Divergent functions of histone acetyltransferases KAT2A and KAT2B in keratinocyte self-renewal and differentiation.

The mammalian epidermis undergoes constant renewal, replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology that are orchestrated, in part, by epigenetic modifiers. Here, we define the role of the histone acetyltransferase KAT2A in epidermal homeostasis and provide a comparative analysis that reveals key functional divergence with its paralog KAT2B. In contrast to the reported function of KAT2B in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whereas loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B-mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes use a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes.

Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction.

Argonaute 2 (AGO2) is a ubiquitously expressed protein critical for regulation of mRNA translation and vital to animal development. AGO2 protein is found in both cytoplasmic and nuclear compartments, and although its cytoplasmic role is well studied, the biological relevance of nuclear AGO2 is unclear. Here, we address this problem in vivo using spermatogenic cells as a model. We find that AGO2 transiently binds both chromatin and nucleus-specific mRNA transcripts of hundreds of genes required for sperm production during male meiosis in mice, and that germline conditional knockout (cKO) of Ago2 causes depletion of the encoded proteins. Correspondingly, Ago2 cKO males show abnormal sperm head morphology and reduced sperm count, along with reduced postnatal viability of offspring. Together, our data reveal an unexpected nuclear role for AGO2 in enhancing expression of developmentally important genes during mammalian male reproduction.

Evaluating the Impact of the Novel Geographic Preferences Section on Interview Rate and Residency Match Outcomes.

BACKGROUND: The American Association of Medical Colleges trialed residency application initiatives including geographic preferences and preference signals in 2022. OBJECTIVE: To assess the impact of geographic preferences on application outcomes during the 2022 residency match year. DESIGN: Cross-sectional. PARTICIPANTS: Applicants to categorical and preliminary internal medicine during the 2022 application cycle who completed the Texas Seeking Transparency in Applications to Residency survey. MAIN MEASURES: The primary outcome was interview rate (interview offers/total applications) and whether an application resulted in a match. The key dependent variables were geographic preferences and program-specific preference signals. We also assessed differences in utilization of geographic preferences between specialties. KEY RESULTS: A total of 970 applicants into categorical (n = 884) and preliminary (n = 86) internal medicine were included in our study. A total of 704 (72.6%) applicants submitted at least one geographic preference and 424 (43.7%) submitted three preferences. On average, applicants who submitted a geographic preference had a higher interview rate than those who did not (46.0% vs. 41.8%). Applications submitted with both a preference signal and geographic preference were significantly more likely to receive an interview offer (OR: 3.2, p < 0.01) and match (OR: 6.4, p < 0.01) than applications with neither a preference signal nor a geographic preference. Geographic preferences were associated with an increase in the odds of an application receiving an interview offer, even in the setting of a preference signal (OR: 1.4, p < 0.01). CONCLUSIONS: Both preference signals and geographic preferences have significant associations with odds of an application receiving an interview and matching for both categorical and preliminary internal medicine applicants. This study can be used to inform applicants, advisors, and programs how novel application strategies can affect important application outcomes for US medical school graduates. As more specialties pilot alternative processes, it will be important to study all application outcomes among varying applicant populations.

Tracheostomy-related durable medical equipment: Insurance coverage, gaps, and barriers.

PURPOSE: Tracheostomy care is supply- and resource-intensive, and airway-related adverse events in community settings have high rates of readmission and mortality. Devices are often implicated in harm, but little is known about insurance coverage, gaps, and barriers to obtaining tracheostomy-related medically necessary durable medical equipment. We aimed to identify barriers patients may encounter in procuring tracheostomy-related durable medical equipment through insurance plan coverage. MATERIALS AND METHODS: Tracheostomy-related durable medical equipment provisions were evaluated across insurers, extracting data via structured telephone interviews and web-based searches. Each insurance company was contacted four times and queried iteratively regarding the range of coverage and co-pay policies. Outcome measures include call duration, consistency of explanation of benefits, and the number of transfers and disconnects. We also identified six qualitative themes from patient interviews. RESULTS: Tracheostomy-related durable medical equipment coverage was offered in some form by 98.1 % (53/54) of plans across 11 insurers studied. Co-pays or deductibles were required in 42.6 % (23/54). There was significant variability in out-of-pocket expenditures. Fixed co-pays ranged from $0-30, and floating co-pays ranged from 0 to 40 %. During phone interviews, mean call duration was 19 ± 10 min, with an average of 2 ± 1 transfers between agents. Repeated calls revealed high information variability (mean score 2.4 ± 1.5). Insurance sites proved challenging to navigate, scoring poorly on usability, literacy, and information quality. CONCLUSIONS: Several factors may limit access to potentially life-saving durable medical equipment for patients with tracheostomy. Barriers include out-of-pocket expenditures, lack of transparency on coverage, and low-quality information. Further research is necessary to evaluate patient outcomes.

