Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment

alexandrossfakianakis shared this article with you from Inoreader Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment via Clinical Infectious Diseases Advance Access Abstract BackgroundNirmatrelvir/ritonavir, the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease inhibitor, reduces the risk of hospitalization and death by coronavirus disease 2019 (COVID-19) but has been associated with symptomatic rebound after therapy completion. Methods Six individuals with relapse of COVID-19 symptoms after treatment with nirmatrelvir/ritonavir, 2 individuals with rebound symptoms without prior antiviral therapy and 7 patients with acute Omicron infection (controls) were studied. Soluble biomarkers and serum SARS-CoV-2 nucleocapsid protein were measured. Nasal swabs positive for SARS-CoV-2 underwent viral isolation and targeted viral sequencing. SARS-CoV-2 anti-spike, anti–receptor-binding domain, and anti-nucleocapsid antibodies were measured. Surrogate viral neutralization tests against wild-type and Omicron spike protein, as well as T-cell stimulation assays, were performed. Results High levels of SARS-CoV-2 anti-spike immunoglo bulin G (IgG) antibodies were found in all participants. Anti-nucleocapsid IgG and Omicron-specific neutralizing antibodies increased in patients with rebound. Robust SARS-CoV-2–specific T-cell responses were observed, higher in rebound compared with early acute COVID-19 patients. Inflammatory markers mostly decreased during rebound. Two patients sampled longitudinally demonstrated an increase in activated cytokine-producing CD4+ T cells against viral proteins. No characteristic resistance mutations were identified. SARS-CoV-2 was isolated by culture from 1 of 8 rebound patients; Polybrene addition increased this to 5 of 8. Conclusions Nirmatrelvir/ritonavir treatment does not impede adaptive immune responses to SARS-CoV-2. Clinical rebound corresponds to development of a robust antibody and T-cell immune response, arguing against a high risk of disease progression. The presence of infectious virus supports the need for isolation and assessment of longer treatm ent courses.Clinical trials registration. NCT04401436. View on Web

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Acinetobacter baumannii: Pathogenesis, virulence factors, novel therapeutic options and mechanisms of resistance to antimicrobial agents with emphasis on tigecycline

alexandrossfakianakis shared this article with you from Inoreader Acinetobacter baumannii: Pathogenesis, virulence factors, novel therapeutic options and mechanisms of resistance to antimicrobial agents with emphasis on tigecycline via Journal of Clinical Pharmacy and Therapeutics This article summarizes the microbiological and virulence traits in A.baumannii. In addition, in this study, the mechanisms of resistance to tigecycline have been comprehensively investigated and novel therapeutic strategies have been expressed. Abstract What is known and objective Acinetobacter baumannii is one of the most important nosocomial pathogens with the ability to cause infections such as meningitis, pneumonia, urinary tract, septicaemia and wound infections. A wide range of virulence factors are responsible for pathogenesis and high mortality of A. baumannii including outer membrane proteins, lipopolysaccharide, capsule, phospholipase, nutrient- acquisition systems, efflux pumps, protein secretion systems, quarom sensing and biofilm production. These virulence factors contribute in pathogen survival in stressful conditions and antimicrobial resistance. Comment According to the World Health Organization (WHO), A. baumannii is one of the most resistant pathogens of ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.). In recent years, resistance to a wide range of antibiotics in A. baumannii has significantly increased and the high emergence of extensively drug resistant (XDR) isolates is challenging. Among therapeutic antibiotics, resistance to tigecycline as a last resort antibiotic has become a global concern. Several mechanisms are involved in tigecycline resistance, the most important of which is RND (Resistance-Nodulation-Division) family efflux pumps overexpression. The development of new therapeutic strategies to confront A. baumannii infections has been very promising in recent years. What is new and conclusion In the present review we highlight microbiological and virulence traits in A. baumannii and peruse the tigecycline resistance mechanisms and novel therapeutic options. Among the novel therapeutic strategies we focus on combination therapy, drug repurposing, novel antibiotics, bacteriophage therapy, antimicrobial peptides (AMPs), human monoclonal antibodies (Hu-mAbs), nanoparticles and gene editing. View on Web

