Subhazard Ratio Research Articles

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.

Long term mortality trends in people with severe mental illnesses and how COVID-19, ethnicity and other chronic mental health comorbidities contributed: a retrospective cohort study.

People with schizophrenia-spectrum and bipolar disorders (severe mental illnesses; 'SMI') experience excess mortality. Our aim was to explore longer-term trends in mortality, including the COVID-19 pandemic period, with a focus on additional vulnerabilities (psychiatric comorbidities and race/ ethnicity) in SMI. Retrospective cohort study using electronic health records from secondary mental healthcare, covering a UK region of 1.3 million people. Mortality trends spanning fourteen years, including the COVID-19 pandemic, were assessed in adults with clinician-ascribed ICD-10 diagnoses for schizophrenia-spectrum and bipolar disorders. The sample comprised 22 361 people with SMI with median follow-up of 10.6 years. Standardized mortality ratios were more than double the population average pre-pandemic, increasing further during the pandemic, particularly in those with SMI and psychiatric comorbidities. Mortality risk increased steadily among people with SMI and comorbid depression, dementia, substance use disorders and anxiety over 13-years, increasing further during the pandemic. COVID-19 mortality was elevated in people with SMI and comorbid depression (sub-Hazard Ratio: 1.48 [95% CI 1.03-2.13]), dementia (sHR:1.96, 1.26-3.04) and learning disabilities (sHR:2.30, 1.30-4.06), compared to people with only SMI. COVID-19 mortality risk was similar for minority ethnic groups and White British people with SMI. Elevated all-cause mortality was evident in Black Caribbean (adjusted Rate Ratio: 1.40, 1.11-1.77) and Black African people with SMI (aRR: 1.59, 1.07-2.37) during the pandemic relative to earlier years. Mortality has increased over time in people with SMI. The pandemic exacerbated pre-existing trends. Actionable solutions are needed which address wider social determinants and address disease silos.

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.

Dietary Restriction, Socioeconomic Factors, Access to Kidney Transplantation, and Waitlist Mortality.

Dietary restrictions for patients with end-stage kidney disease (ESKD) are burdensome. Kidney transplantation (KT) candidates who lack neighborhood resources and are burdened by dietary restrictions may have decreased access to KT. In our two-center prospective cohort study (2014-2023), 2471 ESKD patients who were evaluated for KT (candidates) reported their perceived burden of dietary restrictions (not at all, somewhat/moderately, or extremely bothered). Neighborhood-level socioeconomic factors were derived from residential ZIP codes. We quantified the association of perceived burden of the dietary restrictions with a chance of listing using Cox models and risk of waitlist mortality using competing risks models. Then we tested whether these associations differed by neighborhood-level socioeconomic factors. At evaluation, 18% of KT candidates felt extremely bothered by dietary restrictions. Those who felt extremely bothered were less likely to be listed for KT (adjusted hazard ratio [aHR]=0.75, 95% confidence interval [CI]: 0.64-0.87); this association did not differ by neighborhood-level socioeconomic factors. Overall, the burden of dietary restrictions was not associated with waitlist mortality (p=0.62). However, among candidates living in high food insecurity neighborhoods, those who felt extremely bothered had higher waitlist mortality (adjusted subhazard ratio [aSHR]=2.07, 95% CI: 1.14-3.75, p[interaction]=0.02). The association between dietary burden and waitlist mortality did not differ by neighborhood-level healthy food access. The perceived burden of dietary restrictions is associated with a lower chance of listing for KT, and higher waitlist mortality only among candidates residing in neighborhoods with high food insecurity. Transplant centers should identify vulnerable patients and support them with nutrition education and access to food assistance programs.

