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Emma R Berube, Cesar D Lopez, David P Trofa, Charles A Popkin Center for Shoulder, Elbow and Sports Medicine, Department of Orthopedics, Columbia University Medical Center, New York, NY, USACorrespondence: Charles A PopkinCenter for Shoulder, Elbow and Sports Medicine, Department of Orthopedics, Columbia University Medical Center, New York, NY, USATel +1 212-305-4565Email cp2654@columbia.eduBackground: Orthopedic injuries of National Hockey League (NHL) players are common and may significantly affect players’ health and careers. Evidence-based injury management is important in guiding players’ timely return to sport and their ability to play at their pre-injury levels of competition.Purpose: To summarize all data published between January 1980 and March 2020 on orthopedic injuries experienced by professional ice hockey players competing in the NHL.Study Design: Systematic review.Methods: A literature review of studies examining orthopedic injuries in the NHL was performed using the Embase, PubMed, and CINAHL databases. The review included studies focusing on NHL players and players attending the NHL Combine and preseason NHL team camps. Studies pertaining to non-orthopedic injuries and case reports were excluded.Results: A total of 39 articles met the inclusion criteria and were analyzed. The articles were divided by anatomic site of injury for further analysis: hip and pelvis (24%), general/other (14%), ankle (10%), knee (10%), foot (7%), shoulder (7%), thigh (7%), trunk (7%), spine (6%), elbow (4%), and hand and wrist (4%). The majority of articles were Level IV Evidence (51.3%), followed by Level III Evidence (38.5%). Most studies obtained data from publicly available internet resources (24.7%), player medical records (19.5%) or surveys of team physicians and athletic trainers (15.5%). A much smaller number of studies utilized the NHL Injury Surveillance System (NHLISS) (6.5%) or the Athlete Health Management System (AHMS) (2.6%).Conclusion: This systematic review provides NHL team physicians with a single source of the current literature regarding orthopedic injuries in NHL players. Most research was published on hip and pelvis (24%) injuries, did not utilize the NHLISS and consisted of Level IV Evidence.Keywords: ice hockey, National Hockey League, NHL, injuries, epidemiology

Purpose: Metastatic pancreatic adenocarcinoma (mPC) remains a difficult-to-treat disease. Fluorouarcil, oxaliplatin, irinotecan, and leucovorin (FFX) is a standard first-line therapy for mPC for patients with a favorable performance status and good organ function. In a phase I study, devimistat (CPI-613) in combination with modified FFX (mFFX) was deemed safe and exhibited promising efficacy in mPC., Methods: The AVENGER 500 trial (ClinicalTrials.gov identifier: NCT03504423) is a global, randomized phase III trial conducted at 74 sites across six countries to investigate the efficacy and safety of devimistat in combination with mFFX (experimental arm) compared with standard-dose FFX (control arm) in treatment-naïve patients with mPC. Treatment, administered in once-every-2-weeks cycles until disease progression or intolerable toxicity, included intravenous devimistat at 500 mg/m 2 total per day on days 1 and 3 in the experimental arm. The primary end point of the study was overall survival (OS)., Results: Five hundred and twenty-eight patients were randomly assigned (266 in the experimental arm and 262 in the control arm). The median OS was 11.10 months for devimistat plus mFFX versus 11.73 months for FFX (hazard ratio [HR], 0.95 [95% CI, 0.77 to 1.18]; P = .655) and median progression-free survival was 7.8 months versus 8.0 months, respectively (HR, 0.99 [95% CI, 0.76 to 1.29]; P = .94). Grade ≥3 treatment-emergent adverse events with >10% frequency in the devimistat plus mFFX arm versus the FFX arm were neutropenia (29.0% v 34.5%), diarrhea (11.2% v 19.6%), hypokalemia (13.1% v 14.9%), anemia (13.9% v 13.6%), thrombocytopenia (11.6% v 13.6%), and fatigue (10.8% v 11.5%), respectively., Conclusion: Devimistat in combination with mFFX did not improve long- and short-term mPC patient outcomes compared with standard FFX. There were no new toxicity signals with the addition of devimistat.

Background/objectives: Pancreatic ductal adenocarcinoma (PDAC) presents significant diagnostic and prognostic challenges, as current biomarkers frequently fail to accurately stage disease, predict rapid metastatic recurrence (rPDAC), or assess response to neoadjuvant therapy (NAT). We investigated the potential for circulating neoplastic-immune hybrid cells (CHCs) as a non-invasive, multifunctional biomarker for PDAC., Methods: Peripheral blood specimens were obtained from patients diagnosed with PDAC. CHCs were detected by co-expression of pan-cytokeratin and CD45, normalized to 50,000 peripheral blood mononuclear cells. rPDAC was defined as metastatic recurrence within six months of margin-negative pancreatectomy. Cyclic immunofluorescence (CyCIF) analyses compared hybrid phenotypes in blood and tumors., Results: Blood samples were collected from 42 patients with PDAC prior to resection. Those with radiographically occult metastatic disease and rPDAC had higher preoperative CHC numbers compared to patients who did not (65.0 and 74.4, vs. 11.52 CHCs; p < 0.001). Patients with complete or near-complete pathologic responses to NAT had lower preoperative CHC numbers than partial and/or non-responders (1.7 vs. 13.1 CHCs; p = 0.008). When assessed longitudinally, those with partial pathologic response saw CHC levels become undetectable while on treatment but increase in the interval between NAT completion and resection. In contrast, patients with poor responses or development of metastatic disease experienced persistent CHC detection during therapy or rising levels prior to radiographic evidence of metastases. Further, in metastatic PDAC patients, treatment-induced phenotypic changes in hybrid cells mirrored those in paired metastatic tumor samples., Conclusions: CHC enumeration and phenotyping display promise as a real-time indicator of disease burden, recurrence risk, and treatment response in PDAC. CHCs have great potential as tumor-derived biomarkers to optimize therapeutic strategies and improve survival in patients with PDAC.

Neuroendocrine tumors (NETs) are a rare, heterogenous group of neoplasms arising from cells of the neuroendocrine system. Amongst solid tumor malignancies, NETs are notable for overall genetic stability and recent data supports the notion that epigenetic changes may drive NET pathogenesis. In this review, major epigenetic mechanisms of NET pathogenesis are reviewed, including changes in DNA methylation, histone modification, chromatin remodeling, and microRNA. Prognostic implications of the above are discussed, as well as the expanding diagnostic utility of epigenetic markers in NETs. Lastly, preclinical and clinical evaluations of epigenetically targeted therapies in NETs and are reviewed, with a focus on future directions in therapeutic advancement., Competing Interests: Declaration of competing interest I, Hannah McMurry, do not have and financial/personal competing interests related to the contents of the submitted manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Most patients treated with the standard dosing protocol (SDP) of hepatic arterial infusion (HAI) floxuridine require dose holds and reductions, thereby limiting their HAI therapy. We hypothesized that a modified dosing protocol (MDP) with a reduced floxuridine starting dose would decrease dose holds, dose reductions, and have similar potential to convert patients with unresectable colorectal liver metastases (uCRLM) to resection., Patients and Methods: We reviewed our institutional database of patients with uCRLM treated with HAI between 2016 and 2022. In 2019, we modified the floxuridine starting dose to 50% (0.06 mg/kg) of the SDP (0.12 mg/kg). We compared treatment related outcomes between the SDP and MDP cohorts., Results: Of n = 33 patients, 15 (45%) were treated on the SDP and 18 (55%) with our new institutional MDP. The MDP cohort completed more cycles before a dose reduction (mean 4.2 vs. 2), received more overall cycles (median 7.5 vs. 5), and averaged 39 more days of treatment (all P < 0.05). The SDP experienced more dose reductions (1.4 vs. 0.61) and dose holds (1.2 vs. 0.2; both P < 0.01). Of the patients in each group potentially convertible to hepatic resection, three patients (23%) in the SDP and six patients (35%) in the MDP group converted to resection (P = 0.691). Overall, four patients (27%) in the SDP developed treatment ending biliary toxicity compared with one patient (6%) in the MDP., Conclusions: A 50% starting dose of HAI floxuridine provides fewer treatment disruptions, more consecutive floxuridine cycles, and a similar potential to convert patients with initially uCRLM for disease clearance., (© 2024. Society of Surgical Oncology.)

