Distinct Prostate Cancer Survival Outcomes in Firefighters: A Population-Based Study.

Introduction: Survival outcomes for prostate cancer among specific occupational groups prone to regular medical check-ups vis-à-vis the general population have been understudied. For firefighters, a demographic subject to rigorous medical evaluations, possessing above-average medical expertise, and exposed to specific carcinogens of interest, prostate cancer survival in the US has never been studied. Methods: We conducted a retrospective study, utilizing data from the Florida Cancer Data System spanning 2004 to 2014, coupled with firefighter certification records from the Florida State Fire Marshal's Office. Our study cohort consisted of 1058 prostate cancer cases among firefighters as well as prostate cases for the Florida general population (n = 150,623). We compared cause-specific survival between the two using Cox regression models adjusted for demographics and clinical characteristics, including PSA levels, Gleason scores, and treatment modalities. Results: Firefighters demonstrated a higher five-year cause-specific survival rate (96.1%, 95% CI: 94.7-97.1%) than the general population (94.2%, 95%CI: 94.1-94.3%). Overall, firefighters' diagnoses were established at younger ages (median age 63 vs. 67 in the general population), exhibited a higher proportion of localized stage cancers (84.7% vs. 81.1%), and had a greater utilization of surgery (46.4% vs. 37.6%), a treatment modality with a high success rate but potential side effects. In multivariable analysis, firefighters displayed a survival advantage for localized stage (adjusted hazard ratio [aHR] = 0.53; 95%CI: 0.34-0.82). However, for regional or distant stages, firefighters aged 65 and above exhibited a higher risk of death (aHR = 1.84; 95% CI: 1.18-2.86) than the general population. Conclusion: Firefighters experience enhanced prostate cancer survival, primarily in cases diagnosed at localized stages, likely due to increased PSA testing. Nonetheless, for regional or distant stage, survival among older firefighters' lags behind that of the general population. Further investigations are warranted to unravel factors influencing the development of aggressive disease beyond PSA and Gleason scores in this population, as well as to assess the impact of a higher rate of surgical treatment on firefighters' quality of life.

Angioembolization for splenic injuries: does it help? Retrospective evaluation of grade III-V splenic injuries at two level I trauma centers.

Background: Splenic angioembolization (SAE) has increased in utilization for blunt splenic injuries. We hypothesized lower SAE usage would not correlate with higher rates of additional intervention or mortality when choosing initial non-operative management (NOM) or surgery. Study design: Trauma registries from two level I trauma centers from 2010 to 2020 were used to identify patients aged >18 years with grade III-V blunt splenic injuries. Results were compared with the National Trauma Data Bank (NTDB) for 2018 for level I and II centers. Additional intervention or failure was defined as any subsequent SAE or surgery. Mortality was defined as death during admission. Results: There were 266 vs 5943 patients who met inclusion/exclusion criteria at Stanford/Santa Clara Valley Medical Center (SCVMC) versus the NTDB. Initial intervention differed significantly between cohorts with the use of SAE (6% vs 17%, p=0.000). Failure differed significantly between cohorts (1.5% vs 6.5%, p=0.005). On multivariate analysis, failure in NOM was significantly associated with NTDB cohort status, age 65+ years, more than one comorbidity, mechanism of injury, grade V spleen injury, and Injury Severity Score (ISS) 25+. On multivariate analysis, failure in SAE was significantly associated with Shock Index >0.9 and 10+ units blood in 24 hours. On multivariate analysis, a higher risk of mortality was significantly associated with NTDB cohort status, age 65+ years, no private insurance, more than one comorbidity, mechanism of injury, ISS 25+, 10+ units blood in 24 hours, NOM, more than one hospital complications, anticoagulant use, other Abbreviated Injury Scale ≥3 abdominal injuries. Conclusions: Compared with national data, our cohort had less SAE, lower rates of additional intervention, and had lower risk-adjusted mortality. Shock Index >0.9, grade V splenic injuries, and increased transfusion requirements in the first 24 hours may signal a need for surgical intervention rather than SAE or NOM and may reduce mortality in appropriately selected patients. Level of evidence: Level II/III.

