To evaluate association between biomarkers and outcomes in COVID-19 hospitalised patients. COVID-19 pandemic has been a challenge. Biomarkers have always played an important role in clinical decision ...making in various infectious diseases. It is crucial to assess the role of biomarkers in evaluating severity of disease and appropriate allocation of resources.
Systematic review and meta-analysis. English full text observational studies describing the laboratory findings and outcomes of COVID-19 hospitalised patients were identified searching PubMed, Web of Science, Scopus, medRxiv using Medical Subject Headings (MeSH) terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from 1 December 2019 to 15 August 2020 following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines.
Studies having biomarkers, including lymphocyte, platelets, D-dimer, lactate dehydrogenase (LDH), C reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT) and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers.
Composite poor outcomes include intensive care unit admission, oxygen saturation <90%, invasive mechanical ventilation utilisation, severe disease, in-hospital admission and mortality. The OR and 95% CI were obtained and forest plots were created using random-effects models. Publication bias and heterogeneity were assessed by sensitivity analysis.
32 studies with 10 491 confirmed COVID-19 patients were included. We found that lymphopenia (pooled-OR: 3.33 (95% CI: 2.51-4.41); p<0.00001), thrombocytopenia (2.36 (1.64-3.40); p<0.00001), elevated D-dimer (3.39 (2.66-4.33); p<0.00001), elevated CRP (4.37 (3.37-5.68); p<0.00001), elevated PCT (6.33 (4.24-9.45); p<0.00001), elevated CK (2.42 (1.35-4.32); p=0.003), elevated AST (2.75 (2.30-3.29); p<0.00001), elevated ALT (1.71 (1.32-2.20); p<0.00001), elevated creatinine (2.84 (1.80-4.46); p<0.00001) and LDH (5.48 (3.89-7.71); p<0.00001) were independently associated with higher risk of poor outcomes.
Our study found a significant association between lymphopenia, thrombocytopenia and elevated levels of CRP, PCT, LDH, D-dimer and COVID-19 severity. The results have the potential to be used as an early biomarker to improve the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic.
Interferon-inducible human oligoadenylate synthetase-like (OASL) and its mouse ortholog, Oasl2, enhance RNA-sensor RIG-I-mediated type I interferon (IFN) induction and inhibit RNA virus replication. ...Here, we show that OASL and Oasl2 have the opposite effect in the context of DNA virus infection. In Oasl2−/− mice and OASL-deficient human cells, DNA viruses such as vaccinia, herpes simplex, and adenovirus induced increased IFN production, which resulted in reduced virus replication and pathology. Correspondingly, ectopic expression of OASL in human cells inhibited IFN induction through the cGAS-STING DNA-sensing pathway. cGAS was necessary for the reduced DNA virus replication observed in OASL-deficient cells. OASL directly and specifically bound to cGAS independently of double-stranded DNA, resulting in a non-competitive inhibition of the second messenger cyclic GMP-AMP production. Our findings define distinct mechanisms by which OASL differentially regulates host IFN responses during RNA and DNA virus infection and identify OASL as a negative-feedback regulator of cGAS.
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•Loss of human OASL and mouse Oasl2 inhibits DNA virus infection•OASL and Oasl2 inhibit cGAS-mediated IFN induction•OASL specifically binds to cGAS to inhibit cGAS enzyme activity•OASL binds to cGAS independently of double-stranded DNA
The interferon (IFN)-stimulated gene OASL enhances RNA-sensor RIG-I-mediated IFN induction to inhibit RNA virus replication. In contrast, Ghosh et al. show that during DNA virus infection, OASL binds to the DNA sensor cGAS to inhibit IFN induction and enhance DNA virus replication. These findings highlight the distinct regulation of IFN induction by OASL during RNA and DNA virus infection.
Background and Purpose
Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome characterized by reversible segmental vasoconstriction of cerebral arteries. Digital subtraction and ...noninvasive angiograms are typically used to detect vasospasm; however, due to the dynamic nature of RCVS these tests are often negative initially and may need to be repeated multiple times. Transcranial Doppler (TCD) offers many advantages as it is a noninvasive and nonradiating modality. Studies investigating its diagnostic utility for capturing vasospasm and studying temporal evolution of RCVS are limited.
Methods
We conducted a retrospective analysis on all patients admitted with suspected RCVS from 2009 to 2014 to a single center at Jackson Memorial Hospital.
