1-year Hazard Ratio Research Articles

Evaluating the Impact of Post-Esophagectomy Exercise on 2- and 5-Year Survival: Findings from the PERFECT Trial.

Despite recent treatment advances, esophageal cancer still has poor survival and a high morbidity. Exploratory evidence suggests that exercise can reduce cancer-related mortality and recurrence rates. Here, we investigated the effects of an exercise intervention in the first year after esophagectomy on survival in participants of the Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT)-trial. In the PERFECT-trial, esophageal cancer patients who had undergone esophagectomy were randomized to a 12-week exercise program (EX) or the control group (CG). We assessed 2- and 5-year (progression-free) survival. (Un)adjusted Cox Proportional-Hazards models were used to calculate hazard ratios (HRs) for comparison between the trial arms. Sensitivity analyses, excluding patients with events within the exercise intervention period, were performed. In total, 120 participants (EX = 61; CG = 59) were included in the PERFECT-trial. After 2-year follow-up, no significant difference in the risk of death or progression between EX and CG was found (adjusted HR = 1.65, 95% CI [0.75-3.63] and 1.38, 95% CI [0.76-2.50], respectively). After excluding patients with events during the intervention period (EX = 8; CG = 4), 2-year HRs for death (1.03, 95% CI [0.41-2.56]) and progression (1.26, 95% CI [0.64-2.48]) both decreased and remained insignificant. No significant effects were found on 5-year mortality (1.03, 95% CI [0.57-1.84]) and progression (1.21, 95% CI [0.72-2.04]) either. Sensitivity-analysis resulted in attenuated 5-year HRs for mortality (0.82, 95% CI [0.42-1.58]) and progression (1.08, 95% CI [0.61-1.92]). The results indicate no benefit of a 12-week exercise program in the first year post-esophagectomy on 2- and 5-year (progression-free) survival in esophageal cancer patients. The absence of beneficial effects may be explained by the relatively short exercise program, which was performed after treatment completion.

No Increased Risk of All-cause Revision up to 10 Years in Patients Who Underwent Bariatric Surgery Before Single-level Lumbar Fusion.

Retrospective cohort study. This study aimed to assess whether prior bariatric surgery (BS) is associated with higher 10-year surgical complication and revision rates in lumbar spine fusion compared with the general population and morbidly obese patients. Obesity accelerates degenerative spine processes, often necessitating lumbar fusion for functional improvement. BS is explored for weight loss in lumbar spine cases, but its impact on fusion outcomes remains unclear. Existing literature on BS before lumbar fusion yields conflicting results, with a limited investigation into long-term spine complications. Utilizing the PearlDiver database, we examined patients undergoing elective primary single-level lumbar fusion, categorizing them by prior BS. Propensity score matching created cohorts from (1) the general population without BS history and (2) morbidly obese patients without BS history. Using Kaplan-Meier and Cox proportional hazard modeling, we compared 10-year cumulative incidence rates and hazard ratios (HRs) for all-cause revision and specific revision indications. Patients who underwent BS exhibited a higher cumulative incidence and risk of decompressive laminectomy and irrigation & debridement (I&D) within 10 years postlumbar fusion compared with matched controls from the general population [decompressive laminectomy: HR = 1.32; I&D: HR = 1.35]. Compared with matched controls from a morbidly obese population, patients who underwent BS were associated with lower rates of adjacent segment disease (HR = 0.31) and I&D (HR = 0.64). However, the risk of all-cause revision within 10 years did not increase for patients who underwent BS compared with matched or unmatched controls from the general population or morbidly obese patients (P > 0.05). Prior BS did not elevate the 10-year all-cause revision risk in lumbar fusion compared with the general population or morbidly obese patients. However, patients who underwent BS were associated with a lower 10-year risk of I&D when compared with morbidly obese patients without BS. Our study indicates comparable long-term surgical complication rates between patients who underwent BS and these control groups, with an associated reduction in risk of infectious complications when compared with morbidly obese patients. Although BS may address medical comorbidities, its impact on long-term lumbar fusion revision outcomes is limited.

Abstract Mo050: Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: Evidence From a Nationwide Nested Case-Control Study Paralleled With Matched Experimental Models

Background and Aims: Fluoroquinolones (FQ) have been linked to aortic aneurysms and dissections (AA/AD), resulting in an official warning. However, recent large-scale epidemiological studies have reported lack of FQ-AA/AD association. This study aimed to scrutinize FQ-AA/AD risk by implementing a combined epidemiological and experimental approach. Methods: Danish nationwide registers (2003-2021) were used for a nested case-control analysis. FQ-AA/AD risk was evaluated in a main and high-risk FDA cohort. Further, mortality and aortic interventions linked to FQ were investigated in patients with aortic disease. Additionally, ciprofloxacin (100 mg/kg/day, 2x2 weeks) was administered to wild-type, hypertensive or Marfan mice. Aortic diameters and pulse wave velocity (PWV) were measured longitudinally to investigate aortic remodelling. Results: The main cohort comprised 5.10 million individuals with 58,919 cases and 1,767,510 sampled controls. Compared with amoxicillin exposure. FQ exposure was not associated with increased AA/AD risk (30-day hazard ratios (HR) 1.00 [95% confidence intervals (CI): 0.74-1.34]; 90-day HR 1.07 [CI 0.94-1.22]; 1-year HR 0.95 [0.90-1.01]). In a high-risk cohort, there was no FQ-AA/AD association (30-day HR 0.83 [0.61-1.12]; 90-day HR 0.99 [0.86-1.15]; 1-year HR 0.97 [0.90-1.05]). In patients with aortic disease, FQ were not associated with increased aortic interventions or mortality (30-day HR 0.98 [0.79-1.22]; 90-day HR 1.06 [0.95-1.19]). Additionally, ciprofloxacin did not affect aortic diameters or PWV in wild type, hypertensive, and Marfan mice, while differences between models proved the sensitivity of the methodology. Conclusion: The data clearly do not support the current precautions and warnings pertaining to risks of aortopathies and FQ should not be discouraged when clinically indicated.

