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Summary This nutshell review discusses the pathophysiology, diagnostic features, treatment strategies and avenues for future research in a recently identified thrombotic entity, monoclonal gammopathy of thrombotic significance (MGTS). MGTS is an anti‐platelet factor 4 (PF4) antibody‐mediated disorder distinct from heparin‐induced thrombocytopenia (HIT) and vaccine‐induced thrombotic thrombocytopenia (VITT), as it involves the production of persistent, monoclonal anti‐PF4 antibodies. Several subtypes of MGTS, including ‘HIT‐like’, ‘VITT‐like’ and ‘non‐HIT/VITT‐like’, exhibit unique serological profiles that can complicate diagnosis. Recognition of ‘HIT‐like’ MGTS is critical to avoid heparin exposure in these patients, which can result in adverse effects like those seen in heparin‐exposed HIT patients. ‘Non‐HIT/VITT‐like’ MGTS antibodies have only been detected in PF4‐enhanced functional testing; therefore, we recommend using these platelet‐based tests as the front‐line assay for detecting MGTS antibodies. Mass profiling using mass spectrometry is critical for the ‘fingerprinting’ of monoclonal antibodies to establish a diagnosis of MGTS. Treatments used in HIT and VITT, such as non‐heparin anticoagulants and intravenous immunoglobulin G, are typically insufficient for managing MGTS. Emerging MGTS therapies, such as plasma cell‐directed drugs and Bruton tyrosine kinase inhibitors, are discussed. The review concludes with an emphasis on areas of future research in MGTS.

Background Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is a rare subset of primary cutaneous lymphoma known for its aggressive behavior, poor prognosis, and limited treatment options, particularly in the relapsed or refractory setting. We report a case of a patient diagnosed with PCDLBCL-LT who achieved a clinically significant response and sustained remission for seven months with acalabrutinib, a covalent inhibitor of Bruton’s tyrosine kinase (BTK), before disease progression. Case presentation An 88-year-old woman presented with a rapidly enlarging ulcerated lesion on the left lower leg. Histopathological and immunohistochemical analyses confirmed the diagnosis of PCDLBCL-LT. She was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemoimmunotherapy, followed by external beam radiation therapy (RT). These interventions resulted in only a partial response, and the disease progressed within several months. The patient was receiving direct oral anticoagulant (DOAC) therapy for left lower limb deep vein thrombosis, and she also had a history of hypertension. Considering the increased risk of major bleeding associated with DOAC use and the elevated risk of cardiovascular adverse events previously reported with ibrutinib, an alternative BTK inhibitor was considered. Accordingly, she was initiated on acalabrutinib at a dose of 100 mg orally twice daily. The patient exhibited a rapid and robust clinical response, with complete resolution of cutaneous lesions and sustained remission lasting seven months. Ultimately, the disease progressed, and given her advanced age and overall poor performance status, she was transitioned to hospice care. She subsequently died 14 months after initiating acalabrutinib. Conclusion This report documents the first known case of successful treatment of relapsed/refractory PCDLBCL-LT with acalabrutinib. Despite advanced age and poor performance status, the patient experienced rapid symptom resolution and durable remission without treatment-related adverse events. These findings suggest that BTK inhibitors may represent a promising therapeutic approach for PCDLBCL-LT, either as monotherapy or in combination with anti-CD20 antibodies. Further investigation into novel targeted therapies is urgently needed for this rare and aggressive lymphoma subtype.

