Citations

As plastic surgery has grown, leaders within the field have advocated transforming plastic surgery divisions into independent departments. This shift raises critical questions regarding departmental identity, resource allocation, and potential administrative conflicts. The purpose of this study was to explore the potential implications of these institutional hierarchies from the perspective of plastic surgery program chairs. An anonymous online survey was distributed to chairs of accredited plastic surgery programs. Thirty-five of 103 (34.0%) individuals responded to the online questionnaire. Twenty-eight of 33 (84.8%) programs were classified as divisions of surgery, whereas 5 of 33 (15.2%) were independent departments. Nine of 28 (32.1%) respondents believed their division had lost patients to other surgical specialties because their program was not an independent department. Eighteen of 33 (54.5%) respondents believed that plastic surgery is negatively impacted when institutional programs are not independent departments. Respondents who indicated losing patients to other specialties, compared with those who did not, were 22.4 times more likely to be critical of institutional hierarchies ( P =0.004). Respondents from independent departments were 12.6 times more likely to also express a negative view ( P =0.049). Our findings provide a nuanced understanding of the institutional structures within plastic surgery programs. The extent to which institutional hierarchies negatively impact plastic surgery remains unclear. The significant association between patient loss and negative perceptions implies that direct clinical or financial repercussions strongly shape opinions. Moreover, chairs from independent departments may be more critical of institutional hierarchies because they have a deeper appreciation for the advantages that come with departmental status.

Abstract Background: BTX-9341 is a first-in-class bifunctional degrader of cyclin dependent kinase (CDK)4 and CDK6 that also inhibits the transcription of CDK2 and Cyclin E. Preclinical data highlight its superiority compared with approved CDK4/6 inhibitors (CDK4/6i) in inhibition of phosphorylation of retinoblastoma (p-RB), cell cycle arrest, and in vivo efficacy in breast cancer (BC) xenografts. BTX-9341 is active in CDK4/6i-resistant models with p-RB half-maximal inhibitory concentrations (IC50s) of 1-15 nM and can overcome key mechanisms that drive CDK4/6i resistance. Here we report early monotherapy data from the first-in-human study of BTX-9341 in patients (pts) with advanced and/or metastatic HR+/HER2- BC. Methods: BTX-9341-101 is a multicenter, nonrandomized, open-label trial to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of orally administered BTX-9341 in pts with RB1 wild type advanced and/or metastatic HR+/HER2- BC who received prior CDK4/6i therapy. An accelerated titration and Bayesian Optimal Interval design (BOIN) were used. The primary objective of dose escalation is to determine the maximum tolerated dose (MTD) or maximum evaluable dose (MED) of BTX-9341 monotherapy and in combination with fulvestrant. Secondary objectives include the characterization of BTX-9341 on PK and efficacy; exploratory objectives include the assessment of BTX-9341 on PD and PK/PD relationships. Results: As of June 9, 2025, 12 pts were evaluated at the following BTX-9341 once daily (QD) dose levels: 50 mg (dose level [DL]1), 100 mg (DL2), and 75 mg (DL3) monotherapy, and 50 mg in combination with fulvestrant (DLA). Pts received up to 4 lines of therapy in the metastatic setting prior to enrollment. No dose-limiting toxicities (DLTs) were observed at any dose levels during the 28-day DLT period. The most common adverse events (AEs) during the DLT period were decreased neutrophil and white blood cell counts (Grades 1-4). There were no dose reductions in DL1. The starting dose was reduced in all pts in DL2; DL3 is currently enrolling. At least 2-fold accumulation was observed after QD dosing, and steady-state trough concentrations were in the range of in vitro IC50 values at DL1 and higher dose levels. Serum thymidine kinase activity (sTKa), a clinical biomarker for tumor response to CDK4/6 inhibition, showed >50% reduction at Cycle 2 Day 1 (C2D1) compared with baseline for 7 of 8 evaluable monotherapy pts, with 6 pts below the sTKa detectable level. “On target” PD reductions in CDK4, CDK6, CDK2, and Cyclin E levels were observed in peripheral blood mononuclear cells. Of the 8 evaluable monotherapy pts, the best overall responses in pts with measurable disease included 1 pt with a confirmed partial response (PR) and 3 pts with stable disease ([SD] first assessed at 8 weeks; i.e., the first time point for assessment in the protocol), and in pts with non-measurable disease, 2 pts had non-complete response (CR)/non-progressive disease. For all pts, the longest duration on treatment was 10 cycles. A clinical benefit rate (defined as a best overall response of CR, PR, or SD for pts with measurable disease or non-CR/non-progressive disease for pts with non-measurable disease, per RECIST v1.1 at Week 24) of 66.7% was observed in the completed cohorts (DL1 and DL2). Conclusion: BTX-9341 monotherapy shows a favorable safety profile, with the most common AEs being decreased neutrophil and white blood cell counts, at doses that show encouraging preliminary PK/PD and efficacy, enabling further evaluation of monotherapy and in combination with fulvestrant. The trial is actively enrolling with anticipated completion of dose escalation enrollment by the end of 2025 (Clinical trial: NCT06515470). Citation Format: A. Patnaik, M. Block, M. Cristofanilli, Q. Liu, H. Majeski, A. Shakya, P. Rajagopalan, C. Deshpande, T. Marmon, S. Padam, D. Powell, A. H. Chourasia, R. Urbanski, M. Goetz, R. M. Layman. First-in-human Phase 1 study of BTX-9341, a CDK4/6 bifunctional degrader, as monotherapy and in combination with fulvestrant in patients with advanced and/or metastatic HR+/HER2- breast cancer - first emerging data [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-06-04.

