Risk Factor For Mortality Research Articles

Abstract A111: Leveraging African American women as change agents to reduce obesity-related breast cancer risk: An evaluation of a network-based pilot intervention promoting the Mediterranean diet

Abstract BACKGROUND: Obesity is a key risk factor for breast cancer (BC) incidence, recurrence, and mortality among post-menopausal African American (AA) women. Many older AA women are likely to report fewer healthy dietary behaviors, and those who are overweight or obese are likely to share similar dietary patterns as their social networks (SNs). AA women are also likely to receive information on BC risk from their SNs. Thus, AA women who share information on healthy dietary behaviors are well-positioned to become change agents toward reducing obesity and improving BC outcomes among their SNs. This presents a novel opportunity to increase the impact of evidence-based (EB) interventions focused on reducing obesity-related BC risk. This study aimed to assess the effects of the MedDiet-SN pilot intervention among participants trained as change agents to improve obesity-related BC risk reduction behaviors for themselves and their SNs through EB information sharing. Methods: MedDiet-SN was a 10-week, pre-/post- pilot intervention promoting the uptake of the Mediterranean diet, with participant training on effective EB information sharing. A community-based participant advisory board informed the pilot. Study procedures were IRB approved. Eligible participants were AA women, ≥60 years old, overweight or obese, Chicago area residents, and with no severe health conditions. Sixteen women participated, and 30 of their SN members (age ≥18 years) were recruited through participant referral. Predictors included time from pre- to post-study and session dosage for participants, and participant EB information sharing on healthy eating for SN members. Outcomes for both groups included BC and diet knowledge, dietary change attitudes (motivation, self-efficacy), dietary behavior change, and BMI. EB information sharing on healthy eating was an additional outcome for participants. Bivariate and multivariate analyses were performed to assess outcomes. Results: In crude and adjusted time models, participants showed improved knowledge, behavior change, BMI, and EB information sharing (p<0.05). In adjusted dosage models, participants showed improved knowledge, attitudes, and EB information sharing (p<0.05). SN members showed improved attitudes and behavior change based on participant EB information sharing on healthy eating (p<0.05). In addition, there was a high concordance between participant EB information sharing and SN EB information learned (>70%). CONCLUSION: This research is innovative in that it 1) shows the effectiveness of a network-based intervention promoting healthy dietary behaviors for obesity-related BC risk reduction among AA women, 2) supports the value of scaling up interventions by leveraging participants as change agents for EB information sharing among SNs, and 3) provides a contribution to emerging research on positive intervention spillover effects to SNs. It is anticipated that results from this study will inform the development of future network-based interventions that aim to reduce obesity-related BC risk and improve health outcomes for AA women. Citation Format: Nyahne Bergeron, Mona Strahan, Patricia Hardmon, Marja Stanford- Leak, Anita Stevens, Annie Young, Devyanne Ward, Lois White, Eunhye Lee, Lisa Tussing-Humphreys, Marian Fitzgibbon, Yamilé Molina. Leveraging African American women as change agents to reduce obesity-related breast cancer risk: An evaluation of a network-based pilot intervention promoting the Mediterranean diet [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A111.

Clinical manifestations and outcomes in adults hospitalized with respiratory syncytial virus and influenza A/B: A multicenter observational cohort study

Abstract Background Respiratory syncytial virus (RSV) and influenza cause significant health challenges, particularly for individuals with comorbidities and older adults. However, information on the clinical manifestiations and outcomes of adults hospitalized with RSV in Europe remains limited. Methods This multicenter observational cohort study of adults hospitalized with RSV or influenza A or B from March 2016 to April 2020 investigated the clinical manifestations, mortality risk factors, and association with 90-days mortality by logistic regression analysis after adjustment for covariates. Results Of 988 patients hospitalized with either virus, 353 had RSV, 347 had influenza A, and 288 had influenza B infection. Patients with RSV more often had comorbidities (83% vs. 72%, p=0.030 vs. 74%, p=0.001) and pneumonia (41% vs. 29%, p=0.028, and 24%, p<0.001) compared to influenza A and B, respectively. After adjustment for covariates, RSV infection was associated with an increased all-cause mortality within 90 days compared to influenza B infection (OR 2.16 [1.20-3.87], p=0.010) but not influenza A (OR 1.38 [0.84-2.29], p=0.207). Increasing age and present pneumonia were identified as independent risk factors of mortality in patients with RSV. Conclusion Older adults hospitalized with RSV infections are at a higher risk of dying within 90 days of hospitalization than patients admitted with influenza B, but similar to those admitted with influenza A, emphasizing the detrimental effects and severity of older patients being infected with RSV. Our findings underscore the need for strategic testing and vaccination approaches to mitigate the impact of RSV among older adults.

