Hope for Motherhood: Pregnancy After Allogeneic Hematopoietic Cell Transplantation - a National Multicenter Study.

Improved long-term survival rates after allogeneic hematopoietic cell transplantation (alloHCT) make family planning for young adult cancer survivors an important topic. However, treatment-related infertility risk poses challenges. To assess pregnancy and birth rates in a contemporary cohort, we conducted a national multicenter study using data from the German Transplant Registry, focusing on adult women aged 18-40 who underwent alloHCT between 2003 and 2018. Out of 2,654 transplanted women, 50 women experienced 74 pregnancies, occurring at a median of 4.7 years post-transplant. Fifty-seven of these resulted in live births (77%). The annual first birth rate among HCT recipients was 0.45% (95%CI: 0.31 - 0.59%), which is more than six times lower than in the general population. The probability of a live birth 10 years after HCT was 3.4 % (95%CI: 2.3- 4.5%). Factors associated with an increased likelihood of pregnancy were younger age at alloHCT, non-malignant transplant indications, no total-body-irradiation (TBI) or a cumulative dose of <8 Gray, and non-myeloablative/reduced-intensity conditioning. 72% of pregnancies occurred spontaneously, with assisted reproductive technologies (ART) used in the remaining cases. Preterm delivery and low birth weight were more common than in the general population. This study represents the largest dataset reporting pregnancies in a cohort of adult female alloHCT recipients. Our findings underscore a meaningful chance of pregnancy in alloHCT recipients. ART techniques are important and funding should be made available. However, the potential for spontaneous pregnancies should not be underestimated, and patients should be informed of the possibility of unexpected pregnancy despite reduced fertility. Further research is warranted to understand the impact of conditioning decisions on fertility preservation.

Retrospective analysis of the incidence and outcome of late acute and chronic graft-versus-host disease-an analysis from transplant centers across Europe.

Introduction: Chronic graft-versus-host disease (cGvHD) is a serious late complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: This multicenter analysis determined the cumulative incidence (CI) of cGvHD and late acute GvHD (laGvHD) and its impact on transplantation-related mortality (TRM), relapse (R), and overall survival (OS) in 317 patients [296 adults, 21 pediatrics (<12 years of age)] who underwent their first allo-HSCT in 2017. Results: The CI of laGvHD was 10.5% in adults and 4.8% in pediatrics, and the CI of cGvHD was 43.0% in all adult transplant patients and 50.2% in the adult at-risk cohort at the study end. The onset of cGvHD was de novo in 42.0% of patients, quiescent in 52.1%, and progressive in 5.9%. In adults, prophylactic use of antithymocyte globulin or posttransplant cyclophosphamide was associated with a significantly lower incidence of cGvHD (28.7%) vs. standard prophylaxis with calcineurin inhibitors (30.6%) and methotrexate/mycophenolate mofetil (58.4%) (all p < 0.01). TRM was significantly higher in patients with aGvHD (31.8%) vs. cGvHD (12.6%) and no GvHD (6.3%) (all p = 0.0001). OS in the adult at-risk cohort was significantly higher in patients with cGvHD (78.9%) vs. without (66.2%; p = 0.0022; HR 0.48) due to a significantly lower relapse rate (cGvHD: 14.5%; without cGvHD: 27.2%; p = 0.00016, HR 0.41). OS was also significantly higher in patients with mild (80.0%) and moderate (79.2%) cGvHD vs. without cGvHD (66.2%), excluding severe cGvHD (72.7%) (all p = 0.0214). Discussion: The negative impact of severe cGvHD on OS suggests a focus on prevention of severe forms is warranted to improve survival and quality of life.

Ruxolitinib for the treatment of acute graft-versus-host disease: a retrospective analysis.

