Competing Risk Analysis Research Articles

Interleukin 6 in asymptomatic patients with nonsevere aortic valve stenosis: a post-hoc study of the SEAS trial

Abstract Background Inflammation plays a pivotal role in the pathogenesis of aortic valve stenosis (AS) through cytokine-mediated valve calcification. Studies of explanted valves found associations of an elevated pro-inflammatory cytokine, Interleukin 6 (IL-6), with increased postoperative mortality. However, limited knowledge exists regarding the prognostic value of elevated circulating IL-6 in asymptomatic patients with nonsevere AS. Purpose To investigate the hypothesis that elevated plasma IL-6 concentration ≥7 pg/mL (above the upper limit of normal 95th percentile) correlates with more severe AS and a higher risk of adverse outcomes in asymptomatic patients with nonsevere AS. Methods We analyzed data of 1574 asymptomatic patients who had mild-to-moderate AS, preserved systolic and kidney function, no overt cardiovascular diseases, and an event-free follow-up one year after enrollment in the randomized Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. We ascertained the correlation of year-0 and year-1 IL-6 levels with echocardiographic AS severity, defined as moderate-severe AS in the presence of ≥2 measurements at year-0: aortic valve area <1 cm², mean pressure gradient ≥40 mmHg, maximal transaortic velocity ≥4 m/s, and velocity ratio <0.25. Multivariable regression examined correlations between IL-6 at year-0 and clinical variables. Cox proportional hazard models and competing risk analyses examined associations of elevated IL-6 at year-1 and 4-year risk of the primary composite endpoint of major cardiovascular events (MACE) comprising the first event of cardiovascular death, aortic valve replacement, hospitalization with heart failure, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or ischemic stroke. Results At year-0, among 1574 patients with a mean (SD) age of 67.5 (9.7) years, 629 (40.0%) were women, 263 (16.7%) had moderate-severe AS, and 194 (12.3%) had elevated IL-6. The median relative IL-6 change from year-0 to year-1 was 1.0 (IQR, 0.8-1.4) across AS-severity groups (P=0.12) (Figure 1). In adjusted models, IL-6 at year-0 did not correlate with AS-severity (P=0.30). In mild AS, an elevated IL-6 at year-1 was associated with an increased 4-year MACE risk (HR 1.40; 95% CI, 1.02-1.92; p=0.04) in adjusted Cox regression analyses (Figure 2A). In sensitivity analyses, the annual IL-6 increase >50% combined with normal IL-6 was associated with an increased 4-year MACE-risk of HR 1.48 (95% CI, 1.10-2.00; P=0.009) in patients with mild AS and 1.82 (95% CI, 0.68-1.74; P=0.73) in patients with moderate-severe AS (all P for interaction>0.25) (Figure 2C-D). Conclusion In asymptomatic patients with nonsevere AS, circulating IL-6 remains stable within the reference range in 7 out of 8 patients during a 1-year follow-up, regardless of AS severity. An elevated IL-6 was associated with a 1.4-fold increased 4-year MACE-risk in patients with mild AS, suggesting its possible role as an early risk marker.Figure 1Figure 2

Cardiovascular outcomes in acute coronary syndrome patients with cancer: a statewide population-linkage study

Abstract Background Advances in oncology treatment have led to an increase in the number of cancer survivors. As a result, the number of acute coronary syndrome (ACS) patients with cancer is increasing and the outcomes of these patients are not well described. Purpose This study aimed to examine revascularisation strategies and all cause and cardiovascular death in ACS patients with and without cancer. Methods Hospitalised patients in New South Wales, Australia, from July 2006 to December 2020 with a primary diagnosis of ACS were identified from the statewide Admitted Patient Data Collection database. Patients were stratified into those with or without a history of cancer (non-melanoma skin cancers excluded). Propensity scoring matching (PSM) for the variables of age, gender and cardiovascular risk factors was performed with each cancer patient matched to two non-cancer patients. Cox proportional hazards regression model was used to evaluate the hazard ratios of all-cause mortality between individuals with a history of cancer in the 5 years preceding their hospital admission, and those without. Additionally, Fine-Gray competing risk analysis was performed for cardiovascular death with non-cardiovascular mortality as the competing event. Results During the study period, 193,848 patients were admitted with ACS. 12,543 patients had a history of cancer and were PSM to 25,085 patients without cancer. The median age was 75 (Q1-Q3 67-82) years with 69% male and hypertension the most prevalent risk factor (55%) (Table 1). ACS patients with cancer had clinically comparable, rates of percutaneous revascularisation (36 vs 37%, p=0.07) and coronary artery bypass grafting (11 vs 13%, p<0.001) with ACS patients without cancer. During a median follow up of 8.6 (95% CI 8.4-8.8) years, ACS patients with a history of cancer had a significant higher risk of all cause death (HR 1.42 95% CI [1.38-1.46]) and cardiovascular death (SHR 1.14 [1.11-1.18]). The cumulative incidence function demonstrated cardiovascular death in those with a cancer history occurred in 20% by approximately 1.4 years follow up compared to 2.5 years in those without cancer (Figure 1). Conclusion ACS patients with cancer have a higher risk of all cause death and cardiovascular death compared to those without a history of cancer with clinically comparably revascularisation rates. Further studies to determine the cause of increased cardiovascular death in ACS patients with cancer are required.Figure 1

