COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Objective To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the frst pandemic wave, Lombardia. Methods Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions We detected an increased incidence of GBS in COVID-19 patients which can refect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures

Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression

The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Tumori stromali gastro-intestinali (GISTs): aspetti prognostici e terapeutici

Gli aspetti prognostico-predittivi dei tumori stromali gastro-intestinali (GISTs) costituiscono motivo di ifferente valutazione. Il loro comportamento biologico è solo ipotizzabile, valutando la durata della sintomatologia, la sede e le dimensioni della neoplasia, la presenza di aree emorragiche o di necrosi, le modificazioni citologiche e soprattutto la conta mitotica: la presenza di 5 o più mitosi per 50 HPF è da considerarsi significativa di malignità. L’esperienza personale dell’ultimo trentennio è di 40 GISTs a sede prevalente gastrica. Sono stati tutti operati di semplice escissione o di resezione d’organo parziale o totale. Nei GISTs benigni la sopravvivenza attesa è mancata solo in 5 casi (su 26); dei 6 GISTs borderline, in 4 casi a rapida evoluzione, il diametro della neoplasia era > 5 cm e le mitosi > 5 x 50 HPF. Anche nei GISTs maligni è stata constatata una buona correlazione tra sopravvivenza, parametri anatomo-clinici e grading istopatologico. Anche da questa esperienza si evince che il comportamento biologico dei GISTs è di difficile interpretazione. Tuttavia le dimensioni, le alterazioni genetiche e la conta mitotica possono essere considerate sufficientemente significative di malignità. Sono sempre indicati interventi chirurgici resettivi e l’invasione di organi viciniori imporrà l’allargamento dell’atto operativo

Factors affecting prognosis in patients with short bowel syndrome

Aim of the study is to analyse physiopathological implications of massive intestinal resection and factors affecting prognosis in patients with short bowel syndrome. Twenty massive intestinal resections were performed. The causes of bowel resection were: intestinal infarction (11 cases), Crohn’s disease (5 cases), small bowel volvulus (4 cases). All intestinal resec - tions were more than 50-60% of the intestinal length. In eighteen patients intestinal anastomosis was performed immediately. In all the patients postoperative therapy with parenteral nutrition (PN) was performed. The operative morbidity and thirty-day mortality were respectively 30% (6 cases) and 35 % (7 cases). The diarrhea was the dominant symptom. The average weight was 20% lower compared to the initial weight. The length of residual small bowel and type of anastomosis strongly affect survival of patients underwent massive intestinal resec - tions. Parenteral nutrition (PN) has great importance in postopera - tive treatment. A useful treatment, in severe short bowel syndrome, can be small bowel transplantation