Cox Proportional Hazards Analysis Research Articles

Intra-Tumoral CD8+:CD3+ Lymphocyte Density Ratio in Appendix Cancer Is a Tumor Volume- and Grade-Independent Predictor of Survival

Background: The immune contexture of solid tumors plays a critical role in cancer progression and response to immunotherapy. However, immunologic characterization of appendiceal cancer (AC) has lagged behind advancements in other gastrointestinal malignancies. This study aims to define the AC immune microenvironment by quantifying CD3+ and CD8+ lymphocyte densities and assessing their prognostic significance. Methods: Archival tissue samples from 95 AC patients were analyzed using immunohistochemistry to assess CD3+ and CD8+ T cell densities and their ratios. Associations between lymphocyte density and clinical, pathologic, and oncologic variables were examined using Spearman’s correlation, Kruskal–Wallis tests, and Cox proportional hazards analysis. Results: Tumor samples exhibited substantial immunologic heterogeneity with significant rightward skew. CD3+ and CD8+ densities were higher in low-grade tumors (p = 0.02 and p = 0.01, respectively) and low-grade histologic subtypes (p = 0.01 and p = 0.006). Lymphocyte density was inversely associated with patient age and was significantly lower in high-grade and non-mucinous tumors. The CD8+:CD3+ ratio emerged as an independent prognostic marker for progression-free survival (HR = 0.39, p = 0.004), whereas absolute CD3+ and CD8+ densities were less predictive. Conclusions: This study highlights the diverse immune microenvironment in AC, with immune infiltration patterns correlating with tumor grade and histologic subtype. The CD8+:CD3+ ratio is a potential prognostic biomarker for patient stratification, underscoring its clinical significance. Future studies should expand immune biomarker panels and explore immunomodulatory therapies for lymphocyte-rich AC subsets.

Associations between depressive and anxiety symptoms and incident kidney failure in patients with diabetic nephropathy

ObjectiveThis study aimed to analyze the associations between depressive and anxiety symptoms and risk of incident kidney failure in patients with biopsy-proven diabetic nephropathy (DN).MethodsThis retrospective study enrolled 241 type 2 diabetic patients with biopsy-proven DN. Huaxi Emotional-Distress Index (HEI) was used to evaluate the depression and anxiety status of patients on admission. According to the HEI score, DN patients were divided into HEI score ≤ 8 group (without depression and anxiety) and HEI score > 8 group (with depression and anxiety). The study endpoint was defined as progression to kidney failure. The cox proportional hazard analysis was performed to investigate the risk factors for progression to kidney failure in DN patients.ResultsTwenty-three patients had HEI score > 8, accounting for about 9.5% of all patients. Compared with HEI score ≤ 8 group, those with HEI score > 8 had more severe proteinuria, higher systolic blood pressure, and lower baseline eGFR and serum albumin levels. During a median follow-up of 28 months, the outcome event occurred in 89 (36.9%) of all the patients. After multivariable adjustment, HEI score > 8 (HR 1.825, 95% CI 1.050–3.172) was associated with an increased risk of progression to kidney failure.ConclusionDepressive and anxiety symptoms might be associated with an increased risk of progression to kidney failure in patients with DN, which implied psychosocial issues should be early screened, assessed and intervened to delay the progression of DN.

Comparative Effectiveness of Rosuvastatin Versus Atorvastatin in Acute Ischemic Stroke Treatment.

Research specifically addressing the efficacy of rosuvastatin versus atorvastatin in patients with ischemic stroke is insufficient. Using a large stroke registry, we investigated whether 2 commonly used statins, rosuvastatin and atorvastatin, differ in their effectiveness in reducing the risk of vascular events in patients with acute ischemic stroke. We analyzed data from a nationwide stroke registry in South Korea between January 2011 and April 2022. Patients with acute ischemic stroke within 7 days of onset who were prescribed either atorvastatin or rosuvastatin at discharge were included. The primary outcome was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause mortality within 1 year. A total of 43 512 patients (age, 69.2±12.5 years; male, 59.8%) were analyzed in this study. Atorvastatin was used in 84.8% (n=36 903), and rosuvastatin was used in 15.2% (n=6609). The 1-year cumulative event rate of the composite of recurrent stroke, myocardial infarction, and all-cause mortality was significantly lower in the rosuvastatin group than in the atorvastatin group (9.7% [95% CI, 9.0-10.5] versus 10.7% [95% CI, 10.4-11.0]; P=0.049). Cox proportional hazards analysis revealed that rosuvastatin, compared with atorvastatin, was significantly associated with less risk of 1-year composite of recurrent stroke, myocardial infarction, and all-cause mortality, with an absolute risk reduction of 1% [95% CI, -1.8 to -0.2] and a relative risk reduction of 11% (hazard ratio, 0.89 [95% CI, 0.82-0.97]). However, there were discrepancies in the statistical significance of the results between the propensity score matching and stabilized inverse probability of treatment weighting analysis. The results of this analysis of a large cohort of patients with ischemic stroke suggested that, compared with atorvastatin, rosuvastatin was significantly associated with a reduced risk of a 1-year composite of recurrent stroke, myocardial infarction, and all-cause mortality in patients with acute ischemic stroke. However, in real clinical practice, rosuvastatin is used less than one-fifth as frequently as atorvastatin in patients with acute ischemic stroke. This study serves as a hypothesis-generating function.

