Search

We sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy.Retrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis.Assessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease-free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS.Gestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity.

Inquiry-driven teaching methods allow students to take on an active role in their own education. Through this framework, students are able to cultivate an understanding of scientific concepts and their connections while experimenting in the classroom. Our project centered around teaching students about habitats of urban moths, which are abundant in most environments. Based on the students’ hypotheses on where moths might be, homemade moth traps were placed either in a local nature preserve or in the school playground over the course of two nights. Overall, 27 moths were captured. Students then learned how to pin moth specimens and assessed what they could infer from how many moths were captured in each of the collection areas. This project created an environment for students to approach Next Generation Science Standards performance expectations about the diversity of life and how organisms interact with their environments.

The incidence of anal squamous cell carcinoma (ASCC) has been increasing, particularly in populations with HIV. Human papillomavirus (HPV) is the causal factor in 85% to 90% of ASCCs, but few studies evaluated HPV genotypes and integrations in relation to genomic alterations in ASCC. Using whole-exome sequence data for primary (n = 56) and recurrent (n = 31) ASCC from 72 patients, we detected HPV DNA in 87.5% of ASCC, of which HPV-16, HPV-18, and HPV-6 were detected in 56%, 22%, and 33% of HIV-positive (n = 9) compared with 83%, 3.2%, and 1.6% of HIV-negative cases (n = 63), respectively. Recurrent copy-number variations (CNV) involving genes with documented roles in cancer included amplification of PI3KCA and deletion of APC in primary and recurrent tumors; amplifications of CCND1, MYC, and NOTCH1 and deletions of BRCA2 and RB1 in primary tumors; and deletions of ATR, FANCD2, and FHIT in recurrent tumors. DNA damage response genes were enriched among recurrently deleted genes in recurrent ASCCs (P = 0.001). HPV integrations were detected in 29 of 76 (38%) ASCCs and were more frequent in stage III–IV versus stage I–II tumors. HPV integrations were detected near MYC and CCND1 amplifications and recurrent targets included NFI and MUC genes. These results suggest HPV genotypes in ASCC differ by HIV status, HPV integration is associated with ASCC progression, and DNA damage response genes are commonly disrupted in recurrent ASCCs.Implications:These data provide the largest whole-exome sequencing study of the ASCC genomic landscape to date and identify HPV genotypes, integrations, and recurrent CNVs in primary or recurrent ASCCs.

Supplemental Table S1. Clinical characteristics and outcomes by HIV status. Supplemental Table S2. HPV integration sites detected in patient WXS data. Supplemental Table S3. Curated list of 981 cancer-related genes considered in this study.

Supplemental Table S4. Functional ontology enrichment of genes within recurrent CNVs in all ASCC tumors, primary ASCC tumors, and recurrent or metastatic ASCC tumors

Supplemental Figure S1. HPV-18 genome coverage in ASCC. Supplemental Figure S2. Copy number variation in 81 ASCCs.

Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs ∼US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age ≤40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction can be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care. [Cancer Res 2009;69(8):3650–6]