Existing clinical biomarkers do not reliably predict treatment response or disease progression in patients with advanced intrahepatic cholangiocarcinoma (ICC). Circulating neoplastic-immune hybrid cells (CHCs) have great promise as a blood-based biomarker for patients with advanced ICC. Peripheral blood specimens were longitudinally collected from patients with advanced ICC enrolled in the HELIX-1 phase II clinical trial (NCT04251715). CHCs were identified by co-expression of pan-cytokeratin (CK) and CD45, and levels were correlated to patient clinical disease course. Unsupervised machine learning was then performed to extract their morphological features to compare them across disease courses. Five patients were included in this study, with a median of nine specimens collected per patient. A median of 13.5 CHCs per 50,000 peripheral blood mononuclear cells were identified at baseline, and levels decreased to zero following the initiation of treatment in all patients. Counts remained undetectable in three patients who demonstrated end-of-trial clinical treatment response and conversely increased in two patients with evidence of therapeutic resistance. In the post-trial surveillance period, interval counts increased prior to or at the time of clinical progression in three patients and remain undetectable in one patient with continued long-term disease stability. Using our machine learning platform, treatment-resistant CHCs exhibited upregulation of CK and downregulation of CD45 relative to treatment-responsive CHCs. CHCs represent a promising blood-based biomarker to supplement traditional radiographic and biochemical measures.

Background: South Texas and the Rio Grande Valley (RGV) are medically underserved-communities near the Texas-Mexico border with the highest incidence of end-stage renal disease (ESRD) in the nation, and a shortage of available full-time equivalent (FTE) specialty-physicians., Methods: Data on the incidence/prevalence of ESRD and workforce projections on vascular-surgeons and nephrologists were collected from the United States Renal Data System and Texas Department of State Health Services. We then merged data from both datasets to identify population-specific healthcare-trends., Results: Texas had the highest rates of ESRD from 2016 to 2020, with its border regions leading the state. By 2032, vascular-surgery and nephrology are projected to have the 1st and 4th worst physician-shortages in the state respectively, with the percentage of these FTE specialty-physicians available to meet the need of the RGV ranging from 42.3 to 58.4 ​%., Conclusions: The RGV is experiencing increased rates of ESRD, while having a paradoxical-decline in specialty-physicians available to provide adequate care., Competing Interests: Declaration of competing interest I Valentine S. Alia on behalf of all authors included in this paper wish to confirm that there are no known conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Immunotherapy is considered first line in patients with dMMR metastatic colorectal cancer (CRC). Recent studies have also shown promising results with neoadjuvant immunotherapy in locally advanced CRC. We report a case in which neoadjuvant immunotherapy with pembrolizumab resulted in complete pathologic response at time of resection as well as saved the patient the morbidity associated with a hepatectomy. We also completed a scoping review of the literature which suggests promising tumor responses with treatment in dMMR CRC. Further randomized control trials to determine the magnitude of response and optimal regimen are needed., Competing Interests: All authors have no conflicts of interest to disclose., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Head and neck cancer (HNC) patients benefit from craniofacial reconstruction, but no clear guidance exists for rehabilitation timing. This meta-analysis aims to clarify the impact of oncologic treatment order on implant survival. An algorithm to guide placement sequence is also proposed in this paper. PubMed, Embase, and Web of Science were searched for studies on HNC patients with ablative and fibula-free flap (FFF) reconstruction surgeries and radiotherapy (RTX). Primary outcomes included treatment sequence, implant survival rates, and RTX dose. Of 661 studies, 20 studies (617 implants, 199 patients) were included. Pooled survival rates for implants receiving >60 Gy RTX were significantly lower than implants receiving < 60 Gy (82.8% versus 90.1%, P =0.035). Placement >1 year after RTX completion improved implant survival rates (96.8% versus 82.5%, P =0.001). Implants receiving pre-placement RTX had increased survival with RTX postablation versus before (91.2% versus 74.8%, P <0.001). One hundred seventy-seven implants were placed only in FFF with higher survival than implants placed in FFF or native bone (90.4% versus 83.5%, P =0.035). Radiotherapy is detrimental to implant survival rates when administered too soon, in high doses, and before tumor resection. A novel evidence-based clinical decision-making algorithm was presented for utilization when determining the optimal treatment order for HNC patients. The overall survival of dental prostheses is acceptable, reaffirming their role as a key component in rehabilitating HNC patients. Considerations must be made regarding RTX dosage, timing, and implant location to optimize survival rates and patient outcomes for improved functionality, aesthetics, and comfort., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Objective: The present study aimed to investigate the risk factors, complication profiles, and clinical outcomes of cleft and noncleft patients undergoing single jaw (mandibular or LeFort 1) and bimaxillary (BSSO + LeFort 1)., Design: Retrospective Cross-sectional Study Setting: National Surgical Quality Improvement Program database 2018-2019., Patients: Pediatric patients., Interventions: Outcomes for mandibular, LeFort 1, and bimaxillary osteotomy were retrospectively evaluated for cleft and noncleft patients., Main Outcome Measures: Multivariate logistic regression was used to determine the odds of complications and length of stay for cleft and noncleft patients undergoing single jaw and double jaw surgery., Results: 669 pediatric patient underwent orthognathic surgery in the study period; the majority received LF1 only (n = 385; 58.3%), followed by mandible only (n = 179; 27.1%), and bimaxillary (n = 105; 15.9%%). Cleft differences were present in 56% of LFI patients, 32% of mandibular patients, and 22% of bimaxillary patients. After multivariate adjustment, ASA class III was associated with nearly 400% increased odds of any complication including readmission and reoperation (OR = 5.99; CI [[1.54-23.32]], p < 0.01, and 65% increased LOS (β-coefficient = 1.65, CI [1.37-1.99], p < 0.01). Presence of cleft was not significantly associated with odds of any complication (p = 0.69) nor increased LOS (p = 0.46) in this population., Conclusion: Complications remained low between surgery types among cleft and noncleft patients. The most significant risk factor in pediatric orthognathic surgery was not the presence of cleft but rather increased ASA class. Though common in patients seeking orthognathic surgery, cleft differences did not cause additional risk after adjustment for other variables.

