Early noninvasive ventilation in general wards for acute respiratory failure: an international, multicentre, open-label, randomised trial.

Background: The impact of noninvasive ventilation (NIV) managed outside the intensive care unit in patients with early acute respiratory failure remains unclear. We aimed to determine whether adding early NIV prevents the progression to severe respiratory failure.

Methods: In this multinational, randomised, open-label controlled trial, adults with mild acute respiratory failure (arterial oxygen partial pressure/fraction of inspiratory oxygen [Pao/FiO] ratio ≥200) were enrolled across 11 hospitals in Italy, Greece, and Kazakhstan.

A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors.

To fully harness mesenchymal-stromal-cells (MSCs)' benefits during Normothermic Machine Perfusion (NMP), we developed an advanced NMP platform coupled with a MSC-bioreactor and investigated its bio-molecular effects and clinical feasibility using rat and porcine models. The study involved three work packages: 1) Development (n = 5): MSC-bioreactors were subjected to 4 h-liverless perfusion; 2) Rat model (n = 10): livers were perfused for 4 h on the MSC-bioreactor-circuit or with the standard platform; 3) Porcine model (n = 6): livers were perfused using a clinical device integrated with a MSC-bioreactor or in its standard setup. MSCs showed intact stem-core properties after liverless-NMP.

Meta-analysis of the factor structure of the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS).

Introduction: The SAPS and SANS was designed to measure two broad factors, but the majority of factor analyses conducted have found substantially more dimensions. To investigate their structure a meta-analysis was conducted of SAPS and SANS factor analysis.

Method: A total of 42 articles reporting 55 factor analyses were retrieved from database searches (PubMed, PsychINFO) supplemented by searches of references.

Incidence, predictability, and outcomes of systemic venous congestion following a fluid challenge in initially fluid-tolerant preload-responders after cardiac surgery: a pilot trial.

Background: Fluid administration has traditionally focused on preload responsiveness (PR). However, preventing fluid intolerance, particularly due to systemic venous congestion (VC), is equally important. This study evaluated the incidence and predictability of VC following a 7 ml/kg crystalloid infusion in fluid-tolerant preload-responders and its association with adverse outcomes.

Cryopreserved apoptotic mesenchymal stromal cells retain functional efficacy in suppressing an allergic inflammation in a murine model.

Mesenchymal stromal cell (MSC) apoptosis is required for in vivo immunosuppression. However, the induction of apoptosis is heavily dependent on the recipient's immune system. In graft-versus-host disease (GvHD), patients who fail to respond to MSCs are in fact those whose immune cells are unable to induce MSC apoptosis ex vivo.

Macrophage activation markers are associated with infection and mortality in patients with acute liver failure.

Background And Aims: Acute liver failure is a multisystem disorder with a high mortality and frequent need for emergency liver transplantation. Following massive innate immune system activation, soluble markers of macrophage activation are released during liver damage and their association with disease severity and prognosis requires exploration.

Methods: Patients ALF from the United States Acute Liver Failure Study Group (USALFSG, n = 224) and King's College Hospital (n = 40) together with healthy controls (HC, n = 50) were recruited.

Cellular uptake and in vivo distribution of mesenchymal-stem-cell-derived extracellular vesicles are protein corona dependent.

Extracellular vesicles (EVs) derived from mesenchymal stem cells are promising nanotherapeutics in liver diseases due to their regenerative and immunomodulatory properties. Nevertheless, a concern has been raised regarding the rapid clearance of exogenous EVs by phagocytic cells. Here we explore the impact of protein corona on EVs derived from two culturing conditions in which specific proteins acquired from media were simultaneously adsorbed on the EV surface.

Bone marrow-derived mesenchymal stromal cells obstruct AML-targeting CD8 clonal effector and CAR T-cell function while promoting a senescence-associated phenotype.

