Multivariate Proportional Hazards Regression Analysis Research Articles

The prognostic significance of synchronous metastasis in glioblastoma multiforme patients: a propensity score-matched analysis using SEER data

BackgroundGlioblastoma multiforme (GBM) with synchronous metastasis(SM) is a rare occurrence. We extracted the data of GBM patients from the SEER database to look into the incidence of SM in GBM, determine the prognostic significance of SM in GBM, and assess therapeutic options for patients presenting with SM.MethodsFrom 2004 to 2015, information on GBM patients was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The propensity score matching (PSM) method was employed to mitigate confounding factors between SM and non-SM groups, subsequently investigating the prognostic significance of SM in patients with GBM. Multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic variables for GBM patients with SM. A forest plot was used to visualize the results.ResultsA cohort of 19,708 patients was obtained from the database, among which 272 (1.4%) had SM at the time of diagnosis. Following PSM at a 3:1 ratio, in both univariate and multivariate cox regression analysis, SM (HR = 1.27, 95% CI: 1.09–1.46) was found to be an independent predictive predictor for GBM patients. Furthermore, the Cox proportional hazard forest plot demonstrated that independent risk variables for GBM patients with SM included age (Old vs. Young, HR = 1.44, 95% CI: 1.11–1.88), surgery (biopsy vs. no surgery, HR = 0.67, 95% CI: 0.46–0.96;Subtotal resection vs. no surgery, HR = 0.47, 95% CI: 0.32–0.68;Gross total resection vs. no surgery, HR = 0.44, 95% CI: 0.31–0.62), radiotherapy (HR = 0.58, 95% CI: 0.41–0.83), and chemotherapy (HR = 0.51, 95% CI: 0.36–0.72).ConclusionThe predictive value of SM in GBM was determined by this propensity-matched analysis using data from the SEER database. Radiotherapy, chemotherapy, and surgery constitute an effective treatment regimen for patients with SM. A more positive approach toward the use of aggressive treatment for GBM patients with SM may be warranted.

Infective Endocarditis Among Women Who Inject Drugs

In the US and Canada, women comprise approximately one-third of people who inject drugs (PWID); however, clinical characteristics and outcomes of injection drug use complications in women are poorly described. To identify clinical characteristics and outcomes of infective endocarditis (IE) among women who inject drugs (WWID). This is a retrospective cohort study of PWID with definite IE (per 2023 Duke-International Society for Cardiovascular Infectious Diseases criteria) admitted from April 5, 2007, to March 15, 2018, at 5 tertiary-care hospitals in London, Ontario, and Regina, Saskatchewan, Canada. Data were analyzed from June 1, 2023, to August 2, 2024. Descriptive analyses were conducted for baseline characteristics at index hospitalization and stratified by sex. The primary outcome was the difference in 5-year survival between female and male PWID with IE. The secondary outcome was 1-year survival. Multivariable time-dependent Cox proportional hazards regression analyses were conducted for variables of clinical importance to evaluate 5-year mortality. Of 430 PWID with IE, 220 (51.2%) were women; of 332 non-PWID with IE, 101 (30.4%) were women. WWID with IE were younger than men (median [IQR] age, 31.5 [27.0-38.5] vs 38.5 [31.0-49.0] years), and 11 of 220 (5.0%) were pregnant at index hospitalization, although only 12 of 220 (5.5%) had contraceptive use documented. Women had a larger proportion of right-sided IE than men (158 of 220 women [71.8%] vs 113 of 210 men [53.8%]). WWID living in urban areas had higher mortality than WWID in rural areas (adjusted hazard ratio [aHR], 2.70; 95% CI, 1.15-6.34; P = .02). Overall mortality was lower among PWID referred for substance use disorder counseling in centers with inpatient services compared with centers with only outpatient referrals (aHR, 0.29; 95% CI, 0.17-0.51; P < .001). Overall mortality was lower with right-sided heart disease for both women (aHR, 0.44; 95% CI, 0.27-0.71; P < .001) and men (aHR, 0.22; 95% CI, 0.10-0.50; P < .001) and was higher with congestive heart failure for both women (aHR, 2.32; 95% CI, 1.29-4.18; P = .005) and men (aHR, 1.73; 95% CI, 1.07-2.79; P = .02). In this cohort of PWID with IE, women were overrepresented. Reasons for women's disproportionately high IE incidence need further study. Inpatient substance use disorder services, contraception counseling, and enhanced social support for WWID living in urban areas need to be prioritized.

