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Summary: Our study examined associations of the CXC motif chemokine ligand 9 (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with musculoskeletal function in elderly men. We found in certain outcomes both cross-sectional and longitudinal significant associations of CXCL9 with poorer musculoskeletal function and increased mortality in older men. This requires further investigation. Purpose: We aim to determine the relationship of (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with both cross-sectional and longitudinal musculoskeletal outcomes and mortality in older men. Methods: A random sample from the Osteoporotic Fractures in Men (MrOS) Study cohort (N = 300) was chosen for study subjects that had attended the third and fourth clinic visits, and data was available for major musculoskeletal outcomes (6 m walking speed, chair stands), hip bone mineral density (BMD), major osteoporotic fracture, mortality, and serum inflammatory markers. Serum levels of CXCL9 were measured by ELISA, and the associations with musculoskeletal outcomes were assessed by linear regression and fractures and mortality with Cox proportional hazards models. Results: The mean CXCL9 level of study participants (79.1 ± 5.3 years) was 196.9 ± 135.2 pg/ml. There were significant differences for 6 m walking speed, chair stands, physical activity scores, and history of falls in the past year across the quartiles of CXCL9. However, higher CXCL9 was only significantly associated with changes in chair stands (β = − 1.098, p < 0.001) even after adjustment for multiple covariates. No significant associations were observed between CXCL9 and major osteoporotic fracture or hip BMD changes. The risk of mortality increased with increasing CXCL9 (hazard ratio quartile (Q)4 vs Q1 1.98, 95% confidence interval 1.25–3.14; p for trend < 0.001). Conclusions: Greater serum levels of CXCL9 were significantly associated with a decline in chair stands and increased mortality. Additional studies with a larger sample size are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Honey bees assume a pivotal role as primary pollinators, but they are currently facing a growing crisis of colony losses on a global scale. This sector is important for generating essential products, preserving ecosystems, and crop pollination. This study includes the sampling of 179 beehives from three apiaries in the traditional beekeeping area of Extremadura (Spain) vital beekeeping sector and was carried out between 2020 and 2021 using the decision trees-based model. Some studies have tried to identify the primary causative factors of this issue. However, it is insufficient because the approach disregards potential nonlinear interactions among the various factors. For this reason, through meticulous exploration of different causative factors including Varroa destructor, Nosema ceranae, Deformed Wing Virus (DWV), Chronic Bee Paralysis Virus (CBPV), and strength factors, our study employed for first time machine learning methods to identify the most important variables generating colony loss. Our analysis underscores the importance of brood levels (operculated and open), pollen and honey, Varroa destructor infestation, virus (DWV), and honey bee populations as key determinants of colony survival. These findings hold promise for guiding efficacious colony management strategies and underscoring the latent potential of machine-learning applications in the realm of beekeeping. [ABSTRACT FROM AUTHOR]

Pasteurella spp. can cause fatal zoonotic infections in humans. We performed a multicenter study to investigate the prevalence and clinical features of Pasteurella infections in South Korea during 2018‒2022. We also conducted a collaborative systematic review and metaanalysis of the global burden of Pasteurella bacteremia. The study included 283 cases and found an increasing trend in Pasteurella infections. Blood cultures were positive in 8/35 (22.9%) cases sampled, for an overall bacteremia-associated rate of 2.8% (8/283). Aging was a significant risk factor for bacteremia (odds ratio 1.05 [95% CI 1.01–1.10]), according to multivariate analyses. For the meta-analysis, we included a total of 2,012 cases from 10 studies. The pooled prevalence of bacteremia was 12.4% (95% CI 7.3%–18.6%) and of mortality 8.4% (95% CI 2.7%–16.5%). Our findings reflect the need for greater understanding of the increase in Pasteurella infections and the global burden of Pasteurella bacteremia to determine appropriate case management. [ABSTRACT FROM AUTHOR]

Background: Critically ill patients with chronic obstructive pulmonary disease (COPD) face significant mortality after hospital discharge. Delirium is common in patients with COPD, but its impact on long-term mortality in critically ill COPD patients who survive to discharge remains uncertain. Methods: Critically ill patients with COPD who survived to discharge were selected from the Medical Information Mart for Intensive Care IV database. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. The primary outcome was 365- and 180-day mortality after discharge. The secondary outcomes included 90- and 30-day mortality following discharge, length of intensive care unit (ICU) and hospital stays, and nursing care needs after hospital discharge. Results: Of the 2621 survivors of critically ill COPD patients, 982 had suffered delirium during their ICU stay and 709 died within 365 days after hospital discharge. Delirium was significantly associated with 365-day mortality after hospital discharge (adjusted hazard ratio [HR] 1.22; 95% confidence interval [CI] 1.02–1.47). The results were consistent for 180-, 90-, and 30-day post-discharge mortality (adjusted HR [95% CI]: 1.35 [1.09–1.66], 1.48 [1.16–1.89], and 1.68 [1.21–2.32], respectively). Additionally, patients with delirium had longer ICU and hospital stay (adjusted β 2.75; 95% CI 2.35–3.16 and 4.25; 95% CI 3.51–4.98, respectively) and increased nursing care needs after hospital discharge (adjusted odds ratio, 1.56; 95% CI 1.13–2.14). Conclusion: ICU delirium was an independent risk factor for both long-term and short-term mortality in critically ill patients with COPD who survived to discharge. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Limited evidence is available on the most effective diagnostic approaches, management strategies, and long-term outcomes for CAP in patients who have undergone solid organ transplantation. What is the acute and long-term morbidity and mortality after CAP in organ transplant recipients? We retrospectively analyzed hospitalizations for CAP in solid organ recipients at the largest German transplant center. The study included patients admitted between January 1, 2010, and May 31, 2021. The reported outcomes are in-hospital and 1-year mortality, risk of cardiovascular events during hospitalization and at 1 year, admission to the ICU, and risk of pneumonia with Pseudomonas aeruginosa. Multivariable binary logistic regression using stepwise forward selection was performed to determine predictive factors for pneumonia with P aeruginosa. We analyzed data from 403 hospitalizations of 333 solid organ recipients. In > 60% of cases, patients had multiple comorbidities, with cardiovascular and chronic kidney disease being the most prevalent. More than one-half of the patients required oxygen supplementation after admission. In-hospital mortality (13.2%) and the death rate at 1 year postevent (24.6%) were higher than data reported from immunocompetent patients. We also observed high rates of acute cardiovascular events and events occurring 1 year after admission. Early blood cultures and bronchoscopy in the first 24 h significantly increased the odds of establishing an etiology. In our low-resistance setting, the burden of antimicrobial resistance was driven by bacteria from chronically colonized patients, mostly lung transplant recipients. This comprehensive analysis highlights the high morbidity associated with CAP after transplantation. It also emphasizes the need for prospective multicenter studies to guide evidence-based practices and improve outcomes for these vulnerable patients. [ABSTRACT FROM AUTHOR]

Small airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases, and progression to COPD over time. Whether SAO predicts mortality is largely unknown. Is spirometry-defined SAO associated with increased mortality? Data were analyzed from 252,877 adult participants, aged 40 to 69 years at baseline, in the UK Biobank who had provided good-quality spirometry measurements. SAO was defined as the ratio of the forced expiratory volume in 3 s to the forced expiratory volume in 6 s less than the lower limit of normal. SAO was considered to be isolated if present when the FEV 1 /forced expiratory volume in 6 s ratio was normal (ie, greater than the lower limit of normal). A multivariable Cox regression model was used to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. Sex differences were investigated in these associations, and the primary analysis was repeated, excluding those who ever smoked. All models were adjusted for potential confounders such as sex, BMI, smoking status, smoking pack-years, assessment center, Townsend deprivation index, and ethnicity. A total of 59,744 participants with SAO were identified, of whom 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (hazard ratio [HR], 1.31; 95% CI, 1.26-1.36), cardiovascular (HR, 1.39; 95% CI, 1.29-1.51), respiratory (HR, 2.20; 95% CI, 1.92-2.51), and neoplasm (HR, 1.23; 95% CI, 1.17-1.29) mortality risk. These associations were not modified by sex. However, in those who never smoked, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR, 1.14; 95% CI, 1.07-1.20). Individuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are needed to determine whether SAO causes mortality or is a marker of underlying disease. [Display omitted] [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objective of this study was to investigate the dynamic profiles of myocardial injury biomarkers and their association with mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). DESIGN: A retrospective cohort study. SETTINGS: Union Hospital in Wuhan, China. PATIENTS: A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 580 patients with SFTS were enrolled in the study, comprised of 469 survivors and 111 nonsurvivors, with a 21-day fatality rate of 19.1%. The elevation of troponin I (TnI) was observed in 61.6% patients (357/580) with SFTS upon admission, and 68.4% patients (397/580) developed an abnormal TnI level during hospitalization. Multivariate logistic regression identified age, viral load, platelet count, creatinine level, and TnI level as potential risk factors for mortality in patients with SFTS. The results of restricted cubic splines revealed that when the TnI level (baseline TnI: 1.55 [lg (ng/L+1)], peak value: TnI 1.90 [lg (ng/L+1)]) exceeded a certain threshold, the predicted mortality of patients with SFTS increased alongside the rise in TnI levels. Mortality rate surpassed 40% among patients with SFTS with TnI greater than or equal to 10 times the upper limit of normal at admission (43.8%) or during hospitalization (41.7%). Older age, a history of cardiovascular disease, and higher D-dimer levels were potential risk factors for elevated TnI levels in patients with SFTS. CONCLUSIONS: Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality. We hypothesized that LPMV strategies deployed as a pragmatic protocol reduces mortality in PARDS. DESIGN: Multicenter prospective before-and-after comparison design study. SETTING: Twenty-one PICUs. PATIENTS: Patients fulfilled the Pediatric Acute Lung Injury Consensus Conference 2015 definition of PARDS and were on invasive mechanical ventilation. INTERVENTIONS: The LPMV protocol included a limit on peak inspiratory pressure (PIP), delta/driving pressure (DP), tidal volume, positive end-expiratory pressure (PEEP) to FIO2 combinations of the low PEEP acute respiratory distress syndrome network table, permissive hypercarbia, and conservative oxygen targets. MEASUREMENTS AND MAIN RESULTS: There were 285 of 693 (41[middle dot]1%) and 408 of 693 (58[middle dot]9%) patients treated with and without the LPMV protocol, respectively. Median age and oxygenation index was 1.5 years (0.4-5.3 yr) and 10.9 years (7.0-18.6 yr), respectively. There was no difference in 60-day mortality between LPMV and non-LPMV protocol groups (65/285 [22.8%] vs. 115/406 [28.3%]; p = 0.104). However, total adherence score did improve in the LPMV compared to non-LPMV group (57.1 [40.0-66.7] vs. 47.6 [31.0-58.3]; p < 0[middle dot]001). After adjusting for confounders, adherence to LPMV strategies (adjusted hazard ratio, 0.98; 95% CI, 0.97-0.99; p = 0.004) but not the LPMV protocol itself was associated with a reduced risk of 60-day mortality. Adherence to PIP, DP, and PEEP/FIO2 combinations were associated with reduced mortality. CONCLUSIONS: Adherence to LPMV elements over the first week of PARDS was associated with reduced mortality. Future work is needed to improve implementation of LPMV in order to improve adherence. [ABSTRACT FROM AUTHOR]

