Predicting Mortality after Autologous Transplant: Development of a Novel Risk Score.

There have been several efforts to predict mortality after autologous stem cell transplantation (ASCT), such as the hematopoietic cell transplant-comorbidity index (HCT-CI), described for allogeneic stem cell transplantation and validated for ASCT, but there is no composite score in the setting of ASCT combining comorbidities with other clinical characteristics. Our aim is to describe a comprehensive score combining comorbidities with other clinical factors and to analyze the impact of this score on nonrelapse mortality (NRM), overall survival (OS), and early morbidity endpoints (mechanical ventilation, shock or dialysis) after ASCT. For the training cohort, we retrospectively reviewed data of 2068 adult patients who received an ASCT in Argentina (October 2002 to June 2017) for multiple myeloma or lymphoma. For the validation cohort, we analyzed 2168 ASCTs performed in the Medical College of Wisconsin and Spanish stem cell transplant group (Grupo Español de Trasplante Hematopoyético (GETH)) (January 2012 to December 2018). We first performed a multivariate analysis for NRM in order to select and assign weight to the risk factors included in the score (male patients, aged 55 to 64 and ≥65 years, HCT-CI ≥3, Hodgkin lymphoma and non-Hodgkin lymphoma). The hazard ratio for NRM increased proportionally with the score. Patients were grouped as low risk (LR) with a score of 0 to 1 (686, 33%), intermediate risk (IR) with a score of 2 to 3 (1109, 53%), high risk (HR) with a score of 4 (198, 10%), and very high risk (VHR) with a score of ≥5 (75, 4%). The score was associated with a progressive increase in all the early morbidity endpoints. Moreover, the score was significantly associated with early NRM (day 100: 1.5% versus 2.4% versus 7.6% versus 17.6%) as well as long term (1 to 3 years; 1.8% to 2.3% versus 3.8% to 4.9% versus 11.7% to 14.5% versus 25.0% to 27.4%, respectively; P< .0001) and OS (1 to 5 years; 94% to 73% versus 89% to 75% versus 76% to 47% versus 65% to 52% respectively; P < .0001). The score was validated in an independent cohort (N = 2168) and was significantly associated with early and late events. In conclusion, we developed and validated a novel score predicting NRM and OS in 2 large cohorts of more than 2000 autologous transplant patients. This tool can be useful for tailoring conditioning regimens or defining risk for transplant program decision making.

Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma.

The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.

[Dual antiplatelet therapy for secondary stroke prevention in patients with acute ischemic stroke. CIERTO group recommendation]. / Doble terapia antiagregante en pacientes con accidente cerebrovascular isquémico agudo. Recomendación del grupo CIERTO.

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.

El inicio precoz del tratamiento con antiagregantes plaquetarios es considerado el estándar de cuidado para pacientes con accidente cerebrovascular isquémico agudo. Distintos esquemas de antiagregación se han comparado con resultados que sugieren que la combinación de múltiples antiagregantes se asocian a menor riesgo de recurrencia de accidente cerebrovascular (ACV) pero a expensas de un aumento en el riesgo de sangrado, lo que a largo plazo termina opacando dichos beneficos. Sin embargo, considerando que el riesgo de recurrencia de ACV es mayor en el periodo inmediato al evento, la indicación de doble tratamiento antiagregante por tiempos limitados podría asociarse a beneficios relevantes. Con este concepto, se realizó una revisión sistemática rápida con el objetivo de evaluar el efecto del tratamiento con doble antiagregación por un periodo corto intentando maximizar el beneficio y reducir al mínimo el riesgo de sangrado. Se incluyeron todos los estudios primarios identificados en los que se comparó un esquema de doble antiagregación, iniciado en el periodo agudo del evento índice (ACV o accidente isquémico transitorio - AIT), contra un esquema de simple antiagregación. El cuerpo de la evidencia mostró que la intervención (doble antiagregación) reduce el riesgo de recurrencia de ACV y probablemente se asocie a un aumento marginal en el riesgo de sangrado mayor. Sugerimos indicar doble esquema antiplaquetario para el tratamiento inicial de pacientes con ACV isquémico menor (Score NIH < o igual a 3 o AIT).

