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Background: It has been widely reported that anticoagulants (ACs) are underused for primary and secondary prevention of ischemic stroke in patients with atrial fibrillation (AFib). Furthermore, precise evidence-based guidelines about the best timing for AC initiation after acute stroke are currently lacking., Methods and Results: In this retrospective, observational study, we analyzed prescription trends in AFib patients with acute ischemic stroke who were hospitalized in four neurologic stroke units of our region (Lombardia, Italy). In-hospital antithrombotic prescription was performed in highly heterogeneous patterns. A prestroke treatment with AC was the leading factor enhancing AC prescription during hospitalization. The other factors promoting AC were male gender, younger age, lower prestroke disability and stroke severity, and smaller stroke volumes. AFib subtype influenced AC prescription only in AC-naïve patients. Interestingly, Congestive heart failure, Hypertension, Age higher than 75 years, Diabetes, previous Stroke or TIA or thromboembolism, Vascular disease, Age 64-75 years, female Sex (CHA 2 DS 2 -VASc) and Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INRs, Elderly, Drugs and alcohol (HAS-BLED) scores were not associated with AC prescription. However, patients who were treated with AC, including early treatment (<48 hours), showed a low rate of bleeding., Conclusions: Our findings potentially suggest that, although apparently neglecting the common risk stratification tools, our neurologists were able to select the more suitable candidates for prompt AC treatment. Further studies are needed to develop new scoring systems to aid ischemic and hemorrhagic risk estimation in the secondary prevention of stroke., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated., Methods: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH., Results: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones., Conclusions: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study., Methods and Results: Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39-1.32; P=0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33-1.21; P=0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04-0.81; P=0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05-0.68; P=0.011)., Conclusions: PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation., (© 2016 American Heart Association, Inc.)

Background and Purpose: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease, Methods: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis., Results: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease., Conclusions: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series., (© 2016 American Heart Association, Inc.)

Aims: Our aim was to assess the effects on clinical outcomes of endovascular treatment vs. thrombolysis alone in patients with ischaemic stroke., Methods and Results: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for randomised trials comparing endovascular treatment vs. intravenous thrombolysis alone in acute ischaemic stroke. Data were pooled by meta-analysis using a fixed-effects or a random-effects model, as appropriate. Eight studies enrolling 2,423 participants were included. Compared with thrombolysis alone, endovascular treatment was associated with higher rates of 90-day modified Rankin Scale (mRS) scores of 0-2 (42.4% vs. 31.8%, odds ratio [OR] 1.71, 95% confidence interval [CI]: 1.17-2.49, p=0.005, number needed to treat to benefit [NNTB]=8), and of recanalisation at 24-30 hours (76.9% vs. 39.6%, OR 4.49, 95% CI: 2.41-8.38, p<0.001, NNTB=2.9), with similar risk of symptomatic intracranial haemorrhage (5.4% vs. 4.9%, OR 1.08, 95% CI: 0.75-1.56, p=0.67) and all-cause death (15.3% vs. 16.6%, OR 0.86, 95% CI: 0.69-1.07, p=0.18). In subgroup analysis the benefits of endovascular treatment were restricted to studies where stent retriever systems were routinely employed., Conclusions: In patients with acute ischaemic stroke, endovascular treatment is a safe and more effective strategy than intravenous thrombolysis alone.

Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). T he identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 ± 9.5 years) underwent a TTE evaluation; 63 patients (7.4%) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3%) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2%) among whom 51 (9.3%) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7%. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95% CI 1.06-4.29, p = 0.033) and CHA2DS2-VASc score (OR 1.22; 95% CI 1.04-1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon.

Background and Purpose: The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke., Methods: The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke., Results: Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003)., Conclusions: Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants., (© 2015 American Heart Association, Inc.)

