No Reduction in the 226-Hz Probe Tone Acoustic Reflex Amplitude Following Severe Inner Hair Cell Loss in Chinchillas

alexandrossfakianakis shared this article with you from Inoreader No Reduction in the 226-Hz Probe Tone Acoustic Reflex Amplitude Following Severe Inner Hair Cell Loss in Chinchillas via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractThe relationship between the middle ear acoustic reflex (AR) and inner hair cell (IHC) loss is currently unknown. Given that IHC are believed to convey nearly all acoustic information to the central auditory nervous system, it has been assumed that loss of IHC would significantly impact the AR. To evaluate this relationship, we assessed the presence and amplitude of the AR in chinchillas before and after treatment with carboplatin, an anticancer drug that reliably and selectively destroys IHC in this species. Baseline measures of hearing sensitivity, including auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAE), were assessed and then re-evaluated following carboplatin treatment. Post-carboplatin ABR thresholds and DPOAE were found to b... View on Web

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Case volume regionalization and volume‐based outcome differences in cutaneous head and neck melanoma

alexandrossfakianakis shared this article with you from Inoreader Case volume regionalization and volume‐based outcome differences in cutaneous head and neck melanoma via Head & Neck Abstract Background Hospital volume has emerged as a prognostic factor in oncology but is not currently known whether volume is associated with improved outcomes for cutaneous head and neck (HN) melanoma. Methods A total of 556 079 cutaneous melanoma cases reported by the 2004–2016 National Cancer Database were separated into two cohorts (HN and non-HN) and facilities within each cohort were classified by case volume. Analysis employed chi-square, analysis of variance, Kaplan–Meier, and Cox proportional hazards models. Results Only 41 facilities (3.1% of 1326) treating HN melanoma and 50 facilities (3.7% of 1344) treating non-HN melanoma were classified as high-volume facilities (HVFs). The estimated 5-year overall survival (OS) was 62.7% (standard error [SE]: 0.4%) for patients with HN at low-volume facilities (LVFs), 69.3% (SE: 0.4%) at IVFs, and 71.8% (SE 0.4%) at HVFs (p < 0.001). Differences in OS remained significant between HVFs versus LVFs after adjusting for confounders. Conclusion Volume is independently associated with OS and improved surgical outcomes for HN melanoma. View on Web

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Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV

alexandrossfakianakis shared this article with you from Inoreader Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV via Clinical Infectious Diseases Advance Access Abstract Background Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with HIV who have heightened immune activation and cardiovascular risks. Methods Among 609 post-menopausal women (1,234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis – carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. Results Women (mean age = 51, 80% HIV+) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio = 0.57; 95% CI = [0.40, 0.80]; p < 0.01), 2.51 µm less progression of CIMT per year (95% CI = [-4.60, -0.41]; p = 0.02), and marginally lower incidence of plaque over ∼7 years (risk ratio = 0.38; 95% CI = [0.14, 1.03]; p = 0.06), compared with never users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. Conclusions HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low. View on Web

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Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial

alexandrossfakianakis shared this article with you from Inoreader Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial via Clinical Infectious Diseases Advance Access Abstract Background This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation. Methods PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation <95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in th e number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18. Results Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib. Conclusions Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. View on Web

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Stool interleukin-1β differentiates Clostridioides difficile infection from asymptomatic carriage and non-C.difficile infection diarrhea

