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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.

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.

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

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

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)..

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.

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.

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 (

The sixth Coupled Model Intercomparison Project (CMIP6) constitutes the latest update on expected future climate change based on a new generation of climate models. To extract reliable estimates of future warming and related uncertainties from these models, the spread in their projections is often translated into probabilistic estimates such as the mean and likely range. Here, we use a model weighting approach, which accounts for the models' historical performance based on several diagnostics as well as model interdependence within the CMIP6 ensemble, to calculate constrained distributions of global mean temperature change. We investigate the skill of our approach in a perfect model test, where we use previous-generation CMIP5 models as pseudo-observations in the historical period. The performance of the distribution weighted in the abovementioned manner with respect to matching the pseudo-observations in the future is then evaluated, and we find a mean increase in skill of about 17 % compared with the unweighted distribution. In addition, we show that our independence metric correctly clusters models known to be similar based on a CMIP6 “family tree”, which enables the application of a weighting based on the degree of inter-model dependence. We then apply the weighting approach, based on two observational estimates (the fifth generation of the European Centre for Medium-Range Weather Forecasts Retrospective Analysis – ERA5, and the Modern-Era Retrospective analysis for Research and Applications, version 2 – MERRA-2), to constrain CMIP6 projections under weak (SSP1-2.6) and strong (SSP5-8.5) climate change scenarios (SSP refers to the Shared Socioeconomic Pathways). Our results show a reduction in the projected mean warming for both scenarios because some CMIP6 models with high future warming receive systematically lower performance weights. The mean of end-of-century warming (2081–2100 relative to 1995–2014) for SSP5-8.5 with weighting is 3.7 ∘C, compared with 4.1 ∘C without weighting; the likely (66%) uncertainty range is 3.1 to 4.6 ∘C, which equates to a 13 % decrease in spread. For SSP1-2.6, the weighted end-of-century warming is 1 ∘C (0.7 to 1.4 ∘C), which results in a reduction of −0.1 ∘C in the mean and −24 % in the likely range compared with the unweighted case.

Risk of complications following hernia repair is the key parameter to assess risk/benefit ratio of a technique. As mesh devices are permanent, their risks are life-long. Too many reports in the past assessed mesh safety prematurely after short follow-ups. We aimed to explore what length of follow up would reveal the full extent of complications. Time lapses between implantation and excision were analyzed in 460 cases of meshes excised for complications after hernia repair. Patterns of percentage growth and time lapses at 50th and 95th percentiles were used to compare groups of different hernia type, age, gender and reason for excision. The 50th and 95th case percentiles in the dataset were at 3.75 and 15.0 years between mesh implantation and excision. For hernia types, the longest time lapses were for groin hernias (4.0 and 16.11 years at 50th and 95th percentiles). The shortest were for umbilical hernias (2.16 and 9.68 years). Males had later excisions than females (4.11 and 16.1 vs. 2.47 and 9.79 years). Younger patients (

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The Earth System Model Evaluation Tool (ESMValTool), a community diagnostics and performance metrics tool for evaluation and analysis of Earth system models (ESMs), is designed to facilitate a more comprehensive and rapid comparison of single or multiple models participating in the Coupled Model Intercomparison Project (CMIP). The ESM results can be compared against observations or reanalysis data as well as against other models including predecessor versions of the same model. The updated and extended version (v2.0) of the ESMValTool includes several new analysis scripts such as large-scale diagnostics for evaluation of ESMs as well as diagnostics for extreme events, regional model and impact evaluation. In this paper, the newly implemented climate metrics such as effective climate sensitivity (ECS) and transient climate response (TCR) as well as emergent constraints for various climate-relevant feedbacks and diagnostics for future projections from ESMs are described and illustrated with examples using results from the well-established model ensemble CMIP5. The emergent constraints implemented include constraints on ECS, snow-albedo effect, climate–carbon cycle feedback, hydrologic cycle intensification, future Indian summer monsoon precipitation and year of disappearance of summer Arctic sea ice. The diagnostics included in ESMValTool v2.0 to analyze future climate projections from ESMs further include analysis scripts to reproduce selected figures of chapter 12 of the Intergovernmental Panel on Climate Change's (IPCC) Fifth Assessment Report (AR5) and various multi-model statistics.

