Otolaryngology-head and neck surgery resident and medical school characteristics: Current paradigm amidst changing application criteria.

PURPOSE: To determine the characteristics of current US Otolaryngology-Head and Neck Surgery (Oto-HNS) residents and their medical school. METHODS: Data were manually collected between Dec 2022 and Jan 2023 for 1649 residents attending 163 US-based ACGME accredited Oto-HNS residency programs, reflecting the 2018-2022 cohort. All data were collected from publicly available sources including residency and medical school program websites, web of science, and professional networking sites (ex: LinkedIn, Doximity). Data were analyzed to determine the "feeder" schools which contributed the greatest number and percent of residents. Using univariable linear regression models, we characterized factors which were associated with feeder school status. RESULTS: Of 1649 residents analyzed, 364 (22 %) matched to their home program and 918 (56 %) stayed in the region of their medical school. The median [IQR] number of published papers and abstracts was 5 [3, 9] with an h-index of 2 [1,4]. Factors associated with producing a greater percent of Oto-HNS residents include presence of an interest group, presence of a home program, USNWR research rank of the medical school, Doximity reputation rank of the home residency program, average pre-residency h-index of the school's graduates, and total NIH research funding (each p < 0.001). CONCLUSIONS: In the changing landscape of residency applications after the USMLE Step 1 exam's transition in January 2022 to pass/fail scoring, it is important to objectively characterize current Oto-HNS residents. Findings from this study will inform prospective residents and residency programs seeking to improve access to Oto-HNS. Future small-scale studies may help further identify driving factors within medical school curricula.

The Increasing Problem of Syphilis Manifesting as Head and Neck Cancer: A Case Series.

Syphilis is an infectious disease caused by the spirochete Treponema pallidum. Rates have been rising in the US and globally. Known as the "Great Imitator," syphilis can involve head and neck subsites, and often can masquerade as possible carcinoma of the head and neck. Here, we present three distinct cases of syphilis presenting as suspected head and neck malignancy involving the oropharynx, larynx and oral cavity. All cases were diagnosed on surgical pathologic examination of diseased tissues and treated. It is important for practicing otolaryngologists to understand head and neck manifestations of syphilis to facilitate proper diagnosis and treatment. Laryngoscope, 134:236-239, 2024.

Navigating Informed Consent and Patient Safety in Surgery: Lessons for Medical Students and Junior Trainees.

AbstractIn the operating room, patient safety is of paramount importance. Medical students and junior trainees, despite their primary role as students, may play active roles in assessing patient safety and reporting suspected errors. Active consent is one layer of patient safety that is continuously assessed by several team members. This article examines an instance where patient consent may have been violated. Through the lens of trainee and senior perspectives, we discuss the ethical principles at stake and provide recommendations for medical student and junior trainee involvement in patient care when an error is suspected.

Disparities in Pediatric Orthopedic Surgery Care During the COVID-19 Pandemic Pre-vaccine and Post-Vaccine Availability.

BACKGROUND: The COVID-19 pandemic has led to significant disruptions in medical care, resulting in an estimated 40% of US adults avoiding care. However, the return to baseline health care utilization following COVID-19 restrictions within the pediatric orthopedic population remains unexplored. We sought to analyze the visit volume and demographics of pediatric orthopedic patients at 3 timepoints: prepandemic (2019), pandemic (2020), and pandemic post-vaccine availability (2021), to determine the impact of COVID-19 restrictions on our single-center, multisite institution. METHODS: We performed a retrospective cohort study of 6318 patients seeking treatment at our institution from May through August in 2019, 2020, and 2021. Patient age, sex, address, encounter date, and ICD-10 codes were obtained. Diagnoses were classified into fractures and dislocations, non-fracture-related trauma, sports, elective, and other categories. Geospatial analysis comparing incidence and geospatial distribution of diagnoses across the time periods was performed and compared with the Centers for Disease Control (CDC) social vulnerability index (SVI). RESULTS: The total number of pediatric orthopedic visits decreased by 22.2% during the pandemic ( P <0.001) and remained 11.6% lower post-vaccine availability compared with prepandemic numbers ( P <0.001). There was no significant difference in age ( P =0.097) or sex ( P =0.248) of the patients across all 3 timepoints; however, patients seen during the pandemic were more often White race (67.7% vs. 59.3%, P <0.001). Post-vaccine availability, trauma visits increased by 18.2% ( P <0.001) and total fractures remained 13.4% lower than prepandemic volume ( P <0.001). Sports volume decreased during the pandemic but returned to prepandemic volume in the post-vaccine availability period ( P =0.298). Elective visits did not recover to prepandemic volume and remained 13.0% lower compared with baseline ( P <0.001). Geospatial analysis of patient distribution illustrated neighborhood trends in access to care during the COVID-19 pandemic, with fewer patients from high SVI and low socioeconomic status neighborhoods seeking fracture care during the pandemic than prepandemic. Post-vaccine availability, fracture population distribution resembled prepandemic levels, suggesting a return to baseline health care utilization. CONCLUSION: Pediatric orthopedic surgery visit volume broadly decreased during the COVID-19 pandemic and did not return to prepandemic levels. All categories increased in the post-vaccine availability time point except elective visits. Geospatial analysis revealed that neighborhoods with a high social vulnerability index (SVI) were associated with decreased fracture visits during the pandemic, whereas low SVI neighborhoods did not experience as much of a decline. Future research is needed to study these neighborhood trends and more completely characterize factors preventing equitable access to care in the pediatric orthopedic population. LEVEL OF EVIDENCE: Retrospective Study, Level III.