Background: Osteocutaneous fibula free flaps (FFFs) are a fundamental component of reconstructive surgery in the head and neck region, particularly after traumatic injuries or oncologic resections. Despite their utility, FFFs are associated with various postoperative complications, such as infection, flap failure, and donor site morbidity, impacting up to 54% of cases. This study aimed to investigate the influence of socioeconomic variables, with a particular focus on median household income (MHI), on the incidence of postoperative complications in FFF reconstruction for head and neck cancer., Methods: A retrospective analysis of 80 patients who underwent FFF reconstruction for head and neck cancer at a single center from 2016 to 2022 was conducted. Demographic and patient characteristics, including race, MHI, insurance type, history of radiation therapy, and TNM (tumor, node, metastasis) cancer stage, were evaluated. Logistic regression, controlling for comorbidities, was used to assess the impact of MHI on 30-, 90-, and 180-day postoperative complications., Results: The patient population was predominantly male (n = 51, 63.8%) and White (n = 63, 78.8%), with the majority falling within the $55,000 to $100,000 range of MHI (n = 51, 63.8%). Nearly half of the patients had received neoadjuvant radiation treatment (n = 39, 48.75%), and 36.25% (n = 29) presented with osteoradionecrosis. Logistic regression analysis revealed that the $55,000-$100,000 MHI group had significantly lower odds of developing complications in the 0- to 30-day postoperative period when compared with those in the <$55,000 group (odds ratio [OR], 0.440; 95% confidence interval [CI], 0.205-0.943; P = 0.035). This trend persisted in the 31- to 90-day period (OR, 0.136; 95% CI, 0.050-0.368; P < 0.001) and was also observed in the likelihood of flap takeback. In addition, the $100,000-$150,000 group had significantly lower odds of developing complications in the 31- to 90-day period (OR, 0.182; 95% CI, 0.035-0.940; P = 0.042). No significant difference was found in the >$150,000 group., Conclusions: Median household income is a significant determinant and potentially a more influential factor than neoadjuvant radiation in predicting postoperative complications after FFF reconstruction. Disparities in postoperative outcomes based on income highlight the need for substantial health care policy shifts and the development of targeted support strategies for patients with lower MHI., Competing Interests: Conflict of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Tissue expansion has been widely used to reconstruct soft tissue defects following burn injuries in pediatric patients, allowing for satisfactory cosmetic and functional outcomes. Factors impacting the success of tissue expander (TE)-based reconstruction in these patients are poorly understood. Herein, we aim to determine the risk factors for postoperative complications following TE-based reconstruction in pediatric burn patients., Methods: A retrospective review of pediatric patients who underwent TE placement for burn reconstruction from 2006 to 2019 was performed. Primary outcomes were major complications (TE explantation, extrusion, replacement, flap necrosis, unplanned reoperation, readmission) and wound complications (surgical site infection and wound dehiscence). Descriptive statistics were calculated. The association between primary outcomes, patient demographics, burn characteristics, and TE characteristics was assessed using the chi-squared, Fisher's exact, and Mann-Whitney U tests., Results: Of 28 patients included in the study, the median [interquartile range (IQR)] age was 6.5 (3.3-11.8) years, with a follow-up of 12 (7-32) months. The majority were males [n = 20 (71%)], Black patients [n = 11 (39%)], and experienced burns due to flames [n = 78 (29%)]. Eleven (39%) patients experienced major complications, most commonly TE premature explantation [n = 6 (21%)]. Patients who experienced major complications, compared to those who did not, had a significantly greater median (IQR) % total body surface area (TBSA) [38 (27-52), 10 (5-19), P = 0.002] and number of TEs inserted [2 (2-3), 1 (1-2), P = 0.01]. Ten (36%) patients experienced wound complications, most commonly surgical site infection following TE placement [n = 6 (21%)]. Patients who experienced wound complications, compared to those who did not, had a significantly greater median (IQR) %TBSA [35 (18-45), 19 (13-24), P = 0.02]., Conclusion: Pediatric burn injuries involving greater than 30% TBSA and necessitating an increasing number of TEs were associated with worse postoperative complications following TE-based reconstruction., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Tissue expansion is a powerful tool for reconstruction of pediatric soft-tissue pathologies, but complication rates for children have been reported as high as 40%. Infection and implant extrusion lead to premature removal and delays in reconstruction. Expanding the head and neck is uniquely challenging because the confluence of facial aesthetic units must be respected. These challenges have prompted the senior author's creation of an aesthetic-unit based algorithm., Methods: A retrospective study of pediatric patients who underwent cervicofacial tissue expander placement by the senior author (R.J.R) was performed over a 17-year period. Predictor variables included age, sex, race, indication, number of expanders placed at each operation, serial expansion, expander type, expander size, home versus clinic inflation, and prophylactic antibiotics. Univariate and multivariate analyses were performed to identify risk factors for complications., Results: An aesthetic-unit based reconstructive algorithm is proposed. Forty-eight pediatric patients had 111 cervicofacial tissue expanders placed. Twenty expanders were associated with complications (18%) for surgical site-infection (12.6%), extrusion (4.5%), and expander deflation (6.3%). Expanders placed for congenital nevi (p=0.042) and use of textured expander (p=0.027) were significantly associated with decreased complications. When controlling for covariates, serial expansion of the same site was associated with increased rates of readmission (p=0.027) after having just one prior expander. Iatrogenic ectropion occurred in 13.5% of the study population; expanders with at least one complication during tissue expansion were significantly associated with incidence of iatrogenic ectropion (p=0.026)., Conclusion: By using an aesthetic-unit based algorithm, reconstructive outcomes can be optimized for pediatric cervicofacial tissue expansion., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Background:  Calvarial defects are severe injuries that can result from a wide array of etiologies. Reconstructive modalities for these clinical challenges include autologous bone grafting or cranioplasty with biocompatible alloplastic materials. Unfortunately, both approaches are limited by factors such as donor site morbidly, tissue availability, and infection. Calvarial transplantation offers the potential opportunity to address skull defect form and functional needs by replacing "like-with-like" tissue but remains poorly investigated., Methods:  Three adult human cadavers underwent circumferential dissection and osteotomy to raise the entire scalp and skull en-bloc. The vascular pedicles of the scalp were assessed for patency and perfused with color dye, iohexol contrast agent for computed tomography (CT) angiography, and indocyanine green for SPY-Portable Handheld Imager assessment of perfusion to the skull., Results:  Gross changes were appreciated to the scalp with color dye, but not to bone. CT angiography and SPY-Portable Handheld Imager assessment confirmed perfusion from the vessels of the scalp to the skull beyond midline., Conclusion:  Calvarial transplantation may be a technically viable option for skull defect reconstruction that requires vascularized composite tissues (bone and soft tissue) for optimal outcomes., Competing Interests: None declared., (Thieme. All rights reserved.)

Background:  It can be argued that individuals in the transgender and gender nonbinary (TGNB) community suffer from a similar impact on quality of life in the face of gender dysphoria, with psychosocial and physical consequences. Indications for penile allotransplantation for patients wishing to undergo gender affirmation surgery have yet to be elucidated, but technical lessons for feasibility can be gleaned from penis transplants that have already been performed on cisgender males to date., Methods:  This study investigates the theoretical feasibility for penile-to-clitoral transplantation, prior penile transplants, and current multidisciplinary gender affirmation health care modalities., Results:  Penile allotransplantation offers a potential solution for individuals in the TGNB community for a more aesthetic penis, improved erectile function without the need of a prosthesis, optimal somatic sensation, and improved urethral outcomes., Conclusion:  Questions remain about ethics, patient eligibility, and immunosuppressive sequelae. Before these issues are addressed, feasibility of this procedure must be established., Competing Interests: None declared., (Thieme. All rights reserved.)

Asparagine synthetase (ASNS) catalyzes the biosynthesis of asparagine from aspartate and glutamine. Cells lacking ASNS, however, are auxotrophic for asparagine. Use of L-asparaginase to promote asparagine starvation in solid tumors with low ASNS levels, such as pancreatic ductal adenocarcinoma (PDAC), is a rationale treatment strategy. However, tumor cell resistance to L-asparaginase has limited its clinical utility. Our preclinical studies show that RAS/MAPK signaling circumvents L-asparaginase-induced tumor killing, but L-asparaginase and MEK inhibition potentiated tumor killing; suggesting that this combination may provide meaningful clinical benefit to patients with PDAC. This Phase I trial (NCT05034627) will evaluate the safety and tolerability of the MEK inhibitor, cobimetinib, in combination with pegylated L-asparaginase, L calaspargase pegol-mknl, in patients with locally-advanced or metastatic PDAC.

