Is antibody titer useful to verify the immunization after VZV Vaccine in MS patients treated with Fingolimod? A case series.

BACKGROUND: Fingolimod (FTY720, Gilenya) is a second line therapy to treat relapsing MS not responding to first-line treatments and/or with a high disease activity (according to Italian Regulatory authorities). Before starting Fingolimod, patients' immunity to varicella zoster virus (VZV) needs to be assessed and seronegative patients vaccinated. To test susceptibility and response, IgG antibodies are tested after immunization. Since Fingolimod determines a reduction of circulating B lymphocytes and immunoglobulins, we aimed at describing the trend of VZV antibodies in seronegative vaccinated patients with MS before and after treatment. METHODS: A total of 23 patients vaccinated for VZV before starting Fingolimod treatment, were recruited in this observational retrospective study involving five MS Centers in Campania (Italy). Of these, 12 patients were excluded for missing data. Patients received two doses of Varivax® Vaccine. After vaccination patients were re-tested and were all positive for IgG-VZV. We re-tested IgG-VZV in the same laboratory after a mean time of 2.42 years from Fingolimod therapy start. RESULTS: During Fingolimod therapy we observed a global reduction of antibody titer and a disappearance in 7/11 patients. Titer disappearance was more probable in patients with lower post-vaccination titer. Of the 7 patients with vanishing IgG-VZV, three suspended Fingolimod for adverse event. In two of them, we observed a reappearance of antibody titer after treatment cessation. In one patient chickenpox infection occurred one year later. DISCUSSION AND CONCLUSIONS: Our observational study shows that Fingolimod could influence antibody titer probably through its effect on B lymphocytes, but the efficacy of the vaccination should be verified. In conclusion, it is necessary to pay attention to therapies acting on B lymphocytes as they could influence the antibody titer and efficacy of vaccination making the search for other markers of vaccine efficacy desirable such as cell-mediated immunity with proliferation and induction of memory T lymphocytes in response to viral glycoproteins.

Clinical predictors of Dimethyl Fumarate response in multiple sclerosis: a real life multicentre study.

BACKGROUND: Dimethyl-fumarate (DMF) was effective and safe in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials. We aimed to evaluate the efficacy and safety of DMF and factors related to drug response in real-life setting. METHODS: We analysed prospectively collected demographic and clinical data for patients treated with DMF in six multiple sclerosis (MS) centers from 2015 to 2017 in Campania region, Italy. We performed univariate and multivariate analyses to assess relationships between baseline parameters and DMF efficacy outcomes, Annualized Relapse Rate (ARR), Expanded Disability Status Scale (EDSS) progression and No Evidence of Disease Activity (NEDA-3) status. RESULTS: we analyzed data of 456 patients (67% female subjects, mean age 40 ± 12 years, mean disease duration 9 ± 9 years, mean treatment duration 18 ± 11 months, median EDSS 2.5, 0-8). Proportion of Naïve versus pretreated with other DMTs patients was 149/307 (32.7%), with 122 patients switching to DMF for disease activity (26.7%) and 185 for safety and tolerability issues (40.6%). During treatment with DMF, the annualized relapse rate was reduced by 75% respect to the pre-treatment ARR [incidence-rate-ratio (IRR) = 0.25, p < 0.001, CI 0.18-0.33]. Factors influencing ARR rate while on DMF were relapsing remitting (RR) MS course (IRR = 2.0, p = <0.001, CI 1.51-2.73) and previous DMTs status: de-escalating from second-line therapies was associated to higher risk of relapsing (IRR = 1.8, p < 0.001, CI 1.39-2.31). At multivariable Cox proportional hazard model, only age of onset was related with rate or relapses, with younger age being protective (HR 0.96, p = 0,02). EDSS remained stable in 88% of patients. Disease duration was associated with higher rate of NEDA-3 failure, that was instead maintained in 65% of patients at 24 months. 109 patients (22%) discontinued therapy after a mean of 1.1 ±+ 0.7 years. Reasons for DMF discontinuation over time were lack of efficacy (50%), safety issues (30%), tolerability (7%), poor compliance (7%), and pregnancy (4%). Higher pre-treatment EDSS was associated with DMF discontinuation (p = 0.009). Only 33 patients dropped out due to safety reasons (7%), the most frequent safety issues driving to drop out being lymphopenia, liver/pancreatic enzymes increase, gatrointestinal severe tolerability issues. We recorded 95 cases (24%) of lymphopenia: 60 grade I (13%), 31 grade II (7%) and 4 grade III (1%). CONCLUSIONS: We confirm that DMF shows a good efficacy in both naïve patients and patients switching from other first-line DMTs, especially in patients with early onset of disease. Higher baseline EDSS was a risk factor for discontinuing DMF therapy, while shorter disease duration was protective for both EDSS progression and NEDA-3 status maintenance.

