Targeting STMN2 for neuroprotection and neuromuscular recovery in Spinal Muscular Atrophy: evidence from in vitro and in vivo SMA models.

The development of ground-breaking Survival Motor Neuron (SMN) replacement strategies has revolutionized the field of Spinal Muscular Atrophy (SMA) research. However, the limitations of these therapies have now become evident, highlighting the need for the development of complementary targets beyond SMN replacement. To address these challenges, here we explored, in in vitro and in vivo disease models, Stathmin-2 (STMN2), a neuronal microtubule regulator implicated in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), as a novel SMN-independent target for SMA therapy.

Extracellular Vesicles from Human Induced Pluripotent Stem Cells Exhibit a Unique MicroRNA and CircRNA Signature.

Extracellular vesicles (EV) have emerged as promising cell-free therapeutics in regenerative medicine. However, translating primary cell line-derived EV to clinical applications requires large-scale manufacturing and several challenges, such as replicative senescence, donor heterogeneity, and genetic instability. To address these limitations, we used a reprogramming approach to generate human induced pluripotent stem cells (hiPSC) from the young source of cord blood mesenchymal stem/stromal cells (CBMSC).

Off-the-Shelf Cord-Blood Mesenchymal Stromal Cells: Production, Quality Control, and Clinical Use.

Unlabelled: Background Recently, mesenchymal stromal cells (MSCs) have gained recognition for their clinical utility in transplantation to induce tolerance and to improve/replace pharmacological immunosuppression. Cord blood (CB)-derived MSCs are particularly attractive for their immunological naivety and peculiar anti-inflammatory and anti-apoptotic properties.

Objectives: The objective of this study was to obtain an inventory of CB MSCs able to support large-scale advanced therapy medicinal product (ATMP)-based clinical trials.

Effects of Froggy Mouth Appliance in Pediatric Patients with Atypical Swallowing: A Prospective Study.

Atypical swallowing has a high incidence in growing subjects. Orthopedic treatment with orthodontic appliances and speech therapy are the main approaches to this problem. The aim of this prospective study was to evaluate the changes in the dental arches induced by one year of treatment with the Froggy Mouth myofunctional appliance designed to correct atypical swallowing.

Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial.

Background: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies.

Methods: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021.

Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review.

Background: Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs.

Validation of an automated cell counting method for cGMP manufacturing of human induced pluripotent stem cells.

Human induced pluripotent stem cells (hiPSCs) must be manufactured as advanced therapy medicinal products (ATMPs) for innovative tissue replacement clinical applications. Yet, production of hiPSCs under current Good Manufacturing Practice (cGMP) presents many hurdles, such as the large-scale cell expansion needed to reach therapeutically-relevant hiPSC doses. For the monitoring of this phase, a fast and reliable cell counting method should be used.

Kidney Involvement in Acute Hepatic Porphyrias: Pathophysiology and Diagnostic Implications.

Porphyrias are a group of rare disorders originating from an enzyme dysfunction in the pathway of heme biosynthesis. Depending on the specific enzyme involved, porphyrias manifest under drastically different clinical pictures. The most dramatic presentation of the four congenital acute hepatic porphyrias (AHPs: acute intermittent porphyria-AIP, ALAD deficiency, hereditary coproporphyria-HCP, and porphyria variegata-VP) consists of potentially life-threatening neurovisceral attacks, for which givosiran, a novel and effective siRNA-based therapeutic, has recently been licensed.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.

Critical Analysis of cGMP Large-Scale Expansion Process in Bioreactors of Human Induced Pluripotent Stem Cells in the Framework of Quality by Design.

Human induced pluripotent stem cells (hiPSCs) are manufactured as advanced therapy medicinal products for tissue replacement applications. With this aim, the feasibility of hiPSC large-scale expansion in existing bioreactor systems under current good manufacturing practices (cGMP) has been tested. Yet, these attempts have lacked a paradigm shift in culture settings and technologies tailored to hiPSCs, which jeopardizes their clinical translation.

Lack of Cost-Effectiveness of Preoperative Erythropoiesis-Stimulating Agents and/or Iron Therapy in Anaemic, Elective Surgery Patients: A Systematic Review and Updated Analysis.

Objectives: For anaemic elective surgery patients, current clinical practice guidelines weakly recommend the routine use of iron, but not erythrocyte-stimulating agents (ESAs), except for short-acting ESAs in major orthopaedic surgery. This recommendation is, however, not based on any cost-effectiveness studies. The aim of this research was to (1) systematically review the literature regarding cost effectiveness of preoperative iron and/or ESAs in anaemic, elective surgery patients and (2) update existing economic evaluations (EEs) with recent data.