The majority of occupational lung diseases have long latency periods, with disease manifesting at an older age. We conducted an extensive literature review and analyzed data for age-related mortality, the impact of age on the lungs and occupational lung diseases, changes in the workforce, and considerations for surveillance to maintain a healthy workforce. Age is a major factor in occupational lung diseases, which in turn predisposes older adults to other health conditions and reduces their quality of life and life expectancy. More specifically, age-related changes in the lungs increase the susceptibility to environmental exposure-induced lung injuries and are linked to poor prognosis. Data from the Work-Related Lung Disease Surveillance Report published by the National Institute for Occupational Safety and Health (NIOSH, 2008) indicated that death from occupational lung diseases among U.S. residents peaked in the age group 75--84 years. Interestingly, the age group 65--74 years recorded a substantial number of deaths, second to the age group 75--84 years. This trend represents a shift in U.S. mortality for all diseases, which peaks at ≥85 years. Improved surveillance and early detection will be instrumental in reducing the burden of occupational lung injury in older adults, many of whom are staying in the workforce longer. [ABSTRACT FROM AUTHOR]

Recent randomized controlled trials (RCTs) have shown a benefit of brexpiprazole in managing agitation in patients with Alzheimer's disease (AD). However, its efficacy and safety remain unclear. We systematically searched PubMed, Embase, and Cochrane Library for RCTs comparing brexpiprazole with placebo in patients with agitation and AD. Three studies comprising 1,048 patients were included. In patients with agitation and AD, brexpiprazole significantly improved the Cohen-Mansfield Agitation Inventory total score (CMAI) at any dose (MD -3.05; 95% CI -5.12, -0.98; p < 0.01; I2 = 19%) and at 2 mg (MD -4.36; 95% CI -7.02, -1.70; p < 0.01; I2 = 0%) over 12 weeks. Brexpiprazole at any dose and 2 mg also showed benefit in the Clinical Global Impression − Severity of illness (CGI-S) score as related to agitation over 12 weeks (MD -0.20; 95% CI -0.36, -0.05; p < 0.01; I2 = 35%). There is no significant difference between the groups in the incidence of at least one treatment-emergent adverse events (TEAEs; RR 1.14; 95% CI 0.95, 1.37; p = 0.16; I2 = 45%) and all-cause mortality (RR 1.99; 95% CI 0.37, 10.84; p = 0.42; I2 = 0%). Brexpiprazole at any dose significantly increased the Simpson-Angus Scale (SAS; MD 0.47; 95% CI 0.28, 0.66; p < 0.01). Our results suggest that brexpiprazole is more efficacious than placebo in the treatment of agitation in AD patients. Further studies are still necessary to confirm long-term effects of brexpiprazole. Prospero registry: CRD42023486694. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the time-to-surgery of a centre of excellence in hip fractures of the elderly and its influence on inpatient mortality and postoperative complications. Methods: A cross-sectional cohort study was conducted. The sample universe consisted of 4,364 patients admitted to a university clinic in Chía, Colombia during the year 2018 to 2023 with ICD-10 diagnoses corresponding to femur fractures. After eliminating duplicates and application of inclusion and exclusion criteria, the final sample included was 269 patients. Qualitative and quantitative variables were analysed, such as: sex, age, age group, type of fracture, type of surgical procedure, time-to-surgery, time to discharge, inpatient mortality and postoperative complications. Results: The mean time-to-surgery from admission was 70.16 h or 2.92 days (IQR 37–87). Patients were divided into three subgroups of time in which they were taken to surgery: <24 h (11.89%), 24–48 h (33.82%) and > 48 h (54.27%). The overall mortality rate was 1.85% for a total of five deceased patients, two of whom belonged to the 24–48-hour group and three to the > 48 h group. Higher rates of postoperative complications were observed in the > 48-hours group (n: 39, 14.49%), followed by the 24–48-hour group (n: 25, 9.29%) and the < 24-hour group (n: 7, 2.6%). Conclusions: Patients operated for a hip fracture in > 48 h since admission had a slightly higher rate of postoperative complications. No significant difference was observed regarding inpatient mortality when compared to the 24–48-hour group. [ABSTRACT FROM AUTHOR]

Many pension schemes offer annuities pooling mortality risk across members. Such pooling has been criticized for having a regressive bias benefitting risk classes with the longest expected longevity. However, knowledge on mortality risk unfolds over the life‐course, and it is optimal for risk averse households to annuitize all old‐age consumption already as young buying pooled contracts, even if fair annuities are available later in life or risk class is private information. Borrowing constraints impair such frontloading but are lessened by a mandated pooled annuity targeting the middle‐aged, improving welfare for all risk classes and the first‐best allocation may be implementable. [ABSTRACT FROM AUTHOR]

• Myocardial infarction (MI) is an important driver of both morbidity and mortality. • Socioeconomic and psychosocial factors (SPF) impact on treatments and outcomes. • MI patients with SPF had an aggravated cardiovascular profile. • SPF was not associated with an underuse of interventional treatments, but with lower CABG rate. • SPF was not associated with increased in-hospital case-fatality in MI. Myocardial infarction (MI) is an important driver of both morbidity and mortality on a global scale. Elucidating social inequalities may help to identify vulnerable groups as well as treatment imbalances and guide efforts to improve care for MI. All hospitalized patient-cases with confirmed MI 2005-2020 in Germany were included in the study and stratified for socioeconomic or psychosocial factors (SPF) and the impact of SPF on treatment usage and adverse in-hospital events was analyzed. Overall, 4,409,597 hospitalizations of MI patients were included; of these, 17,297 (0.4 %) were coded with SPF. These patients were more often of female sex (49.4 % vs. 36.9 %, P<0.001), older (median 77.0 [IQR: 65.0–84.0] vs. 73.0 [62.0–81.0] years, P<0.001) and revealed an aggravated cardiovascular profile. Although SPF were independently associated with increased usage of cardiac catheterization (OR 1.174 [95 %CI 1.136-1.212]) and percutaneous coronary intervention (OR 1.167 [95 %CI 1.130-1.205]), they were accompanied by higher risk for a prolonged length of in-hospital stay >7 days (OR 1.236 [95 %CI 1.198-1.276]) and >10 days (OR 1.296 [95 %CI 1.254-1.339]). While SPF were associated with increased risk for deep venous thrombosis and/or thrombophlebitis (OR 1.634 [95 %CI 1.427-1.870]), pulmonary embolism (OR 1.337 [95 %CI 1.149-1.555]), and acute renal failure (OR 1.170 [95 %CI 1.105-1.240), these SPF were inversely associated with in-hospital case-fatality (OR 0.461 [95 %CI 0.433-0.490]). This study demonstrates that SPF in hospitalized MI patients have significant impacts on treatments and outcomes. Fortunately, our data did not revealed an underuse of interventional treatments in MI patients with SPF. [ABSTRACT FROM AUTHOR]

Income inequality has been increasing for decades and is now known to be related to many downstream health outcomes, where greater inequality is a predictor of poorer health. Results of investigations into the relationship between income inequality and suicidality have been mixed. This study leverages the most recent data available from the National Longitudinal Mortality Study to investigate the relationship between state-level income inequality and suicide mortality. A series of rigorously controlled logistic regression models, employing multiple measures of inequality, and various suicide mortality case-control specifications are used to investigate the phenomenon. Results indicate that the odds of suicide mortality increase with inequality, and this result is invariant across all models. A reduction in the Gini coefficient from the highest to lowest values of income inequality observed in U.S. states may reduce the odds of suicide mortality by 20 percent to 55 percent or more. Findings have application for social workers and other mental health professionals with respect to clinical assessment and treatment. Likewise, community organizers, policy advocates, and legislators should be aware that policy solutions reducing income inequality in the United States are a mechanism for alleviating the suicide mortality burden. [ABSTRACT FROM AUTHOR]

Secular trends of mortality and disability-adjusted life years (DALY) in type 2 diabetes mellitus (T2DM) attributable to PM2.5 exposure in China remain unclear. This study applied the joinpoint regression analysis and age-period-cohort model to assess the secular trends. There was a slight alternation in age-standardized rate of mortality and DALY in the total population, while the changes were increased in males and decreased in females from 1990 to 2019. Meanwhile, the changes attributable to ambient particular matter pollution exposure (APE) increased significantly and reduced household air pollution from solid fuels exposure (HPE). Longitudinal age curves showed that T2DM mortality and DALY increased with age. Period rate ratios (RR) attributable to APE increased but fell to HPE. Similar trends were observed in the cohort RR. PM2.5 exposure is more harmful to males and older people. The type of air pollution responsible for T2DM has changed from HPE to APE. [ABSTRACT FROM AUTHOR]

