule Medications: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Randomised controlled trials historically under-represent marginalised racial and ethnic populations. As incidence and prevalence of Crohn's disease in these groups rise, it is important to characterise their inclusion in randomised controlled trials on first-line and pipe-line medications. METHODS: PubMed was searched systematically for randomised controlled trials of biologic and small molecule inhibitor [SMI] medications, with a primary outcome related to efficacy following PRISMA guidelines. We used descriptive statistics to summarise demographic variables and meta-regression analyses to estimate temporal trends in racial inclusion. RESULTS: More than a half of trials did not report any racial/ethnic demographics [53.7%] and several reported racial demographics for only one race [20.9%]. When racial data were reported, Whites made up 90.2% of participants. Percentages of Black, Asian, Native American/Pacific Islander, and participants considered 'Other' averaged 2.9%, 11.6%, 0.5%, and 1.6% out of the total sample sizes of 3901, 3742, 828 and 4027, respectively. Proportional representation of White participants decreased over time [p <0.01] and proportional representation of Asian participants increased over time [p = 0.047]. In ordinal logistic regression, mean year of trial enrolment significantly increased the number of racial groups reported [p <0.001]. CONCLUSIONS: Half of published randomised controlled trials in Crohn's disease contain no racial or ethnic demographics, and the remaining often only have limited inclusion of Black, Native American/Pacific Islander, and Hispanic patients. Further work should characterise representation in observational and prospective trials. Researchers should work to: 1] increase reporting of racial and ethnic demographics; and 2] improve recruitment and retention of marginalised populations.

Human Immunodeficiency Virus (HIV) Treatment With Antiretroviral Therapy Mitigates the High Risk of Mental Health Disorders Associated With HIV Infection in the US Population.

Background: Whether treatment of human immunodeficiency virus (HIV) with antiretroviral therapy (ART) is associated with lower risk of mental health disorders (MHDs) among people with HIV (PWH) remains unknown. We aim to determine the association between HIV and MHDs and whether ART alters the risk of MHDs among PWH in the US adult population. Methods: We conducted a real-world study using the Merative MarketScan claims database (2016-2020), identifying individuals with HIV (diagnosed using International Classification of Diseases, Tenth Revision, Clinical Modification codes) and those without HIV. A multivariable stratified Cox proportional hazard regression model was conducted to examine the association of HIV treatment status with MHDs, adjusting for potential confounders. Additionally, we sought to determine the effect modification of ART on the relationship between living with HIV and MHDs. Results: A total of 313 539 individuals, with a mean age of 44.2 (standard deviation, 11.4) years, predominantly males (81.2%), residing in the South region of the US (50.9%) were included in the present analysis. During 671 880 person-years of follow-up, 46 235 incident MHD cases occurred. In the multivariable Cox proportional hazard model, living with HIV was associated with higher risk of incident MHDs. Relative to those without HIV, the adjusted hazard ratio was 1.85 (95% confidence interval [CI], 1.79-1.92; P < .001) for those with HIV on treatment, and 2.70 (95% CI, 2.59-2.82; P < .001) for those with HIV without any treatment. Stronger associations between HIV and MHDs were observed in men relative to women, among those aged 18-34 years relative to those aged 55-63 years, and among those with no overweight/obesity relative to obese individuals (Pinteraction < .001 for all). Conclusions: HIV was associated with an increased risk of developing MHDs. However, HIV treatment mitigated the risk.

An integrated pipeline for prediction of Clostridioides difficile infection.