Supplementary Table 1 Legends and References from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Supplementary Table 1 from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Other Supporting Colleagues from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Supplementary Table 2 from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Key Points A dust devil frequency of occurrence of between 1.3 and 3.4 dust devils km−2 sol−1 was derived from MEDA-RDS observations for the first 365 sols, displaying the maximum activity at around noon and increasing as we move from spring into summer We find an average dust devil diameter of 29 m (or a median diameter of 25 m) and maximum and minimum diameters of 132 ± 63.4 m and 5.6 ± 5.5 m Dust devil migration directions are in agreement with the MEDA background wind direction measurements The Mars Environmental Dynamics Analyzer, onboard the Perseverance rover, is a meteorological station that is operating on Mars and includes, among other sensors, the radiometer Radiation and Dust Sensor (RDS). From RDS irradiance observations, a total of 374 dust devils (DDs) were detected for the first 365 sols of the mission (Ls = 6°–182°), which along with wind and pressure measurements, we estimated a DD frequency of formation at Jezero between 1.3 and 3.4 DD km−2 sol−1 (increasing as we move from spring into summer). This frequency is found to be smaller than that estimated at the Spirit or Pathfinder landing sites but much greater than that derived at InSight landing site. The maximum in DD frequency occurs between 12:00 and 13:00 local true solar time, which is when the convective heat flux and lower planetary boundary layer IR heating are both predicted to peak in Jezero crater. DD diameter, minimum height, and trajectory were studied showing (a) an average diameter of 29 m (or a median of 25 m) and a maximum and minimum diameter of 132 ± 63.4 and 5.6 ± 5.5 m; (b) an average minimum DD height of 231 m and a maximum minimum-height of 872 m; and (c) the DD migration direction is in agreement with wind measurements. For all the cases, DDs decreased the UV irradiance, while at visible or near-IR wavelengths both increases and decreases were observed. Contrary to the frequency of formation, these results indicate similar DD characteristics in average for the studied period. This work has been funded by the Spanish Ministry of Economy and Competitiveness, through the projects no. ESP2014-54256-C4-1-R (also -2-R, -3-R and -4-R); Ministry of Science, Innovation and Universities, projects no. ESP2016-79612-C3-1-R (also -2-R and -3-R); Ministry of Science and Innovation/State Agency of Research (10.13039/501100011033), projects no. ESP2016-80320-C2-1-R, RTI2018-098728-B-C31 (also -C32 and -C33), RTI2018-099825-B-C31. RH and ASL were supported by the Spanish project PID2019-109467GB-I00 funded by MCIN/AEI/10.13039/50110001103 and by Grupos Gobierno Vasco IT1742-22. The US co-authors performed their work under sponsorship from NASA’s Mars 2020 project, from the Game Changing Development programme within the Space Technology Mission Directorate and from the Human Exploration and Operations Directorate. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). G.M. acknowledges JPL funding from USRA Contract Number 1638782. ML is supported by contract 15-712 from Arizona State University and 1607215 from Caltech-JPL. Peerreview

Groin hernia repair is performed increasingly more often as an outpatient procedure across the world. However, the rates are extremely different and vary between below 10% and above 90%. The outpatient procedure appears to negatively impact the proportion of laparo-endoscopic repairs. To date, only very few studies have compared inpatient vs outpatient groin hernia repair. All outpatient and inpatient primary elective unilateral groin hernia repairs performed between 2010 and 2019 were identified in the Herniamed Registry and their treatment and outcomes compared. The 737 participating hospitals/surgeons performed a total of 342,072 primary elective unilateral groin hernia repairs from 2010 to 2019. The proportion of outpatient repairs was 20.2% in 2013 and 14.3% in 2019. Whereas the proportion of laparo-endoscopic repairs among the inpatient cases was 71.9% in 2019, the last year for which data are available, it was only 34.3%.for outpatient repairs. In outpatient groin hernia repairs, the rates of patients aged ≥ 60 years, with ASA score III and IV and risk factors were highly significantly lower. Given this rigorous patient selection for outpatient groin hernia repair, a more favorable perioperative outcome was achieved. At 1-year follow-up there were no significant differences in the pain and recurrence rates. With an appropriate patient selection, outpatient primary elective unilateral groin hernia repair can be performed with acceptable risks and good outcomes. Since to date no studies have compared inpatient vs outpatient groin hernia repair, the impact of a higher rate of outpatient groin hernia repair cannot currently be evaluated.

International audience; Two >130-meter-diameter impact craters formed on Mars during the later half of 2021. These are the two largest fresh impact craters discovered by the Mars Reconnaissance Orbiter since operations started 16 years ago. The impacts created two of the largest seismic events (magnitudes greater than 4) recorded by InSight during its 3-year mission. The combination of orbital imagery and seismic ground motion enables the investigation of subsurface and atmospheric energy partitioning of the impact process on a planet with a thin atmosphere and the first direct test of martian deep-interior seismic models with known event distances. The impact at 35°N excavated blocks of water ice, which is the lowest latitude at which ice has been directly observed on Mars.

