Oral HPV infection clearance and acquisition after nonavalent vaccination in men who have sex with men and transgender women: a prospective analysis.

Oral HPV infection is the main risk factor for the development of oropharyngeal carcinoma. Men who have sex with men (MSM), especially if living with HIV (PLWH), are at increased risk of infection and consequently of cancer development. Aim of this study is to evaluate the impact of nonavalent vaccine on oral HPV infection in a cohort of MSM and transgender women (TGW). This prospective study included all MSM and TGW who started nonavalent HPV vaccination from May 2019 to September 2021. Oral rinse was collected before each vaccine administration and after six months of follow up. Descriptive statistics were used. Kaplan Meier probability curves and Cox regression models for HPV acquisition and clearance were calculated. The analysis included 211 individuals (202 MSM and 9 TGW). PLWH were 138 (65.4%). Baseline oral rinse was positive in 30 subjects (14.2%). Positivity rate did not change over time (p = 0.742), even when restricting the analysis only to high-risk genotypes (p = 0.575) and to genotypes covered by vaccine (p = 0.894). The risk to acquire HPV infection was 12.8% at one year and 33.4% at two years after vaccination. The probability to clear the infection was 67.6% at one year and 87.9% at two years. HIV infection had no impact on vaccine efficacy. Age above 45 years was the only factor associated to HPV acquisition (aHR 4.06, 95% CI 1.03-15.98, p = 0.045). Prevalence of oral HPV infection was higher in PLWH, but HIV had no impact on viral clearance or acquisition after vaccination.

Meropenem-Vaborbactam for the Treatment of Post-Neurosurgical Meningitis Caused by KPC Producer Klebsiella Pneumoniae: A Case Report and Review of the Literature.

Meningitis and ventriculitis, due to carbapenem-resistant Enterobacterales, are frequently associated with significant morbidity and mortality. In the case of multi-drug-resistant pathogens, it is necessary to consider the limited susceptibility profile as well as the penetration of the antimicrobials into the brain. Limited data are available regarding the treatment of central nervous system infections caused by carbapenem-resistant Enterobacterales. We report a study of a patient treated with meropenem-vaborbactam in the case of post-neurosurgical meningitis due to carbapenemase-producing Klebsiella pneumoniae (CPKP).

Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model.

Introduction: SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins. Objective: This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity and lung injury in vitro and in vivo. Results: Human SP-A can bind both SARS-CoV-2 S protein and hACE2 in a dose-dependent manner (p<0.01). Pre-incubation of SARS-CoV-2 (Delta) with human SP-A inhibited virus binding and entry and reduced viral load in human lung epithelial cells, evidenced by the dose-dependent decrease in viral RNA, nucleocapsid protein (NP), and titer (p<0.01). We observed significant weight loss, increased viral burden, and mortality rate, and more severe lung injury in SARS-CoV-2 infected hACE2/SP-A KO mice (SP-A deficient mice with hACE2 transgene) compared to infected hACE2/mSP-A (K18) and hACE2/hSP-A1 (6A2) mice (with both hACE2 and human SP-A1 transgenes) 6 Days Post-infection (DPI). Furthermore, increased SP-A level was observed in the saliva of COVID-19 patients compared to healthy controls (p<0.05), but severe COVID-19 patients had relatively lower SP-A levels than moderate COVID-19 patients (p<0.05). Discussion: Collectively, human SP-A attenuates SARS-CoV-2-induced acute lung injury (ALI) by directly binding to the S protein and hACE2, and inhibiting its infectivity; and SP-A level in the saliva of COVID-19 patients might serve as a biomarker for COVID-19 severity.

