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El objetivo es estudiar la relación entre los parámetros estructurales, de remodelado, de sincronía y de función sistólica del ventrículo izquierdo (VI) mediante gSPECT. Obtener los valores de corte del VI para el índice de la forma telediastólica (iFTD), el índice de la forma telesistólica (iFTS), el índice de excentricidad (iEX) y la velocidad máxima de vaciado (VMV). Desarrollar un nuevo índice para evaluar diferentes patrones de función sistólica del VI. Analizamos prospectivamente 238 pacientes (edad: 63,4 ± 13 años) estudiados mediante gSPECT de esfuerzo-reposo (grupo-control, n = 148; pacientes con infarto de miocardio [IM] previo, n = 90). Estudio aprobado por el Comité de Ética del Hospital (PR[AG]168.2010). En el grupo-control, el índice del volumen telediastólico (iVTD) y el iEX influyeron en el iFTD (r2: 0,52, p < 0,001). El iVTD, la VMV, ser varones y el iEX (r2: 0,44; p < 0,001) influyeron en el iFTS. El iFTD, iFTS, la fracción de eyección VI (FEVI) y el volumen de eyección sistólica (r2: 0,62; p < 0,001) influyeron en el iEX. La FEVI, la frecuencia cardíaca, el ancho de banda (AB) y la desviación estándar influyeron (r2: 0,76; p < 0,001) en la VMV. Los valores de corte para iFTD, iFTS, iEX y VMV fueron 0,59, 0,42, 0,87 y −3,3 respectivamente. La VMV, el iFTS y el AB fueron los parámetros mejor relacionados con los pacientes con IM previo (AUC: 0,89), y sumados a la FEVI permitieron obtener distintos patrones de función sistólica (índice PERRS). Los parámetros de remodelado, sincronía y función sistólica del VI deben interpretarse simultáneamente, ya que esto permite obtener distintos patrones de función sistólica del VI. The aim of this study is to assess the relationship between structural, remodeling, synchrony, and systolic left ventricular (LV) function parameters using gated-SPECT myocardial-perfusion-images (gSPECT-MPI). In addition, obtaining the cut-off values for end-diastolic LV-shape-index (EDLVsi), end-systolic LV-shape-index (ESLVsi), ECC (eccentricity-index) and PER, and developing a new index to evaluate different patterns of the LV systolic function. The study was approved by the Hospital's Ethical-Committee (PR[AG]168.2010), and all patients gave their informed consent. We analyzed prospectively 238 patients (age 63.4 ± 13 years) who underwent stress-rest gSPECT-MPI (control-group, n = 148; patients with previous myocardial infarction [MI], n = 90). In the control group, with regard to remodeling parameters: the end-diastolic-volume-index (EDV) and the ECC were the parameters that influenced the EDLVsi (r 2: 0.52, P <.001). EDV, PER, men, and the ECC were the parameters (r 2: 0.44; P <.001) which influenced the ESLVsi. EDLVsi, ESLVsi, LVEF and the stroke-volume were the parameters (r 2: 0.62; P <.001) which influenced the ECC. With regards to PER: LVEF, heart-rate, bandwidth, and the standard-deviation were the influencing parameters (r 2: 0.76; P <.001). The cut-off values for EDLVsi, ESLVsi, ECC, and PER were 0.59, 0.42, 0.87, and 3.3, respectively. The PER, the ESLVsi and the bandwidth were the parameters related to patients with previous MI (AUC: 0.89); and they allow the assessment of different patterns of systolic function (PERRS-index: Peak-Emptying-Rate, left ventricular-Remodeling and Synchrony). The remodeling, synchrony and the systolic function parameters of the LV should be interpreted together (PERRS-index). In this way, we obtain different patterns of LV systolic function. [ABSTRACT FROM AUTHOR]

