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OBJECTIVES/HYPOTHESIS The aim of the present study is to validate and compare four of the most widely used staging systems for juvenile angiofibroma on a homogeneous cohort of patients. STUDY DESIGN Retrospective case series. METHODS A retrospective review of patients treated with endoscopic or endoscopic-assisted surgical resection between 1999 and 2020 was carried out. Each case was classified according to the following staging systems: Andrews-Fisch (1989), Radkowski (1996), University of Pittsburgh Medical Center (2010), and Janakiram (2017). Spearman's rank correlation test and areas under the curve of receiver operator curves were used to assess the correlation between outcomes of interests (blood loss, surgical time, need for transfusion, and persistence of disease) and stage of disease. RESULTS Seventy-nine patients were included, with a median follow-up time of 25 months (range 12-127 months). Median surgical time was 217 minutes (range 52-625). Median blood loss was 500 mL (range 40-5200) and 27 patients (34.2%) required blood transfusions. Seven patients (8.9%) showed persistence of disease. All classification systems showed a similar association with blood loss, surgical time, persistence of disease, and need for transfusion. CONCLUSIONS Involvement of the infratemporal fossa and intracranial extension was identified as red flags for surgical planning and preoperative counseling, as associated with increased risk for transfusion and persistent/recurrent disease, respectively. No classification system was found to be better than the others in predicting the most important outcomes. Therefore, the simplest and most easily applicable system would be the preferred one to be used in clinical practice. LEVEL OF EVIDENCE Level 4 case series Laryngoscope, 2021.

Background The incretin-based medicines GLP1 analogues (GLP1a) and dipeptidyl peptidase-4 inhibitors (DPP4i) are hypoglycaemic agents licensed for the treatment of type 2 diabetes mellitus (T2DM). Although these drugs possess comparable efficacy and low risk of hypoglycaemia, differences in terms of route of administration (subcutaneous versus oral), effect on body weight and gastrointestinal tolerabily can impact their actual use in clinical practice. This study aimed to describe the real-world utilization of incretin-based medicines in the Italian clinical practice. Methods A multi-database, population-based, descriptive, cohort study was performed using administrative data collected between 2008 and 2014 from three Italian geographic areas. Subjects aged ≥18 were selected. New users were defined as those with ≥1 dispensing of GLP1a or DPP4i during the year of interest and none in the past. Trends of cumulative annual incidence of use in the general adult population were observed. New users of GLP1a or DPP4i were respectively described in terms of demographic characteristics and use of antidiabetic drugs during 1 year before and after the first incretin dispensing. Results The overall study population included 4,943,952 subjects. A total of 7357 new users of GLP1a and 41,907 of DPP4i were identified during the study period. Incidence of use increased between 2008 (0.2‰ for both GLP1a and DPP4i) and 2011 (GLP1a = 0.6‰; DPP4i = 2.5‰) and slightly decreased thereafter. In 2014, 61% of new GLP1a users received once-daily liraglutide while 52% of new DPP4i users received metformin/DPP4i in fixed-dose. The percentage of new DPP4i users older than 65 years of age increased from 30.9 to 62.6% during the study period. Around 12% of new users had not received any antidiabetic before starting an incretin. Conclusions During the study period, DPP4i rapidly became the most prescribed incretin-based medicine, particularly among older new user. The choice of the specific incretin-based medicine at first prescription appeared to be directed towards those with higher convenience of use (e.g. oral DPP4i rather than subcutaneous GLP1a, once-daily liraglutide rather than twice-daily exenatide). The non-negligibile use of incretin-based medicines as first-line pharmacotherapy for T2DM warrants further effectiveness and safety evaluations to better define their place in therapy. Electronic supplementary material The online version of this article (10.1186/s12902-019-0334-y) contains supplementary material, which is available to authorized users.

Recently WHO has declared novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Acute respiratory syndrome seems to be the most common manifestation of COVID-19. Besides pneumonia, it has been demonstrated that SARS-CoV-2 infection affects multiple organs, including brain tissues, causing different neurological manifestations, especially acute cerebrovascular disease (ischemic and hemorrhagic stroke), impaired consciousness and skeletal muscle injury. To our knowledge, among neurological disorders associated with SARS-CoV2 infection, no Posterior Reversible Encephalopathy Syndrome (PRES) has been described yet. Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.

BackgroundClinical trials and observational studies have demonstrated the benefit of thrombectomy up to 16 or 24 hours after the patient was last known to be well. This study aimed to evaluate the outcome of stroke patients treated beyond 24 hours from onset.MethodsWe analyzed the outcome of 34 stroke patients (mean age 70.7±12.3 years; median National Institutes of Health Stroke Scale (NIHSS) score 13) treated with endovascular thrombectomy beyond 24 hours from onset who were recruited in the Italian Registry of Endovascular Thrombectomy in Acute Stroke. Selection criteria for patients were: pre-stroke modified Rankin scale (mRS) score of ≤2, non-contrast CT Alberta Stroke Program Early CT score of ≥6, good collaterals on single phase CT angiography (CTA) or multiphase CTA, and CT perfusion mismatch with an infarct core size ≤50% of the total hypoperfusion extent or involving less than one-third of the extent of the middle cerebral artery territory evaluated by visual inspection. The primary outcome measure was functional independence assessed by the mRS at 90 days after onset. Safety outcomes were 90 day mortality and the occurrence of symptomatic intracranial hemorrhage (sICH).ResultsSuccessful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was present in 76.5% of patients. Three month functional independence (mRS score 0–2) was observed in 41.1% of patients. The case fatality rate was 26.5%. and the incidence of sICH was 8.8%.ConclusionsThese findings suggest that, in a real world setting, very late endovascular therapy is feasible in appropriately selected patients.

Background: Little is known about the comparative risk of death with atypical or conventional antipsychotics (APs) among persons with cardiovascular or cerebrovascular disease (CCD). Research design and methods: A cohort study was conducted using five Italian claims databases. New atypical AP users with CCD aged ≥65 (reference) were matched to new conventional AP users. Mortality per 100 person-years (PYs) and hazard ratios (HR), estimated using Cox models, were reported. Incidence and risk of death were estimated for persons having drug–drug interactions. Outcome occurrence was evaluated 180 days after AP initiation. Results: Overall 24,711 and 27,051 elderly new conventional and atypical AP users were identified. The mortality rate was 51.3 and 38.5 deaths per 100 PYs for conventional and atypical AP users. Mortality risk was 1.33 (95%CI: 1.27–1.39) for conventional APs. There was no increased mortality risk with single drug–drug interactions (DDIs) vs. no DDI. AP users with ≥1 DDI had a 29% higher mortality risk compared to no DDI in the first 90 days of treatment (HR: 1.29 (95% CI: 1.00–1.67)). Conclusions: Conventional APs had a higher risk of death than atypical APs among elderly persons with CCD. Having ≥1 DDI was associated with an increased risk of death.