Background: Rapid skeletal muscle loss adversely affects the clinical outcomes of liver cirrhosis. However, the relationships between the annual changes in skeletal muscle area (ΔSMA/year) and the etiology of cirrhosis, factors associated with muscle loss, and risk of mortality remains unclear. Methods: A total of 384 patients who underwent multiple computed tomography (CT) scans between March 2004 and June 2021 were enrolled in this study (median age, 67 years; 64% men; median model for end-stage liver disease score, 9). Body composition and ΔSMA/year were estimated using a 3D image analysis system and data from at least two distinct CT scans. Differences in ΔSMA/year among different etiologies of cirrhosis, factors associated with rapid muscle loss (defined as ΔSMA/year ≤ − 3.1%), and the association between ΔSMA/year and mortality were examined. Results: Patients with alcohol-associated liver disease (ALD) cirrhosis experienced more rapid muscle loss (ΔSMA/year, − 5.7%) than those with hepatitis B (ΔSMA/year, − 2.8%) and hepatitis C cirrhosis (ΔSMA/year, − 3.1%). ALD cirrhosis was independently associated with ΔSMA/year ≤ − 3.1% after adjusting for age, sex, and liver functional reserve. Over a median follow-up period of 3.8 years, ALD cirrhosis, ΔSMA/year ≤ − 3.1%, and low subcutaneous adipose tissue level were found to be significantly associated with reduced survival. ALD cirrhosis (hazard ratio [HR], 2.43; 95% confidence interval [CI] 1.12–5.28) and ΔSMA/year ≤ − 3.1% (HR, 3.68; 95% CI 2.46–5.52) were also predictive of mortality. Conclusions: These results suggest that ALD cirrhosis increases the risk of rapid muscle loss and mortality in affected patients. [ABSTRACT FROM AUTHOR]

Background: The neutrophil–lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) are emerging inflammatory markers related to cardiovascular outcomes. This study investigated their relationships with cardiovascular disease (CVD) and mortality among individuals with prediabetes or diabetes and assessed their predictive roles. Methods: A cohort of 6871 individuals with diabetes or prediabetes from the NHANES (2001–2018) was included. Weighted multivariate logistic regression models assessed NLR and SII associations with CVD risk, while survey-weighted Cox proportional hazards models evaluated their links to mortality. The predictive accuracy of the biomarkers for mortality was quantified by receiver-operating characteristic (ROC) curve analysis. Results: Individuals in the higher NLR and SII groups exhibited a high incidence of CVD. A total of 1146 deaths occurred throughout an average follow-up duration of 191 months, of which 382 were caused by CVD. Participants with higher NLR markedly increased the risk of all-cause (HR = 1.82) and cardiovascular mortality (HR = 2.07). A similar result was observed in the higher SII group. RCS analysis identified a linear correlation between NLR and CVD risk and mortality (p > 0.05), while SII showed a nonlinear correlation (p < 0.05). ROC results demonstrated that NLR exhibited a higher predictive ability in mortality than SII. Conclusions: Elevated levels of NLR and SII correlated with an increased risk of CVD and both all-cause and cardiovascular mortality in individuals with diabetes or prediabetes. The NLR appears to be particularly valuable for assessing risk and predicting outcomes in these patients. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a most prevalent neurologic disorder characterized by cognitive dysfunction, amyloid-β (Aβ) protein accumulation, and excessive neuroinflammation. It affects various life tasks and reduces thinking, memory, capability, reasoning and orientation ability, decision, and language. The major parts responsible for these abnormalities are the cerebral cortex, amygdala, and hippocampus. Excessive inflammatory markers release, and microglial activation affect post-synaptic neurotransmission. Various mechanisms of AD pathogenesis have been explored, but still, there is a need to debate the role of NF-κB, Nrf2, inflammatory markers, CREB signaling, etc. In this review, we have briefly discussed the signaling mechanisms and function of the NF-ĸB signaling pathway, inflammatory mediators, microglia activation, and alteration of autophagy. NF-κB inhibition is a current strategy to counter neuroinflammation and neurodegeneration in the brain of individuals with AD. In clinical trials, numbers of NF-κB modulators are being examined. Recent reports revealed that molecular and cellular pathways initiate complex pathological competencies that cause AD. Moreover, this review will provide extensive knowledge of the cAMP response element binding protein (CREB) and how these nuclear proteins affect neuronal plasticity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate whether associations between sitting time and all-cause and heart disease mortality are modified by physical activity in adults with diabetes. RESEARCH DESIGN AND METHODS: Data came from 6,335 U.S. adults with diabetes from National Health and Nutrition Examination Survey 2007–2018 (baseline), with mortality follow-up through 2019. Sitting time and moderate to vigorous physical activity (MVPA) were self-reported. Cox models were adjusted for sociodemographics, lifestyle factors, and medical conditions. RESULTS: Over a median follow-up of 5.9 years, 1,278 all-cause and 354 heart disease deaths were documented (mean age, 59.6 years; 48.3% female). Longer sitting time was associated with greater all-cause and heart disease mortality risk in inactive (MVPA <10 min/week) or insufficiently active (MVPA 10 to <150 min/week) adults with diabetes, but not in active adults (MVPA ≥150 min/week) (all-cause mortality: P = 0.003 for interaction; heart disease mortality: P = 0.008 for interaction). CONCLUSIONS: In adults with diabetes, meeting guideline-recommended physical activity may offset the elevated all-cause and heart disease mortality risk associated with excessive sitting time. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Adequate transfer of passive immunity (TPI) is a cornerstone for a proper health status of calves. In the literature, there is limited information on the prevalence of failure of TPI in dairy-beef crossbred calves and its effect on morbidity, mortality, and ADG during the preweaning period. Therefore, this study aimed to evaluate the association between TPI with morbidity, mortality, and ADG in preweaning dairy-beef crossbred calves. A total of 1,055 newborn dairy-beef crossbred calves were enrolled upon arrival at a calf-raising facility in California from January to August 2021. Farm of origin, genetic breed group, sex, and BW were recorded upon arrival. Blood was collected at 24 ± 1 h after arrival to evaluate serum IgG concentration, serum total protein (TP), and packed cell volume. Morbidity (diarrhea and respiratory treatment records) and mortality were recorded daily until 60 d of life. Calves were grouped into 2 genetic breed groups: Holstein × Beef (Ho × Be, 49.6%) and Jersey × Beef crossbred calves (Je × Be, 50.4%). Descriptive statistics and Cox proportional hazard models were created to evaluate the association of TPI categories for serum IgG (TPI-IgG: poor: <10.0 g/L, fair: 10.0–17.9 g/L, good: 18.0–24.9 g/L, and excellent: ≥25.0 g/L) and TP (TPI-TP: poor: <5.1 g/dL, fair: 5.1–5.7 g/dL, good: 5.8–6.1 g/dL, and excellent: ≥6.2 g/dL), sex, and genetic breed group with morbidity and mortality. Additionally, a mixed linear regression was performed to evaluate the association of sex, genetic breed group, and TPI categories with ADG. Overall morbidity and mortality were 84.8% (n = 895) and 2.5% (n = 26). Calves classified as TPI-IgG excellent were associated with the lowest (43.2% less) hazard of being treated compared with TPI-IgG poor calves. For mortality, dairy-beef crossbred calves with TPI-IgG excellent were associated with a reduction of 82.0% in the hazard of dying compared with TPI-IgG poor. The TPI-IgG poor and TPI-IgG fair calves were associated with a decreased ADG of 101.0 and 98.8 g/d, respectively, in comparison with TPI-IgG good calves. Average daily gain of TPI-IgG good and TPI-IgG excellent calves were not different. In our study, dairy-beef crossbred calves enrolled may have endured challenging conditions that increased morbidity. This reinforces the importance of high IgG levels to decrease morbidity and mortality and maximize ADG in dairy-beef crossbred calves raising systems. Further research should evaluate the long-term effects of TPI categories on the health and performance of dairy-beef crossbred calves. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) has emerged as a potential alternative for aortic valve surgery to treat aortic valve stenosis. There is limited evidence on the comparative outcomes of TAVI access approaches, specifically the percutaneous (PC) vs surgical cutdown (SC) approach. This study aimed to assess the short-term outcomes in patients undergoing PC vs SC access for transfemoral transcatheter aortic valve replacement. PubMed, SCOPUS, and EMBASE were searched to identify relevant studies. The primary outcomes were short-term all-cause mortality, bleeding, vascular complications, and length of in-hospital stay for patients who underwent transfemoral TAVI. Both matched and unmatched observational studies were included and subgroup analyses were performed. This systematic review and meta-analysis was performed in line with the PRISMA guidelines. Fifteen observational studies involving 7,545 patients (3,033 underwent the PC approach and 2,466 underwent the SC approach) were included. There were no clinically significant between-group differences in short-term mortality, bleeding, length of in-hospital stay, or major vascular complications. However, minor vascular complications were significantly higher in patients who underwent PC-TAVI (p=0.007). In the matched subgroup, all outcomes were comparable between both groups, with the largest difference being observed in minor vascular complications more frequently occurring in the PC group (p=0.08). The evidence shows that outcomes were comparable between the two methods of access, rendering both the PC and SC approaches equally effective for transfemoral TAVI. However, it is worth noting that minor vascular complications were more pronounced in the PC group. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is associated with high mortality, but there are limited reports on the underlying cause of death. This study reports short-, medium- and long-term cause-specific mortality following first-ever HF hospitalisation in New Zealand. First-ever HF hospitalisations were identified from hospital discharge coding between 2010 and 2013. Mortality outcomes were obtained via anonymised linkage to national datasets. Short (0–30 days), medium (31–364 days), and long-term (1–5 years) mortality rates were identified. Cause of death was identified from death certification coding and classified as cardiovascular and non-cardiovascular. Cox regression analysis was performed to adjust for confounding variables. A cohort of 34,264 individuals with first-ever HF hospitalisation were identified. Mean age was 75.8±13 years and 50.5% were male. A total of 21,637 (63.1%) died within 5 years of hospitalisation; 4,122 (12.0%) within the first 30 days, 6,358 (18.6%) between 31–364 days, and 11,157 (32.6%) between 1 and 5 years. Older age, male gender, Māori ethnicity, higher socioeconomic deprivation and increased comorbidity were independent factors associated with higher all-cause mortality. Cardiovascular causes accounted for 51% of total deaths. Cardiovascular mortality was 6.0%, 9.5%, and 16.7% at 30 days, 31–364 days, and 1–5 years, respectively. The most common causes of non-cardiovascular mortality were neoplasms, chronic respiratory diseases and infections, accounting for 14.6%, 11.0%, and 5.5% of total deaths respectively. Comorbidity was associated with higher non-cardiovascular mortality (hazard ratio [HR] 3.35; 95% confidence interval [CI] 3.16–3.55) but not cardiovascular mortality (HR 0.79; 95% CI 0.72–0.86). In New Zealand, mortality following first-ever HF hospitalisation is high. Non-cardiovascular death is common and there are ethnic inequities. [ABSTRACT FROM AUTHOR]