Several breakthroughs in hepatocellular carcinoma (HCC) therapy across tumor stages provide hope to improve its dismal prognosis. Although surgical and local ablative therapies have few significant changes in technique, an improved understanding of tumor biology has facilitated increase numbers of patients who are now eligible to undergo curative-intent procedures. Most notably, acceptable post-transplant outcomes can be achieved in well selected patients whose tumors are downstaged into Milan Criteria. Adjuvant therapy in patients at high risk of recurrence also significantly improves recurrence-free survival after resection or ablation. For patients with liver-localized disease who are not eligible for curative-intent procedures, transarterial chemoembolization (TACE) was historically the treatment modality of choice, regardless of tumor burden; however, there is now increased recognition of patients who are "TACE unsuitable" and may be better treated with systemic therapy. The greatest evolution in HCC treatment options has occurred with systemic therapy, where several new agents are now available in the first- and second-line setting, including immune checkpoint inhibitor combinations. Objective responses are observed in approximately 30% of patients and median survival is approaching 2 years. The availability of immune checkpoint inhibitors has renewed interest in combination therapies for earlier tumor stages, with several phase III trials ongoing. Considering increasing complexities of HCC care, requiring decisions between therapies delivered by different providers, multidisciplinary care is critical and is associated with improved clinical outcomes. In this review, we detail major breakthroughs in HCC therapy, how these breakthroughs can be applied in clinical practice, and remaining areas in need of further research. [ABSTRACT FROM AUTHOR]

Los radiotrazadores con afinidad ósea como el [99mTc]Tc-DPD han demostrado una alta sensibilidad y especificidad en el diagnóstico no invasivo de la amiloidosis cardíaca (AC) por transtirretina (ATTR-AC). Este estudio tiene como objetivo validar el uso de la SPECT/TC y evaluar la utilidad de la cuantificación de la captación (cargaDPD) en el tejido miocárdico como información potencial sobre la carga amiloide. Se trata de un análisis retrospectivo de 46 pacientes con sospecha de AC, en el que 23 casos con ATTR-AC fueron sometidos a dos métodos de cuantificación para estimar la carga amiloide (cargaDPD) a través de imágenes planares y de una SPECT/TC. La SPECT/TC aportó un valor añadido significativo en el diagnóstico del paciente con AC (p < 0,05). La estimación de la carga amiloide comprobó que la pared del VI más afectada es el tabique interventricular en la mayoría de los casos, y la existencia de una relación significativa entre la captación de Perugini y la carga de DPD. Validamos la necesidad de la SPECT/TC como complemento de la imagen planar en el diagnóstico de la AC-TTR. Por su parte, el cálculo de la carga amiloide continúa siendo un área de investigación compleja y requiere de más estudios, con un mayor número de pacientes, que permitan validar un método estandarizado de cuantificación de la carga de amiloide, tanto para el diagnóstico como para el seguimiento del tratamiento. Bone tracers such as [99mTc]Tc-DPD have shown high sensitivity and specificity in the non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-AC). This study aims to validate SPECT/CT and assess the usefulness of uptake quantification (burdenDPD) in the myocardial tissue as potential information on the amyloid burden. In a retrospective analysis of 46 patients with suspected CA, 23 cases with ATTR-AC had two quantification methods conducted to estimate amyloid burden (burdenDPD) through planar scintigraphic scans and a SPECT/CT. SPECT/CT significantly provided an added value in the patient's diagnosis with CA (P <.05). The estimation of the amyloid burden substantiated that the most affected wall of the LV is the interventricular septum in most cases and the existence of a significant relationship between the Perugini score uptake and the burdenDPD. We validate the need for SPECT/CT to complement planar imaging in diagnosing ATTR-AC. For its part, quantifying the amyloid load continues to be a complex area of research. It requires further studies with a larger number of patients to validate a standardized method of amyloid load quantification, both for diagnosis and treatment monitoring. [ABSTRACT FROM AUTHOR]

• Risk score predicts risk of MACE in patients with ischaemic cardiomyopathy. • Risk score comprises eight readily available variables. • The risk score's ease of use may allow its implementation in clinics. Ischaemic cardiomyopathy is a leading cause of heart failure and is associated with a poor prognosis. To evaluate predictors of major adverse cardiovascular events (MACE) and to develop a risk score for the disease. All patients with ischaemic cardiomyopathy referred to a tertiary hospital between 2010 and 2018 for stress-rest gated single-photon emission computed tomography (SPECT) were included retrospectively (n = 747). Clinical and gated SPECT-derived variables were analysed as predictors of MACE, a combined endpoint of cardiovascular mortality, heart failure hospitalization or myocardial infarction during follow-up. A multivariable Cox model using backwards stepwise regression with competing risks was used to select the best parsimonious model. After a median follow-up of 4.7 years, 313 patients had MACE (41.9%). Independent predictors of MACE were previous heart failure admission, worsening angina or dyspnoea, estimated glomerular filtration rate ≤60 mL/min/1.73 m2, age > 73 years, diabetes, atrial fibrillation, end-diastolic volume index > 83 mL/m2 and > 12% of scarred myocardium. A risk score ranging from 0 to 12 classified patients as at intermediate risk (event rate of 4.0 MACE per 100 person-years), high risk (11.3 MACE per 100 person-years) or very high risk (27.8 MACE per 100 person-years). The internally validated area under the curve was 0.720 (95% confidence interval 0.660–0.740) and calibration was adequate (Hosmer-Lemeshow test P = 0.28) for MACE. In patients with ischaemic cardiomyopathy, a simple risk score using dichotomic and readily available variables obtained from clinical assessment and gated SPECT accurately predicts the risk of MACE. [ABSTRACT FROM AUTHOR]