Background and objective To describe our single-center experience in the treatment of cavernous internal carotid artery (ICA) acute bleeding with flow diverter stent (FDS), as a single endovascular procedure or combined with an endoscopic endonasal approach. Methods We analyze a case series of 5 patients with cavernous ICA acute bleeding, i.e., 3 iatrogenic, 1 post-traumatic, and 1 erosive neoplastic. After an immediate nasal packing to temporarily bleeding control, patients underwent digital subtraction angiography (DSA) to identify the site of the ICA injury. A concomitant balloon occlusion test (BOT) was performed, to exclude post-occlusive ischemic neurological damage. An FDS was placed with parallel intravenous infusion of abciximab in 3 cases and tirofiban in 2 cases. In two patients, an innovative “sandwich technique” combining the endovascular reconstruction with an extracranial intrasphenoidal cavernous ICA resurfacing with autologous flaps or grafts by endoscopic endonasal approach was performed. Results No patient had periprocedural ischemic-hemorrhagic complications. All patients had a regular clinical evolution, without general complications or new onset of focal neurological deficits. No further bleeding occurred in 3 patients, while 2 cases experienced a mild rebleeding in a period ranging from 5 to 15 days after the endovascular procedure. In these two cases, we proceeded with an endoscopic endonasal procedure to resurface the exposed ICA wall in the sphenoid sinus. Conclusions Although the treatment of choice for cavernous ICA acute bleeding remains the occlusion of the injured vessel, in cases of poor hemodynamic compensation at the BTO, the endovascular FDS emergency placement can be effective. A combined endoscopic endonasal technique to support the extracranial side of the vessel using autologous flaps or grafts can be performed to prevent the risk of rebleeding.

Since December 2019, a novel Severe Acute Respiratory Syndrome coronavirus 2 from China has rapidly spread worldwide. Although respiratory involvement is the mainstay of coronavirus disease 2019 (COVID-19), systemic involvement has recently drawn more attention. In particular, a number of recent articles have shed light on the nervous system as one of the possible targets. At our institution, we observed 15 patients with acute brain vascular manifestations; most interesting, we had a higher prevalence of the posterior circulation acute impairment. In our series, 7 patients had acute posterior cerebral injury: 1, hemorrhagic posterior reversible encephalopathy syndrome; 5, posterior circulation ischemic stroke; and 1, parieto-occipital hemorrhagic stroke. On the basis of our evidence and previous basic science reports, we believe a common etiopathogenetic thread may connect ischemic/hemorrhagic events of the posterior circulation and posterior reversible encephalopathy syndrome in the setting of COVID-19.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent responsible for coronavirus disease 2019 (COVID-19). Respiratory and gastrointestinal manifestations of SARS-CoV-2 are well described, less defined is the clinical neurological spectrum of COVID-19. We reported a case of COVID-19 patient with acute monophasic Guillain-Barré syndrome (GBS), and a literature review on the SARS-CoV-2 and GBS etiological correlation. Case Description A 68 years-old man presented to the emergency department with symptoms of acute progressive symmetric ascending flaccid tetraparesis. Oropharyngeal swab for SARS-CoV-2 tested positive. Neurological examination showed bifacial nerve palsy and distal muscular weakness of lower limbs. The cerebrospinal fluid assessment showed an albuminocytologic dissociation. Electrophysiological studies showed delayed distal latencies and absent F waves in early course. A diagnosis of Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP) subtype of GBS was then made. Conclusions Neurological manifestations of COVID-19 are still under study. The case we described of GBS in COVID-19 patient adds to those already reported in the literature, in support of SARS-CoV-2 triggers GBS. COVID-19 associated neurological clinic should probably be seen not as a corollary of classic respiratory and gastrointestinal symptoms, but as SARS-CoV-2-related standalone clinical entities. To date, it is essential for all Specialists, clinicians and surgeons, to direct attention towards the study of this virus, to better clarify the spectrum of its neurological manifestations.

Intravitreal anti-vascular endothelial growth factor (VEGF) drugs aflibercept and ranibizumab are used in neovascular retinal diseases but may be associated with non-ocular haemorrhage. Our objective was to compare the risk of non-ocular haemorrhage with intravitreal aflibercept versus intravitreal ranibizumab and with individual intravitreal anti-VEGFs versus intravitreal dexamethasone. A retrospective cohort study was conducted using four Italian claims databases, covering 18 million inhabitants from 2011 to 2016. Incident aflibercept users were matched 1:4 to incident ranibizumab users. The outcome was incident non-ocular haemorrhage requiring hospitalisation. Incidence per 1000 person-years (PYs) was estimated. Patients were followed for 180 days using an intention-to-treat (ITT) approach. An as-treated (AT) approach was also employed, using grace periods of 60 or 90 days. Analyses were repeated for aflibercept versus dexamethasone and ranibizumab versus dexamethasone. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. We identified incident users of intravitreal ranibizumab (n = 21,766), aflibercept (n = 3150) and dexamethasone (n = 3900). The incidence of haemorrhage was four events per 1000 PYs for each drug. Aflibercept was not associated with increased risk versus ranibizumab at 180 days (HR 0.97 [95% CI 0.37–2.56]). Results were consistent in the AT analysis (HR 1.19 [95% CI 0.52–2.75]). No increased risk was found for aflibercept and ranibizumab at 180 days versus dexamethasone (HR 0.70 [95% CI 0.30–2.60] and HR 0.67 [95% CI 0.33–1.38], respectively). No association was identified between intravitreal aflibercept and non-ocular haemorrhage versus ranibizumab. A comparable risk for these intravitreal anti-VEGFs and intravitreal dexamethasone was observed.

A recent study found a decreased risk of Parkinson disease (PD) associated with the β2 adrenergic agonist (β2-agonist) salbutamol. However, other mechanisms might explain this apparent association. Using the UK Clinical Practice Research Datalink, we formed a cohort of 2,430,884 patients aged 50 years or older between 1995 and 2016. During follow-up, 8,604 cases of PD were identified and matched to 86,040 controls on sex, age, date of cohort entry, and duration of follow-up, after applying a 1-year latency time window. Incidence rate ratios of PD associated with use of β2-agonists were estimated using conditional logistic regression. Ever-use of β2-agonists was associated with a 17% decreased rate of PD (rate ratio = 0.83, 95% confidence interval: 0.75, 0.91) compared with no use. However, this association was limited to early short-term use and was no longer observed after more than 2 years of cumulative duration of use (rate ratio = 0.97, 95% confidence interval: 0.80, 1.17). A similar pattern was observed when stratifying by time since first β2-agonist prescription and by duration of follow-up. The apparent association of β2-agonists with a decreased risk of PD is likely the result of reverse causality rather than a biological effect of these drugs on the risk of PD.