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Pediatric vs Adult Septoplasty Revision Rates

alexandrossfakianakis shared this article with you from Inoreader Pediatric vs Adult Septoplasty Revision Rates via JAMA Otolaryngology–Head & Neck Surgery Online First This cohort study used data from the IBM MarketScan Commercial Database to compare rates of revision surgery among pediatric vs adult patients undergoing septoplasty. View on Web

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BMI and Venous VTE Rates in Patients on Standard Chemoprophylaxis Regimens After H&N Surgery

alexandrossfakianakis shared this article with you from Inoreader BMI and Venous VTE Rates in Patients on Standard Chemoprophylaxis Regimens After H&N Surgery via JAMA Otolaryngology–Head & Neck Surgery Online First This cohort study assesses whether there is an association bet ween body mass index (BMI) and postoperative venous thromboembolism (VTE) and hematoma rates in patients treated with prophylactic enoxaparin 30 mg twice daily. View on Web

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Chemical behavior of 20%–22% carbamide peroxide gels in at‐home bleaching: Randomized crossover in situ trial

alexandrossfakianakis shared this article with you from Inoreader Chemical behavior of 20%–22% carbamide peroxide gels in at‐home bleaching: Randomized crossover in situ trial via Journal of Esthetic and Restorative Dentistry Abstract Objective To evaluate if distinct 20%–22% carbamide peroxide bleaching gels present similar decomposition pattern and pH during the clinical use in both arches, as well as gels viscosity. Methods Participants randomly received treatments with carbamide peroxide gels (n = 10): OPF (OpalescencePF-20%); PNT (Polanight-22%); and WPC (Whiteness Perfect-22%) in three different days, with 2-day washout. Decomposition pattern was assessed by peroxide concentration. Both PC and pH of bleaching gels were measured in different time points in upper and lower trays during a total of 120 min of clinical use. Viscosity of bleaching gels was measured in triplicate. ANOVA and Tukey's test were applied (α = 0.05). Results Regarding decomposition pattern, no significant differences were observed for the interaction between gel, time, and tray position factors. The peroxide concentration progressively reduced until 120 min of trays use (p < 0.001), being overall more notable in lower trays (p < 0.001). Regarding pH, the lowest values were verified in WPC within time. At 120 min, an increase of pH was observed for both WPC and OPF (p < 0.001) compared to baseline means. PNT exhibited constant pH values over time. The values of viscosity were: OPF (1.682.000 ± 19 cP)a, WPC (1.388.667 ± 172.63 cP)ab, PNT (579.567 ± 0.98 cP)b. Conclusions The bleaching gels presented overall decomposition pattern clinically equivalent, being more notable in lower trays over time. Nevertheless, distinct pH and viscosities were observed among the products. Clinical Significance Although the manufacturers recommend different times of use for bleaching gels with similar peroxide concentrations, the commercial products tested did not exhibit clinically relevant difference in the decomposition pattern during the 120 min of clinical procedure. View on Web

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Active Surveillance for PTMC warranted for the UK population?

alexandrossfakianakis shared this article with you from Inoreader Active Surveillance for PTMC warranted for the UK population? via Clinical Otolaryngology Abstract Background The incidence of thyroid cancer is increasing globally due to the increase in detection of subclinical, low volume papillary thyroid microcarcinomas (PTMC) (<1cm). Several international groups have recommended an active surveillance approach for this low-risk disease. In contrast to many other countries, the UK's approach to thyroid nodules is to avoid detection of incidental lesions where appropriate. Objective This study aims to establish the proportion of patients with thyroid cancer in the UK that would benefit from active surveillance. Design, participants, and outcome measures Individuals with PTMC in NHS Lothian from 2009-2020 were reviewed from a local thyroid cancer database. The mode of detection of PTMC and proportion of patients who might benefit from active surveillance were established. Results From 651 individuals with differentiated thyroid cancer managed over 12-year period, 185 individuals with PTMC were identified (28.4%). The majority of PTMC 151/185 (81.6%) were either diagnosed post-operatively following thyroidectomy for benign disease or with nodal disease. Only 24 individuals with PTMC were identified following palpable thyroid nodule, incidental finding on imaging and surveillance screening. Therefore, when the indication for surgery was considered, only 24/651 (3.7%) patients were identified pre-operatively and would therefore be realistic candidates for active surveillance. Conclusion Less than 4% of patients with thyroid cancer in the UK would be appropriate for active surveillance. Rather than developing programs to deal with this minority of patients, focus should be maintained on minimizing detection of these low-risk cases. View on Web

