Citations

ABSTRACT Thrombocytopenic purpura (TTP) is a hematologic emergency that may occur with PD‐L1 immunotherapy. New or worsening anemia and thrombocytopenia in patients started on PD‐L1 inhibitors should raise suspicion for TTP and prompt workup for thrombotic microangiopathy.

Purpose: An Adult Cochlear Implant Aural Rehabilitation Special Interest Group was formed in 2023. Members represent interdisciplinary collaborators, including audiologists, speech-language pathologists, surgeons, nonclinical administrators, manufacturer/industry representatives, and researchers. Current perspectives of adult cochlear implant (CI) recipients regarding aural rehabilitation (AR) remain unknown and understudied. The aim of this study is to survey adult CI recipients to determine their perspectives on the AR process. Method: A web-based national survey was sent to adult CI recipients through multiple channels. The survey asked recipients about their demographics, state of residence, hearing loss history, and device configuration. Questions probed recipients' experiences of learning about AR options, services used, definitions of AR, and perceived value of services received. Questions were also asked about barriers to AR services, preoperative counseling, and satisfaction with their decision to pursue a CI. Results: A total of 115 CI recipients responded to the survey. Results revealed a relative lack of information provided to many CI recipients regarding AR services. Many CI recipients reported wishing they had received additional resources in the areas of music training and equipment troubleshooting. Most participants reported that both one-on-one clinician-guided AR and independent listening practice were effective methods of AR. Conclusions: Findings shed light on current gaps in providing the most effective AR services, which will need to be addressed to optimize hearing health care and outcomes for adult CI recipients. Future work should include outreach to a broader representation of CI users to expand our understanding of AR resources, education, and limitations.

Abstract The purpose of the current study was to identify the influence of individual characteristics on differences in body fat percentage between air displacement plethysmography and dual-energy X-ray absorptiometry (change in body fat percentage) in 360 collegiate student-athletes. Body fat percentage was obtained from air displacement plethysmography and dual-energy X-ray absorptiometry. A 2 (sex)×3 (Brozek body fat percentage, Siri body fat percentage, and dual-energy x-ray absorptiometry body fat percentage) analysis of variance was used to evaluate the difference between the body fat percentages obtained from air displacement plethysmography and dual-energy x-ray absorptiometry in men and women. The agreement between air displacement plethysmography and dual-energy X-ray absorptiometry was evaluated via Bland–Altman plot and linear regression. Multiple linear regression was used to identify the influence of sex, race, height, and body mass on the change in body fat percentages. Dual-energy X-ray absorptiometry yielded greater body fat percentages in both men (4.8±2.8; p < 0.001) and women (2.2±2.9; p < 0.001) compared to air displacement plethysmography measurements. Proportional and systematic biases were observed between air displacement plethysmography and dual-energy X-ray absorptiometry. Race, height, and mass were significant predictors of the body fat percentage difference between air displacement plethysmography and dual-energy X-ray absorptiometry (R 2=0.445, p<0.001, and standard error of the estimate=2.527). The present study suggests that air displacement plethysmography underestimates body fat percentages when compared to dual-energy X-ray absorptiometry and this underestimation may not be the same for every athlete due to their individual characteristics.

PURPOSE For patients with advanced biliary tract cancer (BTC), cancer-related time spent in health care systems, time toxicity, represents a critical but understudied burden affecting quality of life. This study aimed to quantify time toxicity in patients receiving first-line systemic therapy and evaluate whether the addition of durvalumab to gemcitabine plus cisplatin (GC) increases health care contact time. METHODS This international, multicenter, retrospective cohort study included patients with advanced BTC seen between January 2019 and April 2024 at Mayo Clinic Enterprise (US), and between January 2021 and April 2024 at Kyorin University Hospital (Japan), and Hospital Israelita Albert Einstein (Brazil). Patients received GC plus durvalumab (GCD) or GC. Time toxicity was recorded from treatment initiation until discontinuation or last follow-up during first-line systemic therapy. Multiple regression analysis identified factors associated with high time toxicity. RESULTS Among 193 patients (102 GCD, 91 GC; median age 65 years; 50% male; 49% Eastern Cooperative Oncology Group performance status [PS] 0), median time on treatment (TOT) was 156 days (95% CI, 122 to 190). The median proportion of total time toxicity was 14.4% (IQR, 10.9-20.6). Planned visits accounted for 11.9%, while unplanned visits were infrequent (1.8%). Time toxicity strongly correlated with TOT ( r = 0.824) and progression-free survival ( r = 0.827). Despite longer treatment in the GCD group than the GC group (212 v 134 days; P = .027), total time toxicity was similar (27 v 18 days; P = .19). Younger age and poor PS were independent factors of higher time toxicity. CONCLUSION Time toxicity represents a meaningful metric that allows for more comprehensive integration of the net benefit in patients with advanced BTC with a limited lifespan.

