Cox Regression Research Articles

Persons with metabolic dysfunction‐associated steatotic liver disease are at increased risk of severe depression

AbstractBackground and AimFew population‐based studies have investigated the association between metabolic dysfunction‐associated steatotic liver disease (MASLD) and depression. Additionally, it remains unclear if depression affects progression to major adverse liver outcomes (MALO) in MASLD.MethodsAll patients in Sweden with newly diagnosed MASLD between 2006 and 2020 were identified from the National Patient Register. Each patient was matched on age, sex, inclusion year, and municipality with up to 10 comparators from the general population. Cox regression was used to compare rates of severe depression in persons with MASLD to the comparators. In persons with MASLD, Cox regression was used to estimate rates of MALO using severe depression before baseline or diagnosed during follow‐up as a time‐varying exposure.ResultsWe included 11 301 persons with MASLD and 104 205 comparators who were followed for a median of 3.9 (IQR 1.5–7.6) and 4.9 years (IQR 2.3–8.7), respectively. The median age was 56 years and 5576 of 11 301 (49.3%) persons with MASLD were male. Incident severe depression developed in 228 of 11 301 (2.0%) persons with MASLD and 1160 of 104 205 (1.1%) comparators (fully adjusted hazard ratio [HR] = 1.8, 95% CI = 1.5–2.1). Of persons with MASLD, 25 of 1229 (2.0%) of those with severe depression before or after baseline progressed to MALO compared to 322 of 10 326 (3.1%) of those without severe depression (fully adjusted HR = 1.0, 95% CI = .6–1.5).ConclusionsWe confirm an association between MASLD and severe depression. However, no association between severe depression and incident MALO was found, but conclusions are limited by few observed outcomes.

The association between weight loss medications and cardiovascular complications.

Obesity and its cardiovascular complications are major causes of morbidity and mortality. Little is known in real-world settings about the effect of newly approved antiobesity medications (AOMs) on cardiovascular complications among patients with obesity. This retrospective cohort study examined the association between newly approved AOM use and cardiovascular events among Medicare patients with obesity using data from 2020 to 2022. Patient age, gender, comorbidity scores, socioeconomic status, and baseline cardiovascular comorbidities were compared descriptively. Subgroup analysis compared variables by medication type. Relative risk and absolute risk of cardiovascular disease (CVD) events were estimated using Cox and Aalen regression models. The analysis included 5926 patients treated with semaglutide and tirzepatide, including Ozempic (5404 patients), Wegovy (375 patients), or Mounjaro (147 patients). Hypertension, type 2 diabetes, and hyperlipidemia were the most common comorbidities. For patients with AOMs, less incidence of heart failure (4.89% vs. 6.13%, p < 0.0001), atrial fibrillation (3.83% vs. 5.17%, p < 0.0001), arrhythmia (3.59% vs. 4.14%, p < 0.0153), and peripheral vascular disease (3.44% vs. 2.94%, p < 0.0395) was found versus patients without AOMs. Patients receiving AOMs showed an 8% risk reduction in any CVD. Protective effect on CVD was apparent over the first 375 days. Results suggest that utilization of AOMs effectively alleviates the high prevalence of CVD.

Dietary fatty acids and incident hip fractures in cohorts of women and men. A relative validation and follow-up study

