Multivariate Cox Proportional Hazards Regression Research Articles

Association Between Changes in Smoking Habits and Incident Fracture After Acute Ischemic Stroke.

Survivors of stroke, particularly the older population, are at an increased risk of falls and incident fractures. Smoking is a widely recognized risk factor for fractures. However, the association between changes in smoking habits before and after an index stroke and increased risk of fracture remains unelucidated. Using the Korean National Health Insurance program, patients with ischemic stroke between 2010 and 2016 were enrolled. Individuals were classified by smoking habits: "never smoker," "former smoker," "smoking quitter," "new smoker," and "sustained smoker." The primary outcome was the composite outcome of the vertebral, hip, and any fractures. Multivariable Cox proportional hazards regression analysis was conducted, using the never-smoker group as the reference. Among 177 787 patients with health screening data within 2 years before and after ischemic stroke, 14 991 (8.43%) patients had any fractures. After multivariable adjustment, the sustained smokers had a significantly increased risk of composite primary outcomes of any, vertebral, and hip fractures (adjusted HR [aHR], 1.222 [95% CI, 1.124-1.329]; aHR, 1.27 [95% CI, 1.13-1.428]; aHR, 1.502 [95% CI, 1.218-1.853], respectively). Additionally, the new smoker group exhibited a similar or higher risk of any fractures and hip fractures (aHR, 1.218 [95% CI, 1.062-1.397]; aHR, 1.772 [95% CI, 1.291-2.431], respectively). Sustained smokers had a significantly increased risk of vertebral and hip fractures after an ischemic stroke. The risk of any hip fractures was higher in new smokers after ischemic stroke. As poststroke fractures are detrimental to the rehabilitation process of patients with stroke, physicians should actively advise patients to stop smoking.

Optimal use of antithrombotic agents in recent small subcortical strokes accompanied by atrial fibrillation.

This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis. AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone.

Association between lipid profile and clinical outcomes in COVID-19 patients.

High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies.

In-hospital survival of critically ill COVID-19 patients treated with glucocorticoids: a multicenter real-world data study

The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital—Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 – 128], 133 days in the HighC group [95% CI: 124 – 141] and 144 days in the NoC group [95% CI: 121 – 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

Long-time exposure to sunlight is associated with the risk of sudden cardiac arrest and coronary heart disease

Abstract Background With ongoing climate change, the duration of sunshine hours will likely increase over the coming decades that escalating air temperature. Little is known about the potential cardiovascular risk from this climate factor. Purpose The aim of this study was to test whether duration of sunlight exposure is associated with incident sudden cardiac arrest (SCA), coronary heart disease (CHD), and hospitalization for heart failure (HF) and whether this association depends on seasonal variation. Methods A total of 308,851 participants from UK Biobank were included and were followed for a median time of 11.8 years. Participants reported how many hours they respectively spent the daylight outdoors on summer and winter typical days. Extreme outliers (>12 hours/day in summer and >8 hours/day in winter) were excluded. Average exposure time was calculated to unify the daylight outdoors time standard. Duration of sunlight exposure (average, summer, and winter) were categorized using quantiles and a restricted cubic spline for outcomes. Multivariate cox proportional hazard regression adjusted by age, sex, demographics, lifestyle, clinical and environmental factors was used for the analysis. Results During a follow-up, 1,572 (0.51%), 11,557 (3.74%) and 2,145 (0.68%) participants were diagnosed with SCA, CHD and hospitalization for HF. Compared with the participants exposed to short-time sunlight (average ≤ 1.5 hours/day), those who exposed to long-term sunlight (average ≥ 3.5 hours/day) had increased risk of SCA (HR 1.22, 95% CI 1.06 to 1.40) and CHD (HR 1.22, 95% CI 1.06 ~1.40). The associations between long-time exposure to sunlight and SCA were largely attributable to summer (HR 1.22, 95% CI 1.06 to 1.39) and not winter (HR 1.02, 95% CI 0.86 to 1.20), respectively. An hour increase of sunlight exposure was associated with increased risk of SCA in summer (HR, 1.03; 95% CI, 1.01 to 1.05), but not in winter (HR, 1.03, 95% CI, 0.99 to 1.06). Subgroup analysis identified that exposure to long-term sunlight was consistently increased risk of SCA, regardless of age, sex, body mass index, previous cardiovascular diseases, total physical activity, types of physical activity in last 4 weeks, use of sun/UV protection, sedentary time, natural environment percentage (buffer 1000m), and PM2.5. Finally, long-time exposure to sunlight was also associated with increased risk of CHD, but not associated with increased risk of HF hospitalization. Conclusions Findings from the present study indicate that daily long-time exposure to sunlight that increase in air temperature is a risk factor for SCA and CHD. These associations revealed graded relationship according to the duration of exposure to sunlight and more pronounced in summer. Our results suggest that public health efforts to reduce cardiovascular risk should take a wide range of exposure time to sunlight into account.

