Low levels of α-Klotho are associated with cardiovascular and overall mortality in patients with CKD: a case series

Introduction Diabetes mellitus (DM) is a widespread chronic disease associated with a high risk of cardiovascular complications. Identifying reliable Score for predicting cardiovascular and overall mortality in diabetic patients is crucial for early intervention. Purpose This study aims to evaluate the prognostic significance of the systemic immune-inflammation index (SII), calculated from platelet, neutrophil, and lymphocyte counts, as a novel strategy for risk assessment in diabetic individuals. Methods We performed a systematic review and meta-analysis, searching PubMed, Embase, and Cochrane databases to identify studies examining the relationship between SII and mortality in patients with DM. We followed PRISMA reporting guidelines. Eligible studies were analysed using a random-effects model, pooled as hazard ratio (RR), and heterogeneity was assessed using the I² statistic. We used Review Manager 4.1 for statistical analysis. Results A total of 31,841 diabetic patients from five studies were included in the analysis. Higher levels of SII were significantly associated with an increased risk of both cardiovascular and overall mortality in patients with DM. The HR for overall mortality was 1.27, with all the values adjusted for potential confounders (95% CI 1.01–1.59; p=0.04; Figure 1A). Similarly, there was also an association between higher SII and CV mortality, with a HR of 1.50 (95% CI: 1.05–2.16; p=0.03; Figure 1B). Conclusion This systematic review and meta-analysis identified the SII as an important marker for overall mortality and cardiovascular mortality in patients with diabetes. Additional studies are warranted to evaluate the independent prognostic value of SII in this population.

Left ventricular systolic function is a good indicator of cardiac function and a powerful predictor of adverse cardiovascular (CV) outcomes. High ratio of pre-ejection period (PEP) to ejection time (ET) is associated with reduced left ventricular systolic function. Brachial PEP (bPEP) and brachial ET (bET) can be automatically calculated from an ankle-brachial index (ABI)-form device and bPEP/bET was recently reported to be a new and useful parameter of cardiac performance. However, there were no studies evaluating the utility of bPEP/bET for prediction of CV and overall mortality in patients with acute myocardial infarction (AMI). We included 139 cases of AMI admitted to our cardiac care unit consecutively. ABI, bPEP, and bET were obtained from the ABI-form device within the 24 hours of admission. There were 87 overall and 22 CV mortality and the median follow-up to mortality event was 98 months. After multivariable analysis, high bPEP/bET was not only associated with increased long-term CV mortality (hazard ratio (HR) = 1.046; 95% confidence interval (CI): 1.005–1.088; P = 0.029), but also associated with long-term overall mortality (HR = 1.023; 95% CI: 1.001–1.045; P = 0.042). In addition, age was also a significant predictor for CV and overall mortality after the multivariable analysis. In conclusion, bPEP/bET was shown to be a significant predictor for CV and overall mortality in AMI patients after multivariable analysis. Therefore, by means of this novel parameter, we could easily find out the high-risk AMI patients with increased CV and overall mortality.

Unequal Arterial Stiffness With Overall and Cardiovascular Mortality in Patients Receiving Hemodialysis

Background Previous studies have shown elevated lactate was a good predictor for the prognosis of pulmonary embolism (PE). However, due to low number of patients and different expression of blood lactate in separate study, these results are inconsistent. Therefore, the aim of this meta-analysis is to evaluate the relationship between increased lactate levels and adverse outcome in acute PE. Method The literatures search was conducted in PubMed, Web of Science, and EMBASE until May 29, 2021. Results Finally, 6 studies with 1706 patients were included in our meta-analysis. High lactate levels were markedly associated with overall mortality both in unselected PE patients (OR 5.13, 95% CI: 3.36–7.86, p < .00,001) and normotensive PE patients (OR 4.54, 95% CI: 2.64–7.80, p < .00,001), and PE-related short-term mortality in patients with elevated lactate was significantly higher than that in patients with normal levels (OR 9.05, 95% CI :4.08–20.10, p < .00,001). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of lactate for predicting overall mortality in patients with acute PE were 0.67 (95% CI: 0.43–0.85), 0.73 (95% CI: 0.60–0.83), 2.5 (95% CI: 2.0–3.1), and 0.45 (95% CI: 0.26–0.78), respectively. The area under SROC curve (AUC) was 0.76 (95% CI: 0.73–0.80). Conclusion The result of our meta-analysis indicate that elevated blood lactate is a good predictor for overall mortality and short-term mortality in patients with acute PE, and can be routinely measured in risk stratification, but its prognostic role in patients with different risk classes still need to be verified.

Background and Aim: The risk and benefit of non-selective propranolol in patients with tense ascites are controversial. This study aimed to investigate the effect of propranolol as secondary prophylaxis on varix rebleeding and overall mortality in patients with tense ascites. Methods: This study used a database of the Health Insurance Review and Assessment Service (HIRAS), which provides health insurance to 97.2% of the total population in Korea. A total of 80,071 patients first variceal bleeding as the first decompensated complication enrolled from 2007 to 2014. Results: There were 2274 patients with large-volume ascites prescribed propranolol as secondary prophylaxis after first varix bleeding. The average prescription dose of propranolol as secondary prophylaxis was 74 mg/day in patients with large-volume ascites. The mean duration of rebleeding was 22.8 months. Result of analysis showed that low-dose propranolol (40–120 mg/day) compared to inadequate propranolol dose (<40 mg/day) as secondary prophylaxis decreased overall mortality and varix rebleeding in patients with tense ascites. Conclusions: Low-dose propranolol (40–120 mg/day) as secondary prophylaxis for variceal re-bleeding decreased overall mortality and varix rebleeding recurrence in patients with tense ascites.

Background: Anemia is a commonly occurring comorbidity in patients with heart failure (HF). Although there are a few reports of a higher prevalence of mortality and hospitalization-related outcomes due to accompanying anemia, other studies suggest that anemia does not have an adverse impact on the prognostic outcomes of HF. Two meta-analyses in the past decade had reported the adverse impact of anemia on both mortality and hospitalization- related outcomes. However, only one of these studies had evaluated the outcome while using multivariable adjusted hazard ratios. Moreover, several studies since then reported the prognostic influence of anemia in HF. In this present study, we evaluate the prognostic impact of anemia on mortality and hospitalization outcomes in patients with HF.Methods: We carried out a systematic search of the academic literature in the scientific databases EMBASE, CENTRAL, Scopus, PubMed, Cochrane, ISI Web of Science, clinicaltrial.gov, and MEDLINE based on the PRISMA guidelines. Meta-analysis was then performed to evaluate the effect (presented as risk ratio) of anemia on the overall mortality and hospitalization outcome in patients with HF.Results: Out of 1,397 studies, 11 eligible studies were included with a total of 53,502 (20,615 Female, 32,887 Male) HF patients (mean age: 71.6 ± 8.3-years, Hemoglobin: 11.9 ± 1.5 g/dL). Among them, 19,794 patients suffered from anemia (Hb: 10.5 ± 1.6), and 33,708 patients did not have anemia (Hb: 13.2 ± 1.7 g/dL). A meta-analysis revealed a high-odds ratio (OR) for the overall mortality in patients with anemia (OR: 1.43, 95% CI: 1.29–1.84). A high-risk ratio was also reported for hospitalization as the outcome in patients with anemia (1.22, 1.0–1.58).Conclusion: This systematic review and meta-analysis provide evidence of the high risk of mortality and hospitalization-related outcomes in patients with HF and anemia. The study confirms the findings of previously published meta-analyses suggesting anemia as an important and independent risk factor delineating the prognostic outcome of chronic HF.

