Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e.g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci.
Most providers prescribed opioids after FESS. There was no significant difference in the number of opioids prescribed based on geography or practice setting. There was significant heterogeneity in the adjuvant pain management strategy between academic and private practitioners. Most members provided patient education and few reported poor pain control. However, there was a gap in understanding of appropriate medication disposal and evidence-based postoperative pain management.
ImportanceThere is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue–modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials.ObjectiveTo establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting.Design, Setting, and ParticipantsThis retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy.Main Outcomes and MeasuresPer-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing.ResultsOf 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days.Conclusions and RelevanceThis cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay’s performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.
Abdominal cocoon is the idiopathic fibrotic encasement of abdominal organs. It classically presents as small bowel obstruction in young women. In this case report, we present a rare example of a patient presenting solely with massive ascites of presumed gynecologic origin, who upon surgical exploration was found to have abdominal cocoon. We discuss the patient’s unique disease presentation, unrevealing work-up and the treatment strategy pursued, and provide a review of the literature.
A 35-year-old man with history of schizophrenia presented 3 weeks after placing a screw in his right nostril. Initial imaging showed a screw in the right ethmoid sinus with the tip penetrating the right cribriform plate. On exam, the patient was hemodynamically stable with purulent drainage in the right nasal cavity but no visible foreign body. While most nasal foreign bodies occur in children and are generally removed at the bedside, intranasal foreign bodies in adults tend to require further assessment. The foreign body in this case was concerning for skull base involvement and the patient was brought to the operating room (OR) with neurosurgery for endoscopic sinus surgery (ESS) and removal of foreign body. The screw was removed and the patient recovered with no signs of cerebrospinal fluid (CSF) leak postoperatively. Any concern for skull base or intracranial involvement should call for a full evaluation of the mechanism of injury and intervention in a controlled environment.
6060 Background: While there are several HPV biomarker assays, a commercially available assay evaluating tumor tissue modified viral DNA (TTMV-HPV DNA) (NavDx, Naveris Inc, Natick, MA) has shown impressive results in clinical trials and small cohort studies. Our aim was to establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary, real-world clinical setting. Methods: In this retrospective analysis, we evaluated the accuracy of the TTMV-HPV DNA assay in detecting HPVOPSCC in the diagnostic (pre-treatment) and surveillance phases of care between April 2020 and October 2022. For the diagnostic cohort, patients with OPSCC and at least one TTMV-HPV DNA measurement prior to initiation of primary therapy were included in the analysis. For the surveillance cohort, all TTMV-HPV DNA tests performed 3 months after completion of primary therapy for pathologically confirmed HPV-associated OPSCC were evaluated, regardless of pre-treatment TTMV-HPV DNA testing. Patients with suspected recurrence, but without pathologic confirmation, were excluded. HPV status was defined utilizing positive p16 staining on immunohistochemistry (93.2% diagnosis; 97.9% surveillance) or HPV polymerase chain reaction/in situ hybridization (79.6% diagnosis; 89.7% surveillance). Results: In the diagnostic cohort, 163 patients were included. The cohort included mostly men (87%) with median age 63, of which 93.3% had HPVOPSCC versus 6.7% had HPV negative OPSCC. The sensitivity in pre-treatment diagnosis was 91.5%; its specificity was 100%. In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. 23 patients had pathologically confirmed recurrences. The assay demonstrated 79.2% sensitivity and 100% specificity in detecting the recurrences. Positive predictive value was 100% and negative predictive value was 98.2%. The median lead time from positive test to pathologic confirmation was 28 days, 6/18 (30%) had lead time >50 days (maximum 507 days). Conclusions: The commercially available NavDx TTMV-HPV DNA assay demonstrated 100% specificity, and therefore excellent positive predictive value, in both diagnosis and surveillance. However, the sensitivity was lower, 91.5% for the diagnosis cohort and 79.2% for the surveillance cohort, signifying that a negative value may require further work-up. Further studies will be required to determine the optimal timing of testing and how results should inform treatment decisions. [Table: see text]
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