Trends in ototoxicity monitoring among cisplatin-treated patients with cancer.

PURPOSE: This study aims to characterize patterns in ototoxicity monitoring and identify potential barriers to audiologic follow-up. METHODS: We performed a single-institution retrospective cohort study on adult (≥ 18 years old) cancer patients treated with cisplatin from January 2014 to September 2021. Our primary outcomes were rates of baseline and post-treatment audiograms at the following time points: 3, 6, 12, and greater than 12 months. Time-to-event analyses were performed to describe additional insights to ototoxicity monitoring patterns. RESULTS: Nine hundred fifty-five patients with cancer were included for analysis. The most common primary cancer sites were head and neck (64%), followed by cervical (24%). Three hundred seventy-three patients (39%) underwent baseline audiometric assessment, 38 patients (4%) received audiologic evaluation during chemotherapy, and 346 patients (36%) obtained at least one post-treatment audiogram. Audiologic follow-up was greatest within 3 months of completing chemotherapy (26%), but this tapered dramatically to less than 10% at every other post-treatment time point. Patients with head and neck cancer achieved higher rates of audiologic follow-up at every time point than patients with non-head and neck cancer except for during treatment. CONCLUSIONS: Ototoxicity monitoring is an inconsistent practice, particularly during chemotherapy and for long-term surveillance of hearing loss. Patients with non-head and neck cancer may be at increased risk for loss of audiologic follow-up. IMPLICATIONS FOR CANCER SURVIVORS: Cisplatin ototoxicity is a common occurrence that can be effectively managed with auditory rehabilitation. Therefore, referrals to audiology and counseling on treatment-related ototoxicity are recommended throughout chemotherapy and cancer survivorship.

US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery.

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

From Diabetes to Oncology: Glucagon-like Peptide-1 (GLP-1) Receptor Agonist's Dual Role in Prostate Cancer.

Glucagon-like peptide-1 (GLP-1), an incretin hormone renowned for its role in post-meal blood sugar regulation and glucose-dependent insulin secretion, has gained attention as a novel treatment for diabetes through GLP-1 receptor agonists (GLP-1-RA). Despite their efficacy, concerns have been raised regarding the potential associations between GLP-1-RA and certain malignancies, including medullary thyroid cancer. However, evidence of its association with prostate cancer (PCa) remains inconclusive. This review delves into the intricate relationship between GLP-1-RA and PCa, exploring the mechanisms through which GLP-1-Rs may impact PCa cells. We discuss the potential pathways involving cAMP, ERK, AMPK, mTOR, and P27. Furthermore, we underscore the imperative for additional research to elucidate the impact of GLP-1-RA treatment on PCa progression, patient outcomes, and potential interactions with existing therapies. Translational studies and clinical trials are crucial for a comprehensive understanding of the role of GLP-1-RA in PCa management.

Hearing Loss and Associated 7-Year Cognitive Outcomes Among Hispanic and Latino Adults.

