Subhazard Ratio Research Articles

Risk of Post-Transplant Malignancy After Isolated Heart Transplant Among Adult Patients With Congenital Heart Disease.

Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated. Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. T primary outcome was a composite outcome of PTM or death due to malignancy. Multivariable Fine-Gray competing-risk regression was used to estimate the subhazard ratio (SHR) of primary and secondary outcomes. Of the total of 29717 patients with HT were included, 1017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with a higher risk of the primary outcome (SHR 1.43, 95% CI 1.15-1.80). Among patients who developed PTM, the median time to diagnosis of first PTM (median 36vs. 46 months, p = 0.027) was shorter in patients with CHD. Among patients with CHD, survival after PTM was significantly lower compared with patients without malignancy (HR 3.32, 95% CI 2.03-5.43). Among adult patients with HT, CHD was associated with an increased risk of PTM. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.

Impact of Underlying Disease and Total Body Irradiation on the Incidence of Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation.

Multiple factors have been described to influence the risk of acute or chronic graft-versus-host disease (aGVHD or cGVHD) after allogeneic hematopoietic cell transplantation (HCT), including underlying chronic myeloid leukemia (CML) and high-dose total body irradiation (TBI). However, the impact of the underlying disease or low-dose TBI on the risk of GVHD in the modern era has not been determined. To determine risk factors for GVHD in the modern era in the setting of antithymocyte globulin (ATG)-based GVHD prophylaxis. This retrospective study included 1219 patients with hematologic malignancy who underwent first peripheral blood allogeneic HCT using myeloablative fludarabine and busulfan conditioning ± low-dose total body irradiation, along with ATG, cyclosporine, and methotrexate as GVHD prophylaxis. The adjusted cumulative incidence of GVHD was compared between patient subgroups using multivariable competing risks regression. When disregarding the underlying disease, risk factors for grade 2-4 aGVHD were donor type other than matched sibling donor (non-MSD) and lack of low-dose TBI (non-TBI). Risk factors for grade 3-4 aGVHD were non-MSD, non-TBI, and CMV donor negative/recipient positive serostatus (D-R+). Risk factors for moderate-severe cGVHD were ≤9/10 HLA match, nonmale/male, and non-TBI. In models including the underlying disease, additional significant risk factors were chronic lymphocytic leukemia (CLL) for grade 2 to 4 aGVHD (sub-hazard ratio over acute myeloid leukemia [SHR] 3.16, 95% CI 1.97-5.08, P < .001); CLL and acute lymphoblastic leukemia (ALL) for grade 3-4 aGVHD (SHR for CLL 3.54, 95% CI 1.54-8.17, P = .003 and SHR for ALL 2.26, 95% CI 1.26-4.04, P = .006); and myelofibrosis (MF) for moderate-severe cGVHD (SHR 2.14, 95 CI 1.34-3.41, P = .001). In the modern era when using ATG for GVHD prophylaxis, newly identified risk factors include CLL and non-TBI for grade 2-4 aGVHD; CLL, ALL, and non-TBI for grade 3-4 aGVHD; and MF and non-TBI for moderate-severe cGVHD. These findings, if confirmed in a separate cohort, should be taken into consideration when tailoring the prophylaxis of and monitoring for GVHD.

ORAL HYGIENE AND THE INCIDENCE OF FUNCTIONAL DECLINE IN OLDER ADULTS AGED ≥75 YEARS: THE OHSAKA STUDY

Abstract Poor oral health has been identified as a risk factor for overall health. Management of oral problems is highly significant in the field of public health. This retrospective cohort study aimed to clarify the association between the oral hygiene and the incidence of functional decline in 134,957 participants aged 75 years or older, who underwent public dental checkups in Japan. The oral hygiene levels were scored by dentists as excellent, good, or poor. The outcome was the identification of functional decline based on Long-term Care Insurance certification. An association between the oral hygiene and the incidence of functional decline were assessed using the Fine and Gray model adjusted for clinically relevant factors. During the median observational period of 36 months, the incidence of functional decline was observed in 3,360 (5.3%) men and 2,693 (3.8%) women. The multivariable-adjusted model showed that poor oral hygiene was associated with functional decline in both men and women, respectively (Sub-hazard ratios [95% confidence interval] of Excellent, Good, and Poor: 1.00 [reference], 1.10 [0.99–1.24], and 1.57 [1.33–1.84], respectively for men; 1.00 [reference], 1.29 [1.14–1.46], and 1.56 [1.23–1.97], respectively for women). The findings of the present study suggest that municipal healthcare planning and home care should recommend oral hygiene in older adults aged ≥75 years.

