Citations

Background: There is limited data on Vedolizumab utilization in elderly patients. Our study aims to assess the effectiveness and safety of Vedolizumab in this subset population. Materials and Methods: Databases including Cochrane Central, Embase, Medline (via Ovid), Scopus, and Web of Science were searched in August 2022 to identify studies that assessed Vedolizumab therapy in elderly patients. Pooled proportion and risk ratios (RR) were calculated. Results: Total 11 studies with 3546 IBD patients (1314 elderly and 2232 young) were included in the final analysis. Pooled rate of overall and serious infections in the elderly cohort was 8.45% (95% CI=6.27-11.29; I223%) and 2.59% (95% CI=0.78-8.29; I276%), respectively. However, there was no difference in overall infection rates between elderly and young patients. Pooled rate of endoscopic, clinical, and steroid-free remission for elderly IBD patients was 38.45% (95% CI=20.74-59.56; I293%), 37.95% (95% CI=33.08-43.06; I213%), and 38.8% (95% CI=31.6-46.4; I277%), respectively. Elderly patients had lower steroid-free remission rates [RR 0.85, 95% CI=0.74-0.99; I20%, P=0.03]; however, there was no difference in rates of clinical (RR 0.86, 95% CI=0.72-1.03; I20%, P=0.10) or endoscopic remission (RR 1.06, 95% CI=0.83-1.35; I20%, P=0.63) compared with younger patients. Pooled rate of IBD-related surgery and IBD-related hospitalizations was 9.76% (95% CI=5.81-15.92; I278%) and 10.54% (95% CI=8.37-13.2; I20%), respectively for the elderly cohort. There was no statistical difference in IBD-related surgeries between elderly and young IBD patients, RR 1.20 (95% CI=0.79-1.84; I216%), P=0.4. Conclusions: Vedolizumab is equally safe and effective for clinical and endoscopic remission in elderly and younger populations.

Abstract Introduction: While CT lung cancer screening reduces lung cancer-specific mortality, there are remaining challenges. Radiomic tools promiss to address these challenges, however, they are subject to interobserver variability if semi-automated segmentation techniques are used. Herein we report interobserver variability for two validated radiomic tools, BRODERS (Benign versus aggRessive nODule Evaluation using Radiomic Stratification) and CANARY (Computer-Aided Nodule Assessment and Risk Yield). Methods We retrospectively analyzed the CT images of 95 malignant lung nodules of the adenocarcinoma spectrum using BRODERS and CANARY. Cases were identified at Mayo Clinic (n = 45) and Vanderbilt University Medical Center and Nashville/Veteran Administration Tennessee Valley Health Care System (n = 50). Three observers with different training levels (medical student, internal medicine resident and thoracic radiology fellow) each performed lung nodule segmentation. All methods were carried out in accordance with relevant guidelines and regulations Results Interclass correlation coefficients (ICC) of 0.77, 0.98 and 0.97 for the average nodule volume, BRODERS cancer probability and Score Indicative of Lesion Aggression (SILA) which summarizes the distribution of the CANARY exemplars indicated good to excellent reliability, respectively. The dice similarity coefficient was 0.79 and 0.81 for the data sets from the two institutions. Conclusion: BRODERS and CANARY are robust radiomics tools with excellent interobserver variability. These tools are simple and reliable regardless the observer/operator’s level of training.

Abstract Background National Cancer Institute-Children’s Oncology Group Pediatric Molecular Analysis for Therapy Choice assigns patients aged 1-21 years with refractory solid tumors, brain tumors, lymphomas, and histiocytic disorders to phase II trials of molecularly targeted therapies based on detection of predefined genetic alterations. Patients whose tumors harbored EZH2 mutations or loss of SMARCB1 or SMARCA4 by immunohistochemistry were treated with EZH2 inhibitor tazemetostat. Methods Patients received tazemetostat for 28-day cycles until disease progression or intolerable toxicity (max 26 cycles). The primary endpoint was objective response rate; secondary endpoints included progression-free survival and tolerability of tazemetostat. Results Twenty patients (median age = 5 years) enrolled, all evaluable for response and toxicities. The most frequent diagnoses were atypical teratoid rhabdoid tumor (n = 8) and malignant rhabdoid tumor (n = 4). Actionable alterations consisted of SMARCB1 loss (n = 16), EZH2 mutation (n = 3), and SMARCA4 loss (n = 1). One objective response was observed in a patient with non-Langerhans cell histiocytosis with SMARCA4 loss (26 cycles, 1200 mg/m2/dose twice daily). Four patients with SMARCB1 loss had a best response of stable disease: epithelioid sarcoma (n = 2), atypical teratoid rhabdoid tumor (n = 1), and renal medullary carcinoma (n = 1). Six-month progression-free survival was 35% (95% confidence interval [CI] = 15.7% to 55.2%) and 6-month overall survival was 45% (95% CI = 23.1% to 64.7%). Treatment-related adverse events were consistent with prior tazemetostat reports. Conclusions Although tazemetostat did not meet its primary efficacy endpoint in this population of refractory pediatric tumors (objective response rate = 5%, 90% CI = 1% to 20%), 25% of patients with multiple histologic diagnoses experienced prolonged stable disease of 6 months and over (range = 9-26 cycles), suggesting a potential effect of tazemetostat on disease stabilization.

