Description and preliminary experience with Virtual Visit Assessment (ViVA) during the COVID-19 pandemic, a structured virtual management protocol for patients with multiple sclerosis.

In people with multiple sclerosis (PwMS), strict follow-up is essential. Telemedicine has the potential to overcome many of the difficulties in routine management. Herein, we present a structured protocol that can be used to remotely manage patients with MS, describing in detail the steps to be taken and exams needed at each stage. A working group was established which developed a tailored protocol that can be adapted to a variety of settings. The overall protocol consisted of 5 phases: enrolment, document sharing phase, pre-evaluation, virtual visit, and post-visit phase, which was divided into 14 individual steps. As of October 2020, 25 virtual visits have been carried out, all via Skype. The patient's caregiver was present during visits and had an active role. The average duration of the virtual visit was 24 min, and that of the pre-visit and post-visit were around 15 min each. Overall satisfaction as rated by physicians was considered high (8.0 ± 0.5). Using the system usability scale (SUS), patients also favorably rated the virtual visit (96.6 ± 6.1). In 20% of cases, the virtual visit was not sufficient to provide adequate information and an in-person clinical visit was recommended. The described protocol has the potential to provide benefits for the healthcare system as well as patients and their caregivers both during and beyond COVID-19 pandemic.

Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis investigating the influence of acetylcholinesterase inhibitors (AChEIs) therapy on nutritional status and weight across observational and interventional studies. Two authors searched major electronic databases from inception until 10/14/2015 for longitudinal, open-label and randomised double-blind placebo controlled (randomised controlled trials (RCTs)) studies of AChEIs in patients with dementia reporting nutritional status outcome data. Out of 3551 initial hits, 25 studies (12 open-label trials, 9 RCTs and 4 longitudinal studies) including 10 792 patients with dementia were meta-analysed. In longitudinal studies (median follow-up 6 months), a significant cumulative incidence of weight loss between baseline and follow-up evaluation was observed (studies=2; 5%; 95% CI 1% to 34%, p<0.0001; I2=95%). These findings were confirmed in open-label trials (6%; 95% CI 4% to 7%, p<0.0001; I2=78%). In 9 RCTs (median follow-up 5 months), those taking AChEIs more frequently experienced weight loss than participants taking placebo (OR=2.18; 95% CI 1.50 to 3.17, p<0.0001; I2=29%). AChEIs therapy contributes to weight loss in patients with dementia, with a 2-fold increased risk observed in the meta-analysis of RCTs. Clinicians should carefully consider the benefit and risk of prescribing AChEIs. Nutritional status should be routinely evaluated in patients with dementia treated with AChEIs.

Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients.

OBJECTIVE: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). METHODS: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. RESULTS: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. CONCLUSIONS: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients.

The Pamela study: main findings and perspectives.

PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) is an epidemiological study, originally designed to determine the normality of home and ambulatory blood pressure values. The study was performed on 3,200 subjects, aged 25 to 74 years, randomly selected from the general population of Monza (Milan, Italy). In the study context we performed clinical, home and ambulatory blood pressure measurements, echocardiographic assessment of cardiac structure and function as well as laboratory examinations (glucose and lipids). Personal and family histories were collected. The same procedures were repeated 10 years later. During a 12-year follow-up, the incident cardiovascular events were validated. Cardiovascular and all-cause fatal events were collected for a 16-year follow-up. This article will review the main results of the PAMELA study, with particular emphasis on (1) the prognostic value of the different blood pressure measurements, (2) the relationships between metabolic variables and blood pressure and (3) the clinical relevance and prognostic importance of left ventricular mass values and alterations.

Assessment of 2021/22 influenza epidemic scenarios in Italy during SARS-CoV-2 outbreak.

