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Background Secondary lymphedema frequently occurs following surgery, malignancy, trauma, or radiation and is characterized by limb swelling, discomfort, and recurrent infections. Two advanced supermicrosurgical techniques—lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT)—have recently gained popularity as treatment options. However, long-term outcome data for these procedures remain limited. This systematic review and meta-analysis aim to evaluate the long-term efficacy of LVA and VLNT in patients with secondary lymphedema followed for more than 2 years postoperatively, focusing on outcomes such as cellulitis rates and limb circumference. Methods This study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria encompassed studies involving adult patients with secondary lymphedema treated with LVA or VLNT and with at least 24 months of follow-up. The primary outcomes were annual cellulitis incidence and limb circumference change, analyzed separately for upper and lower extremities. Meta-analysis was conducted using R version 4.3.1. Pooled effect sizes were estimated using random-effects models. Subgroup and sensitivity analyses were also performed. Results A total of 23 studies met the inclusion criteria, covering 648 limbs treated with either LVA (n = 216) or VLNT (n = 432). The weighted average patient age was 56.3 years, and the cohort was predominantly female (99.9%). For LVA, the pooled mean reduction in annual cellulitis events was −1.13 (95% confidence interval [CI], −1.70 to −0.57) for upper extremities and −1.32 (95% CI, −2.08 to −0.55) for lower extremities. VLNT yielded greater reductions in cellulitis, with pooled mean differences of −2.43 (95% CI, −3.36 to −1.50) and −1.38 (95% CI, −2.11 to −0.65) for upper and lower limbs, respectively. Additionally, VLNT reduced limb circumference by 42.7% (95% CI, 36.7–49.7) in upper extremities and 21.98% (95% CI, 19.8–24.4) in lower extremities. Conclusion LVA and VLNT both result in durable, long-term improvements in cellulitis rates, and VLNT was shown to reduce limb circumference. Given the significant impact on patient quality of life, these interventions should remain integral to the treatment algorithm for secondary lymphedema.

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behaviour, often resulting in subtherapeutic concentrations. Limited evidence suggests that posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum drug concentration drawn ≥5 days after posaconazole initiation. The primary outcome was attainment of therapeutic drug concentrations. Secondary outcomes included time to therapeutic serum concentration, adverse drug events, and frequency of occluded EFT. Results Of the included patients, 48 received IR suspension and 100 received DR tablets. Baseline characteristics and severity of illnesses were well balanced. Among IR suspension and crushed DR tablet recipients, 39% and 80% achieved therapeutic concentrations, respectively (P = 0.002). After adjusting for age, sex, BMI, drug interactions, posaconazole indication and malabsorptive conditions, crushed DR tablets were significantly more likely than IR suspension to achieve therapeutic posaconazole concentrations within 30 days (HR 5.22, 95% CI 2.35–11.61). Occluded EFTs were more frequent among crushed DR tablet recipients (27% versus 10%, P = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalaemia. Conclusions With EFT administration, crushed posaconazole DR tablets were associated with a greater likelihood of achieving therapeutic concentrations compared with IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation.

ABSTRACT We report the optimization of a 38‐parameter spectral flow cytometry panel to identify, phenotype, and assess lineage plasticity of human regulatory T cells (Tregs). Tregs are an indispensable T cell lineage with pleiotropic tolerogenic functions whose activities contribute critically to numerous disease settings including cancer, autoimmunity, and infectious disease, among others. Phenotypic and functional heterogeneity within the Treg lineage has been appreciated, but the etiology and impact of Treg plasticity across disease states remain incompletely understood. Better tools are thus needed to deeply characterize human Treg phenotypic heterogeneity at the single cell level to advance discovery of Treg‐based biomarkers in disease and to assess the effects of Treg‐directed therapeutics. To this end, our 38‐parameter panel consists of a 13‐marker PBMC backbone module to broadly phenotype PBMCs while specifically discriminating Tregs, and a 25‐marker Treg phenotyping module to determine Treg differentiation state, activation profile, and lineage subtype. In contrast to many high‐parameter OMIPs that rely on surface staining only, we incorporated several intracellular targets in this panel. This afforded the opportunity to thoroughly evaluate binding characteristics of all antibodies in both pre‐fixation and post‐fixation and permeabilization settings; we identify several antibodies eligible for overnight post‐fixation staining that require substantially reduced titers as compared to traditional pre‐fixation staining, resulting in significant cost savings. Dimensionality reduction and semi‐supervised clustering on healthy donor PBMC‐derived Tregs profiled by our panel reveal up to 14 discrete Treg phenotypes. In sum, this panel enables deep phenotypic characterization of human Treg heterogeneity in peripheral blood specimens by spectral flow cytometry.

