Citations

50 Background: A+B is commonly used as first line systemic therapy in HCC patients with CP-B liver function, although in the IMbrave150 clinical trial, its efficacy was only assessed in patients with CP-A liver function. We evaluated outcomes in patients with CP-B liver function and compared to those with CP-A. Methods: We completed a multi-institution, retrospective review of patients with HCC from Mayo Clinic and University Hospitals Seidman Cancer Center, who had received A+B in the first line setting between March 2018 and November 2023. CP score was calculated at time of treatment, response was assessed, and progression free (PFS) and overall (OS) survival were determined using the Kaplan Meier method. Results: Among 322 patients with HCC, median age was 66.5 years, 78.6% were male, and 82.6% were white. Eighty-six patients (27%) had CP-B liver function, while 226 (70%) had CP-A and 10 (3%) had CP-C. Etiology of liver disease in patients with CP-B included hepatitis B in 7.0%, hepatitis C in 38.4%, alcohol use in 30.2%, and metabolic associated steatohepatitis in 20.9%. Median OS in patients with CP-B liver function was 6.4 months, while mOS was 21.6 months for those with CP-A ( p<0.0001). Further stratifying, mOS in those with CP-B7 was 9.1 months, CP-B8 was 5.5 months, and CP-B9 was 4.0 months. 12-month OS in patients with CP-B was 32.4%, compared to 69.3% in CP-A. Median PFS was 4.8 months in those with CP-B and 8.9 months in those with CP-A. Median PFS in those with CP-B7, -B8, and -B9 was 6.4 months, 2.7 months, and 2.7 months, respectively. Among those with CP-B, 1 patient had a complete response, 17 (19.8%) had a partial response, 29 (33.7%) had stable disease, and 37 (43.0%) had progressive disease. Adverse events in CP-B patients included hypertension in 14.0% (grade 3 in 1 patient), bleeding in 16.3% (grade 3 or greater in 11.6%), fatigue in 38.4%, and an immune-related adverse event in 17.4% (grade 3 in 5.8%). Conclusions: Patients with advanced HCC and CP-B7 liver function may still benefit from A+B. Importantly, no additional safety risks were identified in this subgroup. Those with CP-B8 and CP-B9 have significantly worse survival than those with CP-B7 and the likelihood of benefit from systemic therapy is minimal. It is important for providers to address the impact of baseline liver function on expected outcomes in patient with HCC.

Abstract Background Levodopa‐induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2 . Objectives Our goal was to investigate the effects of genetic variants on risk and time to LID. Methods We performed a genome‐wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores (PRS) including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1612 PD patients with and 3175 without LID. Results We found that GBA1 variants were associated with LID risk (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.21–2.26; P = 0.0017) and LRRK2 variants with reduced time to LID onset (hazard ratio [HR] = 1.42; 95% CI, 1.09–1.84; P = 0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (OR fourth_quartile = 1.27; 95% CI, 1.03–1.56; P = 0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HR third_quartile = 1.38; 95% CI, 1.07–1.79; P = 0.0128; HR fourth_quartile = 1.38; 95% CI = 1.06–1.78; P = 0.0147). Conclusions This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Abstract Background The legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis. Methods A total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples. Results Overall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use. Conclusion This geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication.

PURPOSE The enhanced, electronic health record (EHR)–facilitated cancer symptom control (E2C2) trial is a cohort cluster-randomized, stepped-wedge, hybrid type II trial that leverages EHR systems to facilitate a collaborative care model (CCM) approach with the goal of improving cancer symptom management. Understanding factors that influence care team adoption of EHR systems remains a critical understudied area of research. This study examines how oncology care teams' perceptions regarding the feasibility, acceptability, and appropriateness of E2C2 EHR systems preimplementation were associated with adoption 3 months after implementation and characterizes differences in adoption by individual- and system-level factors. METHODS Care team members completed an electronic survey before and 3 months after implementation of E2C2 for their respective sequence. Adoption was defined as frequency of use to statements aligned with care team–directed EHR systems designed to facilitate CCM approaches. Chi-square tests assessed differences in adoption while logistic regression models estimated associations between baseline mean scores of acceptability, feasibility, and appropriateness on care team adoption at 3 months. RESULTS Results from 94 care team members (37.2% oncologists, 72.6% female, 55.3% in their role for 6+ years) found that adoption rates ranged from 48.9% to 71.7%, with significant differences observed by location (community-based health care systems v tertiary medical center) and professional role. Adjusting for professional role, care team members reporting higher levels of perceived acceptability and appropriateness at baseline had greater odds of adopting EHR systems at 3 months. CONCLUSION EHR systems perceived as acceptable and appropriate are more likely to be adopted by oncology care teams in our sample. Future implementation efforts should consider tailored strategies to facilitate adoption of EHR systems designed to promote CCM-based approaches to improve cancer symptom management.

