Age Cohorts Research Articles

Non-metastatic gastric cancer (GC) in patients aged 80 years or older: Immediate and long-term outcomes of combined treatment.

453 Background: Comorbidities and increased risk of chemotherapy-induced toxicity in elderly patients presents significant challenges in management of GC. Here we presents a single-center experience in treatment patients aged 80 years or older with non-metastatic GS, reporting both immediate and long-term outcomes of surgical treatment (ST). Methods: This retrospective analysis includes 61 patients (pts) diagnosed with non-metastatic GC or cardio-esophageal junction (CEJ) cancer. The primary endpoint was relapse-free survival (RFS); secondary endpoints included overall survival (OS) and the incidence of surgical complications (SC). Results: Among the 61 pts (median age 82.7 years, range 80.0-89.2) 39.3% were men. ECOG PS was 0-1 in 49 pts (80.6%) and 2 – in 12 pts (19.4%). The primary tumor site was the stomach in 57 pts (93.4%) and the CEJ in 4 pts (6.6%). Tumor stage had been defined as cT 1-2 in 33.3% pts, cT 3-4 in 57.1%; cN 0 – in 36.1%, stage remained unknown in 6.3%. Radical surgery was performed in pts 78.7% (n=48), 29 pts (47.5%) of them underwent ST only without perioperative chemotherapy (CT). Neoadjuvant CT (NACT) received 23 pts (37.7%): platinum-based doublet regimen – 82.6% (n=19), while 17.4% (n=4) received capecitabine only. ST was performed in 47.8% (n=11) pts received NACT, other 12 pts didn’t undergo ST due to progression of disease (8.3%), comorbidities (33.3%), or patient preference (16.7%) in 1, 4 and 2 cases, respectively. Adjuvant CT was administered to 9 pts (14.3%). Surgical interventions included gastrectomy in 16.6% pts (n=9), proximal or distal resection – in 8.3% (n=4) and 74.1% (n=35), respectively. R0-resection was achieved in 42 pts (88.6%). SC has 20.8% (n=10) pts: classified as Clavien-Dindo grade (G) II – 4.4%, G IIIa – 8.9%, G IIIb - 8.9%; these included anastomotic leakage (6.7%), abscess formation (2.2%), cardiac events and thrombosis (4.4%), and eventration (2.2%). SC G IV or V not reported. The median duration of postoperative hospitalization was 8 days. In the overall cohort, the 3-y RFS was 53% (95%CI 28.9-53.9), 3-y OS – 67% (95%CI 27.9-75.2). Among the pts with stage IA (n=15), the 3-y RFS was 72% (95%CI 49.1-85.1), with a maximum follow-up period of 80 months and no cancer-related deaths. In patients with cT 2-4 N any 3-y RFS was 70% in the overall cohort and 74% in the surgery-only group (HR 1.09; 95%CI 0.45-2.65, p=1). Conclusions: Our findings demonstrate that over 65% of patients aged 80 years or older survive for at least 3 years following surgery for GC, with 53% living without evidence of metastases. Additionally, the rate of SC in this elderly cohort is comparable to that observed in younger populations. The role of perioperative or neoadjuvant CT in this age group remains a topic of ongoing research and discussion. It is critical to manage such population at referral oncological centers with expertise in treating elderly cancer pts.

Cognitive Impairment is common and unrecognized in vascular surgery patients

ObjectivesPatients’ capacities to understand and act upon healthcare information is crucial to decision-making and high-quality care. Cognitive impairment (CI) has been associated with adverse outcomes across a range of diseases and surgeries. Despite the importance of CI, there is little to no information on its prevalence and severity in vascular surgery patients in the United States. We therefore conducted a prospective observational study to better characterize the prevalence and severity of CI in a contemporary vascular surgery practice. MethodsWe enrolled 111 outpatients attending a vascular surgery clinic using pragmatic consecutive sampling. Patients were excluded if they had a previous diagnosis of blindness, deafness, or dementia. Subjects completed a demographic survey and the Montreal Cognitive Assessment (MoCA), which was administered by a trained proctor. Chart review was used to assess comorbidities. The MoCA is a validated tool consisting of tasks such as clock drawing for assessing CI. It has a lower educational bias and higher sensitivity for detecting mild impairment compared to other exams. The MoCA is scored from 0-30 based on an objective grading system. Scores between 0-9, 10-17, 18-25, and 26-30 indicate severe, moderate, mild, and no CI respectively. Statistical analysis, including multivariable modeling was performed using SAS. ResultsOf 163 patients, our analysis included 111 consecutive vascular patients who completed the MoCA. The average age of the entire cohort was 64.1 years, and 58.6% were male. The majority of the patients in the study were white (80.1%). The mean MoCA score of the entire cohort was 22.6 (mild CI). Of all subjects, 77% had CI: 68% with mild and 9% with moderate CI. Hypertension (p=.024), congestive heart failure (CHF) (p=.028), fewer years of education (p=.032), and Medicaid enrollment (p=.046) all had significant univariate associations with CI. There was no statistically significant difference between age (p=.11) or the primary vascular diagnosis disease for which the patient sought treatment and CI (p=.49). Multivariable models demonstrated that only CHF (OR 3.8, p=.046) was statistically significantly associated with risk of CI. ConclusionIn this first-time prospective study of the entire spectrum of vascular patients in the U.S., we found that nearly 4 out of every 5 vascular surgery patients have undiagnosed cognitive impairment. Furthermore, we found that having CHF was associated with a higher likelihood of CI. Given the implications on consent, decision-making, and postoperative care, future work should focus on enrollment of a larger cohort along with an examination of the impact of CI on mortality, length of stay, and other outcomes.