Global mitigation strategies to tackle the threat posed by SARS-CoV-2 have produced a significant decrease of the severity of 2020/21 seasonal influenza, which might result in a reduced population natural immunity for the upcoming 2021/22 influenza season. To predict the spread of influenza virus in Italy and the impact of prevention and control measures, we present an age-structured Susceptible-Exposed-Infectious-Removed (SEIR) model including the role of social mixing patterns and the impact of age-stratified vaccination strategies and Non-Pharmaceutical Interventions (NPIs) such as school closures, partial lockdown, as well as the adoption of personal protective equipment and the practice of hand hygiene. We find that vaccination campaigns with standard coverage would produce a remarkable mitigation of the spread of the disease in moderate influenza seasons, making the adoption of NPIs unnecessary. However, in case of severe seasonal epidemics, a standard vaccination coverage would not be sufficiently effective in fighting the epidemic, thus implying that a combination with the adoption of NPIs is necessary to contain the disease. Alternatively, our results show that the enhancement of the vaccination coverage would reduce the need to adopt NPIs, thus limiting the economic and social impacts that NPIs might produce. Our results highlight the need to respond to the influenza epidemic by strengthening the vaccination coverage.

Parkinson-like features in ALS with predominant upper motor neuron involvement.

Owing to the frequent observation of poverty of movements, facial hypomimia and balance impairment, amyotrophic lateral sclerosis (ALS) variant with predominance of upper motor neuron involvement (UMN-ALS) is prone to be diagnosed with Parkinsonism. A clinical assessment, including the velocity-dependent stretch response test to differentiate between pyramidal and extrapyramidal stiffness; the Unified Parkinson's Disease Rating Scale and the Berg Balance Scale to assess degree of bradykinesia and postural instability; and (123)I-FP-CIT scintigraphy evaluation to investigate the nigrostriatal circuit involvement, were carried out to characterize Parkinson-like features in UMN-ALS patients. Sixteen UMN-ALS patients were included in the study. The velocity-dependent stretch response indicated spasticity in all the muscles tested. The degree of stiffness was found to be related to bradykinesia and postural instability. Eleven patients (70%) showed a reduction in striatal (123)I-FP-CIT uptake found to be related to disease duration and patients' ages but not to scores of the functional scales. Slowness of movements and postural instability noted in our patients could be mostly attributed to spasticity. The lack of any correlation between UPDRS or BBS scores and the degree of nigrostriatal impairment on DaTSCAN seems to disprove nigrostriatal circuit involvement in these extrapyramidal-like features.

Telemedicine monitoring in the follow-up of kidney transplant recipients: consensus indications from an Italian panel of surgeons and nephrologists after the COVID-19 experience.

The quality of follow-up has clearly emerged as a key factor for long-term kidney graft survival. Currently, many clinics are facing difficulties in delivering optimal surveillance because of the increased number and complexity of kidney transplant recipients, and because of the COVID-19 pandemic. Additional ways of performing follow-up visits are needed and telemedicine has emerged as a tool to strengthen patient care intensity. Six Italian transplant surgeons and nephrologists convened via teleconference to develop a consensual model of video visits for the follow-up of kidney transplant recipients. Issues discussed were: profile of eligible patients; assessments that can be carried out; video visit organization and medical professionals involved; supporting tools and implementation. The video visit was consensually recognized as the most relevant for the follow-up of kidney transplant recipients. Eligible patients should have basic electronic devices and the skills to correctly use them and be in clinically stable condition. With the exception of physical and instrumental examination, and kidney biopsy, all other assessments are feasible during a video visit and can be implemented by specific training and use of supporting tools. The video visit model is simple and adaptable to most transplant patients. It is not intended to replace face-to-face examinations, but is an additional tool for improving the intensity of follow-up of kidney transplant recipients, which can be integrated into current monitoring protocols.

LEAP Virtual Visit Assessment (VIVA): a structured protocol for virtual visits for patients with heart failure.

AIMS: Telemedicine may be of benefit in patients with heart failure (HF), although virtual visits are often carried out on an ad hoc basis. Herein, we discuss a structured protocol that defines all the steps needed for virtual visits, LEAP Virtual Visit, which includes guides and support kits for clinicians and patients. METHODS: A working group of clinicians was established to develop a protocol for virtual visits. The virtual model for monitoring HF patients was based on measurement and sizing of patient flows, type of services, and critical organizational points. The process of virtual visits was broken down to identify the specific activities, players, roles, and support tools needed for implementation in daily practice. RESULTS: In the protocol developed, sections were included on patient eligibility, exams, supportive tools, and practical organizational aspects. IT requirements were also considered and the most widely used teleconference platforms were compared according to features that were considered to be priority for virtual visits. Protocols and support kits were developed, including guides for clinicians and patients, two questionnaires to assess the level of satisfaction, patient diary, disease awareness brochure, and template to monitor key performance indicators. The phases include an enrolment phase, document sharing phase, pre-evaluation phase, the virtual visit itself, and the post-visit phase. The protocol for the virtual visit was divided into 8 sequential steps to be carried out between the clinic and patient/caregiver. CONCLUSION: The protocol described can be expected to have a number of benefits for the patient, clinic, and healthcare structure.

