Probiotics-Supplemented Low-Protein Diet for Microbiota Modulation in Patients with Advanced Chronic Kidney Disease (ProLowCKD): Results from a Placebo-Controlled Randomized Trial

The probiotics-supplemented low-protein diet in chronic kidney disease (ProLowCKD) was a single-centre, double-blind, placebo-controlled, randomised trial that was conducted to investigate whether the association between a low protein diet (LPD) and a new formulation of probiotics (Bifidobacterium longum and Lactobacillus reuteri) was effective at reducing traditional uremic, microbiota-derived, and proatherogenic toxins in sixty patients affected by advanced CKD. After 2 months of a LPD—a reduction in blood urea nitrogen (52 ± 17 vs. 46 ± 15 mg/dL, p = 0.003), total cholesterol (185 ± 41 vs. 171 ± 34 mg/dL, p = 0.001), and triglycerides (194 ± 148 vs. 161 ± 70 mg/dL, p = 0.03) was observed; 57 subjects were then randomized to receive probiotics or a placebo for the subsequent 3 months. A total of 27 patients in the placebo group showed increased serum values of total cholesterol (169 ± 36 vs. 185 ± 40 mg/dL, p = 0.01), LDL cholesterol (169 ± 36 vs. 185 ± 40 mg/dL, p = 0.02), lipoprotein-associated phospholipase A₂ (155.4 ± 39.3 vs. 167.5 ± 51.4 nmol/mL/min, p = 0.006), and indoxyl-sulphate (30.1 ± 17.6 vs. 34.5 ± 20.2 μM, p = 0.026), while the 24 subjects in the probiotics group showed a trend in the reduction of microbiota toxins. A reduction of antihypertensive and diuretic medications was possible in the probiotics group. This study shows that associating probiotics to LPD may have an additional beneficial effect on the control and modulation of microbiota-derived and proatherogenic toxins in CKD patients.     

Risk Assessment of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients during 1 Year of Ocrelizumab Treatment

Background: Progressive multifocal leukoencephalopathy (PML) caused by the JC virus is the main limitation to the use of disease modifying therapies for treatment of multiple sclerosis (MS). Methods: To assess the PML risk in course of ocrelizumab, urine and blood samples were collected from 42 MS patients at baseline (T0), at 6 (T2) and 12 months (T4) from the beginning of therapy. After JCPyV-DNA extraction, a quantitative-PCR (Q-PCR) was performed. Moreover, assessment of JCV-serostatus was obtained and arrangements’ analysis of non-coding control region (NCCR) and of viral capsid protein 1 (VP1) was carried out. Results: Q-PCR revealed JCPyV-DNA in urine at all selected time points, while JCPyV-DNA was detected in plasma at T4. From T0 to T4, JC viral load in urine was detected, increased in two logarithms and, significantly higher, compared to viremia. NCCR from urine was archetypal. Plasmatic NCCR displayed deletion, duplication, and point mutations. VP1 showed the S269F substitution involving the receptor-binding region. Anti-JCV index and IgM titer were found to statistically decrease during ocrelizumab treatment. Conclusions: Ocrelizumab in JCPyV-DNA positive patients is safe and did not determine PML cases. Combined monitoring of ocrelizumab’s effects on JCPyV pathogenicity and on host immunity might offer a complete insight towards predicting PML risk.     

Lipoprotein‐associated phospholipase A2 predicts lower limb ischemia in hemodialysis subjects

Hemodialyzed patients (HD) have high prevalence of peripheral arterial disease. In the general population, lipoprotein‐associated phospholipase A2 (Lp‐PLA²) is associated with peripheral arterial disease but no data are available for renal subjects. The aim of this study was to evaluate the relationship between Lp‐PLA₂ and lower limb ischemia among dialyzed patients. One hundred and two dialyzed subjects, with median (IQR) age of 71 (59‐78) years, enrolled in June 2013 and followed until June 2018, were investigated for Lp‐PLA₂ activity and the occurrence of peripheral arterial disease and lower limb ischemia. The median (IQR) levels of Lp‐PLA₂ were 184 nmol/min/mL (156.5‐214.5). The 43 HD patients with abnormal Lp‐PLA₂ activity (>194 nmol/min/mL) had higher levels of total and LDL‐cholesterol, ApoB/A1 ratio, and higher occurrence of lower limb ischemia during the follow up (44% vs 17%, P = .003). In multivariate analysis, Lp‐PLA₂ activity (P = .018) and diabetes (P < .001) were independently associated with time to lower limb ischemia, and when the presence of previous PAD was added to the multivariate model, only presence of previous PAD (P < .001) and Lp‐PLA₂ (P = .003) remained associated. Lp‐PLA₂ is an independent predictor of lower limb ischemia in dialyzed patients.     

The spatial alignment effect in near and far space: a kinematic study

The present experiment aimed at verifying whether the spatial alignment effect modifies kinematic parameters of pantomimed reaching-grasping of cups located at reachable and not reachable distance. The cup’s handle could be oriented either to the right or to the left, thus inducing a grasp movement that could be either congruent or incongruent with the pantomime. The incongruence/congruence induced an increase/decrease in maximal finger aperture, which was observed when the cup was located near but not far from the body. This effect probably depended on influence of the size of the cup body on pantomime control when, in the incongruent condition, cup body was closer to the grasp hand as compared to the handle. Cup distance (near and far) influenced the pantomime even if it was actually executed in the same peripersonal space. Specifically, arm and hand temporal parameters were affected by actual cup distance as well as movement amplitudes. The results indicate that, when executing a reach-to-grasp pantomime, affordance related to the use of the object was instantiated (and in particular the spatial alignment effect became effective), but only when the object could be actually reached. Cup distance (extrinsic object property) influenced affordance, independently of the possibility to actually reach the target.