Association between PCSK9 inhibitor with cause-specific morality amongst cancer survivors

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has emerged as a novel pharmacotherapy for dyslipidemia and been shown to be effective in reducing the risks of atherosclerotic cardiovascular diseases. PCSK9 is aberrantly expressed in a broad spectrum of cancers and has been demonstrated to contribute to cancer prognosis. However, no prior study has investigated the associations between PCSK9 inhibitors (PCSK9i) with cardiovascular and cancer mortality amongst cancer survivors. Purpose This study investigated the effects of PCSK9i on cause-specific mortality amongst cancer survivors. Methods This retrospective study used data from the Tianjin Coronary Artery Disease Cohort, which included medical data from 71 secondary or tertiary hospitals in Tianjin, China. Adult patients with coronary artery disease (CAD) diagnosed with incident cancer between 2017 and 2023 were enrolled in this study. Propensity score matching with a 1:3 ratio for PCSK9i users versus non-users was performed. The primary outcomes included all-cause mortality, cardiovascular mortality, and cancer mortality. Multivariable Cox regression was used to test associations between PCSK9i with outcomes, adjusting for age, gender, cardiovascular and non-cardiovascular comorbidities, lipid-lowing agents and other medication use, lipid level, as well as cancer characteristics. Multivariable competing risk analysis was used as sensitivity analysis. Results A total of 62,341 incident cancer patients were identified. After matching, 424 PCSK9i users and 1,272 non-users were included in this study. During a median follow-up of 1,009 days, 315 patients died, among which 98 died due to cardiovascular cause, 146 died due to cancer cause. Compared to non-users, cancer patients treated with PCSK9i presented with significantly lower risk of all-cause mortality (hazard ratio [HR], 0.33; 95% confidence interval [CI] 0.23-0.47; p <0.001), after adjusting for potential confounders. In addition, PCSK9i therapy was associated with a 63% lower risk of cardiovascular mortality (HR, 0.37; 95%CI 0.20-0.69; p=0.002) and a 75% lower risk of cancer-related mortality (HR, 0.25; 95%CI 0.14-0.45; p<0.001), in relation to non-PCSK9i group. Sensitivity analysis using multivariable competing risk model also suggested a significant association between PCSK9i treatment with reduced risk of cardiovascular mortality (HR, 0.41; 95%CI 0.22-0.76; p=0.005) and cancer mortality (HR, 0.26; 95%CI 0.15-0.48; p<0.001) among cancer survivors. Conclusion The use of PCSK9i was associated lower risks of all-cause, cardiovascular-related, and cancer-related mortality amongst cancer survivors. These findings potentially indicate benefits of PCSK9i beyond adverse cardiovascular events related to atherosclerosis.

Impact of Residual Vein Venous Thrombosis in Consecutive Patients with Cancer-Associated Thrombosis Treated with Tinzaparin-A Cohort Study.

