Recent studies suggest that vitamin D deficiency represents an additional cofactor of renal anemia, with several mechanisms accounting for this relationship. In line with it, the administration of ...vitamin D or its analogues has been associated with an improvement of anemia. There are no data, however, about a direct effect of paricalcitol on hemoglobin (Hb) levels. Therefore, we conducted a study to determine whether paricalcitol, compared to calcitriol, improves anemia in patients with chronic kidney disease (CKD).
In this randomized trial 60 CKD patients stage 3b-5 and anemia (Hb levels: 10-12.5 g/dL) were assigned (1:1) to receive low doses of calcitriol (Group Calcitriol) or paricalcitol (Group Paricalcitol) for 6 months. All the patients had normal values of plasma calcium, phosphorus and PTH, a stable iron balance, and normal values of C-Reactive Protein. The primary endpoint was to evaluate the effects of the two treatments on Hb levels; the modifications in 24hr-proteinuria (UProt) were also evaluated.
A significant Group x Time interaction effect was observed in the longitudinal analysis of Hb levels (F(1,172)=31.4, p<0.001). Subjects in Paricalcitol experienced a significant monthly increase of Hb levels equal to +0.16 g/dL 95% C.I. 0.10 to +0.22, p<0.001) while in Group Calcitriol, Hb decrease throughout the follow-up with an average monthly rate of -0.10 g/dL (95% C.I.: -0.17 to -0.04, p<0.001). In Group Paricalcitol, UProt was significantly reduced after 6 months 0.35 (0.1-1.2) vs 0.59 (0.2-1.6), p<0.01, whereas no significant difference emerged in Group Calcitriol. Plasma levels of calcium, phosphate, PTH and of inflammation markers remained in the normal range in both groups throughout the study.
Short-term exposure to paricalcitol results in an independent increase in Hb levels, which occurred with no modification of iron balance, inflammatory markers, and PTH plasma concentrations, and was associated with a decrease in UProt.
ClinicalTrials.gov NCT01768351.
The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell membrane receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. Its expression is increased in ...many human cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), and correlates with a poor prognosis and early invasion and metastasis. uPAR is able to control, through a cross-talk with tyrosine kinase receptors, the shift between tumor dormancy and proliferation, that usually precedes metastasis formation. Therefore, we investigated the role of uPAR expression in RAS mutated NSCLC and CRC cells. In this study we provided evidence, for the first time, that RAS mutational condition is functionally correlated to uPAR overexpression in NSCLC and CRC cancer cell lines and patient-derived tissue samples. Moreover, oncogenic features related to uPAR overexpression in RAS mutated NSCLC and CRC, such as adhesion, migration and metastatic process may be targeted, in vitro and in vivo, by new anti-uPAR small molecules, specific inhibitors of uPAR-vitronectin interaction. Therefore, anti-uPAR drugs could represent an effective pharmacological strategy for NSCLC and CRC patients carrying RAS mutations.
Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed ...as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.
Quantitative high resolution computed tomography (HRCT) may objectively assess systemic sclerosis (SSc)-interstitial lung disease (ILD) extent, using three basic densitometric measures: mean lung ...attenuation (MLA), skewness, and kurtosis. This prospective study aimed to develop a composite index - computerized integrated index (CII) - that accounted for MLA, skewness, and kurtosis by means of Principal Component Analysis over HRCTs of 83 consecutive SSc subjects, thus eliminating redundancies. Correlations among CII, cardiopulmonary function and immune-inflammatory biomarkers (e.g. sIL-2Rα and CCL18 serum levels) were explored. ILD was detected in 47% of patients at visual HRCT assessment. These patients had worse CII values than patients without ILD. The CII correlated with lung function at both baseline and follow-up, and with sIL-2Rα and CCL18 serum levels. The best discriminating CII value for ILD was 0.1966 (AUC = 0.77; sensitivity = 0.81 95%CI:0.68-0.92; specificity = 0.66 95%CI:0.52-0.80). Thirty-four percent of patients without visual trace of ILD had a CII lower than 0.1966, and 67% of them had a diffusing lung capacity for CO <80% of predicted. We showed that this new composite CT index for SSc-ILD assessment correlates with both lung function and immune-inflammatory parameters and could be sufficiently sensitive for capturing early lung density changes in visually ILD-free patients.
