Cox Proportional Hazards Regression Analysis 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.

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.

Proteinuria and risk of ocular motor cranial nerve palsy: a nationwide population-based study

Understanding the association between dipstick-detected proteinuria and oculomotor cranial nerve palsy (CNP) could have significant implications for understanding the mechanism of CNP development and for developing preventive strategies against CNP development in patients with proteinuria. This study aimed to determine the relationship between dipstick-determined proteinuria and ocular motor CNP using National Sample Cohort (NSC) database from Korea’s National Health Insurance Service (NHIS). A nationwide population-based cohort study was conducted using data from the NSC database of Korea’s NHIS. These data were collected from 2009 to 2018. A one-year time lag was established to prevent a situation in which the causal link was inverted. Participants aged 20 years or more who were diagnosed with proteinuria in 2009 were included. Individuals with specific pre-existing CNP, missing data, and those who were newly diagnosed with CNP or who died within one year of being tested were excluded. The study population was classified into six groups according to the degree of proteinuria (negative, trace, or between 1 + and 4 +) based on the urine dipstick test. A Cox proportional hazard regression analysis was performed to determine the linkage between the degree of proteinuria and ocular motor CNP. A total of 5,807 (0.14% of subjects) with ocular motor CNP were assigned to the ocular motor CNP group and 4,047,205 subjects were assigned to the control group. After full adjustment of comorbidities, hazard ratios (HRs) for 1 + , 2 + , 3 + and 4 + proteinuria groups were 1.449 (95% confidence interval [CI] 1.244–1.687), 2.081 (1.707–2.538), 1.96 (1.322–2.904), and 3.011 (1.507–6.014), respectively, for developing ocular motor CNP compared to the proteinuria-negative group. In subgroup analysis, the HR of patients with proteinuria for the development of ocular motor CNP was higher in the younger age group (less than 40 years) (P = 0.0242) and the group with DM (P = 0.04). Our population-based cohort study demonstrated a significant association between proteinuria and the incidence of CNP, suggesting that urine protein level could be a new clinical marker for predicting the development of CNP.

Genetic, sociodemographic, lifestyle, and clinical risk factors of heart failure aggravation events: data from the UK Biobank

Abstract Background Heart failure (HF) is the leading cause of readmission and hospitalization. Purpose This study examined the associations and clinical utilities of genetic, sociodemographic, lifestyle, laboratory, and clinical risk factors on HF aggravation. Methods Data were from 5,345 UK Biobank middle-aged adults with established HF at enrolment. We performed Cox proportional hazard regression analyses to investigate the associations related to HF admission after enrolment utilizing 24 variables encompassing sociodemographic, clinical, lifestyle, and laboratory data. To assess the impact of genetic factors, we additionally adjusted each polygenic risk score (PRS) for the three medical histories: hypertension, atrial fibrillation (AF), and coronary heart disease (CHD), where the hazard ratios were statistically significant. Results Over a median follow-up of 11.5 [10.9-12.2] years, 247 (4.6%) HF admission events occurred. Among the 24 variables, statistically significant hazard ratios were observed for 10 variables, with hypertension (3.31, 2.19-5.02), AF (2.06, 1.53-2.75), current smoking (1.63, 1.09-2.46), and coronary heart disease (1.58, 1.17-2.13) showing the highest hazard ratios, while female gender (0.65, 0.46-0.91) exhibited the smallest hazard ratio. After adjusting for each PRS individually, HTN PRS (HR 1.06, 0.94-1.21) and AF PRS (HR 1.02, 0.90-1.16) were not statistically significant, whereas CHD PRS (HR 1.15, 1.02-1.31) showed significance in relation to HF admission. In the HF admission prediction model, the C index was 0.859 (0.838-0.880) with clinical variables, and it marginally increased to 0.864 (0.843-0.885) when all factors, including the genetic factor, were applied. Conclusions Sociodemographic, clinical, laboratory, lifestyle, and genetic factors are each associated with HF aggravation with male gender, hypertension, AF, low eGFR, cigarette smoking, and CHD PRS.

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.

#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.