Background: The role of residual venous thrombosis (RVT) as a risk factor for recurrent venous thromboembolism (VTE) in patients with cancer-associated thrombosis (CAT) remains controversial. Methods: We conducted a cohort study on consecutive patients with CAT treated with tinzaparin recruited between 2007 and 2022. Primary outcome: RVT. Secondary outcomes: identification of variables associated with RVT and the role of RVT in VTE recurrences or clinically relevant bleeding (CRB). Results: Among 511 patients with CAT (age 64.1 years ± 13.4 years; 53.5% males) followed for 17.6 months (p25-75: 7.9-34), 35.8% (n = 183) presented RVT (at 6 months, 55.5%). Variables identified as being associated with RVT were ECOG performance status > 1, metastasis, and cancer location. Within 5 years, there were 57 CRB (11.2%; 95% CI: 8.6-14.2) and 67 VTE recurrences (13.1%, 95%CI: 10.3-16.4). Competing risk analysis identified that RVT at 6 months was associated with VTE recurrence within 5 years (sub-hazard ratio: 2.1; 95% CI: 1.2-3.7; p = 0.006), but not with CRB. Multivariate analysis confirmed that RVT at 6 months (HR: 2.1; 95% CI: 1.2-3.7) and metastases (HR: 1.7; 95% CI: 1.1-2.9) were associated with VTE recurrence within 5 years. Conclusions: RVT is high in patients with CAT. The presence of RVT at 6 months was associated with an increased risk of recurrent VTE over 5 years.

Protective Effect of Extra Virgin Olive Oil on Cancers, Gastrointestinal Cancers, and All-Cause Mortality: A Competing Risk Analysis in a Southern Italian Cohort.

This study investigates the association between extra virgin olive oil (EVOO) consumption and mortality risk in a cohort of Italian adults adhering to the Mediterranean diet. In a 17-year follow-up study involving participants from Castellana Grotte, Italy (2005-2023), we analyzed dietary intake and mortality data. Participants were categorized into three EVOO consumption groups: <30 g/day, 30-50 g/day, and >50 g/day. Mortality Hazard Ratios (HR) and Subdistribution Hazard Ratios (SHR) were calculated to assess the relationship between EVOO intake and all-cause and cancer mortality. Higher EVOO consumption was associated with significantly reduced cancer and all-cause mortality. Specifically, the daily intake of 30-50 g of EVOO was linked to a 24% lower risk of all-cause mortality (HR 0.77; 95% CI 0.63-0.93), while the consumption of more than 50 g/day was associated with a 20% reduction (HR 0.80; 95% CI 0.65-0.98). The most pronounced benefit was observed for gastrointestinal cancers, with a 60% lower mortality risk for those consuming over 50 g/day (SHR 0.39; 95% CI 0.21-0.73). A 50% reduction in mortality risk from other cancers was also noted for the highest consumption category (SHR 0.50; 95% CI 0.31-0.81). The findings support the beneficial role of EVOO in reducing cancer mortality, particularly with higher consumption levels. The results underscore EVOO's potential as a dietary intervention for cancer prevention, aligning with the Mediterranean diet's overall health benefits. Further research is needed to confirm these findings and explore the underlying mechanisms.

Clinical Outcomes and Relevance of Composite V12 Gy in Patients With Four or More Brain Metastases Treated With Single Fraction Stereotactic Radiosurgery

AimsTissue V12Gy (total brain volume receiving 12Gy including target) can predict for late toxicity in single target benign disease treated with stereotactic radiosurgery (SRS). The value of this metric remains uncertain for multiple brain metastases. This retrospective cohort study reports the outcomes and evaluates the predictors of toxicity in patients with four or more brain metastases treated with single-fraction SRS. Materials and methodsTwo hundred twenty-six patients with 2160 metastases treated from 2014-21 were retrospectively studied. Symptomatic late toxicity (new/progressive neurological symptoms ≥3 months post SRS) with magnetic resonance imaging (MRI) changes suggestive of treatment effect were analysed. Kaplan–Meier and competing risk analysis was used to assess survival and toxicity respectively. Resultsmedian number of metastases/patient was 6 (range: 4-41) and median composite tissue V12Gy (inclusive of planning target volume (PTV)) was 11.3 cc (IQR: 6.1 cc–17.1 cc). Sixteen out of the 226 patients developed symptomatic late radiation adverse event (R-AE), and the cumulative incidence was 4.9% at 1 year and 6.9% at 2 years. The total target volume was significantly predictive of the risk of late R-AE. Volume of the largest lesion, V12Gy and V15Gy did not predict for late R-AE, but plotted graphs showed suggestions of linear relationships between dosimetric parameters and late R-AE. ConclusionWithin the limitations of this study, the cumulative incidence of symptomatic toxicity remains acceptable despite routinely accepting a composite tissue V12Gy in excess of 10 cc to treat multiple brain metastases. Advances in knowledgeV12Gy has limitations as a plan quality metric in multiple brain metastases treated with SRS. There is insufficient evidence to have a defined target limit as <10 cc.

Impact of Heart Transplant Allocation Change on Waitlist Mortality and Posttransplant Mortality in Patients With Left Ventricular Assist Devices.