Steroid-refractory acute graft-versus-host disease (aGvHD) is a serious complication after allogeneic hematopoietic stem cell transplantation, associated with significant mortality. Ruxolitinib was the first drug approved for aGvHD, based on results of the REACH2 trial; however, real-world data are limited. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of aGvHD at our center from March 2016 to August 2022 and assessed biomarkers of risk. We identified 49 patients receiving ruxolitinib as second- (33/49), third- (11/49), fourth- (3/49), or fifth-line (2/49) treatment. Ruxolitinib was started on median day 11 (range, 7-21) after aGvHD onset; median duration of administration was 37 days (range, 20-86), with 10 patients continuing treatment at last follow-up. Median follow-up period was 501 days (range, 95-905). In the primary analysis at the 1-month assessment, overall response rate was 65%, and failure-free survival was 78%. Infectious complications ≥ CTCAE Grade III were observed in 10/49 patients within 1-month followup. Patients responding to ruxolitinib therapy required fewer steroids and exhibited lower levels of the serum biomarkers regenerating islet-derived protein 3-alpha, suppression of tumorigenicity 2, and the Mount Sinai Acute GVHD International Consortium algorithm probability. A univariate regression model revealed steroid-dependent aGvHD as a significant predictor of better response to ruxolitinib. Within 6-months follow-up, four patients experienced recurrence of underlying malignancy, and eight died due to treatment-related mortality. Overall, ruxolitinib was welltolerated and showed response in heavily pretreated patients, with results comparable to those of the REACH2 trial. Biomarkers may be useful predictors of response to ruxolitinib.

Efficacy and safety of ruxolitinib in the treatment of chronic graft-versus-host disease: a retrospective analysis.

Steroid-refractory chronic graft-versus-host disease (cGvHD) is associated with significant morbidity and mortality, with ruxolitinib being the first drug approved for its treatment. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of cGvHD at our center between 07/2015 and 12/2022 and identified 48 patients receiving ruxolitinib as second (18/48) or advanced (30/48) treatment line. Ruxolitinib was started on median day 340 (range 119-595) after cGvHD onset; median duration of administration was 176 (range, 79-294) days with 16/48 patients continuing treatment at last follow-up. National Institutes of Health organ grading and the intensity of immunosuppression were assessed at the start of ruxolitinib treatment and repeated after 1, 3, 6, and 12 months. Response assessment was terminated at the start of any additional new immunosuppressant treatment. The median time of follow-up was 582 (range, 104-1161) days. At the primary analysis after six months on ruxolitinib treatment, the overall response rate was 33%, and failure-free survival was 58%. Infectious adverse events ≥ CTCAE grade III were observed in 10/48 patients. The response rate was not associated with the severity of cGvHD, number of previous treatment lines, or number of additional agents combined with ruxolitinib applying a univariate regression model. At the time of the 12-month follow-up, four patients experienced recurrence of the underlying malignancy and two patients had experienced non-relapse-related mortality. Overall, ruxolitinib was relatively well-tolerated and showed outcomes comparable to the REACH3 trial in a heavily pretreated patient population.

Management of complications of chimeric antigen receptor T-cell therapy: a report by the European Society of Blood and Marrow Transplantation.

CAR-T cells are in standard clinical use to treat relapsed or refractory hematologic malignancies, such as non-Hodgkin's lymphoma, multiple myeloma and acute lymphoblastic leukemia. Owing to the rapidly progressing field of CAR-T cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between European centers in prevention, diagnosis and management of short- and long-term complications. To capture the current CAR-T cell management among EBMT centers and to determine the medical need and specific areas for future clinical research the EBMT Transplant Complications Working Party performed a survey among 227 EBMT CAR-T cell centers. We received complete servey answers from 106 centers (47%) addressing questions in the areas of product selection, CAR-T cell logistics, management of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome as well as management in later phases including prolonged cytopenias. We identified common patterns in complication management, but also significant variety in clinical management of the centers in important aspects. Our results demonstrate a high medical need for treatment harmonization and future clinical research in the following areas: treatment of steroid-refractory and very severe CRS/neurotoxicity, treatment of cytopenia, early discharge and outpatient management, as well as immunoglobulin substitution.

Treatment of newly diagnosed moderate or severe chronic graft-versus-host disease with prednisone and everolimus (PredEver first): a prospective multicenter phase IIA study.