Weight-adjusted waist index is positively and linearly associated with all-cause and cardiovascular mortality in metabolic dysfunction-associated steatotic liver disease: findings from NHANES 1999-2018

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Body mass index (BMI) is the most used obesity index but has important limitations. The weight-adjusted waist index (WWI) is a novel obesity metric and accurately reflects body composition. We explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in MASLD.MethodsAdult participants with MASLD were included from NHANES 1999-2018. WWI was calculated by dividing the waist circumference (WC) by the square root of body weight. MASLD was diagnosed by the presence of hepatic steatosis and at least one cardiometabolic risk factor in the absence of other causes of steatosis. A fatty liver index ≥60 suggested the presence of hepatic steatosis. Mortality data was obtained by prospectively linking to the National Death Index. Multivariate Cox proportional hazards regression analyses were used to explore these associations and multiple adjustment models were constructed including crude, partial, and fully adjusted models.ResultsAfter adjusting for all covariates including BMI, WWI remained positively and linearly associated with all-cause and CVD mortality in MASLD (hazard ratios [HR] 1.247 and 1.218, respectively). Higher WWI was associated with a significantly increased risk of mortality (both p for trend &amp;lt;0.05). There was an “obesity paradox” between BMI and all-cause mortality in MASLD, with significantly lower all-cause mortality in those with overweight/obesity compared to normal BMI (HR 0.625 and 0.596, respectively, p for trend = 0.024), and no association between BMI and CVD mortality. Interaction analyses indicated that these associations were influenced by several demographic variables and disease status. Time-dependent receiver operating characteristic curves indicated that the predictive value of WWI for mortality in MASLD was higher than that of BMI, WC, and waist-to-height ratio across all follow-up durations.ConclusionsWWI was positively and linearly associated with all-cause and CVD mortality in MASLD, whereas BMI did not accurately reflect mortality risk. WWI provided the optimal predictive value for mortality compared to traditional obesity indicators. These findings emphasize the potential use of WWI as a novel obesity indicator for mortality risk assessment, stratification, and prevention in MASLD.

The association between anemia, hospitalization, and all-cause mortality in patients with heart failure managed in primary care: An analysis of the Swedish heart failure registry

BackgroundMany patients with heart failure (HF) are managed in primary care, and comorbidities are common. Anemia is one frequent comorbidity. The aim of this study was to assess the prevalence, comorbidities, and prognosis of HF patients in primary care who have anemia. MethodWe linked data on 9300 patients managed in primary care from the nationwide SwedeHF registry with other Swedish national register data. A multivariable logistic regression model with anemia as a dependent variable was performed. Multivariate Cox proportional hazards regression analysis was used to model the time to event. ResultsThe median age (IQR) was 81 (74–86) years, and 45 % of the patients were female. A total of 2852 (30.7 %) had anemia. Anemia was more common in men, in those ≥75 years, and in those with kidney dysfunction. A total of 695 (10.8 %) of patients without and 520 (18.2 %) with anemia had cancer. Cancer was independently associated with anemia (OR 1.5, 95 % CI 1.3–1.7). Other comorbidities significantly associated with anemia were peripheral artery disease (OR 1.39, 95 % CI 1.18–1.65), diabetes (OR 1.29, 95 % CI 1.16–1.44), and liver disease (OR 1.64, 95 % CI 1.09–2.46). If anemia was present, prognosis was worse. Risk of all-cause hospitalization was higher (adjusted HR 1.3, 95 % CI 1.2–1.4), as was risk of all-cause mortality (adjusted HR 1.4, 95 % CI 1.3–1.5). ConclusionsAnemia is common in primary care patients with HF. It is associated with worse prognosis and comorbidities, most notably cancer.

Symptom severity reported by older adults with cancer and its impact on survival prognostication

