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Moreover, we do believe that "peer teaching" is promoted through these sessions given that within the same group, advanced students support and lead their teammates in the project.4 The positive results of these sessions have largely been accepted by students and professors who consider this program a valuable asset in the medical curriculum.4 ACKNOWLEDGEMENTS We would like to express our gratitude to professor García-Seoane and Doctor Ji for sharing their final degree thesis in this project. Active learning and Clinical case, CREDE, Medical Education, Peer teaching Keywords: Active learning and Clinical case; CREDE; Medical Education; Peer teaching EN Active learning and Clinical case CREDE Medical Education Peer teaching 442 442 1 08/06/21 20210801 NES 210801 We read with great interest the article by Ferenchak et al.1 describing how the CREDE (The Center for Research in Education, Diversity, and Excellence) framework could improve medical education. [Extracted from the article]

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3+ T cells, CD8+ T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4+ T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4+ T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning. [ABSTRACT FROM AUTHOR]

Objectives: Umbilical cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) modalities have been developed to offset the lack of matched donors. In this study, we compare the transfusion requirements of patients undergoing UCBT and haplo‐HSCT in a single institution with the aim of providing additional information for clinicians to choose the most adequate alternative graft for HSCT. Methods: The study reviewed 67 and 46 patients undergoing UCBT and haplo‐HSCT, respectively. Results: There were no significant differences for RBC and PLT requirements according to the transplantation modality. Median time to RBC transfusion independence was 35 and 25.5 days in patients who received an UCBT and haplo‐HSCT, respectively (P = 0.38), while median time to platelet transfusion independence was 31 days for UCBT patients and 23 for haplo‐HSCT patients (P < 0.001). Days until neutrophils > 0.5 × 109/L were the only variable that significantly influenced RBC and PLT requirements for both transplantation modalities. Cumulative incidence of RBC and PLT transfusion independence at 90 days after transplantation was similar for both UCBT and haplo‐HSCT. Conclusions: Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Induction. • Magnetic nanoparticles (MNPs) synthesis and functionalization. • Antimicrobial activity of MNPs. • Antimicrobial drug delivery by MNPs. • MNPs biodistribution and toxicity. Abstract In the last years, the antimicrobial resistance against antibiotics has become a serious health issue, arise as global threat. This has generated a search for new strategies in the progress of new antimicrobial therapies. In this context, different nanosystems with antimicrobial properties have been studied. Specifically, magnetic nanoparticles seem to be very attractive due to their relatively simple synthesis, intrinsic antimicrobial activity, low toxicity and high versatility. Iron oxide NPs (IONPs) was authorized by the World Health Organization for human used in biomedical applications such as in vivo drug delivery systems, magnetic guided therapy and contrast agent for magnetic resonance imaging have been widely documented. Furthermore, the antimicrobial activity of different magnetic nanoparticles has recently been demonstrated. This review elucidates the recent progress of IONPs in drug delivery systems and focuses on the treatment of infectious diseases and target the possible detrimental biological effects and associated safety issues. [ABSTRACT FROM AUTHOR]

A 66-year-old patient with myelodysplastic syndrome under prophylactic platelet transfusion support experienced malaise, chills, and a sudden drop in blood pressure 15 minutes after starting the transfusion of a single donor platelet's unit. 3 Ramirez-Arcos S, Alport T, Goldman M. Intermittent bacteremia detected in an asymptomatic apheresis platelet donor with repeat positive culture for Escherichia coli: a case report. Platelet concentrates (PCs), stored at room temperature, have the highest risk of bacterial contamination among labile blood components.1 We report the case of an apheresis platelet product contaminated with I Klebsiella oxytoca i showing an amorphous mass on the platelet's bag. [Extracted from the article]

Traumatic brain injury represents one of the main health problems in developed countries. Growth hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for four days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted a greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury. [ABSTRACT FROM AUTHOR]