The Cdc14 phosphatase family is highly conserved in fungi. InSaccharomyces cerevisiae,Cdc14 is essential for down-regulation of cyclin-dependent kinase activity at mitotic exit. However, this essential function is not broadly conserved and requires a small fraction of normal Cdc14 activity. It remains unclear what fungal Cdc14 functions require high Cdc14 activity. We identified an invariant motif in the disordered C-terminal tail of fungal Cdc14 enzymes that is required for full enzyme activity. Mutation of this motif reduced Cdc14 catalytic rate and provided a tool for studying the biological significance of high Cdc14 activity. AS. cerevisiaestrain expressing the reduced-activity hypomorphic mutant allele (cdc14hm) as the sole source of Cdc14 exhibited an unexpected sensitivity to cell wall stresses, including chitin-binding compounds and echinocandin antifungal drugs. Sensitivity to echinocandins was also observed inSchizosaccharomyces pombeandCandida albicansstrains lackingCDC14, suggesting this phenotype reflects a conserved function of Cdc14 orthologs in mediating fungal cell wall integrity. InC. albicans, the orthologouscdc14hmallele was sufficient to elicit echinocandin hypersensitivity and perturb cell wall integrity signaling. It also caused striking abnormalities in septum structure and the same cell separation and hyphal differentiation defects previously observed withcdc14gene deletions. Since hyphal differentiation is important forC. albicanspathogenesis, we assessed the effect of reducing Cdc14 activity on virulence inGalleria mellonellaand mouse models of invasive candidiasis. Partial reduction in Cdc14 activity viacdc14hmmutation severely impairedC. albicansvirulence in both assays. Our results reveal that high Cdc14 activity promotes fungal cell wall integrity and, inC. albicans, is needed to orchestrate septation and hyphal differentiation, and for pathogenesis. Cdc14 may therefore be worth future exploration as an antifungal drug target.AUTHOR SUMMARYInvasive fungal infections are a serious concern for the immune-compromised. Antifungal drugs to treat invasive infections are limited and pathogens are developing resistance to them. Novel targets for antifungal drug development are needed. In this study we developed a system to test if partial therapeutic reduction in activity of a protein phosphatase called Cdc14 could reduce virulence of the opportunistic human pathogenCandida albicans.This idea arose from prior studies in fungal pathogens of plants, where Cdc14 was unexpectedly required for host infection through an unknown mechanism. We found that successfulC. albicansinfections in two animal models of invasive candidiasis were dependent on high Cdc14 activity. Moreover, we made the surprising observation that integrity of theC. albicanscell wall is also dependent on high Cdc14 activity, with Cdc14-deficient cells becoming hypersensitive to cell wall-targeted antifungal drugs. We conclude that even modest reduction in Cdc14 activity could have therapeutic benefit for human fungal infections and possibly help overcome resistance to some antifungal drugs. Cdc14 structure and specificity are unique among phosphatases and highly conserved in pathogenic fungi, suggesting that highly selective inhibitors can be developed that would be useful against a broad range of fungal pathogens.