ObjectivesHip fractures are associated with a high burden of morbidity and mortality. Diet is essential for preventing fragility fractures, but the role of dietary fatty acids on the risk of hip fracture is uncertain. The aim was to investigate how intake of different dietary fatty acids relates to the risk of hip fracture. A relative validation of the long-term intake of dietary fatty acids estimated from food frequency questionnaires (FFQs) was also performed. Design, settings and participantsWe used data collected in two population-based cohorts, the Swedish Mammography Cohort and the Cohort of Swedish men (n = 83,603, 54% men, aged 45–82 years). Data from the repeated investigations in the cohorts and cross-sectional data from their clinical sub-cohorts were used. MeasurementsDiet data was collected in FFQs. Incident hip fractures were gathered by individual linkage to national registers. We performed Cox regression analysis to investigate associations between dietary fatty acids and hip fracture. Follow-up time was between January 1st, 1998 and December 31st, 2020. The validation was performed using correlation analyses, comparing fatty acids measured in adipose tissue with estimated fatty acid intakes from FFQs. ResultsDuring up to 23 years of follow-up (mean 18 years) and 1,538,627 person-years at risk, 7345 participants (2840 men) experienced a hip fracture. A low linoleic acid (LA) and high intakes of long-chain n-3 fatty acids were associated with higher hip fracture risk in a non-linear way. In quartile 4 compared to quartile 1 of LA, the multivariable-adjusted hazard ratio of hip fracture was 0.89 (95% Confidence Interval: 0.81, 0.97). The study confirmed the validity of FFQs to capture the intake of the specific dietary long-chain n-3 fatty acids. The estimated intake of LA, α-linolenic acid, and myristic acid were also adequately captured by the FFQs. Validity was confirmed in both women and men. ConclusionA low to moderate intake of linoleic acid and a higher intake of long-chain n-3 fatty acids were associated with a higher risk of hip fractures. The results indicate that attention should be paid to dietary fatty acid composition for the optimal prevention of fragility fractures.

Extended-duration antibiotics are not associated with a reduction in surgical site infection in patients with ovarian cancer undergoing cytoreductive surgery with large bowel resection

Objective(s)To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. MethodsA retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. ResultsIn total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). Conclusion(s)In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.

A Predictive Model for Graft Failure in Femtosecond Laser-Assisted Penetrating Keratoplasty Among Chinese Patients: A 2-Year Study.

Graft failure is a major challenge in femtosecond laser-assisted penetrating keratoplasty (Fs-PKP). This study focuses on the development and validation of a clinical predictive model aimed at identifying the risk of graft failure in individuals undergoing Fs-PKP in China, offering a tailored approach to improve surgical outcomes. This retrospective cohort study at Nanjing First Hospital involved 238 patients and followed the TRIPOD statement. The cohort was divided into a training set (n = 166) and a validation set (n = 72) in a 7:3 ratio. It analyzed 23 predictor variables related to recipient, donor, and surgical factors, defining graft failure as "visually significant and irreversible corneal stromal edema, haze, or scarring." A comprehensive nomogram was created using univariate and multivariate Cox regression analyses and assessed by concordance index (C-index), time-dependent receiver operating characteristics (ROC) curve, calibration plots, and decision curve analysis (DCA). Five critical risk factors were identified: recipients' history of systemic autoimmune disorders, ocular trauma, prior penetrating keratoplasty (PKP) history, donors' diabetes history, and the endothelial cell density of the donor cornea. The nomogram showed a C-index of 0.72 (95% CI 0.65-0.79) in the training group and 0.66 (95% CI 0.55-0.76) in the validation group, indicating robust predictive accuracy. Time-dependent ROC curves, calibration plots, and DCA consistently validated the model's reliability, predictive power, and clinical utility across both training and validation cohorts. Our study developed and validated a model incorporating five key factors, enhancing preoperative prediction and management for Chinese patients with Fs-PKP graft failure.

The effect of care interruptions on mortality in adults resuming antiretroviral therapy.

To estimate the relative rate of all-cause mortality amongst those on antiretroviral treatment (ART) with a history of interruptions compared with those with no previous interruptions in care. Retrospective cohort study. We used data from four South African cohorts participating in the International epidemiology Databases to Evaluate AIDS Southern Africa collaboration. We included adults who started ART between 2004 and 2019. We defined a care interruption as a gap in contact longer than 180 days. Observation time prior to interruption was allocated to a 'no interruption' group. Observation time after interruption was allocated to one of two groups based on whether the first interruption started before 6 months of ART ('early interruption') or later ('late interruption'). We used Cox regression to estimate hazard ratios. Sixty-three thousand six hundred and ninety-two participants contributed 162 916 person-years of observation. There were 3469 deaths. Most participants were female individuals (67.4%) and the median age at ART initiation was 33.3 years (interquartile range: 27.5-40.7). Seventeen thousand and eleven (26.7%) participants experienced care interruptions. Those resuming ART experienced increased mortality compared with those with no interruptions: early interrupters had a hazard ratio of 4.37 (95% confidence interval (CI) 3.87-4.95) and late interrupters had a hazard ratio of 2.74 (95% CI 2.39-3.15). In sensitivity analyses, effect sizes were found to be proportional to the length of time used to define interruptions. Our findings highlight the need to improve retention in care, regardless of treatment duration. Programmes to encourage return to care also need to be strengthened.