Next-Generation Sequencing in Clinical Practice: Is It a Cost-Saving Alternative to a Single-Gene Testing Approach?

OBJECTIVES: This study aimed to compare the costs of a next-generation sequencing-based (NGS-based) panel testing strategy to those of a single-gene testing-based (SGT-based) strategy, considering different scenarios of clinical practice evolution. METHODS: Three Italian hospitals were analysed, and four different testing pathways (paths 1, 2, 3, and 4) were identified: two for advanced non-small-cell lung cancer (aNSCLC) patients and two for unresectable metastatic colon-rectal cancer (mCRC) patients. For each path, we explored four scenarios considering the current clinical practice and its expected evolution. The 16 testing cases (4 scenarios × 4 paths) were then compared in terms of differential costs between the NGS-based and SGT-based approaches considering personnel, consumables, equipment, and overhead costs. Break-even and sensitivity analyses were performed. Data gathering, aimed at identifying the hospital setup, was performed through a semi-structured questionnaire administered to the professionals involved in testing activities. RESULTS: The NGS-based strategy was found to be a cost-saving alternative to the SGT-based strategy in 15 of the 16 testing cases. The break-even threshold, the minimum number of patients required to make the NGS-based approach less costly than the SGT-based approach, varied across the testing cases depending on molecular alterations tested, techniques adopted, and specific costs. The analysis found the NGS-based approach to be less costly than the SGT-based approach in nine of the 16 testing cases at any volume of tests performed; in six cases, the NGS-based approach was found to be less costly above a threshold (and in one case, it was found to be always more expensive). Savings obtained using an NGS-based approach ranged from €30 to €1249 per patient; in the unique testing case where NGS was more costly, the additional cost per patient was €25. CONCLUSIONS: An NGS-based approach may be less costly than an SGT-based approach; also, generated savings increase with the number of patients and different molecular alterations tested.

Natural history of upper motor neuron-dominant ALS.

A new amyotrophic lateral sclerosis (ALS) category named 'UMN-dominant ALS' and defined as 'due predominantly to UMN signs but with minor electromyogram (EMG) denervation or LMN signs on examination' has been proposed. The clinical and laboratory features of 20 patients with UMN-dominant ALS are described here, their disease course is analysed longitudinally according to their disability progression, and all these parameters are compared with those of typical ALS patients. Ten women and 10 men diagnosed with UMN-dominant ALS were evaluated. Their mean age at disease onset was 58.6 years. At the most recent evaluation, after a mean disease duration of 7.7 years, all patients progressed to a tetrapyramidal syndrome with pseudobulbar features of varying degree. No patient had respiratory problems. Cognitive impairment was observed in eight patients. The differences in disease progression between the UMN-dominant ALS and typical ALS patients proved significant (p <0.02) both with regard to the total ALSFRS-R score at six months and to each single region subscore at 12 months. Our findings suggest that there is both a different pattern of disability and longer survival in UMN-dominant ALS compared to classic ALS patients.

TDP-43 in skeletal muscle of patients affected with amyotrophic lateral sclerosis.

TAR DNA binding protein (TDP-43) is the pathologic substrate of neuronal and glial aggregates in amyotrophic lateral sclerosis (ALS). Pathologic TDP-43 is hyperphosphorylated and cleaved to generate abnormal protein species that accumulate in the cytoplasm. To assess the hypothesis of TDP-43 pathology as a systemic disorder in ALS we analysed the immunohistochemical and biochemical profile of TDP-43 in muscle biopsies of 30 ALS patients and 30 controls. In all ALS muscle biopsies we observed that TDP-43 was constantly present in an intranuclear localization and TDP-43 Western blotting showed only a 43-KDa band as controls. Our results suggest that TDP-43 pathology is probably confined to the central nervous system in ALS.

Constrictive Pericarditis with Extensive Calcification and Caseous Necrosis.

