Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

Case report: Better late than never, but sooner is better: switch from CSII to sulfonylureas in two patients with neonatal diabetes due to KCNJ11 variants

Neonatal diabetes mellitus (NDM) is a rare genetic disease characterized by severe hyperglycemia requiring insulin therapy with onset mostly within the first 6 months and rarely between 6-12 months of age. The disease can be classified into transient (TNDM) or permanent neonatal diabetes mellitus (PNDM), or it can be a component of a syndrome. The most frequent genetic causes are abnormalities of the 6q24 chromosomal region and mutations of the ABCC8 or KCNJ11 genes coding for the pancreatic beta cell’s potassium channel (KATP). After the acute phase, patients with ABCC8 or KCNJ11 mutations treated with insulin therapy can switch to hypoglycemic sulfonylureas (SU). These drugs close the KATP channel binding the SUR1 subunit of the potassium channel and restoring insulin secretion after a meal. The timing of this switch can be different and could affect long-term complications. We describe the different management and clinical outcome over the time of two male patients with NDM due to KCNJ11 pathogenetic variants. In both cases, continuous subcutaneous insulin infusion pumps (CSII) were used to switch therapy from insulin to SU, but at different times after the onset. The two patients kept adequate metabolic control after the introduction of glibenclamide; during the treatment, insulin secretion was evaluated with c-peptide, fructosamine, and glycated hemoglobin (HbA1c), which were within the normal range. In neonates or infants with diabetes mellitus, genetic testing is an indispensable diagnostic tool and KCNJ11 variants should be considered. A trial of oral glibenclamide must be considered, switching from insulin, the first line of NDM treatment. This therapy can improve neurological and neuropsychological outcomes, in particular in the case of earlier treatment initiation. A new modified protocol with glibenclamide administered several times daily according to continuous glucose monitoring profile indications, was used. Patients treated with glibenclamide maintain good metabolic control and prevent hypoglycemia, neurological damage, and apoptosis of beta cells during long‐term administration

La popularité de Tariq Ramadan au Maroc

Sunier, J.T. [Promotor

Rehabilitative of COVID-19 patients with acute lower extremity Ischemia and amputation.

Objective: To evaluate the clinical characteristics and rehabilitation management of patients who undergo amputation for COVID-19-associated coagulopathy. Methods: Clinical and laboratory data for 3 patients were analysed and their rehabilitative management discussed. Results: The medical records of 3 patients who had undergone amputation due to acute lower extremity ischaemia and who were provided with rehabilitation in the COVID-19 unit at San Raffaele Scientific Insitute, Milan Italy were reviewed. Conclusion: Coagulation changes related to SARSCoV- 2 may complicate recovery from this devastating disease. The rehabilitation management of amputated patients for COVID-19 acute lower extremity ischaemia is based on a multilevel approach for clinical, functional, nutritional and neuropsychological needs. Based on this limited experience, a dedicated programme for this specific group of patients seems advantageous to warrant the best functional outcome and quality of life

Anthropometric and metabolic characteristics of the study population according to eGFR stratified for percentiles, age and sex dependent, based on NKF-K/DOQI Guidelines.

<p>Anthropometric and metabolic characteristics of the study population according to eGFR stratified for percentiles, age and sex dependent, based on NKF-K/DOQI Guidelines.</p

Anthropometric and metabolic characteristics of the study population according to uric acid.

<p>Anthropometric and metabolic characteristics of the study population according to uric acid.</p

Partial correlations between uric acid and microalbuminuria, eGFR and other cardiometabolic variables.

<p>Partial correlations between uric acid and microalbuminuria, eGFR and other cardiometabolic variables.</p

Clinical and biochemical features of the study population according to sex.

<p>Clinical and biochemical features of the study population according to sex.</p

Partial correlations between eGFR and microalbuminuria, uric acid and other cardiometabolic variables.

<p>Partial correlations between eGFR and microalbuminuria, uric acid and other cardiometabolic variables.</p