Introduction: Symptom burden is a crucial factor for survival prognostication, but older adults may report fewer and less severe symptoms than younger patients. We investigated the impact of age on symptom severity and its prognostic implications in the prognostic model for advanced cancer (PRO-MAC).Materials and Methods: Eight hundred forty subjects with incurable cancer, who were reviewed by palliative medicine at a tertiary university hospital, were categorized into four groups based on age: < 65 (young), 65–74 (young-old), 75–84 (old-old), and ≥ 85 (oldest-old) for comparison. The study compared individual symptoms reported on the Edmonton Symptom Assessment System-revised (ESAS-r) and analyzed the significance of each prognostic variable in the PRO-MAC model using multivariate Cox proportional hazards regression analysis for all age categories. We generated the log-rank test for each age group to evaluate the effectiveness of PRO-MAC across age groups.Results: The older adults had significantly lower unadjusted mean scores in pain, tiredness, anxiety, wellbeing, and ESAS-r summative score compared to young adults. There was a higher proportion of older adults with no symptoms. The ESAS-r summative score remained a significant prognostic factor only in the young and young-old groups. More participants in the older age groups had dementia, which may impact reporting of symptom severity. Despite these findings, the PRO-MAC model remains applicable across all age groups as a multi-domain 90-day survival prognostication tool.Discussion: Symptom burden, including pain, tiredness, anxiety, wellbeing, as well as summative ESASr scores, are lower in older adults with cancer. This could affect the prognostication of survival using symptom burden. However, a multi-dimensional prognostic model like PRO-MAC remains effective for older adults with advanced cancer. Further research is needed to explore tools that can help older adults express the severity of their symptoms and incorporate this into survival prognostication.

Oncological and reproductive outcomes after fertility-sparing surgery in patients with stage Ⅱ-Ⅲ borderline ovarian tumor

Objective: To evaluate oncological and reproductive outcomes of women ≤40 years undergoing fertility-sparing surgery (FSS) for stage Ⅱ or Ⅲ borderline ovarian tumor (BOT). Methods: The patients with BOT and ≤40 years old with stage Ⅱ-Ⅲ BOT who underwent FSS enrolled from the First Affiliated Hospital of Zhengzhou University between January 2011 and March 2023 were analyzed retrospectively. The clinical data and follow-up results were obtained and analyzed. The univariate and multivariate Cox proportional hazard regression analysis were used to explore high-risk factors associated with prognosis. Additionally, pregnancy outcomes were also analyzed. Results: (1) A total of 79 patients with stage Ⅱ-Ⅲ BOT who have been treated with FSS were conducted, with an average age of (27.5±6.7) years old. The median tumor maximum diameter were 10.4 cm (range: 4.8-90.0 cm). The International Federation of Gynecology and Obstetrics (FIGO) stage was stage Ⅱ in 45 cases and stage Ⅲ in 34 cases. According to the pathological types, there were 48 cases of serous tumor, 21 cases of mucinous tumor, 1 case of endometrioid tumor, and 9 cases of mixed types. There were 41 cases of unilateral ovarian involvement, 38 cases of bilateral ovarian involvement. There were 5 cases of microinvasion, 17 cases of micropapillary subtype. Extra-ovarian invasive implants were found in 5 cases, and there were 31 cases of merged ascites. (2) Tumor outcomes: the median follow-up time from primary cytoreduction were 58 months (range: 8-146 months). At the end of the observation period, 24 cases (30%, 24/79) recurred, among them 5 cases had two recurrences and 2 cases had three recurrences. There were 2 cases (3%, 2/79) of death and 1 case (1%, 1/79) of survival with tumor. (3) Analysis of prognostic risk factors: the results of univariate analysis showed that mucinous tumor, tumor maximum diameter >13.15 cm, FIGO stage Ⅲ, merged ascites, micropapillary subtype, invasive implantation, and bilateral ovarian involvement were independent risk factors (all P<0.05) for disease-free survival (DFS). FIGO stage Ⅲ (HR=4.555, 95%CI: 1.525-13.607; P=0.007) and micropapillary subtype (HR=2.396, 95%CI: 1.003-5.725; P=0.049) were found to be related to DFS through the multivariable Cox proportional hazard regression analysis. (4) Pregnancy outcomes: among the patients with fertility intentions 36 cases (46%,36/79), 29 cases (81%, 29/36) had successful pregnancies, and 27 cases (75%, 27/36) had successful births. Conclusions: Patients with stage Ⅱ-Ⅲ BOT underwent FSS have favorable survival and pregnancy rates. Micropapillary subtypes and FIGO staging (stage Ⅲ) are the significant risk factors of DFS.

Alteration of cardiac structure and function and its prognostic value in patients with Takayasu arteritis: a cardiac magnetic resonance study.