The Careggi Collateral Score (CCS) (qualitative–quantitative evaluation) was developed from a single-centre cohort as an angiographic score to describe both the extension and effectiveness of the pial collateral circulation in stroke patients with occlusion of the anterior circulation. We aimed to examine the association between CCS (quantitative evaluation) and 3-month modified Rankin Scale (mRS) score in a large multi-center cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1284 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery (ACA)-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Using CCS of 4 as reference, CCS grades were associated in the direction of unfavourable outcome on 3-month mRS shift (0 to 6); significant difference was found between CCS of 0 and CCS of 1 and between CCS of 3 and CCS of 4. CCS ≥ 3 was the optimal cut-off for predicting 3-month excellent outcome, while CCS ≥ 1 was the optimal cut-off for predicting 3-month survival. CCS of 0 and CCS

AIM This study aimed to discuss the use of flow modulation in treating ruptured aneurysms of the proximal segment of the anterior cerebral artery (A1 aneurysms). A1 aneurysms are rare, constituting approximately 1% of all intracranial aneurysms. MATERIAL AND METHODS We report a left A1 aneurysm with a wide neck and small sac (3 × 1.8 mm). In order to treat the lesion, a flow diverter (4 × 12-18 mm, FRED, Microvention) was placed from M1 to the proximal end of the paraophthalmic internal carotid artery, without directly covering the neck of the aneurysm. No procedural bleeding occurred. During stent deployment, abciximab was infused. A day after the procedure, double antiplatelet therapy was initiated for 1 month, followed by single antiplatelet therapy for another 3 months. RESULTS Due to the aneurysm morphology, we opted for a competitive flow diversion, covering the parent artery origin and leaving the A1A neck uncovered. A decreased flow into the aneurysmal parent artery gradually promoted aneurysm sac thrombosis. Both digital subtraction angiography at a 12-month follow-up and computed tomography angiography 24-month follow-up confirmed the regular patency of the stent and resolution of the aneurysm. In addition, the competitive modulation of flow in the ipsilateral anterior cerebral artery results in the narrowing of the vessel. CONCLUSION A1 aneurysm endovascular treatment is often challenging. Coiling or assisted coiling is the most frequently employed. Although flow diverter stent (FDS) is a consolidated technique for treating ruptured intracranial blister-like and dissecting aneurysms, its role in treating intracranial saccular ruptured aneurysms has to be elucidated. However, more number of case studies is needed to confirm the efficacy and safety of an FDS in treating ruptured A1 aneurysms.

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment., Highlights • Posterior reversible encephalopathy syndrome is increasingly being reported in COVID-19 patients. • Weaning from assisted ventilation may be a critical moment in seizure development. • No evidence of viral genome in the cerebrospinal fluid in this cohort

This review focuses on the use of “new” generation of non-adhesive liquid embolic agents (NALEA). In literature, non-adhesive liquid embolic agents have mainly been used in the cerebral district; however, multiple papers describing the use of NALEA in the extracranial district have been published recently and the aim of this review is to explore and analyze this field of application. There are a few NALEA liquids such as Onyx, Squid, and Phil currently available in the market, and they are used in the following applications: mainly arteriovenous malformations, endoleaks, visceral aneurysm or pseudoaneurysm, presurgical and hypervascular lesions embolization, and a niche of percutaneous approaches. These types of embolizing fluids can be used alone or in combination with other embolizing agents (such as coils or particles) so as to enhance its embolizing effect or improve its possible defects. The primary purpose of this paper is to evaluate the use of NALEAs, predominantly used alone, in elective embolization procedures. We did not attempt a meta-analysis due to the data heterogeneity, high number of case reports, and the lack of a consistent follow-up time period.

Background The flow-diverter devices (FDDs) safety and effectiveness have been demonstrated by large series and meta-analyses. Due to the high occlusion rates and the acceptable morbidity rates of FDDs, the indications for their use are continuously expanding. We presented our Italian multicentric experience using the second generation of DERIVO® Embolization Device (DED®; Acandis, Pforzheim, Germany) to cure cerebral aneurysms, evaluating both middle and long-term safety and efficacy of this device. Methods Between July 2016 and September 2017 we collected 109 consecutive aneurysms in 108 patients treated using DED® during 109 endovascular procedures in 34 Italian centers (100/109 aneurysms were unruptured, 9/109 were ruptured). The collected data included patient demographics, aneurysm location and characteristics, baseline angiography, adverse event and serious adverse event information, morbidity and mortality rates, and pre- and post-treatment modified Rankin Scale scores. Midterm and long-term clinical, angiographic and cross-sectional CT/MR follow-up were recorded and collected until December 2018. Results In 2/109 cases, DED® placement was classified as technical failures. The overall mortality and morbidity rates were respectively 6.5% and 5.5%. Overall DERIVO® related mortality and morbidity rates were respectively 0% and 4.6% (5 out of 108 patients). Midterm neuroimaging follow-up showed the complete or nearly complete occlusion of the aneurysm in 90% cases, which became 93% at long-term follow-up. Aneurysmal sac shrinking was observed in 65% of assessable aneurysms. Conclusions Our multicentric experience using DED® for endovascular treatment of unruptured and ruptured aneurysms showed a high safety and efficacy profile, substantially equivalent or better compared to the other FDDs.

Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090.

Background Obesity-associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk. Aims To explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women. Methods Serum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women. Results Resistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P = 0.013); conversely hsCRP were ~ 2X higher in T2DM women than in controls (P = 0.0132) without any difference according to CHD history. At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independently associated to resistin levels at stepwise regression analysis. Resistin levels were independently associated to CHD, increasing the risk by 1.15 times (0.986–1.344 95% CI), together with age, tHcy, LDL-C and hypertension. Conclusions Circulating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.

Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor of the nasal cavity that predominantly affects young boys. Surgical removal remains the gold standard for the management of this disease. Preoperative intra-arterial embolization (PIAE) is useful for reductions in intraoperative blood loss and surgical complications. In our series of 79 patients who underwent preoperative embolization from 1999 to 2020, demographics, procedural aspects, surgical management and follow-up outcome were analyzed. Embolization was performed in a similar fashion for all patients, with a superselective microcatheterization of external carotid artery (ECA) feeders and an injection of polyvinyl alcohol (PVA) particles, followed, in some cases, by the deployment of coils . Procedural success was reached in 100% of cases, with no complications such as bleeding or thromboembolic occlusion, and surgical intraoperative blood loss was significantly decreased. In conclusion, PIAE is a safe and effective technique in JNA treatment, minimizing intraoperative bleeding.

During the COVID-19 outbreak, the Neurology and Stroke Unit (SU) of the hospital of Varese had to serve as a cerebrovascular hub, meaning that the referral area for the unit doubled. The number of beds in the SU was increased from 4 to 8. We took advantage of the temporary suspension of the out-patient clinic and reshaped our activity to guarantee the 24/7 availability of recombinant tissue Plasminogen Activator (rtPA) intravenous therapy (IVT) in the SU, and to ensure we were able to admit patients to the SU as soon as they completed endovascular treatment (EVT). In 42 days, 46 stroke patients were admitted to our hospital, and 34.7% of them underwent IVT and/or EVT, which means that we treated 0.38 patients per day; in the baseline period from 2016 to 2018, these same figures had been 23.5% and 0.23, respectively. The mean values of the door-to-first CT/MRI and the door-to-groin puncture, but not of the onset-to-door and the door-to-needle periods were slightly but significantly longer than those observed in the baseline period in 276 patients. On an individual basis, only one patient exceeded the door-to-groin puncture time limit computed from the baseline period by about 10 min. None of the patients had a major complication following the procedures. None of the patients was or became SARS-CoV2 positive. In conclusion, we were able to manage the new hub-and-spoke system safely and without significant delays. The reshaping of the SU was made possible by the significant reduction of out-patient activity. The consequences of this reduction are still unknown but eventually, this emergency will suggest ways to reconsider the management and the allocation of health system resources.

INTRODUCTION: A direct aspiration first pass technique (ADAPT) is an alternative technique as first-line thrombectomy for large vessel occlusion in acute ischemic stroke, still debated when compared to first-line stent retriever. To retrospectively evaluate technical and clinical outcomes of the ADAPT as first-line treatment for anterior circulation acute ischemic stroke with large-bore reperfusion catheters. METHODS: A multicentric data collection from 14 medical centers was retrospectively analyzed. Large-bore catheters had a distal diameter between 0.64 and 0.71 in; stent retriever was added when aspiration alone failed. Baseline characteristics, technical and clinical variables were collected, including NIHSS, thrombolysis in cerebral infarction (TICI), peri-procedural complications, 90-day mRS and 90-day mortality. RESULTS: Overall, 501 patients were treated. No statistically significant difference in terms of baseline features or tPA administration was recorded between patients treated with ADAPT and with additional stent retriever. ADAPT alone was successful in achieving TICI ≥ 2b in 71.8% with a median of 1.55 aspiration attempts. In terms of TICI ≥ 2b, ADAPT alone was better than additional stent retriever (p

Despite the mechanization process implemented in arboriculture, logging tasks are still manually performed by chainsaw operators, which therefore are exposed to the risk of developing hand-wrist musculoskeletal disorders. Our research aimed to: (a) define whether the slight changes observed in 2017 showed an evolution to overt diseases, (b) study some risk determinants for these diseases such as age, working experience, and performing a secondary job. We recruited in a two-year follow-up study, 38 male forestry workers performing logging tasks employed in the Sicilian Forestry Department located in Enna. All the subjects underwent: (1) personal data collection, (2) administration of questionnaire addressed at upper limbs symptoms with a hand chart, (3) physical examination of the upper limbs, including Tinel’s and Phalen’s maneuvers, (4) ultrasound investigation of the hand-wrist area. In the two-year follow-up study we registered an overall increasing in wrist disorders, thus we can assume that forestry workers may be a target population for wrist diseases and deserve a particular attention in workers’ health surveillance programs. Interestingly, the prevalence of wrist-hand disorders resulted to be higher in younger workers.

Forestry workers are exposed to harsh environmental conditions, awkward postures, and high intensity load handling that might lead to low back injuries. The objectives of our study were 1) to define the trunk postures associated with risk of low back injury in a sample of forestry workers involved in tree felling, delimbing and bucking tasks and 2) to identify prevention strategies that reduce the risk of low back injury. Forty loggers were selected among the population of forestry workers in the province of Enna, Sicily-Italy. Each worker was required to perform for a period of 30 min the three main tasks: felling, delimbing and bucking for a total of 90 min of working activity. All subjects involved in the study wore a Zephyr Bioharness device on their trunk, which enabled the recording of sagittal inclination of the trunk, heart rate, breathing rate, and an estimate of body temperature. The results indicated that the felling task required loggers to work more time in awkward postures. Additionally, sagittal inclination of the trunk was greater than 60° for the 13% of the time, compared with delimbing (3%), and bucking (11%). The percentage of time spent with the trunk in sagittal inclination greater than 60° was correlated with the use of heavy (>7,2 kg) chainsaws during the felling and in the delimbing tasks. The study results indicated that the trunk posture during tree delimbing and felling tasks contributed significantly to the risk of biomechanical overload among the loggers. Preventive strategies should focus on specific interventions that reduce biomechanical stress including worker training and implementation of ergonomic designed tool.

One-hundred four persons aged ≥ 18 years (62 males and 42 females) who were admitted for traumatic brain injury (TBI) underwent brain computed tomography (CT) scan and assay of serum cortisol, insulin-like growth factor 1 (IGF-1), thyrotropin (TSH) and free thyroxine (FT4). The main purpose was to assess any gender difference and the rate of empty sella (ES).Women were more likely to have empty sella (19/42 [45.2%] vs 19/62 [30.6%], P = 0.15, OR = 1.9), which was more frequently total ES or TES (16/19 [84.2%] vs 3/19 [15.8%], P = 0.0025, OR = 11.6). Neuroradiology was normal in the remaining 65 patients. Patients with TES were approximately 20–30 years older than both patients with partial ES (PES) and normal sella, but only the comparison with normal sella was significant (P = 0.001 all patients, P = 0.005 males). Presumed deficiency of IGF-1, cortisol or TSH occurred in 33 persons (31.7%; 20 Males [32.2%], 13 Females [30.9%]), 14 (13.5%; 10 M [16.2%], 4F [9.5%]) or 8 (7.7%; 1 M [1.7%], 7F [16.7%]), with only TSH deficiency having significant intergender difference (P = 0.007). The highest or lowest rates of IGF-1 deficiency occurred in men with PES (41.7%) or men with TES (14.3%), of cortisol deficiency in men with PES (33.3%) or women with PES (zero), and TSH deficiency in women with TES (18.7%) or both men and women with PES (zero) and men with normal sella (zero). Within ES, males with no deficiency were older compared to males with at least one hormone deficiency (75.7 ± 17.4 vs 55.6 ± 18.9, P = 0.022); in turn, the former males were also older compared with normal sella males having no hormone deficiency (54.1 ± 25.2, P = 0.023).In conclusion, ES is detectable in almost 40% of persons who undergo CT within 24 h from TBI. A number of intergender differences concerning ES and the hormones evaluated are apparent. Keywords: Traumatic brain injury, Post-traumatic hypopituitarism, Empty sella, Computed tomography

Background The primary aim of this study was to provide additional data of neuroimaging features of coronavirus disease 2019 (COVID-19) in a large-scale population admitted in several northern Italy institutions. The secondary aim was to analyze acute cerebrovascular disease (CVD) prevalence in COVID-19. Methods A database of confirmed COVID-19 hospitalized patients who developed acute neurological symptoms and underwent any neuroimaging was retrospectively gathered from twelve institutions based in Lombardy from February 21st to July 10th. To assess the prevalence of CVD we conducted a scoping review following the PRISMA extension guidelines for scoping reviews. We searched PubMed/Medline, SCOPUS and EMBASE databases for peer-reviewed in-press or published studies from December to January 2021 reporting CVD in COVID-19 patients. Results Out of 90 COVID-19 patients who were referred to neuroimaging, 78 (87%) showed CVD, in particular 65 had acute ischemic strokes (AIS), 8 had intracerebral hemorrhages, 2 subarachnoid hemorrhages (SAH) and 3 showed clinical and imaging findings in keeping with posterior reversible encephalopathy syndrome (PRES); 6 patients (7%) showed clinical and imaging findings highly suggestive of encephalitis; 3 patients (3%) showed demyelinating diseases: 1 case of MS progression, 1 case of newly diagnosed MS and 1 case of acute disseminated encephalomyelitis (ADEM); 2 cases (2%) acuity of chronic subdural hematoma (cSDH); 1 patient (1%) with Guillain Barré syndrome. In addiction two patients with CVD developed cauda polyradiculitis and tetraparesis. In our scoping review out of 3275 studies, 24 satisfied the inclusion criteria: in a pooled total population of 136198 patients, the pooled prevalence of CVD was 0.9%. In particular 0.8% of AIS and 0.1% of ICH and 0.003% of PRES. Conclusions Our study shows a high prevalence of CVD among patients who developed acute neurological symptoms, which is in line with papers reporting data comparable to ours. The heterogeneity of clinical reports, however, constitutes a limitation when comparing our findings with those of the clinical papers. Nonetheless, CVD could be a frightening association with COVID-19, particularly in critically ill patients. Healthcare policymakers and clinicians should be prepared to a likely increase in workload and to rearrange the strategy of healthcare delivery.

Background and aims Untreated Familial Hypercholesterolemia (FH) leads to premature morbidity and mortality. In France, its epidemiology and management are understudied in ambulatory care. We described the clinical profile, pharmacological management, and clinical outcomes in a French sample of FH patients. Methods This was a retrospective longitudinal study on patients from The Health Improvement Network (THIN®) database in France, between October 2016-June 2019. Patients ≥18 years, with probable/definite FH based on the Dutch Lipid Clinic Network (DLCN) criteria were included. Baseline characteristics, lipid profile, lipid-lowering therapy (LLT), low-density lipoprotein-cholesterol (LDL-C) goal achievement; and disease management at 6-month of follow-up were analyzed. Results 116 patients with probable (n = 70)/definite (n = 46) FH were included (mean age:57.8±14.0 years; 56.0% women; 9.5% with personal history of cardiovascular events); 90 patients had data available at follow-up. At baseline, 77.6% of patients had LDL-C>190 mg/dL, 27.6% were not receiving LLTs, 37.9% received statins alone, 20.7% statins with other LLTs, and 7.7% other LLTs. High-intensity statins were prescribed to 11.2% of patients, 30.2% received moderate-intensity statins, and 8.6% low-intensity statins. Only 6.0% of patients achieved LDL-C goal. At 6-month of follow-up, statins discontinuation and switching were 22.7% and 2.3%, respectively. None of the patients received proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors at baseline nor follow-up. Conclusions Despite the existence of effective LLTs, FH patients are suboptimally-treated, do not achieve LDL-C goal, and exhibit worsened pharmacological management over time. Future studies with longer follow-up periods and assessment of factors affecting LDL-C management, including lifestyle and diet, are needed.

Background and objective: The aim of the present study was to evaluate associations between cumulative and peak formaldehyde exposure and occurrence of acute myeloid leukemia. Material and Methods: A comprehensive search was performed using the PubMed and Embase databases. We included studies presenting information about the role of formaldehyde in leukemic occurrence and mortality risk. Then, full texts of the selected references were assessed, and references of included studies were checked to identify additional articles. Result: The information was then summarized and organized in the present review. A total of 81 articles were obtained from the search. Conclusion: Findings from the review of the literature do not support the hypothesis that formaldehyde is a cause of acute myeloid leukemia.

IntroductionAnalgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids are commonly used among elderly persons. The aim of this study was to describe the demographic and clinical characteristics of elderly analgesic users and to measure the frequency of analgesic use, including the frequency of potentially inappropriate analgesic use.MethodsThe Arianna database was used to carry out this study. This database contains prescription data with associated indication of use for 1,076,486 inhabitants registered with their general practitioners (GPs) in the Caserta Local Health Unit (Caserta district, Campania region in Italy). A cohort of persons aged ≥65 years old with >1 year of database history having at least one analgesic drug (NSAIDs, strong or weak opioids) between 2010 and 2014 were identified. The date of the first analgesic prescription in the study period was considered the index date (ID).ResultsFrom a source population of 1,076,486 persons, 116,486 elderly persons were identified. Of these, 94,820 elderly persons received at least one analgesic drug: 36.6% were incident NSAID users (N = 36,629), while 13.2% were incident weak opioid users (N = 12,485) and 8.1% were incident strong opioid users (N = 7,658). In terms of inappropriate analgesic use, 9.2% (N = 10,763) of all elderly users were prescribed ketorolac/indomethacin inappropriately, since these drugs should not be prescribed to elderly persons. Furthermore, at least half all elderly persons with chronic kidney disease or congestive heart failure were prescribed NSAIDs, while these drugs should be avoided.ConclusionAnalgesics are commonly used inappropriately among elderly persons, suggesting that prescribing practice in the catchment area may yet be improved.

Several studies have demonstrated the efficacy of intravenous thrombolytic therapy with recombinant plasminogen activator (rt-PA) on functional recovery at 3-18 months following the treatment. The objectives of this study were to investigate differences between thrombolytic or no thrombolytic treatment and if could be a relationship between patients who have underwent the thrombolytic treatment in terms of depressive symptoms and cognitive impairment. In this retrospective study, we evaluated 92 patients affected by ischemic stroke recruited from our rehabilitation center, coming from a Stroke Unit. All the eligible subjects were assessed at admission (T0) and two months later, at discharge, upon concluded the rehabilitation program (T1). The patients were divided into two groups: Thrombolysis Group (n.40 subjects) and no Thrombolysis Group (n.52 subjects). Cognitive functions were evaluated with the Montreal Overall Cognitive Assessment. Functional status were evaluated with the Barthel Index and the Functional Independent Misure. We administered Beck Depression Inventory-II to verify the presence of a depressive state. We found that at three months after stroke, the prevalence of depressive symptoms and cognitive improvement, among patient who had undergone thrombolytic treatment, and who had not, was not different. Conversely, we found an improvement of depressive symptoms in each group.

Measles is a highly contagious airborne disease. Unvaccinated pregnant women are not only at risk of infection but also at risk of severe pregnancy complications. As measles causes a dysregulation of the entire immune system, we describe immunological variations and how immune response mechanisms can lead to adverse pregnancy outcomes. We evaluated data during the measles outbreak reported in the province of Catania, Italy, from May 2017 to June 2018. We controlled hospital discharge records for patients admitted to hospital obstetric wards searching the measles diagnostic code. We have indicated the case as “confirmed” when the IgM was found to be positive with the ELISA method. We registered 843 cases of measles and 51% were females (430 cases). 24 patients between the ages of 17 and 40 had measles while they were pregnant. Adverse pregnancy outcomes included 2 spontaneous abortions, 1 therapeutic abortion, 1 foetal death, and 6 preterm deliveries. Respiratory complications were more prevalent in pregnant women (21%) than in nonpregnant women with measles (9%). 14 health care workers (1.7%) were infected with measles, and none of these had been previously vaccinated. Immune response mechanisms were associated with adverse pregnancy outcomes in women with measles. To reduce the rate of measles complications, gynaecologists should investigate vaccination history and antibody test results in all women of childbearing age. During a measles outbreak, gynaecologists and midwives should be active proponents of vaccination administration and counteract any vaccine hesitancy not only in patients but also among health care workers.

Background A direct carotid-cavernous fistula (CCF) is a rare complication that typically occurs in closed head injuries. The balloon-assisted occlusion is the most used treatment. However, this technique requires multiple inflation/deflations, which could be problematic in a vessel with acute vessel injury. Case Description In this study we reported a case of 72-year-old male patient with posttraumatic CCF, treated endovascularly with a transarterial Comaneci-assisted coiling embolization, highlighting the advantages and pitfalls of this innovative endovascular treatment. Conclusions The Comaneci-assisted coiling technique has proven to be advantageous both in the microcatheterization of the CCF and during coiling with remodeling technique. In addition, this device does not interrupt the vascular flow compared to balloon-assisted coiling and does not require long-term antiaggregation therapy with respect to the stent placement.

Background There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. Aims We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. Methods From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. Results The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p Conclusions Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits.

Aim: The aim of this study was to assess if pre- and post- event related potentials (ERPs) components after visual stimulation training admitted differences exist in subacute stroke patients and to...

Background The applicability of the current models for predicting functional outcome after thrombectomy in strokes with large vessel occlusion (LVO) is affected by a moderate predictive performance. Aims We aimed to develop and validate a nomogram with pre- and post-treatment factors for prediction of the probability of unfavorable outcome in patients with anterior and posterior LVO who received bridging therapy or direct thrombectomy Methods We conducted a cohort study on patients data collected prospectively in the Italian Endovascular Registry (IER). Unfavorable outcome was defined as three-month modified Rankin Scale (mRS) score 3–6. Six predictors, including NIH Stroke Scale (NIHSS) score, age, pre-stroke mRS score, bridging therapy or direct thrombectomy, grade of recanalization according to the thrombolysis in cerebral ischemia (TICI) grading system, and onset-to-end procedure time were identified a priori by three stroke experts. To generate the IER-START, the pre-established predictors were entered into a logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve (AUC-ROC). Results A total of 1802 patients with complete data for generating the IER-START was randomly dichotomized into training ( n = 1219) and test ( n = 583) sets. The AUC-ROC of IER-START was 0.838 (95% confidence interval [CI]): 0.816–0.869) in the training set, and 0.820 (95% CI: 0.786–0.854) in the test set. Conclusions The IER-START nomogram is the first prognostic model developed and validated in the largest population of stroke patients currently candidates to thrombectomy which reliably calculates the probability of three-month unfavorable outcome.

Background: Measurement of serum thyroperoxidase autoantibodies (TPOAb) during gestation as a classical marker for the risk of postpartum thyroiditis (PPT) predicts PPT in 1/3 to 1/2 of women. Very few studies have measured serum thyroid hormone Ab (THAb) during gestation, and none as a possible marker for PPT. Methods: In 412 women who were followed up from 7 to 11 weeks of gestation through 12 months after delivery, we measured THAb (T3.IgM, T3.IgG, T4.IgM, T4.IgG), thyroglobulin autoantibodies (TgAb) and TPOAb at study entry (7–11 week of gestation). Results: Sixty-three women (15.3%) developed PPT, which progressed to permanent hypothyroidism (PH) in 34/63 (54%). THAb+ve were 21/412 women (5.1%), the frequency being greater in those who then developed PPT (12/63 [19.0%] vs. 9/349 [2.6%], P = 4.6 × 10−8), and in the PH subgroup (26.5% [9/34] vs. 10.3% [10/29], P = 0.12). THAb positivity occurred in 9/76 women (11.8%) who were TgAb and/or TPOAb+ve compared to 12/336 women who were TgAb and TPOAb negative (3.6%, P = 0.0031). Of these 9 THAb+ve, TgAb and/or TPOAb+ve women, all (100%) developed PPT compared to 3/11 (27.3%, P = 0.0011) THAb+ve, TgAb and/or TPOAb negative women. Of these 9 and 3 PPT women, 8 and 1 progressed to PH (88.9% and 33.3%, respectively, P = 0.12). Conclusions: Gestational positivity of THAb enhance enormously the predictivity for PPT of gestational positivity of TPOAb/TgAb. However, their low frequency (5.1%) and their sensitivity (17.5% [21/63]) go against their application in lieu of TPOAb/TgAb. Keywords: Thyroid autoimmunity, Thyroid hormone autoantibodies, Pregnancy, Postpartum, Postpartum thyroiditis

In 2004, the U.S. Preventive Services Task Force (USPSTF) published a Grade D recommendation for both testicular self-examination (TSE) and clinical evaluation to screen for testicular cancer in asymptomatic males. This review committee reaffirmed these recommendations in 2009 and again in 2011 (Testicular Cancer: Screening Release Date: April 2011. Final Update Summary: Testicular Cancer: Screening. U.S. Preventive Services Task Force. September 2016). The 2011 USPSTF review found no significant evidence that would warrant a change from the last full review in 2004. We believe that the USPSTF erred in its assessments. As acknowledged in the task force report, testicular cancer is not believed to be preventable, and treatment of early detected testicular cancer is generally associated with very favorable outcomes; it is our belief therefore that every encouragement should be given to early detection. We are therefore requesting that the USPSTF review the D rating for testicular examination, both in a clinical setting and as self-examination. We are requesting this, as recent studies and public health warrant a change in grade. The new studies build on earlier studies that support the benefits of regular screening by individuals and their physicians. Further, and equally important, we believe that the current grade and attendant information confuses men and boys about the importance of self-care and wellness and continues to inadvertently reinforce negative cultural attitudes. We believe that adjusting the rating to a Grade B is both warranted and necessary.

This survey evaluated resources available to men and boys at the state level including state public health departments (SPHDs), other state agencies, and governor’s offices. Most of the resources and programs are found in the SPHDs and these administer state-initiated and federally funded health programs to provide services and protection to a broad range of populations; however, many men’s health advocates believe that SPHDs have failed to create equivalent services for men and boys, inadvertently creating a health disparity. Men’s Health Network conducts a survey of state resources, including those found in SPHDs, every 2 years to identify resources available for men and women, determine the extent of any disparity, and establish a relationship with SPHD officials. Data were obtained from all 50 states and Washington, D.C. An analysis of the 2016 survey data indicates that there are few resources allocated and a lack of readily available information on health and preventive care created specifically for men and boys. The data observed that most health information intended for men and boys was scarce among states or oftentimes included on websites that primarily focused on women’s health. A potential result of this is a loss of engagement with appropriate health-care providers due to a lack of information. This study continues to validate the disparity between health outcomes for women and men. It continues to highlight the need for better resource allocation, outreach, and health programs specifically tailored to men and boys in order to improve overall community well-being.

Background. Organic solvents cause diseases of the vestibular system. However, little is known regarding the correlation between vestibular damage and exposure to organic solvents below threshold limit values. The best measure by which to evaluate vestibular disorders is static and dynamic posturography. Objective. The aim of this study was to evaluate equilibrium disorders via static and dynamic posturography in workers without clear symptoms and exposed to low doses of mixed solvents. Methods. 200 subjects were selected. Using an Otometrics device (Madsen, Denmark), all subjects endured static and dynamic posturography testing with both eyes-open and eyes-closed conditions. Results were compared with a control group of unexposed individuals. Result. Based on the obtained data, the following results can be drawn: (a) subjects exposed to mixtures of solvents show highly significant differences regarding all static and dynamic posturography parameters in comparison to the control group; (b) posturography testing has proven to be a valid means by which to detect subliminal equilibrium disorders in subjects exposed to solvents. Conclusion. We can confirm that refinery workers exposed to mixtures of solvents can present subliminal equilibrium disorders. Early diagnosis of the latter is made possible by static and dynamic posturography.

After encountering two women with serum thyrotropin (TSH) levels greater in periovulatory phase than in other days of the menstrual cycle, we hypothesized that TSH levels could be sensitive to changes in circulating estrogens in women.The objective of this study was to evaluate whether serum TSH increases after an induced acute increase of serum estradiol, and compare serum TSH increase with that of prolactin (PRL) which is a classic estradiol-upregulated pituitary hormone.In this retrospective study, we resorted to stored frozen sera from 55 women who had undergone the GnRH agonist (buserelin)-acute stimulation test of ovarian steroidogenesis. This test, that is preceded by dexamethasone administration to suppress adrenal steroidogenesis, had been performed to show an increased buserelin-stimulated response of 17-hydroxyprogesterone, a response that is frequent in polycystic ovary syndrome. Fifty-five women had enough serum volume at pertinent times (first observation early in the follicular phase and all times of the test) to permit assay of serum estradiol, TSH and PRL.Before dexamethasone administration, estradiol averaged 26.4 ± 15.5 pg/ml (reference range 23–139, follicular phase), TSH 1.78 ± 0.86 mU/L (reference range 0.3–4.2) and PRL 409.4 ± 356 mU/L (reference range 70.8–556) (mean ± SD).Serum estradiol, TSH and PRL averaged 47.2 ± 27 pg/ml, 0.77 ± 0.48 mU/L and 246.4 ± 206.8 mU/L just prior to the buserelin injection, but they peaked at 253.4 ± 113.5 pg/ml (nv 83–495, midcycle), 3.30 ± 1.65 mU/L and 540.3 ± 695.2 mU/L after injection. The responses to buserelin of estradiol, TSH and PRL were of wide magnitude. There was a significant correlation between TSH peak and serum estradiol peak, betweeen AUC0-24 h-TSH and AUC0-24 h-estradiol, or between PRL peak and estradiol peak and AUC0-24 h -PRL and AUC0-24 h-estradiol in only a subgroup of women.Therefore, women with estradiol-dependent increase in serum TSH do exist. Reference bands of serum TSH dependent on the phases of the menstrual cycle should be available. Keywords: Thyrotropin, Prolactin, Menstrual cycle, Estradiol, Polycystic ovary syndrome, Buserelin

Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. OBJECTIVES: This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients. METHODS: In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations. RESULTS: Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively. CONCLUSIONS: Screening probands with clinically suspected AFD significantly increased diagnostic yield. The heart was the organ most commonly involved, independent of the clinical setting in which the patient was first evaluated. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Objective: The objective of this study was to investigate the relationship between adherence to statin therapy and the risk of exacerbation among elderly individuals affected by chronic obstructive pulmonary disease and cardiovascular disease. Methods: Using the healthcare utilisation databases of five Italian territorial units accounting for nearly 35% of the Italian population, we recruited a cohort of 6263 elderly persons (i.e. aged 65 years or older) with co-existing chronic obstructive pulmonary disease and cardiovascular disease who initiated statin therapy. Exposure was adherence to statins measured by the proportion of days of follow-up covered. Outcome was the first hospital admission for chronic obstructive pulmonary disease occurring in the period of observation. A proportional hazards model was used to estimate the hazard ratio and 95% confidence intervals for the exposure–outcome association, after adjusting for several covariates. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. Results: During an average follow-up of about 4 years, 1307 cohort members experienced the outcome. Compared with patients with low adherence (proportion of days of follow-up covered ≤ 40%), those with intermediate (proportion of days of follow-up covered 41–80%) and high (proportion of days of follow-up covered > 80%) adherence exhibited a lower risk of exacerbation of 16% (95% confidence interval 3–27) and 23% (95% confidence interval 10–34). Conclusions: In a real-world setting, we observed evidence that adherence to statin therapy markedly reduced the risk of chronic obstructive pulmonary disease exacerbations in elderly patients with co-existing chronic obstructive pulmonary disease and cardiovascular disease. Given the limited and controversial evidence from trials, more randomised controlled trials are urgently needed to better examine the potential benefits of statins as adjunct therapy in chronic obstructive pulmonary disease.

Objectives To describe NSAID utilization for musculoskeletal conditions in a large cohort of Italian elderly with cerebro/cardiovascular disease, a population in which NSAIDs should be generally avoided due to the prothrombotic potential. Methods Administrative data from five Italian geographic areas were analyzed. Patients aged ≥ 65 with a cerebro/cardiovascular event recorded between 2008 and 2011 (cohort entry) were selected. Prescription NSAIDs reimbursed for musculoskeletal conditions and dispensed during 1 year follow-up were retrieved to describe (i) prevalence of use, (ii) average amount of defined daily doses of NSAIDs claimed by users per day of follow-up, and (iii) distribution of the received daily dose (RDD) among patients with ≥ 2 dispensings. Among new users, i.e., patients without NSAID dispensings during 2 years before cohort entry, the first dispensed NSAID molecule was observed. Results Overall, 511,989 patients were selected. Across the five geographic areas, prevalence of use ranged from 48 to 21% and average consumption ranged between 30 and 67 DDD/1000 users/day. Around 10% of patients in the overall cohort had a RDD > 1. Nimesulide (9.6%) and diclofenac (7.5%) had the highest prevalence of use. The most consumed NSAIDs were nimesulide and coxibs with 10.6 and 7.5 DDD/1000 users/day, respectively. Among new users recruited in 2011, 30% had diclofenac or a coxibs as the first prescription. Conclusions NSAID use was common in the study cohort, particularly in central-southern areas. In contrast with current recommendations, coxibs and diclofenac were among the most prescribed active principles, even in new users. Interventions to promote appropriateness of use are warranted. Electronic supplementary material The online version of this article (10.1007/s00228-018-2411-y) contains supplementary material, which is available to authorized users.

Adolescence overweight and obesity have increased considerably, and the misperception of their weight status could reduce the efficiency of intervention programs. The aim of this study was to evaluate the prevalence rate of misperception and to assess the relationship between weight perception and anthropometric parameters, self-perception, physical activity, and adherence to the Mediterranean diet. A total of 1643 young adolescents (11–16 years old) were surveyed in a cross-sectional investigation during two scholastic years (period October–May of 2012–2013 and 2013–2014) in 15 secondary schools of Sicily, southern Italy. Data on demographic information, anthropometric characteristics (bioelectrical impedance), physical activity level, The Children and Youth Physical Self-Perception Profile, weight perception, and dietary habits (KIDMED) were collected. Misperception was found in the 27.6 % of the young adolescents, and boys were more likely to underestimate their weight status, while girls had a high percentage of overestimation. The strong association with weight misperception was with socioeconomic status, waist circumference, physical activities, and physical self-worth. Moreover, a good adherence to the Mediterranean diet was inversely associated with both overestimation and underestimation in both boys and girls. These findings highlight that almost one-third of the participants had a weight misperception that was associated with several anthropometric, social, and lifestyle factors. Future intervention to prevent overweight and obesity should consider not only gender-specific differences, but also parental SES, perception, and satisfaction of body weight status.

Local drug delivery of an anti-proliferative drug from balloon catheter systems to the site of arterial injury has been attempted repeatedly over the years with limited success in drug uptake and retention. Accessibility of the drug at the site is critical to combat the body's response to the procedural trauma of angioplasty. Recently, formulations have been designed which achieve delivery of therapeutic doses of the anti-proliferative drug paclitaxel to arteries with higher efficiency and longer tissue retention. These formulations succeed through formation of a drug reservoir in the artery wall enabling release after the initial angioplasty procedure. These formulations have become the cornerstone of several drug coated balloon (DCB) technologies which have found an initial, broad therapeutic application in the treatment of stenosis of the superficial femoral artery (SFA). DCBs achieve drug delivery while leaving no implant behind and represent a new class of combination products developed at the interface of engineering, chemistry and medical science. This review article summarizes the development of the LUTONIX® drug coated balloon catheter. The introduction of DCB technology has provided clinicians and patients with new SFA treatment options while ongoing clinical evidence in additional vascular beds is generated.

The aim of the study was to evaluate the effects on serum insulin and serum thyroid profile of a dietary supplement, myo-inositol, given alone or in combination with melatonin to women during menopausal transition.Forty women aged 45-55 years and at least 6 months of amenorrhea were enrolled in this study. They were randomly assigned to two groups of 20 each. One group took myo-inositol (myo-Ins) (2 g twice a day) and the other group took 2 g/d myo-Ins plus 3 g/d melatonin before sleeping. At the beginning of the study and after 6 months, all women were evaluated for the following indices: waist circumference, body mass index, blood pressure, endometrial thickness, as well as serum concentrations of TSH, FT3, FT4 and insulin.Both at baseline and at 6 months, the two groups were statistically similar for each of the considered indices. If percent changes (Δ%, 6 months over baseline) are contrasted in the two groups, serum TSH decreased in the myo-Ins group but increased in the latter, while serum insulin decreased in both groups.The combination of myo-Ins plus melatonin seems to affect positively glucose metabolism, while myo-Ins only seems to improve thyroid function.

Objectives To assess the association of the anticholinergic medication burden with hospitalization and mortality in nursing home elderly patients and to investigate the role of coronary artery disease (CAD). Design Longitudinal (5-year) retrospective observational study. Setting Nursing homes in Italy. Participants A total of 3761 nursing home older residents. Measurements A comprehensive clinical and functional assessment was carried out through the interRAI long-term care facility instrument. The anticholinergic burden was assessed through the anticholinergic cognitive burden (ACB) scale. Occurrence of hospitalization/all-cause mortality was the primary composite outcome. First hospitalization and all-cause mortality were the secondary outcomes of the study. Hazard ratios (HRs) and subdistribution HRs were obtained through Cox and competing risk (death as competing event for hospitalization) models. Results Within the sample (mean age 83 ± 7 years; 72% females) the incidence rate of the primary outcome was 10/100 person-year. After adjusting for potential confounders and compared with participants with an ACB of 0, those with an ACB of 1 [HR 1.46; 95% confidence interval (CI) 1.12–1.90] and ABC of 2+ (HR 1.41; 95% CI 1.11–1.79) presented an increased risk of developing the primary outcome. After stratification, the risk for the primary outcome increased along with the anticholinergic burden, only for participants affected by CAD (HR 1.53; 95% CI 0.94–2.50 and HR 1.71; 95% CI 1.09–2.68 for the ACB of 1 and ACB of 2+ groups). An ACB score of 2+ was marginally associated with first hospitalization, considering death as a competing risk, only for those with CAD (subdistribution HR 3.47; 95% CI 0.99–12.3). Conclusions Anticholinergic medication burden is associated to hospitalization and all-cause mortality in institutionalized older adults. CAD increases such risk. The effectiveness and safety profile of complex drug regimens should be reconsidered in this population.

Background: In a globally aging population, chronic conditions with a high impact on healthcare costs and quality of life, such as osteoporosis and associated fractures, are a matter of concern. For osteoporosis, several drug treatments are available, but evidence on adverse cardiovascular and cerebrovascular (CCV) events, and in particular the risk of atrial fibrillation (AF), related to anti-osteoporotic drug use is inconclusive. The objective of this study was to evaluate the association between the use of bisphosphonates (BPs), strontium ranelate (SR), and other anti-osteoporosis drugs and the risk of AF and CCV events in a large cohort of patients affected by CCV diseases. Methods: Based on a cohort of patients aged 65 years and over, discharged from the hospitals of five large Italian areas after a CCV event between 2008 and 2011, two nested case-control studies were conducted. Cases were patients with a subsequent hospital admission for AF or CCV; four controls for each case were randomly selected and matched by age group, sex and follow-up time. A total of three exposure measures were tested: ever use, adherence and recency of use. In the conditional logistic regression models, patients not treated with any anti-osteoporotic medication were considered as the reference category. Results: The initial cohort accounted for 657,246 patients. Neither BPs nor SR use was associated with an increased risk of AF regardless of the adherence and recency of use. Overall BP and SR use was associated with a slightly increased risk of CCV; however, results reversed when considering higher adherence: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.71-0.92 for BPs and OR 0.71, 95% CI 0.52-0.97 for SR. Conclusions: BPs do not increase cardiovascular risk and can be prescribed to elderly patients for osteoporosis treatment. However, patients with pre-existing cerebrovascular/cardiovascular conditions should be carefully monitored.

Background and Purpose— As a reliable scoring system to detect the risk of symptomatic intracerebral hemorrhage after thrombectomy for ischemic stroke is not yet available, we developed a nomogram for predicting symptomatic intracerebral hemorrhage in patients with large vessel occlusion in the anterior circulation who received bridging of thrombectomy with intravenous thrombolysis (training set), and to validate the model by using a cohort of patients treated with direct thrombectomy (test set). Methods— We conducted a cohort study on prospectively collected data from 3714 patients enrolled in the IER (Italian Registry of Endovascular Stroke Treatment in Acute Stroke). Symptomatic intracerebral hemorrhage was defined as any type of intracerebral hemorrhage with increase of ≥4 National Institutes of Health Stroke Scale score points from baseline ≤24 hours or death. Based on multivariate logistic models, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve. Results— National Institutes of Health Stroke Scale score, onset-to-end procedure time, age, unsuccessful recanalization, and Careggi collateral score composed the IER-SICH nomogram. After removing Careggi collateral score from the first model, a second model including Alberta Stroke Program Early CT Score was developed. The area under the receiver operating characteristic curve of the IER-SICH nomogram was 0.778 in the training set (n=492) and 0.709 in the test set (n=399). The area under the receiver operating characteristic curve of the second model was 0.733 in the training set (n=988) and 0.685 in the test set (n=779). Conclusions— The IER-SICH nomogram is the first model developed and validated for predicting symptomatic intracerebral hemorrhage after thrombectomy. It may provide indications on early identification of patients for more or less postprocedural intensive management.