Renal Arterial and Venous Doppler in Cardiorenal Syndrome: Pathophysiological and Clinical Insights.

In recent decades, there has been considerable effort in investigating the clinical utility of renal Doppler measurements in both cardiovascular and renal disorders. In particular, a measure of renal arterial resistance, the renal resistive index (RRI), has been demonstrated to predict chronic kidney disease progression and acute kidney injury in different clinical settings. Furthermore, it is linked to a poorer prognosis in individuals suffering from chronic heart failure. Examining the renal venous flow through pulsed Doppler can offer additional insights into renal congestion and cardiovascular outcomes for these patients. This review seeks to summarize the existing data concerning the clinical significance of arterial and venous renal Doppler measurements across various cardiovascular and renal disease contexts.

Sarcopenia in subjects with Alzheimer's disease: prevalence and comparison of agreement between EGWSOP1, EGWSOP2, and FNIH criteria.

BACKGROUND: Sarcopenia is an age-related clinical syndrome characterized by the progressive loss of muscle mass and muscle strength. It appears to be closely linked to dementia, particularly Alzheimer's disease (AD); however, its prevalence among AD patients remains unclear. In this study, we assessed differences in sarcopenia prevalence between non-demented individuals and AD patients. Moreover, we assessed sex-specific differences in sarcopenia prevalence and explored the diagnostic value of the Muscle Quality Index (MQI) for diagnosing sarcopenia among AD patients. METHOD: Cross-sectional study including 145 patients with probable AD and 51 older adults with normal cognition. Sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP1 and EWGSOP2) and of the Foundation for the National Institutes of Health (FNIH). The MQI was computed as the ratio of handgrip strength to skeletal muscle mass. RESULTS: No significant difference in sarcopenia prevalence was observed between AD patients and controls. Prevalence ranged from 3.4 to 23.4% in AD patients and from 2 to 11.8% in controls, depending on diagnostic criteria. Prevalence was higher using EWGSOP1 and decreased using EWGSOP2 and FNIH. Prevalence was higher in males than in females with AD. The MQI was lower in AD patients than in controls (95%CI: - 0.23, - 0.05, p < 0.001), but displayed poor diagnostic accuracy in identifying sarcopenia cases. CONCLUSIONS: AD patients and controls show comparable sarcopenia prevalence. Sarcopenia prevalence is higher in males than females among AD patients and higher when using EWGSOP1 compared to FNIH and EWGSOP2 criteria.

Narcissistic Personality Disorder as Prodromal Feature of Early-Onset, GRN-Positive bvFTD: A Case Report.

Background: Behavioral variant frontotemporal dementia (bvFTD) typically involves subtle changes in personality that can delay a timely diagnosis. Objective: Here, we report the case of a patient diagnosed of GRN-positive bvFTD at the age of 52 presenting with a 7-year history of narcissistic personality disorder, accordingly to DSM-5 criteria. Methods: The patient was referred to neurological and neuropsychological examination. She underwent 3 Tesla magnetic resonance imaging (MRI) and genetic studies. Results: The neuropsychological examination revealed profound deficits in all cognitive domains and 3T brain MRI showed marked fronto-temporal atrophy. A mutation in the GRN gene further confirmed the diagnosis. Conclusions: The present case documents an unusual onset of bvFTD and highlights the problematic nature of the differential diagnosis between prodromal psychiatric features of the disease and primary psychiatric disorders. Early recognition and diagnosis of bvFTD can lead to appropriate management and support for patients and their families. This case highlights the importance of considering neurodegenerative diseases, such as bvFTD, in the differential diagnosis of psychiatric disorders, especially when exacerbations of behavioral traits manifest in adults.

Atrial paced rhythm and heart rate-dependent worsening of left atrial and ventricular function.

