Citations

ABSTRACT Background Despite histologic remission (HR) being important in management of ulcerative colitis, the impact of endoscopic sampling on newer scoring systems remains uncertain. This study examines the outcome of applying PICaSSO Histologic Remission Index (PHRI) scoring on biopsies collected during routine clinical care and investigates the impact of endoscopic sampling variation on PHRI scoring and HR status. Methods A retrospective survey of UC endoscopic biopsies ( N = 128, 559 bites, 1–13 bites/biopsy) was evaluated using standard H&E stain and myeloperoxidase (MPO) immunohistochemistry to aid neutrophil identification. Convolutional neural networks (CNN), trained on colonic tissue architecture and cytomorphology features, were deployed alongside pathologist interpretations. In silico modeling of bite‐derived virtual biopsies ( N = 19,760) was investigated to determine the impact of sampling variation on PHRI scores and compared with ground truth clinical samples. Results PHRI MPO scoring displayed improved sensitivity and specificity for identifying neutrophils, compared with PHRI H&E . CNN‐derived PHRI scoring was most accurate for chronic active and chronic active with ulceration categories, with greatest variability observed in chronic inactive biopsies. Virtual patient biopsies comprised of < 5 endoscopic bites were impacted most by sampling permutations. Limited variability in PHRI scores was observed in samples consisting of ≥ 5 bites. Conclusions HR status (PHRI = 0) determination was slightly impacted by sampling. Biopsies consisting of < 5 endoscopic bites exhibited the most variability. Conservative sampling of 5–7 endoscopic bites may produce more accurate assessments of microscopic heterogeneity in clinical studies employing quantitative histologic measurements to assess disease activity and remission. Additionally, incorporating MPO increased the sensitivity and specificity of detecting active inflammation for PHRI scoring.

Abstract Exercise training improves cardiovascular health and reduces the risk for future cardiovascular events and mortality. However, emerging evidence suggests that Masters athletes may have a higher prevalence of cardiovascular abnormalities, such as atrial arrhythmias, coronary atherosclerosis, aortic dilatation, and myocardial fibrosis, compared to their less active peers. The clinical management of Masters athletes may be challenging as available guidelines for such conditions are generally based on data derived from symptomatic sedentary patients, limiting their applicability to highly trained individuals. Other unique challenges in the clinical assessment of Masters athletes include differences in symptomatic presentations compared to sedentary individuals, potential resistance to the initiation of pharmacologic treatment, and the increasing availability of consumer wearable health data that may provide relevant information on their cardiovascular health status. The purpose of this joint EAPC/ESC and ACC Clinical Consensus Statement is to provide an in-depth update on the current state of knowledge on abnormal cardiovascular findings in Masters athletes. We present an expert-based approach on the diagnostic assessment, management, and prognosis of (i) atrial fibrillation, (ii) bradyarrhythmias, (iii) ventricular arrhythmias, (iv) coronary atherosclerosis, (v) aortic dilatation, (vi) myocardial fibrosis, and (vii) exercise-induced arrhythmogenic cardiomyopathy. Clinical challenges, areas of ongoing controversy, and uncertainty and the potential underlying mechanisms are discussed. We also present future perspectives and research directives to further refine current best practice strategies. This includes the need for clinical outcome studies, dedicated randomized controlled trials in athletes, and international registries with diverse populations and longitudinal follow-up to evaluate the natural history of cardiac abnormalities and facilitate development of evidence-based approaches in the clinical management of Masters athletes with cardiovascular abnormalities.

ABSTRACT Objective With regulatory approval of HPV‐specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted. Data Sources and Methods RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability. Results Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case‐by‐case basis. HPV ‐specific immunotherapy that induces an HPV ‐specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first‐line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second‐line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally‐administered adjuvant should be considered. Conclusion This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options. Level of Evidence 5