The impact of sex and body mass index in liver transplantation for acute-on-chronic liver failure.

There have been no studies evaluating how body mass index (BMI) impacts on waitlist and post-liver transplant (LT) mortality in acute-on-chronic liver failure (ACLF) by sex. We aimed to determine these impacts using the United Network for Organ Sharing (UNOS) database. Adults listed for LT with estimated ACLF (Est-ACLF) (2005-2023) were identified and subdivided by sex and BMI (high/middle/low). Competing-risk analyses evaluated impacts on waitlist mortality. Kaplan-Meier analyses assessed post-LT survival. Multivariable Cox regression identified risk factors. Of 37 251 Est-ACLF patients, 14 534 (39.0%) were female. Females had higher 90-day waitlist mortality than males (subhazard ratio [sHR]: 1.20, p < .01). High/low BMI patients had higher mortality than middle (sHR: 1.08/1.11, p < .01). In females, high BMI was associated with higher mortality than low (sHR: 1.10, p = .02); in males, low BMI was associated with higher mortality than high/middle (sHR: 1.16/1.16 vs. high/middle, p < .01). Multivariable analyses showed in females, high BMI was a significant risk factor for waitlist mortality (sHR:1.21, p < .01), while low was not; in males, high/low BMI was significant, with low having higher sHR (1.17) than high (1.09). Post-LT survival showed no significant difference in females; in males, low BMI showed worse post-3-/5-year-LT survival (p < .01). Multivariable Cox regression showed for females, neither low nor high BMI was significant for post-LT survival; for males, low BMI was significant for 1-/3-/5-year-LT survival (HR: 1.30/1.30/1.22, p < .01). Our analysis of BMI's impact on LT outcomes in ACLF by sex enables risk stratification and provides a basis for adjusting BMI.

Delisting From Liver Transplant List for Improvement and Re-compensation Among Decompensated Patients at one-year.

Data are limited regarding etiology-specific trends for delisting and re-compensation for liver disease improvement among liver transplant (LT) listed candidates in the US. A retrospective cohort (2002-2022) using UNOS database examined etiology-specific trends for delisting and re-compensation due to liver disease improvement among candidates listed for LT. Of 120,451 listings in adults, 34,444 (2002-08), 38,296 (2009-2015), 47,711 (2016-2022) were analyzed. A total of 7196 (6.2%) were delisted for liver disease improvement, with 5.6, 7.2, 5.3% in three respective time periods, Armitage trend p<0.001. Delisting for improvement of liver disease was 8.1, 5.8, 4.0, 3.9, and 3.1% among listings for alcohol-associated liver disease (ALD n=41,647), hepatitis C virus infection (HCV n=38,797), autoimmune (n=12,131), metabolic associated steatotohepatitis (MASH n=22,162), hepatitis B virus infection (HBV n=3027), and metabolic liver disease (MLD n=2687) respectively. 1122 (15.6% or 0.9%) delisted for improvement at 1-yr. with cumulative incidence competing for waitlist mortality and receipt of LT of 1.18, 1.17, 0.64, 0.59, 0.50, 0.34 for ALD, HBV, HCV, MASH, MLD, and autoimmune respectively. In a fine and gray model, compared to metabolic, sub-hazard ratio (95% CI) on delisting at 1-yr. was 3.47 (31.6-3.81) and 3.44 (2.96-3.99), P<0.001 for ALD and for HBV respectively. Of 7196 delisting for improvement, 567 of 5750 (9.9%) decompensated at listing had re-compensation, 19.5% for HBV, 16.6% MLD and autoimmune, 9.9% ALD, 8.6% for HCV, and 6.9% MASH. In a logistic regression model among delisted candidates for improved liver disease, HBV vs. MASH etiology was associated with re-compensation, 2.37 (1.40-4.03), P<0.001. ALD and HBV are most frequent etiologies for delisting due to liver disease improvement. About 10% of delisted patients develop re-compensation, with HBV etiology most likely to recompensate. Models and biomarkers are needed to identify these candidates for optimal use of deceased donor livers.

Hospital-Acquired Complications in Critically Ill Children and PICU Length of Stay, Duration of Respiratory Support, and Economics: Propensity Score Matching in a Single-Center Cohort, 2015-2020.