BackgroundIncreased plasma levels of alkaline phosphatase (ALP) have been associated to a worse prognosis in several types of diseases. In the present review, the authors aimed to study the relationship between plasma levels of ALP and overall mortality in patients with stroke.MethodsA systematic review was carried out, searching two databases: Web of Science and Medline/PubMed.ResultsA total of nine studies that included data on overall mortality in stroke patients were selected. The selected studies were published between 2010 and 2022 and were predominantly from Asia. The articles reviewed quantified ALP levels through different methods: highest versus lowest quintiles of plasma ALP (three reports); highest versus lowest quartiles of plasma ALP (four reports); and plasma ALP levels in deceased versus in surviving patients (two reports). All selected studies showed an increased mortality associated to elevated ALP levels, irrespective of stroke type and length of follow-up, from a mean of 10 days to 2.5 years. The studies comparing the highest to the lowest ALP quintiles showed an aggregate value of 1.8 times greater risk of mortality for the former, when compared to the latter. Whereas, the studies comparing the highest to the lowest ALP quartiles showed an aggregate value of 2.4 times greater risk of mortality for the former, when compared to the latter.ConclusionsElevated ALP levels are associated with increased mortality in stroke patients and provide cost effective prognostic indicators of mortality in stroke.

Evidence on whether long-term exposure to air pollution increases the mortality risk in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to investigate the associations of long-term exposure to particulate matter with diameter <10 µm (PM10) and nitrogen dioxide (NO2) with overall and disease-specific mortality in COPD patients. We conducted a nationwide retrospective cohort study of 121,423 adults ⩾40 years diagnosed with COPD during 1 January to 31 December 2009. Exposure to PM10 and NO2 was estimated for residential location using the ordinary kriging method. We estimated the risk of overall mortality associated with 1-, 3-, and 5-years average concentrations of PM10 and NO2 using Cox proportional hazards models and disease-specific mortality using the Fine and Gray method adjusted for age, sex, income, body mass index, smoking, comorbidities, and exacerbation history. The adjusted hazard ratios (HRs) for overall mortality associated with a 10 µg/m3 increase in 1-year PM10 and NO2 exposures were 1.004 [95% confidence interval (CI) = 0.985, 1.023] and 0.993 (95% CI = 0.984, 1.002), respectively. The results were similar for 3- and 5-year exposures. For a 10-µg/m3 increase in 1-year PM10 and NO2 exposures, the adjusted HRs for chronic lower airway disease mortality were 1.068 (95% CI = 1.024, 1.113) and 1.029 (95% CI = 1.009, 1.050), respectively. In stratified analyses, exposures to PM10 and NO2 were associated with overall mortality in patients who were underweight and had a history of severe exacerbation. In this large population-based study of patients with COPD, long-term PM10 and NO2 exposures were not associated with overall mortality but were associated with chronic lower airway disease mortality. PM10 and NO2 exposures were both associated with an increased risk of overall mortality, and with overall mortality in underweight individuals and those with a history of severe exacerbation.