Percutaneous mitral balloon commissurotomy (PMBC) is the standard treatment option for patients with rheumatic mitral stenosis (MS), according to current guidelines. This study aimed to compare the outcomes of rheumatic mitral valve repair (rMVR) and PMBC in this patient population. Baseline, clinical, and follow-up data from 703 patients with rheumatic heart disease who underwent PMBC or rMVR at the current centre were collected and analysed. A 1:1 propensity score (PS) matching method was used to balance the differences in baseline characteristics between the two groups. The primary outcome was mitral valve reoperation, and the secondary outcome was all-cause mortality. Propensity score matching generated 101 patient pairs for comparison. In the matched population, there were no significant differences in the early clinical outcomes between the groups. The median follow-up time was 40.9 months. Overall, patients in the rMVR group had a statistically significantly lower risk of mitral valve reoperation than those in the PMBC group (HR 0.186; 95% CI 0.041–0.835; p=0.028). Regarding all-cause mortality, no statistically significant differences were observed between the rMVR and PMBC groups (HR 4.065; 95% CI 0.454–36.374; p=0.210). Compared with PMBC, rMVR has more advantages for the correction of valve lesions; therefore, it may offer a better prognosis than PMBC in select patients with rheumatic MS. However, this finding needs to be verified in future studies with larger sample sizes and longer follow-up periods. [ABSTRACT FROM AUTHOR]

Aim: To assess mortality and complication trends in people with type 1 diabetes during the 11 years before the SARS‐CoV2 pandemic (2009–2019). Materials and Methods: Sequential cohorts of people in England with type 1 diabetes aged ≥20 years from the National Diabetes Audit (2006/2007 to 2016/2017) were analysed. Discretized Poisson regression models, adjusted for age, sex, ethnicity, socioeconomic deprivation and duration of diabetes, were used to calculate mortality and hospitalization rates. Results: Demographic characteristics changed little; average diabetes duration increased. All‐cause mortality was unchanged. Cardiovascular and kidney disease mortality declined. Mortality from respiratory disease, diabetes and dementia increased in younger people (aged 20–74 years) as did mortality from liver disease and dementia in the elderly (aged ≥75 years). Younger Asian and Black people had lower all‐cause mortality than those of White ethnicity; elderly Mixed, Asian and Black people had lower all‐cause mortality. People from more deprived areas had higher all‐cause mortality. The deprivation gradient for mortality was steeper at younger ages. In younger people, rates of hospitalization increased for myocardial infarction, stroke, heart failure and kidney disease but only for kidney disease in the elderly. Rates of a composite measure of cardiovascular hospitalizations increased in younger people (rate ratio [RR] 1.07, 95% confidence interval [CI] 1.03–1.11) but declined in the elderly (RR 0.91, 95% CI 0.86–0.95). Conclusion: Between 2009 and 2019, hospitalizations for cardiovascular disease increased at younger ages (20–74 years) and hospitalizations for kidney disease increased at all ages, but mortality from cardiovascular and kidney disease declined. All‐cause mortality rates were unchanged. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the impact of non‐alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. Methods: Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two‐sample Mendelian randomization study using genome‐wide association study statistics explored NAFLD's potential causal link to cardio‐cerebrovascular events. Results: In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21‐1.95)], mortality because of cardio‐cerebrovascular diseases [HR 1.63 (95% CI 1.12‐2.37)], heart disease [HR 1.58 (95% CI 1.00‐2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48‐10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis‐4 (FIB‐4) score >2.67, exhibited associations with overall mortality, cardio‐cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end‐stage kidney disease [ESKD; HR 2.17 (95% CI 1.41‐3.34)], while elevated FIB‐4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio‐cerebrovascular events. Conclusions: In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB‐4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio‐cerebrovascular events. [ABSTRACT FROM AUTHOR]

Aim: To assess the association between urinary albumin‐to‐creatinine ratio (UACR) categories within the normal range with mortality and adverse cardiovascular outcomes. Materials and Methods: PubMed and Embase were systematically searched for real‐world evidence studies. Studies were manually evaluated according to predefined eligibility criteria. We included prospective and retrospective cohort studies of the association between UACR categories <30 mg/g and cardiovascular outcomes or mortality. Published information regarding study design, participants, UACR categorization, statistical methods, and results was manually collected. Two UACR categorization approaches were defined: a two‐category (UACR <10 mg/g vs. 10‐30 mg/g) and a three‐category division (UACR <5 mg/g vs. 5‐10 and 10‐30 mg/g). A random effects meta‐analysis was performed on studies eligible for the meta‐analysis. Results: In total, 22 manuscripts were identified for the systematic review, 15 of which were eligible for the meta‐analysis. The results suggest an association between elevated UACR within the normal to mildly increased range and higher risks of all‐cause mortality, cardiovascular death, and coronary heart disease, particularly in the range of 10‐30 mg/g. Compared with UACR <10 mg/g, the hazard ratio [HR (95% confidence interval, CI)] for UACR between 10 and 30 mg/g was 1.41 (1.15, 1.74) for all‐cause mortality and 1.56 (1.23, 1.98) for coronary heart disease. Compared with UACR <5 mg/g, the risk of cardiovascular mortality for UACR between 10 and 30 mg/g was more than twofold [HR (95% CI): 2.12 (1.61, 2.80)]. Intermediate UACR (5‐10 mg/g) was also associated with a higher risk of all‐cause mortality [HR (95% CI): 1.14 (1.05, 1.24)] and cardiovascular mortality [HR (95% CI): 1.50 (1.14, 1.99)]. Conclusions: We propose considering higher UACR within the normoalbuminuric range as a prognostic factor for cardiovascular morbidity and mortality. Our findings underscore the clinical significance of even mild increases in albuminuria. [ABSTRACT FROM AUTHOR]

Whether the anaesthetic agent used influences postoperative mortality in older patients remains unclear. We evaluated the effect of total intravenous anaesthesia (TIVA) vs inhalation anaesthesia on long-term mortality in older patients after noncardiac surgery. We retrospectively analysed 45,879 patients aged ≥60 yr who underwent noncardiac surgery under general anaesthesia (for ≥2 h) between January 2011 and June 2019. They were divided into two groups according to the type of maintenance anaesthetic. The primary outcome was all-cause mortality within 1 yr after surgery. Secondary outcomes included postoperative complications (postoperative pulmonary complications, perioperative adverse cardiovascular events, and acute kidney injury), and 3-yr and 5-yr mortality after surgery. The stabilised inverse probability of treatment weighting method was used to adjust for potential confounders. Among 45,879 patients, 7273 (15.9%) patients received TIVA and 38,606 (84.1%) patients received inhalation anaesthesia. After adjustment with inverse probability of treatment weighting, there was no association between the type of anaesthetic agent and 1-yr mortality (hazard ratio=0.95; 95% confidence interval [CI] 0.84−1.08). Results for 3-yr and 5-yr mortality were similar. However, inhalation anaesthesia was associated with increased risk of postoperative complications (odds ratio [OR]=1.30; 95% CI 1.22−1.37 for postoperative pulmonary complications, OR=1.34; 95% CI 1.22−1.48 for perioperative adverse cardiovascular events, and OR=2.19; 95% CI 1.88−2.57 for acute kidney injury). In the subgroup analysis, the choice of anaesthetic agent showed differential effects on 1-yr mortality for female patients and emergency surgery. The choice of anaesthetic agent during the intraoperative period was not associated with 1-yr mortality in older patients undergoing noncardiac surgery. Clinical Research Information Service of the Republic of Korea (KCT 0006363). [ABSTRACT FROM AUTHOR]