Abstract Objectives To implementation an automated multi-institutional pipeline that delivers breast-cancer risk integrated with polygenic risk scores, monogenic variants, family history, and clinical factors, emphasizing operational challenges and their solutions. Materials and Methods A five-stage process was executed at ten sites. Data streams from REDCap surveys, PRS and monogenic reports, and MeTree pedigrees were normalized and forwarded through a REDCap plug-in to the CanRisk API. Results Integrated risk was returned to >10 000 women; 3.6% were ≥25 % lifetime risk and 0.9% carried pathogenic variants. Pipeline generated score aligns well with manual generated ones. Major barriers such as heterogeneous pedigree formats, missing data, edge-case handling, and evolving model versions were identified and resolved through mapping rules, imputations, and iterative testing. Discussion Cross-platform data harmonization and stakeholder alignment were decisive for success. Borderline-risk communication and model-version drift remain open issues. Conclusion Large-scale PRS-integrated breast-cancer risk reporting is feasible but requires robust interoperability standards and iterative governance.

Obstructive sleep apnea (OSA), a sleep disorder that is associated with exposure to repeated bouts of hypoxia overnight. Evidence suggests that the oxyhemoglobin dissociation curve (ODC) may be shifted rightward with OSA. Nitric oxide (NO) functions as an allosteric regulator of hemoglobin oxygen-binding properties, possibly shifting the ODC curve leftward. Nitrate/nitrite supplementation increases NO bioavailability and attenuates the physiological responses to hypoxia which may be due to changes in the ODC. Therefore, we explored the hypothesis that dietary nitrate supplementation improves oxygen re-saturation following inspiratory hypoxia in subjects with OSA. Fourteen subjects with untreated mild-moderate OSA (53 ± 10yr, 8M/6F; Apnea-hypopnea Index, 17.8 ± 8.1 events) completed two separate study visits. Each visit consisted of two hypoxic bouts separated by ~2 hours and the consumption of one of two beetroot juice beverages (Placebo [BR P ] containing 5-10 mg nitrate, no detectable nitrite, or Active [BR A ] containing 500mg nitrate and 40mg nitrite). For each hypoxia bout, subjects’ pulse oxygen saturation (%SpO 2 ) was titrated to ≤80% over 3-5min by blending a 10% FiO2 gas cylinder with room air. Once ≤80% SpO 2 was achieved, subjects inhaled normoxic room air (~21% FiO2) and oxygen saturation was monitored until SpO 2 returned to baseline (recovery). During recovery, SpO 2 was averaged into 5 sec bins from the end of hypoxia (nadir) up to +15 SpO 2 % above nadir. The ‘hypoxic load’ during recovery was calculated as ( i =1 ∑ n ∣Value i −nadir+15∣) and reflects a total sum of each 5 sec bin ( n ). BR A increased plasma nitrite (248 ± 155 to 738 ± 427nM, P < 0.05), whereas there was no change following BR P (266 ± 153 to 277 ± 164nM, P = 0.87). The level of desaturation (SpO 2 nadir) at the end of hypoxia did not differ within or between trials (BR A : Pre 78 ± 2 vs. 78 ± 3; BR P : Pre 78 ± 2 vs. 78 ± 2, condition x time interaction P = 0.21). Hypoxia load increased following BR P (162.7 ± 36.6 vs. 231.8 ± 65.7, P < 0.001), but was unchanged following BR A (174.3 ± 54.2 vs. 191.2 ± 52, P = 0.32). In summary, our study suggests that acute nitrate supplementation may cause a leftward shift in the ODC in patients with untreated OSA. This is supported by a reduced hypoxic load following a repeat bout of inspiratory hypoxia. These findings may have implications for the health of patients with OSA. Foundation for the National Institutes of Health, K12 AR084222 (Joshua Bock) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background/Objectives: Spinoplastic surgery is an emerging multidisciplinary field developed to