Although most patients with chronic graft-versus-host disease (cGVHD) show initial response to first-line therapy, long-term clinically meaningful success of first-line treatment remains rare. In a prospective multicentre phase II trial in 6 German centers, patients with newly diagnosed moderate or severe cGVHD received prednisone and everolimus for 12 months followed by a 1-year follow-up period. Primary endpoint was treatment success (TS) at 6 months defined as patient being alive, achieving PR or CR of cGVHD, having no relapse of underlying disease and requiring no secondary treatment for cGVHD. Of the 34 patients evaluable for efficacy, 19 (56%) had TS at 6 months with 22 and 52% of the patients in a CR and PR respectively. Overall 30 patients (88%) had a CR or PR as best response, nearly all responses (29/30) occurring within the first 6 weeks of treatment. The cumulative incidence of treatment failure at 1 year was 63%, corresponding to 37% TS. Predefined safety endpoint (thrombotic microangiopathy, pneumonitis, and avascular necrosis) were not observed in any patient. Addition of everolimus to prednisolone is well tolerated and may improve long-term treatment success. Larger studies are necessary to ascertain the possible role of everolimus in first-line treatment of cGVHD.

Tocilizumab administration in cytokine release syndrome is associated with hypofibrinogenemia after chimeric antigen receptor T-cell therapy for hematologic malignancies.

Chimeric antigen receptor (CAR-) T cell therapy causes serious side effects including cytokine release syndrome (CRS). CRS-related coagulopathy is associated with hypofibrinogenemia that is thus far considered the result of disseminated intravascular coagulation (DIC) and liver dysfunction. We investigated incidence and risk factors for hypofibrinogenemia in 41 consecutive adult patients with hematologic malignancies (median age 69 years, range 38-83 years) receiving CAR-T cell therapy between 01/2020 and 05/2023 at the University Medical Center Regensburg. CRS occurred in 93% of patients and was accompanied by hypofibrinogenemia already from CRS grade 1. Yet, DIC and liver dysfunction mainly occurred in severe CRS (≥ grade 3). After an initial increase during CRS, fibrinogen levels dropped after administration of tocilizumab in a dose dependent manner (r = -0.44, p = 0.004). In contrast, patients who did not receive tocilizumab had increased fibrinogen levels. Logistic regression analysis identified tocilizumab as an independent risk factor for hypofibrinogenemia (odds ratio = 486, p < 0.001). We thus hypothesize that fibrinogen synthesis in CRS is upregulated in an interleukin-6-dependent acute phase reaction compensating for CRS-induced consumption of coagulation factors. Tocilizumab inhibits fibrinogen upregulation resulting in prolonged hypofibrinogenemia. These observations provide novel insights into the pathophysiology of hypofibrinogenemia following CAR-T cell therapy and emphasize the need for close fibrinogen monitoring after tocilizumab treatment of CRS.

ERS/EBMT clinical practice guidelines on treatment of pulmonary chronic graft-versus-host disease in adults.

Chronic graft-versus-host disease (cGvHD) is a common complication after allogeneic haematopoietic stem cell transplantation, characterised by a broad disease spectrum that can affect virtually any organ. Although pulmonary cGvHD is a less common manifestation, it is of great concern due to its severity and poor prognosis. Optimal management of patients with pulmonary cGvHD is complicated and no standardised approach is available. The purpose of this joint European Respiratory Society (ERS) and European Society for Blood and Marrow Transplantation task force was to develop evidence-based recommendations regarding the treatment of pulmonary cGvHD phenotype bronchiolitis obliterans syndrome in adults. A multidisciplinary group representing specialists in haematology, respiratory medicine and methodology, as well as patient advocates, formulated eight PICO (patient, intervention, comparison, outcome) and two narrative questions. Following the ERS standardised methodology, we conducted systematic reviews to address these questions and used the Grading of Recommendations Assessment, Development and Evaluation approach to develop recommendations. The resulting guideline addresses common therapeutic options (inhalation therapy, fluticasone-azithromycin-montelukast, imatinib, ibrutinib, ruxolitinib, belumosudil, extracorporeal photopheresis and lung transplantation), as well as other aspects of general management, such as lung functional and radiological follow-up and pulmonary rehabilitation, for adults with pulmonary cGvHD phenotype bronchiolitis obliterans syndrome. These recommendations include important advancements that could be incorporated in the management of adults with pulmonary cGvHD, primarily aimed at improving and standardising treatment and improving outcomes.

