Late Diagnosis of Langerhans Cell Histiocytosis by Skin Biopsy in a Lung Transplant Candidate Patient.

We present the case of a lung transplant candidate under veno-venous membrane oxygenation assistance (VV ECMO) whose diagnosis of emphysema of undetermined etiology was redefined as Langerhans cell histiocytosis (LCH) due to a scalp skin biopsy performed years after the beginning of his respiratory symptoms. A 20-year-old patient started three years before his admission with progressive dyspnea leading to a diagnosis of bullous emphysema of undetermined cause, which evolved into respiratory failure and evaluation for bilateral lung transplant. Three years later, he developed bilateral pneumonia requiring mechanical ventilation. When refractory hypoxemia ensued, he had to be placed on VV ECMO. Under these conditions, he was transferred to our center and listed for a bilateral pulmonary transplantation. Forty-eight hours after admission, and due to intense polyuria, central diabetes insipidus was diagnosed. In this clinical context, the presence of cutaneous lesions on the scalp was reconsidered and biopsied under the presumption of possible LCH, with pathology analysis confirming the diagnosis. He continued to be assisted with VV ECMO for 66 more days as a bridge to transplantation, developing multi-organ failure and passing away before a donor organ was available. The diagnosis of LCH should be considered in any adult patient with bullous emphysema of undetermined cause. Given the possibility of early therapeutic interventions, the search for its clinical associations (e.g., diabetes insipidus and/or skin lesions) should be a systematic part of the etiologic workup. The availability of skin specimens to reach a diagnosis makes its thorough search an important part of the diagnostic approach.

S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity.

BACKGROUND: Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown. RESULTS: Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features. CONCLUSIONS: These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.

Mixed T Helper1/T Helper2/T Cytotoxic Profile in Subjects with Chronic Chagas Disease with Hypersensitivity Reactions to Benznidazole.

Dermatitis is the most common adverse event during treatment with benznidazole in chronic Chagas disease and is probably mediated by T cells. A set of molecules representative of the different type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of Trypanosoma cruzi-infected subjects presenting dermatitis during benznidazole administration. Through cytometric bead assays and enzyme-linked immunosorbent assay capture techniques, the serum levels of cytokines, chemokines, proapoptotic molecules, and mediators of the activation and migration of eosinophils and T cells were measured in subjects infected with Trypanosoma cruzi who exhibited skin adverse events (n = 22) and compared with those without adverse events (n = 37) during benznidazole therapy. Serum levels of interleukin- 5 (IL-5), soluble Fas cell surface death receptor ligand (FAS-L), and interferon γ-induced protein (IP-10) significantly increased at 7 to 30 days posttreatment with benznidazole and decreased thereafter in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis than in those without. Two patterns emerged in the skin biopsies: a T helper 1/T cytotoxic profile and a T helper 2/T cytotoxic profile with the presence of CD4+ and CD8+ T cells. Increased low-density lipoprotein (LDL), glutamic-oxaloacetic transaminase (GOT), uremia, and T cell activation emerged as risk factors for the development of dermatitis during benznidazole administration. These results support a delayed-type hypersensitivity reaction to benznidazole, involving CD4+ and CD8+ T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for better management of adverse drug reactions to benznidazole. IMPORTANCE This study identified the risk factors for the development of adverse reactions to benznidazole and identified a set molecule to monitor the appearance of these reactions. This knowledge might improve the safety of benznidazole administration.

Evidence of Continued CD4+ and CD8+ T Cell Activity After SARS-COV-2 Clearance in a Late COVID-19 Pneumonia Heart Transplant Patient.

We have studied an unvaccinated heart transplant 64-year-old patient admitted for low-grade fever, dry cough, general malaise, and bilateral interstitial infiltrates, after two months of a diagnosis of coronavirus disease 2019 (COVID-19) bilateral pneumonia. A bronchoalveolar lavage and transbronchial biopsy were performed. Bacterial, mycotic and viral infections were ruled out including repeated reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diffuse thickening of alveolar septa with fibrosis and infiltration of lymphocytes and macrophages into the alveolar septa with aggregates of CD4+ and CD8+ T cells with positive immunolabelling for granzyme B were observed, indicating a continuing cytotoxic process that might have induced proliferation and fibrosis. An intense ongoing immunopathological cellular reaction, potentially triggered by SARS-CoV-2 overcoming the anti-inflammatory and immunomodulatory effects of the immunosuppressive drugs is suggested by these findings, opening to debate the usual approach of minimizing immunosuppression after COVID-19 in transplant patients when presence of SARS-CoV-2 has been ruled out.