To identify the health and economic costs of hospital-acquired complications (HACs) in children who require PICU admission. Propensity score matched cohort study analyzing routinely collected medical and costing data collected by the health service over 6 years (2015-2020). Tertiary referral PICU in Queensland, Australia. All children admitted to the PICU were included. None. We assessed ventilator- and respiratory support-free days at 30 days post-PICU admission, length of PICU stay, prevalence of individual HACs, and attributable healthcare costs. A total of 8437 admissions, representing 6054 unique patients were included in the analysis. Median (interquartile range) for cohort age was 2.1 years (0.4-7.7 yr), 56% were male. Healthcare-associated infections contributed the largest proportion of HACs (incidence rate per 100 bed days, 46.5; 95% CI, 29.5-47.9). In the propensity score matched analyses (total 3852; 1306 HAC and 1371 no HAC), HAC events were associated with reduced ventilator- (adjusted subhazard ratio [aSHR], 0.88 [95% CI, 0.82-0.94]) and respiratory support-free days (aSHR, 0.74 [95% CI, 0.69-0.79]) and increased PICU length of stay (aSHR, 0.63 [95% CI, 0.58-0.68]). Healthcare costs for children who developed a HAC were higher compared with children with no HAC, with mean additional cost ranging from Australian dollar (A$) 77,825 (one HAC [95% CI, $57,501-98,150]) to $310,877 (≥ 4 HACs [95% CI, $214,572-407,181]; in 2022, the average conversion of A$ to U.S. dollar was 0.74). In our PICU (2015-2020), the burden of HAC for critically ill children was highest for healthcare-associated infections. Further high-quality evidence regarding HAC prevention and prospective risk assessment could lead to improved patient outcomes and reduced costs.

HIV Treatment Outcomes After 10 years on ART in the TREAT Asia Observational Database and Australian HIV Observational Database.

Increasing numbers of people with HIV have received prolonged antiretroviral therapy (ART). We assessed long-term immunological and survival outcomes among people with HIV from Asia (TREAT Asia HIV Observational Database) and Australia (Australian HIV Observational Database). People with HIV receiving ART for ≥10 years were included. Factors associated with CD4 counts in years 11-15 of ART were analyzed using repeated measures linear regression. Survival after 10 years was analyzed using competing risk regression. There were 7139 people included: 4867 (68%) from the TREAT Asia HIV Observational Database and 2272 (32%) from the Australian HIV Observational Database. Higher CD4 levels after 10 years were observed if the nadir CD4 in the first decade was higher (CD4 (cells/µL) 101-200: difference = 35, 95% CI: 18 to 51; >200: difference = 125, 95% CI: 107 to 142) compared with ≤50. The same patterns were observed in those who achieved CD4 ≥500 cells/µL, which subsequently decreased to <500 (difference = 225, 95% confidence interval [CI]: 213 to 236), or in those who achieved and maintained CD4 ≥500 cells/µL (difference = 402, 95% CI: 384 to 420), compared with always <500 in the previous decade. Previous protease inhibitor (PI)-based regimen (difference=-17, 95% CI -33 to -1) compared with no PI, and previous treatment interruptions (TI) of 14 days to 3 months and >6 months were associated with lower CD4 counts after 10 years (difference = -38, 95% CI -62 to -15 and difference=-44, 95% CI -61 to -27, respectively) compared with no TI. The mortality rate was 1.04 per 100 person-years. Virological failure was associated with subsequent mortality (subhazard ratio = 1.34, 95% CI: 1.04 to 1.71). Sustaining high CD4 levels and minimizing TI has far-reaching benefits well beyond the first decade of ART.

Weight Loss Intentionality and Frailty are Associated with Pre-Kidney Transplant Outcomes.