Transarterial Chemoembolization With or Without Systemic Therapy for Unresectable Hepatocellular Carcinoma: A Retrospective Comparative Study.

Standard treatments provide limited benefits for patients with intermediate- or advanced-stage hepatocellular carcinoma (HCC). This retrospective observational study aimed to assess the potential improvements in outcomes associated with systemic therapies in patients receiving transarterial chemoembolization (TACE) for initially unresectable HCC. Between February 2019 and March 2023, we reviewed patients diagnosed with intermediate-to-advanced HCC who were treated with either TACE or TACE combined with antiangiogenic agents and immune checkpoint inhibitors (combination therapy) as their initial treatment. To address potential confounding biases, patients were further stratified into surgical and non-surgical cohorts, and separate analyses were conducted. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety profiles also evaluated. Among 279 patients with initially unresectable intermediate or advanced HCC, 156 successfully underwent curative-intent liver resection after preoperative treatments (TACE group, n = 69; combination group, n = 87), while 123 patients continued with non-surgical treatments (TACE group, n = 31; combination group, n = 92). After propensity score matching, 26 matched patient pairs were generated within the non-surgical cohort. The combination group exhibited significantly improved PFS in non-surgical patients compared with the TACE group (9.4 vs. 7.2 months, p = 0.043). Cox proportional hazards analysis further confirmed that combination therapy was associated with improved PFS (hazard ratio = 0.476, 95% confidence interval: 0.257-0.883, p = 0.019). For surgical patients exceeding the up-to-seven criteria, the combination group demonstrated superior median PFS (18.0 vs. 14.6 months, p = 0.03) and OS (not reached vs. 50.1 months, p = 0.049) compared with the TACE group. Adverse events were manageable, with no treatment-related fatalities reported. Combination therapy with TACE demonstrated enhanced survival benefits for patients with intermediate to advanced HCC, particularly in surgical patients with higher tumor burdens.

The usefulness of Charlson Comorbidity Index (CCI) scoring in predicting all-cause mortality in Outpatients with Clinical Diagnoses of COPD.

Since comorbid conditions are frequently present in chronic obstructive pulmonary disease (COPD) and affect outcome, a composite scoring system to quantify comorbidity might be helpful in assessing mortality risk. We tested the hypothesis that the Charlson Comorbidity Index (CCI) score at the time of an outpatient medical clinic encounter for COPD predicts all-cause mortality. Cox Proportional Hazards analyses were used in 200 randomly selected patients to relate CCI scores to all-cause mortality out to 5 years. Mean age was 62 ± 10 years, 56% were female, FEV1 was 62%, CCI was 3.08 ± 2.30, and 30% had a CCI ≥ 4, indicating 3 or more comorbid conditions. All-cause mortality was 8.5% and 20% at 3 and 5 years, respectively. In univariate testing, the CCI score and hospitalizations predicted mortality, but FEV1 did not. In multivariable testing, which included covariates of age, sex, socioeconomic status, race, FEV1 percent-predicted, and all-cause hospitalizations in the preceding year, CCI expressed as a continuous variable strongly predicted mortality: hazard ratio (HR) 1.38 for each unit increase in the score (p < 0.0001). While 1 or 2 comorbid conditions were not significantly related to mortality, 3 or more comorbid conditions (compared to none) strongly predicted mortality: HR 9.80, 95% CI 3.80 to 25.00. Comorbidity, assessed with the CCI, is strongly predictive of mortality in outpatients with a clinical diagnosis of COPD, and this relationship appears to be non-linear. This instrument may be useful in determining prognosis in this population.

The relationship between probiotics and prebiotics, kidney dysfunction and mortality - Results from a longitudinal cohort study and Mendelian randomization.

The benefits of probiotics/prebiotics consumption on chronic kidney disease (CKD) and mortality remains controversial. This study investigates the association of probiotics/prebiotics consumption with chronic kidney disease (CKD) and mortality. Clinical data were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2005-2016 database. Weighted multivariable logistic and liner regression models, cox proportional hazards models and stratified analysis were used to analyse the relationships between consumption of probiotics/prebiotics, renal parameters, CKD and mortality. We also conducted a two-sample Mendelian randomization (MR) analysis of single nucleotide polymorphisms (SNPs) related to different genera of gut microbiota to assess their causal relationships with CKD and mortality. 15,291 subjects were analysed (897 with consumption of probiotics/ prebiotics and 14,394 without). The use of probiotics/prebiotics showed an inverse correlation with urinary albumin-to-creatinine ratio (UACR) (P < 0.05). Probiotics/prebiotics use was associated with lower risk of CKD in subjects with hypertension, hyperlipidaemia and diabetes mellitus. The consumption of probiotics/prebiotics was associated with a significantly lower risk of all-cause mortality in different regression models (P <0.001, for all), but the lower risk of cardiovascular mortality did not reach statistical significance (P >0.05, for all)]. MR analysis showed negative associations between the genetically predicted genus Flavonifractor and risk of CKD and diabetic kidney disease (DKD). After multivariable regression, and cox proportional hazards analysis, we found that the use of probiotics/prebiotics was associated with improved kidney and mortality outcomes in the general population from NHANES database. The two-sample MR analysis provided further genetic evidence that a distinct genus of gut microbiota was associated with reduced risk of CKD, DKD and mortality.