Importance: Hearing loss appears to have adverse effects on cognition and increases risk for cognitive impairment. These associations have not been thoroughly investigated in the Hispanic and Latino population, which faces hearing health disparities. Objective: To examine associations between hearing loss with 7-year cognitive change and mild cognitive impairment (MCI) prevalence among a diverse cohort of Hispanic/Latino adults. Design, Setting, and Participants: This cohort study used data from a large community health survey of Hispanic Latino adults in 4 major US cities. Eligible participants were aged 50 years or older at their second visit to study field centers. Cognitive data were collected at visit 1 and visit 2, an average of 7 years later. Data were last analyzed between September 2023 and January 2024. Exposure: Hearing loss at visit 1 was defined as a pure-tone average (500, 1000, 2000, and 4000 Hz) greater than 25 dB hearing loss in the better ear. Main outcomes and measures: Cognitive data were collected at visit 1 and visit 2, an average of 7 years later and included measures of episodic learning and memory (the Brief-Spanish English Verbal Learning Test Sum of Trials and Delayed Recall), verbal fluency (word fluency-phonemic fluency), executive functioning (Trails Making Test-Trail B), and processing speed (Digit-Symbol Substitution, Trails Making Test-Trail A). MCI at visit 2 was defined using the National Institute on Aging-Alzheimer Association criteria. Results: A total of 6113 Hispanic Latino adults were included (mean [SD] age, 56.4 [8.1] years; 3919 women [64.1%]). Hearing loss at visit 1 was associated with worse cognitive performance at 7-year follow-up (global cognition: ß = -0.11 [95% CI, -0.18 to -0.05]), equivalent to 4.6 years of aging and greater adverse change (slowing) in processing speed (ß = -0.12 [95% CI, -0.23 to -0.003]) equivalent to 5.4 years of cognitive change due to aging. There were no associations with MCI. Conclusions and relevance: The findings of this cohort study suggest that hearing loss decreases cognitive performance and increases rate of adverse change in processing speed. These findings underscore the need to prevent, assess, and treat hearing loss in the Hispanic and Latino community.

Quantification and molecular correlates of tertiary lymphoid structures in primary prostate cancer.

OBJECTIVE: To morphologically describe tertiary lymphoid structures (TLS) in prostatectomy specimens and correlate them with clinical and transcriptomic features. METHODOLOGY: A total of 72 consecutive cases of entirely submitted radical prostatectomy (RP) patients tested with the Decipher Genomic Classifier were included in the study. Images were manually annotated using QuPath tools to denote tumor regions and each cluster of TLS. Clusters of lymphocytes that were surrounded on all four sides by tumor were defined as intra-tumor TLS (IT-TLS). Clusters of lymphocytes at the leading edge of carcinoma with either the prostatic pseudocapsule or benign parenchyma at one end were defined as peri-tumor TLS (PT-TLS). A classification algorithm to distinguish lymphocytes from non-lymphocytic cells using a supervised machine learning model was used. The associations between TLS formation and 265 gene expression-based signatures were examined. RESULTS: The magnitude of total TLS correlations with primary tumor gene expression signatures was moderate (~0.35-0.5) with several HLA, T-cell and B-cell Cluster signatures, showing positive correlation with various metrics for quantification of TLS. On the other hand, immune suppressive signatures (Treg, MDSC) were negatively correlated. While signatures for macrophages, NK cells and other immune cell types were uncorrelated for the most part. PT-TLS was associated with MHC signatures while IT TLS correlated with MHC and T-cell signatures. CONCLUSIONS: Clusters of inflammatory cells in the RP specimen can be divided spatially into PT TLS and IT-TLS, each with its unique molecular correlates of tumor immune microenvironment. The presence of TLS is positively correlated with MHC signatures, T- cell and B-cell cluster signatures but, negatively correlated with immune suppressive signatures. A subset of prostate cancer demonstrate a robust inflammatory response, and warrant further characterization in larger cohorts.

How Active Are Our Patients in the First 6 Weeks Following Total Knee Arthroplasty?

BACKGROUND: Patient activity after total knee arthroplasty (TKA) surgery has been estimated through patient-reported outcome measures. The use of data from an implanted sensor that transmits daily gait activity provides a more objective, complete recovery trajectory. METHODS: In this retrospective analysis of 794 patients who received a TKA with sensors in the tibial extension between October 4, 2021, and January 13, 2023, the average age of the patients was 64 years, and the cohort was 54.9% women. During the 6-week postoperative period, 90.3% of patients transmitted data. Patient activity in terms of qualified step count, cadence, walking speed, stride length, functional tibial range of motion (ROM), and functional knee ROM were compared at 1 week, 3 weeks, and 6 weeks postoperatively. RESULTS: All gait parameters increased in the first 6 weeks postsurgery: qualified step count increased 733%, cadence increased 22%, walking speed increased 50%, stride length increased 17%, tibial ROM increased 19%, and functional knee ROM increased 14%. There were statistically significant differences at both postoperative periods (P = .029, P < .001, and P < .001 at 3 and 6 weeks, respectively) in step counts for different body mass index (BMI) categories, with qualified step counts decreasing with increasing BMI. Patients under 65 years tended to have a higher qualified step count than those 65 and older at all time points, but these differences were not statistically significant. Men had significantly higher step counts than women (P < .001 at 1, 3, and 6 weeks). CONCLUSIONS: Initial results with an implanted sensor that collects data during activities of daily living confirm that 90% of patients transmit objective gait metrics daily after TKA surgery. Those results differ by sex and BMI. LEVEL OF EVIDENCE: III Retrospective Cohort Study.

