Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two ...exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies.
The immunological mechanisms underlying the clinical presentation of SARS-CoV-2 infection and those influencing the disease outcome remain to be defined. Myeloid-derived suppressor cells (MDSC) have ...been described to be highly increased during COVID-19, however, their role remains elusive. We performed an in depth analysis of MDSC in 128 SARS-CoV-2 infected patients. Polymorphonuclear (PMN)-MDSC expanded during COVID-19, in particular in patients who required intensive care treatments, and correlated with IL-1β, IL-6, IL-8, and TNF-α plasma levels. PMN-MDSC inhibited T-cells IFN-γ production upon SARS-CoV-2 peptides stimulation, through TGF-β- and iNOS-mediated mechanisms, possibly contrasting virus elimination. Accordingly, a multivariate regression analysis found a strong association between PMN-MDSC percentage and fatal outcome of the disease. The PMN-MDSC frequency was higher in non-survivors than survivors at the admission time, followed by a decreasing trend. Interestingly, this trend was associated with IL-6 increase in non-survivors but not in survivors. In conclusion, this study indicates PMN-MDSC as a novel factor in the pathogenesis of SARS-CoV2 infection, and open up to new therapeutic options.
Background
For the diagnosis of prosthetic joint infection, real evidence-based guidelines to aid clinicians in choosing the most accurate diagnostic strategy are lacking.
Aim and Methods
To address ...this need, we performed a multidisciplinary systematic review of relevant nuclear medicine, radiological, orthopaedic, infectious, and microbiological literature to define the diagnostic accuracy of each diagnostic technique and to address and provide evidence-based answers on uniform statements for each topic that was found to be important to develop a commonly agreed upon diagnostic flowchart.
Results and Conclusion
The approach used to prepare this set of multidisciplinary guidelines was to define statements of interest and follow the procedure indicated by the Oxford Centre for Evidence-based Medicine (OCEBM).
The prevalence of SARS-CoV-2 infection among health care workers (HCWs) provides information about the spread of COVID-19 within health care facilities, and the risk groups.
We aimed to describe the ...rate of SARS-CoV-2 seroprevalence and its determinants among HCWs.
We used Web of Science, PubMed, Scopus, MEDLINE, EBSCOhost and Cochrane Library.
We included the reports of SARS-CoV-2 seroprevalence with a sample size of minimum 1000 HCWs.
The study was registered at the International Prospective Register of Systematic Reviews (PROSPERO, no. CRD42021230456). We used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The keywords were “COVID-19”, “SARS-CoV-2”, “Coronavirus”, “seroprevalence”, “health care workers” and “risk factors”.
In total 4329 reports were retrieved, duplications were removed; after filtering according to the title and abstract, 25 studies were selected. Risk of bias was assessed in 25 studies; it was low in 13 studies, medium in four studies, and high in eight studies. In meta-analysis using the random effect model, the weighted average of seroprevalence was calculated as 8% (95% CI 6–10%). The pooled seroprevalence rates of the selected variables that have a rate above the average were male HCWs with 9% (95% CI 7–11%); HCWs from ethnic minorities with 13% (95% CI 9–17%); high exposure 9% (95% CI 6–13%); exposure to the virus outside the health care setting 22% (95% CI 14–32%).
Our analysis indicates a SARS-CoV-2 seroprevalence rate of 8% among studies that included >1000 HCWs for the year 2020, before vaccinations started. The most common risk factors associated with higher seroprevalence rate were ethnicity, male gender and having a higher number of household contacts. Working as a frontline HCW was inconsistent in its association with higher seroprevalence.
In the last decades, probiotics have been widely used as food supplements because of their putative beneficial health effects. They are generally considered safe but rare reports of serious ...infections caused by bacteria included in the definition of probiotics raise concerns on their potential pathogenic role in patients with particular predisposing factors. Patients with hereditary hemorrhagic telangiectasia (HHT) are exposed to infections because of telangiectasias and arteriovenous malformations (AVMs). We describe what is, to our knowledge, the first case of infective endocarditis (IE) caused by Lactobacillus rhamnosus in a patient with HHT. A systematic review of the relevant medical literature is presented.
