In the landscape of cancer treatments, the efficacy of coadjuvant molecules remains a focus of attention for clinical research with the aim of reducing toxicity and achieving better outcomes. Most of ...the pathogenetic processes causing tumour development, neoplastic progression, ageing, and increased toxicity involve inflammation. Inflammatory mechanisms can progress through a variety of molecular patterns. As is well known, the ageing process is determined by pathological pathways very similar and often parallel to those that cause cancer development. Among these complex mechanisms, inflammation is currently much studied and is often referred to in the geriatric field as 'inflammaging'. In this context, treatments active in the management of inflammatory mechanisms could play a role as adjuvants to standard therapies. Among these emerging molecules, Silibinin has demonstrated its anti-inflammatory properties in different neoplastic types, also in combination with chemotherapeutic agents. Moreover, this molecule could represent a breakthrough in the management of age-related processes. Thus, Silibinin could be a valuable adjuvant to reduce drug-related toxicity and increase therapeutic potential. For this reason, the main aim of this review is to collect and analyse data presented in the literature on the use of Silibinin, to better understand the mechanisms of the functioning of this molecule and its possible therapeutic role.
Interleukin-6 to lymphocyte (IL-6/Lym) ratio has been identified as a potential prognostic tool in patients with SARS-CoV2 related pneumonia. The aim of our study was to compare the prognostic power ...of IL-6/Lym ratio with other biomarkers in patients initially admitted in a non intensive unit and suffering for respiratory failure associated with SARS-CoV2 related pneumonia.
IL-6/Lym ratio, IL-6, D-Dimer, D-Dimer/fibrinogen ratio, fibrinogen, C-reactive protein (CRP), lymphocytes count and neutrophil/lymphocyte (N/L) ratio collected at hospital admission were tested as prognosticators of negative outcome, defined as combined endpoint in-hospital mortality and/or Intensive Care Unit (ICU) admission requiring oro-tracheal intubation (OTI).
Study population encompassed two hundreds and twenty-three patients (46% females) with mean age ± DS 69.4 ± 13.3 years. Eighty-nine patients (39.9%) suffered for severe respiratory failure and required non invasive ventilation, helmets and/or high flow nasal cannula. Fourty-one patients (18.3%) died during hospital stay and/or required OTI. In these patients mean values of IL-6/Lym ratio, IL-6, CRP and N/L were significantly higher and lymphocytes count was significantly lower compared with patients discharged alive and/or not requiring OTI, while no difference was found in mean values of D-Dimer, D-Dimer/Fibrinogen ratio and fibrinogen. AUC (0.797, 95% CI: 0.738–0.848) of IL-6/Lym ratio was the highest compared with those of all the other analyzed biomarkers and the difference was significant with the exception of IL-6. At multivariate logistic regression IL-6/Lym ratio > 66.5 resulted the only independent biomarker associated with mortality and/or OTI (OR 5.65; 95% 1.63–19.54).
IL-6/Lym ratio seems to be an optimal prognosticator in SARS-CoV2 related pneumonia. Its routinary use in COVID-19 patients could be warranted.
Despite Tocilizumab is now recognized as a concrete therapeutic option in patients with severe SARS-CoV-2 related respiratory failure, literature lacks about factors influencing the response to it in ...this context. Therefore, the aim of our study was to provide evidence about predictors of poor outcome in Tocilizumab treated patients in the real-world practice.
We retrospectively analyzed clinical, laboratory and chest computer tomography (CCT) data of patients firstly admitted in non Intensive Care Units (ICU) and suffering from severe respiratory failure, who were treated with the IL-6 antagonist Tocilizumab. We compared patients who died and/or required admission to ICU with oro-tracheal intubation (OTI) with those who did not.
Two hundreds and eighty-seven patients (29.9% females) with mean age ± SD 64.1 ± 12.6 years were the study population. In-hospital mortality was 18.8%, while the composite endpoint in-hospital mortality and/or ICU admission with OTI occurred in 23.7%. At univariate analysis, patients who died and/or were admitted to ICU with OTI were significantly older and co-morbid, had significantly higher values of creatinine, C-reactive protein (CRP) and procalcitonin and lower lymphocytes count, PaO2/FiO2 ratio (P/F) and room air pulsossimetry oxygen saturation (RAO2S) at hospital admission. Computed tomography ground glass opacities (CT-GGO) involving the pulmonary surface ≥ 50% were found in 55.4% of patients who died and/or were admitted to ICU with OTI and in 21.5% of patients who did not (p=0.0001). At multivariate analysis, age ≥ 65 years (OR 17.3, 95% CI: 3.7-81.0), procalcitonin ≥ 0.14 (OR 9.9, 95%CI: 1.7-56.1), RAO2S ≤ 90% (OR 4.6, 95%CI: 1.2-17.0) and CCT-GGO involvement ≥ 50% (OR 5.1, 95%CI: 1.2-21.0) were independent risk factors associated with death and/or ICU admission with OTI.