PNPLA3 rs738409, environmental factors and liver-related mortality in the U.S. Population

Background & AimsLittle is known about the interplay between patatin-like phospholipase domain protein 3 (PNPLA3 rs738409 C>G), environmental factors, and the risk of liver-related death (LRD). Methods4,361 adults were selected from NHANES III, 1991–1994. All participants were linked to the National Death Index until 2019 (mean follow-up: 23.2 years). LRD was the study outcome. Associations of PNPLA3, diet, light alcohol intake, smoking, and BMI (kg/m2) with LRD were examined using competing risk regression models. ResultsPNPLA3 G–allele was significantly associated with LRD (adjusted subhazard ratio [adj.sHR]: 2.9, 95% CI: 1.4-5.8). Non-heavy alcohol intake (adj.sHR: 2.2, 95% CI: 1.1-4.5), top quartiles of monounsaturated fat (MUFA) (adj.sHR: 0.43, 95% CI: 0.12-0.99), and cholesterol (adj.sHR: 2.6, 95% CI: 1.00-8.8) and coffee intake ≥3 cups/day (adj.sHR: 0.05, 95% CI: 0.06-0.10), former/current smoking (adj.sHR: 1.8, 95% CI: 1.2-2.6), BMI (adj.sHR: 1.1, 95% CI: 1.03-1.2), and healthy eating index (HEI) (adj.sHR: 0.96, 95% CI: 0.93-0.98) were associated with LRD.Joint effects between PNPLA3 and environmental factors showed that the risk of LRD was significantly increased in carriers of the G-allele with non-heavy alcohol intake (adj.sHR: 3.7), higher consumption (top quartile) of cholesterol (adj.sHR: 4.1), former (adj.sHR: 4.3) or current (adj.sHR: 3.5) smoking, or BMI ≥30 (adj.sHR: 4.0) kg/m2. The effects of the G-allele on the risk of LRD were significantly attenuated in those with top quartile consumption of MUFA (adj.sHR: 0.5) or ≥3 cups/day of coffee (adj.sHR: 0.09). HEI was inversely associated with LRD across all PNPLA3 genotypes (adj.sHR: 0.94, 0.96, and 0.97 for CC, CG, and GG, respectively). ConclusionsPNPLA3 is associated with LRD and this relationship is significantly modified by anthropometric and environmental factors.

Abstract A086: Racial and ethnic disparities in prostate cancer survival in the Multiethnic Cohort Study (MEC)

Abstract Background: Prostate cancer (PCa) survival has improved over the past 20 years due to advancements in treatment and screening. However, racial and ethnic disparities in PCa survival remain. Studying population differences in PCa survival may help identify underlying contributing factors. Methods: We conducted survival analyses among 10,651 African American, Latino, Native Hawaiian, Japanese American, and non-Hispanic White (NHW) men with an incident PCa diagnosis since 1993 who were part of the Multiethnic Cohort Study. Sub- hazard ratios (SHRs) and 95% confidence intervals (CI) were estimated using the Fine and Grey Subdistribution Hazards Model to account for competing risks in PCa-specific mortality, with age since diagnosis as the time metric. Multivariable models included age at PCa diagnosis, Gleason score, stage at diagnosis, and baseline values of education, initial treatment (radiation, surgery, hormone therapy, chemotherapy, or no active treatment), diabetes history, physical activity, BMI, smoking status, and dietary intakes linked to PCa progression (tomatoes, whole milk, fatty fish, processed meat, saturated fat, and alcohol). We also performed stratified analyses by tumor stage (localized or regional/distant) and Gleason score (≤7 or &amp;gt;7). Associations were considered statistically significant at P &amp;lt; 0.05. Results: Of 10,651 men diagnosed with PCa over 27 years of follow-up (mean duration, 8.4 years), 1,324 (12.4%) died of PCa. Those with lower Gleason scores were less likely to die than those with higher scores (6.8% of men with Gleason score ≤7 vs 21.3% of men with Gleason score &amp;gt;7, p&amp;lt;0.001). Likewise, men with localized disease were less likely to die than men with regional/distant disease (7.5% of men with localized disease vs. 29.2% of men with regional/distant disease, p&amp;lt;0.001). Japanese Americans had significantly lower mortality compared with NHWs (SHR=0.63, 95% CI:0.51, 0.79, p&amp;lt;0.001), consistently observed across stage and Gleason score: localized (SHR=0.64, 95% CI: 0.48, 0.87, p&amp;lt;0.001); regional/distant (SHR=0.63, 95% CI: 0.45, 0.88, p=0.01); Gleason ≤7 (SHR=0.61, 95% CI: 0.44, 0.86, p&amp;lt;0.001); and Gleason score &amp;gt;7 (SHR=0.59, 95% CI: 0.43, 0.79, p&amp;lt;0.001). PCa-specific mortality was significantly higher among African Americans compared to NHWs (SHR=1.31, 95% CI: 1.08-1.60, p=0.01). This difference was more pronounced for less aggressive tumors: localized (SHR=1.50, 95% CI: 1.15, 1.96, p&amp;lt;0.001); Gleason ≤7 (SHR=1.28, 95% CI: 0.95, 1.71, p=0.11). Lastly, we did not observe significant differences in PCa mortality for Latinos and Native Hawaiians compared to NHWs overall or by disease severity. Conclusions: Japanese American have ∼40% lower and African Americans have ∼30% higher PCa-specific mortality relative to NHWs, even after accounting for lifestyle/behavioral factors, stage, Gleason score, and treatment. Further investigations are needed to explore social and cultural factors that impact care as well as tumor-based characteristics that may vary between populations to understand these disparities in PCa mortality. Citation Format: Wei Xiong, Fei Chen, Ann S. Hamilton, David Conti, Raymond Hughley, David Bogumil, Anqi Wang, Song-Yi Park, Peggy Wan, Lynne R. Wilkens, Loïc Le Marchand, Brenda Y. Hernandez, Christopher A. Haiman. Racial and ethnic disparities in prostate cancer survival in the Multiethnic Cohort Study (MEC) [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A086.

