The diagnostic, therapeutic and assistance pathway for amyotrophic lateral sclerosis in a north-eastern Italian region: satisfaction of patients and their caregivers.

In order to evaluate the users' satisfaction degree for the diagnostic, therapeutic and assistance services for amyotrophic lateral sclerosis (ALS) in the Italian region Friuli-Venezia Giulia (FVG), a self-compiled anonymous multiple-choice questionnaire was administered to ALS patients and their caregivers. The questionnaire explored 41 different issues covering the following areas: (a) access to diagnostic pathway and communication among patients, families and health professionals; (b) quality of disease monitoring and effectiveness of interventions aimed at mitigating ALS symptoms; (c) easiness of access to assistive devices (e.g. wheelchair, ankle-foot-orthosis) and home assistance; (d) patient' choices sharing and health professionals empathy. The same issues were proposed both to patients and carers, appropriately adapting the questions, during the period between June and December 2019. The answers were categorised according to criticality level. Median with interquartile range of the numeric variables and percentages of the categorical variables and of the answers to questions were calculated. The mean percentage of satisfied users was 72.8%, considering all the areas. Pain treatment and easiness of access to ambulance transport were the most positive aspects (95.7% and 92.5% of satisfied respondents, respectively), while information about possible enrolment in clinical trials and about possible registration to the regional ALS association were the most critical issues (30.9% and 43.4% of satisfied users). Although the satisfaction level of ALS patients and their caregivers for the services provided resulted generally good, there were some areas that have to be improved. For this purpose, enhancement of multidisciplinary collaboration, sharing of points of view from users and different practitioners and rising awareness among healthcare professionals through clinical audits could be useful. Further research is needed to identify a wider range of users' unexplored unmet needs.

Stroke management during the coronavirus disease 2019 (COVID-19) pandemic: experience from three regions of the north east of Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige).

BACKGROUND: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke. METHODS: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies. RESULTS: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers. CONCLUSIONS: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.

Epidemiology of paraneoplastic neurological syndromes: a population-based study.

BACKGROUND: The epidemiology of paraneoplastic neurological syndromes (PNS) remains to be defined. We present here the first population-based incidence study and report the clinical spectrum and antibody profile of PNS in a large area in Northeastern Italy. METHODS: We performed a 9-year (2009-2017) population-based epidemiological study of PNS in the provinces of Udine, Pordenone and Gorizia, in the Friuli-Venezia Giulia region (983,190 people as of January 1, 2017). PNS diagnosis and subgroups were defined by the 2004 diagnostic criteria. Age- and sex-adjusted incidence rates were calculated. RESULTS: We identified 89 patients with a diagnosis of definite PNS. Median age was 68 years (range 26-90), 52% were female. The incidence of PNS was 0.89/100,000 person-years. PNS incidence rates increased over time from 0.62/100,000 person-years (2009-2011), 0.81/100,000 person-years (2012-2014) to 1.22/100,000 person-years (2015-2017). The prevalence of PNS was 4.37 per 100,000. Most common PNS were limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%). Among antibody (Ab)-positive cases, most frequent specificities included: Yo (30%), Hu (26%), and Ma2 (22%), while the most frequent associated tumors were lung (17%) and breast cancer (16%), followed by lymphoma (12%). PNS developed in 1 in every 334 cancers in our region. Statistically significant associations were observed between cancer type and Ab-specificity (P < 0.001), and between neurological syndrome and Ab-specificity (P < 0.001). CONCLUSIONS: This first population-based study found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/100,000. Moreover, the incidence of PNS is increasing over time, probably due to increased awareness and improved detection techniques.

CHA2DS2-VASc score predicts short- and long-term outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis.

The CHA2DS2-VASc score is a validated tool to assess the thromboembolic risk in patients with atrial fibrillation. Pre-stroke CHA2DS2-VASc score may predict outcome in patients with acute ischemic stroke (AIS) without atrial fibrillation. The aim of this study was to investigate if the pre-stroke CHA2DS2-VASc score is able to predict short- and long-term outcomes in AIS patients treated with intravenous thrombolysis (IVT). The study group consisted of 256 consecutive patients admitted to the Udine University Hospital with AIS and underwent IVT between January 2015 to March 2017. The pre-stroke CHA2DS2-VASc score for each patient was calculated from the collected baseline data. Patients were classified into three groups according to their pre-stroke CHA2DS2-VASc score: a score of 0 of 1, a score of 2 or 3 and a score above 3. Primary outcome measures were: rate of favorable outcome at 90-days and at 1-year, and mortality at 90-days and at 1-year. Data on functional outcome and mortality 1 year after stroke were collected in 165 patients (65% of the entire sample). Favorable outcome was defined as a modified Rankin Scale score ≤ 2. Compared with the CHA2DS2-VASc score 0-1 group, patients with higher CHA2DS2-VASc scores had a worse outcome and a higher mortality 3 months and 1 year after stroke. The diagnostic performance of the CHA2DS2-VASc score as judged with AUC-ROC was 0.70 (95% CI, 0.64-0.76; p < 0.001) for favorable outcome at 90-days, 0.78 (95% CI, 0.71-0.85; p < 0.001) for favorable outcome at 1-year, 0.71 (95% CI 0.61-0.79) for mortality at 90-days, 0.73 (95% CI 0.64-0.80; p < 0.001) for mortality at 1-year. Pre-stroke CHA2DS2-VASc score represents a good predictor for short- and long-term outcomes in AIS patients treated with IVT.