Doble terapia antiagregante en pacientes con accidente cerebrovascular isquémico agudo: Recomendación del grupo CIERTO / Dual antiplatelet therapy for secondary stroke prevention in patients with acute ischemic stroke. CIERTO group recommendation

El inicio precoz del tratamiento con antiagregantes plaquetarios es considerado el estándar de cuidado para pacientes con accidente cerebrovascular isquémico agudo. Distintos esquemas de antiagregación se han comparado con resultados que sugieren que la combinación de múltiples antiagregantes se asocian a menor riesgo de recurrencia de accidente cerebrovascular (ACV) pero a expensas de un aumento en el riesgo de sangrado, lo que a largo plazo termina opacando dichos beneficos. Sin embargo, considerando que el riesgo de recurrencia de ACV es mayor en el periodo inmediato al evento, la indicación de doble tratamiento antiagregante por tiempos limitados podría asociarse a beneficios relevantes. Con este concepto, se realizó una revisión sistemática rápida con el objetivo de evaluar el efecto del tratamiento con doble antiagregación por un periodo corto intentando maximizar el beneficio y reducir al mínimo el riesgo de sangrado. Se incluyeron todos los estudios primarios identificados en los que se comparó un esquema de doble antiagregación, iniciado en el periodo agudo del evento índice (ACV o accidente isquémico transitorio - AIT), contra un esquema de simple antiagregación. El cuerpo de la evidencia mostró que la intervención (doble antiagregación) reduce el riesgo de recurrencia de ACV y probablemente se asocie a un aumento marginal en el riesgo de sangrado mayor. Sugerimos indicar doble esquema antiplaquetario para el tratamiento inicial de pacientes con ACV isquémico menor (Score NIH < o igual a 3 o AIT).

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.

Adherencia a hormonoterapia en pacientes con carcinoma ductal in situ de mama / Adherence to hormonal therapy in patients with ductal carcinoma in situ of the breast

Introducción Las pacientes con Carcinoma Ductal in Situ de mama (cdis) tienen mayor riesgo de desarrollar carcinoma invasor. Aquellas con receptores hormonales positivos se beneficiarían con hormonoterapia. El largo período de tratamiento y los efectos adversos asociados al mismo hacen dificultosa la adherencia. Objetivos El objetivo del presente trabajo es analizar la adherencia a la hormonoterapia en pacientes operadas por Carcinoma Ductal in Situ en el Hospital Universitario Austral. Material y método Es un estudio observacional, analítico, de corte transversal. Se incluyeron pacientes con diagnóstico de Carcinoma Ductal in Situ que fueron intervenidas quirúrgicamente en el Hospital Universitario Austral en el período comprendido entre el 24 de julio de 2000 y el 5 de julio de 2017. Los datos fueron recopilados a través de una encuesta. Resultados Se obtuvieron 100 encuestas. La adherencia fue del 82%. La misma no se modificó según edad, conocimiento de riesgos y beneficios del tratamiento, tipo y número de cirugías, radioterapia y número de consultas. Las reacciones adversas a la medicación fueron la causa más frecuente de abandono al tratamiento. Conclusiones El tratamiento multidisciplinario podría asegurar un óptimo nivel de adherencia

Introduction Patients with Ductal Carcinoma in Situ of the breast (dcis) have a higher risk of developing invasive carcinoma. Those with hormone receptor-positive would benefit from hormonal therapy. The long period of treatment and the associated adverse events make adherence difficult. Objectives The aim of this study is to analyze the adherence of hormonal therapy in operated patients with Ductal Carcinoma in Situ at Hospital Universitario Austral. Materials and method It is an observational, analytical and cross-sectional study. Patients diagnosed with Ductal Carcinoma in Situ who underwent surgery at Hospital Universitario Austral in the period between 07/24/2000 and 07/05/2017 were included. The data was collected through a survey. Results 100 surveys were obtained. The adherence was 82%. It was not modified according to age, knowledge of risks and benefits of the treatment, type and number of surgeries, radiotherapy and number of consultations. Adverse events were the most frequent cause of discontinue of treatment. Conclusions Multidisciplinary treatment could ensure an optimal level of adherence

FUSARIUM SOLANI SUBRETINAL ABSCESS IN A PATIENT WITH ACUTE MYELOID LEUKEMIA.