Effect of Chemotherapy and Surgery Timing on Mortality in Upper and Lower Extremity Osteosarcoma

Abstract Background Surgery with both neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests that up-front surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care (“Neoadjuvant First”) vs upfront surgery first followed by adjuvant chemotherapy (“Surgery First”). Patients and methods Using Surveillance, Epidemiology, and End Results data, we identified patients age 5-29, diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups. Results Adjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8% to 13.7% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage 3-4 disease (vs stage 1-2 disease). Conclusion The evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the peri-surgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.

Mortality Risk and Antibiotic Therapy for Patients with Infections Caused by Elizabethkingia Species—A Meta-Analysis

Background and Objectives: Patients with infections caused by Elizabethkingia species require prompt identification and effective antibiotic treatment since these spp. are typically resistant to multiple antibiotics and variable susceptibility patterns. Understanding the mortality risk of this disease is difficult because of the relatively low incidence of infections caused by Elizabethkingia spp. and the lack of published systematic evaluations of the risk factors for mortality. The aim of the present study was to investigate risk factors for mortality in patients with infections caused by Elizabethkingia spp. by conducting a meta-analysis of existing studies on these infections. Materials and Methods: Studies comparing patients who died from infections caused by Elizabethkingia spp. with patients who survived were considered for inclusion. Studies that reported one or more risk factors for mortality were considered. Clinical predisposing variables, predisposing comorbidities, and clinical outcomes of antibiotic treatment were among the risk factors for mortality. Results: The meta-analysis included twenty studies with 990 patients, and 298 patients (30.1%) died. The following risk factors for mortality were identified: intensive care unit admission, the need for mechanical ventilation, immunosuppressive or steroid therapy use, pneumonia, comorbid liver disease, and the use of inappropriate antimicrobial therapy. Conclusions: The use of appropriate antimicrobial therapy is critical for the effective management of infections caused by Elizabethkingia spp. Antimicrobial susceptibility testing would be a more reliable means of guiding treatment. The identification of the best antimicrobial drugs is needed to ensure optimal treatment recommendations for treating Elizabethkingia-related infections.

Clinical predictors of poor outcome of bacterial meningitis in infants less than 90 days: a systematic review

Backgroundbacterial meningitis (BM) is more common in infants than at any other time in life and remains a devastating disease with considerable risk of death and morbidity. This article aims to gather the currently available evidence to perform a systematic review of clinical factors that may predict or be associated with BM death and/or sequelae in infants < 90 days of age.MethodsThe Medline/PubMed, Cochrane Library and Embase databases were systematically searched for prognostic studies that described risk factors for mortality and sequelae in infants aged <90d with BM. The databases were searched from the beginning of the database to December 31st, 2022.The quality of cohort studies was assessed by the Newcastle-Ottawa Scale (NOS). The quality of cross-section studies was assessed by the Agency for Healthcare Research and Quality (AHRQ). A systematic review was undertaken to ascertain the prognostic factors proven to be noteworthy.ResultsOf the 1,431 studies retrieved, 20 were eligible for the final analysis including 11 cohort and 9 cross-sectional studies were identified. Four risk factors predicting poor outcome were mentioned mostly in those studies, including prematurity or low birth weight (LBW), seizures, coma, and elevated CSF protein. But only preterm, coma and elevated CSF protein were identified by multivariate analyses in more than one study.ConclusionsThis study demonstrates several potential predictive factors to the poor outcomes of BM in infant. But with large heterogeneity, these predictors should be evaluated by further well-designed prospective studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/, identifier CRD42017074949.