Purpose: Polyethylene glycol drug-eluting microspheres (PEG-DEMs) can be loaded to elute doxorubicin. The current study evaluated the pharmacokinetic profile and safety of PEG-DEMs in the treatment of patients with hepatocellular carcinoma (HCC).Materials and Methods: The current prospective, multicenter, dose-escalation study enrolled 25 patients (68% men) with early or intermediate stage HCC and a performance status of 0. Patients in Cohort I were assigned to receive target doxorubicin doses of 75, 100, or 150 mg. Analyses were performed on the basis of the specific dose of doxorubicin that the patients received because some patients received less than the assigned dose. Patients in Cohort II received the maximum safe tested dose. Adverse events were classified according to the Common Terminology Criteria for Adverse Events version 4.03. The tumor response was evaluated every 3 months according to the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors.Results: The maximum tested safe dose of doxorubicin was 150 mg. For the groups that received ≤75, 75-100, and 101-150 mg of doxorubicin, the peak plasma concentrations were 286.7 ng/mL ± 220.1, 157.1 ng/mL ± 94.6, and 245.4 ng/mL ± 142.8, respectively; the areas under the curves calculated from 0 to 24 h were 421.7 (ng × h)/mL ± 221.2, 288.1 (ng × h)/mL ± 100.9, and 608.3 (ng × h)/mL ± 319.3, respectively, with almost complete clearance at 24 h. There was no death within 30 d. The best objective response rate was 81%, and the disease control rate was 91%. The median overall survival was 27.2 months (95% confidence interval [CI], 17.5 months to not evaluated [n.e.]); the median progression-free survival was 9.8 months (95% CI, 5.5 months to n.e.).Conclusions: PEG-DEMs demonstrated a favorable safety profile with low systemic concentration of doxorubicin, and promising efficacy. [ABSTRACT FROM AUTHOR]

La captación miocárdica en la gammagrafía ósea se ha convertido en un método útil para la detección de la amiloidosis cardiaca secundaria al depósito de transtirretina (ATTR-CA). El objetivo de este estudio fue evaluar la prevalencia de captación miocárdica en pacientes mayores de 18 años sin sospecha clínica de amiloidosis cardiaca (AC) y a los que se realizó una gammagrafía ósea. Se trata de un estudio observacional, retrospectivo y multicéntrico realizado en 21 hospitales de España (de septiembre a noviembre de 2019). De las 9.864 gammagrafías analizadas (de forma local y central), en 71 pacientes (0,72%), se observó captación cardiaca incidental, con una prevalencia que aumentó con la edad. En el 16,9% de los pacientes con captación positiva se detectó un diagnóstico previo de insuficiencia cardiaca (IC), con > 50% de los pacientes en un grado II de la clasificación de la NYHA. En 10 pacientes se realizó el diagnóstico de ATTR-CA, con un retraso medio de 10,4 meses (IC 95%: 5,1-15,7). Todos ellos eran mayores de 70 años, principalmente varones y presentaban una mayor hipertrofia ventricular izquierda (HVI) respecto a los pacientes sin diagnóstico confirmado (p < 0,0001). Los pacientes con ATTR-CA presentaron una mayor tasa de hipotensión ortostática (30,0% vs. 3,8% en los pacientes sin ATTR-CA; p = 0,025). Se trata del primer estudio retrospectivo, de ámbito nacional y multicéntrico que evalúa la prevalencia de captación cardiaca incidental en gammagrafías óseas realizadas por motivos extracardiacos, y que muestra una prevalencia del 0,72% en esta población. La derivación de estos pacientes puede facilitar el diagnóstico precoz de la AC con el consiguiente beneficio para los mismos. Myocardial uptake on bone scintigraphy has become useful for the detection of transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to assess the prevalence of myocardial uptake in patients over 18 years of age with no clinical suspicion of cardiac amyloidosis (CA) who had undergone bone scintigraphy. This was an observational, retrospective, multicenter study across 21 Spanish hospitals (September–November 2019). Of the 9864 scans analyzed (locally and centrally), incidental cardiac uptake was observed in 71 patients (0.72%), a prevalence that increased with age. A previous diagnosis of heart failure was found in 16.9% of patients with positive uptake, with >50% in NYHA II. ATTR-CA was diagnosed in 10 patients, with a mean delay of 10.4 months (95% CI: 5.1-15.7). All were >70 years old, primarily male, and had greater left ventricular hypertrophy than patients without a confirmed diagnosis (p < 0.0001). ATTR-CA patients had higher rates of orthostatic hypotension (30.0% vs. 3.8% in non-ATTR-CA; p = 0.025). This is the first retrospective, national, multicenter study evaluating the prevalence of incidental cardiac uptake in bone scintigraphy performed for non-cardiac reasons, showing a prevalence of 0.72% in this population. Referral of these patients may facilitate early diagnosis of CA with a resulting benefit for patients. [ABSTRACT FROM AUTHOR]