There are hardly any studies on the outcome of scrotal compared with medial and lateral inguinal hernias. Therefore, this present multivariable analysis of data from the Herniamed Registry compared the outcome of scrotal vs. lateral vs. medial inguinal hernias and explored the relationship between hernia localization and outcomes. Included in the analysis were all primary elective unilateral inguinal hernias in men with scrotal, lateral or medial defect localization whose details had been entered into the Herniamed Registry by 712 participating institutions (status February 1, 2019). The relation of the hernia localization with the outcome parameters adjusted for pre-defined confounding patient- and procedure-related variables was analyzed via multivariable binary logistic models. Details of 98,321 patients were thus available for multivariable analysis. These related to 65,932 (67.1%) lateral, 29,697 (30.2%) medial and 2,710 (2.7%) scrotal inguinal hernias. Scrotal hernias were associated with higher patient age, higher BMI, higher ASA score, larger defect, more risk factors and more frequent use of Lichtenstein repair. On the other hand, scrotal hernias were associated less commonly with preoperative pain. Multivariable analysis revealed that scrotal hernias had a highly significantly unfavorable association with postoperative complications, complication-related reoperations and general complications. But scrotal hernias had a highly significantly favorable relation with the pain rates at 1-year follow-up. Medial hernias were the hernia type most often related with recurrence and also had an unfavorable association with the pain rates at 1-year follow-up. Scrotal inguinal hernias demonstrated a very unfavorable relation with the postoperative complication rate, the rate of complication-related reoperations and the rate of general complications. But a very favorable association with chronic pain rates was identified at 1-year follow-up. Medial inguinal hernia had an unfavorable relation with the recurrence and pain rates.

Inguinal hernias are among the most common surgical diseases in Africa. The current International HerniaSurge Guidelines recommend mesh-based surgical techniques in Low Resource Settings (LRS). This recommendation is currently unachievable in large parts of Africa due to the unaffordability of mesh and lack of appropriate training of the few available surgeons. There is, therefore, a need for formal training in mesh surgery. There is an experience in Hernia Repair for the Underserved in Central and South America, however, inadequate evidence of structured training in Africa. Since 2016, the aid Organizations, Surgeons for Africa and Operation Hernia have developed and employed a structured hernia surgical training program for postgraduate surgical trainees and medical doctors in Rwanda. This course consists of lectures on relevant aspects of hernia surgery and hands-on training in operating theatres. The lectures emphasize anatomy and surgical technique. All parts of the training were evaluated. Formal pre-course evaluation was conducted to assess the personal surgical experience of the trainees. Over a 3-year period, a structured hernia training programme was employed to train a total of 36 surgical trainees in both mesh and also non mesh hernia surgery. The key principle in this course is the continuous competence assessment and feedback. Evidence is provided to demonstrate improvement in surgical skills as well as knowledge of surgical anatomy which is essential to acquiring surgical competency. With self-assessment, expressed on a Likert scale, the participants could improve the theoretical knowledge about hernias from median 4.4 (on a scale of 1–10) before training to 8.4 after the training. The specific knowledge about anatomy could be improved in the same assessment from 4.8 before training to 8.1. after the training. After training course 12 of the 36 participants (33.33%) were able to carry out both suture- and mesh-based operations of simple inguinal hernias completely and independently. 20 of the 36 participants (55.55%) required only minimal supervision and only four participants (11.11%) required surgical supervision even after the completion of the course. We have demonstrated that, medical personnel in Africa can be trained in mesh and non-mesh hernia surgery using a structured training programme.

