Haploidentical versus Cord Blood Transplantation in Pediatric AML. A Retrospective Outcome Analysis on Behalf of the Pediatric Subcommittee of GETH (Grupo Español de Trasplante Hematopoyético).

Haploidentical stem cell transplantation (Haplo-SCT) and cord blood transplantation (CBT) are both effective alternative treatments in patients suffering from acute myeloid leukemia (AML) and lacking a matched HLA donor. In the last years, many centers have abandoned CBT procedures mostly due to concern about poorer immune recovery compared with Haplo-SCT. We conducted a retrospective multicenter study comparing the outcomes using both alternative approaches in AML. A total of 122 transplants (86 Haplo-SCTs and 36 CBTs) from 12 Spanish centers were collected from 2007 to 2021. Median age at hematopoietic stem cell transplantation (HSCT) was 7 years (0.4-20). Thirty-nine patients (31.9%) showed positive minimal residual disease (MRD) at HSCT and a previous HSCT was performed in 37 patients (30.3%). The median infused cellularity was 14.4 × 106/kg CD34+ cells (6.0-22.07) for Haplo-SCT and 4.74 × 105/kg CD34+ cells (0.8-9.4) for CBT. Median time to neutrophil engraftment was 14 days (7-44) for Haplo-SCT and 17 days (8-29) for CBT (P = .03). The median time to platelet engraftment was 14 days (6-70) for Haplo-SCT and 43 days (10-151) for CBT (P < .001). Graft rejection was observed in 13 Haplo-SCTs (15%) and in 6 CBTs (16%). The cumulative incidence of acute graft versus host disease (GvHD) grades II-IV was 54% and 51% for Haplo-SCT and CBT, respectively (P = .50). The cumulative incidence of severe acute GvHD (grades III-IV) was 22% for Haplo-SCT and 25% for CBT (P = .90). There was a tendency to a higher risk of chronic GvHD in the Haplo-SCT group being the cumulative incidence of 30% for Haplo-SCT and 12% for CBT (P = .09). The cumulative incidence of relapse was 28% and 20% for Haplo-SCT and CBT, respectively (P = .60). We did not observe statistically significant differences in outcome measures between Haplo-SCT and CBT procedures: 5-year overall survival (OS) was 64% versus 57% (P = .50), 5-year disease-free survival (DFS) 58% versus 57% (P = .80), GvHD-free and relapse-free survival (GFRFS) 41% versus 54% (P = .30), and cumulative incidence of transplant-related mortality (TRM) 14% versus 15% (P = .80), respectively. In the multivariate analysis, MRD positivity and a disease status >CR1 at the time of HSCT were significantly associated with poorer outcomes (P < .05). In conclusion, our study supports that both haploidentical and cord blood transplantation show comparable outcomes in pediatric AML patients. We obtained comparable survival rates, although CBT showed a trend to lower rates of chronic GvHD and higher GFRFS, demonstrating that it should still be considered a valuable option, particularly for pediatric patients.

Study on the Interaction of Polymeric Chemical Additives with Phase Change Materials in Air Lime Renders.

The interaction of microencapsulated phase change materials (PCMs) with polymeric chemical additives in an air lime binding matrix was studied. These polymer-based additives included an adhesion booster (derived from starch) and a superplasticizer (polycarboxylate ether). Two different PCMs with melting points of 18 °C and 24 °C were assayed. The microcapsules were composed of melamine, with paraffin-based PCM cores. Measurements of zeta potential, particle size distribution, adsorption isotherms, and viscosity analyses were performed to comprehend the behavior of the polymer-based additives within the air lime matrix and their compatibility with PCMs. Zeta potential experiments pointed to the absence of a strong interaction between the lime particles and the microcapsules of PCMs. At the alkaline pH of the lime mortar, the negative charge resulting from the deprotonation of the melamine shell of the microcapsules was shielded by cations, yielding high positive zeta potential values and stable dispersions of lime with PCMs. The polycarboxylate ether demonstrated the ability to counteract the increase in mixing water demand caused by the PCM addition in the lime matrix. The dispersing action of the superplasticizer on the lime particles was seen to exert a collateral dispersion of the PCMs. Conversely, despite the positive values of zeta potential, the addition of the starch-based additive resulted in the formation of large PCM-lime clumps. Air lime renders incorporating 5, 10, and 20% PCMs by weight with various dosages of these chemical additives were experimented with until the optimal formulation for the specific application of the mortars as renderings was achieved. This fine-tuned formulation effectively tackled issues commonly associated with the addition of PCMs to mortars, such as poor adhesion, crack formation, and reduced fluidity.