With the expansion of electronic health records(EHR)-linked genomic data comes the development of machine learning-enable models. There is a pressing need to develop robust pipelines to evaluate the performance of integrated models and minimize systemic bias. We developed a prediction model of symptomatic Clostridioides difficile infection(CDI) by integrating common EHR-based and genetic risk factors(rs2227306/IL8). Our pipeline includes (1) leveraging phenotyping algorithm to minimize temporal bias, (2) performing simulation studies to determine the predictive power in samples without genetic information, (3) propensity score matching to control for the confoundings, (4) selecting machine learning algorithms to capture complex feature interactions, (5) performing oversampling to address data imbalance, and (6) optimizing models and ensuring proper bias-variance trade-off. We evaluate the performance of prediction models of CDI when including common clinical risk factors and the benefit of incorporating genetic feature(s) into the models. We emphasize the importance of building a robust integrated pipeline to avoid systemic bias and thoroughly evaluating genetic features when integrated into the prediction models in the general population and subgroups.

Associations of Food Addiction Symptomatology and Disordered Eating Behaviors in a Pre-Surgical Bariatric Population.

The construct of food addiction (FA) has been highly debated in recent years particularly in the fields of disordered eating, medical weight management, and bariatric surgery. Some researchers have argued that FA symptoms are distinct, highly prevalent, and present a barrier for patients seeking medical treatment for obesity. The purpose of this study is to evaluate the cross-sectional associations between FA symptomatology, binge eating disorder (BED) and other appetitive traits, as well as dietary quality in a sample of adults with obesity seeking bariatric surgery. This post hoc analysis was conducted on a prospectively collected dataset from August 2020 to August 2022 at a single academic medical center. Descriptive statistics were used to characterize the sample. Additional analyses included: correlation coefficients, multivariable linear regression, and analysis of variance. A total of 587 patients were included in this analysis with low average scores for FA symptoms (mean: 1.48; standard deviation (SD): 2.15). Those with no BED symptoms had the lowest average FA symptoms scores (mean: 0.87; SD: 1.52) and those with both bingeing and LOCE had the highest average scores (mean: 3.35; SD: 2.81). This finding supports the hypothesis that, while related, FA and BED may represent different cognitions and behaviors.

Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.

BACKGROUND: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. METHODS: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes. RESULTS: Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. CONCLUSIONS: Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

Factors associated with pediatric febrile illnesses in 27 countries of Sub-Saharan Africa.

BACKGROUND: Evidence on the relative importance of various factors associated with febrile illness in children and their heterogeneity across countries can inform the prevention, identification, and management of communicable diseases in resource-limited countries. The objective of the study is to assess the relative significance of factors associated with childhood febrile illness in 27 sub-Saharan African countries. METHODS: This cross-sectional study of 298,327 children aged 0 to 59 months assessed the strengths of associations of 18 factors with childhood fevers, using Demographic and Health Surveys (2010-2018) from 27 sub-Saharan African countries. A total of 7 child level factors (i.e., respiratory illness, diarrhea, breastfeeding initiation; vitamin A supplements; child's age; full vaccination; sex), 5 maternal factors (maternal education; maternal unemployment; antenatal care; maternal age, and maternal marriage status) and 6 household factors (household wealth; water source; indoor pollution, stool disposal; family planning needs and rural residence) were assessed. Febrile illness was defined as the presence of fever in 2 weeks preceding the survey. RESULTS: Among the 298,327 children aged 0 to 59 months included in the analysis, the weighted prevalence of fever was 22.65% (95% CI, 22.31%-22.91%). In the pooled sample, respiratory illness was the strongest factor associated with fever in children (adjusted odds ratio [aOR], 5.46; 95% CI, 5.26-5.67; P < .0001), followed by diarrhea (aOR, 2.96; 95% CI, 2.85-3.08; P < .0001), poorest households (aOR, 1.33; 95% CI,1.23-1.44; P < .0001), lack of maternal education (aOR, 1.25; 95% CI, 1.10-1.41; P < .0001), and delayed breastfeeding (aOR, 1.18; 95% CI, 1.14-1.22; P < .0001. Febrile illnesses were more prevalent in children older than >6 months compared to those 6 months and younger. Unsafe water, unsafe stool disposal, and indoor pollution were not associated with child fever in the pooled analysis but had a large country-level heterogeneity. CONCLUSIONS: Major causes of fevers in sub-Saharan Africa could be attributed to respiratory infections and possibly viral infections, which should not be treated by antimalarial drugs or antibiotics. Point-of-care diagnostics are needed to identify the pathogenic causes of respiratory infections to guide the clinical management of fevers in limited-resource countries.

