Citations

The performance of a deep learning model was not different from that of radiologists in the detection of clinically significant prostate cancer at MRI, and gradient-weighted class activation maps localized the tumor.

Abstract INTRODUCTION Tau‐positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis. METHODS Using head‐to‐head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed “CenTauR” [CTR]). JPM is a statistical model that simultaneously models the relationships between head‐to‐head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale. RESULTS A strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach. DISCUSSION Preliminary findings using the JPM support the development and adoption of a universal scale for tau‐PET quantification. Highlights Tested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed “CenTauRs”. Tested a Centiloid‐like linear regression approach. Using five cohorts with head‐to‐head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Purpose To determine the relationship between cam morphology of the hip and ipsilateral sacroiliac motion compared to the native hip in a cadaveric model. Methods A simulated cam state was created using a 3‐dimensional printed cam secured to the head‐neck junction of 5 cadaveric hips. Hips were studied using a computed tomography–based optic metrology system and a 6 degree‐of‐freedom robot to exert an internal rotation torque at 3 different torque levels (6 N‐m, 12 N‐m, 18 N‐m). Outcomes included translational and rotational movement about 3 axes and composite (total) translational motion at the ipsilateral sacroiliac (SI) joint. Statistical analysis included a linear mixed model regression with repeated measures. Results The presence of a simulated cam was associated with medial motion in the coronal plane ( P = .03) and posterior motion in the sagittal plane ( P < .01) but not composite motion ( P = .37). Motion in the axial plane was in an inferior direction ( P = .08). Cam morphology significantly changed rotation in the sagittal plane ( P < .01) but not in the coronal ( P = .63) or axial plane ( P = .18). Composite motion was related to the amount of torque applied to the hip ( P < .01). The amount of torque applied to the hip was related to rotation in the coronal plane ( P < .01), axial plane ( P < .01), and sagittal plane ( P < .01) with increased effects as torque increased. Torque was not associated with translation movement in any of the anatomic planes. Conclusions The presence of simulated cam morphology is associated with motion in a more medial, inferior, and posterior direction at the ipsilateral SI joint relative to a native state. Increasing torque affects the magnitude of translation, but not its direction, which in this study is primarily influenced by cam morphology. Clinical Relevance This biomechanical connection between cam‐type femoroacetabular impingement syndrome and the ipsilateral SI joint provides insight into SI joint dysfunction in patients with femoroacetabular impingement syndrome.

Hypertension is among the most important risk factors for cardiovascular disease, chronic kidney disease, and dementia. The artificial intelligence (AI) field is advancing quickly, and there has been little discussion on how AI could be leveraged for improving the diagnosis and management of hypertension. AI technologies, including machine learning tools, could alter the way we diagnose and manage hypertension, with potential impacts for improving individual and population health. The development of successful AI tools in public health and health care systems requires diverse types of expertise with collaborative relationships between clinicians, engineers, and data scientists. Unbiased data sources, management, and analyses remain a foundational challenge. From a diagnostic standpoint, machine learning tools may improve the measurement of blood pressure and be useful in the prediction of incident hypertension. To advance the management of hypertension, machine learning tools may be useful to find personalized treatments for patients using analytics to predict response to antihypertension medications and the risk for hypertension-related complications. However, there are real-world implementation challenges to using AI tools in hypertension. Herein, we summarize key findings from a diverse group of stakeholders who participated in a workshop held by the National Heart, Lung, and Blood Institute in March 2023. Workshop participants presented information on communication gaps between clinical medicine, data science, and engineering in health care; novel approaches to estimating BP, hypertension risk, and BP control; and real-world implementation challenges and issues.

