Real life experience on the use of Remdesivir in patients admitted to COVID-19 in two referral Italian hospital: a propensity score matched analysis.

Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p < 0.0001). Moreover, the patients taking Remdesivir were less frequently vaccinated against COVID-19. All the other clinical, radiological, and pharmacological parameters were balanced between the two groups. The use of Remdesivir in our cohort was associated with a significantly lower risk of mortality during the follow-up period (HR 0.56; 95% CI 0.37-0.86; p = 0.007). Moreover, RDV was associated with a significantly lower incidence of non-invasive ventilation (OR 0.27; 95% CI 0.20-0.36). Furthermore, in the 365 patients taking Remdesivir, we observed two cases of mild renal failure requiring a reduction in the dosage of Remdesivir and two cases in which the physicians decided to interrupt Remdesivir for bradycardia and for QT elongation. Our study suggests that the use of Remdesivir in hospitalized COVID-19 patients is a safe therapy associated with improved clinical outcomes, including halving of mortality and with a reduction of around 75% of the risk of invasive ventilation. In a constantly changing COVID-19 scenario, ongoing research is necessary to tailor treatment decisions based on the latest scientific evidence and optimize patient outcomes.

Markers for the detection of Lewy body disease versus Alzheimer's disease in mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Mild cognitive impairment (MCI) may evolve into dementia. Early recognition of possible evolution to Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) is of importance, but actual diagnostic criteria have some limitations. In this systematic review and meta-analysis, we aimed to find the most accurate markers that can discriminate patients with DLB versus AD, in MCI stage. METHODS: We searched several databases up to 17 August 2023 including studies comparing markers that may distinguish DLB-MCI from AD-MCI. We reported data regarding sensitivity, specificity, and the area under the curves (AUCs) with their 95% confidence intervals (CIs). RESULTS: Among 2219 articles initially screened, eight case-control studies and one cohort study were included for a total of 832 outpatients with MCI. The accuracy of cerebrospinal fluid (CSF) markers was the highest among the markers considered (AUC > 0.90 for the CSF markers), with the AUC of CSF Aß42/Aß40 of 0.94. The accuracy for clinical symptom scales was very good (AUC = 0.93), as evaluated in three studies. Although limited to one study, the accuracy of FDG-PET (cingulate island sign ratio) was very good (AUC = 0.95) in discriminating DLB from AD in MCI, while the accuracy of SPECT markers and EEG frequencies was variable. CONCLUSIONS: Few studies have assessed the accuracy of biomarkers and clinical tools to distinguish DLB from AD at the MCI stage. While results are promising for CSF markers, FDG-PET and clinical symptoms scales, more studies, particularly with a prospective design, are needed to evaluate their accuracy and clinical usefulness. CLINICAL TRIAL REGISTRATION: Prospero (CRD42023422600).

Sarcopenia using muscle mass prediction model and cognitive impairment: A longitudinal analysis from the English longitudinal study on ageing.

BACKGROUND: Literature on the association between sarcopenia and cognitive impairment is largely unclear and mainly limited to non-European populations. Therefore, the aim of this study is to explore if the presence of sarcopenia at the baseline could increase the risk of cognitive impairment in a large cohort of older people participating to the English Longitudinal Study of Ageing (ELSA), over ten years of follow-up. METHODS: Sarcopenia was diagnosed as having low handgrip strength and low skeletal muscle mass index at the baseline, using a muscle mass prediction model; cognitive function was evaluated in the ELSA through several tests. The results are reported in the whole sample adjusted for potential baseline confounders and after matching sarcopenic and non-sarcopenic participants with a propensity score. RESULTS: 2738 people (mean age: 68.7 years, 54.4% males) were included. During the ten years of follow-up, sarcopenia was associated with significantly lower scores in memory (p < 0.001), verbal fluency (p < 0.001), immediate word recall (p <0.001), delayed word recall (p = 0.018), and in recall summary score (p < 0.001). After adjusting for eight potential confounders, the presence of sarcopenia was significantly associated with poor verbal fluency (odds ratio, OR= 1.417, 95% confidence intervals, CI= 1.181-1.700) and in propensity-score matched analyses (OR=1.272, 95%CI= 1.071- 1.511). CONCLUSIONS AND IMPLICATIONS: Sarcopenia was found to be associated with a significantly higher incidence of poor cognitive status in a large population of elderly people followed up for 10 years, suggesting it may be an important potential risk factor for dementia.