Intracranial malignant peripheral nerve sheath tumor: A case report and comprehensive literature review.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are rare malignant soft-tissue sarcomas arising from peripheral nerves. Little data exist regarding MPNST originating intracranially. Here, we present a 7th/8th nerve complex MPNST, discuss the treatment strategy and patient outcome, and provide a comprehensive review of existing literature. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed and crossed references were queried, yielding 37 publications from 1952 to the present. Fifty-three cases of primary intracranial and extra-axial MPNST were identified. Results: We additionally report a 40-year-old female presented with acute onset dizziness and subsequent hearing loss with associated right-sided facial numbness. Magnetic resonance imaging revealed a 0.5 cm × 1.7 cm enhancing lesion within the right internal auditory canal extending into the cerebellopontine angle. The patient was initially treated with retro sigmoid craniotomy for tumor resection followed by a trans labyrinth approach for residual tumor resection. She completed adjuvant fractionated radiation therapy and underwent facial nerve transfer to restore complete hemifacial paralysis. The most common cranial nerves involved were V and VIII (43.4% each), with 66% of patients male and 34% female. The average age was 43.4 ± 17.4 years. The mean survival time for reported non-survivors after tissue diagnosis was 15 ± 4 months. Two-year survival for patients receiving gross total resection was 33.3% versus 22.8% with subtotal resection. Conclusion: MPNSTs comprise a group of highly aggressive neoplasms that rarely arise intracranially. Gross total surgical resection should be pursued when feasible.

Durability of doravirine with dolutegravir dual regimen compared with other dolutegravir-based dual combinations.

OBJECTIVES: The availability of doravirine (DOR) allowed clinicians to prescribe a dolutegravir (DTG)-based two-drug regimen (2DR) in individuals not eligible to receive lamivudine (3TC) or rilpivirine (RPV). The aims of this study were to describe the durability of DTG + DOR compared with DTG/3TC and DTG/RPV and the rate of virological failure and target not-detected maintenance over time. METHODS: This retrospective, monocentric analysis included all subjects who started a DTG-based 2DR from 2018 to 2022 as a simplification. Descriptive statistics and non-parametric tests to describe and compare the groups were applied. Kaplan-Meier probability curves and Cox regression models for regimens durability were used. RESULTS: The study enrolled 710 individuals: 499 treated with DTG/3TC, 140 with DTG/RPV, and 71 with DTG + DOR. A 2DR with DOR was prescribed to older subjects who had a longer infection, greater exposure to different antiretroviral regimens, a higher proportion of resistance-associated mutations, and a worse immune-virologic status. Over a cumulative follow-up of 68 152 weeks, 42 discontinuations were registered (5.9%). DTG + DOR had a risk of treatment interruption of 7.8% at 48 weeks and 9.8% at 96 weeks, significantly higher than the other 2DRs. In the multivariate Cox model, DTG + DOR and DTG/RPV were significantly associated with discontinuation. The maintenance of target not detected during follow-up was similar among groups. The rate of virological failure was higher for DTG + DOR through different event definitions. CONCLUSIONS: DTG + DOR durability was high over a long follow-up albeit lower than for other 2DRs. This combination might be an effective option in people with HIV that has proven difficult to treat.

A case of chronic bacterial prostatitis due to Mycoplasma genitalium.

Mycoplasma genitalium (MG) is a common cause of non-gonococcal urethritis, but a role in acute or chronic prostatitis has not been described. We describe the case of a 42-year-old man with recurrent urinary tract infections since 2018 who developed chronic prostatitis despite several and prolonged antibiotic courses. Multiparametric prostatic magnetic resonance showed peripheral inflammatory alterations. A 4-glass Meares-Stamey test detected MG in the third voided bladder (VB3) sample. Moxifloxacin 400 mg daily for 28 days resulted in sustained clinical and microbiological cure.

The Effects of COVID-19 Surges on Otolaryngology Consults.

