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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Rapid selection of sotrovimab escape variants in SARS-CoV-2 Omicron infected immunocompromised patients

alexandrossfakianakis shared this article with you from Inoreader Rapid selection of sotrovimab escape variants in SARS-CoV-2 Omicron infected immunocompromised patients via Clinical Infectious Diseases Advance Access Abstract Background Monoclonal antibodies (mAb) targeting SARS-CoV-2 are predominantly less effective against Omicron variants. Immunocompromised patients often experience prolonged viral shedding and are therefore at increased risk for viral escape mutations, when mAbs are used as monotherapy. Methods In an observational, prospective cohort, 57 patients infected with Omicron variants receiving sotrovimab alone or in combination with remdesivir were followed. The study endpoints were a decrease in SARS-CoV-2-RNA <106 copies/ml in nasopharyngeal swabs at day 21 and the emergence of resistance mutations at days 7, 14, and 21 after sotrovimab administration. All SARS-CoV-2 samples were analyzed by whole-genome sequencing, individual variants within the quasispecies were subsequently quantified and further characterized by a pseudovirus neutralization assay. Results 47/57 patients (82.5%) were infected with Omicron/BA .1 and 10/57 (17.5%) with Omicron/BA.2. The vast majority of patients (43/57, 75.4%) were immunodeficient, predominantly due to immunosuppression after organ transplantation or hematologic malignancies. 21 days after sotrovimab administration, 12/43 (27.9%) of immunodeficient patients had prolonged viral shedding compared to 1/14 (7.1%) immunocompetent patients (p = 0.011). Longitudinal sequencing revealed that 14/43 (32.6%) immunodeficient patients had in part Omicron-specific viral spike protein mutations (e.g., P337S and/or E340D/V) that substantially reduced susceptibility to sotrovimab in a pseudovirus neutralization assay. Combination therapy with remdesivir significantly reduced the selection of escape variants. Conclusions Immunocompromised patients face a considerable risk of prolonged viral shedding and emergence of escape mutations after early therapy with sotrovimab. These findings underscore the importance of careful monitoring and the need to conduct dedic ated clinical trials for this patient population. View on Web

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Clinical Presentation, Treatment Response and Virology Outcomes of Women who Seroconverted in the Dapivirine Vaginal Ring Trials – The Ring Study and DREAM

alexandrossfakianakis shared this article with you from Inoreader Clinical Presentation, Treatment Response and Virology Outcomes of Women who Seroconverted in the Dapivirine Vaginal Ring Trials – The Ring Study and DREAM via Clinical Infectious Diseases Advance Access Abstract Background Participants who HIV seroconverted in The Ring Study, a Phase III trial of Dapivirine Vaginal Ring (DVR), or in the open-label extension trial DREAM, were offered enrollment in an observational cohort study (IPM 007) to assess clinical presentation and response to antiretroviral treatment (ART). Methods Participants' HIV infection was managed at local treatment clinics according to national treatment guidelines. IPM 007 study visits occurred 3 and 6 months after enrollment, and every 6 months thereafter. Assessments included plasma HIV-1 RNA, CD4+ T-cell counts, and recording of HIV/AIDS-associated events and ARV use. Post-hoc virology analyses were performed for participants identified with virologic failure. Results One-hundred-and-fifty-one of 179 eligible participants (84.4%) enrolled into IPM 007; 103 had previously received the DVR in the Ring or DREAM studies; 48 had received placebo in The Ring Stu dy. HIV-1 RNA and CD4+ T-cell counts after 12 months' follow-up were similar for participants who used the DVR in The Ring Study and DREAM, compared to those who received placebo. Of the 78 participants with a study visit approximately 6 months after ART initiation, 59 (75.6%) had HIV-1 RNA <40 copies/mL (The Ring Study: placebo: 13/23; 56.5%; DVR: 32/39; 82.1%; DREAM [DVR]: 14/16; 87.5%). Post-hoc virology analysis indicated that genotypic patterns observed at virologic failure were as expected of an NNRTI-based regimen. Conclusions Seroconversion during DVR use did not negatively affect clinical presentation or treatment outcome. Mutation patterns at virologic failure were in line with individuals failing an NNRTI-based regimen. 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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Irinotecan dose schedule for the treatment of Ewing sarcoma

alexandrossfakianakis shared this article with you from Inoreader Irinotecan dose schedule for the treatment of Ewing sarcoma via Pediatric Blood & Cancer Abstract Irinotecan and temozolomide achieve objective responses in patients with Ewing sarcoma that recurs after initial therapy. Optimal dose schedules have not been defined. We reviewed published series of patients treated with irinotecan and temozolomide for Ewing sarcoma that recurred after initial therapy. We compared objective response rates for patients who received 5-day irinotecan treatment schedules to response rates for patients who achieved 10-day irinotecan treatment schedules. Among 89 patients treated with a 10-day irinotecan schedule, there were 47 objective responses (53%). Among 180 patients treated with a 5-day irinotecan schedule, there were 52 responses (29%). In the treatment of recurrent Ewing sarcoma, investigators should consider the use of a 10-day schedule for administration of irinotecan. View on Web

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Anaplastic lymphoma kinase positive histiocytosis presenting as hemocytopenia in an infant

alexandrossfakianakis shared this article with you from Inoreader Anaplastic lymphoma kinase positive histiocytosis presenting as hemocytopenia in an infant via Pediatric Blood & Cancer View on Web

