Citations

Background: Polydactyly surgery rates and trends are poorly characterized. The purpose of this study was to characterize national pediatric polydactyly management by examining operative and procedural trends over time, evaluating timing of treatment, identifying factors associated with interventions, and comparing costs and complications. Methods: We used the PearlDiver national administrative claims database to identify pediatric patients aged 18 and under with a diagnosis of polydactyly (2010-2023). We analyzed patients who received procedures coded as surgical correction or suture ligation, then characterized rates and factors associated with each intervention, and investigated postoperative complication rates. Results: Of 42 543 polydactyly patients, 3880 patients (9.1%) underwent surgery, and 5612 patients (13.2%) underwent procedures coded as suture ligation. Over the past decade, the incidence of polydactyly diagnosis and surgery has decreased, while rates of procedures coded as suture ligation have not changed significantly. In 2010, 12.0% of patients underwent surgery, compared to 7.3% in 2020. Patients of ages 1 to 2 years comprised the greatest proportion of the population who underwent surgical operations at 1729 patients (36.0%), and patients of ages 0 to 1 year comprised the greatest proportion of the population who underwent suture ligations at 3327 patients (51.0%) ( P < .001). Younger age at diagnosis and higher comorbidity index were associated with a greater likelihood of surgery, while greater mean family income was associated with a lower likelihood. Among treatment categories, surgery was associated with greater 1-year and total payer-reimbursed costs ( P < .05). Conclusions: We observed a declining incidence of pediatric polydactyly and polydactyly surgery. These findings may inform future guideline development and discourse for pediatric hand care.

Abstract Members of the Transient Receptor Potential (TRP) family of ion channels have a nearly ubiquitous role in human physiology, tuning cell signaling to remarkably diverse physical and chemical stimuli. Although there is extensive structural data on TRP channels, a systematic and unbiased interrogation of structure-function relations in these proteins is required to fully elucidate their mechanisms of function. By focusing on a critical pore region of the TRPM8 channel, which is the main detector of cold and cooling agents in sensory neurons, we show how deep mutational scanning can be used in combination with the available structural data to understand how TRP channels respond to stimuli. We define a novel mechanism whereby the extracellular pore loop, which has only been resolved in structures representing desensitized states of the channel, plays an essential role in the response of TRPM8 to menthol or cold by coordinating the movement of the S6 helices that line and gate the pore, and the ion-selectivity filter that binds permeant cations. Moreover, our screen reveals sequence determinants along the S6 helices that explain how their architecture sustains gating and, together, provide strong support for a structural mechanism of TRPM8 pore opening in response to menthol and cold.

Introduction Individuals with inborn errors of immunity (IEI) are increasingly reaching reproductive age, yet guidance on fertility preservation, genetic counseling, medication adjustments in pregnancy and breastfeeding, monitoring for complications, and multidisciplinary coordination is lacking. This joint effort between two committees of the Clinical Immunology Society (CIS), the Women of the Clinical Immunology Society (WCIS) and the Adult Immune Deficiency Committee (AID) survey aimed to characterize current reproductive care practices for IEI patients. Methods A survey was disseminated to 809 CIS members. The response rate was 6.43% (52 respondents). The 24-item questionnaire addressed management of pregnancy in IEI, medications adjustment, participation in hematopoietic stem cell transplant (HSCT) care and fertility preservation, and maternal/neonatal outcomes. Results Because survey items were optional, the number of respondents varies by question. Forty-two participants completed core items: 64% (27/42) allergists/immunologists, 71% (30/42) practicing at academic centers, and 48% (20/42) with &gt;50% immunology-focused practices. Most respondents (78%, 41/52) currently or previously cared for pregnant/planning IEI patients. Preconception counseling was common (90%, 37/41), yet only 2% (1/41) have access to a formal reproductive multidisciplinary team. Among clinicians involved in HSCT care, 45% (13/29) referred patients for fertility preservation. More than half, 52% (22/42), observed reduced fertility in IEI patients, and 56% (20/36) observed adverse maternal outcomes. Medication management varied: 61% (24/39) discontinued known teratogenic medications, and 64% (25/39) adjusted dosing during pregnancy. Regarding immunoglobulin replacement therapy, 79% adjusted dosing based on IgG levels and 42% increased dosing by trimester. Conclusions This CIS survey reveals practice variability and notable gaps in reproductive health support for individuals with IEIs. Due to the relatively low response rate, generalizability across providers and practice settings is challenging. However, the results of this survey suggest that although most clinicians provide preconception counseling and manage IgG and immunomodulatory therapy during pregnancy, formal multidisciplinary structures are rare. High rates of reported fertility concerns and maternal complications underscore the need for enhanced collaboration with obstetrics/gynecology and the development of structured, evidence-based, multidisciplinary guidelines for reproductive care in IEI. Tabular data are included as downloadable supplement files.