ECLIM-SEHOP: how to develop a platform to conduct academic trials for childhood cancer.

INTRODUCTION: ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation. METHODS: The platform's database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted. RESULTS: ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months. DISCUSSION: ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.

Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

AIMS: The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. METHODS AND RESULTS: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. CONCLUSIONS: In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.

Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach.

Introduction: Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer with high cure rate, but poses a significant medical challenge in adults and relapsed patients. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype, with approximately half of cases characterized by CRLF2 overexpression and frequent concomitant IKZF1 deletions. Methods: To address the need for efficient, rapid, and cost-effective detection of CRLF2 alterations, we developed a novel RT-qPCR technique combining SYBR Green and highresolution melting analysis on a single plate. Results: The method successfully identified CRLF2 expression, P2RY8::CRLF2 fusions, and CRLF2 and JAK2 variants, achieving a 100% sensitivity and specificity. Application of this method across 61 samples revealed that 24.59% exhibited CRLF2 overexpression, predominantly driven by IGH::CRLF2 (73.33%). High Resolution Melting analysis unveiled concurrent CRLF2 or JAK2 variants in 8.19% of samples, as well as a dynamic nature of CRLF2 alterations during disease progression. Discussion: Overall, this approach provides an accurate identification of CRLF2 alterations, enabling improved diagnostic and facilitating therapeutic decision-making.

Trajectory of Urine Albumin-Creatinine Ratio in Patients with Acute Heart Failure.

INTRODUCTION: Albuminuria is prevalent in patients with chronic heart failure and is a risk factor for disease progression. However, its clinical meaning in acute heart failure remains elusive. This study analyzed the trajectory of urine albumin to creatinine ratio (UACR) between admission and discharge and its association with decongestion. METHODS: In this prospective observational study, 63 patients were enrolled. UACR, B-type natriuretic peptide (BNP), and clinical congestion score (CCS) were obtained at admission and discharge. We used linear mixed regression analysis to compare changes in the natural logarithm of UACR (logUACR) and its association with changes in markers of decongestion. Estimates were reported as least squares mean with their respective 95% CIs. RESULTS: The median age of the study population was 87 years, 68.5% were women, and 69.8% had a left ventricular ejection fraction >50%. LogUACR at discharge significantly decreased in the overall population compared to admission (Δ -0.47, 95% CI: -0.78 to -0.15, p value = 0.003). The magnitude of UACR drop at discharge was associated with changes in surrogate markers of decongestion. Patients who showed a greater reduction in BNP at discharge exhibited a greater reduction in UACR (p = 0.016). The same trend was also found with clinical decongestion, as assessed by changes in CCS, however, without achieving statistical significance (p = 0.171). UACR change at discharge was not associated with changes in serum creatinine (p value = 0.923). CONCLUSION: In elderly patients with AHF and volume overload, the level of UACR significantly decreased upon discharge compared to admission. This reduction in UACR was closely linked to decreases in BNP.

Transition mechanism of the coverage-dependent polymorphism of self-assembled melamine nanostructures on Au(111).

Molecular self-assembled films have recently attracted increasing attention within the field of nanotechnology as they offer a route to obtain new materials. However, careful selection of the molecular precursors and substrates, as well as exhaustive control of the system evolution is required to obtain the best possible outcome. The three-fold rotational symmetry of melamine molecules and their capability to form hydrogen bonds make them suitable candidates to synthesize this type of self-assembled network. In this work, we have studied the polymorphism of melamine nanostructures on Au(111) at room temperature. We find two coverage-dependent phases: a honeycomb structure (α-phase) for submonolayer coverage and a close-packed structure (ß-phase) for full monolayer coverage. A combined scanning tunnel microscopy and density functional theory based-calculations study of the transition regime where both phases coexist allows describing the mechanism underlying this coverage driven phase transition in terms of the changes in the molecular lateral tension.

Frequency of surgical bone augmentation methods complementary to dental implant placement: A study evaluated with cone beam computed tomography.