PD-1+ T lymphocyte proportions and hospitalized exacerbation of COPD: a prospective cohort study

ObjectiveTo evaluate the predictive value of PD-1 expression in T lymphocytes for rehospitalization due to acute exacerbations of COPD (AECOPD) in discharged patients.Methods115 participants hospitalized with COPD (average age 71.8 ± 6.0 years) were recruited at Fujian Provincial Hospital. PD1+T lymphocytes proportions (PD1+T%), baseline demographics and clinical data were recorded at hospital discharge. AECOPD re-admission were collected at 1-year follow-up. Kaplan-Meier analysis compared the time to AECOPD readmissions among groups stratified by PD1+T%. Multivariable Cox proportional hazards regression and stratified analysis determined the correlation between PD1+T%, potential confounders, and AECOPD re-admission. ROC and DCA evaluated PD1+T% in enhancing the clinical predictive values of Cox models, BODE and CODEX.Results68 participants (59.1%) were AECOPD readmitted, those with AECOPD readmission exhibited significantly elevated baseline PD-1+CD4+T/CD4+T% and PD-1+CD8 + T/CD8 + T% compared to non-readmitted counterparts. PD1+ T lymphocyte levels statistically correlated with BODE and CODEX indices. Kaplan-Meier analysis demonstrated that those in Higher PD1+ T lymphocyte proportions had reduced time to AECOPD readmission (logRank p < 0.05). Cox analysis identified high PD1+CD4+T and PD1+CD8+T ratios as risk factors of AECOPD readmission, with hazard ratios of 1.384(95%CI [1.043–1.725]) and 1.401(95%CI [1.013–1.789]), respectively. Notably, in patients aged < 70 years and with fewer than twice AECOPD episodes in the previous year, high PD1+T lymphocyte counts significantly increased risk for AECOPD readmission(p < 0.05). The AECOPD readmission predictive model, incorporating PD1+T% exhibited superior discrimination to the Cox model, BODE index and CODEX index, AUC of ROC were 0.763(95%CI [0.633–0.893]) and 0.734(95%CI [0.570–0.899]) (DeLong’s test p < 0.05).The DCA illustrates that integrating PD1+T% into models significantly enhances the utility in aiding clinical decision-making.ConclusionEvaluation of PD1+ lymphocyte proportions offer a novel perspective for identifying high-risk COPD patients, potentially providing insights for COPD management.Trial registrationChinese Clinical Trial Registry (ChiCTR, URL: www.chictr.org.cn/), Registration number: ChiCTR2200055611 Date of Registration: 2022-01-14.

#934 Mortality predictors in advanced chronic kidney disease patients on conservative kidney management: insights from a retrospective multicenter study

Abstract Background and Aims In general, patients with advanced chronic kidney disease (ACKD) on dialysis have a better survival than patients on conservative kidney management (CKM). However, in elderly and frail individuals, with multiple comorbidities, the survival benefits of dialysis seem to be lost. Although the focus of CKM is not quantity but quality of life (QoL), it is important to identify survival modifiers and mortality predictors that may eventually influence QoL and the development of symptoms. Method An observational retrospective and multicenter study of ACKD patients on CKM was conducted from July/2015 to December/2023. Data was retrieved from electronic records, encompassing kidney function, analytical parameters, functional and fragility state, and symptoms evaluation (using Palliative Outcome Scale—Renal). The Kaplan-Meier curves and Cox proportional hazards multivariable regression were used for survival analysis and to evaluate 180-day mortality predictors. Results A total of 212 patients (56.6% females), with a mean age of 83 years old and a mean follow up time of 220 ± 239 days, were included. The follow-up time was determined by the end of the observational period or the patient's death. 56.1% died before a 180-day follow-up period. The main causes for the ACKD were multifactorial (29.7%) and indeterminate (25.9%). The majority (80.7%) had nephrologist oversight before a CKM team initiated its follow-up, and 63.6% opted for CKM as their first treatment choice. Survival at 180 days (Fig. 1) differed significantly depending on sex (51.3 vs 65.6, p = 0.021), age under 80 years-old (51.3 vs 73.9, p = 0.000), provenance (0 vs 39.4 vs 83 vs 93.8, p = 0.000), albumin value (32.7 vs 65.5, p = 0.032), and symptoms such as anorexia and pain (53 vs 95.5, p = 0.000; and 54.5 vs 88.9, p = 0.000). Regarding to mortality predictors (Table 1), albumin under 3g/dL, anorexia and pain were independent predictors of mortality. Conclusion Understanding factors associated with increased mortality and higher rates of survival in CKM patients is crucial to better manage this population. Pain, albumin &amp;lt;3g/dL and anorexia, which may reflect patients with worse nutritional status, were shown to be independent predictors of mortality. Therefore, controlling these symptoms, which often impair QoL, and improving nutritional status appears to have an impact not only on QoL but also on survival of ACKD patients on CKM.

