Reduced Risk Of Mortality Research Articles

Reviving Decades-Old Wisdom: Longitudinal Analysis of Renin-Angiotensin System Inhibitors and Its Effects on Acute Ischemic Stroke to Improve Outcomes.

While renin-angiotensin system (RAS) inhibitors have a longstanding history in blood pressure control, their suitability as first-line in-patient treatment may be limited due to prolonged half-life and kidney failure concerns. Using a cohort design, we assessed the impact of RAS inhibitors, either alone or in combination with beta-blockers, on mortality, while exploring interactions, including those related to end-stage renal disease and serum creatinine levels. Eligible subjects were Acute Ischemic Stroke (AIS) patients aged 18 or older with specific subtypes who received in-patient antihypertensive treatment. The primary outcome was mortality rates. Statistical analyses included cross-sectional and longitudinal approaches, employing generalized linear models, G-computation, and discrete-time survival analysis over a 20-day follow-up period. In our study of 3,058 AIS patients, those using RAS inhibitors had significantly lower in-hospital mortality (2.2%) compared to non-users (12.1%), resulting in a relative risk (RR) of 0.18 (95% CI: 0.12-0.26). Further analysis using G-computation revealed a marked reduction in mortality risk associated with RAS inhibitors (0.0281 vs. 0.0913, risk difference [RD] of 6.31% or 0.0631, 95% CI: 0.046-0.079). Subgroup analysis demonstrated notable benefits, with individuals having creatinine levels below and above 1.3 mg/dl exhibiting statistically significant RD (RD -0.0510 vs. -0.0895), and a significant difference in paired comparison (-0.0385 or 3.85%, CI 0.023-0.054). Additionally, longitudinal analysis confirmed a consistent daily reduction of 0.93% in mortality risk associated with the intake of RAS inhibitors. RAS inhibitors are associated with a significant reduction in in-hospital mortality in AIS patients, suggesting potential clinical benefits in improving patient outcomes.

Identification of the Microbiome Associated with Prognosis in Patients with Chronic Liver Disease.

We investigated the prognostic role of the gut microbiome and clinical factors in chronic liver disease (hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]). Utilizing data from 227 patients whose stool samples were collected over the prior 3 years and a Cox proportional hazards model, we integrated clinical attributes and microbiome composition based on 16S ribosomal RNA sequencing. HCC was the primary cause of mortality, with the Barcelona Clinic Liver Cancer staging system-derived B/C significantly increasing the mortality risk (hazard ratio [HR] = 8.060; 95% confidence interval [CI]: 3.6509-17.793; p < 0.001). Cholesterol levels < 140 mg/dL were associated with higher mortality rates (HR = 4.411; 95% CI: 2.0151-9.6555; p < 0.001). Incertae sedis from Ruminococcaceae showed a protective effect, reducing mortality risk (HR = 0.289; 95% CI: 0.1282 to 0.6538; p = 0.002), whereas increased Veillonella presence was associated with a higher risk (HR = 2.733; 95% CI: 1.1922-6.2664; p = 0.017). The potential of specific bacterial taxa as independent prognostic factors suggests that integrating microbiome data could improve the prognosis and treatment of chronic liver disease. These microbiome-derived markers have prognostic significance independently and in conjunction with clinical factors, suggesting their utility in improving a patient's prognosis.

Abstract MP24: Contemporary Trends in Incident Ischemic Stroke, Intracranial Hemorrhage, and Mortality in Individuals With Atrial Fibrillation