To investigate the prevalence and characteristics of late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) and its prognostic value in patients with Takayasu arteritis (TA). Sixty TA patients with a CMR examination were retrospectively included. All TA patients were divided into with LGE-positive and LGE-negative groups. Bi-ventricular function and location, distribution, and pattern of left ventricular (LV) LGE were evaluated in both LGE-positive and LGE-negative groups. Primary outcome was defined as a composite of cardiovascular death, hospitalization for heart failure, coronary artery revascularization, and stroke. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the association between variables and primary outcomes. Sixty consecutive TA patients were enrolled in this study. The mean age was 38.2 ± 13.8 years and 54 patients (54/60, 90.0%) were female. LGE-positive was observed in twenty-one (21/60, 35%) patients in the total patients with TA. LGE was predominantly distributed in the middle wall and subendocardial. The patchy and infarcted LGE patterns were the most common. Compared with the LGE-negative group, the LGE-positive group had reduced LV ejection fraction (P = 0.033), elevated LV end-diastolic volume index (P = 0.008), LV end-systolic volume index (P = 0.012), and LV mass (P = 0.008). During a median follow-up period of 1,892 days (interquartile range: 1,764-1,988 days), the primary outcomes occurred in thirteen patients. In the univariate analysis, LGE-positive (hazard ratio [HR] = 4.478, 95% confidence interval [CI]: 1.376-14.570; P = 0.013) were independently associated with the primary outcomes. However, LGE-positive did not retain its value as an independent predictor of primary outcomes in the multivariate analysis. Instead, LVMI (HR = 1.030, 95%CI: 1.013-1.048; P = 0.001) was the strongest independent predictor of primary outcomes in patients with TA. The Kaplan-Meier plot revealed that patients with LVMI ≥ 57.5 g/m2 have a worse prognosis. LGE-positive detected by CMR was observed in 35% of total TA patients with different distributions and patterns. LGE is associated with adverse LV remodeling and worsen cardiac function. However, LVMI rather than LGE can provide independent prognostic information in patients with TA.

No medication prescription and residential distance from the hospital are important factors associated with nonsurgical weight-loss treatment discontinuance in Japanese patients with high-degree obesity: a retrospective study

BackgroundAlthough the percentage of the population with a high degree of obesity (body mass index [BMI] ≥ 35 kg/m2) is low in Japan, the prevalence of obesity-related diseases in patients with high-degree obesity is greater than that in patients with a BMI < 35 kg/m2. Therefore, treatment for high-degree obesity is important. However, clinical studies have reported that 20–50% of patients with obesity discontinue weight-loss treatment in other countries. The circumstances surrounding antiobesity agents are quite different between Japan and other countries. In this study, we investigated the predictors of treatment discontinuation in Japanese patients with high-degree obesity.MethodsWe retrospectively reviewed the medical charts of 271 Japanese patients with high-degree obesity who presented at Toho University Sakura Medical Center for obesity treatment between April 1, 2014, and December 31, 2017. The patients were divided into non-dropout and dropout groups. Patients who discontinued weight-loss treatment within 24 months of the first visit were defined as “dropouts.” Multivariate Cox proportional hazards regression analysis and Kaplan–Meier survival analysis were performed to examine the factors predicting treatment withdrawal.ResultsAmong the 271 patients, 119 (43.9%) discontinued treatment within 24 months of the first visit. The decrease in BMI did not significantly differ between the two groups. No prescription of medication and residential distance from the hospital exceeding 15 km were the top contributors to treatment discontinuation, and the absence of prescription medication was the most important factor. The dropout-free rate was significantly higher in patients with medication prescriptions than in those without and in patients who lived within 15 km of the hospital than in those who lived farther than 15 km from the hospital.ConclusionsNo medication prescription and longer residential distance from the hospital were associated with treatment dropout in Japanese patients with high-degree obesity; therefore, the addition of antiobesity medications and telemedicine may be necessary to prevent treatment discontinuation in such patients.

Prognostic impact of interstitial lung disease on pulmonary high-grade neuroendocrine carcinoma

Pulmonary high-grade neuroendocrine carcinomas (HGNECs) have poor prognoses and require multimodal treatment, and interstitial lung disease (ILD) restricts sufficient treatment of patients with lung cancer. We aimed to clarify ILD’s prognostic impact on pulmonary HGNEC, which has previously gone unreported. We retrospectively analyzed 53 patients with HGNEC who underwent resections at our department between 2006 and 2021 and evaluated the clinicopathological prognostic features, including ILD. The patients’ mean age was 70 years; 46 (87%) were male, and all were smokers. Large-cell neuroendocrine and small-cell lung carcinomas were diagnosed in 36 (68%) and 17 (32%) patients, respectively. The pathological stages were stage I, II, and III in 31 (58%), 11 (21%), and 11 (21%) patients, respectively. Nine patients (17%) had ILD, which was a significant overall survival prognostic factor in a multivariate Cox proportional hazards regression analysis (p = 0.048), along with lymph node metastasis (p = 0.004) and non-administration of platinum-based adjuvant chemotherapy (p = 0.003). The 5 year survival rate of the ILD patients was 0%, significantly worse than that of patients without ILD (58.7%; p = 0.003). Patients with HGNEC and ILD had a poor prognosis owing to adjuvant therapy’s limited availability for recurrence and the development of acute exacerbations associated with ILD.