PURPOSE: To report on a case of Fusarium solani subretinal abscess in a patient with acute myeloid leukemia treated with an allogenic bone marrow transplant. METHODS: A 47-year-old male with a history of acute myeloid leukemia with intermediate cytogenetic risk was admitted in our hospital. The disease relapsed after two cycles of chemotherapy. He was then treated with an allogenic bone marrow transplant, with busulfan, cyclophosphamide, and thymoglobulin. One week after the procedure, a sepsis of unknown origin in neutropenia occurred. Blood cultures and sputum were negative for bacteria and fungi. At the eighth week after the procedure, the patient had acute vision loss of the right eye. Funduscopy in the right eye revealed an inferior temporal yellowish white elevated lesion of approximately 10 disk areas and superficial perifoveal and perilesional hemorrhages. RESULTS: Vitrectomy was performed and samples from the vitreous and the subretinal abscess material were sent for analysis. Vitreous and subretinal specimens grew colonies of a fungus morphologically consistent with F. solani. CONCLUSION: Fusarium solani should be included in the differential diagnosis of subretinal abscesses.

Liver transplantation for hepatocellular carcinoma: evaluation of the alpha-fetoprotein model in a multicenter cohort from Latin America.

BACKGROUND & AIMS: The French alpha-fetoprotein (AFP) model has recently shown superior results compared to Milan criteria (MC) for prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin-American cohort. METHODS: Three hundred twenty-seven patients with HCC were included from a total of 2018 patients transplanted at 15 centres. Serum AFP and imaging data were both recorded at listing. Predictability was assessed by the Net Reclassification Improvement (NRI) method. RESULTS: Overall, 82 and 79% of the patients were within MC and the AFP model respectively. NRI showed a superior predictability of the AFP model against MC. Patients with an AFP score >2 points had higher risk of recurrence at 5 years Hazard Ratio (HR) of 3.15 (P = 0.0001) and lower patient survival (HR = 1.51; P = 0.03). Among patients exceeding MC, a score ≤2 points identified a subgroup of patients with lower recurrence (5% vs 42%; P = 0.013) and higher survival rates (84% vs 45%; P = 0.038). In cases treated with bridging procedures, following restaging, a score >2 points identified a higher recurrence (HR 2.2, P = 0.12) and lower survival rate (HR 2.25, P = 0.03). A comparative analysis between HBV and non-HBV patients showed that the AFP model performed better in non-HBV patients. CONCLUSIONS: The AFP model could be useful in Latin-American countries to better select patients for LT in subgroups presenting with extended criteria. However, particular attention should be focused on patients with HBV.

Fulminant presentation of autoimmune hepatitis: clinical features and early predictors of corticosteroid treatment failure.

BACKGROUND AND AIMS: Classical features of autoimmune hepatitis (AIH) may be altered during the abrupt onset of the disease. Corticosteroid therapy can be life-saving, but its use in the fulminant presentation of AIH (F-AIH) remains controversial. We aimed to assess the clinical features of patients with F-AIH and to describe the role of corticosteroids in this population. PATIENTS AND METHODS: We retrospectively analyzed 154 adult patients with fulminant hepatic failure who were admitted to six liver transplantation (LT) programs. The AIH simplified criteria were used to identify patients with F-AIH. RESULTS: We identified 40 (26%) patients with F-AIH. Compared with other etiologies, patients with F-AIH presented a longer interval from jaundice to encephalopathy (26 vs. 16 days, P=0.02) and a lower Model for End-Stage Liver Disease (MELD) score on admission (29 vs. 33, P=0.002). Overall, 25 (62%) patients with F-AIH underwent LT, eight (20%) patients survived, and seven (18%) died without LT. Seventeen patients received corticosteroids therapy, of whom seven (41%) survived without LT. Among the treated patients, higher MELD score and encephalopathy grade of 3 or more were associated significantly with corticosteroid failure. CONCLUSION: Patients with F-AIH have a more indolent presentation compared with the non-F-AIH population. Altogether, only eight (20%) patients presenting with F-AIH survived without LT. A subset of patients with F-AIH and an initial MELD score less than 27 and low-grade hepatic encephalopathy might benefit from administration of corticosteroids.