There are many studies on the polymorphism of the HLA system in healthy donor populations, such as registries of unrelated bone marrow donors. Investigations on the characterization of the HLA complex in hematopoietic stem cell transplant (HSCT) patients, however, are scarce, at least in the Spanish population. This study presents a large‐scale analysis of allelic diversity and HLA distribution at a high‐resolution level in 2886 patients undergoing HSCT in Spanish centres of the "Grupo Español de Trasplante Hematopoyético y Terapia Celular" during a period of 11 years. Allelic diversity analysis identified 67 HLA‐A, 133 HLA‐B, 60 HLA‐C, 63 HLA‐DRB1, 24 HLA‐DQB1 and 27 HLA‐DPB1 different alleles. Rare alleles were detected among which 33 alleles had not been reported in the European catalog of common and well‐documented HLA alleles. Regarding the distribution of five genes‐haplotypes, it was observed that the five most frequent extended haplotypes found in our population were between the most common in other Spanish populations, both in patients and in healthy subjects. However, some particular haplotypes were also detected. Bilocus associations HLA‐C ~ B and ‐DRB1 ~ DQB1 were analyzed in order to predict the probability of finding 10/10 matched donors in registries. We found HLA‐B alleles showing a great diversity of combinations with HLA‐C alleles and unusual associations involving a negative predicting factor. In the field of adoptive therapies, our work supports the necessity to expand further research of TCR‐engineered cells, adoptive transfer of virus‐specific T‐cells and vaccines to target HLA alleles other than A*02:01. HLA alleles such as A*01:01, A*03:01, A*24:02, B*44:03, B*07:02 or B*51:01, might be considered new targets due to its high frequency in our population. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of CD34+ selected ex vivo T‐cell depletion (TCD) vs post‐transplant cyclophosphamide, sirolimus, and mycophenolate mofetil (PTCy‐Sir‐MMF) as graft‐vs‐host disease (GVHD) prophylaxis. Methods: We retrospectively included patients who underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT) with either TCD (n = 38) or PTCy‐Sir‐MMF (n = 91). Results: Cumulative incidence of neutrophil and platelet recovery was 92% vs 99% (P =.06) and 89% vs 97% (P =.3) in TCD and PTCy‐Sir‐MMF, respectively. Cumulative incidences of aGHVD grade II‐IV, III‐IV, and moderate to severe cGVHD were 11% vs 19% (P =.2), 3% vs 2% (P =.9), and 3% vs 36% (P <.001) in TCD and PTCy‐Sir‐MMF, respectively. The 2‐year non‐relapse mortality, relapse, disease‐free and overall survival were 25% vs 8% (P =.01), 20% vs 16% (P =.2), 55% vs 76% (P =.004), 57% vs 83% (P =.004) for TCD and PTCy‐Sir‐MMF, respectively. Cumulative incidence of cytomegalovirus and Epstein‐Barr infection requiring therapy was 76% vs 40% (P <.001) and 32% vs 0% (P <.001) in TCD and PTCy‐Sir‐MMF, respectively. PTCy‐Sir‐MMF platform showed faster T‐cell reconstitution. Conclusions: PTCy‐Sir‐MMF provides better survival outcomes but is associated with higher risk of cGVHD compared to TCD. [ABSTRACT FROM AUTHOR]