Comparison of Clinical Outcomes Using Left and Right Liver Grafts in Adult-to-adult Living-donor Liver Transplantation: A Retrospective Cohort Study Using the Korean Organ Transplantation Registry

Background. Living-donor liver transplantation has been widely performed as an alternative to the scarce liver grafts from deceased donors. More studies are reporting favorable outcomes of left liver graft (LLG). This study compared the clinical outcomes between living-donor liver transplantation using LLG and right liver graft (RLG) with similar graft-to-recipient body weight ratios. Methods. This study analyzed 4601 patients from a multicenter observational cohort using the Korean Organ Transplantation Registry between 2014 and 2021. After matching the Model for End-stage Liver Disease score and graft-to-recipient body weight ratios because of the extremely different number in each group, the LLG and RLG groups comprised 142 (25.1%) and 423 (74.9%) patients, respectively. Results. For donors, the median age was higher in the LLG group than in the RLG group (34 y [range, 16–62 y] versus 30 y [16–66 y] ; P = 0.002). For recipients, the LLG group showed higher 90-d mortality than the RLG group (11 [7.7%] versus 9 [2.1%]; P = 0.004). The long-term graft survival was significantly worse in the LLG group (P = 0.011). In multivariate Cox proportional hazards regression analysis for graft survival, LLG was not a significant risk factor (hazard ratio, 1.01 [0.54-1.87]; P = 0.980). Otherwise, donor age (≥40 y; 2.18 y [1.35-3.52 y]; P = 0.001) and recipients’ body mass index (&lt;18.5 kg/m2; 2.98 kg/m2 [1.52-5.84 kg/m2]; P = 0.002) were independent risk factors for graft survival. Conclusions. Although the short-term and long-term graft survival was worse in the LLG group, LLG was not an independent risk factor for graft survival in multivariate analysis. LLGs are still worth considering for selected donors and recipients regarding risk factors for graft survival.

Incremental value of tricuspid annular enlargement to progressive tricuspid regurgitation in patients with longstanding persistent atrial fibrillation.

Tricuspid annular enlargement in patients with atrial fibrillation (AF) can induce tricuspid regurgitation (TR). However, risk factors associated with TR progression in patients with AF have not been defined. This study aimed to clarify an association between tricuspid annular diameter (TAD) and TR progression in patients with longstanding persistent AF. We retrospectively analyzed data from 228 patients who had longstanding persistent AF for > 1year and mild or less TR on baseline echocardiograms. We defined significant TR as moderate or greater TR, graded according to the jet area and vena contracta. The optimal cut-off value of the TAD index (TADI), based on body surface area for predicting progression to significant TR, was estimated using receiver operating characteristic (ROC) curves. The independence and incremental value of the TADI were evaluated using multivariate Cox proportional hazard regression analysis and likelihood ratio tests. Over a median follow-up of 3.7years, 55 (24.1%) patients developed significant TR. The optimal cut-off value of 21.1mm/m2 for the TADI at baseline and ROC curves predicted TR progression with 70.4% sensitivity and 86% specificity. Furthermore, TADI was an independent predictor of TR progression (hazard ratio, 1.32; 95% confidence interval, 1.17-1.49, P < 0.001) and had a significant incremental value that exceeded that of models constructed using clinical parameters. In conclusion, TADI was significantly associated with TR progression and was an independent predictor of TR progression in longstanding persistent AF.

Relationship between smoking experience and risk of suicide mortality in South Korean adults: A nationwide population-based retrospective cohort study