Abstract Background The IEC exposure index (EI), deviation index (DI), and target exposure index (EI T ), represent critical standardized metrics for the evaluation of exposure and quality in radiographic imaging. Purpose This work develops and validates a systematic procedure to estimate the EI T for eight of the most common radiography imaging protocols utilizing automatic exposure control (AEC) from measurements acquired under reference conditions. Methods A model was developed to define the relationship between a systems AEC logic, and an estimation of the EI under flat‐field conditions (EIFFC). Separately, clinical data and acquisition protocol information for resultant EI during patient studies were also collected for the eight protocols studied: Chest posteroanterior (PA), Chest lateral, Abdomen anteroposterior (AP), Pelvis AP, L‐Spine AP, C‐Spine AP, T‐Spine AP, and Ribs AP. Data were collected from 41 x‐ray units spanning seven institutions. For each protocol on each unit the EIFFC was computed based on the acquisition protocol, as well as median EI from clinical exams to produce a scaling factor (SF). Kruskal–Wallis statistical tests were used to compare SF's between vendors and AEC cell configurations. Results SFs for eight radiographic imaging protocols have been produced per vendor and per AEC cell selection. A workflow has been established for end‐users to follow to apply these SFs to flat‐field measurements taken at their own locations to establish local EI T . Conclusions The study results show that in seven of the eight imaging protocols, the SFs for most units included in the study report SFs within 1 DI (± 25%) of their respective final vendor reported SF (218/228). The ribs protocol is the exception to this finding (n = 26). SFs have high utility for establishing EI T values on individual x‐ray units and normalizing EI value distributions for quality assurance purposes.

Abstract Cerebral blood flow is stabilized through dynamic adjustments across both macro‐ and microvascular compartments. While dynamic cerebral autoregulation (dCA) quantifies upstream pressure–flow coupling, downstream microvascular responses are less well characterized and may represent a distinct but functionally linked process. This study tested whether a two‐component cascade model, treating dCA and an empirically derived index of microvascular function (MF) as sequential stages can represent the integrated regulation of cortical oxygenation. Data from 41 healthy adults (20–45 years) were analysed. Beat‐to‐beat mean arterial pressure (MAP), middle cerebral artery flow velocity (CBFV) and cortical oxyhaemoglobin (O 2 Hb) were recorded during supine spontaneous oscillations and forced oscillations at 0.05 Hz using repeated sit–stand manoeuvres. Transfer function analysis quantified frequency‐domain gain, phase and coherence for MAP→CBFV (dCA), CBFV→O 2 Hb (MF) and MAP→O 2 Hb (total pathway). The cascade model was computed as the product of dCA and MF transfer functions. The cascade model derived indices showed strong correlations with total pathway gain, phase and coherence measures during both spontaneous and forced oscillations, with improved linear coupling under forced oscillations. These results support the applicability of a two‐component cascade model for integrated cerebrovascular regulation and suggest that serial interactions between macrovascular and microvascular regulatory mechanisms jointly shape the frequency‐dependent propagation of arterial pressure to brain‐tissue oxygenation dynamics. image Key points Cerebral blood flow is stabilized by coordinated regulation across large arteries and microvessels, but their dynamic interaction has not been experimentally modelled. We examined whether a two‐component cascade model linking upstream dynamic cerebral autoregulation and downstream microvascular function can explain how blood pressure oscillations influence cortical oxygenation. In 41 healthy adults, we recorded beat‐to‐beat blood pressure, middle cerebral artery blood flow velocity and near‐infrared spectroscopy‐derived oxygenation during rest and sit–stand manoeuvres, and analysed them using transfer function analysis. Gains, phases and coherences derived from the cascade model closely matched those from the direct blood pressure–O 2 Hb relationship, particularly under forced oscillations during sit–stand, demonstrating the model's physiological relevance. The cascade model provides a mechanistic framework to separate and quantify large‐ and small‐vessel contributions to cerebral blood flow regulation, with potential application in future studies of ageing and cerebrovascular disease.