Short and long-term outcomes after combined intravenous thrombolysis and mechanical thrombectomy versus direct mechanical thrombectomy: a prospective single-center study.

Recent clinical trials demonstrated that mechanical thrombectomy (MT) using second-generation endovascular devices has beneficial effects in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, it remains controversial if intravenous thrombolysis (IVT) prior to MT is superior compared to direct mechanical thrombectomy (DMT). The aims of this study were to compare short and long-term outcomes between IVT + MT and DMT patients. We prospectively recruited AIS patients with LVO in the anterior or posterior circulation eligible for MT with and without prior IVT. Modified Rankin Scale (mRS) and mortality were assessed at baseline, at discharge, 90-days and 1-year after stroke. Favorable outcome was defined as a mRS score ≤2. Of the 66 patients included, 33 (50%) were in IVT + MT group and 33 (50%) were in DMT group. Except for a higher prevalence of patients using anticoagulants at admission in DMT group, baseline characteristics did not differ in the two groups. Procedural characteristics were similar in IVT + MT and DMT group. Rate of favorable outcome was significantly higher in IVT + MT patients than DMT ones both 90-days (51.5 vs. 18.2%; p = 0.004) and 1-year (51.5 vs. 15.2%; p = 0.002) after stroke. DMT patients were six times more likely to die during the 1-year follow-up compared to IVT + MT patients. This study suggests that bridging therapy may improve short and long-term outcomes in patients eligible for endovascular treatment. Further studies with larger patient numbers and randomized design are needed to confirm our findings.

Kounis syndrome following canned tuna fish ingestion.

Kounis syndrome (KS) is a complex of cardiovascular symptoms and signs following either allergy or hypersensitivity and anaphylactic or anaphylactoid insults. We report the case of 57-year-old man, with hypertension and history of allergy, referred for facial rash and palpitations appeared after consumption of canned tuna fish. Suddenly, the patient collapsed: electrocardiogram showed ST-elevation in inferior leads. The patient was transferred from the spoke emergency room for coronary angio, which did not show any sign of coronary atherosclerosis. A transient coronary spasm was therefore hypothesized and the final diagnosis was KS. To the best of our knowledge, this is one of the first cases of KS following the ingestion of tuna fish. KS secondary to food allergy has also been reported, and shellfish ingestion has been considered as one of the most active KS inducer foods. Canned tuna fish too is well known as an allergy inducer. Tuna fish allergy should be considered, however, within the context of scombroid food poisoning, also called histamine fish poisoning. Fish with high levels of free histidine, the enzyme substrate converted to histamine by bacterial histidine decarboxylase, are those most often implicated in scombroid poisoning. Inflammatory mediators such as histamine constitute the pathophysiologic basis of Kounis hypersensitivity-associated acute coronary syndrome. Patients with coronary risk factors, allergic reaction after food ingestion, and suspected scombroid poisoning should be therefore carefully monitored for a prompt diagnosis of possible coronary complications.

Lymphocyte subset characterization in patients with early clinical presentation of coronary heart disease.

This study aimed to investigate lymphocyte populations in non-diabetic patients with early clinical presentation of coronary heart disease (CHD). Twenty-five consecutive middle-aged (<55 years) out-patients with CHD (acute myocardial infarction in the previous 3 months) and stable clinical conditions (>1 month) underwent venous blood sampling in order to determinate CD3+ (T-lymphocytes), CD19+ (B-lymphocytes), CD4+ (helper/inducer lymphocytes) and CD8+ (suppressor/cytotoxic lymphocytes) populations. Patients with diabetes, heart failure symptoms, recent revascularization (<30 days) were excluded. Twenty-five patients matched for age, gender and risk factors were enrolled as controls. All patients with CHD previously underwent coronary angiography. CHD patients showed lower CD3+ levels (70.96 ± 4.72 vs. 74.12 ± 4.93 %, p < 0.05) and CD8+ (37.80 ± 7.15 vs. 46.36 ± 5.22 %, p < 0.001) but higher CD4+ (37.32 ± 7.99 vs. 31.64 ± 4.72 %, p < 0.01) and CD4+/CD8+ ratio (1.06 ± 0.43 vs. 0.69 ± 0.13, p < 0.001). Difference in CD19+ levels was not statistically significant. Subjects with an impaired (≤55 %) left ventricular ejection fraction were characterized by lower levels of CD8+ (33.23 ± 7.04 vs. 43.76 ± 7.40 %, p < 0.05) and higher levels of CD4+ (38.31 ± 8.23 vs. 32.73 ± 6.08 %, p < 0.05) and CD4+/CD8+ ratio (1.06 ± 0.38 vs. 0.79 ± 0.34, p < 0.05). CD8+ levels inversely related to severity of coronary atherosclerosis (r = -0.37, p < 0.01). In conclusion, subjects with early clinical presentation of CHD are characterized by an altered CD4+/CD8+ ratio and lower CD3+ levels.