Design and Rationale of Prolonged Nightly Fasting for Multiple Myeloma Prevention (PROFAST): Protocol for a Randomized Controlled Pilot Trial.

BACKGROUND: Obesity is an established, modifiable risk factor of multiple myeloma (MM); yet, no lifestyle interventions are routinely recommended for patients with overweight or obesity with MM precursor conditions. Prolonged nightly fasting is a simple, practical dietary regimen supported by research, suggesting that the synchronization of feeding-fasting timing with sleep-wake cycles favorably affects metabolic pathways implicated in MM. We describe the design and rationale of a randomized controlled pilot trial evaluating the efficacy of a regular, prolonged nighttime fasting schedule among individuals with overweight or obesity at high risk for developing MM or a related lymphoid malignancy. OBJECTIVE: We aim to investigate the effects of 4-month prolonged nightly fasting on body composition and tumor biomarkers among individuals with overweight or obesity with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or smoldering Waldenström macroglobulinemia (SWM). METHODS: Individuals with MGUS, SMM, or SWM aged ≥18 years and a BMI of ≥25 kg/m2 are randomized to either a 14-hour nighttime fasting intervention or a healthy lifestyle education control group. Participants' baseline diet and lifestyle patterns are characterized through two 24-hour dietary recalls: questionnaires querying demographic, comorbidity, lifestyle, and quality-of-life information; and wrist actigraphy measurements for 7 days. Fasting intervention participants are supported through one-on-one telephone counseling by a health coach and automated SMS text messaging to support fasting goals. Primary end points of body composition, including visceral and subcutaneous fat (by dual-energy x-ray absorptiometry); bone marrow adiposity (by bone marrow histology); and tumor biomarkers, specifically M-proteins and serum free light-chain concentrations (by gel-based and serum free light-chain assays), are assessed at baseline and after the 4-month study period; changes therein from baseline are evaluated using a repeated measures mixed-effects model that accounts for the correlation between baseline and follow-up measures and is generally robust to missing data. Feasibility is assessed as participant retention (percent dropout in each arm) and percentage of days participants achieved a ≥14-hour fast. RESULTS: The PROlonged nightly FASTing (PROFAST) study was funded in June 2022. Participant recruitment commenced in April 2023. As of July 2023, six participants consented to the study. The study is expected to be completed by April 2024, and data analysis and results are expected to be published in the first quarter of 2025. CONCLUSIONS: PROFAST serves as an important first step in exploring the premise that prolonged nightly fasting is a strategy to control obesity and obesity-related mechanisms of myelomagenesis. In evaluating the feasibility and impact of prolonged nightly fasting on body composition, bone marrow adipose tissue, and biomarkers of tumor burden, this pilot study may generate hypotheses regarding metabolic mechanisms underlying MM development and ultimately inform clinical and public health strategies for MM prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05565638; http://clinicaltrials.gov/ct2/show/NCT05565638. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51368.

Liver machine perfusion technology: Expanding the donor pool to improve access to liver transplantation.