Validation of the R3-AFP model for risk prediction of HCC recurrence after liver transplantation in the SiLVER randomized clinical trial.

Explant-based models for assessing HCC recurrence after liver transplantation serve as the gold standard, guiding post-liver transplantation screening and immunosuppression adjustment. Incorporating alpha-fetoprotein (AFP) levels into these models, such as the novel R3-AFP score, has notably enhanced risk stratification. However, validation of these models in high-evidence data is mandatory. Therefore, the aim of the present research was to validate the R3-AFP score in a randomized clinical trial. We analyzed the intention-to-treat population from the 2-arm SiLVER trial (NCT00355862), comparing calcineurin-based ([calcineurin inhibitors]-Group A) versus mammalian target of rapamycin inhibitors-based (sirolimus-Group B) immunosuppression for post-liver transplantation HCC recurrence. Competing risk analysis estimated sub-hazard ratios, with testing of discriminant function and calibration. Overall, 508 patients from the intention-to-treat analysis were included (Group A, n = 256; Group B, n = 252). The R3-AFP score distribution was as follows: 42.6% low-risk (n = 216), 35.7% intermediate-risk (n = 181), 19.5% high-risk (n = 99), and 2.2% very-high-risk (n = 11) groups. The R3-AFP score effectively stratified HCC recurrence risk, with increasing risk for each stratum. Calibration of the R3-AFP model significantly outperformed other explant-based models (Milan, Up-to-7, and RETREAT), whereas discrimination power (0.75 [95% CI: 0.69; 0.81]) surpassed these models, except for the RETREAT model ( p = 0.49). Subgroup analysis showed lower discrimination power in the mammalian target of rapamycin group versus the calcineurin inhibitors group ( p = 0.048). In conclusion, the R3-AFP score accurately predicted HCC recurrence using high-quality evidence-based data, exhibiting reduced performance under mammalian target of rapamycin immunosuppression. This highlights the need for further research to evaluate surveillance schedules and adjuvant regimens.

Effect of transjugular intrahepatic portosystemic shunt insertion on waitlist mortality and access to liver transplantation in budd-chiari syndrome.