Abstract Purpose: Rearranged during transfection (RET) alterations are oncogenic drivers across solid tumors. Selective RET inhibitors (SRI) selpercatinib and pralsetinib have transformed outcomes for patients with RET-altered malignancies. Limited knowledge exists on genomic mechanisms of resistance to SRI. Experimental Design: We established “RETgistry,” a global consortium of patients with advanced RET-altered solid tumors who received SRI and underwent postprogression tissue or plasma biopsies assessed by next-generation sequencing. Frequencies of secondary RET resistance mutations and acquired non-RET gene alterations were determined. Progression-free survival (PFS) and time to treatment discontinuation (TTD) on first SRI were estimated with the Kaplan–Meier method. Results: RETgistry included 109 patients with RET-altered advanced solid tumors (lung, n = 94; thyroid, n = 15) who underwent 143 post-SRI progression biopsies (tissue, 91; plasma, 52). The median PFS and TTD were 13.9 months [95% confidence interval (CI), 10.1–16.6] and 17.3 months (95% CI, 14–20.2), respectively. Secondary RET mutations were detected in 20 (14%) biopsies [lung cancer, 15 (12.4%) and thyroid carcinoma, 5 (22.7%)]. Common acquired off-target alterations involved MET (18.2%; amplification, 15%), TP53 (8.2%), APC (7.6%), KRAS (7.1%), KEAP1 (5.9%), and CDKN2A/B (5.3%). MET alterations were enriched in post-SRI versus pre-SRI specimens (full cohort, 17.6% vs. 2.0%, P = 0.022; lung cancer, 19.1% vs. 2.1%, P = 0.022). Conclusions: The prevalence of secondary RET mutations after SRI was low, underscoring a greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide the development of novel therapeutic strategies.

Sharing research code in an open access version-controlled repository offers significant benefits for both science as a whole and for individual researchers. In this article, we focus on this practice, which is fully aligned with the NIH’s Gold Standard Science (GSS) program as well as FAIR (findable, accessible, interoperable, reusable) and TRUST (transparency, responsibility, user focus, sustainability, technology) principles. Gold Standard Science supports open science by emphasizing transparency, reproducibility, and the use of best practices that enable others to verify and extend research. Pairing a research article’s cited data snapshot with a versioned, environment-specific code release, deposited in a companion code repository, ensures that, upon submission to a medical journal, readers and reviewers can directly verify results. An executable and updatable companion code repository complements, rather than replaces, established research data repositories. When code underlying medical research results is made openly available, then other scientists can inspect, run, and validate analyses. These activities enhance reproducibility, which is a core aim of GSS. Shared code also facilitates collaborative innovation by allowing researchers to extend the utility of the code to new datasets and applications. For researchers, code sharing can increase visibility, credibility, and citation impact. Demonstrating transparency through shared executable and updatable code builds trust with journal readers, peer reviewers, funders, and peers. Shared code in an open access repository signals adherence to high standards of scientific integrity and attracts opportunities for collaboration. A researcher who shares code receives recognition as a leader in reproducible, trustworthy research consistent with NIH’s GSS principles.

Background: Arthroscopic treatment of excessive acetabular coverage with pincer morphology or coxa profunda can be challenging. In patients with excessive acetabular coverage with nondistractible hips, an outside-in capsuolotomy can be considered to gain safe and efficient intra-articular access to the hip. Indications: The indications for an outside-in capsulotomy include patients with acetabular retroversion, a lateral center-edge angle >40°, coxa profunda or protrusio, or stiff, older male patients who remain hip preservation candidates. Technique Description: The outside-in capsulotomy is performed once it is recognized that traction on the operative extremity will not provide adequate working space for safe intra-articular access. Traction is taken off the operative extremity, and an anterolateral portal is localized to the 12:00 position on the hip joint with the use of fluoroscopy. The camera is then placed in a juxta-capsular location, and a modified anterior portal is created under direct arthroscopic visualization. We then proceed with extracapsular dissection to identify the indirect head of the rectus. An outside-in capsulotomy is then performed parallel to the indirect head of the rectus, approximately 5 mm distal to its insertion on the acetabular rim. Prior to deep completion of the capsulotomy, the hip joint is flexed to 30° to protect the articular cartilage of the femoral head. Once intra-articular access is obtained, traction can be reapplied, and one can proceed with hip arthroscopy in a standard fashion. Results: This technique decreases the traction time needed, given that the capsulotomy is performed without traction applied. Additionally, the amount of force required for hip distraction is decreased once the capsuolotomy has been completed, through usual sectioning of the iliofemoral ligament. The presented technique is both safe and efficacious, with no published difference in complications as compared to standard inside-out access. A published series of patients with severe pincer morphology and lateral overcoverage who undergo hip arthroscopy with outside-in access demonstrates satisfactory postoperative improvements in patient-reported outcome measures. Discussion/Conclusion: The outside-in capsulotomy provides a means for safe access to the hip joint in otherwise limited or nondistractible hips.