The last 5 years have witnessed relevant advances in the systemic treatment of hepatocellular carcinoma. New data have emerged since the development of the EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma in 2018. Drugs licensed in some countries now include 4 oral multi-tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 4 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, nivolumab and pembrolizumab in monotherapy). Prolonged survival in excess of 2 years can be expected in most patients with sensitive tumours and well-preserved liver function that renders them fit for sequential therapies. With different choices available in any given setting, the robustness of the evidence of efficacy and a correct matching of the safety profile of a given agent with patient characteristics and preferences are key in making sound therapeutic decisions. The recommendations in this document amend the previous EASL Clinical Practice Guidelines and aim to help clinicians provide the best possible care for patients today. In view of several ongoing and promising trials, further advances in systemic therapy of hepatocellular carcinoma are foreseen in the near future and these recommendations will have to be updated regularly. [ABSTRACT FROM AUTHOR]

The design and execution of clinical trials relies on strict definitions and criteria to avoid heterogeneous decisions by investigators at different sites. Ideally, definitions and decision making in clinical practice should mimic those implemented in trials, but this is not the case. Target populations are narrowly defined in trials, with the goal of evaluating activity and toxicity, and ultimately, demonstrating a survival benefit. In real-world practice, patients may not fit into the stringent inclusion/exclusion criteria of clinical trials. The evaluation of activity may also differ and the common policy to stop therapy upon progression may not be followed if progression is minor. Indeed, registration of progression may not reflect treatment failure or resistance. Parameters such as response according to RECIST criteria, time to progression and progression-free survival are not fully informative and cannot be assumed as a definitive surrogate for survival, which is the hardest endpoint in therapeutic cancer studies. This difference is because of the varying methods used to evaluate drug activity and tumour evolution, which ultimately dictates patient outcome. This expert opinion exposes the current discrepancies between research trials and clinical practice. Understanding the origin and limitations of such a conundrum should be the first step in refining the criteria that define drug activity, toxicity and treatment failure. Otherwise, evidence-based clinical practice and precision oncology will be an unattainable reality. [ABSTRACT FROM AUTHOR]

Hepatic epithelioid hemangioendothelioma is an ultra-rare hepatic vascular tumor, diagnosed more frequently in females. The knowledge about this tumor derives mainly from small case series with sub-optimal treatment outcomes. The aim of this study is to identify the clinical and radiological issues helpful to develop an international prospective registry. We conducted an international multicentric and retrospective study of patients with hepatic hemangioendothelioma. The clinical, pathological and radiological images collected during follow-up were reviewed. Central radiological revision was performed and 3 patterns of contrast were defined. Between 1994 and 2016, 27 patients with hepatic hemangioendothelioma were identified in three institutions but the final diagnosis was hepatic angiosarcoma in one. The majority were females, median age was 38.7-years and 17 patients were asymptomatic at diagnosis. No patient had Two out of ten (20%) patients had surgical specimens with positive macro-vascular invasion and 50% had extrahepatic disease, and the most frequent pattern was the progressive-central-contrast-uptake. After a median follow-up of 6.7-years, the 5- and 10-year survival rates are 91.5% and 51.9%, respectively. This multicentric study shows the heterogeneous profile of patients with hepatic hemangioendothelioma, reflecting the need to establish a reference network in order to better characterize these patients and ultimately develop a personalized treatment strategy. [ABSTRACT FROM AUTHOR]

