Citations

Aging is a major risk factor for increased morbidity and mortality following acute respiratory virus infections. To elucidate the immune determinants underlying viral pathogenesis and delayed lung repair in the aged lung, a comprehensive time-course study was conducted. Single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry were utilized to compare lungs from young and aged mice infected with influenza A virus (IAV). Aged hosts displayed diminished alveolar macrophage (AM) and dendritic cell (DC) but elevated monocyte-derived macrophage (MoM) and interstitial macrophage (IM) presence following infection. Additionally, enhanced accumulation of adaptive immune cells, including CD4+ tissue-resident helper (TRH) cells, CD8+ tissue-resident memory (TRM) cells, and a B cell subset resembling age-associated B cells, was observed in the memory phase. Pathway analysis revealed that elevated type I and II interferon (IFNα/γ) signaling, especially in MoM/IM subsets, distinguished the aged hosts from the young. Inhibition of IFNα/γ signaling after viral clearance improved long-term respiratory outcomes and reduced both IM and TRH populations in aged mice. These findings highlight the pivotal role of IFNα/γ signaling, likely within MoM/IM subsets, in driving the exuberant persistence of adaptive immune cells and chronic immunopathology in the aged lung following acute viral infection.

Aging is a major risk factor for increased morbidity and mortality following acute respiratory virus infections. To elucidate the immune determinants underlying viral pathogenesis and delayed lung repair in the aged lung, a comprehensive time-course study was conducted. Single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry were utilized to compare lungs from young and aged mice infected with influenza A virus (IAV). Aged hosts displayed diminished alveolar macrophage (AM) and dendritic cell (DC) but elevated monocyte-derived macrophage (MoM) and interstitial macrophage (IM) presence following infection. Additionally, enhanced accumulation of adaptive immune cells, including CD4+ tissue-resident helper (TRH) cells, CD8+ tissue-resident memory (TRM) cells, and a B cell subset resembling age-associated B cells, was observed in the memory phase. Pathway analysis revealed that elevated type I and II interferon (IFNα/γ) signaling, especially in MoM/IM subsets, distinguished the aged hosts from the young. Inhibition of IFNα/γ signaling after viral clearance improved long-term respiratory outcomes and reduced both IM and TRH populations in aged mice. These findings highlight the pivotal role of IFNα/γ signaling, likely within MoM/IM subsets, in driving the exuberant persistence of adaptive immune cells and chronic immunopathology in the aged lung following acute viral infection.

Background and Objectives: Genitourinary syndrome of menopause (GSM), previously known as vulvovaginal atrophy, is a chronic, progressive hypoestrogenic condition affecting vulvovaginal, urinary and sexual health in women. Common symptoms include vaginal dryness, itching, dyspareunia, urinary urgency and recurrent urinary tract infections (UTIs). Despite the high prevalence, GSM is underdiagnosed and undertreated, thereby negatively impacting women’s quality of life. To illustrate the practical aspects of GSM diagnosis and provide evidence-based management, we present a case-based narrative review synthesizing recently published, high-quality evidence. Materials and Methods: Evidence was drawn from multiple sources through targeted searches of databases, and included the 2025 AUA/SUFU/AUGS guideline (AUA), the 2024 NICE network meta-analyses (NICE), a 2025 systematic review/meta-analysis in breast-cancer survivors, the 2020 Menopause Society GSM Position Statement, the 2018 NAMS/ISSWSH breast cancer consensus, several primary source citations and other high quality peer-reviewed publications. Results: Five illustrative composite case vignettes of GSM are presented to highlight the evaluation strategy and evidence-supported treatment choices. Nonhormonal options are the first line treatments for mild GSM symptoms, either with or without the addition of vaginal estrogen therapy. For moderate to severe GSM, low-dose vaginal estrogen, vaginal DHEA, and ospemifene are all effective FDA-approved options. In breast cancer survivors, individualized decisions with oncology input are warranted. Maximal caution and a shared decision-making approach is required for women using Aromatase Inhibitors (AIs) for breast cancer risk reduction when choosing treatments for GSM. Conclusions: Treating GSM improves vaginal, sexual and urinary outcomes and quality of life of women. Clinicians need to proactively screen for GSM and offer evidence-based treatment options. The treatment decisions in breast cancer survivors are nuanced, requiring a shared-decision approach.