Centralisation of perioperative care for small children to a limited number of specialised paediatric centres has many theoretical advantages, but neither the optimal balance nor the current distribution of paediatric anaesthesia on a national scale are well elucidated. The aim of this study was to describe the distribution, adverse events, and mortality in children undergoing anaesthesia in Sweden. In this cohort study, data from all paediatric anaesthesia procedures registered in Sweden during the years 2019–22 were extracted from the Swedish Perioperative Register (SPOR). Data were analysed according to hospital level of care and ASA physical status. Data from 81 hospitals were analysed. During the 4-yr period, 214,964 procedures were registered. Most procedures in neonates and infants were managed in paediatric (73%) and other university hospitals (21%). Adverse events occurred in 2.71% of cases and severe adverse events in 0.067%. The all-cause 24-h mortality rate was 6.6:10,000 anaesthetics and the all-cause 30-day mortality was 14.7:10,000 anaesthetics. The 30-day all-cause estimated mortality was highest in paediatric hospitals (95% confidence interval [CI] 30–39) compared with other university hospitals (95% CI 6.1–12), county (95% CI 1.9–4.8), district (95% CI 0.07–2.2), and smaller hospitals (95% CI 0.0–22). Most procedures in neonates and infants were performed in tertiary centres, with county hospitals managing mainly older children, in accordance with national recommendations. Mortality was more common in tertiary centres, reflecting increased comorbidity and centralisation of anaesthesia of neonates and infants. [ABSTRACT FROM AUTHOR]

Limited information exists on age and racial disparities in sleep duration and mortality in the United States (US) population. This study compared the association between mortality and sleep duration within distinct races and age groups in the US. This study used data on 26,915 US citizens (≥ 18 years) from the 2004 wave of the National Health Interview Survey, linked to the National Death Index prospective mortality through 2019. Cox proportional hazard models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality by sleep duration, race (Whites, Black/African Americans, and Others (AIAN, Asian, and Native Hawaiian or other Pacific Islander)), and age (< 40, 40–60, and ≥ 60 years), while controlling for covariates such as sex, education, smoking status, disease history, and other vital factors. Race and age significantly modified the sleep duration-mortality relationship. Compared to other races, White participants exhibited higher mortality risks at all hours except at 5–6 h [HR: 0.993, 95% CI: 0.923–1.069]. Likewise, sleep duration associated mortality risks varied by age. Those at greater risk included < 40 years sleeping for 1–4 h [HR: 2.461, 95% CI: 1.446–4.187], 40–< 60 years sleeping for less than 7 h and more than 8 h, and ≥ 60 years sleeping for 9 h [HR: 1.309, 95% CI: 1.162–1.475] and ≥ 10 h [HR: 1.662, 95% CI: 1.486–1.858]. Age and race were significant effect modifiers in the sleep duration-mortality relationship. Thus, it is important to consider these factors when evaluating mortality risks associated with sleep patterns. [ABSTRACT FROM AUTHOR]

Traumatic subaxial cervical spine fractures are a significant public health concern due to their association with spinal cord injuries (SCI). Despite being mostly caused by low-energy trauma, these fractures significantly contribute to morbidity and mortality. Currently, research regarding early mortality based on the choice of treatment following these fractures is limited. Identifying predictors of early mortality may aid in postoperative patient monitoring and improve outcomes. This study aimed to identify predictors of 30-days, 90-days, and 1-year mortality in adults treated for subaxial fractures. A retrospective review of the nationwide Swedish Fracture Register (SFR). All adult patients in the SFR who underwent treatment for a subaxial cervical fracture (n = 1,963). Analyzed variables included age, sex, injury mechanism, neurological function, fracture characteristics, and treatment type. The primary endpoints were 30-days, 90-days, and 1-year mortality. About 1,963 patients in the SFR, treated for subaxial cervical fractures between 2013 and 2021, were analyzed. Surgical procedures included anterior, posterior, or anteroposterior approaches. Nonsurgical treatment included collar treatment or medical examinations without intervention. Stepwise regression and Cox regression analysis were used to determine predictors. Model performance was tested using the area under the receiver operating characteristic curve (AUC). A total of 620 patients underwent surgery and 1,343 received nonsurgical treatment. Surgical cases had primarily translation fractures, with 323 (52%) displaying no neurological deficits. Mortality rates at 30 days, 90 days, and 1 year were 22/620 (3.5%), 35/620 (5.6%), and 53/620 (8.5%), respectively. Age and SCI were predictors of mortality. Nonsurgically treated patients mostly had compression fracture, with 1,214 (90%) experiencing no neurological deficits. Mortality rates at 30 days, 90 days, and 1 year were 41/1,343 (3.1%), 71/1,343 (5.3%), and 118/1,343 (8.7%). Age, male sex, SCI and fractures occurring at the C3 or C6 levels were predictors of mortality. An intact neurological function was a positive predictor of survival among nonsurgically treated patients (AUC >0.78). Age and SCI emerged as significant predictors of early mortality in both surgically and nonsurgically treated patients. An intact neurological function served as a protective factor against early mortality in nonsurgically treated patients. Fractures at C3 or C6 vertebrae may impact mortality. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) are at an elevated risk of cardiovascular disease (CVD) and premature mortality compared to the general population. This study aimed to investigate whether the excess risk of CVD events and death among patients with CKD could be reduced or eliminated through strict control of blood pressure (systolic blood pressure: <130 mm Hg), lipids (low-density lipoprotein cholesterol: <2.6 mmol/L), and glucose (fasting blood glucose: <6.1 mmol/L). The authors included 20,254 patients with CKD who were free of CVD or end-stage renal disease and matched them with 35,236 control individuals based on age (±2 years) and sex from the Kailuan study. During a median follow-up period of 12.2 to 12.8 years, 3,875 deaths, 1,888 cases of stroke, 513 cases of myocardial infarction, and 4,825 cases of CKD progression were documented. Among patients with CKD, risk factor controls showed an association with a reduction in myocardial infarction, stroke, CKD progression, and all-cause mortality risk in a dose-dependent manner. Moreover, compared to the non-CKD control individuals, having all 3 risk factors within the target ranges could theoretically eliminate the excess risk of CVD and mortality associated with CKD. Among patients with CKD who had all 3 risk factors controlled, the HRs were 0.80 (95% CI: 0.56-1.14) for myocardial infarction, 0.93 (95% CI: 0.78-1.12) for stroke, and 1.10 (95% CI: 0.98-1.24) for all-cause mortality compared to the non-CKD control individuals. Patients with CKD who had controlled blood pressure, lipids, and glucose showed no excess risk of death, myocardial infarction, or stroke compared to the general population. [ABSTRACT FROM AUTHOR]

Purposes: Enterococcal BSI is associated with significant morbidity and mortality, with fatality rates of approximately 20–30%. There are microbiological and clinical differences between E. faecalis and E. faecium infections. The aim of this study was to investigate differences in predisposing factors for E. faecalis and E. faecium BSI and to explore prognostic factors. Methods: This study was a post-hoc analysis of PROBAC, a Spanish prospective, multicenter, cohort in 2016–2017. Patients with E. faecalis or E. faecium BSI were eligible. Independent predictors for BSI development in polymicrobial and monomicrobial BSI and in-hospital mortality in the monomicrobial group were identified by logistic regression. Results: A total of 431 patients were included. Independent factors associated with E. faecium BSI were previous use of penicillins (aOR 1.99 (95% CI 1.20–3.32)) or carbapenems (2.35 (1.12–4.93)), hospital-acquired BSI (2.58 (1.61–4.12)), and biliary tract source (3.36 (1.84–6.13)), while congestive heart failure (0.51 (0.27–0.97)), cerebrovascular disease (0.45 (0.21–0.98)), and urinary tract source (0.49 (0.26–0.92)) were associated with E. faecalis BSI. Independent prognostic factors for in-hospital mortality in E. faecalis BSI were Charlson Comorbidity Index (1.27 (1.08–1.51)), SOFA score (1.47 (1.24–1.73)), age (1.06 (1.02–1.10)), and urinary/biliary source (0.29 (0.09–0.90)). For E. faecium BSI, only SOFA score (1.34 (1.14–1.58) was associated with in-hospital mortality. Conclusions: The factors associated with E. faecium and E. faecalis BSI are different. These variables may be helpful in the suspicion of one or other species for empiric therapeutic decisions and provide valuable information on prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus aureus prosthetic valve endocarditis (SAPVE) is a serious infection with high mortality. The main objective of this study was to identify factors associated with in-hospital mortality. Methods: From January 2008 to December 2021, consecutive patients from a Spanish cohort of infective endocarditis with a definitive diagnosis of SAPVE were analyzed. Results: During the study period, 219 cases of definitive SAPVE were diagnosed, which accounted for 16.7% of a total of 1309 cases of definitive prosthetic valve endocarditis (PVE). Patients presented advanced age and marked comorbidity. There was a higher incidence of persistent bacteremia, septic shock, stroke, and acute kidney injury than in cases of PVE caused by other microorganisms. Methicillin resistance was not associated with differences in clinical presentation, echocardiographic findings, or mortality. Only 50.6% of the patients with surgical indications (88 patients) underwent surgery. Overall, in-hospital mortality was 47.9%. The variables associated with in-hospital mortality were age (OR:1.03, 95% CI: 1.00-1.05; p = 0.016), heart failure (OR:2.86, 95% CI: 1.53–5.32; p = 0.001), acute kidney injury (OR:2.42, 95%CI:1.28–4.58; p = 0.006), stroke (OR:3.53, 95%CI:1.79–6.96; p < 0.001) and surgery indicated but not performed (OR:2.01, 95%CI:1.06–3.8; p = 0.030). On the other hand, the performance of surgery per se in patients with SAPVE, regardless of whether there was a surgical indication according to the guidelines, was not associated with a reduction in in-hospital mortality. Conclusions: SAPVE is characterized by high mortality, which is more marked in patients who present a surgical indication but do not undergo surgery. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the role of CT in septic patients presenting to the emergency department (ED). Materials and methods: We performed a retrospective secondary analysis of 192 septic patients from a prospective observational study, i.e., the "LIFE POC" study. Sepsis was diagnosed in accordance with the Sepsis-3 definition. Clinical and radiological data were collected from the hospital administration and radiological systems. Information on mortality and morbidity was collected. Time-to-CT between CT scan and sepsis diagnosis (ttCTsd) was calculated. Diagnostic accuracy was assessed with the final sepsis source as reference standard. The reference standard was established through the treating team of the patient based on all available clinical, imaging, and microbiological data. Results: Sixty-two of 192 patients underwent a CT examination for sepsis focus detection. The final septic source was identified by CT in 69.4% (n = 43). CT detected septic foci with 81.1% sensitivity (95% CI, 68.0–90.6%) and 55.6% specificity (95% CI, 21.2–86.3%). Patients with short versus long ttCTsd did not differ in terms of mortality (16.1%, n = 5 vs 9.7, n = 3; p = 0.449), length of hospital stay (median 16 d, IQR 9 d 12 h–23 d 18 h vs median 13 d, IQR 10 d 00 h–24 d 00 h; p = 0.863), or duration of intensive care (median 3d 12 h, IQR 2 d 6 h–7 d 18 h vs median 5d, IQR 2 d–11 d; p = 0.800). Conclusions: Our findings show a high sensitivity of CT in ED patients with sepsis, confirming its relevance in guiding treatment decisions. The low specificity suggests that a negative CT requires further ancillary diagnostic tests for focus detection. The timing of CT did not affect morbidity or mortality outcomes. Clinical relevance statement: In patients with sepsis who present to the ED, CT can be used to identify infectious foci on the basis of clinical suspicion, but should not be used as a rule-out test. Scientific evidence for the optimal timing of CT beyond clinical decision-making is currently missing, as potential mortality benefits are clouded by differences in clinical severity at the time of ED presentation. Key Points: • In patients with sepsis who present to the ED, CT for focus identification has a high sensitivity and can thereby be valuable for patient management. • As the specificity is considerably lower, a thorough microbiological assessment is important in these cases. • The timing of CT did not affect morbidity and mortality outcomes in this study, which might be due to variability in clinical severity at the time of ED presentation. [ABSTRACT FROM AUTHOR]