Associations of small vessel disease and acute symptomatic seizures in ischemic stroke patients.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs), markers of small vessel disease are frequent in ischemic stroke, yet the association with acute symptomatic seizures (ASS) has not been well characterized. METHODS: A retrospective cohort of hospitalized patients with anterior circulation ischemic stroke. The association of CMBs with acute symptomatic seizures was assessed using a logistic regression model and causal mediation analysis. RESULTS: Of 381 patients, 17 developed seizures. Compared with patients without CMBs, those with CMBs had a three-fold higher unadjusted odds of seizures (unadjusted OR: 3.84, 95% 1.16-12.71, p = 0.027). After adjusting for confounders such as stroke severity, cortical infarct location, and hemorrhagic transformation, the association between CMBs and ASS was attenuated (adjusted OR: 3.11, 95%CI: 0.74-11.03, p = 0.09). The association was not mediated by stroke severity. CONCLUSION: In this cohort of hospitalized patients with anterior circulation ischemic stroke, CMBs were more likely to be found in patients with ASS than those without ASS, an association that was attenuated when accounting for stroke severity, cortical infarct location, and hemorrhagic transformation. Evaluation of the long-term risk of seizures associated with CMBs and other markers of small vessel disease is warranted.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Mushroom consumption and risk of gastric cancer: a pooled analysis within the stomach cancer pooling project and a combined meta-analysis with other observational studies.

Edible mushrooms have high concentrations of vitamins and minerals. They are considered 'functional foods' for their disease-prevention properties. Mushroom consumption may reduce the risk of gastric cancer, the fifth most common cancer worldwide. We investigated the association between mushroom consumption and gastric cancer risk in a pooled analysis within the Stomach Cancer Pooling (StoP) Project and in a meta-analysis that also included previously published studies. A total of 3900 gastric cancer cases and 7792 controls from 11 studies were included in the StoP analysis. Mushroom consumption was measured using food frequency questionnaires. Higher mushroom consumption was associated with a lower risk of gastric cancer [relative risk (RR) for the highest vs. lowest consumption categories, 0.82; 95% confidence interval (CI), 0.71-0.95]. The corresponding RRs were 0.59 (95% CI, 0.26-1.33) in a meta-analysis of four previously published studies and 0.77 for all studies combined (95% CI, 0.63-0.95; n = 15 studies). In geographic subgroup analysis, the pooled risk in Western Pacific countries was (RR, 0.59; 95% CI, 0.40-0.87; n = 6). The stronger effect in Asian countries may reflect high level of antioxidants in mushroom species consumed in Asia.

Gun violence in United States during the second year of the COVID-19 pandemic.

Objective: In the first year of the COVID-19 pandemic, gun violence (GV) rates in the United States (US) rose by 30%. We estimate the relative risk of GV in the US in the second year compared to the first year of the pandemic, in time and space. Methods: Daily police reports of gun-related injuries and deaths in the 50 states and the District of Columbia from March 1, 2020, to February 28, 2022, were obtained from the GV Archive. Generalized linear mixed-effects models in the form of Poisson regression analyses were utilized to estimate state-specific rates of GV. Results: Nationally, GV rates during the second year of the pandemic (March 1, 2021, through February 28, 2022) remained the same as that of the first year (March 1, 2020, through February 28, 2021) (Intensity Ratio = 0.996; 95% CI 0.98, 1.01; p = 0.53). Nevertheless, hotspots of GV were identified. Nine (18%) states registered a significantly higher risk of GV during the second year of the pandemic compared to the same period in the first year. In 10 (20%) states, the risk of GV during the second year of the pandemic was significantly lower compared to the same period in the first year. Conclusion: GV risk in the US is heterogeneous. It continues to be a public health crisis, with 18% of the states demonstrating significantly higher GV rates during the second year of the COVID-19 pandemic compared to the same timeframe 1 year prior.