#2291 ANCA negative vasculitis—the unmet need within small vessel vasculitis

Abstract Background and Aims ANCA negative small vessel vasculitis with renal involvement has been described in a number of cohorts. Though comprehensive studies comparing these individuals to ANCA positive patients are lacking and they are routinely excluded from clinical trials. Whilst the numbers are smaller than those with ANCA positivity, they still make up a large proportion of small vessel vasculitidies (Fig. 1). The absence of detectable circulating ANCA is thought to indicate a distinct spectrum of the disease. There remains unanswered questions regarding the pathophysiology, diagnosis and management of patients with seronegative AAGN. We present data from Croatian referral center. Method Study included 106 AAV patients with biopsy proven renal involvement in the period from 2007-2017. Category variables were analysed with Fisher Exact test and continuous with Kruskal-Wallis test. Statistical difference was then analysed post hoc with Chi-square test. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between clinical phenotypes and finding significant predictors regarding outcomes which were defined as combined outcome end-stage renal disease and death (ESRDD), ESRD alone, the death outcome alone and relapse rate. Results 106 AAV patients with renal involvement were included: 66 (61.1%) MPA, 20 (18.5%) GPA, 20 (18.5%) RLV. 14 (13%) were PR3-ANCA positive, 57 (52.8%) MPO ANCA positive, 5 (4.6%) PR3-ANCA+MPO-ANCA and 32 (29.6%) ANCA negative patients. ANCA negative patients were comparatively younger (p = 0.02) and presented with more renal limited vasculitis (RLV; p &amp;lt; 0.001), lower BVAS (p = 0.003) and lower CRP (p = 0.001). ANCA negative patients usually presented with nephrotic syndrome compared to positive ones which presented with rapid progressive nephritic syndrome or acute nephritic syndrome (p = 0.027). 24-hour proteinuria levels were higher in ANCA negative group (p = 0.003). Though statistical difference was not reached, there was tendency for ANCA negatives to receive less plasmapheresis (p = 0.074). Histologically there were no differences between ANCA positive and ANCA-negative patients. On sub analysis ANCA negatives versus individual seropositive groups, there was tendency that ANCA negatives and MPO-ANCA patients had lower percentage of glomerular crescents (p = 0.092) but more acute tubular damage (p = 0.087). There were no differences in clinical outcomes between the groups. Conclusion ANCA negative vasculitis form a large proportion of small vessel vasculitidies and present with different clinical laboratory and histological (renal) characteristics than ANCA positive ones. More often than not disease seems to be renal limited and patients tend to be younger. Due to the rarity of the disease, there remains unanswered questions regarding the pathophysiology, diagnosis and management of these patients. This study highlights noteworthy distinctions between the two groups. Whether these differences warrant adjustments in treatment algorithms or a reconsideration of the classification of small vessel vasculitis remains to be determined. Further investigation into the pathogenetic mechanisms of seronegative AAVs is essential.