Introduction: Transcribing disordered speech can be useful when diagnosing motor speech disorders such as primary progressive apraxia of speech (PPAOS), who have sound additions, deletions, and substitutions, or distortions and/or slow, segmented speech. Since transcribing speech can be a laborious process and requires an experienced listener, using automatic speech recognition (ASR) systems for diagnosis and treatment monitoring is appealing. This study evaluated the efficacy of a readily available ASR system (wav2vec 2.0) in transcribing speech of PPAOS patients to determine if the word error rate (WER) output by the ASR can differentiate between healthy speech and PPAOS and/or among its subtypes, whether WER correlates with AOS severity, and how the ASR's errors compare to those noted in manual transcriptions. Method: Forty-five patients with PPAOS and 22 healthy controls were recorded repeating 13 words, 3 times each, which were transcribed manually and using wav2vec 2.0. The WER and phonetic and prosodic speech errors were compared between groups, and ASR results were compared against manual transcriptions. Results: Mean overall WER was 0.88 for patients and 0.33 for controls. WER significantly correlated with AOS severity and accurately distinguished between patients and controls but not between AOS subtypes. The phonetic and prosodic errors from the ASR transcriptions were also unable to distinguish between subtypes, whereas errors calculated from human transcriptions were. There was poor agreement in the number of phonetic and prosodic errors between the ASR and human transcriptions. Conclusions: This study demonstrates that ASR can be useful in differentiating healthy from disordered speech and evaluating PPAOS severity but does not distinguish PPAOS subtypes. ASR transcriptions showed weak agreement with human transcriptions; thus, ASR may be a useful tool for the transcription of speech in PPAOS, but the research questions posed must be carefully considered within the context of its limitations. Supplemental Material: https://doi.org/10.23641/asha.26359417

AbstractThis case describes a pediatric patient with a history of ichthyosis vulgaris and global anhidrosis who was diagnosed with erythema ab igne (EAI), a rare dermatosis resulting from chronic heat exposure. After developing progressive, reticulated brown patches on his extremities and abdomen, extensive diagnostic investigations were conducted to rule out autoimmune, vascular, and genetic etiologies. Bloodwork was unrevealing and biopsies showed histologic features closely resembling keratosis lichenoides chronica. Ultimately, after discovering the patient had prolonged exposure to a space heater, the diagnosis of EAI was made. This case underscores the diagnostic challenges in pediatric EAI cases and emphasizes the importance of careful history taking as part of a comprehensive evaluation.

Abstract Osteoporosis and other metabolic bone diseases are prevalent in the aging population. While bone has the capacity to regenerate throughout life, bone formation rates decline with age and contribute to reduced bone density and strength. Identifying mechanisms and pathways that increase bone accrual in adults could prevent fractures and accelerate healing. G protein-gated inwardly rectifying K+ (GIRK) channels are key effectors of G protein-coupled receptor signaling. Girk3 was recently shown to regulate endochondral ossification. Here, we demonstrate that deletion of Girk3 increases bone mass after 18 weeks of age. Male 24-week-old Girk3-/- mice have greater trabecular bone mineral density and bone volume fraction than wildtype (WT) mice. Osteoblast activity is moderately increased in 24-week-old Girk3-/- mice compared to WT mice. In vitro, Girk3-/- bone marrow stromal cells (BMSCs) are more proliferative than WT BMSCs. Calvarial osteoblasts and BMSCs from Girk3-/- mice are also more osteogenic than WT cells, with altered expression of genes that regulate the wingless-related integration site (Wnt) family. Wnt inhibition via Dickkopf-1 (Dkk1) or β-catenin inhibition via XAV939 prevents enhanced mineralization, but not proliferation, in Girk3-/- BMSCs and slows these processes in WT cells. Finally, selective ablation of Girk3 from cells expressing Cre recombinase from the 2.3 kb-Col1a1 promoter, including osteoblasts and osteocytes, is sufficient to increase bone mass and bone strength in male mice at 24 weeks of age. Taken together, these data demonstrate that Girk3 regulates progenitor cell proliferation, osteoblast differentiation, and bone mass accrual in adult male mice.