Factors predicting family history (FH) of premature arterial thrombosis in young patients with ischaemic stroke (IS) have not been extensively investigated, and whether they might influence the risk of post-stroke recurrence is still unknown. In the present study we analysed 1,881 consecutive first-ever IS patients aged 18-45 years recruited from January 2000 to January 2012 as part of the Italian Project on Stroke in Young Adults (IPSYS). FH of premature arterial thrombosis was any thrombotic event [IS, myocardial infarction or other arterial events event] < 45 years in proband's first-degree relatives. Compared with patients without FH of premature arterial thrombosis, those with FH (n = 85) were more often smokers (odds ratio [OR], 1.94; 95 % confidence interval [CI], 1.21-3.09) and carriers of procoagulant abnormalities (OR, 3.66; 95 % CI, 2.21-6.06). Smoking (OR, 2.48; 95 % CI, 1.20-5.15), the A1691 mutation in factor V gene (OR, 3.64; 95 % CI, 1.31-10.10), and the A20210 mutation in the prothrombin gene (OR, 8.40; 95 % CI 3.35-21.05) were associated with FH of premature stroke (n = 33), while circulating anti-phospholipids to FH of premature myocardial infarction (n = 45; OR, 3.48; 95 % CI, 1.61-7.51). Mean follow-up time was 46.6 ± 38.6 months. Recurrent events occurred more frequently in the subgroup of patients with FH of premature stroke [19.4 %); p = 0.051] compared to patients without such a FH. In conclusion, young IS patients with FH of premature arterial thrombosis exhibit a distinct risk-factor profile, an underlying procoagulant state and have worse vascular prognosis than those with no FH of juvenile thrombotic events.

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0-2) or unfavourable (score of 3-6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88-1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40-0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5-6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86-1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00-3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.

Background: Platypnoea-Orthodeoxia Syndrome (P-OS) is a rare disease characterised by arterial desaturation exacerbated by the upright position and relieved by recumbency. Patent foramen ovale (PFO) may lead to a P-OS causing a right-to-left shunt in the course of particular diseases that induce atrial deformation. Percutaneous closure of the defect usually allows prompt improvement of the clinical status., Methods: A series of patients with P-OS was treated with percutaneous PFO closure, according to standard clinical practice. Procedural monitoring was performed by transoesophageal two-dimensional-echocardiography (2D-echo)., Results: PFO percutaneous closure was initially effective in only half of the patients because of high rates of acute residual shunt. This unexpected result was related to the very complex anatomy evaluation with 2D-echo, mainly due to a peculiar atrial deformation occurring in P-OS. A second device delivery allowed it to achieve complete defect closure in the remaining patients. Technical issues arising during the procedures are widely discussed., Conclusions: Percutaneous closure of PFO in patients with P-OS is feasible but some technical issues should be considered when PFO anatomy is not clear with traditional imaging techniques., (Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background and Purposes: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion., Methods: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time., Results: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0-1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9-11.1) and mortality or disability (OR 5.0; 95% CI 2.9-8.7) at 90 days., Conclusions: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: This study was designed to assess the impact of minimally invasive surgery (MIS) for the treatment of patients with metastatic epidural spinal cord compression (MESCC) and vertebral body fracture, in terms of feasibility, clinical improvement, and morbidity., Methods: Twenty-five consecutive patients with diagnosis of MESCC from solid primary tumors were treated between January 2008 and June 2010 at our institution. All patients, after multidisciplinary assessment, were considered with poor prognosis because of their disease's extension and/or other clinical conditions. Mini-invasive percutaneous surgery was performed in all patients followed by radiotherapy within 2 weeks postoperatively. Clinical outcome was evaluated by modified visual analog scale for pain, Frankel Scale for neurologic deficit, and magnetic resonance imaging or computed tomography scan., Results: Clinical remission of pain was obtained in the vast majority of patients (96%). Improvement of neurological deficit was observed in 22 patients (88%). No major morbidity or perioperative mortality occurred. The average hospital stay was 6 days. Local recurrence occurred in two patients (8%). Median survival was 10 (range, 6-24) months. Overall survival at 1 year was 43%., Conclusions: For patients with MESCC and body fracture, with limited life expectancy, minimally invasive spinal surgery followed by radiotherapy, is feasible and provides clinical benefit in most of patients, with low morbidity. We believe that a minimally invasive approach can be an alternative surgical method compared with more aggressive or demanding procedures, which in selected patients with metastatic spinal cord compression with poor prognosis could represent overtreatment.