In October 2018, the US heart transplant (HT) allocation system was revised giving patients with left ventricular assist device (LVAD) intermediate priority status. Few studies have examined the impact of this policy change on outcomes among patients with LVAD. We sought to determine how the allocation change impacted waitlist and posttransplant mortality in patients with LVAD. We retrospectively assessed the United Network for Organ Sharing registry for patients with LVAD who were listed for or underwent HT between October 2016 and October 2021. We evaluated waitlist mortality using competing risks analysis and a multivariable Fine-Gray model, and posttransplant mortality using Kaplan-Meier survival analysis and a multivariate proportional hazards model. We analyzed data from 3835 patients with LVAD listed for HT and 3486 patients with LVAD who underwent HT during the study period. Listing for HT preallocation change was significantly associated with an increased risk of waitlist mortality (Gray P=0.0058) compared with postallocation change. After adjustment for covariates, mortality differences by listing era were attenuated, but LVAD brand was significantly associated with waitlist mortality (HM3 versus HMII; hazard ratio, 0.38 [95% CI, 0.21-0.69]; P=0.002; HVAD versus HMII; hazard ratio, 0.79 [95% CI, 0.48-1.30]; P=0.36; overall P=0.004). In contrast, HT postallocation change was associated with increased posttransplant mortality (log-rank P=0.0172) compared with preallocation change. In a multivariable analysis, the association with posttransplant mortality between transplant eras was attenuated, but ischemic time (hazard ratio, 1.16 [95% CI, 1.07-1.26]; P<0.001) and status at time of HT (Status 1-3 versus 4; hazard ratio, 1.29 [95% CI, 1.04-1.61]; P=0.02) were significantly associated with posttransplant mortality. Among patients with LVAD, lower waitlist mortality postallocation change was likely driven by improved LVAD technology. Higher posttransplant mortality following the allocation change was largely attributable to longer ischemic times and patient acuity.

Long-Term Outcome of Patients with Atrial Fibrillation and High Risk of Stroke Treated with Oral Anticoagulation or Left Atrial Appendage Occlusion: A Cardinality Matched Analysis

Introduction: Atrial fibrillation (AF) poses a significant risk of stroke. Left atrial appendage occlusion (LAAO) is an alternative for patients with contraindications to oral anticoagulation (OAC) or with high risk of bleeding. This study aims to compare the outcomes of LAAO versus conventional stroke prevention in high-risk AF-patients. Methods: This secondary analysis incorporates data from the prospective Swiss-AF and Beat-AF cohorts, and the Zurich LAAO Registry. Cardinality matching was performed to create two comparable cohorts: conventional treatment (92% OAC) and LAAO. The primary endpoint was a composite of stroke, cardiovascular (CV) death, and clinically relevant bleeding. Kaplan-Meier method with competing risk analysis was used. Results: Each group included 468 patients (age 76.4 [70.5, 82.0] years, 33% female). The LAAO group exhibited higher baseline bleeding risk (HAS BLED 2.0 [1.0–3.0] versus 3.0 [3.0–4.0]; p < 0.001). Median follow-up time: 6.0 (4.7–7.0) years in conventional treatment group and 4.0 (1.5–6.1) in LAAO group. No significant difference in the primary composite endpoint (HR 0.87, 95% CI: 0.72–1.06, p = 0.18), stroke risk (HR 1.14, 95% CI: 0.66–1.97, p = 0.64), or CV mortality (HR 1.08, 95% CI: 0.82–1.42, p = 0.60) was observed between groups. LAAO correlated with a significantly lower risk of clinically relevant bleeding (HR 0.61, 95% CI: 0.47–0.80, p < 0.001). Conclusion: In this cardinality matched analysis with long-term follow-up, LAAO showed similar stroke and CV death rates but lower clinically relevant bleeding risk compared to conventional therapy in high-risk AF-patients.