Constrictive pericarditis is a disease where loss of pericardial elasticity and restriction of filling of the cardiac chambers occurs. It is most often seen as an associated symptom of heart failure. Pericardiectomy provides effective treatment for patients with symptomatic constrictive pericarditis, although high rates of morbidity and mortality are related to the procedure. We present a case with extensive calcification, massive caseous necrosis and an important impairment of right ventricular function successfully operated in our institution.

Muscle histopathology in upper motor neuron-dominant amyotrophic lateral sclerosis.

The distinction between primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) still remains debated. Recently, PLS patients displaying lower motor neuron (LMN) signs have been defined as 'upper motor neuron (UMN)-dominant ALS', using 'clinically pure PLS' diagnosis to those with no LMN signs. To further characterize the LMN involvement in UMN-dominant ALS we investigated the presence and the extent of neurogenic abnormalities in the skeletal muscle of patients affected with a pyramidal syndrome consistent with UMN-dominant ALS. A total of nine patients affected with UMN-dominant ALS were analysed. In all cases, muscle biopsies showed the presence of scattered or clustered atrophic angulated fibres in small groups, and a mild to moderate fibre type-grouping. Target and targetoid fibres were detected in two cases only. Three patients had a second muscle biopsy which demonstrated a roughly unchanged pattern of chronic denervation with still moderate reinnervation phenomena. This study suggests that in UMN-dominant ALS muscle denervation may be characterized by an early chronic impairment of a restricted number of LMNs. The extent rather than the presence of LMN signs may allow to categorize patients with motor neuron disease involving mainly UMN into distinct entities.

Heart Injury with Projectile Lodged Inside the Heart.

Penetrating heart injuries present high mortality rates. Increasing rates of urban violence have contributed to a significant rise in the number of heart injuries by firearm projectiles. Such injuries are associated with the highest mortality rates among penetrating cardiac injuries and may involve one or more cardiac chambers. We present the case of a police officer who, in an approach to five robbers, suffered a transfixed cardiac injury by firearm with the projectile having been lodged inside the right ventricle. This patient was successfully operated, 65 days after the injury, at our institution.

Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers.

BACKGROUND: Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden. PURPOSE: The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. PATIENTS AND METHODS: The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated. RESULTS: Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed. CONCLUSION: The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage.

Constrictive pericarditis with extensive calcification and caseous necrosis

Abstract Constrictive pericarditis is a disease where loss of pericardial elasticity and restriction of filling of the cardiac chambers occurs. It is most often seen as an associated symptom of heart failure. Pericardiectomy provides effective treatment for patients with symptomatic constrictive pericarditis, although high rates of morbidity and mortality are related to the procedure. We present a case with extensive calcification, massive caseous necrosis and an important impairment of right ventricular function successfully operated in our institution.

Neuroadrenergic disarray in pseudo-resistant and resistant hypertension.

Several studies have investigated the behavior of sympathetic cardiovascular drive in essential hypertension, providing conclusive evidence of the adrenergic activation characterizing this condition. These studies have also shown the importance of neuroadrenergic overdrive in the development and progression of the hypertensive state as well as in the pathogenesis of hypertension-related end-organ damage. The information available on the sympathetic nervous system's behavior in 'pseudo-resistant' and 'true resistant' hypertension is much more scarce. This paper will review the available knowledge on this issue by examining the data collected via indirect and direct approaches to investigate adrenergic function in resistant hypertension as well as the effects of pharmacological and non-pharmacological interventions.

Long-term sympathoinhibitory effects of surgically induced weight loss in severe obese patients.

