Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294

A relaxed-inertial forward-backward-forward algorithm for Stochastic Generalized Nash equilibrium seeking

In this paper we propose a new operator splitting algorithm for distributed Nash equilibrium seeking under stochastic uncertainty, featuring relaxation and inertial effects. Our work is inspired by recent deterministic operator splitting methods, designed for solving structured monotone inclusion problems. The algorithm is derived from a forward-backward-forward scheme for solving structured monotone inclusion problems featuring a Lipschitz continuous and monotone game operator. To the best of our knowledge, this is the first distributed (generalized) Nash equilibrium seeking algorithm featuring acceleration techniques in stochastic Nash games without assuming cocoercivity. Numerical examples illustrate the effect of inertia and relaxation on the performance of our proposed algorithm

Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma

This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ≥65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression/intolerance. The phase 1 portion used a 3+3 dose-escalation scheme to determine the maximum tolerated dose of weekly carfilzomib: 12 patients received wKCyd with carfilzomib doses of 45, 56 and 70 mg/m 2. The recommended phase 2 dose was established at 70 mg/m 2 and 54 patients (phase 1 and 2) received weekly carfilzomib 70 mg/m 2: 85% of them achieved ≥partial response (PR), 66% ≥very good PR, 30%≥near-complete response (CR) and 15% CR. Responses improved in 40 patients who started maintenance: 98% achieved ≥PR, including 29% CR and 10% stringent CR. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 53.2% and 81%, respectively. The most frequent grade 3-5 toxicities were neutropenia (22%) and cardiopulmonary adverse events (9%). This is the first study of weekly carfilzomib plus an alkylating agent in elderly patients with NDMM. wKCyd was effective, with an acceptable risk/benefit ratio, and thus can be a valid option in this setting

Extracorporeal hemoadsorption therapy as a potential therapeutic option for rapid removal of Apixaban in high risk-surgical patients: a case report

Background: Apixaban is a non-vitamin K antagonist oral anticoagulant (NOACs) recently emerged as an effective alternative to conventional vitamin K antagonists (VKAs) in the treatment of several thromboembolic disorders. However, in case of overdose or in patients requiring emergency surgery there is a high bleeding rate and severe adverse side effects due to the absence of an antidote. There is promising data from in vitro and clinical studies, that certain antithrombotic agents (that is Rivaroxaban and Ticagrelor) have been successfully removed by the extracorporeal hemoadsorption therapy CytoSorb. Here, we present the case of a patient successfully treated with CytoSorb as a kind of antidote to enable emergency surgery for bilateral nephrostomy. Case presentation: A 82-year-old Caucasian man was admitted to the Emergency Room with acute kidney injury (AKI) in the context of severe bilateral hydroureteronephrosis. The patient’s medical history included chronic obstructive pulmonary disease, arterial hypertension, atrial fibrillation (anticoagulated with Apixaban) and a locally advanced prostate adenocarcinoma treated with trans-ureteral resection of the bladder and radiotherapy in the previous months. The indication for a bilateral nephrostomy could not be considered immediately given the major bleeding risk due to Apixaban, which was discontinued and replaced with calciparin. After 36 hours of continuous renal replacement therapy (CRRT), the Apixaban blood level was still elevated and it was decided to install CytoSorb into the running CRRT to accelerate the drug clearance. After 2 hours 30 minutes, there was good reduction of Apixaban from 139 to 72 ng/ml (reduction rate of 48.2%) registered, and this allowed for an easy placement of bilateral nephrostomies without complications. Four days after surgery renal function parameters further normalized, the patient did not require additional dialysis treatments and Apixaban therapy was prescribed again once the patient returned home. Conclusions: In this case we report the findings of a patient with post-renal AKI requiring emergency nephrostomy placement while on chronic anticoagulation with Apixaban therapy. Combined treatment with CRRT and CytoSorb was associated with the rapid and effective removal of Apixaban allowing for prompt and urgent surgery while simultaneously ensuring the low risk of bleeding as well as an uneventful post-operative course

Detection of influenza A(H1N1)pdm09 virus in a patient travelling from Shanghai to Italy in July 2018: An uncommon clinical presentation in a non-seasonal period