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Differentiation of eosinophilic and non‐eosinophilic chronic rhinosinusitis on preoperative computed tomography using deep learning

alexandrossfakianakis shared this article with you from Inoreader Differentiation of eosinophilic and non‐eosinophilic chronic rhinosinusitis on preoperative computed tomography using deep learning via Clinical Otolaryngology Abstract Objective This study aimed to develop deep learning (DL) models for differentiating between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS (NECRS) on preoperative CT. Methods A total of 878 chronic rhinosinusitis (CRS) patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University (Hubei, China) between October 2016 to June 2021 were included. Axial spiral CT images were pre-processed and used to build the dataset. Two semantic segmentation models based on U-net and Deeplabv3 were trained to segment the sinus area on CT images. All patient images were segmented using the better-performing segmentation model and used for training and testing of the transferred efficientnet_b0, resnet50, inception_resnet_v2, and Xception neural networks. Additionally, we evaluated the performances of the models trained using each image and each patient as a unit. The precision of each model was assessed based on the receiver operating characteristic curve. Further, we analyzed the confusion matrix and accuracy of each model. Results The Dice coefficients of U-net and Deeplabv3 were 0.953 and 0.961, respectively. The average area under the curve and mean accuracy values of the four networks were 0.848 and 0.762 for models trained using a single image as a unit, while the corresponding values for models trained using each patient as a unit were 0.893 and 0.853, respectively. Conclusion Combining semantic segmentation with classification networks could effectively distinguish between patients with ECRS and those with NECRS based on preoperative sinus CT images. Furthermore, labeling each patient to build a dataset for classification may be more reliable than labeling each medical image. This article is protected by copyright. All rights reserved. View on Web

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Is COVID‐19 to Blame for Sensorineural Hearing Deterioration? A Pre/Post COVID‐19 Hearing Evaluation Study

alexandrossfakianakis shared this article with you from Inoreader Is COVID‐19 to Blame for Sensorineural Hearing Deterioration? A Pre/Post COVID‐19 Hearing Evaluation Study via The Laryngoscope Our study aimed to evaluate the associations between COVID-19 infection and deterioration in sensorineural hearing thresholds among a cohort of patients from Meuhedet healthcare services (the third largest of four public healthcare provider organizations in Israel) that had undergone hearing evaluations pre- and post-COVID-19. Our findings suggest that COVID-19 does not appear to be associated with deterioration of the sensorineural hearing among unvaccinated patients who had known hearing loss pre-infection, after correcting for age-related hearing loss. Moreover, our findings do not validate previous reports of a greater deterioration in the hearing of infected patients who possess background risk factors such as smoking, hypertension, and diabetes, suggesting no interaction between risk factors and hearing deterioration post-infection. Objectives Here, we aimed to (a) determine whether a clinically significant sensorineural hearing loss (SNHL) change could be detected in post-coronavirus disease (COVID-19) hearing levels on comparing them with pre-infection hearing levels after controlling for the effect of age and (b) to identify risk factors, such as hypertension, diabetes, and smoking, which increase the likelihood of hearing loss in COVID-19 patients. Methods We retrospectively analyzed hearing thresholds in unvaccinated patient's pre- and post-COVID-19 infection. Thresholds were controlled for age and the duration between the pre- and post-COVID-19 hearing evaluations. Correlations between additional COVID-19-related symptoms, hypertension, diabetes, and smoking and hearing threshold changes were analyzed. Results A significant (but not clinical) threshold elevation was found post-COVID-19 infection. However, on controlling for age and the duration between the pre- and post-COVID-19 hearing evaluations, no significant threshold elevation was found. No significant correlation was found between hearing threshold changes and additional COVID-19-related symptoms, hypertension, diabetes, or smoking. Conclusion COVID-19 did not lead to a significant hearing threshold elevation in our cohort, even among patients with additional COVID-19 symptoms, hypertension, or diabetes mellitus or among those who smoked. Level of Evidence 3. nonrandomized controlled cohort, follow-up study Laryngoscope, 2022 View on Web