Comparison of long-term outcomes for neoadjuvant chemoradiation (NA-CRT) followed by surgery versus (V) definitive chemoradiation (D-CRT) in localized gastroesophageal cancer (GEC): A single-center analysis.

371 Background: The therapeutic approach in locally advanced GEC is evolving. NA-CRT followed by surgery has been recommended based on the CROSS trial. The SANO trial reports active surveillance may be an alternative in clinically complete response after D-CRT in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). SCC and AC in GEC are different diseases with differences in tumor location, etiology, and biology. Despite the evolving landscape, there still may be a role for both CROSS and SANO approaches. In our large observational cohort study, we sought to compare the long-term outcomes in localized GEC across all histological subtypes treated with NA-CRT+Surgery V D-CR+Surveillance. Methods: A retrospective analysis comparing NA-CRT + surgery V D-CRT in localized GEC between 2007-2023 treated at the Princess Margaret Cancer Centre was completed. Baseline characteristics including age, gender, race, performance status and Charlson Comorbidity index (CCI) were reviewed. The primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS), respectively and to compare these outcomes in both histologies. Cox proportional hazards analysis and Kaplan-Meier methods were employed. Outcomes were adjusted for baseline characteristics. Results: There were 529 patients (pts) included, 321 (61%) received NA-CRT+Surgery and 208 (39%) D-CR+Surveillance. Median age was 64yrs, 75% were male and 66% had N1+ disease. The proportion of pts with SCC treated with NA-CRT+Surgery and D-CR+Surveillance was 25% and 63%, respectively. There was a statistically significant difference in median OS and DFS between pts who received NA-CRT+surgery and D-CRT+surveillance (Table). Multivariate regression analysis shows a significant association between OS and age (adjusted HR 1.02, p=0.005), male sex (HR 1.55, p=0.003) but no significant association between OS and CCI (HR 1.1 p=0.36). In our subgroup analyses, there was no statistically significant difference in OS (p=0.33) and DFS (p=0.18) between SCC and AC. However, this was significant in D-CRT (OS p&lt;0.0001, DFS p&lt;0.001) favoring SCC. Conclusions: In contrast to the SANO trial, we found that NA-CRT+surgery was associated with a significantly better OS and DFS compared to D-CRT when subtypes were combined. However, in the D-CRT subgroup, SCC was associated with improved OS and DFS compared to AC. Thus, we continue to recommend current approaches in SCC. Awaited updates from SANO will inform whether active surveillance may also be appropriate in pts with AC subtype. Median (95% CI)NA-CRT Surgery Median (95% CI)D-CRT Log-rank test p-value OS (mo) 28.2 (15.1, 57.6) 15.6 (7.7, 33.7) P=&lt;0.0001 DFS (mo) 17.9 (9.6, 40.8) 9.4 (5.0, 20.7) P=&lt;0.0001 pathCR (%) 14 - R0 resection (%) 89 -

Associations of early life body size and pubertal timing with breast density and postmenopausal breast cancer risk: A mediation analysis.

Whether breast density mediates associations between early life body size and pubertal timing with postmenopausal breast cancer is underexplored. We studied 33,939 Danish women attending the Capital Mammography Screening Program at ages 50-69 years. Early life anthropometry and pubertal timing information came from the Copenhagen School Health Records Register. Postmenopausal breast cancer information came from the Danish Breast Cancer Group database (n = 833). Breast density (BI-RADS) was categorized as low (n = 25,464; 75 %) or high. Risk ratios (RR) and hazard ratios (HR) were estimated using generalized linear regression and Cox proportional hazards analyses. Counterfactual mediation analyses were conducted. Evidence was limited for associations between birthweight and pubertal timing with breast density or breast cancer. Childhood BMI was inversely associated with high breast density (age 13y, RR=0.77 [0.72-0.81] for a z-score of 0.6 versus 0) and breast cancer (HR=0.90 [0.83-0.96] per z-score). Breast density mediated 37 % (17-170 %) of this association. Although childhood height was associated with breast density and breast cancer, there were few indications of mediation by breast density. Breast density may partially explain the inverse association between childhood BMI and postmenopausal breast cancer, but not the positive association between childhood height and postmenopausal breast cancer.

Weight and Blood-Based Markers of Cachexia Predict Disability, Hospitalization and Worse Survival in Cancer Immunotherapy Patients.