Adoptive transfer of donor B lymphocytes: a phase 1/2a study for patients after allogeneic stem cell transplantation.

ABSTRACT: Immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is slow and patients carry a high and prolonged risk of opportunistic infections. We hypothesized that the adoptive transfer of donor B cells can foster after HSCT immuno-reconstitution. Here, we report, to our knowledge, the results of a first-in-human phase 1/2a study aimed to evaluate the feasibility and safety of adoptively transferred donor B cells and to test their activity upon recall vaccination. Good manufactoring practice (GMP) B-cell products were generated from donor apheresis products using 2-step magnetic cell separation. Fifteen patients who had undergone allo-HSCT were enrolled and treated after taper of immunosuppression (median, day +148; range, 130-160). Patients received 4 different doses of B cells (0.5 × 106 to 4.0 × 106 B cells per kg body weight). To test the activity of infused donor memory B cells in vivo, patients were vaccinated with a pentavalent vaccine 7 days after B-cell transfer. We observed the mobilization of plasmablasts and an increase in serum titers against vaccine antigens, with a stronger response in patients receiving higher B-cell numbers. Analysis of immunoglobulin VH-sequences by next-generation sequencing revealed that plasmablasts responding to vaccination originated from memory B-cell clones from the donor. Donor B-cell transfer was safe, as no Epstein-Barr virus (EBV) reactivation was observed, and only low-grade graft-versus-host disease (GVHD) occurred in 4 out of 15 patients. This pilot trial may pave the way for further studies exploring the adoptive transfer of memory B cells to reduce the frequency of infections after allo-HSCT. This trial was registered at ClinicalTrial.gov as #NCT02007811.

A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes.

Introduction: Data on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce. Methods: We performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host disease (sGvHD), fitting proportional hazard and subdistributional models to data of n=1,392 recipients of European ancestry from three centres. Results: The single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene (SEMA3C), was genome-wide significantly associated with event-free survival (p=7.0x10-8) and sGvHD (p=7.5x10-8). Further associations were detected for SNPs in the Paxillin gene (PXN) with death without prior relapse or sGvHD, as well as for SNPs of the Plasmacytoma Variant Translocation 1 gene (PVT1, a long non-coding RNA gene), the Melanocortin 5 Receptor (MC5R) gene and the WW Domain Containing Oxidoreductase gene (WWOX), all associated with the occurrence of sGvHD. Functional considerations support the observed associations. Discussion: Thus, new genes were identified, potentially influencing the outcome of HSCT.

Management of Patients Undergoing CAR-T Cell Therapy in Germany.

INTRODUCTION: Chimeric antigen receptor positive T cell (CAR-T cell) treatment became standard therapy for relapsed or refractory hematologic malignancies, such as non-Hodgkin's lymphoma and multiple myeloma. Owing to the rapidly progressing field of CAR-T cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between centers in the prevention, diagnosis, and management of short- and long-term complications. METHODS: To capture the current CAR-T cell management among German centers to determine the medical need and specific areas for future clinical research, the DAG-HSZT (Deutsche Arbeitsgemeinschaft für Hämatopoetische Stammzelltransplantation und Zelluläre Therapie; German Working Group for Hematopoietic Stem Cell Transplantation and Cellular Therapy) performed a survey among 26 German CAR-T cell centers. RESULTS: We received answers from 17 centers (65%). The survey documents the relevance of evidence in the CAR-T cell field with a homogeneity of practice in areas with existing clinical evidence. In contrast, in areas with no - or low quality - clinical evidence, we identified significant variety in management in between the centers: management of cytokine release syndrome, immune effector cell-related neurotoxicity syndrome, IgG substitution, autologous stem cell backups, anti-infective prophylaxis, and vaccinations. CONCLUSION: The results indicate the urgent need for better harmonization of supportive care in CAR-T cell therapies including clinical research to improve clinical outcome.

