We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID‐19) in Spain until 13 ...July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range IQR: 52‐70), and 66% were male. The incidence of COVID‐19 in SOT recipients was two‐fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18‐131). Infection was hospital‐acquired in 13% of cases. No donor‐derived COVID‐19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon‐β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow‐up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio OR: 2.5; 95% CI: 1.4‐4.6), age >60 years (OR: 3.7; 95% CI: 2.5‐5.5), and hospital‐acquired COVID‐19 (OR: 3.0; 95% CI: 1.9‐4.9).
The authors report the Spanish nationwide experience with solid organ and hematopoietic stem cell transplant recipients diagnosed with COVID‐19, revealing a higher incidence and more aggressive course of infection than in the general population.
Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the ...outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation. Results Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion Post-transplantation cyclophosphamide-based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic GVHD than MUD transplantation.
The number of HLA-haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and ...non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for transplantation, and choosing the best HLA-haploidentical donor for transplantation remains a challenge. Several approaches to haploidentical transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting haploidentical donors for transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms.
In this research work, the suitability of short carbon fibre-reinforced polyamide 6 in pellet form for printing an aeronautical mould preform with specific thermomechanical requirements is ...investigated. This research study is based on an extensive experimental characterization campaign, in which the principal mechanical properties of the printed material are determined. Furthermore, the temperature dependency of the material properties is characterized by testing samples at different temperatures for bead printing and stacking directions. Additionally, the thermal properties of the material are characterized, including the coefficient of thermal expansion. Moreover, the influence of printing machine parameters is evaluated by comparing the obtained tensile moduli and strengths of several manufactured samples at room temperature. The results show that the moduli and strengths can vary from 78% to 112% and from 55% to 87%, respectively. Based on a real case study of its aeronautical use and on the experimental data from the characterization stage, a new mould design is iteratively developed with multiphysics computational guidance, considering 3D printing features and limitations. Specific design drivers are identified from the observed material’s thermomechanical performance. The designed mould, whose mass is reduced around 90% in comparison to that of the original invar design, is numerically proven to fulfil thermal and mechanical requirements with a high performance.
Accurate estimates of tree diameter, height, volume, and biomass are important for numerous economic and ecological applications. In this study, we report exponential equations to predict tree DBH ...(cm), stem volume over bark (VOB, m3), and total above-stump biomass (TASB, kg) using three varying levels of input data for Pinus radiata D. Don, Eucalyptus globulus Labill., and Eucalyptus nitens (H.Deane & Maiden) Maiden planted trees. The three sets of input data included: (1) tree height (HT, m), (2) tree HT and ground projected living crown area (CA, m2), and (3) tree HT, CA, and additional stand parameters. The analysis was performed using a large dataset covering the range of distribution of the species in central Chile and included stands of varying ages and planting densities. The first set of equations using only HT were satisfactory with Adj-R2 values ranging from 0.78 to 0.98 across all species and variables. For all three species, estimation of DBH, VOB, and TASB as a function of HT improved when CA was added as an additional independent variable, increasing Adj-R2 and reducing RMSE. The inclusion of stand variables, such as age and stand density, also resulted in further improvement in model performance. The models reported in this study are a robust alternative for DBH, VOB, and TASB estimations on planted stands across a wide range of ages and densities, when height and CA are known, especially when input data are derived from remote sensing techniques.
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has shown favorable results in the treatment of hematological malignancies. Despite the use of post-transplant cyclophosphamide ...(PTCy), graft
host disease (GVHD) remains as one of the main complications in this setting. Since the skin appears affected in up to 80% of cases of acute GVHD (aGVHD), its prognosis and diagnosis are essential for the correct management of these patients. Plasma concentration of elafin, an elastase inhibitor produced by keratinocytes, has been described elevated at the diagnosis of skin GVHD, correlated with the grade of GVHD, and associated with an increased risk of death. In this study we explored elafin plasma levels in the largest series reported of T cell-replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed ("discovery cohort"). Elafin levels at days +15 were no associated with chronic GVHD, non-relapse mortality, relapse, therapy-resistant GVHD, or overall survival. In our series, elafin levels at day +30 were not associated with post-transplant complications. On the other hand, elafin plasma levels at day +15 were higher in patients with severe skin aGVHD (21,313
14,974 pg/ml; p = 0.01). Of note, patients with higher elafin plasma levels at day +15 presented a higher incidence of stage III-IV skin aGVHD (HR = 18.9; p < 0.001). These results were confirmed (HR = 20.6; p < 0.001) in an independent group of patients (n = 62), i.e. the "validation cohort." These data suggest that measurement of elafin in patients undergoing haplo-HSCT with PTCy might be useful for an early identification of those patients who are at higher risk of suffering severe skin aGVHD and thus, improve their treatment and prognosis.