Bone marrow mesenchymal stromal cells (MSCs) have been described as potent regulators of T-cell function, though whether they could impede the effectiveness of immunotherapy against acute myeloid leukemia (AML) is still under investigation. We examine whether they could interfere with the activity of leukemia-specific clonal cytotoxic T-lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells, as well as whether the immunomodulatory properties of MSCs could be associated with the induction of T-cell senescence. Co-cultures of leukemia-associated Wilm's tumor protein 1 (WT1) and tyrosine-protein kinase transmembrane receptor 1 (ROR1)-reactive CTLs and of CD123-redirected switchable CAR T cells were prepared in the presence of MSCs and assessed for cytotoxic potential, cytokine secretion, and expansion.

Haploidentical Transplant with Post-Transplant Cyclophosphamide for Acute Myeloid Leukaemia and Myelodysplastic Syndromes Patients: The Role of Previous Lines of Therapy.

Background: Allogeneic haematopoietic stem-cell transplant is an option, potentially curative, for high-risk acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Post-transplant cyclophosphamide administration allows for the selection of haploidentical donors in patients who are eligible for the procedure but do not have a fully matched donor since it can overcome the HLA barrier. There is still an active debate on whether intensifying the conditioning regimen is necessary with haploidentical donors when peripheral blood stem cells are used as the graft source.

Apoptosis in mesenchymal stromal cells activates an immunosuppressive secretome predicting clinical response in Crohn's disease.

In vivo apoptosis of human mesenchymal stromal cells (MSCs) plays a critical role in delivering immunomodulation. Yet, caspase activity not only mediates the dying process but also death-independent functions that may shape the immunogenicity of apoptotic cells. Therefore, a better characterization of the immunological profile of apoptotic MSCs (ApoMSCs) could shed light on their mechanistic action and therapeutic applications.

Perioperative Renal Ultrasonography of Arterio-to-Venous Coupling Predicts Postoperative Complications after Major Laparoscopic Urologic Surgery.

Point-of-care ultrasonography (POCUS) with concomitant venous and arterial Doppler assessment enables clinicians to assess organ-specific blood supply. To date, no studies have investigated the usefulness of including a comprehensive perioperative POCUS assessment of patients undergoing major laparoscopic surgery. The primary aim of the present study was to evaluate whether the combined venous and arterial renal flow evaluation, measured at different time points of perioperative period, may represent a clinically useful non-invasive method to predict postoperative acute kidney injury (AKI) after major laparoscopic urologic surgery.

Fludarabine-Melphalan-Campath, Followed by Unmanipulated Peripheral-Blood Haematopoietic Stem Cells, Can Still Cure Lymphoma.

Background: The second decade of this millennium was characterized by a widespread availability of chimeric antigen receptor T-cell (CAR-T) therapies to treat relapsed and refractory lymphomas. As expected, the role and indication of allogeneic haematopoietic stem cell transplant (allo-HSCT) in the management of lymphoma changed. Currently, a non-neglectable proportion of patients will be considered candidate for an allo-HSCT, and the debate of which transplant platform should be offered is still active.

Engineering tandem CD33xCD146 CAR CIK (cytokine-induced killer) cells to target the acute myeloid leukemia niche.

In acute myeloid leukemia (AML), malignant stem cells hijack the normal bone marrow niche where they are largely protected from the current therapeutic approaches. Thus, eradicating these progenitors is the ultimate challenge in the treatment of this disease. Specifically, the development of chimeric antigen receptors (CARs) against distinct mesenchymal stromal cell subpopulations involved in the maintenance of leukemic stem cells within the malignant bone marrow microenvironment could represent a new strategy to improve CAR T-cell therapy efficacy, which is still unsuccessful in AML.

The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair.

Mesenchymal stromal cells (MSCs) have been extensively tested for the treatment of numerous clinical conditions and have demonstrated good safety but mixed efficacy. Although this outcome can be attributed in part to the heterogeneity of cell preparations, the lack of mechanistic understanding and tools to establish cell pharmacokinetics and pharmacodynamics, as well as the poorly defined criteria for patient stratification, have hampered the design of informative clinical trials. We and others have demonstrated that MSCs can rapidly undergo apoptosis after their infusion.

