Microbial Cell-Free DNA Identifies the Causative Pathogen in Infective Endocarditis and Remains Detectable Longer Than Conventional Blood Culture in Patients with Prior Antibiotic Therapy

alexandrossfakianakis shared this article with you from Inoreader Microbial Cell-Free DNA Identifies the Causative Pathogen in Infective Endocarditis and Remains Detectable Longer Than Conventional Blood Culture in Patients with Prior Antibiotic Therapy via Clinical Infectious Diseases Advance Access Abstract Background The diagnosis of infective endocarditis (IE) can be difficult, particularly if blood cultures fail to yield a pathogen. This study evaluates the potential utility of microbial cell-free DNA (mcfDNA) as a tool to identify the microbial etiology of IE. Methods Blood samples from patients with suspected IE were serially collected. mcfDNA was extracted from plasma and underwent next-generation sequencing (NGS). Reads were aligned against a library containing DNA sequences belonging to >1400 different pathogens. mcfDNA from organisms present above a statistical threshold were reported and quantified in molecules/mL (MPM). Additional mcfDNA was collected on each subject every 2-3 days for a total of 7 collections or until discharge. Results Of 30 enrolled patients with suspected IE, 23 had Definite IE, 2 had Possible IE, and IE was Rejected in 5 patients by modified Duke Criteria. Only the 23 patients with Defi nite IE were included for analysis. Both mcfDNA and blood cultures achieved a sensitivity of 87%. The median duration of positivity from antibiotic treatment initiation was estimated to be approximately 38.1 days for mcfDNA vs 3.7 days for blood culture (proportional Odds 2.952, p= 0.02771), using a semi-parametric survival analysis. mcfDNA (log10) levels significantly declined (-0.3 MPM log10 units, 95% credible interval -0.45, -0.14) after surgical source control was performed (pre- vs post-procedure, posterior probability >0.99. Conclusion mcfDNA accurately identifies the microbial etiology of IE. Sequential mcfDNA levels may ultimately help to individualize therapy by estimating a patient's burden of infection and response to treatment. View on Web

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FAM19A4/miR124-2 methylation testing and HPV16/18 genotyping in HPV-positive women under the age of 30 years

alexandrossfakianakis shared this article with you from Inoreader FAM19A4/miR124-2 methylation testing and HPV16/18 genotyping in HPV-positive women under the age of 30 years via Clinical Infectious Diseases Advance Access Abstract Introduction HSIL or CIN2/3 lesions in HPV-positive women <30 years have high spontaneous regression rates. To reduce overtreatment, biomarkers are needed to delineate advanced CIN lesions that require treatment. We analysed the FAM19A4/miR124-2 methylation test and HPV16/18 genotyping in HPV-positive women <30 years aiming to identify CIN2/3 lesions in need of treatment. Methods A European multicentre retrospective study was designed evaluating the FAM19A4/miR124-2 methylation test and HPV16/18 genotyping in cervical scrapes of 1,061 HPV-positive women aged 15-29 years (690 ≤CIN1, 166 CIN2 and 205 CIN3+). A subset of 62 CIN2 and 103 CIN3 were immunohistochemically characterized by HPV E4 expression, a marker for a productive HPV infection and p16ink4a and Ki-67, markers indicative for a transforming infection. CIN2/3 lesions with low HPV E4 expression and high p16ink4a/Ki-67 expression were considered as non-productive, transforming CIN, compatible with advanced CIN2/3 lesions in need of treatment. Results FAM19A4/miR124-2 methylation positivity increased significantly with CIN grade and age groups (<25, 25-29 and ≥30 years), while HPV16/18 positivity was comparable across age groups. FAM19A4/miR124-2 methylation positivity was HPV type independent. Methylation-positive CIN2/3 lesions had higher p16ink4a/Ki-67-immunoscores (p = 0.003) and expressed less HPV E4 (p = 0.033) compared with methylation-negative CIN2/3 lesions. These differences in HPV E4 and p16ink4a/Ki-67 expression were not found between HPV16/18-positive and non-16/18 HPV-positive lesions. Conclusions Compared with HPV16/1 8 genotyping, the FAM19A4/miR124-2 methylation test detects non-productive, transforming CIN2/3 lesions with high specificity in women <30 years, providing clinicians supportive information about the need for treatment of CIN2/3 in young HPV-positive women. View on Web