[Access to health care for asthma in Italian children and adolescents]. / Ricorso alle cure per asma in bambini e adolescenti italiani.

Bronchial asthma represents the most frequent chronic illness in the paediatric age. Although a number of guidelines for the diagnosis, treatment and prevention of the disease exist, some studies have shown that their application on a large scale is still lacking, in this way leading to the inadequate treatment of symptoms and the frequent use of emergency visits and hospitalization. Within the scope of the SIDRIA-2 project, this article describes the main aspects of diagnosis, management and treatment of asthma in children (6/7 years old) and adolescents (13/14 years old). The information was obtained from the SIDRIA questionnaire completed by the parents. The analysis of data demonstrated some relevant differences between the actual management of asthma in the paediatric age in Italy and the suggestions available from the guidelines and the literature. Moreover, some choices in the management of asthma were associated to the socio-economic level of families of children and adolescents, such as a lower use of spirometry and a higher frequency of hospitalization in disadvantaged subjects.

Influence of HLA antigens and OSAS in childhood: a preliminary report.

Several studies have emphasized the role of familial factors and familial aggregation in increasing susceptibility to obstructive sleep apnea syndrome (OSAS); the aim of the present study was to investigate the possible influence of human leukocyte antigen (HLA) in the development of sleep disordered breathing and OSAS of children. Between January 2000 and January 2003, all the 370 children [193 males; median age: 5.2 years (range: 1-12 years)] with sleep disordered breathing referred to our Center were screened by a 41-item multiple-choice questionnaire. All habitual snores children underwent a polisomnographic evaluation, and those with an apnea/hypopnea index >3 were diagnosed as having OSAS. All children with OSAS or primary snoring were HLA typed for class I and II. According to nocturnal polygraphic monitoring study, 41 patients were diagnosed as having OSAS and 32 as primary snoring. Patients in the two diagnostic groups were homogeneous for demographic and clinical characteristics. HLA-B65 was found to be significantly more expressed in children with sleep disordered breathing as compared with controls (10.5% versus 3.61; Pypc < 0.04) while no difference was found for the other tested antigens. A logistic regression analysis found cough (P < 0.02) and persistent wheeze (P < 0.008) the sole risk factors for OSAS development. Our preliminary data suggest that HLA does not play a key role in the pathogenesis of OSAS, however more studies are needed to clarify this issue.

Pathogenic role of mtDNA duplications in mitochondrial diseases associated with mtDNA deletions.

We estimated the frequency of multiple mtDNA rearrangements by Southern blot in 32 patients affected by mitochondrial disorders associated with single deletions in order to assess genotype-phenotype correlations and elucidate the pathogenic significance of mtDNA duplications. Muscle in situ hybridization studies were performed in patients showing mtDNA duplications at Southern blot. We found multiple rearrangements in 12/32 (37.5%) patients; in particular, mtDNA duplications were detected in 4/4 Kearns-Sayre syndrome (KSS), in 1 Pearson's syndrome, in 1/3 encephalomyopathies with progressive external ophthalmoplegia (PEO), and in 2/23 PEO. In situ studies documented an exclusive accumulation of deleted mtDNAs in cytochrome c oxidase negative fibers of patients with mtDNA duplications. The presence of mtDNA duplications significantly correlated with onset of symptoms before age 15 and occurrence of clinical multisystem involvement. Analysis of biochemical data documented a predominant reduction of complex III in patients without duplications compared to patients with mtDNA duplications. Our data indicate that multiple mtDNA rearrangements are detectable in a considerable proportion of patients with single deletions and that mtDNA duplications do not cause any oxidative impairment. They more likely play a pathogenic role in the determination of clinical expression of mitochondrial diseases associated with single mtDNA deletions, possibly generating deleted mtDNAs in embryonic tissues by homologous recombination.

Human mitochondrial DNA with large deletions repopulates organelles faster than full-length genomes under relaxed copy number control.

Partially-deleted mitochondrial DNA (DeltamtDNA) accumulates during aging of postmitotic tissues. This accumulation has been linked to decreased metabolic activity, increased reactive oxygen species formation and the aging process. Taking advantage of cell lines with heteroplasmic mtDNA mutations, we showed that, after severe mtDNA depletion, organelles are quickly and predominantly repopulated with DeltamtDNA, whereas repopulation with the wild-type counterpart is slower. This behavior was not observed for full-length genomes with pathogenic point mutations. The faster repopulation of smaller molecules was supported by metabolic labeling of mtDNA with [3H]thymidine during relaxed copy number control conditions. We also showed that hybrid cells containing two defective mtDNA haplotypes tend to retain the smaller one as they adjust their normal mtDNA copy number. Taken together, our results indicate that, under relaxed copy number control, DeltamtDNAs repopulate mitochondria more efficiently than full-length genomes.