Cardiovascular Burden of the V142I Transthyretin Variant

Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments. To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population. A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024. V142I carrier status (n = 754, 3.2%). Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data. Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant. Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.

Chronic Oral Corticosteroid Use and 10-Year Incidence of Major Complications Following Total Knee Arthroplasty

BackgroundOral corticosteroids are the primary treatment for several autoimmune conditions. The risk of long-term implant, bone health, and infectious-related complications in patients taking chronic oral corticosteroids before total knee arthroplasty (TKA) is unknown. We compared the 10-year cumulative incidence of revision, periprosthetic joint infection (PJI), fragility fracture (FF), and periprosthetic fracture following TKA in patients who had and did not have preoperative chronic oral corticosteroid use. MethodsA retrospective cohort analysis was conducted using a national database. Primary TKA patients who had chronic preoperative oral corticosteroid use were identified using Current Procedural Terminology and International Classification of Disease 9 and 10 codes. Exclusion criteria included malignancy, osteoporosis treatment, trauma, and < 2-year follow-up. Primary outcomes were 10-year cumulative incidence and hazard ratios (HRs) of all-cause revision (ACR), aseptic revision, PJI, FF, and periprosthetic fracture. A Kaplan-Meier analysis and a multivariable Cox proportional hazards model were utilized. Overall, 611,596 patients were identified, and 5,217 (0.85%) were prescribed chronic corticosteroids. There were 10,000 control patients randomly sampled for analysis. ResultsCorticosteroid patients had significantly higher 10-year HR of FF (HR; 95% confidence interval); P value (1.47; 1.34 to 1.62; P < .001)], ACR (1.21; 1.05 to 1.40; P = .009), and PJI (1.30; 1.01 to 1.69; P = .045) when compared to the control. ConclusionsPatients prescribed preoperative chronic oral corticosteroids had higher risks of ACR, PJI, and FF within 10 years following TKA compared to patients not taking corticosteroids. This information can be used by surgeons during preoperative counseling to educate this high-risk patient population about their increased risk of postoperative complications.

(147) Analysis of Sexual Dysfunction Development among Male and Female Living Kidney Donors

Abstract Introduction The need for kidney donations in patients with end-stage kidney disease has continued to exceed the number of deceased donor transplants, signifying the need for the continued growth, sustainability, and success of living kidney donation. Following donation, living kidney donors have excellent survival rates with mixed data regarding long-term outcomes of renal failure, hypertension, and proteinuria. However, no studies to our knowledge have looked at differences in the development of long-term sexual dysfunction following living kidney donation, a potentially serious quality of life issue. Objective To analyze differences in five-year sexual dysfunction outcomes among male and female living kidney donors using the US Collaborative Network within the TriNetX database, a federated network of EMR data from multiple healthcare organizations across the United States. Methods We used the TriNetX database to perform a propensity score-matched cohort study comparing five-year outcomes of sexual dysfunction development among adult (≥18) male living kidney donors (Male) and female living kidney donors (Female) from December 2013 to December 2022. Living kidney donors were defined as the presence of one diagnostic code and one procedural code. Patients were excluded from the study if they had any instance of diagnosed transplant status (by ICD-10) or transplantation procedures (by CPT) prior to the kidney donor status. Patients were matched on age, sex, race, ethnicity, marital status, diabetes mellitus, cardiovascular disease, personal history of genitourinary disease, presence of urogenital implants, mood disorders, BMI, tobacco and alcohol use, and problems related to lifestyle and socioeconomic circumstances. Primary outcomes analysis included 5-year hazard ratio of diagnosed decreased libido, sexual dysfunction (composite of new diagnosed male ED, vaginismus/dyspareunia, infertility, orgasmic disorders, arousal/desire disorders, or unspecified), UTI, and STDs. Secondary outcomes included sex counseling or problems in relationship with spouse or partner. Results There were 2,821 patients in each cohort after matching (Male, Female). Mean age of the cohort was 42.7 ± 12.7, 73.3% were White, and 10.8% were Hispanic/Latino (p &amp;gt;0.05). At 5-years, Kaplan-Meier analysis revealed that the Male donor cohort had a significantly higher hazard ratio (HR) than Female donors for sexual dysfunction (HR: 3.006, 95% Confidence Interval [CI]: 1.761,5.131). Between the cohorts, 39 (1%) Male patients developed ED and ~10 (&amp;lt;1%) Female patients developed vaginismus/dyspareunia within 5 years. No significant difference was found for the development of sexual arousal disorders/desire disorders (0.17% vs 0.06%, p = 0.052), orgasmic disorders (0.03% vs 0.03%, p = 0.99), decreased libido (0.48% vs 0.85%, p =0.94) and STD’s (0.72% vs 0.89%, p = 0.70). For secondary outcomes, no significant difference was found for the 5-year hazard of need for sex counseling or interpersonal relationship issues. Conclusions In our analysis of this large, real-world database, we found that male living kidney donors had higher rates of sexual dysfunction development 5-years post-living kidney donation. While living kidney donation is a safe, viable, and excellent alternative to deceased kidney donation, clinicians and living donors should both be aware about the potential association of developing sexual dysfunction post-donation. Disclosure No.