Unintentional weight loss, a hallmark of frailty, predicts worse post-kidney transplantation (KT) outcomes. However, weight loss in candidates with obesity is often recommended to enhance transplant eligibility. We tested whether pre-evaluation weight change is associated with listing/waitlist mortality, considering intentionality and frailty. We leveraged data on body mass index (BMI), weight loss intentionality, (one-year pre-evaluation and at evaluation), and frailty (four-component Physical Frailty Phenotype at evaluation) for 1,361 candidates (895 listed) with obesity (BMI≥30kg/m2) enrolled in a prospective multi-center cohort study. We estimated the association between pre-evaluation weight change (stable, gain, unintentional/intentional loss) with chance of listing/waitlist mortality using Cox proportional hazards/competing risk models. Among candidates with obesity, 48% had stable weight, 17% had weight gain, 16% had unintentional weight loss, and 20% had intentional weight loss over the year prior to evaluation. Among frail candidates with obesity, stable weight was associated with 27% lower chance of listing (adjusted hazard ratio [aHR]:0.73,95% confidence intervals [CI]:0.55-0.96), weight gain with 47% lower chance of listing (aHR:0.53,95%CI:0.34-0.80), and unintentional weight loss with 48% lower chance of listing (aHR:0.52,95%CI:0.32-0.84) compared to non-frail candidates with stable weight. However, in frail candidates with obesity, intentional weight loss was not associated with a significantly lower chance of listing compared to non-frail candidates with stable weight. Additionally, among frail candidates with obesity, stable weight (adjusted sub-hazard ratio [aSHR]:1.72,95%CI:1.01-2.90), unintentional weight loss (aSHR:2.78,95%CI:1.23-6.27), and intentional weight loss (aSHR:2.26,95%CI:1.05-4.85) were associated with higher waitlist mortality compared to non-frail candidates with stable weight. Among non-frail candidates, no associations were observed for weight change and frailty status with either chance of listing or waitlist mortality. Among frail candidates with obesity, unintentional pre-KT weight loss is associated with lower chance of listing; however, any weight loss is associated with higher waitlist mortality. Our findings suggest that frail candidates with obesity may benefit from clinician supervision of pre-KT weight loss.

Long-term risk of adverse limb outcomes in older patients after endovascular femoral artery revascularization: The Boston femoral artery endovascular revascularization outcomes (Boston FAROUT) study.

Older patients may be denied endovascular revascularization of the superficial femoral artery (SFA) for peripheral artery disease (PAD) due to concerns of worse limb outcomes than younger patients. We assessed adverse outcomes in patients after an index revascularization stratified by age (age<65, 65-75years, and>75years) from two centers between 2003 and 2011 and followed a median 9 (25%-75%: 7, 11) years. Outcomes included major adverse limb events (MALE) or minor repeat revascularization, death, and major adverse cardiac and cerebrovascular events (MACCE). We used cause-specific and competing-risks analyses with clustering by patient to determine the hazard ratios (HR), sub-hazard ratios (SHR), 95% confidence intervals (95%CI) for outcomes according to older age. There were 253 limbs revascularized in 202 patients with a high use of lipid lowering therapy (91%) and aspirin anti-platelet therapy (96%). In oldest age group (>75years), 71 limbs were revascularized and patients were less likely to be active smokers and had poorer tibial runoff than younger patients. In competing risks multivariable models, patients >75years old had similar risks over 10years of MALE or minor revascularization (SHR=0.92, 95%CI=0.53, 1.62) and MACCE (SHR=1.12, 95%CI=0.58, 2.18) to younger patients. All-cause death was more common in older patients (HR=1.99, 95%CI=1.25, 3.17). After adjusting for the competing risk of death, patients >75years had similar incidence of adverse limb outcomes and MACCE to younger patients after endovascular revascularization of the femoral artery. Consequently, older patients should be considered for endovascular revascularization when indicated.

Abstract 4138488: Association Between Guideline-directed Medical Therapy and Reintervention Risk at 2 Years Following Peripheral Vascular Interventions