Relapsing Fever Caused by Borrelia lonestari after Tick Bite in Alabama, USA.

We report an immunocompromised patient in Alabama, USA, 75 years of age, with relapsing fevers and pancytopenia who had spirochetemia after a tick bite. We identified Borrelia lonestari by using PCR, sequencing, and phylogenetic analysis. Increasing clinical availability of molecular diagnostics might identify B. lonestari as an emerging tickborne pathogen.

Trends in acute ischemic stroke treatments and mortality in the United States from 2012 to 2018.

OBJECTIVE: The establishment of mechanical thrombectomy (MT) as a first-line treatment for select patients with acute ischemic stroke (AIS) and the expansion of stroke systems of care have been major advancements in the care of patients with AIS. In this study, the authors aimed to identify temporal trends in the usage of tissue-type plasminogen activator (tPA) and MT within the AIS population from 2012 to 2018, and the relationship to mortality. METHODS: Using a nationwide private health insurance database, 117,834 patients who presented with a primary AIS between 2012 and 2018 in the United States were identified. The authors evaluated temporal trends in tPA and MT usage and clinical outcomes stratified by treatment and age using descriptive statistics. RESULTS: Among patients presenting with AIS in this population, the mean age was 69.1 years (SD ± 12.3 years), and 51.7% were female. Between 2012 and 2018, the use of tPA and MT increased significantly (tPA, 6.3% to 11.8%, p < 0.0001; MT, 1.6% to 5.7%, p < 0.0001). Mortality at 90 days decreased significantly in the overall AIS population (8.7% to 6.7%, p < 0.0001). The largest reduction in 90-day mortality was seen in patients treated with MT (21.4% to 14.1%, p = 0.0414) versus tPA (11.8% to 7.0%, p < 0.0001) versus no treatment (8.3% to 6.3%, p < 0.0001). Age-standardized mortality at 90 days decreased significantly only in patients aged 71-80 years (11.4% to 7.8%, p < 0.0001) and > 81 years (17.8% to 11.6%, p < 0.0001). Mortality at 90 days stagnated in patients aged 18 to 50 years (3.0% to 2.2%, p = 0.4919), 51 to 60 years (3.8% to 3.9%, p = 0.7632), and 61 to 70 years (5.5% to 5.2%, p = 0.2448). CONCLUSIONS: From 2012 to 2018, use of tPA and MT increased significantly, irrespective of age, while mortality decreased in the entire AIS population. The most dramatic decrease in mortality was seen in the MT-treated population. Age-standardized mortality improved only in patients older than 70 years, with no change in younger patients.

Relationship of Water Content With Silicon and Fluorine Contents of Silicone-Hydrogel Contact Lens Materials.