Trajectories of triglyceride-glucose index changes and their association with all-cause and cardiovascular mortality: a competing risk analysis

BackgroundThe association between changes in insulin resistance, reflected by the triglyceride-glucose (TyG) index, and mortality remains unclear. This study investigated whether longitudinal trajectories of TyG index changes are associated with all-cause and cardiovascular disease (CVD) mortality.MethodsThis retrospective cohort study analyzed data from 233,546 adults aged ≥ 19 years from the Korea National Health Insurance Service-National Sample Cohort. Participants were categorized as having increasing, stable, or decreasing TyG index changes during a 4-year exposure period (2009–2014). Mortality outcomes were assessed during an 8.13-year follow-up period (2015–2021). Cox proportional hazards regression and competing risk analysis were used to evaluate all-cause and CVD mortality.ResultsA total of 7918 mortality events, including 651 CVD deaths, were recorded. Compared with the stable group, adjusted hazard ratios for all-cause mortality were 1.09 (95% CI 1.03–1.15) in the increasing group and 1.23 (95% CI 1.01–1.50) for CVD mortality. An increased TyG index was significantly associated with all-cause mortality in individuals aged < 50 years; men; and individuals with obesity, hypertension, diabetes, and/or dyslipidemia. For CVD mortality, significant associations were found in individuals aged 50–69 years, with obesity, with diabetes, or without dyslipidemia.ConclusionAn increasing TyG index from baseline during follow-up was independently associated with higher risks of all-cause and CVD mortality. Serial monitoring of TyG index changes could enhance risk stratification and inform targeted interventions to reduce insulin resistance, and ultimately lower mortality risk.

Temporal Trends and Mortality Patterns in Peripheral Arterial Disease: A Comprehensive Analysis of Hospitalized Patients in Kazakhstan between 2014 and 2021.

Peripheral artery disease (PAD) is a global health concern associated with arterial narrowing or blockage, leading to significant morbidity and mortality. The aim of this study is to assess the disease burden and trends in mortality utilizing nationwide administrative health data. This retrospective study utilized data from the Unified National Electronic Healthcare System (UNEHS) from 2014 to 2021. Patients meeting PAD criteria were included, with demographic and clinical data analyzed. Cox regression and Competing Risk Analysis assessed mortality risks. Between 2014 and 2021, 19,507 individuals were hospitalized due to PAD, with 8,332 (43%) being women and 11,175 (57%) men. The incidence of PAD increased markedly over the observation period, rising from 79 individuals per million population (PMP) in 2014 to 309 PMP in 2021. Concurrent heart failure (HF), acute myocardial infarction (AMI), diabetes, and essential hypertension were prevalent in 50%, 27%, 27%, and 26% of the PAD patients, respectively. Competing Risk Analysis showed a subdistribution hazard ratio (SHR) of 6.53 [95% CI: 4.65-9.19] for individuals over 80 years. Heart failure was associated with lower all-cause HR [0.80, 95% CI: 0.76-0.86, p < 0.001] but higher SHR [1.30, 95% CI: 1.18-1.44, p < 0.001]. Comorbidities such as heart failure, stroke, and acute myocardial infarction significantly increased mortality risks, while essential hypertension was associated with lower risk of death. The significant rise in the incidence rate of PAD underscores the growing burden of the disease, highlighting the urgent need for targeted preventive and management strategies in Kazakhstan.

The relationship between serum HDL-cholesterol, cardiovascular disease and mortality in community-based people with type 2 diabetes: the Fremantle Diabetes Study phase 2

BackgroundOlder general population-based studies found an inverse association between serum HDL-cholesterol and both cardiovascular disease (CVD) events and mortality, but more recent data have suggested a U-shaped relationship. Whether this applies to type 2 diabetes is uncertain. The aim of this study was to assess the prognostic significance of serum HDL-cholesterol concentrations in representative, community-based participants from the Fremantle Diabetes Study Phase II (FDS2).MethodsWe followed 1,479 FDS2 participants with confirmed type 2 diabetes (713 females, mean age 65.6 years; 763 males, mean age 65.9 years) from entry (2008–2011) to death/end-2021. Major adverse cardiovascular events (non-fatal myocardial infarction (MI), non-fatal stroke, cardiovascular death; 3-point MACE), and all-cause mortality were ascertained from prospectively collected data and validated administrative databases. Independent associates of 3-point MACE by sex, excluding participants with prior MI/stroke, were assessed using Cox and competing risk models with sex-specific quintiles of HDL-cholesterol added to the most parsimonious models. Predictors of all-cause mortality were identified using Cox proportional hazards modelling.ResultsIn females, with baseline serum HDL-cholesterol quintile 2 (1.04–1.22 mmol/L) as reference, both quintiles 1 (< 1.04 mmol/L) and 5 (> 1.59 mmol/L) were significant independent predictors of 3-point MACE (P < 0.027) and all-cause death (P < 0.019) after adjustment for a full range of demographic, clinical and laboratory variables. In males, serum HDL-cholesterol quintile did not add to the most parsimonious model for 3-point MACE, but quintile 1 (< 0.90 mmol/L) was a significant predictor of death (P = 0.026 versus quintile 4 (1.15–1.31 mmol/L) as reference) after adjustment. Competing risk analyses for 3-point MACE showed similar results to the Cox models for both sexes.ConclusionThere was a significant U-shaped relationship between serum HDL-cholesterol and both 3-point MACE and all-cause death in females with type 2 diabetes after adjustment for confounders. There was no such relationship for 3-point MACE in males but a low HDL-cholesterol was associated with all-cause mortality. These data have sex-specific implications for assessment of serum lipid profiles in the clinical management of type 2 diabetes.