Background: The prognosis for atrial fibrillation (AF) patients is based on data that is decades old. Given evolving standards of clinical practice that may now include lifestyle factor modification, catheter ablation, and DOACs, we evaluated temporal trends in clinically important outcomes among patients with AF. Methods: California’s Department of Health Care Access and Information databases were used to identify adults aged ≥18 years with AF receiving hospital-based care in California. We compared 3 time-periods in this population-based cohort corresponding to 2005-2009, 2010-2014, and 2015-2019. The outcomes were incident ischemic stroke, intracranial hemorrhage, and mortality. Results: We included 1,859,901 patients with AF (52.7% males, 71.0% Whites, and mean age of 74.8 years), divided in 3 cohorts: 2005-2009 (n=680,872), 2010-2014 (n=558,365), and 2015-2019 (n=620,664). Each of these outcomes became substantially less common with time: compared to 2005-2009 ( Figure 1A ), AF patients diagnosed in 2015-2019 experienced a 42% (adjusted hazard ratio [HR] 0.58, 95% CI 0.57-0.60), 17% (HR 0.83, 95% CI 0.80-0.88), and 28% (HR 0.72, 95% CI 0.71-0.73) reduction in risk of incident ischemic stroke, intracranial hemorrhage, and mortality, respectively. Between 2005-2009 and 2015-2019, the decline in the incidence rate of adverse outcomes was greater in patients aged ≥65 years (p&lt;.001), females (p=.02), and Whites (p&lt;.001) for ischemic stroke; more pronounced in patients aged ≥65 years (p=.008), females (p=.02), and Whites and Asians (p=.005) for intracranial hemorrhage; and greater in patients aged ≥65 years (p&lt;.001), in males (p=.04), and in Whites (p&lt;.001) for mortality ( Figure 1B ). Conclusion: The risk of stroke, intracranial hemorrhage, and mortality have significantly declined among AF patients, although significant disparities in the magnitude of improvement of these outcomes by demographic groups were observed. Estimates of the prognosis for AF patients should be updated to reflect contemporary care.

Abstract 19: Time-Varying Exposure to Food Retailers and Cardiovascular Disease Incidence and Mortality in the Netherlands: A Nationwide Prospective Cohort Study

Background: The food environment is suggested as a risk factor of cardiovascular disease (CVD), but current evidence is inconsistent and does not account for changes in the food environment. We aimed to explore if time-varying exposure to the food environment was associated with hospitalisation and mortality due to total and specific types of CVD in The Netherlands. We hypothesized that favourable time-varying trends in food environment exposure would be associated with decreased risk of CVD, stroke, heart failure (HF), and coronary heart disease (CHD) morbidity and mortality among the Dutch general population. Methods: A prospective cohort study was performed among all Dutch residents aged 35+ years who did not change residence in 2002-2018 without CVD in 2004, identified through registry data from Statistics Netherlands (n=4,641,435; 51.3% female, 91.2% Dutch). Time-varying Food Environment Healthiness Index (FEHI) scores (range: -5 to 5) and time-varying Kernel density of six specific food retailers (food delivery outlets, fast food outlets, restaurants, local food shops, supermarkets and convenience stores) around the home location were based on bi-annual updates between 2004-2018. Hospitalisation and mortality due to overall CVD, stroke, HF, and CHD occurring between 2004 and 2020 were used as outcomes, based on hospital and death registries. Models were adjusted for age, sex, ethnic origin, household composition, income, marital status and neighbourhood urbanisation level and effect modification by age, sex, urbanization and income was studied. Results: Each unit increase in the FEHI, representing a 10% improvement, was associated with a lower hospitalisation and mortality of CVD (hospitalization Hazard Ratio (HR h )=0.90, 0.89-0.91, mortality Hazard Ratio (HR m )=0.85, 0.82-0.89), CHD (HR h =0.88, 0.85-0.91, HR m =0.80, 0.75-0.86), stroke (HR h =0.89, 0.84-0.93, HR m =0.89, 0.82-0.98), and HF (HR h =0.90, 0.84-0.96, HR m =0.84, 0.76-0.92). Increased density of local food shops, fast food outlets, supermarkets and convenience stores, and decreased density of food delivery outlets and restaurants were associated with a higher risk of CVD, CHD, stroke and HF incidence and mortality, albeit with small effect sizes. Stratified analyses suggest slightly stronger associations in highly urbanized areas, younger adults and those with higher incomes. Conclusions: Favourable trends in time-varying food retailer exposure were associated with a risk reduction in CVD hospitalisation and mortality, in particular in urbanized areas and for younger adults and those with higher incomes.