Barriers and Facilitators in Continuous Medical Education Related to Allogeneic Stem Cell Transplantation: A Qualitative Study of Physicians.

INTRODUCTION: This study explored qualitatively, in a sample of German hematologists working in clinical allogeneic hematopoietic stem cell transplantation (alloHSCT), perceptions of barriers and facilitators to participate in continuous medical education (CME), to provide detailed information on how to improve participation in CME activities related to alloHSCT, which may also be applicable to other areas of medicine. METHODS: Based on a recruitment campaign of the German Association for Hematopoietic Stem Cell Transplantation (DAG-HSZT), 21 semi-structured telephone interviews were conducted, transcribed, and analyzed using framework analysis. RESULTS: Three clusters of barriers were identified that explain why alloHSCT physicians may or may not participate in CME: individual constraints (e.g., better networking, young physicians being overwhelmed by the complexity of alloHSCT), structural constraints (e.g., time and financial issues, tailoring CME courses according to the targeted audience), and content-related constraints (e.g., requirement of CME sessions, provision of an overview of CME courses, more flexible offers). We discuss the ten most frequently raised issues, including the use of incentives and the need for support at the start of residency, staff shortages, and requirements for learning sessions. CONCLUSION: There is a need for a paradigm shift in CME related to alloHSCT toward a more individualized and needs-based approach. Close monitoring of residents' needs and learning progress, as well as feedback systems, could help identify appropriate CME courses that should be integrated into a tiered learning system. CME should be more targeted to specific audiences (i.e., residents, fellows, and attendees) to provide training that is tailored to individual CME needs. On-demand courses can help balance work and family obligations. Finally, peer-reviewed, up-to-date information platforms should be expanded.

Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation.

Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic haematopoietic stem-cell transplantation (HSCT). In the last 3 years, there has been regulatory approval of new drugs and considerable change in clinical approaches to prophylaxis and management of GVHD. To standardise treatment approaches, the European Society for Blood and Marrow Transplantation (EBMT) has updated its clinical practice recommendations. We formed a panel of one methodologist and 22 experts in the field of GVHD management. The selection was made on the basis of their role in GVHD management in Europe and their contributions to the field, such as publications, presentations at conferences, and other research. We applied the GRADE process to ten PICO (patient, intervention, comparator, and outcome) questions: evidence was searched for by the panel and graded for each crucial outcome. In two consensus meetings, we discussed the evidence and voted on the wording and strengths of recommendations. Key updates to the recommendations include: (1) primary use of ruxolitinib in steroid-refractory acute GVHD and steroid-refractory chronic GVHD as the new standard of care, (2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors, and (3) the addition of belumosudil to the available treatment options for steroid-refractory chronic GVHD. The EBMT proposes to use these recommendations as the basis for routine management of GVHD during allogenic HSCT. The current recommendations favour European practice and do not necessarily represent global preferences.

Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation.

The microbiome is a predictor of clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT). Microbiota-derived metabolites can modulate these outcomes. How bacteria, fungi and viruses contribute to the production of intestinal metabolites is still unclear. We combined amplicon sequencing, viral metagenomics and targeted metabolomics from stool samples of patients receiving allo-SCT (n = 78) and uncovered a microbiome signature of Lachnospiraceae and Oscillospiraceae and their associated bacteriophages, correlating with the production of immunomodulatory metabolites (IMMs). Moreover, we established the IMM risk index (IMM-RI), which was associated with improved survival and reduced relapse. A high abundance of short-chain fatty acid-biosynthesis pathways, specifically butyric acid via butyryl-coenzyme A (CoA):acetate CoA-transferase (BCoAT, which catalyzes EC 2.8.3.8) was detected in IMM-RI low-risk patients, and virome genome assembly identified two bacteriophages encoding BCoAT as an auxiliary metabolic gene. In conclusion, our study identifies a microbiome signature associated with protective IMMs and provides a rationale for considering metabolite-producing consortia and metabolite formulations as microbiome-based therapies.