OBJECTIVES: The relationship between water (W) content and silicon (Si) content of silicone-hydrogel (SiHy) contact lens materials was inspected using identical methodologies, equipment, and operators for materials composing 16 types of commercially available SiHy contact lenses. Fluorine (F) content was included in the analysis for the three materials also containing a fluoropolymer. One type of lens consisted of a bulk SiHy material coated with thin layers of conventional hydrogel. METHODS: SiHy materials were obtained in the form of 16 contact lens brands purchased on the open market in a common range of refractive powers from -3 to +6 D in single lots. All test lenses were equilibrated at room temperature in a standard saline recommended in the American National Standards Institute Z80.20-2016 and International Organization for Standardization (ISO) 18369-4:2017 standards. W content was obtained gravimetrically, in %, according to those standards for 16 lenses of each SiHy material. Si content was determined in % using inductively coupled plasma optical emission spectroscopy for four digested lenses of each material. F content was determined in % using an ion-selective electrode for four combusted lenses of each of the three fluorinated SiHy materials. W and Si contents of the bulk SiHy material of the coated lens were estimated by computational exclusion of the hydrogel layers. RESULTS: The linear coefficients of determination (R, n=16) were -0.7576 (relating mean dry Si content [n=4] to mean W content [n=16]) and -0.8819 (relating mean hydrated Si content [n=4] to mean W content [n=16]). When the 4 SiHy materials that were fluorinated or coated were excluded from the analysis, the R values (n=12) were -0.8869 and -0.9263, respectively. When F contents and the coating were added to the assessments, the linear coefficients of determination (R, n=16) became -0.8948 (relating mean dry [Si+F] content to mean W content) and -0.9397 (relating mean hydrated [Si+F] content to mean W content). CONCLUSIONS: There is a fundamental negative linear relationship between Si and W contents for SiHy contact lens materials above 35% W content that is followed when F content and hydrogel coatings are empirically added to the analysis below 35% W content. The relationship was tightest for hydrated (Si+F) content and W content, for which the regression equation had an R of -0.9397: (Si+F)=-0.3073 (W)+22.148. The relationship between (Si+F) and W therefore seems to be based on composition rather than structure of available SiHy contact lens materials.

Discovery and Characterization of Human-Urine Utilization by Asymptomatic-Bacteriuria-Causing Streptococcus agalactiae.

Streptococcus agalactiae causes both symptomatic cystitis and asymptomatic bacteriuria (ABU); however, growth characteristics of S. agalactiae in human urine have not previously been reported. Here, we describe a phenotype of robust growth in human urine observed in ABU-causing S. agalactiae (ABSA) that was not seen among uropathogenic S. agalactiae (UPSA) strains isolated from patients with acute cystitis. In direct competition assays using pooled human urine inoculated with equal numbers of a prototype ABSA strain, designated ABSA 1014, and any one of several UPSA strains, measurement of the percentage of each strain recovered over time showed a markedly superior fitness of ABSA 1014 for urine growth. Comparative phenotype profiling of ABSA 1014 and UPSA strain 807, isolated from a patient with acute cystitis, using metabolic arrays of >2,500 substrates and conditions revealed unique and specific l-malic acid catabolism in ABSA 1014 that was absent in UPSA 807. Whole-genome sequencing also revealed divergence in malic enzyme-encoding genes between the strains predicted to impact the activity of the malate metabolic pathway. Comparative growth assays in urine comparing wild-type ABSA and gene-deficient mutants that were functionally inactivated for the malic enzyme metabolic pathway by targeted disruption of the maeE or maeK gene in ABSA demonstrated attenuated growth of the mutants in normal human urine as well as synthetic human urine containing malic acid. We conclude that some S. agalactiae strains can grow in human urine, and this relates in part to malic acid metabolism, which may affect the persistence or progression of S. agalactiae ABU.

Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile.

BACKGROUND: Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient's gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice. RESULTS: A total of nine samples from three human donors, recipient's pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01%). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8%, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55%, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2-4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7% of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10%. CONCLUSION: We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections.

The effects of differences in pspA alleles and capsular types on the resistance of Streptococcus pneumoniae to killing by apolactoferrin.

Pneumococcal surface protein A (PspA) is the only pneumococcal surface protein known to strongly bind lactoferrin on the bacterial surface. In the absence of PspA Streptococcus pneumoniae becomes more susceptible to killing by human apolactoferrin (apo-hLf), the iron-free form of lactoferrin. In the present study we examined diverse strains of S. pneumoniae that differed by 2 logs in their susceptibility to apo-hLf. Among these strains, the amount of apo-hLf that bound to cell surface PspA correlated directly with the resistance of the strain to killing by apo-hLf. Moreover examination of different pspA alleles on shared genetic backgrounds revealed that those PspAs that bound more lactoferrin conferred greater resistance to killing by apo-hLf. The effects of capsule on killing of pneumococci by apo-hLf were generally small, but on one genetic background, however, the lack of capsule was associated with 4-times as much apo-hLf binding and 30-times more resistance to killing by apo-hLf. Overall these finding strongly support the hypothesis that most of the variation in the ability of apo-hLf is dependent on the variation in the binding of apo-hLf to surface PspA and this binding is dependent on variation in PspA as well as variation in capsule which may enhance killing by reducing the binding of apo-hLf to PspA.