IntroductionLimited studies are available for predicting mortality in patients with spontaneous bacterial peritonitis (SBP) based on ascitic fluid analysis. Recently, a proposition has been made regarding the role of ascitic fluid lactate as a better prognostic indicator of mortality in cirrhotic patients with SBP. Therefore, we aimed to evaluate the utility of ascitic fluid lactate in predicting mortality in cirrhotic patients with SBP.MethodsThis was a prospective, observational study that was conducted in the Hepato-Gastroenterology Department of Sindh Institute of Urology and Transplantation (SIUT), Karachi from 1 January 2022 to 31 December 2022. All the patients having liver cirrhosis with ascites, aged between 18 and 65 years, and presenting with fever and/or abdominal pain were recruited in the study in the first six months (i.e., from 1 January 2022 to 30 June 2022) and were followed for six more months for the outcome. However, those patients on dialysis or those with hepatocellular carcinoma, any other malignancy as per a history of solid organ transplant, a history of HIV infection, or those underlying systemic sepsis or infections other than SBP were excluded from the study. The presence or absence of SBP was confirmed by doing the ascitic fluid analysis. Ascitic fluid lactate levels were also requested in each patient. Mortality was assessed at one, two, three, and six months, respectively. All the data were analyzed using SPSS version 23.0. The area under the receiver operating curve (AUROC) was obtained for ascitic fluid lactate for predicting mortality in SBP. At an optimal cutoff, the diagnostic accuracy of ascitic fluid lactate was obtained.ResultsThe total number of cirrhotic patients included in the study was 123. The majority of the patients belong to Child Turcotte Pugh (CTP) class C (n = 88; 71%). Two third of the patients (65.8%; n = 81) had viral hepatitis i.e., hepatitis B, D, and/or C, as the cause of cirrhosis. Overall mortality was observed in 51(41.5%) patients. Ascitic fluid lactate was significantly raised in patients with SBP than in patients with non-SBP (p = 0.004). The AUROC of ascitic fluid lactate was highest at three months (AUROC = 0.88) followed by six months (AUROC = 0.84), two months (AUROC = 0.804), and one month (AUROC=0.773). At an optimal cut-off of more than or equal to 22.4 mg/dl, ascitic fluid lactate had a sensitivity of 84.9%, specificity of 85.7%, positive predictive value (PPV) of 97.3%, negative predictive value of 42.8% with diagnostic accuracy of 85% in predicting overall mortality in patients with SBP. On sub-analysis, the diagnostic accuracy of ascitic fluid lactate was highest at six months followed by at three, two, and one month, respectively.ConclusionAscitic fluid lactate showed a good diagnostic utility in predicting the overall mortality in patients with SBP with the best diagnostic accuracy in predicting long-term (six months) mortality. However, further studies are required to validate our results.

This population-based propensity score-matching study aimed to investigate the survival outcomes of patients with biopsy- and transurethral resection of the prostate (TURP)-diagnosed prostate cancer (PC). We obtained data from the Surveillance, Epidemiology and End Results (SEER) database, PC patients diagnosed by biopsy and TURP from 1975 to 2019 were enrolled. Cohort data were baseline-matched using a propensity score-matching (PSM) study. Compared with biopsy-confirmed PC (BPC) patients, prostate cancer-specific mortality (CSM) and overall mortality (OM) in patients with transurethral resection of the prostate (TURP)-diagnosed PC (TPC) were analyzed. A total of 26,027 cases were obtained for this study, of which 4770 cases (18.3%) were TPC patients and 21,257 cases (81.7%) were BPC patients. The proportion of TPC patients showed an increasing trend. The prognosis of TPC patients seemed worse, the ratios of CSM and OM were higher, and the median survival time was shorter (all p &lt; 0.05). After PSM, TPC patients still had a worse prognosis. Compared with BPC patients, TPC patients’ CSM and OM risks increased by 42.0% and 43.0%, respectively (p &lt; 0.001). The results of subgroup analysis indicated earlier the stage of TPC patients, the higher the risk of OM, while systemic treatment after surgery may bring declines of CSM and OM (all p for interaction &lt; 0.001). To our knowledge, we first used a large sample size to find that clinically suspected PC patients with obstruction, directly TURP will increase the risk of CSM and OM.

BackgroundProgressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of JC virus, almost in patients with immunosuppressive conditions. PML is a fatal infection with a reported 3-month mortality rate of 30–50% and a 2-month mortality rate of up to 90% in the non-human immunodeficiency virus (HIV) population. Despite high mortality, studies on PML are still lacking due to its low prevalence and incidence. Therefore, this study aimed to figure out long-term prognosis of PML and prognostic factors for mortality through a long observation period.MethodsWe retrospectively reviewed 68 PML patients with admitted to two tertiary hospitals in South Korea from 1999 to 2021. A total of 47 PML patients were finally enrolled after exclusion. The primary endpoint was long-term overall mortality. For survival analysis, Kaplan-Meier curve and Cox proportional hazards model were used. Each patient was followed up until death or until the end of the study period, whichever came first.ResultsThe median follow-up duration was 20 (interquartile range [IQR], 3–79) months. The median age was 46 years, 27 (57.4%) were diagnosed with HIV, 19 (40.4%) were using immunosuppressive drugs. The median last follow-up modified Rankin Scale (mRS) was higher in non-HIV PML patients group (5 [IQR, 4–6] vs 4 [IQR, 2–5], p=0.020). The median survival duration was 184 (IQR 74–1,566) days in the non-HIV group and 1,564 (IQR 254–3,444) days in the HIV group. The overall mortality rate of PML patients was significantly higher in non-HIV group (80.0% vs 40.7%, p=0.007), also confirmed by the Kaplan-Meier curve and log-rank test (p=0.007). Initial mRS (HR 1.685, 95% CI: 1.028–2.762, p=0.038), HIV patients with highly active antiretroviral therapy (HAART) (HR 0.374, 95% CI: 0.172–0.815, p=0.013) had a significant effect on overall mortality.ConclusionWith the widespread adoption of HAART, the survival duration of HIV patients with PML has been extended, but the mortality rate is still high. Also, the prognosis for PML in non-HIV patients is still frustrated. Initial mRS is a significant risk factor for long-term overall mortality in PML patients. Early detection of PML and early initiation of HAART in HIV patients may improve the patient's prognosis.DisclosuresAll Authors: No reported disclosures.

IntroductionInfective endocarditis (IE) is a severe and fatal infection with high in-hospital and overall mortality rates of approximately up to 30%. Valve culture positivity was associated with in-hospital mortality and postoperative complications; however, few studies have analyzed the relationship between valve cultures and overall mortality over a long observation period. This study aimed to compare the association of valve culture positivity with overall mortality in patients with IE who underwent valve surgery.MethodsA total of 416 IE patients admitted to a tertiary hospital in South Korea from November 2005 to August 2017 were retrospectively reviewed. A total of 202 IE patients who underwent valve surgery and valve culture were enrolled. The primary endpoint was long-term overall mortality. Kaplan–Meier curve and Cox proportional hazards model were used for survival analysis.ResultsThe median follow-up duration was 63 (interquartile range, 38–104) months. Valve cultures were positive in 22 (10.9%) patients. The overall mortality rate was 15.8% (32/202) and was significantly higher in valve culture-positive patients (36.4%, p = 0.011). Positive valve culture [hazard ratio (HR) 3.921, p = 0.002], Charlson Comorbidity Index (HR 1.181, p = 0.004), Coagulase-negative staphylococci (HR 4.233, p = 0.001), new-onset central nervous system complications (HR 3.689, p < 0.001), and new-onset heart failure (HR 4.331, p = 0.001) were significant risk factors for overall mortality.ConclusionsValve culture positivity is a significant risk factor for long-term overall mortality in IE patients who underwent valve surgery. The importance of valve culture positivity needs to be re-evaluated, as the valve culture positivity rate increases with increasing early surgical intervention.

The frailty index (FI) predicts clinical outcomes in oncology. However, in the acute myeloid leukemia (AML) setting, its predictive ability is poorly understood. We assessed whether the FI predicts complete remission (CR), intensive care unit (ICU) admission, and 1-year all-cause mortality in younger and older adults with AML receiving intensity chemotherapy. This was a secondary analysis of a prospective study. In total, 237 patients (n = 140 younger and n = 97 older adults) were classified as non-frail, prefrail, or frail. Frail younger adults were less likely to achieve CR compared with non-frail younger adults. Pre-frail and frail younger adults were more likely to be admitted to the ICU compared with their non-frail counterparts. The FI was not predictive of 1-year all-cause mortality. The FI predicts CR and ICU admission in younger but not older adults. Disease biology may be more important than frailty in predicting 1-year overall mortality in patients with AML undergoing chemotherapy.