(269) Analysis of Sexual Dysfunction Development Among Male and Female Living Kidney Donors

Abstract Introduction The need for kidney donations in patients with end-stage kidney disease has continued to exceed the number of deceased donor transplants, signifying the need for the continued growth, sustainability, and success of living kidney donation. Following donation, living kidney donors have excellent survival rates with mixed data regarding long-term outcomes of renal failure, hypertension, and proteinuria. However, no studies to our knowledge have looked at differences in the development of long-term sexual dysfunction following living kidney donation, a potentially serious quality of life issue. Objective To analyze differences in five-year sexual dysfunction outcomes among male and female living kidney donors using the US Collaborative Network within the TriNetX database, a federated network of EMR data from multiple healthcare organizations across the United States. Methods We used the TriNetX database to perform a propensity score-matched cohort study comparing five-year outcomes of sexual dysfunction development among adult (≥18) male living kidney donors (Male) and female living kidney donors (Female) from December 2013 to December 2022. Living kidney donors were defined as the presence of one diagnostic code and one procedural code. Patients were excluded from the study if they had any instance of diagnosed transplant status (by ICD-10) or transplantation procedures (by CPT) prior to the kidney donor status. Patients were matched on age, sex, race, ethnicity, marital status, diabetes mellitus, cardiovascular disease, personal history of genitourinary disease, presence of urogenital implants, mood disorders, BMI, tobacco and alcohol use, and problems related to lifestyle and socioeconomic circumstances. Primary outcomes analysis included 5-year hazard ratio of diagnosed decreased libido, sexual dysfunction (composite of new diagnosed male ED, vaginismus/dyspareunia, infertility, orgasmic disorders, arousal/desire disorders, or unspecified), UTI, and STDs. Secondary outcomes included sex counseling or problems in relationship with spouse or partner. Results There were 2,821 patients in each cohort after matching (Male, Female). Mean age of the cohort was 42.7 ± 12.7, 73.3% were White, and 10.8% were Hispanic/Latino (p &amp;gt;0.05). At 5-years, Kaplan-Meier analysis revealed that the Male donor cohort had a significantly higher hazard ratio (HR) than Female donors for sexual dysfunction (HR: 3.006, 95% Confidence Interval [CI]: 1.761,5.131). Between the cohorts, 39 (1%) Male patients developed ED and ~10 (&amp;lt;1%) Female patients developed vaginismus/dyspareunia within 5 years. No significant difference was found for the development of sexual arousal disorders/desire disorders (0.17% vs 0.06%, p = 0.052), orgasmic disorders (0.03% vs 0.03%, p = 0.99), decreased libido (0.48% vs 0.85%, p =0.94) and STD’s (0.72% vs 0.89%, p = 0.70). For secondary outcomes, no significant difference was found for the 5-year hazard of need for sex counseling or interpersonal relationship issues. Conclusions In our analysis of this large, real-world database, we found that male living kidney donors had higher rates of sexual dysfunction development 5-years post-living kidney donation. While living kidney donation is a safe, viable, and excellent alternative to deceased kidney donation, clinicians and living donors should both be aware about the potential association of developing sexual dysfunction post-donation. Disclosure No.

Association of adverse cardiovascular events with gabapentin and pregabalin among patients with fibromyalgia.