BACKGROUND AND AIM OF THE STUDY: The response to the increase in heart rate (HR) could be characterized by failure in both left ventricular (LV) and left atrial (LA) functions. This study aimed to evaluate the relationship between the increase in paced HR and the changes in LV and LA functions, assessed by two-dimensional speckle tracking analysis. METHODS: In a group of patients with an implantable cardioverter defibrillator (ICD) or pacemaker, the atrial paced rhythm was progressively increased from 60 to 70, from 70 to 80, and from 80 to 90 beats per minute (bpm). For each paced HR, using two-dimensional speckle tracking analysis, LA reservoir (LAr), LA conduit (LAc), LA contraction (LAct), and LV global longitudinal strain (LV-GLS) were evaluated every 10 bpm. RESULTS: Of the 45 patients enrolled, a significant reduction in LAr was observed at higher HR. However, when the patients were dichotomized according to the HR-related response of LV-GLS, the worsening of LAr was observed in those with LV-GLS worsening and not in those without (maximum LAR absolute changes -2.7 ± 7.2% vs. +2.7 ± 7.2%, respectively, p .028). Moreover, the worsening of LA and LV strain measures was associated with an increase in the estimated filling pressures. CONCLUSIONS: In patients with atrial paced rhythm, the increase in HR could be associated with worsening of LA and LV functions, as assessed by two-dimensional speckle tracking analyses. These results offer new data on HR-related atrioventricular function and could be useful for guiding the optimal HR responsiveness of the implanted devices.

Renal resistance index independently predicts worsening of renal function after coronary angiography.

The renal resistance index (RRI) has been demonstrated to be a useful parameter that can detect patients at a high risk of worsening of renal function (WRF). This study was designed to evaluate the role of the RRI in predicting WRF mediated by the intravascular administration of contrast media. We enrolled patients who were referred for coronary angiography. Renal arterial echo-color Doppler was performed to calculate the RRI. WRF was defined as an increase of > 0.3 mg/dL and at least 25% of the baseline value in creatinine concentration 24-48 h after coronary angiography. Among the 148 patients enrolled in this study, 18 (12%) had WRF. In the multivariate logistic analysis, the RRI was independently associated with WRF (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.09-1.36; p = 0.001). After angiography, the RRI significantly increased in both patients with and without WRF. In the receiver operating characteristic curve analyses for WRF, the RRI at baseline and after angiography showed similar accuracy, and the best cutoff value for predicting WRF was 70%. In patients undergoing coronary angiography, the RRI is independently associated with WRF, probably because it provides more accurate information about cardiorenal pathophysiological factors and reflects kidney hemodynamic status and flow reserve.

Sarcopenia screening in elderly with Alzheimer's disease: performances of the SARC-F-3 and MSRA-5 questionnaires.

BACKGROUND: The 3-item SARC-F (SARC-F-3) and the 5-item Mini Sarcopenia Risk Assessment (MSRA-5) questionnaires have been recently proposed to screen elderly people regarding the risk of sarcopenia. However, no studies have investigated their performances in Alzheimer's disease (AD). METHODS: We conducted a single-center observational study, including 130 consecutive AD patients (mean age: 70.71 ± 8.50 y, 54.6% women) who attended a center for neurodegenerative diseases. Sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People of 2010 (EWGSOP1) and of 2018 (EWGSOP2) criteria. Sensitivity, specificity, positive and negative likelihood ratio, and the area under the receiver operating characteristic curve (AUC) were used to assess the diagnostic performance of SARC-F-3 and MSRA-5. RESULTS: SARC-F-3 showed a sensitivity of 9.7%, a specificity of 82.8% and an AUC of 0.41 using EWGSOP1, whereas the sensitivity was of 16.7%, specificity of 84.7% and AUC of 0.58 using EWGSOP2. The MSRA-5 displayed a sensitivity of 3.2%, a specificity of 89.9% and an AUC of 0.41 using EWGSOP1, whereas sensitivity was of 0%, specificity of 91.1% and the AUC of 0.55 using EWGSOP2 criteria. The questionnaires showed a moderate agreement (Cohen's k = 0.53). CONCLUSIONS: In our sample of AD patients, a sizable number of sarcopenic individuals were misidentified by SARC-F-3 and MSRA-5, making those questionnaires unsuitable for sarcopenia screening. Considering that sarcopenia has a high prevalence in dementia and that its correct and timely identification is paramount for optimal management of patients, the development and validation of an ad-hoc sarcopenia screening tool for AD patients is highly desirable.

