Instituto Cardiovascular de Buenos Aires

Leishmaniases remain a significant global public health threat, with Leishmania amazonensis and Leishmania infantum representing the etiological agents of the cutaneous and visceral forms in the Americas, respectively. Building on our previous identification of Phospholipase A1 (PLA1) in Leishmania braziliensis, this study provides a comprehensive molecular, immunological, and biochemical characterization of PLA1 in L. amazonensis and L. infantum promastigotes. We analyzed PLA1 activity and expression, purified the recombinant enzyme from L. amazonensis, and validated protein expression using a specific anti-PLA1 serum. The major contribution of this research is the first description of the subcellular localization of a PLA1 within the Leishmania genus. Moreover, our results reveal an unprecedented association between PLA1 and lipid droplets within the parasites. This discovery is of particular interest as it provides the first evidence linking this enzyme to lipid storage organelles in Leishmania. Given that PLA1 is an established virulence factor in other trypanosomatids, these findings suggest a specialized role for the enzyme in parasite lipid metabolism and potentially in its pathogenic mechanisms, opening new perspectives for understanding Leishmania biology.

C3 glomerulopathy is an ultra-rare kidney disease driven by dysregulation of the alternative complement pathway fluid phase C3 convertase. We report the case of a previously healthy 13-year-old girl who presented with concurrent nephrotic and nephritic syndrome and low complement C3. Her initial kidney biopsy surprisingly showed mesangioproliferative glomerulonephritis with dominating IgA deposits resulting in a diagnosis of IgA nephropathy. Despite standard immunosuppressive treatment with prednisone and mycophenolic acid plus angiotensin-converting enzyme inhibitors, she achieved only partial remission and subsequently relapsed, exhibiting severe, persistent C3 consumption (6-8mg/dl) and sustained C5b9 activation (1059ng/ml). A repeat biopsy 1.2years later established the definitive diagnosis of C3 glomerulonephritis (C3GN) with a membranoproliferative pattern. C3NEF antibodies were negative, and no pathological variant was detected in the genetic study. After 1year and 9months without response to immunosuppressive treatment, the C3 inhibitor pegcetacoplan was initiated. The patient achieved rapid and complete remission within 3months, marked by normalization of proteinuria, from 2747mg/day (urine protein-to-creatinine ratio [UPCR] 2.66mg/mg) pre-treatment to 19mg/d (UPCR 0.02mg/mg) and complement activation markers (from 1162ng/ml pre-treatment to C5b9 92ng/ml; reference value 30-150ng/ml). This case highlights the inherent diagnostic complexity of C3GN, suggesting the critical role of repeat biopsies in treatment-refractory, complement-dysregulated glomerulonephritis. It strongly supports the potential efficacy of C3 inhibition as a targeted therapeutic approach for patients with C3GN.

Introducción: La afectación del ventrículo derecho (VD) es una manifestación frecuente en la amiloidosis cardíaca por transtiretina (AC-TTR), especialmente en etapas avanzadas, y puede tener implicancias pronósticas relevantes. La evaluación ecocardiográfica del VD, sin embargo, continúa siendo desafiante. En este contexto, la relación entre el desplazamiento sistólico del anillo tricúspideo (TAPSE) y la presión sistólica de la arteria pulmonar (PSAP), así como la relación de la onda S por Doppler tisular (S’TDI) y la PSAP, han sido propuestas como marcadores del desacoplamiento VD-arteria pulmonar (VD-AP), lo que podría reflejar con mayor precisión la carga funcional del VD. Objetivo: Analizar el valor pronóstico de las relaciones TAPSE/PSAP y S’TDI/PSAP en pacientes con AC-TTR, y compararlas con otros predictores clínicos y ecocardiográficos tradicionales, en relación con el riesgo de hospitalización por insuficiencia cardíaca (IC). Material y métodos: Se realizó un análisis retrospectivo de pacientes con diagnóstico confirmado de AC-TTR bajo seguimiento ambulatorio en una clínica especializada en miocardiopatías. Se recolectaron datos clínicos, bioquímicos y ecocardiográficos al momento del diagnóstico, y se documentaron eventos de hospitalización por insuficiencia cardíaca (HIC) durante el seguimiento. El desenlace primario fue la primera HIC. Se emplearon modelos de regresión de Cox univariado y multivariado para identificar predictores independientes, y análisis de Kaplan Meier para evaluar curvas de supervivencia libre de eventos. Los puntos de corte óptimos de las variables continuas se definieron por el índice de Youden. Resultados: Se incluyeron 191 pacientes (edad media 80 ± 7,9 años, 88,5 % hombres), todos con fracción de eyección del ventrículo izquierdo preservada o levemente reducida, con mediana 53% y rango intercuartílico (RIC) 43-61, y evidencia ecocardiográfica de disfunción del VD, con medianas de TAPSE 18 mm (RIC 15-20), y onda S'TDI 9,5 (RIC 8-10). Durante un seguimiento mediano de 391 días (RIC 84-704), 32 % de los pacientes presentó al menos una HIC. En el análisis univariado una mayor relación TAPSE/PSAP se asoció con menor riesgo de hospitalización (HR 0,149; p = 0,039), al igual que valores más altos de TAPSE de forma aislada (HR 0,959 p=0,040) y mayor edad (HR 1,066; p=0,010), mientras que la PSAP aislada no fue significativa (HR 1,014; p=0,100). En el análisis multivariado, una relación TAPSE/PSAP ≤ 0,5 (punto de corte óptimo con sensibilidad 78 %, especificidad 67 % y área bajo la curva ROC 0,60) se asoció de manera independiente con mayor riesgo de hospitalización (HR 2,05; IC95 % 1,10–4,33; p = 0,025). En contraste, la relación S’TDI/PSAP no mostró asociación independiente (p = 0,843). Conclusiones: En pacientes con AC-TTR, el desacoplamiento VD–AP, estimado por una relación TAPSE/PSAP ≤ 0,5, se asocia con mayor riesgo de HIC, aun con fracción de eyección preservada. En contraste, la relación S’TDI/PSAP no aportó valor pronóstico. La relación TAPSE/PSAP, por su simplicidad y disponibilidad, podría incorporarse como herramienta complementaria de estratificación de riesgo en esta población