Copper complexation screen reveals compounds with potent antibiotic properties against methicillin-resistant Staphylococcus aureus.

Macrophages take advantage of the antibacterial properties of copper ions in the killing of bacterial intruders. However, despite the importance of copper for innate immune functions, coordinated efforts to exploit copper ions for therapeutic interventions against bacterial infections are not yet in place. Here we report a novel high-throughput screening platform specifically developed for the discovery and characterization of compounds with copper-dependent antibacterial properties toward methicillin-resistant Staphylococcus aureus (MRSA). We detail how one of the identified compounds, glyoxal-bis(N4-methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent antibacterial properties on MRSA. Our data indicate that the activity of the GTSM-copper complex goes beyond the general antibacterial effects of accumulated copper ions and suggest that, in contrast to prevailing opinion, copper complexes can indeed exhibit species- and target-specific activities. Based on experimental evidence, we propose that copper ions impose structural changes upon binding to the otherwise inactive GTSM ligand and transfer antibacterial properties to the chelate. In turn, GTSM determines target specificity and utilizes a redox-sensitive release mechanism through which copper ions are deployed at or in close proximity to a putative target. According to our proof-of-concept screen, copper activation is not a rare event and even extends to already established drugs. Thus, copper-activated compounds could define a novel class of anti-MRSA agents that amplify copper-dependent innate immune functions of the host. To this end, we provide a blueprint for a high-throughput drug screening campaign which considers the antibacterial properties of copper ions at the host-pathogen interface.

How Does Lacking a Home Program Impact Otolaryngology Applicants?

OBJECTIVES: To compare otolaryngology interview and match outcomes between applicants with and without home residency programs. METHODS: Otolaryngology applicants from US allopathic medical schools during the 2019-2023 cycles who responded to the Texas Seeking Transparency in Application to Residency (STAR) survey were identified. Students were stratified based upon whether their medical school had an affiliated otolaryngology residency program. The primary outcomes were number of interviews and match rate. Wilcoxon-rank sum and χ2 testing was used to assess associations between home program status and interview and match outcomes. RESULTS: Of the 633 fourth-year medical students applying to otolaryngology during the 2019-2023 application cycles, 89 had no home program (NHP) and 544 had a home program (HP). Applicants with NHP completed significantly more away rotations than applicants with a HP (2.2 vs. 1.5; p < 0.01). There was no difference in mean number of applications submitted between applicants with NHP and applicants with a HP. However, applicants with a HP received a significantly greater number of interviews (14.7 vs. 11.8; p < 0.01), attended more interviews (12.4 vs. 11.3; p = 0.02), attended a lower percentage of their offered interviews (84.4% vs. 95.8%), and had a higher match rate (81.8% vs. 70.8%; p = 0.02) than applicants with NHP. Applicants with NHP interviewed at (1.9 vs. 1.3; p < 0.01) and matched at (33.7% vs. 23.9%; p = 0.048) significantly more away rotation institutions than applicants with a HP. CONCLUSION: Applicants with NHP received fewer interviews and had lower match rates. Away rotations may be especially important for applicants with NHP. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Does Geographic Region of Away Rotations Predict Otolaryngology Match Outcomes?