BackgroundKorea has one of the highest suicide rates in the world. Many factors associated with suicidal thoughts or behaviors are known. This study examines the association between 1) smoking status or intensity (pack-years) and 2) risk of suicide mortality in South Korea. MethodsWe analyzed data from 3,966,305 individuals aged ≥20 who underwent health examinations conducted by the South Korean National Health Insurance Service in 2009 and were followed until December 2021. Participants were categorized based on their baseline smoking status and intensity. We performed a Multivariate Cox proportional hazards regression analysis with subgroup analysis by age, sex, body mass index, alcohol consumption, regular exercise, and depression. ResultsDuring an 11.1-year follow-up period, 12,326 individuals died by suicide. Compared with never-smokers, increased hazard ratios of suicide mortality were observed in current smokers (1.64, 95 % CI = 1.56–1.72), but not in ex-smokers. The suicide mortality risk of current smokers increased for all types of smoking intensity without a dose–response relationship. The association between smoking and suicide mortality risk was stronger among women, non-drinkers, adults aged <40 years, non-obese patients, and individuals without depression. LimitationGiven that the study used retrospective data, the causal relationship remains unclear. ConclusionCurrent smoking is associated with a significant increased risk of suicide mortality. Smoking cessation is crucial to prevent suicide, especially among young adults, non-obese individuals, non-drinkers, women, and those without depression. Government policies in South Korea should focus on raising awareness about smoking hazards and providing cessation education to reduce the suicide mortality.

Increased risk of subsequent neoplasm after hematopoietic stem cell transplantation in 5-year survivors of childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) survivors are at risk for developing subsequent neoplasms, but there is limited information on long-term risks and risk factors for both subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs). We analyzed long-term risk and risk factors for SMNs and SNMNs among 3291 5-year ALL survivors from the Dutch Childhood Cancer Survivor Study-LATER cohort (1963–2014). We calculated standardized incidence ratios (SIRs) and cumulative incidences and used multivariable Cox proportional hazard regression analyses for analyzing risk factors. A total of 97 survivors developed SMNs and 266 SNMNs. The 30-year cumulative incidence was 4.1% (95%CI: 3.5–5.3) for SMNs and 10.4%(95%CI: 8.9–12.1) for SNMNs. Risk of SMNs was elevated compared to the general population (SIR: 2.6, 95%CI: 2.1–3.1). Survivors treated with hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI) (HR:4.2, 95%CI: 2.3–7.9), and without TBI (HR:4.0,95%CI: 1.2–13.7) showed increased SMN risk versus non-transplanted survivors. Cranial radiotherapy (CRT) was also a risk factor for SMNs (HR:2.1, 95%CI: 1.4–4.0). In conclusion, childhood ALL survivors have an increased SMN risk, especially after HSCT and CRT. A key finding is that even HSCT-treated survivors without TBI treatment showed an increased SMN risk, possibly due to accompanied chemotherapy treatment. This emphasizes the need for careful follow-up of HSCT and/or CRT-treated survivors.

U-shaped association between triglyceride glucose-body mass index with all-cause and cardiovascular mortality in US adults with osteoarthritis: evidence from NHANES 1999–2020

The association between insulin resistance (IR) and the risk of all-cause mortality and cardiovascular mortality among osteoarthritis (OA) patients remains uncertain. This study aims to clarify the correlation between a novel marker of IR, the triglyceride glucose-body mass index (TyG-BMI), and the risk of all-cause mortality and cardiovascular mortality in OA patients. Data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020 were analyzed. Multivariable Cox proportional hazards regression analysis and restricted cubic spline plots were employed to elucidate the association between the TyG-BMI index and the risk of all-cause mortality or cardiovascular mortality in OA patients. Additionally, subgroup analysis was conducted to explore potential interactions and identify populations at elevated risk of mortality. The study cohort comprised 4097 OA patients who were followed up for a period of 20 years, during which 1197 cases of all-cause mortality and 329 cases of mortality attributed to cardiovascular disease were recorded. Our findings revealed a U-shaped nonlinear relationship between the TyG-BMI index and the risk of all-cause mortality or cardiovascular mortality in OA patients, with the lowest mortality risk thresholds identified at 282 and 270, respectively. Moreover, surpassing these thresholds was associated with a 3% increase in the risk of all-cause mortality and a 5% increase in the risk of cardiovascular mortality for every 10-unit increment in TyG-BMI level. Among American OA patients, a U-shaped nonlinear relationship exists between the TyG-BMI index and the risk of all-cause mortality or cardiovascular mortality. These findings underscore the significant role of IR in the progression of OA.