Chemotherapy selection for advanced or metastatic pancreatic cancer using machine learning models trained with multi-center datasets.

738 Background: Several factors must be considered when selecting the chemotherapeutic regimen for advanced or metastatic pancreatic cancer. The decision between FOLFIRINOX and Gemcitabine/Nab-paclitaxel (GnP) as the first-line therapy is challenging, as survival is influenced by the efficacy and toxicity profiles of these treatments, along with individual patient characteristics and therapeutic vulnerabilities. This study aims to facilitate the selection of an appropriate first-line regimen for advanced or metastatic pancreatic cancer by employing machine learning (ML) methods trained on multi-center datasets. Methods: Our study is based on a cohort of 191 patients who underwent systemic chemotherapy for advanced or metastatic pancreatic cancer at the Gangneung Asan Hospital and Asan Medical Center in South Korea between 2014 and 2023. The dataset consisted of 17 types of demographic and clinical characteristics, as well as time-course of response and survival outcomes. We divided the cohort into training and test groups (4:1) in a stratified manner. ML models predicting overall survival (OS) were trained on the former group using the CatBoost method. The models utilizing a minimal subset of variables were selected with respect to ROC-AUC during 5-fold cross validation. A patient was classified as having high risk to a therapy when the predicted probability of death following treatment initiation was above the threshold value as determined during training of the respective model. Results: The median age of the entire cohort was 62 years, with 64% being male. The ML models achieved ROC-AUCs of 0.81 and 0.82 when predicting early death within 12 months following the initial administration of FOLFIRINOX or GnP, respectively. The predictive accuracies of the models were 0.77 and 0.80 for the unseen datasets from the two treatment groups, respectively. The median OS of the high- versus low-risk groups of FOLFIRINOX predicted by the ML models were significantly different (9 vs 15 months, P <0.0001), with a hazard ratio (HR) of 2.8. Similarly, the median OS of the high- and low-risk groups of GnP were significantly different (9 vs 18 months, P <0.01, HR of 2.5). We observed that 27% of the patients predicted as high risk to FOLFIRINOX therapy were predicted as low risk to GnP and vice versa for 32% of the patients predicted as high risk to GnP therapy. Conclusions: We developed ML models to compute the probability of early death following FOLFIRINOX or GnP therapy from routinely collected data of the patients with advanced or metastatic pancreatic cancer. After confirming robust predictive performance with multi-center datasets, we believe that these models may assist clinicians in selecting a first-line regimens, potentially enhancing personalized treatment strategies for this challenging disease.

Overall survival (OS) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line (1L) FOLFIRINOX (FFX): Bridging the gap between the NAPOLI 3 trial and real-world practice.

690 Background: NALIRIFOX (liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin) demonstrated significantly improved OS compared to 1L gemcitabine + nab-paclitaxel in the phase 3 NAPOLI 3 trial (NCT04083235). The median OS (95% CI) in the NALIRIFOX intention-to-treat population (N= 383) was 11.1 (10.0, 12.1) months. However, the relative efficacy of NALIRIFOX versus FFX (irinotecan + 5-fluorouracil/leucovorin + oxaliplatin), another standard of care for 1L treatment of mPDAC, has not been studied. To further contextualize findings from NAPOLI 3 trial, the current study described OS among patients treated with 1L FFX in the real-world setting. Methods: Three cohorts of patients with mPDAC treated with 1L FFX were identified from the Flatiron Health database. The all-comer cohort included all adult patients with mPDAC treated with 1L FFX since January 2014. Among them, the trial-aligned cohort included patients with mPDAC treated with 1L FFX between January 1, 2020 and July 31, 2022 (to align with the time period of NAPOLI 3 trial) who met the eligibility criteria of NAPOLI 3. Finally, a subgroup of patients in the trial-aligned cohort who received modified FFX (mFFX) regimen composed the trial-aligned mFFX cohort. OS was assessed using Kaplan-Meier analysis. Results: The all-comer cohort consisted of 3,271 patients. The trial-aligned cohort included 219 patients, of whom 154 (70%) were treated with mFFX. The distribution of baseline characteristics was similar across three cohorts (Table). The median age of the trial-aligned cohort was 65 years old, with 46% of patients being female, 67% being White, and 47% having ECOG score of 1. The median OS (95% CI) in the all-comer cohort and trial-aligned cohort was 9.0 (8.5, 9.3) months and 9.1 (7.8, 10.9) months, respectively; the median OS (95% CI) was 8.6 (7.3, 10.5) months in the trial-aligned mFFX cohort. Conclusions: NALIRIFOX regimen in the NAPOLI 3 trial showed numerically improved OS compared to FFX, including mFFX, in the real-world setting. Analysis adjusting for baseline characteristics are warranted and will provide further insights for the comparative efficacy of the two regimens. Characteristics of real-world FOLFIRINOX cohorts. All-comer cohort(N=3,271) Trial-aligned cohort(N=219) Trial-aligned mFFX cohort (N=154) Baseline characteristics Age, years, mean (SD) 63.5 (9.0) 64.6 (8.2) 65.1 (8.5) Female, n (%) 1,377 (42.1) 100 (45.7) 68 (44.2) White, n (%) 2,118 (64.8) 146 (66.7) 100 (64.9) ECOG score = 1, n (%) 1,327 (48.9)* 103 (47.0) 77 (50.0) Endpoint Median OS, months (95% CI) 9.0 (8.5, 9.3) 9.1 (7.8, 10.9) 8.6 (7.3, 10.5) Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; OS, overall survival; SD, standard deviation. *Proportion calculated based on 2,711 patients with ECOG available at baseline.