We characterize vortex and dust devils (DDs) at Jezero from pressure and winds obtained with the Mars Environmental Dynamics Analyzer (MEDA) instrument on Mars 2020 over 415 Martian days (sols) (Ls = 6°–213°). Vortices are abundant (4.9 per sol with pressure drops >0.5 Pa correcting from gaps in coverage) and they peak at noon. At least one in every five vortices carries dust, and 75% of all vortices with Δp > 2.0 Pa are dusty. Seasonal variability was small but DDs were abundant during a dust storm (Ls = 152°–156°). Vortices are more frequent and intense over terrains with lower thermal inertia favoring high daytime surface-to-air temperature gradients. We fit measurements of winds and pressure during DD encounters to models of vortices. We obtain vortex diameters that range from 5 to 135 m with a mean of 20 m, and from the frequency of close encounters we estimate a DD activity of 2.0–3.0 DDs km−2 sol−1. A comparison of MEDA observations with a Large Eddy Simulation of Jezero at Ls = 45° produces a similar result. Three 100-m size DDs passed within 30 m of the rover from what we estimate that the activity of DDs with diameters >100 m is 0.1 DDs km−2sol−1, implying that dust lifting is dominated by the largest vortices in Jezero. At least one vortex had a central pressure drop of 9.0 Pa and internal winds of 25 ms−1. The MEDA wind sensors were partially damaged during two DD encounters whose characteristics we elaborate in detail. The authors are very grateful to the entire Mars 2020 science operations team. The authors would also like to thank Lori Fenton and an anonymous reviewer for many suggestions that greatly improved the manuscript. This work was supported by Grant PID2019-109467GB-I00 funded by MCIN/AEI/10.13039/501100011033/ and by Grupos Gobierno Vasco IT1742-22 and by the Spanish National Research, Development and Innovation Program, through the Grants RTI2018-099825-B-C31, ESP2016-80320-C2-1-R, and ESP2014-54256-C4-3-R. Baptiste Chide is supported by the Director's Postdoctoral Fellowship from the Los Alamos National Laboratory. M. Lemmon is supported by contract 15-712 from Arizona State University and 1607215 from Caltech-JPL. R. Lorenz was supported by JPL contract 1655893. Germán Martínez acknowledges JPL funding from USRA Contract Number 1638782. A. Munguira was supported by Grant PRE2020-092562 funded by MCIN/AEI and by “ESF Investing in your future.” A. Vicente-Retortillo is supported by the Spanish State Research Agency (AEI) Project No. MDM-2017-0737 Unidad de Excelencia “María de Maeztu”-Centro de Astrobiología (INTA-CSIC), and by the Comunidad de Madrid Project S2018/NMT-4291 (TEC2SPACE-CM). Part of the research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). Finnish researchers acknowledge the Academy of Finland Grant 328 310529. Researchers based in France acknowledge support from the CNES for their work on Perseverance.

Rectus abdominis diastasis (RAD) ± concomitant hernia is a complex hernia entity of growing significance in everyday clinical practice. Due to a multitude of described surgical techniques, a so far missing universally accepted classification and hardly existing comparative studies, there are no clear recommendations in guidelines. Therefore, “RAD ± concomitant hernia” will be documented as a separate hernia entity in the Herniamed Registry in the future. For this purpose, an appropriate case report form will be developed on the basis of the existing literature. A systematic search of the available literature was performed in March 2021 using Medline, PubMed, Google Scholar, Scopus, Embase, Springer Link, and the Cochrane Library. 93 publications were identified as relevant for this topic. In total 45 different surgical techniques for the repair of RAD ± concomitant hernia were identified in the surgical literature. RAD ± concomitant hernia is predominantly repaired by plastic but also by general surgeons. Classification of RAD ± concomitant hernia is based on a proposal of the German Hernia Society and the International Endohernia Society. Surgical techniques are summarized as groups subject to certain aspects: Techniques with abdominoplasty, open techniques, mini-less-open and endoscopic sublay techniques, mini-less-open and endoscopic subcutaneous/preaponeurotic techniques and laparoscopic techniques. Additional data impacting the outcome are also recorded as is the case for other hernia entities. Despite the complexity of this topic, documentation of RAD ± concomitant hernia has not proved to be any more cumbersome than for any of the other hernia entities when using this classification. Using the case report form described here, the complex hernia entity RAD ± concomitant hernia can be recorded in a registry for proper analysis of comparative treatment options.