The imbalance between organ supply and demand continues to limit the broader benefits of organ transplantation. Machine perfusion (MP) may increase the supply of donor livers by expanding the use of extended-criteria donors. Using the United Network for Organ Sharing/Organ Procurement and Transplantation Network and the Standard Transplant Analysis and Research dataset, we reviewed the effect of MP implementation on the behavior of transplant centers. We identified 15 high-utilizing MP centers that were matched to suitable controls based on volume and geographical proximity. We conducted a differences-in-differences analysis using linear regression to estimate the impact of MP adoption on the transplant centers' donor utilization. We found a significant increase in cold ischemia time and organs with donor warm ischemia time over 30 minutes (P < .05). After removing one outlier center, the analysis showed that these centers through MP accepted overall more donation after circulatory death donors, donation after circulatory death donors over 50 years old, donors with macrovesicular steatosis greater than 30% on liver biopsy, and donor warm ischemia time over 30 minutes (P < .05). MP has allowed centers to expand their use of extended-criteria donors beyond traditional cutoffs and to increase patient access to liver transplantation.

Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population.

ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma with few known risk factors. The emergence of mass spectrometry (MS) for the detection of MGUS has provided new opportunities to evaluate its risk factors. In total, 2628 individuals at elevated risk for multiple myeloma were enrolled in a screening study and completed an exposure survey (PROMISE trial). Participant samples were screened by MS, and monoclonal proteins (M-proteins) with concentrations of ≥0.2 g/L were categorized as MS-MGUS. Multivariable logistic models evaluated associations between exposures and MS outcomes. Compared with normal weight (body mass index [BMI] of 18.5 to <25 kg/m2), obesity (BMI of ≥30 kg/m2) was associated with MS-MGUS, adjusting for age, sex, Black race, education, and income (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.21-2.47; P = .003). High physical activity (≥73.5 metabolic equivalent of task (MET)-hours per week vs <10.5 MET-hours per week) had a decreased likelihood of MS-MGUS (OR, 0.45, 95% CI, 0.24-0.80; P = .009), whereas heavy smoking and short sleep had increased likelihood of MS-MGUS (>30 pack-years vs never smoker: OR, 2.19; 95% CI, 1.24-3.74; P = .005, and sleep <6 vs ≥6 hours per day: OR, 2.11; 95% CI, 1.26-3.42; P = .003). In the analysis of all MS-detected monoclonal gammopathies, which are inclusive of M-proteins with concentrations of <0.2 g/L, elevated BMI and smoking were associated with all MS-positive cases. Findings suggest MS-detected monoclonal gammopathies are associated with a broader range of modifiable risk factors than what has been previously identified. This trial was registered at www.clinicaltrials.gov as #NCT03689595.

Single-Port vs Multiport Robot-Assisted Partial Nephrectomy: A Meta-Analysis.

Background: Several centers have reported their experience with single-port robot-assisted partial nephrectomy (SP-RAPN); however, it is uncertain if utilization of this platform represents an improvement in outcomes compared to multiport robot-assisted partial nephrectomy (MP-RAPN). To evaluate this, we performed a meta-analysis to compare the perioperative, oncological, and functional outcomes between SP-RAPN and MP-RAPN. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 1, 2023. A meta-analysis has been reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and assessing the methodological quality of systematic reviews (AMSTAR) guidelines. The odds ratio (OR) and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 374 retrieved abstracts, 29 underwent full-text review, and 8 studies were included in the final analysis, comprising a total cohort of 1007 cases of RAPN (453 SP-RAPN cases and 554 MP-RAPN cases). Compared to MP-RAPN, the SP-RAPN group had a significantly longer ischemia time (MD = 4.6 minutes, 95% CI 2.8 to 6.3, p < 0.001), less estimated blood loss (MD = -12.4 mL, 95% CI -24.6 to -0.3, p = 0.045), higher blood transfusion rate (OR = 2.97, 95% CI 1.33 to 6.65, p = 0.008), and higher postoperative estimated glomerular filtration rate (eGFR) at 6 months (MD = 4.9 mL/min, 95% CI 0.2 to 9.7, p = 0.04). There was no significant difference in other outcomes between the two approaches, including the intraoperative complication, overall postoperative complication, minor postoperative complication (Clavien-Dindo I - II), major postoperative complication (Clavien-Dindo III-V), conversion to radical nephrectomy, pain score on day #1, pain score on discharge, morphine milligram equivalent usage, hospital stay, positive surgical margins, and postoperative eGFR. Conclusions: SP-RAPN represents an emerging technique using a novel platform. Initial studies have demonstrated that SP-RAPN is a safe and feasible approach to performing partial nephrectomy, although with inferior outcomes for ischemia time and blood transfusion rates. Further studies will be necessary to define the best usage of SP-RAPN within the surgeon's armamentarium.