The impact of transjugular intrahepatic portosystemic shunt (TIPS) on waitlist mortality and liver transplantation (LT) urgency in Budd-Chiari Syndrome (BCS) patients remains unclear. We analyzed BCS patients listed for LT in the UNOS database(2002-2024) to assess TIPS's impact on waitlist mortality and LT access via competing-risk analysis. We compared trends across two phases:Phase1(2002-2011) and Phase2(2012-2024). Of 815 BCS patients, 263(32.3%) received TIPS at listing. TIPS group had lower MELD-Na scores(20vs22,p<0.01), milder ascites(p=0.01), and fewer Status1 patients(those at risk of imminent death while awaiting LT)(2.7%vs8.3%,p<0.01) at listing compared to those without TIPS. TIPS patients had lower LT rates(43.3%vs56.5%,p<0.01) and longer waitlist times(350vs113d,p<0.01). TIPS use increased in Phase2(64.3%vs35.7%,p<0.01). Of 426 transplanted patients, 134(31.5%) received TIPS, showing lower MELD-Na scores(24vs27,p<0.01) and better medical conditions(Intensive care unit:14.9%vs21.9%,p<0.01) at LT. Status1 patients were fewer (3.7%vs12.3%,p<0.01), with longer waiting days(97vs26d,p<0.01) in TIPS group. TIPS use at listing increased from Phase1(25.6%) to Phase2(37.7%). From Phase1 to Phase2, ascites severity improved, re-LT cases decreased(Phase1:9.8%vsPhase2:2.2%,p<0.01), and cold ischemic time slightly decreased(Phase1:7.0vsPhase2:6.4 hours,p=0.14). Median donor body mass index significantly increased. No significant differences were identified in patient/graft survival at 1-/5-/10-year intervals between phases or TIPS/non-TIPS patients. While 90-day waitlist mortality showed no significant difference(p=0.11), TIPS trended towards lower mortality(subHazard ratio[sHR]:0.70[0.45-1.08]). Multivariable analysis indicated that TIPS was a significant factor in decreasing mortality(sHR:0.45[0.27-0.77],p<0.01). TIPS group also showed significantly lower LT access(sHR:0.65[0.53-0.81],p<0.01). Multivariable analysis showed that TIPS was a significant factor in decreasing access to LT(sHR:0.60[0.46-0.77],p<0.01). Sub-group analysis excluding Status1 or HCC showed similar trends. TIPS in BCS patients listed for LT reduces waitlist mortality and LT access, supporting its bridging role.

HIV treatment outcomes after 10 years on ART in the TREAT Asia Observational Database (TAHOD) and Australian HIV Observational Database (AHOD).

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 (TAHOD) and Australia (AHOD). People with HIV receiving ART for ≥10 years were included. Factors associated with CD4 counts in years 11-15 of ART were analysed using repeated measure linear regression. Survival after 10 years was analysed using competing risk regression. There were 7139 people included: 4867 (68%) from TAHOD and 2272 (32%) from AHOD. Higher CD4 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, 51; >200: difference=125, 95%CI 107, 142) compared to ≤50. The same patterns were observed in those who achieved CD4 ≥500 cells/µL which subsequently decreased to <500 (difference=225, 95%CI 213, 236); or those who achieved and maintained CD4 ≥500 cells/µL (difference=402, 95%CI 384, 420), compared to always <500 in the previous decade. Prior protease inhibitor (PI) -based regimen (difference=-17, 95%CI -33, -1) compared to 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, -15; and difference=-44, 95%CI -61, -27, respectively) compared to no TI. The mortality rate was 1.04 per 100 person-years. Virological failure was associated with subsequent mortality (sub-hazard ratio=1.34, 95%CI 1.04, 1.71). Sustaining high CD4 levels and minimising TI has far-reaching benefits well beyond the first decade of ART.

The impact of VEGF signalling pathway inhibitors and/or immune checkpoint inhibitors on kidney function over time: a single centre retrospective analysis

BackgroundDrugs targeting angiogenesis and immunotherapy have transformed outcomes in renal cancer but may contribute to progressive kidney disease.MethodsWe linked healthcare databases in the West of Scotland (spanning 2010–2020) to identify adults with renal cancer who received one or both classes of drugs. Over two years following initiation, estimated glomerular filtration rate (eGFR) slope was modelled using linear mixed-effects models. Additional renal outcomes used competing risk regression considering the competing risk of death.ResultsAmongst 357 adults (62.5% male; median age 63.0 years, IQI 55.0–71.0), there was no significant change in eGFR (annual eGFR change +1.03 mL/min/1.73 m²/year, 95%CI −1.64 to +3.70), nor in subgroups of patients who had nephrectomy, metastatic cancer or an eGFR < 60 mL/min/1.73 m² prior to systemic therapy. A ≥ 40% decline in eGFR occurred in 82 people (23.0%) within one year of starting systemic therapy and was associated with pre-existing diabetes (subhazard ratio 1.89, 95%CI 1.05–3.41).DiscussionAnti-angiogenic and immune therapy had no substantial impact on the average change in eGFR but people with diabetes are at higher risk of clinically significant renal events. With appropriate monitoring, more widespread use of these agents in patients with renal impairment may be warranted.