IMPORTANCE Neoadjuvant chemoimmunotherapy has high rates of pathologic response and improved prognosis among solid tumors. Its role in head and neck squamous cell carcinoma (HNSCC) remains understudied. OBJECTIVE To summarize the efficacy associated with neoadjuvant chemoimmunotherapy regimens in HNSCC and to compare the efficacy associated with neoadjuvant chemoimmunotherapy vs immunotherapy alone in locoregionally advanced resectable HNSCC prior to definitive surgery. DATA SOURCES A librarian-led systematic review was conducted using multiple electronic databases, including Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, following Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. Databases were queried from inception to October 2024. STUDY SELECTION Inclusion criteria included prospective interventional trials that have completed accrual, with results published in English. Only trials of resectable, treatment-naive HNSCC were included. Exclusion criteria included lack of reporting on pathologic response or Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 response. DATA EXTRACTION AND SYNTHESIS Two investigators independently conducted title, abstract, and full-text reviews per PRISMA guidelines. Primary outcomes extracted were major pathologic response (MPR) and complete pathologic response (CPR) at surgery and complete response (CR) on imaging by RECIST 1.1. Secondary outcomes included 1-year overall survival (OS) and toxic effects. MAIN OUTCOMES AND MEASURES A meta-analysis was performed using a binary random-effects model to determine the pooled proportion of primary outcomes in the immunotherapy and chemoimmunotherapy groups. Heterogeneity was reported as I 2 . RESULTS A total of 751 patients (502 [77%] male; age range, 27-87 years) across 23 studies were included in the meta-analysis, including 357 patients (47%) who underwent chemoimmunotherapy, 102 patients (14%) who underwent dual-agent immunotherapy, and 292 patients (39%) who underwent single-agent immunotherapy. Pooled rates of MPR plus CPR were 66% (95% CI, 58%-73%; I 2 = 0.59) for chemoimmunotherapy, 18% (95% CI, 6%-29%; I 2 = 0.65) for dual-agent immunotherapy, and 6% (95% CI, 3%-9%; I 2 < 0.01) for single-agent immunotherapy. Across all groups, 1-year OS rates ranged from 88% to 96% for single-agent immunotherapy, 88% to 96% for dual-agent immunotherapy, and 88% to 100% for chemoimmunotherapy. Grade 3 to 5 adverse events were reported in 61 of 210 patients (29%), 2 of 67 patients (3.0%), and 36 of 210 patients (17%) among the reporting studies in the single-agent immunotherapy, dual-agent immunotherapy, and chemoimmunotherapy groups, respectively. CONCLUSIONS AND RELEVANCE These findings suggest that neoadjuvant chemoimmunotherapy regimens were associated with higher pathologic and radiographic response rates compared with immunotherapy alone in locoregionally advanced HNSCC. These results call for phase 3 trials comparing these neoadjuvant regimens head to head.

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.

Background: Long COVID, the chronic sequela of SARS-CoV-2 infection, has affected millions of people worldwide. However, its pathogenesis and treatment remain unknown. To address this critical gap, the National Institutes of Health (NIH) developed the Researching COVID to Enhance Recovery (RECOVER) Initiative that included the Viral Persistence and Reactivation, and Immune Dysregulation (RECOVER-VITAL) study as one of the first of five NIH-sponsored, integrated platform protocols to support the rigorous and rapid investigation of potential interventions for Long COVID. Methods: Experts across academia, the NIH, and the community of patients and caregivers were brought together to design the RECOVER-VITAL protocol. We present the challenges and rationale underpinning critical components of this protocol and provide evidence for use of the platform for efficient execution of current and future Long COVID clinical trials. Facets of the RECOVER-VITAL protocol, including inclusion criteria, intervention groups, study procedures, investigation of biomarkers, and endpoints, were carefully crafted to advance the current and future science and operations of Long COVID clinical trials, particularly in the absence of existing data. The initial trial within the RECOVER-VITAL platform evaluated two durations of an antiviral drug, nirmatrelvir/ritonavir, to test the proposed etiology of viral persistence on the Long COVID symptom clusters of autonomic dysfunction, cognitive dysfunction, and exercise intolerance. The primary outcome measures were patient-reported, and secondary outcomes included performance-based measures for each of the symptom clusters of interest. Conclusions: The RECOVER-VITAL platform protocol has substantial implications for the design and conduct of future Long COVID clinical trials.