Understanding the Termination of Urologic Cancer Clinical Trials: Insights and Challenges.

PURPOSE: Clinical trials are valuable evidence for managing urologic malignancies. Early termination of clinical trials is associated with a waste of resources and may substantially affect patient care. We sought to study the termination rate of urologic cancer clinical trials and identify factors associated with trial termination. METHODS: A cross-sectional search of ClinicalTrials.gov identified completed and terminated kidney, prostate, and bladder cancer clinical trials started. Trials were assessed for reasons for termination. Multivariable analyses were conducted to determine the significant factors associated with the termination. RESULTS: Between 2000 and 2020, 9,145 oncology clinical trials were conducted, of which 11.30% (n = 1,033) were urologic cancer clinical trials. Of the urologic cancer clinical trials, 25.38% (n = 265) were terminated, with low patient accrual being the most common reason for termination, 52.9% (n = 127). Multivariable analysis showed that only the university funding source odds ratio (OR) of 2.20 (95% CI, 1.45 to 3.32), single-center studies OR of 2.11 (95% CI, 1.59 to 2.81), and sample size of <50 were significant predictors of clinical trial termination OR of 5.26 (95% CI, 3.85 to 7.69); all P values are <.001. CONCLUSION: The termination rate of urologic cancer clinical trials was 25%, with low accrual being the most frequently reported reason. Trials funded by a university, single-center trials, and small trials (sample size <50) were associated with early termination. A better understanding of these factors might help researchers, funding agencies, and other stakeholders prioritize resource allocations for multicenter trials that aim to recruit a sufficient number of patients.

Helicobacter pylori Burden in the United States According to Individual Demographics and Geography: A Nationwide Analysis of the Veterans Healthcare System.

BACKGROUND & AIMS: There are no contemporary large-scale studies evaluating the burden of Helicobacter pylori in the United States according to detailed demographics. The primary objective was to evaluate H pylori positivity in a large national healthcare system according to individual demographics and geography. METHODS: We conducted a nationwide retrospective analysis of adults in the Veterans Health Administration who completed H pylori testing between 1999 and 2018. The primary outcome was H pylori positivity overall, as well as according to zip code-level geography, race, ethnicity, age, sex, and time period. RESULTS: Among 913,328 individuals (mean, 58.1 years; 90.2% male) included between 1999 and 2018, H pylori was diagnosed in 25.8%. Positivity was highest in non-Hispanic black (median, 40.2%; 95% confidence interval [CI], 40.0%-40.5%) and Hispanic (36.7%; 95% CI, 36.4%-37.1%) individuals and lowest in non-Hispanic white individuals (20.1%; 95% CI, 20.0%-20.2%). Although H pylori positivity declined in all racial and ethnic groups over the timeframe, the disproportionate burden of H pylori in non-Hispanic black and Hispanic compared with non-Hispanic white individuals persisted. Approximately 4.7% of the variation in H pylori positivity was explained by demographics, with race and ethnicity accounting for the vast majority. CONCLUSIONS: The burden of H pylori is substantial in the United States among veterans. These data should (1) motivate research aimed at better understanding why marked demographic differences in H pylori burden persist so that mitigating interventions may be implemented and (2) guide resource allocation to optimize H pylori testing and eradication in high-risk groups.

Cognitive behavioral therapy versus general health education for smoking cessation: A randomized controlled trial among diverse treatment seekers.

