INFECTIOUS ENTEROCOLITIS IN HEMATOPOIETIC CELL TRANSPLANT WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE.

Background: Despite the high incidence of diarrhea in hematopoietic cell transplant (HCT) recipients, data on infectious enterocolitis with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remain limited.

Objectives: Evaluate the characteristics, incidence, risk factors, and impact on outcomes of infectious enterocolitis in patients with hematologic malignancies undergoing HCT from matched sibling, matched unrelated, and haploidentical donors using PTCy as GVHD prophylaxis.

Study Design: Retrospective analysis of infectious enterocolitis episodes in 399 patients undergoing HCT at a single institution.

Billion-Scale Expansion of Functional hiPSC-Derived Cardiomyocytes in Bioreactors Through Oxygen Control and Continuous Wnt Activation.

Generation of upscaled quantities of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), for therapeutic or testing applications, is both expensive and time-consuming. Herein, a scalable bioprocess for hiPSC-CM expansion in stirred-tank bioreactors (STB) is developed. By combining the continuous activation of the Wnt pathway, through perfusion of CHIR99021, within a mild hypoxia environment, the expansion of hiPSC-CM as aggregates is maximized, reaching 4 billion of pure hiPSC-CM in 2L STB.

Barcoded Hybrids of Extracellular Vesicles and Lipid Nanoparticles for Multiplexed Analysis of Tissue Distribution.

Targeted delivery of therapeutic agents is a persistent challenge in modern medicine. Recent efforts in this area have highlighted the utility of extracellular vesicles (EVs) as drug carriers, given that they naturally occur in bloodstream and tissues, and can be loaded with a wide range of therapeutic molecules. However, biodistribution and tissue tropism of EVs remain difficult to study systematically.

Incidence, Risk Factors, and Outcomes of BK Hemorrhagic Cystitis in Hematopoietic Stem Cell Transplantation From HLA-Matched and Haploidentical Donors With Post-Transplant Cyclophosphamide.

BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic stem cell transplantation (HSCT), particularly when posttransplant cyclophosphamide (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes. This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis.

Gastric Bleeding in Stem Cell Transplantation: A Focus on Gastric Vascular Ectasia Under Post-Transplant Cyclophosphamide, Sirolimus, and Mycophenolate Mofetil Prophylaxis.

Gastrointestinal bleeding (GIB) is a serious complication following allogeneic hematopoietic stem cell transplantation (HSCT), with limited data on its incidence and characteristics, particularly for upper gastrointestinal bleeding (UGIB) of gastric origin. We aimed to evaluate the incidence, clinical, endoscopic, and histopathologic features, and outcomes of UGIB, with a focus on gastric vascular ectasias (GVEs) in patients undergoing HSCT with graft-versus-host disease (GVHD) prophylaxis using post-transplant cyclophosphamide (PTCY), sirolimus or calcineurin inhibitors, and mycophenolate mofetil. This retrospective, single-center study included all adult patients who underwent allogeneic HSCT at a single institution between January 2017 and December 2023.

Incidence, risk factors and therapy response of acute graft-versus-host disease after myeloablative hematopoietic stem cell transplantation with posttransplant cyclophosphamide.

Posttransplant cyclophosphamide, sirolimus and mycophenolate mofetil (PTCy/siro/MMF) constitutes an innovative and well-tolerated acute graft-versus-host disease (aGVHD) prophylaxis after allogeneic stem cell transplantation (allo-HSCT), but risk factors for aGVHD incidence and therapy failure in this setting are scarce. This study prospectively registered all consecutive adult patients with hematologic malignancies who received a myeloablative allo-HSCT using PTCy/siro/MMF prophylaxis at our institution between 2017 and 2023. A total of 385 patients were included, of whom 44%, 34% and 22% were transplanted from matched sibiling, matched unrelated and haploidentical donors, respectively.

Portuguese validation of the foot health status Questionnaire in patients with diabetic foot disease.

Purpose: This study aims to adapt and validate the Foot Health Status Questionnaire, developed by Bennett et al., in Portuguese patients with diabetic foot.

Materials And Methods: A cross-sectional study was conducted with 143 patients with diabetic foot.

Longitudinal outcome over four decades of allogeneic stem cell transplantation: a single center experience.

This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine.

A roadmap towards manufacturing extracellular vesicles for cardiac repair.

