Hematopoietic Stem Cell Transplantation in Neuromyelitis Optica-Spectrum Disorders (NMO-SD): State-of-the-Art and Future Perspectives

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune inflammatory disorders of the central nervous system (CNS). Understanding of the molecular basis of these diseases in the last decades has led to an important improvement in the treatment of this disease, in particular, to the use of immunotherapeutic approaches, such as monoclonal antibodies and Hematopoietic Stem Cell Transplantation (HSCT). The aim of this review is to summarize the pathogenesis, biological basis and new treatment options of these disorders, with a particular focus on HSCT applications. Different HSCT strategies are being explored in NMOSD, both autologous and allogeneic HSCT, with the new emergence of therapeutic effects such as an induction of tolerance to auto-antigens and graft versus autoimmunity effects that can be exploited to hopefully treat a disease that still has prognosis

In vivo antimicrobial activity of 0.6% povidone-iodine eye drops in patients undergoing intravitreal injections: a prospective study

To investigate the antimicrobial activity of a preservative-free 0.6% povidone-iodine eye drop as an antiseptic procedure in decreasing the conjunctival bacterial load in eyes scheduled for intravitreal treatment and to compare its efficacy to the untreated fellow eye used as the control group. Prospective cohort analysis in which 208 patients received preservative-free 0.6% povidone-iodine eye drops three times a day for three days before intravitreal injection. Before and after the prophylactic treatment, a conjunctival swab was collected from both the study eye and the untreated contralateral eye, used as control. The swab was inoculated on different culture media and the colony-forming units were counted. Bacteria and fungi were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Treatment with 0.6% povidone-iodine eye drops significantly reduced the conjunctival bacterial load from baseline (p < 0.001 for blood agar and p < 0.001 for chocolate agar) with an eradication rate of 80%. The most commonly isolated pathogen at each time-point and in both groups was coagulase-negative Staphylococci, isolated in 84% of the positive cultures. The study provides evidence about the effectiveness of 0.6% povidone-iodine eye drops treatment in reducing the conjunctival bacterial load in eyes scheduled for intravitreal treatment

Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules

Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl2, 10% of autologous thrombin, 10% of a mixture of CaCl2 + thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl2, thrombin, and CaCl2/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl2/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF-β1 that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl2 induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic

Sustained virological response after ten days of triple anti-hepatitis C virus (HCV) therapy with telaprevir plus pegylated interferon and ribavirin in an HIV/HCV co-infected cirrhotic woman

The introduction of first-generation protease inhibitors for the treatment of chronic hepatitis C in subjects infected with hepatitis C virus (HCV) genotype 1 has significantly improved the sustained virological response (SVR) rate. As liver cirrhosis reduces the probability of achieving SVR, current guidelines discourage response-guided therapy in cirrhotic patients. We report the first case of a cirrhotic woman with chronic HCV and HIV co-infection achieving virological response after an ultra-short course of therapy. A 40-year-old HIV/HCV co-infected woman with compensated liver cirrhosis was treated with anti-HCV triple therapy containing telaprevir plus pegylated interferon and ribavirin. Baseline plasma HCV RNA was 3.6 log IU/ml and transaminases were within the normal range. She harboured IL28B rs12979860 C/C alleles. Ten days after starting therapy, the patient stopped treatment because of mild anorexia and nausea. Virological response was detected at treatment discontinuation and was maintained up to 24 weeks. This case describes an unexpected SVR after a 10-day course of antiviral therapy in a cirrhotic HIV/HCV co-infected woman presenting positive predictive factors for a response (low viral load, IL28B genotype). Nonetheless, there is no evidence to suggest a shorter duration of treatment in this subset of patients

Diabetes and metabolic disorders. Their impact on cardiovascular events in liver transplant patients

Cardiovascular diseases are currently one of the most important causes of morbidity and mortality in liver transplant patients over the long term. Therefore, evaluating prognostic factors for cardiovascular events (CVEs) in this population is essential for taking preventive measures. The aim of this study was to identify the impact of diabetes and other metabolic disorders on CVEs in liver transplant patients. Three hundred fifty-six liver transplant recipients who survived at least 6 months after surgery were enrolled. Patients were followed for a median time of 118 months (12–250 months). All cardiovascular events were carefully recorded and detailed in the patients’ charts. Demographic data, diabetes, hypertension, dyslipidemia, weight changes, and a diagnosis of metabolic syndrome both before and after transplantation were noted to assess their possible relationship with CVE. The presence of a diagnosis of metabolic-associated fatty liver disease (MAFLD) was also evaluated. Immunosuppressive therapy was included in the analysis. Diabetes mellitus (DM), especially when present before transplantation, was strongly associated with CVEs (hazard risk HR 3.10; 95% confidence interval CI: 1.60–6.03). Metabolic syndrome was found to be associated with CVEs in univariate analysis (HR 3.24; 95% CI: 1.36–7.8), while pretransplantation and de novo MAFLD were not. Immunosuppressive therapy had no influence on predisposing transplanted patients to CVEs during follow-up. Further prospective studies may be useful in investigating the risk factors for CVEs after liver transplantation and improving the long-term survival of transplant patients

Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis

The last decade has seen exponentially growing efforts to exploit the effects of adipose derived stromal cells (ADSC) in the treatment of a wide range of chronic degenerative diseases, including osteoarthritis (OA), the most prevalent joint disorder. In the perspective of developing a cell-free advanced therapy medicinal product, a focus has been recently addressed to the ADSC secretome that lends itself to an allogeneic use and can be further dissected for the selective purification of small extracellular vesicles (sEVs). sEVs can act as "biological drug carriers" to transfer information that mirror the pathophysiology of the providing cells. This is important in the clinical perspective where many OA patients are also affected by the metabolic syndrome (MetS). ADSC from MetS OA patients are dysfunctional and "inflammatory" primed within the adipose tissue. To mimic this condition, we exposed ADSC to IL-1 beta, and then we investigated the effects of the isolated sEVs on chondrocytes and synoviocytes, either cultured separately or in co-culture, to tease out the effects of these "IL-1 beta primed sEVs" on gene and protein expression of major inflammatory and catabolic OA markers. In comparison with sEVs isolated from unstimulated ADSC, the IL-1 beta primed sEVs were able to propagate NF-kappa B activation in bystander joint cells. The effects were more prominent on synoviocytes, possibly because of a higher expression of binding molecules such as CD44. These findings call upon a careful characterization of the "inflammatory fingerprint" of ADSC to avoid the transfer of an unwanted message as well as the development of in vitro "preconditioning" strategies able to rescue the antiinflammatory/anticatabolic potential of ADSC-derived sEVs

new tailor made bio organoclays for the remediation of olive mill waste water

A systematic study aimed at obtaining new organoclays for the treatment of Olive Mill Waste water (OMW) has been performed. Several organoclays have been prepared by loading different amounts of the biocompatible surfactant Tween20 onto the K10 montmorillonite (MMT). Complementary kinetic and equilibrium studies on the adsorption of the Tween20 onto the MMT have been carried out and the characterization of the new tailor-made bio-materials has been performed by means of the XRD and FT-IR measurements. Finally the prepared bio-organoclays have been successfully applied for the OMW remediation and they proved to be highly effective in decreasing the organic content (OC) to an extent that depends on both the amount of loaded surfactant and the experimental protocols applied

Molecular remission is an independent predictor of progression-free survival in patients with Waldenström macroglobulinemia treated with chemo-immunotherapy: Results from the FIL_BIOWM study

Waldenström macroglobulinemia (WM) is a mature B-cell neoplasm characterized by bone marrow (BM) infiltration by lymphoplasmacytic lymphoma and a monoclonal IgM protein in the serum.1 The past 2 decades have witnessed important treatment advances, with the introduction of chemo-immunotherapy (CIT) in the early 2000s and ibrutinib in more recent years. Despite these progresses, most patients eventually relapse after treatment. The depth of clinical response following rituximab-based therapy has revealed an important predictor of progression-free survival (PFS).International Waldenstrom's Macroglobulinemia Foundation

Early diagnosis, disease stage and prognosis in wild‐type transthyretin amyloid cardiomyopathy: The DIAMOND study

Aims: Disease staging and prognostic scoring in wild-type transthyretin-related cardiac amyloidosis (ATTRwt-CA) can be captured by two systems (NAC and Columbia scores). However, uncertainty remains as epidemiology of the disease is evolving rapidly. We evaluated features associated with staging systems across ATTRwt-CA patients from different diagnostic pathways, and their association with prognosis. Methods: We performed an analysis on DIAMOND patients with available data to evaluate NAC and Columbia score. DIAMOND was a retrospective study from 17 Italian referral centres for CA, enrolling 1281 patients diagnosed between 2016 and 2021, and aimed at describing characteristics of pathways leading to ATTRwt-CA diagnosis. Of the original cohort, 811 patients were included in this analysis. Each patient had NAC and Columbia score calculated. Patients were grouped according to NAC and Columbia scoring classes. We described characteristics of patients according to staging classes and diagnostic pathways at diagnosis. Prevalence of early diagnoses, defined as NAC Ia, NYHA class I, no use of diuretics, no history of heart failure (HF) hospitalizations nor of atrial fibrillation prior to diagnosis, was investigated. Finally, prognostic variables were tested alone and grouped as NAC or Columbia scores in Cox univariate and multivariate regression analyses. Prognosis was investigated as all-cause mortality, in the whole population and dividing patients in HF versus other diagnostic pathways. Results: Only 1% of the study population had an early ATTRwt-CA diagnosis. Distribution of prognostic variables and of NAC and Columbia classes was heterogeneous across diagnostic pathways. The prevalence of NAC III and Columbia III was higher in the HF diagnostic pathway, but all NAC and Columbia classes were present in all pathways. Both NAC and Columbia scores were associated with all-cause mortality at univariate Cox regression analysis in the whole population, in patients from the HF diagnostic pathway and in those from other pathways. At multivariate analysis, Columbia score remained significantly associated with the outcome, together with age at diagnosis, left ventricular ejection fraction and maximal wall thickness. Conclusions: In this contemporary nationwide cohort, an ATTRwt-CA early diagnosis was very rare. Disease staging with NAC and Columbia scoring systems determined classes of patients with heterogeneous features. Both scores were significantly associated with mortality, but other variables also had prognostic significance

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51