OBJECTIVE: Racial and ethnic disparities in smoking cessation persist. This randomized controlled trial compared the efficacy of group cognitive behavioral therapy (CBT) for cessation among African American/Black, Latino/Hispanic, and White adults. METHOD: African American/Black (39%), Latino/Hispanic (29%), and White (32%) adults (N = 347) were randomly assigned to eight group sessions of CBT or general health education (GHE), both including nicotine patch therapy. Biochemically confirmed 7-day point prevalence abstinence (7-day ppa) was measured at the end-of-therapy, and at 3-, 6-, and 12-month follow-ups. Generalized linear mixed models and logistic regressions tested abstinence rates by condition, stratified by race and ethnicity, and interaction effects. RESULTS: CBT led to greater abstinence than GHE across 12-months of follow-up (AOR = 1.84, 95% CI [1.59, 2.13]) overall [12-month follow-up: CBT = 54% vs. GHE = 38%] and within racial and ethnic groups [12-months: African American/Black (CBT = 52%, GHE = 29%), Latino/Hispanic (CBT = 57%, GHE = 47%), and White (CBT = 54%, GHE = 41%)]. African American participants were less likely than White participants to quit irrespective of condition, as were persons with lower education and income. Socioeconomic status indicators positively predicted abstinence among racial and ethnic minority participants, but not White participants. CONCLUSIONS: Group CBT was efficacious compared with GHE. However, cessation patterns suggested that intensive group interventions were less beneficial over the longer term among lower socioeconomic African American and Latino individuals, compared with White participants. Tobacco interventions should target racial and ethnic and socioeconomic differences, via culturally specific approaches and other means. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Utility of noninvasive biomarker testing and MRI to predict a prostate cancer diagnosis.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.

Site-Specific Dolasynthen Antibody-Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios.

Key defining attributes of an antibody-drug conjugate (ADC) include the choice of the targeting antibody, linker, payload, and the drug-to-antibody ratio (DAR). Historically, most ADC platforms have used the same DAR for all targets, regardless of target characteristics. However, recent studies and modeling suggest that the optimal DAR can depend on target expression level and intratumoral heterogeneity, target internalization and trafficking, and characteristics of the linker and payload. An ADC platform that enables DAR optimization could improve the success rate of clinical candidates. Here we report a systematic exploration of DAR across a wide range, by combining THIOMAB protein engineering technology with Dolasynthen, an auristatin-based platform with monomeric and trimeric variants. This approach enabled the generation of homogeneous, site-specific ADCs spanning a discrete range of DARs 2, 4, 6, 12, and 18 by conjugation of trastuzumab IgG1 THIOMAB constructs with 1, 2, or 3 engineered cysteines to monomeric or trimeric Dolasynthen. All ADCs had physicochemical properties that translated to excellent in vivo pharmacology. Following a single dose of ADCs in a HER2 xenograft model with moderate antigen expression, our data demonstrated comparable pharmacokinetics for the conjugates across all DARs and dose-dependent efficacy of all test articles. These results demonstrate that the Dolasynthen platform enables the generation of ADCs with a broad range of DAR values and with comparable physiochemical, pharmacologic, and pharmacokinetics profiles; thus, the Dolasynthen platform enables the empirical determination of the optimal DAR for a clinical candidate for a given target.

Active narcotic use and post-peroral endoscopic myotomy outcomes in esophageal motility disorders.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a minimally invasive technique used to treat esophageal motility disorders. Opioid use has been demonstrated to adversely affect esophageal dysmotility and is associated with an increased prevalence of esophageal motility disorders. Our aim was to investigate the effect of narcotic use on success rates in patients undergoing POEM. METHODS: This was a single-center, retrospective study of patients undergoing POEM between February 2017 and September 2021. Primary outcomes were post-POEM Eckardt score (ES), distensibility index, and length of procedure. Secondary outcomes included technical success, myotomy length, length of stay, adverse events, reintervention rates, and postprocedure GERD. RESULTS: During the study period, 90 patients underwent POEM for treatment of esophageal dysmotility disorders. Age, sex, race, indications for POEM, and body mass index were not significant between those with or without narcotic use. There were no differences in procedure time, preprocedure ESs, or length of stay. Postprocedure ESs were higher in the group with active narcotic use compared to the group with no prior history (2.73 vs 1.2, P = .004). Distensibility indexes measured with EndoFLIP (Medtronic, Minneapolis, Minn, USA) were not different in patients using narcotics compared with opioid-naïve patients. CONCLUSION: Active narcotic use negatively affects symptom improvement after POEM for the treatment of esophageal motility disorders.