Real-world evaluation of multimodal treatment practice in older oesophageal cancer patients

Abstract OBJECTIVES Elderly-specific data for multimodal treatment of oesophageal cancer (EC) is lacking. This study aimed to evaluate the safety and efficacy of multimodal treatment in older EC patients and to compare the impact of neoadjuvant chemotherapy (NCT) and neoadjuvant chemoradiotherapy (NCRT). METHODS Patients diagnosed with oesophageal squamous cell carcinoma or adenocarcinoma who received NCT/NCRT were identified in the National Cancer Database (NCDB, 2004–2015). First, we compared baseline and post-treatment characteristics between younger (<70 years) and older patients (≥70 years). Logistic regression was used to investigate risk factors of postoperative mortality. Second, we evaluated the effect of neoadjuvant chemotherapy on postoperative mortality and overall survival in the older cohort. Inverse probability of treatment weights (IPTW) and multivariable analyses were used to compensate for differences in baseline covariates. RESULTS We first compared outcomes of neoadjuvant therapy plus oesophagectomy in 14778 eligible EC patients. The older group experienced higher rates of postoperative mortality at 30 days (5.8%) and 90 days (13.5%) compared to younger patients. Postoperative mortality was significantly related to the Charlson-Deyo score and treatment-related factors including NAT type and minimally invasive technique. Second, among the 3,141 older patients (with a median follow-up of 57.8 months and 2029 deaths), those receiving NCT obtained significantly lower postoperative mortality and improved overall survival compared with NCRT (IPTW-Adjusted P = 0.05; HR, 0.85; 95% Cl, 0.72–0.99). CONCLUSIONS Neoadjuvant therapy plus oesophagectomy carries increased short-term mortality risk in older EC patients. NCT in older EC patients showed lower postoperative mortality but no statistically significant differences in overall survival with a point estimate favoring NCT compared to the NCRT group, making NCT a potential option for consideration in specific cases.

Early B lymphocyte subsets in blood predict prognosis in sepsis

BackgroundB lymphocytes play a key role in immunosuppression. This study investigated the prognostic value of B cell subsets in sepsis.MethodsFlow cytometry was used to assess peripheral B cell subsets from patients with sepsis on the first and seventh days following admission, as well as 111 healthy controls. The patients were divided into survivors and non-survivors, based on 28-day prognosis.ResultsThe analysis showed abnormal distribution and selective depletion of B cells and its subsets in the early stages of sepsis. On day 1, compared with survivors, non-survivors showed significant decreases in the proportion and absolute count of transitional (Tr) B cells, reductions in the proportion of CD5+ B cells, and increases in the proportion of double-negative (DN) B cells. On day 7, the proportions and absolute counts of Tr and CD5+ B cells significantly decreased whereas the proportion of DN B cells significantly increased in non-survivors. Ninety-four survivors and 15 non-survivors were included in our paired-sample rank-sum test. Compared to day 1, only the survivors showed significant increases in absolute B, Tr B, and CD5+ B cell counts by day 7. Multivariate Cox regression analysis showed that the proportion of DN B cells on day 1 (hazard ratio = 1.092 [95% confidence interval: 1.035–1.152], P = 0.001) was a risk factor for mortality, and Kaplan–Meier survival curve analysis showed that patients with proportions of DN B cells > 11.81% on day 1 had poorer prognoses. Receiver operating characteristic curve analysis showed that B cell subset parameters could predict mortality (area under the receiver operating characteristic curve [AUC], 0.741) and enhanced the prognostic value of the Acute Physiology and Chronic Health Evaluation II score (AUC, 0.840).ConclusionOur study revealed that deficiencies of B, Tr B, and CD5+ B cells, as well as a persistent increase in the proportion of DN B cells, were associated with poor prognosis—and that B cell subsets showed predictive value to mortality. These results provide new insights into the roles of B cell subsets in sepsis, as well as ways to better manage its progression and predict its course.

Polygenic Interactions With Environmental Exposures in Blood Pressure Regulation: The HUNT Study.

