Impact of Disease-Modifying Therapies on Gut-Brain Axis in Multiple Sclerosis.

Multiple sclerosis is a chronic, autoimmune-mediated, demyelinating disease whose pathogenesis remains to be defined. In past years, in consideration of a constantly growing number of patients diagnosed with multiple sclerosis, the impacts of different environmental factors in the pathogenesis of the disease have been largely studied. Alterations in gut microbiome composition and intestinal barrier permeability have been suggested to play an essential role in the regulation of autoimmunity. Thus, increased efforts are being conducted to demonstrate the complex interplay between gut homeostasis and disease pathogenesis. Numerous results confirm that disease-modifying therapies (DMTs) used for the treatment of MS, in addition to their immunomodulatory effect, could exert an impact on the intestinal microbiota, contributing to the modulation of the immune response itself. However, to date, the direct influence of these treatments on the microbiota is still unclear. This review intends to underline the impact of DMTs on the complex system of the microbiota-gut-brain axis in patients with multiple sclerosis.

Electrocardiographic Eligibility for Subcutaneous Implantable Cardioverter Defibrillator: Evaluation during Bicycle Exercise.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is used in patients at risk of sudden death. Our aim was to assess clinical predictors of electrocardiographic ineligibility for S-ICD, and the impact of exercise on S-ICD eligibility in an unselected series of patients requiring ICD therapy. METHODS: 102 patients at risk of sudden death were evaluated at rest and during exercise. Electrocardiograph screening using limb lead electrodes (to simulate the S-ICD sensing vectors) was performed at rest and during bicycle ergometer exercise. RESULTS: R wave amplitude in lead D3 during exercise >16mV, baseline QTc and the sum of amplitudes of the R waves at supine >30mV were predictors of ineligibility for S-ICD. Eligibility increased from 90% to 100% of patients when evaluated with an "any of the three leads" criterion compared to current recommendations. A more restrictive criterion based on two of three ECG leads caused an eligibility drop at 66%, that further decreased to 56% during exercise; these figures improved to 79% and 81%, respectively, when an "any 2 of 3 leads" criterion was used. CONCLUSIONS: Huge ECG amplitude and QTc duration are associated with ineligibility in the current S-ICD release. By performing exercise testing, lead suitability changes in one patient out of 14 (7% of tested patients) and eligibility is decreased by use of a more stringent criterion for eligibility (ECG criteria satisfied in two of three leads). A dynamic selection of sensing vectors aiming at situation-specific suitability (any of three leads) would increase S-ICD eligibility to 100% of patients.

The use of alteplase, although safe, does not offer clear clinical advantages when mild stroke is non-disabling.

Introduction: It is unknown whether alteplase is effective and safe in patients with mild acute ischemic stroke (AIS). Determining whether symptoms are "disabling" or not is a crucial factor in the management of these patients. This study aimed to investigate the efficacy and safety of alteplase in patients with mild, non-disabling AIS. Methods: We included all consecutive patients admitted for AIS at our institution from January 2015 to May 2022 who presented a baseline NIHSS score of 0-5 and fit the criteria to receive intravenous thrombolysis. In order to select only subjects with non-disabling AIS, we excluded patients who scored more than 1 point in the following NIHSS single items: vision, language, neglect, and single limb. Patients who scored at least 1 point in the NIHSS consciousness item were excluded as well. This study is a retrospective analysis of a prospectively collected database. Results: After the application of the exclusion criteria, we included 319 patients, stratified into patients receiving and not receiving alteplase based on non-disabling symptoms. The two groups were comparable regarding demographic and clinical data. Rates of a 3-month favorable outcome, defined as a 3-month mRS score of 0-1, were similar, being 82.3% and 86.1% in the treated and untreated patients, respectively. Hemorrhagic complications and mortality occurred infrequently and were not affected by alteplase treatment. Discussion: This observational study suggests that the use of alteplase, although safe, is not associated with a better outcome in highly selected patients with non-disabling AIS.

Atrial fibrillation: adverse effects of "pill-in-the-pocket" treatment and propafenone-carvedilol interaction.

Propafenone and carvedilol share a common hepatic metabolism involving the oxidative pathway (CYP2D6). Therefore, oral loading with propafenone (as "pill-in-the-pocket" treatment of recent-onset atrial fibrillation) in a patient on concurrent carvedilol treatment may lead to a pharmacokinetic interaction, with high plasma levels of propafenone and potential drug-related adverse effects. In clinical practice, in order to improve the safety of "pill-in-the-pocket" treatment, use of propafenone loading should, in our view, be discouraged in patients on concurrent treatment with carvedilol.