Abstract P022: Investigating the role of the tumor microenvironment in the rectal cancer response to preclinical radio-immunotherapy combinations

Abstract Background: Locally-advanced rectal cancer (LARC) is traditionally treated with neoadjuvant chemoradiotherapy before surgery, however, response heterogeneity necessitates the development of novel treatment combinations. Immune checkpoint blockade (ICB) with or without radiotherapy (RT) elicits clinical benefit in various solid tumors, yet ICB’s effectiveness so far is limited to colorectal tumors with microsatellite instability and the role of the tumor microenvironment (TME) is unclear. We present a novel orthotopic immunocompetent mouse model of LARC, where combinations of RT and ICB are tested to elucidate the role of TME in the response to treatment. Methods: Autochthonous murine tumor-derived organoids expressing common driver mutations (Apcfl/fl; KrasG12D/+; p53fl/fl; Tgfbr1fl/fl: ‘AKPT’) were orthotopically injected into syngeneic C57Bl/6 immunocompetent mice. Tumor response to RT-ICB was studied on timepoint and aging cohorts of mice with tumors growing in different TME settings: (a) in the rectal submucosa of wildtype mice, (b) subcutaneously in wildtype mice, and (c) in the rectal submucosa of mice lacking the iCCR locus (CCR1, CCR2, CCR3, and CCR5: ‘iCCRKO ’), which inhibits inflammatory monocyte recruitment into the TME. Radiation was delivered as 15Gy in 3# (Mon-Wed-Fri) using a Small Animal Radiation Research Platform on day 13 following tumor engraftment for the orthotopic models and on day 7 for the subcutaneous. PD-1 inhibition (PD-1i) was administered intraperitoneally (10mg/kg twice weekly) 3 days pre-RT until endpoint. Mice in the timepoint experiments were sampled 5 days following RT, while aging mice were sampled at clinical endpoint or 100 days, whichever came first. Results: RT and PD-1i offered significant survival extension and tumor control in the orthotopic wildtype setting (a). Transcriptomic characterization at 5 days revealed that untreated and irradiated tumors harbored a stroma-rich microenvironment, low in immune cells, which PD-1i partly reversed. This phenotypic ‘switch’ was also evident in an aging cohort, suggesting that RT + PD-1i have long-lasting effects on the stroma. In the subcutaneous setting (b), RT significantly increased tumor control but PD-1 blockade offered little additional advantage. Interestingly, subcutaneous AKPT tumors had significantly more CD8+ cells at baseline than orthotopic ones, highlighting the inherent immune permissiveness of the subcutaneous TME. Finally, tumors growing in the iCCRKO setting (c) were more radio-sensitive, leading to 3 instances of tumor clearance: one in the RT group and two in the RT + PD-1i. Conclusion: Our findings demonstrate the synergistic potential of RT and PD-1i to sensitize an inherently radio-resistant orthotopic mouse model of LARC. Tumor location and inflammatory monocytes emerged as key regulators of the immune response to RT-ICB, which could have important implications for LARC modeling. Importantly, we highlight that TME components can facilitate treatment resistance and give rise to targets that can be therapeutically exploited. Citation Format: Lydia Melissourgou-Syka, Michael A. Gillespie, Lily V.S. Hillson, Kathryn Gilroy, Katrina Stevenson, Susanti Susanti, Tamsin R.M. Lannagan, Eoghan Mulholland, Philip D. Dunne, Joanne Edwards, Sean M. O'Cathail, Colin W. Steele, Owen J. Sansom, Campbell S.D. Roxburgh.Investigating the role of the tumor microenvironment in the rectal cancer response to preclinical radio-immunotherapy combinations.[abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr P022

Poisoned in their homes - Red blood cell abnormalities in lead-exposed residents of a Pakistani Industrial Zone.

The present study investigated the clinical and hematological effects of chronic lead exposure in the population residing in Shadi Pura, a small industrial zone in Lahore, Pakistan. A cross-sectional analysis of 149 participants recruited through health camps was conducted to explore the hematological manifestations of environmental lead exposure, focusing on various red blood cell (RBC) indices and morphology. Moreover, the study examined the differences in the impact of lead exposure on RBC indices and morphology between men, women, and children. Participants exhibited symptoms of lead poisoning, including fatigue, muscle pain, and headache, with a significant percentage of women (44%) reporting miscarriages. Iron deficiency anemia was highly prevalent among all sub-groups of the study population, with adult females showing a significantly higher prevalence than adult males. Male children were the most affected subgroup, with 93% displaying anemia. The RBC count in children remained unchanged, while 31% of male and 7% of female participants displayed elevated RBC counts. RBC indices, mainly mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), were below normal levels, with children being more affected than adults and adult males being the least affected group. Furthermore, RBC morphology was severely affected, with a considerable proportion of females and children displaying hypochromic microcytic morphology. Our results highlight variations in the hematological impacts of lead exposure in different sex and age cohorts. Overall, our findings underscore the urgency of addressing the issue of environmental lead exposure in similar industrial zones. It is critical to implement appropriate measures to reduce lead exposure and enhance the infrastructure for safe drinking water and waste disposal to protect the health of populations in such areas.

Which patients with negative PSMA-PET imaging can safely avoid biopsy for prostate cancer? a novel step towards PSMA-based biopsy-free strategy.