The Relationship Between Muscle Strength and Cognitive Performance Across Alzheimer's Disease Clinical Continuum.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive cognitive decline, mostly prominent in the domain of memory, but also associated with other cognitive deficits and non-cognitive symptoms. Reduced muscle strength is common in AD. However, the current understanding of its relationship with cognitive decline is limited. This study investigates the relationship between muscle strength and cognition in patients with AD and mild cognitive impairment (MCI). We enrolled 148 consecutive subjects, including 74 patients with probable AD dementia, 37 MCI, and 37 controls. Participants underwent neuropsychological evaluation focused on attention, working memory, declarative memory and learning. Muscle strength and muscle mass were measured through hand dynamometer and bio-electrical impedance analysis, respectively. Patients with AD dementia were divided with respect to the severity of cognitive impairment into mild and moderate-to-severe patients. Moderate-to-severe patients with AD presented lower handgrip strength than MCI and controls. No differences were observed in muscle mass. In MCI and AD dementia, handgrip strength was associated with overall cognitive functioning, attentional and memory performance. The routine implementation of handgrip strength assessment in the clinical work-up of patients with MCI and AD could potentially represent a simple method to monitor functional and cognitive decline along the disease course.

Role of plasma phosphorylated neurofilament heavy chain (pNfH) in amyotrophic lateral sclerosis.

The phosphorylated neurofilament heavy chain (pNfH) is a promising biomarker in amyotrophic lateral sclerosis (ALS). We examined plasma pNfH concentrations in order to corroborate its role as a diagnostic and prognostic biomarker in ALS. Incident ALS cases enrolled in a population-based registry were retrospectively selected and matched by sex and age with a cohort of healthy volunteers. Plasma pNfH levels were measured by an ELISA kit and correlated with clinical parameters. Discrimination ability of pNfH was tested using receiving operating characteristic (ROC) curves. Kaplan-Meier (KM) analysis and Cox proportional hazard models were used for survival analysis. Plasma pNfH was significantly higher in patients compared to controls. An optimal cut-off of 39.74 pg/ml discriminated cases from controls with an elevated sensitivity and specificity. Bulbar-onset cases had higher plasma pNfH compared to spinal onset (p = 0.0033). Furthermore, plasma pNfH positively correlated with disease progression rate (r = 0.19, p = 0.031). Baseline plasma pNfH did not influence survival in our cohort. Our findings confirmed the potential utility of plasma pNfH as a diagnostic biomarker in ALS. However, further studies with longitudinal data are needed to corroborate its prognostic value.

Arrhythmic myocarditis in an adolescent male: A unique presentation of multi-organ inflammatory syndrome (MIS-C).

Although children with Covid-19 generally present with mild symptoms or are often asymptomatic, there is increasing recognition of a delayed multi-organ inflammatory syndrome (MIS-C) following SARS-CoV-2 infection. We report the case of MIS-C associated arrhythmic myocarditis which recovered after anti-inflammatory therapy and immunoglobulin infusion.

The Role of Age on Beta-Amyloid1-42 Plasma Levels in Healthy Subjects.

