Citations

ImportanceAlthough prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown.ObjectiveTo estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer.Design, Setting, and ParticipantsThis decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy. Inputs used were from the literature and a retrospective cohort study conducted at 2 institutions. The base case analysis assumed modest benefits of earlier detection and treatment, and scenario analyses considered prostate-specific antigen (PSA) level at imaging and different outcomes of earlier vs delayed treatment. The analysis was performed between April 1, 2023, and May 1, 2024.Exposures(1) Immediate PSMA-PET imaging, (2) conventional imaging (computed tomography and bone scan [CTBS]) followed by PSMA-PET if CTBS findings were negative or equivocal, and (3) CTBS alone.Main Outcomes and MeasuresThe main outcomes were detection of metastases, deaths from prostate cancer, and life-years and quality-adjusted life-years (QALYs) gained.ResultsThe model estimated that per 1000 simulated patients with BCR (assumed median age, 66 years), PSMA-PET is expected to diagnose 611 (95% uncertainty interval [UI], 565-656) patients with metastasis compared with 630 (95% UI, 586-675) patients diagnosed using CTBS followed by PSMA-PET and 297 (95% UI, 202-410) patients diagnosed using CTBS alone. Moreover, the estimated number of prostate cancer deaths was 512 (95% UI, 472-552 deaths) with PSMA-PET, 520 (95% UI, 480-559 deaths) with CTBS followed by PSMA-PET, and 587 (95% UI, 538-632 deaths) with CTBS alone. Imaging with PSMA-PET yielded the highest number of QALYs, which were 824 (95% UI, 698-885) higher than CTBS. These results differed by PSA level at the time of testing, with the highest incremental life-years and QALYs and lowest number of deaths from prostate cancer among patients with PSA levels of at least 5.0 ng/mL. Finally, the estimates were sensitive to the expected benefit of initiating therapy for recurrent prostate cancer earlier in the disease course.Conclusions and RelevanceThe results of this decision-analytic model suggest that upfront PSMA-PET imaging for the evaluation of BCR is expected to be associated with reduced cancer mortality and gains in life-years and QALYs compared with the conventional imaging strategy, assuming modest benefits of earlier detection and treatment.

Abstract Neuronal dysfunction in specific brain regions or across distributed brain networks is a known feature of Alzheimer’s disease. An often reported finding in the early stage of the disease is the presence of increased functional MRI (fMRI) blood oxygenation level-dependent signal under task conditions relative to cognitively normal controls, a phenomenon known as ‘hyperactivation’. However, research in the past decades yielded complex, sometimes conflicting results. The magnitude and topology of fMRI hyperactivation patterns have been found to vary across the preclinical and clinical spectrum of Alzheimer’s disease, including concomitant ‘hypoactivation’ in some cases. These incongruences are likely due to a range of factors, including the disease stage at which the cohort is examined, the brain areas or networks studied and the fMRI paradigm utilized to evoke these functional abnormalities. Additionally, a perennial question pertains to the nature of hyperactivation in the context of Alzheimer’s disease. Some propose it reflects compensatory mechanisms to sustain cognitive performance, while others suggest it is linked to the pathological disruption of a highly regulated homeostatic cycle that contributes to, or even drives, disease progression. Providing a coherent narrative for these empirical and conceptual discrepancies is paramount to develop disease models, understand the synergy between hyperactivation and the Alzheimer’s disease pathological cascade and tailor effective interventions. We first provide a comprehensive overview of functional brain changes spanning the course from normal ageing to the clinical spectrum of Alzheimer’s disease. We then highlight evidence supporting a close relationship between fMRI hyperactivation and in vivo markers of Alzheimer’s pathology. We primarily focus on task-based fMRI studies in humans, but also consider studies using different functional imaging techniques and animal models. We then discuss the potential mechanisms underlying hyperactivation in the context of Alzheimer’s disease and provide a testable framework bridging hyperactivation, ageing, cognition and the Alzheimer’s disease pathological cascade. We conclude with a discussion of future challenges and opportunities to advance our understanding of the fundamental disease mechanisms of Alzheimer’s disease, and the promising development of therapeutic interventions incorporating or aimed at hyperactivation and large-scale functional systems.