address and reduce the complication of pseudoarthrosis following complex spinal reconstructions. While the number of spinal fusion procedures continues to rise every year, fusion failure rates remain as high as 40%. Although pseudoarthrosis may not always manifest clinically, it remains a leading cause of persistent pain and need for subsequent revision surgeries. The multidisciplinary collaboration between spine and plastic surgeons in spinoplastic surgery has therefore emerged as a proactive strategy aimed at preventing complications, particularly in patients identified as high-risk for pseudoarthrosis. As the patient population expands and spinoplastic surgery continues to evolve, refining patient selection criteria becomes essential for achieving optimal surgical outcomes. This review aims to provide a comprehensive overview of recent advancements in spinoplastic surgery, highlighting current indications, surgical techniques, recent case reports, and strategies for identifying suitable candidates. Methods: We performed a narrative review of English language literature through April 2025. Spinoplastic case reports and case series published within the last 20 years were included in the review. Results: Indications for use of a spinoplastic approach clustered into prior fusion failure, extensive oncologic resection, severe spinal deformity, procedures requiring extensive spinal involvement, and/or patients at risk for impaired bone healing. Succesful radiographic union and improvement of symptoms were widely reported across all 9 case reports/series. Conclusions: Although evidence is presently limited, spinoplastic surgery appears to achieve high bone graft fusion rates with acceptable morbidity and functional improvement in a carefully selected group of high-risk spinal reconstruction patients. Still, larger prospective studies are warranted to refine patient selection and validate functional benefit.

Abstract Several complications are associated with total shoulder arthroplasty (TSA), including glenoid loosening and joint instability. These complications are linked to imbalances in glenohumeral muscle forces, which cause eccentric loading that occurs on the outer edge of the glenoid component, rather than in the center of the glenoid, and can be damaging to the implant and destabilizing the joint. The purpose of this study was to develop musculoskeletal models of TSA patients using their skeletal geometry acquired from CT and their kinematics acquired with high-speed stereo radiography (HSSR) to predict glenohumeral joint loading and muscle forces for abduction and flexion and describe how these loads differ from their native contralateral side. CT data was collected for both shoulders of 6 TSA patients (three anatomic and three reverse). Models were developed using CT reconstructions of each patient’s scapula and humerus, and placed implant geometry with CT-derived alignment. Mesh morphing was used to create personalized muscle attachment sites on the scapula. Simulation of abduction and flexion to quantify muscle and joint forces was driven with limb-specific HSSR kinematics. At 90 deg abduction, reverse TSA increased superior shear force by 11.2% bodyweight (BW) and decreased medial compressive force by 27.5%BW compared to each patient’s contralateral shoulder. Lateral deltoid elevation moment arms and stability ratios increased 9.61 mm and 0.58, respectively. At 90 deg abduction, anatomic TSA patients increased humeral internal rotation by 52.7 deg and decreased rotator cuff force by 9.4%BW. Patient-specific musculoskeletal models quantified differences in glenohumeral joint mechanics. This study revealed muscle and kinematic mechanisms that could lead to edge loading and glenoid loosening in TSA and can inform personalized surgical planning for implant alignment with the goal of improving patient outcomes.