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Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons

alexandrossfakianakis shared this article with you from Inoreader Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons via Clinical Infectious Diseases Advance Access ABSTRACT In a cohort of 483 high-risk patients treated with nirmatrelvir/ritonavir for coronavirus disease-2019, two patients (0.4%) required hospitalization by day 30. Four patients (0.8%) experienced rebound of symptoms, which were generally mild, at median of 9 days after treatment, and all resolved without additional COVID-19-directed therapy. View on Web

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Alterations in kinematics of temporomandibular joint associated with chronic neck pain

alexandrossfakianakis shared this article with you from Inoreader Alterations in kinematics of temporomandibular joint associated with chronic neck pain via Journal of Oral Rehabilitation Abstract Background Temporomandibular disorder (TMD) is an umbrella term for pain and dysfunction of the temporomandibular joint (TMJ) and its associated structures. Patients with TMD show changes in TMJ kinematics and masticatory muscle activation. TMD is commonly comorbid with non-specific chronic neck pain (NCNP), which may be one of the risk factors for TMD. Objectives This study aimed to investigate whether patients with NCNP have altered TMJ kinematics and masticatory muscle activity. Methods This was a cross-sectional exploratory study including 19 healthy participants and 20 patients with NCNP but without TMD symptoms. TMJ kinematics was measured during mouth opening and closing, jaw protrusion and jaw lateral deviation. Surface electromyography was used to record the muscle activity of the anterior temporalis, masseter, sternocleidomastoid, and upper trapezius while clenching. Furthermore, cervical posture, cervical range of motion (ROM), and pressure pain threshold of the neck and masticatory muscles were measured. Results Compared with the healthy group, the NCNP group showed significantly reduced upper cervical rotation ROM (p=0.041), and increased condylar path length (p=0.02), condylar translation (opening p=0.034, closing p=0.011), and mechanical pain sensitivity of the upper trapezius (p=0.018). Increased condylar translation was significantly correlated with reduced upper cervical mobility and poor cervical posture (r=−0.322 to −0.397; p=0.012–0.046). Conclusion Increased condylar translation and path length in patients with NCNP may indicate poor control of TMJ articular movement, which may result from neck pain or may be a compensation for limited neck mobility. Evaluation of excessive TMJ translation may be considered in patients with NCNP. View on Web

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Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial

alexandrossfakianakis shared this article with you from Inoreader Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial via ScienceDirect Publication: The Lancet Infectious Diseases Publication date: Available online 13 June 2022 Source: The Lancet Infectious Diseases Author(s): Sean R Bennett, James M McCarty, Roshan Ramanathan, Jason Mendy, Jason S Richardson, Jonathan Smith, Jeff Alexander, Julie E Ledgerwood, Paul-André de Lame, Sarah Royalty Tredo, Kelly L Warfield, Lisa Bedell View on Web

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Correlation between the intensity of Helicobacter pylori colonization and severity of gastritis: Results of a prospective study