Background The prevalence and mortality risk of depression in people with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy (ART) is higher than in the general population, yet biomarkers for therapeutic targeting are unknown. In the current study, we aimed to identify plasma metabolites associated with depressive symptoms in people with HIV receiving ART. Methods This is a prospective study of ART-treated HIV-infected adults with or without depressive symptoms assessed using longitudinal Beck Depression Inventory scores. Plasma metabolite profiling was performed in 2 independent cohorts (total n = 99) using liquid and gas chromatography and tandem mass spectrometry. Results Participants with depressive symptoms had lower neuroactive steroids (dehydroepiandrosterone sulfate [DHEA-S], androstenediols, and pregnenolone sulfate) compared with those without depressive symptoms. The cortisol/DHEA-S ratio, an indicator of hypothalamic-pituitary-adrenal axis imbalance, was associated with depressive symptoms (P < .01) because of low DHEA-S levels, whereas cortisol was similar between groups. The odds of having depressive symptoms increased with higher cortisol/DHEA-S ratios (adjusted odds ratio, 2.5 per 1-unit increase in z score; 95% confidence interval, 1.3–4.7), independent of age and sex. The kynurenine-to-tryptophan ratio showed no significant associations. Conclusions These findings suggest that altered neuroactive steroid metabolism may contribute to the pathophysiological mechanisms of depression in ART-treated HIV-infected adults, representing a potential biological pathway for therapeutic targeting., Depression is a major challenge for people with human immunodeficiency virus (HIV). Adults with depressive symptoms had lower neuroactive steroid metabolites than those without depressive symptoms, highlighting the importance of hypothalamic-pituitary-adrenal axis dysregulation in HIV-infected adults with depression.

To characterize the recurrence of head and neck paragangliomas and the factors associated with disease progression after treatment.Retrospective cohort study.Tertiary care center.In total, 173 adults with 189 paragangliomas (41.3% carotid body, 29.1% glomus jugulare, 19.0% glomus tympanicum, and 10.6% glomus vagale) treated between 1990 and 2010 were evaluated to determine the incidence and risk of recurrence using Cox proportional hazards.The mean (SD) follow-up duration was 8.6 (9.1) years. The incidence was 2.92 recurrences per 100 person-years. The rate of recurrence was 8.2% (95% confidence interval [CI], 3.7-12.7) after 4 years and 17.1% (95% CI, 10.2-24.0) after 10 years. Glomus jugulare tumors were more likely to recur (hazard ratio [HR], 3.69; 95% CI, 1.70-8.01;Recurrence is more common with glomus jugulare tumors and less common with carotid body tumors. Radiation may have a lower risk of recurrence or progression than surgery for some paraganglioma types. Metastasis is rare but more likely with recurrent disease. Surveillance neck imaging is recommended every several years for decades after treatment.

Poorly differentiated thyroid cancer (PDTC) is a rare but aggressive subtype of thyroid cancer that portends a poor prognosis. There remains a paucity of literature on PDTC outcomes. The aim of our study was to evaluate outcomes of PDTC in our tertiary care facility.We identified all histologically confirmed PDTC cases from 1997-2018 treated at our Institution and collected data points in an IRB-approved registry. We then conducted a retrospective study to assess outcomes and identified factors associated with inferior outcomes.Twenty-three patients were identified with a median age at diagnosis of 60 years (range=39-89 years). Nineteen (83%) underwent total thyroidectomy. Eight (42%) patients had lymph node dissections and 2 (11%) underwent adjuvant radiation. Thirteen (68%) patients were treated with radioactive iodine (RAI). Those who underwent total thyroidectomy had a median overall survival (mOS) of 88 months, 5 year-OS of 56%, 5 year-local recurrence-free survival (LRFS) of 45%, and 5 year-distant recurrence-free survival (DRFS) of 36%. T4 disease had worse mOS (14 vs. 87 m, p=0.0082), and 5 year-LRFS rate (12 vs. 74%, p=0.0312) compared to T1-3. N0 disease had an improved mOS (172 vs. 32 m, p=0.0013), 5 year-LRFS rate (63 vs. 17%, p=0.0033), and 5 year-DRFS (57 vs. 0%, p=0.0252). Eight out of 23 patients (35%) were alive at last follow-up, with a median of 68 months (range=20-214). The most common cause of death was distant recurrence (73%). Six patients received systemic therapy with various tyrosine kinase inhibitors with a median duration on treatment of 7 months (range=1-30 months).Advanced T and N stage were factors associated with significantly inferior outcomes. While select patients benefited with systemic treatment, it remains unclear if intensified locoregional therapy should be considered in patients with PDTC.