Early predictors of renal dysfunction in cirrhotic patients after liver transplantation.

BACKGROUND: Assessment of renal function 12 months after liver transplantation (LT) predicts chronic renal failure on long-term follow up. OBJECTIVE: To evaluate pre- and post- LT factors associated with development of renal dysfunction (RD) in cirrhotic patients. METHODS: Between June 2005 and June 2010, 104 cirrhotic patients were selected from 268 consecutively transplanted adult patients. RD was defined as a calculated glomerular filtration rate (cGFR) < 50 ml/min/1.73m2 by modification of diet in renal disease (MDRD), 12 months after LT. RESULTS: Baseline pre-LT creatinine was 1.0 ± 0.7 mg/dL and cGFR was 64 ± 32.8 mL/min. At 12 month follow up, creatinine was 1.3 ± 0.6 mg/dL and cGFR was 47 ± 18 mL/min. The prevalence of RD was 55%. Variables related to RD on univariate analysis were age (P = 0.007), pre-L T GFR (P = 0.012) and 7th day post-L T GFR (P = 0.003). Risk factors associated with RD on multivariate stepwise regression analysis were patient age [Odds ratio (OR) 1.04 (95% confidence interval (CI) 0.99- 1.09, P = 0.06)] and 7 day post-LT GFR [OR 0.97 (95% CI 0.96-0.99, P = 0.013)]. ROC curve analysis for 7th day post-LT GFR was 0.71 (95% CI 0.61-0.81). CONCLUSION: The 7th day post-LT GFR in cirrhotic patients may be a useful clinical tool to identify which patients might benefit from earlier nephroprotective immunosuppression.

Insuficiencia renal aguda en el pos-trasplante hepático / Acute kidney injury following liver transplantation

Objetivo: Estudiar la incidencia de Insuficiencia renal aguda (IRA) en el postrasplante hepático, sus factores de riesgo y evaluar mortalidad en la internación y al año postrasplante. Material y métodos: Se realizó un análisis retrospectivo de 157 pacientes trasplantados hepáticos mayores de 18 años en el período comprendido entre diciembre de 2001 a mayo 2011. Fue analizada la función renal dentro de las 48 hs. previas al trasplante y postrasplante durante la internación. Se definió IRA al aumento de creatinina sérica en 1.5 veces el valor basal. Resultados: la incidencia de IRA postrasplante hepático fue del 33% (n=53). En el análisis multivariado la edad y la diabetes mostraron una asociación significativa con la presencia de IRA postrasplante hepático. La estadía hospitalaria entre los pacientes del grupo IRA promedió los 20 días (15-31) versus 14 días (11-23) del grupo no IRA (p=0,009). La mortalidad hospitalaria del grupo IRA fue de 16.9% (n=9) versus 3.8%(n=4) del grupo no IRA (p=0.005). La mortalidad al año postrasplante del grupo IRA fue de 26.4%(n=14) versus 7.6%(n=8) del grupo no IRA (p=0.001). Conclusión: la IRA en el postrasplante hepático es una complicación frecuente que está asociada a un aumento de la estadía hospitalaria, mortalidad a corto plazo y menor sobrevida al año postrasplante. La edad y la diabetes fueron factores independientes asociados a la presencia de IRA postrasplante hepático.