The use of continuous positive airway pressure during the second and third waves of the COVID-19 pandemic.

Background: In a preliminary study during the first COVID-19 pandemic wave, we reported a high rate of success with continuous positive airway pressure (CPAP) in preventing death and invasive mechanical ventilation (IMV). That study, however, was too small to identify risk factors for mortality, barotrauma and impact on subsequent IMV. Thus, we re-evaluated the efficacy of the same CPAP protocol in a larger series of patients during second and third pandemic waves.

Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV.

Selective homing of CAR-CIK cells to the bone marrow niche enhances control of the acute myeloid leukemia burden.

Acute myeloid leukemia (AML) is a hematological malignancy derived from neoplastic myeloid progenitor cells characterized by abnormal clonal proliferation and differentiation. Although novel therapeutic strategies have recently been introduced, the prognosis of AML is still unsatisfactory. So far, the efficacy of chimeric antigen receptor (CAR)-T-cell therapy in AML has been hampered by several factors, including the poor accumulation of the blood-injected cells in the leukemia bone marrow (BM) niche in which chemotherapy-resistant leukemic stem cells reside.

Electrocardiographic Time-Intervals Waveforms as Potential Predictors for Severe Acute Kidney Injury in Critically Ill Patients.

Background: Acute kidney injury (AKI) is common in critically ill patients admitted to intensive care units (ICU) and is frequently associated with poorer outcomes. Hence, if an indicator is available for predicting severe AKI within the first few hours of admission, management strategies can be put into place to improve outcomes. Materials and methods: This was a prospective, observational study, involving 63 critically ill patients, that aimed to explore the diagnostic accuracy of different Doppler parameters in predicting AKI in critically ill patients from a mixed ICU.

Assessing the immunosuppressive activity of alginate-encapsulated mesenchymal stromal cells on splenocytes.

Mesenchymal stromal cells (MSCs) show immunosuppressive effects both cell-to-cell contact (direct) with immune cells and by producing paracrine factors and extracellular vesicles (indirect). A key challenge in delivering this therapeutic effect is retaining the MSCs at the site of injection. One way to address this is by encapsulating the MSCs within suitable biomaterial scaffolds.

Ultrasound localization of central vein catheter tip by contrast-enhanced transthoracic ultrasonography: a comparison study with trans-esophageal echocardiography.

Background: To assess the usefulness of pre-operative contrast-enhanced transthoracic echocardiography (CE-TTE) and post-operative chest-x-ray (CXR) for evaluating central venous catheter (CVC) tip placements, with trans-esophageal echocardiography (TEE) as gold standard.

Methods: A prospective single-center, observational study was performed in 111 patients requiring CVC positioning into the internal jugular vein for elective cardiac surgery. At the end of CVC insertion by landmark technique, a contrast-enhanced TTE was performed by both the apical four-chambers and epigastric bicaval acoustic view to assess catheter tip position; then, a TEE was performed and considered as a reference technique.

CD14 positive cells accelerate hematopoietic stem cell engraftment.

The improvement of hematopoietic stem and progenitor cell (HSPC) engraftment remains a high-priority goal when limited cell doses are available, such as in cord blood (CB) transplantation and HSC gene therapy. We observed that monocytes are highly effective at improving the engraftment of both CB-CD34 and lentivirus-transfected CD34 cells in a xenogeneic model of HSC transplantation. Moreover, monocytes, in particular the CD14CD16 classical subset, in co-culture systems increase survival and stemness of CB-CD34 cells.

Relationship Between Gender and Clinician's Subjective Experience during the Interaction with Psychiatric Patients.

Introduction: The clinician's subjective experience can be a valuable element for diagnosis and treatment. A few factors have been recognized that affect it, such as the patient's personality, the severity of psychopathology, and diagnosis. Other factors, such as patient's and clinician's gender, have not been specifically investigated.