Citations

The NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget’s disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Breast Cancer focuses on the recommendations for the management of recurrent or stage IV (M1) metastatic breast cancer. It summarizes the treatment strategies stratified by tumor biology, including hormone receptor status and HER2 expression, as well as clinical factors such as prior therapy and disease-free interval. Throughout all treatment lines, supportive care, quality of life preservation, toxicity minimization, and clinical trial participation are emphasized as integral components of patient care.

Moderate traumatic brain injury (TBI) is a prevalent entity with a wide, dynamic, and heterogeneous injury spectrum. It has its own characteristics. However, it does not receive enough attention, as evidenced by the scarce representation in the literature and the absence of specific guidelines. Its changing epidemiological profile allows us to predict an increase in its incidence in the future, especially in the fragile population. Moderate TBI is not adequately categorized, and the risk of neuroworsening is elevated. The mortality of moderate TBI is not negligible and its functional outcomes are poor. Non-invasive neuromonitoring tools may have a key role in the initial evaluation and categorization of moderate TBI. Moderate TBI has cloudy, dark, and sunny aspects. To analyze these aspects and to propose management strategies constitute the main objective of this narrative review.

Background Surgeons face elevated risks of musculoskeletal disorders due to prolonged operating times, awkward postures, and repetitive tasks, which can impair performance and well-being. Microbreaks have emerged as a potential ergonomic intervention to reduce discomfort and fatigue during surgery. Objective The main goal of this study was to investigate and compare the intraoperative usability and effectiveness of two break scheduling strategies using the OR-Stretch TM Web-App. Furthermore, surgeons’ feedback on the primary barriers to implementation of the OR-Stretch Web-App was recorded. Methods This study used a randomized, within-subjects crossover design. Fourteen surgeons (eight females) performed three surgical procedures with the following microbreak schedules; (1) microbreaks every 30 min with an optional ten-minute snooze (Break-30), (2) microbreaks every 60 min with an optional ten-minute snooze (Break-60), or (3) no microbreaks (Baseline). Outcomes were measured using self-reported subjective surveys (e.g., discomfort, fatigue, workload, and usability). Results Surgeons found both Break-30 and Break-60 conditions aided physical performance, mental focus, body pain/discomfort, and level of fatigue (self-reported improvement between 28.6% and 78.6%). No significant differences were observed in surgeons’ subjective evaluations of the Break-30 and Break-60 conditions; however, the data suggest that Break-60 is preferable to the Break-30 condition. Conclusions This study provides evidence supporting the OR-Stretch Web-App as a potential surgical ergonomic intervention. However, enhancing the Web-App's user-friendliness and developing strategies to synchronize microbreaks with appropriate times during surgeries, to avoid disrupting the surgical workflow, are critical areas for future studies.

TAF7, a core subunit of the general transcription factor TFIID, regulates transcription and additionally functions as an RNA chaperone that directs nascent nuclear RNAs to cytoplasmic polysomes, thereby influencing protein synthesis. Here, we identify a set of novel cytoplasmic interactors and a previously unappreciated cytoplasmic role for TAF7 in oncogenesis. BioID-mediated proximity labeling identified STAT3 and the CCT and WASH complexes as prominent cytoplasmic interactors of TAF7. These interactions were validated by co-immunoprecipitation and proximity ligation assays. We further showed that cytoplasmic TAF7 levels increased during oncogenesis in proportion to cancer cell pathogenicity. Notably, TAF7 engagement with STAT3, CCT and WASH complexes is markedly enhanced during cellular transformation, consistent with their functions in cancer progression. Together, these findings reveal a cytoplasmic TAF7 interactome and implicate elevated cytoplasmic TAF7 as associated with oncogenesis.

Abstract Hemorrhagic shock is a common emergency that accounts for more than 10% of global mortality and up to 40% of trauma-related mortality. The Advanced Trauma Life Support (ATLS) guidelines outline resuscitation strategies in patients with massive hemorrhage based on clinical trial and observational data. Early intervention with fluids and/or blood products is recommended during resuscitation as key to maintaining vascular patency, stabilizing a patient’s blood pressure, maintaining tissue oxygenation, and limiting shock. From a transfusion perspective, there is wide heterogeneity in the quality of blood products due to donor and manufacturing variation. The optimal transfusion strategy for massive hemorrhage remains unclear. In silico models of resuscitation may offer a means to evaluate the effectiveness and safety of various resuscitation protocols. Here we describe a stochastic multicompartment model of fluid balance and resuscitation that includes (i) cardiovascular hemodynamics, (ii) body fluid compartments and capillary solute exchange, (iii) the ability to alter hemorrhage, resuscitation, and hemostasis parameters, and (iv) tissue oxygenation and capillary-alveolar gas exchange. Building upon deterministic frameworks, this stochastic model more faithfully reflects the clinical heterogeneity of bleeding patients at a level I trauma center. This allows for a proof of concept in silico trial comparing crystalloids, conventional component therapy (CCT), i.e. red cell, platelet and plasma components, to cold-stored low titer group O whole blood (LTOWB). In an in silico cohort of ATLS class III (>30% and ≤40% blood volume lost) hemorrhage, LTOWB resuscitation reduced the time spent in the critical hemostatic window (platelet count <50x109/L, INR≥2, hemoglobin (Hgb) <8 g/dL and fibrinogen <150 mg/dL) compared with CCT (90.59 vs. 147.62 minutes; p=0.04), with no difference in predicted event-free survival (t = 240 minutes; cardiac < 1.5, fluid overload > 10% or SBP > 150% of the starting SBP, or Hgb < 3.0 g/dL). In a separate cohort of ATLS class IV (>40% blood volume lost) hemorrhage, LTOWB yielded a higher predicted event-free survival (74%) versus the CCT arm (69%, p < 0.01). We demonstrate how this in silico platform can function as a digital twin for hemorrhagic trauma enabling precision transfusion strategies, and in parallel, an operational twin to support blood banks to forecast blood product demand and inform massive transfusion protocols and clinical trial design.