Objectives: Assessing: a).- The incidence of Acute Kidney Injury (AKI) in post-liver transplantation and its risk factors; b).- Mortality during hospitalization and one year after the transplantation. Materials and Methods: A retrospective analysis in 157 liver transplantation patients over 18 years of age was conducted from December of 2001 to May of 2011. Kidney function was assessed within 48 hours prior to the transplantation and during hospitalization after the transplantation. AKI was defined as a 1.5-fold serum creatinine increase from baseline. Results: AKI incidence following liver transplantation was 33% (n=53). In the multivariate analysis, age and diabetes showed significant association with the presence of AKI following liver transplantation. Average length of stay in hospital among patients in the AKI group was 20 days (15-31) versus 14 days (11- 23) in the non-AKI group (p=0.009). Hospital mortality in the AKI group was 16.9% (n=9) versus 3.8% (n=4) in the non-AKI group (p=0.005). Mortality one year following transplantation in the AKI group was 26.4% (n=14) versus 7.6%(n=8) in the non-AKI group (p=0.001).Conclusion: AKI following liver transplantation is a common complication which is associated withan increased stay in hospital, short-term mortality, and lower survival one year after transplantation. Age and diabetes were independent factors associated with the presence of AKI following liver transplantation.

Insuficiencia renal aguda en el pos-trasplante hepático / Acute kidney injury following liver transplantation

Objetivo: Estudiar la incidencia de Insuficiencia renal aguda (IRA) en el postrasplante hepático, sus factores de riesgo y evaluar mortalidad en la internación y al año postrasplante. Material y métodos: Se realizó un análisis retrospectivo de 157 pacientes trasplantados hepáticos mayores de 18 años en el período comprendido entre diciembre de 2001 a mayo 2011. Fue analizada la función renal dentro de las 48 hs. previas al trasplante y postrasplante durante la internación. Se definió IRA al aumento de creatinina sérica en 1.5 veces el valor basal. Resultados: la incidencia de IRA postrasplante hepático fue del 33% (n=53). En el análisis multivariado la edad y la diabetes mostraron una asociación significativa con la presencia de IRA postrasplante hepático. La estadía hospitalaria entre los pacientes del grupo IRA promedió los 20 días (15-31) versus 14 días (11-23) del grupo no IRA (p=0,009). La mortalidad hospitalaria del grupo IRA fue de 16.9% (n=9) versus 3.8%(n=4) del grupo no IRA (p=0.005). La mortalidad al año postrasplante del grupo IRA fue de 26.4%(n=14) versus 7.6%(n=8) del grupo no IRA (p=0.001). Conclusión: la IRA en el postrasplante hepático es una complicación frecuente que está asociada a un aumento de la estadía hospitalaria, mortalidad a corto plazo y menor sobrevida al año postrasplante. La edad y la diabetes fueron factores independientes asociados a la presencia de IRA postrasplante hepático.(AU)

Objectives: Assessing: a).- The incidence of Acute Kidney Injury (AKI) in post-liver transplantation and its risk factors; b).- Mortality during hospitalization and one year after the transplantation. Materials and Methods: A retrospective analysis in 157 liver transplantation patients over 18 years of age was conducted from December of 2001 to May of 2011. Kidney function was assessed within 48 hours prior to the transplantation and during hospitalization after the transplantation. AKI was defined as a 1.5-fold serum creatinine increase from baseline. Results: AKI incidence following liver transplantation was 33% (n=53). In the multivariate analysis, age and diabetes showed significant association with the presence of AKI following liver transplantation. Average length of stay in hospital among patients in the AKI group was 20 days (15-31) versus 14 days (11- 23) in the non-AKI group (p=0.009). Hospital mortality in the AKI group was 16.9% (n=9) versus 3.8% (n=4) in the non-AKI group (p=0.005). Mortality one year following transplantation in the AKI group was 26.4% (n=14) versus 7.6%(n=8) in the non-AKI group (p=0.001).Conclusion: AKI following liver transplantation is a common complication which is associated withan increased stay in hospital, short-term mortality, and lower survival one year after transplantation. Age and diabetes were independent factors associated with the presence of AKI following liver transplantation.(AU)