The association between systemic scleroderma and malignancy is well-documented, but there is limited data on the relationship between morphea and malignancy. This study aims to assess the incidence and types of malignancies in morphea patients, comparing demographics, clinical characteristics, treatments, and outcomes between those with and without malignancy. We conducted a retrospective study of 204 morphea patients treated at Rabin Medical Center between 2012 and 2023. Data on demographics, clinical subtypes, comorbidities, treatments, and outcomes were collected. Patients were categorized based on malignancy status and the timing of malignancy relative to their morphea diagnosis. Among the 204 patients (154 women and 50 men, mean age 53.7 ± 20 years), 47 (23%) developed malignancies. In 29 patients (61.7%), malignancy occurred before the onset of morphea; in 23 patients (48.9%), it occurred after morphea. Five patients (10.6%) had malignancies both before and after the diagnosis of morphea. Patients with malignancy were significantly older than those without (64.7 ± 15.1 years vs. 50.3 ± 20 years, p < 0.0001). The all-cause mortality rate was higher in the malignancy group compared to those without malignancy (23.4% vs. 3.8%, p = 0.00002). Moreover, mortality was higher in patients whose malignancy occurred after morphea than in those whose malignancy preceded morphea (26% vs. 17.2%). The most common post-morphea malignancies in our cohort included non-melanoma skin cancer, cervical cancer, breast cancer, stomach cancer, and lung cancer. The most common pre-morphea malignancies included breast cancer, non-melanoma skin cancer, colon cancer, prostate cancer, and testicular cancer. This study suggests potential associations between morphea and malignancies, influenced by patient age, sequence of diagnosis, and treatment regimens. Further control studies are needed to explore these relationships more definitively. [ABSTRACT FROM AUTHOR]

Background and Objective: Breast cancer has a high prevalence and mortality rate in the world and also in Iran. Neoadjuvant chemotherapy (NAC) is one of the treatment methods to improve patient survival. This study aimed to determine the response rate to NAC in patients with locally advanced breast cancer based on common molecular receptors. Methods: This descriptive-analytical study was conducted on 100 patients with breast cancer (mean age= 41.14±10.06 years) referring to the surgical clinic of the Fifth Azar Educational and Therapeutic Center in Gorgan, Iran during 2013-18. Patients without distant metastasis underwent NAC treatment regimen followed by surgery. Demographic characteristics, types of drugs, and molecular receptor characteristics, and their response to treatment were recorded in a checklist. Treatment response and overall patient survival were evaluated. Results: The mean tumor size before NAC was 3.01±2.47 cm (range= 0-8, median= 2) and 16% were determined to be grade one, 52% were determined to be grade 2, and 32% were determined to be grade 3. Thirty-six percent of patients had a positive family history. Forty-six percent were estrogen receptor (ER) positive, 40% were PR positive, 22% were human epidermal growth factor receptor 2 (Her-2) positive, and 78% were Her-2 negative. Thirty-six percent had a Ki-67 index greater than 30%. Eighteen percent of patients had a complete pathological response, and 82% had a partial or negative response. In terms of family history of breast cancer, Her2, ER, progestrone receptor (PR), Ki-67 receptor status, histological grade, tumor size, and axillary lymph nodes, there was a significant statistical difference between the two groups with and without complete pathological response (P<0.05). Conclusion: The rate of complete pathological response to NAC in patients with locally advanced breast cancer was 18%. [ABSTRACT FROM AUTHOR]

Objective: Many current trauma mortality prediction tools are either too intricate or rely on data not readily available during a trauma patient's initial evaluation. Moreover, none are tailored to those necessitating urgent or emergent surgery. Our objective was to design a practical, user-friendly scoring tool using immediately available variables, and then compare its efficacy to the widely-known Revised Trauma Score (RTS). Methods: The adult 2017-2021 Trauma Quality Improvement Program (TQIP) database was queried to identify patients ≥18 years old undergoing any urgent/emergent operation (direct from Emergency Department to operating room). Patients were divided into derivation and validation groups. A three-step methodology was used. First, multiple logistic regression models were created to determine risk of death using only variables available upon arrival. Second, the weighted average and relative impact of each independent predictor was used to derive an easily calculated Immediate Operative Trauma Assessment Score (IOTAS). We then validated IOTAS using AUROC and compared it to RTS. Results: From 249 208 patients in the derivation-set, 14 635 (5.9%) died. Age ≥65, Glasgow Coma Scale score <9, hypotension (SBP <90 mmHg), and tachycardia (>120/min) on arrival were identified as independent predictors for mortality. Using these, the IOTAS was structured, offering scores between 0-8. The AUROC for this was .88. A clear escalation in mortality was observed across scores: from 4.4% at score 1 to 60.5% at score 8. For the validation set (250 182 patients; mortality rate 5.8%), the AUROC remained consistent at .87, surpassing RTS's AUROC of .83. Conclusion: IOTAS is a novel, accurate, and now validated tool that is intuitive and efficient in predicting mortality for trauma patients requiring urgent or emergent surgeries. It outperforms RTS, and thereby may help guide clinicians when determining the best course of action in patient management as well as counseling patients and their families. [ABSTRACT FROM AUTHOR]

Background: Cardiac pacemaker implantation may be indicated in patients with refractory bradycardia following a cervical spinal cord injury (CSCI). However, evidence about the impact of this procedure on outcomes is lacking. We planned a study to assess whether the implantation of a pacemaker would decrease mortality and hospital resource utilization in patients with CSCI. Methods: Adult patients with CSCI in the Trauma Quality Improvement Program (TQIP) database between 2016 and 2019 were retrospectively analyzed. Patients were divided into "pacemaker" and "non-pacemaker" groups, and their baseline characteristics and clinical outcomes were analyzed. Results: A total of 6774 cases were analyzed. The pacemaker group showed higher in-hospital rates of cardiac arrest, myocardial infarction, and longer duration of mechanical ventilation and ICU stay than the non-pacemaker group. Nevertheless, pacemaker placement was associated with a significant decrease in mortality (4.2% vs 26.0%, P < .01). Conclusions: Patients with CSCI requiring a pacemaker placement had better survival than those treated without a pacemaker. Pacemaker implantation should be highly considered in patients who develop refractory bradycardia after CSCI. [ABSTRACT FROM AUTHOR]

Introduction: We have recently shown that readmission after EGS procedures carries a 4-fold higher mortality rate when compared to those not readmitted. Understanding factors associated with death after readmission is paramount to improving outcomes for EGS patients. We aimed to identify risk factors contributing to failure-to-rescue (FTR) during readmission after EGS. We hypothesized that most post-readmission deaths in EGS are attributable to FTR. Methods: A retrospective cohort study using the NSQIP database 2013-2019 was performed. Patients who underwent 1 of 9 urgent/emergent surgical procedures representing 80% of EGS burden of disease, who were readmitted within 30 days post-procedure were identified. The procedures were classified as low- and high-risk. Patient characteristics analyzed included age, sex, BMI, ASA score comorbidities, postoperative complications, frailty, and FTR. The population was assessed for risk factors associated with mortality and FTR by uni- and multivariate logistic regression. Results: Of 312,862 EGS cases, 16,306 required readmission. Of those, 10,748 (3.4%) developed a postoperative complication. Overall mortality after readmission was 2.4%, with 90.6% of deaths attributable to FTR. Frailty, high-risk procedures, pulmonary complications, AKI, sepsis, and the need for reoperation increased the risk of FTR. Discussion: Death after a complication is common in EGS readmissions. The impact of FTR could be minimized with the implementation of measures to allow early identification and intervention or prevention of infectious, respiratory, and renal complications. [ABSTRACT FROM AUTHOR]

