Evaluation of the prognostic value of impaired renal function on clinical progression in a large cohort of HIV-infected people seen for care in Italy

Whilst renal dysfunction, especially mild impairment (60 die;ve (Icona) Foundation Study collected between January 2000 and February 2014 with at least two creatinine values available. eGFR (CKD-epi) and renal dysfunction defined using a priori cut-offs of 60 (severely impaired) and 90 ml/min/1.73m2 (mildly impaired). Characteristics of patients were described after stratification in these groups and compared using chi-square test (categorical variables) or Kruskal Wallis test comparing median values. Follow-up accrued from baseline up to the date of the CCVD or AIDS related events or death or last available visit. Kaplan Meier curves were used to estimate the cumulative probability of occurrence of the events over time. Adjusted analysis was performed using a proportional hazards Cox regression model. We included 7,385 patients, observed for a median follow-up of 43 months (interquartile range [IQR]: 21-93 months). Over this time, 130 cerebro-cardiovascular events (including 11 deaths due to CCVD) and 311 AIDS-related events (including 45 deaths) were observed. The rate of CCVD events among patients with eGFR >90, 60-89, <60 ml/min, was 2.91 (95% CI 2.30-3.67), 4.63 (95% CI 3.51-6.11) and 11.9 (95% CI 6.19-22.85) per 1,000 PYFU respectively, with an unadjusted hazard ratio (HR) of 4.14 (95%CI 2.07-8.29) for patients with eGFR <60 ml/min and 1.58 (95%CI 1.10-2.27) for eGFR 60-89 compared to those with eGFR ≥90. Of note, these estimates are adjusted for traditional cardiovascular risk factors (e.g. smoking, diabetes, hypertension, dyslipidemia). Incidence of AIDS-related events was 9.51 (95%CI 8.35-10.83), 6.04 (95%CI 4.74-7.71) and 25.0 (95% CI 15.96-39.22) per 1,000 PYFU, among patients with eGFR >90, 60-89, <60 ml/min, respectively, with an unadjusted HR of 2.49 (95%CI 1.56-3.97) for patients with eGFR <60 ml/min and 0.68 (95%CI 0.52-0.90) for eGFR 60-89. The risk of AIDS events was significantly lower in mild renal dysfunction group even after adjustment for HIV-related characteristics. Our data confirm that impaired renal function is an important risk marker for CCVD events in the HIV-population; importantly, even those with mild renal impairment (90<60)&gt

Telemedicine and telehealth services in the age of demographic transition: the screening of the municipality of Cremona on the autonomy and self-sufficiency of the population over 60

Raccolta degli abstract dei convegni "Nuovi modelli di assistenza sanitaria" e "Health Complexity in Aging", nell'ambito della Healthy Aging Week 2023, organizzata ad Alba, dal 6 all'11 novembre 2023, dalla Fondazione Piera Pietro e Giovanni Ferrero in collaborazione con l'Accademia di Medicina di Torino, l'Università Cattolica del Sacro Cuore di Milano, il Karolinska Institutet di Stoccolm

A comparative screening of laccase‐mediator systems by white‐rot fungi laccases for biocatalytic benzyl alcohol oxidation

Production of value-added compounds from waste materials is of utmost importance for the development of a sustainable society especially regarding their use as catalysts in industrially relevant synthetic reactions. Herein, we show the production of laccases from four white-rot fungi, which were grown on agricultural residues, specifically Trametes versicolor 11269, Pleurotus ostreatus 1020, Panus tigrinus 707 and Lentinula edodes SC-495. The produced laccases were tested on a laccase-mediator system (LMS) for the biocatalytic oxidation of the model substrate benzyl alcohol into benzaldehyde. The LMS was carried out in the presence both of tetrahydrofuran as co-solvent and of the mediator 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) due to its high redox potential and its ability to perform the oxidation. Tolerance studies showed that the dialyzed solutions were able to tolerate 1% (99:1 v/v) of co-solvent, whereas a concentration of 10% v/v had a detrimental activity. Performances in the biocatalytic oxidation of laccase solutions from different purification steps were compared. Similar conversion was observed for laccase in dialysis (raw) and gel filtration (GF) product versus commercial T. versicolor laccase. The latter oxidized almost 99% of substrate while the other laccase solutions were able to reach a conversion from 91% for the laccase solution from P. tigrinus 707 after dialysis, to 50% for the laccase solution from P. ostreatus 1020 after gel filtration. This work highlights the potential of unpurified laccase solutions to be used as catalysts in synthetic reactions