The essential hypertension phenotype results from an interplay between genetic and environmental factors. The influence of lifestyle exposures such as excess adiposity, alcohol consumption, tobacco use, diet, and activity patterns on blood pressure (BP) is well established. Additionally, polygenic risk scores for BP traits are associated with clinically significant phenotypic variation. However, interactions between genetic and environmental risk factors in hypertension morbidity and mortality are poorly characterized. We used genotype and phenotype data from up to 49 234 participants from the HUNT (Trøndelag Health Study) to model gene-environment interactions between genome-wide polygenic risk scores for systolic BP and diastolic BP and 125 environmental exposures. Among the 125 environmental exposures assessed, 108 and 100 were independently associated with SBP and DBP, respectively. Of these, 12 interactions were identified for genome-wide PRSs for systolic BP and 4 for genome-wide polygenic risk scores for diastolic BP, 2 of which were overlapping (P < 2 × 10-4). We found evidence for gene-dependent influence of lifestyle factors such as cardiorespiratory fitness, dietary patterns, and tobacco exposure, as well as biomarkers such as serum cholesterol, creatinine, and alkaline phosphatase on BP. Individuals that are genetically susceptible to high BP may be more vulnerable to common acquired risk factors for hypertension, but these effects appear to be modifiable. The gene-dependent influence of several common acquired risk factors indicates the potential of genetic data combined with lifestyle assessments in risk stratification, and gene-environment-informed risk modeling in the prevention and management of hypertension.

Hyperhomocysteinemia in Chronic Kidney Disease: A Meta-Analysis

Background: Hyperhomocysteinemia, an elevated level of homocysteine in the blood, has been implicated in the progression of chronic kidney disease (CKD). This meta-analysis aims to comprehensively evaluate the association between hyperhomocysteinemia and CKD and its potential impact on clinical outcomes. Methods: This study systematically searched electronic databases (PubMed, Embase, Cochrane Library) for studies published between 2018 and 2024 investigating the relationship between hyperhomocysteinemia and CKD. Studies reporting data on the association between hyperhomocysteinemia and CKD progression, cardiovascular events, or mortality were included. We extracted relevant data and performed a meta-analysis using random-effects models. Results: The meta-analysis included 25 studies comprising 5,672 patients with CKD. Hyperhomocysteinemia was significantly associated with an increased risk of CKD progression (pooled odds ratio [OR] 1.85, 95% confidence interval [CI] 1.52-2.24), cardiovascular events (pooled OR 1.63, 95% CI 1.31-2.02), and all-cause mortality (pooled OR 1.48, 95% CI 1.17-1.87) in CKD patients. Subgroup analyses revealed a consistent association across different CKD stages and etiologies. Conclusion: Hyperhomocysteinemia is an independent risk factor for CKD progression, cardiovascular events, and mortality. Monitoring and managing hyperhomocysteinemia may represent a potential therapeutic target to improve outcomes in CKD patients.

Glucose-Free Solutions Mediated Inhibition of Oxidative Stress and Oxidative Stress-Related Damages in Peritoneal Dialysis: A Promising Solution

Oxidative stress (OxSt) and inflammation are common in end-stage renal disease and dialysis patients; they are known risk factors for cardiovascular disease and mortality. In peritoneal dialysis (PD), OxSt and inflammation are even further increased compared to the already increased oxidative stress of their pre-dialysis phase. This is due to the high glucose-based solutions currently used, whose continuous contact with the peritoneal membrane can induce significant long-term morphological and functional changes (mesothelial to mesenchymal transition, thickening, neo-angiogenesis and fibrosis) of the peritoneal membrane. Oxidative stress plays a very important role in these processes, which may compromise the peritoneal dialysis procedure. There is, therefore, the need for more biocompatible dialysis fluids with polymers other than glucose to prevent and treat OxSt and inflammation. The most known and used of such glucose-free and more biocompatible peritoneal dialysis solutions is icodextrin, which has shown a protective effect from oxidative stress. This has supported the consideration of the use of glucose-free-based peritoneal dialysis fluids in order to reduce oxidative stress and improve peritoneal membrane survival. Studies investigating peritoneal dialysis with the use of osmo-metabolic agents (L-carnitine, xylitol and their combination) in peritoneal fluids replacing glucose-based fluids are, in fact, ongoing. They represent a promising strategy to reduce OxSt, preserve the peritoneal membrane’s integrity and improve patients’ outcome.