In this study, we propose two new mathematical models able to quantify glucagon secretion during a graded glucose infusion, in the presence and absence of amino acids. The models provide an index of α-cell responsivity, G 50 , i.e., the glucose increase required to suppress glucose secretion rate (GSR) by 50%. Results show that the presence of amino acids reduced α-cell responsivity to glucose.

Abstract Endogenous Cushing syndrome (CS) is a rare disorder resulting from chronic exposure to excessive concentrations of cortisol. It is likely underdiagnosed because many clinical signs and symptoms are non-specific and overlap with those of common conditions. Furthermore, biochemical testing to diagnose CS can be complex and challenging, especially in milder cases. CS is characterized by excessive daily cortisol production, but it is also associated with a disrupted circadian rhythm of cortisol secretion. Traditional cortisol monitoring techniques rely on single-time-point measurements or a cumulation of measurements, which are unable to capture the complete daily rhythm of cortisol fluctuations. Currently, the utility of assessing individual patients’ cortisol circadian rhythm during diagnosis and treatment of CS is not well characterized. In this review, we will discuss how cortisol is measured in clinical practice and the potential benefit of measurement and normalization of the cortisol circadian rhythm.

Abstract Forward genetic screens are powerful tools for novel biological discoveries because they do not require a priori knowledge of genes controlling a phenotype of interest. The Sleeping Beauty (SB) transposon system is one of many commonly employed genetic screen tools used to induce both gain and loss of gene function mutations via insertional mutagenesis. In the past, SB screens have been successfully utilized to discover several cancer driver genes that could serve as potential therapeutic targets. More recently, SB technologies have been extended to other applications, including the discovery of mechanisms contributing to drug resistance and novel targets for immunotherapy. Importantly, existing tools for SB screen data analysis do not support data-driven case–control comparisons capable of analyzing screens with this design. To this end, we developed a network-based common insertion site (NetCIS) analysis tool to robustly identify common insertion sites (CISes) in a case–control phenotype selection screen. NetCIS uses an efficient graph-based algorithm for discovering statistically significant CISes that differ between cases and controls. We benchmark NetCIS against other insertional mutagenesis analysis tools using a previously published SB dataset and show that NetCIS is able to prioritize previous biologically validated genes similarly or better than competing methods, is the only method that effectively utilizes a case–control experimental setup, and can identify CISes involving unannotated regions of the genome that are overlooked by existing methods. Code for NetCIS and an accompanying tutorial can be found at https://github.com/RogersLabGroup/NetCIS.

Abstract Chimeric antigen receptor T (CAR T)-cell therapy is revolutionizing cancer treatment in hematologic malignancies, but challenges related to the tumor microenvironment have hindered CAR T success, especially in solid tumors. Myeloid cells in particular have been implicated in CAR T efficacy. In this review, we discuss the roles of myeloid cells in CAR T–associated toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome, along with strategies to treat these toxicities by modulating myeloid cells. The review also explores myeloid cell–mediated suppression or enhancement of CAR T function. Finally, strategies used to target myeloid cells in combination with CAR T-cell therapy will be investigated.

Abstract Context Most of the patients included in the clinical trials and real-world studies with osilodrostat only include patients with adrenocorticotropic hormone dependent Cushing syndrome (CS), while data on the efficacy and safety of osilodrostat in patients with adrenal CS is scarce. Objective To assess the efficacy and safety of osilodrostat in adrenal CS. Methods International study of patients with adrenal CS: patients treated with osilodrostat at any time were enrolled in the safety evaluation and those treated for longer than 4 weeks, in the efficacy evaluation. Patients were classified as responders if they experienced a reduction in urinary free cortisol (UFC) &gt;50% (complete responders when UFC levels were below the upper limit of normal [ULN] and partial responders if there was a reduction &gt;50% but not normalization). Results Twenty-eight patients with adrenal CS were enrolled: 16 with adrenocortical carcinoma and 12 with benign disease. Osilodrostat was used in monotherapy in 22 patients and in combination with metyrapone in 6 cases. In those patients treated for longer than 4 weeks (n = 21), 66.7% were classified as responders (28.6% with complete response and 38.1% with partial response), and for those treated for longer than 12 weeks, the rate of response increased to 87.5% The use of osilodrostat as a nonfirst-line therapy (odds ratio 15.0, P = .010) was a predictor of response. Osilodrostat led to a significant decrease in systolic blood pressure and body weight (P &lt; .05). Nine patients developed one or more adverse events and in 56% (n = 5) led to osilodrostat discontinuation. Conclusion Osilodrostat controls hypercortisolism in 66.7% of patients with adrenal CS treated for longer than 4 weeks and in 87.5% of cases treated for longer than 12 weeks, with a positive impact on blood pressure and body weight. Patients who received osilodrostat after other previous steroidogenesis inhibitors have a higher probability of response.