Abstract Objective To estimate the incidence of de novo chronic rhinosinusitis and identify associated risk factors in kidney and liver transplant recipients without pre‐existing sinonasal complaints. Study design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Records of all patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022 were reviewed. Patients with documented sinonasal complaints prior to transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic and clinical variables were collected, and multivariable logistic regression was used to identify predictors of de novo chronic rhinosinusitis. Results Among 1459 transplant recipients (mean age 55.1 years, 59.8% male), the cumulative 2‐year incidence of de novo chronic rhinosinusitis was 2.4% (24/986) in kidney and 2.3% (11/473) in liver transplant recipients ( P = .89). The overall incidence rate was 12.0 cases per 1000 person‐years, exceeding general population estimates. Transplant rejection (OR 3.2, 95% CI 2.5‐3.9, P < .001) and additional organ transplantation (OR 5.0, 95% CI 3.4‐6.5, P = .041) were independently associated with chronic rhinosinusitis development. Conclusion Kidney and liver transplant recipients experience a higher incidence of de novo chronic rhinosinusitis compared to the general population. Transplant rejection and additional organ transplantation significantly increase this risk. Early recognition and management of chronic rhinosinusitis in this population may support improved postoperative outcomes.

A 75-year-old male was admitted with worsening anemia and spontaneous bruising in the left abdominal wall and paraspinal region. Laboratory workup revealed low factor XIII (FXIII) activity levels. Cryoprecipitate transfusions raised his FXIII level, but still fluctuated drastically, ranging from 4 to 43% was discharged 3 days later once his bleeding was managed. Three days later, he was readmitted for severe pain and new bruising in his latissimus dorsi and lateral right thigh. CT-scan revealed hemothorax and arterial bleeding requiring an urgent angiogram with embolization. Chromogenic and functional FXIII assays were unable to elucidate an inhibitor at this time. Management included FXIII concentrate, rituximab, and prednisone; the patient was discharged 12 days later with FXIII levels of 50%. After prednisone tapering, FXIII levels decreased drastically. This case exemplified that higher levels of FXIII are required to prevent bleeding diatheses rather than the previously reported minimum of 5% activity. Despite the diagnostic uncertainty of laboratory testing, the shortened half-life of FXIII activity following replacement therapy and favorable response to immunotherapy indicates that the bleeding diathesis was caused by an acquired inhibitor.

Background: Anterior cervical discectomy and fusion (ACDF) is a widely performed procedure for treating degenerative cervical spine conditions. While it effectively addresses neural decompression and restores segmental alignment, the interplay of baseline alignment and implant-specific factors on postoperative segmental alignment remains underexplored. This study evaluates the influence of preoperative cervical alignment and interbody cage design on segmental alignment changes following 1- to 3-level ACDF. Methods: Following institutional review board approval, we identified 258 patients undergoing ACDF for degenerative pathology between 1 January 2010 and 31 December 2023. Preoperative and postoperative radiographs were analyzed for cervical alignment, disc height, and segmental lordosis. Cage dimensions, lordosis, and positioning relative to vertebral landmarks were recorded. Multivariable linear regression models evaluated predictors of postoperative disc height, segmental lordosis, and their respective changes. Results: Postoperative disc height was positively associated with greater cage height (β = 1.13 mm per mm, p < 0.001) and negatively associated with greater cage lordosis (β = −0.10 mm per °, p = 0.001). Segmental lordosis was positively influenced by cage height (β = 0.78° per mm, p = 0.002) and lordosis (β = 0.42° per °, p = 0.002) but was negatively correlated with the distance of the cage from the anterior edge of the cranial vertebra (β = −1.76° per mm, p = 0.004). Greater preoperative segmental kyphosis predicted more significant postoperative lordosis correction (β = −1.07° per °, p < 0.001). Conclusions: This study underscores the importance of preoperative alignment and interbody cage design in achieving optimal segmental correction following ACDF. While cage height primarily drives disc height restoration, surgical technique, particularly anterior placement of the cage, is pivotal for enhancing segmental lordosis. These findings support personalized surgical planning to optimize alignment and patient outcomes.

