Search

Background: Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression., Methods: Here, we have investigated plasma samples derived from n = 71 symptomatic fCCM patients (40 female/31 male) and n = 17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches., Findings: Biomarkers as sCD14 (p = 0.00409), LBP (p = 0.02911), CXCL4 (p = 0.038), ICAM-1 (p = 0.02013), ANG2 (p = 0.026), CCL5 (p = 0.00403), THBS1 (p = 0.0043), CRP (p = 0.0092), and HDL (p = 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p = 0.011), THBS1 (p = 0.011) and CXCL4 (p = 0.011), were correlated to CCM genotype. sROBO4 (p = 0.014), TM (p = 0.026) and CRP (p = 0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM., Interpretation: Overall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease., Funding: Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro (AIRC), ERC, Leducq Transatlantic Network of Excellence, Swedish Research Council., Competing Interests: Declaration of interests B.B is inventor of patents on PTX3 and obtains royalties on PTX3-related reagents. N.B. serves on Advisory Board and Speakers Bureau for Celgene and Janssen, and on Speakers Bureau for Takeda, Amgen., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The role of uric acid (UA) on the arterial stiffness progression has been evaluated only in three studies. Our aim was to evaluate its role as a possible determinant of the pulse wave velocity (PWV) progression over a 3.7 ± 0.5 years follow-up period in hypertensive patients. Specific sex analysis was done due to the well-known sex interaction with UA levels. We enrolled 422 consecutive hypertensive outpatients. At baseline anamnestic, blood pressure (BP) and laboratory data as well as PWV were assessed. PWV was performed again at follow-up examination. Hyperuricemia was defined as a UA > 6 mg/dL for women and > 7 mg/dL for men. Baseline age was 53.2 ± 13 years, 58% were males, systolic and diastolic BP (SBP/DBP) 141.7 ± 17.7/86.8 ± 10.8 mm Hg, UA 5.2 ± 1.4 mg/dL, and PWV 8.5 ± 1.9 m/s. At follow-up, despite better BP values (-8.5 ± 24.6 for SBP and -7.5 ± 15.4 for DBP), PWV increases to 9.1 ± 2.3 m/s (P < 0.001) with mean ΔPWV of+ 0.5 ± 2.2 m/s. A total of 61 patients were hyperuricemic (14.4%), and they present higher PWV baseline (9.0 ± 2.5 vs 8.5 ± 1.8 m/s, P = 0.03) without significant differences in ΔPWV. Hyperuricemic female (6.2%, 11 patients) presents higher baseline PWV without significant differences in ΔPWV. No differences were found in arterial stiffness in hyperuricemic males (20.4%, 50 patients). UA showed association with baseline and ΔPWV in the whole population but it loses statistical significance at the linear regression model. Same figures were also for sex analysis. Our findings provide evidence that baseline UA levels are not determinants of PWV progression over a median follow-up of 3.8 years' in hypertensive patients., (©2019 Wiley Periodicals, Inc.)

Dientamoebiasis is globally distributed and detected in a large number of subjects with diarrhea, abdominal discomfort, flatulence, fatigue and loss of appetite. The life cycle and transmission of Dientamoeba fragilis are poorly understood. Microscopic examination of permanent stained smears is traditionally employed to diagnose the infection. However, this approach is time-consuming and the success in detecting D. fragilis depends on the microscopist's experience. Hence, only a few laboratories routinely carry out tests for D. fragilis. Consequently, the prevalence of D. fragilis infection is probably underestimated. Although novel, rapid and more sensitive diagnostic tests are becoming available for detecting intestinal parasites, they also possess some limitations. The aim of this study was to emphasize the importance of performing microscopic examination of permanent stained smears from at least one fresh stool specimen after sample arrival at the laboratory, as a mandatory practice for the diagnosis of dientamoebiasis, particulary where it is not possible to perform molecular assays.

Influenza can cause severe complications in HIV infected individuals leading to increases in hospitalisation and mortality. Vaccination is recommended for such individuals, but some studies reported that immunisation against influenza may stimulate an increase of HIV viral load and decrease of CD4+ cells count. A review of published studies, including our study carried out in HIV former drug addicts, indicates that vaccination against influenza is well tolerated in both children and adult individuals with HIV, but response to vaccination is lower than that observed in immunocompetent individuals. Most studies, including our own, show that vaccination does not induce significant changes in viral load and CD4+ cell counts. In studies reporting modifications of such parameters there is a general agreement that the increased viral replication is usually transient and unable to determine a clear, measurable progression of the underlying HIV disease. Therefore, vaccination against influenza can be safely administered to HIV infected people.

The immunogenicity of an anti-influenza vaccine was assessed in 409 former intravenous drug user volunteers and its effect on the levels of HIV-1 RNA, proviral DNA and on CD4+ lymphocyte counts in a subset HIV-1-positive subjects was measured. HIV-1-positive individuals (n = 72) were divided into three groups on the basis of their CD4+ lymphocyte counts, while the 337 HIV-1-negative participants were allocated into group four. Haemagglutination inhibiting (HI) responses varied from 45.8 to 70% in the HIV-1-positive subjects and were significantly higher in group four (80.7% responses to the H1N1 strain, 81.6% to the H3N2 strain, and 83% to the B strain). The percentage of subjects with HI protective antibody titres (> or = 1:40) increased significantly after vaccination, especially in HIV-1 uninfected subjects. Immunization caused no significant changes in CD4+ counts and in neither plasma HIV-1 RNA nor proviral DNA levels. Therefore, vaccination against influenza may benefit persons infected by HIV-1., (Copyright 2001 Wiley-Liss, Inc.)