Background: Acute traumatic patellar dislocations may cause intra-articular derangements of the knee in the setting of acute and chronic instability which may not always be appropriately identified on magnetic resonance imaging (MRI). Purpose: To determine the rates of coexisting intra-articular pathology in patients with patellar instability requiring medial patellofemoral ligament (MPFL) reconstruction and to report discrepancies between preoperative magnetic resonance imaging (MRI) findings and diagnostic arthroscopy results. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: Patients who underwent MPFL reconstruction at a single institution between 2010 and 2023 were identified. Operative reports and preoperative MRIs were reviewed. Records without full MRI reports as read by a radiologist or cases in which a diagnostic arthroscopy was not conducted were excluded. Intra-articular pathologies noted on MRI and confirmed by arthroscopy were documented. MRI findings were considered to be discordant from arthroscopic findings if a lesion was identified on diagnostic arthroscopy that was not present in the full MRI report and that lesion resulted in additional surgical procedures. Results: There were 331 arthroscopic procedures conducted within the study population of 508 patients who underwent diagnostic arthroscopy at the time of their patellar stabilization procedures. These procedures included 180 loose body removals, 95 osteochondral lesions treated via a variety of interventions including open reduction and internal fixation (26 cases), particulated allograft chondral grafting (30 cases), osteochondral allograft transplantation (9 cases), and microfracture (30 cases), and 39 meniscal tears resulting in 33 partial meniscectomies and 6 meniscal repairs. Among these 508 patients, 105 (21%) demonstrated discordance of preoperative MRI and arthroscopic findings that necessitated additional procedures. This discordance was responsible for a total of 109 (33%) of the 331 arthroscopic procedures. These included 75 loose body removals, 2 osteochondral fracture fixation procedures, 2 microfractures for full-thickness cartilage loss, 16 partial meniscectomies, and 2 meniscal repairs, among others. Conclusion: Among patients undergoing patellar stabilization, 21% had intra-articular lesions not identified on preoperative MRI detected at the time of diagnostic arthroscopy that resulted in surgical intervention. This study, representing the largest cohort to date of patellar stabilization surgeries with both MRI and arthroscopy findings, underscores the importance of diagnostic arthroscopy for improving diagnostic accuracy and addressing associated intra-articular pathology.

Abstract Background Abdominal arterial calcification is a well-established predictor of cardiovascular events and mortality in kidney failure. Autosomal dominant polycystic kidney disease (ADPKD), a common genetic cause of kidney failure, presents with a distinct vascular profile. However, the burden of abdominal arterial calcification in ADPKD remains inadequately characterized. Clarifying these differences may improve cardiovascular risk stratification and transplant timing. Methods We conducted a retrospective cohort study of 4088 adult patients listed for kidney transplant at three Mayo Clinic sites (2005–2024). Patients were categorized by kidney failure cause: ADPKD vs. non-ADPKD. Abdominal arterial calcification was quantified on non-contrast computed tomography (CT) scans using a modified Agatston scoring method. Propensity score matching (1:1) adjusted for age, sex, race, lipid levels, left ventricular ejection fraction, dialysis exposure, coronary artery disease, neurovascular disease, and smoking history, was performed. Abdominal arterial calcification scores were compared between matched groups, and subgroup analyses evaluated abdominal arterial calcification severity across dialysis durations in ADPKD patients. Results After matching, 309 patients with ADPKD were compared with 309 non-ADPKD chronic kidney disease (CKD) controls. Abdominal arterial calcification scores were significantly lower in the ADPKD group (median: 425.3; IQR: 0.0–2033.5) than in the non-ADPKD group (median: 1256.8; IQR: 96.5–5033.8). Among ADPKD patients, abdominal arterial calcification scores increased with dialysis duration (P < .001). Conclusion ADPKD patients exhibit lower abdominal arterial calcification scores than their non-ADPKD counterparts after adjusting for clinical variables. Abdominal arterial calcification progression with dialysis highlights the importance of early transplant evaluation. This study introduces a novel adaptation of coronary calcium scoring software for quantifying abdominal calcification, offering a standardized approach to vascular risk assessment in kidney transplant candidates.

Abstract Objective Effective communication with humans and automated voice assistants (AVA) is essential for full participation in modern life. Because AVA relies on intelligible speech, individuals with speech impairments, such as those treated for oral cavity cancer (OCC), may face barriers when interacting with AVA. We assessed self‐reported communication difficulty in patients treated for OCC related to AVA and humans. Study Design Prospective cross‐sectional cohort study. Setting Out‐patient clinics in two tertiary care centers. Methods This study was conducted between July 2024 and March 2025 and included adults (≥18 years) diagnosed with and surgically treated for OCC (experimental group) and those without speech impairments (controls). Participants completed the Speech Communication Experience Survey (SCES), which assessed perceived intelligibility when communicating with familiar partners, strangers, and AVA; and, as reported elsewhere, the Speech Handicap Index (SHI). Results In total, 159 participants were included (69 OCC, 90 controls). OCC participants were more likely to report that familiar partners, strangers, and AVA “almost always” or “always” had difficulty understanding their speech ( P < .05). Free flap reconstruction and maxillectomy were associated with greater reported communication difficulty. AVA usage frequency and overall opinions toward AVA did not significantly differ between groups. Conclusion Patients treated for OCC report significantly greater difficulty being understood by both AVA and human listeners compared to controls. These perceptions may inform peri‐operative counseling and guide the development of more inclusive AVA technologies capable of accommodating diverse speakers. Level of Evidence : 3.