Purpose: With the increasing prevalence of sleeve gastrectomy, complications and insufficient weight loss have become more common, making conversion to Roux-en-Y gastric bypass (RYGB) a frequent revisional approach. Given the higher risk of revisional surgery, we aimed to compare primary versus conversion RYGB surgery and assess whether robotic assistance impacts outcomes. Method: This retrospective study included 378 patients after 2:1 propensity score matching based on demographic and clinical characteristics, comparing primary Roux-en-Y gastric bypass (P-RYGB) with sleeve gastrectomy–to–Roux-en-Y gastric bypass (SG-RYGB). The matched cohort included both robotic and laparoscopic cases performed at a single tertiary center between 2012 and 2024. A secondary 2:1 matched sub-analysis of robotic cases ( n = 297) evaluated whether robotic assistance reduced differences between primary and revisional surgery. Weight-loss outcomes were assessed at 6 and 12 months in the full cohort, with an additional sub-analysis limited to SG-RYGB performed for weight-loss indications. Results: In the full cohort ( n = 378), SG-RYGB was associated with longer operative time, greater blood loss ( P < .001), longer hospital stay ( P = .04), and higher late complication rates ( P = .04). In the robotic-only matched analysis ( n = 297), differences in operative time and blood loss were no longer significant, and early and late outcomes were comparable, although length of stay still remained longer for SG-RYGB ( P = .05). Among patients undergoing SG-RYGB for weight loss purposes only, total body weight loss percentage reached 16.5% ± 6.6% at 6 months and 20.4% ± 7.1% at 12 months but remained lower than that observed in the P-RYGB group ( P < .001). Conclusion: SG-RYGB conversion demonstrated favorable outcomes and meaningful weight loss. Robotic assistance was associated with improved operative time, reduced blood loss, and fewer late complications in the SG-RYGB group, further narrowing differences with P-RYGB, supporting its role in complex revisional bariatric surgery at high-volume centers.

Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitor (BCL2i)–containing regimens significantly improve survival outcomes in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Results from randomized clinical trials have demonstrated that time-limited treatment with BCL2i-containing regimens resulted in higher rates of undetectable measurable residual disease (uMRD) than BTKi monotherapy or chemoimmunotherapy (CIT). Pirtobrutinib (a noncovalent BTKi) and lisocabtagene maraleucel (CD19-directed CAR T-cell therapy) are newer options for relapsed or refractory disease after prior therapy with BTKi and BCL2i-contining regimens. Histologic transformation of CLL/SLL to diffuse large B-cell lymphoma (Richter transformation) is associated with a poor prognosis. Molecular analysis to determine whether there is clonal relationship between CLL/SLL and transformed diffuse large B-cell lymphoma is useful to select an appropriate treatment option. These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for the treatment of CLL/SLL and Richter transformation.

Background: NCCN publishes evidence-based guidelines across the cancer care continuum that are commonly used as the standard for clinical management and policy in cancer care. Our study aimed to assess the content of survivorship recommendations within disease-based NCCN Guidelines. Methods: In January 2024, we downloaded 64 disease-based guidelines from the NCCN website; 10 were excluded. The remaining 54 guidelines were reviewed for survivorship-focused content. Content of the guidelines was systematically categorized across domains of the Quality of Cancer Survivorship Care Framework, and the level of detail was rated as not addressed, briefly addressed, mostly addressed, or fully addressed. Guidelines were re-reviewed for updates in April 2025. Results: Of 54 guidelines reviewed in 2025, 16 (30%) included a dedicated survivorship section with focused content, although sections, titles, and formats varied. Other guidelines included survivorship recommendations in algorithms and/or discussion sections. A total of 18 guidelines (33%) had neither a dedicated section nor reference to the NCCN Survivorship Guidelines. Guidelines with a dedicated section, as well as those referencing the NCCN Survivorship Guidelines (65%), generally provided more detailed survivorship content. Across all guidelines, the surveillance for recurrences/new cancers domain was most commonly included (96%) and typically the most detailed. Information on physical (81%) and psychosocial (72%) effects and health promotion (65%) was often included, but the level of detail varied. Chronic disease management (31%) was seldomly included. Information on care coordination/communication and patient education was present in 50% of the guidelines. Compared with the guidelines reviewed in 2024, the 2025 updates had limited expansion of survivorship content. Conclusions: Cancer survivorship content is inconsistently presented across disease-specific NCCN Guidelines. As these guidelines evolve, there is an opportunity to tailor, expand, and standardize the recommendations, making them easier to find by clearly labeling and integrating them within each guideline to improve accessibility and better support clinicians in delivering patient-centered care.

BACKGROUND: Morel-Lavallée lesions (MLLs) are closed degloving injuries that occur throughout the body and present treatment challenges due to their rarity and variability in management. We aimed to compare characteristics and outcomes for MLL patients undergoing early (less than 48 hours) vs late (more than 48 hours) surgical intervention, hypothesizing decreased length of stay (LOS) with early intervention. STUDY DESIGN: Fifteen centers participated in this prospective observational study, including all adult patients who sustained a MLL and underwent surgery. No patients were excluded. Bivariate comparisons for early vs late intervention cohorts were performed. RESULTS: Of 150 MLL patients, 101 (67.3%) underwent early intervention. Both cohorts had comparable ages, BMI, vitals, Charlson Comorbidity Index, and injury severity scores (all p > 0.05). However, early intervention patients more commonly had abdominal (37% vs 6.3%, p < 0.001) MLLs, whereas late intervention patients more often had hip (16.7% vs 3.0%, p = 0.01) and thigh (41.7% vs 22%, p = 0.03) MLLs. Early patients had shorter ICU LOS (2 vs 5, p = 0.003) but statistically similar hospital LOS (12 vs 20, p = 0.06). There was no difference in wound-related complications (19.8% vs 24.5%, p = 0.51) or mean number of additional surgeries (p = 0.41) between cohorts. CONCLUSIONS: Over two-thirds of MLL patients underwent early operation. These patients had decreased ICU LOS and a statistically similar albeit clinically shorter overall LOS, despite similar demographics, comorbidities, injury severity, and number of additional surgeries. Therefore, early operation appears beneficial and should be pursued in MLL patients when clinically indicated and feasible.