Beta-amyloid (Aß) plaques have been observed in the brain of healthy elderlies with frequencies strongly influenced by age. The aim of the study is to evaluate the role of age and other biochemical and hematological parameters on Aß1-42 plasma levels in cognitively and neurologically normal individuals. Two-hundred and seventy-five normal subjects stratified by age groups (<35 years, 35-65 years, and >65 years) were included in the study. Aß1-42 plasma levels significantly correlated with age (rs = 0.27; p < 0.0001) in the whole sample, inversely correlated with age in the first age group (rs = -0.25, p = 0.01), positively correlated in the second group (rs = 0.22, p = 0.03), while there was no significant correlation in the older group (rs = 0.02, p = 0.86). Both age (ß-estimate = 0.08; p < 0.001) and cholesterol (ß-estimate = 0.03; p = 0.009) were significantly associated with Aß1-42 plasma level in multivariable analysis. However, only the association with age survived post hoc adjustment for multiple comparisons. The different effects of age on the Aß level across age groups should be explored in further studies to better understand the age-dependent variability. This could better define the value of plasma Aß as a biomarker of the Alzheimer neuropathology.

Biomarkers in Cardiorenal Syndrome.

Cardiorenal syndrome is a clinical manifestation of the bidirectional interaction between the heart and kidney diseases. Over the last years, in patients with cardiovascular diseases, several biomarkers have been studied in order to better assess renal function as well as to identify patients prone to experiencing chronic or acute worsening of renal function. The aim of this review is to focus on the possible clinical usefulness of the most recent biomarkers in the setting of cardiorenal syndrome.

Chromogranin-A serum levels in patients with takotsubo syndrome and ST elevation acute myocardial infarction.

BACKGROUND: Sympathergic hyperactivity is considered one of the main trigger precipitating takotsubo syndrome (TTS). Chromogranin-A (CgA), a prognostic biomarker of sympatho-adrenal activation, is markedly high in acute coronary syndrome (ACS) and heart failure (HF), but its role in TTS is unknown. METHODS: CgA serum levels from patients with TTS and symptoms onset <24 hours were consecutively evaluated and compared with anterior ST-elevation myocardial infarction (STEMI) patients from November 2016 to December 2019. Short and long-term follow-up data were recorded. RESULTS: Eleven women with TTS and 10 subjects with anterior STEMI were analyzed and compared; differences were not significant in terms of age, gender and cardiovascular risk factors. NT-pro-BNP levels were similar (9,887 ± 12,170 vs 8,969 ± 15,053 pg/ml, p = .88), while troponin-I levels were higher in patients with STEMI (4 ± 3.2 vs 13.3 ± 10 ng/dl, p = .03). CgA admission levels were significantly lower in TTS patients (2.2 ± 1.5 vs 7.3 ± 6.2 nMol/l, p = .017), even after multivariable correction for principal bias. CgA levels correlated with NTproBNP levels (p = .02) and were higher in subjects with in-hospital events (3.7 ± 1.1 vs 1.6 ± 1.2 nMol/l, p = .03), even after multivariable forward stepwise analysis (p < .01). CgA levels <3.25 nMol/l (AUC 0.754, 95% C.I. 0.54-0.968) were able to discriminate TTS from anterior STEMI (negative predictive power of 99%). CONCLUSIONS: Systemic CgA levels in the acute phase of TTS are lower than in anterior STEMI, possibly indicating a greater myocardial catecholamine release rather than adrenal.

Telemedicine for Delivery of Care in Frontotemporal Lobar Degeneration During COVID-19 Pandemic: Results from Southern Italy.

BACKGROUND: The COVID-19 pandemic is changing clinical practice in neurology, after the governments decided the introduction of social distancing and interruption of medical non-emergency services in many countries. Teleneurology is an effective tool for the remote evaluation of patients but its adoption for frontotemporal lobar dementia (FTD) is in a preliminary stage. OBJECTIVE: We evaluated multidisciplinary assessment of patients with FTD using telehealth during the COVID-19 pandemic. METHODS: All patients received a diagnosis of FTD during 2018-2019 according to international criteria. A structured questionnaire and Clinical Dementia Rating Scale (CDR)-FTD were used by the neurologist with patients and/or caregivers. Index symptoms of COVID-19 infection were searched. RESULTS: Twenty-eight clinical interviews were completed with caregivers and four with both patients/caregivers. Most patients and caregivers were satisfied with the neurological interview and expressed their willingness to continue to be included in remote evaluation programs (90%). Fifty percent of patients experienced significant worsening of clinical picture and quality of life since the start of social distancing. The CDR-FTD scale revealed a significant worsening of behavior (p = 0.01) and language functions (p = 0.009), compared to the last in-person evaluation at the center. One patient presented index symptoms of COVID-19 infection and was confirmed to be positive for COVID-19 with pharyngeal swab. CONCLUSION: The study was conducted in Italy, one of the countries hit particularly hard by the COVID-19 pandemic, with interruption of all non-emergency medical services. Our study indicates that telemedicine is a valid tool to triage patients with FTD to increase practice outreach and efficiency.