#1062 Effect of intradialytic resistance exercise on patient survival: a multicenter non-randomized cohort study

Abstract Background and Aims Intradialytic exercise significantly benefits the physical function of patients undergoing hemodialysis. Prior research into its impact on patient longevity has been constrained by small participant numbers and the lack of a control group. This study investigates the influence of exercise therapy during hemodialysis on patient lifespan in a broad multicenter cohort. Method This forward-looking, multicenter, non-randomized clinical investigation included 17 outpatient clinics from the Kaikoukai Medical Group, recruited between April and December 2018. Participants were voluntarily enlisted in an exercise regimen during their dialysis sessions and segregated into exercising and non-exercising cohorts. The trial was not blinded. The intradialytic regimen comprised stretching and four types of resistance exercises utilizing elastic tubes, conducted thrice weekly. Baseline data encompassing age, gender, stature, baseline weight, duration of hemodialysis treatment, and concurrent diabetic conditions were collected. Additional data regarding hemodialysis, including Kt/V ratio, hemodialysis blood flow rate (QB), dialysate volume (QD), and duration of dialysis, were recorded. Laboratory parameters such as albumin (Alb), calcium (Ca), potassium (K), hemoglobin (Hb), C-reactive protein (CRP), and creatinine (Cr) levels were extracted from medical records. Patient outcomes were monitored until either the occurrence of death or the study's culmination in December 2021. In statistical analyses, missing values were addressed using multiple imputation techniques, and baseline characteristics between groups were compared using an unpaired t-test. Cox proportional hazards regression analysis was employed to examine the relationship between the exercise intervention and survival, adjusting for multiple confounding variables. Three models were constructed for analysis: Model 1 incorporated basic patient data, Model 2 included hemodialysis parameters, and Model 3 involved laboratory data. The study was approved by the Ethical Committee of Nagoya Kyoritsu Hospital. Results The study encompassed 2006 subjects (average age 70.1±0.3 years), with 512 (25.5%) in the exercise group and 1494 (74.5%) in the control group. Initial comparisons indicated that the exercise group had significantly lower average height (160.9±0.3 vs. 159.7±0.4 cm, p=0.03), baseline weight (57.2±0.3 vs. 55.9±0.5 kg, p=0.04), Kt/V ratio (1.59±0 vs. 1.64±0, p=0.01), and QD (494±0.9 vs. 486.8±1.9 ml, p&amp;lt;0.01). Over the median observation period of 25 months, 338 (16.9%) patients, comprising 58 (11.3%) from the exercise group and 280 (18.7%) from the control group, succumbed. Survival analysis revealed a significant association between exercise intervention and mortality reduction, adjusted for confounders in Model 1 (HR 0.6, 95%CI 0.4-0.9, p=0.01), Model 2 (HR 0.55, 95%CI 0.37-0.8, p=0.02), and Model 3 (HR 0.57, 95%CI 0.38-0.87, p=0.01). Conclusion This research is the first to demonstrate a significant association between intradialytic resistance training and improved survival in hemodialysis patients within a multicenter, non-randomized cohort. This relationship remained significant after adjusting for multiple confounding factors, suggesting that incorporating resistance training into standard hemodialysis care could markedly enhance patient survival outcomes.

#2268 Dialysis patients survival in HD centres from Belgium, Estonia, Spain, and Sweden—association with BMI and hypocalcemia