Background The PREPARE trial (Pragmatic Randomized trial Evaluating Pre-operative Alcohol skin solutions in Fractured Extremities), published in February 2024, demonstrated that 0.7% iodine povacrylex in 74% isopropyl alcohol reduced surgical site infections in patients with closed fractures compared with chlorhexidine gluconate in 70% isopropyl alcohol. Prior studies have shown that the translation of clinical trial findings into routine clinical practice and surgical procedures frequently takes longer than a decade, and strategies to accelerate implementation in orthopaedic surgery remain poorly defined. Engaging in a multifaceted implementation strategy with minimal barriers to entry for providers may be able to reduce this time to widespread adoption. Questions/purposes (1) Can the low-cost single-center dissemination efforts of the PREPARE trial results change antiseptic usage? (2) If a true practice change occurs, can the change be sustained over time without additional dissemination efforts? (3) Does the adoption of new evidence vary between fellowship-trained orthopaedic trauma surgeons and orthopaedic trauma surgeons who are not fellowship-trained? (4) What is the economic impact of a practice change to iodine povacrylex on hospital purchasing costs? Methods This was a retrospective, historically controlled comparative study of patients who underwent operative treatment of an extremity fracture at a single, urban, Level I academic trauma center before and after a dissemination effort aimed at increasing PREPARE trial awareness. A multifaceted dissemination strategy consisting of surgeon and nursing education, posted reminders, and supply chain support was implemented at the study site in February 2024. Patients were analyzed across three time periods: before dissemination (January 2020 to January 2024), during the transition (February 2024), and after dissemination (March 2024 to July 2025). An electronic medical record query identified patients with operative fracture management procedural codes who had a recorded antiseptic skin prep in the surgical flow sheet between January 2020 and July 2025. A total of 4822 patients were identified, and 222 duplicate entries were excluded, leaving 4600 patients for analysis (3351 before dissemination, 49 transitional, and 1200 after dissemination). To validate the completeness of our electronic health record query, we performed manual random sampling of monthly operative case logs, confirming that this query strategy successfully identified all patients with the relevant Current Procedural Terminology codes (that is, there were no exclusions for lack of antiseptic documentation). There were no differences in patient demographics, including sex, ethnicity, open fractures, or the distribution of upper and lower extremity fractures. Choice of surgical skin antiseptic was compared before and after dissemination using a log-binomial model. Results Dissemination efforts changed antiseptic use patterns with an immediate increase in iodine povacrylex use from 0.8% (27 of 3351) before intervention to 86% (1033 of 1200) after intervention (OR 765 [95% confidence interval 488 to 1197]; p < 0.001). This high level of use remained stable throughout the 17-month postintervention period without any additional dissemination efforts (p = 0.20 for trend). Adoption was higher among fellowship-trained trauma surgeons (94.8% increase) compared with surgeons without trauma fellowship training (34.7% increase). Hospital antiseptic product purchasing data, which reflect usage and restocking and were used as a secondary metric of practice change, also demonstrated an increase in iodine povacrylex demand and decline in chlorhexidine demand. Conclusion A targeted and multifaceted dissemination strategy led to rapid adoption of iodine povacrylex for use as the preferred surgical skin antisepsis in fracture surgery at our institution, which was sustained over the 17-month postintervention period. This finding contrasts with a historically slow uptake of surgical trial evidence into clinical practice. Pragmatic, low-cost approaches such as surgeon leadership, team-based multidisciplinary education, workflow reminders, and supply chain readiness may help to accelerate translation of evidence into orthopaedic practice. Future studies should evaluate the long-term sustainability of practice changes, surgical site infection outcomes, and generalizability across institutions. Level of Evidence Level III, therapeutic study.