Results
We identified 9 patients (88.9% women, age 46.6 ± 13.5 years) who met diagnostic criteria for RCVS. All patients presented with headache, 5 developed nonaneurysmal subarachnoid hemorrhage, 5 developed ischemic stroke, and 1 developed posterior reversible encephalopathy syndrome. At initial TCD, 8 patients had increased flow velocities in at least one large intracranial artery and ultimately all patients had abnormal middle cerebral artery flow velocity over the course of RCVS. We found that the number of vessels with abnormal velocities increases gradually and peaks between 13 and 14 days after first symptom onset. Finally, mean flow velocity of affected vessels also increases around the same time frame and normalizes at 60 days.
Conclusions
In this case series, we found TCD to be useful in detecting vasospasm and monitoring the temporal evolution of RCVS. TCD could be a helpful clinical tool to diagnose and monitor RCVS.
Purpose
The study aimed to measure the percentage of preventable adverse drug reactions that lead to the hospitalization (PADR
Ad
) and to explore the heterogeneity in its estimation through subgroup ...analysis of study characteristics.
Methods
Two investigators independently searched in electronic databases and related bibliography for prospective studies involving PADR
Ad
. We excluded studies investigating medication errors and spontaneous and retrospective reporting. The primary outcome was PADR
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percentage. To explore the heterogeneity, we performed subgroup analysis based on study region, wards, age groups, adverse drug reaction (ADR) definitions, preventability assessment, ADR identification methods, study duration and sample size. We explored fatal PADR
Ad
and causative drugs as a secondary outcome. We used the generic inverse variance method with random effect model to compute meta-analytic summary.
Results
Of the 68 full-text articles assessed, we included 22 studies. The mean PADR
Ad
percentage was 45.11 % (95 % CI = 33.06–57.15;
I
2
= 99 %). Studies including elderly (63.31 %) and all age groups (49.03 %) showed higher percentages than paediatric population (16.40 %). Studies examining all hospital populations showed higher percentages than specific wards. We observed high percentages in studies using Edwards and Aronson as an ADR definition and Hallas et al. as a preventability assessment tool. After age group adjustment, ADR detection methods did not show significant difference. The fatal PADR
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percentage was 1.58 % (95 % CI = −0.60 to 3.76;
I
2
= 47 %). Paediatric and elderly studies showed a different causative drug pattern.
Conclusion
Variation in PADR
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across the studies can be explained by difference in study populations and data collection methods. Extrapolation of preventable reactions should be carried out considering all these factors with caution.
Female reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly ...explored. Herein, we examined the gut-vaginal microbiota axis in infertile women.
We recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31).
Compared with the controls, α-diversity and β-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05). Hungatella, associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genus Lactobacillus, with Lactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such as Leptotrichia and Snethia, occurred in the controls.
The gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.
In the current scenario, considerable attention is being given to the enzyme L-glutaminase (EC 3.5.1.2). It belongs to the amidohydrolase class adherent to the family of serine-reliant β-lactamases ...and the penicillin-binding proteins due to its higher affinity to polymerize and modify peptidoglycan synthesis. However, based on the catalytic proficiency, L-glutaminase is characterized as a proteolytic endopeptidase that cleaves peptide linkage and emancipates various byproducts, viz. ammonia along with glutamate. L-glutamine is considered the key amino acid reportedly involved in multiple metabolic pathways such as nitrogen metabolism. The present review is focused on the recent development and aspects concomitant to the biotechnological applicability of L-glutaminase predominantly from the marine habitat. Additionally, a majority of L-glutaminases finds application in cancer therapy as therapeutic agents, especially for acute lymphocytic leukaemia. The in vitro studies have been effective against various human cancer cell lines. L-glutaminase enhances the growth of probiotic bacteria. Apart from all these applications, it is suitably applicable in fermented foods as a flavour enhancer especially the umami flavour and content. Marine habitats have largely been exploited for their bio-catalytic potential but very scarcely for therapeutic enzymes. Some of the reports of such marine bacterial isolates from
Bacillus
sp.,
Pseudomonas
sp. and
Vibrio
sp. are in the domain, but none highlights the therapeutic applications predominantly as anticancer and anti-proliferative agents.
Key points
The exploration of marine habitats along the Gujarat coasts mainly for bacteria secreting L-glutaminase is scarcely reported, and even more scarce are the amidohydrolases from these marine niches as compared to their terrestrial counterparts.
Microbial sourced amidohydrolase has wide bio-applicability that includes food, cosmetics and therapeutics especially as anticancer/anti-proliferative agent making it of immense biotechnological significance
.