Abstract Background The Grading Recommendations, Assessment, Development, and Evaluations (GRADE) framework is widely applied in clinical guidelines to facilitate transparent evidence evaluation. While developing Infectious Diseases Society of America (IDSA) guidelines on the management of patients with coronavirus disease 2019 (COVID-19), panel members suggested developing and implementing a visual aid to enable quicker identification of key information by providers at bedside seeking guidance. Methods We conducted a mixed-methods study evaluating the usability of a newly designed infographic/icon using a survey and focus groups. The survey incorporated a simulated COVID-19 IDSA guideline with and without the icon, followed by comprehension questions. Focus group discussions provided qualitative feedback on the GRADE methodology and icon usability. Results The survey was returned by 289 health care providers. There was no statistical difference in the correct response rates between icon-aided and non-icon-aided guideline questions (McNemar's chi-square test, P > .1 for both questions). Interactions with the icon notably increased the time taken and number of clicks required to respond to the first question (Wilcoxon signed-rank test, P < .01). In contrast, response time did not differ between versions for the second question (P = .38). Most subjects (85%) indicated that the icon improved the readability of the guidelines. A focus group follow-up suggested alternative designs for the icon. Conclusions This study highlights the promise of iconography in clinical guidelines, although the specific icons tested did not measurably improve usability metrics. Future research should focus on icon design and testing within a formal usability framework, considering the impact of GRADE language on user experience.

Précis: Analysis of Centers for Medicare and Medicaid Services (CMS) Physician Payment data found that physician certification year, degree of urbanization, and estimated income by zip code were significant in predicting the proportion of traditional glaucoma procedures performed by each provider in the United States. Objective: The prevalence of microinvasive glaucoma surgery (MIGS) compared with traditional procedures has been increasing in glaucoma management. It is important to understand whether the uptake of new glaucoma procedures is associated with aspects of the physician practice. Methods: In this cross-sectional study, data on glaucoma procedure distribution, degree of urbanization, and physician certification in the United States were extracted from the 2019 CMS Physician Payment and American Board of Ophthalmology databases. The distribution of traditional and MIGS procedure numbers for metropolitan versus non-metropolitan providers was visualized with boxplots and statistically compared using Mann-Whitney U tests. We used two-dimensional histograms and regression analyses to assess the relationship between certification year and volume of traditional versus MIGS procedures. A multivariable linear regression model was created using certification year, rural-urban commuting area code, and estimated income by practice zip code to predict the number and proportion of each type of glaucoma procedure. Results: This study included 2625 providers from the CMS physician payment data who performed only traditional procedures (n = 370), MIGS procedures (n = 1727), or both procedure types (n = 528) in 2019. The median number of MIGS procedures performed by each provider was greater in non-metropolitan areas (31 vs 29, P = 0.015), whereas the proportion of traditional procedures performed by each provider was greater in metropolitan areas (0.24 vs 0.08, P < 0.001). Regression analysis showed a positive relationship between the certification year and the proportion of traditional procedures performed by each provider (P < 0.001). Multivariable regression models found that certification year, rural-urban commuting area code, and estimated income of practice location were all significant predictors (P < 0.02) of the proportion of traditional procedures performed by each provider. Conclusion: In the United States, physicians in metropolitan areas and more recent certification years are more likely to perform a larger proportion of traditional procedures. This finding suggests that the distribution of glaucoma procedure types is related to physician factors such as degree of urbanization and duration of practice. More research is needed to better understand how such differences affect patient access and outcomes.

Abstract Background Sarcoidosis is a disease characterized by non-caseating granulomas and may affect any organ system. Cardiac involvement may lead to conduction abnormalities, heart failure, or malignant ventricular arrhythmias. As sarcoidosis may present with heterogeneous manifestations, a detailed past medical history may provide clues that help guide further workup. We present a rare case of a patient with undiagnosed oral sarcoidosis who subsequently experienced cardiac arrest from cardiac involvement. Case summary A 43-year-old male with a history of palpitations and periodontitis consistent with oral sarcoidosis presents after experiencing sudden cardiac arrest. He was subsequently diagnosed with cardiac and pulmonary sarcoidosis. With contemporary management (both immunosuppression and antiarrhythmics), he has not experienced any recurrent arrhythmias. Discussion In the setting of cardiac arrest and non-ischaemic cardiomyopathy, a careful clinical history and targeted cardiac testing may help clinicians determine when to consider cardiac sarcoidosis as a diagnosis. While oral sarcoidosis is a very rare condition, this case highlights how infrequent manifestations of sarcoidosis may be encountered in the clinical setting.