PURPOSE GBM AGILE (ClinicalTrials.gov identifier: NCT03970447 ) is a phase II/III Bayesian adaptive platform registration trial testing multiple arms against a common control; the primary end point is overall survival (OS). Regorafenib, a multikinase inhibitor, showed OS benefit in recurrent (RD) glioblastoma in the phase II REGOMA trial and entered GBM AGILE as the first investigational arm. METHODS Patient subtypes included in the regorafenib arm of GBM AGILE were newly diagnosed unmethylated (NDU) and RD glioblastoma. Prospective defined sets of subtypes, or arm signatures, were NDU, RD, and all (NDU + RD). As the first investigational arm in GBM AGILE, regorafenib was equally randomized to the control arm. Treatment in the control arm is temozolomide + radiotherapy (in newly diagnosed) or lomustine (in RD). Efficacy was assessed by OS hazard ratio (HR), arm/control, and demonstrated when the Bayesian probability of benefit (HR <1.00) was ≥98%. Analysis was performed monthly for limited efficacy, which occurs when the Bayesian predictive power is <25% for all signatures, and determines stopping enrollment. Follow-up continued for 12 months after accrual stopped. RESULTS When the predictive power was <25% in all predefined signatures for regorafenib, accrual stopped for limited efficacy. The final analysis did not demonstrate OS improvement in the regorafenib arm in RD nor NDU glioblastoma. Median HRs were 1.05 (NDU), 1.07 (RD), and 1.07 (all) with final probabilities of benefit (HR <1.00) of 0.421 (NDU), 0.312 (RD), and 0.296 (all). Regorafenib was associated with increased toxicity relative to control. CONCLUSION GBM AGILE did not show superiority of regorafenib over control in RD (lomustine) or NDU (temozolomide + radiotherapy) glioblastoma, yet caused increased toxicities. Regorafenib has been removed from National Comprehensive Cancer Network guidelines as a treatment option for RD.

Lung transplantation presents numerous intraoperative challenges, particularly related to pulmonary artery and vein anastomotic integrity and hemodynamic stability. We present 3 cases where intraoperative transesophageal echocardiography (TEE) provided real-time diagnostic insights that directly altered surgical decision-making. Case 1 highlights pulmonary vein flow acceleration initially concerning for ostial stenosis, ultimately diagnosed as external compression from a retractor. Case 2 demonstrates true right pulmonary vein stenosis requiring immediate revision. Case 3 illustrates severe right pulmonary artery narrowing, detected by TEE and corrected intraoperatively to prevent early graft dysfunction. These cases underscore the critical role of intraoperative TEE in detecting subtle anastomotic abnormalities, distinguishing functional from structural stenosis, and guiding timely surgical correction. Incorporating comprehensive 2D and 3D TEE evaluation into routine lung transplant protocols enhances diagnostic accuracy, reduces postoperative complications, and contributes to improved long-term allograft function. Intraoperative 3D TEE should be considered an essential imaging modality in cardiothoracic transplantation and an invaluable educational tool for perioperative teams.