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Τετάρτη 10 Αυγούστου 2022

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

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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.

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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

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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.
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Τρίτη 9 Αυγούστου 2022

Evaluation of Virtual Grid Processed Clinical Chest Radiographs

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imageObjectives We evaluated the different Virtual Grid software ratios (Fujifilm, Tokyo, Japan) on gridless clinical chest radiographs with visual grading analysis (VGA). In addition, we investigated the 2 image quality assessment algorithms (IQAAs). Materials and Methods Gridless chest radiographs of 50 different intensive care unit patients were collected and afterward processed with Virtual Grid software. Different software (SW) grid ratios—6:1, 10:1, 13:1, 17:1, and 20:1—were applied to investigate the image quality (IQ) improvement. Image quality improvement was assessed by 4 radiologists in a relative VGA study where the reference image was processed with SW grid ratio of 10:1. One of the IQAAs used to analyze the radiographs was implemented in our department but was originally developed by the research group of the Duke University Medical Center. A general IQ score (IQS) was calculated based on contrast, detail, and noise. Another IQAA—NIQE (naturalness image quality evaluator)—available in Matlab (MATLAB Research R2019b; the MathWorks, Inc) was evaluated. Both methods were compared with VGA. Results Visual grading analysis scores of gridless radiographs are significantly lower (P
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3-Dimensional Fluid and White Matter Suppression Magnetic Resonance Imaging Sequence Accelerated With Compressed Sensing Improves Multiple Sclerosis Cervical Spinal Cord Lesion Detection Compared With Standard 2-Dimensional Imaging

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imageObjectives Fluid and white matter suppression (FLAWS) is a recently proposed magnetic resonance sequence derived from magnetization-prepared 2 rapid acquisition gradient-echo providing 2 coregistered datasets with white matter– and cerebrospinal fluid–suppressed signal, enabling synthetic imaging with amplified contrast. Although these features are high potential for brain multiple sclerosis (MS) imaging, spinal cord has never been evaluated with this sequence to date. The objective of this work was therefore to assess diagnostic performance and self-confidence provided by compressed-sensing (CS) 3-dimensional (3D) FLAWS for cervical MS lesion detection on a head scan that includes the cervical cord without changing standard procedures. Materials and Methods Prospective 3 T scans (MS first diagnosis or follow-up) acquired between 2019 and 2020 were retrospectively analyzed. All patients underwent 3D CS-FLAWS (duration: 5 minutes 40 seconds), axial T2 turbo spin echo covering cervical spine from cervicomedullary junction to the same inferior level as FLAWS, and sagittal cervical T2/short tau inversion recovery imaging. Two readers performed a 2-stage double-blind reading, followed by consensus reading. Wilcoxon tests were used to compare the number of detected spinal cord lesions and the reader's diagnostic self-confidence when using FLAWS versus the reference 2D T2-weighted imaging. Results Fifty-eight patients were included (mean age, 40 ± 13 years, 46 women, 7 ± 6 years mean disease duration). The CS-FLAWS detected significantly more lesions than the reference T2-weighted imaging (197 vs 152 detected lesions, P
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Could red cell distribution width be used for predicting cardiac injury in neonates with COVID‐19?

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ABSTRACT

Background

Coronavirus disease 2019 (COVID-19) can affect people of all age groups and it can occasionally cause life-threatening clinical illness in immunologically immature population, especially in newborns. High red cell distribution width (RDW) values were used as early prognostic biomarker of some neonatal diseases. We aimed to determine the prognostic value of red cell distribution width in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infected neonates.

Methods

Newborns with positive SARS-CoV-2 polymerase chain reaction (PCR) test from a nasopharyngeal swab sample, who had refractory fever (>38°C and lasting more than 24 hours during hospitalization) screened for multisystem inflammatory syndrome in newborns (MIS-N), systemic inflammatory indexes calculated and cardiologic evaluation performed to these patients. Due to troponin levels (high: >45 ng/L and low: ≤45 ng/L) patients were grouped.

Results

Of the 68 SARS-CoV-2 PCR-positive newborns, 26 patients had refractory fever. Comparison of laboratory findings between the high and low troponin groups showed that RDW and neutrophil/lymphocyte ratio values were significantly higher in patients with high troponin levels (p = 0.022 and p = 0.030, respectively). The cut-off values with optimal sensitivity and specificity were determined as 1.00 for neutrophil/lymphocyte ratio (p = 0.205) and 16.6 for red cell distribution width (p = 0.014). None of the patients died.

Conclusions

Neonatal coronavirus disease 2019 generally has a benign prognosis, but can progress to severe disease and cases of MIS-N are rare. RDW could be prognostic in diagnosis and management of neonates with SARS-CoV-2 infection with high troponin levels.

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A case of primary neuroendocrine carcinoma of the mandibular gingiva treated using multimodal therapy

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Publication date: Available online 8 August 2022

Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

Author(s): Tomoaki Hamana, Shigeru Sakurai, Atsuko Hamada, Shinnichi Sakamoto, Hisako Furusho, Shigeaki Toratani

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

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

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

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

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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.

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Δευτέρα 8 Αυγούστου 2022

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

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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.
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