Assessing Decision Regret in Patients with Same-Day Discharge Pathway After Robot-Assisted Radical Prostatectomy.

Introduction: After the introduction of same-day discharge (SDD) pathways for various surgeries, these pathways have demonstrated comparable complication rates and a reduced overall cost of care. Outpatient robot-assisted radical prostatectomy (RARP) is introduced in high-volume centers; however, patients' perspectives on the SDD RARP protocol are not well understood. Materials and Methods: A questionnaire consisting of 24 questions, including the Likert Decisional Regret Scale, was distributed to patients who underwent RARP at our center. The overall decision regret score was calculated as described in the literature. We used 15 as a cutoff point for differentiating between high- and low-regret rates. Median and interquartile range were determined for non-normally distributed variables, while mean ± standard deviation was calculated for continuous data. Results: Of the 72 patients who completed the questionnaire, 65.7% (n = 44) of patients felt no regret about their decision of choosing the SDD RARP protocol and 90.3% (n = 65) of men stated that they would have made the same decision. At the same time, 97.1% (n = 68) of patients would also recommend this procedure to others. The median decisional regret score of the cohort (n = 67) was 0 (0-10). Fifty-four of 67 (80.6%) patients were in the low-regret score group, while 13 (19.4%) were in the high-regret group. Patients in the high-regret group were more likely to have low household income (<$30,000 a year) and they experienced postoperative pain more frequently compared with patients in the lower regret group (7.7% vs 1.9%, p = 0.626, and 61.5% vs 38.9%, p = 0.212, respectively). Conclusions: Most patients expressed low regret about choosing the SDD pathway for RARP, underscoring the importance of thorough explanation of the procedure and discharge process to enhance patient experience. However, a subset of patients did express regret, possibly due to an interplay of patient- and procedure-related factors.

Locoregional Therapies for Hepatocellular Carcinoma prior to Liver Transplant: Comparative Pathologic Necrosis, Radiologic Response, and Recurrence.

PURPOSE: To compare pathologic tumor necrosis rates after locoregional therapies (LRTs) for hepatocellular carcinoma (HCC) prior to liver transplantation and evaluate radiologic-pathologic correlation along with posttransplant HCC recurrence. MATERIALS AND METHODS: Consecutive patients with solitary HCC bridged or downstaged with LRT from 2010 to 2022 were included. LRTs were transarterial chemoembolization (TACE), radioembolization (yttrium-90 [90Y]), ablation, and stereotactic body radiotherapy (SBRT). Upfront combination therapy options were TACE/ablation and TACE/SBRT. Subsequent therapy crossover due to local recurrence was allowed. Posttreatment imaging closest to the time of transplant, explant histopathologic necrosis, and tumor recurrence after transplant were reviewed. RESULTS: Seventy-three patients met inclusion criteria, of whom 5 (7%) required downstaging. 90Y alone (n = 36) and multimodal therapy (pooled upfront combination and crossover therapy, n = 23) resulted in significantly greater pathologic necrosis compared with TACE alone (n = 14; P = .01). High dose 90Y radiation segmentectomy (≥190 Gy; n = 27) and TACE/ablation (n = 7) showed highest rates of complete pathologic necrosis (CPN)-63% (n = 17) and 71% (n = 5), respectively. Patients with CPN had a mean lesion size of 2.5 cm, compared with 3.2 cm without CPN (P = .04), irrespective of LRT modality. HCC recurrence was more common in patients without CPN (16%, 6/37) than in those with CPN (3%, 1/36; P = .11). Using Liver Imaging Reporting and Data System (LI-RADS), a nonviable imaging response was 75% sensitive and 57% specific for CPN. CONCLUSIONS: Radiation segmentectomy and multimodal therapy significantly improved CPN rates compared with TACE alone. A LI-RADS treatment response of nonviable did not confidently predict CPN.