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Myasthenia gravis (MG) is a rare, autoimmune, neurological disorder. Most MG patients have autoantibodies against acetylcholine receptors (AChRs). Some have autoantibodies against muscle-specific tyrosine kinase (MuSK) or lipoprotein-receptor-related protein 4 (LRP4), and some are seronegative. Standard of care, which includes anti-cholinesterase drugs, thymectomy, corticosteroids (CS), and off-label use of non-steroidal immunosuppressive drugs (NSISTs), is bounded by potential side effects and limited efficacy in refractory generalized MG (gMG) patients. This highlights the need for new therapeutic approaches for MG. Eculizumab, a monoclonal antibody that inhibits the complement system, has been recently approved in Italy for refractory gMG. A panel of 11 experts met to discuss unmet therapeutic needs in the acute and chronic phases of the disease, as well as the standard of care for refractory patients. Survival was emphasized as an acute phase outcome. In the chronic phase, persistent remission and early recognition of exacerbations to prevent myasthenic crisis and respiratory failure were considered crucial. Refractory patients require treatments with fast onset of action, improved tolerability, and the ability to slow disease progression and increase life expectancy. The Panel agreed that eculizumab would presumably meet the therapeutic needs of many refractory gMG patients. The panel concluded that the unmet needs of current standard of care treatments for gMG are significant. Evaluating new therapeutic options accurately is essential to find the best balance between efficacy and tolerability for each patient. Collecting real-world data on novel molecules in routine clinical practice is necessary to address unmet needs., Competing Interests: Declarations Conflict of Interest RM received funding for Travel, Meeting attendance or Advisory Board participation from Alexion, Argenx, Biomarin, Catalyst, SANOFI, Regeneron and UCB.FS received public speaking honoraria from Alexion, argenx, Biogen, Genpharm, Medpharma, Medison Pharma, Mylan, Neopharm Israel, Novartis, Roche, Sanofi, Zai Lab; compensation for advisory boards from Alexion, Almirall, argenx, Astrazeneca, Avexis, Biogen, Forward Pharma, Dianthus, Lexeo Therapeutics, Merk, Novartis GmBh, Reata, Roche, Sandoz, Sanofi, Takeda; consultation fees from Alexion, Dianthus, EPG Comunication Holding ltd, Forward Pharma, Medscape, Novatek,PeerView, Vitaccess; he has been clinical trial principal investigator for Alexion, argenx, Dianthus, Immunovant, Lediant, Novartis, Prilenia, Sanofi.GA declares conference honoraria, advisory board and travel grants from Kedrion, Jannsen, Alnylam, Alexion, Argenx, Takeda.DMB declares advisory board honoraria from Argenx, Alexion, Roche; research support as PI for Roche and Alexion; speaker's Honoraria from Argenx, Alexion, UCB.AE has no competing interests to declare.FH has no competing interests to declare.RL declares lecture fees, advisory board, videointerview, fees for meeting chairing and scientific organization from Summeet, Alexion Pharma Italy, UCB Pharma, Med Stage, Amicus Therapeutics, Alfasigma, ECM network, Healthware group, PTS, Aim Education, Sanofi Genzyme Corporation.EP reports personal fees from Biogen, Roche, Novartis, Alexion and UCB Biopharma outside the submitted work. EP is part of the advisory boards for Biogen, Roche, Alexion, UCB Pharma.CR received honoraria for speaking, advisory boards and compensation for congress participations from Alexion, Argenx, and UCB, outside the submitted work.AS, MS and GP have no competing interests to declare., (© 2024. Fondazione Società Italiana di Neurologia.)

Objective: To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA)., Methods: Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6)., Results: We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14., Conclusions: Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear., Competing Interests: Competing interests: LM has received honoraria for speaking and compensation for congress participations from: Sanofi Genzyme and Biogen. LB reports speaker honoraria from PTC Therapeutics, participation in advisory boards for PTC Therapeutics and Sarepta Therapeutics and participation in research sponsored by Santhera Pharmaceuticals. SB received funds for travel and congress participation from Sanofi Genzyme and Biogen. LP has received compensation for congress participations from: Sanofi Genzyme and Biogen. MG received honoraria for speaking and grants to attend scientific meetings from Sanofi-Genzyme and Pfizer. VB compensation for congress participations from Biogen and Sanofi Genzyme. LC received compensation for congress participations from Biogen. RP has received compensation for congress participation from Sanofi Genzyme and Biogen. RT has received compensation for congress participations from Sanofi Genzyme, Biogen and Roche. ES has received compensation for congress participations from: Biogen. GR has received compensation for congress participations from Sanofi Genzyme, CSL Behring, Santhera and Biogen. RZ has received funds for travel and congress participation from Biogen. MS has received speaker’s honoraria from ITALFARMACO, PIAM, Boheringer and Novartis Pharmaceuticals. LP received compensation for congress participations from Biogen Inc, Italy. AS received honoraria for speaking and grants to attend scientific meetings from Sanofi-Genzyme, Alnylam Pharmaceuticals, Akcea Therapeutics and Pfizer. LV has received compensation