Over the past several decades, molecular imaging techniques to assess cellular processes in vivo have been integral in advancing our understanding of disease pathogenesis. 18F-fluorodeoxyglucose ...(18-FDG) positron emission tomography (PET) imaging in particular has shaped the field of atherosclerosis research by highlighting the importance of underlying inflammatory processes that are responsible for driving disease progression. The ability to assess physiology using molecular imaging, combining it with anatomic delineation using cardiac coronary angiography (CCTA) and magnetic resonance imaging (MRI) and lab-based techniques, provides a powerful combination to advance both research and ultimately clinical care. In this review, we demonstrate how molecular imaging studies, specifically using 18-FDG PET, have revealed that early vascular disease is a systemic process with multiple, concurrent biological mechanisms using inflammatory diseases as a basis to understand early atherosclerotic mechanisms in humans.
Psoriasis is an immune-mediated inflammatory disease with increased risk of myocardial infarction. Preclinical studies in psoriasis models show an association between chronic inflammation and immune ...cell proliferation in the spleen and bone marrow (BM). We sought to test the hypothesis that splenic and BM 18F-fluorodeoxyglucose (18F-FDG) uptake is heightened in psoriasis and that higher uptake associates with systemic inflammation and subclinical atherosclerotic disease measures in this cohort.
Multimodality imaging and biomarker assays were performed in 240 participants (210 with psoriasis and 30 healthy). Splenic and BM uptake was obtained using 18F-FDG positron emission tomography/computed tomography (PET/CT). Coronary artery plaque characteristics including non-calcified burden (NCB) and lipid rich necrotic core (LRNC) were quantified using a dedicated software for CT angiography. All analyses were performed with StataIC 16 (Stata Corp., College Station, TX, USA).
Splenic and BM 18F-FDG uptake was increased in psoriasis (vs. healthy volunteers) and significantly associated with proatherogenic lipids, immune cells and systemic inflammation. Higher splenic 18F-FDG uptake associated with higher total coronary burden (β = 0.37; p<0.001), NCB (β = 0.39; p<0.001), and LRNC (β = 0.32; p<0.001) in fully adjusted models. Similar associations were seen for BM 18F-FDG uptake in adjusted models (β = 0.38; β = 0.41; β = 0.24; respectively, all p<0.001).
Heightened splenic and BM uptake of 18F-FDG is associated with proatherogenic lipids, immune cells, inflammatory markers and coronary artery disease. These findings provide insights into atherogenic mechanisms in psoriasis and suggest that immune cell proliferation in the spleen and BM is associated with subclinical atherosclerosis.
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•Splenic and bone marrow (BM) uptake represents heightened immune cell proliferation.•Splenic and BM uptake relates to atherogenic lipid, immune and inflammatory measures.•Splenic and BM uptake relates to non-calcified burden and lipid rich necrotic core.
Patients with myocardial ischemia without obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) and associated increased risk of cardiovascular (CV) events and ...anginal hospitalizations. Epicardial adipose tissue (EAT) covers much of the myocardium and coronary arteries and when dysfunctional, secretes proinflammatory cytokines and is associated with CV events. While oxidative stress and systemic inflammation are associated with CMD, the relationship between EAT and CMD in women is not well known.
Women diagnosed with CMD (n = 21) who underwent coronary computed tomography with coronary artery calcium (CAC) scoring were compared to a reference group (RG) of women referred for CAC screening for preventive risk assessment (n = 181). EAT attenuation (Hounsfield units (HU)) was measured adjacent to the proximal right coronary artery, along with subcutaneous adipose tissue (SCAT). Two-sample t-tests with unequal variances were utilized.
Mean age of the CMD group was 56 ± 8 years and body mass index (BMI) was 31.6 ± 6.8 kg/m2. CV risk factors in the CMD group were prevalent: 67 % hypertension, 44 % hyperlipidemia, and 33 % diabetes. Both CMD and RG had similar CAC score (25.86 ± 59.54 vs. 24.17 ± 104.6; p = 0.21. In the CMD group, 67 % had a CAC of 0. Minimal atherosclerosis (CAD-RADS 1) was present in 76 % of women with CMD. The CMD group had lower EAT attenuation than RG (−103.3 ± 6.33 HU vs. −97.9 ± 8.3 HU, p = 0.009, respectively). There were no differences in SCAT attenuation. Hypertension, smoking history, age, BMI, and CAC score did not correlate with EAT in either of the groups.
Women with CMD have decreased EAT attenuation compared to RG women. EAT-mediated inflammation and changes in vascular tone may be a mechanistic contributor to abnormal microvascular reactivity. Clinical trials testing therapeutic strategies to decrease EAT may be warranted in the management of CMD.
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•Coronary microvascular dysfunction (CMD) isimplicated in women with angina and ischemia without obstructive coronary disease.•Epicardial adipose tissue (EAT) is a metabolically active fat depot associated with subclinical atherosclerosis.•In this study, women with CMD have decreased EAT attenuation compared to reference group women.•EAT-mediated inflammation and vascular tone changes may mechanistically contribute to abnormal microvascular reactivity in women.
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