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

Evaluation of Two Different Approaches for Selecting Patients for Postoperative Radiotherapy in Deep-Seated High-Grade Soft Tissue Sarcomas in the Extremities and Trunk Wall.

Two national sarcoma centers have had different approaches for selecting patients with grade 2-3 deep-seated soft tissue sarcomas (STS) for postoperative radiotherapy (RT). We evaluated potential differences in local recurrence in patients treated at the two centers. At Sarcoma Center 1 (SC1), RT was the standard treatment for all tumors except certain small tumors excised with a margin wider than 1 cm. Sarcoma Center 2 (SC2) avoided RT for tumors regardless of tumor size if removed with a margin wider than 1 cm and/or a solid barrier. We included 386 patients (SC1/SC2 = 196/190) over 18 years of age diagnosed with a non-metastatic grade 2-3, deep-seated STS of the extremities or trunk wall, who underwent primary surgical treatment (only tumors excised with a negative margin) from 1 January 2000, to 31 December 2016. Kaplan-Meier survival analysis, competing risk analysis, and cause-specific Cox regression were applied. A total of 284 patients received primary RT, 163 (83%) at SC1 and 121 (64%) at SC2 (p < 0.001). The cumulative incidence of local recurrence at five years was 15% (95% CI: 10-19%) at SC1 and 14% (95% CI: 9-19%) at SC2. Multivariate analysis showed no significant differences in local recurrence between the centers. We concluded that when entering all available patients into the analysis using an intention-to-treat principle, a more selective approach to postoperative RT in patients with grade 2-3 deep-seated STS did not lead to a higher local recurrence rate. However, with this study design, we cannot rule out if the local recurrence rate could have been lower if RT was administered to all tumors removed with a margin wider than 1 cm and/or a solid barrier.

Effect of frail phenotype on cardiorenal risk and healthcare utilization in older patients with chronic kidney disease.

Introduction Limited data have addressed frailty's role in cardiorenal risk among older adult patients with chronic kidney disease (CKD). We investigated whether frailty could predict major renal and cardiovascular events, healthcare utilization, and mortality in these patients. Methods We conducted a prospective cohort enrolling patients ≥ 75 years with a stable estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73 m2. Frailty phenotype consists of shrinking, low activity, exhaustion, weakness, and slowness, scored 0 to 5. The primary composite renal outcome was a ≥ 25 % decrease in eGFR concurrent with CKD stage progression or dialysis initiation. Secondary outcomes included major adverse cardiovascular events (MACE), emergency room (ER) visits, all-cause mortality, and hospitalization. Using multivariate Cox models with/without competing risk analyses, we explored frailty's impact on these outcomes. Results Among 203 older CKD patients (mean age 81.6 ± 5.0 years, female 40.9 %, diabetes 33.0 %, body mass index 24.9 ± 3.7 kg/m2), 67.9% were frail. Over 3.47 years, 38.9% faced composite renal outcomes, 13.3% MACE, 15.3% mortality, and more than half utilized healthcare. Every one-point frailty elevated composite renal outcome risk by 28.0 % (HR: 1.28, 95% CI:1.03-1.59) and significantly increased secondary outcomes (hospitalization [HR: 1.24, 95% CI: 1.06-1.46], unexpected ER visit [HR: 1.20, [95% CI:1.03-1.39], and mortality [HR: 1.51, 95% CI: 1.06-2.16]) but not for MACE [HR: 1.43, 95% CI: 0.99-2.08]. Results were consistent across subgroups and competing risk analysis. Conclusion In CKD patients ≥ 75 years, frailty was associated with progressive kidney disease, increased mortality and healthcare utilization.