Effectiveness of Iron Supplementation With or Without Erythropoiesis-Stimulating Agents on Red Blood Cell Utilization in Patients With Preoperative Anaemia Undergoing Elective Surgery: A Systematic Review and Meta-Analysis.

Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened.

How to implement of patient blood management pillar 1: An Italian expert opinion based on a "bundles" approach.

Worldwide iron anemia is a common disorder with a significant economic burden on health-care systems. Red blood cell transfusion is the mainstay to correct anemia in surgical settings, but it is also an overused procedure and recent data support its possible role in worsening patient outcomes. Patient Blood Management (PBM) is a multidisciplinary approach to optimize hemostasis, manage anemia, minimize iatrogenic blood loss, and improve tolerance to anemia.

Tongue rehabilitation through the froggy mouth device: case series.

Based on the knowledge supporting the position of the tongue in relation to the palate to be the guiding factor of oro-dental growth and the key factor in long-term orthodontic stability after treatment, 6 different case reports show how the Froggy Mouth device changes treatment strategy in rehabilitation of dysfunctional swallowing by relying on the subcortical process, following the principles established by pioneering studies on memorization mechanisms conducted by Eric Kandel (year 2000 Nobel Prize winner in medical field for his research on memorization process).

Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) Working Group.

Background And Objectives: Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce.

Froggy mouth: a new myofunctional approach to atypical swallowing.

Introduction: Atypical swallowing has a high incidence in adult and child populations. The treatment of the latter is generally achieved by the adoption of orthodontic appliances in conjunction with speech therapy. The aim of this article is to describe the clinical protocol of Froggy Mouth, an innovative myofunctional appliance designed to correct the atypical swallowing.

Patient blood management knowledge and practice among clinicians from seven European university hospitals: a multicentre survey.

Background And Objectives: The aim of this survey was to evaluate the knowledge about Patient Blood Management (PBM) principles and practices amongst clinicians working in seven European hospitals participating in a European Blood Alliance (EBA) project.

Materials And Methods: A web-based questionnaire was sent to 4952 clinicians working in medical, surgery and anaesthesiology disciplines. The responses were analysed, and the overall results as well as a comparison between hospitals are presented.

Can pegylated interferon improve the outcome of polycythemia vera patients?

Pegylated interferon (peg-IFN) was proven by phase II trials to be effective in polycythemia vera (PV); however, it is not clear whether it could improve patient outcome compared to hydroxyurea (HU). Here, we present an observational study on 65 PV patients aged 65 years or younger, who received either peg-IFN (30) or HU (35) according to the physician choice. Median follow-up was 75 months.

Charge-based precipitation of extracellular vesicles.

Vesicular-mediated communication between cells appears critical in many biological processes. Extracellular vesicles (EVs) released from healthy and diseased cells are involved in a network of exchange of biologically active molecules. Since EVs present in biological fluids carry the signature of the cell of origin, they are potential biomarkers for ongoing physiological or pathological processes.

Phytochemical investigations on Artemisia alba Turra growing in the North-East of Italy.

Artemisia alba Turra (Asteraceae) is an Euro-Mediterranean plant used in Veneto (North-East of Italy) as traditional medicine for the treatment of various diseases. A. alba is a taxonomically problematic species, characterised by common polymorphism leading to a quite high variability in secondary metabolites content.

Patient Blood Management in Europe: surveys on top indications for red blood cell use and Patient Blood Management organization and activities in seven European university hospitals.

Background And Objectives: Patient Blood Management (PBM) in Europe is a working group of the European Blood Alliance with the initial objective to identify the starting position of the participating hospitals regarding PBM for benchmarking purposes, and to derive good practices in PBM from the experience and expertise in the participating teams with the further aim of implementing and strengthening these practices in the participating hospitals.

Methods: We conducted two surveys in seven university hospitals in Europe: Survey on top indications for red blood cell use regarding usage of red blood cells during 1 week and Survey on PBM organization and activities.

Results: A total of 3320 units of red blood cells were transfused in 1 week at the seven hospitals.

The Use of Invisalign® System in the Management of the Orthodontic Treatment before and after Class III Surgical Approach.

The approach to skeletal dysmorphisms in the maxillofacial area usually requires an orthodontic treatment by means of fixed appliances, both before and after the surgical phase. Since its introduction, Invisalign system has become a popular treatment choice for the clinicians because of the aesthetics and comfort of the removable clear aligners compared with the traditional appliances. Therefore, the aim of the present report was to illustrate the management of a malocclusion by means of Invisalign system associated with the traditional surgical technique.