Telemedicine is a useful tool to deliver care to patients with Amyotrophic Lateral Sclerosis during COVID-19 pandemic: results from Southern Italy.

BACKGROUND: Teleneurology is an effective tool for the rapid evaluation of patients in remote locations with a well-established use in stroke and epilepsy. To date its adoption for Amyotrophic Lateral Sclerosis (ALS) care is still in a preliminary stage. We evaluated the feasibility of multidisciplinary assessment of patients with ALS, using telememedicine during the emergency determined by the COVID-19 pandemic. Methods: All patients included in this survey had received a diagnosis of ALS according to international criteria after a complete clinical and paraclinical assessment during 2019. A structured questionnaire was used by the neurologist with the patient or the caregiver. A video interaction was offered but refused by all patients because they did not feel comfortable or did not have smartphone. Results: Out of 31 clinical interviews 8 were completed directly with the patients and 23 with patients' caregivers. In a successive survey, most of patients were satisfied with the neurological interview (85%), the possibility to interact directly with the clinician being at home (85%) and reduction of economic and time costs because they avoided unnecessary travel to the clinic. Most of subjects expressed their willingness to continue to be included in remote evaluation programs (90%). Notably, none of the patients presented index symptoms of Covid-19 infection. Conclusion: Our study indicates that telemedicine is a valid tool to triage patients with ALS to increase practice outreach and efficiency. Delivery of care via telemedicine was effective and successful in people with ALS in the dramatic and sudden crisis determined by Covid-19 outbreak.

Right Ventricular Function in Chronic Heart Failure: From the Diagnosis to the Therapeutic Approach.

There is growing attention for the study of the right ventricle in cardiovascular disease and in particular in heart failure. In this clinical setting, right ventricle dysfunction is a significant marker of poor prognosis, regardless of the degree of left ventricular dysfunction. Novel echocardiographic methods allow for obtaining a more complete evaluation of the right ventricle anatomy and function as well as of the related abnormalities in filling pressures. Specific and effective therapies for the right ventricle dysfunction are still not well defined and this represents the most difficult and important challenge. This article focuses on available diagnostic techniques for studying right ventricle dysfunction as well as on the therapies for right ventricle dysfunction.

Incidence of frontotemporal lobar degeneration in Italy: The Salento-Brescia Registry study.

OBJECTIVE: The goal of the present work, based on a collaborative research registry in Italy (the Salento-Brescia Registry), was to assess the incidence of frontotemporal lobar degeneration (FTLD) and to define the frequencies of different FTLD phenotypes in the general population. METHODS: The study was conducted from January 1, 2017, to December 31, 2017, in 2 Italian provinces: Lecce (in Puglia) in the south (area 2,799.07 km2, inhabitants 802,082) and Brescia (in Lombardy) in the north (area 4,785.62 km2, inhabitants 1,262,678). During the study period, all new cases of FTLD (incident FTLD) were counted, and all patients' records were reviewed. The incidence was standardized to the Italian general population in 2017. RESULTS: In the 2 provinces, 63 patients with FTLD were diagnosed. The incidence rate for FTLD was 3.05 (95% confidence interval [CI] 2.34-3.90) per 100,000 person-years (py), while the age-sex standardized incidence rate was 3.09 (95% CI 2.95-3.23) per 100,000 py. In the Italian population, the lifetime risk was 1:400. There was a progressive increase in FTLD incidence across age groups, reaching its peak in the 75- to 79-year-old group, with an incidence rate of 15.97 (95% CI 8.94-26.33) per 100,000 py. The behavioral variant of frontotemporal dementia was the most common phenotype (37%). No difference in crude incidence rate between the 2 provinces was observed. CONCLUSION: FTLD is a more common form of dementia than previously recognized, with a risk spanning in a wide age range and with maximum incidence in the mid-70s. Improved knowledge of FTLD epidemiology will help to provide appropriate public health service policies.