An overview of the study designs and statistical methods used in the determination of predictors of melioidosis mortality in Malaysia: 2010-2021

&lt;b&gt;Background:&lt;/b&gt; In Malaysia, the mortality from melioidosis infection was reported to be higher than in other infectious diseases. The research on melioidosis is still limited in Malaysia but slightly increasing.&lt;br /&gt; &lt;b&gt;Objectives: &lt;/b&gt;The objective of the study was to give an overview of the study designs, statistical methods, and comparison of research in identifying the predictors of melioidosis mortality in Malaysia between January 2010 to December 2021.&lt;br /&gt; &lt;b&gt;Data sources:&lt;/b&gt; Pubmed/Medline.&lt;br /&gt; &lt;b&gt;Study eligibility criteria:&lt;/b&gt; Original English-language articles were abstracted. The articles that identified the predictors of melioidosis from mortality in Malaysia only included. Letters to the editor, editorials, reviews, systematic reviews, meta-analysis, case reports, and any other ineligible articles were excluded.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; A total of eight studies were identified related to predictors of melioidosis mortality in Malaysia. From the selected articles, 87.5% were retrospectively collected. Five out of eight articles (62.5%) used the logistic regression in identifying the predictors of melioidosis mortality. Only one (12.5%) used advanced survival analysis methods of Cox regression analysis. Another 25.0% used Chi-square test.&lt;br /&gt; &lt;b&gt;Conclusions:&lt;/b&gt; Logistic regression methods remain the most common methods of analysis in publications on predictors of melioidosis mortality in Malaysia while retrospective research designs are preferred. There is a limitation of research in predictors of melioidosis mortality and the use of advanced statistical techniques reported using the melioidosis data in Malaysia. More published research on melioidosis will provide input to the clinicians on a more detailed understanding of how to improve the diagnosis of melioidosis and the prognosis factors of this disease.

Membrane Palmitoylated Protein 2 Serves as a Potential Biomarker for Colon Adenocarcinoma through Promoting CGAS-STING Pathway

This research investigated the role of Membrane Palmitoylated Protein 2 (MPP2) in colon adenocarcinoma (COAD), the third most prevalent form of colorectal cancer. Utilizing TCGA, GEPIA, and HPA datasets alongside Western blotting, we examined MPP2 expression in normal versus cancerous tissue. Kaplan-Meier plots from GEPIA indicated lower MPP2 levels in COAD patients correlating with worse overall survival (P &lt; 0.05). Moreover, MPP2 was identified as a distinct prognostic indicator for COAD and significantly associated with clinicopathological features (P &lt; 0.05), assessed via chi-square tests and Cox regression models. We further explored MPP2’s link to COAD immune cells using Cibersort, revealing its correlation with the infiltration of 8 immune cells (P &lt; 0.05). In vivo and in vitro experiments demonstrated that elevated MPP2 levels might enhance cell proliferation and migration while suppressing apoptosis. Applying Gene Set Enrichment Analysis (GSEA), we predicted MPP2’s involvement in tumor progression via the DNA sensing pathway, a finding supported by cellular studies. In summary, COAD patients exhibit decreased MPP2 expression, which inversely correlates with prognosis. MPP2 appears to influence immunosuppression and tumor progression through various mechanisms, suggesting its potential as an independent prognostic marker in COAD. Further investigation into MPP2’s implications is warranted.

Autoimmune hepatitis with confluent necrosis indicates severe liver injury but responds well to standard immunosuppressive therapy.

