Citations

An accurate differential diagnosis for diffuse lung disease can be confidently established by using a systematic approach to identify the predominant radiographic pattern, determine the distribution of disease, and assess for architectural or volume change.

ABSTRACT The role of DNA topoisomerase II beta (TOP2B) in cardiomyocyte differentiation is poorly understood. To address this, human induced pluripotent stem cells (hiPSC) were differentiated into cardiomyocytes (CM) that were wild type (WT) or contained a genomic deletion of Topoisomerase 2B (BKO). Both WT and BKO hiPSC could be induced to differentiate into sheets of beating cardiomyocytes. BKO hiPSC take slightly longer to differentiate into sheets of beating CM than WT iPSC. RNA was prepared from both undifferentiated and differentiated WT and BKO hiPSC. RNA-seq was used to examine gene expression changes when the WT and BKO hiPSC were differentiated into CM. Gene expression changes following differentiation of BKO cells were largely similar to those in WT cells. In addition, the differentiated WT CM were treated with dexrazoxane (ICRF-187), a TOP2 catalytic inhibitor that targets both TOP2A and TOP2B, or topobexin, a new TOP2B selective catalytic inhibitor. Topobexin inhibition partially phenocopied a TOP2B deletion and thereby providing an alternative to TOP2B gene knockout in many cell lines. In future, hiPSC derived CM with and without TOP2B and inhibition by topobexin ex vivo CM could be used to study anthracycline-induced cardiotoxicity and to screen for cardioprotectants.

<p class="MsoNormal"> <span lang="EN-US">The Semantic Web has the ultimate goal of making a machine understand Internet data. To enable the encoding of semantics with the data, well-known technologies are used such as RDF (Resource Description Framework) and OWL (Web Ontology Language). These technologies formally represent the meaning involved in information. For example, ontology can describe concepts, relationships between things, and categories of things. These embedded semantics offer significant advantages such as reasoning over data and dealing with heterogeneous data sources.<o:p></o:p></span> </p>

PURPOSE Adherence to operative standards and thorough documentation of surgical technique are critical, particularly in multidisciplinary clinical trials. We sought to evaluate variability in the performance and documentation of oncologically relevant aspects of technical surgery among patients enrolled in Alliance A021501, a phase 2 National Clinical Trials Network randomized clinical trial of neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma. METHODS We reviewed the primary operative and pathology reports of all enrolled patients who underwent complete pancreatic resection. Operative techniques and pathologic end points with potential to influence recurrence and survival were evaluated. RESULTS Fifty-one of 126 study participants (40.5%) underwent complete pancreatectomy. The extent of lymphadenectomy was documented in 36 (70.6%) operative reports, and 5 (9.8%) reports outlined the specific lymph node stations removed. Periadventitial dissection of the superior mesenteric artery was described in 25 of 50 (50.0%) operative reports. Immediate histopathologic analysis of the hepatic duct and pancreatic parenchyma margins was documented in 29 of 50 (58.0%) and 32 of 49 (65.3%) reports, respectively, and presence or absence of residual disease following resection was documented in 9 of 51 (17.6%) reports. Specimen orientation was documented in 19 of 51 (37.3%) pathology reports, and 30 of 49 (61.2%) pathology reports stated the distance between the tumor and final SMA margin. CONCLUSION Even in this rigorously controlled, multicenter, randomized pancreatic cancer clinical trial, performance of key elements of technical surgery was inconsistent, and documentation was incomplete. Standardization of technique and documentation in clinical trials and within clinical practice should be addressed to improve quality assurance and trial interpretability.

