Endothelial damage and fibro-proliferative vasculopathy of small vessels are pathological hallmarks of systemic sclerosis (SSc). The consequence is the detachment of resident elements that become ...circulating endothelial cells (CECs). The aim of our study was to evaluate the potential of CECs as biomarker in SSc. We enrolled 50 patients with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subset of SSc, who underwent clinical evaluation to establish the organ involvement. CECs were measured by flow-cytometry utilizing a polychromatic panel. An evident difference was observed in CEC counts comparing controls to SSc patients (median 10.5 vs. 152 cells/ml, p < 0.0001) and for the first time, between the two subsets of disease (median lcSSc 132 vs. dcSSc 716 CEC/ml, p < 0.0001). A significant correlation was established between CECs and some SSc clinical parameters, such as digital ulcers, skin and pulmonary involvement, presence of Scl-70 antibodies, nailfold videocapillaroscopy patterns and EUSTAR activity index. After 12 months, CECs correlated with clinical worsening of patients, showing that a number higher than 414 CEC/ml is a strong negative prognostic factor (RR 5.70). Our results indicate that CECs are a direct indicator of systemic vascular damage. Therefore, they can be used as a reliable marker of disease severity.
The objective of our study was to determine the joint protective effect of a previous SARS-CoV-2 infection and vaccination on the risk of a new infection and hospitalization. Two case-control studies ...nested in a cohort of COVID-19 patients cared for by the Local Health Unit (LHU) of Vercelli, Italy, were performed, one to estimate the risk of infection and the second to estimate the risk of hospitalization. Each new infection and hospitalization was matched with up to 4 disease-free subjects who were the same age, sex and index date (i.e., controls). Study subjects were followed up from cohort entry date to disease outcome, end of follow-up or emigration. Vaccination was associated with a 36% (OR 0.64; 95%CI 0.62-0.66) and 90% (OR 0.10; 95%CI 0.07-0.14) reduction in the risk of infection and hospitalization, respectively. Prior infection was associated with a 65% (OR 0.35; 95%CI 0.30-0.40) and 90% (OR 0.10; 95%CI 0.07-0.14) reduction in the risk of infection and hospitalization, respectively. Vaccinated and recovered subjects showed a 63% (OR 0.37; 95%CI 0.34-0.14) and 98% (OR 0.02; 95%CI 0-0.13) reduction in the risk of infection and hospitalization, respectively. Vaccination remains an essential public health tool for preventing severe forms of COVID-19. Our study shows that vaccination or previous infection has a strong protective effect against Sars-CoV-2 hospitalization. The protective role against infection appears to be present although with a lower efficacy rate than that presented in the RCTs.
The Mediterranean diet (MD) and Western diet (WD) are poles apart as dietary patterns. Despite the availability of epidemiological tools to estimate the adherence to MD, to date, there is a lack of ...combined scores. We developed MEDOC, a food frequency questionnaire (FFQ) designed to calculate a combined adherence score for both diets and validated it on 213 subjects. The test–retest reliability revealed all frequency questions falling within the acceptable range of 0.5 to 0.7 (Pearson correlation coefficient) in younger (<30 years old) subjects, while 1 question out of 39 fell below the range in older (>30 years old) participants. The reproducibility for portion size was less satisfying, with, respectively, 38.2% and 70.5% of questions falling below 0.5 (Cohen’s Kappa index) for younger and older subjects. The good correlation (R = 0.63, p < 0.0001 for subjects younger than 30 years and R = 0.54, p < 0.0001 for subjects older than 30 years, Pearson’s correlation coefficient) between the MEDOC score and the MediDietScore (MDS) confirmed the validity of the MEDOC score in identifying patients who adhere to the MD. Harnessing the capabilities of this innovative tool, we aim to broaden the existing perspective to study complex dietary patterns in nutritional epidemiology studies.