Predictors of Complications in Autologous Breast Reconstruction Using DIEP Flaps: Implications for Management.

BACKGROUND: Deep inferior epigastric perforator (DIEP) flaps are the standard for autologous breast reconstruction. This study investigated risk factors for DIEP complications in a large, contemporary cohort to optimize surgical evaluation and planning. METHODS: This retrospective study included patients who underwent DIEP breast reconstruction between 2016 and 2020 at an academic institution. Demographics, treatment, and outcomes were evaluated in univariable and multivariable regression models for postoperative complications. RESULTS: In total, 802 DIEP flaps were performed in 524 patients (mean age, 51.2 ± 9.6 years; mean body mass index, 29.3 ± 4.5). Most patients (87%) had breast cancer; 15% were BRCA -positive. There were 282 (53%) delayed and 242 (46%) immediate reconstructions and 278 (53%) bilateral and 246 (47%) unilateral reconstructions. Overall complications occurred in 81 patients (15.5%), including venous congestion (3.4%), breast hematoma (3.6%), infection (3.6%), partial flap loss (3.2%), total flap loss (2.3%), and arterial thrombosis (1.3%). Longer operative time was significantly associated with bilateral immediate reconstructions and higher body mass index. Prolonged operative time (OR, 1.16; P = 0.001) and immediate reconstruction (OR, 1.92; P = 0.013) were significant predictors of overall complications. Partial flap loss was associated with bilateral immediate reconstructions, higher body mass index, current smoking status, and longer operative time. CONCLUSIONS: Prolonged operative time is a significant risk factor for overall complications and partial flap loss in DIEP breast reconstruction. For each additional hour of surgical time, the risk of developing overall complications increases by 16%. These findings suggest that reducing operative time through co-surgeon approaches, consistency in surgical teams, and counseling patients with more risk factors toward delayed reconstructions may mitigate complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Incidence of Venous Thromboembolism Based on Caprini Score in Deep Inferior Epigastric Perforator Flap Breast Reconstruction.

BACKGROUND: Deep inferior epigastric perforator (DIEP) flaps are commonly used for autologous breast reconstruction, but reported rates of venous thromboembolism (VTE) are up to 6.8%. This study aimed to determine the incidence of VTE based on preoperative Caprini score following DIEP breast reconstruction. METHODS: This retrospective study included patients who underwent DIEP flaps for breast reconstruction between January 1, 2016 and December 31, 2020 at a tertiary-level, academic institution. Demographics, operative characteristics, and VTE events were recorded. Receiver operating characteristic analysis was performed to determine the area under the curve (AUC) of the Caprini score for VTE. Univariate and multivariate analyses assessed risk factors associated with VTE. RESULTS: This study included 524 patients (mean age 51.2 ± 9.6 years). There were 123 (23.5%) patients with the Caprini score of 0 to 4, 366 (69.8%) with scores 5 to 6, 27 (5.2%) with scores 7 to 8, and 8 (1.5%) patients with scores >8. Postoperative VTE occurred in 11 (2.1%) patients, at a median time of 9 days (range 1-30) after surgery. VTE incidence by the Caprini score was 1.9% for scores 3 to 4, 0.8% for scores 5 to 6, 3.3% for scores 7 to 8, and 13% for scores >8. The Caprini score achieved an AUC of 0.70. A Caprini score >8 was significantly predictive of VTE on multivariable analysis relative to scores 5 to 6 (odds ratio = 43.41, 95% confidence interval = 7.46-252.76, p < 0.001). CONCLUSION: In patients undergoing DIEP breast reconstruction, VTE incidence was highest (13%) in Caprini scores greater than eight despite chemoprophylaxis. Future studies are needed to assess the role of extended chemoprophylaxis in patients with high Caprini scores.

