Citations

Abstract Background Unresectable hepatocellular carcinoma (uHCC) is a leading cause of cancer death. FDA-approved first-line systemic therapies include atezolizumab/bevacizumab (atezo/bev) and durvalumab/tremelimumab (durva/treme); however, there is a lack of comparative data. Methods We reviewed outcomes of patients with uHCC who initiated atezo/bev or durva/treme between 2017 and 2024, across six institutions. Overall survival (OS) and time to treatment discontinuation (TTD) were analyzed using the Kaplan–Meier and Cox models, adjusting for baseline characteristics. Results Four hundred fifty-two uHCC pts were included. Median age: 68 years; 77% male; 81% white. Most common etiologies were viral hepatitis (38.9%) and metabolic dysfunction-associated steatohepatitis (19.5%). Disease progression was the primary reason for treatment discontinuation, atezo/bev (56%) and durva/treme (42%). Outcomes were not statistically significant (median OS [month, m]: 14.0 vs 14.6 [P = .66]; median TTD [m]: 4.9 vs 3.9 [P = .42] for atezo/bev vs durva/treme). Outcomes were significantly different between Child-Pugh classes (CP: A, B7, B8/9, C) respectively, median OS(m): 19.0, 6.1, 5.1, 2.0 (P < .001); median TTD(m): 6.1, 2.3, 3.0, 1.3 (P < .001). Conclusions In this real-world study of uHCC, no significant difference in clinical outcomes was observed between atezo/bev and durva/treme in the first-line setting. CP scores were a key prognostic variable with both regimens.

Background: Longitudinal genomic profiling through serial circulating tumor DNA (ctDNA) testing offers a noninvasive method to monitor clonal evolution in advanced prostate cancer. This study evaluated the frequency and nature of newly emergent and potentially actionable genomic alterations detected through serial testing in a real-world setting. Methods: We conducted a retrospective analysis of advanced prostate cancer patients who underwent multiple Guardant360 ctDNA tests between October 2020 and March 2023. The study focused on identifying new genomic alterations absent in the initial test, with particular attention to alterations relevant for on-label therapies, therapies approved in other oncologic indications (i.e., off-label), or a clinical trial. Results: Among 479 patients with at least two ctDNA tests, the median interval between the first and second evaluable tests was 207 days. New and potentially actionable alterations emerged in 57.8% of patients, including potential targets for on-label therapies (16.7%), off-label therapies (16.5%), and clinical trials (55.7%). Tumor mutational burden (TMB) increased from “low” to “high” in 11% of patients, although none had microsatellite instability or mismatch repair deficiency. In a Mayo Clinic subset, ten patients received olaparib based on treatment-emergent alterations, but none achieved a prostate-specific antigen (PSA) response. Two patients who transitioned from low to high TMB received pembrolizumab, both with progressive disease as best response. Conclusions: In a large real-world cohort, serial ctDNA testing frequently identified new alterations that were not detected at baseline and are potentially actionable therapeutic targets, highlighting the value of serial genomic profiling for capturing clonal dynamics. Additional research is needed to better establish a framework for retesting and to clarify how these results should influence subsequent treatment decisions.

ImportanceStudies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.ObjectiveTo evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023.InterventionsParticipants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months.Main Outcomes and MeasuresThe primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder.ResultsAmong 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, −0.32; 95% CI, −0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, −0.40; 95% CI, −1.81 to 0.93), meeting the success criterion for safety (noninferiority margin <3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93).Conclusions and RelevanceAmong 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection.Trial RegistrationClinicalTrials.gov Identifier: NCT03386539