Abstract Background and Aims Several factors are known to influence the morbidity and mortality of ESKD patients, among them cardiovascular disease, nutritional status, delivered dialysis dose, uremic toxins levels, and infectious diseases. This observational study aimed to analyse factors that impact the survival of ESKD patients on haemodialysis. Method We analysed 3- and 5-year survival of 76 patients during the period of 2018-2023 (17 females, 59 males, aged 63.6 ± 15.9 years) from four separate dialysis centres from countries with diverse life expectancies, renal replacement therapy incidences, and kidney transplant rates: North Estonia Medical Centre, Tallinn, Estonia (21 patients); Linköping University Hospital, Linköping, Sweden (21 patients); Ghent University Hospital, Ghent, Belgium (14 patients) and Fundación Jiménez Díaz University Hospital Health Research Institute, Madrid, Spain (20 patients). We included stable chronic haemodialysis patients receiving three times per week post-dilution ol-HDF treatment. Patients with central dialysis catheter, acute coronary syndrome or stroke within three months were excluded. Cox proportional-hazard regression analysis was used to detect the factors affecting the survival of patients. In the Cox model, the 3-year survival was set as a dependent parameter. Age, gender, BMI, and serum levels of creatinine, phosphate, calcium, total protein, and uric acid were set as independent parameters. Kaplan-Meier survival analysis was performed to study survival in the subgroups of patients. Results Out of 76 patients, 22 died in 3-years and 34 in five years (Fig. 1a and b). Our Cox model (adjusted with the age, gender, creatinine, phosphate, total protein, and uric acid serum levels) indicated patients' body mass index (BMI, p = 0.014) and calcium (p = 0.033) levels as statistically significant factors in 3-year survival. Kaplan-Meier survival analysis showed statistically significant increased survival in the group where BMI was higher than 27.6 kg/m2 (Fig. 2a) and in the group where serum calcium levels were higher than 2.25 mmol/L (Fig. 2b). Conclusion This study shows that among prevalent haemodialysis patients 3-year survival is about 65% and 5-year survival 45%, and a higher risk of mortality could be associated with low BMI and low serum calcium levels. Our findings are in accordance with previous studies, where survival benefit for haemodialysis patients with higher BMI is shown [1, 2]. It is proposed that this phenomenon among advanced CKD patients with higher BMI could be due to better nutritional reserve that helps resist chronic inflammation and wasting. The negative effects of excess calcium load for haemodialysis patients are well known, and nowadays, non-calcium-based phosphorus binders, calcimimetics, and low-calcium concentrates in haemodialysis are used more often, thus putting the patients at risk of hypocalcaemia. Though less studied, long-term hypocalcaemia is shown to increase mortality among haemodialysis patients [3], as concurs with our results. Safe calcium concentration limits for these patients are still debatable and need further investigation.

#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.

Elevations in presepsin, PCT, hs-CRP, and IL-6 levels predict mortality among septic patients in ICU.

Aim to investigate the predictive value of changes in presepsin (PSEP), procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) levels to for mortality in septic patients in intensive care unit (ICU). This study enrolled septic patients between November 2020 and December 2021. Levels of PSEP, PCT, hsCRP, and IL-6 were measured on 1st (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and 3rd day (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional-hazards regression (Cox) analysis, △PSEP (= PSEP_3- PSEP_0) > 211.49 pg/ml (hazard ratio (HR) 2.70, 95% confidence interval (CI) 1.17-6.22), △PCT (= PCT_3- PCT_0) > -0.13 ng/ml (HR 7.31, 95% CI 2.68-19.80), △hsCRP (= hsCRP_3- hsCRP_0) > -19.29 mg/L (HR 6.89, 95% CI 1.61-29.40), and △IL-6 (= IL-6_3- IL-6_0) > 1.00 pg/ml (HR 3.13, 95% CI 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all four distinct biomarkers was highest (concordance index 0.83, 95% CI 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the APACHE Ⅱ and SOFA scores, the combination of the four biomarkers had a larger net benefit. Interestingly, IL-6 was predominantly produced by monocytes upon LPS stimulation in PBMCs. △PSEP, △PCT, △hsCRP, and △IL-6 are reliable biomarkers for predicting mortality in septic patients in ICU, and their combination has the best performance.

The number of resected lymph nodes from the upper mediastinal area predicts long-term outcomes of esophageal squamous cell carcinoma after minimally invasive esophagectomy.

