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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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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Impact of respiratory infection and chronic comorbidities on early pediatric antibiotic dispensing in the United States

alexandrossfakianakis shared this article with you from Inoreader Impact of respiratory infection and chronic comorbidities on early pediatric antibiotic dispensing in the United States via Clinical Infectious Diseases Advance Access Abstract Background In the United States, children under age 5 receive high volumes of antibiotics, which may contribute to antibiotic resistance. It has been unclear what role preventable illnesses and chronic comorbidities play in prompting antibiotic prescriptions. Methods We conducted an observational study with a cohort of 124,759 children under age 5 born in the United States between 2008 and 2013 with private medical insurance. Study outcomes included the cumulative number of antibiotic courses dispensed per child by age 5 and the proportion of children for whom at least one antibiotic course was dispensed by age 5. We identified which chronic medical conditions predicted whether a child would be among the top 20% of antibiotic recipients. Results Children received a mean of 6.8 (95% confidence interval [CI] 6.7, 6.9) antibiotic courses by age five, and 91% (95% CI 90, 92) of children had received at least one antibiotic course by age five. Most antibiotic courses (71%, 95% CI 70, 72) were associated with respiratory infections. Presence of a pulmonary/respiratory, otologic, and/or immunological comorbidity substantially increase a child's odds of being in the top 20% of antibiotic recipients. Children with at least one of these conditions received a mean of 10.5 (95% CI 10.4, 10.6) antibiotic courses by age 5. Conclusions Privately insured children in the US receive high volumes of antibiotics early in their lives, largely related to respiratory infections. Antibiotic dispensing is unequally distributed among children, with substantially more antibiotics dispensed to children with select comorbidities. 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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Inhibition of TRPC6 suppressed TGFβ-induced fibroblast-myofibroblast transdifferentiation in renal interstitial NRK-49F cells

alexandrossfakianakis shared this article with you from Inoreader Inhibition of TRPC6 suppressed TGFβ-induced fibroblast-myofibroblast transdifferentiation in renal interstitial NRK-49F cells via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 4 October 2022 Source: Experimental Cell Research Author(s): Shan Jiang, Lifei Gu, Yixin Hu, Younan Ren, Zhao Yang, Chengzhi Chai, Boyang Yu, Haitao Ge, Zhengyu Cao, Fang Zhao View on Web

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Imaging of pediatric neuroblastoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric neuroblastoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer ABSTRACT Neuroblastoma is the most common extracranial solid neoplasm in children. This manuscript provides consensus-based imaging recommendations for pediatric neuroblastoma patients at diagnosis and during follow-up. 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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Refractory pediatric acute myeloid leukemia expressing NUP98‐NSD1 fusion gene responsive to chemotherapy combined with venetoclax and decitabine

alexandrossfakianakis shared this article with you from Inoreader Refractory pediatric acute myeloid leukemia expressing NUP98‐NSD1 fusion gene responsive to chemotherapy combined with venetoclax and decitabine via Pediatric Blood & Cancer View on Web

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