Trasplante cardíaco en miocardiopatía chagásica: 23 años de experiencia en un centro de referencia / Heart Transplantation in Chagas Cardiomyopathy: 23-Year Follow-Up in a Referral Center

RESUMEN Introducción: La enfermedad de Chagas afecta aproximadamente a 6 millones de personas en América Latina. El 25 a 35% evoluciona hacia la Miocardiopatía Chagásica (MCh). Una opción terapéutica en sus estadios avanzados es el trasplante cardíaco (TxC). Objetivos: Comparar la supervivencia de pacientes con TxC por MCh frente a otras etiologías. Analizar la incidencia de la reactivación (Ra) de enfermedad de Chagas y su impacto en la supervivencia en este subgrupo de pacientes. Material y métodos: Se evaluaron retrospectivamente pacientes con TxC entre agosto 1998 y marzo 2021. Se analizó la supervivencia mediante curvas de Kaplan-Meier y log rank test. El diagnóstico de Ra se realizó mediante métodos moleculares, prueba de Strout en sangre periférica, tejido miocárdico y/o cutáneo. Resultados: De 606 pacientes con TxC, 39 (6,4%) presentaban MCh. Seguimiento medio 4,4 años (Rango Intercuartilo 1,2-8,6). Edad subgrupo MCh 51 años (RIC 45-60). Hombres 28 (72%). Se documentó Ra en el 38,5% de los pacientes. Supervivencia a 1, 5 y 10 años en TxC por MCh con Ra versus no Ra: 85%, 76% y 61% versus 72%, 55% y 44% (p = 0,3). Supervivencia a 1, 5 y 10 años en TxC por MCh versus TxC por otras causas: 79%, 65% y 50% versus 79%, 62% y 47% (p = 0,5). Conclusión: En nuestra serie no se encontró diferencia estadísticamente significativa en la supervivencia de los pacientes trasplantados cardíacos por MCh en comparación con aquellos trasplantados por otras causas; así como tampoco entre los pacientes que reactivaron la enfermedad de Chagas y los que no lo hicieron.

ABSTRACT Background: Chagas disease affects about 6 million people in Latin America, and 25 to 35% progress to Chagas cardiomyopathy (ChCM). Heart transplantation (HTx) is a therapeutic option in advanced stages. Objectives: The aim of this study is to compare survival of patients with HTx due to ChCM versus those transplanted for other etiologies and to analyze the incidence of Chagas disease reactivation (Ra) and its impact on survival in this group of patients. Methods: Patients undergoing HTx between August 1998 and March 2021 were retrospectively evaluated. Survival was analyzed using Kaplan-Meier curves and the log-rank test. The diagnosis of Ra was performed by molecular methods, Strout's test in peripheral blood, myocardial tissue or skin tissue. Results: Of 606 patients with Htx, 39(6,4%) presented ChCM. Median follow up was 4.4 years (interquartile range 1.2-8.6). Median age of the subgroup with ChCM was 51 years (IQR 45-60) and 28 were men (72%). Reactivation was documented in 38.5% of the patients. Survival at 1, 5 and 10 years in HTx recipients due to ChCM and Ra versus no Ra was 85%, 76% and 61% versus 72%, 55% and 44%, respectively (p = 0.3). Survival at 1, 5 and 10 years in HTx recipients due to ChCM versus HTx for other causes was 79%, 65% and 50% versus 79%, 62% and 47%, respectively (p = 0.5). Conclusion: In our series we did not find statistically significant differences in survival of heart transplant recipients due to ChCM versus those transplanted due to other reasons. Survival in patients with Chagas disease reactivation and those without reactivation was also similar.

Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression.

Trypanosoma cruzi infection in humans leads to progression to chronic chagasic myocarditis (CCM) in 30% of infected individuals, paralleling T cell inflammatory infiltrates in the heart tissue. T-cell trafficking into the hearts of CCM patients may be modulated by in situ expression of chemotactic or haptotactic molecules, as the chemokine CXCL12, the cytokine tumor necrosis factor-alpha (TNF-α), and extracellular matrix proteins (ECM), such as fibronectin. Herein we evaluated the expression of fibronectin, CXCL12, and TNF-α in the myocardial tissue of T. cruzi seropositive (asymptomatic or with CCM), as well as seronegative individuals as healthy controls. Hearts from CCM patients exhibited enhanced expression of these three molecules. CXCL12 and TNF-α serum levels were also increased in CCM individuals. We then evaluated T lymphocytes from chronic chagasic patients by cytofluorometry, in terms of membrane expression levels of molecules involved in cell activation and cell migration, respectively, HLA-DR and the VLA-4 (very late antigen-4, being one integrin-type fibronectin receptor). Indeed, the expression of HLA-DR and VLA-4 was enhanced on T lymphocytes from chagasic patients, especially in the CCM group. To further approach the dynamics of T cell migratory events, we performed fibronectin-, TNF-α-, and CXCL12-driven migration. Peripheral blood mononuclear cells (PBMCs) and T cells from CCM patients presented an ex vivo enhanced migratory capacity driven by fibronectin alone when this ECM protein was placed in the membrane of transwell migration chambers. When TNF-α was previously placed upon fibronectin, we observed a further and significant increase in the migratory response of both PBMCs and T lymphocytes. Overall, these data suggest the existence in patients with chronic Chagas disease of a cardiac inflammatory infiltrate vector that promotes the recruitment and accumulation of activated T cells, driven in part by enhanced tissue expression of fibronectin and TNF-α, as well as the respective corresponding VLA-4 and TNF receptors.