Influenza is one of the most common infectious diseases in travellers, especially in those returning from subtropical and tropical regions. In late June 2018 an influenza A(H1N1)pdm09 virus infection was diagnosed in a 36-years-old man, returned from a travel in Shanghai and hospitalized at the Ospedale Policlinico San Martino, Genoa, Italy, with a diagnosis of fever and an uncommon clinical presentation characterised by a persistent leukopenia. Phylogenetic analysis revealed a closeness with influenza A(H1N1)pdm09 strains circulating in the US in May-June 2018. Prompt recognition of influenza infection led to a proper case management, demonstrating the crucial role of the continuous influenza surveillance programme

Comprehensive analysis of mitochondrial and nuclear DNA variations in patients affected by hemoglobinopathies: a pilot study

The hemoglobin disorders are the most common single gene disorders in the world. Previous studies have suggested that they are deeply geographically structured and a variety of genetic determinants influences different clinical phenotypes between patients inheriting identical β-globin gene mutations. In order to get new insights into the heterogeneity of hemoglobin disorders, we investigated the molecular variations on nuclear genes (i.e. HBB, HBG2, BCL11A, HBS1L and MYB) and mitochondrial DNA control region. This pilot study was carried out on 53 patients belonging to different continents and molecularly classified in 4 subgroup: β-thalassemia (β+/β+, β0/β0 and β+/β0)(15), sickle cell disease (HbS/HbS)(20), sickle cell/β-thalassemia (HbS/β+ or HBS/β0)(10), and non-thalassemic compound heterozygous (HbS/HbC, HbO-Arab/HbC)(8). This comprehensive phylogenetic analysis provided a clear separation between African and European patients either in nuclear or mitochondrial variations. Notably, informing on the phylogeographic structure of affected individuals, this accurate genetic stratification, could help to optimize the diagnostic algorithm for patients with uncertain or unknown origin

Spinal infection: state of the art and management algorithm

Spinal infection is a rare pathology although a concerning rising incidence has been observed in recent years. This increase might reflect a progressively more susceptible population but also the availability of increased diagnostic accuracy. Yet, even with improved diagnosis tools and procedures, the delay in diagnosis remains an important issue. This review aims to highlight the importance of a methodological attitude towards accurate and prompt diagnosis using an algorithm to aid on spinal infection management. METHODS: Appropriate literature on spinal infection was selected using databases from the US National Library of Medicine and the National Institutes of Health. RESULTS: Literature reveals that histopathological analysis of infected tissues is a paramount for diagnosis and must be performed routinely. Antibiotic therapy is transversal to both conservative and surgical approaches and must be initiated after etiological diagnosis. Indications for surgical treatment include neurological deficits or sepsis, spine instability and/or deformity, presence of epidural abscess and upon failure of conservative treatment. CONCLUSIONS: A methodological assessment could lead to diagnosis effectiveness of spinal infection. Towards this, we present a management algorithm based on literature findings

Application of an updated methodology to estimate the burden of healthcare-associated infections in Italy, 2022

Background: Accurate burden estimates are necessary to inform priority setting and rational resource allocation. Weighting prevalence inversely proportional to time-at-risk has been proposed as a solution for length-biased sampling, an important limitation affecting prevalence to incidence conversion for healthcare-associated infections (HAIs). Aim: This study aimed to update Italian burden estimates by calculating HAI incidence, attributable mortality and disability-adjusted life years (DALYs). Further, we describe an adapted methodology for burden estimations. Methods: We used data from the latest European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs, conducted in Italy in November 2022, to calculate the burden of five major HAIs at national level. We adapted the Burden of Communicable Diseases in Europe (BCoDE) methodology to include inverse probability weighting and compared results of na & iuml;ve and weighted calculations. Results: The national sample included 18,397 patients. Overall, 564.8 DALYs per 100,000 general population resulted from weighted calculations (95% uncertainty interval (UI): 450.04-694.38), with an annual incidence of 685.42 cases per 100,000 general population (95% UI: 611.09-760.86) and 33.23 deaths per 100,000 general population per year (95% UI: 28.62-38.33). Concerning na & iuml;ve estimates, overall 1,017.81 DALYs per 100,000 general population were calculated (95% UI: 855.16-1,190.59). In both calculations, healthcare-acquired bloodstream infections had the highest burden in terms of DALYs per 100,000 hospitalised and general population. Conclusion: Our study confirmed the substantial burden of HAIs in Italy and renews the need to prioritise resources for infection prevention and control interventions