The inclusion of electrospun nanofiber veils was revealed as an effective method for enhancing the mechanical properties of fiber-reinforced epoxy resin composites. These veils will eventually allow ...the incorporation of nanomaterials not only for mechanical reinforcement but also in multifunctional applications. Therefore, this paper investigates the effect of electrospun nanofibrous veils made of polyamide 6 modified with TiO2 nanoparticles on the mechanical properties of a carbon-fiber/epoxy composite. The nanofibers were included in the carbon-fiber/epoxy composite as a single structure. The effect of positioning these veils in different composite positions was investigated. Compared to the reference, the use of unmodified and TiO2 modified veils increased the flexural stress at failure and the fracture toughness of composites. When TiO2 modified veils were incorporated, new antibacterial properties were achieved due to the photocatalytic properties of the veils, widening the application area of these composites.
Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative procedure for several hematological malignancies. Haploidentical HSCT (haplo-HSCT) using high-dose post-transplantation ...cyclophosphamide (PTCy) makes transplantation possible for patients with no HLA-matched sibling donor. However, this treatment can cause complications, mainly infection, graft-vs.-host disease (GVHD), and conditioning-related toxicity. In recent years, different biomarkers in the form of tissue-specific proteins have been investigated; these may help us to predict complications of allo-HSCT. In this study we explored two such biomarkers, suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3α (REG3α), in the largest series reported of T cell-replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed. ST2 and REG3α levels at day +15 were not associated with post-transplant complications. ST2 levels at day +30 were higher in patients with grade II-IV acute GVHD, mainly those who received reduced intensity conditioning (RIC; median 2,503 vs. 1,830 ng/ml;
= 0.04). Of note, patients with higher plasma ST2 levels at day +30 also presented a higher incidence of non-relapse mortality (HR, 7.9;
= 0.004) and lower 2-year overall survival (25 vs. 44 months;
= 0.02) than patients with lower levels. Patients with REG3α levels higher than 1,989 pg/ml at day +30 presented a higher incidence of acute gastrointestinal GVHD in the whole cohort (HR, 8.37;
= 0.003) and in the RIC cohort (HR 6.59;
= 0.01). These data suggest that measurement of ST2 and REG3α might be useful for the prognosis and prediction of complications in patients undergoing haplo-HSCT with PTCy.
iPSC (induced pluripotent stem cells) banks of iPSC lines with homozygous HLA (human leukocyte antigen) haplotypes (haplobanks) are proposed as an affordable and off-the-shelf approach to allogeneic ...transplantation of iPSC derived cell therapies. Cord blood banks offer an extensive source of HLA-typed cells suitable for reprogramming to iPSC. Several initiatives worldwide have been undertaken to create national and international iPSC haplobanks that match a significant part of a population.
To create an iPSC haplobank that serves the Spanish population (IPS-PANIA), we have searched the Spanish Bone Marrow Donor Registry (REDMO) to identify the most frequently estimated haplotypes. From the top ten donors identified, we estimated the population coverage using the criteria of zero mismatches in HLA-A, HLA-B, and HLA-DRB1 with different stringencies: high resolution, low resolution, and beneficial mismatch.
We have calculated that ten cord blood units from homozygous donors stored at the Spanish cord blood banks can provide HLA-A, HLA-B, and HLA-DRB1 matching for 28.23% of the population.
We confirm the feasibility of using banked cord blood units to create an iPSC haplobank that will cover a significant percentage of the Spanish and international population for future advanced therapy replacement strategies.
Delamination and brittle matrix fracture have long since been the biggest problems in fibre-reinforced composites. Recently, the incorporation of electrospun nanofibre veils has been shown to be an ...effective method for improving the mechanical properties of these composites, without causing process problems and negatively affecting other mechanical properties. Thus, these nanofibres have the potential to be used as thickness-reinforcing materials in composites. This paper investigates the effect of incorporating standalone electrospun nanofibre veils made of two different types of polyamide 6 (PA6) on the mechanical properties of carbon fibre/epoxy composites. The influence of positioning the electrospun veils at different interlaminar positions of the laminate has also been investigated.
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