Tocilizumab has shown to improve outcome in patients with severe respiratory failure associated to SARS-CoV-2 related pneumonia. In our multicentre study focusing on Tocilizumab treated severe COVID-19 patients, age ≥ 65 years, procalcitonin ≥ 0.14 ng/mL, RAO2S ≤ 90% and CCT-GGO involvement ≥ 50% were independent factors associated with poor outcome.
Few data exists on predictive factors of hemorrhagic transformation (HT) in real-world acute ischemic stroke patients. The aims of this study were: (i) to identify predictive variables of HT (ii) to ...develop a score for predicting HT.
We retrospectively analyzed the clinical, radiographic, and laboratory data of patients with acute ischemic stroke consecutively admitted to our Stroke Unit along two years. Patients with HT were compared with those without HT. A multivariate logistic regression analysis was performed to identify independent predictors of HT on CT scan at 24 hours to develop a practical score.
The study population consisted of 564 patients with mean age 77.5±11.8 years. Fifty-two patients (9.2%) showed HT on brain CT at 24 hours (4.9% symptomatic). NIHSS score ≥8 at Stroke Unit admission (3 points), cardioembolic etiology (2 points), acute revascularization by systemic thrombolysis and/or mechanical thrombectomy (1 point), history of previous TIA/stroke (1 point), and major vessel occlusion (1 point) were found independent risk factors of HT and were included in the score (Hemorrhagic Transformation Empoli score (HTE)). The predictive power of HTE score was good with an AUC of 0.785 (95% CI: 0.749-0.818). Compared with 5 HT predictive scores proposed in the literature (THRIVE, SPAN-100, MSS, GRASPS, SITS-SIC), the HTE score significantly better predicted HT.
NIHSS score ≥8 at Stroke Unit admission, cardioembolism, urgent revascularization, previous TIA/stroke, and major vessel occlusion were independent predictors of HT. The HTE score has a good predictive power for HT. Prospective studies are warranted.
Subclinical paroxysmal atrial fibrillation (AF) is one of the main occult causative mechanisms of embolic stroke of undetermined source (ESUS). Aim of this study was to identify AF predictors, and to ...develop a score to predict the probability of AF detection in ESUS.
We retrospectively analyzed ESUS patients undergoing 2-week external electrocardiographic monitoring. Patients with and without AF detection were compared. On the basis of multivariate analysis, predictors of AF were identified and used to develop a predictive score, which was then compared with other existing literature scores.
Eighty-two patients, 48 females, mean age±SD 72±10 years, were included. In 36 patients (43.9%) AF was detected. The frequency of age 75 years or above and arterial hypertension, and the median CHA 2 DS 2 -VASc score were significantly higher in patients with AF compared with those without. National Institutes of Health Stroke Scale (NIHSS) score ≥8 was the only independent variable associated with AF detection. We derived the Empoli ESUS-AF (E 2 AF) score (NIHSS ≥8 5 points, arterial hypertension 3 points, age 75 years or above 2 points, age 65 to 74 years 1 point, history of coronary/peripheral artery disease 1 point, left atrial enlargement 1 point, posterior lesion 1 point, cortical or cortical-subcortical lesion 1 point), whose predictive power in detecting AF was good (area under the curve: 0.746, 95% confidence interval: 0.638-0.836) and higher than that of CHA 2 DS 2 -VASc and other scores.
In our study NIHSS score ≥8 was the only independent predictor of post-ESUS-AF detection. The E 2 AF score appears to have a good predictive power for detecting AF. External validations are required.
Background and Aims
Mixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a ...sustained virologic response (SVR) over a medium‐term to long‐term period.
Approach and Results
Direct‐acting antiviral–treated cryoglobulinemic patients, consecutively enrolled in the multicentric Italian Platform for the Study of Viral Hepatitis Therapy cohort, were prospectively evaluated. Cumulative incidence Kaplan‐Meier curves were reported for response, clinical deterioration, relapse and relapse‐free survival rates. Cox regression analysis evaluated factors associated with different outcomes. A clinical response was reported in at least one follow‐up point for 373 of 423 (88%) patients with CV who achieved SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A full complete response (FCR) was reached by 164 (38.8%) patients in at least one follow‐up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration, 19 months). In patients who achieved FCR and had an available follow‐up (137 patients) a relapse was observed in 13% and it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24 months, respectively. After achieving SVR, a clinical nonresponse was associated with older age and renal involvement; a clinical deterioration/relapse was associated with high pretreatment rheumatoid factor values, and FCR was inversely associated with age, neuropathy, and high cryocrit levels.
Conclusion
In patients with CV, HCV eradication may not correspond to a persistent clinical improvement, and clinical response may fluctuate. This implies an attentive approach to post‐SVR evaluation through prognostic factors and tailored treatment.
Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of ...HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort.
Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used.
Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively.
Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.
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