ABSTRACT The prevalence of invasive candidiasis caused by non- albicans Candida species is increasing. Candida guilliermondii is an infrequent cause of candidemia but has been associated with decreased susceptibility to triazoles. Clinical data related to the infection with C. guilliermondii are sparse. Our study evaluated the antifungal susceptibility testing (AST) for C. guilliermondii isolates submitted to a reference laboratory over a 12-year period (2012–2023). AST patterns were examined using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) epidemiological cutoff values (ECVs) and breakpoints. Where isolates were identified from patients treated at our institution, retrospective chart review was performed to describe patient risk factors, treatment approaches, and outcomes associated with C. guilliermondii fungemia. One hundred twelve blood culture isolates of C. guilliermondii were identified, and clinical data were available for 21 fungemic patients. A significant number of isolates (9.8–20.5%) were observed to be non-wild type for various triazoles. All isolates were susceptible to micafungin. A majority (76.2%) of cases of C. guilliermondii fungemia treated at our tertiary care center were hospital-acquired, and two-thirds of patients were immunocompromised at the time of diagnosis. Ten of the 21 patients died within 60 days of fungemia, although mortality was directly or partially attributed to C. guilliermondii fungemia in only four cases (19.0%). Echinocandins may be used for empiric therapy for C. guilliermondii until the results of AST are available. Further research is required to determine appropriate clinical breakpoints for triazoles. IMPORTANCE Our study addresses a significant knowledge gap in the clinical management of this non- Candida albicans species. Our retrospective review includes comprehensive AST data for 112 Candida guilliermondii isolates, which is the largest number of isolates reported from the United States to date. Susceptibility data are supplemented by clinical outcomes, where isolates were identified for patients treated at Mayo Clinic. Key findings from our study include the observation that a notable proportion of C. guilliermondii isolates exhibit non-wild-type profiles for various triazoles. Importantly, all isolates remained susceptible to echinocandins, suggesting their efficacy as first-line therapy in the absence of timely susceptibility results. Furthermore, our study highlights the high mortality associated with C. guilliermondii fungemia in immunocompromised patients, emphasizing the urgent need for optimized treatment strategies.

AbstractObjectiveThe profunda artery perforator (PAP) flap has gained popularity in head and neck reconstruction with a favorable donor site providing a relatively hidden scar and the ability to harvest a large amount of pliable tissue with consistent vascular anatomy. The primary aim of this study is to evaluate the safety and efficacy of this PAP flap in head and neck reconstruction.Data SourcesPUBMED, EMBASE, Web of Science, Google Scholar (January 1948‐February 2022).Review MethodsA systematic review of the English language literature was conducted for studies with at least 3 patients 18 years or older undergoing head and neck reconstruction utilizing the PAP. Study quality and risk of bias were evaluated using the MINORS scoring system. Main analysis endpoints were flap failure rate, donor site morbidity, and complication rate.ResultsNine articles and 206 total PAP flaps were included. The rate of flap‐related and medical complications was 33%, with only 2 (0.97%) instances of complete flap failure. Other complications included partial flap failure (10, 4.86%) and donor site wound complications (12, 5.83%). A total of 16 flaps (7.77%) required subsequent revision in the operating room. Average MINORS score of the studies suggested a moderate to high risk of bias.ConclusionBased on limited quality evidence, this review suggests that the PAP flap is a safe and feasible tool for head and neck reconstruction, with comparable complication and success rates as other free flaps. Further large‐scale studies are warranted.

Background: Anterior cruciate ligament (ACL) reconstruction (ACLR) can be successful in restoring knee stability. However, secondary ACL injury, either through graft failure or contralateral injury, is a known complication and can significantly impact the ability of a patient to return successfully to previous activities. Purpose: To develop and internally validate an interpretable machine learning model to quantify the risk of graft failure and contralateral ACL injury in a longitudinal cohort treated with ACLR. Study Design: Case-control study; Level of evidence, 3. Methods: An established geographic database of >600,000 patients was used to identify patients with a diagnosis of ACL rupture between 1990 and 2016 with a minimum 2-year follow-up. Medical records were reviewed for relevant patient information and 4 candidate machine learning algorithms were evaluated for prediction of graft failure and contralateral ACL injury in patients after ACLR as identified either on magnetic resonance imaging or via arthroscopy. Performance of the algorithms was assessed through discrimination, calibration, and decision curve analysis. Model interpretability was enhanced utilizing global variable importance plots and partial dependence curves. Results: A total of 1497 patients met inclusion criteria. Among them, 140 (9.4%) had graft failure and 128 (8.6%) had a contralateral ACL injury after index surgery at a median follow-up of 140.7 months (interquartile range, 77.2-219.2 months). The best performing models achieved an area under the receiver operating characteristics curve of 0.70 for prediction of graft failure and 0.67 for prediction of contralateral ACL injury, outperforming a logistic regression fitted on the identical feature set. Notable predictors for increased risk of graft failure included younger age at injury, body mass index (BMI) <30, return to sports <13 months, initial time to surgery >75 days, utilization of allograft, femoral/tibial fixation with suspension/expansion devices, concomitant collateral ligament injury, and active or former smoking history. Predictors of contralateral ACL injury included greater preoperative pain, younger age at initial injury, BMI <30, active smoking history, initial time to surgery >75 days, history of contralateral knee arthroscopies, and involvement in contact sports. Conclusion: Less than 18% of all patients who undergo ACLR should be expected to sustain either a graft failure or contralateral ACL injury. Machine learning models outperformed logistic regression and identified greater preoperative pain, younger age, BMI <30, earlier return to higher activity, and time to surgical intervention >75 days as common risk factors for both graft failure as well as contralateral ACL injury after ACLR. Surgeon-modifiable risk factors for graft failure included allograft and femoral/tibial fixation with a suspension/expansion combination.