Cancer-associated cachexia can inhibit immune checkpoint inhibitor (ICI) therapy efficacy. Cachexia's effect on ICI therapy has not been studied in large cohorts of cancer patients aside from lung cancer. We studied associations between real-world routinely collected clinical cachexia markers and disability-free, hospitalization-free and overall survival of cancer patients. A retrospective study was conducted of electronic health records (EHR) of patients with lung, renal cell, melanoma and other cancers treated with ICI therapy at Northwestern Medicine of Chicago, IL, United States, between March 2011 and January 2022. Weight, body mass index, absolute neutrophil and lymphocyte counts, albumin and C-reactive protein (CRP) measures were analysed to calculate the Fearon consensus criteria for cachexia, weight loss grading system (WLGS) score, neutrophil-lymphocyte ratio (NLR), Prognostic Nutritional Index (PNI) and modified Glasgow Prognostic Score (mGPS) at ICI therapy initiation. Kaplan-Meier and Cox proportional hazards analyses were used to determine associations between these metrics and disability-free, hospitalization-free and overall survival. EHR analysis uncovered 3285 cancer patients on ICI therapy (54% > 65 years of age, 50.7% male, 77.7% White). At ICI therapy initiation, 1282 (39.0%) patients had cachexia (consensus criteria), 1641 (50.0%) had a WLGS score ≥ 2, 1806 (55.0%) had an NLR > 3, 1087 (33.1%) had albumin < 3.5 g/dL and 1318 (40.1%) had a PNI < 44. Missing measurements included CRP missing for 98.2% and mGPS missing for 98.6% of patients. Disability-free (n = 1373), hospitalization-free (n = 2374) and overall survival (n = 1599) events were analysed with 1-year rates of 65% (64%-67%), 35% (34%-37%) and 65% (63%-66%), respectively. Multivariate Cox model analyses showed hazard ratios (HR) for cachexia at 1.58 (95% CI 1.38-1.80), 1.47 (95% CI 1.33-1.63) and 1.97 (95% CI 1.75-2.23) for disability, hospitalization and death, respectively. HRs for WLGS ≥ 2 were 1.45 (95% CI 1.28-1.66), 1.37 (95% CI 1.24-1.51) and 1.91 (95% CI 1.69-2.17). HRs for NLR > 3 were 1.57 (95% CI 1.35-1.83), 1.40 (95% CI 1.25-1.58) and 1.95 (95% CI 1.67-2.27). HRs for albumin < 3.5 g/dL were 1.33 (95% CI 1.15-1.54), 1.67 (95% CI 1.50-1.86) and 2.09 (95% CI 1.84-2.36). HRs for PNI < 44 were 1.60 (95% CI 1.39-1.84), 1.46 (95% CI 1.31-1.63) and 2.07 (95% CI 1.80-2.37). Fearon consensus criteria, WLGS, NLR, albumin and PNI were routinely collected at ICI initiation in regular clinical practice and predictive of worse disability-free, hospitalization-free and overall survival in cancer patients receiving ICI therapy. These routine clinical measures may aid prognostication and decision-making in cancer patients with cachexia.

Real-world validation of the Khorana risk score in gastric cancer patients receiving immune checkpoint inhibitors.

363 Background: Thrombosis is a common cancer-related complication, particularly in gastric cancer. Studies show that immune checkpoint inhibitors (ICIs) increase the risk of venous thromboembolism (VTE) and arterial thrombosis. The Khorana risk score is widely used to assess thrombosis risk before starting chemotherapy. This study aimed to validate the Khorana score in gastric cancer patients receiving ICIs using a large global database. Methods: We used the TriNetX Global Collaborative Network, which contains de-identified data from over 120 million patients. We included patients diagnosed with gastric cancer who received ICIs between January 2014 and July 2023. The Khorana risk score was calculated based on lab values and BMI within two weeks before ICI initiation. Patients were divided into two cohorts: elevated risk (score 3-6) and intermediate risk (score 2). Cox-proportional hazard analyses were conducted over a one-year follow-up. The primary outcome was VTE (deep vein thrombosis [DVT] and pulmonary embolism [PE]). Secondary outcomes were arterial thrombosis, including myocardial infarction (AMI) and ischemic stroke, and all-cause mortality. Results: The study included 551 patients, with 362 in the intermediate risk and 189 in the elevated risk cohorts. The mean age was 64 in both cohorts, with the elevated group consisting of more males (76% vs. 63%) and a higher proportion of Black patients (11% vs. 6%). Pembrolizumab (49%) and nivolumab (47%) were the most used ICIs. Patients with elevated risk had a significantly higher risk of VTE (HR 1.74, 95% CI 1.18-2.58), DVT (HR 1.82, 95% CI 1.07-3.10), and PE (HR 1.74, 95% CI 1.07-2.84). However, no significant associations were found with arterial thrombosis (HR 1.28, 95% CI 0.74-2.20), including cerebral infarction (HR 1.05, 95% CI 0.51-2.16), or AMI (HR 1.46, 95% CI 0.70-3.05). The elevated risk cohort also had significantly higher mortality (HR 1.44, 95% CI 1.11-1.87). Conclusions: An elevated Khorana risk score is associated with a higher risk of VTE, but not arterial thrombosis, in gastric cancer patients treated with ICIs. Further studies are needed to determine how the Khorana score can be applied to predict ICI-related thrombosis and guide prophylactic anticoagulation. Outcomes Khorana risk score 3-6 Khorana risk score 2 Hazard ratio(95% CI) P-value(Log-rank) At risk patients Cases At risk patients Cases Venous thromboembolism 189 45 362 58 1.74 (1.18-2.58) 0.005 Deep vein thrombosis 189 25 362 30 1.82 (1.07-3.10) 0.025 Pulmonary embolism 189 29 362 36 1.74 (1.07-2.84) 0.025 Arterial thrombosis 189 21 362 34 1.28 (0.74-2.20) 0.375 Cerebral infarction 189 11 362 22 1.05 (0.51-2.16) 0.901 Acute myocardial infarction 189 12 362 17 1.46 (0.70-3.05) 0.317 All-cause mortality 189 93 362 145 1.44 (1.11-1.87) 0.006

