Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC)

Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.

     

Cell-wall preparation containing poly-γ-d-glutamate covalently linked to peptidoglycan,a straightforward extractable molecule,protects mice against experimental anthrax infection

Bacillus anthracis is the causative agent of anthrax that is characterized by septicemia and toxemia. Many vaccine strategies were described to counteract anthrax infection. In contrast with veterinary live vaccines, currently human vaccines are acellular with the protective antigen, a toxin component, as the main constituent. However, in animal models this vaccine is less efficient than the live vaccine. In this study, we analyzed the protection afforded by a single extractable surface element. The poly-γ-d-glutamate capsule is covalently linked to the peptidoglycan. A preparation of peptidoglycan-linked poly-γ-d-glutamate (GluPG) was tested for its immunogenicity and its protective effect. GluPG injection, in mice, elicited the production of specific antibodies directed against poly-glutamate and partially protected the animals against lethal challenges with a non-toxinogenic strain. When combined to protective antigen, GluPG immunization conferred full protection against cutaneous anthrax induced with a fully virulent strain.     

Clinical and molecular characteristics of pediatric low-grade glioma complicated with ventriculo-peritoneal shunt related ascites

Journal of Neuro-Oncology - Ventriculo-peritoneal shunt (VPS) related ascites is a rare complication of pediatric low grade gliomas (pLGG). Physiopathology of this complication is not fully...     

Sleep quality and disturbances in patients with different-sized rotator cuff tear

Introduction

The literature is unanimous in saying that shoulder pain, due to rotator cuff tear (RCT), may be mostly at night; to our knowledge, this statement is not supported by scientific evidence. Our aim was to investigate sleep quality and disturbances in patient with RCT and in a control group.

Materials and methods

A case–control design study was used. We enrolled 324 consecutive patients (Group A) (156M–168F, mean age ± SD: 64.94 ± 6.97; range 47–74) who underwent arthroscopic rotator cuff repair. Tear size was determined intraoperatively. The control group (Group B) included 184 subjects (80M–104F, mean age ± SD = 63.34 ± 6.26; range 44–75) with no RCT. All participants were submitted to two standardized self-reported questionnaires evaluating sleep quality and disturbances: the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Data were submitted to statistics.

Results

We found no significant differences between the two groups according to both PSQI (Group A: 5.22 ± 2.59; Group B: 5.21 ± 2.39) and ESS (Group A: 2.59 ± 2.54; Group B: 5.76 ± 2.63), p > 0.05. Patients with small tears had average PSQI and ESS higher than patients with large and massive lesions (p < 0.005). Pearson’s test showed that tear severity was negatively correlated with both sleep latency (r ² = ?0.35, β = 0.069, p < 0.005) and sleep disturbances (r ² = ?0.65, β = 0.053, p < 0.001).

Conclusions

RCT is only one of the responsible causes for sleep disturbance in middle-aged and elderly subjects. Patients with small tears have a poorer sleep quality with respect to those with a more severe tear; particularly, they not only take more time to fall asleep, but also have a more disturbed sleep compared to patients with large and massive tears.

Level of evidence

III.

     

Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis‐associated colorectal cancer acting on Notch signaling and gut microbiota

Inflammatory bowel diseases are associated with increased risk of developing colitis‐associated colorectal cancer (CAC). Epidemiological data show that the consumption of ω‐3 polyunsaturated fatty acids (ω‐3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid‐free fatty acid (EPA‐FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA‐FFA are unknown in CAC. We tested the effectiveness of substituting EPA‐FFA, for other dietary fats, in preventing inflammation and cancer in the AOM‐DSS model of CAC. The AOM‐DSS protocols were designed to evaluate the effect of EPA‐FFA on both initiation and promotion of carcinogenesis. We found that EPA‐FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA–FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear β‐catenin expression, whilst it increased apoptosis. In both arms, EPA‐FFA treatment led to increased membrane switch from ω‐6 to ω‐3 PUFAs and a concomitant reduction in PGE₂ production. We observed no significant changes in intestinal inflammation between EPA‐FFA treated arms and AOM‐DSS controls. Importantly, we found that EPA‐FFA treatment restored the loss of Notch signaling found in the AOM‐DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA‐FFA is an excellent candidate for CRC chemoprevention in CAC.