Objectives We aimed to evaluate the effects COVID-19 surges had on an otolaryngology service's consultation data. Methods After obtaining Upstate University Hospital institutional review board exemption to perform this research, a retrospective review analyzing otolaryngology consults at a single institution during COVID-19 surges in the years 2020 to 2021 was performed. The total consult volume and emergency department, inpatient, pediatric, adult, weekday, night, and weekend consults were assessed. Statistical analysis was used to compare these findings to the otolaryngology consult volumes and characteristics during the same time frames as the COVID-19 surges in the years 2014 to 2019. Results Based on bivariate analysis, an upward trend in otolaryngology consult volume was found over the study period. Although there was not a significant difference in consult volume during COVID-19 surges compared to historical data (p = 0.718, p = 0.695), both surge periods had significantly lower proportions of emergency department and pediatric consults (p < 0.001 for both). Conclusion Our study demonstrated that despite increasing cases of COVID-19 infection, otolaryngology consult volume remained high during surges. It was found that there has been an increase in otolaryngology consult volume at our academic center from the year 2014 to the present, a finding that was also seen in previous studies from our institution. Interestingly, consult parameters that changed when compared to the historical data included a decreased percentage of emergency department and pediatric consults during COVID-19 surges. The summation of these findings can be used to provide insight into how hospitals and otolaryngology services can prepare for the anticipated fluctuations in COVID-19 cases and associated hospitalizations.

Impact of COVID-19 on Public Interest in Breast Cancer Screening and Related Symptoms: Google Trends Analysis.

BACKGROUND: The COVID-19 pandemic has led to a decrease in cancer screening due to the redeployment of health care resources and public avoidance of health care facilities. Breast cancer is the most common cancer diagnosed in female individuals, with improved survival rates from early detection. An avoidance of screening, resulting in late detection, greatly affects survival and increases health care resource burden and costs. OBJECTIVE: This study aimed to evaluate if a sustained decrease in public interest in screening occurred and to evaluate other search terms, and hence interest, associated with that. METHODS: This study used Google Trends to analyze public interest in breast cancer screening and symptoms. We queried search data for 4 keyword terms ("mammogram," "breast pain," "breast lump," and "nipple discharge") from January 1, 2019, to January 1, 2022. The relative search frequency metric was used to assess interest in these terms, and related queries were retrieved for each keyword to evaluate trends in search patterns. RESULTS: Despite an initial drastic drop in interest in mammography from March to April 2020, this quickly recovered by July 2020. After this period, alongside the recovery of interest in screening, there was a rapid increase in interest for arranging for mammography. Relative search frequencies of perceived breast cancer-related symptoms such as breast lump, nipple discharge, and breast pain remained stable. There was increase public interest in natural and alternative therapy of breast lumps despite the recovery of interest in mammography and breast biopsy. There was a significant correlation between search activity and Breast Cancer Awareness Month in October. CONCLUSIONS: Online search interest in breast cancer screening experienced a sharp decline at the beginning of the COVID-19 pandemic, with a subsequent return to baseline interest in arranging for mammography followed this short period of decreased interest.

Human Surfactant Protein A Alleviates SARS-CoV-2 Infectivity in Human Lung Epithelial Cells.

SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins. This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity. The interactions between human SP-A and SARS-CoV-2 S protein and hACE2 receptor, and SP-A level in COVID-19 patients were assessed by ELISA. The effect of SP-A on SARS-CoV-2 infectivity was analyzed by infecting human lung epithelial cells (A549-ACE2) with pseudoviral particles and infectious SARS-CoV-2 (Delta variant) pre-incubated with SP-A. Virus binding, entry, and infectivity were assessed by RT-qPCR, immunoblotting, and plaque assay. The results showed that human SP-A can bind SARS-CoV-2 S protein/RBD and hACE2 in a dose-dependent manner (p<0.01). Human SP-A inhibited virus binding and entry, and reduce viral load in lung epithelial cells, evidenced by the dose-dependent decrease in viral RNA, nucleocapsid protein, and titer (p<0.01). Increased SP-A level was observed in the saliva of COVID-19 patients compared to healthy controls (p<0.05), but severe COVID-19 patients had relatively lower SP-A levels than moderate COVID-19 patients (p<0.05). Therefore, SP-A plays an important role in mucosal innate immunity against SARS-CoV-2 infectivity by directly binding to the S protein and inhibiting its infectivity in host cells. SP-A level in the saliva of COVID-19 patients might serve as a biomarker for COVID-19 severity.

Improving the accuracy of revised cardiac risk index with HbA1C: Hemoglobin ratio (HH ratio) - A retrospective cohort study.