Background and Purpose: The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients., Methods: ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0-2) or unfavorable (score of 3-6). Safety outcomes were death and any intracranial bleeding., Results: Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03-3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36-3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87-58.71; P=0.068) in the cases than in the controls., Conclusions: In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

The renin-angiotensin system (RAS) is a major regulatory system of cardiovascular and renal function. Many new aspects of this system have been revealed in recent years, leading to new therapeutic approaches. It's well known that RAS blocking agents have potent antiatherosclerotic effects, which are mediated by their antihypertensive, anti-inflammatory, antiproliferative, and oxidative stress lowering properties. Inhibitors of RAS are now first-line treatments for hypertensive target organ damage. Their effects are greater than expected by their ability to lower blood pressure. Angiotensin receptor blockers reduce the frequency of atrial fibrillation and stroke, are also able to prevent cardiovascular and renal events in diabetic patients. Thus, blockade of RAS represents one of the most important strategies in order to reduce cardiovascular risk.

This work describes the results of the implementation of a workflow management system integrated into the electronic clinical chart of a Stroke Unit. The workflow logic is based on the rules provided by the SPREAD guidelines for stroke management. In this way, the already existing clinical chart has been transformed into an evidence-based, real-time decision support system, meanwhile maintaining the same look the users were familiar with. Since the final aim of the work was to improve evidence-based behavior and detect possible organizational bottlenecks, non-compliance to the clinical practice guidelines, before and after the system introduction, have been analyzed, as well as the accuracy of the clinical chart compilation, some care process variables, and system usability. Results show that the system enhances the clinical practice without boring users. Moreover, non-compliance analysis gives rise to ideas for further improvement.

Background: Carbon dioxide (CO2), a very high density gas, tends to stratify at the lowest levels of the atmosphere. It can be produced by neutral geothermal emissions, fermentative processes or by human and industrial activity. When carbon dioxide concentrations rise to a very high level in a confined and poorly ventilated space, the anoxic hazard is a very important cause of severe accidents that can involve workers and rescuers. At CO2 levels higher than 20% there is a very high risk of a fatal accident, also considering the odourless feature of this gas., Object: Two fatal accidents in workers are described which occurred during inspection of a concrete well, built as a part of sewerage network in a rural area. In the weeks after the accident, composition and concentration of gases inside the well were analysed. We also considered the influence of an organic fertilizer called "pollina" which was found on the ground around the concrete well, in order to ascertain whether fermentation could alter the gas composition inside the well., Methods: Samples of air and water were collected in the well and samples of the organic fertilizer (pollina) on the ground surrounding the concrete well were also taken. Different quantities of organic fertilizer (pollina) with or without water were incubated in airtight glass bottles and placed in a dark room at 20 degrees C temperature; analysis of air inside the glass bottles was performed after 7 and 18 days of incubation. All the samples of air and water were analysed by gas-chromatographic-mass-spectrometry., Results: Analysis of the air samples collected inside the well after 2, 16 and 18 weeks after the accident showed a low concentration of O2 (range 4.2-9%), a high concentration of CO2 (range 5.9-12.3%), a normal level of N2 (range 78-85%) and a concentration of N2O between 0.03 and 0.19%. In water collected 2 weeks after the accident at the bottom of the concrete well, CO2 and N2O concentrations of respectively 222 mg/L and 2 mg/L were measured. In the bottles with "pollina" we found, at different times of incubation, high concentrations of CO2 (highest value 25.2%), low levels of O2 (lowest value 0.5%) and negligible concentrations of N2O (< 0.015%)., Conclusions: All these findings suggest that the atmosphere inside the concrete well was altered by the fermentative processes of pollina. The death of the two workers, caused by a poorly oxygenated atmosphere with a high concentration of carbon dioxide, can be classified under the confined space hypoxic syndrome (CSHS).

Pupillometry is a simple non-invasive technique which allows early detection of an altered functioning of both branches of the Autonomic Nervous System (ANS). In the present study, the pupillometric findings (dark and light diameters and light reflex) obtained in 14 Multiple System Atrophy (MSA) patients (5 with the striatonigral degeneration (SND) type and 9 with the olivopontocerebellar (OPCA) type were compared with those of a sex- and age-matched control group and with a group patients suffering from idiopathic parkinsonism who had never undergone treatment previously. MSA patients showed larger pupils after dark and light adaptation, high degrees of anisocoria after light adaptation and a complex impairment of pupil response to light (mainly occurring in the OPCA-type of MSA) represented by an increase in latency, contraction time and a reduction in contraction amplitude. These data point to the existence in MSA (particularly of OPCA-type) of a pupillary imbalance, mainly involving the parasympathetic branch of the ANS, which is likely to be due to an impairment of the central pathways subserving pupil response to light and is probably detectable in the early stages of the disease by means of dynamic pupillometric evaluation.