[Ischemic cardiogenic shock and short-term mechanical circulatory support as bridge to transplantation]. / Shock cardiogénico en infarto agudo de miocardio y soporte circulatorio puente al trasplante.

Cardiogenic shock (CS) has a high mortality rate and often requires advanced therapies such as mechanical circulatory support (MCS) and heart transplantation (HT). Those patients who presented an acute myocardial infarction (AMI) with CS and required support through MCS as bridge to HT were retrospectively analyzed in a single Center. Between January 1997 and June 2020, 524 patients received HT, 203 for ischemic-cardiomyopathy, 103 were in emergency waiting list. Eleven patients met the inclusion criteria (mean age 53 ± 11 years old; men 73%). Five primary angioplasties and 2 emergency myocardial revascularization surgeries were performed. Four patients had coronary anatomy not subject to revascularization. All received inotropic and vasopressor treatment and required intra-aortic balloon pump (IABP). Subsequently, two required support with a left univentricular centrifugal pump (BioMedicus®, Medtronic) and two with peripheral veno-arterial extracorporeal membrane oxygenator (VA-ECMO) (Maquet®, Getinge Group). The median between AMI and HT was 15 days (range 7-21) and the mean age of the donors 28 ± 11 years. All had extensive AMI (necrotic amount 35 ± 5%) with histopathological signs of transmural necrosis and reperfusion injury. The median follow-up was 9 years (range 1-15). None died in hospitalization or during the first year after transplantation. Survival at 5 and 10 years was 73% and 55%. Emergency HT may be the best option for selected patients with acute myocardial infarction and cardiogenic shock refractory to conventional therapy.

El shock cardiogénico (SC) presenta una elevada mortalidad y puede requerir de terapéuticas avanzadas como la asistencia circulatoria mecánica (ACM) y el trasplante cardíaco (TC). Se analizaron en forma retrospectiva, en un único centro, aquellos pacientes que presentaron un infarto agudo de miocardio (IAM), SC y requirieron ACM puente al TC. Entre enero 1997 y junio 2020, 524 pacientes recibieron un TC, 203 por cardiopatía isquémica, 103 en lista de emergencia. Se incluyeron once pacientes con los criterios mencionados (edad media 53 ± 11 años; hombres 73%). Se realizaron 5 angioplastias primarias y 2 cirugías de revascularización miocárdica de urgencia. Cuatro pacientes presentaban anatomía coronaria no pasible de revascularización. Todos recibieron tratamiento inotrópico y vasopresor y requirieron soporte con balón de contrapulsación intra aórtico (BCIA). Dos requirieron el implante de bomba centrífuga univentricular izquierda (BioMedicus®, Medtronic) y 2 de oxigenador de membrana extracorpóreo veno-arterial (ECMO-VA) periférico (Maquet®, Getinge Group). La mediana entre IAM y TC fue 15 días (rango 7-21) y la edad de los donantes 28 ± 11 años. Todos presentaron un IAM extenso (monto necrótico 35 ± 5%) con signos histopatológicos de necrosis transmural e injuria de reperfusión. La mediana de seguimiento fue 9 años (rango 1-15). Ninguno falleció en la internación ni durante el primer año post trasplante. La supervivencia a los 5 y 10 años fue 73% y 55%. El TC en situación de emergencia ha demostrado ser, en nuestro medio, la mejor opción en aquellos pacientes con IAM y SC refractario a la terapia convencional.