Background: The current Lee's Revised cardiac risk index (RCRI) was created in 1999. Validation studies have found RCRI to be only moderately discriminant. The "Diabetes Mellitus on insulin" component of the score does not accurately reflect the severity of the disease. A previously studied HbA1C:Hemoglobin ratio shows an improved association with outcomes than individual components alone. Study design: A retrospective cohort study was performed in diabetic patients undergoing non-cardiac surgery. Ethics approval was obtained. The study compares the predictive value of RCRI and substitution of the "DM on insulin" component with HH ratio for 30- and 90-day mortality, and postoperative acute myocardial injury (AMI) and acute kidney injury (AKI). Results: A total of 20,099 adult patients were included in the final analysis. The incidence of 30- and 90-day mortality was at 4.2 and 6.5%, respectively. Substitution of HH ratio in RCRI resulted in 687 more patients being in the moderate to high-risk category. The substituted HH-RCRI score had better prediction for 30-day (AUC 0.66 vs. 0.69, p < 0.001) and 90-day mortality (AUC 0.67 vs. 0.70, p < 0.001), and postoperative AMI (AUC 0.69 vs. 0.71, p < 0.001) and AKI (AUC 0.57 vs. 0.62, p < 0.001). Conclusion: Although currently not an universal practice, substitution of "DM on insulin" with HbA1C:Hemoglobin ratio in RCRI score improves the accuracy of the RCRI risk prediction model in diabetic patients going for non-cardiac surgery.

Impact of treatment with direct-acting antivirals on inflammatory markers and autoantibodies in HIV/HCV co-infected individuals.

HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCV/HIV co-infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co-infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIV/HCV co-infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti-thyroglobulin Ab, anti-thyroid peroxidase Ab, ANCA, ASMA, anti-LKM, anti-DNA, AMA, ANA, T CD4+ and CD8+ cell count, and CD4/CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals: 51.9% with a F0-F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4; ferritin, anti-thyroglobulin Ab, and C4 fraction at EOT; total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p < .001). T CD4+ cell slightly increased at SVR12, but with an increase also in CD8+ resulting in stable CD4/CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p = .099): they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4/CD8 ratio over a follow up of 12 weeks.

Adherence to Multidisciplinary Tumor Board Recommendations in Patients With Curable Esophageal and Gastric Cancers.

BACKGROUND: Multidisciplinary tumor board (MDT) discussion is standard practice in the management of Upper Gastrointestinal (UGI) cancers. However, poor adherence to MDT recommendations may account for the lack of improved oncological outcomes with MDTs. We aim to quantify adherence rates and compare outcomes between adherent and non-adherent patients. METHODS: We included all patients with potentially curable primary UGI carcinomas who were discussed at UGI MDT from 2017 to 2018. MDT recommendations were compared to actual treatment received. Oncological and survival outcomes were compared between both groups. RESULTS: Amongst 153 patients, 64 (41.8%) were non-adherent to MDT recommendations. Reasons for non-adherence were patient refusal (50.0%), treatment-related complications (31.3%), disease factors (17.2%) and clinician decision (1.56%). Univariate analysis showed that non-adherent patients were older (71.6 vs 65.2 years, p < 0.001), with higher clinical stage at point of diagnosis (p = 0.028), pathological stage after resection (p < 0.001) and were more likely to be recommended for multimodal therapy. No significant factors were associated with non-adherence at multivariate analysis. Non-adherent patients had worse median overall survival (19.5 months) compared to adherent patients (not reached at follow-up) with both unmatched and propensity-score matched analysis. Patients who received only part of the intended adjuvant chemotherapy course had worse median overall survival and disease-free survival compared to patients who completed or did not initiate adjuvant chemotherapy. CONCLUSIONS: Non-adherence to MDT recommendations was associated with advanced age and tumor stage, and potentially contributes to the worse oncological outcomes in a group of patients already predisposed to poor outcomes.

Cost-effectiveness comparison of delayed versus immediate coloanal anastomosis following ultralow anterior resection for rectal cancer.

