ObjectivesHealthcare workers (HCWs) are at high risk of developing SARS-CoV-2 infection. The aim of this single-centre prospective study was to evaluate the trend of SARS-CoV-2 seroprevalence in HCWs ...working at the primary referral centre for infectious diseases and bioemergencies (eg, COVID-19) in Northern Italy and investigate the factors associated with seroconversion.MethodsSix hundred and seventy-nine HCW volunteers were tested for anti-SARS-CoV-2 antibodies three times between 4 March and 27 May 2020 and completed a questionnaire covering COVID-19 exposure, symptoms and personal protective equipment (PPE) training and confidence at each time.ResultsSARS-CoV-2 seroprevalence rose from 3/679 to 26/608 (adjusted prevalence: 0.5%, 95% CI 0.1 to 1.7% and 5.4%, 95% CI 3.6 to 7.9, respectively) between the first two time points and then stabilised, in line with the curve of the COVID-19 epidemic in Milan. From the first time point, 61.6% of the HCWs had received training in the use of PPE and 17 (61.5%) of those who proved to be seropositive reported symptoms compatible with SARS-CoV-2 infection. Contacts with ill relatives or friends and self-reported symptoms were independently associated with an increased likelihood of seroconversion (p<0.0001 for both), whereas there was no significant association with professional exposure.ConclusionThe seroprevalence of SARS-CoV-2 among the HCWs at our COVID-19 referral hospital was low at the time of the peak of the epidemic. The seroconversions were mainly attributable to extrahospital contacts, probably because the hospital readily adopted effective infection control measures. The relatively high number of asymptomatic seropositive HCWs highlights the need to promptly identify and isolate potentially infectious HCWs.
Procedural pain during Peripheral Venous Catheterization (PVC) is a significant issue for patients. Reducing procedure-induced pain improves the quality of care and reduces patient discomfort. We ...aimed to compare a non-pharmacological technique (distraction) to anaesthetic cream (EMLA) for the reduction of procedural pain during PVC, in patients undergoing Computerized Tomography (CT) or Nuclear Magnetic Resonance (NMR) with contrast.
This is a Prospective, Randomized Controlled Trial. The study was carried out during the month of October 2015. A total of 72 patients undergoing PVC were randomly assigned to the experimental group (distraction technique, n=36) or control group (EMLA, n=36). After PVC, pain was evaluated by means of the numeric pain-rating scale (NRS). Pain perception was compared by means of Mann-Whitney Test.
The average pain in the distraction group was 0.69 (SD±1.26), with a median value of 0. The average pain in the EMLA group was 1.86 (SD±1.73), with a median value of 2. The study showed a significant improvement from the distraction technique (U=347, p<.001, r=.42) with respect to the local anaesthetic in reducing pain perception. Conclusions/Implication for practice: Distraction is more effective than local anaesthetic in reducing of pain-perception during PVC insertion. This study is one of few comparing the distraction technique to an anaesthetic. It confirms that the practitioner-patient relationship is an important point in nursing assistance, allowing the establishment of trust with the patient and increasing compliance during the treatment process.
Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed ...to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification.
We examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank UKBB cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS (PRS-HFC), and then adjusted for HSD17B13 (PRS-5).
In the NAFLD cohort, the adjusted impact of genetic risk variants on HCC was proportional to the predisposition to fatty liver (p = 0.002) with some heterogeneity in the effect. PRS predicted HCC more robustly than single variants (p <10-13). The association between PRS and HCC was mainly mediated through severe fibrosis, but was independent of fibrosis in clinically relevant subgroups, and was also observed in those without severe fibrosis (p <0.05). In the UKBB cohort, PRS predicted HCC independently of classical risk factors and cirrhosis (p <10-7). In the NAFLD cohort, we identified high PRS cut-offs (≥0.532/0.495 for PRS-HFC/PRS-5) that in the UKBB cohort detected HCC with ~90% specificity but limited sensitivity; PRS predicted HCC both in individuals with (p <10-5) and without cirrhosis (p <0.05).
Our results are consistent with a causal relationship between hepatic fat and HCC. PRS improved the accuracy of HCC detection and may help stratify HCC risk in individuals with dysmetabolism, including those without severe liver fibrosis. Further studies are needed to validate our findings.
By analyzing variations in genes that contribute to fatty liver disease, we developed two risk scores to help predict liver cancer in individuals with obesity-related metabolic complications. These risk scores can be easily tested in the clinic. We showed that the risk scores helped to identify the risk of liver cancer both in high-risk individuals and in the general population.
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•Genetic predisposition to liver fat accumulation predisposes to cirrhosis and HCC.•Hepatic fat promotes carcinogenesis, partly via fibrosis.•Polygenic risk scores may improve HCC risk stratification during dysmetabolism.
Background:
Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking ...disease-modifying drugs.
Methods:
A modified Delphi consensus process (October 2017–June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017.
Results:
Recommendations include the need for an ‘infectious diseases card’ of each patient’s infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received.
Conclusion:
Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.
The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent ...scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.