The total number of resected lymph nodes (LNs) is an important determinant of longer survival after esophagectomy for esophageal squamous cell carcinoma (ESCC). However, the resected LN counts from areas that affect long-term outcomes remain unclear. This study included 406 patients who underwent minimally invasive esophagectomies (MIEs) at Kobe University Hospital. Resected LN counts were evaluated in the following areas: upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd). Cut-off values for LN counts from each area were determined using receiver operating characteristics analysis of the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. The cut-off values for large or small numbers of resected LN counts in the UM, MM, LM, and Abd areas were 4, 8, 5, and 18, respectively, in patients with upper and middle thoracic (Ut/Mt) ESCC and 7, 6, 5, and 24, respectively, in patients with lower thoracic (Lt) ESCC. Multivariate analysis in patients with Ut/Mt ESCC revealed that tumor invasion depth, LN metastasis, and the resected LN count from the UM area were independent risk factors for overall survival [hazard ratio (HR), 7.04; 95% confidence interval (CI) 4.47-11.1; HR, 4.01; 95% CI 1.96-8.21; HR, 2.18; 95% CI 1.24-3.82, respectively]. In patients with Lt ESCC, tumor invasion depth, LN metastasis, and pulmonary complications were independent risk factors for overall survival (HR, 4.23; 95% CI 2.14-8.35; HR, 3.83; 95% CI 1.75-8.38; HR, 2.80; 95% CI 1.38-5.65, respectively). Resected LN counts from no areas were prognostic factors. The number of resected LNs from the UM area influenced the survival outcomes of patients with Ut/Mt ESCC after MIE.

Sodium–glucose cotransporter-2 inhibitors improve cardiovascular outcomes post-acute coronary syndrome complicated by acute heart failure

BackgroundAcute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium–glucose cotransporter-2 (SGLT2) inhibitors post-ACS in patients with acute HF (AHF) and diabetes.MethodsWe conducted a retrospective observational cohort study employing propensity score matching. This study involved patients with diabetes admitted with ACS complicated by AHF, defined as either new clinical HF requiring diuretics during the index admission or having an ejection fraction (EF) of &amp;lt;40%. The study population was divided into two groups; (1) SGLT2 inhibitor users and (2) SGLT2 inhibitor non-users. The Cox proportional hazard regression analysis was used to evaluate the outcomes.ResultsA total of 465 patients (93% male; mean age, 55 ± 10 years) were included in this study. Using a 1 : 1 propensity score matching, 78 patients were included per arm with an absolute standardized difference of &amp;lt;0.1 for all baseline characteristics. The use of SGLT2 inhibitors resulted in lower composite outcomes of ACS, HF hospitalization, and all-cause mortality at 1 month and 12 months [1 month: 2.6% vs. 11.5%, HR = 0.20 (0.04–0.94), p = 0.041; 12 months: 14.1% vs. 23.1%, HR = 0.46 (0.22–0.99), p = 0.046].ConclusionThe findings suggest that SGLT2 inhibitors may confer cardioprotective effects in ACS-induced AHF, thereby widening the spectrum for indications of SGLT2 inhibitors.

A study on vertebral refracture and scoliosis after percutaneous kyphoplasty in patients with osteoporotic vertebral compression fractures

PurposeTo analyze the association between scoliosis and vertebral refracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fractures (OVCFs).MethodsA retrospective study was conducted on 269 patients meeting the criteria from January 2014 to October 2022. All patients underwent PKP with complete data and were followed-up for > 12 months. First, it was verified that scoliosis was a risk factor in 269 patients. Second, patients with scoliosis were grouped based on the Cobb angle to evaluate the impact of the post-operative angle. The cox proportional hazards regression analysis and survival analysis were used to calculate the hazard ratio and recurrence time.ResultsA total of 56 patients had scoliosis, 18 of whom experienced refractures after PKP. The risk factors for vertebral refractures included a T-score < − 3.0 and presence of scoliosis (both p < 0.001). The results indicated that the vertebral fractured arc (T10 − L4) was highly influential in scoliosis and vertebral fractures. When scoliotic and initially fractured vertebrae were situated within T10 − L4, the risk factors for vertebral refracture included a postoperative Cobb angle of ≥ 20° (p = 0.002) and an increased angle (p = 0.001). The mean recurrence times were 17.2 (10.7 − 23.7) months and 17.6 (7.9 − 27.3) months, respectively.ConclusionOsteoporosis combined with scoliosis significantly increases the risk of vertebral refractures after PKP in patients with OVCFs. A postoperative Cobb angle of ≥ 20° and an increased angle are significant risk factors for vertebral refractures when scoliotic and initially fractured vertebrae are situated within T10 − L4.