Introduction: Patients with peripheral artery disease (PAD) undergoing peripheral vascular interventions (PVI) face frequent reinterventions. The association between the use of guideline-directed medical therapy (GDMT) and reintervention risk is unclear, we therefore aimed to study the association between GDMT and 2-year reintervention risk using the largest national vascular registry. Methods: PVI procedures in patients with claudication or chronic limb-threatening ischemia between 2017-2018 were abstracted from the Vascular Quality Initiative (VQI) registry. GDMT was defined as statin, antiplatelet, and ACE/ARB if hypertensive prescribed at discharge. Reintervention was obtained from Medicare claims data. Propensity score of no GDMT vs. GDMT was calculated using 22 preprocedural variables followed by 1:1 matching of patients. The 2-year cumulative incidence of reintervention and subhazard ratios (sHR) for 2-year reintervention risk in no GDMT vs. GDMT were assessed using Aalen-Johansen method and Fine-Gray model, respectively, to account for the competing risk of death. Results: A total of 13,244 patients (6,622 by GDMT group) were included after 1:1 matching (mean age 72.0 ± 9.9, female 38.9%, white 79.4% Black or African American 15.3%) . At 2 years, the cumulative incidence of reintervention was 43.0% (95% CI 41.0%-44.9%) for patients with no GDMT vs. 41.2% (95%CI 39.4-43.0) for the GDMT group (P=0.293). Not receiving GDMT was not associated with 2-year risk of reintervention (sHR: 1.03 95%CI 0.97-1.10; P=0.293). Conclusion: Around 40% of patients undergoing a PVI will have a reintervention at 2 years. The receipt of GDMT at discharge was not associated with a lower reintervention risk at 2 years, as currently assessed. Further granular measures of GDMT should integrate adherence information, as well as information on other lifestyle and cardiovascular risk management to obtain a more complete assessment of a potential association with reintervention risk.

Abstract 4118018: Increased Risk of Post-Transplant Malignancy After Isolated Heart Transplant in Adult Patients with Congenital Heart Disease

Introduction: Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated. Methods: Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. Outcomes were PTM and hematologic malignancy (either leukemia, lymphoma or post-transplant lymphoproliferative disorder). Multivariable Fine-Gray competing-risk regression adjusting for age, sex, race, prior cardiac surgery, smoking, diabetes, induction immunosuppression, recipient and donor cytomegalovirus and Ebstein-Bar virus status was used to estimate subhazard ratio (SHR). Results: Of the total of 29,717 patients with HT were included, 1,017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and more likely to have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with higher risk of PTM (aSHR 1.44, 95% CI 1.15 – 1.80) and hematologic malignancy (aSHR 2.09, 95% CI 1.28 – 3.42). Among patients &lt; 45 years old, CHD had an unadjusted SHR of 1.55 (95% CI 1.11 – 2.16) of PTM, Figure. Conclusions: Among adult patients with HT, CHD was associated with increased risk of PTM and hematologic malignancy. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.

Alcohol consumption and risk of rheumatoid arthritis: results from the UK Women’s Cohort Study

While some studies have suggested that moderate alcohol consumption may be beneficial for rheumatoid arthritis (RA) prevention(1), the role of competing events have not been considered and may lead to misinterpretation of the magnitude of the risk between alcohol intake and RA incidence. We aimed to investigate the relationship between alcohol consumption and RA incidence when the competing risk of death is accounted for in the survival analysis.Data from the UK Women’s Cohort Study (UKWCS), a prospective cohort study of 35,372 middleaged women established between 1995 and 1998, was used for the analyses(2). Alcohol intake was assessed at baseline by asking for the number of specified units of each type of alcoholic beverage (beer, wine, sherry, and spirits) consumed per week. Cases who developed RA were identified through linkage with Hospital Episode Statistics (HES) up to March 2019 (International Classification of Diseases, ICD-10 code M05-M06). Data linkage with the Health and Social Care Information Centre (HSCIC) allowed cause of death to be identified using ICD codes (9th/10th version). We used directed acyclic graphs, competing risk regression modelling, and subgroup analyses to examine the effect of alcohol intake on RA incidence.Among 29,830 women linked to the HES data (666,857 person-years), 255 cases of rheumatoid arthritis were identified, with a median follow-up of 22.5 years. After adjustment for confounders, in both competing risk regression and cox proportional hazards models, regular drinking was associated with a reduced risk of RA. In the competing risk model, with occasional drinkers (less than 1 serving of alcohol per week) as the reference, the subhazard ratios (SHRs) for non-drinkers were: SHR, 0.67, 95% CI: 0.43-1.07; regular drinkers: SHR, 0.70, 95% CI: 0.53−0.94. Every additional unit of alcohol per week was associated with a 3% lower risk of rheumatoid arthritis (SHR (95% CI): 0.97(0.96−0.99)). BMI modified the linear associations between alcohol intake and risk of RA(Pinteraction = 0.01). The incidence of RA in participants with a BMI &lt; 30 kg/m2 (227 cases, 27,015 participants) was 2% lower for each additional serving of alcohol consumed per week (0.98(0.96−0.99)),no statistically significant effect was seen for alcohol in those with a BMI 30+kg/m2, though numbers were smaller in this group.