Introduction: Evidence about outcomes in ECMO in trauma-related ARDS from middle-income countries is absent, and mortality scores have never been validated in this environment. We characterised outcomes and complications of poly-traumatised adults treated with ECMO and assessed the accuracy of APACHE II, Injury Severity Score (ISS) and RESP score. Methods: We conducted an ambispective, multicentre cohort across four Argentine ECMO centres (2015-2024). All adults (≥18 yr) cannulated for refractory hypoxaemia after polytrauma were included. Pre-defined variables—demographics, injury pattern, ECMO configuration/duration, anticoagulation strategy and International Society on Thrombosis and Haemostasis (ISTH) bleeding categories—were extracted from electronic charts. Survivors underwent structured telephone follow-up with EQ-5D-3L and Katz Index. Model performance for in-hospital mortality was quantified by AUROC (discrimination) and Brier score + Spiegelhalter z (calibration). Institutional review boards approved the protocol, and survivors provided informed consent. Results: Thirty-two patients (mean age 32 ± 16 yr; 84 % male) received ECMO—31 venovenous, 1 veno-arterial. Median ISS was 34 (IQR 25–50); 63 % had concomitant traumatic brain injury. Time from intubation to cannulation was 4 d (1–6) and ECMO ran for 7 d (3–11). Heparin was administered in 59 %. Device-related events were common: oxygenator/circuit thrombosis 22 %, deep-vein thrombosis 19 %, any bleeding 28 % (major 16 %). Overall in-hospital mortality was 40.6 % (95 % CI 24–59) and occurred early (ECMO day 3 [1–7] vs 9.5 [6–11.8] in survivors, p = 0.009). Prognostic scores performed only moderately: ISS AUROC 0.63/Brier 0.224, RESP 0.56/0.240, APACHE II 0.54/0.241; pairwise AUROC differences were non-significant (p = 0.75). Nineteen patients survived to discharge; 11 (58 %) were interviewed a median 7 yr later. Median EQ-5D utility was 0.74 (0.65–0.83) and Katz 6 (5–6), yet chronic pain persisted in 55 % and anxiety/depression in 73 %. Conclusions: In this first Latin-American series, ECMO delivered 59 % long-term survival with high functional independence, but bleeding/thrombotic burdens were substantial and existing scores predicted mortality poorly. Trauma-specific risk models and structured post-ICU rehabilitation are urgently needed.

Una proporción importante de pacientes con estenosis aórtica (EAo) grave poseen comorbilidades que incrementan el riesgo de la cirugía de reemplazo valvular aórtico. El implante percutáneo de válvula protésica surge como una alternativa en este grupo de pacientes. Se comunican dos casos de pacientes de edad avanzada portadores de EAo grave a los que se les realizó con éxito el implante percutáneo de una prótesis valvular aórtica CoreValve y se describen los criterios para la selección de pacientes y la técnica de implante percutáneo.