OBJECTIVE. To describe technical aspects and surgical outcomes of endoscopic resection and mucosal reconstitution with epidermal grafting (ie, the Maddern procedure) in the treatment of idiopathic subglottic stenosis. STUDY DESIGN. Medical record abstraction. SETTING. Johns Hopkins Hospital. METHODS. Retrospective series of 9 adults with idiopathic subglottic stenosis who underwent the Maddern procedure by a single surgeon over a 5-year period. Prespecified outcomes included (1) perioperative outcomes (Clavien-Dindo grade 4/5 complications, need for staged tracheostomy, hospital length of stay), (2) postoperative outcomes (peak expiratory flow rate [PEFR], need for subsequent airway surgery, tracheostomy at follow-up), and (3) patient-reported quality-of-life outcomes (Clinical COPD Questionnaire, Voice Handicap Index–10, Eating Assessment Tool–10, and 12-Item Short Form Version 2). Wilcoxon matched-pairs signed rank test and Kaplan-Meier analysis were performed. RESULTS. There were no Clavien-Dindo grade 4/5 complications; 2 patients required unplanned staged tracheostomy; and the median length of stay was 3 days. Following endoscopic resection and stent removal, a median of 2 laser resurfacing procedures were required. Two patients developed recurrent stenosis requiring cricotracheal resection (CTR). There were significant improvements in PEFR, Clinical COPD Questionnaire, and Voice Handicap Index–10, without significant difference in Eating Assessment Tool–10. The 12-Item Short Form Version 2 approximated the population norm. Kaplan-Meier analysis demonstrated significant improvement in time to surgery after the final laser resurfacing. CONCLUSION. The Maddern procedure has a low complication rate and offers durable physiologic improvement in PEFR, limiting need for additional procedures. Risks included need for CTR salvage, temporary tracheostomy, phlegm accumulation, and laryngospasm. It is a surgical option for patients with short dilation intervals who prefer to avoid the risks of CTR.

Nerves in bone play well‐established roles in pain and vasoregulation and have been associated with progression of skeletal disorders, including osteoporosis, fracture, arthritis, and tumor metastasis. However, isolation of the region‐specific mechanisms underlying these relationships is limited by our lack of quantitative methods for neuroskeletal analysis and precise maps of skeletal innervation. To overcome these limitations, we developed an optimized workflow for imaging and quantitative analysis of axons in and around the bone, including validation of Baf53b‐Cre in concert with R26R‐tdTomato (Ai9) as a robust pan‐neuronal reporter system for use in musculoskeletal tissues. In addition, we created comprehensive maps of sympathetic adrenergic and sensory peptidergic axons within and around the full length of the femur and tibia in two strains of mice (B6 and C3H). In the periosteum, these maps were related to the surrounding musculature, including entheses and myotendinous attachments to bone. Three distinct patterns of periosteal innervation (termed type I, II, III) were defined at sites that are important for bone pain, bone repair, and skeletal homeostasis. For the first time, our results establish a gradient of bone marrow axon density that increases from proximal to distal along the length of the tibia and define key regions of interest for neuroskeletal studies. Lastly, this information was related to major nerve branches and local maps of specialized mechanoreceptors. This detailed mapping and contextualization of the axonal subtypes innervating the skeleton is intended to serve as a guide during the design, implementation, and interpretation of future neuroskeletal studies and was compiled as a resource for the field as part of the NIH SPARC consortium. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Organ preservation (OP) treatment for advanced laryngeal cancer has increased compared to primary total laryngectomy. Our study compares oncologic and functional outcomes between these approaches.Retrospective cohort study.Single tertiary care institution.Retrospective review of patients receiving primary total laryngectomy or OP for laryngeal cancer between 1/1/2000 and 12/31/2018.A total of 118 patients received primary total laryngectomy and 119 received OP. Overall survival was similar between total laryngectomy and OP. When stratified by T stage, disease-free survival was worse among T3 patients receiving OP versus total laryngectomy. In T3 patients, 28 OP patients experienced local recurrence (28.9%) compared to 3 total laryngectomy patients (7.1%; p 0.01). In total, 20 OP patients with local recurrence received salvage surgery. These patients had similar overall survival to patients who underwent initial total laryngectomy (TL). About 14 OP patients with local recurrence did not receive salvage surgery. About 89 (75.4%) TL patients achieved normal diet as compared to 64 (53.8%) OP patients (p 0.001). In TL patients, 106 (89.8%) received primary or secondary tracheoesophageal-prosthesis, 82 (77.4%) of whom achieved completely understandable speech.There was no difference in survival by treatment in T4 patients, possibly because of strict patient selection. However, disease-free survival was worse in T3 patients receiving OP, likely due to a high local recurrence rate. Approximately 40% of patients with local recurrence were not eligible for salvage laryngectomy. TL patients had comparable swallowing and speech outcomes with OP patients.3 Laryngoscope, 2022.