Objective Bronchopulmonary dysplasia (BPD) is the most common late morbidity for premature infants. Continuous neuromuscular blockade (CNMB) is suggested for the most unstable phase of BPD, despite no outcome data. We explored the association between duration of CNMB for severe BPD and mortality. Design Medical record review of children <5 years old admitted from 2016 to 2022 with BPD and one or more course of CNMB for ≥14 days. Results Twelve children received a total of 20 episodes of CNMB for ≥14 days (range 14–173 d) during their hospitalization. Most (10/12) were born at <28 weeks' gestation and most (11/12) with birth weight <1,000 g; 7/12 were of Black race/ethnicity. All were hospitalized since birth. Most (10/12) were initially transferred from an outside neonatal intensive care unit (ICU), typically after a >60-day hospitalization (9/12). Half (6/12) of them had a ≥60-day stay in our neonatal ICU before transferring to our pediatric ICU for, generally, ≥90 days (8/12). The primary study outcome was survival to discharge: 2/12 survived. Both had shorter courses of CNMB (19 and 25 d); only one child who died had a course ≤25 days. Just two infants had increasing length Z-scores during hospitalization; only one infant had a final length Z-score > − 2. Conclusion In this case series of infants with severe BPD, there were no survivors among those receiving ≥25 days of CNMB. Linear growth, an essential growth parameter for infants with BPD, decreased in most patients. These data do not support the use of ≥25 days of CNMB to prevent mortality in infants with severe BPD. Key Points This is a case series of neuromuscular blockade for severe BPD. Neuromuscular blockade did not improve linear growth. Ten out of 12 infants who were on prolonged neuromuscular blockade died. [ABSTRACT FROM AUTHOR]

Objective We aimed to examine the association between respiratory severity score (RSS; mean airway pressure × fraction of inspired oxygen) and neurodevelopmental outcomes in extremely preterm infants. Study Design This was a single-center, retrospective cohort study. We analyzed data from extremely preterm infants who were admitted to the neonatal intensive care unit at Okayama Medical Center between 2010 and 2019. Infants without invasive respiratory management during the first day of life were excluded. The exposure variable was the highest RSS during the first day of life. RSS was categorized into two groups: low (<3.5) and high (≥3.5) RSS. The primary outcome was death or neurodevelopmental impairment at age 3 years, defined as cognitive impairment (developmental quotient <70) or the presence of cerebral palsy. Secondary outcomes were the components of the primary outcome. We conducted robust Poisson regression analyses to investigate the association between RSS category and primary and secondary outcomes, adjusting for perinatal confounders. Results The cohort included 97 infants with neurodevelopmental data, of whom 34 and 63 infants were in the low- and high-RSS categories, respectively. The median (interquartile range) gestational age and birth weight were 26.0 (24.7–26.9) and 25.7 (24.6–26.7) weeks and 761 (584–866) and 806 (618–898) g for infants in the low- and high-RSS categories, respectively. Compared with infants in the low-RSS category, those in the high-RSS category had a greater risk of death or neurodevelopmental impairment at age 3 years (26.3 vs. 42.3%; adjusted risk ratio [RR], 2.0; 95% confidence interval [CI], 1.1–3.5) and neurodevelopmental impairment at age 3 years (17.6 vs. 28.6%; adjusted RR, 2.7; 95% CI, 1.3–5.9). Conclusion High RSS (≥3.5) during the first day of life was associated with an increased risk of neurodevelopmental impairment at age 3 years in extremely preterm infants. Key Points RSS is a valuable tool for assessing respiratory failure. RSS = Mean airway pressure × fraction of inspired oxygen. RSS at age 1 day was associated with neurodevelopment. [ABSTRACT FROM AUTHOR]

Objective Intercenter variation and trends in postnatal steroids (PNS) use among preterm infants for prevention or treatment of bronchopulmonary dysplasia (BPD) is known. Understanding intracenter PNS use patterns facilitate implementation of center-specific change interventions to optimize outcomes. This study aimed to (i) quantify the proportion of infants who received PNS, and describe the timing, type, trends over time, regimen used, and deviations, and (2) describe the clinical characteristics and unadjusted outcomes of infants who received PNS. Study Design This was a cohort study in a quaternary neonatal intensive care unit including infants born at less than 33 weeks, and who received PNS for prevention or treatment of BPD between 2011 and 2021. Following data were included: proportion of babies who received PNS; type of PNS; age at initiation and duration; trends over time; deviation from published regimen; morbidity, mortality, and cointerventions. Results One hundred and eighty four infants (8% of <33 week' infants) received PNS. The median (interquartile range [IQR]) gestational age and birth weight were 25 (24–26) weeks and 720 (625–841) grams, respectively. The median (IQR) day of initiation and duration of PNS use were 29 (19–38) and 10 (10–22) days, respectively. One hundred and fifty-seven (85%) infants received dexamethasone (DX) and 22 (12%) received hydrocortisone as the first PNS course, and 71 (39%) infants received multiple courses. The proportion of infants receiving PNS remained unchanged, but the cumulative median dose received for BPD per patient increased by 56%. Nearly one-third of cumulative PNS dose came from PNS used for non-BPD indications. Forty-six percent infants had a deviation from published regimen (±20% deviation in duration or ±10% deviation in dose). Survival, survival without major morbidity, moderate-to-severe BPD, and technology dependence at discharge were 87, 2, 91, and 67%, respectively. Conclusion Increased variation in PNS use, deviation from published regimen, and concurrent PNS exposure from non-BPD indication offer insights into implementing interventions to improve processes. Key Points In this quaternary NICU, 8% of infants born before 33 weeks were administered postnatal steroids (PNS). The percentage of infants given PNS remained stable; however, the cumulative dose per patient for BPD rose. The study identified targeted interventions to minimize clinical practice variations at the center. [ABSTRACT FROM AUTHOR]

With the seeming end of the COVID-19 epidemic, international focus is rethinking its spillover consequences, such as on the routine provision and usage of healthcare. This study uses China's national death records to estimate the potential spillover effects of the COVID-19 pandemic on the mortality of non-COVID diseases in China, such as chronic diseases and mental disorders. A longitudinal study. Using the difference-in-difference strategy, our results showed a sizeable increase in total non-COVID deaths and mortality from cardiovascular diseases, chronic kidney disease, diabetes, mental diseases, and suicide. Notably, the deaths from diabetes and suicide increased by 4.60% and 7.08%, respectively, relative to the regions without pandemic cases in the first outbreak and escalated by 3.57% and 5.00%, respectively, when the control group switched to the same period in 2019. These results documented adverse spillover effects of COVID-19 on mortality of non-COVID diseases, suggesting inadequate provision and utilization of regular healthcare. The government and healthcare industry should adopt expedient policies for non-epidemic diseases and reallocate health resources to mitigate future pandemics like COVID-19. [ABSTRACT FROM AUTHOR]

Purpose: This study has a purpose to investigate the side effects of three EGFR-TKIs targeted therapeutic agents (gefitinib, erlotinib, and afatinib) and all-cause mortality in patients with metastatic lung cancer. Methods: We performed a prospective cohort study. We selected all patients with newly diagnosed metastatic lung cancer between January and November 2019. Main exposure was daytime versus nighttime use of targeted EGFR TKIs. The study outcome was a symptom change using the mobile application, and all-cause mortality between January 2019 and March 2023. Results: Among the 87 study participants, 35 (40%) took their medication at night. Among the 87 study participants, 35 (40%) took their medication at night. At 6 weeks of treatment, acne (1.36; 95% confidence interval [CI] 1.09, 1.64; p for interaction = 0.04) and dry skin (1.35; 95% CI 1.09, 1.61, p for interaction = 0.01) in the day group showed a much increase from baseline compared to the night group. In contrast, the night group reported greater reductions in lung cancer–related symptoms from baseline compared to the day. During follow-up (median 43 months), the night group had a lower risk of all-cause death than the day group, especially in younger patients (adjusted hazard ratio = 0.34; 95% CI 0.13, 0.87). Conclusions: The group taking EGFR-TKIs at night experienced fewer side effects and had longer overall survival compared to the day group. Clinicians should consider recommending that lung cancer patients take their once-daily oral anticancer drugs in the evening rather than the morning to improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: The main focus of traumatic brain injury (TBI) management is prevention of secondary injury. Therapeutic hypothermia (TH), the induction of a targeted low core body temperature, has been explored as a potential neuroprotectant in TBI. The aim of this article is to synthesize the available clinical data comparing the use of TH with the use of normothermia in TBI. Methods: A systematic search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized clinical trials including one or more outcome of interest associated with TH use in TBI. Independent reviewers evaluated quality of the studies and extracted data on patients with TBI undergoing TH treatment compared with those undergoing normothermia treatment. Pooled estimates, confidence intervals (CIs), and risk ratios (RRs) or odds ratios were calculated for all outcomes. Results: A total of 3,909 patients from 32 studies were eligible for analysis. Pooled analysis revealed a significant benefit of TH on mortality and functional outcome (RR 0.81, 95% CI 0.68–0.96, I2 = 41%; and RR 0.77; 95% CI 0.67–0.88, I2 = 68%, respectively). However, subgroup analysis based on risk of bias showed that only studies with a high risk of bias maintained this benefit. When divided by cooling method, reduced poor functional outcome was seen in the systemic surface cooling and cranial cooling groups (RR 0.68, 95% CI 0.59–0.79, I2 = 35%; and RR 0.44, 95% CI 0.29–0.67, I2 = 0%), and no difference was seen for the systemic intravenous or gastric cooling group. Reduced mortality was only seen in the systemic surface cooling group (RR 0.63, 95% CI 0.53–0.75, I2 = 0%,); however, this group had mostly high risk of bias studies. TH had an increased rate of pneumonia (RR 1.24, 95% CI 1.10–1.40, I2 = 32%), coagulation abnormalities (RR 1.63, 95% CI 1.09–2.44, I2 = 55%), and cardiac arrhythmias (RR 1.78, 95% CI 1.05–3.01, I2 = 21%). Once separated by low and high risk of bias, we saw no difference in these complications in the groups with low risk of bias. Overall quality of the evidence was moderate for mortality, functional outcome, and pneumonia and was low for coagulation abnormalities and cardiac arrhythmias. Conclusions: With the addition of several recent randomized clinical trials and a thorough quality assessment, we have provided an updated systematic review and meta-analysis that concludes that TH does not show any benefit over normothermia in terms of mortality and functional outcome. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to assess long-term outcome in patients with spontaneous intracerebral hemorrhage admitted to the intensive care unit. Methods: Mortality and Glasgow Outcome Scale, Barthel Index, and 5-level EQ-5D version (EQ-5D-5L) scores were analyzed in a multicenter cohort study of three Spanish hospitals (336 patients). Mortality was also analyzed in the Medical Information Mart for Intensive Care III (MIMIC-III) database. Results: The median (25th percentile-75th percentile) age was 62 (50–70) years, the median Glasgow Coma Score was 7 (4–11) points, and the median Acute Physiology and Chronic Health disease Classification System II (APACHE-II) score was 21 (15–26) points. Hospital mortality was 54.17%, mortality at 90 days was 56%, mortality at 1 year was 59.2%, and mortality at 5 years was 66.4%. In the Glasgow Outcome Scale, a normal or disabled self-sufficient situation was recorded in 21.5% of patients at 6 months, in 25.5% of patients after 1 year, and in 22.1% of patients after 5 years of follow-up (4.5% missing). The Barthel Index score of survivors improved over time: 50 (25–80) points at 6 months, 70 (35–95) points at 1 year, and 90 (40–100) points at 5 years (p < 0.001). Quality of life evaluated with the EQ-5D-5L at 1 year and 5 years indicated that greater than 50% of patients had no problems or slight problems in all items (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). In the MIMIC-III study (N = 1354), hospital mortality was 31.83% and was 40.5% at 90 days and 56.2% after 5 years. Conclusions: In patients admitted to the intensive care unit with a diagnosis of nontraumatic intracerebral hemorrhage, hospital mortality up to 90 days after admission is very high. Between 90 days and 5 years after admission, mortality is not high. A large percentage of survivors presented a significant deficit in quality of life and functional status, although with progressive improvement over time. Five years after the hemorrhagic stroke, a survival of 30% was observed, with a good functional status seen in 20% of patients who had been admitted to the hospital. [ABSTRACT FROM AUTHOR]