#1643 Long-term cohort study on the prognostic impact of mesangial IgM deposition in IgA nephropathy

Abstract Background and Aims The prognostic importance of mesangial immunoglobulin (Ig) M deposition in IgA nephropathy (IgAN) is not well-understood and is subject to ongoing debate. Moreover, mesangial IgM deposition could also reflect lectin complement system activation. Thus, our study sought to examine the long-term prognostic implications of mesangial IgM deposition in a cohort of IgAN patients. Method We carried out a single-center retrospective study involving 93 consecutive IgAN patients (median age 41 years, 68% male, eGFR 48.7 mL/min, proteinuria 1.1 g/g) from 2010 to 2015. The follow-up period extended until the onset of end-stage kidney disease (ESKD), death, or January 2021, with a median duration of 7 years. An independent pathologist assessed the IgM immunofluorescence pattern, Oxford MEST-C score, and transmission electron microscopy (TEM) lesions using a detailed protocol. Results In our study, 70% (n = 65) of patients exhibited mesangial IgM-positive deposits, while 30% (n = 28) did not show IgM deposition. Both IgM-positive and IgM-negative groups were comparable in terms of age (40 vs 43 years, p 0.6), sex (69 vs 64% male, p 0.6), arterial hypertension prevalence (69 vs 64%, p 0.6), Charlson comorbidity scores (2 vs 1, p 0.3), kidney function (eGFR 46 vs 55 mL/min, p 0.1 and proteinuria 1.2 vs 0.7, p 0.1), pathology findings (including Oxford MEST-C score, IgG and C3 immune deposition), TEM analysis, as well as in their treatment with renin-angiotensin-system inhibitors (63 vs 71%, p 0.4) and immunosuppression (39 vs 39%, p 0.9), and mortality rates (11 vs 7%, p 0.5). However, a notable difference emerged in the progression to ESKD, with 37% of IgM-positive patients advancing to this stage compared to only 11% of those in the IgM-negative group (p 0.01). The multivariate Cox proportional hazards regression analysis identified lower eGFR (HR 0.94, 95% CI: 0.92, 0.97), higher Oxford MEST-C score (HR 1.53, 95% CI: 1.16, 2.02), and mesangial IgM deposits (HR 4.75, 95% CI: 1.25, 17.99) as independent predictors of reduced kidney survival. Conclusion Our study identifies mesangial IgM deposition as a potential risk factor for ESKD in advanced IgAN, suggesting a need for further investigation. Future research should explore whether IgM's activation of the lectin complement pathway and resultant damage, as proven in ischemia-reperfusion injury models, are applicable to IgAN.

#2755 NURTuRE-CKD: outcomes by primary renal diagnosis

Abstract Background and Aims Chronic kidney disease (CKD) represents a major global healthcare challenge, affecting approximately 850 million people worldwide [1], and is an independent risk factor for the progression to kidney replacement therapy (KRT) and all-cause mortality [2]. However, CKD encompasses various causes, each with unique pathophysiology and rates of progression [3]. Here we describe the outcomes from NURTuRE-CKD, an ongoing, multicenter prospective cohort study of 2996 non-dialysis CKD patients, by primary renal diagnosis, aiming to describe the differing rates of progression, ESKD and mortality by CKD cause and provide insights into those at greatest risk. Method Patients with an eGFR of 15–59 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73 m2 with a uACR &amp;gt;30 mg/mmol were enrolled, in addition to 86 controls. The full study design and methods of NURTuRE-CKD have previously been reported [4]. Outcomes: ESKD, eGFR &amp;lt;15 mL/min/1.73 m2, Transplantation, initiation of KRT, all-cause mortality and serial eGFR data were sourced from the UK Renal Registry. ESKD was defined as initiation of KRT or eGFR &amp;lt;15 mL/min/1.73 m2. Rate of progression was determined via eGFR slope. ERA diagnostic categories were used for primary renal diagnoses, with ‘glomerular diseases’ split into glomerulonephritis (GN) and vasculitis. The Chi-squared test was used to compare categorical variables, and the Kruskal-Wallis test for continuous variables. A multivariable Cox proportional hazards regression analysis predicting the time to ESKD by primary diagnosis was undertaken, using vasculitis as the reference category. Model 2 included adjustments for baseline eGFR. Results Table 1 depicts both the baseline characteristics and outcomes by the 8 diagnosis categories. Average follow-up duration was 53.8 months, not significantly different between the groups, but all other baseline variables differed significantly. The hypertensive/renovascular group were oldest and familial group youngest at 71 and 53 years, respectively. At baseline the diabetic nephropathy (DN) group had the lowest eGFR 28 ml/min/1.73 m2 and highest uACR 88.3 mg/mmol. However, the familial group had the steepest pre-enrolment eGFR decline slope. Delta eGFR during the follow-up period was steepest in the familial group and DN groups at −3.4 and −3.0 ml/min/1.73 m2, respectively, whereas the vasculitis group had slowest progression −0.7 ml/min/1.73 m2. Overall rate of ESKD was 24.7%; lower in the vasculitis (14%), systemic disease (17.7%) and tubulointerstitial (18.8%) groups, and higher in the DN (36.7%) and familial (31.6%) groups. All-cause mortality was greatest in the DN group at 40.4%. Despite being the fastest progressors defined by eGFR slope, the familial group had the lowest mortality rate (5.2%), but they were of younger age and had a high rate of kidney transplantation (10.1%). Unadjusted HRs for ESKD, were significantly higher for all diagnoses except tubulointerstitial and systemic diseases compared to the vasculitis group; DN evidenced the highest hazard ratio at 3.15 (2.18-4.55). When adjusted for baseline eGFR, HRs for the glomerulonephritis 2.04 (1.89-4.03), diabetes 1.5 (1.04-2.16) and familial 2.76 (1.89-4.03) remained significantly higher. Conclusion Rates of progression and incidence of clinically meaningful outcomes differ between CKD causes in NURTuRE. Those with DN and familial conditions had faster eGFR decline and had higher rates of ESKD, with associations persisting despite controlling for baseline eGFR. Recognising that CKD progresses at different rates is crucial, not only for providing personalised care, but also key to understanding differing pathophysiologic mechanisms of progression. NURTuRE-CKD will also explore novel biomarkers, with the aim of illuminating mechanisms of progression, improving risk prediction and highlighting novel drug targets.