Shock cardiogénico en infarto agudo de miocardio y soporte circulatorio puente al trasplante / Ischemic cardiogenic shock and short-term mechanical circulatory support as bridge to Transplantation

Resumen El shock cardiogénico (SC) presenta una elevada mortalidad y puede requerir de terapéuticas avanzadas como la asistencia circulatoria mecánica (ACM) y el trasplante cardíaco (TC). Se analizaron en forma retrospectiva, en un único centro, aquellos pacientes que presentaron un infarto agudo de miocardio (IAM), SC y requirieron ACM puente al TC. Entre enero 1997 y junio 2020, 524 pacientes recibieron un TC, 203 por cardiopatía isquémica, 103 en lista de emergencia. Se incluyeron once pacientes con los criterios mencionados (edad media 53 ± 11 años; hombres 73%). Se realizaron 5 angioplastias primarias y 2 cirugías de revascularización miocárdica de urgencia. Cuatro pacientes presentaban anatomía coronaria no pasible de revascularización. Todos recibieron tratamiento inotrópico y vasopresor y requirieron soporte con balón de contrapulsación intra aórtico (BCIA). Dos requirieron el implante de bomba centrífuga univentricular izquierda (BioMedicus®, Medtronic) y 2 de oxigenador de membrana extracorpóreo veno-arterial (ECMO-VA) periférico (Maquet®, Getinge Group). La mediana entre IAM y TC fue 15 días (rango 7-21) y la edad de los donantes 28 ± 11 años. Todos presentaron un IAM extenso (monto necrótico 35 ± 5%) con signos histopatológicos de necrosis transmural e injuria de reperfusión. La mediana de seguimiento fue 9 años (rango 1-15). Ninguno falleció en la internación ni durante el primer año post trasplante. La supervivencia a los 5 y 10 años fue 73% y 55%. El TC en situación de emergencia ha demostrado ser, en nuestro medio, la mejor opción en aquellos pacientes con IAM y SC refractario a la terapia convencional.

Abstract Cardiogenic shock (CS) has a high mortality rate and often requires advanced therapies such as mechanical circulatory support (MCS) and heart transplantation (HT). Those patients who presented an acute myocardial infarction (AMI) with CS and required support through MCS as bridge to HT were retrospectively analyzed in a single Center. Between January 1997 and June 2020, 524 patients received HT, 203 for ischemic-cardiomyopathy, 103 were in emergency waiting list. Eleven patients met the inclusion criteria (mean age 53 ± 11 years old; men 73%). Five primary angioplasties and 2 emergency myocardial revasculariza tion surgeries were performed. Four patients had coronary anatomy not subject to revascularization. All received inotropic and vasopressor treatment and required intra-aortic balloon pump (IABP). Subsequently, two required support with a left univentricular centrifugal pump (BioMedicus®, Medtronic) and two with peripheral veno-arterial extracorporeal membrane oxygenator (VA-ECMO) (Maquet®, Getinge Group). The median between AMI and HT was 15 days (range 7-21) and the mean age of the donors 28 ± 11 years. All had extensive AMI (necrotic amount 35 ± 5%) with histopathological signs of transmural necrosis and reperfusion injury. The median follow-up was 9 years (range 1-15). None died in hospitalization or during the first year after transplantation. Survival at 5 and 10 years was 73% and 55%. Emergency HT may be the best option for selected patients with acute myocardial infarction and cardiogenic shock refractory to conventional therapy.

Retrasplante pulmonar con cross-match positivo en trasplante pulmonar primario complicado con rechazo mediado por anticuerpos / Lung Retransplantation with Positive Crossmatch in Primary Lung Transplantation Complicated by Antibody-Mediated Rejection

La hipertensión arterial pulmonar (HAP) representa el 2,6% de los trasplantes pulmonares (TP), con una mediana de supervivencia condi cional (desde los 30 días del TP) de 9,8 años. Son frecuentes, el rechazo celular agudo (ACR) y la disfunción crónica del injerto (CLAD), mientras que es infrecuente el rechazo mediado por anticuerpos (AMR). El retrasplante pulmonar (RTP) constituye el 4% del TP mundial, debido a complicaciones en la vía aérea, disfunción primaria del injerto, ACR y CLAD. Mujer de 22 años, portadora de HAP idiopática (HAPI) desde el año 2013, trasplantada bipulmonar (TBP) en enero de 2018. A los 16 meses presentó neumonía adquirida en la comuni dad. En una internación posterior, presentó ACR y a pesar de pulsos de metilprednisolona, progresó a requerimientos de cánula de alto flujo y ventilación mecánica no invasiva hospitalaria, caída del VEF1, y tomografía de tórax con vidrio esmerilado difuso y engrosamiento irregular reticular del intersticio subpleural; interpretándose como CLAD a predominio de síndrome de bronquiolitis obliterante (BOS), con presencia de anticuerpos específicos contra el donante (DSA). En enero de 2020 se realizó nuevo TP y ante cross-match positivo, se realizó plasmaféresis y reposición de IgG. Al mes del egreso, no se observaron signos de rechazo en control de biopsias transbronquiales. Entre 2 y 10% de los pacientes con indicación primaria de TP por HAPI son sometidos a retrasplante pulmonar (RTP). La presencia de DSA y el miss-match de HLA, no son contraindicaciones para el RTP.