Руководство по вопросам водоснабжения и канализации при экстремальных погодных явлениях

Частота и интенсивность экстремальных погодных явлений, включая наводнения и засухи, растет. Они влияют на работу инфраструктуры водоснабжения и канализации, а также на функционирование установок для очистки (обезвреживания) сточных вод, воздействуя, таким образом, на охрану общественного здоровья. Для разработки этого руководства стороны, подписавшие Протокол по проблемам воды и здоровья, в рамках широкого консультативного процесса провели обзор имеющегося в Европе опыта и методов передовой практики. В данной публикации описано, как в стратегиях по адаптации к изменению климата необходимо учитывать новые риски в связи с экстремальными погодными явлениями, как могут быть определены уязвимые звенья и какие процедуры управления можно применять для обеспечения устойчивой защиты здоровья населения. Для того чтобы проводить оценку и управление рисками, а также решать проблемы, специфические для различных условий (например городские и сельские, небольшие и крупные централизованные системы водоснабжения), необходим интегрированный подход с точки зрения охраны окружающей среды и здравоохранения, работа над решением междисциплинарных вопросов, таких как роль секторов здравоохранения и охраны окружающей среды при экстремальных погодных явлениях, а также диалог по вопросам политики и многосекторальное сотрудничество. Публикация предназначена для широкой аудитории, включая лиц, ответственных за разработку политики, специалистов в области экологии, здравоохранения и водных ресурсов, а также руководителей служб водоснабжения и санитарии.

Guidance on water supply and sanitation in extreme weather events

Extreme weather events, including floods and droughts, occur increasingly often. They affect the operational efficiency and sustainability of water supply, drainage and sewerage infrastructure, and wastewater treatment services, and threaten their protection of public health and the environment. The guidance in this publication summarizes how basic disaster preparedness and early warning procedures can be implemented in the water and wastewater sector, and identifies the specific challenges of extreme weather events to vulnerable areas. It provides advice on the implementation of water safety plans as a tool for risk assessment and management, giving specific attention to small-scale water supply and sanitation systems; and on multisector cooperation, including communication. Finally, based on a review of experience and good practice in the European Region, it summarizes proven adaptation measures for water utilities, drainage and sewerage, and wastewater treatment systems during extreme weather events.

Hindbrain hernia headache and syncope in type I Arnold-Chiari malformation.

We describe two young women affected with syncopal episodes and occipital headache exacerbated by cough, sneezing, rising, or effort. MRI revealed in both patients type I Arnold-Chiari malformation. A craniospinal pressure dissociation with brainstem compression may be involved in the pathogenesis of headache and syncope.

Antiphospholipid antibodies in young adults with cerebrovascular ischemic disease.

In this survey we reviewed some of the most recent laboratory and clinical studies on cerebral ischemia in young patients with antiphospholipid antibodies (aPLs). A strong association between aPLs and cerebrovascular ischemic disease has been documented, but the underlying pathogenetic mechanism remains unclear. Furthermore, long-term prognosis is not clear since too few controlled longitudinal studies had been reported. Further prospective clinical trials are needed to define risk factors, to identify different subgroups of patients, and to lead to an effective therapy.

Sneddon's syndrome, anticardiolipin antibodies and anticardiolipin cofactor. A case report.

Sneddon's syndrome is a rare entity characterized by idiopathic livedo reticularis and cerebrovascular lesions. A case of a young woman with livedo reticularis and progressive cerebral arteriopathy is described. Abnormalities of sexual and gonadotropic hormones were present. Anticardiolipin and anticardiolipin-cofactor complex antibodies were not found.

Spinal cord injury: some epidemiological data. A review of 233 cases.

Two hundred thirty-three consecutive cases of traumatic para- and tetraplegia admitted to a department of Neurosurgery in Naples within ten years were reviewed and categorized according to etiology, level of lesion and clinical features. The age of the patients at the time of injury varied from 7 to 74 years with a mean age of 37.1 +/- 17.1 (male mean age = 35.8 +/- 16.7; female mean age = 41.5 +/- 18.2). The male/female sex ratio was 4.8. Of these patients 66 were paraplegic and 167 were tetraplegic. The analysis of the various causes of the spinal cord injury showed that the occupational activities take the first place (32.2%); injuries in recreational activities and road accidents accounted for the majority of the remaining cases.

Relationship of neurological and psychological signs to physical and metabolic risk factors in elderly persons living in retirement facilities: a multidisciplinary approach.

A multidisciplinary study was performed on 128 elderly subjects living in retirement facilities to correlate the occurrence of neurological signs with the presence of physical or metabolic risk factors, and cognitive impairment. Primitive reflexes were significantly correlated with ankle/arm ratio, Hachinski dementia score, Plutchik GRS score, and hypomimia. The contemporary presence of snout reflex, glabella tap, and palmomental reflex was consistently associated with dementia.

Long-term observation of two cases of locked-in syndrome with recovery. Clinical and CT-scan features.

We report clinical features of two patients suffering from Locked-In Syndrome (LIS) who made a moderate recovery, some years after the onset: a 29-year-old man, with mitral valve stenosis, and a 41-year-old diabetic woman. CT scan findings showing cerebellar and brain stem atrophy, as well as hypodensity areas in the ventral pons, are described.