Abstract Background Multiplexed immunofluorescence (MxIF) enables high-dimensional immune cell phenotyping and detailed characterization of the tumor immune microenvironment (TIME), but complex cyclic staining can introduce signal degradation and uncertainty in cell-level measurements. In routine practice, pathologists rely on hematoxylin and eosin (H&E) staining as the primary reference for tissue morphology and frequently cross-reference H&E to interpret MxIF findings. Methods We present a framework for aligning H&E and MxIF images at the tissue microarray (TMA) core level to support cross-modal analysis. Cell nucleus detections from each modality are used as anchor points, formulating the task as a point-set alignment problem. Coherent Point Drift (CPD) is applied for global alignment, followed by graph-matching–based refinement to improve local consistency. Evaluation on ovarian TMAs demonstrates consistent alignment performance for both restained and serial sections. We further explore the use of restained H&E as a reference for MxIF interpretation and investigate virtual H&E generation from MxIF data as a complementary approach when restained H&E is unavailable. Results The aligned images enable quantitative assessment of cross-modal feature concordance between MxIF-derived measurements and H&E morphology. The generated virtual H&E demonstrated similar cell population compared to the real H&E. Conclusions Cell-centric alignment can facilitate integrative multimodal histopathology analysis for TMA cores in spatial co-localization, cell feature validation, and virtual H&E generation.

Objectives Comparing clinical outcomes after cardiopulmonary bypass with hemodsorption (HA) versus cardiopulmonary bypass without HA in patients undergoing cardiac surgery in terms of mortality and major complications. Methods PubMed, Scopus, and Web of Science databases were searched for relevant randomized control trials (RCTs) that compared postoperative clinical outcomes between patients receiving intraoperative HA with cardiopulmonary bypass versus patients receiving cardiopulmonary bypass without intraoperative HA in cardiac surgery. Results Sixteen RCTs with 851 patients (433 in the HA group and 418 in the control group), were included in our meta-analysis. Our meta-analysis found no significant differences between the intraoperative HA group and the control group in patients undergoing cardiac surgery in terms of 30-days/in-hospital mortality, new-onset atrial fibrillation, stroke or cerebrovascular events, postoperative delirium, renal failure/acute kidney injury, need for renal replacement, postoperative liver dysfunction, thrombocytopenia, bleeding, volume of blood loss, pneumonia, sepsis, respiratory insufficiency, duration of postoperative ventilation, distributive/septic shock, pericardial tamponade, need for extracorporeal membrane oxygenation (ECMO) support, sequential organ failure assessment (SOFA) score at ICU admission, plasma-free hemoglobin levels, and fibrinogen levels. However, the pooled analysis showed a significant association between HA and decreased albumin at ICU admission (MD = − 0.28, 95% CI [0.55 to 0.01], p -value = 0.04), decreased length of ICU stay (MD = −0.66, 95% CI [−1.24 to 0.08], p -value = 0.03), and decreased length of hospital stay (MD = −0.99, 95% CI [−1.88 to −0.10], p -value = 0.03). Conclusion Our findings suggest that there is not enough evidence to endorse the role of routine intraoperative HA during cardiopulmonary bypass in improving clinical outcomes after cardiac surgery. Factors such as patient risk profile, procedure complexity, and cost implications should be taken into account when considering this adjunct therapy.

Importance Opioid prescribing has decreased in the US for more than a decade. However, less is known about how prescribing trends differ by prescriber specialty and separately for short-term and long-term opioid prescribing for which the indications, clinical decision-making, and potential for harm vary substantially. Objective To characterize opioid analgesic prescribing trends in the US between January 1, 2010, and December 31, 2024, by prescriber specialty, analyzing short-term and long-term opioid use episodes separately. Design, Setting, and Participants This cross-sectional study used administrative claims data for commercially insured and Medicare Advantage patients (aged ≥65 years and &amp;lt;65 years with long-term disability) with at least 90 days of enrollment in medical and prescription coverage. Statistical analysis was performed from May 2025 to September 2025. Main Outcomes and Measures Prescribing volume, daily dose, and prescription duration. Results The study identified 110 288 218 opioid fills by 14 959 612 patients during the 15-year study period. Among opioid fills, 59.4% were attributed to female patients; the median (IQR) age at opioid fill was 61 (50-71) years. From 2010 to 2024, decreases in opioid prescribing were greater for long-term than short-term opioid use episodes (eg, commercial cohort: 81.3% reduction [from 33.2 fills per 100-person years in 2010 to 6.2 in 2024] and 74.6% reduction [from 36.2 fills per 100-person years in 2010 to 9.2 in 2024]), respectively. The proportion of all opioid fills written by primary care clinicians decreased (eg, Medicare Advantage with disability cohort: from 52.2% to 47.2%), whereas those written by pain medicine specialists increased (eg, Medicare Advantage with disability cohort: from 17.1% to 25.7%). Distinct trends for short-term and long-term opioid use episodes were observed in prescription characteristics, such as daily dose and duration. Conclusions and Relevance In this cross-sectional study of opioid prescribing trends in the US between 2010 and 2024, decreases in prescribing were greatest in long-term opioid use episodes, and prescribing was increasingly concentrated among pain medicine specialists. These findings suggest the need to balance reductions in opioid prescribing with provision of nonopioid pain treatments and raise concerns about access to care for patients taking opioids for chronic pain management.