AVANCES EN BIOMATERIALES METÁLICOS PARA IMPLANTES BIOMÉDICOS: UNA REVISIÓN INTEGRATIVA

Objective: The aim of this study is to investigate advancements in metallic biomaterials for biomedical implants, with the goal of enhancing patient safety and reducing mortality risks associated with medical procedures. Theoretical Framework: In this study, the theoretical framework draws upon concepts such as biocompatibility, advanced manufacturing techniques, and the role of artificial intelligence in improving implant performance and patient outcomes. These theories provide a solid foundation for understanding the context and significance of the research. Method: The methodology adopted for this research comprises an integrative literature review model. Specific steps included formulating a guiding question using the PICO/PIO/PEO strategy, establishing inclusion and exclusion criteria for studies, categorizing selected research, and analyzing and interpreting the results. Data collection involved selecting articles from reputable databases such as Web of Science, Springer Nature Librarian, and Wiley Online Library, using relevant keywords related to biomedical materials and human health. Results and Discussion: The results of the integrative literature review provide a systematic synthesis of research findings on metallic biomedical materials. These findings are contextualized within the theoretical framework, emphasizing the importance of continuous research efforts in developing safer and more effective materials for medical implants. The discussion highlights the implications of these findings for enhancing healthcare technologies and patient outcomes. Research Implications: The practical implications of this research include informing the development of safer and more effective materials for biomedical implants, thereby improving patient safety and quality of life. These implications extend to various sectors involved in healthcare technology and biomedical engineering. Originality/Value: This study contributes to the literature by synthesizing existing knowledge and providing valuable insights into the field of metallic biomaterials for medical applications.

Systematic review and meta-analysis of left atrial appendage closure's influence on early and long-term mortality and stroke

ObjectiveLeft atrial appendage closure (LAAC) concomitant to heart surgery in patients with underlying atrial fibrillation (AF) has gained attention because of long-term reduction of thromboembolic complications. As of mortality benefits in the setting of non-AF, data from both observational studies and randomized controlled trials are conflicting. MethodsOn-line databases were screened for studies comparing LAAC versus no LAAC concomitant to other heart surgery. End points assessed were all-cause mortality and stroke at early and longest-available follow-up. Subgroup analyses stratified on preoperative AF were performed. Risk ratios (RR) with 95% CIs served as primary statistics. ResultsElectronic search yielded 25 studies (N = 660 [158 patients]). There was no difference between LAAC and no LAAC in terms of early mortality. In the overall population analysis, LAAC reduced long-term mortality (RR, 0.86; 95% CI, 0.74-1.00; P = .05; I2 = 88%), reduced early stroke risk by 19% (RR, 0.81; 95% CI, 0.72-0.93; P = .002; I2 = 57%), and reduced late stroke risk by 13% (RR, 0.87; 95% CI, 0.84-0.90; P < .001; I2 = 58%). Subgroup analysis showed lower mortality (RR, 0.85; 95% CI, 0.72-1.01; P = .06; I2 = 91%), short-, and long-term stroke risk reduction only in patients with preoperative AF (RR, 0.81; 95% CI, 0.71-0.93; P = .003; I2 = 71% and RR, 0.87; 95% CI, 0.84-0.91; P < .001; I2 = 70%, respectively). No benefit of LAAC in patients without AF was found. ConclusionsConcomitant LAAC was associated with reduced stroke rates at early and long-term and possibly reduced all-cause mortality at the long-term follow-up but the benefits were limited to patients with preoperative AF. There is not enough evidence to support routine concomitant LAAC in non-AF settings.

The Role of Hospital Characteristics in Clinical and Quality Outcomes for Gastrointestinal Bleeding in a National Cohort.