BACKGROUND: Patients with cervical artery dissection (CeAD) may experience a recurrent dissection, but its frequency, risk factors, and clinical implications are not well defined. We aimed to determine the risk, associated factors, and clinical impact of recurrent CeAD. METHODS: The STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection) was a multicenter international retrospective observational study of patients with CeAD treated between January 2015 and June 2022. Recurrent dissection was defined as a CeAD occurring at least 7 days after the diagnosis of the index event that affects a different artery or a different segment of the same artery. Patients were followed from day 7 up to 2 years. The absolute risk of recurrent CeAD over time was calculated using Kaplan-Meier survival estimates. Multivariable logistic and Cox regression models were used to assess predictors of CeAD recurrence. RESULTS: Of the 4023 patients included in STOP-CAD, 3836 (median age 46 years, 45% women) were eligible for this analysis. During a median (interquartile range) follow-up of 295 (97–720) days, 88 (2.29%) patients had a CeAD recurrence. Median time-to-recurrent CeAD was 53 (interquartile range, 18–157) days. The estimated risk of recurrent CeAD at 2 years was 3.22% (95% CI, 2.59%–4.00%). In multivariable analyses, younger age (adjusted odds ratios, 0.98 [95% CI, 0.96–0.99]), migraine (adjusted odds ratio, 1.88 [95% CI, 1.14–3.07]), and fibromuscular dysplasia (adjusted odds ratio, 2.90 [95% CI, 1.66–5.06]) were associated with CeAD recurrence, while presenting with an ischemic stroke was associated with a lower likelihood of recurrence (adjusted odds ratio, 0.47 [95% CI, 0.29–0.75]). These associations with CeAD recurrence over time were confirmed by Cox regression analyses. Among the 88 patients with recurrent CeAD, only 5 had accompanying ischemic events (3 strokes, 2 transient ischemic attacks). CONCLUSIONS: In this retrospective study, recurrent CeAD was uncommon, approximately half of the events were diagnosed within the first 2 months of the index event, and recurrent events rarely caused new ischemic events. Younger age, migraine, absence of ischemic stroke at presentation, and signs of fibromuscular dysplasia may help identify high-risk patients.

Abstract Background Catheter related bloodstream infections (CRBSI) are associated with increased resource use, treatment costs, and mortality among patients with cancer. Coagulase-negative staphylococci (CoNS) are the most common cause of central venous catheter (CVC) infection in this population. While CVC removal remains the gold standard, CRBSI with CoNS is sometimes managed with CVC salvage, despite incomplete safety and efficacy data in patients with hematological malignancy.Table 1.Baseline Demographic and Clinical DataTable 2.Baseline Characteristics by Treatment Strategy Methods A retrospective review was conducted of adult patients at Mayo Clinic Rochester from 2013 to 2024 diagnosed with hematological malignancy and CRBSI with CoNS. Patients were included in a “CVC removed” group if the line was removed within 5 days of bacteremia onset, and all others were included in a “CVC retained” group. Electronic medical records were evaluated for relevant clinical comorbidities, risk factors, and management. The primary outcomes of interest were 90-day mortality and relapse. To control for baseline differences between groups, we employed a propensity weighted analysis based on inverse probability of treatment weighting using the propensity score.Weighted cumulative event rates for Relapse and Mortality Results A total of 140 cases were included, of whom 95 (67.9%) had undergone BMT and 111 (80.4%) were neutropenic at time of CRBSI. The predominant CoNS identified was Staphylococcus epidermidis (88.6%). 79 (56.4%) patients had the CVC retained and 61 (43.6%) underwent CVC removal. Those in whom the CVC was retained were more likely to be BMT recipients (p=0.007). However, line removal was more common with PICC lines (p&lt; 0.001) and in those hospitalized for management of line-associated bacteremia (p=0.022). Within 90 days, there were 10 patients (cumulative incidence 8.2%) who had microbiological relapse (2 [4.3%] in the CVC removed group and 8 [11.1%] in the CVC retained group). Propensity weighted analysis demonstrated significantly higher rate of microbiologic relapse with CVC retention (p=0.043) but no difference in mortality (p=0.128), as shown by weighted cumulative event rate curves in Figure 1. Conclusion Despite the finding of increased risk of relapse associated with CVC retention, there was no significant difference in mortality between CVC removal and retention among individuals with CoNS CRBSI and hematological malignancy. Disclosures All Authors: No reported disclosures