#100 Hospital readmissions for fluid overload among individuals with diabetes mellitus

Abstract Background and Aims Hospital readmissions due to recurrent fluid overload in diabetes can be avoided with evidence-based interventions. To identify at-risk individuals, we evaluated the incidence and risk factors associated with fluid overload-related hospital readmissions and developed risk prediction models for readmissions for fluid overload in people with diabetes. Method Single-centre retrospective cohort study of 1531 adults with diabetes and hospitalized in Singapore General Hospital for fluid overload, congestive heart failure, pulmonary edema and generalized edema between 2015 and 2017. Patients were included if they had diabetes mellitus identified by the SingHealth Diabetes Registry according to diagnosis codes, laboratory results and/or the use of glucose-lowering medication and had follow up visits, but excluded if their estimated glomerular filtration rate (eGFR) &amp;lt;15 ml/min/1.73 m2. Baseline data on demographics, comorbidities, biochemistry and medication use during admission were retrieved from electronic medical records up till 30 December 2018. The outcomes were fluid overload- related readmissions within 30 days and 90 days of discharge of the index hospitalization. Multivariable Cox proportional-hazards regression analysis was performed with inclusion of covariates with p≤0.10 on univariate analysis. Multivariable regression models developed were compared with the LACE index with net reclassification index (NRI). Results Among 1531 patients, median age was 73 (IQR 64, 81) and readmissions for fluid overload within 30 days and 90 days occurred in 131 (8.6%) and 264 (17.2%) patients, respectively. Individuals with 30- or 90-day readmissions were more likely to have prior hospitalization for fluid overload and more frequent ED visits within 6 months before the index hospitalization, cardiovascular disease, hypertension, and required high-dose intravenous furosemide during the index hospitalization, or current smoker. Clinical and clinico-psychosocial models for 30- and 90-day readmissions for fluid overload were developed (Table 1). The clinical and clinico-psychosocial models showed better discrimination and calibration than LACE index for predicting 30- and 90-day readmissions for fluid overload. The NRIs for clinical models were i. 30-day readmissions: +22.1%, ii. 90-day readmissions: +27.9% respectively, while the NRIs for clinico-psychosocial models were i. 30-day readmissions: +22.4%, ii. 90-day readmissions: +28.9% respectively (Fig. 1). Conclusion Patients with diabetes who are at-risk of readmission for fluid overload can be identified for targeted interventions to reduce preventable hospitalizations.

The prognostic value of selective neck dissection in early-stage major salivary gland carcinoma: a population-based analysis.