OBJECTIVE: To assess whether the geographic region where medical students complete an away rotation predicts the same site, region-specific, or overall interview offers and match success in otolaryngology. STUDY DESIGN: Cross-sectional. SETTING: US medical schools. METHODS: We queried the Texas Seeking Transparency in Application to Residency database to analyze outcomes of otolaryngology applicants during the 2018 to 2020 and 2022 match cycles. Outcomes included a number of interviews offered, geographic location of interviews, and match results, including region-specific and overall match success rate. RESULTS: Of 455 otolaryngology applicants, 402 (90.3%) completed an away rotation. Among these, 368 (91.8%) were offered an interview and 124 (30.9%) matched to the program where they completed an away rotation. Applicants who completed away rotations outside their home region received more interview offers from that region than those who did not (Northeast: 4.2 vs 2.9; South: 4.3 vs 3.0; Central: 4.8 vs 3.0; West: 3.8 vs 1.6, P < .01 for all). Completing a remote away rotation increased the odds of receiving an interview from and matching within that region. After excluding programs where an away rotation was completed, a remote away rotation increased the odds of receiving an interview in the central and western regions (Central: odds ratio [OR]: 1.2 [1.1, 1.5]); West OR: 1.9 [1.7, 2.2]; and the odds of matching in the western region (OR: 2.9 [1.2, 7.4], all P < .01). CONCLUSION: Away rotations are associated with increased odds of interviewing and matching at that away program, with possible associations across the region, most evident for the West coast.

Impact of Applicants' Characteristics and Geographic Connections to Residency Programs on Preference Signaling Outcomes in the Match.

PURPOSE: To assess the impact of applicant and residency program characteristics on preference signaling outcomes in the Match during the first 2 years of implementation across 6 specialties. METHOD: Data were obtained from the Texas Seeking Transparency in Application to Residency survey for applicants applying into otolaryngology during the 2020-2021 and 2021-2022 application cycles and into dermatology, internal medicine (categorical and preliminary year), general surgery, and urology during the 2021-2022 application cycle. The primary outcome was signal yield, defined as the number of interviews at signaled programs divided by the total number of signals sent. Associations with applicant-reported characteristics and geographic connections to residency programs were assessed using Wilcoxon rank sum testing, Spearman's rank correlation testing, and ordinary least squares regression. RESULTS: 1,749 applicants with preference signaling data were included from internal medicine (n = 884), general surgery (n = 291), otolaryngology (n = 217), dermatology (n = 147), urology (n = 124), and internal medicine preliminary year (n = 86). On average 60.9% (standard deviation 32.3%) of signals resulted in an interview (signal yield). There was a stepwise increase in signal yield with the percentage of signals sent to programs with a geographic connection (57.3% for no signals vs. 68.9% for 5 signals, P < .01). Signal yield was positively associated with applicant characteristics, such as United States Medical Licensing Exam Step 1 and 2 scores, honors society membership, and number of publications ( P < .01). Applicants reporting a lower class rank quartile were significantly more likely to have a higher percentage of their interviews come from signaled programs ( P < .01). CONCLUSIONS: Signal yield is significantly associated with geographic connections to residency programs and applicant competitiveness based on traditional metrics. These findings can inform applicants, programs, and specialties as preference signaling grows.

Association of Medical School Gap Year Research and Degree Programs With Otolaryngology Interview and Match Outcomes.

OBJECTIVE: To investigate whether a gap year for either research or a master's degree is associated with interview offers or match outcomes among otolaryngology applicants. METHODS: Using the Texas Seeking Transparency in Application to Residency (Texas STAR) database, we conducted a cross-sectional analysis of otolaryngology applicants from 2018 to 2022. Applicants were stratified based on the presence and type of gap year during medical school. Applicant characteristics, signaling, research productivity, and application costs were analyzed, with primary outcomes including number of interview offers and match status. RESULTS: Among 564 otolaryngology applicant respondents to the Texas STAR survey, 160 (28%) reported a gap year, including 64 (40%) applicants participating in a research year, 65 (41%) completing a Master of Public Health or Science (MPH and MSc), and 31 (19%) completing a Master of Business Administration, Education, or other degree (MBA and MEd). Gap-year applicants who completed a research year or MPH/MSc degree received more interview offers (P < .01) than MBA, MEd applicants, or those without a gap year. Applicants with a research year had the most publications, oral presentations, abstracts, posters, and research experiences (all P < .01). When controlling for USMLE scores, clerkship honors, and applications submitted, applicants completing a research year or an MPH/MSc-degree received increased interview offers (P < .01). No significant differences were seen in expenditures or match rates. CONCLUSIONS: Research and MPH/MSc gap years were associated with increased residency interview offers but not increased match success. Further longitudinal studies are needed to assess how yearlong experiences affect long-term career outcomes.