Multimorbidity increases the risk of dementia: a 15 year follow-up of the SHARE study.

AIMS: the literature regarding the association between multimorbidity and dementia is still unclear. Therefore, we aimed to explore the potential association between multimorbidity at the baseline and the risk of future dementia in the SHARE (Survey of Health, Ageing and Retirement in Europe) study, a large European research survey, with a follow-up of 15 years. METHODS: in this longitudinal study, multimorbidity was defined as the presence of two or more chronic medical conditions, among 14 self-reported at the baseline evaluation. Incident dementia was ascertained using self-reported information. Cox regression analysis, adjusted for potential confounders, was run and hazard ratios (HRs), with their 95% confidence intervals (CIs), that were estimated in the whole sample and by 5 year groups. RESULTS: among 30,419 participants initially considered in wave 1, the 23,196 included participants had a mean age of 64.3 years. The prevalence of multimorbidity at baseline was 36.1%. Multimorbidity at baseline significantly increased the risk of dementia in the overall sample (HR = 1.14; 95% CI: 1.03-1.27) and in participants younger than 55 years (HR = 2.06; 95% CI: 1.12-3.79), in those between 60 and 65 years (HR = 1.66; 95% CI: 1.16-2.37) and in those between 65 and 70 years (HR = 1.54; 95% CI: 1.19-2.00). In the overall sample, high cholesterol levels, stroke, diabetes and osteoporosis increased the risk of dementia, particularly if present among participants between 60 and 70 years of age. CONCLUSIONS: multimorbidity significantly increases the risk of dementia, particularly in younger people, indicating the need for early detection of multimorbidity for preventing cognitive worsening.

Suicide risk in caregivers of people with dementia: a systematic review and meta-analysis.

BACKGROUND: Interest in physical and mental health outcomes in caregivers of patients with dementia is increasing. However, there is limited data available on the prevalence of suicidal ideation, suicidal attempts, and suicide rates among caregivers of those with dementia. Therefore, we aimed to systematically review these outcomes to address this gap in the literature and thus provide information to inform future policy and intervention for the benefit of caregivers of dementia patients. METHODS: We searched several databases from inception to the 10th November 2021, for studies investigating suicidal ideation, suicidal attempts, and suicide rates of caregivers of patients with dementia. We report data regarding suicidal ideation as prevalence, with the 95% confidence intervals (CIs), applying a random-effect model; since less than three studies were available for suicide attempt and suicide, these data are reported descriptively. RESULTS: Among 194 articles, eight comprising 1,209 informal caregivers of people with dementia (mean age: 63.9 years, 74% females) were included. The prevalence of suicide ideation was 32.32% (95% CI: 16.01-48.64%; I2 = 98.5%, p < 0.0001). The prevalence of suicide ideation varied between studies from 4.69% to 77.78%. Two studies reported the rate of suicidal attempt in caregivers of patients with dementia, with the prevalence ranging from 5.9% to 16.1%. One study reported one in 17 caregivers of patients with dementia died by suicide. CONCLUSIONS: The prevalence of suicide ideation is high, affecting several caregivers of patients with dementia. These findings suggest intervention and/or policy are urgently needed to address suicidal behavior in this at-risk population.

Effect of COVID-19 quarantine on cognitive, functional and neuropsychiatric symptoms in patients with mild cognitive impairment and dementia.