alexandrossfakianakis shared this article with you from Inoreader Correlation between the intensity of Helicobacter pylori colonization and severity of gastritis: Results of a prospective study via Helicobacter Abstract Helicobacter pylori infection is strongly associated with chronic gastritis and is probably the main course of chronic inflammation in the gastric mucosa. Gradually, H. pylori gastritis will result in gastric atrophy and intestinal metaplasia. Identifying the relationship between intensity of colonization and activity of gastritis helps the clinician in more effective treatment and post-treatment follow-ups. The aim of our work was to analyze the relationship between the density of H. pylori colonization of the gastric mucosa and the severity of histological parameters of gastritis (inflammation activity, gastric atrophy, and intestinal metaplasia). This was a prospective monocentric study conducted from January 2020 to December 2020, collecting patients naive to any anti-H. pylori treatment and having a chronic H. pylori infection documented by histological examination. Epidemiological, endoscopic, and anathomopathological da ta were collected. Ninety-seven patients with a mean age of 42.6 years [18–65 years] and a sex ratio of M/F = 0.64 were included. The density of H. pylori colonization was mild (+) in 43.3% of patients, moderate (++) in 47.4% of patients, and significant (+++) in 9.3% of patients. Nearly, ten per cent of patients had no gastritis, 33% had mild gastritis, 50.5% had moderate gastritis, and 6.2% had severe gastritis. Gastric atrophy and intestinal metaplasia were found in 44.3% and 10.3% of our population, respectively. Patients with mild H. pylori colonization rates had the highest level of mild activity (59.5%). There was a statistically significant association between the severity of H. pylori infection and gastritis activity (p < .001). Gastric atrophy was significantly associated with the intensity of H. pylori colonization (p = .049). No significant relationship was found between the in tensity of colonization and metaplasia (p = .08). Our study shows that there is a statistically significant association between the density of H. pylori and histopathological findings including gastritis activity and intestinal atrophy. View on Web

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NSAIDs in sciatica (NIS): study protocol for an investigator-initiated multicentre, randomized placebo-controlled trial of naproxen in patients with sciatica

alexandrossfakianakis shared this article with you from Inoreader NSAIDs in sciatica (NIS): study protocol for an investigator-initiated multicentre, randomized placebo-controlled trial of naproxen in patients with sciatica via Trials - Latest Articles Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat sciatica, despite insufficient evidence from placebo-controlled trials. NSAIDs may cause serious side effects; hence, there is a strong ne... View on Web

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A Nomogram to Predict Nodal Response after Induction Chemotherapy for Hypopharyngeal Carcinoma

alexandrossfakianakis shared this article with you from Inoreader A Nomogram to Predict Nodal Response after Induction Chemotherapy for Hypopharyngeal Carcinoma via The Laryngoscope This study is the first to establish and validate a nomogram based on five critical predictors, including tumor differentiation degree (DD), T classification, metastatic lymph node size (LS), number of lymph node metastases (NOL), and cervical nodal necrosis (CNN), to predict the response of metastatic lymph nodes after induction chemotherapy (ICT) for hypopharyngeal carcinoma patients. Our nomogram yielded relatively good accuracy in predicting the regional ICT response, which will be a useful tool to assist clinicians in future decision-making. Background For hypopharyngeal carcinoma, metastatic neck nodes with a low response to induction chemotherapy (ICT) should not be managed with concomitant chemoradiotherapy (CCRT), and the prediction of chemosensitivity before ICT could prevent adverse events from occurring during chemotherapy. In this study, we developed a nomogram to predict the regional response to ICT. Methods A total of 153 hypopharyngeal carcinoma patients with regional metastasis treated with ICT in our institution from January 2010 to September 2020 were retrospectively studied. According to ICT response evaluated by RECIST 1.1, patients were divided into chemo-insensitive (PR < 70%/SD/PD) (group 1) and chemosensitive (CR/PR ≥ 70%) (group 2) groups. Patients' clinical, image, and hematologic data before ICT were collected. The nomogram was built based on multivariate analysis and stepwise logistic regression and was evaluated from the aspects of discrimination and calibration. Results A nomogram based on five critical predictors, namely, tumor differentiation degree, T classification, metastatic lymph node size, number of lymph node metastases, and cervical nodal necrosis, was developed. The areas under the curve (AUC) values were 0.76 and 0.70 after adjusting the results using bootstrap methods. The calibration curve showed relatively good agreement between the predicted and observed probabilities. Conclusions Our nomogram yielded good accuracy in predicting the regional ICT response and will be a useful tool to assist clinicians in decision making. Level of Evidence 4 Laryngoscope, 2022 View on Web

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