Human-specific epigenomic states in spermatogenesis.

Infertility is becoming increasingly common, affecting one in six people globally. Half of these cases can be attributed to male factors, many driven by abnormalities in the process of sperm development. Emerging evidence from genome-wide association studies, genetic screening of patient cohorts, and animal models highlights an important genetic contribution to spermatogenic defects, but comprehensive identification and characterization of the genes critical for male fertility remain lacking. High divergence of gene regulation in spermatogenic cells across species poses challenges for delineating the genetic pathways required for human spermatogenesis using common model organisms. In this study, we leveraged post-translational histone modification and gene transcription data for 15,491 genes in four mammalian species (human, rhesus macaque, mouse, and opossum), to identify human-specific patterns of gene regulation during spermatogenesis. We combined H3K27me3 ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data to define epigenetic states for each gene at two stages of spermatogenesis, pachytene spermatocytes and round spermatids, in each species. We identified 239 genes that are uniquely active, poised, or dynamically regulated in human spermatogenic cells distinct from the other three species. While some of these genes have been implicated in reproductive functions, many more have not yet been associated with human infertility and may be candidates for further molecular and epidemiologic studies. Our analysis offers an example of the opportunities provided by evolutionary and epigenomic data for broadly screening candidate genes implicated in reproduction, which might lead to discoveries of novel genetic targets for diagnosis and management of male infertility and male contraception.

Nationwide trends in intensive care unit utilization in the elective endovascular treatment of unruptured intracranial aneurysms.

OBJECTIVE: Multiple studies suggest routine post-operative intensive care unit (ICU) stays after endovascular treatment (EVT) of unruptured intracranial aneurysms (UIAs) is unnecessary, though rates of ICU utilization nationwide are unknown. We aim to evaluate rates and characteristics of ICU utilization in patients undergoing elective endovascular repair of UIAs. METHODS: This is a retrospective cohort study utilizing a nationwide private-payer database in the United States to evaluate the ICU utilization in patients undergoing elective endovascular repair of UIAs between 2005 and 2019. Demographics and pre-operative comorbidities as well as post-procedural complications and discharge status were compared. An analysis of charges and costs was also performed. RESULTS: Among 6218 patients who underwent elective EVT of a UIA, 4890 (78.6%) were admitted to the ICU post-operatively. There were no differences in age, sex, or Charlson comorbidity scores in patients admitted to the ICU post-operatively compared to those admitted elsewhere. ICU utilization was more common in urban locations compared to rural. 12.7% of patients had ICU-specific needs sufficient to be billed by a critical care provider. Total provider costs were significantly higher in patients utilizing the ICU post-operatively, even among uncomplicated patients with routine discharges. CONCLUSION: Most patients undergoing elective endovascular UIA repair in the United States are admitted to the ICU postoperatively. Only 12.7% have ICU needs, and these patients are predictable from pre-operative characteristics or peri-operative complications. Reducing ICU use in this subgroup of patients may be an important target to improve healthcare value in this patient population.

Utility of bioselection with neoadjuvant chemotherapy for organ preservation in patients with T4 laryngeal cancer.

BACKGROUND: Neoadjuvant chemotherapy for induction selection of definitive treatment (IS) protocols have shown excellent outcomes for organ preservation and survival in patients with T3 laryngeal squamous cell carcinoma (LSCC). We seek to evaluate survival and organ preservation outcomes in T4 LSCC patients treated with IS protocols. METHODS: Retrospective cohort of advanced T3 and T4 LSCC patients who underwent IS protocols based upon potential for preserving a functional larynx. Patients received one neoadjuvant cycle of platinum-based chemotherapy with either 5-fluorouracil or docetaxel or with two cycles of platinum-based chemotherapy with docetaxel and a Bcl-2 inhibitor. Patients who achieved ≥ 50 % response as determined by radiographic review and/or endoscopic evaluation received definitive chemoradiation. Patients who had < 50 % response after IS underwent total laryngectomy (TL) followed by post-operative radiation +/- chemotherapy. RESULTS: Amongst T4 patients, 114 met inclusion criteria including 89 who underwent IS protocols and 25 who received an upfront TL. In total, 76.0 % of T3 patients and 71.9 % of T4 patients responded to IS and underwent definitive chemoradiation. There was no significant difference in hazard of death between T4 IS and T4 TL patients (HR: 0.9, p = 0.86). Among responders, there was no significant difference in 5-year laryngectomy-free survival (T3 - 59.6 %, T4 44.3 %, p = 0.15) or laryngeal preservation by T stage (T3 - 72.8 %, T4 - 73.0 %, p = 0.84). CONCLUSIONS: Select T4 patients may benefit from organ preservation using IS protocols with similar response rates to patients with T3 tumors, without compromising survival when compared to upfront TL.