The associations between dietary omega-6, omega-3, and omega 6 to omega 3 ratio fatty acids and hypertension risk among adults: A prospective cohort study.

Previous studies have yielded mixed results on the connection between dietary omega-3 and omega-6 intakes and the risk of hypertension (HTN) incidents. Therefore, we conducted a study to survey the connection between baseline dietary intake of omega-3, omega-6, and omega-6 to omega 3 (omega-6/3) fatty acids (FA) and the risk of hypertension. We conducted a prospective cohort study and assessed dietary intake through a 118-item food frequency questionnaire (FFQ). To determine the relationship between dietary omega-3, omega-6, and omega-6/3 ratio intake and the risk of developing hypertension, we applied Cox proportional hazards analysis to determine hazard ratios (HR) and 95% confidence intervals (CIs). After following 7359 participants who did not have hypertension at the beginning of the study for 6.4±1.33 years, we identified 597 new cases of hypertension (8.11%). Our analysis, which controlled for all confounders, did not identify any significant link among the highest versus lowest quartile of dietary omega-3 intake (HR: 0.87, 95% CI: 0.63, 1.18; P trend: 0.34), omega-6 intake (HR: 1.04; 95% CI: 0.81, 1.34; P trend: 0.82), and omega-6/3 ratio intakes (HR: 1.06, 95% CI: 0.82, 1.36; P trend: 0.66) and HTN risk. To sum up, our study revealed that dietary omega-3, omega-6, and omega-6/3 ratio were not associated with the hypertension risk.

The 5-factor modified frailty index as a prognostic factor following stereotactic radiosurgery for metastatic disease to the brain from non-small cell lung cancer: A multi-center cohort analysis.

Non-small cell lung cancer (NSCLC) patients often develop brain metastases (BMs), complicating management. We have shown that increasing frailty is associated with decreased overall survival (OS) and central nervous system progression free survival (PFS) for patients undergoing stereotactic radiosurgery (SRS) to BMs. Leveraging the International Radiosurgery Research Foundation, we sought to expand upon these findings, in NSCLC specifically. Across four institutions, 193 patients with (≥1) NSCLC derived BMs with minimum 3months of clinical/radiographic follow-up were analyzed. Primary outcomes included OS and PFS. Patients were stratified utilizing the mFI-5 into pre-frail (0-1), frail (2), and severely frail (3+). Increased frailty was associated with diminished OS (frail hazard ratio (HR)=2.49, 95% CI [1.61-3.85]; severely frail HR = 2.65, 95% CI [1.57-4.45]). The 6-month post-SRS survival rate was 86.1%, 69.5% and 54.5% for pre-frail, frail and severely frail patients, respectively (p<0.001). Frailty was not significantly predictive of time to PFS on multivariate Cox Proportional Hazards analysis although there was a trend towards diminished PFS with increasing frailty (median PFS was 18.4, 8.0, and 7.4months for pre-frail, frail, and severely frail, respectively (p=0.11). As age>65 was also predictive of shorter OS (HR=1.78, 95% CI [1.23-2.56]). We generated a novel scoring system incorporating age and frailty status. The median survival of patients that scored 0, 1, 2, and 3 points were 21.1, 18.3, 8.9, and 5.6months, respectively (p<0.001). The area under the curve of the validation cohort using a logistic regression model was 0.77. Our results indicate that the MFI-5 is a promising metric with application at the point of care to provide decision support for patients with NSCLC derived BMs.

Negative Impact of High FOXP3 Status in Lymph Nodes of Esophageal Squamous Cell Carcinoma Patients.

Available data on the immune profiles of regional lymph nodes in individuals with esophageal squamous cell carcinoma (ESCC) are limited. This study investigated the immune profiles of proximal regional lymph nodes (PLNs) and evaluated the association between PLNs and the outcomes of patients with ESCC. This study included 39 patients with ESCC who underwent subtotal esophagectomy with three-field lymph node dissection. The immune profiles of tumor-infiltrating lymphocytes and PLNs were evaluated through immunohistochemistry. Furthermore, the impact of this immune profile on long-term outcomes was analyzed. Cox proportional-hazards analysis for overall survival revealed that ypT ≥3 [hazard ratio (HR)=8.91; 95% confidence interval (CI)=1.59-49.8] and high FOXP3 status in PLNs (HR=4.29; 95%CI=1.06-17.4) are significant independent prognostic factors. Meanwhile, analysis of disease-free survival (DFS) revealed that ypT ≥3 (HR=5.52; 95%CI=1.15-26.6) and ypN ≥1 (HR=7.74; 95%CI=1.58-37.9) are independent prognostic factors. Furthermore, high FOXP3 status in PLNs was associated with low DFS rate, although the association was not statistically significant (HR=1.70; 95%CI=0.58-5.02). High FOXP3 status in PLNs is associated with poor prognosis in patients with ESCC.