There is substantial variability in patient outcomes for gastrointestinal bleeding (GIB) across hospitals. This study aimed to identify hospital factors associated with GIB outcomes. This was a retrospective cohort study of Medicare fee-for-service beneficiaries hospitalized for GIB from 2016 to 2018. These data were merged with the American Hospital Association Annual Survey data to incorporate hospital characteristics. We used generalized linear mixed-effect models to estimate the effect of hospital-level characteristics on patient outcomes after adjusting for patient risk factors including anticoagulant and antiplatelet use, recent GIB, and comorbidities. The primary outcome was 30-day mortality, and secondary outcomes included length of stay and a composite outcome of 30-day readmission or mortality. Factors associated with improved GIB 30-day mortality included large hospital size (defined as beds >400, odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90-0.97), greater case volume (OR 0.97, 95% CI 0.96-0.98), increased resident and nurse staffing (OR 0.88, 95% CI 0.83-0.94), and blood donor center designation (OR 0.93, 95% CI 0.88-0.99). Patients treated at a hospital with multiple advanced capabilities, such as availability of advanced endoscopy, advanced intensive care unit (ICU) capabilities (both a medical-surgical ICU and cardiac ICU), blood donor center, and liver transplant center, had a 22% reduction in 30-day mortality risk, compared with those hospitalized in a hospital with none of these services (OR 0.78, 95% CI 0.68-0.91). However, length of stay increased with additional services. Patients hospitalized for GIB at hospitals with multiple advanced specialized capabilities have lower mortality but longer lengths of stay. Further research should examine the processes of care linked to these services that contribute to improved mortality in GIB.

Worsening of health disparities across COVID-19 pandemic stages in Korea.

With the end of the coronavirus disease 2019 (COVID-19) pandemic, the health outcomes of this disease in Korea must be examined. We aimed to investigate health outcomes and disparities linked to socioeconomic status during the COVID-19 pandemic in Korea and to identify risk factors for hospitalization and mortality. This nationwide retrospective study incorporated an analysis of individuals with and without COVID-19 in Korea between January 1, 2020 and December 31, 2022. The study period was divided into 4 stages. Prevalence, hospitalization, mortality, and case-fatality rates were calculated per 100,000 population. Multivariate logistic regression was performed to identify risk factors for COVID-19 hospitalization and mortality. Overall, the incidence rate was 40,601 per 100,000 population, the mortality rate was 105 per 100,000 population, and the case-fatality rate was 259 per 100,000 cases. A total of 12,577,367 new cases (24.5%) were recorded in stage 3 and 8,979,635 cases (17.5%) in stage 4. Medical Aid recipients displayed the lowest 3-year cumulative incidence rate (32,737 per 100,000) but the highest hospitalization (5,663 cases per 100,000), mortality (498 per 100,000), and case-fatality (1,521 per 100,000) rates. Male sex, older age, lower economic status, non-metropolitan area of residence, high Charlson comorbidity index, and disability were associated with higher risk of hospitalization and death. Vaccination was found to reduce mortality risk. As the pandemic progressed, surges were observed in incidence, hospitalization, and mortality, exacerbating disparities associated with economic status and disability. Nevertheless, Korea has maintained a low case-fatality rate across all economic groups.

Efficacy of cytoreductive radical cystectomy in metastatic urothelial bladder cancer based on site and number of metastases

BackgroundRecent studies have highlighted the overall survival (OS) benefit of cytoreductive radical cystectomy (CRC) in metastatic bladder cancer (mBCa). Cytoreductive surgery has been established in other urologic cancers. However, the efficacy of CRC and optimal criteria for patient selection in mBCa is unclear. This study investigated the oncologic efficacy of CRC, particularly emphasizing the location and number of metastasis sites as a predictor of survival and treatment response. MethodsA retrospective analysis of cT2-4N0-3M1 mBCa patients treated with multiagent chemotherapy between 2004 and 2019 was conducted using the National Cancer Database. Patients were classified by additional treatment with CRC or conservative local treatment (CLT), consisting of transurethral resection of bladder tumor, radiation, or no local treatment and propensity score (PS) matched. Kaplan-Meier analysis and multivariate Cox Proportional Hazards model assessed the effect of CRC or CLT on OS within the matched cohort and in four subgroups (1) patients with only distant lymph node (LN) metastasis vs. any organ metastasis, (2) patients with single metastasis vs. multiple metastases. Sensitivity analysis estimated the influence of unmeasured confounders on CRC OS benefit. ResultsPropensity matching yielded 247 and 251 patients treated with CRC and CLT, respectively. Median OS in patients who received CRC was greater than that of patients treated with CLT (20.4 months vs. 12.0 months, P < 0.001). CRC was associated with reduced mortality risk in patients with only distant LN metastases (HR = 0.545, P = 0.039), any organ metastasis (HR = 0.421, P < 0.001), and single visceral metastasis (HR = 0.483, P = 0.002). However, CRC did not significantly improve OS in patients with multiple metastases (HR = 0.501, P = 0.064). ConclusionThese findings demonstrate an OS benefit of CRC with multiagent chemotherapy and pinpoint multiple visceral metastases as a potential contraindication for CRC. Although limited by the influence of unmeasured confounders, these findings may inform future prospective investigations into CRC.