Association between aspirin and mortality in critically ill patients with atrial fibrillation: a retrospective cohort study based on mimic-IV database

BackgroundAtrial fibrillation (AF) is a prevalent issue among critically ill patients, and the availability of effective treatment strategies for AF is limited.AimThe objective of this study was to evaluate the mortality rate associated with AF in critically ill patients who were either aspirin or non-aspirin users.MethodsThis cohort study incorporated critically ill patients with AF from the Medical Information Mart for Intensive Care database. The study compared incidences of 28-day mortality, 90-day mortality, and 1-year mortality between patients with and without aspirin prescriptions. To assess the association between aspirin and the endpoints, Kaplan-Meier analysis and Cox proportional hazards regression analyses were conducted.ResultsIn this study, a total of 13,330 critically ill patients with atrial fibrillation (AF) were included, of which 4,421 and 8,909 patients were categorized as aspirin and non-aspirin users, respectively. The 28-day, 90-day, and 1-year mortality rates were found to be 17.5% (2,330/13,330), 23.9% (3,180/13,330), and 32.9% (4,379/13,330), respectively. The results of a fully-adjusted Cox proportional hazard model indicated that aspirin use was negatively associated with the risk of death after adjusting for confounding factors (28-day mortality, HR 0.64, 95% CI 0.55–0.74; 90-day mortality, HR 0.65, 95% CI 0.58–0.74; 1-year mortality, HR 0.67, 95%CI 0.6∼0.74). The results of the subgroup analysis indicate a more robust correlation, specifically among patients under the age of 65 and those without a history of congestive heart failure or myocardial infarction.ConclusionsThe utilization of aspirin may exhibit a correlation with a reduction in risk-adjusted mortality from all causes in critically ill patients diagnosed with atrial fibrillation. However, additional randomized controlled trials are necessary to elucidate and confirm this potential association.

Peroxiredoxin 2 as a potential prognostic biomarker associated with angiogenesis in cervical squamous cell cancer.

Peroxiredoxins (Prxs) are a ubiquitously expressed family of antioxidant enzymes that either facilitate or inhibit tumorigenesis, depending on the cancer type and Prx isoform. Prx2 is a typical Prx that has a dual role in tumorigenesis and tumor progression. However, the expression of Prx2 and its precise role in cervical cancer remains to be elucidated. Therefore, the present study aimed to investigate the expression of Prx2 and its association with the progression and prognosis of cervical squamous cell cancer (CSCC). In the present study, the clinicopathological data of 105 patients diagnosed with CSCC were collected from the medical record system at Jingzhou Central Hospital, Tongji Medical College of Huazhong University of Science and Technology (Jingzhou, China). Prx2 protein was also detected in 105 CSCC tissues and 40 adjacent peri-tumoral tissues by immunohistochemical staining. The relationships between Prx2 expression and clinicopathological features, vascular endothelial growth factor A (VEGF-A) expression and micro-vessel density (MVD) in CSCC were then analyzed. Progression-free survival (PFS) was also assessed using both univariate and multivariate analyses. The results of the present study demonstrated that the expression of Prx2 was upregulated in CSCC tissues compared with the adjacent peri-tumoral tissues (P<0.001). In addition, higher Prx2 expression was associated with greater depth of stromal invasion (P=0.023) and positive lymph vascular space invasion (P=0.044), while the Prx2 expression level was not associated with age, tumor size, histological grade, lymph node (LN) metastasis or International Federation of Gynecology and Obstetrics (FIGO) stage (all P>0.05). Furthermore, increased Prx2 expression was associated with high MVD (P=0.016), while expression of VEGF-A was not associated with Prx2 expression (P>0.05). Kaplan-Meier analysis showed that patients with high Prx2 expression (log-rank test, P=0.039), high MVD (log-rank test, P=0.015), a higher FIGO stage (log-rank test, P=0.021) and LN metastasis (log-rank test, P=0.022) had a shorter PFS time than patients with low Prx2 expression, low MVD, a lower FIGO stage and without LN metastasis, respectively. Cox proportional hazard regression analysis revealed that expression of Prx2 [hazard ratio (HR), 2.551; 95% confidence interval (CI), 1.056-6.162; P=0.037], MVD (HR, 2.436; CI, 1.034-5.735; P=0.042) and FIGO stage (HR, 1.543; CI, 1.027-2.319; P=0.037) were independent factors for PFS time. In conclusion, the results of the present study suggested that Prx2 could act as a potential biomarker for predicting CSCC progression and prognosis and could be a novel target for antiangiogenic therapy of CSCC.