Assessing the Predictive Utility of the C-Reactive Protein-to-Lymphocyte Ratio for Mortality in Isolated Traumatic Brain Injury: A Single-Center Retrospective Analysis

Introduction: Early identification of high-risk traumatic brain injury (TBI) patients is crucial for optimizing treatment strategies and improving outcomes. The C-reactive protein-to-lymphocyte ratio (CLR) reflects systemic immunology and inflammation function and serves as a new biomarker for patient stratification. This study aimed to assess the predictive value of the CLR for mortality in patients with isolated moderate to severe TBI. Methods: A retrospective analysis of trauma registry data from 2009 to 2022 was conducted, including 1641 adult patients with isolated moderate to severe TBI. Patient demographics, the CLR, injury characteristics, and outcomes were compared between deceased and surviving patients. Univariate and multivariate analyses were performed to identify mortality risk factors. The optimal CLR cut-off value for predicting mortality was determined using receiver operating characteristic (ROC) curve analysis. Results: The CLR was significantly higher in deceased patients compared to survivors (60.1 vs. 33.9, p &lt; 0.001). The optimal CLR cut-off value for predicting mortality was 54.5, with a sensitivity of 0.328 and a specificity of 0.812. The area under the ROC curve was 0.566, indicating poor discriminative ability. In the multivariate analysis, the CLR was not a significant independent predictor of mortality (OR 1.03, p = 0.051). After propensity score matching to attenuate the difference in baseline characteristics, including sex, age, comorbidities, conscious level, and injury severity, the high-CLR group (CLR ≥ 54.5) did not have significantly higher mortality compared to the low-CLR group (CLR &lt; 54.5). Conclusion: While the CLR was associated with mortality in TBI patients, it demonstrated poor discriminative ability as a standalone predictor. The association between a high CLR and worse outcomes may be primarily due to other baseline patient and injury characteristics, rather than the CLR itself.

Risk Factors for Mortality in Critically Ill Patients with Coagulation Abnormalities: A Retrospective Cohort Study.

Coagulation abnormalities are common and prognostically significant in intensive care units (ICUs) and are associated with increased mortality. This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities. This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022. The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0. Patients were followed up for 28 days, and multivariate logistic regression analysis was utilized to identify risk factors for mortality. Of the 451 patients analyzed, 115 died, and 336 were alive at the end of the 28-day period. Multivariate analysis revealed that elevated thrombin-antithrombin complex (TAT), tissue plasminogen activator inhibitor complex (tPAIC), prolonged prothrombin time, and thrombocytopenia were independent risk factors for mortality. For nonovert disseminated intravascular coagulation (DIC) patients, older age and thrombocytopenia were associated with increased risks of mortality, whereas elevated levels of plasmin α2-plasmin inhibitor complex (PIC) were found to be independent predictors of survival. In patients with overt DIC, elevated levels of tPAIC were independently associated with increased risks of mortality. Nevertheless, thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC. Coagulation markers such as the TAT, tPAIC, PIC, and platelet count were significantly associated with mortality, underscoring the importance of maintaining a balance between coagulation and fibrinolysis. These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.

TBI related death has become the new epidemic in polytrauma: a 10-year prospective cohort analysis in severely injured patients.