ADHD Pharmacotherapy and Mortality in Individuals With ADHD

Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first. ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings). Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05). Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses.

The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

Unveiling the impact of an Indian-specific heart failure checklist on heart failure with reduced ejection fraction management in the South Indian population

BackgroundThe study assessed the impact of the Indian Specific Heart Failure (ISHF) checklist, guided by healthcare professionals, on promoting guideline-directed medical therapy (GDMT), enhancing medication adherence, improving quality of life (QoL), and influencing clinical outcomes. MethodsThe study enrolled 200 HFrEF patients for one year, dividing them into control and intervention groups. The control group received standard treatment, while a specialized team administered the ISHF checklist to the intervention group. The ISHF checklist was a reminder tool to ensure GDMT adherence, provide personalized education, and conduct regular QoL assessments during follow-ups. Statistical analysis encompassed mean values, percentages, Chi-square tests, and linear regression models. Data analysis employed JAMOVI and R software. ResultsMedication adherence improved over 12 months (p ≤ 0.001), with higher GDMT usage in the intervention group (IG: 59.3% vs. CG: 40.6%). The intervention group showed improved ejection fraction over 12 months (29.1 ± 7.6 to 36.4 ± 8.1, p = 0.05), fewer rehospitalizations (IG: 30.4% vs. CG: 49.6%, p ≤ 0.001), and lower mortality (IG: 3.8% vs. CG: 8.3%, p = 0.05). The hazard ratio for mortality (HR 0.57) favoured the intervention, indicating reduced mortality risk. GDMT showed marginal significance in predicting QoL in the intervention group suggesting its potential influence on patient-reported outcomes in the IG (estimate = −5.41, SE = 2.76, p = 0.05). ConclusionThe ISHF checklist could facilitate smooth transitions, optimize GDMT usage, reduce readmissions and mortality rates, significantly elevate care standards, and provide substantial benefits to the healthcare system.

Weight telemonitoring of heart failure versus standard of care in a real-world setting: Results on mortality and hospitalizations in a 6-month nationwide matched cohort study.

Evaluating the benefit of telemonitoring in heart failure (HF) management in real-world settings is crucial for optimizing the healthcare pathway. The aim of this study was to assess the association between a 6-month application of the telemonitoring solution Chronic Care Connect™ (CCC) and mortality, HF hospitalizations, and associated costs compared with standard of care (SOC) in patients with a diagnosis of HF. From February 2018 to March 2020, a retrospective cohort study was conducted using the largest healthcare insurance system claims database in France (Système National des Données de Santé) linked to the CCC telemonitoring database of adult patients with an ICD-10-coded diagnosis of HF. Patients from the telemonitoring group were matched with up to two patients from the SOC group based on their high-dimensional propensity score, without replacement, using the nearest-neighbour method. A total of 1358 telemonitored patients were matched to 2456 SOC patients. The cohorts consisted of high-risk patients with median times from last HF hospitalization to index date of 17.0 (interquartile range: 7.0-66.0) days for the telemonitoring group and 27.0 (15.0-70.0) days for the SOC group. After 6 months, telemonitoring was associated with mortality risk reduction (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.56-0.89), a higher risk of first HF hospitalization (HR 1.81, 95% CI 1.55-2.13), and higher HF healthcare costs (relative cost 1.38, 95% CI 1.26-1.51). Compared with the SOC group, the telemonitoring group experienced a shorter average length of overnight HF hospitalization and fewer emergency visits preceding HF hospitalizations. The results of this nationwide cohort study highlight a valuable role for telemonitoring solutions such as CCC in the management of high-risk HF patients. However, for telemonitoring solutions based on weight and symptoms, consideration should be given to implement additional methods of assessment to recognize imminent worsening of HF, such as impedance changes, as a way to reduce mortality risk and the need for HF hospitalizations. Further studies are warranted to refine selection of patients who could benefit from a telemonitoring system and to confirm long-term benefits in high-risk and stable HF patients.