Integrated bioinformatics analysis and experimental validation reveal the relationship between ALOX5AP and the prognosis and immune microenvironment in glioma

BackgroundTreatment of gliomas, the most prevalent primary malignant neoplasm of the central nervous system, is challenging. Arachidonate 5-lipoxygenase activating protein (ALOX5AP) is crucial for converting arachidonic acid into leukotrienes and is associated with poor prognosis in multiple cancers. Nevertheless, its relationship with the prognosis and the immune microenvironment of gliomas remains incompletely understood.MethodsThe differential expression of ALOX5AP was evaluated based on public Databases. Kaplan–Meier, multivariate Cox proportional hazards regression analysis, time-dependent receiver operating characteristic, and nomogram were used to estimate the prognostic value of ALOX5AP. The relationship between ALOX5AP and immune infiltration was calculated using ESTIMATE and CIBERSORT algorithms. Relationships between ALOX5AP and human leukocyte antigen molecules, immune checkpoints, tumor mutation burden, TIDE score, and immunophenoscore were calculated to evaluate glioma immunotherapy response. Single gene GSEA and co-expression network-based GO and KEGG enrichment analysis were performed to explore the potential function of ALOX5AP. ALOX5AP expression was verified using multiplex immunofluorescence staining and its prognostic effects were confirmed using a glioma tissue microarray.ResultALOX5AP was highly expressed in gliomas, and the expression level was related to World Health Organization (WHO) grade, age, sex, IDH mutation status, 1p19q co-deletion status, MGMTp methylation status, and poor prognosis. Single-cell RNA sequencing showed that ALOX5AP was expressed in macrophages, monocytes, and T cells but not in tumor cells. ALOX5AP expression positively correlated with M2 macrophage infiltration and poor immunotherapy response. Immunofluorescence staining demonstrated that ALOX5AP was upregulated in WHO higher-grade gliomas, localizing to M2 macrophages. Glioma tissue microarray confirmed the adverse effect of ALOX5AP in the prognosis of glioma.ConclusionALOX5AP is highly expressed in M2 macrophages and may act as a potential biomarker for predicting prognosis and immunotherapy response in patients with glioma.

Impact of Diabetes Mellitus and Obesity Comorbidities on Survival Outcomes after Hepatocellular Carcinoma Resection: A Multicenter Retrospective Study

Introduction: This study aimed to evaluate the association of obesity and diabetes mellitus (DM) comorbidity with hepatocellular carcinoma (HCC) recurrence and survival. Methods: We investigated 1,644 patients who underwent hepatic resection for solitary HCC without vascular invasion using computed tomography. Patients were categorized into four groups according to the combination of obesity and DM comorbidities: OB (+) or (−) and DM (+) or (−). Postoperative cumulative recurrence rates within and beyond 2 years and beyond 5 years were assessed. Results: Multivariate Cox proportional hazard regression analysis revealed that the adjusted hazard ratios (HRs) of reduced recurrence-free survival was 1.10 (95% confidence interval [CI]: 0.91–1.33; p = 0.31), 0.94 (95% CI: 0.78–1.12; p = 0.48), and 1.24 (95% CI: 1.01–1.54; p = 0.045) in the OB(+)DM(−), OB(−)DM(+), and OB(+)DM(+) groups compared with the OB(−)DM(−) group, respectively. Additionally, the corresponding adjusted HRs of reduced overall survival were 0.93 (p = 0.57), 0.97 (p = 0.76), and 1.38 (p = 0.013) for OB(+)DM(−), OB(−)DM(+), and OB(+)DM(+) groups, respectively. No significant difference in the early recurrence rate was determined among the four groups. The OB(+)DM(+) group demonstrated an increased risk for late recurrence beyond 2 years and 5 years postoperatively compared with the OB(−)DM(−) group (HR: 1.51; p = 0.024 and HR: 2.53; p = 0.046, respectively). The OB(+)DM(−) and OB(−)DM(+) groups demonstrated an increased risk for late recurrence beyond 5 years postoperatively (HR: 3.83; p < 0.001 and HR: 1.95; p = 0.037, respectively). Conclusions: Obesity and DM coexistence increased late recurrence and worsened prognosis in patients with HCC undergoing hepatic resection. The results help surgeons develop possible different surveillance protocol and need to focus on diabetes/obesity control during life-long surveillance for patients with HCC.

Association Between Changes in Skeletal Muscle Quality and Prognosis in Postoperative Patients with Early Gastric Cancer.