Predictive value of laboratory indicators for in-hospital death in children with community-onset sepsis: a prospective observational study of 266 patients

Background and objectivesThis study aimed to identify predictors of sepsis-associated in-hospital mortality from readily available laboratory biomarkers at onset of illness that include haematological, coagulation, liver and kidney function, blood...

Association between the triglyceride-glucose index and in-hospital major adverse cardiovascular events in patients with acute coronary syndrome: results from the Improving Care for Cardiovascular Disease in China (CCC)-Acute Coronary Syndrome project

ObjectiveAlthough the TyG index is a reliable predictor of insulin resistance (IR) and cardiovascular disease, its effectiveness in predicting major adverse cardiac events in hospitalized acute coronary syndrome (ACS) patients has not been validated in large-scale studies. In this study, we aimed to explore the association between the TyG index and the occurrence of MACEs during hospitalization.MethodsWe recruited ACS patients from the CCC-ACS (Improving Cardiovascular Care in China-ACS) database and calculated the TyG index using the formula ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). These patients were classified into four groups based on quartiles of the TyG index. The primary endpoint was the occurrence of MACEs during hospitalization, encompassing all-cause mortality, cardiac arrest, myocardial infarction (MI), and stroke. We performed Cox proportional hazards regression analysis to clarify the correlation between the TyG index and the risk of in-hospital MACEs among patients diagnosed with ACS. Additionally, we explored this relationship across various subgroups.ResultsA total of 101,113 patients were ultimately included, and 2759 in-hospital MACEs were recorded, with 1554 (49.1%) cases of all-cause mortality, 601 (21.8%) cases of cardiac arrest, 251 (9.1%) cases of MI, and 353 (12.8%) cases of stroke. After adjusting for confounders, patients in TyG index quartile groups 3 and 4 showed increased risks of in-hospital MACEs compared to those in quartile group 1 [HR = 1.253, 95% CI 1.121–1.400 and HR = 1.604, 95% CI 1.437–1.791, respectively; p value for trend < 0.001], especially in patients with STEMI or renal insufficiency. Moreover, we found interactions between the TyG index and age, sex, diabetes status, renal insufficiency status, and previous PCI (all p values for interactions < 0.05).ConclusionsIn patients with ACS, the TyG index was an independent predictor of in-hospital MACEs. Special vigilance should be exercised in females, elderly individuals, and patients with renal insufficiency.

Type and approach of hysterectomy and oncological survival of women with stage II cancer of endometrium: a large retrospective cohort study.

To explore the association between the Type and approach of hysterectomy and oncological survival of women with stage II cancer of the endometrium. 684 women with stage II endometrial cancer were included. Eligible cases were grouped by type of hysterectomy (simple hysterectomy or radical hysterectomy)and approach of hysterectomy (laparoscopy or laparotomy). The baseline characteristics were compared among groups. The survival outcomes (disease-free survival and overall survival) were calculated and compared among groups, and the underlying confounding factors were adjusted by the Cox proportional hazard regression analysis. The radical hysterectomy group and the simple hysterectomy group had 217 cases and 467 cases, respectively. Between the groups, the difference in 5-year disease-free survival (87.3% versus 87.9%, HR=0.97, P=0.87) and 5-year overall survival (83.8% versus 83.8%, HR=0.95, P=0.95) was not statistically significant. The laparotomy group and the laparoscopy group had 277 cases and 407 cases, respectively. Between the groups, the difference in 5-year disease-free survival (88.7% versus 87.1%, HR=1.22, P=0.34) and 5-year overall survival (85.5% versus 82.7%, HR=1.00, P=0.99) was not statistically significant. For long-term oncological survival, radical hysterectomy is not superior to total hysterectomy in stage II endometrial cancer. Also, for stage II cancer of the endometrium, laparoscopic hysterectomy is as oncologically safe as open hysterectomy.