Whole-body cross-sectional imaging has largely replaced skeletal survey as the standard for evaluating hematologic malignancies and bone marrow disorders, but the practical choice between whole-body low-dose CT (WBCT) and whole-body MRI (WBMRI) remains incompletely resolved. This clinical review provides a practical, scenario-based comparison of WBCT and WBMRI across diagnosis, staging, treatment response, and surveillance. We emphasize real-world practical considerations, including scanner access, expertise, patient tolerance, radiation considerations, and cost. In multiple myeloma, with available comparative evidence, we include a focused research synthesis of 3 studies (152 patients) demonstrating high pooled CT-MRI concordance of 0.895 (95% CI: 0.834-0.935) with no detectable heterogeneity ( I 2 =0%), supporting either modality as a reasonable first-line depending on the clinical question. Across all included disease categories, the broader pooled concordance estimate was 0.797 (95% CI: 0.667-0.885) with substantial heterogeneity reflecting variability in clinical context, reference standard, and protocol. WBMRI dominates in non-neoplastic marrow disorders where marrow characterization is essential. In lymphoma, FDG-PET/CT remains the standard for adult disease, with WBMRI most indicated in pediatrics and adolescents. Emerging CT techniques, including dual-energy CT with virtual noncalcium images and photon-counting detector CT, are extending CT into the marrow imaging space and narrowing the historical gap with MRI. Modality selection should be guided by the specific clinical scenario, available resources, and patient factors rather than by global judgments of modality superiority.

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

ABSTRACT Objectives Alar reconstruction is common, yet high‐quality outcomes data are limited. This review synthesizes the available literature to guide evidence‐informed reconstructive choices. Methods A systematic review identified 35 eligible studies reporting defect characteristics, techniques, and aesthetic, functional, and graft/flap outcomes. Single‐patient case reports, purely technical papers, and studies without outcome data were excluded. Results Full‐thickness skin grafts (FTSG), FTSG with cartilage, and composite grafts have been used with acceptable aesthetic outcomes for small defects. Local flaps are most common for small to intermediate defects, while regional flaps, particularly melolabial (MLF) and paramedian forehead flaps (PMFF), are the primary options for larger defects. PMFFs have higher reported cosmetic satisfaction but may require more secondary procedures. Conclusions Standard data and evidence reporting for alar subunit reconstruction is very limited, with a predominance of retrospective and technique‐driven studies and gestalt‐based outcomes. Standardized reporting of defect size, functional outcomes, and validated patient‐reported measures is needed. Until higher‐quality data is available, reconstructive decisions should be individualized.

Objective Respiratory syncytial virus (RSV) is an important viral pathogen in children, older adults and adults with certain high-risk conditions. In our prospective community-based cohort study of adults 50 years and older before the COVID-19 pandemic, the incidence of RSV acute respiratory infection (ARI) was 48.6 cases/1000 person-years (PY), which decreased to near zero during the COVID-19 pandemic. Our objective was to determine the incidence of RSV-ARI during the 2 years following the initial phase of the pandemic (2021–2022 and 2022–2023). Design This is a community-based prospective cohort study. Setting Adults living in southeast Minnesota from October 2021 to September 2022 (year 3) and October 2022 to September 2023 (year 4). Participants Adults≥50 years (n=2500). Primary and secondary outcomes We calculated incidence and attack rates for RSV-ARI as primary outcome and reported hospitalisations, pneumonia and death following ARI as secondary outcome. Results There were 2500 participants in the study with a mean age of 68.2 years (SD 9.3) at the start of year 3. Participants were predominantly female (60%), non-Hispanic white (96%) and residing in urban areas (76%). The incidence rate of RSV-ARI was 6.12/1000 PY (95% CI 3.42 to 10.09) in 2021–2022 and 16.40/1000 PY (95% CI 11.66 to 22.42) in 2022–2023. We noted higher attack rates of RSV-ARI during the winter months. There were no hospitalisations, pneumonia or deaths within 30 days of RSV-ARI. Conclusions Compared with the period before the COVID-19 pandemic, RSV-ARI incidence was lower in both 2021–2022 and 2022–2023 periods. In 2022–2023, the incidence increased 2.7-fold compared with the 2021–2022 period. The observed incidence rates, particularly the significant increase in the most recent season, underscore the continued public health relevance of RSV-ARI and support the rationale for ongoing RSV vaccination efforts to mitigate its overall burden in the population.