This population-based study aims to assess the survival benefits of selective neck dissection (SND) compared to neck observation in patients with T1/T2N0M0 major salivary gland malignancy (MSGC). We conducted a retrospective review of T1/T2N0M0 MSGC patients who underwent primary tumor surgical extirpation with or without elective neck dissection in the Surveillance, Epidemiology, and End Results database (SEER) from 2004-2015. The impact of SND and clinical variables on overall survival (OS) and disease-specific survival (DSS) was evaluated using Univariate and Multivariate Cox proportional hazards regression models. Kaplan-Meier survival curves were generated, and survival rates were assessed via the log-rank test. Of 3778 post-operative T1-T2N0M0 MSGC patients, 2305 underwent elective neck dissection, while 1473 did not. Median follow-up was 106 months. Univariate and Multivariate analysis identified SND as a prognostic factor for OS in all the study population. After stratified analysis, we found that in the poorly high-grade (differentiated and undifferentiated) patients, the survival showed a significant OS and DSS benefit after receiving SND compared with the neck observations [HR for OS (95%CI): 0.571(0.446-0.731), P<0.001] and [HR for DSS (95%CI): 0.564(0.385-0.826), P=0.003], other than in the well differentiated or moderately differentiated subgroup. Especially, when the pathological is squamous cell carcinoma, the results show that the people underwent SND had better prognosis, not only in OS [HR (95%CI): 0.532(0.322-0.876), P=0.013], but also in DSS [HR (95%CI): 0.330(0.136-0.797), P=0.014]. The multivariate analysis also yielded encouraging results, compared with neck observation, receiving SND bought about a significant independent OS (adjusted HR, 0.555; 95% CI, 0.328-0.941; P=0.029) and DSS (adjusted HR, 0.349; 95% CI, 0.142-0.858; P=0.022) advantage in high grade squamous cell carcinoma MSGC patients. The Kaplan-Meier survival curves also demonstrated that adjusted SND still had significantly better OS(P=0.029) and DSS(P=0.022) than the observation group in patients with high-grade squamous cell carcinoma of MSGC. Poorly differentiated and undifferentiated T1/T2N0M0 major salivary gland malignancy treated with selective neck dissection demonstrated superior survival compared to neck observation, especially in the pathological subtype of squamous cell carcinoma. These findings suggest the potential benefits of multimodal therapy for appropriately selected patients, emphasizing significant clinical implications.

C-reactive protein to albumin ratio and risk of incident metabolic syndrome in community-dwelling adults: longitudinal findings over a 12-year follow-up period.

The C-reactive protein to albumin (CRP/Alb) ratio has emerged as a novel biomarker for various inflammatory diseases. This study aimed to evaluate the association between the CRP/Alb ratio and incident metabolic syndrome (MetS) with a large-sample, community-based Korean cohort over a 12-year follow-up period. Among 10,030 participants, a total of 6205 participants aged 40-69 years without MetS were selected from the Korean Genome and Epidemiology Study (KoGES). The baseline CRP/Alb ratio was divided into quartiles. The definition of newly developed MetS was the one proposed by the 2009 Joint Interim Statement of Circulation. Hazard ratios (HRs) with 95% confidence intervals (CIs) for incident MetS were calculated using multivariable Cox proportional hazards regression models after adjusting for potentially confounding variables. During the 12-year follow-up period, MetS developed in 2535 subjects (40.9%, 2535/6205) with an incidence rate of 5.6-11.9 (over 2 years). Compared to the reference first quartiles, the HRs (95% CIs) of incident MetS in the second, third, and fourth quartiles increased in a dose-response manner. Compared to the reference quartile, the HRs (95% CIs) of the incidence of MetS for the second, third, and fourth quartiles of CRP/Alb ratio were 1.12 (0.99-1.27), 1.24 (1.11-1.40), and 1.51 (1.34-1.69) after adjusting for age, sex, smoking status, alcohol intake, physical activity, total cholesterol, mean arterial pressure, HOMA-IR, and total energy intake. High CRP/Alb ratio at baseline may be a useful surrogate indicator of future incident MetS.

Derivation and validation of a nomogram incorporating modifiable lifestyle factors to predict development of colorectal adenomas after negative index colonoscopy

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan–Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.

Elevated Cardiac Troponin I as a Mortality Predictor in Hospitalised COVID-19 Patients.