• Neurologic complications are relatively common after allogeneic stem cell transplantation. • The most frequent neurologic complication was encephalopathy, followed by neuropathy and myopathy. 17% of the peripheral nervous system complications were immune-mediated. • Central nervous system, but not peripheral nervous system, neurologic complications are associated with poor overall survival. • Alternative donor, age >40 years, and development of acute or extensive chronic graft-versus-host disease were associated with an increased risk of neurologic complications. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be associated with neurologic complications, data on noninfectious etiologies are scanty. Therefore, we analyzed the incidence, clinical characteristics, risk factors, and influence on outcomes of noninfectious neurologic complications (NCs) in 971 consecutive patients with hematologic malignancies undergoing allo-HSCT at our center between January 2000 and December 2016. We evaluated NCs affecting the central nervous system (CNS) and peripheral nervous system (PNS). The median duration of follow-up of survivors was 71 months (range, 11 to 213 months). A total of 467 patients received a matched sibling donor (MSD) transplant, 381 received umbilical cord blood (UCB), 74 received a haploidentical transplant, and 49 received a matched unrelated donor (MUD) transplant. One hundred forty-nine (15.3%) NCs were documented at a median of 78 days after transplantation (range, 5 days before to 3722 days after). The cumulative incidence risk of developing NC was 7.5% (95% confidence interval, 6% to 8.2%) at day +90 and 13% at 5 years. The 5-year cumulative incidence of NCs was 10.8% after MSD allo-HSCT and 15.3% after alternative donor (UCB, MUD, haploidentical) allo-HSCT (P =.004). There were 101 (68%) CNS complications, including encephalopathy, n = 46 (31%); headache, n = 20 (13%); stroke, n = 15 (10%); seizures, n = 9 (6%), posterior reversible encephalopathy syndrome, n = 6 (4%), and myelopathy, n = 5 (3%). PNS complications (32%) included neuropathies, n = 25 (17%), and myopathies and neuromuscular junction disorders, n = 23 (17%), with 17% of the total PNS complications being immune-related. In multivariable analysis, donor type other than MSD, age ≥40 years, development of acute graft-versus-host disease (GVHD) grade II-IV (hazard ratio [HR], 3.3; P <.00001), and extensive chronic GVHD (HR, 3.2; P =.0002) were independently associated with increased risk of NCs. The 5-year overall survival (OS) was 21% in patients who developed NCs and 41% for those who did not (P <.0001). This difference in OS was observed in patients developing CNS NCs, but not in those developing PNS complications. In conclusion, our study reveals NCs as a frequent and heterogeneous complication that, when affecting CNS, is associated with poor prognosis following allo-HSCT. [ABSTRACT FROM AUTHOR]

Objective: Characteristics and risk factors (RFs) of invasive fungal disease (IFD) have been little studied in the setting of umbilical cord blood transplantation (UCBT). Method: We retrospectively included 205 single‐unit myeloablative UCBT recipients with a median follow‐up of 64 months. Results: Fifty‐six episodes of IFD were observed in 48 patients (23%) at a median time of 123 days after stem cell infusion. Invasive mold disease (IMD) occurred in 42 cases, 38 of them (90%) caused by invasive aspergillosis whereas invasive yeast disease (IYD) occurred in 14 cases, most of them due to candidemia (n = 12, 86%). The 5‐year cumulative incidence of IFD, IMDs, and IYDs was 24% 19%, and 7%, respectively. In multivariate analysis, three RFs for IMDs were identified: age >30 years (HR 3.5, P = 0.017), acute grade II‐IV graft‐versus‐host disease (HR 2.3, P = 0.011), and ≥1 previous transplant (HR 3.1, P = 0.012). The probability of IMDs was 2.5%, 14%, and 33% for recipients with none, 1, or 2‐3 RFs, respectively (P < 0.001). Among IFD, IMDs had a negative effect on non‐relapse mortality in multivariate analysis (HR 1.6, P = 0.039). IMDs showed a negative impact on overall survival (HR 1.59, P = 0.018). Conclusion: Invasive mold disease were very common and serious complication after UCBT. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation has been considered a risk factor for development of platelet transfusion refractoriness. The objective of this study was to assess the platelet transfusion refractoriness rate in patients undergoing allogeneic hematopoietic stem cell transplantation from different sources. We retrospectively reviewed the charts and transfusion records of patients who underwent allogeneic stem cell transplantation at our institution between 2013 and 2015. The evaluation of post-transfusion platelet count was assessed for each transfusion given, from day of progenitor infusion to day 30 after transplantation. Of 167 patients included in this study, 101 received peripheral blood stem cell transplantation (PBSCT) and 66 received umbilical cord blood transplantation (UCBT). Overall, the percentage of platelet transfusions with a 14-h CCI lower than 5000 was 59.3%, being these data significantly higher for UCBT (67.6%) than for PBSCT (31.0%). Seventy-eight percent of patients underwent UCBT become refractory, while 38.6% of patients who received PBSCT were refractory. Factors associated to platelet refractoriness were lower CD34+ cell dose infused, higher number of antibiotics used, presence of anti-HLA I antibodies, and reduced-intensity conditioning regimen. Platelet refractoriness is a frequent and complex adverse event and remains a therapeutic challenge in the management of patients undergoing HSCT. There is a higher rate of platelet refractoriness in patients who received UCBT as compared to patients who received PBSCT. [ABSTRACT FROM AUTHOR]