Background and Aims:In Taiwan, approximately 90% of patients with end-stage renal disease receive maintenance hemodialysis. Although studies have reported the survival predictability of multiclinical factors, the higher-order interactions among these factors have rarely been discussed. Conventional statistical approaches such as regression analysis are inadequate for detecting higher-order interactions. Therefore, this study integrated receiver operating characteristic, logistic regression, and balancing functions for adjusting the ratio in risk classes and classification errors for imbalanced cases and controls using multifactor-dimensionality reduction (MDR-ER) analyses to examine the impact of interaction effects between multiclinical factors on overall mortality in patients on maintenance hemodialysis.Meterials and Methods:In total, 781 patients who received outpatient hemodialysis dialysis three times per week before 1 January 2009 were included; their baseline clinical factor and mortality outcome data were retrospectively collected using an approved data protocol (201800595B0).Results:Consistent with conventional statistical approaches, the higher-order interaction model could indicate the impact of potential risk combination unique to patients on maintenance hemodialysis on the survival outcome, as described previously. Moreover, the MDR-based higher-order interaction model facilitated higher-order interaction effect detection among multiclinical factors and could determine more detailed mortality risk characteristics combinations.Conclusion:Therefore, higher-order clinical risk interaction analysis is a reasonable strategy for detecting non-traditional risk factor interaction effects on survival outcome unique to patients on maintenance hemodialysis and thus clinically achieving whole-scale patient care.

Background Aortic stenosis (AS) is the most prevalent valvular disease requiring intervention. While therapeutic options have expanded, clinical decision-making is challenged by the diversity of patients’ profiles. Existing risk models often fail to account for population-specific factors and healthcare system variations. Developing predictive models tailored to specific populations and focused on robust endpoints may improve treatment decision-making. Objective To develop an easy-to-use predictive model for overall mortality in patients with severe AS, integrating patient characteristics and possible therapeutic approaches based on a prospective AS cohort. Methods This prospective observational study included patients with severe AS enrolled in the AS Integrated Care Process at a tertiary hospital in Spain from 2018 to 2022, with follow-up data updated to November 2024 (PROCEAS cohort). Clinical, echocardiographic and laboratory parameters were analysed alongside with treatment modality and clinical outcomes. A stratified cox proportional hazards model was elaborated to predict overall mortality (dependant variable). Patients were categorized into three subgroups based on treatment type: surgical or transcatheter (TAVR) valve replacement or conservative. Initially, only candidate variables meeting the proportional hazard’s assumption across all subgroups were included in a first stratified Cox model. The best possible model was then selected on the basis of Akaike information criterion (AIC). The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC). Results The PROCEAS cohort comprised 988 patients, of whom 984 were included in the final analysis (mean age: 77±8.4 years; 42.2% female). Treatment distribution was as follows: surgery in 432 patients, TAVR in 490 patients, and conservative in 62 patients. Overall mortality was 26.8% during a mean follow-up of 39±19.4 months, highest in the conservative group, followed by TAVR and surgery (p&amp;lt;0.0001). Five relevant predictors were included in the treatment-stratified final cox model: diabetes mellitus, atrial fibrillation, cardiac damage stage in AS (as defined by Généreux et al.), sex, and age (Table 1). A nomogram was elaborated to facilitate clinical application, providing individualized 1-year and 2-year mortality risk estimates based on treatment strategy (Figure 2). Model performance metrics showed an AUC of 0.69 for 1-year mortality (sensitivity: 57%, specificity: 76%) and 0.72 for 2-year mortality (sensitivity: 70%, specificity: 65%). Conclusions This study presents a pilot clinically applicable predictive model for overall mortality in severe AS patients, depending on the treatment modality. The PROCEAS nomogram may aid personalised risk assessment and guide therapeutic decisions in a Spanish population. External validation is needed to confirm broader applicability. Figure 1.PROCEAS Mortality risk nomogram