This study aimed to identify if a subset of men can safely avoid or delay prostate biopsy based on negative results of prostate-specific membrane antigen positron emission tomography (PSMA-PET). Among 341 consecutive cases in a prospective biopsy cohort (NCT05073653), 111 treatment-naïve men with negative PSMA-PET (PRIMARY-score 1/2) were included. All participants underwent PSMA-PET and histopathological examinations. Clinically significant prostate cancer (csPCa) was defined as Grade Group ≥ 2. Multivariate logistic regression was employed to identify predictors of non-csPCa. Receiver operating characteristic (ROC) analysis was performed to detect non-csPCa on prostate pathology. PSMA-postive patients were additionally reviewed to assess the imaging and pathological outcomes. Younger age was identified as an independent predictor (P = 0.006) for the absence of csPCa. ROC analysis of csPCa revealed the largest areas under the curve of 0.77 (0.67-0.87) and 0.78 (0.68-0.88) for individual age in the entire PSMA-negative cohort and the MRI subset, respectively (both P < 0.001). The negative predictive value (NPV) of PSMA-PET for csPCa detection improved with a decreasing age, from 88% in all, to 98% in men aged under 65 yrs (98% vs. 88%, P = 0.021), and to 100% in men aged under 60 yrs (100% vs. 88%, P = 0.040). The NPV of PSMA-PET improved from 88 to 94% when combined with negative MRI, and to 100% in men with negative MRI and aged under 65 yrs. The prevalence was 57% for csPCa and 65% for PCa of any grade. We preliminarily propose that omission or postponement of prostate biopsy should be considered for men under the age of 65 yrs with negative PSMA-PET scored as PRIMARY 1 or 2. Conversely, prostate biopsy might be considered in biopsy-naïve men aged 65 yrs or older with strong clinical suspicion of PCa, despite negative PSMA-PET. Further prospective and external evaluation is needed to prove the robustness of this novel strategy.

Associations of cathepsins with pulmonary arterial hypertension mediated by circulating metabolites: A Mendelian randomization study.

The correlation between cathepsins and pulmonary arterial hypertension (PAH) is well-established, but the causative link between them remains uncertain. This study aimed to explore the causal role of circulating metabolites mediating cathepsins in PAH using Mendelian randomization (MR). A 2-sample 2-step MR method was used to identify causal relationship between cathepsins and PAH; causal relationship between circulating metabolites and PAH; and mediated effects of these circulating metabolites. GWAS summary statistics on circulating metabolites were from the Canadian longitudinal study on aging cohort, human plasma cathepsins from The INTERVAL study, and PAH from FinnGen version R10. Two-sample MR analyses involving 9 cathepsins (cathepsin B, E, F, G, H, L2, O, S, and Z). Cathepsin S was associated with high risk of PAH (OR: 1.346, 95% CI: 1.039-1.742, P = .024), and positively with circulating metabolite 1-oleoylglycerol (18:1) levels (OR: 1.062, 95% CI: 1.018-1.108, P = .005). Finally, mediation analysis showed evidence of mediated effect of cathepsin S on PAH through 1-oleoylglycerol (18:1) levels (OR: 0.062, CI: 0.0183-0.106) with a mediated proportion of 20.9% of the total effect. This study reveals cathepsin S increases the risk of PAH mediating by circulating metabolite 1-oleoylglycerol (18:1) levels.

The association of visceral and subcutaneous fat areas with phenotypic age in non-elderly adults, mediated by HOMA-IR and HDL-C

BackgroundAgeing results in diminished adaptability, as well as declines in physiological and psychological functions and resilience. The epigenetic clock ‘Phenotypic Age’ (PhenoAge) represents ‘preclinical ageing’. Phenotypic Age Acceleration (PhenoAgeAccel) is defined as the residual from a linear regression model predicting PhenoAge on the basis of chronological age. Abdominal subcutaneous adipose tissue, visceral adipose tissue, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and high-density lipoprotein cholesterol (HDL-C) have all been shown to correlate with ageing; however, the connections between these factors and PhenoAge are still insufficiently investigated.MethodsData for this study were sourced from the National Health and Nutrition Examination Survey (2015–2018), comprising 2580 participants. Complex survey designs were considered. To examine the association between body fat area and PhenoAgeAccel, logistic regression was applied. Additionally, subgroup analysis was used to identify variations in population characteristics. The dose‒response relationship between body fat area and PhenoAgeAccel was determined via restricted cubic spline analysis. Mediation and interaction analyses were further employed to investigate the roles of the HOMA-IR and HDL-C in this association.ResultsIn nonelderly adults, the relationships between body fat area and PhenoAgeAccel differed chronological age. For abdominal subcutaneous fat area (SFA), this relationship was nonlinear in individuals aged 18–44 years and 45–59 years, with thresholds of 2.969 m² and 3.394 m², respectively. In contrast, a nonlinear relationship of visceral fat area (VFA) with PhenoAgeAccel was observed in individuals aged 18–44 years, while this relationship was linear in individuals aged 45–59 years, with thresholds of 0.769 m² and 1.220 m², respectively. Mediation effect analysis revealed that the HOMA-IR had a more pronounced mediation effect in individuals aged 18–44 years, accounting for 13.4% of the relationship between VFA and PhenoAgeAccel and 6.9% of the relationship between SFA and PhenoAgeAccel. Conversely, HDL-C had a greater mediating effect in individuals aged 45–59 years, accounting for 21.7% of the relationship between VFA and PhenoAgeAccel and 11.6% of the relationship between abdominal SFA and PhenoAgeAccel. HOMA-IR ≥ 2.73 or VFA > 0.925 m², as well as HOMA-IR ≥ 2.73 or abdominal SFA > 3.137 m², accelerated PhenoAge, whereas 1.60 < HDL-C ≤ 3.90 mmol/L combined with abdominal SFA ≤ 3.137 m² or VFA ≤ 0.925 m² decelerated PhenoAge.ConclusionIn this study, the nonlinear relationships among abdominal SFA, VFA, and PhenoAgeAccel were elucidated, while characteristic thresholds across different age groups were identified. The results of this study emphasize the complex influence of fat distribution on the ageing process and refine the roles of HOMA-IR and HDL-C in various age cohorts. These findings provide a biological basis for future screening for accelerated ageing and appropriate intervention in high-risk populations and offer valuable insights for guiding personalized clinical interventions and health management strategies.