A Joint Model Based on Post-Treatment Longitudinal Prognostic Nutritional Index to Predict Survival in Nasopharyngeal Carcinoma.

a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. In this retrospective study using data from the Chang Gung Research Database (2007-2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients.

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment.

JOURNAL/nrgr/04.03/01300535-202504000-00029/figure1/v/2024-07-06T104127Z/r/image-tiff Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients, with evidence suggesting exercise may reduce mortality risks and aid neural regeneration. The role of the small ubiquitin-like modifier (SUMO) protein, especially post-exercise, in cancer progression, is gaining attention, as are the potential anti-cancer effects of SUMOylation. We used machine learning to create the exercise and SUMO-related gene signature (ESLRS). This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers. We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers, specifically highlighting how murine double minute 2 (MDM2), a component of the ESLRS, can be targeted by nutlin-3. This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation. Using comprehensive CRISPR screening, we validated the effects of specific ESLRS genes on low-grade glioma progression. We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation. Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway. Its efficacy decreased with MDM2 overexpression, and this was reversed by Nutlin-3a or exercise. Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation. Notably, both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells. These results suggest the potential for Nutlin-3a, an MDM2 inhibitor, with physical exercise as a therapeutic approach for glioma management. Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise, natural products, and immune regulation in cancer treatment.

Night eating in timing, frequency, and food quality and risks of all-cause, cancer, and diabetes mortality: findings from national health and nutrition examination survey.

To investigate the association of timing, frequency, and food quality of night eating with all-cause, cancer, and diabetes mortality. This study included 41,744 participants from the US National Health and Nutrition Examination Survey (2002-2018). Night eating information was collected by 24-h dietary recall and the exposures were timing, frequency, and food quality of night eating. Food quality was assessed by latent class analysis. The outcomes were all-cause, cancer, and diabetes mortality, which were identified by the National Death Index and the International Classification of Diseases 10th Revision. Adjusted hazard ratios [aHR] with 95% confidence intervals [CI] were computed by Cox regression. During a median follow-up of 8.7 years, 6066 deaths were documented, including 1381 from cancer and 206 from diabetes. Compared with no night eating (eating before 22:00), the later timing of night eating was associated with higher risk of all-cause and diabetes mortality (each P-trend <0.05) rather than cancer mortality, with the highest risk of eating being 00:00-1:00 (aHR 1.38, 95% CI 1.02-1.88) and being 23:00-00:00 (aHR 2.31, 95% CI 1.21-4.40), respectively. However, the increased risks were not observed for 22:00-23:00. Likewise, one time or over frequency of night eating was associated with higher all-cause and diabetes mortality (each P < 0.05). That risks were further observed in high-dietary-energy-density group of night eating (all-cause mortality: aHR 1.21 [95% CI 1.06-1.38]; diabetes mortality: aHR 1.97 [95% CI 1.13-3.45]), but not in low-dietary-energy-density group. Finally, correlation analysis found positive associations of night eating with glycohemoglobin, fasting glucose, and OGTT. Night eating was associated with increased all-cause, cancer and diabetes mortality; however, reduction of excess mortality risk was observed when eating before 23:00 or low-dietary-energy-density foods.

Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection

The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.

Outdoor gardening activity with different frequency and duration may be associated with reduction of total and cause-specific mortality risk for general U.S. adults: Findings from the NHANES