A patient with HHT and an aortic bioprosthesis was admitted because of prolonged fever not responding to antibiotics. The patient had a history of repeated serious infections with hospitalizations and prolonged use of antibiotics, and used to assume large amounts of different commercial products containing probiotics. Weeks before the onset of symptoms the patient had been treated with nasal packings and with surgical closure of a nasal bleeding site because of recurrent epistaxis. A diagnosis of IE of the aortic bioprosthesis was made. All blood coltures were positive for L. rhamnosus. The patients responded to a cycle of 6 weeks of amoxicillin/clavulanate plus gentamicin. A systematic review of IE linked to consumption of probiotics, and of infective endocarditis in patients with HHT was conducted. 10 cases of IE linked to probiotics consumption and 6 cases of IE in patients with HHT were found.
Consumption of probiotics can pose a risk of serious infections in patients with particular predisposing factors. Patients with HHT can be considered at risk because of their predisposition to infections. Prophylaxis with antibiotics before nasal packings in patients with HHT can be considered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients.
Objectives
To evaluate the pharmacokinetics of ...remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients.
Methods
Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method.
Results
We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure.
Conclusions
We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.
...monoclonal antibodies have substantially reduced effectiveness against recently emerged strains,1 and should be tailored to the variants. ...antiviral compounds, specifically ...nirmatrelvir–ritonavir, molnupiravir, and remdesivir, when used promptly at the onset of SARS-CoV-2 infection, are currently the most effective drug therapies for inhibiting viral replication. In the outpatient setting, both nirmatrelvir–ritonavir and molnupiravir administered for 5 days have led to greater reductions in the relative risk of hospitalisation or death versus placebo in unvaccinated patients at high risk of severe COVID-19, with an associated decrease in nasopharingeal viral load.2,3 However, recently reported cases of virological rebound after completion of a 5-day course of nirmatrelvir–ritonavir have raised concerns around the real world effectiveness of antivirals againstSARS-CoV-2.4 In The Lancet Infectious Diseases, Wong and colleagues5 assessed the incidence of viral burden rebound, and evaluated associated risk factors and clinical outcomes, in a retrospective cohort of consecutive hospitalised patients with non-oxygen-dependent COVID-19 during the omicron BA.2.2 wave (from Feb 26 to July 3, 2022) in Hong Kong. Given that no association was found between oral antiviral treatment and viral burden rebound, the study by Wong and colleagues emphasises the importance of continuing to offer antivirals to individuals with COVID-19 who are at increased risk of progression to severe COID-19.
The case fatality rate (CFR) of coronavirus disease 2019 (COVID-19) varies significantly between countries. We aimed to describe the associations between health indicators and the national CFRs of ...COVID-19.
We identified for each country health indicators potentially associated with the national CFRs of COVID-19. We extracted data for 18 variables from international administrative data sources for 34 member countries of the Organization for Economic Cooperation and Development (OECD). We excluded the collinear variables and examined the 16 variables in multivariable analysis. A dynamic web-based model was developed to analyse and display the associations for the CFRs of COVID-19. We followed the Guideline for Accurate and Transparent Health Estimates Reporting (GATHER).
In multivariable analysis, the variables significantly associated with the increased CFRs were percentage of obesity in ages >18 years (β = 3.26; 95%CI = 1.20, 5.33; p 0.003), tuberculosis incidence (β = 3.15; 95%CI = 1.09, 5.22; p 0.004), duration (days) since first death due to COVID-19 (β = 2.89; 95%CI = 0.83, 4.96; p 0.008), and median age (β = 2.83; 95%CI = 0.76, 4.89; p 0.009). The COVID-19 test rate (β = –3.54; 95%CI = –5.60, –1.47; p 0.002), hospital bed density (β = –2.47; 95%CI = –4.54, –0.41; p 0.021), and rural population ratio (β = –2.19; 95%CI = –4.25, –0.13; p 0.039) decreased the CFR.