Cannabis Use and Self-Reported Bothersome Symptoms in People with HIV

Objective: While cannabis use is common among people with HIV (PWH), there have been few studies examining the association of use with health outcomes among PWH. We aimed to evaluate the association between cannabis use and bothersome physical and mental health symptoms using both self-report and a direct biomarker for cannabis use. Method: The Medications, Alcohol and Substance use in HIV Study (MASH) is a cross-cohort study focused on polypharmacy and substance use among PWH. Participants were enrolled from October 2018 to May 2022 in the Swiss HIV Cohort Study (SHCS), Kaiser Permanente Northern California (KPNC) HIV Cohort, and 7 sites (Atlanta, GA; Bronx, NY; Washington, DC; Houston, TX; Los Angeles, CA; New York, NY; and Nashville, TN) in the Veterans Aging Cohort Study - HIV (VACS-HIV). Participants submitted self-reported information on the presence/absence of symptoms in the prior 4 weeks, along with bothersome level, using the HIV Symptom Index, which is comprised of 20 symptoms commonly reported in PWH, including fatigue, diarrhea, fever, anxiety, and weight loss, among others. Concurrent self-reported substance use information was also collected, and participants provided nail clippings to be tested for cannabis use. We used logistic regression models, adjusted for age, sex, race/ethnicity, and cohort, to examine associations of self-report and biomarker-identified cannabis use with self-reported bothersome symptoms. Results: The analytic sample included 1,226 PWH who were predominantly male (85%), non-white (64%), with an average age of 57 years; 20% tested positive for cannabis use, and 23% reported recent cannabis use. Agreement between self-report and biomarker cannabis use was substantial (agreement 89%, kappa = 0.67). Put together, 27% either reported cannabis use or tested positive. Of the 20 symptoms included in the HIV Symptom Index, 19 were more prevalent at a bothersome level among those with cannabis use compared to those without. In adjusted models, the patterns of association remained for both self-reported and biomarker-confirmed cannabis use, and they were particularly substantial for memory, depression, anxiety, and nausea. Conclusions: Cannabis use was common among PWH and was associated with a number of bothersome symptoms. While cannabis use may be used to treat loss of appetite, nausea/vomiting, and weight loss, the associations of cannabis use with depression, anxiety, and memory loss are concerning and deserve investigation.

Osteonecrosis of the Humerus: Trends in Surgical Management of a Nationwide Sample From 2010 to 2021.

The humeral head is the second most common site for osteonecrosis but its epidemiology is poorly described. This study aimed to better understand its treatment in the United States by 1) evaluating total operative procedures with rates normalized to the annual surgical volume; 2) determining trends of non-joint preserving (shoulder arthroplasty) vs. joint preserving procedures; and 3) quantifying rates of operative techniques in different aged cohorts (<50 vs. ≥50 years old). A nationwide database was queried for patients with humeral osteonecrosis who underwent surgery between January 1st, 2010 and April 30, 2021, yielding 9,307 cases. Patients classified under non-joint preserving procedures included those who underwent shoulder arthroplasty (total and reverse) (N = 5,752) and hemiarthroplasty (N = 2,086). Joint preserving procedures included humeral head core decompression and arthroscopic débridement (N = 1,469). The percentage of patients annually managed by each operative procedure was calculated and normalized to the overall annual surgical population from our sample. Linear regression modelling was performed to evaluate trends/differences in procedural volume over time based on the type of procedure (joint preserving vs. non-preserving) and age cohort (under versus over 50 years old). P-values < 0.05 were significant. Within this nationwide sample, the number of procedures to treat shoulder osteonecrosis relative to all shoulder procedures was 0.85% (9,307/1,092,726). Overall, shoulder arthroplasty (total and reverse) was the most commonly performed procedure (N = 5,752; 61.8%), followed by hemiarthroplasty (N = 2,086; 22.4%), and core decompression/arthroscopic débridement (N = 1,469; 15.8%). Non-joint preserving comprised 7,838 procedures (84.2%), while 1,469 (15.8%) were joint preserving. On age group subanalysis, there were significantly more joint preserving procedures in patients aged <50 years (25.8% vs. 14.1%, P < 0.001). Core decompression/arthroscopic débridement as a proportion of all procedures in patients younger than 50 increased over the study period (22.1% to 35.6%, P = 0.035). Procedures used to manage humeral osteonecrosis comprise less than 1% of all shoulder surgeries. These procedures continue to be predominantly shoulder arthroplasty; however, the utilization of joint preserving procedures seem to be growing over time, notably in patients <50 years of age. Shoulder surgeons may use this data to better educate patients about treatment options during the decision-making process. Future studies should be aimed towards further characterizing patterns in the diagnosis and treatment of humeral osteonecrosis.

