High levels of mid-regional proadrenomedullin in ARDS COVID-19 patients: the experience of a single, Italian Center.

OBJECTIVE: This study evaluated the ability of mid-regional proadrenomedullin (MR-proADM) to identify disease severity in Coronavirus disease 2019 (COVID-19) patients in comparison to conventional inflammatory biomarkers and clinical scores. PATIENTS AND METHODS: In an observational trial, COVID-19 acute respiratory distress syndrome (ARDS) patients were enrolled. MR-proADM, C-reactive protein (CRP), procalcitonin (PCT) and lactic acid (LA) were measured in all patients at admission (T0), at 24 hours (T1) and in the third (T3) and fifth day (T5) of hospitalization. The aims of this study were to determine the role of MR-proADM to detect patients with high risk of mortality and compare the prognostic value of MR-proADM with commonly used clinical scores (Sequential Organ Failure Assessment score - SOFA score, Acute Physiologic Assessment and Chronic Health Evaluation II score - APACHE II score, and Simplified Acute Physiological score II - SAPS II score). RESULTS: Twenty-one COVID-19 ARDS patients admitted to the Intermediate Care Unit (IMCU) were enrolled. The median MR-proADM values were 2.28, 2.41, 1.96 and 1.89 nmol/L at T0, T1, T3 and T5, respectively. The 30-day all-cause mortality rate was 52.4%. Mean MR-proADM T0 value was significantly higher in non-survivors compared with survivors (3.5 vs. 1.1 nmol/L, p < 0.05). No significant differences were found for the other inflammatory biomarkers. In terms of the area under the receiver-operating characteristic curve (AUC), MR-proADM showed a similar discriminatory power compared with APACHE II, SOFA and SAPS II score (0.81, 0.91, 0.70 and 0.78, respectively). The optimal MR-proADM cut-point cut-off point was 1.07 nmol/L, which corresponds to a sensitivity of 91% and a specificity of 71%. CONCLUSIONS: MR-proADM, in addition to the clinical scores, could be useful to predict outcome in COVID-19 ARDS patients.

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study.

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.

Not every PRP-gel is born equal. Evaluation of growth factor availability for tissues through four PRP-gel preparations: Fibrinet, RegenPRP-Kit, Plateltex and one manual procedure.

BACKGROUND: The rationale for using topical platelet gel therapy is to provide the healing tissues with concentrated platelet-derived factors. Several systems are available to prepare platelet-rich plasma (PRP) and from these, the platelet gel. These systems produce two- to six-fold platelet and growth factor-enriched concentrations. The bioavailability of growth factors in tissue healing depends on the amount of growth factors stored in platelets but a portion of these is lost during platelet manipulation. Very few data have been reported on the kinetics of growth factor release from PRP-gels. The aim of this study is to assess the growth factor recovery and its bioavailability to tissues in four different PRP and PRP-gel preparation techniques. MATERIALS AND METHODS: Three commercially available devices (Fibrinet, RegenPRP-Kit, Plateltex) and one manual procedure (home made, HM) were evaluated with reference to resulting platelet concentration, growth factor content and the kinetics of growth factor release from gel. RESULTS: Platelet concentration increased from 1.65- to 4.4-fold in comparison with whole blood initially used. The final platelet concentration (x 10(3)/microl) was: Fibrinet 1358 +/- 419, Regen 430 +/- 109, HM 1196 +/- 188, and Plateltex 1160 +/- 164. A high variation (5- to 27-fold) was found in growth factor concentration in relation to the method used and also a high variation in the kinetics of growth factor release from gels. CONCLUSIONS: Similar methods for platelet gel preparation revealed different performances concerning growth factor recovery and the kinetics of its release from the gel. It is unclear whether these noticeable differences are important for clinical management.

Hepatitis C virus heteroduplex tracking assay for genotype determination reveals diverging genotype 2 isolates in Italian hemodialysis patients.

A heteroduplex tracking assay (HTA) was developed for genetic analyses of the hepatitis C virus (HCV) using single-stranded probes from the core (C)/E1 region. Nucleotide sequencing of reverse transcriptase (RT)-PCR products from 15 Italian dialysis patients confirmed the specificity and accuracy of the HTA genotyping method, which identified 5 of 15 (33.3%) 1b, 7 of 15 (46.7%) 3a, and 3 of 15 (20%) type 2 infections. The genotypes of an additional 12 HCV antibody-positive blood donors from different geographical locations were also in agreement with the genotypes determined by the Inno-LiPA HCV II kit (Innogenetics) and/or restriction fragment length polymorphism (RFLP). Isolates which had between 35 to 40% nucleotide divergence from control subtype 1a, 1b, 2a, 2b, or 3a standards could be typed. Surprisingly, HTA detected one 1b-2 coinfection which was missed by DNA sequencing. Three samples that were designated non-2a or 2b type 2 by HTA were found to be type 2a by both RFLP and direct nucleotide sequencing of the 5' untranslated region. The genetic distance between patient type 2 and control 2a, 2b, and 2c isolates indicated that a new subtype was present in the population being studied. Serotyping (RIBA serotyping strip immunoblot assay kit) of 23 dialysis patients showed that the genotype could be determined in 6 of 8 (75%) C/E1 RT-PCR-negative and 15 of 23 (65.2%) RT-PCR-positive samples, indicating that the two tests complement each other.

Epitope mapping of the NS4 and NS5 gene products of hepatitis C virus and the use of a chimeric NS4-NS5 synthetic peptide for serodiagnosis.

Specific domains of the NS4 and NS5 gene products of hepatitis C virus have been identified using hydrophilicity profiles for the prediction of potential immunogenic regions, and epitope scanning techniques. Peptides synthesised on the basis of such data show excellent reactivity in the ELISA format. Introduction of a glycine-glycine spacer between two peptides (NS4-12 and NS5-44) to give a single chimeric peptides does not appear to impair immunoreactivity. An ELISA based on the chimeric peptide and a Core-NS3 recombinant protein correctly diagnoses a cohort of haemodialysed patients, three commercial HCV panels and the sera of a negative control population.

[Seroepidemiology of HIV-1 and HIV-2 in the USSL 76 area--Casale M.To. Preliminary study]. / Sieroepidemiologia di HIV-1 ed HIV-2 nell'area dell'USSL 76--Casale M.to. Studio preliminare.

The reported results show a prevalence of HIV-1 antibodies in drug addicts by ELISA and Western Blot. In this case report the presence of persons (drug addicts) whose sera have antibodies to HIV-1 and HIV-2 by ELISA and Western Blot advise that further epidemiological studies are necessary to assess the real HIV-2 circulation in Italy.

Lymphocytoplasmapheresis in multiple sclerosis: one-year results in 6 patients.

6 patients with definite MS underwent lymphocytoplasmapheresis for one year. Clinical data, evoked potential recordings and peripheral blood lymphocyte helper/suppressor ratio were assessed before and after the treatment and were compared with those of a control group of 10 multiple sclerosis patients. Lymphocytoplasmapheresis did not significantly modify clinical and laboratory findings compared with the control group.

Lymphocytoplasmapheresis in multiple sclerosis: preliminary laboratory findings.

Short-term treatment with lymphocytoplasmapheresis was evaluated in 6 multiple sclerosis patients with special reference to the electrophysiological and immunological findings. Visual, somatosensory, brainstem auditory evoked potentials, flicker fusion test, helper/suppressor blood lymphocyte ratio, serum immunocomplexes and immunoglobulins and Kurtzke scores were evaluated in each patient before and after treatment. No statistically significant results were obtained.