Background and Objectives: SARS-CoV-2 affects multiple organ systems, including the cardiovascular system, leading to immediate and long-term cardiovascular complications. Acute myocardial injury is one of the earliest and most common cardiac issues in the acute phase of COVID-19. This study aimed to evaluate the prognostic value of cardiac troponin I (cTnI) levels in predicting in-hospital mortality among hospitalised COVID-19 patients. Materials and Methods: A retrospective observational cohort study included 2019 adult patients hospitalised with a confirmed COVID-19 infection stratified by cTnI levels on admission into three groups: <19 ng/L (1416 patients), 19-100 ng/L (431 patients), and >100 ng/L (172 patients). Myocardial injury was defined as blood serum cTnI levels increased above the 99th percentile upper reference limit. Depersonalised datasets were extracted from digital health records. Statistical analysis included multivariable binary logistic and Cox proportional hazards regressions. Results: Overall, 29.87% of patients experienced acute myocardial injury, which development was associated with age, male sex, chronic heart failure, arterial hypertension, obesity, and chronic kidney disease. Among patients with cTnI levels of 19-100 ng/L, the odds ratio for requiring invasive mechanical ventilation was 3.18 (95% CI 2.11-4.79) and, for those with cTnI > 100 ng/L, 5.38 (95% CI 3.26-8.88). The hazard ratio for in-hospital mortality for patients with cTnI levels of 19-100 ng/L was 2.58 (95% CI 1.83-3.62) and, for those with cTnI > 100 ng/L, 2.97 (95% CI 2.01-4.39) compared to patients with normal cTnI levels. Conclusions: Increased cardiac troponin I, indicating myocardial injury, on admission is associated with a more adverse clinical disease course, including a higher likelihood of requiring invasive mechanical ventilation and increased risk of in-hospital mortality. This indicates cardiac troponin I to be a beneficial biomarker for clinicians trying to identify high-risk COVID-19 patients, choosing the optimal monitoring and treatment strategy for these patients.

Chemotherapy, immunotherapy, or combination first-line treatment for metastatic urothelial carcinoma of the bladder: A large real-world experience

IntroductionFirst-line systemic therapy for metastatic urothelial carcinoma of the bladder (mUC) consists of platinum-based chemotherapy in most patients and PD1/L1 inhibitors in selected patients. Multiple combination chemoimmunotherapy trials failed to show a clear benefit over chemotherapy alone. We used real-world data to evaluate clinical and sociodemographic factors associated with receipt of first-line chemotherapy, immunotherapy, or combination chemoimmunotherapy treatment for metastatic bladder cancer and examined differences in overall survival (OS). Materials and MethodsWe used the National Cancer Database to identify patients with stage IV mUC diagnosed between 2014 and 2018, who were treated with first-line immunotherapy, chemotherapy, or combination treatment. We performed multivariable logistic regression modeling to determine factors associated with treatment receipt Adjusted Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between treatment and OS. ResultsIn our cohort of 4,169 patients, multivariable analysis identified increasing age (RRR: 1.07, 95%CI, 1.06–1.08) and comorbidity burden (, as independent predictors of receiving immunotherapy. Treatment at an academic facility was associated with increased likelihood of combination treatment (RRR: 1.29, 95%CI, 1.01–1.65). After IPTW, we found that combination therapy (hazard ratio [HR]: 0.72; 95%CI, 0.62–0.83) was associated with improved survival compared to chemotherapy. ConclusionsPatients with older age and more comorbidities were more likely to receive immunotherapy than chemotherapy for first-line treatment of metastatic urothelial carcinoma of the bladder. Utilization of chemoimmunotherapy was observed to be higher in academic centers and was associated with improved survival compared to chemotherapy.

Comparison of Mini Nutritional Assessment Tool and Geriatric Nutrition Risk Index in Predicting 12-Y Mortality Among Community-Dwelling Older Persons