Aryl hydrocarbon receptor repressor ( AHRR ) methylation predicts risk of vascular disease: A cohort study of the general population.

Smoking is a risk factor for cardiovascular disease, but there is currently no clinically established biomarker for its cardiovascular damage. We aimed to investigate the hypothesis that aryl hydrocarbon receptor repressor ( AHRR ) methylation at CpG site cg05575921, a biomarker of smoking behavior, is associated with the risk of peripheral artery disease (PAD) and aortic aneurysm (AA) in the general population. In this prospective cohort study of the general population, we measured AHRR methylation in individuals from three visits to the Copenhagen City Heart Study. Information on risk factors was collected at visits with 10 years intervals; visit 1 (1991-1994), visit 2 (2001-2003), and visit 3 (2011-2015). Individuals were followed up in the Danish National Patient Register for PAD and AA until December 2018. Subhazard ratios were calculated using Fine and Gray competing risk regression. In 11332 individuals from visit 1 ( n =9234), visit 2 ( n =5384), and visit 3 ( n =4387), there were 613 and 219 events of PAD and AA during up to 26.5 years of follow-up. AHRR hypomethylation was associated with a higher risk of PAD and AA with multivariable-adjusted subhazard ratios of 2.82 (1.91; 4.15) for PAD and 2.88 (1.42; 5.88) for AA in individuals within the lowest versus highest methylation quintile. We found that AHRR methylation, a strong biomarker for smoking, was associated with the risk of PAD and AA. AHRR methylation could be a useful tool in more personalized risk prediction of PAD and AA.

TM6SF2-rs58542926 genotype has opposing effects on incidence of hepatic and cardiac events in a community cohort: TM6SF2 effects on liver and cardiac outcomes.

TM6SF2-rs58542926-T is associated with increased cirrhosis and modestly decreased coronary artery disease prevalence. However, relative effects of TM6SF2 genotype on major adverse cardiovascular events (MACE) vs. liver-related events (LRE) is not known. We utilized the UK Biobank, a prospective cohort with genetic and inpatient diagnosis data. The primary predictor was TM6SF2-rs58542926 genotype and the primary outcomes were MACE and LRE. Effects were reported as subhazard ratios (sHR) and 10-year cumulative incidence by Fine-Gray competing risk analyses. >430,000 individuals met inclusion criteria. TM6SF2-rs58542926-TT genotype (vs. CC) was associated with higher incidence of LRE (adjusted sHR 3.16, 95% confidence interval [CI] 1.86-5.37) and lower incidence of MACE (adjusted sHR for TT vs. CC genotype 0.76, 95% CI 0.63-0.91 ). In individuals with Fibrosis-4 (FIB4) <1.3, 1.3-2.67, and >2.67, 10-year LRE incidence in TM6SF2-rs58542926-TT vs. CC individuals was 0.08% vs. 0.06% (p>0.05), 0.81% vs. 0.20% (p<0.0001), and 10.5% vs. 3.4% (p=0.00094), respectively. The corresponding values for MACE were 3.8% vs. 5.1% (p=0.032), 6.4% vs. 8.2% (p=0.040), and 17.1% vs. 12.4% (p>0.05). The absolute decrease in MACE with rs58542926-TT (vs. CC) genotype exceeded the absolute increase in LRE in all groups but FIB4>2.67. Associations of TM6SF2 genotype with LRE/MACE were significant in men but not women. TM6SF2-rs58542926-T allele was also associated with increased hepatic steatosis and corrected T1 time by magnetic resonance imaging, with greater effect sizes in men than women. TM6SF2 genotype has opposite effects on LRE vs. MACE incidence, and absolute effects on MACE were greater except in those with highest FIB4 scores. Effects were strongest in men. These findings clarify implications of TM6SF2 genotype based on personalized clinical risk.