We aimed to study the effects of different extensive confluent necrosis on complete biochemical remission, side effects of immunosuppressants, and outcomes in patients with autoimmune hepatitis (AIH). Patients with liver biopsy, receiving standard immunosuppressive therapy (IST), and regular follow-up were retrospectively recruited. Demographic and clinicopathological characteristics between Ishak confluent necrosis scores ≤4 (the non-severe AIH group) and ≥5 (the severe AIH group) were compared. The Kaplan-Meier Survival analysis, Cox regression analysis, and log-rank test were performed. Bilateral p<0.05 was considered statistical significance. One hundred and forty-two patients were enrolled, the median age was 56.0, and 83.8% were female. There were no significant differences in aminotransferases and immunological markers between the two groups. Patients in the severe AIH group had significantly worse liver synthetic function, a higher proportion of cirrhosis, and histologically a higher degree of portal inflammation, interface hepatitis, fibrosis stage, and a higher histological activity index score (all p<0.05). Patients in the severe AIH group had a lower response than the other group after four weeks (57.1% vs. 86.3%, p=0.002). However, differences in complete biochemical remission (CBR) were insignificant. Eight patients experienced end-point events. Kaplan-Meier survival analysis showed no significant difference between the two groups (p=0.343). For adverse effects of IST, patients in the severe group tended toward a higher incidence of corticosteroid adverse effects without statistical significance. Our study indicated that patients with histologically severe confluent necrosis (Ishak score≥5) had significantly worse liver synthetic function and a higher degree of liver fibrosis before IST. Compared with their counterparts, this subgroup of patients showed delayed biochemical response but eventually comparable CBRs, side effects, and long-term outcomes.

Stanniocalcin-2: A Potential Predictor of Residual Breast Cancer After Neoadjuvant Chemotherapy

Compared to patients of pathological complete response (pCR), patients of residual lesion afterwards neoadjuvant chemotherapy (NAC) have worse prognosis and higher distant metastasis. Irrespective, there exists limited data on effective indicators and treatment methods for these patients. In our study, we evaluated the relationship between stanniocalcin-2 (STC2) marker and the prognosis of breast cancer patients of residual lesion after receiving NAC. The relationship between STC2 and patients’ prognosis was evaluated by transcriptome analysis. The impact of the level of STC2 on cell migration, invasion, and proliferation was evaluated at the cellular level. Immunohistochemistry was performed on 293 patients with residual disease after NAC to assess STC2 protein levels. The relationship between STC2 and survival rate was estimated using Cox regression model and Kaplan Meier analysis. The results demonstrated that high level of STC2 significantly inhibited migration, invasion, and proliferation of breast cancer cells. Compared to patients with low STC2, high STC2 were directly proportional to overall survival (OS) and disease-free survival (DFS) (OS: 86.96 vs. 84.62 months, P = 0.017 DFS: 77.33 vs. 66.95 months, P-value &lt; 0.001). In conclusion, our research suggested that the of level STC2 may be a promising prognostic marker or therapeutic targe for breast cancer patients with residual lesion after NAC.

Mortality Risk of Low BMI in Life Insurance Applicants.

-This study seeks to quantify the mortality effect of low levels of body mass index (BMI) on life insurance applicants who, based on their laboratory profile and other information, appear to be suitable for life insurance coverage. -It has been demonstrated that low BMI is associated with higher mortality risk than normal or near-normal BMI. -Data were collected from over 4.7 million life insurance applicants with available BMI tested between 1995 and 2021, and vital status was assessed via the Social Security Death Master File. Cox models treating BMI as continuous and as a categorical variable were constructed, controlling for age, and split by sex after excluding those with laboratory or biometric test results, which were far enough outside the normal range to imply elevated mortality. -Models treating BMI as a continuous variable and allowing an interaction term for age showed that low BMI was strongly associated with mortality at ages 50 and above in both sexes. In the categorical models, only the lowest category of BMI (below the 1st percentile) in men aged 40-60, the lowest 2 categories (below the 5th percentile) in women aged 40-60, and the lowest 3 categories (below the 10th percentile) in those aged 60-80 years, were significantly associated with elevated mortality. No elevated mortality was detected in those under age 40 with low BMI. -Based on this study, low BMI is associated with elevated mortality in otherwise healthy applicants, but this association is dependent on age.

Monogenic diabetes in a Chinese population with young-onset diabetes: A 17-year prospective follow-up study in Hong Kong.