Background: Tissue expansion is a well-established approach to soft tissue reconstruction in the pediatric population for lower extremity pathologies. Unfortunately, complication rates range from 19% to 40% in literature, including infection and implant extrusion, leading to delays in reconstruction. These challenges have prompted investigation toward categorizing risk factors for lower extremity tissue expander placement., Methods: A retrospective study of pediatric patients who underwent lower extremity tissue expander placement by the senior author (R.J.R.) was performed over a 16-year period. Patient charts were reviewed to categorize baseline and operative characteristics. Primary outcome variables were surgical-site infection, expander extrusion, and expander deflation. Univariate and multivariate logistic regressions were performed ( α < 0.05)., Results: There were 59 tissue expanders in our cohort. The overall complication rate was 27.1% with a 77.2% successful reconstruction rate. Greater number of expanders placed during 1 operation is associated with 2.5 increased odds of having any complication and is associated with 0.4 decreased odds of having a successful reconstruction. Incisions made in scar tissue for expander placement appear to be associated with a greater than 7 times increased odds of readmission., Conclusions: Reconstruction of soft tissue pathologies using lower extremity tissue expanders in the pediatric population is an effective yet challenging technique. This study identified that the number of expanders inserted during 1 operation, incisions made over scar tissue, and expanders placed in the anterior thigh were correlated with having a negative impact on reconstructive outcomes. Extra care should be taken with patients who require multiple expanders during 1 operation and with choosing the location and incision of expander placement., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Penile transplantation has become an emerging option for patients with severe genital defects. Only transplantation restores anatomy, sexual, and reproductive function of the penis. However, penile transplantation comes with important technical, psychosocial, ethical, and surgical challenges that must be considered for successful implementation. Indications for penile transplantation have yet to be clearly elucidated., Recent Findings: Since 2006, only five penile transplants have been performed globally. Four of the five transplants have been performed following traumatic defects, and one was performed following a total penectomy from squamous cell carcinoma. Only two of the five penile transplants remain intact. However, long-term outcomes are encouraging with optimal surgical planning, patient selection, and immunologic compliance. Clinical implications and ethical considerations are discussed., Summary: Penile transplantation is a novel solution for penile defects not amenable to traditional reconstructive approaches. With an evidence-based surgical technique, potential advantages include improved urinary function, sensation, and cosmesis. While patient selection is challenging, there is an ongoing effort to identify potential candidates. Indications are discussed in this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of this study was to compare mortality and complication rates among geriatric patients who sustained a hip fracture before the coronavirus disease (COVID-19) pandemic began to those who presented during the peak of the pandemic. Patients greater than or equal to 50 years of age who presented with a diagnosis of hip fracture from March 16, 2020 to May 1, 2020 were compared with a historical control group who presented between December 1, 2019 and January 16, 2020. Minimum follow up was 30 days. The primary outcome was a 30-day mortality rate. Thirty-day mortality was significantly different between groups, with no deaths of 24 patients in the pre-COVID-19 cohort versus six deaths of 23 patients (26.1%) in the COVID-19 cohort (chi-squared test, p-value = 0.02). The study concluded that the COVID-19 pandemic increased mortality risk for geriatric hip fracture patients. (Journal of Surgical Orthopaedic Advances 32(4):232-237, 2023).