Dimethylaminomicheliolide Sensitizes Cancer Cells to Radiotherapy for Synergistic Combination with Immune Checkpoint Blockade.

Radiotherapy (RT) has demonstrated synergy with immune checkpoint blockade (ICB) in preclinical models. However, its potential as an immunoadjuvant is limited by low immunogenicity at low radiation doses and immunosuppression at high radiation doses. It is hypothesized that radiosensitizers can enhance both the anticancer and immunogenic effects of low-dose radiation. Herein the authors report the antitumor immunity of combined RT and immunotherapy with dimethylaminomicheliolide (DMAMCL), a prodrug of the anti-inflammatory sesquiterpene lactone micheliolide (MCL). DMAMCL sensitized cancer cells to a single fraction of RT in vitro by inducing apoptosis and DNA double-strand breaks. DMAMCL with 5 fractions of 2 Gy focal X-ray irradiation led to significant anticancer efficacy in subcutaneous and spontaneous models of murine cancer. DMAMCL-sensitized RT upregulated programmed death-ligand 1 (PD-L1) expression in the tumors. Combination of DMAMCL-sensitized RT with anti-PD-L1 ICB significantly enhanced antitumor efficacy by increasing tumor-infiltrating CD4+ and CD8+ T cells and establishing immune memory.

Synergistic checkpoint-blockade and radiotherapy-radiodynamic therapy via an immunomodulatory nanoscale metal-organic framework.

Checkpoint blockade elicits durable responses in immunogenic cancers, but it is largely ineffective in immunologically 'cold' tumours. Here we report the design, synthesis and performance of a bismuth-based nanoscale metal-organic framework that modulates the immunological and mechanical properties of the tumour microenvironment for enhanced radiotherapy-radiodynamic therapy. In mice with non-immunogenic prostate and pancreatic tumours irradiated with low X-ray doses, the intratumoural injection of the radiosensitizer mediated potent outcomes via the repolarization of immunosuppressive M2 macrophages into immunostimulatory M1 macrophages, the reduction of the concentration of intratumoural transforming growth factor beta (TGF-ß) and of collagen density, and the inactivation of cancer-associated fibroblasts. When intravenously injected in combination with checkpoint-blockade therapy, the radiosensitizer mediated the reversal of immunosuppression in primary and distant tumours via the systemic reduction of TGF-ß levels, which led to the downregulation of collagen expression, the stimulation of T-cell infiltration in the tumours and a robust abscopal effect. Nanoscale radiosensitizers that stimulate anti-tumour immunity and T-cell infiltration may enhance the therapeutic outcomes of checkpoint blockade in other tumour types.

Nanoscale metal-organic frameworks for x-ray activated in situ cancer vaccination.

Cancer vaccines have been actively pursued to bolster antitumor immunity. Here, we designed nanoscale metal-organic frameworks (nMOFs) as locally activable immunotherapeutics to release danger-associated molecular patterns (DAMPs) and tumor antigens and deliver pathogen-associated molecular patterns (PAMPs) for in situ personalized cancer vaccination. When activated by x-rays, nMOFs effectively generate reactive oxygen species to release DAMPs and tumor antigens while delivering CpG oligodeoxynucleotides as PAMPs to facilitate the maturation of antigen-presenting cells. Together, DAMPs, tumor antigens, and PAMPs expand cytotoxic T cells in tumor-draining lymph nodes to reinvigorate the adaptive immune system for local tumor regression. When treated in combination with an immune checkpoint inhibitor, the local therapeutic effects of nMOF-based vaccines were extended to distant tumors via attenuating T cell exhaustion. Our work demonstrates the potential of nMOFs as x-ray-activable in situ cancer vaccines to awaken the host's innate and adaptive immune systems for systemic antitumor immunity.