The effects of underlying inflammatory bowel disease on the outcomes of primary sclerosing cholangitis liver transplant recipients

IntroductionInflammatory bowel disease (IBD) influences primary sclerosing cholangitis (PSC) severity, however, the impact of IBD on PSC liver transplantation (LT) outcomes is poorly understood. We aimed to elucidate the impact of IBD in modulating PSC LT outcomes. MethodsUsing UNOS data from 2010 through 2021, we identified PSC LT candidates with and without (±) IBD. We used adjusted competing-risk regression analysis to evaluate waitlist outcomes, Kaplan-Meier analysis to assess graft survival, and Cox proportional hazards modeling to identify factors associated with graft survival. ResultsOut of 5,586 PSC candidates added to the waitlist, 3,652 patients had IBD. Older age (SHR 1.01; 95 %CI 1.01–1.02) and initial MELD/PELD (SHR 1.03; 95 %CI 1.02–1.04) were associated with increased risk of waitlist mortality, while private insurance (SHR 0.00; 95 %CI 0.00–0.01) with reduced risk. PSC-IBD LT recipients had increased prevalence of cholangiocarcinoma (4.8 % vs 3.4 %, p=0.005). Longer donor cold ischemia times (HR 1.06; 95 %CI 1.03–1.09), presence of recipient diabetes (HR 1.52; 95 %CI 1.13–2.05), and employment (HR 0.75, 95 %CI 0.60–0.94) had an increased risk of graft failure among PSC patients with IBD, not seen in those without IBD. ConclusionRegardless of IBD, LT for PSC results in excellent outcomes. Certain clinicodemographic factors impacted waitlist and recipient mortality highlighting potential targets to enhance outcomes.

The impact of non-structured PSA testing on prostate cancer-specific mortality on New Zealand Māori men

ObjectivesTo assess the impact of differences in Prostate-Specific Antigen (PSA) testing rates on prostate cancer (PCa) diagnosis and PCa-specific mortality among Māori men in a New Zealand (NZ) population.Patients and MethodsMāori men aged 40 years or older, without a history of PCa, with a PSA test between 2006 and 2018 were included. The cohort was divided into two groups; the “screened group” (ScG) consisting of men who had at least one PSA test every four years or less, and the “non-screened group” (non-SG). We measured the rate of cancer diagnoses and used competing risk analysis to assess survival.ResultsThe study cohort included 63,939 Māori men, with 37,048 (58%) in the ScG. PCa was more frequently diagnosed in the ScG (3.7% vs. 3.0%, P < 0.001). A higher proportion of high-grade cancers were found in the non-SG (32.7% vs. 25.6%, P = 0.001). The 10-year cancer-specific survival was significantly higher in the ScG (99.4% vs. 98.5%, P < 0.001). In a multivariable risk model, PSA testing frequency was an independent predictor of PCa mortality. (HR 2.43, [95% CI 1.97–3.01], P < 0.001).ConclusionsIn a cohort of only Māori men, lower PSA testing rates were associated with a higher risk of PCa-related death. Therefore, regular PSA testing for Māori could improve cancer-specific survival among Māori men. Regular PSA testing should be considered a priority area for improving PCa survival in this population.

Recurrent Clostridioides difficile infections in solid organ transplant recipients: The international CALIPSO study

To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n=114,59.7%), vancomycin+metronidazole (n=39,20.4%), metronidazole (n=26,13.6%), fidaxomicin (n=9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p<.001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p=.001) were factors independently associated with recurrence. Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.

Microwave Ablation of Refractory Oligometastatic Non–Small Cell Lung Cancer in the Liver

PurposeTo evaluate safety and effectiveness of microwave ablation (MWA) in the treatment of liver metastases (LMs) secondary to non–small cell lung cancer (NSCLC). Materials and MethodsThis retrospective study included patients with NSCLC who underwent MWA of LM from March 2015 to July 2022. Local tumor progression-free survival (LTPFS) and overall survival (OS) were estimated using competing risk analysis and the Kaplan-Meier method. Postprocedural adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. ResultsTwenty-three patients with 32 LMs were treated in 27 MWA sessions. The mean dimension of the largest index tumor was 1.96 cm (SD ± 0.75). Technical success was 100%. Technical effectiveness was achieved in 26 (81.3%) of 32 tumors. The median length of follow-up was 37.7 months (interquartile range, 20.5–54.5 months). The median LTPFS was 16.3 months (95% confidence interval [CI], 7.87–44.10 months). The median OS was 31.7 months (95% CI, 11.1–65.8 months). Ablation margin was a significant factor for LTPFS, with tumors ablated without a measurable margin being more likely to progress than those with measurable margins (subdistribution hazard ratios [HRs], 0.008–0.024; P < .001). Older age (HR, 1.18; 95% CI, 1.09–1.28; P < .001) and presence of synchronous lung metastases (HR, 14.73; 95% CI, 1.86–116.95; P = .011) were significant predictors of OS. Serious adverse events (CTCAE Grade ≥3) within 30 days occurred in 2 (7.4%) of 27 sessions, including pulmonary embolus and severe abdominal pain. ConclusionsPercutaneous MWA is a safe treatment for NSCLC LM, with longer survival noted in younger patients and those without synchronous lung tumors.