for congress participation from Sanofi Genzyme and Biogen. RM received compensation for participating on advisory boards in relation to MG clinical trial design, congress participations and research support in the last 5 years from: Catalyst Pharmaceuticals, Alexion Pharmaceuticals, ARGENX Pharma, Biomarin. RL has received: Lecture fees from LT3 s.r.l., NICO s.r.l., SUMMEET s.r.l. and GALEN SYMPOSION s.r.o.; fees for consultancy (Advisory Board) from LT3 s.r.l. and PREX s.r.l.; fees for scientific meeting organization from I & C s.r.l.; Chair meeting fees from PLANNING CONGRESSI s.r.l. GC in the last two years has received compensation for advisory board compensation from: Sanofi Genzyme, Spark, Roche, Lupin and Santhera, congress participations from: Sanofi Genzyme, CSL Behring, Sarepta and Biogen. ILS received compensation for congress participation from Biogen, Italy. TM has received compensation for Scientific Board participations from Sanofi Genzyme; for congress participation from Biogen. GC received compensation for participation ad advisory board for Roche, Sarepta and Italfarmaco. EP reports personal fees from Sarepta, grants and non-financial support from Santhera, personal fees and non-financial support from PTC Pharmaceuticals, non-financial support from Genzyme, personal fees from Roche, outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the efficacy of orvepitant (10 or 30 mg given once daily, orally for 4 weeks), a neurokinin-1 receptor antagonist, compared with placebo in reducing the intensity of epidermal growth factor receptor inhibitor (EGFRI)-induced intense pruritus., Design: Randomised, double-blind, placebo-controlled clinical trial., Setting: 15 hospitals in Italy and five hospitals in the UK., Participants: 44 patients aged ≥18 years receiving an EGFRI for a histologically confirmed malignant solid tumour and experiencing moderate or intense pruritus after EGFRI treatment., Intervention: 30 or 10 mg orvepitant or placebo tablets once daily for 4 weeks (randomised 1:1:1)., Primary and Secondary Outcome Measures: The primary endpoint was change from baseline in mean patient-recorded numerical rating scale (NRS) score (over the last three recordings) at week 4. Secondary outcome measures were NRS score, verbal rating scale score, Skindex-16 and Leeds Sleep Evaluation Questionnaire at each study visit (baseline, weeks 1, 4, 8); rescue medication use; EGFRI dose reduction; and study withdrawal because of intense uncontrolled pruritus., Results: The trial was terminated early because of recruitment challenges; only 44 of the planned 90 patients were randomised. All patients were analysed for efficacy and safety. Mean NRS score change from baseline to week 4 was -2.78 (SD: 2.64) points in the 30 mg group, -3.04 (SD: 3.06) points in the 10 mg group and -3.21 (SD: 1.77) points in the placebo group; the difference between orvepitant and placebo was not statistically significant. No safety signal was detected. Adverse events related to orvepitant (asthenia, dizziness, dry mouth, hyperhidrosis) were all of mild or moderate severity., Conclusions: Orvepitant was safe and well tolerated. No difference in NRS score between the orvepitant and placebo groups was observed at the week 4 primary endpoint. A number of explanations for this outcome are possible., Trial Registration Number: EudraCT2013-002763-25., Competing Interests: Competing interests: MT is a current employee and ER is a past employee of NeRRe Therapeutics, and both are inventors on a granted patent on novel uses of orvepitant. BV and PG received payment from NeRRe as investigators in this study. AD received payment from NeRRe for service as the chief medical officer for this study. DJ is an employee of Cromsource, who received payment from NeRRe for statistical analysis of this study. PH has received payment from NeRRe as a consultant. MEL reports receiving personal fees from Legacy Healthcare Services, AdgeroBio Pharmaceuticals, Amryt Pharma, Celldex Therapeutics, Debiopharm, Galderma Research and Development, Johnson & Johnson, Novocure, Lindi Skin, Merck Sharp and Dohme, Helsinn Healthcare, Janssen Research & Development, Menlo Therapeutics, Novartis Pharmaceuticals, F Hoffmann-La Roche, AbbVie, Boehringer Ingelheim Pharma, Allergan, Amgen, ER Squibb & Sons, EMD Serono, AstraZeneca Pharmaceuticals, Genentech, Leo Pharma, Seattle Genetics, Bayer, Männer SAS, Lutris Pharma, Pierre Fabre, Paxman Cooler, Adjucare, Dignitana, Biotechspert, Teva Pharmaceuticals Mexico, Parexel, OnQuality Pharmaceuticals, Novartis, Our Brain Bank, Millennium Pharmaceuticals, and research funding from Berg Health, Bristol-Myers Squibb, Lutris Pharma, Novocure, Paxman, Biotest and Veloce BioPharma. GT reports no conflicts of interest. AW reports receiving payment from NeRRe as chair of the advisory board and from Advent Life Sciences for consultancy, Canbex Therapeutics as a non-executive director (past position), Calcico Therapeutics as chairman (past position) and a non-executive director (past position), and the Wellcome Trust as a member of grant committees. SS reports receiving payment from NeRRe as a member of the advisory board and from Almirall, Astellas Pharma, Beiersdorf, Celgene, Chugai Pharma, Creabilis, Daiichi Sankyo, Galderma, Helsinn, Kiniska Pharmaceuticals, Kneipp, Maruho, Merz Pharma, Novartis, Pierre Fabre Laboratories, Sienna Biopharmaceuticals and Ziarco as a member of their advisory boards and from Menlo Therapeutics as an investigator and participation as an investigator in trials sponsored by