(1) Background: Cancer is a leading cause of death worldwide and each year, approximately 400,000 children develop cancer. Early detection of cancer greatly increases the chances for successful ...treatment, while screening aims to identify individuals with findings suggestive of specific cancer or pre-cancer before they have developed symptoms. Precise detection, however, often mainly relies on human experience and this could suffer from human error and error with a visual inspection. (2) Methods: The research of statistical approaches to analyze the complex structure of data is increasing. In this work, an entropy-based fuzzy clustering technique for interval-valued data (EFC-ID) for cancer detection is suggested. (3) Results: The application on the Breast dataset shows that EFC-ID performs better than the conventional FKM in terms of AUC value (EFC-ID = 0.96, FKM = 0.88), sensitivity (EFC-ID = 0.90, FKM = 0.64), and specificity (EFC-ID = 0.93, FKM = 0.92). Furthermore, the application on the Multiple Myeloma data shows that EFC-ID performs better than the conventional FKM in terms of Chi-squared (EFC-ID = 91.64, FKM = 88.26), Accuracy rate (EFC-ID = 0.71, FKM = 0.60), and Adjusted Rand Index (EFC-ID = 0.33, FKM = 0.21). (4) Conclusions: In all cases, the proposed approach has shown good performance in identifying the natural partition and the advantages of the use of EFC-ID have been detailed illustrated.
Drugs are the most important treatment option for most diseases, and the majority of medical consultations result in a prescription. Women and men receive different drug prescriptions and differ in ...therapeutic response to pharmacological therapy. This disparity is due to biological factors (sex differences) or/and behavior, lifestyle and life experience (gender differences). Sex differences in drug use have been demonstrated in several therapeutic areas; however, there is a lack of overviews on sex and gender differences of drug use in an entire population.
We conducted a descriptive cross - sectional drug use study, involving the entire Italian population in 2012, aimed at showing and analyzing differences between men and women as regards their exposure to drugs. The data source was IMS LifeLink Treatment DynamicsTMLRx Database and it included all prescribed drugs reimbursed by the Italian National Healthcare System in 2012 and covered 90% of the entire Italian population. The information about the prescriptions was stratified by men and women and age. Drug consumption was expressed as DDD/ 1000 ab die. Exposure to drug prescriptions was expressed as period prevalence (the proportion of the population dispensed ≥1 prescription in 2012 per 1000 inhabitants). Differences of prevalence between men and women were expressed as crude and age adjusted risk ratios with 95% CI.
Our findings suggested that the largest differences in drug prescriptions regarded drugs affecting bone structure and mineralization (RR 15.9), calcium (RR 8.6) and thyroid therapy (RR 5.4), dispensed more to women than men. Otherwise ACE inhibitors were more commonly used in men.
This is the first study exploring difference in drug use between men and women and carried out on the entire Italian population. Our findings showed substantial differences between men and women in term of prevalence of drug prescriptions. Some differences in drug use may be explained by sex differences (variations in disease prevalence and severity, pathophysiology, or by other biological differences), other differences need further investigation to explain the apparent lack of a rational medical explanation for some findings. The findings may subsequently be used to plan future studies to address differences suggesting inequity in treatment approaches.
Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We ...will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (
= 0.0082) and calcification (
< 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5,
= 0.02) and the AS VICs (+7.6 ± 0.5,
= 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.