BACKGROUND: During the last two years, COVID-19 affected older people with dementia or mild cognitive impairment (MCI), but conflicting and sparse results are still present. The objective of this study was to investigate the frequency and type of changes in functional, cognitive and behavioral and psychological symptoms of dementia (BPSD), and caregiver's stress during the period of quarantine in 2020 in patients affected by dementia/MCI living in Palermo, Sicily. METHODS: Outpatients affected by MCI/dementia were evaluated before and after COVID-19 quarantine. Functional status was investigated using basic and instrumental activities of daily living (ADL); cognitive performance with the mini-mental state examination; BPSD through the neuropsychiatric inventory (NPI). All scales were reported as pre/post-COVID-19 quarantine and a logistic regression analysis was performed for investigating the factors associated with worsening in NPI in patients and their caregivers. RESULTS: One hundred patients (mean age 77.1; females = 59%) were evaluated over a median of 10 months. In the sample as whole, a significant decline in functional and cognitive status was observed (p < 0.001 for both comparisons). The NPI significantly increased by 3.56 ± 8.96 points after the COVID-19 quarantine (p < 0.0001), while the caregivers' stress increased by 1.39 ± 3.46 points between the two evaluations (p < 0.0001). The decline was more evident in people with milder dementia. Higher values of instrumental ADL at baseline were associated with a significant lower worsening in NPI and caregiver's stress. CONCLUSIONS: COVID-19 quarantine negatively affected functional, cognitive, and neuropsychiatric symptoms in older people affected by dementia/MCI, highlighting the impact of COVID-19 quarantine for this population.

Nutrition, Physical Activity, and Other Lifestyle Factors in the Prevention of Cognitive Decline and Dementia.

Multiple factors combined are currently recognized as contributors to cognitive decline. The main independent risk factor for cognitive impairment and dementia is advanced age followed by other determinants such as genetic, socioeconomic, and environmental factors, including nutrition and physical activity. In the next decades, a rise in dementia cases is expected due largely to the aging of the world population. There are no hitherto effective pharmaceutical therapies to treat age-associated cognitive impairment and dementia, which underscores the crucial role of prevention. A relationship among diet, physical activity, and other lifestyle factors with cognitive function has been intensively studied with mounting evidence supporting the role of these determinants in the development of cognitive decline and dementia, which is a chief cause of disability globally. Several dietary patterns, foods, and nutrients have been investigated in this regard, with some encouraging and other disappointing results. This review presents the current evidence for the effects of dietary patterns, dietary components, some supplements, physical activity, sleep patterns, and social engagement on the prevention or delay of the onset of age-related cognitive decline and dementia.

Verbal Fluency in Mild Alzheimer's Disease: Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex.

BACKGROUND: Recent studies showed that in healthy controls and in aphasic patients, inhibitory trains of repetitive transcranial magnetic stimulation (rTMS) over the right prefrontal cortex can improve phonemic fluency performance, while anodal transcranial direct current stimulation (tDCS) over the left prefrontal cortex can improve performance in naming and semantic fluency tasks. OBJECTIVE: This study aimed at investigating the effects of cathodal tDCS over the left or the right dorsolateral prefrontal cortex (DLPFC) on verbal fluency tasks (VFT) in patients with mild Alzheimer's disease (AD). METHODS: Forty mild AD patients participated in the study (mean age 73.17±5.61 years). All participants underwent cognitive baseline tasks and a VFT twice. Twenty patients randomly received cathodal tDCS to the left or the right DLPFC, and twenty patients were assigned to a control group in which only the two measures of VFT were taken, without the administration of the tDCS. RESULTS: A significant improvement of performance on the VFT in AD patients was present after tDCS over the right DLPFC (p = 0.001). Instead, no difference was detected between the two VFTs sessions after tDCS over the left DLPFC (p = 0.42). Furthermore, these results cannot be related to task learning effects, since no significant difference was found between the two VFT sessions in the control group (p = 0.73). CONCLUSION: These data suggest that tDCS over DLPFC can improve VFT performance in AD patients. A hypothesis is that tDCS enhances adaptive patterns of brain activity between functionally connected areas.

Benign and malignant mimickers of infiltrative hepatocellular carcinoma: tips and tricks for differential diagnosis on CT and MRI.