Identifying accurate prognostic factors is crucial for postoperative management of early gastric cancer (EGC) patients. Skeletal muscle quality (SMQ), defined by muscle density on computed tomography (CT) images, has been proposed as a novel prognostic factor. This study compared the prognostic significance of SMQ changes with the well-established factor of body weight (BW) loss in the postoperative EGC setting. This single-center retrospective study included 297 postoperative EGC patients (median age 69 years, 68.4% male) who had preoperative and 1-year-postoperative gastrectomy CT images. SMQ was defined as the modified intramuscular adipose tissue content (mIMAC = skeletal muscle density-subcutaneous fat density on CT images) and the change as ΔmIMAC. Log-rank test, Kaplan-Meier survival, and Cox proportional hazards regression analyses were used to assess the associations between prognosis and either ΔmIMAC or BW change (ΔBW). Prognosis prediction by ΔmIMAC and ΔBW was compared by using the area under the curve (AUC) of the receiver operating characteristic curve. ΔmIMAC was significantly associated with prognosis (log-rank test; P = 0.037), but ΔBW was not (P = 0.243). Prognosis was significantly poorer in the severely decreased mIMAC group than in the preserved group (multivariate Cox proportional hazards regression analysis; P = 0.030) but was unaffected by BW changes (P = 0.697). The AUC indicated a higher prognostic value for ΔmIMAC than ΔBW (ΔmIMAC: AUC = 0.697, ΔBW: AUC = 0.542). One-year post-gastrectomy SMQ changes may be better prognostic EGC predictors than BW changes.

Association between geniquin therapy and the risk of developing periodontal disease in patients with primary Sjögren's syndrome: A population-based cohort study from Taiwan.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that causes dysfunction of salivation and harmful oral conditions. The association between periodontal disease (PD) and pSS with or without geniquin therapy remains controversial. This study evaluated the association between geniquin therapy and the risk of subsequent development of PD in pSS patients. From Taiwan's National Health Insurance Research Database, we selected a control cohort of 106,818 pSS patients, followed up from 2000 to 2015, matched (1:4) by age and index year with 427,272 non-pSS patients. We also analyzed 15,149 pSS patients receiving geniquin therapy (cohort 1) and 91,669 pSS patients not receiving geniquin therapy (cohort 2). After adjusting for confounding factors, multivariate Cox proportional hazards regression analysis was used to compare the risk of PD over the 15-year follow-up. In the control cohort, 11,941 (11.2%) pSS patients developed PD compared to 39,797 (9.3%) non-pSS patients. In cohorts 1 and 2, 1,914 (12.6%) pSS patients receiving geniquin therapy and 10,027 (10.9%) pSS patients not receiving geniquin therapy developed PD. The adjusted hazard ratio (HR) for subsequent PD in pSS patients was 1.165 (95% confidence interval [CI] = 1.147-1.195, p < 0.001) and in pSS patients receiving geniquin therapy was 1.608 (95% CI = 1.526-1.702, p < 0.001). The adjusted HR for PD treatment was 1.843. Patients diagnosed with pSS showed an increased risk of developing subsequent PD and receiving PD treatment than patients without pSS, while pSS patients receiving geniquin therapy showed even higher risks.

Association between metabolic score for insulin resistance and regression to normoglycemia from prediabetes in Chinese adults: A retrospective cohort study.

Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.

Impact of clozapine once-daily versus multiple-daily dosing regimen on relapse in patients with treatment-resistant schizophrenia:A1-year retrospective cohort study.

Clozapine, the standard treatment for treatment-resistant schizophrenia (TRS), is generally recommended in a multiple-daily dosing regimen. However, it is commonly administered once daily in clinical practice. Few studies have compared the longitudinal clinical outcomes of these two dosing regimens. To investigate the effect of once-daily versus multiple-daily dosing regimens of clozapine on relapse in patients with TRS. This retrospective cohort study included patients with TRS who commenced treatment with clozapine during hospitalization and were discharged between April 2012 and January 2022 from a tertiary psychiatric hospital in Japan. Relapse, defined as a psychiatric exacerbation requiring re-hospitalization within the first-year post-discharge, was analyzed. Multivariable Cox proportional hazards regression analysis compared the relapse risk between once-daily and multiple-daily dosing regimens. A subgroup analysis was conducted to examine the potential interactions between dosing regimen and dose category (low versus high dose). Among 179 patients, 107 (59.8%) received clozapine once daily. No significant difference in the relapse risk was observed between once-daily and multiple-daily dosing regimens (adjusted hazard ratio [aHR]: 1.16; 95% confidence interval [CI]: 0.68-1.99; p = 0.58). However, in patients receiving high doses of clozapine (> 300mg/day), multiple-daily dosing increased the relapse risk compared to once-daily dosing (aHR: 2.23; 95% CI: 1.00-4.97; p = 0.049). Once-daily clozapine dosing may not be associated with an increasedrelapse risk. The increased relapse risk in high-dose multiple-daily dosing may be confounded by unmeasured non-adherence. Further randomized controlled trials are required to validate these findings.