Background: The COVID-19 pandemic significantly impacted hospital resources and patient care, although its effect on free tissue transfer procedures is poorly understood. We conducted the current study to investigate the potential impact of COVID-19 and its accompanying system shut-downs on the surgical outcomes of patients undergoing free flap procedures., Methods: Patients undergoing free tissue transfer procedures were identified from the National Surgical Quality Improvement Program (NSQIP) database from 2016 to 2020. We used 2016-2019 as baseline (pre-pandemic) data to compare with 2020 (peri-pandemic). We divided the patients into the following 3 groups: all patients undergoing free tissue transfer, breast reconstruction free tissue transfer, and non-breast free tissue transfer cases. Outcomes of interest included patient morbidity/mortality, time to surgery, time to takeback, and length of hospital stay. We used Pearson's chi-square and Fisher's exact tests to assess categorical variables. Wilcoxon's ranked sign tests and ANOVA tests were used for non-parametric and parametric continuous variables, respectively. Significance was set at alpha < 0.05., Results: When comparing peri-pandemic to pre-pandemic rates, patient morbidity and mortality and unplanned primary or secondary takeback operations were both significantly higher in all 3 groups peri-pandemic. Median time to primary or secondary takeback operation was also significantly greater peri-pandemic., Conclusion: Patients undergoing flap procedures peri-pandemic had an overall increase in median morbidity and mortality, unplanned primary or secondary takebacks, and median number of days to takebacks compared to the pre-pandemic period. This is concerning given that any future protocols instituted can have detrimental effects on patients who receive a free tissue transfer procedure., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: The socioeconomic diversity of residents, fellows, and faculty members in any medical or surgical specialty is currently unknown making it difficult to understand socioeconomic status (SES) disparities and create programs to improve diversity. Additionally, the career trajectories of residents and faculty members who come from different SES backgrounds have not been explored. We have performed a survey-based research study to understand the SES composition and career trajectories of residents and faculty members within U.S. Plastic and Reconstructive Surgery (PRS) residency programs., Methods: An anonymous online survey was administered to 754 recipients within plastic surgery residency programs in the United States. Self-reported SES information such as household income prior to age 18 and parental education level was collected. Data regarding career trajectories was obtained through questions about away rotations and research productivity., Results: A total of 196 fellows, and faculty members participated in the study, with an estimated survey respondent rate of 25.9%. Only 9.9% (10 of 101) of residents and fellows reported a childhood (under age 18) family income less than $40,000. When analyzing parental education and occupation (EO-status), 42.6% (43 of 101) of residents and fellows had at least 1 parent in an executive, managerial, or professional position with a doctorate/professional degree. Low-income and low EO-status were associated with increased utilization of federal and state assistance programs (p = 0.0001) and approval for AAMC's Fee Assistance Program (FAP) (p = 0.0001). Residents and fellows who identified as White were not as likely to be from low EO-status households as those who identified as Asian (OR 0.3 and p = 0.015 vs. OR 2.9 and p = 0.038). Residents and fellows from low EO-status backgrounds were more likely to take a gap in education (87% vs. 65.4%, p = 0.047) compared to their high EO-status peers. Notably, more current residents and fellows performed away rotations and had first-author publications during or before medical school compared to full professors (p = 0.0001)., Conclusion: Understanding the backgrounds and career trajectories of trainees and faculty in medicine is essential, yet it has not been performed at the resident or faculty level. This survey is the first to demonstrate the lack of socioeconomic diversity in a specialty (PRS) and identifies variation in career trajectories among those from different SES backgrounds. Large-scale research efforts are necessary to understand current SES diversity and barriers encountered by trainees and educators from low-SES backgrounds in all medical and surgical specialties., Competing Interests: Declaration of Competing Interest The authors report no financial or nonfinancial conflicts., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Children are uniquely vulnerable to injury because of near-complete dependence on caregivers. Unintentional injury is leading cause of death in children under the age of 14. Burns are one of the leading causes of accidental and preventable household injuries, with scald burns most common in younger children and flame burns in older ones. Education is a key tool to address burn prevention, but unfortunately these injuries persist. Critically, there is a paucity of literature investigating adult comprehension with respect to potential risks of household burns. To date, no study has been performed to assess management readiness for these types of injuries without seeking medical care., Methods: Qualtrics™ surveys were distributed to laypersons via Amazon Mechanical Turk. Demographics were self-reported. The survey was divided into two parts, management knowledge, and risk identification. The management part involved a photograph of a first-degree pediatric burn injury and required identification of the degree of injury and three potential initial managements. The risk-identification section required correctly identifying the most common mechanisms of burn injury for different age groups followed by general identification of 20 household burn risks. Survey responses were analyzed using two-tailed Student's t-tests and chi-square analyses, univariate and multivariate analysis, and linear regression., Results: Of the 467 respondents, the mean age was 36.57 years, and was 59.7% (279) male. Only 3.2% of respondents were able to correctly identify all 20 potential risks listed in our survey. Additionally, only 4.5% of respondents correctly identified all three appropriate initial management options (cool water, sterile gauze, and over-the-counter analgesics) without misidentifying incorrect options. However, 56.1% of respondents were able to select at least one correct management option. For image-based injury classification, the most common response was incorrectly second-degree with 216 responses (42.2%) and the second-most common response was correctly first-degree with 146 responses (31.3%). Most respondents claimed they would not seek medical attention for the injury presented in the photograph (77.7%). When comparing the responses of individuals with children to those without, there were no statistically significant differences in ability to assess household risks for pediatric burns. For the entire population of respondents, the mean score for correctly identifying risks was 38%., Conclusion: This study revealed a significant gap in public awareness of household risks for pediatric burns. Furthermore, while most individuals would not seek medical care for a first-degree pediatric burn injury, they were readily available to identify proper initial management methods. This gap in knowledge and understanding of household pediatric burn injuries should be addressed with increased burn injury prevention education initiatives and more parental counseling opportunities., Competing Interests: Conflicts of interest and source of funding The authors declare no conflicts of interest and no sources of funding., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Background: Monosodium glutamate (MSG) has been identified as a trigger of abdominal pain in irritable bowel syndrome (IBS), but the mechanism is unknown. This study examined whether MSG causes visceral hypersensitivity using a water-avoidance stress (WAS) mouse model of visceral pain., Methods: Mice were divided into four groups receiving treatment for 6 days: WAS + MSG gavage, WAS + saline gavage, sham-WAS + MSG gavage, and sham-WAS + saline gavage. The acute effects of intraluminal administration of 10 μM MSG on jejunal extrinsic afferent nerve sensitivity to distension (0-60 mmHg) were examined using ex vivo extracellular recordings. MSG was also applied directly to jejunal afferents from untreated mice. Glutamate concentration was measured in serum, and in the serosal compartment of Ussing chambers following apical administration., Key Results: Acute intraluminal MSG application increased distension responses of jejunal afferent nerves from mice exposed to WAS + MSG. This effect was mediated by wide dynamic range and high-threshold units at both physiologic and noxious pressures (10-60 mmHg, p < 0.05). No effect of MSG was observed in the other groups, or when applied directly to the jejunal afferent nerves. Serum glutamate was increased in mice exposed to WAS + MSG compared to sham-WAS + saline, and serosal glutamate increased using WAS tissue (p = 0.0433)., Conclusions and Inferences: These findings demonstrate that repeated exposure to MSG in mice leads to sensitization of jejunal afferent nerves to acute ex vivo exposure to MSG. This may contribute to visceral hypersensitivity reported in response to MSG in patients with IBS., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background:  Calvarial defects are severe injuries that can result from a wide array of etiologies. Reconstructive modalities for these clinical challenges include autologous bone grafting or cranioplasty with biocompatible alloplastic materials. Unfortunately, both approaches are limited by factors such as donor site morbidly, tissue availability, and infection. Calvarial transplantation offers the potential opportunity to address skull defect form and functional needs by replacing "like-with-like" tissue but remains poorly investigated., Methods:  Three adult human cadavers underwent circumferential dissection and osteotomy to raise the entire scalp and skull en-bloc. The vascular pedicles of the scalp were assessed for patency and perfused with color dye, iohexol contrast agent for computed tomography (CT) angiography, and indocyanine green for SPY-Portable Handheld Imager assessment of perfusion to the skull., Results:  Gross changes were appreciated to the scalp with color dye, but not to bone. CT angiography and SPY-Portable Handheld Imager assessment confirmed perfusion from the vessels of the scalp to the skull beyond midline., Discussion/conclusion:  Calvarial transplantation may be a technically viable option for skull defect reconstruction that requires vascularized composite tissues (bone and soft tissue) for optimal outcomes., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The MORPHEUS platform comprises multiple open-label, randomized, phase Ib/II trials designed to identify early efficacy and safety signals of treatment combinations across cancers. Atezolizumab (anti-programmed cell death 1 ligand 1 [PD-L1]) was evaluated in combination with PEGylated recombinant human hyaluronidase (PEGPH20)., Methods: In 2 randomized MORPHEUS trials, eligible patients with advanced, previously treated pancreatic ductal adenocarcinoma (PDAC) or gastric cancer (GC) received atezolizumab plus PEGPH20, or control treatment (mFOLFOX6 or gemcitabine plus nab-paclitaxel [MORPHEUS-PDAC]; ramucirumab plus paclitaxel [MORPHEUS-GC]). Primary endpoints were objective response rates (ORR) per RECIST 1.1 and safety., Results: In MORPHEUS-PDAC, ORRs with atezolizumab plus PEGPH20 (n = 66) were 6.1% (95% CI, 1.68%-14.80%) vs. 2.4% (95% CI, 0.06%-12.57%) with chemotherapy (n = 42). In the respective arms, 65.2% and 61.9% had grade 3/4 adverse events (AEs); 4.5% and 2.4% had grade 5 AEs. In MORPHEUS-GC, confirmed ORRs with atezolizumab plus PEGPH20 (n = 13) were 0% (95% CI, 0%-24.7%) vs. 16.7% (95% CI, 2.1%-48.4%) with control (n = 12). Grade 3/4 AEs occurred in 30.8% and 75.0% of patients, respectively; no grade 5 AEs occurred., Conclusion: Atezolizumab plus PEGPH20 showed limited clinical activity in patients with PDAC and none in patients with GC. The safety of atezolizumab plus PEGPH20 was consistent with each agent's known safety profile. (ClinicalTrials.gov Identifier: NCT03193190 and NCT03281369)., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Prepectoral implant-based breast reconstruction is often supplemented by autologous fat grafting to optimize aesthetic outcomes. This usually entails several rounds of modest fat transfer to minimize risk of necrosis; however, the limits of fat grafting at expander exchange are not known., Methods: A single-institution retrospective review from July 2016 to February 2022 was performed of all patients who underwent (1) mastectomy, (2) prepectoral tissue expander placement, (3) expander exchange for implant, and (4) at least one round of autologous fat transfer. Student t test and χ 2 test were used., Results: A total of 82 breasts underwent a single round of fat grafting during implant placement (group 1); 75 breasts underwent fat grafting that occurred in multiple rounds and/or in delay to implant placement (group 2). Group 1 received more fat at the time of implant placement (100 mL; interquartile range, 55-140 mL; P < 0.001) and underwent fewer planned operative procedures compared with group 2 (1.0 vs 2.2, P < 0.001). Total fat volume in group 2 did not significantly exceed that of group 1 until after 3 rounds of fat transfer (128.5 