Summary Background & aim The addition of prebiotics to infant formula modifies the composition of intestinal microflora. Aim of the study was to test the hypothesis that prebiotics reduce the ...incidence of intestinal and respiratory infections in healthy infants. Methods A prospective, randomized, placebo-controlled, open trial was performed. Healthy infants were enrolled and randomized to a formula additioned with a mixture of galacto- and fructo-oligosaccharides or to a control formula. The incidence of intestinal and respiratory tract infections and the anthropometric measures were monitored for 12 months. Results Three hundred and forty two infants (mean age 53.7 ± 32.1 days) were enrolled. The incidence of gastroenteritis was lower in the supplemented group than in the controls (0.12 ± 0.04 vs. 0.29 ± 0.05 episodes/child/12 months; p = 0.015). The number of children with more than 3 episodes tended to be lower in prebiotic group (17/60 vs. 29/65; p = 0.06). The number of children with multiple antibiotic courses/year was lower in children receiving prebiotics (24/60 vs. 43/65; p = 0.004). A transient increase in body weight was observed in children on prebiotics compared to controls during the first 6 months of follow-up. Conclusions Prebiotic administration reduce intestinal and, possibly, respiratory infections in healthy infants during the first year of age.
Epidemiological studies show that BCG-vaccinated population seems to be more likely protected from COVID-19 infection, but WHO gave a stark warning on use of BCG vaccine without confirmed COVID-19 ...trials. The aim of the study is to evaluate whether TB vaccination, performed several years earlier, could confer protection against COVID-19.
After the Ethical Committee authorization, professional orders were used to contact physicians with an online survey. Specialty, COVID-19 infection and previous BCG vaccination were recorded. Statistical data analysis was performed.
1906 physicians answered the questionnaire, (M = 1068; F = 838; mean age 50.7 ± 13.3 years; range 24-87), more than half (1062; 55.7%) experienced BCG vaccination. Professional activity was recorded, and only 49 subjects (2.6%) of them were infected by SARS-CoV2. Among the group of infected people, asymptomatic form occurred in 12 subjects (24.5%); a pauci-symptomatic form in 24 subjects (49.0%); and a severe form (pneumonia and/or respiratory distress) in 13 (26.5%). Considering only the clinically relevant form of COVID-19, period prevalence was 2.2% (23/1062) in the vaccinated group and 1.7% (14/844) in the unvaccinated group (OR: 1.31, 95% C.I.: 0.68-2.63,
= 0.427).
Our experience does not confirm the possible protective role of BCG vaccination, performed years earlier, against COVID-19. Although recent epidemiological studies point out in BCG-vaccinated population a lower prevalence of SARS-CoV2 infection, in our cohort of physicians no significant difference was found in terms of prevalence of COVID-19 infection. Our data underline the necessity to follow the WHO warning about the indiscriminate use of BCG vaccine, until clear evidence of protection by BCG vaccination against COVID-19 is fully demonstrated.
Immune responses play a significant role in hypertension, though the importance of key inflammatory mediators remains to be defined. We used a systematic literature review and meta-analysis to study ...the associations between key cytokines and incident hypertension.
We performed a systematic search of Pubmed/Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), for peer-reviewed studies published up to August 2022. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg and/or the use of antihypertensive medications. Random effects meta-analyses were used to calculate pooled hazard ratios (HRs)/risk ratios (RRs) and 95% confidence intervals by cytokine levels (highest vs. lowest quartile).
Only IL-6 and IL-1β levels have evidence allowing for quantitative evaluation concerning the onset of hypertension. Six studies (10406 participants, 2932 incident cases) examined the association of IL-6 with incident hypertension. The highest versus lowest quartile of circulating IL-6 was associated with a significant HR/RR of hypertension (1.61, 95% CI: 1.00 to 2.60; I2 =87%). After adjusting for potential confounders, including body mass index (BMI), HR/RR was no longer significant (HR/RR: 1.24; 95% CI, 0.96 to 1.61; I2 = 56%). About IL-1β, neither the crude (HR/RR: 1.03; 95% CI, 0.60 to 1.76; n = 2) nor multivariate analysis (HR/RR: 0.97, 95% CI, 0.60 to 1.56; n = 2) suggested a significant association with the risk of developing hypertension.
A limited number of studies suggest that higher IL-6, but not IL-1β, might be associated with the development of hypertension.
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