Prevalence and clinical features of progressive pulmonary fibrosis in patients with unclassifiable idiopathic interstitial pneumonia: A post hoc analysis of prospective multicenter registry.

Idiopathic interstitial pneumonias (IIPs) may remain unclassifiable owing to inadequate, nonspecific, or conflicting clinical, radiological, or histopathological findings despite multidisciplinary discussion (MDD). Unclassifiable IIP (UCIIP) is a heterogeneous disease that can present with progressive pulmonary fibrosis (PPF). This study aimed to investigate the prevalence and clinical features of PPF in patients with UCIIP. In this post hoc analysis of a prospective multicenter registry of 222 patients with IIPs, 71 with UCIIP diagnosed using MDD were enrolled. PPF was defined based on worsening symptoms and radiological and physiological progression using the guideline criteria within 12 months or the criteria from the INBUILD trial within 24 months. The median age was 72 years, and surgical lung biopsy was performed in 19.7%. Of the 66 patients with adequate follow-up data, 30 (45.5%) met either criterion and were diagnosed with PPF. UCIIP patients with PPF had significantly higher serum surfactant protein-D level and percentage of bronchoalveolar fluid neutrophils, lower %forced vital capacity and %diffusing capacity for carbon monoxide, and a higher proportion of honeycombing on high-resolution computed tomography and desaturation on exertion than those without PPF. Additionally, they had significantly more anti-fibrotic therapy and long-term oxygen therapy, a higher incidence of acute exacerbation, and a poorer prognosis than those without PPF. Cox proportional hazards analysis revealed that PPF was a significant poor prognostic factor, regardless of the criteria. PPF is common and associated with poor prognosis in patients with UCIIP. Appropriate evaluation and management of PPF are essential for UCIIP.

Severe secondary tricuspid regurgitation is associated with nonfatal heart failure hospitalization but not with mortality in patients with chronic heart failure aged 80 years or older

Abstract Background Previous studies have shown that tricuspid regurgitation secondary to heart failure (HF) is common with considerable effect on their outcomes. However, impact of secondary tricuspid regurgitation (sTR) on survival and hospitalization in patients with ultra-elderly HF are uncertain. Purpose To investigate impact of severe sTR in ultra-elderly HF. Methods We retrospectively enrolled 163 patients (median age, 87 years, 72 male) with HF aged ≥ 80 years-old admitted to our hospital for the treatment of decompensated HF. Clinical characteristics including echocardiographic data were obtained before discharge. In the present study, severe sTR was defined as vena contracta width ≥ 7mm based on the current guidelines. The date of discharge was considered the entry time-point of observation. Primary outcomes were defined as all-cause death, cardiac death or nonfatal HF hospitalization. Results Severe sTR was present in 35 patients (21.5%). During a median follow-up period of 500 (interquartile range, 255-1268) days, 60 all-cause deaths, 41 cardiac deaths and 51 nonfatal HF hospitalizations were occurred. In univariate Cox proportional hazards analysis, age, body mass index, albumin, hemoglobin, B-type natriuretic peptide (BNP), estimated glomerular filtration rate and the ratio of peak early diastolic trans-mitral flow velocity to annular velocity (E/e’) were associated with all-cause death. In multivariate Cox proportional hazards analysis, hemoglobin [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.90, p = 0.0037] and BNP levels (HR 1.003, 95%CI 1.001-1.004, p = 0.0008) were independently associated with all-cause death. Similarly, age, body mass index, presence of ischemic heart disease, albumin, hemoglobin, BNP and E/e' were associated with cardiac death in univariate analysis, and multivariate analysis showed that hemoglobin (HR 0.74, 95%CI 0.58-0.93, p = 0.013) and BNP (HR 1.003, 95%CI 1.001-1.004, p = 0.0034) were independently associated with cardiac death. Severe sTR was not associated with mortality even in univariate analysis. On the other hand, univariate analysis showed that age, albumin, hemoglobin and severe sTR were associated with nonfatal HF hospitalization, and multivariate analysis revealed that severe sTR (HR 1.91, 95%CI 1.02-3.42, p = 0.044) was the only factor independently associated with nonfatal HF hospitalization. Conclusion In ultra-elderly patients with chronic HF aged ≥ 80 years, severe sTR was associated with nonfatal HF hospitalizations but not with both cardiac and all-cause deaths. This result may indicate that percutaneous therapies should focus on the optimal timing of intervention in patients with severe sTR with respect to overall survival and quality of life.

Trajectory of the arterial-alveolar oxygen gradient in COPD for a decade.