Multiple sclerosis (MS) is a debilitating autoimmune condition primarily affecting young adults, and its rise is evident globally. Despite this, its precise etiology remains elusive. Both genetic and ...environmental factors contribute to MS susceptibility; however, the link between diet and MS lacks substantial evidence due to limited large-scale studies. We exploited the UK Biobank resources to explore the nexus between diet, lifestyle, and MS risk. The dietary and lifestyle habits of MS incident cases, derived from a general food frequency questionnaire (FFQ) completed by all participants at study enrollment, were compared to those of subjects who did not develop MS during the follow-up. Our findings suggest the protective role of moderate oily fish consumption and weekly alcohol intake. Furthermore, by analyzing food intake data obtained through 24 h recall, completed by a subset of participants, we found a protective, though non-significant, trend of an increased adherence to the Mediterranean diet (MD). These findings, derived from the analysis of the UK Biobank and representing an unprecedented approach for this inquiry, warrant further exploration and integration in future research.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the joints. The multifactorial etiopathogenesis of RA has been heavily investigated, but is still only partially understood. ...Diet can represent both a risk factor and a protective factor, based on some evidence that suggests specific properties of certain foods and their ability to increase/reduce inflammation. To date, the studies done on this topic provide discordant results and are heterogeneous in terms of design and cohort size. In this work, we investigated for the first time the relationship between nutrition and the risk of RA onset using a sample size of about half a million subjects from one of the largest publicly available biobanks that is the UK biobank. Results showed that oily fish, alcohol, coffee and breakfast cereals have protective roles in RA; whereas, tea can increase the risk of RA. In conclusion, the obtained results confirm that diet plays key roles in RA, either by promoting or by preventing RA onset and development. Future research should focus on unravelling the effects of dietary habits on immune-mediated diseases to establish better preventive strategies.
Sars-Cov-2 infection causes fever and cough that may rapidly lead to acute respiratory distress syndrome (ARDS). Few biomarkers have been identified but, unfortunately, these are individually poorly ...specific, and novel biomarkers are needed to better predict patient outcome. The aim of this study was to evaluate the diagnostic performance of circulating platelets (PLT)-derived extracellular vesicles (EVs) as biomarkers for Sars-Cov-2 infection, by setting a rapid and reliable test on unmanipulated blood samples. PLT-EVs were quantified by flow cytometry on two independent cohorts of Sars-CoV-2+ (n = 69), Sars-Cov-2- (n = 62) hospitalized patients, and healthy controls. Diagnostic performance of PLT-EVs was evaluated by receiver operating characteristic (ROC) curve. PLT-EVs count were higher in Sars-Cov-2+ compared to Sars-Cov-2- patients or HC. ROC analysis of the combined cohorts showed an AUC = 0.79 and an optimal cut-off value of 1472 EVs/μL, with 75% sensitivity and 74% specificity. These data suggest that PLT-EVs might be an interesting biomarker deserving further investigations to test their predictive power.
Background & Aims Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin increases the risk of upper gastrointestinal bleeding (UGIB). Guidelines suggest avoiding ...certain drug combinations, yet little is known about the magnitude of their interactions. We estimated the risk of UGIB during concomitant use of nonselective (ns)NSAIDs, cyclooxygenase -2 selective inhibitors (COX-2 inhibitors), and low-dose aspirin with other drugs. Methods We performed a case series analysis of data from 114,835 patients with UGIB (930,888 person-years of follow-up) identified from 7 population-based health care databases (approximately 20 million subjects). Each patient served as his or her own control. Drug exposure was determined based on prescriptions of nsNSAIDs, COX-2 inhibitors, or low-dose aspirin, alone and in combination with other drugs that affect the risk of UGIB. We measured relative risk (incidence rate ratio IRR during drug exposure vs nonexposure) and excess risk due to concomitant drug exposure (relative excess risk due to interaction RERI). Results Monotherapy with nsNSAIDs increased the risk of diagnosis of UGIB (IRR, 4.3) to a greater extent than monotherapy with COX-2 inhibitors (IRR, 2.9) or low-dose aspirin (IRR, 3.1). Combination therapy generally increased the risk of UGIB; concomitant nsNSAID and corticosteroid therapies increased the IRR to the greatest extent (12.8) and also produced the greatest excess risk (RERI, 5.5). Concomitant use of nsNSAIDs and aldosterone antagonists produced an IRR for UGIB of 11.0 (RERI, 4.5). Excess risk from concomitant use of nsNSAIDs with selective serotonin reuptake inhibitors (SSRIs) was 1.6, whereas that from use of COX-2 inhibitors with SSRIs was 1.9 and that for use of low-dose aspirin with SSRIs was 0.5. Excess risk of concomitant use of nsNSAIDs with anticoagulants was 2.4, of COX-2 inhibitors with anticoagulants was 0.1, and of low-dose aspirin with anticoagulants was 1.9. Conclusions Based on a case series analysis, concomitant use of nsNSAIDs, COX-2 inhibitors, or low-dose aspirin with SSRIs significantly increases the risk of UGIB. Concomitant use of nsNSAIDs or low-dose aspirin, but not COX-2 inhibitors, with corticosteroids, aldosterone antagonists, or anticoagulants produces significant excess risk of UGIB.