Fibromyalgia, a chronic pain disorder, impacts approximately 2% of adults in the US. Gabapentin and pregabalin are common treatments to manage fibromyalgia-related pain. Our recent study showed the risk of adverse cardiovascular events increased in diabetic neuropathy patients who were prescribed gabapentin or pregabalin. Here, we investigated whether the prescription of gabapentin or pregabalin has similar cardiovascular risk in patients with fibromyalgia. This retrospective cohort study leveraged electronic health records from 64 US healthcare organizations with 112 million patients. The study population included 105,602 patients first diagnosed with fibromyalgia and followed by a prescription of gabapentin, pregabalin, or other FDA-approved drugs for treating fibromyalgia from 2010 to 2019. Outcomes were deep venous thrombosis (DVT), myocardial infarcts (MI), peripheral vascular disease (PVD), strokes, heart failure, and pulmonary embolism (PE). In propensity-score-matched cohorts, 1-year and 5-year hazard ratios (HRs) were computed with their respective 95% confidence intervals (CIs). Additionally, we conducted sensitivity analyses on the subpopulations without other possible indications. For 5-year follow-up, gabapentin increased the risk of PVD (HR = 1.46, 95% CI = 1.17-1.80), MI (HR = 1.31, 95% CI = 1.03-1.66), heart failure (HR = 1.27, 95% CI = 1.10-1.48), DVT (HR = 1.80, 95% CI = 1.33-2.44), and PE (HR = 2.23, 95% CI = 1.62-3.07). Pregabalin increased the risk of DVT (HR = 1.49, 95% CI = 1.01-2.20), and PE (HR = 2.24, 95% CI = 1.43-3.50). For 1-year follow-up, gabapentin increased the risk of PVD (HR = 1.32, 95% CI = 1.11-1.57), DVT (HR = 1.35, 95% CI = 1.09-1.68), and PE (HR = 1.36, 95% CI = 1.17-1.57). Pregabalin increased the risk of PVD (HR = 1.32, 95% CI = 1.06-1.63) and PE (HR = 1.25, 95% CI = 1.03-1.52). Sensitivity analyses showed similar trends. In fibromyalgia patients, the prescription of gabapentin and pregabalin moderately increased the risk of several adverse cardiovascular events. This risk, together with benefits and other adverse reactions, should be considered when prescribing these medications for fibromyalgia patients.

Risk of Postoperative Ischemic Stroke and Myocardial Infarction in Patients Operated for Cancer.

Risk assessment for ischemic stroke (IS) and myocardial infarction (MI) is done routinely before surgery, but the increase in risks associated with surgery is not known. The aim of this study is to assess the risk of arterial ischemic events during the first year after oncological surgery. We used Swedish healthcare databases to identify 443,300 patients who underwent cancer surgery between 1987 and 2016 and 4,127,761 matched comparison subjects. We estimated odds ratios (ORs) for myocardial infarction and ischemic stroke during the hospitalization with logistic regression and calculated 1-year cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) for the outcomes after discharge. The cumulative incidences of myocardial infarction and ischemic stroke during the first postoperative year were 1.33% and 1.25%, respectively. In the comparison cohort, the corresponding 1-year cumulative incidences were 1.04% and 1.00%. During the hospitalization, the OR for myocardial infarction was 8.81 (95% CI 8.24-9.42) and the OR for ischemic stroke was 6.71 (95% CI 6.22-7.23). After discharge, the average HR during follow-up for 365 days was 0.90 (95% CI 0.87-0.93) for myocardial infarction and 1.02 (95% CI 0.99-1.05) for ischemic stroke. We found an overall increased risk of IS and MI during the first year after cancer surgery that was attributable to events occurring during the hospitalization period. After discharge from the hospital, the overall risk of myocardial infarction was lower among the cancer surgery patients than among matched comparison subjects.

Incidence, predictors, and prognostic impact of rehospitalization after transcatheter aortic valve implantation.

Despite rehospitalization being common after transcatheter aortic valve implantation (TAVI), an in-depth analysis on this topic is missing. This study sought to report on the incidence, predictors, and prognostic impact of rehospitalization within 1 year following TAVI. All consecutive patients treated with TAVI between 2016 and 2020 in East Denmark were included. Medical records of all patients were reviewed to validate rehospitalizations up to 1 year after discharge from the index admission. The study population consisted of 1397 patients, of whom 615 (44%) had an unplanned rehospitalization within the first year post-TAVI. The rehospitalization incidence rate was three-fold higher in the early period (within 30 days) compared with the late period (30 days to 1 year; 2.5 vs. 0.8 per patient-year, respectively; P<0.001). Predictors of early unplanned rehospitalization were procedure-related complications and prior stroke, whereas late unplanned rehospitalization was associated with preexisting comorbidities. Predictors of heart failure (HF) rehospitalization included ischaemic heart disease, the extent of cardiac damage, atrial fibrillation, and New York Heart Association class at baseline. HF rehospitalization within 30 days and 1 year post-TAVI was associated with a markedly increased 1- and 5-year mortality risk [hazard ratio (HR) of 4.3 and 3.2 for 1-year mortality and HR of 3.2 and 2.9 for 5-year mortality, respectively; P<0.001]. Rehospitalization after TAVI is frequent in real-world practice. Early rehospitalization is mostly procedure related, whereas late rehospitalization is related to preexisting comorbidities. HF rehospitalization is associated with poor long-term survival and could be validated as a prognostically relevant endpoint for TAVI trials.

Abstract 19130: Is Early Hospital Discharge Safe After Adult Heart Transplantation?