Abstract Aims Operating on patients with severe degenerative mitral regurgitation (DMR) is based on ACC/AHA or ESC/EACTS guidelines. Doubts persist on best surgical indications and their potential association with postoperative survival loss. We sought to investigate whether guideline-based indications lead to late postoperative survival loss in DMR patients. Methods and results We analysed outcome of 2833 patients from the Mitral Regurgitation International Database registry undergoing surgical correction of DMR. Patients were stratified by surgical indications: Class I trigger (symptoms, left ventricular end-systolic diameter ≥ 40 mm, or left ventricular ejection fraction &lt; 60%, n = 1677), isolated Class IIa trigger [atrial fibrillation (AF), pulmonary hypertension (PH), or left atrial diameter ≥ 55 mm, n = 568], or no trigger (n = 588). Postoperative survival was compared after matching for clinical differences. Restricted mean survival time (RMST) was analysed. During a median 8.5-year follow-up, 603 deaths occurred. Long-term postoperative survival was lower with Class I trigger than in Class IIa trigger and no trigger (71.4 ± 1.9, 84.3 ± 2.3, and 88.9 ± 1.9% at 10 years, P &lt; 0.001). Having at least one Class I criterion led to excess mortality (P &lt; 0.001), while several Class I criteria conferred additional death risk [hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.42–1.66]. Isolated Class IIa triggers conferred an excess mortality risk vs. those without (HR: 1.46, 95% CI: 1.00–2.13, P = 0.05). Among these patients, isolated PH led to decreased postoperative survival vs. those without (83.7 ± 2.8% vs. 89.3 ± 1.6%, P = 0.011), with the same pattern observed for AF (81.8 ± 5.0% vs. 88.3 ± 1.5%, P = 0.023). According to RMST analysis, compare to those operated on without triggers, operating on Class I trigger patients led to 9.4-month survival loss (P &lt; 0.001) and operating on isolated Class IIa trigger patients displayed 4.9-month survival loss (P = 0.001) after 10 years. Conclusion Waiting for the onset of Class I or isolated Class IIa triggers before operating on DMR patients is associated with postoperative survival loss. These data encourage an early surgical strategy.

Abstract T-cell/histiocyte–rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19–directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the Center for International Blood and Marrow Transplant Research registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART therapy between 2018 and 2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range, 1-7) prior therapies and were treated with axicabtagene ciloleucel (69%). At median follow-up of 23 months after CART therapy, 2-year overall and progression-free survival were 42% (95% confidence interval [CI], 27-57) and 29% (95% CI, 17-43), respectively. In univariable analysis, poor performance status before CART therapy was associated with higher mortality (hazard ratio, 2.35; 95%CI, 1.02-5.5). The 2-year cumulative incidences of relapse/progression and nonrelapse mortality were 69% and 2%, respectively. Grade ≥3 cytokine release syndrome and immune effector cell–associated neurologic syndrome occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART therapy for R/R THRLBCL, ∼30% of patients were alive and progression free 2 years after CART therapy. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CARTs.

AbstractObjectiveWe performed a pilot stroke incidence study, focused on feasibility and inclusion of the CONSIDER reporting guidelines, to model the design of a future population‐based study aiming to definitively determine stroke incidence, antecedents, treatment, and outcomes.Study designProspective stroke incidence study (pilot study).Setting, participantsAll people aged 15 years or older who lived in postcode‐defined areas of South Australia and Northern Territory (885 472 people, including 45 127 Aboriginal people [5.1%]) diagnosed with stroke for the first time during 1 October – 31 December 2015 and admitted to public hospitals or stroke and transient ischaemic attack clinics.Main outcome measuresFeasibility of a prospective population‐based stroke incidence study.ResultsOf the 123 participants with first strokes, ten were Aboriginal (8%); the median age of Aboriginal people was 45 years (interquartile range [IQR], 33–55 years), of non‐Indigenous people 73 years (IQR, 62–84 years). For Aboriginal people, the age‐standardised incidence of stroke was 104 (95% confidence interval [CI], 84–124) per 100 000 person‐years, for non‐Indigenous people 33 (95% CI, 22–44) per 100 000 person‐years. We found that a prospective population‐based stroke incidence study in Aboriginal people was feasible, including with respect to establishing an adequate sample size, diagnostic confirmation, identification of incident stroke, confirming stroke subtypes, establishing a stable statistical population, standardising data reporting for comparison with other stroke incidence studies, and ethical research reporting that conforms to CONSIDER guidelines.ConclusionsA larger, population‐based study of the incidence of stroke in Aboriginal people is both feasible and needed to provide robust estimates of stroke incidence, antecedents, treatments and outcomes to help guide strategies for reducing the risk of and outcomes of stroke in Aboriginal people.

Abstract Background Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. Methods In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. Results Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P = .61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function. Conclusions Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment. Clinical Trials Registration EudraCT 2020-005416-22; Clinical Trials.gov NCT04745351.