Τρίτη 24 Μαΐου 2022

Duration of replication-competent SARS-CoV-2 shedding among patients with severe or critical coronavirus disease 2019 (COVID-19)

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Abstract
Background
Patterns of shedding replication-competent SARS-CoV-2 in severe or critical COVID-19 are not well-characterized. We investigated the duration of replication-competent SARS-CoV-2 shedding in upper and lower airway specimens from patients with severe or critical COVID-19.
Methods
We enrolled patients with active or recent severe or critical COVID-19 who were admitted to a tertiary care hospital intensive care unit (ICU) or long-term acute care hospital (LTACH) because of COVID-19. Respiratory specimens were collected at predefined intervals and tested for SARS-CoV-2 using virus culture and RT-qPCR. Clinical and epidemiologic metadata were reviewed.
Results
We collected 529 respiratory specimens from 78 patients. Replication-competent virus was detected in 4 of 11 (36.3%) immunocompromised patients up to 45 days after symptom onset, and in 1 of 67 (14.9%) immunocompetent patients 10 days after symptom onset (P = 0.001). All culture-positive patients were in the ICU cohort and had persistent or recurrent symptoms of COVID-19. Median time from symptom onset to first specimen collection was 15 days (range, 6-45) for ICU patients and 58.5 days (range, 34-139) for LTACH patients. SARS-CoV-2 RNA was detected in 40 of 50 (80%) ICU patients and 7 of 28 (25%) LTACH patients.
Conclusions
Immunocompromise and persistent or recurrent symptoms were associated with shedding of replication-competent SARS-CoV-2, supporting the need for improving respiratory symptoms in addition to time as criteria for discontinuation of transmission-based precautions. Our results suggest that the period of potential infectiousness among immunocompetent patients with severe or critical COVID-19 may be similar to that reported for patients with milder disease.
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Hepatoprotective effect of the radiation countermeasure flagellin in the long term after irradiation of mice

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Utility of prophylactic percutaneous endoscopic gastrostomy tube in head and neck cancer patients undergoing concurrent chemoradiation: A prospective observational cohort

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Publication date: Available online 23 May 2022

Source: American Journal of Otolaryngology

Author(s): Tanadech Dechaphunkul, Pawitra Soonthornrak, Sarayut Lucien Geater, Arunee Dechaphunkul

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Therapeutic targeting of prenatal pontine ID1 signaling in diffuse midline glioma

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Abstract
Background
Diffuse midline gliomas (DMG) are highly invasive brain tumors with rare survival beyond two years past diagnosis and limited understanding of the mechanism behind tumor invasion. Previous reports demonstrate upregulation of the protein ID1 with H3K27M and ACVR1 mutations in DMG, but this has not been confirmed in human tumors or therapeutically targeted.
Methods
Whole exome, RNA, and ChIP-sequencing was performed on the ID1 locus in DMG tissue. Scratch-assay migration and transwell invasion assays of cultured cells were performed following shRNA-mediated ID1-knockdown. In vitro and in vivo genetic and pharmacologic [cannabidiol (CBD)] inhibition of ID1 on DMG tumor growth was assessed. Patient-reported CBD dosing information was collected.
Results
Increased ID1 expression in human DMG and in utero electroporation (IUE) murine tumors is associated with H3K27M mutation and brainstem location. ChIP-sequencing indicates ID1 regulatory regions are epigenetically active in human H3K27M-DMG tumors and prenatal pontine cells. Higher ID1-expressing astrocyte-like DMG cells share a transcriptional program with oligo/astrocyte-precursor cells (OAPCs) from the developing human brain and demonstrate upregulation of the migration regulatory protein SPARCL1. Genetic and pharmacologic (CBD) suppression of ID1 decreases tumor cell invasion/migration and tumor growth in H3.3/H3.1K27M PPK-IUE and human DIPGXIIIP* in vivo models of pHGG. The effect of CBD on cell proliferation appears to be non-ID1 mediated. Finally, we collected patient-reported CBD treatment data, finding that a clinical trial to standardize dosing may be beneficial.
Conclusions
H3K27M-mediated re-activation of ID1 in DMG results in a SPARCL1+ migratory transcriptional program that is therapeutically targetable with CBD.
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Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy

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Abstract
Background
Glioblastoma (GBM) is a highly lethal malignancy for which neoangiogenesis serves as a defining hallmark. The anti-VEGF antibody, bevacizumab, has been approved for the treatment of recurrent GBM, but resistance is universal.
Methods
We analyzed expression data of GBM patients treated with bevacizumab to discover potential resistance mechanisms. Patient-derived xenografts (PDXs) and cultures were interrogated for effects of phosphofructokinase-1, muscle isoform (PFKM) loss on tumor cell motility, migration, and invasion through genetic and pharmacologic targeting.
Results
We identified PFKM as a driver of bevacizumab resistance. PFKM functions dichotomize based on subcellular location: Cytosolic PFKM interacted with KIF11, a tubular motor protein, to promote tumor invasion, whereas nuclear PFKM safeguarded genomic stability of tumor cells through interaction with NBS1. Leveraging transcriptional profiles, bu pivacaine phenocopied genetic targeting of PFKM and enhanced efficacy of bevacizumab in preclinical GBM models in vivo.
Conclusion
PFKM drives novel molecular pathways in GBM, offering a translational path to a novel therapeutic paradigm.
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Antiseptic Skin Agents to Prevent Surgical Site Infection After Incisional Surgery: A Randomized, Three-armed Combined Non-inferiority and Superiority Clinical Trial (NEWSkin Prep Study)

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imageObjective: To compare SSI rates between the skin preparation agents: PI-Aq, povidone-iodine with alcohol (PI-Alc), and chlorhexidine with alcohol (C-Alc). Background: Guidelines suggest that alcohol-containing chlorhexidine solutions are the gold standard for skin preparation before surgery. It remains difficult to determine whether it is the chlorhexidine component or the addition of alcohol that confers the most benefit. Methods: We conducted a multicenter, prospective, combined non-inferiority (PI-Alc vs C-Alc) and superiority (PI-Alc vs PI-Aq) randomized clinical trial. Participants were randomized 1:1:1 to receive either C-Alc, PI-Alc, or PI-Aq. The primary outcome was SSI rate as defined by the Centers for Disease Control. Secondary outcomes were complication rates, length of hospital stay, readmissions, and skin reactions. Results: Between January 2015 and December 2018, 3213 patients were randomized (C-Alc: 1076, PI-Alc: 1075, and PI-Aq: 1062). Mean age of participants was 57% and 55% were female. SSI rates were: C-Alc 11.09%, PI-Alc 10.88%, and PI-Aq 12.56%. PI-Alc was found to be non-inferior to C-Alc (mean difference, −0.21%; 95% confidence interval, −2.85 to 2.44; P = 0.0009 non-inferiority), whereas PI-Alc was not superior to PI-Aq (mean difference, −1.68%; 95% confidence interval, −4.40 to 1.05; P = 0.2302). There were no differences seen in secondary outcomes between groups and no treatment related adverse events or deaths occurred. Conclusions: PI-Alc is non-inferior to C-Alc and not superior to PI-Aq. This is at odds with current guidelines that suggest alcohol-based chlorhexidine solutions should routinely be used for surgical skin preparation. Trial Registration: Australia and New Zealand Clinical Trials Registry: ANZCTRN12615000021571. www.anzctr.org.au
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Sentinel Node Biopsy Imaging in Breast Cancer: Scatter Reduction Using 3-Dimensionally Printed Lead Shields

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imageBackground Point of injection scatter (SPI) confounds breast cancer sentinel lymph node detection. Round flat lead shields (FLSs) incompletely reduce SPI, requiring repositioning. We designed lead shields that reduce SPI and acquisition time. Methods Two concave lead shields, a semioval lead shield (OLS) and a semispherical lead alloy shield (SLS), were created with a SICNOVA JCR 1000 3D printer to cover the point of injection (patent no. ES1219895U). Twenty breast cancer patients had anterior and anterior oblique imaging, 5 minutes and 2 hours after a single 111 MBq nanocolloid in 0.2 mL intratumoral or periareolar injection. Each acquisition was 2 minutes. Absolute and normalized background corrected scatter counts (CSCs) and scatter reduction percentage (%SR) related to the FLS were calculated. Repositionings were recorded. Differences between means of %SR (t test) and between means of CSC (analysis of variance) with Holm multiple comparison tests were determined. Results Mean %SR was 91.8% with OLS and 92% using SLS in early images (P = 0.91) and 87.2%SR in OLS and 88.5% in late images (P = 0.66). There were significant differences between CSC using FLS and OLS (P
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Advanced Achalasia Mimicking Delayed Gastric Emptying During Standard Gastric Emptying Scintigraphy

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imageAn 82-year-old man underwent outpatient nuclear medicine gastric-emptying scintigraphy (GES) for dysphagia and regurgitation. Standard solid-meal GES showed significant elongated tracer retention with calculated 96% retention rate at 3 hours, with a presumed diagnosis of delayed gastric emptying. Subsequent CT of the chest and abdomen and upper gastrointestinal fluoroscopy instead showed normal size and function of the stomach but an enormously dilated esophagus with food debris, compatible with achalasia. Attention should be made on the location and shape of the visualized "stomach" and recognize that significantly di lated esophagus can mimic an elongated stomach during GES.
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