Introduction: The impact of early hospital discharge (EHD) after adult heart transplantation (HT) on longitudinal outcomes is unclear. Many HT recipients are intentionally kept in the hospital for extended stays for continued clinical monitoring. However, there is growing interest in implementing EHD protocols and initiatives to improve patient throughput, optimize hospital resources and bed capacity, and reduce costs. Hypothesis: This study evaluated the impact of EHD on HT outcomes. Methods: The United Network for Organ Sharing (UNOS) database was utilized to identify adult (≥ 18 years old) HT recipients surviving to hospital discharge between January 2010 and December 2022. EHD was defined as occurring within 7 days of HT. Kaplan-Meier analysis was used to estimate survival probability of EHD recipients at 30-days, 90-days, 1-year, 1-year conditional on 30-day survival and 1-year conditional on 90-day survival. Multivariable Cox regression was used for risk adjustment. Results: Of the 31,638 total HTs performed in the study period, 30,720 (97.1%) survived to hospital discharge of which 1,033 (3.36%) were classified as EHD. In an unadjusted analysis, HT recipients survival rates were: [(30-days: ED 99.5% vs non-EHD 98.4%, log-rank p= 0.004), (90-days: EHD 98.8% vs non-EHD 96.4%, log-rank p&lt; 0.001), (1-year: EHD 96.5% vs non-EHD 92.9%, log-rank p&lt; 0.001), (1-year conditional on 30-day survival: EHD 96.9% vs non-EHD 94.5%, log-rank p&lt; 0.001), and (1-year conditional on 90-day survival: EHD 97.6% vs non-EHD 96.4%, log-rank p= 0.036)] (Figure 1). After risk adjustment, the Hazard Ratio (HR) of mortality for EHD recipients was: [30-days HR: 0.37 (0.15-0.89, p=0.027), 90-days HR: 0.39 (0.22-0.70, p=0.001), 1-year HR: 0.57 (0.39-0.82, p=0.003), 1-year conditional on 30-day survival HR: 0.60 (0.40-0.90, p=0.013), and 1-year conditional on 90-day survival HR: 0.75 (0.47-1.18, p=0.213)]. Conclusions: HT patients with EHD have lower complication rates than non-EHD patients. Although a minority of patients have EHD after HT, these data suggest it can be done safely with excellent longitudinal outcomes. Efforts to share best practices and protocols allowing for EHD may be prudent to broadening this practice nationwide in appropriate cases.

Significance of 8-OHdG Expression as a Predictor of Survival in Colorectal Cancer.

The incidence of colorectal cancer (CRC) is increasing worldwide. 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the most prevalent DNA alterations, is known to be upregulated in several carcinomas; however, 8-OHdG has not been used to predict the prognosis of patients with CRC. We aimed to determine 8-OHdG levels in patients with CRC using immunohistochemistry and conducted a survival analysis according to the pathological stage. The 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs) of the low 8-OHdG subgroup were 1.41 (95% confidence interval (CI): 1.01-1.98, p = 0.04) and 1.60 (95% CI: 1.12-2.28, p = 0.01), respectively. When tumor node metastasis (TNM) staging and 8-OHdG expression were combined, the 5-year EFS and DSS HRs of patients with CRC with low 8-OHdG expression cancer at the same TNM stage (stage Ⅲ/Ⅳ) were 1.51 (95% CI: 1.02-2.22, p = 0.04) and 1.64 (95% CI: 1.09-2.48, p = 0.02), respectively, compared to those with high 8-OHdG expression cancer, indicating a poor prognosis. Therefore, low 8-OHdG expression is a significant predictive factor for 5-year EFS and DSS in patients with CRC, and it can serve as an essential biomarker of CRC.

The association between the Mediterranean Diet Score and death from cancer of the head and neck.

The association between diet quality, captured by the Mediterranean Diet Score (MDS), and mortality was studied among 1184 individuals diagnosed with head and neck cancer (HNC) who reflected on the year preceding diagnosis about their usual diet using National Cancer Institute's Diet History Questionnaire (DHQ). Intakes of nine dietary components were scored and summed to construct the MDS (sample: median = 4; range (0-9); lower MDS reflected poorer diet quality; 5-year survival probability = 0.62). Cox regression estimated 5-year hazard ratios (HR) and 95% confidence intervals (95CI) for all-cause mortality and for HNC-specific death for contrasts of MDS quintiles. Effect measure modification (EMM) by tumor features [human papillomavirus (HPV) positivity; anatomic site] and sociodemographic behavioral factors [race, body mass index (BMI), smoking, alcohol consumption] was explored. The 5-year [HR (95CI); P-trend] for all-cause mortality and HNC-specific mortality for highest versus lowest MDS quintile contrasts were [0.51 (0.33, 0.80); 0.014] and [0.43 (0.22, 0.85); 0.004], respectively. A unit increase in MDS adherence resulted in a 15% reduction of the 5-year HR for HNC-specific death for tumors located at the oral cavity [HR (95CI): 0.85 (0.75, 0.96)]. Poor diet quality (MDS ≤ 4) interacted with lower BMI (kg/m2 < 25) and separately with ever-using alcohol to produce 5-year HRs for all-cause and HNC-specific mortality that were statistically significantly larger than the sum of the individual HRs representing each combination (Poor diet quality + lower BMI; Poor diet quality + ever-using alcohol). Greater adherence to a Mediterranean diet pattern prior to HNC diagnosis may reduce post-diagnosis mortality.

Dynamic evaluation based on acute-on-chronic liver failure predicts survival of patients after liver transplantation: a cohort study.

Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation survival. This study included 637 adults (overall cohort) with benign end-stage liver diseases. We compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF3 were defined as ACLF-3 cohort (n = 158). The primary outcome was 1-year mortality. ΔMELD and ΔCLIF-OF represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve (AUC). Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality. Patients were grouped as deterioration group, stable group, and improvement group. The deterioration group (ΔCLIF-OF ≥ 2) was more likely to receive national liver allocation (P=0.012) but experienced longer cold ischemia time (P=0.006) than other groups. The AUCs for ΔCLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to ΔMELD (P<0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of deterioration group were 12.57 (6.72-23.48) for overall cohort and 7.00 (3.73-13.09) for ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), ΔCLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while ΔCLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF3 patients showed a higher survival rate than patients with ACLF-3 in all groups (P=0.002 for I, P=0.005 for S and P=0.001 for D). This was the first ACLF-based dynamic evaluation study. ΔCLIF-OF was a more powerful predictor of post-LT mortality than ΔMELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, ΔCLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.

Diabetes Interacts with Latinx/Hispanic Ethnicity to Increase Major Amputations After Peripheral Vascular Intervention for Chronic Limb-threatening Ischemia

Latinx/Hispanic patients treated for chronic limb-threatening ischemia (CLTI) have higher amputation rates after controlling for presenting Wound, Ischemia, and foot Infection (WIfI) status. We hypothesize that a higher incidence of diabetes mellitus (DM) in Latinx/Hispanic patients may contribute to this disparity. The Vascular Quality Initiative peripheral vascular intervention dataset (2016-2022) was queried for CLTI. Inclusion criteria were reported WIfI stage and White race or Latinx/Hispanic ethnicity. The primary endpoint was 1-year major amputation (through tibia/fibula or more proximally). A multivariate hierarchical Fine Gray analysis was performed controlling for hospital-level variation and competing risk of death. The analysis was stratified by WIfI stage, and DM was treated as an interaction term with race and ethnicity. Overall, 38,079 (45%) cases met inclusion criteria and 3247 (12%) were Latinx/Hispanic with a higher incidence of DM in Latinx/Hispanic patients (77% vs 61%; P < .01). Proportions of WIfI stages were similar between White race and Latinx/Hispanic ethnicity, respectively: stage 1 (29% vs 30%), stage 2 (38% vs 32%), stage 3 (19% vs 21%), and stage 4 (14% vs 18%). The cumulative incidence of major amputation was highest for Latinx/Hispanic patients with DM (Figure). On multivariate analysis, the 1-year subdistribution hazard ratio (SHR) for amputation was highest for Latinx/Hispanic patients with DM at 1.8 (95% confidence interval [CI], 1.3-2.4; P < .01); and 1.4; 95% CI, 0.7-2.6; P = .29) for Latinx/Hispanic without DM, and 1.4 (95% CI, 1.1-1.6; P < .01) for White race with DM compared to White race without DM. When stratified by WIfI stage, the interaction of Latinx/Hispanic ethnicity with DM conferred the greatest increase in 1-year SHR for WIfI stages 2 (SHR, 1.9; 95% CI, 1.1-3.2; P = .03) and 3 (SHR, 2.1; 95% CI, 1.2-3.7; P < .01), compared to White race without DM. Latinx/Hispanic ethnicity requiring insulin treatment for DM had the highest hazard of amputation (SHR, 2.0; 95% CI, 1.4-2.7; P < .01) (Table). The increase in major amputations for Latinx/Hispanic patients after peripheral vascular intervention for CLTI is modified by the interaction with DM with a stepwise increase for those requiring insulin treatment. This study suggests that DM prevention and treatment is a cornerstone in addressing disparities for Latinx/Hispanic patients with limb threat and reducing their amputation risk.TableSubdistribution hazard ratios (SHR) by diabetes mellitus (DM) TreatmentSHR95% CIP valueWhite racea Diet controlled0.80.5-1.2.29 Noninsulin treatment1.20.9-1.6.07 Insulin treatment1.51.2-1.8<.01Latinx/Hispanic ethnicitya No DM diagnosis1.40.8-2.6.29 Diet controlled1.50.6-3.8.26 Noninsulin treatment1.50.9-2.5.09 Insulin treatment2.01.4-2.7<.01CI, Confidence interval.Model adjusted for age, primary insurer, WIfI stage, end-stage renal disease, prior amputation, and intervention level. Boldface entries indicate statistical significance.aReference group for all: White race with no DM diagnosis. Open table in a new tab

FFR CT and Static Computed Tomography Myocardial Perfusion Imaging for Therapeutic Decision-making and Prognosis in Patients With Coronary Artery Disease.