Advances in trauma care have attributed to a decrease in mortality and change in cause of death. Consequently, exsanguination and traumatic brain injury (TBI) have become the most common causes of death. Exsanguination decreased by early hemorrhage control strategies, whereas TBI has become a global health problem. The aim of this study was to investigate trends in injury severity,physiology, treatment and mortality in the last decade. In 2014, a prospective cohort study was started including consecutive severely injured trauma patients > 15years admitted to a Level-1 Trauma Center ICU. Demographics,physiology,resuscitation, and outcome parameters were prospectively collected. Five hundred and seventy-eight severely injured patients with predominantly blunt injuries (94%) were included. Seventy-two percent were male with a median age of 46 (28-61) years, and ISS of 29 (22-38). Overall mortality rate was 18% (106/578) with TBI (66%, 70/106) being the largest cause of death. Less than 1% (5/578) died of exsanguination. Trend analysis of the 10-year period revealed similar mortality rates despite an ISS increase in the last 2years. No significant differences in demographics,and physiology in ED were noted. Resuscitation strategy changed to less crystalloids and more FFP. Risk factors for mortality were age,brain injury severity,base deficit,hypoxia,and crystalloid resuscitation. TBI was the single largest cause of death in severely injured patients in the last decade. With an aging population TBI will increase and become the next epidemic in trauma. Future research should focus on brain injury prevention and decreasing the inflammatory response in brain tissue causing secondary damage, as was previously done in other parts of the body.

Predictive Mortality of the Prognostic Nutritional Index Combined with APACHE II Score for Critically Ill Tuberculosis Patients.

High mortality rates are commonly found in critically ill patients with tuberculosis (TB), which is due partially to limitations in the existing prognostic evaluation methods. Therefore, we aimed to find more effective prognostic evaluation tools to reduce the mortality rate. Data from critically ill patients with TB admitted to the intensive care unit of The Second Hospital of Nanjing, Nanjing, China, between January 2020 and December 2022 were analyzed retrospectively. A total of 115 patients were enrolled and divided into a survival group (n = 62) and a death group (n = 53) according to 30-day survival. Univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were used to investigate the risk factors for 30-day death in critically ill patients with TB. A prediction model for risk of 30-day mortality was developed for critically ill patients with TB in the intensive care unit. The LASSO regression model showed that the prognostic nutritional index (PNI) and Acute Physiology and Chronic Health Status (APACHE II) scores on the third day after admission to the intensive care unit were independent risk factors for 30-day mortality in critically ill patients with TB (P <0.05). The area under the curve value and that PA3 represents the combination of the PNI and APACHE II score on the third day, which was 0.952 (95% CI: 0.913-0.991, P <0.001), was significantly higher than that of the PNI or the APACHE II score on the third day. The new model is as follows: PA3 = APACHE II score (on the third day) × 0.421 - PNI × 0.204. The PNI combined with the APACHE II score on the third day could well predict the 30-day mortality risk of critically ill patients with TB.

The influence of comorbidities on treatment outcomes in patients with tuberculosis

Aim. To study the association of comorbidities and treatment outcomes in tuberculosis (TB) patients. Materials and methods. A retrospective study includes all TB patients aged 18 years and older registered for treatment in Moscow in period 2021 the end of the 3rd quarter of 2022 using data of regional epidemiological TB monitoring system, a total of 3039 patients. The frequency and spectrum of comorbidities, its impact on the risk of adverse treatment outcome (ATO) and mortality using univariate and regression analysis were assessed. Results. Comorbidities were identified in 1528 (50.3%) patients (95% confidence interval – CI 48.5–52.1); HIV infection (18.0%), chronic nonspecific lung disease (9.6%) and cardiovascular disease (8.2%) were predominant. The presence of comorbid pathology increased the odds of uneffective treatment (odds ratio – OR 2.56, 95% CI 2.22–3.03) and death (OR 2.45, 95% СI 1.67–3.59). Independent risk factors for ATO were HIV infection (OR 4.10, 95% CI 3.36–5.10), substance use (OR 2.57, 95% CI 1.70–3.66), chronic nonspecific lung disease (OR 1.39, 95% CI 1.04–1.88), diabetes mellitus (OR 1.69, 95% CI 1.15–2.48), liver pathology (OR 2.10, 95% CI 1.46–3.03), mental illness (OR 2.01, 95% CI 1.32–3.06). The death rate was 13.4%; the most significant predictors of mortality were HIV infection (OR 3.89, 95% CI 2.42–6.22) and liver disease (OR 1.90, 95% CI 1.27–2.82). A comorbidome model was constructed to assess the importance of different comorbidities for patient prognosis. Conclusion. The presence of comorbidity (predominantly HIV infection and liver disease) is a significant risk factor for ATO and mortality in TB patients, which should be taken into account when organizing and providing TB care to comorbid patients.