Abstract Background The increased frequency of spinal surgeries has led to a rise in postoperative spine infections (PSIs), now recognized as the third most common surgical complication. Currently, there is no standardized definition of PSI, complicating clinical management and research. This meta-epidemiological study aimed to develop clear diagnostic criteria to assist clinicians and researchers in identifying and reporting PSIs consistently. 2020 PRISMA flow diagram Sankey diagram showing the distribution of combination of criteria or definitions used by the authors. This refers to 21 articles that used a definition derived by the authors. Methods Following PRISMA guidelines, a comprehensive literature search was conducted by a medical librarian using Ovid MEDLINE (March 14, 2024). Studies were included if they reported on at least ten adult patients diagnosed with PSI and provided clear diagnostic definitions. The primary objective was to evaluate existing PSI diagnostic criteria and categorize them into thematic clusters. We constructed standardized diagnostic combinations using 13 predefined criteria derived from clinical practice guidelines and prior research (Table 1).Characteristics of the included studies*Total can be more than 100% since some variables can be present in multiple categories.This refers to 21 articles that used a definition derived by the authors. For articles #411 and #630 categorization was not possible as the definition provided only information about the depth of infection and not the criteria for diagnosis. Article #1148 was included as, defining “presumed aspetic” cases meant, by definition, also defining infectious cases.Abbreviations. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), Centers for Disease Control and Prevention (CDC), The National Healthcare Safety Network (NHSN), Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA), Magnetic Resonance Imaging (MRI) Results From an initial 1,466 studies screened, 101 were included (Figure 1). Most studies were retrospective (91/101, 92.1%), and a majority (77/101, 76.2%) relied on established criteria such as those from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) or the CDC. Seven studies combined predefined criteria with additional detailed explanations. Among the remaining studies using independent definitions, clinical signs and symptoms were the most common criteria (13/24, 54.2%) (Table 1). Criteria were grouped into clinical, microbiological, and radiological categories, with most studies primarily using clinical criteria alone or in combination with microbiological or imaging findings (Figure 2). Conclusion There was no clear consensus in the literature on what defines a PSI. Our findings emphasize the necessity of establishing a standardized PSI definition that integrates clinical, microbiological, and radiological criteria. Implementing such a unified framework could enhance diagnostic accuracy, address existing limitations associated with hardware complications, wound drainage interpretations, and imaging ambiguities, and improve upon the current shortcomings of surveillance systems. Disclosures Jeremy D. Shaw, MD, Globus: Grant/Research Support|Purgo Scientific: Advisor/Consultant|Purgo Scientific: Stocks/Bonds (Private Company)

Abstract Background Spinal implant infections (SII) are serious complications following instrumented spinal fusion. Debridement with implant retention requires antibiotic therapy, yet the optimal duration remains unclear. We assessed whether longer antibiotic duration is associated with reduced risk of treatment failure. Methods We conducted a multicenter retrospective cohort study of adult patients diagnosed with acute postoperative SII (≤90 days from index surgery) between January 1, 2017, and December 31, 2022. All patients underwent debridement with implant retention. Treatment failure was defined as unplanned reoperation, clinical recurrence, or infection-related death. A Cox proportional hazards model assessed whether being on antibiotics was protective, treating antibiotic use as a time-dependent covariate, adjusting for relevant clinical variables, and including death not attributable to infection as a competing event. A second Cox model evaluated whether shorter antibiotic duration was associated with increased risk of failure with landmark analysis at six weeks. Results There were 531 patients included in the study. Patient demographics are described in Table 1. During a median follow-up of 1,168 days (IQR 576-1,817), 151 patients experienced treatment failure. There was a non-significant trend toward decreased hazard of failure while on antibiotics (HR 0.70; 95% CI 0.46–1.05; p=0.087). Among 363 patients without early failure, 60 (16.5%) received ≤6 weeks of antibiotics and 303 (83.5%) received &gt;6 weeks. Longer antibiotic duration was not associated with a differential risk of failure (HR 0.75, 95% CI 0.43–1.33; p=0.34). Conclusion Continuing antibiotic therapy after debridement and implant retention may help reduce the risk of treatment failure in SII. However, it remains unclear whether extending antibiotic treatment beyond a certain duration continues to offer additional benefits. Prospective studies are needed to better define the optimal duration and approach to antibiotic therapy in these scenarios. Disclosures Sandra B. Nelson, MD, UpToDate Wolters Kluwer Health: Author, Editor