Asians have a high prevalence of young-onset diabetes, but the pattern of monogenic diabetes is unknown. We aimed to determine the prevalence of monogenic diabetes in Chinese patients with young-onset diabetes and compare the clinical characteristics and outcome between patients with and without monogenic diabetes. We sequenced a targeted panel of 33 genes related to monogenic diabetes in 1021 Chinese patients with non-type 1 diabetes diagnosed at age ≤40years. Incident complications including cardiovascular disease (CVD), end-stage kidney disease (ESKD) and all-cause death were captured since enrolment (1995-2012) until 2019. In this cohort (mean±SD age at diagnosis: 33.0±6.0years, median[IQR] diabetes duration 7.0[1.0-15.0] years at baseline, 44.9% men), 22(2.2%, 95% confidence interval[CI] 1.4%-3.2%) had monogenic diabetes. Pathogenic (P) or likely pathogenic (LP) variants were detected in GCK (n=6), HNF1A (n=9), HNF4A (n=1), PLIN1 (n=1) and PPARG (n=2), together with copy number variations in HNF1B (n=3). Over a median follow-up of 17.1years, 5(22.7%) patients with monogenic diabetes (incidence rate 12.3[95% CI 5.1-29.4] per 1000 person-years) versus 254(25.4%) without monogenic diabetes (incidence rate 16.7[95% CI 14.8-18.9] per 1000 person-years) developed the composite outcome of CVD, ESKD and/or death (p=0.490). The multivariable Cox model did not show any difference in hazards for composite events between groups. In Chinese with young-onset non-type 1 diabetes, at least 2% of cases were contributed by monogenic diabetes, over 80% of which were accounted for by P/LP variants in common MODY genes. The incidence of diabetes complications was similar between patients with and without monogenic diabetes.

Mesangial Expansion by Morphometry at 5 y After Kidney Transplantation: Incidence, Risk Factors, and Association With Graft Loss.

Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff mm score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss. We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff mm score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME mm (%glomeruli with ME in ≥2 lobules, like Banff mm); (2) %MEany (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss. From 1- to 5-y biopsies, the mean Banff mm score increased from 0.18 to 0.34, whereas %ME mm increased from 2.5% to 13.3%. Banff mm score had modest correlations with morphometric ME measures. Moderate-severe %ME mm was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff mm scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff mm score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %MEany had the highest c-statistic (0.872). Banff mm score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.

Subjective cognitive concerns, APOE ε4, PTSD symptoms, and risk for dementia among older veterans

BackgroundPosttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are associated with self-reported problems with cognition as well as risk for Alzheimer’s disease and related dementias (ADRD). Overlapping symptom profiles observed in cognitive disorders, psychiatric disorders, and environmental exposures (e.g., head injury) can complicate the detection of early signs of ADRD. The interplay between PTSD, head injury, subjective (self-reported) cognitive concerns and genetic risk for ADRD is also not well understood, particularly in diverse ancestry groups.MethodsUsing data from the U.S. Department of Veterans Affairs (VA) Million Veteran Program (MVP), we examined the relationship between dementia risk factors (APOE ε4, PTSD, TBI) and subjective cognitive concerns (SCC) measured in individuals of European (n = 140,921), African (n = 15,788), and Hispanic (n = 8,064) ancestry (EA, AA, and HA, respectively). We then used data from the VA electronic medical record to perform a retrospective survival analysis evaluating PTSD, TBI, APOE ε4, and SCC and their associations with risk of conversion to ADRD in Veterans aged 65 and older.ResultsPTSD symptoms (B = 0.50–0.52, p < 1E-250) and probable TBI (B = 0.05–0.19, p = 1.51E-07 – 0.002) were positively associated with SCC across all three ancestry groups. APOE ε4 was associated with greater SCC in EA Veterans aged 65 and older (B = 0.037, p = 1.88E-12). Results of Cox models indicated that PTSD symptoms (hazard ratio [HR] = 1.13–1.21), APOE ε4 (HR = 1.73–2.05) and SCC (HR = 1.18–1.37) were positively associated with risk for ADRD across all three ancestry groups. In the EA group, probable TBI also contributed to increased risk of ADRD (HR = 1.18).ConclusionsThe findings underscore the value of SCC as an indicator of ADRD risk in Veterans 65 and older when considered in conjunction with other influential genetic, clinical, and demographic risk factors.