Pulmonary arterial hypertension (PAH) represents 2.6% of lung transplantations (LT), with a conditional median survival (from 30 days after LT) of 9.8 years. Acute cellular rejection (ACR) and chronic lung allograft dysfunction (CLAD) are common; whereas the antibody-mediated rejection (AMR) is not. Lung retransplantation (LR) accounts for 4% of global LTs for complications in the airways, primary allograft dys function, ACR and CLAD. 22-year-old woman with idiopathic PAH (IPAH) since 2013, who underwent a double-lung transplantation (DLT) in January 2018. 16 months after transplantation she presented community-acquired pneumonia. During a subsequent hospitalization, she presented ACR. Despite the fact that she received pulse methylprednisolone, she required high-flow cannula therapy and hospital non-invasive mechanical ventilation; the FEV1 was reduced and she underwent a chest tomography with diffuse ground glass opacities and irregular reticular thickening of the subpleural interstitium; interpreting the predominance of BOS (bronchiolitis obliterans syndrome) as CLAD, with presence of donor-specific antibodies (DSA). In January 2020, she received a new DLT and due to a positive crossmatch, she was treated with plasmapheresis and IgG replacement. One month after hospital discharge, no signs of rejection were observed at the BTB (bone-patellar tendon-bone) control. Between 2 to 10% of patients with primary indication of LT for IPAH are subjected to lung retransplantation (LR). The presence of DSA and HLA (human leucocyte antigen) mismatch aren't contraindications to LR.

Transbronchial biopsies' histopathological findings leading to successful late steroid therapy in Covid-19 acute respiratory failure.

We present results from clinical, radiologic, gas exchange, lung mechanics, and fibre-optic bronchoscopy-guided transbronchial biopsies in a case of acute respiratory failure due to SARS-CoV-2 (Covid-19). This report highlights the pulmonary, immunological, and inflammatory changes found during acute diffuse alveolar damage and the later organizing phase. An early diffuse alveolar damage pattern with predominant epithelial involvement with active recruitment of T cells and monocytes was observed followed by a late organizing pattern with pneumocyte hyperplasia, inflammatory infiltration, prominent endotheliitis, and secondary germinal centers. The patient's deterioration paralleling the late immuno-pathological findings based the decision to administer intravenous corticosteroids, resulting in clinical, gasometric, and radiologic improvement. We believe that real-time clinicopathological correlation, along with the description of the immunological processes at play, will contribute to the full clinical picture of Covid-19 and might lead to a more rational approach in the precise timing of anti-inflammatory, anti-cytokine, or steroid therapies.

HIF-1α and CD73 expression in cardiac leukocytes correlates with the severity of myocarditis in end-stage Chagas disease patients.

Chronic Chagas cardiomyopathy is the main infectious myocarditis worldwide. Almost 30% of Trypanosoma cruzi infected individuals develop slow and progressive myocarditis that leads to ventricular dilation and heart failure. Heart transplantation is an established, valuable therapeutic option for end-stage Chagas disease patients. Although the pathophysiology of Chagas disease has been addressed for decades by numerous groups, the cardiac immunologic mechanisms involved in the progression of clinical manifestation are still unknown. Growing evidence demonstrates that hypoxia-inducible factor (HIF)-1α plays indispensable roles in driving immune response by triggering the expression of CD73 purinergic ecto-enzyme. Purinergic system controls the duration and magnitude of purine signals directed to modulate immune cells through the conversion of extracellular ATP (microbicide/proinflammatory) to the immunoregulatory metabolite adenosine. In the present work, we described that infiltrating leukocytes within cardiac explants from patients with end-stage Chagas cardiomyopathy up-regulated HIF-1α and CD73 expression. Moreover, the number of HIF-1α+ and CD73+ leukocytes positively correlated with the myocarditis severity and the local parasite load. Furthermore, we demonstrated a direct relationship between tissue parasite persistence and the influx of immune cells to the infected hearts, which ultimately determine the severity of the myocarditis. These findings provide evidence that CD73-dependent regulatory pathways are locally triggered in the myocardium of patients with end-stage Chagas disease.