Prognostic Value of Pulmonary Artery Systolic Pressure in Severe Rheumatic Mitral Stenosis.

Current guidelines recommend intervention for asymptomatic rheumatic mitral stenosis (MS) with mitral valve area ≤1.5 cm2 based on indicators including pulmonary arterial systolic pressure (PASP) >50 mm Hg and new-onset atrial fibrillation; however, evidence supporting this is lacking. This single-center retrospective study included patients with rheumatic MS between 2006 and 2022. Pulmonary hypertension was evaluated by using echocardiography to estimate PASP. Primary outcomes were major adverse cardiovascular events (MACE), including all-cause mortality, hospitalization for heart failure, and arterial thromboembolic events for up to 5 years. Overall, 287 patients with severe rheumatic MS were enrolled (mean age, 62.5±11.3 years; 74.6% women). During a median follow-up of 2.52 years, MACE occurred in 99 patients. There were no differences in echocardiographic parameters, such as the mean mitral valve pressure gradient, mitral valve area, and proportion of mitral valve area <1.0 cm2, between patients who developed primary outcomes and those who did not. Survival analysis showed a worse prognosis in patients with estimated PASP (ePASP) >50 mm Hg than in those with ePASP ≤50 mm Hg (log-rank P<0.001); however, atrial fibrillation was not a significant prognostic indicator. As a continuous variable, ePASP (mm Hg) was a significant predictor of MACE (adjusted hazard ratio, 1.027 [95% CI, 1.011-1.042]; P<0.001). Receiver operating characteristic analysis revealed an optimal ePASP threshold of >45 mm Hg, which was an independent predictor of MACE in patients with severe rheumatic MS (adjusted hazard ratio, 2.127 [95% CI, 1.424-3.177]; P<0.001). Competing risk analysis considering mitral valve intervention as a competing risk showed similar results. Our study demonstrated the prognostic significance of ePASP, rather than atrial fibrillation, in relation to MACE among patients with severe rheumatic MS. Additionally, we proposed a lower ePASP threshold (>45 mm Hg) as a predictor of an unfavorable prognosis.

Prognostic Impact of Non–Predominant Lepidic Components in Pathologic Stage I Invasive Nonmucinous Adenocarcinoma

IntroductionThis study investigated the prognostic impact of non–predominant lepidic components in invasive nonmucinous adenocarcinoma. MethodsPatients who underwent lobectomy and were diagnosed with pathologic stage I nonmucinous, non–lepidic-predominant invasive adenocarcinoma were included. Tumors were staged according to the eighth edition of TNM classification and categorized on the basis of the presence of lepidic components in the final pathology. Overall survival (OS) and recurrence-free survival (RFS) were analyzed before and after applying inverse probability of treatment weighting. Competing risk analyses for recurrence were also compared in the two groups. ResultsOf the 1270 patients, 858 (67.6%) had lepidic components (+). The pathologic stage and histologic grade were higher in the lepidic (−) group (p < 0.001, respectively). The 5-year OS and RFS were significantly worse in the lepidic (−) group than in the lepidic (+) group (OS: 88.2% versus 94.9%, p < 0.001; RFS: 79.4% versus 91.9%, p < 0.001). These trends were consistent after weighted analysis (OS: 92.4% versus 96.4%, p = 0.029; RFS: 85.6% versus 92.3%, p = 0.007). The 5-year cumulative incidence of any recurrence was 14.0% in the lepidic (−) group and 4.1% in the lepidic (+) group (p < 0.001). Multivariable Fine-Gray regression analysis found that the lepidic (+) group exhibited a lower risk of recurrence than did the lepidic (−) group (hazard ratio = 0.52, 95% confidence interval: 0.29–0.93, p = 0.031). ConclusionsIn pathologic stage I invasive nonmucinous adenocarcinoma, the presence of histologically diagnosed non–predominant lepidic components might be associated with a better prognosis after curative surgery.