A Rare Case of Systemic AL Amyloidosis with Muscle Involvement: A Misleading Diagnosis

Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels. Transmission electron microscopy (TEM) con firmed amyloid fibrils around perimysial vessels associated with collagen fibrils. A stepwise approach to diagnosis and staging of this disorder is critical and involves confirmation of amyloid deposition, identification of the fibril type, assessment of underlying amyloidogenic disorder, and evaluation of the extent and severity of amyloidotic organ involvement

Citrullinated and carbamylated proteins in extracellular microvesicles from plasma of patients with rheumatoid arthritis

Objectives: To investigate the expression of citrullinated and carbamylated proteins in extracellular microvesicles (EMVs) from RA patients. Methods: We enrolled 24 RA naive for biological therapy and 20 healthy donors (HD), matched for age and sex. For each patient, laboratory and clinical data were recorded and clinical indexes were measured (Clinical Disease Activity Index, Simplified Disease Activity Index, DAS28). EMVs in RA patients and HD were purified from plasma and measured by nanoparticle tracking analysis (NanoSight). Further, EMVs were incubated with anti-citrullinated/carbamylated proteins antibodies and processed by flow cytometry and western blot to evaluate the expression of citrullinated/carbamylated antigens. Results: NanoSight revealed a significant increase of EMVs in RA compared with HD. Moreover, cytofluorimetric analysis showed a significative higher expression of citrullinated antigens on EMVs' surface in RA than donors, while no substantial difference was found in the expression of carbamylated antigens. These data were confirmed by western blot which identified vimentin, glycolytic enzyme alpha-enolase 1 and collagen type II as the main citrullinated and carbamylated proteins carried by EMVs. Finally, a relevant correlation between the expression of citrullinated antigens and disease activity was found. Conclusions: The results of this study suggest an involvement of EMVs in the pathogenesis of RA by inducing autoimmunity

MLH1 and MSH2 constitutional mutations in colorectal cancer families not meeting the standard criteria for hereditary nonpolyposis colorectal cancer

Genetic diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) may have a significant impact on the clinical i management of patients and their at-risk relatives. At present, clinical criteria represent the simplest and most useful method for the identification of HNPCC families and for the selection of candidates for genetic testing. However, reports of mismatch repair (MMR) gene mutations in families not fulfilling the minimal diagnostic criteria point out the necessity to identify additional clinical parameters suggestive of genetic predisposition to colorectal cancer (CRC) related to MMR defects. We thus investigated a series of 32 Italian putative HNPCC individuals selected on the basis of one of the following criteria: I) family history of CRC and/or other extracolonic tumors; 2) early-onset CRC; and 3) presence of multiple primary malignancies in the same individual. These patients were investigated for the presence of MLH1 and MSH2 mutations by single-strand conformation polymorphism analysis. Pathogenetic truncating mutations were identified in 4 (12.5%) cases, 3 of them involving MSH2 and I MLH1. In addition, 2 missense MLH1 variants of uncertain significance were observed. All pathogenetic mutations were associated with early age (c:40 years) at onset and proximal CRC location. Our results support the contention that constitutional MMR mutations can also occur in individuals without the classical HNPCC pattern. Moreover, evaluation of the clinical parameters associated with MMR mutations indicates that early onset combined with CRC location in the proximal colon can be definitely considered suggestive of MMR-related hereditary CRC and should be included among the guidelines for referring patients for genetic testing

Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer

Mismatch repair genes MSH2 and MLH1 are considered to be the two major genes that are responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Germline heterozygous inactivating mutations of MSH2 and MLH1 have been identified previously in a substantial fraction of individuals who are predisposed genetically to colorectal carcinoma (CRC) and other tumors of the HNPCC spectrum. With the aim of determining the relevance of these two genes in the Italian population, we submitted to mutational analysis a set of 17 HNPCC families, all of which fulfilled the 'Amsterdam criteria.' A combination of different techniques, including reverse transcription- polymerase chain reaction (RT-PCR) of long fragments and single-strand conformation polymorphism (SSCP) on cDNA and genomic DNA, allowed the identification of ten molecular variants, seven of which are predicted to inactivate mismatch repair function. The mutated predisposing gene was MSH2 in two families and MLH1 in five other families. All of the mutations were characterized by DNA sequencing and appeared to involve different molecular mechanisms, such as short in-frame and out-of-frame deletions, splicing errors, and nonsense mutations. This study also demonstrates that, in the Italian population, a considerable fraction of HNPCC families (at least 41%) is linked to MSH2 and MLH1 mutations