BACKGROUND: Following ultralow anterior resection for distal rectal cancers, a coloanal anastomosis is usually created along with a defunctioning ileostomy (DI). Recent evidence suggests that abdominoperineal pull-through with delayed coloanal anastomosis (DCAA) is a viable alternative to immediate coloanal anastomosis (ICAA), minimizing the risk of anastomotic leakage and avoiding the need for stoma creation with the risk of stoma-associated morbidity. However, DCAA requires a longer initial hospitalization. We aimed to perform a cost-effectiveness analysis to compare DCAA versus ICAA for elective rectal cancer surgery. METHODS: A decision tree model was used to compare the cost-effectiveness of the two strategies. Cost data were obtained from the 2019 to 2020 United Kingdom National Health Service reference costs. Model probabilities were derived from published studies. Univariate and probabilistic sensitivity analyses were used to evaluate the robustness of the results. RESULTS: DCAA was the overall cheaper strategy at £13 541 compared with £14 856 for ICAA in the base case analysis. This was explained by the decreased overall costs of hospitalization/surgery, reduction in costs associated with anastomotic or stoma-related complications, specifically dehydration-induced hospital readmissions and avoidance of stoma maintenance costs. Sensitivity analysis demonstrated that DCAA remained consistently more inexpensive except when the duration of total parenteral nutrition exceeded 14 days. CONCLUSION: Despite a longer index hospitalization with higher initial costs, this economic analysis demonstrates that DCAA without stoma is overall more cost-effective compared with ICAA with DI following ultralow anterior resection. Cost savings should be considered an additional benefit when selecting the DCAA approach for rectal cancer surgery.

Technical insights to multivisceral resections using the da Vinci Xi.

BACKGROUND: There have been few reports on the feasibility and safety of robotic multivisceral surgeries. The da Vinci Xi boasts significant upgrades that improve its applicability in combined resections. We report our early experience of multivisceral, multi-quadrant resections with the Xi system. METHODS: Between May 2015 and August 2019, 13 multivisceral resections were performed. Patient demographics, procedural data, and perioperative outcomes were evaluated. RESULTS: The procedures were completed at a median operative time of 290 (range, 210-535) minutes. The median postoperative length of hospital stay was 3.5 (range, 2-7) days. There was one case of readmission for anastomotic leak, but no positioning injuries, external robot arm collisions or issues arising from trocar position. There were no cases of perioperative mortality. CONCLUSION: Multivisceral resections can be safely accomplished using the Xi. Further studies are necessary to ascertain whether there are benefits of the robotic approach over conventional laparoscopy in these complex cases.

Preoperative shock index in major abdominal emergency surgery.

Introduction: Major abdominal emergency surgery (MAES) patients have a high risk of mortality and complications. The time-sensitive nature of MAES necessitates an easily calculable risk-scoring tool. Shock index (SI) is obtained by dividing heart rate (HR) by systolic blood pressure (SBP) and provides insight into a patient's haemodynamic status. We aimed to evaluate SI's usefulness in predicting postoperative mortality, acute kidney injury (AKI), requirements for intensive care unit (ICU) and high-dependency monitoring, and the ICU length of stay (LOS). Method: We retrospectively reviewed 212,089 MAES patients from January 2013 to December 2020. The cohort was propensity matched, and 3960 patients were included. The first HR and SBP recorded in the anaesthesia chart were used to calculate SI. Regression models were used to investigate the association between SI and outcomes. The relationship between SI and survival was explored with Kaplan-Meier curves. Results: There were significant associations between SI and mortality at 1 month (odds ratio [OR] 2.40 [1.67-3.39], P<0.001), 3 months (OR 2.13 [1.56-2.88], P<0.001), and at 2 years (OR 1.77 [1.38-2.25], P<0.001). Multivariate analysis revealed significant relationships between SI and mortality at 1 month (OR 3.51 [1.20-10.3], P=0.021) and at 3 months (OR 3.05 [1.07-8.54], P=0.034). Univariate and multivariate analysis also revealed significant relationships between SI and AKI (P<0.001), postoperative ICU admission (P<0.005) and ICU LOS (P<0.001). SI does not significantly affect 2-year mortality. Conclusion: SI is useful in predicting postopera-tive mortality at 1 month, 3 months, AKI, postoperative ICU admission and ICU LOS.