Weight loss improves insulin sensitivity and exerts sympathomodulatory effects. No data, however, are available on the effects of the weight loss induced by vertical sleeve gastrectomy on sympathetic neural drive, insulin sensitivity, and their reciprocal cross talks. In 10 severe obese hypertensives (age, 54.0±2.3 years [mean±SEM]), we measured sphygmomanometric blood pressure, heart rate, body mass index, homeostatic model assessment index, plasma leptin, muscle sympathetic nerve traffic (microneurography), and baroreflex sensitivity (vasoactive drug technique). Measurements were performed 2 to 3 days before surgery and repeated 6 and 12 months after the procedure. Ten matched hypertensive obeses not undergoing gastrectomy served as controls. Six months after bariatric surgery, a significant (P<0.05) reduction in body mass index (-9.1±1.4 kg/m(2)), sphygmomanometric systolic blood pressure (-10.2±4.5 mm Hg), heart rate (-11.0±2.4 bpm), homeostatic model assessment index (-3-3±1.3 AU), plasma leptin (-53.6±8.8 µg/L), and muscle sympathetic nerve traffic (-15.0±3.4 bursts/100 heart beats) was observed. The weight loss, the plasma leptin reduction, and the sympathetic inhibition were maintained after 12 months, whereas homeostatic model assessment index showed a tendency to return toward presurgery values. A significant improvement in baroreflex control of sympathetic nerve traffic was observed both 6 (+32.1%; P<0.05) and 12 months (+60.7%; P<0.01) after gastrectomy. No significant changes in the above-mentioned variables were detected in the control group. These data provide evidence that massive weight loss induced by sleeve gastrectomy triggers profound sympathoinhibitory effects, associated with a stable and significant reduction in plasma leptin levels, whereas the improvement in insulin sensitivity was attenuated with time and unrelated to the sympathoinhibition.

Prognostic value of serum uric acid: new-onset in and out-of-office hypertension and long-term mortality.

OBJECTIVE: Serum uric acid (SUA) has been associated with an increased cardiovascular risk, but no conclusive evidence exists on whether it is an independent risk factor or a reflection of other risk factors to which it is related. We examined the relationship of SUA with a number of cardiovascular variables [including risk factors never evaluated before, such as organ damage and out-of-office blood pressure (BP)], as well as its prognostic relevance in the population. METHODS: In 2045 participants of the Pressioni Arteriose Monitorate E Loro Associazioni study, we measured, along with SUA, metabolic, renal, and anthropometric variables, left-ventricular mass index, and office, home and ambulatory BP. Cardiovascular and all-cause mortality was assessed over a 16-year follow-up period, and measurements were repeated 10 years after the initial data collection. RESULTS: Baseline SUA had a near-normal distribution, with a mean value of 4.9 ±â€Š1.3 (SD) mg/dl and a significant direct relationship with BP and metabolic variables, serum creatinine and left-ventricular mass index. It was among the factors independently predicting new-onset home and ambulatory hypertension, the increased risk of developing these conditions for 1  mg/dl increase of SUA after adjustment for all available potential confounders being 34 and 29%, respectively (P = 0.015 and P = 0.014). An increase in SUA of 1  mg/dl also independently predicted cardiovascular and all-cause mortality, the fully adjusted increase in risk being 22% (P = 0.03) and 12% (P = 0.04), respectively. CONCLUSION: In the general population of the Pressioni Arteriose Monitorate E Loro Associazioni study, SUA correlated with a number of cardiovascular risk factors. Nevertheless, it independently predicts new-onset out-of-office hypertension, and long-term cardiovascular and all-cause mortality.

Regional differences in sympathetic activation in lean and obese normotensive individuals with obstructive sleep apnoea.

OBJECTIVE: Obstructive sleep apnoea (OSA) is characterized by a marked sympathetic overdrive, as documented by the elevated sympathetic nerve firing rate detected in peripheral muscle nerves. No data are available, however, on the behaviour of sympathetic drive in vascular regional districts other than the muscle circulation. DESIGN AND METHODS: In 66 middle-aged normotensive individuals classified according to BMI, waist-to-hip ratio and apnoea-hypopnea index as lean individuals without (n = 20) or with (n = 14) OSA and as obese individuals without (n = 13) or with (n = 19) OSA, we measured blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), respectively, via microneurography. Measurements also included SSNA responses to an emotional stimulus. RESULTS: The four groups were matched for age, sex and blood pressure values. Both in lean and obese individuals, presence of OSA was accompanied by MSNA values significantly greater than those found in non-OSA individuals. In contrast, no significant difference was found in SSNA values between OSA and non-OSA patients both in the lean and in the obese groups. This was the case also for the SSNA responses to an emotional arousal. CONCLUSION: These data provide the first evidence that in OSA, the adrenergic overdrive seen in the muscle circulation is not detected in cutaneous circulation and thus it cannot be regarded as a generalized phenomenon affecting the whole cardiovascular system. Further studies are needed to clarify whether in OSA, sympathetic drive of other vascular districts, such as the coronary, renal or cerebral circulation, is activated or normal.