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Incidence of Sinus Inflammation After Endoscopic Skull Base Surgery in the Pediatric Population

alexandrossfakianakis shared this article with you from Inoreader Incidence of Sinus Inflammation After Endoscopic Skull Base Surgery in the Pediatric Population via The Laryngoscope The extended endonasal approach has been utilized in the resection of anterior skull base lesions in the pediatric population. There are unique challenges to these patients in the post-operative setting, including patient compliance with medical therapy and post-operative debridements, and a smaller nasal airway that may increase propensity towards scarring. Our objective for this study is to evaluate the incidence of post-operative radiographic inflammation in this patient population using the Lund-Mackay (LM) score. Background The extended endonasal approach has been utilized in the resection of anterior skull base lesions in the pediatric population. There are unique challenges to these patients in the post-operative setting, including patient compliance with medical therapy and post-operative debridements, and a smaller nasal airway that may increase propensity toward scarring. Our objective for this study is to evaluate the incidence of post-operative radiographic inflammation in this patient population using the Lund-Mackay (LM) score. Methods A single-center, retrospective review of pediatric patients undergoing endoscopic approach to the skull base between 2009 and 2021 was performed. Demographic and clinicopathologic data and pre- and post-operative imaging were analyzed. One-way ANOVA followed by Tukey multiple pairwise comparisons statistical tests were used to compare mean LM scores between groups. Results Seventy-two patients (52 males, 20 females) were identified with a median follow-up of 27 months. All patients underwent an extended endonasal approach for resection of skull base lesions. The mean LM scores were compared between pre-operative MRI, first post-operative MRI > 30 days after surgery, and most recent post-operative MRI. One-way ANOVA was performed with significant differences noted between the groups (p < 0.001). Tukey multiple pairwise comparisons test was then performed and noted significant differences between the pre-operative and first post-operative LM (p < 0.0001) and the first post-operative and most recent LM (p < 0.0001). There was no significant difference noted between the pre-operative LM score and most recent LM score (p = 0.14). Conclusion Despite concerns regarding possible subsequent development of chronic rhinosinusitis following endoscopic skull base surgery in pediatric patients, the current study suggests that transient radiographic evidence of sinus inflammation can be seen up to six months postoperatively, which appears to resolve by approximately two years after surgery. Level of Evidence 4 Laryngoscope, 2022 View on Web

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Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV

alexandrossfakianakis shared this article with you from Inoreader Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV via Clinical Infectious Diseases Advance Access Abstract Background People with HIV on antiretroviral therapy with good CD4 T cell counts make effective immune responses following vaccination against SARS-CoV-2. There are few data on longer term responses and the impact of a booster dose. Methods Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed twelve months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µl. Immune responses to the ancestral strain and variants of concern were measured by anti-spike IgG ELISA, MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, Activation Induced Marker (AIM) assay and T cell proliferation. Findings 54 participants received two doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) one year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titres (MSD), ACE-2 inhibition and IgG ELISA results were significantly higher compared to Day 182 titres (P < 0.0001 for all three). SARS-CoV-2 specific CD4+ T cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4 + and CD8+ T cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. Conclusions In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs. View on Web

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