Abstract Purpose The U.S. population is rapidly aging. The supply of surgeons needed to meet this demand should be evaluated. This study evaluated the trends in supply of Medicare surgeons by specialty and by U.S. state and region. Method All surgeons associated with a National Provider Identifier for cardiothoracic surgery, colorectal surgery, general surgery, gynecologic oncology, hand surgery, neurosurgery, obstetrics-gynecology, ophthalmology, oral and maxillofacial surgery, orthopedic surgery, otolaryngology, plastic and reconstructive surgery, surgical oncology, urology, and vascular surgery from 2013 to 2019 on the Centers for Medicare & Medicaid Services website were included. The absolute number of physicians was adjusted per 100,000 Medicare beneficiaries. Annual change was calculated by linear regression model, and the compound annual growth rate (CAGR) was calculated per specialty. Results The absolute number of physicians per 100,000 beneficiaries increased in 6 of 15 specialties during the study period. Vascular surgery had the largest annual increase (+0.23; CAGR, +2.75%), and obstetrics-gynecology had the largest annual decrease (−1.08; CAGR, −1.44%). Surgical oncology showed the largest positive CAGR (+4.20%). Oral and maxillofacial surgery had the largest negative CAGR (−2.86%). The Northeast was above the national average in supply for each specialty. The Midwest had the most specialties with positive CAGRs. The South did not meet the national average for physicians in any specialty. Conclusions This analysis of 15 surgical specialties provides important context to predicted physician shortages to the Medicare population. The study found geographic variation by region across specialty, which has important implications for health care planning from the level of undergraduate medical education to provision of hospital resources. Overall, the supply of surgeons across all specialties may not be sufficient to meet the demand of the rapidly aging U.S. population. Future study is needed to evaluate why surgeons are leaving the Medicare program.

Importance The randomized clinical trial Cancer and Leukemia Group B (CALGB) 140503 showed that for patients with clinically staged T1N0 non–small cell lung cancer (NSCLC; ≤2 cm), sublobar resections were associated with similar oncological outcomes to those after lobar resection. The association of the extent of parenchymal resection with recurrence and survival in patients with tumors pathologically upstaged to T2 based on visceral pleural invasion (VPI) is controversial. Objective To determine survival and recurrence rates in patients with small peripheral pT2 NSCLC (≤2 cm) that was treated by either lobar or sublobar resection in CALGB 140503. Design, Participants, and Setting CALGB 140503, a randomized multicenter noninferiority trial, included 697 patients with small peripheral NSCLC that was clinically staged as T1N0. Enrollment was from June 2007 through March 2017 at 83 participating institutions, and after a median follow-up of 7 years, the primary outcome of disease-free survival after sublobar resection was noninferior to that after lobar resection. Intervention Lobar or sublobar resection. Main Outcomes and Measures Survival end points were estimated by the Kaplan-Meier estimator. Hazard ratios and 95% CIs were estimated using stratified Cox proportional hazard models. Results Of 679 participants, 390 (57.4%) were female, and the median (range) age was 67.8 (37.8-89.7) years. Among 697 patients randomized, 566 (81.2%) had pT1 tumors (no VPI) and 113 (16.2%) had pT2 tumors (VPI). Five-year disease-free survival was 65.9% (95% CI, 61.9%-70.2%) in patients with pT1 compared with 53.3% (95% CI, 44.3%-64.1%) in patients with pT2 tumors (stratified log-rank: P = .02). Disease recurrence developed in 27.6% of patients with pT1 (locoregional only: 60 [10.8%]; distant only: 81 [14.6%]) and 41.6% of those with pT2 (locoregional only: 17 [15.0%]; distant only: 27 [23.9%]). Five-year recurrence-free survival was 73.1% (95% CI, 69.2%-77.1%) for pT1 tumors and 58.2% (95% CI, 49.2%-68.8%) for pT2 tumors (stratified log-rank: P = .01). There were no intergroup differences in disease-free or recurrence-free survival based on the extent of parenchymal resection. Conclusions and Relevance The results of this secondary analysis suggest that compared with patients with tumors without VPI, patients who had tumors with VPI had worse disease-free and recurrence-free survival and a higher rate of local and distant disease recurrence. These high rates of recurrence were independent of the extent of parenchymal resection, and these data support the inclusion of these patients in adjuvant therapy trials. Trial Registration ClinicalTrials.gov Identifier: NCT0049933