Abstract Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a usually prodromal manifestation of neurodegenerative disorders with α-synuclein pathology: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Clinical trials in the iRBD population face substantial barriers: limited access to well-characterized cohorts, inconsistent assessment protocols across centers, and the absence of validated biomarkers of disease burden. The North American Prodromal Synucleinopathy (NAPS) Consortium was established to address these challenges and facilitate clinical trials for neuroprotective therapies targeting synucleinopathy at the earliest known stages. In this multi-site, longitudinal, observational study, nine academic centers across North America will enroll and follow over 500 individuals with iRBD from existing sleep centers. Sixty control participants, matched for age, sex, and race will also be recruited. A harmonized protocol—including a standardized clinical battery assessing motor, cognitive, autonomic, psychiatric, sensory, and sleep function; structured diagnostic adjudication; biospecimen collection; and centralized analysis of both polysomnography and neuroimaging data—is outlined herein and reflects NAPS Stage 2. Each participants completes these assessments annually, and are replaced in the event of phenoconversion. By unifying assessments and expanding geographic reach, NAPS lays the groundwork for efficient, well-powered clinical trials designed to delay or prevent progression of iRBD to overt PD, DLB, or MSA—ultimately enabling earlier, more effective therapeutic intervention for neurodegenerative disease. Registered at clinicaltrials.gov (NCT05826457).

ABSTRACT Background Individuals with oral cavity cancer (OCC) have negatively impacted functional status and quality of life. Little is known regarding patients' perspectives of their speech impairments. This study compared self‐reported speech function between patients surgically treated for OCC and healthy controls using the Speech Handicap Index (SHI) and identified factors associated with worse scores. Methods This is a multiinstitutional cross‐sectional study of OCC patients and healthy controls recruited between July 2024 and March 2025. Participants completed the SHI and self‐reported speech quality. Demographics, tumor, and treatment details were abstracted from the electronic health record for OCC. Group differences were assessed with t ‐tests, χ 2 , and Fisher's exact tests. Results Among 69 OCC and 90 controls, OCC patients had significantly higher mean SHI scores (50.2 vs. 34.7, p < 0.01) and were less likely to rate their speech as “good” or “excellent” (47.8% vs. 85.6%, p < 0.01). Both speech and psychosocial domain scores were significantly worse among OCC. Free flap reconstruction was associated with worse scores (29.6 vs. 15.5, p = 0.02) and worse self‐rated speech quality. Conclusions Patients with surgically treated oral cavity cancer have significantly impaired self‐perceived speech and psychosocial functioning compared with healthy individuals. Greater deficits were observed in patients who required free flap reconstruction. Despite the functional deficit, nearly half of OCC patients reported satisfaction with their speech quality. These findings highlight the importance of using validated measures for speech function and support the need for early, multidisciplinary rehabilitation including speech therapy in this population, particularly for those undergoing free flap reconstruction.

Cholangiocarcinoma (CCA) represents a biologically and clinically heterogeneous group of biliary tract malignancies. Growing evidence underscores that the 3 major anatomic subtypes—intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA)—are distinct tumor entities rather than a single disease. Each subtype differs in embryologic origin, carcinogenesis mechanisms, molecular landscape, and immunogenic profile, all of which contribute to variability in diagnosis, treatment responsiveness, and prognosis. The importance of understanding these distinctions is reinforced by the rising global incidence of CCA, which highlights the need for precision medicine approaches based on these subtypes. Recent advances have deepened our insight into subtype-specific risk factors, including chronic biliary diseases and metabolic conditions, while artificial intelligence–driven tools are improving diagnostic accuracy and risk stratification. Surgical innovations now allow for more tailored resections and perioperative care, and therapeutic strategies are increasingly guided by molecular and immune profiling. Emerging strategies for early diagnosis and chemoprevention in high-risk populations further emphasize the significance of recognizing the unique biology of each subtype. In this review, we provide a comprehensive overview of the distinct anatomic subsets of CCA, integrating their molecular and biological foundations with clinical management to inform practice and guide future research.