Mortality and prognostic factors among inpatients with systemic lupus erythematosus in China: A 20-year retrospective study.

To summarize the causes of death and clinical characteristics of systemic lupus erythematosus (SLE) hospitalized patients in the last 20 years to improve SLE survival rates by detecting critical SLE early. In this case-control study, 218 SLE death cases were retrospectively analyzed from January 2002 to December 2022, with 110 SLE inpatients chosen at random as controls. The clinical symptoms, causes of death, and risk factors in patients with SLE were investigated. There were 218 deaths among 9538 patients with SLE, including 188 women and 30 men. The death rate fell steadily from 4.14% in 2002 to 1.96% in 2013 and remained at 1.84% from 2014 to 2022. The standardized mortality ratio (SMR) was 4.98 [95% CI (4.06-5.89)] from 2002 to 2012 and 3.39 [95% CI (2.74-4.04)] from 2013 to 2022. Infection, lupus-induced multiple organ failure syndrome (MODS), and neuropsychiatric lupus (NPLE) were the leading causes of death, accounting for 31.19%, 15.14%, and 11.47% of overall deaths. Age had a significant association with the major causes of death. Logistic regression analysis showed NPLE[OR = 10.772,95% CI (3.350,34.633), p < 0.001], lupus pulmonary involvement (LP)[OR = 3.844,95%CI (1.547,9.552), p = 0.004], pneumonia[OR = 3.439,95%CI(1.552,7.621), p = 0.002], thrombocytopenia[OR = 14.941,95%CI (4.088,54.604), p < 0.001], creatinine>177μmol/L[OR = 8.644,95%CI (2.831,26.388), p < 0.001], glutamic transaminase(AST) > 60U/L[OR = 5.762,95%CI (2.200,15.088), p < 0.001], total bilirubin > 34μmol/L[OR = 16.701,95%CI (3.349,83.294), p = 0.001], higher SLE Disease Activity Index (SLEDAI)[OR = 1.089,95%CI (1.032,1.149), p = 0.002] and SLE Damage Index (SDI)[OR = 3.690,95%CI (2.487,5.474), p < 0.001] correlated positively with death. From 2002 to 2013, the mortality rate among patients with SLE fell steadily but remained unchanged from 2014 to 2022. Patients with SLE had significantly higher SMR than the general population. Childhood-onset SLE had a poorer prognosis than adult-onset SLE. Infection, MODS, and NPLE were the three leading causes of death. Major organ involvement and high disease activity were risk factors for mortality.

Myeloid-Specific JAK2 Contributes to Inflammation and Salt Sensitivity of Blood Pressure.

Salt sensitivity of blood pressure (SSBP), characterized by acute changes in blood pressure with changes in dietary sodium intake, is an independent risk factor for cardiovascular disease and mortality in people with and without hypertension. We previously found that elevated sodium concentration activates antigen-presenting cells (APCs), resulting in high blood pressure, but the mechanisms are unknown. Here, we hypothesized that APC-specific JAK2 (Janus kinase 2) through STAT3 (signal transducer and activator of transcription 3) and SMAD3 (small mothers against decapentaplegic homolog 3) contributes to SSBP. We performed bulk or single-cell transcriptomic analyses following in vitro monocytes exposed to high salt and in vivo high sodium treatment in humans using a rigorous salt-loading/depletion protocol to phenotype SSBP. We also used a myeloid cell-specific CD11c+ JAK2 knockout mouse model and measured blood pressure with radiotelemetry after N-omega-nitro-L-arginine-methyl ester and a high salt diet treatment. We used flow cytometry for immunophenotyping and measuring cytokine levels. Fluorescence in situ hybridization and immunohistochemistry were performed to spatially visualize the kidney's immune cells and cytokine levels. Echocardiography was performed to assess cardiac function. We found that high salt treatment upregulates gene expression of the JAK/STAT/SMAD pathway while downregulating inhibitors of this pathway, such as suppression of cytokine signaling and cytokine-inducible SH2, in human monocytes. Expression of the JAK2 pathway genes mirrored changes in blood pressure after salt loading and depletion in salt-sensitive but not salt-resistant humans. Ablation of JAK2, specifically in CD11c+ APCs, attenuated salt-induced hypertension in mice with SSBP. Mechanistically, we found that SMAD3 acted downstream of JAK2 and STAT3, leading to increased production of highly reactive isolevuglandins and proinflammatory cytokine IL (interleukin)-6 in renal APCs, which activate T cells and increase production of IL-17A, IL-6, and TNF-α (tumor necrosis factor-alpha). Our findings reveal the APC JAK2 signaling pathway as a potential target for the diagnosis and treatment of SSBP in humans.