Abstract Introduction Readmission due to acute heart failure (AHF) attributed to residual congestion at discharge is frequent and associated with a higher risk of worsening heart failure (WHF) events. Recently, the HFA-ESC has recommended pre-discharge decongestion goals, incorporating inferior vena cava (IVC) ultrasound, lung ultrasound (LUS), and NT-ProBNP. The combination of these variables and their prognostic impact post-discharge has not been explored. Objective To evaluate the prognostic impact of a multiparametric combination of IVC, LUS, and NT-ProBNP on 90-day clinical outcomes, including AHF readmission, unplanned visits due to WHF, or all-cause mortality. Methods This substudy is derived from a randomized controlled trial that included adult patients with AHF. NT-proBNP was measured at admission and discharge, and daily IVC and lung ultrasounds were performed until discharge using a quantitative protocol. These were conducted by independent physicians not involved in patient management and reported by an external core lab composed of 3 physicians. According to the HFA-ESC consensus, patients were categorized as "Optimal" if they met the following criteria: <5 B-lines on LUS, IVC <21 mm, collapsibility index >50%, and a >30% reduction in NT-ProBNP between admission and discharge. Patients not meeting all three combined criteria were categorized as "Non-optimal." The primary endpoint was a composite of AHF readmission, unplanned visit due to WHF, or death at 90 days. Results Sixty patients were included. The mean age was 76.7 ± 13 years, 68.3% were male, and the mean left ventricular ejection fraction (LVEF) was 44% ± 15. Patients had a high prevalence of comorbidities, including hypertension (75.8%), atrial fibrillation (53%), anemia (34.8%), and chronic kidney disease (42.4%). Forty-seven percent (n=27) of the cohort was discharged under optimal decongestion criteria. A significant reduction in AHF readmission, unplanned visits due to WHF, or death at 90 days was observed in the Optimal group (Optimal 0% vs. Non-optimal 42.4%; log-rank p <0.001). Figure 2 shows the Kaplan-Meier curve for the primary endpoint, comparing the Optimal versus Non-optimal groups. Conclusion The combination of multiple subclinical congestion parameters, including IVC ultrasound, lung ultrasound, and NT-ProBNP, identified a group of AHF patients with a very low risk of WHF events and mortality at 90 days post-discharge. These findings support the most recent HFA-ESC recommendations and suggest that multiparametric assessment may be superior to individual parameter evaluation in guiding discharge timing and reducing the risk of events. Larger-scale studies are needed to validate these results and assess their impact on clinical practice.

IntroducciónLa diabetes mellitus se ha identificado como un fuerte predictor independiente de iniciación y progresión de la enfermedad cardiovascular y se ha reconocido como un factor de riesgo de mortalidad luego de la cirugía coronaria. La cirugía de revascularización miocárdica sin circulación extracorpórea se ha establecido como una alternativa eficaz de revascularización coronaria comparable a la técnica convencional, con resultados que muestran una disminución en la morbilidad del procedimiento y, en pacientes de riesgo alto, una mortalidad posoperatoria menor. ObjetivosComparar los resultados posoperatorios tempranos y alejados de pacientes con y sin diabetes mellitus luego de cirugía de revascularización miocárdica sin circulación extracorpórea con puentes arteriales múltiples y determinar si la hiperglucemia posoperatoria es un predictor independiente de morbimortalidad temprana. Material y métodos Entre enero de 2004 y diciembre de 2008 se efectuó cirugía de revascularización miocárdica sin circulación extracorpórea con puentes arteriales múltiples en 1.002 pacientes en forma consecutiva. La población se dividió en pacientes con diabetes mellitus (n = 234) y sin diabetes mellitus (n = 768). Se efectuó un análisis de las complicaciones posoperatorias y se identificaronpredictores independientes de mortalidad hospitalaria. El seguimiento promedio fue de 1.038 ± 517 días y fue completo en el 95,7%.Resultados Los pacientes con diabetes mellitus presentaron mayor incidencia de bajo gasto cardíaco (p = 0,005), fibrilación auricular (p = 0,005) e infección esternal profunda (p = 0,005). Fueron predictores de mortalidad hospitalaria la edad (OR = 1,11), la cirugía no electiva (OR= 5,88) y la glucemia posoperatoria > 200 mg/dl (OR = 6,9).Los pacientes con diabetes mellitus tuvieron menor sobrevida alejada a los 5 años (p = 0,01). Fueron predictores de menor sobrevida alejada la diabetes mellitus (HR = 2,1), la edad (HR = 1,06), la fracción de eyección del ventrículo izquierdo < 40% (HR = 2,45) y la creatinina posoperatoria > 1,6 mg/dl (HR = 2,46).ConclusionesLos pacientes con diabetes mellitus tuvieron igual mortalidad hospitalaria que los no diabéticos. La presencia de hiperglucemia posoperatoria fue un predictor de mayor mortalidad hospitalaria. La diabetes mellitus y la creatinina > 1,6 mg/dl fueron predictores independientes de menor sobrevida alejada.