The purpose of this study was to investigate the effect of integrated evaluation of resting static computed tomography perfusion (CTP) and coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR CT ) on therapeutic decision-making and predicting major adverse cardiovascular events (MACEs) in patients with suspected coronary artery disease. In this post hoc analysis of a prospective trial of CCTA in patients assigned to either CCTA or CCTA plus FFR CT arms, 500 patients in the CCTA plus FFR CT arm were analyzed. Both resting static CTP and FFR CT were evaluated by using the conventional CCTA. Perfusion defects in the myocardial segments with ≥50% degree of stenosis in the supplying vessels were defined as resting static CTP positive, and any vessel with an FFR CT value of ≤0.80 was considered positive. Patients were divided into 3 groups: (1) negative CTP-FFR CT match group (resting static CTP-negative and FFR CT -negative group); (2) mismatch CTP-FFR CT group (resting static CTP-positive and FFR CT -negative or resting static CTP-negative and FFR CT -positive group); and (3) positive CTP-FFR CT match group (resting static CTP-positive and FFR CT -positive group). We compared the revascularization-to-invasive coronary angiography ratio and the MACE rate among 3 subgroups at 1- and 3-year follow-ups. The adjusted Cox hazard proportional model was used to assess the prognostic value of FFR CT and resting static CTP to determine patients at risk of MACE. Patients in the positive CTP-FFR CT match group were more likely to undergo revascularization at the time of invasive coronary angiography compared with those in the mismatch CTP-FFR CT group (81.4% vs 57.7%, P =0.033) and the negative CTP-FFR CT match group (81.4% vs 33.3%, P= 0.001). At 1- and 3-year follow-ups, patients in the positive CTP-FFR CT match group were more likely to have MACE than those in the mismatch CTP-FFR CT group (10.5% vs 4.2%, P= 0.046; 35.6% vs 9.4%, P <0.001) and the negative CTP-FFR CT match group (10.5% vs 0.9%, P <0.001; 35.6% vs 5.4%, P <0.001). A positive CTP-FFR CT match was strongly related to MACE at 1-year (hazard ratio=8.06, P= 0.003) and 3-year (hazard ratio=6.23, P <0.001) follow-ups. In patients with suspected coronary artery disease, the combination of FFR CT with resting static CTP could guide therapeutic decisions and have a better prognosis with fewer MACE in a real-world scenario.

Twenty-four-Year Trends in Incidence and Mortality of Nephrotic Syndrome: A Population-Based Cohort Study.

With the increasing prevalence of risk factors for nephrotic syndrome, updated epidemiologic data on the syndrome are needed. We examined its age- and sex-specific incidence, histopathology, and mortality over 24 years. This nationwide cohort study included all adults with first-time-recorded nephrotic syndrome in Denmark during 1995-2018 using the Danish National Patient Registry. We obtained data on age, sex, hospital-diagnosed comorbidities, and histopathologic findings. We computed overall, and age- and sex-specific, incidence rates of nephrotic syndrome, 1- and 5-year mortality by calendar period, and 1-year hazard ratios (HRs) of death using Cox models. We identified 3,970 adults with first-time nephrotic syndrome diagnosis. Incidence was highest in men and increased with age to 11.77 per 100,000 person-years (95% confidence interval [CI]: 10.21-13.32) in men aged 80+ years, and 6.56 per 100,000 person-years (95% CI: 5.71-7.41) in women aged 80+ years. Incidence of nephrotic syndrome increased from 3.35 per 100,000 person-years (95% CI: 3.12-3.58) in 1995-2000 to 4.30 per 100,000 person-years (95% CI: 4.05-4.54) in 2013-2018. Over time, 1-year mortality of nephrotic syndrome was stable at 13%-16%, but HR of death was 0.54 (95% CI: 0.42-0.69), adjusted for age, sex, and comorbidities, in 2013-2018 compared with 1995-2000. Subdistribution of glomerulopathies was stable over time with membranous nephropathy and minimal change disease being the most common. During 1995-2018, the incidence of recorded adult nephrotic syndrome increased slightly, and the adjusted mortality of nephrotic syndrome decreased markedly. Whether these findings reflect changes in epidemiology or awareness and coding of nephrotic syndrome, remains to be clarified.

The Association Between Beta-blocker and Renin–Angiotensin System Inhibitor Use After Heart Failure With Reduced Ejection Fraction Hospitalization and Outcomes in Older Patients

IntroductionBeta-blockers (BB) and renin–angiotensin system inhibitors (RASi) are foundational for the treatment of heart failure with reduced ejection fraction (HFrEF). However, given the increased risk of side effects in older patients, uncertainty remains as to whether, on net, older patients benefit as much as the younger patients studied in trials. Methods and ResultsUsing the Get With The Guidelines–Heart Failure registry linked with Medicare data, overlap propensity weighted Cox proportional hazard models were used to examine the association between BB and RASi use at hospital discharge and 30-day and 1-year outcomes among patients with HFrEF. Among the 48,711 patients (aged ≥65 years) hospitalized with HFrEF, there were significant associations between BB and/or RASi use at discharge and lower rates of 30-day and 1-year mortality, including those over age 85 (30-day hazard ratio 0.56, 95% confidence interval 0.45–0.70; 1-year hazard ratio 0.69, 95% confidence interval 0.61–0.78). In addition, the magnitude of benefit associated with BB and/or RASi use after discharge did not decrease with advancing age. Even among the oldest patients, those over age 85, with hypotension, renal insufficiency or frailty, BB and/or RASi use at discharge was still associated with lower 1-year mortality or readmission. ConclusionsAmong older patients hospitalized with HFrEF, BB and/or RASi use at discharge is associated with lower rates of 30-day and 1-year mortality across all age groups and the magnitude of this benefit does not seem to decrease with advancing age. These data suggest that, absent a clinical contraindication, BB and RASi should be considered in all patients hospitalized with HFrEF before or at hospital discharge, regardless of age.