Background: The success of dental implants largely depends on the quantity and quality of available bone. Occasionally, it is necessary to perform additional surgical techniques alongside implant placement to increase the available bone volume and ensure the success and survival of treatments. The objective of this study was to evaluate, through cone beam computed tomography, the need for supplementary bone augmentation methods in implant placement. Additionally, the study aimed to assess the frequency of such techniques based on gender, anatomical sectors, and types of bone augmentation procedures. Material and Methods: The analysis included 106 cone beam computed tomography images obtained from 77 patients over the age of 18 who sought oral rehabilitation with implants at the University Clinic of the Master's Program in Oral Implantology at the European University of Valencia. Results: A total of 201 edentulous sextants were analyzed. It was observed that 63.68% of the sextants required a bone augmentation technique, and there was a statistically significant difference (p=0.039) regarding the need for supplementary techniques in women. The need for bone augmentation by sectors was most prevalent the horizontal type (48.11%) and in the mandible (29.41%). About crestal and lateral approaches for sinus elevation, there was a higher need for the lateral technique (49.38%), and a statistically significant difference was evident (p=0.015). Conclusions: A high frequency of bone augmentation need for implant placement was demonstrated. It was shown that some form of supplementary surgical method was required in implant placement (63.68%). The highest need for bone augmentation was observed in the posterior maxillary sector, primarily in the vertical type (29.27%), accompanied by lateral window sinus elevation technique (49.38%). Key words:Bone graft, Dental implant, Guided bone regeneration, Sinus floor augmentation, Cone beam computed tomography.

Osteosintesis asistida con navegación 2D con tornillos iliacosacros percutáneos en lesiones del anillo pélvico posterior / Assisted osteosynthesis with 2D navigation with percutaneous iliacosacral screws in posterior pelvic ring injuries

Introducción: La osteosíntesis percutánea sacroiliaca guiada por radioscopia en lesiones del anillo pélvico posterior sigue siendo la técnica de referencia. Sin embargo, el desarrollo de técnicas como la cirugía asistida por navegación 2D/3D o por tomografía han mejorado la facilidad y seguridad en la colocación de los tornillos. Objetivo: Presentar la técnica de fijación asistida por navegación en 2D y los resultados clínicos y radiológicos obtenidos. Materiales y métodos: Se revisaron 23 pacientes con disrupción del anillo pélvico posterior (luxación y/o fractura sacroiliaca) intervenidos mediante fijación percutánea asistida por navegación 2D (Sistema Synergy de Medtronic®) en el hospital desde 2017 hasta la actualidad. Se recogieron variables demográficas, de clasificación, terapéuticas y las complicaciones derivadas. Se utilizó la escala modificada de valoración POS (Multicenter Study Group Pelvis Outcome Scale) para evaluar el resultado clínico, radiológico y social. Resultados: Ocho pacientes presentaban luxación sacro-iliaca y 15 tenían fractura a través del sacro. Se implantaron 40 tornillos iliacosacros. El tiempo quirúrgico medio fue de 20 minutos para cada tornillo. Fueron necesarios ocho pulsos de radioscopia de media por intervención. Hubo tres tornillos (7.5%) mal posicionados. 15 pacientes obtuvieron un resultado bueno o excelente en el formulario POS. Conclusiones: La técnica asistida por navegación es una alternativa con buenos resultados. Facilita al cirujano la colocación correcta de los tornillos en el corredor óseo sacro, acortando el tiempo quirúrgico y con una menor exposición a radiaciones ionizantes. Es útil para todo tipo de lesiones del anillo y cuando son necesarias maniobras de reducción.

Introduction: Radioscopy-guided percutaneous sacroiliac osteosynthesis in posterior pelvic ring lesions continues to be the reference technique. However, the development of techniques such as surgery assisted by 2D/3D navigation or tomography have improved the ease and safety in screw placement. Objective: To present the 2D navigation-assisted fixation technique and the clinical and radiological results obtained. Materials and methods: 23 patients with disruption of the posterior pelvic ring (dislocation and/or sacroiliac fracture) who underwent percutaneous fixation assisted by 2D navigation (Medtronic® Synergy System) at the hospital from 2017 to the present were reviewed. Demographic, classification, therapeutic variables and resulting complications were collected. The modified POS (Multicenter Study Group Pelvis Outcome Scale) assessment scale was used to evaluate the clinical, radiological and social outcome. Results: Eight patients had sacro-iliac dislocation and 15 had a fracture through the sacrum. 40 iliacosacral screws were implanted. The average surgical time was 20 minutes for each screw. An average of eight fluoroscopy pulses were necessary per intervention. There were three screws (7.5%) incorrectly positioned. 15 patients had a good or excellent result on the POS form. Conclusions: The navigation-assisted technique is an alternative with good results. It makes it easier for the surgeon to correctly place the screws in the sacral bone corridor, shortening surgical time and with less exposure to ionizing radiation. It is useful for all types of ring injuries and when reduction maneuvers are necessary.