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Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease which can lead to acute respiratory distress syndrome requiring ventilatory support and intensive care unit admission. The aim of our study is to evaluate the performance of two non-invasive respiratory function indices (the ROX index and the SatO2/FiO2 ratio), as compared to the traditional PaO2/FiO2 ratio, in predicting a clinically relevant composite outcome (death or intubation) in hospitalized patients for COVID-19 pneumonia. Four hospital centers in Northern Italy conducted an observational retrospective cohort study during the first wave of COVID-19 pandemic. Four hundred and fifty-six patients with COVID-19 pneumonia admitted to medical or sub-intensive wards were enrolled. Clinical, laboratory, and respiratory parameters, for the calculation of different indices, were measured at hospital admission. In medical wards (Verona and Padua) the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio were able to predict intubation or death with good accuracy (AUROC for the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio of 75%, 75% and 74%, respectively). Regarding sub-intensive wards (Milan and Mantua), none of the three respiratory function indices was significantly associated with the composite outcome. In patients admitted to medical wards for COVID-19 pneumonia, the ROX index and the SatO2/FiO2 ratio demonstrated not only good performance in predicting intubation or death, but their accuracy was comparable to that of the PaO2/FiO2 ratio. In this setting, where repeated arterial blood gas tests are not always feasible, they could be considered a reliable alternative to the invasive PaO2/FiO2 ratio., (© 2022. The Author(s).)

Total or partial deficiency of the human lysosomal hydrolase alpha-galactosidase A is responsible for Fabry disease, the X-linked inborn error of glycosphingolipid metabolism. Together with the predominant alpha-galactosidase A gene mRNA product encoding the lysosomal enzyme, a weakly regulated alternatively spliced alpha-galactosidase A transcript is expressed in normal tissues, but its overexpression, due to the intronic g.9331G>A mutation, leads to the cardiac variant. We report the molecular characterization of five Fabry patients including two siblings. Sequencing analysis of the alpha-galactosidase A gene coding region and intron/exon boundaries identified the new c.124A>G (p.M42V) genetic lesion as well as a known deletion in three patients, whereas in the two remaining patients, no mutations were identified. To evaluate possible alpha-galactosidase A gene transcription alterations, both predominant and alternatively spliced mRNAs were quantified by absolute real-time PCR on total RNA preparations from the patients' fibroblasts. An impressive reduction in the predominant alpha-galactosidase A transcript was detected in the last patients (Pt 4 and Pt 5). However, the alternatively spliced mRNA was dramatically overexpressed in one of them, carrying a new intronic lesion (g.9273C>T). These findings strongly suggest a correlation between this new intronic mutation and the unbalanced alpha-galactosidase A mRNAs ratio, which could therefore be responsible for the reduced enzyme activity causing Fabry disease. The real-time assay developed here to investigate the two alpha-galactosidase A mRNAs might play a crucial role in revealing possible genetic lesions and in confirming the pathogenetic mechanisms underlying Fabry disease.

Background: In Fabry disease, end-stage renal disease (ESRD) and severe neurologic and cardiac complications represent the leading causes of late morbidity and mortality. A comprehensive Italian nationwide survey study was conducted to explore changes in cardiac status and renal allograft function in Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy (ERT)., Methods: This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals., Results: The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group., Conclusions: Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.

The authors assessed the effectiveness and reliability of a new ultrasound system for evaluating the quality of bone tissue in a series of female patients with suspected type I osteoporosis. Evaluation with ultrasound was performed at the distal metaphysis of the first phalanx of the long fingers of the non-dominant hand. The investigation involves the measurement of the AD-SoS and the evaluation of the screen trace of the US signal transmitted through the phalanx. The data supplied by US were compared with the measurement of BMC through DPA on the ultradistal radius performed on the same day. The study involved 94 patients of age 42 to 73 years. A positive correlation was found between AD-SoS and BMC, r = 0.75, and a negative correlation between AD-SoS and the age of the patients, r = -0.62. Ultrasound investigation enables correct identification in 78% of patients; in particular, none of the patients recognized as pathologic at ultrasound investigation figured as normal at DPA. The authors conclude that the system studied is reliable and supplies important information on the quality of bone tissue, and can usefully complement the methods for measuring BMC.

In nine chronic haemodialysis patients, treated alternately with acetate and bicarbonate, the main critical factors in oxygen supply to the tissues were evaluated: Hb values, blood gas parameters, red cell 2-3 diphosphoglycerate (2-3 DPG), phosphataemia and P50 in vivo. Predialytic P50 was higher than in normal controls. During dialysis, arterial pO2 and pCO2 significantly decreased in acetate dialysis, whereas they were stable in bicarbonate dialysis. Rising alkalinisation was accompanied, both in acetate dialysis and in bicarbonate dialysis, by reduction of P50, while 2-3 DPG did not change. The acute increase in Hb-O2 affinity adversely affected peripheral oxygen release. In acetate dialysis this mechanism might magnify the effects of dialysis-induced hypoxaemia, affecting the clinical tolerance.

Hemorheological measurements were made in 8 stable chronic haemodialysis patients observed in conventional acetate dialysis (AD) with Cuprophan membrane and then in biofiltration (BF) with PAN AN69S membrane. Blood viscosity diminished at the beginning, both during BF and AD, reaching pre-dialytic values again at the end of treatment. Blood and erythrocyte filtration increased after 20 min in AD and throughout the session in BF. Preliminary results suggest an improvement of hemorheological parameters during dialytic treatment, more notable in BF than in AD.