Chronic respiratory failure (CRF) is a critical complication in patients with chronic obstructive pulmonary disease (COPD) and is characterized by an increase in the arterial-alveolar oxygen gradient (A-aDO2). The long-term trajectory and prognostic significance remain unclear. This study aimed to assess the prognostic impact of A-aDO2 and elucidate its trajectory over ten years. We enrolled 170 outpatients with COPD from a prospective cohort study. Arterial blood gas (ABG) analyses were conducted annually for ten years while monitoring the development of CRF. 157 patients completed the observation period, of whom 21 developed CRF (CRF group) and 136 did not (non-CRF group). In the CRF group, there was a gradual increase in A-aDO2 along with decreases in partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) over ten years, although there were no changes in the non-CRF group. The CRF group had higher baseline A-aDO2 and higher ΔA-aDO2 in the first year than the non-CRF group (3.76 vs. 0.42 Torr/year, p = 0.030). Kaplan-Meier analyses, and multivariate Cox proportional hazards analysis revealed that both baseline A-aDO2 and ΔA-aDO2 were significantly associated with the development of CRF. Retrospective tracking from the initiation of long-term oxygen therapy (LTOT) revealed significant increases in A-aDO2 from 5 years prior to LTOT initiation in the CRF group when compared to the non-CRF group. An increasing trend in A-aDO2 may be a significant sign for the future development of CRF. A transition of the annual change of A-aDO2 from a stable state to a deterioration phase can serve as a prognostic factor for developing CRF within 5 years.

Right ventricular stroke work index from echocardiography in patients with pulmonary arterial hypertension, the role in follow-up assessment

Abstract Background Right ventricular (RV) failure cause high mortality in patients with pulmonary arterial hypertension (PAH) (1,2,3,4). RV stroke work index (RVSWI) poses as a possible invasive determinant of outcome. Non-invasively measured RVSWI could be argued useful (5, 6, 7, 8, 9). Echocardiography-derived RVSWI (RVSWIECHO) encompassing either systolic (sPAP) or mean pulmonary arterial pressure (mPAP) is associated with invasive RVSWI (RVSWIRHC). The aim of this study is to evaluate how RVSWI by echocardiography or right heart catheterization (RHC) is altered following PAH-treatment and if RVSWI at baseline is an indicator of outcome in PAH. Methods Fifty-four consecutive patients with PAH (65 ± 13 years, 36 women) analyzed at baseline and at first follow-up visit (141 ± 79 days) were included in the study. Echocardiography and RHC were performed within a median of 0 day [IQR 0-1 days]. PAH-treatment was initiated after baseline examinations. RVSWIRHC was computed as (mPAP-mRAP)xSVIRHC (mRAP: mean right atrial pressure; SVI stroke volume indexed to body surface area). From echocardiography, tricuspid regurgitant (TR) maximum velocity and mean pressure gradient (PG) and SVI were assessed. RVSWIECHO was computed as RVSWIECHO-Max=TRmaxPGxSVIECHO and RVSWIECHO-Mean=TRmeanPGxSVIECHO. Results Invasive sPAP, mPAP and pulmonary vascular resistance (PVR) decreased from baseline to follow-up (sPAP: 76±18 vs 65±20 mmHg; mPAP: 47±11 vs 39±12 mmHg; PVR: 10.3 ±5 to 6.5±3.3 WU; p&amp;lt; 0.01 for all), and SVI increased (29±8 vs 37±10 ml/m2, p&amp;lt;0.01). RVSWIRHC and RVSWIECHOMax-Mean did not differ from baseline to follow-up (RVSWIRHC: 1132±352 vs 1208±467 mmHg*mL*m-2 (p=0.1); RVSWIECHO-Max: 1904±568 vs 1967±727 mmHg*mL*m-2 (p=0.5); RVSWIECHO-Mean: 1090±306 vs 1192±482 mmHg*mL*m-2 (p=0.1)). At long-term follow-up, 40 patients had died. None of the echocardiographic or invasive measures at baseline (including RVSWI) differed between survivors and non-survivors. In univariate Cox proportional hazard analysis, none of the RVSWI methods were associated with long-term mortality. However, age&amp;gt;65 years, six minutes’ walk distance test (6 MWT) &amp;lt;160 m, WHO class III-IV and indexed right atrium volume were associated. Adding these parameters as input in a model of multivariate analysis showed that echocardiography derived RVSWI (RVSWIECHO-Max (HR =1.001; CI 1-1.001; p=0.016); RVSWIECHO-Mean (HR =1.001; CI 1-1.002; p=0.006)) were independently associated with mortality. Conclusion None of the RVSWI methods differed from baseline to follow-up in patients with PAH, despite substantial improvement in conventional hemodynamic parameters. The baseline RVSWI methods were not associated with long-term mortality in univariate analysis. However, when adjusting for clinical variables in a multivariate analysis a significant association between echocardiography-derived RVSWI and mortality could be detected.