Microangiopatía trombótica sistémica asociada a mutaciones del complemento en trasplante renal donante vivo. reporte de caso / Systemic thrombotic microangiopathy associated with complement pathway mutations in living donor kidney transplant. case report

RESUMEN El síndrome urémico hemolítico (SUH) se caracteriza por la presencia de anemia hemolítica, plaquetopenia e insuficiencia renal aguda. Si bien se distingue clásicamente en típico o infeccioso y atípico, es menester reconocer situaciones clínicas en las que se pone de manifiesto, como por ejemplo, embarazo, puerperio inmediato, tumores, trasplante, drogas, etc., condiciones clínicas que han sido denominadas amplificadoras del complemento. La recurrencia postrasplante delsíndrome urémico hemolítico atípico (SUHa) ha sido descrita en porcentajes variables en pacientes con mutaciones del factor H, factor B, factor I y C3, y gen de la trombomodulina, en reportes de casos aislados. Se presenta el caso de una paciente con enfermedad renal crónica (ERC) secundaria a agenesia renal, receptora preemptive de un riñón de donante vivo relacionado que presentó disfunción del injerto renal secundaria a microangiopatía trombótica, asociado a complicación neurológica, hemorragias, disfunción orgánica múltiple y óbito. Se describen los hallazgos del estudio genético y anatomopatológico de necropsia.

ABSTRACT Hemolytic uremic syndrome (HUS) is characterized by the presence of hemolytic anemia, thrombocytopenia and acute kidney injury. Although it is usually distinguished as typical or infectious and atypical, it is necessary to recognize clinical situations in which it is revealed, such as pregnancy, immediate postpartum period, tumors, transplantation, drugs, etc., i.e. clinical conditions that have been called complement-amplifying conditions. Post-transplantation recurrence of atypical hemolytic uremic syndrome (aHUS) has been described in variable percentages in patients with mutations of factor H, factor B, factor I and C3, and thrombomodulin gene, in reports of isolated cases. We present the case of a patient with chronic kidney disease (CKD) secondary to renal agenesis, a preemptive recipient of a related living donor kidney, which presented renal graft dysfunction secondary to thrombotic microangiopathy, associated with neurological complications, hemorrhages, multiple organ dysfunction and death. The findings of the genetic and pathological autopsy study are described.

Chagas disease: Historic perspective.

This review is a perspective on the history of Chagas disease, and it adopts a novel approach from literary studies, historical documents and the science and epidemiology of the nature of the disease. From this analysis, comes the review's working definition of the Contact Zone (CZ): "the space in which geographically and historically separated people come into contact with each other and establish long-lasting relationships, which usually involve coercive conditions, radical inequality and intolerable conflict." In the Patient-Physician CZ, we verified the triple transition phenomena: the American trypanosomiasis shifted from a rural, acute, and vectorial transmitted disease to an urban, chronic and non-vectorial disease. In the Academic CZ, we describe the original disagreements which denied the existence of the disease and the current controversies about pathogenic mechanisms and etiological treatment. From the News from Latin America, and in the Original CZ, we will review the evolution of different forms of transmission. As in any good story, research across broad disciplines is necessary to reveal historical perspectives, scientific approaches, and the epidemiology of the disease, which has a prequel of 9000 years and an open ending: thus, we explore across the Global CZ, with its multiple and unexpected actors.

Urinary Bladder Matrix Scaffolds Promote Pericardium Repair in a Porcine Model.

Pericardium closure after cardiac surgery is recommended to prevent postoperative adhesions to the sternum. Synthetic materials have been used as substitutes, with limited results because of impaired remodeling and fibrotic tissue formation. Urinary bladder matrix (UBM) scaffolds promote constructive remodeling that more closely resemble the native tissue. The aim of the study is to evaluate the host response to UBM scaffolds in a porcine model of partial pericardial resection. Twelve Landrace pigs were subjected to a median sternotomy. A 5 × 7 cm pericardial defect was created and then closed with a 5 × 7 cm multilayer UBM patch (UBM group) or left as an open defect (control group). Animals were survived for 8 wk. End points included gross morphology, biomechanical testing, histology with semiquantitative score, and cardiac function. The UBM group showed mild adhesions, whereas the control group showed fibrosis at the repair site, with robust adhesions and injury to the coronary bed. Load at failure (gr) and stiffness (gr/mm) were lower in the UBM group compared with the native pericardium (199.9 ± 59.2 versus 405.3 ± 99.89 g, P = 0.0536 and 44.23 ± 15.01 versus 146.5 ± 24.38 g/mm, P = 0.0025, respectively). In the UBM group, the histology resembled native pericardial tissue, with neovascularization, neofibroblasts, and little inflammatory signs. In contrast, control group showed fibrotic tissue with mononuclear infiltrates and a lack of organized collagen fibers validated with a histologic score. Both groups had normal ultrasonography results without cardiac motility disorders. In this setting, UBM scaffolds showed appropriate features for pericardial repair, restoring tissue properties that could help reduce postsurgical adhesions and prevent its associated complications.