Introduction: Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. More than 80% of cases and deaths from EC occur within developing countries. In Kenya, cancer is the second leading cause of non-communicable disease deaths, and the trend of cancer deaths is projected to increase as per the 2020 GLOBOCAN report showing 42,116 new cases annually with a mortality of 27,092 cases. EC is the leading cancer in men and the third most common in women in Kenya. The Garissa Regional Cancer Center (GRCC) is one of the three regional cancer centres in Kenya. Despite the rising EC incidence in the region, there is limited data about the clinicopathological features and treatment outcomes of EC, therefore, this is the first study to look at the landscape of EC in the northern Kenya region. Methods: This was a retrospective study involving patients' file review of confirmed EC cases diagnosed or treated at the GRCC from 2019 to 2023. Data collected from each patient's chart included age, sex, risk factors, family history of EC, histological type, stage at diagnosis, treatment type and survival outcomes. For patients who were no longer in contact with the staff through clinic visits, the patients or their next of kin were contacted through phone calls for patients' survival status. Data were collected and stored using the STATA software. Results: Over the study period, 124 esophageal cases were identified, 64 (51.4%) were males and 60 (48.4%) were females with a mean age of 57.56 years. In terms of risk factors, hot beverage consumption was the highest (47 cases, 37.9%), followed by history of peptic ulcer disease (27 cases, 21.8%), smoking (8.9%) and gastresophageal reflux disease (2 cases, 1.6%). Stage of diagnosis at presentation was stage 1 (1 case, 0.8%), stage 2 (22 cases, 17.8%), stage 3 (25 cases, 20.2%), stage 4 (50 cases, 40.3%), not staged (26 cases, 21%). The majority had squamous cell carcinoma (SCC) (105 cases, 84.7%), followed by adenocarcinoma (5 cases, 4%), anaplastic (5 cases, 4%), SCC+ adenocarcinoma (1 case, 0.8%), unknown histology (8 cases, 3.2%). Nearly all patients had triple assessment (Endoscopy, histology and staging scans) accounting for 92 cases (74.2%), 24 cases (20%) had endoscopy+ histology only, and 8 cases (3.2%) had only imaging scans. In terms of family history of EC, 20 cases (16.1%) had a family history of EC. Most of the patients were of ethnic Kenyan-Somali background (108 cases, Kenyan Somali, 87.1%) and majority were from Garissa County 96 cases (77.4%), 12 cases (9.7%) Wajir County, 12 cases (9.7%) from Tana River County and 4 cases (3.2%) from other counties. Many patients lacked health insurance (27 cases, 25.8%), while the majority paid out of pocket (92 cases,74.1%). Only 21% (26 cases) received chemotherapy alone, 5 cases (4%) got radiotherapy alone, 12.9% (16 cases) got chemoradiotherapy and a significant number of patients (77 cases, 62.1%) did not receive hospital-based cancer treatment. Conclusion: This study is the first esophageal study at the GRCC and in northern Kenya in general. Our study confirmed the clinicopathological features of one of the most common cancers in Kenya and more so among Kenyan-Somalis. The study also validates the predominance of histological subtypes of esophageal SCC with the late presentation, short survival and significant loss of follow-up. We recommend future EC studies employing a large prospective design with a large sample size to determine the impact of the new GRCC on the outcomes of EC patients and the local community. [ABSTRACT FROM AUTHOR]

Previous research reported inconsistent results on the efficacy of molnupiravir in treating COVID-19. Moreover, efficacy was not assessed in the intended-use population (IUP), as defined by the FDA. Therefore, we aimed to evaluate the effectiveness and safety of molnupiravir for the treatment of COVID-19 in the IUP. We performed a retrospective cohort study on all IUP in Israel's Clalit Health Services from January 16, 2022, to February 16, 2023. The effectiveness outcome was the incidence of hospitalization or death due to COVID-19, and the safety outcome was the incidence of all-cause mortality within 35 days of SARS-CoV-2 infection. Cox-proportional hazard models were used to analyse the data after 1:5 propensity-score matching. A total of 49 515 patients met the eligibility criteria. Of them, 3957 molnupiravir-treated patients were matched to 19 785 untreated patients. In molnupiravir-treated patients, 70 out of 3957 (5.1 per 10 000 person per day) experienced COVID-19-related hospitalization or death, compared with 699 out of 19 785 untreated patients (10.4 per 10 000 person per day); RR: 0.50 (95% CI, 0.39–0.64). All-cause mortality was also lower in the treated group, with 41 out of 3957 (3.0 per 10 000 person per day) experiencing mortality compared with 414 out of 19 785 untreated patients (6.1 per 10 000 person per day); RR: 0.50 (0.36–0.68). In a real-world cohort of IUP, molnupiravir therapy was associated with a significant reduction in hospitalizations or deaths due to COVID-19 and all-cause mortality. [ABSTRACT FROM AUTHOR]

Current guidelines recommend at least 2 weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear. To perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB. The following are the methods used for this study. We searched MEDLINE, ISI Web of Science, the Cochrane Database and clinicaltrials.gov from inception to March 30, 2024. References of eligible studies were screened and experts in the field contacted for additional articles. All clinical studies, regardless of design, publication status and language. Adult patients with uncomplicated SAB. Long (>14 days; >18 days; 11–16 days) vs. short (≤14 days; 10–18 days; 6–10 days, respectively) DOT with the DOT being defined as the first until the last day of antibiotic therapy. Risk of bias was assessed using the ROBINS-I-tool. The primary outcome was 90-day all-cause mortality. Only studies presenting results of adjusted analyses for mortality were included. Data synthesis could not be performed. Eleven nonrandomized studies were identified that fulfilled the pre-defined inclusion criteria, of which three studies reported adjusted effect ratios. Only these were included in the final analysis. We did not find any RCT. Two studies with 1230 patients reported the primary endpoint 90-day all-cause mortality. Neither found a statistically significant superiority for longer (>14 days; 11–16 days) or shorter DOT (≤14 days; 6–10 days, respectively) for patients with uncomplicated SAB. Two studies investigated the secondary endpoint 30-day all-cause mortality (>18 days; 11–16 days vs. 10–18 days; 6–10 days, respectively) and did not find a statistically significant difference. All included studies had a moderate risk of bias. Sound evidence that supports any duration of antibiotic treatment for patients with uncomplicated SAB is lacking. [ABSTRACT FROM AUTHOR]

The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established. To assess the impact of MDR colonization on SOTR's mortality, infection, or graft loss. Data from PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS were systematically reviewed, spanning from inception until 20 March 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. Cohorts and case–control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae. (CRE), or MDR-pseudomonas, and compared to noncolonized, were included. Two reviewers assessed eligibility, conducted a risk of bias evaluation using the Newcastle-Ottawa Scale, and rated certainty of evidence using the GRADE approach. We employed RevMan for a meta-analysis, using random-effects models to compute pooled odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was determined using the I2 statistic. 15,202 SOTR (33 cohort, six case–control studies) were included, where liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased posttransplant 1-year mortality (OR, 2.35; 95% CI, 1.63–3.38) and mixed infections (OR, 10.74; 95% CI, 7.56–12.26) across transplant types (p < 0.001 and I2 = 58%), but no detected impact on graft loss (p 0.41, I2 = 0). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR, 3.94; mixed infections OR, 24.8; ESBL: mixed infections OR, 10.3; no mortality data) compared to MRSA (Death: OR, 2.25; mixed infection: OR, 7.75) or VRE colonization (Death: p 0.20, mixed infections: OR, 5.71). MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of the evidence, actions to prevent MDR colonization in transplant candidates are warranted. [ABSTRACT FROM AUTHOR]