Dysregulation ofMYBL2has been associated to tumorigenesis and the S427G polymorphism could induce partial inactivation of MYBL2, associating it with cancer risk. It has previously been shown thatMYBL2was over-expressed in some acute myeloid leukemias (AML), portending poor prognosis. However, to date no studies have investigated the S427G or other genetic variants ofMYBL2in AML. This study analyzed the S427G in 197 AML patients and 179 controls and screened theMYBL2sequence in patients. In contrast to other studies in solid tumors, the S427G was not associated with the incidence of AML. This study detected four unannotated genetic alterations, of which the Q67X could be involved in MYBL2 dysfunction. Eight polymorphisms were identified, among which the rs73116571, located in a splicing region, was associated with higher incidence in AML and weakerMYBL2expression, suggesting pre-disposition to AML. Additional functional studies should be performed to verify these genetic variations as possible targets in AML. [ABSTRACT FROM PUBLISHER]

Abstract: The MYBL2 gene encodes a transcription factor implicated in cell proliferation and maturation whose amplification or overexpression has been associated with different human malignancies, suggesting that it could be implicated in tumorigenesis. We analyzed MYBL2 expression and its prognostic value in 291 patients with de novo acute myeloid leukemia (AML) and we also evaluated its association with microRNAs 29 and 30 families. MYBL2 expression in AML patients was increased relative to CD34+ cells. Moreover, MYBL2 overexpression was associated with lower expression of miR-30a (P =0.024), miR-30b (P =0.021) and miR-30c (P =0.009). Multivariate analysis showed that MYBL2 expression was an independent factor for disease-free survival (HR 3.0, 95% CI 1.5–6.0, P =0.002) and cumulative incidence of relapse (HR 2.6, 95% CI 1.2–5.6, P =0.015) in patients with an intermediate-risk karyotype. In conclusion, our data showed that MYBL2 expression analysis could be useful to define subgroups of patients with poor prognosis. [Copyright &y& Elsevier]

Abstract: This study evaluates the incidence and prognostic impact of aberrant methylation of 25 tumor suppressor genes in 40 patients with RARS, a MDS subtype, by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Methylation of at least one gene was detected in 18 patients (45%). The genes methylated were CDKN2B (20%), RASSF1 (18%), RARB (10%), CDH13 (7.5%) and FHIT (5%). Patients with at least one methylated gene had a significantly shorter OS than patients without methylated genes. Aberrant methylation is a frequent event in patients with RARS as in patients with high-risk MDS appears to confer a worse prognosis. [Copyright &y& Elsevier]

Clinical studies focused on outcomes of umbilical cord blood transplantation (UCBT) for patients with chronic myelogenous leukemia (CML) in need of allogeneic stem cell transplantation and lacking an HLA-matched adult donor are limited. We analyzed the outcome of 26 adults with CML receiving single-unit UCBT from unrelated donors after myeloablative conditioning at a single institution. Conditioning regimens were based on combinations of thiotepa, busulfan, cyclophospamide or fludarabine, and antithymocyte globulin. At the time of transplantation, 7 patients (27%) were in first chronic phase (CP), 11 (42%) were in second CP, 2 (8%) were in accelerated phase (AP), and 6 (23%) were in blast crisis (BC). The cumulative incidence (CI) of myeloid engraftment was 88% at a median time of 22 days and was significantly better for patients receiving higher doses of CD34+ cells. The CI of acute graft-versus-host disease (GVHD) grade II-IV was 61%, that of acute GVHD grade III-IV was 39%, and that of chronic extensive GVHD was 60%. Treatment-related mortality (TRM) was 41% for patients undergoing UCBT while in first or second CP and 100% for patients in AP or BC (P < .01). After a median follow-up of 8 years, none of the patients relapsed, giving an overall disease-free survival (DFS) at 8 years of 41%. The DFS for patients undergoing UCBT while in any CP was 59%. These results demonstrate that UCBT from unrelated donors can be a curative treatment for a substantial number of patients with CML. Advances in supportive care and better selection of cord blood units and patients are needed to improve TRM. [ABSTRACT FROM AUTHOR]