Factors associated with pregnancy termination in women of childbearing age in 36 low-and middle-income countries.

Lack of access to safe, affordable, timely and adequate pregnancy termination care, and the stigma associated with abortion in low-middle income countries (LMICs), pose a serious risk to women's physical and mental well-being throughout the lifespan. Factors associated with pregnancy termination and their heterogeneity across countries in LMICs previously have not been thoroughly investigated. We aim to determine the relative significance of factors associated with pregnancy termination in LMICs and its variation across countries. Analysis of cross-sectional nationally representative household surveys carried out in 36 LMICs from 2010 through 2018. The weighted population-based sample consisted of 1,236,330 women of childbearing aged 15-49 years from the Demographic and Health Surveys. The outcome of interest was self-report of having ever had a pregnancy terminated. We used multivariable logistic regression models to identify factors associated with pregnancy termination. The average pooled weighted prevalence of pregnancy termination in the present study was 13.3% (95% CI: 13.2%-13.4%), ranging from a low of 7.8 (95% CI: 7.2, 8.4%) in Namibia to 33.4% (95% CI: 32.0, 34.7%) in Pakistan. Being married showed the strongest association with pregnancy termination (adjusted OR, 2.94; 95% CI, 2.84-3.05; P < 0.001) compared to unmarried women. Women who had more than four children had higher odds of pregnancy termination (adjusted OR, 2.45; 95% CI, 2.33-2.56; P < 0.001). Moreover, increased age and having primary and secondary levels of education were associated with higher odds of pregnancy termination compared to no education. In this study, married women, having one or more living children, those of older age, and those with at least primary level of education were associated with pregnancy termination in these 36 LMICs. The findings highlighted the need of targeted public health intervention to reduce unintended pregnancies and unsafe abortions.

Optimal Duration of Systemic Corticosteroids in Coronavirus Disease 2019 Treatment: A Systematic Review and Meta-analysis.

Background: Corticosteroids confer a survival benefit in individuals hospitalized with coronavirus disease 2019 (COVID-19) who require oxygen. This meta-analysis seeks to determine the duration of corticosteroids needed to optimize this mortality benefit. Methods: Electronic databases were searched to 9 March 2022, for studies reporting corticosteroid versus no corticosteroid treatment in hospitalized COVID-19 patients. We estimated the effect of corticosteroids on mortality by random-effects meta-analyses. Subgroup analyses and meta-analyses were conducted to assess the optimal duration of corticosteroid treatment while adjusting for the severity of disease, age, duration of symptoms, and proportion of control group given steroids. Results: We identified 27 eligible studies consisting of 13 404 hospitalized COVID-19 patients. Seven randomized controlled trials and 20 observational studies were included in the meta-analysis of mortality, which suggested a protective association with corticosteroid therapy (risk ratio [RR], 0.71 [95% confidence interval {CI}, .58-.87]). Pooled analysis of 18 studies showed the greatest survival benefit for a treatment duration up to 6 days (RR, 0.54 [95% CI, .39-.74]). Survival benefit was 0.65 (95% CI, .51-.83) up to 7 days, and no additional survival benefit was observed beyond 7 days of treatment (RR, 0.64 [95% CI, .44-.93]). The survival benefit was not confounded by severity of disease, age, duration of symptoms, or proportion of control group given steroids. Conclusions: In this meta-analysis, optimal duration of corticosteroid treatment for hospitalized COVID-19 patients was up to 6 days, with no additional survival benefit with >7 days of treatment.

Association of COVID-19 with diabetes: a systematic review and meta-analysis.

