Investigations Into Obesity and the Risk of Malignant Disease in Pediatric Thyroid Nodules—Reply

alexandrossfakianakis shared this article with you from Inoreader Investigations Into Obesity and the Risk of Malignant Disease in Pediatric Thyroid Nodules—Reply via JAMA Otolaryngology–Head & Neck Surgery Current Issue In Reply We thank Gallant et al for their interest in our recent publication regarding the association of body mass index (BMI) with thyroid cancer in children with thyroid nodules. We agree that differences in design may account for some discrepancies between our study and theirs. Different methods of calculating BMI z-scores might play a role, although our selection of the Centers for Disease Control and Prevention nomograms reflects their wide use in clinical practice. Similarly, our use of nodule diameter rather than nodule volume reflects current recommendations for thyroid nodule evaluation, and is unlikely to be relevant given the excellent correlation of these measures in our cohort (r = 0.97; 95% CI, 0.96-0.97). View on Web

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Stimulation Rate and Voice Pitch Perception in Cochlear Implants

alexandrossfakianakis shared this article with you from Inoreader Stimulation Rate and Voice Pitch Perception in Cochlear Implants via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com We describe two experiments with 16 Nu cleus® CI users, where we controlled modulation characteristics and carrier rate using Spectral and Temporal Enhanced Processing (STEP), a novel experimental multichannel sound coder. We used a fixed set of threshold and comfortable stimulation levels for each subject, obtained from clinical MAPs. In the first experiment, we determined equivalence for voice pitch ranking and voice gender categorization between the Advanced Combination Encoder (ACE), a widely used clinical strategy in Nucleus® recipients, and STEP for fundamental frequencies (F0) 120–250 Hz. In the second experiment, loudn ess was determined as a function of the input amplitude of speech samples for carrier rates of 1000, 500, and 250 pps per channel. Then, using equally loud soun... View on Web

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The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus

alexandrossfakianakis shared this article with you from Inoreader The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus via Journal of Medical Virology ABSTRACT Hepatitis B Virus (HBV) infections remain a major global health burden with an estimated 296 million people living with a chronic infection and 884,00 HBV-related deaths annually. Notably, patients with a chronic hepatitis B (CHB) infection are at a 30-fold greater risk of developing hepatocellular carcinoma (HCC), the 3rd deadliest cancer worldwide. Several groups have assessed HBV-related aberrant expression of host-cell long non-coding RNAs (lncRNAs) and how altered expression of specific lncRNAs affects HBV replication and progression to associated disease states. Given the challenges in establishing effective HBV models and analyzing transcriptomic data, this review focuses on lncRNA expression data primarily collected from clinical patient samples and primary human hepatocytes (PHHs), with subsequent mechanism of action analysis in cell lines or other model systems. Ultimately, understanding HBV-induced lncRNA-expression dysregulation could lead to new treatments and biomarkers for HBV infection and its associated diseases. This article is protected by copyright. All rights reserved. View on Web

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A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics

alexandrossfakianakis shared this article with you from Inoreader A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics via Neuro-Oncology Advance Access Abstract Background Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive LMD. Methods This multicenter study enrolled 34 LMD patients in a combined Phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the Phase I; the Phase II was limited to HER2-positive breast cancer. Results Intrathecal trastuzumab was well tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended Phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80mg w ere included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for Phase 2 dose treated patients was 8.3 months (95% CI 5.2 to 19.6). The Phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2 to 20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable CSF concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations. Conclusion This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients. View on Web

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Prediction models for carbapenem‐resistant Enterobacterales carriage at liver transplantation: A multicenter retrospective study

alexandrossfakianakis shared this article with you from Inoreader Prediction models for carbapenem‐resistant Enterobacterales carriage at liver transplantation: A multicenter retrospective study via Transplant Infectious Disease Graphical abstract: Abstract Background Carbapenem-resistant Enterobacterales (CRE) colonisation at liver transplantation (LT) increases the risk of CRE infection after LT, which impacts on recipients' survival. Colonization status usually becomes evident only near LT. Thus, predictive models can be useful to guide antibiotic prophylaxis in endemic centres. Aims This study aimed to identify risk factors for CRE colonisation at LT in order to build a predictive model. Methods Retrospective multicentre study including consecutive adult patients who underwent LT, from 2010 to 2019, at two large teaching hospitals. We excluded patients who had CRE infections within 90 days before LT. CRE screening was performed in all patients on the day of LT. Exposure variables were considered within 90 days before LT and included cirrhosis complications, underlying disease, time on the waiting list, MELD and CLIF-SOFA scores, antibiotic use, intensive care unit and hospital stay, and infections. A machine learning model was trained to detect the probability of a patient being colonized with CRE at LT. Results A total of 1544 patients were analyzed, 116 (7.5%) patients were colonized by CRE at LT. The median time from CRE isolation to LT was 5 days. Use of antibiotics, hepato-renal syndrome, worst CLIF sofa score, and use of beta-lactam/beta-lactamase inhibitor increased the probability of a patient having pre-LT CRE. The proposed algorithm had a sensitivity of 66% and a specificity of 83% with a negative predictive value of 97%. Conclusions We created a model able to predict CRE colonization at LT based on easy-to-obtain features that could guide antibiotic prophylaxis View on Web

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Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: a cross‐sectional study

alexandrossfakianakis shared this article with you from Inoreader Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: a cross‐sectional study via Journal of Medical Virology Abstract Multiple human papillomavirus (HPV) infections are common, but their impact on cervical lesions remains controversial. A total of 6225 female patients who underwent colposcopies/conization following abnormal cervical cancer screening results were included in the study. The final pathological diagnosis was determined by the most severe pathological grade among the cervical biopsy, ECC and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between multiple HPV infections and cervical lesions, adjusting for age, HPV genotype, gravidity and parity. In total, 33.3% (n=2076) of the study population was infected with multiple HPV genotypes. Multiple HPV infections were more prevalent in patients younger than 25 years and older than 55 years, with the rate of multiple HPV infections at 52.8% and 44.3%, respectively. HPV16\52\18\58 are the most common HPV genotypes and usually appear as a single infection. Co mpared to single HR-HPV infection, multiple HR-HPV infections do not increase the risk of HSIL+, while single HR-HPV coinfected with LR-HPV seems to reduce the risk of HSIL+ (OR=0.515, CI: 0.370-0.719, P＜0.001). Multiple HR-HPV infections cannot be risk-stratified for triage of HR-HPV-positive women. This article is protected by copyright. All rights reserved. View on Web

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Initiating Intramuscular Depot Medroxyprogesterone Acetate (DMPA-IM) Increases Frequencies of Th17-like Human Immunodeficiency Virus (HIV) Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial

alexandrossfakianakis shared this article with you from Inoreader Initiating Intramuscular Depot Medroxyprogesterone Acetate (DMPA-IM) Increases Frequencies of Th17-like Human Immunodeficiency Virus (HIV) Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial via Clinical Infectious Diseases Advance Access Abstract BackgroundCervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells. Methods Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry. Results Unlike the LNG implant or copper-IUD, DMPA-IM was as sociated with higher frequencies of cervical Th17-like cells within 1 month of initiation (P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and α4β7 (P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD (P = .0002) or LNG implant (P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non–Lactobacillus-dominant microbiome at baseline was associated with more Th17-like cells post–DMPA-IM (P = .03), although this did not influence barrier function. Conclusions Our data suggest that D MPA-IM–driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity. View on Web

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