Comparative evaluation of two immunoassays for cerebrospinal fluid ß-Amyloid1-42 measurement.

AIM OF THE STUDY: Beta-Amyloid 1-42 peptide (ßA42) is a cerebro-spinal fluid (CSF) biomarker, key element of the NIA Alzheimer's disease diagnostic criteria. The enzyme-linked immunosorbent assay (ELISA) has been the mainstay method for ßA42 measurement on cerebrospinal fluid (CSF). Recently, a new ßA42 measurement method in chemiluminescence enzyme immunoassay (CLEIA) is available on Lumipulse G 600 II automatic platform. The aim of the work was to evaluate the concordance of the ELISA and the new method (CLEIA) in the CSF ßA42 levels measurement. MATERIALS AND METHODS: CSF ßA42 levels were assayed in 49 samples using the ELISA method (Innotest ß- amyloid 1-42, Fujirebio Europe N.V., Gent, Belgium) and CLEIA method on Lumipulse G600II fully automatic platform (Lumipulse G ß- amyloid 1-42, Fujirebio Europe N.V., Gent, Belgium). We compared values of the two methods using acceptability interval based on Inherent Combined Imprecision (ICI), the Passing-Bablok regression analysis, the Pearson correlation coefficient (r) and the Bland-Altman plot. RESULTS: The analysis of the ICI showed that the two methods differ substantially. The regression equation (y = -103.04 + 1.52×) highlighted the presence of proportional systematic difference, without significant deviation from linearity (p = .42). The Pearson correlation coefficient was 0.826. The Bland-Altman plot analysis showed a significant systematic difference in the two methods: ELISA measurements were in average -27.06% (95% CI -31.89 to -22.23%) lower compared to CLEIA ones. CONCLUSIONS: Our study highlighted a difference between the two methods. Therefore, the cut-off for the normal levels of ßA42 should be reviewed in the laboratory report.

Plasma ß-amyloid1-42 reference values in cognitively normal subjects.

BACKGROUND: In clinical practice, the use of plasma ß-Amyloid1-42 (Aß1-42) as biomarker for Alzheimer's disease is largely limited by the absence of reference values. The aim of this study was to evaluate Aß1-42 plasma concentrations in cognitively normal subjects and to propose reference values. METHODS: Plasma samples were obtained from 245 subjects, with a wide age-range (19-89 years), enrolled at the Unit of Laboratory Medicine of the "Azienda Ospedaliera Cardinale G. Panico" (younger subjects) and from a population-based study on aging (GreatAGE study) (older subjects). Three different age-groups were established: young (≤ 34), adult (35 ≤ age ≤ 64) and old (>64). The Innogenetics Elisa kit for plasma Aß1-42 was used for the analysis. RESULTS: The mean (SD) concentration of plasma Aß1-42 was 17.65 (5.71) pg/mL. A positive trend was found in Aß1-42 levels across the three age groups (p < .0001): young subjects showed values of Aß1-42 significantly lower than the adult group (p < .0001) and than the old one (p < .0001 overall); no significant differences were found between the adult and the old groups (p = 1.0000). For the entire cohort the lower limit of 90% Reference Interval, double-sided, was 8.12 pg/mL (95% CI 6.77-9.45) and the upper limit was 29.00 pg/mL (95% CI 27.01-31.00). CONCLUSION: The present study proposes reference values for plasma Aß1-42. Nevertheless, further studies are needed to confirm these results and corroborate the use of these reference values in clinical practice.