Role of the otologist/neurotologist in managing auricular and periauricular cutaneous malignancies: A 10-year otologic oncology experience.

Objective: Auricular/periauricular cutaneous malignancies can be challenging to manage surgically due to the complex anatomy of the region. Otologists/neurotologists have unique skillsets that are well-suited to surgically treat these patients. We aim to highlight the role of otologists and neurotologists in providing surgical care of patients with auricular and periauricular malignancies by describing the experience of a single fellowship-trained neurotologist over a 10-year period. Methods: Retrospective chart review of 387 patients with auricular and periauricular malignancy treated by a single neurotologist between 2012 and 2022 was completed. Tumor histology and procedures performed for each patient were extracted. Additional data was collected for a subset of 84 patients with complex cases requiring selective neck dissection, parotidectomy, lateral temporal bone resection, regional advancement or rotational flap reconstruction, and/or free tissue transfer reconstruction. Results: Within the series of 387 patients, squamous cell carcinoma was the most common histology (42.6%, n = 165), followed by basal cell carcinoma (40.8%, n = 158), and melanoma (9.8%, n = 38). Common surgical procedures included wide local excision (61.8%, n = 239), partial/sub-total auriculectomy 18.3% (n = 71), or total auriculectomy 5.2% (n = 20). Within the 84-patient subset, median age at diagnosis was 71.9 years. Dermatologists provided most patient referrals (50.0%, n = 42). Most common tumor locations included: auricular (58.3%, n = 49), pre-auricular (21.4%, n = 18), and parotid (27.4%, n = 23). Revision surgery occurred in 22.6% of cases (n = 19), of which 26.3% (n = 5) for positive margins and 31.6% (n = 6) for recurrence. Mean follow-up was 22.8 months. Disease-specific 5-year survival was 91%. Conclusions: We demonstrate the feasibility of an otologist/neurotologist incorporating the surgical management of auricular and periauricular malignancies into their practice. Level of Evidence: 4.

Impact of applicant and program factors on preference signaling outcomes in otolaryngology.

Objectives: To assess the impact of applicant and program characteristics on preference signaling outcomes during the 2021 and 2022 application cycles in otolaryngology. Methods: The Texas Seeking Transparency in Applications to Residency survey was used for otolaryngology applicants during the 2021 and 2022 match years. The primary outcome of interest was signal yield, defined as the number of interviews at signaled programs divided by the total number of signals sent. Associations with applicant-reported characteristics, geographic connections to programs, and program reputation were assessed. Results: On average 59.5% of signals resulted in an interview (signal yield). There was a positive correlation between the number of signals sent to a program with a reported geographic connection and signal yield, with each additional signal resulting in a 3.4% increase in signal yield (p = .03). Signal yield was positively associated with number of publications (p < .001); number of abstracts, posters, and presentations (p = .04); and whether the applicant took a research year (p = .003). Applicants with higher USMLE Step 1 (p = .01) and Step 2 (p = .003) scores, publications (p = .03), volunteer (p = .008) and leadership (p = .001) experiences received a lower percentage of their total interviews from signaled programs whereas applicants from the 3rd (p < .001) and 4th (p = .03) cumulative class ranked quartiles received a higher percentage of their total interviews from signaled programs. Conclusions: Signal yield appears to have a significant association with geographic connections to programs and applicant competitiveness. This study may help applicants, advisors, and programs maximize the benefit of the preference signaling system.Levels of evidence: Level 4.