For the past two decades researchers have linked extracellular vesicle (EV)-mediated mechanisms to various physiological and pathological processes in the heart, such as immune response regulation, fibrosis, angiogenesis, and the survival and growth of cardiomyocytes. Although use of EVs has gathered momentum in the cardiac field, several obstacles in both upstream and downstream processes during EV manufacture need to be addressed before clinical success can be achieved. Low EV yields obtained in small-scale cultures deter clinical translation, as mass production is a prerequisite to meet therapeutic doses.

Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide.

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors.

Microfiber-reinforced hydrogels prolong the release of human induced pluripotent stem cell-derived extracellular vesicles to promote endothelial migration.

Extracellular vesicle (EV)-based approaches for promoting angiogenesis have shown promising results. Yet, further development is needed in vehicles that prolong EV exposure to target organs. Here, we hypothesized that microfiber-reinforced gelatin methacryloyl (GelMA) hydrogels could serve as sustained delivery platforms for human induced pluripotent stem cell (hiPSC)-derived EV.

Dermatological Side Effects of Cancer Treatment: Psychosocial Implications-A Systematic Review of the Literature.

Cancer is a leading cause of mortality and morbidity all over the world and the second major cause of death in Portugal. Dermatological side effects resulting from cancer treatment have a psychosocial impact on patients' lives, such as quality of life (QoL), body image, cognitive fusion and social inhibition. This systematic review aimed to explore and synthesize the psychosocial impact of dermatological side effects of cancer treatment, answering the following research objectives: (i) Do the dermatological side effects of the cancer treatment present any psychosocial impact for the patients? (ii) How does the psychosocial impact of the dermatological toxicities of the cancer treatment manifest in patients' lives? Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and guided a systematic search through the PubMed, Cochrane Library and PyscNet databases.

Reduced Incidence of Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation with Calcineurin-Free Graft-versus-Host Disease Prophylaxis.

Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are frequently associated with neurologic complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, there is a lack of studies comparing the incidence and characteristics of neurologic complications in patients undergoing HSCT based on CNI-free or CNI-based GVHD prophylaxis. This retrospective single-center study analyzed the neurologic complications in 2 cohorts of patients undergoing HSCT with either CNI-based GVHD prophylaxis (n = 523) or CNI-free prophylaxis with post-transplantation cyclophosphamide, sirolimus, and mycophenolate mofetil (n = 371).

Clinically Expired Platelet Concentrates as a Source of Extracellular Vesicles for Targeted Anti-Cancer Drug Delivery.

The short shelf life of platelet concentrates (PC) of up to 5-7 days leads to higher wastage due to expiry. To address this massive financial burden on the healthcare system, alternative applications for expired PC have emerged in recent years. Engineered nanocarriers functionalized with platelet membranes have shown excellent targeting abilities for tumor cells owing to their platelet membrane proteins.

Stress reduction interventions for patients with chronic diabetic foot ulcers: a qualitative study into patients and caregivers' perceptions.

Background: The present study aimed to assess the perceptions of patients with chronic diabetic foot ulcers (DFUs) and their family caregivers regarding the impact of two stress reduction interventions on DFU and psychological wellbeing. The intervention included progressive muscle relaxation and hypnosis sessions.

Methods: This study used a qualitative exploratory design and included individual interviews with eight patients with chronic DFUs and six family caregivers, using a semi-structured interview guide.

T Cell-Depleted Peripheral Blood versus Unmanipulated Bone Marrow in Matched Sibling Transplantation for Aplastic Anemia.

Bone marrow (BM) is the recommended stem cell source for hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs) in patients with severe aplastic anemia (SAA) for its superior survival and graft-versus-host disease (GVHD) outcomes compared to recipients of unmanipulated peripheral blood (PB) HSCT. Nevertheless, no studies comparing BM with ex vivo T cell-depleted (TCD) PB have been reported to date. The aim of the present study was to compare the transplantation outcomes of MSD HSCT recipients with SAA using PB (with partial ex vivo TCD targeted cell dose grafts) with those of MSD HSCT recipients with SAA using unmanipulated BM.

Expression of Extracellular Vesicle PIWI-Interacting RNAs Throughout hiPSC-Cardiomyocyte Differentiation.

Extracellular Vesicles (EV) play a critical role in the regulation of regenerative processes in wounded tissues by mediating cell-to-cell communication. Multiple RNA species have been identified in EV, although their function still lacks understanding. We previously characterized the miRNA content of EV secreted over hiPSC-cardiomyocyte differentiation and found a distinct miRNA expression in hiPSC-EV driving its bioactivity.