Emerging evidence suggests that coronavirus disease-2019 (COVID-19) may lead to a wide range of post-acute sequelae outcomes, including new onset of diabetes. The aim of this meta-analysis was to estimate the incidence of newly diagnosed diabetes in survivors of COVID-19. We searched MEDLINE, Scopus, Cochrane Central Register of Controlled Trials and the World Health Organization Global Literature on Coronavirus Disease and clinical trial registries for studies reporting the association of COVID-19 and diabetes. Search dates were December 2019-October 16, 2022. Two investigators independently assessed studies for inclusion. Risk of bias was assessed using the Newcastle-Ottawa Scale. We estimated the effect of COVID-19 on incident diabetes by random-effects meta-analyses using the generic inverse variance method. We identified 8 eligible studies consisting of 4,270,747 COVID-19 patients and 43,203,759 controls. Median age was 43 years (interquartile range, IQR 35-49), and 50% were female. COVID-19 was associated with a 66% higher risk of incident diabetes (risk ratio, 1.66; 95% CI 1.38; 2.00). The risk was not modified by age, sex, or study quality. The median risk of bias assessment was 7. In this systematic review and meta-analysis, COVID-19 was associated with higher risk for developing new onset diabetes among survivors. Active monitoring of glucose dysregulation after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is warranted.

Type IV Pili Are a Critical Virulence Factor in Clinical Isolates of Paenibacillus thiaminolyticus.

Hydrocephalus, the leading indication for childhood neurosurgery worldwide, is particularly prevalent in low- and middle-income countries. Hydrocephalus preceded by an infection, or postinfectious hydrocephalus, accounts for up to 60% of hydrocephalus in these areas. Since many children with hydrocephalus suffer poor long-term outcomes despite surgical intervention, prevention of hydrocephalus remains paramount. Our previous studies implicated a novel bacterial pathogen, Paenibacillus thiaminolyticus, as a causal agent of neonatal sepsis and postinfectious hydrocephalus in Uganda. Here, we report the isolation of three P. thiaminolyticus strains, Mbale, Mbale2, and Mbale3, from patients with postinfectious hydrocephalus. We constructed complete genome assemblies of the clinical isolates as well as the nonpathogenic P. thiaminolyticus reference strain and performed comparative genomic and proteomic analyses to identify potential virulence factors. All three isolates carry a unique beta-lactamase gene, and two of the three isolates exhibit resistance in culture to the beta-lactam antibiotics penicillin and ampicillin. In addition, a cluster of genes carried on a mobile genetic element that encodes a putative type IV pilus operon is present in all three clinical isolates but absent in the reference strain. CRISPR-mediated deletion of the gene cluster substantially reduced the virulence of the Mbale strain in mice. Comparative proteogenomic analysis identified various additional potential virulence factors likely acquired on mobile genetic elements in the virulent strains. These results provide insight into the emergence of virulence in P. thiaminolyticus and suggest avenues for the diagnosis and treatment of this novel bacterial pathogen. IMPORTANCE Postinfectious hydrocephalus, a devastating sequela of neonatal infection, is associated with increased childhood mortality and morbidity. A novel bacterial pathogen, Paenibacillus thiaminolyticus, is highly associated with postinfectious hydrocephalus in an African cohort. Whole-genome sequencing, RNA sequencing, and proteomics of clinical isolates and a reference strain in combination with CRISPR editing identified type IV pili as a critical virulence factor for P. thiaminolyticus infection. Acquisition of a type IV pilus-encoding mobile genetic element critically contributed to converting a nonpathogenic strain of P. thiaminolyticus into a pathogen capable of causing devastating diseases. Given the widespread presence of type IV pilus in pathogens, the presence of the type IV pilus operon could serve as a diagnostic and therapeutic target in P. thiaminolyticus and related bacteria.

Prevalence and determinants of meeting minimum dietary diversity among children aged 6-23 months in three sub-Saharan African Countries: The Demographic and Health Surveys, 2019-2020.