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Relationship between the timing of chemotherapy and surgical complications following surgical biopsy in children with malignant solid tumors

alexandrossfakianakis shared this article with you from Inoreader Relationship between the timing of chemotherapy and surgical complications following surgical biopsy in children with malignant solid tumors via Pediatric Blood & Cancer Abstract Background Biopsies for diagnosis before chemotherapy is common in children with malignant solid tumors. Wound healing is delayed by chemotherapy; however, the ideal interval between biopsy and chemotherapy remains unknown. We aimed to summarize the relationship between chemotherapy timing and postoperative surgical complications. Procedure We retrospectively reviewed patients with malignant solid tumors who underwent chemotherapy after surgical biopsy at our institution between January 2014 and August 2020. The primary outcomes were postoperative surgical complications (within 30 days) and the timing of chemotherapy. Results Forty-three patients were analyzed. The types of tumors were neuroblastoma (n = 20), hepatoblastoma (n = 10), Ewing sarcoma (n = 5), germ cell tumor (n = 3), angiosarcoma (n = 1), clear cell sarcoma (n = 1), ganglioneuroblastoma (n = 1), rhabdoid tumor (n = 1), and rhabdomyosarcoma (n = 1). The operative procedures were thoracoscopy (n = 5), laparotomy (n = 17), laparoscopy (n = 14), and superficial (n = 7). The median time [range] to chemotherapy after biopsy was 4 [0–21] days. No surgical complications occurred before chemotherapy, and two (4.7%) patients experienced complications after chemotherapy. These included postoperative hemorrhage (grade 3) and surgical site infection (grade 1). Chemotherapy was initiated 1 and 6 days after biopsy, respectively, in these cases. Complications occurred 10 and 23 days after biopsy, respectively. Conclusion The rate of postoperative surgical complications related to biopsy seems acceptable, even when chemotherapy was initiated in the early postoperative period. Early initiation of chemotherapy after biopsy may be a suitable option, particularly in children with bulky or symptomatic malignant solid tumors. View on Web

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Surgical margins of the oral cavity: is 5 mm really necessary?

alexandrossfakianakis shared this article with you from Inoreader Surgical margins of the oral cavity: is 5 mm really necessary? via Most Recent Articles: Journal of Otolaryngology - Head & Neck Surgery Squamous cell carcinoma is the most common malignancy of the oral cavity. Primary treatment involves surgical resection of the tumour with a surrounding margin. Historically, the most commonly accepted margin ... View on Web

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Characterizing the biology of primary brain tumors and their microenvironment via single-cell profiling methods

alexandrossfakianakis shared this article with you from Inoreader Characterizing the biology of primary brain tumors and their microenvironment via single-cell profiling methods via Neuro-Oncology Advance Access Abstract Genomic and transcriptional heterogeneity is prevalent among the most common and aggressive primary brain tumors in children and adults. Over the past 20 years, advances in bioengineering, biochemistry and bioinformatics have enabled the development of an array of techniques to study tumor biology at single-cell resolution. The application of these techniques to study primary brain tumors has helped advance our understanding of their intra-tumoral heterogeneity and uncover new insights regarding their co-option of developmental programs and signaling from their microenvironment to promote tumor proliferation and invasion. These insights are currently being harnessed to develop new therapeutic approaches. Here we provide an overview of current single-cell techniques and discuss relevant biology and therapeutic insights uncovered by their application to primary brain tumors in children and adults. View on Web

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Oral biofilm dysbiosis during experimental periodontitis

alexandrossfakianakis shared this article with you from Inoreader Oral biofilm dysbiosis during experimental periodontitis via Molecular Oral Microbiology Abstract Objectives We have previously characterized the main osteoimmunological events that occur during ligature periodontitis. This study aims to determine the polymicrobial community shifts that occur during disease development. Methods Periodontitis was induced in C57BL/6 mice using the ligature-induced periodontitis model. Healthy oral mucosa swabs and ligatures were collected every 3-days from 0 to 18 days post-ligature placement. Biofilm samples were evaluated by 16SrRNA gene sequencing (Illumina MiSeq) and QIIME. Timecourse changes were determined by relative abundance, diversity, and rank analyses (PERMANOVA, Bonferroni-adjusted). Results Microbial differences between health and periodontal inflammation were observed at all phylogenic levels. An evident microbial community shift occurred in 25 genera during the advancement of "gingivitis" (3-6d) to periodontitis (9-18d). From day 0–18, dramatic changes were identified Streptococcus levels, with an overall decrease (54.04-0.02%) as well an overall increase of Enterococcus and Lactobacillus (23.7-73.1% and 10.1%-70.2%, respectively). Alpha-diversity decreased to its lowest at 3d, followed by an increase in diversity as disease advancement. Beta-diversity increased after ligature placement, indicating that bone loss develops in response to a greater microbial variability (p = 0.001). Levels of facultative and strict anaerobic bacteria augmented over the course of disease progression, with a total of 8 species significantly different during the 18-day period. Conclusion The data supports that murine gingival inflammation and alveolar bone loss develop in response to microbiome shifts. Bacterial diversity increased during progression to bone loss. These findings further support the utilization of the periodontitis ligature model for microbial shift analysis under different experimental conditions. This article is protected by copyright. All rights reserved View on Web

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