The effect of metformin use on the risk of atrial fibrillation in patients with type 2 diabetes: data from the UK biobank

Abstract Objective The present study aims to investigate the protective role of metformin against atrial fibrillation (AF) and stroke in type 2 diabetes (T2DM) patients treated with other antidiabetic medications. Methods We included 10,011 participants with T2DM from the UK biobank database, with a follow-up for new diagnoses of AF and stroke recorded until 2023. We employed logistic regression analysis and competing risk models to assess the association between metformin use and the incidence of AF or stroke. Results The cross-sectional analysis revealed that, compared with the use of other antidiabetics, metformin was associated with a lower prevalence of AF (odds ratio [OR] 0.71, 95% CI: 0.57–0.89) and stroke (OR 0.70, 95% CI: 0.56–0.86). In the competing risk model, compared to other antidiabetics, metformin may reduce the risk of AF (sub-hazard ratio [SHR] 0.86, 95% CI: 0.75–0.98) and stroke (SHR 0.62, 95% CI: 0.44–0.86) (Figure 1). Subgroup analysis indicated a significantly lower incidence of AF or stroke in patients under 65 years of age (SHRs were 0.80, 95% CI:0.67-0.96 for AF and 0.52, 95% CI: 0.34-0.81 for stroke) and in female patients (SHRs were 0.65, 95% CI:0.52-0.81 for AF and 0.53, 95% CI: 0.30-0.91 for stroke). Notably, metformin significantly reduced the incidence of AF in non-insulin users (SHR 0.80, 95% CI: 0.66-0.97) and the incidence of stroke in insulin users (SHR 0.55, 95% CI: 0.35-0.87) (Figure 2). Conclusion Our findings suggest that metformin use, in comparison to other antidiabetic medications, is associated with a reduced risk of AF and stroke, especially in non-insulin users for AF and insulin users for stroke.

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.

Extracorporeal Membrane Oxygenation for COVID-19 During the Delta and Omicron Waves in North America.

Clinical outcomes for patients with severe acute respiratory failure caused by different variants of the coronavirus disease 2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) are incompletely understood. Clinical characteristics, pre-ECMO management, and hospital mortality at 90 days for adults with COVID-19 who received venovenous ECMO (VV-ECMO) at North American centers during waves predominated by Delta (August 16 to December 12, 2021) and Omicron (January 31 to May 31, 2022) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were compared in a competing risks framework. One thousand seven hundred and sixty-six patients (1,580 Delta, 186 Omicron) received VV-ECMO for COVID-19 during the Delta- and Omicron-predominant waves in North American centers. In the unadjusted competing risks model, no significant difference was observed in risk of hospital mortality at 90 days between patients during the Delta- versus Omicron-predominant wave (subhazard ratio [sHR], 0.94; 95% confidence interval [CI], 0.74-1.19), but patients supported with VV-ECMO during the Omicron-predominant wave had a significantly lower adjusted risk of hospital mortality at 90 days (subhazard ratio, 0.71; 95% CI, 0.51-0.99). Patients receiving VV-ECMO during the Omicron-predominant wave had a similar unadjusted risk of hospital mortality at 90 days, but a significantly lower adjusted risk of hospital mortality at 90 days than those receiving VV-ECMO during the Delta-predominant wave.

Dialysis Facility Staffing Ratios and Kidney Transplant Access Among Adolescents and Young Adults

Patient to staff ratios vary across US dialysis facilities and have been associated with patient outcomes in older adults. To determine whether patient to nurse or patient to social worker staff ratios are associated with access to kidney transplant for adolescents and young adults. Retrospective cohort study including patients aged 12 to 30 years who started dialysis between 2005 and 2019 at 8490 US facilities according to the US Renal Data System, the national end-stage kidney disease registry. Time-updated quartile of patient to nurse and patient to social worker ratios at dialysis facilities. Fine-Gray models were used to relate the exposure to the incidence of waitlisting and kidney transplant, accounting for the competing risk of death. Subgroup analysis by age at dialysis initiation (<22 vs ≥22 years) was performed. Follow-up was censored in January 2020. A total of 54 141 participants were included (median age, 25 years [IQR, 21-28]; 54.4% male; 4.3% of Asian race, 35.3% of non-Hispanic Black race). The median patient to staff ratios were 14.4 patients per nurse (IQR, 10.3-18.9) and 91.0 patients per social worker (IQR, 65.2-115.0). During a median follow-up of 2.6 years, 39.9% of patients (n = 21 598) received a transplant. In adjusted analysis, the highest (vs lowest) quartile of patient to nurse ratios was associated with 14% lower incidence of transplant (subhazard ratio [SHR], 0.86 [95% CI, 0.82-0.91]). The highest (vs lowest) quartile of patient to social worker ratios was associated with lower incidence of waitlisting (SHR, 0.95 [95% CI, 0.91-0.99]) and transplant (SHR, 0.85 [95% CI, 0.81-0.89]). For both staff ratios, there was an interaction with age at dialysis initiation, such that the association was more pronounced in patients starting dialysis at younger than 22 years (SHR, 0.71 [95% CI, 0.65-0.78] for the highest vs lowest quartile for nursing; SHR, 0.74 [95% CI, 0.68-0.80] for social work) compared with those 22 years and older (SHR, 1.00 [95% CI, 0.94-1.06] for nursing; SHR, 0.96 [95% CI, 0.91-1.02] for social work) for the outcome of transplant. Adolescents and young adults receiving care at dialysis facilities with higher patient to staff ratios had reduced access to waitlisting and transplant, particularly if they were younger than 22 years of age at dialysis initiation.