Effects of dietary interventions and intermittent fasting on HDL function in obese individuals with T2DM: a randomized controlled trial

BackgroundCardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM.MethodsBefore the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants’ glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA.ResultsFollowing the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance.ConclusionsA balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality.Trial registrationThe study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070.Graphical

Disinfection byproducts in US drinking water and cancer mortality

ABSTRACT Trihalomethanes, the main drinking water disinfection byproducts, may be carcinogenic and are regulated to amaximum total trihalomethanes (TTHM) of 80 µg/l in the US. We aimed to determine whether total and individual trihalomethanes in drinking water across the US are associated with higher cancer mortality in 6,260 adult participants to the National Health and Nutrition Examination Surveys from 1999 to 2008 followed for mortality until 2019 (median: 14.4 years). At baseline, the geometric mean (standard error) of TTHM in drinking water was 9.61 (0.85) µg/l. During follow-up, 873 deaths occurred, including 207 from cancer. In Cox proportional hazards regression adjusted for relevant covariates, drinking water TTHM (HR: 1.45, 95% CI: 1.16–1.82), chloroform (HR: 1.35, 95% CI: 1.12–1.64), and bromodichloromethane (HR: 1.30, 95% CI: 1.05–1.59) were associated with 30% to 45% higher cancer mortality. Therefore, drinking water trihalomethanes, especially chloroform and bromodichloromethane maybe risk factors for cancer mortality.

Glycaemic control is a modifiable risk factor for hepatocellular carcinoma and liver-related mortality in patients with diabetes.

Optimal glycaemic control has well-established health benefits in patients with diabetes mellitus (DM). It is uncertain whether optimal glycaemic control can benefit liver-related outcomes. To examine the association of optimal glycaemic control with hepatocellular carcinoma (HCC) and liver-related mortality. In a population-based cohort, we identified patients with newly diagnosed DM between 2001 and 2016 in Hong Kong. Optimal glycaemic control was defined as mean haemoglobin A1c (HbA1c) <7% during the 3-year lead-in period after DM diagnosis. By applying propensity score matching to balance covariates, we analysed glycaemic control via competing risk models with outcomes of interest being HCC and liver-related mortality. We identified 146,430 patients (52.2% males, mean age 61.4 ± 11.8 years). During a median follow-up duration of 7.0 years, 1099 (0.8%) and 978 (0.7%) patients developed HCC and liver-related deaths. Optimal glycaemic control, when compared to suboptimal glycaemic control, was associated with reduced risk of HCC (subdistribution hazard ratio [SHR] 0.70, 95% CI 0.61-0.79). The risk of HCC increased with incremental HbA1c increases beyond >7% (SHR 1.29-1.71). Significant associations with HCC were also found irrespective of age (SHR 0.54-0.80), sex (SHR 0.68-0.69), BMI <25 or ≥25 kg/m2 (SHR 0.63-0.75), smoking (SHR 0.61-0.72), hepatic steatosis (SHR 0.67-0.68) and aspirin/statin/metformin use (SHR 0.67-0.75). A lower risk of liver-related mortality in relation to optimal glycaemic control was also observed (SHR 0.70, 95% CI 0.61-0.80). Glycaemic control is an independent risk factor for HCC and liver-related mortality, and should be incorporated into oncoprotective strategies in the general DM population.