Colgajo supraclavicular, revisión de la literatura y serie de casos / Supraclavicular flap, literature review and case series

Los procedimientos reconstructivos en cabeza y cuello son todo un desafío debido a que son áreas expuestas, con gran movimiento, y desempeñan funciones esenciales de la vida como el habla, la alimentación y la respiración. El colgajo supraclavicular es un colgajo locorregional, fasciocutáneo, fino, axial a la arteria supraclavicular, versátil, con baja morbilidad, que se usa ampliamente para cubrir defectos en cuello y sector inferior de la cara ya que proporciona tejido similar al de estas regiones, y técnicamente rápido y sencillo.Se puede usar en asociación con otros colgajos para reconstrucciones complejas. Es un colgajo infrautilizado que es una buena alternativa frente a los colgajos tradicionales musculares regionales y libres. Las principales indicaciones son secuelas de quemaduras como las contracturas esternomentonianas, defectos oncológicos ya sea piel o mucosa oral, faringostomas y fístulas traqueocutáneas. Se mencionan 3 casos clínicos en los cuales se llevó a cabo un colgajo supraclavicular en el Hospital Pasteur, Montevideo, Uruguay.

Reconstructive head and neck procedures are challenging because they are exposed areas, are highly mobile, and perform essential life functions such as speaking, eating, and breathing. The supraclavicular flap is a locoregional, fasciocutaneous, thin flap, axial to the supraclavicular artery, versatile, with low morbidity, which is widely used to cover defects in the neck and lower face since it provides tissue similar to that of these regions, and Technically fast and simple. It can be used in association with other flaps for complex reconstructions. It is an underutilized flap that is a good alternative to traditional regional and free muscle flaps. The main indications are sequelae of burns such as sternomental contractures, oncological defects in the skin or oral mucosa, pharyngostomies and tracheocutaneous fistulas. Three clinical cases are mentioned in which a supraclavicular flap was performed at the Pasteur Hospital, Montevideo, Uruguay

Reconstrucción mamaria con colgajo perforante de arteria epigástrica inferior profunda (DIEP) / Breast reconstruction with DIEP flaps

Introducción. La reconstrucción mamaria sigue siendo hoy en día un verdadero desafío para la cirugía reparadora, que tiene como objetivo principal recuperar la imagen corporal y la calidad de vida de estos pacientes. Para lograr este cometido se cuenta con un amplio arsenal terapéutico. La reconstrucción con implantes es la forma más común de reconstrucción en el mundo. Sin embargo, las técnicas con tejidos autólogos han ganado terreno en los últimos años por su mejor calidad reconstructiva y durabilidad en el tiempo. Material y método. El colgajo DIEP consiste en un colgajo libre, compuesto por piel y tejido celular subcutáneo de la región abdominal inferior, basado en perforantes de la arteria epigástrica inferior profunda. Brinda buenos resultados reconstructivos, sin sacrifi cio funcional de la pared abdominal. El objetivo del trabajo es resaltar algunas de las características más relevantes de esta técnica y la experiencia de nuestro servicio en su utilización para la reconstrucción mamaria. Resultados y discusión. La experiencia del servicio con la utilización de este colgajo ha sido satisfactoria, con buenos resultados, bajas complicaciones y aceptación por parte de las pacientes. Conclusiones. Si bien se trata de un colgajo que requiere una técnica microquirúrgica, con una importante curva de aprendizaje, logra devolver una mama con características similares a la contralateral en forma, volumen y textura, con el benefi cio estético del contorneado corporal abdominal y sin las complicaciones del uso del material protésico, considerándose hoy en día como una herramienta más a tener en cuenta para la reconstrucción mamaria.

