Cerebrospinal fluid neurofilament light chain and total-tau as biomarkers of neurodegeneration in Alzheimer's disease and frontotemporal dementia.

INTRODUCTION: CSF Neurofilament light chain(NfL) is a promising biomarker of neurodegeneration, but its utility in discriminating between Alzheimer's disease(AD) and frontotemporal dementia(FTD) is limited. METHODS: 105 patients with clinical-biological diagnosis of mild cognitive impairment(MCI) due to AD (N = 72) or clinical diagnosis of FTD (N = 33) underwent neuropsychological assessment and CSF Aß42/40, p-tau181, total-tau and NfL quantification. Group comparisons, correlations between continuous variables and ROC curve analysis were carried out to assess NfL role in discriminating between MCI due to AD and FTD, exploring the associations between NfL, ATN biomarkers and neuropsychological measures. RESULTS: NfL levels were significantly lower in the AD group, while levels of total-tau were higher. In the FTD group, significant correlations were found between NfL, p-tau181 and total-tau, and between NfL and cognitive performances. In the AD group, NfL levels were directly correlated with total-tau and p-tau181; Aß42/40 ratio was inversely correlated with total-tau and p-tau181, but not with NfL. Moreover, p-tau181 and t-tau levels were found to be associated with episodic memory and lexical-semantic impairment. Total-tau/NfL ratio differentiated prodromal-AD from FTD with an AUC of 0.951, higher than the individual measures. DISCUSSION & CONCLUSIONS: The results support that NfL and total-tau levels reflect distinct pathophysiological neurodegeneration mechanisms, independent and dependent of Aß pathology, respectively, Combining them may enhance both markers reliability, their ratio showing high accuracy in distinguishing MCI due to AD from FTD. Moreover, our results revealed associations between NfL and disease severity in FTD and between tauopathy and episodic memory and lexical-semantic impairment in prodromal-AD.

Post-dialysis fatigue: Comparison of bicarbonate hemodialysis and online hemodiafiltration.

INTRODUCTION: The present cross-sectional study aimed to compare the prevalence, the characteristics of post-dialysis fatigue and the length of recovery time after hemodialysis in prevalent end-stage renal disease patients (ESRD) receiving bicarbonate hemodialysis (HD) or hemodiafiltration (HDF). METHODS: Patients were suffering from post-dialysis fatigue if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Moreover, each patient was invited to rate the intensity, duration, and frequency of post-dialysis fatigue from 1 to 5. In order to assess RECOVERY TIME AFTER DIALYSIS, patients were invited to answer to the following single open-ended question: "How long does it take you to recover from a dialysis session?" FINDINGS: We included 335 patients: 252 received HD and 83 received HDF. Post-dialysis fatigue was present in 204 patients (60.9%). Prevalence of post-dialysis fatigue did not differ significantly between patients on HD (62.3%) and on HDF (56.6%; p = 0.430). Median recovery time after dialysis was 180 min [180-240] and did not differ significantly between the two subgroups (180 min [130-240] and 240 min [120-332] p = 0.671, respectively). Median post-dialysis fatigue intensity, duration, and frequency were 3 [1-5], 3 [1-5], and 4 [1-5] and did not differ significantly between patients on HD and on HDF. At the multivariate analysis, age, ADL and hemoglobin levels were the independent predictors of the HDF treatment. DISCUSSION: Prevalence and characteristics of post-dialysis fatigue do not differ significantly between patients receiving bicarbonate HD or HDF.

Role of Intestinal Inflammation and Permeability in Patients with Acute Heart Failure.

Background and Objectives: Heart failure (HF) represents a major health burden. Although several treatment regimens are available, their effectiveness is often unsatisfactory. Growing evidence suggests a pivotal role of the gut in HF. Our study evaluated the prognostic role of intestinal inflammation and permeability in older patients with acute HF (AHF), and their correlation with the common parameters traditionally used in the diagnostic-therapeutic management of HF. Materials and Methods: In a single-center observational, prospective, longitudinal study, we enrolled 59 patients admitted to the Emergency Department (ED) and then hospitalized with a diagnosis of AHF, from April 2022 to April 2023. Serum routine laboratory parameters and transthoracic echocardiogram were assayed within the first 48 h of ED admission. Fecal calprotectin (FC) and both serum and fecal levels of zonulin were measured, respectively, as markers of intestinal inflammation and intestinal permeability. The combined clinical outcome included rehospitalizations for AHF and/or death within 90 days. Results: Patients with increased FC values (>50 µg/g) showed significantly worse clinical outcomes (p < 0.001) and higher median levels of NT-proBNP (p < 0.05). No significant correlation was found between the values of fecal and serum zonulin and the clinical outcome. Median values of TAPSE were lower in those patients with higher values of fecal calprotectin (p < 0.05). After multivariate analysis, NT-proBNP and FC values > 50 µg/g resulted as independent predictors of a worse clinical outcome. Conclusions: Our preliminary finding supports the hypothesis of a close relationship between the gut and heart, recognizing in a specific marker of intestinal inflammation such as FC, an independent predictive prognostic role in patients admitted for AHF. Further studies are needed to confirm these results, as well as investigate the reliability of new strategies targeted at modulation of the intestinal inflammatory response, and which are able to significantly impact the course of diseases, mainly in older and frail patients.