BackgroundMalnutrition is a common and dangerous condition in older adults, which has been associated with increased risk of mortality. ObjectivesThis study aimed to evaluate and compare the abilities of Mini Nutritional Assessment short form (MNA-SF), MNA full form (MNA-FF), and geriatric nutritional risk index (GNRI) to predict all-cause and expanded cardiovascular disease (CVD)-related mortality in community-dwelling older adults. MethodsThis research was an observational cohort study conducted in a community setting, with a 12-y follow-up involving 1001 community-living older adults aged 65 y or older who were enrolled in 2009 and followed up until 2021. Nutritional status assessment was carried out in 2009 using MNA-SF, MNA-FF, and GNRI. Multivariate Cox proportional hazards regression was applied to determine adjusted hazard ratios of mortality with 95% CIs. ResultsA total of 368 deaths (36.76%) and 122 expanded CVD-related deaths (12.19%) were observed after a median follow-up of 12 y. Compared with normal nutritional status, poor nutritional status assessed by the MNA-SF, MNA-FF, and GNRI was found to be associated with an increased all-cause mortality in older persons. MNA-SF and MNA-FF, but not GNRI, were associated with expanded CVD-related mortality. The MNA-FF showed better discriminatory accuracy for all-cause (C-statistics: 0.77; 95% CI: 0.63, 0.79) and expanded CVD-related mortality (C-statistics: 0.79; 95% CI: 0.70, 0.83) than MNA-SF (C-statistics: 0.76; 95% CI: 0.73–0.79; and C-statistics: 0.76; 95% CI: 0.72–0.81, respectively) and GNRI (C-statistics: 0.75; 95% CI: 0.73–0.79; and C-statistics: 0.76; 95% CI: 0.72–0.80, respectively). ConclusionsOur findings indicate that MNA-SF, MNA-FF, and GNRI were all independent predictors of all-cause mortality. In particular, the MNA-FF may be the best nutritional assessment tool for predicting all-cause and CVD-related mortality among older persons residing in community, compared with MNA-SF and GNRI.

Physical activity attenuates the excess mortality risk from prolonged sitting time among adults with osteoporosis or osteopenia.

Osteoporosis is a common generalized skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. This study aims to crystallize associations of physical activity (PA) and sedentary behaviour with the survival of adults with osteoporosis or osteopenia. A total of 3103 participants aged 50 years or older from the National Health and Nutrition Examination Survey (NHANES) were included in the study. All participants were diagnosed with osteopenia or osteoporosis. Multivariable Cox proportional hazards regression models were used to assess the association of PA and sedentary behaviour with overall mortality, cancer-related mortality, and cardiovascular disease (CVD)-related mortality. During 21349 person-years of follow-up, 675 deaths were documented. Highly active participants had a lower risk of all-cause (hazard ratios [HR] = 0.61; 95% confidence interval [CI], 0.42-0.87; P for trend = 0.004), cancer-specific (HR = 0.64; 95%CI, 0.35-1.17; P for trend = 0.132), CVD-specific (HR = 0.75; 95%CI, 0.45-1.25; P for trend = 0.452), and other (HR, 0.51; 95%CI, 0.29-0.88; P for trend = 0.005) mortality than inactive participants. And sitting time was not associated with mortality among physically active participants; while among those who were insufficiently active or inactive, longer sitting time was associated with increased risks of all-cause (HR per 1-h increase = 1.05; 95% CI, 1.01-1.09), cancer-specific (HR per 1 h increase = 0.98; 95% CI, 0.90-1.07), CVD-specific (HR per 1-h increase = 1.11; 95% CI = 1.04-1.18), and other (HR per 1-h increase = 1.05; 95% CI, 0.98-1.13) mortality in a dose-response manner. PA can attenuate the excess mortality risk from prolonged sitting for individuals with osteoporosis and/or osteopenia. The combination of prolonged sedentary behaviour with inactive (participants without any PA during a week) PA was associated with an increased risk of mortality. The all-cause mortality risk of individuals who engage in less than 150 min/wk PA and sit more than 8 h/d is 2.02 (95% CI, 1.37-2.99) times higher than that of individuals who engage in more than 150 min/wk PA and sit less than 4 h/d.

Lipid-modifying agents and risk of all-cause, natural and suicide mortality in schizophrenia: nationwide cohort study.

Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied. This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia. This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent. This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association. Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population.

The long-term effects of blood urea nitrogen levels on cardiovascular disease and all-cause mortality in diabetes: a prospective cohort study.

The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes. In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs) of mortality. Of the adult participants with diabetes, 4963 (47.2%) were female. The median (interquartile range) BUN level of participants was 5 (3.93-6.43) mmol/L. After 86,601 person-years of follow-up, 2,441 deaths were documented. After adjusting for variables, the HRs of cardiovascular disease (CVD) and all-cause mortality in the highest BUN level group were 1.52 and 1.35, respectively, compared with those in the lowest BUN level group. With a one-unit increment in BUN levels, the HRs of all-cause and CVD mortality rates were 1.07 and 1.08, respectively. The results remained robust when several sensitivity and stratified analyses were performed. Moreover, BUN showed a nonlinear association with all-cause and CVD mortality. Their curves all showed that the inflection points were close to the BUN level of 5 mmol/L. BUN had a nonlinear association with all-cause and CVD mortality in patients with diabetes. The inflection point was at 5 mmol/L.