Dermascence, Trevi Therapeutics and Vanda Pharmaceuticals., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of this study was to evaluate the epidemiological data regarding congenital and perinatal infections in the Marche region to verify the existence of differences in relation to maternal country of origin. This prospective study was conducted from May 2001 to April 2012, and it involved all the maternity units of the Marche region. A total of 10232 pregnant women were included, 25.1% of whom were of foreign nationality while the number of births totalled 10371. Estimated uptake of antenatal screening was 80.5% for CMV infection, 98.6% for HBV infection, 97.5% for HCV infection, 97.4% for HIV infection, 93.1% for syphilis and 98.5% for toxoplasmosis. For group B streptococcus vaginal and perianal swabs were performed in 81.2% of all women (78.4% in immigrant and 90.4% in Italian women; the difference was statistically significant [p 0.001]) and 13.6% were positive. The overall prevalence for CMV infection was 72.3% (91.9% in immigrant women) while for toxoplasmosis it was 27.5% (28.8% in immigrant women). The rate of seroconversion in pregnant women investigated for CMV infection was 0.28%, while that for toxoplasmosis was 0.09%. The overall prevalence for HBV infection was 0.79% (4.3% in immigrant and 0.4% in Italian pregnant women; the difference was statistically significant [p 0.001]), 0.4% for HCV infection (1% in immigrant and 0.48% in Italian pregnant women; the difference was not statistically significant [p 0.413]), 0.22% for syphilis (0.8% in immigrant and 0.08% in Italian pregnant women; the difference was not statistically significant [p 0.062]), 0.09% for HIV infection, and 0.03% for tuberculosis. The prevalence of congenital CMV infection was 0.04% and that of congenital toxoplasmosis 0.01%. The prevalence of early-onset infection from Group B streptococcus was 0.029%. No cases were observed of congenital syphilis, congenital tuberculosis or maternal and neonatal HSV infections. The study proves that in the Marche region there is a high percentage of women who undergo prenatal screening, including screening for infections, not offered by the National Health Service, such as CMV and HCV. The data also demonstrate that some infections, such as tuberculosis, HIV and HBV, almost exclusively affect immigrant women. Regarding neonatal infections, the data presented are in line with those in the literature, with the exception of congenital CMV infection, in which the low prevalence observed could be linked to the recent and massive migration of already immunized women.

The aim of our study was to consider cellular telephone interference using different cellular telephones and implantable cardioverter defibrillator (ICD) models. Thirty (26 men, 4 women) patients with ICDs were considered during follow-up. The ICD models were: Telectronics (7), CPI (7), Medtronic (7), Ventritex (5), and Ela Medical (4). All patients were monitored with surface ECG; permanent telemetric endo-ECG monitoring was activated. Then, the effect of two different European telephone systems were tested: TACS system (Sony CM-R111, 2W power) and GSM system (Motorola MG1-4A11, 2 W power). For both systems, the effect during call, reception, active conversation (dialogue), and passive conversation (listening) were observed. Cellular telephones were located first in contact with the programming head, then near the leads system, and lastly, in the hands of the patient. At the end of the evaluations, memories were interrogated again to check for false arrhythmia detections. In five of these patients during arrhythmia induction at device implant (first implant or ICD replacement), we also evaluated possible interference between cellular telephones in the reception phase and the ventricular fibrillation detection phase of the ICD. All evaluated models showed significant noise in the telemetric transmission when the cellular telephone (both TACS and GSM) was located near the ICD and the programming head; noise was particularly significant during call and reception, in most cases leading to loss of telemetry. No false arrhythmia detections have been observed during tests with cellular telephones located on the ICDs. During tests performed with cellular telephones located near the leads or in the hands of patients, no telemetric noises orfalse arrhythmia detections were observed. During induced ventricularfibrillation and cellular telephones in reception mode near the device, the arrhythmia recognition was always correct and not delayed. In conclusion, present ICD models seem to be well protected from electromagnetic interference caused by European cellular telephones (TACS and GSM), without under-/oversensing of ventricular arrhythmias. However, cellular telephones disturb telemetry when located near the programming head. ICD patients should not be advised against the use of cellular telephones, but it has to be avoided during ICD interrogation and programming.

The quantity of Listeria species was determined in 49 samples of various types of water (river, brackish water, urban wastewater). Twenty nine strains of Listeria were isolated. These were mainly identified as Listeria monocytogenes (72,4%), but Listeria innocua, Listeria grayi, Listeria ivanohovii and Listeria welshimeri were also present. With the exception of water taken from the estuary, 74.4% of samples contained Listeria in mean concentrations of between 2 MPN/100 ml and 1320 MPN/100 ml in fresh surface water and untreated sewage respectively.