Using registry analyses, a large number of influencing factors on the perioperative outcome of groin hernia repair has been identified. The interactions between several influencing factors and differences in the influencing value have to date been inadequately investigated. This retrospective analysis of prospectively collected data from the Herniamed Registry included all fully documented cases with minimum age of 16 years and groin hernia repair. Patients were assigned to the risk groups unilateral, bilateral, recurrent and emergency groin hernia repair. Multivariable analysis was performed to investigate the influence of confirmatory defined patient- and procedure-related characteristics on the outcome parameters intraoperative, postoperative general and postoperative surgical complications, complication-related reoperation and total perioperative complications. A highly significantly unfavorable association with the total perioperative complication rate was identified for emergency groin hernia repair, scrotal hernia, anticoagulant medication and coagulopathy. A significantly unfavorable relation with the total perioperative complication rate was found for recurrence procedure, bilateral repair, high age, ASA score III/IV, femoral hernia, antithrombotic medication, smoking, COPD and corticosteroid medication. A significantly favorable correlation with the total perioperative complication rate was observed for the laparo-endoscopic techniques, smaller defects, female gender, normal weight and medial hernia. Both the number of potential influencing factors and their influencing value on the perioperative outcome should be considered when estimating the individual risk of a patient with groin hernia repair.

The incidence of anal squamous cell carcinoma (ASCC) has been increasing, particularly in populations with HIV. Human papillomavirus (HPV) is the causal factor in 85% to 90% of ASCCs, but few studies evaluated HPV genotypes and integrations in relation to genomic alterations in ASCC. Using whole-exome sequence data for primary (n = 56) and recurrent (n = 31) ASCC from 72 patients, we detected HPV DNA in 87.5% of ASCC, of which HPV-16, HPV-18, and HPV-6 were detected in 56%, 22%, and 33% of HIV-positive (n = 9) compared with 83%, 3.2%, and 1.6% of HIV-negative cases (n = 63), respectively. Recurrent copy-number variations (CNV) involving genes with documented roles in cancer included amplification of PI3KCA and deletion of APC in primary and recurrent tumors; amplifications of CCND1, MYC, and NOTCH1 and deletions of BRCA2 and RB1 in primary tumors; and deletions of ATR, FANCD2, and FHIT in recurrent tumors. DNA damage response genes were enriched among recurrently deleted genes in recurrent ASCCs (P = 0.001). HPV integrations were detected in 29 of 76 (38%) ASCCs and were more frequent in stage III–IV versus stage I–II tumors. HPV integrations were detected near MYC and CCND1 amplifications and recurrent targets included NFI and MUC genes. These results suggest HPV genotypes in ASCC differ by HIV status, HPV integration is associated with ASCC progression, and DNA damage response genes are commonly disrupted in recurrent ASCCs. Implications: These data provide the largest whole-exome sequencing study of the ASCC genomic landscape to date and identify HPV genotypes, integrations, and recurrent CNVs in primary or recurrent ASCCs.