Creatine kinase mitochondrial 2 promotes the growth and progression of colorectal cancer via enhancing Warburg effect through lactate dehydrogenase B

Creatine kinase mitochondrial 2 promotes the growth and progression of colorectal cancer <i>via</i> enhancing Warburg effect through lactate dehydrogenase B

Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation

BackgroundWilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys.MethodsDifferential gene expression analysis was performed on Wilms tumor transcriptomic data from the GEO and TARGET databases. For biological functional analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized. Out of 24 hub genes identified, nine were found to be prognostic-related through univariate Cox regression analysis. These nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. The key hub genes were validated in the GSE73209 datasets, and cell function experiments were conducted to identify the genes’ functions in WiT-49 cells.ResultsThe enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients’ prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells.ConclusionsEMCN and CCNA1 were identified as key prognostic markers in Wilms tumor, suggesting their potential as therapeutic targets. Differential gene expression and enrichment analyses indicate significant roles in angiogenesis and cell differentiation.

Correlation analysis of patients with diabetic foot ulcers treated with tibial cortex transverse transport surgery and platelet-to-lymphocyte ratio and monocyte-to-neutrophil ratio.

Diabetic foot ulcers (DFUs) represent one of the most severe late-stage complications of diabetes. Tibial cortex transverse transport (TTT) surgery stands as the prevailing method for addressing DFUs. This surgical intervention holds the promise of expediting DFU wound healing and diminishing the rate of amputations, with the mitigation of inflammatory responses playing a pivotal role. In this study, we aim to explore the correlation between inflammation and TTT surgery, with the overarching goal of facilitating swift prognostic assessments in clinical practice. The correlation between the severity of DFUs and clinical test results remains ambiguous. A clinical prediction model was devised to explore the connection between DFU severity and the efficacy of TTT surgery, utilizing straightforward and efficient clinical indicators. Clinical data and examination results were gathered by tracking hospitalized DFU patients who underwent TTT surgery at the First Affiliated Hospital of Guangxi Medical University (Nanning, China). Indicators associated with DFU severity and wound healing time post-surgery were identified through logistic regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Subsequently, a clinical prediction model was constructed. Finally, the intersection of these 2 sets of indicators revealed factors correlated with wound severity and post-operative healing duration. Our study was comprised of 202 patients who were categorized into 2 groups based on Wagner's grading classifications. Utilizing Student's t-tests, LASSO regression and logistic regression analyses, we identified 3 factors indicative of DFU severity: platelet-to-lymphocyte ratio (PLR), mixed lymphocyte reaction (MLR) and hemoglobin (HGB). Univariate COX regression analysis revealed 12 factors such as: white blood cells (WBC), neutrophils (NEUT), monocytes (MO), PLR, MLR, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), age, lymphocytes (LY), monocyte-to-neutrophil ratio (MNR), uric acid (UA), and albumin (ALB) associated with the postoperative healing duration. Ultimately, we identified 2 factors, PLR and MNR, at the intersection of these 2 datasets. Platelet-to-lymphocyte ratio and MNR were identified as factors associated with both the severity of DFUs and the prognosis following TTT surgery.

Systematic screening by a heart team and a machine learning approach contribute to unraveling novel risk factors in revascularization candidates with complex coronary artery disease.

The baseline characteristics affecting mortality following percutaneous or surgical revascularization in patients with left main and / or 3‑vessel coronary artery disease (CAD) observed in real‑world practice differ from those established in randomized controlled trials (RCTs) due to the constraints of inclusion / exclusion criteria. This study aimed to assess whether systematic screening enables identification of novel and registry‑specific baseline patient characteristics influencing long‑term mortality. Least absolute shrinkage and selection operator (LASSO) regression was used to screen 42 baseline patient characteristics shared by the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) trial and a single‑center Polish registry of 1035 consecutive patients with complex CAD who received revascularization and were followed-up for 5 years. After screening, a classic Cox regression analysis was performed to examine the suitability of a linear model for predicting 5‑year mortality, which was then compared with the mortality predicted in the same cohort using the SYNTAX score II 2020 (SS2020). The 5‑year mortality rate in the registry was 12.3%, and the strongest predictors were pulmonary hypertension, chronic obstructive pulmonary disease, and insulin‑dependent diabetes. In an internal validation, the linear model constructed after LASSO screening and combined with a classic Cox regression analysis improved the prediction of 5‑year mortality, as compared with the SS2020 (concordance index of 0.92 and 0.75, respectively). A machine learning approach improved the detection of registry‑specific risk factors in all‑comer patients amenable to surgical or percutaneous revascularization who were evaluated by a heart team. The risk factors identified in RCTs are not necessarily the same as those detected in real clinical practice when systematic screening is applied.