Prevalence of complications and comorbidities associated with obesity: a health insurance claims analysis

BackgroundDespite the substantial burden of obesity in the United States (US), data on the comprehensive range of comorbidities in different age groups is limited. This study assessed the prevalence of various comorbidities among people diagnosed with obesity (as per ICD-10 diagnosis code) across age cohorts and compared how they differ from people without obesity.MethodsThis cross-sectional study analyzed individuals from all four regions (Midwest, Northeast, South, and West) of the US who had continuous insurance coverage from 2018 to 2020, using a large health insurance claims database (Merative™ MarketScan®). Identification of disorders relied on ICD-10 diagnosis code in patient claims and their prevalence was calculated.ResultsOf 6,935,911 individuals, people with a diagnosis of obesity accounted for 22.0%, 33.6%, and 34.4% in the 18–39 years, 40–64 years, and ≥ 65 years age groups, respectively. Within age strata, the mean age of people with obesity was comparable with those without obesity. Comorbidity burden was significantly higher among people with obesity, but increased with age in both obesity and non-obesity groups. Comorbidities with highest prevalence in people with obesity included: (i) hypertension (18–39 years: 29.0%, 40–64 years: 66.2%, ≥ 65 years: 89.4%), (ii) dyslipidemia (18–39 years: 28.1%, 40–64 years: 65.4%, ≥ 65 years: 88.0%), (iii) depression or anxiety (18–39 years: 44.1%, 40–64 years: 39.0%, ≥ 65 years: 38.9%), and (iv) prediabetes (18–39 years: 17.1%, 40–64 years: 32.2%, ≥ 65 years: 35.3%). Notably, increased prevalence of cardiometabolic risk factors such as hypertension and dyslipidemia began at an earlier age in people with obesity as compared with those without obesity. Ratio of prevalence between obesity and non-obesity groups was highest for the 18–39 years age group, as compared to older groups. Disorders such as obstructive sleep apnea, osteoarthritis, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, coronary heart diseases (CHD), and chronic kidney diseases also exhibited substantial burden among those with obesity.ConclusionsIn this claims study, hypertension and dyslipidemia were the leading comorbidities in people with obesity, with an increasing prevalence with age. The burden of cardiometabolic comorbidities among the younger age group suggested potential risk for early onset of CHD in later life. Understanding the range of obesity-related comorbidities seen in this claims data may encourage healthcare professionals and healthcare systems to systematically diagnose and better manage these disorders. Further research using additional data sources can offer a more accurate view of the prevalence of obesity and its impact.

DOP130 Analysis of the circulating methylome in 155 IBD-discordant twin pairs from UK and Scandinavia highlights differential variance and association with active inflammation

Abstract Background Consistent alterations in DNA methylation across the genome have been well-characterised in inception cohorts of North European patients with inflammatory bowel disease [1-3]; these data implicate inherited determinants, active inflammation and the exposome in shaping the methylome. We have recruited a unique group of 155 twin pairs discordant for IBD to allow exploration of the interplay between these factors. Methods Whole blood from twins discordant for diagnosis of IBD was profiled using methylation microarrays (Figure) in two cohorts (UK-1 &amp; Scandinavia-2). We performed analysis of both cohorts with epigenome-wide association study (EWAS), investigation of methylation Shannon’s entropy, methylation variance, and the epigenetic age. Analysis of the methylation correlates of disease activity in cohort 1 (UK) was performed. Additionally, smoking-related methylation was explored. Results The discovery cohort (UK-1) included 64 di- and monozygotic twin pairs while the replication cohort (Scandinavia-2) included 91 sex-matched IBD-discordant twin pairs. The mean age in both cohorts was 53 years and the mean disease duration was 24 years. IBD-discordant twin pairs differed in Shannon’s entropy at individual probes (located in/near IL10RA, IL2RA, IL18RAP, VMP1, CEP72/AHRR), of which three replicated (cg11498228-ARHGEF10, cg07664915-KCTD13/MAPK3, cg20859708-NAA35), and many were located in IBD GWAS regions (such as FOXP1, LPP, MICA). The entropy findings from IBD GWAS regions were partially confirmed in monozygotic twins alone (e.g., TNXB in MHC class III region, bootstrap p.fdr&amp;lt;10-118), despite near-perfect controlling for genetics and early-life exposome. Sites highlighted by differential variance analysis included IBD genes, such as TAS1R3, GALNT2 and CACNA1H (all q-values&amp;lt;5×10-6). No epigenetic age acceleration was identified in patients with IBD. Clinical activity of IBD exhibited a number of associations with the whole blood methylome, including a negative correlation between methylation at a key IBD site RPS6KA2 with faecal calprotectin (Table). In patients with IBD and controls, cross-cohort smoking EWAS replicated multiple smoking-related sites at genome-wide significance, many of which located in AHRR and ALPI loci, both of which are implicated in IBD. Conclusion Methylation level at individual probes related to IBD activity and showed IBD-associated differences in methylation entropy and variance between twins despite shared genetics and early-life exposome, adding new context for understanding established IBD loci and strengthening their role. [Funding-EU's FP7 IBD Character (2858546, JS); Lundbeck (R211-2015-3061), Region of South. Denmark, Univ. of South. Denmark, Univ. Hosp. of South. Denmark Aabenraa (VA)][No AI used.]