The proportion of epigastric hernias in the total collective of all operated abdominal wall hernias is 3.6–6.9%. The recently published guidelines for treatment of epigastric hernias of the European Hernia Society and the Americas Hernia Society recommend the use of a mesh for defect size of ≥ 1 cm, i.e., a preperitoneal flat mesh technique for sizes 1–4 cm, and laparoscopic IPOM technique for defects > 4 cm and/or obesity. Against that background, this analysis of data from the Herniamed Registry now aims to explore trends in epigastric hernia repair. To detect trends, the perioperative outcome was calculated separately for the years 2010 to 2019 and the 1-year follow-up for the years 2010 to 2018 and significant differences were identified. Analysis was based on 25,518 primary elective epigastric hernia repairs. The rates of postoperative surgical complications, pain at rest, pain on exertion, chronic pain requiring treatment and recurrence associated with the various surgical techniques were calculated separately for each year. Fisher’s exact test for unadjusted analysis between years was applied with Bonferroni adjustment for multiple testing. The proportion of laparoscopic IPOM repairs declined from 26.0% in 2013 to 18.2% in 2019 (p

Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence. Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression. Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.

Based on meta-analyses and registry data, the European Hernia Society and the Americas Hernia Society have published guidelines for the treatment of umbilical hernias. These recommend that umbilical hernia should generally be treated by placing a non-absorbable (permanent) flat mesh into the preperitoneal space with an overlap of the hernia defect of 3 cm. Suture repair should only be considered for small hernia defects of less than 1 cm. Hence, the use of a mesh in general is subject to controversial debate particularly for small (

Background Extracellular vesicles (EVs) are nano-sized particles secreted by most cells. EVs carry nucleic acids that hold promise as potential biomarkers in various diseases. Human immunodeficiency virus type 1 (HIV) infects CD4+ T cells and induces immune dysfunction, inflammation, and EV secretion, but little is known about EV small RNA cargo in relation to immune dysregulation in HIV-infected individuals. Here, we characterize small RNA carried by circulating EVs in HIV-positive subjects on antiretroviral therapy (ART) relative to uninfected controls by next-generation RNA sequencing. Results Plasma EVs isolated from HIV-positive and HIV-negative subjects in test (n = 24) and validation (n = 16) cohorts were characterized by electron microscopy, nanoparticle tracking analysis, and immunoblotting for exosome markers. EVs were more abundant in plasma from HIV-positive compared to HIV-negative subjects. Small RNA sequencing of plasma EVs in the test cohort identified diverse small RNA species including miRNA, piRNA, snRNA, snoRNA, tRNA, and rRNA, with miRNA being the most abundant. A total of 351 different miRNAs were detected in plasma EVs, with the top 50 miRNAs accounting for 90% of all miRNA reads. miR-26a-5p was the most abundant miRNA, followed by miR-21-5p and miR-148-3p. qRT-PCR analysis showed that six miRNAs (miR-10a-5p, − 21-5p, −27b-3p, − 122-5p, −146a-5p, − 423-5p) were significantly increased in plasma EVs from HIV-positive compared to HIV-negative subjects in the validation cohort. Furthermore, miR-21-5p, −27b-3p, −146a-5p, and − 423-5p correlated positively with metabolite markers of oxidative stress and negatively with anti-inflammatory polyunsaturated fatty acids. Over-representation and pathway enrichment analyses of miRNAs and their target genes predicted functional association with oxidative stress responses, interferon gamma signaling, Toll-like receptor signaling, TGF beta signaling, and Notch signaling. Conclusions HIV-positive individuals on ART have increased abundance of circulating EVs carrying diverse small RNAs, with miRNAs being the most abundant. Several miRNAs associated with inflammation and oxidative stress are increased in circulating EVs of HIV-positive individuals, representing potential biomarkers of targetable pathways that contribute to disease pathogenesis.