In order to provide a more precise quantification of the association between alcohol consumption and pancreatic cancer risk, we performed a meta‐analysis of relevant dose‐risk results. We conducted a ...PubMed search of all case‐control (N=21) and cohort (N=11) studies published up to March 2009. We computed summary relative risk (RR) estimates using either fixed‐ or, in the presence of heterogeneity, random‐effects models. The pooled RR was 0.92 (95% confidence interval, 95% CI, 0.86–0.97) for <3 drinks/day and 1.22 (95% CI, 1.12–1.34) for ≥3 drinks/day. The increased risk for heavy drinking was similar in women and men, but apparently stronger in cohort studies (RR=1.29), in studies with high quality index (RR=1.30), and did not appear to be explained by residual confounding by either history of pancreatitis or tobacco smoking. This meta‐analysis provides strong evidence for the absence of a role of moderate drinking in pancreatic carcinogenesis, coupled to an increased risk for heavy alcohol drinking. Given the moderate increase in risk and the low prevalence of heavy drinkers in most populations, alcohol appears to be responsible only for a small fraction of all pancreatic cancers.
This study independently confirms increased levels of osteopontin in COVID‐19 patients but also suggests that osteopontin cannot be used as a biomarker of SARS‐CoV‐2 infection, as elevated levels of ...circulating osteopontin are found in inflammatory lung disease regardless of SARS‐CoV‐2 infection.
In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) who were unfit ...for intensive chemotherapy and became the standard of care after the publication of the pivotal RCT VIALE-A. However, it is still not clear to what extent the results observed in the VIALE-A apply to a real-world setting. For this reason, we carried out a systematic review and meta-analysis of real-world studies on newly diagnosed patients with AML, ineligible for intensive induction chemotherapy, receiving first-line VEN+HMA. We then compared their results in term of survival with those from the VIALE-A. Kaplan-Meier curves were extracted from all included studies and individual survival data was reconstructed. We then estimated a pooled survival curve and compared it with the results of the VIALE-A using the log-rank test. We also conducted a secondary analysis including only studies considering VEN plus azacytidine (AZA) as treatment, as this was the schedule originally used in the VIALE-A. Nineteen real-world studies met the inclusion criteria and were included in the systematic review. Most of them reported a worse survival than the VIALE-A. The pooled survival curve was similar to that reported in the VIALE-A during the first three months of treatment but diverged thereafter (p-value = 0.0001). The pooled median survival among the real-world studies was 9.37 months (95%CI 8.81–10.5), substantially lower than that reported in the VIALE-A (14.7 months; 95%CI 11.9–18.7). Results slightly increased when the analysis was restricted to the studies using VEN+AZA as treatment (median survival: 11.5 months; 95%CI 10.2–14.8). Survival of newly diagnosed AML patients treated with VEN+HMAs in a real-world setting seems to be lower than previously reported in the VIALE-A, while the effect of VEN+AZA is more in line with expected results. Future studies are needed to evaluate whether this apparent discrepancy is due to the different characteristics of enrolled patients or to a non-optimal adherence to therapy, and whether alternative regimens can provide better results in terms of safety and effectiveness.
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