Association between delay in diabetes development and mortality in people with obesity: Up to 33 years follow-up of the prospective Swedish Obese Subjects study.

Life expectancy is reduced in people with obesity and is further reduced in those with concomitant type 2 diabetes. The aim of the study was to assess whether a 2-year delay in diabetes development influences life expectancy in people with obesity. Participants from the Swedish Obese Subjects study without diabetes at baseline and known diabetes status at the 2-year follow-up were included: bariatric surgery (n = 1471) and usual obesity care (n = 1392). Median follow-up was 26.1 years (interquartile range: 22.7-28.7 years). The Swedish Cause of Death Register, case sheets and autopsy reports were assessed to determine the direct cause of death. Analyses were adjusted for preselected risk factors: inclusion year, sex, baseline age, body mass index (BMI) and smoking. Across both study arms, 146 participants were newly diagnosed with type 2 diabetes at the 2-year examination, whereas 2717 remained diabetes-free. Most participants diagnosed with diabetes (n = 140) were from the usual care control group. During the follow-up, there were 18.3 deaths per 1000 person-years (95% confidence interval [CI]:14.1-23.9) in the group with diagnosed diabetes at the 2-year follow-up and 10.9 deaths per 1000 person-years (95% CI:10.2-11.8) in the group that remained diabetes-free (adjusted hazard ratio [HRadj] 1.60, 95% CI: 1.19-2.15, p = 0.002). The adjusted median life expectancy in the diabetes group was 3.7 years (95% CI: 1.4-6.0, p = 0.002) shorter than in the diabetes-free group. Specifically, cardiovascular mortality was higher in the group with diabetes (adj sub-hazard ratio [sub-HR] 1.74 [95% CI: 1.09-2.77], p = 0.021). A 2-year delay in diabetes development may be linked to increased life expectancy, possibly due to a reduction in cardiovascular mortality. Future studies should confirm these findings.

Venous Thromboembolism after Hospital Discharge: Temporal Trends in Baseline Characteristics, Prevention, Treatment, and 90-day Outcomes.

Venous thromboembolism (VTE) after hospital discharge poses a serious health risk. Assessments of patient characteristics, prophylaxis, treatment, outcomes, and over time changes lack consistency. Data on 16,901 hospitalized patients in the Registro Informatizado Enfermedad TromboEmbolica registry (2003-2022) were analyzed to evaluate trends in baseline characteristics, prophylaxis, treatments, and 90-day outcomes among medical (6,218) and surgical (10,683) patient cohorts. Multivariable logistic regression was used to assess the risks of the composite of fatal pulmonary embolism (PE) or recurrent VTE and major bleeding. The proportion of patients who presented with PE increased among medical (from 54 to 72%) and surgical patients (from 55 to 58%). Prophylaxis use increased in medical patients (from 53 to 71%), while decreasing in surgical patients (from 67 to 58%). Notably, the 90-day composite of fatal PE or recurrent VTE decreased in medical (from 3.9 to 1.8%) and surgical patients (from 2.9 to 1.2%; p < 0.001 for both). Conversely, major bleeding increased (3.1 to 4.5%) in medical patients (p = 0.008), with no change in surgical patients (from 2.5 to 2.4%). Risk-adjusted analysis showed a yearly decrease in the risk for the composite outcome (subhazard ratio [sHR]: 0.95; 95% confidence interval [CI]: 0.93-0.98) in medical and surgical patients and an increase in the risk for major bleeding in medical patients only (sHR: 1.04; 95% CI: 1.01-1.07). Results were consistent after excluding coronavirus disease 2019 patients. Over 20 years, the composite of fatal PE or recurrent VTE within 90 days had significantly decreased in VTE patients after hospitalization for medical or surgical care. Medical patients, however, exhibited an increase in major bleeding.