Pre-operative pectoralis muscle area index is associated with biomarkers of inflammation and endotoxemia and predicts clinical outcomes after left ventricular assist device implantation: A cohort study.

Pre-left ventricular assist device (LVAD) pectoralis muscle assessment, an estimate of sarcopenia, has been associated with postoperative mortality and gastrointestinal bleeding, though its association with inflammation, endotoxemia, length-of-stay (LOS), and readmissions remains underexplored. This was a single-center cohort study of LVAD patients implanted 1/2015-10/2018. Preoperative pectoralis muscle area was measured on chest computed tomography (CT), adjusted for height squared to derive pectoralis muscle area index (PMI). Those with PMI in the lowest quintile were defined as low-PMI cohort; all others constituted the reference cohort. Biomarkers of inflammation (interleukin-6, adiponectin, tumor necrosis factor-α [TNFα]) and endotoxemia (soluble (s)CD14) were measured in a subset of patients. Of the 254 LVAD patients, 95 had a preoperative chest CT (median days pre-LVAD: 7 [IQR 3-13]), of whom 19 (20.0%) were in the low-PMI cohort and the remainder were in the reference cohort. Compared with the reference cohort, the low-PMI cohort had higher levels of sCD14 (2594 vs. 1850 ng/mL; p = 0.04) and TNFα (2.9 vs. 1.9 pg/mL; p = 0.03). In adjusted analyses, the low-PMI cohort had longer LOS (incidence rate ratio 1.56 [95% confidence interval 1.16-2.10], p = 0.004) and higher risk of 90-day and 1-year readmissions (subhazard ratio 5.48 [1.88-16.0], p = 0.002; hazard ratio 1.73 [1.02-2.94]; p = 0.04, respectively). Pre-LVAD PMI is associated with inflammation, endotoxemia, and increased LOS and readmissions.

Association of Cognitive Frailty With Subsequent All-Cause Mortality Among Middle-Aged and Older Adults in 17 Countries

ObjectivesCognitive frailty refers to the co-occurrence of cognitive impairment and frailty without concurrent Alzheimer's disease or dementia. Studies of cognitive frailty and mortality have been limited to single country or older people. However, frailty and cognitive decline may occur much earlier. We aimed to examine the association between different cognitive frailty status and subsequent all-cause mortality among middle-aged and older people in 17 countries. MethodsParticipants aged 50 and over were drawn from six prospective cohorts of aging. We classified participants according to their cognitive impairment and frailty status into the following groups: none, only cognitive impairment, only frailty and cognitive frailty. Competing-risks regression models were used to evaluate the association of different cognitive frailty status at baseline with subsequent all-cause mortality. ResultsThe cognitive frailty group had a higher mortality risk compared to those without cognitive impairment and frailty groups. Meta-analysis results showed participants with cognitive frailty (pooled subhazard ratio [SHR] = 2.34, 95% confidence interval [CI]: 2.01–2.72, I2 = 68.0%) had a higher mortality risk compared with those with only cognitive impairment status (pooled SHR = 1.36, 95% CI: 1.25–1.48, I2 = 3.0%) or only frailty status (pooled SHR = 1.83, 95% CI: 1.72–1.95, I2 = 31.0%). The association between cognitive frailty and mortality were stronger among those who were aged 70 years and older, males, single and nonconsumers of alcohol. ConclusionsCognitive frailty, frailty or cognitive impairment alone, is associated with an increased risk of all-cause mortality in Asian, European and American countries. Physical and cognitive function screening should be conducted as early as possible in middle-aged and older people, and targeted intervention approaches should be developed to reduce the incidence of adverse health outcomes.