Long-Term Survival with Multiple Myeloma: An Italian Experience

Background/Objectives: Treatments for multiple myeloma (MM) have expanded in the last decade, and the overall survival (OS) of MM patients (pts) is in continuous improvement. With the availability of new treatments and the use of high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation (ASCT), the median OS of newly diagnosed MM (NDMM) pts is 6–8 years. To date, approximately 50% and 28% of MM patients are still alive at 5 years and 10 years. Few data are reported concerning the characteristics of the long-term survival MM pts. Methods: the aim of this observational multicenter study is to analyze the clinical profile of MM pts who have survived 10 years or longer, to identify possible predictors of long-term survival. Conclusions: this is a real-life observation of a cohort of 344 long-term survivors with MM. The median age of the entire cohort was 59 years (range 27–83). The median years from diagnosis was 13.4 (range 11.3–16.3). Our analysis identified age more than 60 years, hypoalbuminemia at diagnosis, and a number of anti-myeloma therapies equal or more than 3 as significant independent prognostic factors for reduced OS. These finding underline the importance of designing prospective studies to identify clinical, biological, and molecular characteristics that could be used to better stratify newly diagnosed multiple myeloma pts in order to incorporate reproducible biomarkers and to identify tailored optimal target therapies.

State or family? Navigating the changing public attitudes towards eldercare responsibilities in China

Public attitudes towards welfare have long been central to welfare state theory. This study examines the evolving public perceptions regarding the allocation of eldercare responsibilities between the state and family in China. Using data from the Chinese General Social Survey spanning 2010–2021, we analyze age, period, and birth cohort effects on public attitudes towards eldercare. Our findings indicate that as individuals age, there is a growing preference for government responsibility in eldercare, highlighting the role of self-interest in shaping welfare attitudes. Notably, attitudinal shifts across birth cohorts deviate from the modernization hypothesis, revealing a tendency among those born in the 1970s and 1980s to view eldercare as a family obligation. Over the last decade, public attitudes towards eldercare have oscillated from an initial embrace of modern perspectives to a return to traditional views, potentially due to demographic pressures on the pension system. This study not only fills empirical gaps in the field but also carries significant policy implications for China’s evolving eldercare landscape.

P0466 Impact of the COVID-19 Pandemic on Clinical Presentation and Management of Inflammatory Bowel Disease: A Multicentre Study in the West Midlands, UK

Abstract Background The COVID-19 pandemic disrupted healthcare systems globally, exacerbating disease severity and delaying management of chronic conditions like inflammatory bowel disease (IBD). This multicentre study investigates the pandemic’s impact on clinical presentation, treatment patterns, and outcomes of ulcerative colitis (UC) and Crohn’s disease (CD) patients at two UK district hospitals. Methods A retrospective study was conducted between July 2017–June 2022 at two district hospitals, comparing pre- and post-COVID outcomes in UC and CD patients. Factors analyzed included disease extent, inflammatory markers, treatment patterns, diagnostic investigations, and patient outcomes, such as emergency surgery. Results Among 602 IBD patients (52.2% UC, 47.8% CD), the median age was 41 years (IQR 29), and 51.3% were male. Post-COVID, UC patients presented with more severe disease: UC E3 (Extensive Colitis) increased from 24.0% to 32.8% (p=0.01), while UC E1 (Proctitis) decreased from 18.4% to 7.4% (p=0.004). Median hospital stays rose from 4 to 6 days (p=0.03), with inflammatory markers showing significant increases—median CRP levels rose from 25 to 35 mg/L (p=0.016), and faecal calprotectin levels increased from 600 to 1800 µg/g (p&amp;lt;0.0001). Treatment patterns shifted, with reduced 5-ASA (77.6% to 59.3%, p=0.001) and immunosuppressant use (19.2% to 9.0%, p=0.004) but increased biologic therapy (27.2% to 31.7%, p=0.001). In CD, disease localization shifted significantly: terminal ileum involvement (CD L1) rose from 30.6% to 46.8% (p=0.001), while ileocolonic disease (CD L3) decreased from 45.9% to 31.1% (p=0.01). Imaging utilization nearly doubled, with CT/MRI use increasing from 36.7% to 71.6% (p&amp;lt;0.001). Post-COVID CD patients were younger, with median age decreasing from 42 to 39 years (p=0.05). Untreated cases in the younger cohort of age &amp;lt;43 years rose from 64% to 84% (p=0.004). Emergency surgery rates in both UC and CD and ITU admission rates remained unchanged pre- and post-COVID. Conclusion Post-COVID, UC patients presented with more extensive colitis, higher inflammatory markers, and longer hospital stays. CD patients showed shifts in disease localization, increased imaging use, and a younger, less-treated demographic. Delayed access to care likely fostered disease progression, compounded by pandemic-related psychological stress and immune dysregulation. Strengthening healthcare systems with robust referral pathways and timely IBD treatment is essential to mitigate impacts of any future systemic disruptions.

Healthy Aging and the Gut Microbiome in People With and Without HIV.

Aging-related comorbidities are more common in people with human immunodeficiency virus (HIV) compared to people without HIV. The gut microbiome may play a role in healthy aging; however, this relationship remains unexplored in the context of HIV. 16S rRNA gene sequencing was conducted on stool from 1409 women (69% with HIV; 2304 samples) and 990 men (54% with HIV; 1008 samples) in the MACS/WIHS Combined Cohort Study. Associations of age with gut microbiome diversity, uniqueness, and genus-level abundance were examined in women and men separately, followed by examining relationships of aging-related genera with frailty (Fried frailty phenotype) and mortality risk (Veterans Aging Cohort Study [VACS] index). Older age was associated with greater microbiome diversity and uniqueness, greater abundance of Akkermansia and Streptococcus, and lower abundance of Prevotella and Faecalibacterium, among others; findings were generally consistent by sex and HIV status. An aging-related microbiome score, generated via combination of 18 age-related genera, significantly increased with age in both women and men independently of demographic, behavioral, and cardiometabolic factors. In general, age was more strongly related to microbiome features (eg, diversity, microbiome score) in men without compared to with HIV, but age-microbiome associations were similar in women with and without HIV. Some age-related genera associated with healthy/unhealthy aging, such as Faecalibacterium (related to reduced frailty) and Streptococcus (related to higher VACS index). Age is associated with consistent changes in the gut microbiome in both women and men with or without HIV. Some aging-related microbiota are associated with aging-related declines in health.