Oral fluoroquinolones and risk of aortic dissection and aortic aneurysm: a nationwide nested case-control study

Abstract Background Oral fluoroquinolones are commonly prescribed antibiotics. Observational studies have shown an association between fluoroquinolone-use and subsequent risk of aortic aneurysm (AA) and aortic dissection (AD) due to a potential collagen degrading effect of fluoroquinolones. Purpose To investigate if fluoroquinolone-use was associated with increased rates of AA or AD in patients without known aortic disease. Secondly, to investigate if fluoroquinolone-use was associated with increased all-cause mortality and aortic interventions in high-risk patients with known aortic disease. Methods We used a nested case-control study design in which individuals aged 30–100 years from 2003 to 2018 were included from Danish nationwide registers. Exclusion criteria were bicuspid aortic valve, coarctation of the aorta, and connective tissue disease. A main cohort and a secondary high-risk cohort were defined. The main cohort comprised patients without history of AA/AD in which two case definitions were used: 1) A broad case definition of first-time AA/AD. 2) A severe case definition of ruptured AA/AD. The high-risk cohort comprised patients surviving index AA/AD admission in which cases were defined as all-cause mortality and aortic interventions. Cases were matched on age, sex, and year of inclusion in a 1:30 ratio with controls. For the main cohort, a potential dose-response effect was investigated using groups of cumulative defined daily doses (cDDD) of fluoroquinolones. Hazard ratios (HR) with 95% confidence intervals (CI) for fluoroquinolone-use compared with amoxicillin as an active comparator were obtained from time-dependent Cox regression models using multiple exposure windows. Results The main cohort comprised 4.81 million individuals with 43,280 cases. Short-term 30-day, intermediate-term 90-day, and long-term 1-year fluoroquinolone use were all not associated with AA/AD (30-day HR 1.18 [95% CI: 0.84 to 1.66]; 90-day HR 1.12 [95% CI 0.96 to 1.30]; 1-year HR 1.00 [95% CI 0.93 to 1.07]). Using a severe case definition of ruptured AA/AD yielded comparable results. For the dose-response analysis, increasing cDDD did not confer increased rates of AA/AD (1–5 cDDD: Reference group; 6–10 cDDD: HR 1.03 [95% CI: 0.87 to 1.23]; &amp;gt;10 cDDD: HR 1.00 [95% CI 0.83 to 1.29]) (Figure 1). The secondary high-risk cohort included 20,195 patients surviving index admission with 9,183 cases of all-cause mortality and 1,768 cases of aortic interventions. The 30-day HR for all-cause mortality was 1.21 (95% CI 0.92 to 1.60) and the 60-day HR 1.06 (95% CI 0.89 to 1.26). No association with aortic interventions was found either (Figure 2). Conclusion Fluroquinolone-use was not associated with AA/AD. Furthermore, fluoroquinolone-use was not associated with all-cause mortality or aortic interventions in potentially susceptible patients with known aortic disease. These findings do not support an increased risk of AA/AD with fluoroquinolone-use. Funding Acknowledgement Type of funding sources: None.

Survival outcomes in a prospective randomized multicenter Phase III trial comparing patients undergoing anatomical segmentectomy versus standard lobectomy for non-small cell lung cancer up to 2 cm

ObjectivesThe oncological equivalence of anatomical segmentectomy for early stage non-small cell lung cancer (NSCLC) is still controversial. Primary aim of this study was survival outcomes in combination with improved quality of life after segmentectomy compared with lobectomy in patients with pathological stage Ia NSCLC (up to 2 cm, 7th edition) Materials and MethodsWe conducted a prospective, randomized, multicenter phase III trial to confirm the non-inferiority of segmentectomy to lobectomy in regard to prognosis (trial No. DRKS00004897). Patients were randomized to undergo either segmentectomy or lobectomy and followed up for 5-years survival and tumor recurrence. The 5-year hazard ratio comparing lobectomy with segmentectomy was required to remain above 0.5. ResultsBetween October 2013 and June 2016, 108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled; 54 were assigned to lobectomy and 54 (1 drop-out) to segmentectomy. In-hospital and 90 days mortality was 0% in both groups. Overall survival at 5 years was 86.52% in the lobectomy compared to 78.21% in the segmentectomy group (HR = 0.61, (95% CI 0.23–1.66), p-value of non-inferiority test, p-ni = 0.687). Disease free survival was 77.29% for the lobectomy and 77.96% for the segmentectomy patients (HR = 1.50, (95% CI 0.60–3.76), p-ni = 0.019). At a median follow-up of 5 years, no differences were noted in either the locoregional or distant recurrent disease in both groups (9.4% vs 7.4%, p-ni = 0.506). ConclusionOverall survival, locoregional and distant recurrences was not significantly difference for patients undergoing either segmentectomy or lobectomy for stage Ia NSCLC. The targeted non-inferiority of segmentectomy to lobectomy could not be proven for primary endpoint overall survival, but was significant for the secondary endpoint of disease free survival.