Risk Stratification in Oral Cancer: A Novel Approach.

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high morbidity and mortality. Currently, treatment decisions are guided by TNM staging, which omits important negative prognosticators such as lymphovascular invasion, perineural invasion (PNI), and histologic differentiation. We proposed nomogram models based on adverse pathological features to identify candidates suitable for treatment escalation within each risk group according to the National Comprehensive Cancer Network (NCCN) guidelines. Methods: Anonymized clinicopathologic data of OSCC patients from 5 tertiary healthcare institutions in Asia were divided into 3 risk groups according to the NCCN guidelines. Within each risk group, nomograms were built to predict overall survival based on histologic differentiation, histologic margin involvement, depth of invasion (DOI), extranodal extension, PNI, lymphovascular, and bone invasion. Nomograms were internally validated with precision-recall analysis and the Kaplan-Meier survival analysis. Results: Low-risk patients with positive pathological nodal involvement and/or positive PNI should be considered for adjuvant radiotherapy. Intermediate-risk patients with gross bone invasion may benefit from concurrent chemotherapy. High-risk patients with positive margins, high DOI, and a high composite score of histologic differentiation, PNI, and the American Joint Committee on Cancer (AJCC) 8th edition T staging should be considered for treatment escalation to experimental therapies in clinical trials. Conclusion: Nomograms built based on prognostic adverse pathological features can be used within each NCCN risk group to fine-tune treatment decisions for OSCC patients.

High prevalence of anal papillomavirus infection in men who have sex with men PrEP users.

OBJECTIVES: Human papillomavirus (HPV) is the most common STI and is associated with a wide range of diseases from anogenital warts to malignancies. Anal HPV infection is considerably more common in men who have sex with men (MSM) living with HIV. Aims of the present study are to (i) describe the prevalence of anal HPV infection in MSM who started pre-exposure prophylaxis (PrEP) and (ii) analyse factors associated with anal infection from genotypes that would be covered by nonavalent vaccination. METHODS: This monocentric, cross-sectional study included all subjects who started PrEP from May 2018 to November 2021. PrEP candidates underwent full behavioural and clinical evaluation, including digital anal rectal examination and swabbing for HPV determination. Descriptive statistics, Mann-Whitney U test for continuous and χ2 tests for categorical variables were adopted. Unadjusted and adjusted regression analyses were performed to assess factors associated with positive anal swabs and to the presence of genotypes covered by the nonavalent vaccination. RESULTS: The analysis included 288 subjects: anal swabs tested positive in 87.2% of cases, 79.2% of the subjects had a high-risk genotype (mainly 16), whereas 67.4% had a genotype covered by nonavalent vaccine. Sexual role was the only factor associated with anal HPV infection. Use of recreational drugs and a diagnosis of ≥2 STIs correlated with the presence of genotypes that would have been covered by vaccine, while previous vaccination had a protective role. CONCLUSIONS: PrEP candidates showed a high prevalence of anal HPV infection, especially due to high-risk genotypes, comparable to what has been reported in MSM living with HIV.

Otitis Media and Hearing Loss in Patients With Nonsyndromic Craniosynostosis: A Multicenter Study.