Hepatocellular carcinoma (HCC) may have an infiltrative appearance in about 8-20% of cases. Infiltrative HCC can be a challenging diagnosis and it is associated with the worst overall survival among HCC patients. Infiltrative HCC is characterized by the spread of multiple minute nodules throughout the liver, without a dominant one, ultimately resulting into macrovascular invasion. On CT and MRI, infiltrative HCC appears as an ill-defined, large mass, with variable degree of enhancement, and satellite neoplastic nodules in up to 52% of patients. On MRI, it may show restriction on diffusion weighted imaging, hyperintensity on T2- and hypointensity on T1-weighted images, and, if hepatobiliary agent is used, hypointensity on hepatobiliary phase. Infiltrative HCC must be differentiated from other liver diseases, such as focal confluent fibrosis, steatosis, amyloidosis, vascular disorders of the liver, cholangiocarcinoma, and diffuse metastatic disease. In cirrhotic patients, the identification of vascular tumor invasion of the portal vein and its differentiation from bland thrombosis is of utmost importance for patient management. On contrast enhanced CT and MRI, portal vein tumor thrombosis appears as an enhancing thrombus within the portal vein, close to the main tumor and results into vein enlargement. The aim of this pictorial review is to show CT and MRI features that allow the diagnosis of infiltrative HCC and portal vein tumor thrombosis. A particular point of interest includes the tips and tricks for differential diagnosis with potential mimickers of infiltrative HCC.

Three-dimensional (3D) versus two-dimensional (2D) laparoscopic adrenalectomy: A case-control study.

INTRODUCTION: Laparoscopic adrenalectomy is today considered the gold standard of treatment for adrenal tumors. The development of high definition cameras does not eliminate the major limitation of two-dimensional (2D) laparoscopy: lack of depth perception and loss of spatial orientation. Tree-dimensional (3D) HD laparoscopy was developed as an alternative to conventional 2D laparoscopy. METHODS: We report our experience with use of 3D vision system for laparoscopic adrenalectomy. Between January 2009 and March 2015 we performed a total of 52 laparoscopic adrenalectomies. In this case-control study we considered 13 laparoscopic adrenalectomies performed with three-dimensional (3D) vision system as case group. The last 26 procedures made with two-dimensional (2D) HD laparoscopic system represented the control group. We considered primary end-points: operative time, intraoperative complications and conversion rate. We evaluated also quality of depth perception and surgical strain. RESULTS: Although the operative time for the entire surgical procedure was shorter in 3D group, there were no significant differences. The surgeon experienced better depth perception with 3D system and subjectively reported less strain using 3D vision system. Residents and medical students confirmed these data on surgical outcome. CONCLUSION: 3D system vision does not seem to influence the operative time of laparoscopic adrenalectomy performed by experienced surgeon because the surgical technique request simple tasks. We obtain the better visualization in depth perception with effect on surgical precision. Comparative studies are necessary to verify if 3D can reduce perioperative complication with similar operative time.

Azithromycin in an older woman with diabetic gastroparesis.

Diabetic neuropathy is a common chronic complication of diabetes and cause of significant morbidity and mortality, because it may involve the autonomous and peripheral nervous systems. Autonomic diabetic neuropathy is a challenging chronic complication of long-standing diabetes manifested with hypotension, syncope, gastroparesis, diarrhea, constipation, bladder dysfunction, sexual dysfunction, cardiac arrest, and/or sudden death. We present a case of diabetic gastroparesis in an older woman. The patient was an 83-year-old woman with a 40-year history of type 2 diabetes who was admitted with hypoglycemia, malnutrition, persistent vomiting, and obstinate constipation. After several unsuccessful attempts with different therapies, we administered intravenous azithromycin (500 mg/day). After 3 days of treatment, vomiting was resolved and the patient evacuated normal feces, with notable improvement in the general conditions and metabolic control. Because diabetic gastroparesis frequently is difficult to manage clinically and there are few beneficial therapeutic choices available at present, the macrolide antibiotic azithromycin, which has strong prokinetic properties, may be a useful option in the treatment of this complex condition.

Blood pressure and cardiovascular risk profiles of Africans who migrate to a Western country.