Biomechanical Features of Reinforced Esophageal Hiatus Repair in a Porcine Model.

Recurrence rates in the laparoscopic repair of the hiatal hernia range from 12% to 59%. Limitation of reinforcement has been principally the risk of adverse events caused by synthetic materials. Biologic and resorbable synthetic materials are valid alternatives. This study compares the host response to all these materials after hiatal hernia repair. A total of 20 Landrace pigs, underwent laparoscopic primary hiatal hernia repair and reinforced with a polypropylene mesh (PROLENE: polypropylene [PP]), an absorbable synthetic scaffold (GOREBIO-A: polyglycolic acid [PGA]), a urinary bladder matrix scaffold, (Gentrix: urinary bladder matrix [UBM]), or without reinforcement, control group (C). Animals were survived for 3 months. Endpoints included gross morphology, biomechanical testing, and histology. Pigs in PP and PGA groups showed fibrosis at the repair site, with robust adhesions. In UBM and C groups, only mild adhesions were found. Load at failure (gr) and stiffness (gr/mm) of PP were higher than C group (PP:2103 ± 548.3 versus C:951.1 ± 372.7, P = 0.02; PP:643.3 ± 301 versus C:152.6 ± 142.7, P = 0.01). PGA and UBM values for both parameters were in between PP and C samples. However, stiffness in UBM was tended to be lower than PP group, and approached a significant difference (643.3 ± 301 versus 243 ± 122.1, P = 0.0536). In UBM group, the histology resembled native tissue. By contrast, PP and PGA groups showed mononuclear infiltrates, fibroencapsulation, necrosis, remnants of mesh, and disorganized tissue that was validated with a histologic score. In this setting, UBM scaffolds showed the most appropriate features for hiatal hernia repair, recovering the tissue properties that can help reduce the possibility of early failure and prevent complications associated with the implanted material.

Fenotipos de disfunción crónica del injerto pulmonar / Phenotypes of chronic pulmonary graft dysfunction

En la actualidad el rechazo crónico en el trasplante pulmonar incluye diferentes formas de presentación clínica englobadas bajo el término "disfunción crónica de injerto", por sus siglas en inglés (CLAD, Chronic lung allograft dysfunction). Se han diferenciado dos fenotipos de CLAD, expresión de rechazo crónico, con presentación clínicoimagenológica, anatomo-patológica y evolutiva diferente. La disfunción crónica del injerto pulmonar con fenotipo obstructivo, correspondiente a la bronquiolitis obliterante (BO) / síndrome de bronquiolitis obliterante (SBO), y la de fenotipo restrictivo correspondiente al síndrome restrictivo del injerto (RAS, restrictive allograft syndrome)1. Se presentan dos casos clínicos de trasplante bipulmonar con disfunción crónica del injerto pulmonar que ejemplifican los fenotipos de rechazo crónico bajo las formas de SBO y RAS, respectivamente. Ambos pacientes recibieron un retrasplante pulmonar. La anatomía patológica de los pulmones explantados confirmó el diagnóstico en ambos casos

[Papillary fibroelastoma: retrospective analysis. Clinical presentation and surgical results]. / Fibroelastoma papilar cardíaco: estudio retrospectivo. Presentación clínica y resultados quirúrgicos.

Papillary ibroelastomas are small benign intracardiac tumors known for their embolic potential. Since the introduction of echocardiography with improved resolution and transesophageal imaging techniques, they are being increasingly detected in clinical practice. In recent series, papillary fibroelastoma is considered the most frequent benign tumor of the heart. Our objective was to analyze characteristics and midterm surgical outcome of histologically-confirmed cases of papillary fibroelastoma. We conducted a retrospective study on patients with cardiac tumors submitted to surgical excision between June 1992 and February 2017. Out of 108 patients, 18 had papillary fibroelastomas. Their mean age was 58 years (22-77); 10 were men. The most frequent localizations were the aortic valve (7) and the mitral valve (5). None had significant valvular dysfunction. By transesophageal echocardiography, the tumor size (larger diameter) was 13.33 ± 5.55 mm (6.6-28.0). Two patients, both with tumor in the aortic valve, had suffered a stroke; other two had dyspnoea and atrial flutter, respectively. The remaining 14 patients were asymptomatic and their tumors were incidental findings. In 15 patients the valve was preserved. There was neither surgical mortality nor recurrence after 2.6 years of follow-up. In conclusion, most papillary fibroelastomas can be surgically removed with valve preservation and favorable clinical outcome. However, until the results of randomized trials support the decision, an aggressive surgical approach in asymptomatic patients needs to be defined in the context of surgical expertise.