Impact of intensive prone position therapy on outcomes in intubated patients with ARDS related to COVID-19

BackgroundPrevious retrospective research has shown that maintaining prone positioning (PP) for an average of 40 h is associated with an increase of survival rates in intubated patients with COVID-19-related acute respiratory distress syndrome (ARDS). This study aims to determine whether a cumulative PP duration of more than 32 h during the first 2 days of intensive care unit (ICU) admission is associated with increased survival compared to a cumulative PP duration of 32 h or less.MethodsThis study is an ancillary analysis from a previous large international observational study involving intubated patients placed in PP in the first 48 h of ICU admission in 149 ICUs across France, Belgium and Switzerland. Given that PP is recommended for a 16-h daily duration, intensive PP was defined as a cumulated duration of more than 32 h during the first 48 h, whereas standard PP was defined as a duration equal to or less than 32 h. Patients were followed-up for 90 days. The primary outcome was mortality at day 60. An Inverse Probability Censoring Weighting (IPCW) Cox model including a target emulation trial method was used to analyze the data.ResultsOut of 2137 intubated patients, 753 were placed in PP during the first 48 h of ICU admission. The intensive PP group (n = 79) had a median PP duration of 36 h, while standard PP group (n = 674) had a median of 16 h during the first 48 h. Sixty-day mortality rate in the intensive PP group was 39.2% compared to 38.7% in the standard PP group (p = 0.93). Twenty-eight-day and 90-day mortality as well as the ventilator-free days until day 28 were similar in both groups. After IPCW, there was no significant difference in mortality at day 60 between the two-study groups (HR 0.95 [0.52–1.74], p = 0.87 and HR 1.1 [0.77–1.57], p = 0.61 in complete case analysis or in multiple imputation analysis, respectively).ConclusionsThis secondary analysis of a large multicenter European cohort of intubated patients with ARDS due to COVID-19 found that intensive PP during the first 48 h did not provide a survival benefit compared to standard PP.

Mast Cell-related Prognosis Signature Characterizes Immune Landscape and Predicts Prognosis of Ovarian Cancer.

Ovarian cancer (OVC) is a common, aggressive, and heterogeneous malignancy, with a widely variable prognosis. With the advances of modern immunology, mast cells (MCs) have been shown to play a significant role in the prognosis of some malignant tumors. However, the role of mast cells in the prognosis of OVC is unknown. In this study, MC-associated prognostic genes (MRGs) were used to classify OVC from The Cancer Genome Atlas (TCGA)-OVC cohort. Genes were evaluated using univariate cox regression analysis. Twenty-nine prognostic gene signatures were identified using LASSO-COX analysis. COX regression models and principal component analysis (PCA) algorithms were used to construct MRG scores and individual MRGs patterns. External validation was performed in the TCGA-breast cancer (BRCA) and IMvigor210 cohorts. Immunity analysis based on MRGs was performed using CIBERSORT, and GSVA methods, and immunotherapy response was evaluated using the TIDE website. Using TCGA-OVC data, we established a model for constructing MRG scores based on the twenty-nine identified prognostic gene signatures using the PCA algorithm. MRG scores were found to be strongly correlated with immune cell infiltration and were excellent predictors of prognosis in patients with OVC. Low MRG scores were associated with better prognosis and better response to immunotherapy and chemotherapy. MC-related prognosis signature characterizes the immune landscape and predicts the prognosis of OVC. Understanding the correlation between MC-related gene signatures and immunotherapy and chemotherapy may improve the development of personalized clinical treatment strategies.