alexandrossfakianakis shared this article with you from Inoreader Stool interleukin-1β differentiates Clostridioides difficile infection from asymptomatic carriage and non-C.difficile infection diarrhea via Clinical Infectious Diseases Advance Access Abstract Background Despite advances in the understanding and diagnosis of Clostridioides difficile Infection (CDI), clinical distinction within the colonization-infection continuum remains an unmet need. Methods By measuring stool cytokines and anti-toxin antibodies in well-characterized cohorts of CDI (diarrhea, Nucleic Acid Amplification Test [NAAT]+), Non-CDI diarrhea (NCD; diarrhea, NAAT-), asymptomatic carriers (ASC; no diarrhea, NAAT+) and hospital controls (CON, no diarrhea, NAAT-), we aim to discover novel biological markers to distinguish between these cohorts. We also explore the relationship of these stool cytokines and anti-toxin antibody with stool toxin concentrations and disease severity. Results Stool interleukin ( IL)-1β, stool IgA, and IgG anti-toxin A had higher (p < 0.0001) concentrations in CDI (n = 120) vs. ASC (n = 43), whereas toxins A, B, and fecal calprotectin did not. Areas Under the Receiver Operator Curve (ROC-AUCs) for IL-1β, IgA, and IgG anti-toxin A were 0.88, 0.83, and 0.83, respectively. A multi-predictor model including IL-1β and IgA anti-toxin A achieved a ROC-AUC of 0.93. Stool IL-1β concentrations were higher in CDI compared to NCD (n = 75), p < 0.0001, and NCD + ASC + CON (CON, n = 75), p < 0.0001, with ROC-AUCs of 0.83 and 0.86, respectively. Stool IL-1β had positive correlations with toxins A (ρA=+0.55) and B (ρB=+0.49) in CDI (p < 0.0001) but not in ASC (p > 0.05). Conclusion Stool concentrations of the inflammasome pathway, pro-inflammatory cytokine IL-1β can accurately differentiate CDI from asymptomatic carriage and non-CDI diarrhea, making it a promising biomarker for CDI diagnosis. Significant positive correlations exist between stool toxins and stool IL-1β in CDI but not in asymptomatic carriers. View on Web

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Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091)

alexandrossfakianakis shared this article with you from Inoreader Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091) via Clinical Infectious Diseases Advance Access Abstract Background Empiric antifungal therapy is considered the standard-of-care for high-risk neutropenic patients with persistent fever. The impact of a pre-emptive, diagnostic-driven approach based on galactomannan (GM) screening and chest CT-scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. Methods Patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (Arm A) or pre-emptively (Arm B). All patients received fluconazole 400 mg daily as prophylaxis. The primary endpoint of this non-inferiority study was overall survival (OS) 42 days after randomization. Results Of 556 patients recruited, 549 were eligible: 275 in Arm A, 274 in Arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemothe rapy and 93% of them were in first induction phase. At day 42, the OS was not inferior in Arm B (96.7%; 95% confidence interval (CI), 93.8 - 98.3%) when compared to Arm A (93.1%; 95% CI, 89.3 - 95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95%CI, 4.5–10.8%) in Arm B versus 6.6% (95%CI, 3.6–9.5%) in Arm A, respectively. The rate of patients receiving caspofungin was significantly lower in Arm B (27%) than in Arm A (63%) (p < 0.001). Conclusions The pre-emptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. View on Web

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Cytocompatibility and bioactive potential of AH Plus Bioceramic Sealer: an in vitro study

alexandrossfakianakis shared this article with you from Inoreader Cytocompatibility and bioactive potential of AH Plus Bioceramic Sealer: an in vitro study via International Endodontic Journal Abstract Abstract Aim To assess the cytocompatibility and bioactive potential of the new calcium silicate cement-based sealer AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared to the epoxy resin-based sealer AH Plus (AHP) and the calcium silicate cement-based sealer Endosequence BC Sealer (ESbcs). Methodology Standardized sample discs and 1:1, 1:2, and 1:4 eluates of the tested materials were prepared. The following assays were performed: surface element distribution via SEM-EDX, cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, osteo/cemento/odontogenic marker expression via RT-qPCR, and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p<0.05. Results A higher peak of Ca2+ was detected from ESbcs compared with AHPbcs and AHP in SEM-EDX. Both AHPbcs and ESbcs showed significantly positive results in the cytocompatibility assays (cell viability, migration/proliferation, attachment, and morphology) compared with a negative control group, while AHP showed significant negative results. Both AHPbcs and ESbcs exhibited an upregulation of at least one osteo/odonto/cementogenic marker compared to the negative and positive control groups. Both ESbcs and AHPbcs showed a significantly higher calcified nodule formation than the negative and positive control groups, indicative of their biomineralization potential, and were also significantly higher than AHP group. Conclusion AH Plus Bioceramic Sealer exhibited a significantly higher cytocompatibility and bioactive potential than AH Plus, and a similar cytocompatibility to that of Endosequence BC Sealer. Endosequence BC Sealer exhibited a significantly higher mineralization potential than the other tested sealers. The results from this in vitro study act as supporting evidence for the use of AH Plus bioceramic sealer in root canal treatment. View on Web

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