AimTo determine if red cell distribution width (RDW) is associated with all-cause mortality in patients on chronic dialysis and to evaluate its prognostic value among validated prognostic biomarkers.MethodsThis is a single center, prospective longitudinal study. At the time of inclusion in January 2011, all patients were physically examined and a routine blood analysis was performed. A sera sample was preserved for determination of NT-pro-brain natriuretic peptide (NT-pro-BNP) and eosinophil cationic protein. Carotid intima media thickness (IMT) was also measured. Following one year, all-cause mortality was evaluated.ResultsOf 100 patients, 25 patients died during the follow-up period of one-year. Patients who died had significantly higher median [range] RDW levels (16.7% [14.3-19.5] vs 15.5% [13.2-19.7], P < 0.001. They had significantly higher Eastern Cooperative Oncology Group (ECOG) performance status (4 [2-4] vs 2 [1-4], P < 0.001), increased intima-media thickness (IMT) (0.71 [0.47-1.25] vs 0.63 [0.31-1.55], P = 0.011), increased NT-pro-BNP levels (8300 [1108-35000] vs 4837 [413-35000], P = 0.043), and increased C-reactive protein (CRP) levels (11.6 [1.3-154.2] vs 4.9 [0.4-92.9], P < 0.001). For each 1% point increase in RDW level as a continuous variable, one-year all cause mortality risk was increased by 54% in univariate Cox proportional hazard analysis. In the final model, when RDW was entered as a categorical variable, mortality risk was significantly increased (hazard ratio, 5.15, 95% confidence interval, 2.33 to 11.36) and patients with RDW levels above 15.75% had significantly shorter survival time (Log rank P < 0.001) than others.ConclusionsRDW could be an additive predictor for all-cause mortality in patients on chronic dialysis. Furthermore, RDW combined with sound clinical judgment improves identification of patients who are at increased risk compared to RDW alone.

Objectives: Receptor for advanced glycation end products (RAGE) ligands/RAGE interactions have been proposed to have a pathogenic role in neuroinflammatory disorders. Our study aimed to assess changes in high-mobility group box (HMGB)1 and its receptor RAGE in peripheral blood (PBL) and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) at the disease onset compared with control subjects. Methods: PBL and CSF were collected from control subjects (n = 30) and MS patients (n = 27) at clinical onset. Soluble RAGE (sRAGE), HMGB1, S100 calcium-binding protein A12 (S100A12), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured in the CSF and plasma by enzyme-linked immunosorbent assay. Gene expression in PBL mononuclear cells (PBMCs) was detected by quantitative PCR for RAGE, HMGB1, S100A12 and several proinflammatory/immunoregulatory cytokines. Results: We found a significantly lower expression of IL-10 (p = 0.031) in the PBMCs of MS patients. The level of sRAGE in the CSF of MS patients was lower (p = 0.021), with the ability to discriminate between MS patients and control subjects. Moreover, PBMC gene expression for HMGB1 and S100A12 positively correlated with IL-6. Conclusions: Our study confirmed that the cytokine network is disturbed in PBL and CSF at MS clinical onset. The deregulated HMGB1/RAGE axis found in our study may present an early pathogenic event in MS, proposing sRAGE as a possible novel therapeutic strategy for MS treatment.

Objectives: Our study focused on the RANKL (receptor activator of nuclear factor-κB ligand)/RANK/OPG (osteoprotegerin) axis and selected proinflammatory/immunoregulatory upstream mediators in the peripheral blood (PBL) and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. Methods: PBL and CSF were collected from healthy controls (n = 35) and MS patients at the clinical onset of the disease (n = 33). In addition, PBL samples were obtained from relapse-remitting (RR)-MS patients (n = 30). Patients were assessed by means of the expanded disability status scale (EDSS) and routine laboratory parameters. Soluble (s)RANKL and OPG were measured in the CSF and plasma; gene expression was detected for RANKL, RANK, OPG, and selected cytokines/chemokines (interleukin [IL]-4, IL-10, IL-17, CCL2, and CXCL12) in PBL mononuclear cells. Results: The OPG level in the CSF was lower in MS patients at clinical onset than in controls. Moreover, the sRANKL/OPG ratio was higher in the CSF of MS patients at clinical onset and in the plasma of RR-MS patients than in controls. Gene expression of RANKL/RANK/OPG in PBL mononuclear cells was higher only in RR-MS patients. IL-4, CCL2, and CXCL12 were positively correlated and IL-10 was negatively correlated with RANKL/RANK expression. OPG was negatively correlated with EDSS and alkaline phosphatase level. Conclusion: Our study revealed that changes of RANKL/RANK/OPG axis are associated with MS, particularly the decreased OPG level in the CSF at disease onset. Therefore, these factors may serve as disease biomarkers and molecular targets of novel therapeutic approaches.

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IntroductionParkinson’s disease (PD) patients have a significantly higher risk of developing dementia in later disease stages, leading to severe impairments in quality of life and self-functioning. Questions remain on how deep brain stimulation (DBS) affects cognition, and whether we can individualize therapy and reduce the risk for adverse cognitive effects. Our aim in this systematic review is to assess the current knowledge in the field and determine if the findings could influence clinical practice.MethodsWe have conducted a systematic review according to PRISMA guidelines through MEDLINE and Embase databases, with studies being selected for inclusion via a set inclusion and exclusion criteria.ResultsSixty-seven studies were included in this systematic review according to the selected criteria. This includes 6 meta-analyses, 18 randomized controlled trials, 17 controlled clinical trials, and 26 observational studies with no control arms. The total number of PD patients encompassed in the studies cited in this review is 3677, not including the meta-analyses.ConclusionCognitive function in PD patients can deteriorate, in most cases mildly, but still impactful to the quality of life. The strongest evidence is present for deterioration in verbal fluency, while inconclusive evidence is still present for executive function, memory, attention and processing speed. Global cognition does not appear to be significantly impacted by DBS, especially if cognitive screening is performed prior to the procedure, as lower baseline cognitive function is connected to poor outcomes. Further randomized controlled studies are required to increase the level of evidence, especially in the case of globus pallidus internus DBS, pedunculopontine nucleus DBS, and the ventral intermediate nucleus of thalamus DBS, and more long-term studies are required for all respective targets.

Aim To assess the effect of social isolation due to the coronavirus disease 2019 (COVID-19) pandemic on physical and mental health of Parkinson’s disease patients treated at the University Hospital Center Rijeka. Methods This cross-sectional telephone study involved Parkinson’s disease patients who had at least one control examination at University Hospital Center Rijeka in 2020 and were Croatian citizens. A questionnaire was used to obtain data on the socio-demographic characteristics and the severity of motor, anxiety, depression, and non-motor symptoms. Results The final sample included 87 patients. Most patients reported subjective worsening of motor symptoms. Patients who lived alone had worse motor scores than those not living alone. The majority of patients reported worsening of anxiety symptoms. Significant worsening of anxiety symptoms was found in patients who lived alone, had a longer disease duration, and had avoided check-ups. Fewer patients had depression symptoms than motor and anxiety symptoms. Significantly higher Hamilton Depression Rating Scale scores were observed in patients with a longer disease duration. Significant worsening of non-motor symptoms was identified in patients who lived alone, were less educated, had a longer disease duration, and had a higher Charlson comorbidity index. Conclusion Patients who live alone, have longer disease duration, are less educated, avoid check-ups, and have more comorbidities are more vulnerable to the negative effects of social isolation.