Search

COVID-19 vaccination is highly recommended to multiple sclerosis (MS) patients. Little is known about the role of patients' clinical and demographic characteristics in determining antibody response.We evaluated safety and efficacy of anti-SARS-CoV-2 vaccines on 143 included MS patients. Then, we analyzed antibody titer in a subgroup, assessing clinical and demographic variables associated with protection and antibody titer.After completing the vaccination cycle, the rate of local adverse events was similar after the first and second dose. A higher proportion of systemic AEs was reported after the second dose (65.7% vs 24.5% after the first dose). Antibody response was evaluated in 97 patients. Higher EDSS (OR 0.6, 95% CI 0.4-0.9, p = 0.006) and treatment with antiCD20 (OR 0.02, 95% CI 0.003-0.098, p 0.001) were associated with a lower chance of having an efficacious response. Higher weight was associated with higher Ab titer (β = 15.2, 95% CI 2.8-27.6, p = 0.017), while treatment with antiCD20 with lower titers (β = - 1092.3, 95% CI - 1477.4 to - 702.2, p 0.001). In patients treated with antiCD20, hypogammaglobulinemia (β - 543, 95% CI - 1047.6 to - 39.1, p = 0.036) and treatment duration (β - 182, 95% CI - 341.4 to - 24.3, p = 0.027) were associated with lower Ab titer.Our study confirms that COVID-19 vaccination in MS patient is safe and effective in preventing symptomatic COVID-19 and should be recommended to all patients. Moreover, we suggest a possible role of hypogammaglobulinemia in reducing Ab response in patients treated with antiCD20 therapies.

Aims Atherosclerotic plaque healing is a dynamic process developing after plaque rupture or erosion, which aims to prevent lasting occlusive thrombus formation and to promote plaque repair. We hypothesized that diabetes mellitus, one of the major conventional cardiovascular risk factors, may influence the healing capacity after plaque destabilization. Methods and results In this single-centre observational cohort study, patients with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) who underwent optical coherence tomography (OCT) imaging at Fondazione Policlinico A. Gemelli–IRCCS, Rome, were included. Patients were divided into two groups (i.e. diabetes vs. no diabetes), and stratified based on diabetes medications (i.e. insulin, vs. oral antidiabetic drugs). OCT analysis of non-culprit coronary segments was performed. 105 patients were included (44 diabetes, 61 no diabetes). Prevalence of HCPs was not significantly different between patients with and without diabetes (3.6% vs. 3.8%, P = 0.854). However, patients with diabetes on insulin showed a lower prevalence of HCPs both at patient-based (7.1% vs. 26.4%, P = 0.116) and at segment-based analysis (1.2% vs. 4.2%, P = 0.020). When comparing HbA1c levels based on the presence or absence of healed plaque at the non-culprit lesions, patients with healed plaque showed significantly lower levels of HbA1c compared to patients without healed plaques (43.5 ± 12.1% vs. 61.2 ± 10.4%, P Conclusions Patients with diabetes have a distinct coronary non-culprit plaque phenotype. Healing capacity may be impaired in patients with advanced diabetes on insulin therapy and in those with a suboptimal control of the disease. Further prospective, larger scale studies are warranted to confirm these findings.

The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.

A practical and scalable route to the SMO antagonist SEN826 1 is described herein, including the discussion of an alternative approach to the synthesis of the target molecule. The optimized route consists of five chemical steps. A new and efficient access to the key intermediate 6 via the bisulfite–aldehyde complex was developed, significantly enhancing the yields and reducing costs. As a result, a synthetic procedure for preparation of multihundred gram quantities of the final product has been developed.

A practical and scalable route to the Wnt inhibitor SEN461 1 is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations....

A practical and scalable route to the SMO receptor antagonist SEN794 1 is described herein. A new and efficient access to the key intermediate 7 via the Krohnke reaction was developed, significantl...

β-Aminocyclopropanols were transformed, in a domino process catalyzed by Pd(II) salts, into the corresponding 2,3-dihydro-lH-pyridin-4-ones. Conversely the use of a Pd(0) derivative, Pd(dba) 2 , afforded the corresponding tetrahydropyrid-4-ones. The saturated derivatives were also obtained, in better yields, using Pd(II) and Cu(OAc) 2 as stoichiometric oxidant.