Background: Our understanding of the risk factors for and effectiveness of prophylactic measures against shoulder periprosthetic joint infections (PJIs) continues to evolve. This study’s objective was to study patient characteristics, procedural characteristics, and various infection prophylactic measures and their effects on the risk of shoulder PJI after primary arthroplasty. Methods: Nine hundred and ninety-eight patients in a longitudinally maintained, single-institution shoulder arthroplasty database who had at least 2 years of clinical follow-up were retrospectively reviewed. Patient and procedural characteristics were collected. Perioperative variables, including the use of intraoperative antibiotics, topical antibiotics, antibiotic-containing irrigation solution, and a postoperative drain, were collected. Patients who developed shoulder PJI were compared with those without shoulder PJI to identify any association with patient or procedural characteristics. Results: Of the 998 patients, 20 (2.0%) met the criteria for shoulder PJI. Cutibacterium was identified as the causative organism in 19 (95%) of 20 culture-positive reoperations. On univariate analysis, patients in the PJI group were more likely to be younger (p < 0.001), to be male (p = 0.014), to have commercial insurance (p = 0.003), to use alcohol (p = 0.048), and to have had a ream-and-run or hemiarthroplasty procedure (p = 0.005). On multivariable analysis, older age was independently associated with a lower risk of PJI (odds ratio [OR] per year = 0.95; 95% confidence interval [CI], 0.91 to 0.99; p = 0.014). Reverse total shoulder arthroplasty (OR, 10.32; 95% CI, 0.92 to 116.33; p = 0.059) and hemiarthroplasty (OR, 8.59; 95% CI, 0.86.30 to 85.50; p = 0.067) trended toward a higher risk of PJI. Conclusions: Younger patients and patients undergoing procedures other than anatomic total shoulder arthroplasty are at higher risk for shoulder PJI. The majority of culture-positive reoperations were a result of Cutibacterium species. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Electronic patient‐reported outcome (ePRO) programs may offer advantages for patients with cancer, clinicians, health care systems, payors, and society in general; but developing and maintaining an ePRO program will require cancer centers to navigate defining meaningful problems, collecting ePROs, implementing action when those ePROs require intervention without over‐burdening clinicians, and monitoring the successes and failures of their ePRO programs. Physician informaticists from the National Comprehensive Cancer Network Electronic Health Record Advisory Group offer 10 guiding principles to consider when contemplating, building, or refining an ePRO program for patients with cancer.

ABSTRACT Background Autosomal dominant polycystic kidney disease (ADPKD) presents with variable disease severity and progression. Advanced imaging biomarkers may provide insights into cystic and non-cystic processes leading to kidney failure in different age groups. Methods This pilot study included 39 ADPKD patients with kidney failure, stratified into three age groups (&lt;46, 46–56, &gt;56 years old). Advanced imaging biomarkers were assessed using an automated instance cyst segmentation tool. The biomarkers were compared with an age- and sex-matched ADPKD cohort in early chronic kidney disease (CKD). Results Ht-total parenchymal volume correlated negatively with age at kidney failure. The median Ht-total parenchymal volume was significantly lower in patients older than 56 years. Cystic burden was significantly higher at time of kidney failure, especially in patients who reached it before age 46 years. The cyst index at kidney failure was comparable across age groups and Mayo Imaging Classes. Advanced imaging biomarkers showed higher correlation with Ht-total kidney volume in early CKD than at kidney failure. Cyst index and parenchymal index were relatively stable over 5 years prior to kidney failure, whereas Ht-total cyst volume and cyst parenchymal surface area increased significantly. Conclusion Age-related differences in advanced imaging biomarkers suggest variable pathophysiological mechanisms in ADPKD patients with kidney failure. Further studies are needed to validate the utility of these biomarkers in predicting disease progression and guiding treatment strategies.

Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.

Abstract Purpose: Preclinical studies in myeloid neoplasms have demonstrated efficacy of bromodomain and extra-terminal protein inhibitors (BETi). However, BETi demonstrates poor single-agent activity in clinical trials. Several studies suggest that combination with other anticancer inhibitors may enhance the efficacy of BETi. Experimental Design: To nominate BETi combination therapies for myeloid neoplasms, we used a chemical screen with therapies currently in clinical cancer development and validated this screen using a panel of myeloid cell line, heterotopic cell line models, and patient-derived xenograft models of disease. We used standard protein and RNA assays to determine the mechanism responsible for synergy in our disease models. Results: We identified PIM inhibitors (PIMi) as therapeutically synergistic with BETi in myeloid leukemia models. Mechanistically, we show that PIM kinase is increased after BETi treatment, and that PIM kinase upregulation is sufficient to induce persistence to BETi and sensitize cells to PIMi. Furthermore, we demonstrate that miR-33a downregulation is the underlying mechanism driving PIM1 upregulation. We also show that GM-CSF hypersensitivity, a hallmark of chronic myelomonocytic leukemia (CMML), represents a molecular signature for sensitivity to combination therapy. Conclusions: Inhibition of PIM kinases is a potential novel strategy for overcoming BETi persistence in myeloid neoplasms. Our data support further clinical investigation of this combination.