Background and aimsEngaging in recommended levels of physical activity (PA) is associated with reduced overall and cause-specific mortality rates. Our study aims to examine the relationship between gardening-specific PA and all-cause and cause-specific mortality based on representative U.S. adults. Methods and resultsA total of 13,812 adults representing 663.5 million non-institutionalized U.S. adults were included in the National Health and Nutrition Examination Survey. Self-reported gardening activity (GA) was assessed by a validated questionnaire, and outcomes of interest were all-cause mortality and mortality specific to certain causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using survey-multivariable Cox proportional hazards models. During a median follow-up period of 16.8 years (Interquartile range = 14.8–18.7), there were 3,476 deaths. After adjusting for potential covariates, we found that participants exposed to GA were more likely to have a lower risk of total mortality [HR (95% CI): 0.76 (0.68, 0.85), P-value < 0.001], cancer-specific mortality [HR (95% CI): 0.81 (0.67, 0.99), P-value < 0.05], cardiovascular disease mortality [HR (95% CI): 0.65 (0.53, 0.80), P-value < 0.001], and respiratory disease mortality [HR (95% CI): 0.66 (0.45, 0.98), P-value < 0.05], compared to those without GA exposure. Furthermore, engaging in GA more frequently and for longer durations was significantly associated with a lower total mortality risk. ConclusionOur study provides evidence that engaging in GA is associated with a decreased risk of overall and cause-specific mortality. However, further longitudinal or interventional studies are needed to investigate the potential benefits of GA.

Concurrent use of continuous kidney replacement therapy during extracorporeal membrane oxygenation: what pediatric nephrologists need to know-PCRRT-ICONIC practice points.

Extracorporeal membrane oxygenation (ECMO) provides temporary cardiorespiratory support for neonatal, pediatric, and adult patients when traditional management has failed. This lifesaving therapy has intrinsic risks, including the development of a robust inflammatory response, acute kidney injury (AKI), fluid overload (FO), and blood loss via consumption and coagulopathy. Continuous kidney replacement therapy (CKRT) has been proposed to reduce these side effects by mitigating the host inflammatory response and controlling FO, improving outcomes in patients requiring ECMO. The Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup and the International Collaboration of Nephrologists and Intensivists for Critical Care Children (ICONIC) met to highlight current practice standards for ECMO use within the pediatric population. This review discusses ECMO modalities, the pathophysiology of inflammation during an ECMO run, its adverse effects, various anticoagulation strategies, and the technical aspects and outcomes of implementing CKRT during ECMO in neonatal and pediatric populations. Consensus practice points and guidelines are summarized. ECMO should be utilized in patients with severe acute respiratory failure despite the use of conventional treatment modalities. The Extracorporeal Life Support Organization (ELSO) offers guidelines for ECMO initiation and management while maintaining a clinical registry of over 195,000 patients to assess outcomes and complications. Monitoring and preventing fluid overload during ECMO and CKRT are imperative to reduce mortality risk. Clinical evidence, resources, and experience of the nephrologist and healthcare team should guide the selection of ECMO circuit.

Metformin use is associated with reduced mortality risk in diabetic patients with Parkinson's disease

IntroductionParkinson’s disease (PD) and type-2 diabetes (T2D) arguably share pathophysiologic mechanisms, resulting in a more severe phenotype and progression and diabetes is currently considered a risk factor of PD. Besides, research suggests antidiabetic therapies as potential disease-modifying strategies. The main aim was to assess the impact of a metformin-inclusive antidiabetic treatment on patient all-cause mortality. MethodsA nested case-control prospective study including newly diagnosed PD patients reporting the onset of T2D within ±2 years from the onset of PD (n=159) and matched (1:5; gender, year of PD onset and age at PD onset) non-diabetic cases (n=795) followed until death or censoring. Patients on a metformin-inclusive treatment regimen were compared to those receiving other oral anti-diabetics (OADs). ResultsAmong patients with T2D, 123 were treated with a drug regimen containing metformin (alone [65.0%] or in combination with other drugs [35.0%]) and 36 were prescribed other OADs. During a median PD duration of 96 months [IQR, 60-144], 171 patients died. Diabetes was not associated with reduced survival: fully-adjusted HR=1.19 [95%CI, 0.81-1.76] (P=0.37). After stratifying for T2D treatment, a metformin-inclusive regimen was not associated with increased risk of death (HR=1.06 [95%CI, 0.61-1.84]; P=0.83), while patients receiving other OADs had reduced survival (HR=1.83 [95%CI, 1.01-3.32]; P=0.034). ConclusionsMetformin use was not associated with increased risk of death in diabetic patients with PD reporting concomitant onset of the two diseases. Metformin appears to be a promising disease-modifying therapy given also the preclinical background, low cost and satisfactory safety and tolerability. Further studies are warranted to investigate its impact on disease progression.