Fibroelastoma papilar cardíaco: estudio retrospectivo: Presentación clínica y resultados quirúrgicos / Fibroelastoma papilar cardíaco: estudio retrospectivo: Presentación clínica y resultados quirúrgicos

Los fibroelastomas papilares cardíacos son pequeños tumores benignos con potencial embolígeno. Con la incorporación de la ecocardiografía y la mejoría en la resolución de las imágenes, el diagnóstico clínico es cada vez más frecuente, y en series recientes su frecuencia supera a la del mixoma cardíaco. Nuestro objetivo fue analizar las características de una serie de casos de fibroelastoma papilar cardíaco con confirmación histológica operados en nuestro hospital. Analizamos retrospectivamente los tumores cardíacos y las características clínicas de los pacientes operados desde junio de 1992 a febrero de 2017. De 108 operados, 18 presentaron fibroelastoma papilar. La edad media del grupo con fibroelastoma papilar fue 58 años (22-77); 10 eran varones. Las localizaciones más frecuentes fueron la válvula aórtica (7) y la válvula mitral (5). Ninguno presentó disfunción valvular significativa. Por ecografía transesofágica, el tamaño (diámetro mayor) fue 13.33 ± 5.55 mm (6.6-28.0). Cuatro pacientes eran sintomáticos; uno presentaba disnea, otro aleteo auricular, dos con fibroelastoma en válvula aórtica habían sufrido un accidente cerebrovascular. Los restantes, asintomáticos, fueron intervenidos preventivamente. En 15 pacientes el tumor se extirpó sin necesidad de reemplazo valvular. No hubo mortalidad quirúrgica ni recidiva tumoral en el seguimiento de 2.6 años. Se concluye que los fibroelastomas papilares cardíacos pueden ser extirpados con buenos resultados a mediano plazo y, en su mayoría, con preservación valvular. Sin embargo, no existen aún estudios aleatorizados que avalen la escisión quirúrgica en pacientes asintomáticos. Por el momento, esta última depende de la experiencia del grupo quirúrgico tratante.

Papillary ibroelastomas are small benign intracardiac tumors known for their embolic potential. Since the introduction of echocardiography with improved resolution and transesophageal imaging techniques, they are being increasingly detected in clinical practice. In recent series, papillary fibroelastoma is considered the most frequent benign tumor of the heart. Our objective was to analyze characteristics and midterm surgical outcome of histologically-confirmed cases of papillary fibroelastoma. We conducted a retrospective study on patients with cardiac tumors submitted to surgical excision between June 1992 and February 2017. Out of 108 patients, 18 had papillary fibroelastomas. Their mean age was 58 years (22-77); 10 were men. The most frequent localizations were the aortic valve (7) and the mitral valve (5). None had significant valvular dysfunction. By transesophageal echocardiography, the tumor size (larger diameter) was 13.33 ± 5.55 mm (6.6-28.0). Two patients, both with tumor in the aortic valve, had suffered a stroke; other two had dyspnoea and atrial flutter, respectively. The remaining 14 patients were asymptomatic and their tumors were incidental findings. In 15 patients the valve was preserved. There was neither surgical mortality nor recurrence after 2.6 years of follow-up. In conclusion, most papillary fibroelastomas can be surgically removed with valve preservation and favorable clinical outcome. However, until the results of randomized trials support the decision, an aggressive surgical approach in asymptomatic patients needs to be defined in the context of surgical expertise.

Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study.

Since the decline in new cases of infection by insect/vector, congenital Chagas disease has become more relevant in the transmission of Chagas disease. Treatment with benznidazole significantly reduces the parasitemia, which constitutes an important factor linked to vertical transmission. The objective of this study was to evaluate whether treatment with benznidazole previously administered to women of childbearing age can prevent or reduce the incidence of new cases of congenital Chagas disease. An historical cohort study that included all women in reproductive age (15-45 years) assisted in our center was designed. We included 67 mothers with chronic Chagas disease; 35 women had not been treated prior to pregnancy, 15 had been treated prior to pregnancy and 17 gave birth prior and after treatment with benznidazole. Eight mothers gave birth to 16 children with congenital Chagas disease (8/67, 12%). The prevalence of congenital Chagas was 16/114 (14%) children born to untreated mothers and 0/42 (0%) children born to benznidazole- treated mothers, p=0.01. No significant differences were observed in clinical, serologic, epidemiological or socioeconomic baseline variables between mothers with and without children born with congenital Chagas. A 32% conversion rate to negative serology was observed in benznidazole-treated women after long-term follow up. Antiparasitic treatment administered to women in reproductive age can prevent the occurrence of congenital Chagas disease.