Exploring predementia: Understanding the characteristics of subjective cognitive decline plus from India.

Subjective cognitive decline (SCD) is the early predementia syndrome. that occurs even before the development of objective cognitive decline. SCD plus refers to an additional set of criteria that increases the likelihood of developing mild cognitive impairment and further progressing to Alzheimer's disease (AD). Studying the progression of SCD-plus participants will help in understanding the importance of diagnosing this condition at an early stage and delaying its onset. The present tries to examine neurocognitive changes in individuals who met the criteria of SCD-plus patients. The study also investigated the imaging correlates of these individuals in both cohorts. This study included 94 participants from Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) and Tata Longitudinal Study of Aging (TLSA) cohorts who satisfy the criteria of SCD plus. Mann-Whitney U test was used to compare the SCD plus participants and healthy controls. Regression analysis was performed to find the association between SCD plus and cognition. The SCD-plus group performed poorer than the healthy group in episodic memory delayed recall (p = 0.049), name face recognition (p = 0.023), and letter fluency (p = 0.004) tasks. The generalized linear model revealed that the SCD-plus group had lower left cerebellar cortex (p = 0.010) and right inferior occipital cortex (p = 0.016) volumes than the healthy control group. The participants in the SCD-plus group performed poorly on memory and language-related tasks, and the volumes of the associated brain regions decreased. This study suggested that the SCD-plus group had characteristics similar to AD group and can help in identifying AD at the earliest.

Impact of frailty and older age on weaning from invasive ventilation: a secondary analysis of the WEAN SAFE study

ObjectiveTo understand the impact of both frailty and chronologic age on outcomes of weaning from invasive mechanical ventilation (MV).MethodsThe study population consisted of patients enrolled in the ‘WorldwidE. AssessmeNt of Separation of pAtients From ventilatory assistancE (WEAN SAFE) study. We defined 4 non-overlapping groups, namely: ‘frail’ (clinical frailty scale [CFS] score > 4; age < 80 years); ‘elderly’ (CFS ≤ 4; age ≥ 80y), ‘frail \\elderly’ (CFS > 4; age ≥ 80 years), and a ‘not frail or elderly’ population. The primary outcome was the impact of frailty and older age on delayed weaning and failed weaning from invasive MV. Secondary outcomes included the impact of frailty and age on ICU and hospital survival.ResultsIn the study population, 760 (17%) were frail, while 360 (8%) were elderly, 197 (4%) were frail and elderly, while 3,176 (70%) were not frail or elderly. The frail and elderly cohorts were more likely to be female, had hypoxemic/hypercapnic respiratory failure or sepsis, and had more comorbidities. The proportion of delayed weaning and of failed weaning from invasive MV was significantly higher in the frail (28 and 23%), the elderly (25 and 19%), and the frail and elderly groups (22% and 25%), compared to the not frail or elderly population (12% and 13%, P < 0.01). ICU and hospital mortality was higher in the frail (21 and 33%), the elderly (19 and 31%), and the frail and elderly groups (26 and 46%), compared to the not frail or elderly population (12% and 18%, P < 0.001). In multivariate analyses, there was an independent association between frailty and delayed weaning initiation and weaning failure. Old age was independently associated with risk of weaning failure.ConclusionsFrailty status had a more consistent impact than older age on weaning outcomes. However, overall outcomes in these cohorts are encouraging once separation attempts have been initiated.

Development and validation of a nomogram to predict the probability of death after surgical evacuation for traumatic intracranial hemorrhage

Here we describe the derivation and validation of a prognostic nomogram for patients with Traumatic Intracranial Hemorrhage (tICH) after surgical evacuation. This is a retrospective study based on 245 patients admitted to the Department of Neurosurgery of Huashan Hospital affiliated to Fudan University, between August 2005, and August 2023. We divided the dataset into primary and validation data by the ratio of 7:3. The LASSO regression model was used for predictor selection. The nomogram was developed using Cox regression models. The predictive performance of the nomogram was assessed by concordance index (C index) and calibration in the primary and validation cohorts. We also used decision curve analysis (DCA) to describe the clinical value. The main outcome was death related to tICH. The nomogram incorporated age, GCS-E, history of hypertension, and cerebellar hematoma, which was selected by the LASSO regression model. The nomogram showed good calibration and discrimination in the primary and validation data, with a 1-year C-index of 0.882 (95% CI, 0.777 to 0.987) and 0.818 (95% CI, 0.669 to 0.968), respectively. Decision curve analysis indicated that the nomogram is clinically useful when the patient or doctor’s threshold probability ranges from 10 to 100%. In this study, we found that the tICH-related mortality rate was 11.42% (28/245). In the elderly cohort aged ≥ 65 years, the mortality rate increased to 28.13%(18/64). The nomogram we developed here can be conveniently used to predict the long-term prognosis of patients with tICH after surgical evacuation.Retrospectively registered: KY2024-860.