Objective: Pulmonary air trapping is critical for diagnosing and prognostication of various lung diseases. Expiratory CT imaging serves as an accessible method to assess air trapping, which correlates with small airway disease outcomes. Air trapping manifests as mosaic attenuation on inspiratory chest CT that is difficult for visual estimation. The primary aim of this study was to develop an automated tool to quantify mosaic attenuation on inspiratory CT and air trapping on paired expiratory CT. Secondary aims included comparing CT-derived parameters with PFT measurements and dyspnea scores. Methods: This retrospective analysis of noncontrast chest CTs from 2 academic hospitals was conducted between January 1, 2018, and December 31, 2019. Patients with paired inspiratory and expiratory CT chest scans and PFTs performed on the same day were included. A chest radiologist manually annotated lung parenchyma in a reference cohort. Several histogram-based metrics were computed from lung parenchymal CT values, with the maximum peak position showing the strongest correlation with manually determined thresholds. This threshold, derived from the histogram peak, was applied in the adaptive thresholding process to quantify mosaic attenuation and air trapping. Results: We analyzed 267 patients (65.5% female, median age 68). Most exhibited normal physiological patterns (44.0%). Patients with elevated residual volume (RV) by PFTs (28.1%) had significantly higher inspiratory CT mosaic attenuation (1629.6 vs. 1311.5 mL, P <0.01) and expiratory CT air trapping volumes (1413.7 vs. 886.2 mL, P <0.01). Correlation analyses demonstrated strong relationships between CT-derived mosaic attenuation and air trapping measures and RV. The correlation with PFT parameters was even stronger in subgroup analyses in patients with obstructive PFT patterns. These models had good predictive ability for an abnormal RV (AUC of 0.92, sensitivity of 72.4%, and specificity of 92.0%) and clinical utility based on good correlation with the mMRC dyspnea score ( r =0.71; 95% CI: 0.65-0.77). Conclusions: This automated adaptive thresholding on inspiratory and expiratory chest CT scans showed a high correlation of lung volume and air trapping parameters with PFTs, revealing that measures of lung function have a complex interplay with air trapping.

ABSTRACT Levator ani syndrome (LAS) explains up to 7.4% of anorectal pain cases. Classic symptoms include rectal pain or pressure with sitting. We present 2 patients, ages 32 and 25 years, presenting initially with “diarrhea” and perianal hyperhidrosis. History revealed rectal discomfort, tenesmus, urgency, and sensation of incomplete evacuation. Puborectalis tenderness was present on digital rectal examination. Therapies were tailored to each patient, including pelvic floor physical therapy with biofeedback, bowel regulation, rectal diazepam, and ileostomy. These presentations offer insights into potential pathophysiological mechanisms in LAS and highlight the importance of considering LAS in non-pain presentations.

Abstract Objectives Effective communication is crucial in healthcare, and for patients with a non-English language preference (NELP), professional interpreters are recognized as the gold standard in supporting bidirectional communication. However, interpreters are not always readily available, prompting the exploration of other options for translation and interpretation. The recent developments in artificial intelligence-based neural network translation tools, namely neural machine translation (NMT) may enable robust interpretation and translation. Materials and Methods We conducted a systematic review (SR) to evaluate the literature on NMT for this purpose. We did a comprehensive search of several databases with guidance from a professional librarian. The search was limited to the year 2000 onwards and English language. Title and abstract screening and full-text review were independently conducted by two reviewers with conflicts resolved by a third reviewer Results 2867 studies were identified with 10 studies included in the final analysis. Among these, six evaluated interpretation in real or simulated clinical settings and four examined translation of discharge materials. Google Translate and ChatGPT were assessed in several studies. Accuracy differed by language, with low-resource languages performing worse. Discussion NMT technologies in healthcare have several advantages including broad language accessibility and potential cost savings for institutions. Despite improved accuracy of these novel tools, due to possible critical errors NMT tools are not yet ready for widespread clinical use. Conclusion Future studies should focus on optimizing evaluation methods as well as how best to integrate these technologies into real-time clinical settings.

Fundamental to medical education, gross anatomy first introduces medical students to human mortality, often provoking stress. Sense of purpose, a key aspect of well-being, may serve as a protective factor. We studied students’ sense of purpose during an anatomy course, examining its links to performance, spirituality, and belief in an afterlife. Fifty medical students who took a 7-week gross anatomy course in 2022 or 2023 completed the Life Engagement Test at the beginning, middle, and end of the course. We collected other data including demographics, religious/spiritual beliefs, and previous exposure to body donors. Practical and final examinations assessed course performance. Strong sense of purpose at the three measurement points was positively correlated with practical exam performance (r = 0.40, P = .004; r = 0.44, P = .003; r = 0.30, P = .047, respectively) but not National Board of Medical Examiners’ anatomy subject exam performance. Staunch believers and non-believers in an afterlife maintained a stable sense of purpose, while students uncertain about the afterlife experienced a decline from the beginning to the middle of the course and even more to the end ( P = .046; P = .008, respectively). These students also had significantly lower practical examination performance as compared to other students (95% CI [−10.84, −0.52]). In conclusion, a strong sense of purpose predicts better performance in a 7-week anatomy course. Both believers and non-believers in an afterlife do well, but students wavering in their beliefs experience a declining sense of purpose and lower grades. Supporting these students when they confront human mortality, including in other contexts such as palliative care/hospice settings, may be beneficial.