The pandemic hits population-dense cities. Available hospital beds should be increased. Test capacity should be increased to enable more effective diagnostic tests. Older patients and patients with obesity and their caregivers should be warned about a potentially increased risk.
During the COVID-19 pandemic, several studies described an increased chance of developing pulmonary embolism (PE). Several scores have been used to predict the occurrence of PE. This systematic ...review summarizes the literature on predicting rules for PE in hospitalized COVID-19 patients (HCPs).
PUBMED and EMBASE databases were searched to identify articles (1 January 2020-28 April 2021) presenting data pertaining to the use of a prediction rule to assess the risk for PE in adult HCPs. The investigated outcome was the diagnosis of PE. Studies presenting data using a single laboratory assay for PE prediction were excluded. Included studies were appraised for methodological quality using the Newcastle - Ottawa Quality Assessment Scale for Cohort Studies (NOS).
We obtained a refined pool of twelve studies for five scoring systems (Wells score, Geneva score, CHADS2/CHA2DS2VASc/M-CHA2DS2VASc, CHOD score, Padua Prediction Score), and 4,526 patients. Only one score was designed explicitly for HCPs. Three and nine included studies were prospective and retrospective cohort studies, respectively. Among the examined scores, the CHOD score seems promising for predictive ability.
New prediction rules, specifically developed and validated for estimating the risk of PE in HCP, differentiating ICU from non-ICU patients, and taking into account anticoagulation prophylaxis, comorbidities, and the time from COVID-19 diagnosis are needed.
On January 9th, 2020, the “World Health Organization” (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a ...diseases (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9th, 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The “L. Spallanzani” National Institute for the Infectious Diseases, IRCCS has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; these recomendations should be considered as expert opinions, which may be modified according to newly produced literature data. *for the INMI COVID-19 Treatment Group – ICOTREG Abdeddaim A, Agrati C, Albarello F, Antinori A, Ascoli Bartoli T, Baldini F, Bellagamba R, Bevilacqua N, Bibas M, Biava G, Boumis E, Busso D, Camici M, Capobianchi MR, Capone A, Caravella I, Cataldo A, Cerilli S, Chinello G, Cicalini S, Corpolongo A, Cristofaro M, D’Abramo A, Dantimi C, De Angelis G, De Palo MG, D’Offizi G, De Zottis F, Di Lorenzo R, Di Stefano F, Fusetti M, Galati V, Gagliardini R, Garotto G, Gebremeskel Tekle Saba, Giancola ML, Giansante F, Girardi E, Goletti D, Granata G, Greci MC, Grilli E, Grisetti S, Gualano G, Iacomi F, Iannicelli G, Ippolito G, Lepore L, Libertone R, Lionetti R, Liuzzi G, Loiacono L, Macchione M, Marchioni L, Mariano A, Marini MC, Maritti M, Mastrobattista A, Mazzotta V, Mencarini P, Migliorisi-Ramazzini P, Mondi A, Montalbano M, Mosti S, Murachelli S, Musso M, Nicastri E, Noto P, Oliva A, Palazzolo C, Palmieri F, Pareo C, Petrone A, Pianura E, Pinnetti C, Pontarelli A, Puro V, Rianda A, Rosati S, Sampaolesi A, Santagata C, Scarcia D’Aprano S, Scarabello A, Schininà V, Scorzolini L, Stazi GV, Taibi C, Taglietti F, Tonnarini R, Topino S, Vergori A, Vincenzi L, Visco-Comandini U, Vittozzi P, Zaccarelli M, Zaccaro G.
PDF