Elevated left atrial stiffness index is a poor prognostic factor in heart failure with preserved ejection fraction undergoing transcatheter aortic valve replacement

Abstract Background Patients with severe aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR) present with a high prevalence of heart failure with preserved ejection fraction (HFpEF). An elevated left atrial stiffness index (LASI) has recently been recognized as a potential prognostic factor for worsened outcomes in HFpEF patients. Purpose This study investigates whether the LASI is a prognostic factor for outcomes following TAVR in HFpEF patients. Methods In this single-center retrospective study, patients with severe aortic valve stenosis who underwent TAVR at our center from February 2020 to May 2023 and had left ventricular ejection fraction &amp;gt;40% were included (Figure 1). The LASI was defined as the ratio of E/e’ to the left atrial reservoir strain from transthoracic echocardiography performed before and one week after TAVR. The primary endpoint was a composite outcome of all-cause mortality and cardiovascular events during the follow-up period. Results We analyzed 178 patients with a median age of 84 years, of whom 69% were female. During a median follow-up period of 549 days, 34 cases (19%) experienced the composite outcome. Multivariate Cox proportional hazards analysis using preoperative indices showed that LASI was independently associated with the occurrence of outcomes (HR 1.84 [95% CI; 1.15-2.95, P = 0.011] per 1.0 increase). A sub-analysis excluding cases had left bundle branch block postoperatively revealed a significant association between postoperative LASI and outcomes (HR 3.62 [95% CI; 2.01-6.51, P = &amp;lt;0.001] per 1.0 increase), particularly pronounced in patients with preoperative grade 2 left ventricular diastolic dysfunction (HR 4.38 [95%CI; 2.07-9.26, P=&amp;lt;0.001] per 1.0 increase) (Figure 2). Conclusion There is potential for LASI as a prognostic factor for outcomes following TAVR in HFpEF patients.

Use of the FHTHWA Index as a Novel Approach for Predicting the Incidence of Diabetes in a Japanese Population Without Diabetes: Data Analysis Study.

Many tools have been developed to predict the risk of diabetes in a population without diabetes; however, these tools have shortcomings that include the omission of race, inclusion of variables that are not readily available to patients, and low sensitivity or specificity. We aimed to develop and validate an easy, systematic index for predicting diabetes risk in the Asian population. We collected the data from the NAGALA (NAfld [nonalcoholic fatty liver disease] in the Gifu Area, Longitudinal Analysis) database. The least absolute shrinkage and selection operator model was used to select potentially relevant features. Multiple Cox proportional hazard analysis was used to develop a model based on the training set. The final study population of 15464 participants had a mean age of 42 (range 18-79) years; 54.5% (8430) were men. The mean follow-up duration was 6.05 (SD 3.78) years. A total of 373 (2.41%) participants showed progression to diabetes during the follow-up period. Then, we established a novel parameter (the FHTHWA index), to evaluate the incidence of diabetes in a population without diabetes, comprising 6 parameters based on the training set. After multivariable adjustment, individuals in tertile 3 had a significantly higher rate of diabetes compared with those in tertile 1 (hazard ratio 32.141, 95% CI 11.545-89.476). Time receiver operating characteristic curve analyses showed that the FHTHWA index had high accuracy, with the area under the curve value being around 0.9 during the more than 12 years of follow-up. This research successfully developed a diabetes risk assessment index tailored for the Japanese population by utilizing an extensive dataset and a wide range of indices. By categorizing the diabetes risk levels among Japanese individuals, this study offers a novel predictive tool for identifying potential patients, while also delivering valuable insights into diabetes prevention strategies for the healthy Japanese populace.

The Triglycerides, total Cholesterol, and Body weight Index (TCBI) associating with frailty and predicting poor outcome after transcatheter aortic valve implantation: Insights from LAPLACE-TAVI registry

Abstract Background The nutritional status and frailty are crucial in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI), as they significantly impact outcomes. We have previously developed an easily calculable nutritional index, TCBI (Triglycerides, total Cholesterol, and Body weight Index), which has been validated as a prognostic indicator in various cardiovascular disease contexts. This study aimed to evaluate the impact of a low TCBI on the frailty and outcomes of patients undergoing TAVI. Methods This study is a part of a Japanese multi-center prospective registry database of TAVI cases (n=824). Participants were categorized into 3 groups based on TCBI tertiles before TAVI. The primary endpoint was all-cause mortality with a follow-up duration of up to 3 years. Results In the lowest TCBI tertile group, motor functions reflecting frailty were substantially impaired, and cumulative incidences of primary endpoint was significantly higher compared to other groups. Multivariate Cox proportional hazard analyses adjusted by risk factors for poor outcomes following TAVI, identified low TCBI significantly associated with an increased risk of the primary endpoint (hazard ratio (HR) and 95% confidence interval (95% CI) of 1 standard deviation lower TCBI for all-cause mortality: 1.52, 1.08-2.13, p=0.015). Moreover, in individuals who experienced serious preprocedural complications, the negative prognostic impact of low TCBI was significantly amplified (HR and 95%CI: 4.9, 1.9-12.5, p&amp;lt;0.001). Conclusions The present findings underscore the importance of nutritional assessment in patients undergoing TAVI. TCBI proved useful for accurate risk stratification and determining TAVI procedural strategies.