mL; interquartile range, 90-130 mL; P < 0.01). There was no difference in the rate of fat necrosis between groups after the first round (15.9% vs 9.3%, P = 0.2) and final round (15.9% vs 12.0%, P = 0.5) of fat grafting. Complication rates were similar between groups (3.7% vs 8.0%, P = 0.2)., Conclusions: A 2-stage approach of prepectoral tissue expander placement with single round of larger volume fat transfer at expander exchange reduces overall number of operative procedures without increased risks., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with nonsyndromic craniosynostosis (NSC) generally undergo corrective surgery before 1 year of age to the mitigate morbidities and risks of delayed repair. The cohort of patients who receive primary corrective surgery after 1 year and factors associated with their gaps to care is poorly characterized in literature., Methods: A nested case-control study was conducted for NSC patients who underwent primary corrective surgery at our institution and affiliates between 1992 and 2022. Patients whose surgery occurred after 1 year of age were identified and matched 1:1 by surgical date to standard-care control subjects. Chart review was conducted to gather patient data regarding care timeline and sociodemographic characteristics., Results: Odds of surgery after 1 year of age were increased in Black patients (odds ratio, 3.94; P < 0.001) and those insured by Medicaid (2.57, P = 0.018), with single caregivers (4.96, P = 0.002), and from lower-income areas (+1% per $1000 income decrease, P = 0.001). Delays associated with socioeconomic status primarily impacted timely access to a craniofacial provider, whereas caregiver status was associated with subspecialty level delays. These disparities were exacerbated in patients with sagittal and metopic synostosis, respectively. Patients with multisuture synostosis were susceptible to significant delays related to familial strain (foster status, insurer, and English proficiency)., Conclusions: Patients from socioeconomically strained households face systemic barriers to accessing optimal NSC care; disparities may be exacerbated by the diagnostic/treatment complexities of specific types of craniosynostosis. Interventions at primary care and craniofacial specialist levels can decrease health care gaps and optimize outcomes for vulnerable patients., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neoadjuvant treatment with nab-paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down-stage tumors to achieve negative surgical margins., Methods: A single-arm, open-label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node-positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m 2 and nab-paclitaxel 125 mg/m 2 on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.4 Gy intensity-modulated radiation over 28 fractions with concurrent fluoropyrimidine chemotherapy. After definitive resection, patients received four additional cycles of gemcitabine and nab-paclitaxel. The primary endpoint was R0 resection rate. Other endpoints included treatment completion rate, resection rate, radiographic response rate, survival, and adverse events., Results: Nineteen patients were enrolled, with the majority having head of pancreas primary tumors, both arterial and venous vasculature involvement, and clinically positive nodes on imaging. Among them, 11 (58%) underwent definitive resection and eight of 19 (42%) achieved R0 resection. Disease progression and functional decline were primary reasons for deferring surgical resection after neoadjuvant treatment. Pathologic near-complete response was observed in two of 11 (18%) resection specimens. Among the 19 patients, the 12-month progression-free survival was 58%, and 12-month overall survival was 79%. Common adverse events were alopecia, nausea, vomiting, fatigue, myalgia, peripheral neuropathy, rash, and neutropenia., Conclusion: Gemcitabine and nab-paclitaxel followed by long-course chemoradiation represents a feasible neoadjuvant treatment strategy for borderline resectable or node-positive pancreatic cancer., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: As the second cycle impacted by COVID-19, the 2022 Plastic and Reconstructive Surgery (PRS) Match maintained virtual interviews while offering a modest lift of subinternship restrictions. The residency application process continues to evolve, with changes such as pass/fail United States Medical Licensing Examination Step 1 reporting prompting programs to reconsider metrics of applicant success. It is critical to address the impact of board scores, mentorship, and resource availability on a diverse applicant population in the PRS Match., Methods: A survey was electronically administered to students applying to a single institutional PRS residency program. The survey inquired about demographics, application statistics, mentorship experience, and match outcomes. Logistic regressions were modeled to assess for odds of matching into plastic surgery., Results: In total, 151 responses were analyzed, a 49.7% response rate. Most participants were female (52.3%), White (68.9%), and not Hispanic/Latino (84.8%). The largest percentage of respondents had a faculty mentor only from their home institution (55.0%) and a resident mentor from only their home institution (32.3%). Participants with a faculty mentor from both a home and outside institution had 7.4 times the odds of matching into PRS ( P = 0.02) than students with no faculty mentorship. Students with dual-institution resident mentorship had 18.5 times higher the odds of matching compared with students with no resident mentorship ( P < 0.001)., Conclusions: Subjective metrics, rather than objective scores, had the most influence on successfully matching into plastic surgery. As the PRS Match continues to become increasingly competitive, it behooves programs to provide equitable access to resources such as mentorship., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved for the treatment of various solid tumors. In gastric cancer, genes commonly harbor mutations in the homologous recombination DNA repair pathway, potentially increasing sensitivity to PARPi. Pamiparib (BGB-290) is a small molecule inhibitor of PARP1 and PARP2., Methods: The PARALLEL-303 study (NCT03427814) investigated the efficacy and safety of pamiparib 60 mg orally (PO) twice daily (BID) versus placebo PO BID as maintenance therapy in patients with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line chemotherapy. The primary endpoint of this double-blind, randomized, global phase 2 study was progression-free survival (PFS) (RECIST version 1.1; per investigator assessment). Secondary endpoints included overall survival (OS) and safety., Results: In total, 136 patients were randomized 1:1 to receive pamiparib (n = 71) or placebo (n = 65). Median PFS was numerically longer with pamiparib versus placebo but did not reach statistical significance (3.7 months [95% confidence interval (CI): 1.9, 5.3] vs. 2.1 months [95% CI: 1.9, 3.8]; hazard ratio 0.8 [95% CI: 0.5, 1.2]; p = 0.1428). Median OS was 10.2 months (95% CI: 8.7, 16.3) in the pamiparib arm versus 12.0 months (95% CI: 8.2, not estimable) in the placebo arm. Overall, 8 patients (11.3%) in the pamiparib arm and 2 patients (3.1%) in the placebo arm experienced ≥1 TEAE leading to treatment discontinuation., Conclusions: Maintenance pamiparib did not meet statistical significance for superiority versus placebo for PFS, but was well tolerated with few treatment discontinuations; no unexpected safety signals were identified., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Following resection of colorectal liver metastasis, most patients have disease recurrence, most commonly intrahepatic. Although the role of resection in colorectal liver metastasis is well-established, there have been limited investigations assessing the benefit of repeat hepatic resection compared with systemic treatment alone for intrahepatic recurrence., Methods: A retrospective single-institution cohort study of patients with recurrent colorectal liver metastasis following curative-intent hepatectomy was performed from 2003 to 2019. The oncologic outcomes, including post-recurrence overall survival, were evaluated using Kaplan-Meier and Cox proportional hazards modeling. Patients undergoing repeat hepatic resection were propensity-matched with patients receiving systemic treatment alone based on relevant clinicopathologic variables., Results: There were 338 patients treated with hepatic resection for colorectal liver metastasis over the study period. Liver recurrence was observed in 147 (43%) patients at a median time of 10 months from prior resection, with a median post-recurrence overall survival of 29 months. There were 37 patients managed with repeat hepatic resection; 33 (89%) received perioperative chemotherapy. On propensity matching, there were no significant clinicopathologic differences between 37 patients having repeat hepatic resection and 37 patients treated with systemic treatment alone. Repeat hepatic resection was independently associated with improved 5-year post-recurrence overall survival compared with systemic treatment alone (median overall survival 41 vs 35 months, 5-year overall survival 19% vs 3%, P = .048)., Conclusion: Disease characteristics of patients with intrahepatic recurrence of colorectal liver metastasis, specifically the number of liver lesions and size of the largest lesion, are most predictive of survival and response to systemic therapy. Patients who recur with oligometastatic liver disease experience improved outcomes and derive benefit from curative-intent repeat hepatic resection with integrated perioperative systemic therapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Mandibular fractures are the most common of pediatric facial fractures. The effect of race on management/outcomes in these injuries has not been previously studied. Given the significant association between race and healthcare outcomes in many other pediatric conditions, an in-depth study of race as related to mandibular fractures in the pediatric patient population is warranted., Methods: This was a 30-year retrospective, longitudinal study of pediatric patients who presented to a single institution with mandibular fractures. Patient data were compared between patients of different races and ethnicities. Demographic variables, injury characteristics, and treatment variables were analyzed to find predictors of surgical treatment and posttreatment complications., Results: One hundred ninety-six patients met inclusion criteria, of whom 49.5% were White, 43.9% were Black, 0.0% were Asian, and 6.6% were classified as "other." Black and "other" patients were more likely than their White counterparts to be injured as pedestrians (P = 0.0005). Black patients were also more likely than White patients or "other" patients to be injured by assault than by sports-related injuries or animal-related accidents (P = 0.0004 and P = 0.0018, respectively). Race or ethnicity were not found to be a predictor of receiving surgical treatment (ORIF) or of posttreatment complications. The posttreatment rates for all the complications observed were comparable among all race and ethnic groups. Higher mandible injury severity score (odds ratio [OR], 1.25), condyle fracture (OR, 2.58), and symphysis fracture (OR, 3.20) were positively correlated with receiving ORIF as treatment. Mandible body fracture (OR, 0.36), parasymphyseal fracture (OR, 0.34), bilateral mandible fracture (OR, 0.48), and multiple mandibular fractures (OR, 0.34) were negatively correlated with receiving ORIF as treatment. Only high mandible injury severity score (OR, 1.10) was identified as an independent predictor of posttreatment complications. Lastly, Maryland's transition to an all-payer model in 2014 also had no impact on treatment modality; treatment of fractures among race and ethnicity were not significantly different pre- and post-2014., Conclusions: There is no difference in how patients are treated (surgically vs nonsurgically) and no difference in outcomes for patients based on race at our institution. This could be due to institutional ideology, services provided by a tertiary care center, or simply the more diverse patient population at baseline., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Since 2006, five penis transplants have been performed worldwide. Mixed outcomes have been reported, and two of the five penile transplants have required explantation. However, the long-term outcomes have been encouraging when compliance is implemented, whether standard induction and triple therapy maintenance, or single therapy maintenance. Follow-up monitoring of transplant recipients has enabled a synthesis of technical considerations for surgical success and has shown stable leukocyte counts and renal function after a donor bone-marrow-based immunomodulatory regimen followed by tacrolimus monotherapy as long as 3 years post-transplant, as well as continuous nerve regeneration of penile allografts 3 years post-transplant. Areas of uncertainty include the ethics of donor-recipient colour mismatch, surveillance for sexually transmitted infections and how to optimize patient compliance. Questions also remain with respect to the long-term immunological sequelae of penile tissue, functional outcomes, psychosocial implications and patient selection. Patient counselling should be modified to mention the possibility of long-term improvement in nerve regeneration and sufficient renal function with single-therapy maintenance, and to build a longitudinal dialogue and partnership between the patient and the multidisciplinary care team regarding the risks of sexually transmitted infection instead of surveillance., (© 2023. Springer Nature Limited.)