The rapid adoption of telemedicine has transformed healthcare delivery in the US, enhancing access and communication for surgical patients across wide geographic areas. However, a critical challenge persists: the need to define and standardize quality metrics specifically for telemedicine in surgery. Existing studies suggest that telemedicine can yield equivalent or improved outcomes compared with in-person visits. Nevertheless, literature remains limited in evaluating patient satisfaction, cost-effectiveness, and diagnostic accuracy. Through expert consensus within the American College of Surgeons Board of Governors Telehealth Pillar, we propose a structured framework for defining and implementing quality metrics for surgical telemedicine. This is based on the Donabedian model, addressing structure, process, and outcome, while also considering the distinct phases of surgical care: preoperative, intraoperative, and postoperative. This framework identifies unique domains of telemedicine in surgical care, emphasizing hospital and organizational structure, patient and provider readiness, and policy alignment. A comparative analysis with existing AHRQ and WHO frameworks highlights gaps in surgical applicability. Finally, we propose an implementation roadmap prioritizing immediate, feasible metrics while identifying areas for future validation. Collaboration among researchers, clinicians, and policymakers will be essential to establish these metrics and ensure that telemedicine delivers on its potential to improve surgical care delivery while addressing disparities in access and outcomes.

ABSTRACT Background A randomized phase II screening trial of gemcitabine, nab‐paclitaxel, and cisplatin with a medically supervised ketogenic diet (MSKD) versus usual diet (non‐MSKD) was conducted in patients with treatment‐naive metastatic pancreatic ductal adenocarcinoma (PDAC). Methods Patients with untreated metastatic PDAC were randomized 1:1 to MSKD or non‐MSKD while receiving gemcitabine, nab‐paclitaxel, and cisplatin on days 1 and 8 of a 21‐day cycle. The MSKD was guided by a remote health care team and daily ketone (beta‐hydroxybutyrate) levels, with goal beta‐hydroxybutyrate of 0.5 to 3.0 mM. The primary endpoint was progression‐free survival (PFS) using a one‐sided alpha level of 0.20. Secondary endpoints included overall survival (OS), safety, and quality of life (QOL). Changes in microbiome were an exploratory endpoint. Findings Overall, there were 32 evaluable patients. In the MSKD arm, 15 of 16 patients achieved nutritional ketosis; the median proportion of days in ketosis was 39.4%. The median PFS was 8.5 months in MSKD patients and 6.2 months in non‐MSKD patients: hazard ratio, 0.53 (95% CI, 0.21–1.37); one‐sided p = .096. The median OS was 13.7 months with MSKD and 10.2 months in the non‐MSKD arm: hazard ratio, 0.58 (95% CI, 0.25–1.37); one‐sided p = .107). All MSKD‐related adverse events were grade 1‐2. There were no significant differences in grade ≥3 chemotherapy‐related adverse events between the arms. MSKD patients had no decline in QOL and had significant enrichment of beneficial taxa in the microbiome ( p < .05, log‐fold change ≥2). Conclusions The MSKD is feasible in patients with PDAC and, although not powered for definitive outcomes, shows trends in improved PFS and OS when combined with gemcitabine, nab‐paclitaxel, and cisplatin, without added toxicity or detriment to QOL. Larger studies are required to confirm these findings and establish the value of the MSKD in pancreatic cancer treatment.

Abstract Platelet‐rich plasma (PRP) continues to generate both excitement and skepticism within orthopaedics and sports medicine. As a biologic derived from autologous blood, PRP offers an appealing, minimally invasive option for treating musculoskeletal pathology through the delivery of concentrated growth factors and cytokines. Evidence across orthopaedic subspecialties remains mixed, however, with studies showing variable efficacy and inconsistent methodologies. Recent data on PRP use for extra‐articular hip pathology, particularly greater trochanteric pain syndrome, hamstring injuries, and piriformis syndrome show encouraging improvements in pain and function, including faster return to sport and favorable patient‐reported outcomes. Yet, significant heterogeneity in study design, PRP preparation, and control interventions limits generalizability and hinders clear clinical guidance. These inconsistencies mirror similar challenges in PRP research for a variety of other orthopaedic pathologies, underscoring the need for standardized preparation protocols and consistent reporting frameworks. Despite these limitations, a signal of efficacy persists within the data, suggesting PRP may indeed provide meaningful benefit for select extra‐articular hip conditions. As surgical alternatives for these pathologies often carry substantial morbidity, continued refinement of PRP formulations and methodology represents a promising step toward establishing biologics as reliable, evidence‐based tools in orthopaedic care.