OBJECTIVES: Africans who live in Western countries have a higher prevalence of hypertension and other cardiovascular risk factors than do age-matched Africans who live in Africa. We conducted a community survey to evaluate cardiovascular risk in Africans who recently migrated to Italy. METHODS: Participants (N=83) from sub-Saharan Africa were recruited from an outpatient clinic for immigrants. Information on immigration date, family history of cardiovascular disease, physical activity, and smoking was obtained for all participants. Anthropometric parameters, blood pressure measurements, and laboratory analyses--including lipid profiles, plasma glucose, renal function, and serum and urinary electrolytes--were performed. RESULTS: Although participants who had recently arrived in Italy had a low cardiovascular risk, the correlations were significant between the length of time in Italy and body weight (r=.47, P<.001), body mass index (r=.59, P<.0001), waist circumference (r=.54, P<.0001), total cholesterol (r=.41, P<.001), low-density lipoprotein cholesterol (r=.46, P<.0001), systolic blood pressure (r=.31, P<.01), and diastolic blood pressure (r=.23, P<.05). The rise in systolic and diastolic blood pressure was positively correlated with body weight, body mass index, and waist circumference (P<.05 for all) and inversely correlated with 24-hour urinary potassium (systolic blood pressure, r=-.35, P<.01; diastolic blood pressure, r=-.42, P<.0001). CONCLUSIONS: The length of residence in Italy is associated with progressive modifications in cardiovascular risk even in a relatively short period of time. The inverse correlation between blood pressure and urinary potassium may reflect dietary changes, with a possible reduction in fruit and vegetable consumption compared with their original diet.

[Current therapeutic approach in patients with Alzheimer disease]. / Attuale approccio terapeutico ai pazienti con malattia di Alzheimer.

Even if a complete recovery is not an available outcome for Alzheimer disease, it is possibile to improve the clinical symptoms (selfsufficiency, cognitive impairment and behavioral disturbances) with pharmacological and non-pharmacological therapies. The treatment of the patient with dementia is a complex one, that cannot rely only on the use of drugs but needs of a global approach that take into account all the different aspect of the disease. The most used drugs are the cholinesterase inhibitors that have been shown to stabilize or slow down cognitive and functional decline and retard institutionalization, but new treatments are on the way. Extremely important is a strong alliance with the family. Non pharmacological cognitive rehabilitation techniques are also useful in potentiating residual cognitive functions in the patient and in supporting the family and the caregivers.

Medium-term effects of bisoprolol administration on renal hemodynamics and function in mild to moderate essential hypertension.

Arterial hypertension is a significant cause of end-stage renal failure; effective treatment of hypertensive patients reduces the rate of progression of this disorder. ss-Blockers, particularly nonselective agents, are associated with deterioration of renal function in patients with chronic renal failure. Previous studies on the interaction of the beta1-selective adrenergic antagonist bisoprolol with kidney function have been performed only acutely and over the short term. This study was designed to evaluate the antihypertensive efficacy and effects on renal hemodynamics and function of bisoprolol during medium-term (6 mo) treatment of patients with mild to moderate essential hypertension. After a 2-wk run-in period on placebo, 87 consecutive hypertensive patients (46 men, 41 women) according to ESH-ESC (European Society of Hypertension/European Society of Cardiology) guidelines, aged from 27 to 64 y (mean age, 50+/-11 y), without renal or cardiovascular disease, were enrolled and assigned to treatment with bisoprolol 5 mg once daily for 6 mo. At recruitment and at 6 mo after treatment, renal function was assessed and renal hemodynamics evaluated in all patients through radioisotope studies. The medium-term effects of bisoprolol included a significant reduction in blood pressure and heart rate (P<.001) without significant adverse drug reactions. Moreover, bisoprolol produced no alteration in renal function or hemodynamics, or in cardiac output. Data presented here indicate that bisoprolol 5 mg given once daily to treat patients with mild to moderate essential hypertension is effective and safe for treatment and for preservation of renal performance when given on a medium-term basis.