Histological deep margins in cutaneous squamous cell carcinoma of the scalp and risk of recurrence.

Consensus is lacking on adequate deep histological margins in cutaneous squamous cell carcinoma (cSCC). Deep clearance for tumours located on the scalp is limited by anatomic constraints. To determine whether clear but close deep histological margins (<1 mm) confer a higher risk of recurrence in cSCCs of the scalp treated by wide local excision, compared to deep histological margins ≥1 mm. Multicentre retrospective observational cohort study and multivariate competing risk analysis to evaluate risk factors for recurrence. In total, 295 patients with 338 cSCCs were included. Close deep histological margins were not associated with an increased cumulative incidence of recurrence (subhazard ratio [SHR] 1.96 [95% CI 0.87-4.41]). However, an increased risk of recurrence was observed for those tumours that presented concurrent invasion of the galea aponeurotica and close deep margins, as opposed to patients without these factors (SHR 3.52 [1.24-10.01]). Tumours with clear but close peripheral margins (<1 mm) also had higher risk of recurrence (SHR 5.01 [1.68-14.97]). Retrospective observational study based on pathology reports. Deep histological margins <1 mm do not confer a greater risk of recurrence as long as the tumour is completely excised and the galea aponeurotica is not involved. Surgical excision of cSCC on the scalp should include the galea to ensure proper assessment of deep margins.

Comparison of infection risk between enzalutamide and abiraterone in patients with prostate cancer.

Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow-up of 10.6 months (interquartile range: 5.3-19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53-0.93], p=.014), pneumonia (adjusted SHR 0.76 [0.59-0.99], p=.040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39-0.79], p=.001), but not urinary tract infection (adjusted SHR 0.91 [0.62-1.35], p=.643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess.

The Impact of Malnutrition on Chronic Obstructive Pulmonary Disease (COPD) Outcomes: The Predictive Value of the Mini Nutritional Assessment (MNA) versus Acute Exacerbations in Patients with Highly Complex COPD and Its Clinical and Prognostic Implications.

Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. This was a prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had a normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear regression models showed that the MNA score was associated with dyspnea and respiratory symptom severity, assessed by the Modified British Medical Research Council (mMRC) scale and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1, and with poorer QoL, as assessed by the EQ-5D-3 questionnaire. Competing risk analysis according to nutritional status based on the MNA Total Score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with sub-hazard ratios of 3.08 (1.40-6.80), p = 0.015, and 4.64 (1.71-12.55), p = 0.0002, respectively. Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

The PATCH study: Prevalence of Hearing Loss During Ageing and Treatment Choices in Osteogenesis Imperfecta: A Danish Nationwide Register-Based Cohort Study

Osteogenesis imperfecta (OI) is a group of rare hereditary collagen disorders. Hearing loss (HL) is a known complication linked to changes in the bones of the middle ear seen in OI. We aimed to determine the prevalence, age at debut, incidence, and risk of HL, surgery on bones of the middle ear, and use of hearing aids. A Danish nationwide, register-based cohort study. Data were extracted from the Danish National Patient register. Anyone with an OI diagnosis between January 1st 1977 and December 31st 2018, matched 1:5 with a reference population (Ref.Pop) on birthyear and sex, were included. 864 persons (487 women) with OI were included in the study and 4276 (2330 women) in the Ref.Pop. The sub-hazard ratio (SHR) for any HL was 4.56 [95% CI 3.64–5.71], with a prevalence of 17.0% and 4.0% in the OI cohort and Ref.Pop. Median age at debut was 42 and 58 years, respectively. The risk of otosclerosis and/or surgery was higher in the OI cohort (SHR 22.51 [95% CI 12.62–40.14]), with a median age at debut of 43 and 32 years in the OI cohort and Ref.Pop, respectively. Hearing aid use was more frequent in the OI cohort (SHR 4.16 [95% CI 3.21–5.40]) than in the Ref.Pop. The median age at debut was 45 and 60 years in the OI cohort and Ref.Pop, respectively. Persons with OI have a higher risk and prevalence of HL, hearing aids, and surgery, debuting younger, and prevalence increases with age.