Purpose: This randomized, open-label trial compared the efficacy and safety of adjuvant nab -paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430)., Methods: We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab -paclitaxel (125 mg/m 2 ) + gemcitabine (1,000 mg/m 2 ) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety., Results: Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab -paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab -paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab -paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab -paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events., Conclusion: The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab -paclitaxel + gemcitabine.

Background: In 2022, the plastic and reconstructive surgery (PRS) match faced unprecedented system-wide transitions that have redefined conventional measures of applicant success. This challenges the equitable assessment of student competitiveness and diversity in the field., Methods: A survey of demography, application content, and 2022 match outcomes was distributed to applicants to a single PRS residency program. Comparative statistics and regression models were performed to assess the predictive value of factors in match success and quality., Results: A total of 151 respondents (response rate 49.7%) were analyzed. Although step 1 and step 2 CK scores were significantly higher among matched applicants, neither examination predicted match success. Most respondents (52.3%) were women, although gender was also not significantly associated with match success. Underrepresented in medicine applicants made up 19.2% of responses and 16.7% of matches, and the plurality of respondents (22.5%) were raised with a household income ≥$300,000. Both Black race and household income ≤$100,000 were associated with lower odds of scoring above a 240 on either step 1 or step 2 CK (Black: OR, 0.03 and 0.06; P < 0.05 and P < 0.001; income: OR, 0.07-0.47 and 0.1 to 0.8, among income subgroups), receiving interview offers (OR, -9.4; P < 0.05; OR, -11.0 to -5.4), and matching into PRS (OR, 0.2; P < 0.05; OR, 0.2 to 0.5), compared with White and high-income applicants, respectively., Conclusions: Systemic inequities in the match process disadvantage underrepresented in medicine candidates and those from lower household incomes. As the residency match continues to evolve, programs must understand and mitigate the impacts of bias in various application components., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Central venous catheters (CVCs) are invaluable devices in large animal research as they facilitate a wide range of medical applications, including blood monitoring and reliable intravenous fluid and drug administration. Specifically, the tunneled multi-lumen Hickman catheter (HC) is commonly used in swine models due to its lower extrication and complication rates. Despite fewer complications relative to other CVCs, HC-related morbidity presents a significant challenge, as it can significantly delay or otherwise negatively impact ongoing studies. The proper insertion and maintenance of HCs is paramount in preventing these complications, but there is no consensus on best practices. The purpose of this protocol is to comprehensively describe an approach for the insertion and maintenance of a tunneled HC in swine that mitigates HC-related complications and morbidity. The use of these techniques in >100 swine has resulted in complication-free patent lines up to 8 months and no catheter-related mortality or infection of the ventral surgical site. This protocol offers a method to optimize the lifespan of the HC and guidance for approaching issues during use.

Objective: As of January 26, 2022, the United States Medical Licensing Examination(USMLE) Step 1 score reporting will be changed from a numeric scoring system to pass/fail. Although the new scoring policy is expected to benefit medical students, there is concern that it will also amplify preexisting disadvantages and worsen disparities for students applying in the already-competitive plastic surgery match. Whether the reporting change will tangibly benefit applicants to plastic surgery has yet to be elucidated., Design: A cross-sectional survey was distributed to medical students and graduates via social media platforms. Data were analyzed using Student t test and Chi-squared statistic, with an alpha level set at 0.05., Setting: Data collection and analysis was performed at Johns Hopkins University School of Medicine., Participants: This study included a sample of 120 American Medical Trainees (AMTs) and International Medical Trainees (IMTs) who are interested in plastic surgery., Results: The plurality of respondents were against the new Step 1 score reporting (AMT: 40.7%; IMT: 44.3%), but differences existed between AMTs when compared to IMTs, especially regarding opinions about the reporting change on stress levels and competitiveness of highly competitive specialties. Regardless of training status, respondents felt that the pass/fail scoring system would increase their likelihood to engage with more research, dual apply, prioritize studying for Step 2 CK, and consider a dedicated research year., Conclusions: While a pass/fail reporting system for Step 1 may alleviate some stress for medical trainees, other issues arise that may perpetuate disparities and bias against students with little resources in the field of plastic surgery. Residency programs should offer anticipatory guidance regarding prioritization of aspects of application to ease this psychosocial and financial pressure, as well as help students reorganize their constrained time., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Importance: Treatment at high-volume centers (HVCs) has been associated with improved overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC); however, it is unclear how patterns of referral affect these findings., Objective: To understand the relative contributions of treatment site and selection bias in driving differences in outcomes in patients with PDAC and to characterize socioeconomic factors associated with referral to HVCs., Design, Setting, Participants: A population-based retrospective review of the Oregon State Cancer Registry was performed from 1997 to 2019 with a median 4.3 months of follow-up. Study participants were all patients diagnosed with PDAC in Oregon from 1997 to 2018 (n = 8026)., Exposures: The primary exposures studied were diagnosis and treatment at HVCs (20 or more pancreatectomies for PDAC per year), low-volume centers ([LVCs] less than 20 per year), or both., Main Outcomes and Measures: OS and treatment patterns (eg, receipt of chemotherapy and primary site surgery) were evaluated with Kaplan-Meier analysis and logistic regression, respectively., Results: Eight thousand twenty-six patients (male, 4142 [52%]; mean age, 71 years) were identified (n = 3419 locoregional, n = 4607 metastatic). Patients receiving first-course treatment at a combination of HVCs and LVCs demonstrated improved median OS for locoregional and metastatic disease (16.6 [95% CI, 15.3-17.9] and 6.1 [95% CI, 4.9-7.3] months, respectively) vs patients receiving HVC only (11.5 [95% CI, 10.7-12.3] and 3.9 [95% CI, 3.5-4.3] months, respectively) or LVC-only treatment (8.2 [95% CI, 7.7-8.7] and 2.1 [95% CI, 1.9-2.3] months, respectively; all P < .001). No differences existed in disease burden by volume status of diagnosing institution. When stratifying by site of diagnosis, HVC-associated improvements in median OS were smaller (locoregional: 10.4 [95% CI, 9.5-11.2] vs 9.9 [95% CI, 9.4-10.4] months; P = .03; metastatic: 3.6 vs 2.7 months, P < .001) than when stratifying by the volume status of treating centers, indicating selection bias during referral. A total of 94% (n = 1103) of patients diagnosed at an HVC received HVC treatment vs 18% (n = 985) of LVC diagnoses. Among patients diagnosed at LVCs, later year of diagnosis and higher estimated income were independently associated with higher odds of subsequent HVC treatment, while older age, metastatic disease, and farther distance from HVC were independently associated with lower odds., Conclusions and Relevance: LVC-to-HVC referrals for PDAC experienced improved OS vs HVC- or LVC-only care. While disease-related features prompting referral may partially account for this finding, socioeconomic and geographic disparities in referral worsen OS for disadvantaged patients. Measures to improve access to HVCs are encouraged.