Background: Breast reconstruction remains as a real challenge for restorative surgery today, with the main objective of recovering the body image and the quality of life of these patients. To achieve this, there is a broad therapeutic arsenal. Reconstruction with implants is the most common form of reconstruction in the world; however, autologous tissue techniques have gained ground in recent years for their improved reconstructive quality and durability over time. Material and Method:The DIEP fl ap is a free fl ap, composed of skin and subcutaneous cellular tissue of the lower abdominal region, based on perforators of the deep inferior epigastric artery, providing good reconstructive results, without functional sacrifi ce of the abdominal wall. The objective of this work is to highlight some of the most relevant characteristics of this technique and the experience of our service in its use for breast reconstruction. Results and Discussion: The experience of the Service with the use of this fl ap has been satisfactory, with good results, low complications and acceptance by the patients. Conclusions: Although it is a fl ap that requires a microsurgical technique, with an important learning curve, it manages to return a breast with similar characteristics to the contralateral in shape, volume and texture, with the esthetic benefi t of abdominal body contouring and without complications of the use of prosthetic material, being considered nowadays as one more tool to take into account for the reconstruction mammary.

Colgajo anterior de muslo en hemipelvectomía externa, reporte de caso / Anterior fl ap on external hemipelvectomy, case report

Introducción. La hemipelvectomía es un procedimiento agresivo para el tratamiento de tumores localmente avanzados. Requiere la conformación de un equipo interdisciplinario. Las opciones de cobertura dependen de la topografía de la lesión, existiendo 3 tipos de colgajo: posterior, anterior, y libre. Material y método. Se presenta el caso clínico de un paciente que presentó una ulcera de Marjolin a nivel de región trocantérica y glútea derecha, en el que se realizó una hemipelvectomía externa extendida, asociada a un colgajo anterior de muslo. Se trató de un colgajo músculo-cutáneo pediculado a los vasos femorales superfi ciales y profundos, compuesto por todos los planos de la logia anterior de muslo. Resultados. En este paciente se alcanzó una adecuada cobertura del defecto, que permitió su pronta rehabilitación. Discusión. Este colgajo es descripto como un colgajo pediculado en los vasos femorales superfi ciales. Creemos que si bien presenta vascularización por estos vasos, su mayor vascularización está dada por la arteria femoral profunda y su rama lateral circunfl eja. Este colgajo permite una adecuada cobertura en lesiones posteriores, con buena calidad de cobertura y menor número de complicaciones que el colgajo posterior. Conclusión. La hemipelevectomía externa es un tratamiento agresivo realizado para lesiones localmente avanzadas, con alta morbimortalidad, y que debe ser realizada por un equipo interdisciplinario. En cuanto a la cobertura, el colgajo anterior presenta buenos resultados dada su buena vascularización.

Background. Hemipelvectomy is an aggressive procedure for the treatment of locally advanced tumors. It requires the formation of an interdisciplinary team. The coverage options depend on the topography of the lesion, being 3 types of fl aps: posterior, anterior, and free. Material and Method. We present a case of a patient presenting an ulcer of Marjolin at the right trochanteric region. In which an extended external hemipelvectomy anterior fl ap is performed. It is a muscle cutaneous fl ap pediculated to the superfi cial and deep femoral vessels, composed of all the planes of the anterior thigh lodge. Results. In our patient we have reached an adequate coverage of the defect, which allowed an early rehabilitation of the patient. Discussion. This fl ap is described as a pedicled fl ap in the superfi cial femoral vessels. We believe that this fl ap is vascularized by these vessels, but its major vascularization is given by the deep femoral artery and its circumfl ex lateral branch. This fl ap allows adequate coverage in posterior lesions, with a good quality of coverage, and a lower number of complications than the posterior fl ap. Comments. External hemipelvectomy is an aggressive treatment performed for locally advanced lesions, with high morbidity and mortality, which must be performed by an interdisciplinary team. Regarding the coverage, we highlight the good results achieved by this fl ap given its good vascularization.