Nanoscale Metal-Organic Framework Co-delivers TLR-7 Agonists and Anti-CD47 Antibodies to Modulate Macrophages and Orchestrate Cancer Immunotherapy.

Nanoscale metal-organic frameworks (nMOFs) are excellent radiosensitizers for radiotherapy-radiodynamic therapy (RT-RDT). Herein, we report surface modification of a Hf-DBP nMOF for the co-delivery of a hydrophobic small-molecule toll-like receptor 7 agonist, imiquimod (IMD), and a hydrophilic macromolecule, anti-CD47 antibody (αCD47), for macrophage modulation and reversal of immunosuppression in tumors. IMD repolarizes immunosuppressive M2 macrophages to immunostimulatory M1 macrophages, while αCD47 blocks CD47 tumor cell surface marker to promote phagocytosis. Upon X-ray irradiation, IMD@Hf-DBP/αCD47 effectively modulates the immunosuppressive tumor microenvironment and activates innate immunity to orchestrate adaptive immunity when synergized with an anti-PD-L1 immune checkpoint inhibitor, leading to complete eradication of both primary and distant tumors on a bilateral colorectal tumor model. nMOFs thus provide a unique platform to co-deliver multiple immunoadjuvants for macrophage therapy to induce systematic immune responses and superb antitumor efficacy.

Nanoscale Metal-Organic Frameworks Stabilize Bacteriochlorins for Type I and Type II Photodynamic Therapy.

Herein we report the design of a bacteriochlorin-based nanoscale metal-organic framework, Zr-TBB, for highly effective photodynamic therapy via both type I and type II mechanisms. The framework of Zr-TBB stabilizes 5,10,15,20-tetra(p-benzoato)bacteriochlorin (TBB) ligands toward oxygen and light via geometrical constraint. Upon 740 nm light irradiation, Zr-TBB efficiently generates various reactive oxygen species, including singlet oxygen, superoxide anion, hydrogen peroxide, and hydroxyl radicals, to afford superb antitumor efficacy on mouse models of breast and colon cancers, with cure rates of 40% and 60%, respectively.

A Nanoscale Metal-Organic Framework to Mediate Photodynamic Therapy and Deliver CpG Oligodeoxynucleotides to Enhance Antigen Presentation and Cancer Immunotherapy.

Checkpoint blockade immunotherapy (CBI) awakes a host innate immune system and reactivates cytotoxic T cells to elicit durable response in some cancer patients. Now, a cationic nanoscale metal-organic framework, W-TBP, is used to facilitate tumor antigen presentation by enabling immunogenic photodynamic therapy (PDT) and promoting the maturation of dendritic cells (DCs). Comprised of dinuclear WVI secondary building units and photosensitizing 5,10,15,20-tetra(p-benzoato)porphyrin (TBP) ligands, cationic W-TBP mediates PDT to release tumor associated antigens and delivers immunostimulatory CpG oligodeoxynucleotides to DCs. The enhanced antigen presentation synergizes with CBI to expand and reinvigorate cytotoxic T cells, leading to superb anticancer efficacy and robust abscopal effects with >97 % tumor regression in a bilateral breast cancer model.

Multifunctional Nanoscale Metal-Organic Layers for Ratiometric pH and Oxygen Sensing.

As a monolayered version of nanoscale metal-organic frameworks (nMOFs), nanoscale metal-organic layers (nMOLs) represent an emerging class of highly tunable two-dimensional materials for hierarchical functionalization and with facile access to analytes. Here we report the design of the first nMOL-based biosensor for ratiometric pH and oxygen sensing in mitochondria. Cationic Hf12-Ru nMOL was solvothermally synthesized by laterally connecting Hf12 secondary building units (SBUs) with oxygen-sensitive Ru(bpy)32+-derived DBB-Ru ligands (bpy = 2,2'-bipyridine). The Hf12-Ru nMOL was then covalently functionalized with pH-sensitive fluorescein isothiocyanate and pH/oxygen-independent Rhodamine-B isothiocyanate through thiourea linkages to afford Hf12-Ru-F/R as a mitochondria-targeted ratiometric sensor for pH and O2 in live cells. High-resolution confocal microscope imaging with Hf12-Ru-F/R revealed a positive correlation between pH and local O2 concentration in mitochondria. Our work shows the potential of nMOL-based ratiometric biosensors in sensing and imaging of biologically important analytes in live cells.