Purpose: This study aimed to develop machine learning (ML) models to predict hospital admission (overnight stay) as well as short-term complications and readmission rates following anterior cruciate ligament reconstruction (ACLR). Furthermore, we sought to compare the ML models with logistic regression models in predicting ACLR outcomes., Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent elective ACLR from 2012 to 2018. Artificial neural network ML and logistic regression models were developed to predict overnight stay, 30-day postoperative complications, and ACL-related readmission, and model performance was compared using the area under the receiver operating characteristic curve. Regression analyses were used to identify variables that were significantly associated with the predicted outcomes., Results: A total of 21,636 elective ACLR cases met inclusion criteria. Variables associated with hospital admission included White race, obesity, hypertension, and American Society of Anesthesiologists classification 3 and greater, anesthesia other than general, prolonged operative time, and inpatient setting. The incidence of hospital admission (overnight stay) was 10.2%, 30-day complications was 1.3%, and 30-day readmission for ACLR-related causes was 0.9%. Compared with logistic regression models, artificial neural network models reported superior area under the receiver operating characteristic curve values in predicting overnight stay (0.835 vs 0.589), 30-day complications (0.742 vs 0.590), reoperation (0.842 vs 0.601), ACLR-related readmission (0.872 vs 0.606), deep-vein thrombosis (0.804 vs 0.608), and surgical-site infection (0.818 vs 0.596)., Conclusions: The ML models developed in this study demonstrate an application of ML in which data from a national surgical patient registry was used to predict hospital admission and 30-day postoperative complications after elective ACLR. ML models developed performed well, outperforming regression models in predicting hospital admission and short-term complications following elective ACLR. ML models performed best when predicting ACLR-related readmissions and reoperations, followed by overnight stay., Level of Evidence: IV, retrospective comparative prognostic trial., (Copyright © 2022. Published by Elsevier Inc.)

Background: Focal cartilage lesions of the knee remain a difficult entity to treat. Current treatment options include arthroscopic debridement, microfracture, autograft or allograft osteochondral transplantation, and cell-based therapies such as autologous chondrocyte transplantation. Osteochondral transplantation techniques restore the normal topography of the condyles and provide mature hyaline cartilage in a single-stage procedure. However, clinical outcomes comparing autograft versus allograft techniques are scarce., Purpose: To perform a comprehensive systematic review and meta-analysis of high-quality studies to evaluate the results of osteochondral autograft and allograft transplantation for the treatment of symptomatic cartilage defects of the knee., Study Design: Systematic review and meta-analysis; Level of evidence, 2., Methods: A comprehensive search of the literature was conducted using various databases. Inclusion criteria were level 1 or 2 original studies, studies with patients reporting knee cartilage injuries and chondral defects, mean follow-up ≥2 years, and studies focusing on osteochondral transplant techniques. Exclusion criteria were studies with nonknee chondral defects, studies reporting clinical outcomes of osteochondral autograft or allograft combined with other procedures, animal studies, cadaveric studies, non-English language studies, case reports, and reviews or editorials. Primary outcomes included patient-reported outcomes and failure rates associated with both techniques, and factors such as lesion size, age, sex, and the number of plugs transplanted were assessed. Metaregression using a mixed-effects model was utilized for meta-analyses., Results: The search resulted in 20 included studies with 364 cases of osteochondral autograft and 272 cases of osteochondral allograft. Mean postoperative survival was 88.2% in the osteochondral autograft cohort as compared with 87.2% in the osteochondral allograft cohort at 5.4 and 5.2 years, respectively ( P = .6605). Patient-reported outcomes improved by an average of 65.1% and 81.1% after osteochondral autograft and allograft, respectively ( P = .0001). However, meta-analysis revealed no significant difference in patient-reported outcome percentage change between osteochondral autograft and allograft ( P = .97) and a coefficient of 0.033 (95% CI, -1.91 to 1.98). Meta-analysis of the relative risk of graft failure after osteochondral autograft versus allograft showed no significant differences ( P = .66) and a coefficient of 0.114 (95% CI, -0.46 to 0.69). Furthermore, the regression did not find other predictors (mean age, percentage of female patients, lesion size, number of plugs/grafts used, and treatment location) that may have significantly affected patient-reported outcome percentage change or postoperative failure between osteochondral autograft versus allograft., Conclusion: Osteochondral autograft and allograft result in favorable patient-reported outcomes and graft survival rates at medium-term follow-up. While predictors for outcomes such as mean age, percentage of female patients, lesion size, number of plugs/grafts used, and treatment location did not affect the comparison of the 2 cohorts, proper patient selection for either procedure remains paramount to the success and potentially long-term viability of the graft.

Introduction: An important challenge in the secondary prevention of cardiovascular diseases is the optimization of risk factors (RFs) after hospital discharge. These have been shown to be insufficiently controlled in clinical practice., Aim: To evaluate whether secondary prevention goals were met at our institution at 12 months after an acute coronary syndrome (ACS) index event, as well as analyzing if achieving these goals was associated with a lower incidence of major adverse cardiovascular events (MACE)., Methods: Retrospective cohort of patients with a former diagnosis of ACS over a period of 4 years. To evaluate the proportion of patients who met RF control goals at 12 months after the index event, we used two sets of preestablished goals: stringent and lenient. During follow-up we evaluated the occurrence of MACE, defined by the following: ACS, coronary revascularization, stroke, hospitalization because of acute heart failure and cardiovascular death., Results: We included 468 patients during the study period. The mean age of the patients was 60 ± 10.76 years, 20.5% were women, and mean follow-up was 41.8 ± 22.0 months. The proportion of patients that met all secondary prevention stringent and lenient goals accounted for 5.5% and 17.2%, respectively, and 8% did not achieve any target. Overall, 9.6% presented the composite of MACE during follow-up. The number of RFs in control at 12 months was associated with a lower rate of MACE, both with stringent and lenient goals., Conclusion: Achieving established goals for modifiable RFs can lower the incidence of MACE during long-term follow-up., (© 2023. Italian Society of Hypertension.)

Considerable controversy exists around the optimal age on which to operate for craniosynostosis. This study aims to use data from the American College of Surgeons National Surgical Quality Improvement Program-Pediatric to assess the impact of operative age on hospital stay and outcomes. After excluding patients who underwent endoscopic cranial vault remodeling, a total of 3292 patients met inclusion criteria in the National Surgical Quality Improvement Program-Pediatric between 2012 and 2019. Median age at surgery was 300 days (interquartile range: 204-494). Patients between 0 and 6 months underwent the highest proportion of complex cranial vault remodeling, Current Procedural Terminology 61,558 ( n =44, 7.7%) and Current Procedural Terminology 61,559 ( n =317, 55.1%). White blood cell counts peaked in the 12 to 18 months group, and were lowest in the 24± months group. Hematocrit was lowest in the 0 to 6 months group and rose steadily to the 24± months group; the inverse pattern was found in platelet concentration, which was highest in the youngest patients and lowest in the oldest. Prothrombin time, international normalized ratio, and partial thromboplastin time were relatively consistent across all age groups. Younger patients had significantly shorter operating room times, which increased with patient age ( P <0.001). Younger patients also had significantly shorter length of stay ( P =0.009), though length of stay peaked between 12 and 18 months. There was a significantly lower rate of surgical site infection in younger patients, which occurred in 0.7% of patients 0 to 12 months and 1.0 to 3.0% in patients over 12 to 24± months. There was no significant difference in the average number of transfusions required in any age group ( P =0.961)., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)