Neurodegenerative diseases (NDs) are often associated with the presence of misfolded protein inclusions. The chaperone HSPB8 is upregulated in mice, the human brain and muscle structures affected ...during NDs progression. HSPB8 exerts a potent pro-degradative activity on several misfolded proteins responsible for familial NDs forms. Here, we demonstrated that HSPB8 also counteracts accumulation of aberrantly localized misfolded forms of TDP-43 and its 25 KDa fragment involved in most sporadic cases of Amyotrophic Lateral Sclerosis (sALS) and of Fronto Lateral Temporal Dementia (FLTD). HSPB8 acts with BAG3 and the HSP70/HSC70-CHIP complex enhancing the autophagic removal of misfolded proteins. We performed a high-through put screening (HTS) to find small molecules capable of inducing HSPB8 in neurons for therapeutic purposes. We identified two compounds, colchicine and doxorubicin, that robustly up-regulated HSPB8 expression. Both colchicine and doxorubicin increased the expression of the master regulator of autophagy TFEB, the autophagy linker p62/SQSTM1 and the autophagosome component LC3. In line, both drugs counteracted the accumulation of TDP-43 and TDP-25 misfolded species responsible for motoneuronal death in sALS. Thus, analogs of colchicine and doxorubicin able to induce HSPB8 and with better safety and tolerability may result beneficial in NDs models.
A considerable proportion of cancer patients are resistant or only partially responsive to immune checkpoint blockade immunotherapy. Tumor‐Associated Macrophages (TAMs) infiltrating the tumor stroma ...suppress the adaptive immune responses and, hence, promote tumor immune evasion. Depletion of TAMs or modulation of their protumoral functions is actively pursued, with the purpose of relieving this state of immunesuppression. We previously reported that trabectedin, a registered antitumor compound, selectively reduces monocytes and TAMs in treated tumors. However, its putative effects on the adaptive immunity are still unclear. In this study, we investigated whether treatment of tumor‐bearing mice with trabectedin modulates the presence and functional activity of T‐lymphocytes.
In treated tumors, there was a significant upregulation of T cell‐associated genes, including CD3, CD8, perforin, granzyme B, and IFN‐responsive genes (MX1, CXCL10, and PD‐1), indicating that T lymphocytes were activated after treatment. Notably, the mRNA levels of the Pdcd1 gene, coding for PD‐1, were strongly increased. Using a fibrosarcoma model poorly responsive to PD‐1‐immunotherapy, treatment with trabectedin prior to anti‐PD‐1 resulted in improved antitumor efficacy. In conclusion, pretreatment with trabectedin enhances the therapeutic response to checkpoint inhibitor‐based immunotherapy. These findings provide a good rational for the combination of trabectedin with immunotherapy regimens.
Trabectedin selectively reduces Tumor‐Associated Macrophages (TAMs) and increases the number of CD8+ lymphocytes and their expression of PD‐1, perforin, and granzyme B in treated tumors. Treatment with anti‐PD‐1, following trabectedin administration, unleashes adaptive immune responses and results in improved antitumor efficacy.
Nanotechnology applications are expected to bring a range of benefits to the food sector, aiming to provide better quality and conservation. In this research, the physiological response of both an
...mono-species biofilm and Caco-2 intestinal cells to sub-lethal concentrations of silver nanoparticles (AgNPs) has been investigated. In order to simulate the anaerobic and aerobic compartments required for bacteria and intestinal cells growth, a simplified semi-batch model based on a transwell permeable support was developed. Interaction between the two compartments was obtained by exposing Caco-2 intestinal cells to the metabolites secreted by
biofilm after its exposure to AgNPs. To the best of the authors' knowledge, this study is the first to investigate the effect of AgNPs on Caco-2 cells that takes into consideration previous AgNP-intestinal biofilm interactions, and at concentrations mimicking real human exposure. Our data show that 1 μg/mL AgNPs in anaerobic conditions (i) promote biofilm formation up to 2.3 ± 0.3 fold in the first 72 h of treatment; (ii) increase reactive oxygen species (ROS) production to 84 ± 21% and change the physiological status of microbial cells after 96 h of treatment; (iii) seriously affect a 72-h old established biofilm, increasing the level of oxidative stress to 86 ± 21%. Moreover, the results indicate that oxygen renders the biofilm more adequate to counteract AgNP effects. Comet assays on Caco-2 cells demonstrated a protective role of biofilm against the genotoxic effect of 1 μg/mL AgNPs on intestinal epithelial cells.
Animal models and few clinical reports suggest the involvement of the complement system in the onset of severe manifestations of coronavirus disease-2019 (COVID-19). However, complement contribution ...to endotheliopathy and hypercoagulability has not been elucidated yet.
To evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients.
In this single-centre cohort study, 148 patients with COVID-19 of different severity were evaluated upon hospital admission and 30 days later. Markers of complement activation (SC5b-9 and C5a) and endothelial perturbation (von Willebrand factor vWF, tissue-type plasminogen activator t-PA, plasminogen activator inhibitor-1 PAI-1, soluble thrombomodulin sTM, and soluble endothelial selectin sE-selectin) were measured in plasma.
The patients had high plasma levels of SC5b-9 and C5a (p = 0.0001 for both) and vWF, t-PA and PAI-1 (p = 0.0001 for all). Their SC5b-9 levels correlated with those of vWF (r = 0.517, p = 0.0001) and paralleled disease severity (severe vs mild p = 0.0001, severe vs moderate p = 0.026 and moderate vs mild p = 0.001). The levels of sE-selectin were significantly increased only in the patients with severe disease. After 30 days, plasma SC5b-9, C5a and vWF levels had significantly decreased (p = 0.0001 for all), and 43% of the evaluated patients had normal levels.
Complement activation is boosted during the progression of COVID-19 and dampened during remission, thus indicating its role in the pathophysiology of the disease. The association between complement activation and the biomarkers of endothelial damage suggests that complement may contribute to tissue injury and could be the target of specific therapy.
•Levels of complement activation products increase with COVID19 severity and activity.•Complement activation is correlated with endothelium damage in COVID19.•Complement mediates the response to SARSCoV2 and gives a rationale for target therapy.
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