Baseline characteristics associated with NEDA-3 status in fingolimod-treated patients with relapsing-remitting multiple sclerosis

Abstract Background Fingolimod is an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS) and there is class I evidence that it is superior to standard care in reducing relapse rate. However, real-world data investigating its effectiveness and potential predictors of response are still scarce. Objective To estimate (i) the proportion of fingolimod-treated patients who achieved the no evidence of disease activity (NEDA-3) status; and (ii) to determine which baseline (i.e. at treatment start) clinical and magnetic resonance imaging (MRI) variables were associated with better outcomes. Methods We collected clinical and MRI data of RRMS patients treated with fingolimod and followed-up for 24 months. The proportion of patients who had NEDA-3 - i.e. absence of relapses, sustained Expanded Disability Status Scale (EDSS) worsening and radiological activity on MRI - was estimated. A Cox proportional hazard model was carried out to investigate which baseline characteristics were associated with the NEDA status at follow-up. Results We collected data of 201 patients who started fingolimod. Of them, 24 (12%) were treatment-naïve, 115 (58%) were switched after failing a self-injectable drug, and 60 (30%) switching from natalizumab. Five patients who discontinued fingolimod early (within 3 months) (bradycardia, n = 2; leukopaenia, n = 2; macular oedema, n = 1) were removed from the analysis. At follow-up, 118 (60%) patients achieved the NEDA-3 status, while 78 experienced clinical and/or MRI activity. The risk of not achieving the NEDA-3 status was associated with higher baseline EDSS score (hazard ratio [HR] = 1.18, p = 0.024) and more relapses in the 12 months prior to fingolimod start (HR = 1.61, p = 0.014). Conclusion Our findings suggest that fingolimod may lead to a better control of the disease if started in patients with a less aggressive disease (i.e. fewer pre-treatment relapses and milder disability level), thus supporting its possible role as an early treatment for MS

The added value of spinal cord lesions to disability accrual in multiple sclerosis

Spinal cord MRI is not routinely performed for multiple sclerosis (MS) monitoring. Here, we explored whether spinal cord MRI activity offers any added value over brain MRI activity for clinical outcomes prediction in MS. This is a retrospective, monocentric study including 830 MS patients who underwent longitudinal brain and spinal cord MRI [median follow-up 7 years (range: < 1–26)]. According to the presence (or absence) of MRI activity defined as at least one new T2 lesion and/or gadolinium (Gd) enhancing lesion, each scan was classified as: (i) brain MRI negative/spinal cord MRI negative; (ii) brain MRI positive/spinal cord MRI negative; (iii) brain MRI negative/spinal cord MRI positive; (iv) brain MRI positive/spinal cord MRI positive. The relationship between such patterns and clinical outcomes was explored by multivariable regression models. When compared with the presence of brain MRI activity alone: (i) Gd + lesions in the spine alone and both in the brain and in the spinal cord were associated with an increased risk of concomitant relapses (OR = 4.1, 95% CI 2.4–7.1, p < 0.001 and OR = 4.9, 95% CI 4.6–9.1, p < 0.001, respectively); (ii) new T2 lesions at both locations were associated with an increased risk of disability worsening (HR = 1.4, 95% CI = 1.0–2.1, p = 0.05). Beyond the presence of brain MRI activity, new spinal cord lesions are associated with increased risk of both relapses and disability worsening. In addition, 16.1% of patients presented asymptomatic, isolated spinal cord activity (Gd + lesions). Monitoring MS with spinal cord MRI may allow a more accurate risk stratification and treatment optimization

Listeria monocytogenes-Induced rhombencephalitis in a patient with multiple sclerosis treated with dimethyl fumarate

Dimethyl fumarate is an oral treatment used for relapsing- remitting multiple sclerosis (MS). Caution is required in pa- tients with severe lymphocytopenia that persists for more than 6 months. We describe a case of rhombencephalitis caused by Listeria monocytogenes in a patient without severe lymphocytopenia who was treated with dimethyl fumarate

Clinical management of hypertensive disorders in postpartum women. A narrative review

