Phenotypic and genetic characterization of a family carrying two Xq21.1-21.3 interstitial deletions associated with syndromic hearing loss

Sensorineural hearing impairment is a common pathological manifestation in patients affected by X-linked intellectual disability. A few cases of interstitial deletions at Xq21 with several different phenotypic characteristics have been described, but to date, a complete molecular characterization of the deletions harboring disease-causing genes is still missing. Thus, the aim of this study is to realize a detailed clinical and molecular analysis of a family affected by syndromic X-linked hearing loss with intellectual disability

Aging in multiple sclerosis: from childhood to old age, etiopathogenesis, and unmet needs: a narrative review

Multiple sclerosis (MS) primarily affects adult females. However, in the last decades, rising incidence and prevalence have been observed for demographic extremes, such as pediatric-onset MS (POMS; occurring before 18 years of age) and late-onset MS (corresponding to an onset above 50 years). These categories show peculiar clinical-pathogenetic characteristics, aging processes and disease courses, therapeutic options, and unmet needs. Nonetheless, several open questions are still pending. POMS patients display an important contribution of multiple genetic and environmental factors such as EBV, while in LOMS, hormonal changes and pollution may represent disease triggers. In both categories, immunosenescence emerges as a pathogenic driver of the disease, particularly for LOMS. In both populations, patient and caregiver engagement are essential from the diagnosis communication to early treatment of disease-modifying therapy (DMTs), which in the elderly population appears more complex and less proven in terms of efficacy and safety. Digital technologies (e.g., exergames and e-training) have recently emerged with promising results, particularly in treating and following motor and cognitive deficits. However, this offer seems more feasible for POMS, being LOMS less familiar with digital technology. In this narrative review, we discuss how the aging process influences the pathogenesis, disease course, and therapeutic options of both POMS and LOMS. Finally, we evaluate the impact of new digital communication tools, which greatly interest the current and future management of POMS and LOMS patients

Circulating miRNA-195-5p and -451a in Patients with Acute Hemorrhagic Stroke in Emergency Department

(1) Background: In our previous study, acute ischemic stroke (AIS) patients showed increased levels of circulating miRNAs (-195-5p and -451a) involved in vascular endothelial growth factor A (VEGF-A) regulation. Here, we evaluated, for the first time, both circulating miRNAs in acute intracerebral hemorrhagic (ICH) patients. (2) Methods: Circulating miRNAs and serum VEGF-A were assessed by real-time PCR and ELISA in 20 acute ICH, 21 AIS patients, and 21 controls. These were evaluated at hospital admission (T0) and after 96 h (T96) from admission. (3) Results: At T0, circulating miRNAs were five-times up-regulated in AIS patients, tending to decrease at T96. By contrast, in the acute ICH group, circulating miRNAs were significantly increased at both T0 and T96. Moreover, a significant decrease was observed in serum VEGF-A levels at T0 in AIS patients, tending to increase at T96. Conversely, in acute ICH patients, the levels of VEGF-A were significantly decreased at both T0 and T96. (4) Conclusions: The absence of a reduction in circulating miRNAs (195-5p and -451a), reported in acute ICH subjects after 96 h from hospital admission, together with the absence of increment of serum VEGF-A, may represent useful biomarkers indicating the severe brain damage status that characterizes acute ICH patients

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Aging in multiple sclerosis: from childhood to old age, etiopathogenesis, and unmet needs: a narrative review

Multiple sclerosis (MS) primarily affects adult females. However, in the last decades, rising incidence and prevalence have been observed for demographic extremes, such as pediatric-onset MS (POMS; occurring before 18 years of age) and late-onset MS (corresponding to an onset above 50 years). These categories show peculiar clinical-pathogenetic characteristics, aging processes and disease courses, therapeutic options, and unmet needs. Nonetheless, several open questions are still pending. POMS patients display an important contribution of multiple genetic and environmental factors such as EBV, while in LOMS, hormonal changes and pollution may represent disease triggers. In both categories, immunosenescence emerges as a pathogenic driver of the disease, particularly for LOMS. In both populations, patient and caregiver engagement are essential from the diagnosis communication to early treatment of disease-modifying therapy (DMTs), which in the elderly population appears more complex and less proven in terms of efficacy and safety. Digital technologies (e.g., exergames and e-training) have recently emerged with promising results, particularly in treating and following motor and cognitive deficits. However, this offer seems more feasible for POMS, being LOMS less familiar with digital technology. In this narrative review, we discuss how the aging process influences the pathogenesis, disease course, and therapeutic options of both POMS and LOMS. Finally, we evaluate the impact of new digital communication tools, which greatly interest the current and future management of POMS and LOMS patients

Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis

Background & Aims: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. Methods: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. Results: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99–1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04–1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. Conclusions: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. Impact and implications: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis

Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis

Background & aims: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. Methods: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. Results: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. Conclusions: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. Impact and implications: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis