Emergency department reorganisation to cope with COVID-19 outbreak in Milan university hospital: a time-sensitive challenge.

BACKGROUND: In March 2020 we faced a huge spread of the epidemic of SARS-CoV2 in northern Italy; the Emergency Departments (ED) and the Emergency Medical Services (EMS) were overwhelmed by patients requiring care. The hospitals were forced to reorganize their services, and the ED was the focal point of this challenge. As Emergency Department in a metropolitan area of the region most affected, we saw an increasing number of patients with COVID-19, and we made some structural and staff implementations according to the evolution of the epidemic. METHODS: We analysed in a narrative way the weaknesses and the point of strength of our response to COVID-19 first outbreak, focusing point by point on main challenges and minor details involved in our ED response to the pandemics. RESULTS: The main stems for our response to the pandemic were: use of clear and shared contingency plans, as long as preparedness to implement them; stockage of as much as useful material can be stocked; training of the personnel to be prepared for a fast response, trying to maintain divided pathway for COVID-19 and non-COVID-19 patients, well-done isolation is a key factor; preparedness to de-escalate as soon as needed. CONCLUSIONS: We evaluated our experience and analysed the weakness and strength of our first response to share it with the rest of the scientific community and colleagues worldwide, hoping to facilitate others who will face the same challenge or similar challenges in the future. Shared experience is the best way to learn and to avoid making the same mistakes.

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity.

BACKGROUND: The approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients. The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting. METHODS: We collected data of all patients starting Sativex between January 2014 and February 2015 from the mandatory Italian medicines agency (AIFA) e-registry. Spasticity assessment by the 0-10 numerical rating scale (NRS) scale is available at baseline, after 1 month of treatment (trial period), and at 3 and 6 months. RESULTS: A total of 1615 patients were recruited from 30 MS centres across Italy. After one treatment month (trial period), we found 70.5% of patients reaching a ≥20% improvement (initial response, IR) and 28.2% who had already reached a ≥30% improvement (clinically relevant response, CRR), with a mean NRS score reduction of 22.6% (from 7.5 to 5.8). After a multivariate analysis, we found an increased probability to reach IR at the first month among patients with primary and secondary progressive MS, (n=1169, OR 1.4 95% CI 1.04 to 1.9, p=0.025) and among patients with >8 NRS score at baseline (OR 1.8 95% CI 1.3-2.4 p<0.001). During the 6 months observation period, 631(39.5%) patients discontinued treatment. The main reasons for discontinuation were lack of effectiveness (n=375, 26.2%) and/or adverse events (n=268, 18.7%). CONCLUSIONS: Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.

Use of herbal remedies by multiple sclerosis patients: a nation-wide survey in Italy.

Though recent progress in multiple sclerosis (MS) treatment is remarkable, numerous unmet needs remain to be addressed often inducing patients to look for complementary and alternative medicines (CAM), especially herbal remedies (HR). HR use, scarcely investigated in MS, may cause adverse reactions (AR) and interfere with conventional treatment. We performed a survey aimed at evaluating use and attitudes towards HR and factor associated to HR use. Other CAM use and attitudes have been investigated as well. Multiple-choice questionnaires were distributed to MS out patients attending 14 Italian referral Centers. Multivariable logistic regression was used to identify HR use determinants. Present/past HR use for either MS or other diseases was reported in 35.6 % of 2419 cases (95 % CI 36.0-40.0 %). CAM use was reported in 42.5 % of cases. Independent predictors of HR use were represented by higher education, geographic area, dissatisfaction with conventional treatment of diseases other than MS and benefit perception from CAM use. Both HR and CAM use were not always disclosed to the healthcare professional. In conclusion, HR and other CAM appear to be popular among MS patients. The involvement of the healthcare professionals appears to be scarce with potential risk of AR or interference with conventional treatments.

Papillary glioneuronal tumor: case report and review of literature.

Papillary glioneuronal tumor (PGNT) is a recently described central nervous system neoplasm that mostly occurs in the supratentorial system, adjacent to the lateral ventricles. In 2007, WHO classified PGNT as grade I neuronal-glial tumor because of the characteristic papillary architecture and bipartite (astrocytic and neuronal/neurocytic) cell population. As a newly established entity of mixed glioneuronal tumor family, PGNT attracted extensive attention recently. In our report we discuss the clinical, neuroradiological and surgical features. The final result is compared with literature data.

A rare localization of cerebral venous sinus thrombosis. Case report.

In this work the Authors report their experience on the treatment of a case of cavernous venous sinus thrombosis. The diagnosis is clinical and neuroradiological, CT, MRN, cerebral angiography and orbital venography have aided in establishing the diagnosis during life. Very interesting is the therapeutic approach.

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

Predictive accuracy of triage nurses evaluation in risk stratification of syncope in the emergency department.

BACKGROUND: Syncope is a common clinical problem that accounts for 1-3% of all emergency department (ED) visits. Its prognosis is extremely variable with a 1-year mortality that may reach 30%. There are no available data about the accuracy of nursing triage in identifying high-risk syncope. The aim of our study was to evaluate the predictive accuracy of nursing triage in identifying high-risk syncope. METHODS: We conducted a retrospective study on 678 consecutive patients who presented with syncope at four EDs. For each patient, nursing triage, comorbidities, clinical features and adverse events that occurred both in the ED and at 10-day follow-up were assessed. Adverse events included death, readmission to ED, need for major therapeutic procedures, cardiopulmonary resuscitation, intensive care unit admittance, acute antiarrhythmic therapy and major causes of syncope identified during the ED evaluation. Predictive accuracy of nursing triage was evaluated. RESULTS: We observed a total of 55 (8.1%) adverse events. Eight of them (9.4%) occurred among the 85 patients who were identified as high priority by nursing triage. Sensitivity (Sn) and specificity (Sp) of urgent nursing triage in identifying adverse outcomes in the ED (19 patients) were 21% (95% CI 3% to 39%) and 88% (95% CI 85% to 90%), while the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were 1.7 and 0.9, respectively. Sn and Sp for 10-day adverse events were 15% (95% CI 5% to 24%) and 88% (95% CI 85% to 90%), respectively, with a LR+ of 1.18 and a LR- of 0.98. CONCLUSIONS: Nursing triage was characterised by a low predictive accuracy in identifying high-risk individuals.

Internal haemorrhagic pachymeningiosis: specific disease or complication of chronic subdural hematoma? Report of five cases surgically treated and literature review.

BACKGROUND: Internal haemorrhagic pachymeningiosis (IHP) is a rare disease characterized by a fibrous thickening and inflammatory infiltration in dural space mimicking chronic subdural hematoma. The pathogenesis of IHP is not entirely clear yet and treatment is still controversial. OBJECTIVE: We want to emphasize the importance of differentiating pachymeningiosis from chronic subdural hematoma as distinct pathological entities. PATIENTS AND METHODS: The records of five selected cases of IHP histologically confirmed were reviewed, focusing onset, neuroimaging, surgery and outcomes. CONCLUSIONS: IHP is most likely underestimated. Only through multidisciplinary approach it is possible to plane the proper therapeutic strategy. The diagnosis of IHP is confirmed by definitive histology but in some cases is possible with intraoperative frozen section.

Social and interpersonal relationship modifications after renal transplant. A statistic and epidemiologic evaluation.

INTRODUCTION: Kidney and liver transplants are the most frequent transplantation procedures carried out in Italy. We report the result of an epidemiological study on kidney transplanted patients resident in the Province of Messina (Italy). METHODS: Seventy-five patients were enrolled between June 2010 march 2011, interviewed and evaluated using an adapted Italian version short-form 36. Socio-economic characteristics, quality of life modifications and involvement in transplant-related charities were studied. The follow-up period was ranging between 52 and 356 months. All subjects gave written informed consent and all results were analysed by chi-square test. RESULTS: No statistically significant differences were found between sexes, social and interpersonal relationship modifications. DISCUSSION: The benefits obtained on quality of life after transplantation is the prerogative of a small percentage of patients and is related to medium and high socio-economic conditions. The possibility of avoiding the haemodialysis represents the primary benefit for the totality of patients.

[Syncope and work: role of the occupational physician and global risk stratification]. / Sincope e rischio lavorativo: ruolo del medico del lavoro e stratificazione globale del rischio.

Safety risk for subjects suffering from syncope while working has not been as yet addressed by occupational medicine. The present study was aimed at evaluating a new developed methodology for job tasks risk stratification in patients with syncope. During a work-shop on syncope and occupational risk, 149 occupational physicians (OP) with about 10 years of clinical experience were asked to fulfil a Visual Analogue Scale (VAS) concerning the doctor's estimated potential damage (D) to the worker and the probability of a damage to occur (P) should syncope take place during the job task. Five job tasks characterized by different risk for safety (1, driving; 2, toxic products handling; 3, job performed closed to hot surfaces o free flames; 4, surgical activity; 5, office job) were identified. OP correctly stratified the risk associated to the different job tasks in patients with syncope. Unexpectedly, task #3 was given a risk similar to that obtained in drivers. This might be of paramount clinical and social importance when patients with syncope have to return to their job tasks.

[Syncope and occupational risk survey: the role of continuing education and multidisciplinary approach]. / Indagine conoscitiva sulla percezione del problema sincope in relazione al rischio lavorativo nella pratica clinica: ruolo della formazione e dell'approccio multidisciplinare.

Syncope is a common disorder characterized most of the times by a positive clinical outcome. However, it may turn to a life threatening event even for working colleagues and third party when occurring during an high risk job. We have recently found that, out of 670 patients admitted to the Emergency Department (ED) for syncope, about 50% were potential workers, being their age between 18 and 65 years. Also, we found that in this group of patients syncope recurrence was as high as 11% at 6 months. It is unknown how physicians address the problem of the occupational risk in patients suffering from syncope and how occupational aspects are taken into account in the clinical judgment before work readmission. One hundred eighty five doctors (149 occupational physicians, OP), participating in a work-shop on syncope, were asked to fulfill a questionnaire about their clinical experience and their attention to the occupational aspects in patients after syncope. Despite long lasting clinical experience, 41% of OP did not scrutinize syncope as a relevant symptom in their daily activity. 65% of the other specialists were used to address the occupational risk aspects in their syncope patients. A multidisciplinary approach involving continuing education on safety at work might reduce work accidents due to syncope relapse and promote a safe and suitable re-employment of patients with syncope. scrutinize syncope as a relevant symptom in their daily activity. 65% of the other specialists were used to address the occupational risk aspects in their syncope patients. A multidisciplinary approach involving continuing education on safety at work might reduce work accidents due to syncope relapse and promote a safe and suitable re-employment of patients with syncope.

Treatment of life-threatening type I refractory coeliac disease with long-term infliximab.

Whereas medical approach to coeliac disease is well defined, treatment of patients who fail to respond to a gluten-free diet remains still problematic. We describe the case of a 68 years DQ-2 positive male who lost response to a strict gluten-free diet after an initial response over a 3-year period. His conditions became critical despite high dose prednisone treatment. After a careful differential diagnosis, the patient was classified as having a type I refractory coeliac disease and a single infusion of infliximab at 5mg/kg was given with excellent clinical results. However, clinical response was lost despite background therapy with azathioprine. Six months after the single infusion an induction therapy with infliximab and, thereafter, maintenance every 8 weeks was administered with excellent clinical results. Since small bowel histology recovered very slowly treatment was continued over the following 2 years with a return to near normal architecture. This case shows that anti-tumour necrosis factor treatment may be used in carefully selected patients with type I refractory coeliac disease.

Locomotor-related networks in the lumbosacral enlargement of the adult spinal cat: activation through intraspinal microstimulation.

It is commonly accepted that locomotor-related neuronal circuitry resides in the lumbosacral spinal cord. Pharmacological agents, epidural electrical stimulation, and sensory stimulation can be used to activate these instrinsic networks in in vitro neonatal rat and in vivo cat preparations. In this study, we investigated the use of low-level tonic intraspinal microstimulation (ISMS) as a means of activating spinal locomotor networks in adult cats with complete spinal transections. Trains of low-amplitude electrical pulses were delivered to the spinal cord via groups of fine microwires implanted in the ventral horns of the lumbosacral enlargement. In contrast to published reports, tonic ISMS applied through microwires in the caudal regions of the lumbosacral enlargement (L7-S1) was more effective in eliciting alternating movements in the hindlimbs than stimulation in the rostral regions. Possible mechanisms of action of tonic ISMS include depolarization of locally oscillating networks in the lumbosacral cord, backfiring of primary afferents, or activation of propriospinal neurons.

Experimental evidence suggesting that nitric oxide diffuses from tissue into blood but not from blood into tissue.

The aim of this study was to evaluate in vivo whether nitric oxide (NO) is able to diffuse from blood into tissues and vice versa from tissues into blood. We used an in vivo model of intestinal ischemia (superior mesenteric artery occlusion) selectively increasing NO levels in intestinal tissue and an infusion of L-arginine selectively increasing NO levels in blood. In this model we followed formation of nitrosyl complexes of hemoglobin (Hb-NO) in blood and nitrosyl-diethyldithiocarbamate-iron complexes (DETC--Fe--NO) in ischemic intestine and normoxic tissues by means of electron paramagnetic resonance spectroscopy. NO trapping by DETC--Fe in the tissues resulted in a reduction of Hb--NO levels in blood accompanied by the formation of water-insoluble DETC--Fe-NO complexes in ischemic intestine and normoxic tissues both during ischemia and during reperfusion. Administration of L-arginine increased NO levels in blood but neither in ischemic intestine nor in normoxic tissue. Our data suggest that NO released in blood from endothelial cells does not diffuse into tissue. In contrast, NO formed in tissue diffuses into blood. The latter indicates that NO formed in tissues may exert its biological activities systematically.

Metabotropic G-protein-coupled glutamate receptors as therapeutic targets.

Metabotropic glutamate receptors have received considerable attention over the past decade in view of their relevance in multiple aspects of glutamatergic transmission. Recent advances in the molecular biology, pharmacology and medicinal chemistry of this family of G-protein-coupled receptors have led to therapeutic opportunities for subtype-selective modulators in brain disorders and diseases such as ischemia and schizophrenia.

IL-6 knock-out mice exhibit resistance to splanchnic artery occlusion shock.

We used IL-6 knock-out (KO) mice to evaluate a possible role for IL-6 in the pathogenesis of splanchnic artery occlusion shock (SAO). SAO shock was induced by clamping both the superior mesenteric artery and the celiac trunk, followed by release of the clamp. There was a marked increase in the peroxynitrite formation in the plasma of the SAO-shocked IL-6 wild-type (WT) mice after reperfusion. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine in the necrotic ileum in shocked IL-6 WT mice. SAO-shocked WT mice developed a significant increase of tissue myeloperoxidase (MPO) and malondialdehyde (MDA) activity and marked histological injury to the distal ileum. SAO shock was also associated with a significant mortality (0% survival). Reperfused ileum tissue sections from SAO-shocked WT mice showed positive staining for P-selectin. Little specific staining was observed in sham-WT mice. Staining of ileum tissue obtained from sham-operated WT mice with anti-ICAM-1 antibody showed weak but diffuse staining, demonstrating that ICAM-1 is constitutively expressed. However, after SAO shock the staining intensity increased substantially in the ileum section from WT mice. Intensity and degree of P-selectin and ICAM-1 were markedly reduced in tissue section from SAO-shocked IL-6 KO mice. SAO-shocked IL-6 KO mice also show significant reduction of neutrophil infiltration into the reperfused intestine, as evidenced by reduced MPO activity, improved histological status of the reperfused tissues, reduced peroxynitrite formation, reduced MDA levels, and improved survival. In vivo treatment with anti-IL-6 significantly prevents the inflammatory process. Our results clearly demonstrate that IL-6 plays an important role in ischemia and reperfusion injury and allows the hypothesis that inhibition of IL-6 may represent a novel and possible strategy. Part of this effect may be due to inhibition of the expression of adhesion molecules and subsequent reduction of neutrophil-mediated cellular injury.

[Syncope and work. STePS study (Short Term Prognosis of Syncope)]. / La sincope in età lavorativa. Studio multicentrico prospettico STePS.

BACKGROUND: Recurrent syncope is a common medical problem responsible for 3-5% of emergency department (ED) accesses and 1-6% of hospital admissions. If syncope occurs in a subject working in a critical safety task, the consequences of this event might be very dangerous for the worker, colleagues, others or for the environment. Therefore, syncope management is a major problem for occupational medicine, converning the general safety at work. AIMS: To evaluate the syncope events in a group of potential workers aged 18 to 65 years; to evaluate the symptoms preceding syncope and the presence of associated illnesses and recurrent events. POPULATION AND RESULTS: This study is part of the prospective study STePS (Short Term Prognosis of Syncope), and included 305 consecutive patients (aged 18-65 years, female 56%) who had syncope as a main symptom and presented at ED of four general hospitals in the Milan area, Italy, between the 23rd of January and 30th of June 2004. The 24% of subjects were hospitalized. In 21% the syncope occurs suddenly without any preceding symptom. The 67% of subjects didn't have any important illness at the time. 50% of subjects had recurrent syncope. In four subjects another syncope occurred in a 10 day follow-up. CONCLUSIONS: occupational medicine should consider syncope scrupulously. Proper diagnostic management is important to permit a correct evaluation of work safety issues.