OBJECTIVES: The objectives of this study were to: (1) determine the prevalence of otitis media with effusion in patients with nonsyndromic craniosynostosis; (2) determine the prevalence of hearing loss in patients with nonsyndromic craniosynostosis; and (3) identify potential patterns and outcomes in patients with nonsyndromic craniosynostosis. METHODS: A retrospective chart review was conducted at 2 academic institutions, St Christopher's Hospital for Children and SUNY Upstate Medical University, from January 2015 through August 2018, to identify patients having nonsyndromic craniosynostosis with a concurrent diagnosis of otitis media and/or hearing loss. The demographic data and categorical variables were analyzed using descriptive statistics and chi-square testing, respectively. RESULTS: In the entire cohort of patients (N = 113, age range 0-123 months), 36% had otitis media with effusion on either history, physical examination, tympanometry, and/or imaging. Half (50%) of patients with coronal synostosis had otitis media with effusion compared to sagittal (40.7%), metopic (26.3%), multiple (25%), and lambdoid (0%). However, these differences were not statistically significant (P = .190). Most patients had normal hearing (91%), while a minority had either conductive (7%) or sensorineural (2%) hearing loss. CONCLUSION: The presence of otitis media in our cohort of patients with nonsyndromic craniosynostosis appears to be at the upper limit of normal when compared to historical rates in normocephalic children. Synostosis subtype did not appear to predict the presence of otitis media. Only 9% of patients with nonsyndromic craniosynostosis were found to have a hearing loss.

Changes in Eustachian Tube Mucosa in Mice After Short-Term Tobacco and E-cigarette Smoke Exposure.

OBJECTIVES: To evaluate histologic changes in middle ear and eustachian tube (ET) mucosa of mice after exposure to tobacco or electronic cigarette (e-cigarette) smoke. To determine whether there were any mitigating effects of middle ear application of anti-IL-13 or the epidermal growth factor receptor antagonist AG1478 on noted changes within ET mucosa. STUDY DESIGN: Controlled animal study. METHODS: Fifty BALB/cJ mice were randomly assigned to one of five groups: A control group with no smoke exposure, two groups exposed to tobacco smoke, and two groups exposed to e-cigarette vapor. Within the exposed groups after 4 weeks of exposure, one ear was infiltrated with a saline hydrogel and the other ear with hydrogel of either Anti-IL-13 or AG1478. After four more weeks of exposure, the animals were euthanized and the ETs were evaluated for mucosal changes. RESULTS: Compared to control animals with no smoke exposure, there were significant decreases in the numbers of goblet cells within the ET mucosa of mice exposed to tobacco smoke and e-cigarette vapor. No significant differences in cilia, mucin, or squamous metaplasia were noted. Neither anti-IL-13 nor AG178 significantly altered goblet cell count in the ET mucosa of mice exposed to tobacco smoke; however, both agents significantly increased goblet cells within the ET mucosa of mice exposed to e-cigarette vapor. CONCLUSION: Short-term tobacco smoke and e-cigarette vapor significantly decrease goblet cell count in mouse ET mucosa. Middle ear application of both anti-IL-13 and AG1478 resulted in an increase in goblet cell count among mice exposed to e-cigarette vapor, but not to tobacco smoke. LEVEL OF EVIDENCE: NA Laryngoscope, 132:648-654, 2022.

A machine learning approach to identify predictive molecular markers for cisplatin chemosensitivity following surgical resection in ovarian cancer.

Ovarian cancer is associated with poor prognosis. Platinum resistance contributes significantly to the high rate of tumour recurrence. We aimed to identify a set of molecular markers for predicting platinum sensitivity. A signature predicting cisplatin sensitivity was generated using the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas databases. Four potential biomarkers (CYTH3, GALNT3, S100A14, and ERI1) were identified and optimized for immunohistochemistry (IHC). Validation was performed on a cohort of patients (n = 50) treated with surgical resection followed by adjuvant carboplatin. Predictive models were established to predict chemosensitivity. The four biomarkers were also assessed for their ability to prognosticate overall survival in three ovarian cancer microarray expression datasets from The Gene Expression Omnibus. The extreme gradient boosting (XGBoost) algorithm was selected for the final model to validate the accuracy in an independent validation dataset (n = 10). CYTH3 and S100A14, followed by nodal stage, were the features with the greatest importance. The four gene signature had comparable prognostication as clinical information for two-year survival. Assessment of tumour biology by means of gene expression can serve as an adjunct for prediction of chemosensitivity and prognostication. Potentially, the assessment of molecular markers alongside clinical information offers a chance to further optimise therapeutic decision making.