Background: Hypertensive disorders in pregnancy could persist postpartum, or appear for the first time after delivery and could require a pharmacological treatment. It was found no evidence in literature about what therapy should be used in puerperal hypertension. Objectives: To determine the effective therapy for the treatment of high postpartum systemic arterial blood pressure in women with hypertension in pregnancy or in women with de novo hypertension. Data sources: Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CCRCT), Embase, Medline, Pubmed Study eligibibility criteria, partecipants and interventions: Postnatal women with hypertension. Therapeutic treatment for management of hypertension compared with placebo or no therapy. Esclusion of preeclampsia/eclampsia. Study appraisal and synthesis methods: Results: 23 studies were included (n=23). Limitations: - Randomised controlled studies plus other experimental study designs (cohort studies, case– control studies and quasi-randomised studies) were included, and no limitations were imposed in terms of language or publication date, resulting in a comprehensive review. - This review highlights significant evidence gaps, demonstrating that further comparative research is required, particularly to clarify postpartum antihypertensive selection. Conclusions: There are insufficient evidence to recommend a particular therapy or model of care, but calcium channel blockers, beta blockers, alpha blockers and Angiotensin converting enzyme inhibitors (ACEIs) appeared variably effective. Key findings: Severe preeclampsia, Hypertension, Pregnancy, Postpartum, Very high blood pressure, Antihypertensive therap

Impact of early diagnosis on clinical characteristics of an Italian sample of people with multiple sclerosis recruited online

Background: In order to anticipate the diagnosis of Multiple Sclerosis (MS), the diagnostic criteria had been reviewed several times in the last years. Objective: We wanted to understand whether earlier diagnoses of MS have impacted on therapeutic management of the disease. Methods: We designed a 22-item survey posted on SMsocialnetwork, a webplatform with a medical supervision, dedicated to Italian MS patients. We collected socio-demographic data, disease and treatment-related information of 1000 patients. Results: The median age at diagnosis significantly decreased over years. In the last decades the time delay between disease onset and diagnosis reduced, the disease phenotypes at diagnosis shifted from progressive form to relapsing ones and clinically isolated syndrome, the number of early treated patients increased over time. Conclusion: We showed, verifying a large sample of patients in a reallife setting, that the improvement of the diagnostic process allowed the anticipation of MS diagnosis over years and had a huge impact in terms of treatment approach

Potential rotective role of pregnancy and breastfeeding in delaying onset symptoms related to multiple sclerosis

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation

Chemo-surgical approach in vulvar leiomyosarcoma: a case report

Introduction:Primary sarcoma of the vulva is an extremely rare entity, representing only 1%-3% of all vulvar malignant neoplasms. Among sarcomas, leiomyosarcoma (LMS) is the most prevalent histologic variant. Due to the rarity of LMS, guidelines are lacking and phase III trials have not been carried out, so clinical management is based on local clinical practice and physician experience.Case presentation:Here, we described a case of primary LMS of the vulva and its successful management, with the adoption of neoadjuvant chemotherapy and surgery. We report a case of a 74-year-old woman with 12.5 cm vulvar LMS. The patient received three cycles of neoadjuvant chemotherapy with a partial response. Radical vulvectomy with vulvar reconstruction with V-F flap was carried out. Surgical margins were negative. Three additional cycles of adjuvant chemotherapy were delivered.Results:One year after treatment, the patient was disease-free.Conclusion:There are no approved therapeutic protocols for this rare neoplasia. Surgery is the mainstay of treatment. However, it is not always feasible, so neoadjuvant chemotherapy was delivered for downstaging the vulvar lesion. We suppose that neoadjuvant chemotherapy has optimized the possibilities of radical surgery. Despite the anectodical nature of this case presentation, neoadjuvant chemotherapy seems a valid therapeutic option for managing patients with bulky vulvar sarcoma. Further large collaborative studies are warranted to identify the best therapeutic option for these patients

Non-invasive treatment of vulvovaginal atrophy in menopause with CO2 laser

Genitourinary syndrome of menopause (GSM) may affect up to 90% of menopausal women, including vulvovaginal atrophy (VVA), burning, pain, bleeding, irritation, dyspareunia, anorgasmia, and urinary symptoms. Vaginal symptoms from lack of estrogens can have a significant impact on the sexual health and quality of life (QoL) in as many as 50% of postmenopausal women. Several therapeutic alternatives, both hormonal and non- hormonal, have been proposed. Microablative CO2 laser is one of the three non-surgical energy-based therapies, with Erbium:YAG laser and temperature-controlled radiofrequency (RF). Microablative CO2 laser induces morphological changes in vaginal tissues and results of several clinical trials suggest that this type of laser improves symptoms of GSM. Moreover, this treatment seems to be safe. Given the increasingly widespread use of laser CO2 as a non-hormonal alternative treatment for GSM, the authors reviewed the current published literature evaluating this therapy, to compare efficacy and safety of different protocols