Estudio comparativo entre soluciones conservadoras con y sin formol en placenta humana / Comparative study between conservative solutions with and without formaldehyde in human placenta

Las técnicas de fijación y conservación anatómica son realizadas habitualmente con soluciones que contienen formol, dado su bajo costo. Estas tienen varias desventajas como el olor irritante, rigidez, cambios de coloración de las estructuras, así como toxicidad con potencial cancerígeno, teratogénico y mutagénico para quien lo manipula. Por esto, es deseable utilizar soluciones sin formol. El objetivo de este trabajo fue comparar 2 métodos de conservación cadavérica, uno con formol (solución de Montevideo) y otro sin formol (método de Prives) utilizando la placenta humana como órgano experimental, evaluando sus parámetros macroscópicos. Se utilizaron 46 placentas humanas de partos normales y gestación a término. Las placentas fueron separadas en dos grupos (n=22 y n=24 respectivamente). El primer grupo de placentas fue perfundido con una solución con formol y el segundo grupo en una solución sin formol. Luego ambos grupos fueron sumergidos y mantenidos en sus soluciones respectivas por dos semanas y posteriormente retiradas dejándolas al aire a temperatura ambiente por 2 semanas más. Se analizaron las variables cuantitativas de peso y diámetro en cada una de las piezas, así como las variables cualitativas de consistencia, color, olor y crecimiento de micro/macro organismos. La recopilación de datos fue realizada previo al lavado, a los 14, 21 y 28 días. Los resultados mostraron que las placentas conservadas con el método de Prives presentaron mejor conservación en relación a su diámetro, consistencia, color y menor olor irritante en relación a las placentas tratadas con solución con formol. En ningún caso hubo crecimiento de micro o macroorganismos. En conclusión, emplear soluciones alternativas que sustituyan ventajosamente al formol como la fórmula de Prives conservan mejor las características macroscópicas de las placentas sin generar un olor irritante, deteniendo el proceso de descomposición.

The fixation and conservation techniques of anatomic material are commonly performed with solutions containing formaldehyde, given its low cost. These have several disadvantages such as the irritating odor, stiffness, discoloration of the structures, toxicity, carcinogenic, teratogenic and mutagenic risk for those who are exposed. Therefore it is desirable to use solutions without formaldehyde. The aim of this study was to compare 2 methods of anatomical conservation, one with formalin (Montevideo's solution) and one without formalin (Prives method) using the human placenta as an experimental organ model evaluating its macroscopic parameters. We used 46 human placentas from normal deliveries and term pregnancy. The placentas were separated into two groups (n=22 and n=24 respectively). The first group of placentas was perfused with formaldehyde solution and the second group in a solution without formaldehyde. Then both groups were immersed and maintained in their respective solutions for two weeks and then withdrawn leaving the air at room temperature for 2 weeks. Quantitative variables were analyzed for weight and diameter of each piece, and qualitative variables as consistency, color, odor and growth of micro/macro organisms were evaluated. Data collection was performed prior to washing at 14, 21 and 28 days. The results showed that conserved placentas with Prives method showed better conservation in relation to its diameter, consistency, color and less irritating odor in relation to placentas treated with formalin solution. In no case was growth of micro or macro organism. In conclusion, using advantageously at alternative solutions to formaldehyde, as the formula of Prives method, better preserved macroscopic characteristics of placentas without generating an irritating smell, stopping the decomposition process.

Divalent cations as modulators of neuronal excitability: Emphasis on copper and zinc

Based on indirect evidence, a role for synaptically released copper and zinc as modulators of neuronal activity has been proposed. To test this proposal directly, we studied the effect of copper, zinc, and other divalent cations on voltage-dependent currents in dissociated toad olfactory neurons and on their firing rate induced by small depolarizing currents. Divalent cations in the nanomolar range sped up the activation kinetics and increased the amplitude of the inward sodium current. In the micromolar range, they caused a dose dependent inhibition of the inward Na+ and Ca2+ currents (INa and ICa) and reduced de amplitude of the Ca2+-dependent K+ outward current (ICa-K). On the other hand, the firing rate of olfactory neurons increased when exposed to nanomolar concentration of divalent cations and decreased when exposed to micromolar concentrations. This biphasic effect of divalent cations on neuronal excitability may be explained by the interaction of these ions with high and low affinity sites in voltage-gated channels. Our results support the idea that these ions are normal modulators of neuronal excitability.