Bioactivity and miRNome Profiling of Native Extracellular Vesicles in Human Induced Pluripotent Stem Cell-Cardiomyocyte Differentiation.

Extracellular vesicles (EV) are an attractive therapy to boost cardiac regeneration. Nevertheless, identification of native EV and corresponding cell platform(s) suitable for therapeutic application, is still a challenge. Here, EV are isolated from key stages of the human induced pluripotent stem cell-cardiomyocyte (hiPSC-CM) differentiation and maturation, i.

Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation.

Human induced pluripotent stem cells (hiPSC) possess significant therapeutic potential due to their high self-renewal capability and potential to differentiate into specialized cells such as cardiomyocytes. However, generated hiPSC-derived cardiomyocytes (hiPSC-CM) are still immature, with phenotypic and functional features resembling the fetal rather than their adult counterparts, which limits their application in cell-based therapies, cardiac disease modeling, and drug cardiotoxicity screening. Recent discoveries have demonstrated the potential of the extracellular matrix (ECM) as a critical regulator in development, homeostasis, and injury of the cardiac microenvironment.

Virtual Reality Rehabilitation's Impact on Negative Symptoms and Psychosocial Rehabilitation in Schizophrenia Spectrum Disorder: A Systematic Review.

Background: Schizophrenia is a chronic psychiatric disorder with symptoms that can severely affect patients' quality of life. While drug administration inhibits most of the positive symptoms, it fails to effectively treat the negative symptoms and in turn relies on rehabilitation therapies. With technological progress, virtual reality (VR) has been the target of recent studies in terms of mental health rehabilitation and has been shown to be a tool with ecological validity in order to introduce the individual to situations similar to their daily life.

Next generation of heart regenerative therapies: progress and promise of cardiac tissue engineering.

The adult heart is a vital and highly specialized organ of the human body, with limited capability of self-repair and regeneration in case of injury or disease. Engineering biomimetic cardiac tissue to regenerate the heart has been an ambition in the field of tissue engineering, tracing back to the 1990s. Increased understanding of human stem cell biology and advances in process engineering have provided an unlimited source of cells, particularly cardiomyocytes, for the development of functional cardiac muscle, even though pluripotent stem cell-derived cardiomyocytes poorly resemble those of the adult heart.

From Livable Communities to Livable Metropolis: Challenges for Urban Mobility in Lisbon Metropolitan Area (Portugal).

Urban mobility plays an important role in addressing urban livability. The complexification and dispersion of travel due to the improvement of transport and the multiplication of our daily living places underline the relevance of multilevel territorial planning, recognizing that the knowledge of local differences is essential for more effective urban policies. This paper aims (1) to comprehend conceptually how urban mobility contributes to the urban livability from the local to metropolitan level and (2) to assess the previous relation toward a livable metropolis based on the readily available statistics for the Lisbon Metropolitan Area.

Adoptive transfer of ex vivo expanded SARS-CoV-2-specific cytotoxic lymphocytes: A viable strategy for COVID-19 immunosuppressed patients?

Cellular and humoral response to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is on focus of research. We evaluate herein the feasibility of expanding virus-specific T cells (VST) against SARS-CoV-2 ex vivo through a standard protocol proven effective for other viruses. The experiment was performed in three different donors' scenarios: (a) SARS-CoV-2 asymptomatic infection/negative serology, (b) SARS-CoV-2 symptomatic infection/positive serology, and (c) no history of SARS-CoV-2 infection/negative serology.

Phosphorus leaching from riparian soils with differing management histories under three grass species.

Plants release carbon-based exudates from their roots into the rhizosphere to increase phosphorus (P) supply to the soil solution. However, if more P than required is brought into solution, additional P could be available for leaching from riparian soils. To investigate this further, soil columns containing a riparian arable and buffer strip soil, which differed in organic matter contents, were sown with three common agricultural and riparian grass species.

Greenhouse gas fluxes from a grazed grassland soil after slurry injections and mineral fertilizer applications under the Atlantic climatic conditions of NW Spain.

The number of studies that investigate how agricultural practices on dairy farms in the North West (NW) of Spain affect greenhouse gas (GHG) fluxes from soils is limited. Thus, the objective of this study was to quantify the effects of the application of mineral fertilizers and cattle slurry injections on GHG fluxes from a grassland soil with grazing dairy cattle, in Galicia (NW Spain). We also aimed to identify the type of fertilizer associated with high grass production and low GHG fluxes.