DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Mod Pathol

In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with impaired survival. Finally, the double-hit assessment does not appear clinically relevant in primary cutaneous large B-cell lymphoma

Competition between hydrogen and deuterium abstraction by methyl radicals in isotopomerically mixed methanol glasses

Rate parameters are reported for hydrogen and deuterium abstraction of methyl radicals embedded in glassy mixtures of CH3OH and CD 3OD. The mole fraction of CH3OH in these isotopomeric mixtures is 0, 0.05, 0.075, 0.10, 0.15, or 1. The nonexponential time dependence of the radical concentration is analyzed in terms of distributions of first-order rate constants. For the isotopomerically pure matrices, lognormal distributions describe the decay satisfactorily. The large difference between characteristic H and D transfer rate constants indicates tunneling. In the mixtures, there is competition between H and D abstraction processes which depends on the local structure about a radical, so that the corresponding rate parameters contain information about this structure. On the basis of earlier work [J. Chem. Phys. 86, 6622 (1987)], the analysis begins with the assumption that the structure about a radical resembles one of the crystalline phases of methanol. The entire set of decay curves is described by a (disordered) \u3b2-phase structure in which the radical replaces a methanol molecule and is located near the position associated with a methyl group. However, this static picture is inadequate because the radical can diffuse through the glass on the time scale of the kinetic measurements. Diffusion allows the radical to encounter more CH3OH molecules than would be expected for the static structure on a statistical basis - the effective mole fraction of CH 3OH in the mixtures is higher than the analytical concentration. For the xH=0.05 mixture, we estimate that on the average the radical encounters approximately 26 methanol molecules before abstraction occurs. This corresponds to diffusion over roughly 1100 pm through the lattice. \ua9 1993 American Institute of Physics.Peer reviewed: YesNRC publication: Ye

A comparison of CDKN2A mutation detection within the Melanoma Genetics Consortium (GenoMEL)

CDKN2A is the major melanoma susceptibility gene so far identified, but only 40% of three or more case families have identified mutations. A comparison of mutation detection rates was carried out by “blind” exchange of samples across GenoMEL, the Melanoma Genetics Consortium, to establish the false negative detection rates. Denaturing high performance liquid chromatography (DHPLC) screening results from 451 samples were compared to screening data from nine research groups in which the initial mutation screen had been done predominantly by sequencing. Three samples with mutations identified at the local centres were not detected by the DHPLC screen. No additional mutations were detected by DHPLC. Mutation detection across groups within GenoMEL is carried out to a consistently high standard. The relatively low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes

Primary Biliary Cholangitis Associated with Skin Disorders: A Case Report and Review of the Literature.

Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease. It is often associated with extrahepatic autoimmune diseases. Skin disorders are sporadically reported in association with PBC. We report an unusual case of PBC associated with acquired reactive perforating dermatosis (ARPD) and present a review of the literature on skin disorders associated with PBC. Our patient presented to the dermatology department with generalized pruritus associated with nodular perforating skin lesions on the trunk, and cholestatic liver disease of unknown origin. After having established both diagnosis of ARPD and PBC, she was managed in an interdisciplinary manner, and both her skin and liver conditions improved gradually. Only one similar case is reported in the literature, in that case, the liver disease was not treated. By reviewing the literature, we found that lichen planus, vitiligo, and psoriasis are the most frequent skin disorders associated with PBC. However, there is only limited data about specific skin disorders associated with PBC. This case report of a patient with PBC associated with ARPD underlines the importance of interdisciplinary management of patients with rare liver diseases combined with rare skin disorders. The present review of the literature shows that probably, immune-mediated skin conditions are not more frequent in PBC patients than in the general population. However, the available data are scant; there is a need for high-quality data on skin conditions associated with PBC