Background: Dietary diversity is an indicator of nutritional adequacy, which plays a significant role in child growth and development. Lack of adequate nutrition is associated with suboptimal brain development, lower school performance, and increased risk of mortality and chronic diseases. We aimed to determine the prevalence and determinants of meeting minimum dietary diversity (MDD), defined as consuming at least five out of eight basic food groups in the previous 24-h in three sub-Saharan African countries. Methods: A weighted population-based cross-sectional study was conducted using the most recent Demographic and Health Surveys (DHS). MDD data were available between 2019 and 2020 for three sub-Saharan African countries (Gambia, Liberia, and Rwanda). The study population included 5,832 children aged 6-23 months. A multivariable logistic regression model was developed to identify independent factors associated with meeting MDD. Results: Overall, the weighted prevalence of children who met the MDD was 23.2% (95% CI: 21.7-24.8%), ranging from 8.6% in Liberia to 34.4% in Rwanda. Independent factors associated with meeting MDD were: age of the child (OR) = 1.96, 95% CI: 1.61, 2.39 for 12-17 months vs. 6-11 months], mothers from highest households' wealth status (OR = 1.86, 95% CI: 1.45-2.39) compared with the lowest, and mothers with secondary/higher education (OR = 1.69, 95% CI: 1.35-2.12) compared with those with no education. Mothers who were employed, had access to a radio, and those who visited a healthcare facility in the last 12 months were more likely to meet the MDD. There was no significant association between the child's sex and the odds of fulfilling the MDD. Conclusions: There is substantial heterogeneity in the prevalence of MDD in these three sub-Saharan African countries. Lack of food availability or affordability may play a significant role in the low prevalence of MDD. The present analysis suggests that policies that will effectively increase the prevalence of meeting MDD should target poor households with appropriate materials or financial assistance and mothers with lower literacy. Public health interventions working with sectors such as education and radio stations to promote health education about the benefits of diverse diets is a critical step toward improving MDD in sub-Saharan Africa and preventing undernutrition.

Myocarditis in SARS-CoV-2 infection vs. COVID-19 vaccination: A systematic review and meta-analysis.

Background: This study aimed to compare the incidence of myocarditis in COVID-19 vaccines and in severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection groups. Methods: Electronic databases (MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the WHO Global Literature on Coronavirus Disease) and trial registries were searched up to May 2022, for randomized controlled trials and observational cohort studies reporting the risk of myocarditis associated with the COVID-19 vaccines and the risk associated with SARS-CoV-2 infection. We estimated the effect of COVID-19 infection and vaccines on rates of myocarditis by random-effects meta-analyses using the generic inverse variance method. Meta-regression analyses were conducted to assess the effect of sex and age on the incidence of myocarditis. Results: We identified 22 eligible studies consisting of 55.5 million vaccinated cohorts and 2.5 million in the infection cohort. The median age was 49 years (interquartile range (IQR): 38-56), and 49% (IQR: 43 to 52%) were men. Of patients diagnosed with myocarditis (in both vaccination and COVID-19 cohort) 1.07% were hospitalized and 0.015% died. The relative risk (RR) for myocarditis was more than seven times higher in the infection group than in the vaccination group [RR: 15 (95% CI: 11.09-19.81, infection group] and RR: 2 (95% CI: 1.44-2.65, vaccine group). Of patients who developed myocarditis after receiving the vaccine or having the infection, 61% (IQR: 39-87%) were men. Meta-regression analysis indicated that men and younger populations had a higher risk of myocarditis. A slow decline in the rates of myocarditis was observed as a function of time from vaccination. The risk of bias was low. Conclusion: In this systematic review and meta-analysis, we found that the risk of myocarditis is more than seven fold higher in persons who were infected with the SARS-CoV-2 than in those who received the vaccine. These findings support the continued use of mRNA COVID-19 vaccines among all eligible persons per CDC and WHO recommendations.

Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.