Análisis de la relación coste-efectividad (RCE) del electrocardiograma de esfuerzo y de la SPECT de perfusión miocárdica esfuerzo-reposo en relación con la revascularización coronaria (RC), eventos cardíacos (EC) y mortalidad total (MT). Se estudiaron 8.496 pacientes con SPECT y seguimiento medio de 5,3 ± 3,5 años. Evaluamos la RCE para la RC quirúrgica (RCQ) y percutánea (RCP) (45,6%/54,4%) de acuerdo con los resultados de la isquemia electrocardiográfica y gammagráfica. La efectividad se evaluó como MT, EC, LYSO (life-year-saved-observed) y EC-LYSO. Los análisis de costes se realizaron desde la perspectiva del pagador de atención médica. El análisis de sensibilidad fue considerando las relaciones RCQ/RCP actuales (12%/88%). Al combinar los resultados del electrocardiograma de esfuerzo y de la gammagrafía, los valores de coste-efectividad para la RCQ variaron entre 112.589 € (isquemia electrocardiográfica y gammagráfica) y 2.814.715 € (sin isquemia)/evento evitado, y entre 38.664 y 2.221.559 €/LYSO; y para la RCP entre 18.824 € (isquemia electrocardiográfica y gammagráfica) y 46.377 € (sin isquemia)/evento evitado, y entre 6.464 y 36.604 €/LYSO. Para el EC: los valores de coste-efectividad de la RCQ y RCP en presencia de isquemia electrocardiográfica y gammagráfica fueron de 269.904 €/EC evitado y de 24.428 €/EC evitado, respectivamente; y los €/LYSO de la RCQ y RCP fueron de 152.488 y 13.801, respectivamente. Se mantuvo la misma RCE para la proporción actual de pacientes revascularizados (12%/88%). El análisis combinado de las imágenes de la SPECT y del electrocardiograma de esfuerzo permite la diferenciación entre grupos de pacientes en donde la RCP y la RCQ son más rentables. La mayor RCE en relación con la RC, EC y MT se da en los pacientes con isquemia electrocardiográfica y gammagráfica. La RCP es más coste-efectiva que la RCQ. The aim was to analyze the cost-effectiveness ratio (CER) of stress electrocardiogram (ES) and stress myocardial perfusion imaging (SPECT-MPI) according to coronary revascularization (CR) therapy, cardiac events (CE) and total mortality (TM). A total of 8,496 consecutive patients who underwent SPECT-MPI were followed-up (mean 5.3 ± 3.5 years). Cost-effectiveness for coronary bypass (CABG) or percutaneous CR (PCR) (45.6%/54.4%) according to combined electrocardiographic ischemia and scintigraphic ischemia were evaluated. Effectiveness was evaluated as TM, CE, life-year saved observed (LYSO) and CE-LYSO; costs analyses were conducted from the perspective of the health care payer. A sensitivity analysis was performed considering current CABG/PCR ratios (12%/88%). When electrocardiogram and SPECT approaches are combined, the cost-effectiveness values for CABG ranged between 112,589 € (electrocardiographic and scintigraphic ischemia) and 2,814,715 € (without ischemia)/event avoided, 38,664 and 2,221,559 €/LYSO; for PCR ranged between 18,824 € (electrocardiographic and scintigraphic ischemia) and 46,377 € (without ischemia)/event avoided, 6,464 and 36,604 €/LYSO. To CE: the cost-effectiveness values of the CABG and CPR in presence of electrocardiographic and scintigraphic ischemia were 269,904 €/CE-avoided and 24,428 €/CE-avoided, respectively; and the €/LYSO of the CABG and PCR were 152,488 and 13,801, respectively. The RCE was maintained for the current proportion of revascularized patients (12%/88%). Combined ES and SPECT-MPI results, allows differentiation between patient groups, where the PCR and CABG are more cost-effective in different economic frameworks. The major CER in relation to CR, CE and TM occurs in patients with electrocardiographic and scintigraphic ischemia. PCR is more cost-effective than CABG. [ABSTRACT FROM AUTHOR]

Background & Aims In a phase 3 trial (RESORCE), regorafenib increased overall survival compared with placebo in patients with hepatocellular carcinoma (HCC) previously treated with sorafenib. In an exploratory study, we analyzed plasma and tumor samples from study participants to identify genetic, microRNA (miRNA), and protein biomarkers associated with response to regorafenib. Methods We obtained archived tumor tissues and baseline plasma samples from patients with HCC given regorafenib in the RESORCE trial. Baseline plasma samples from 499 patients were analyzed for expression of 294 proteins (DiscoveryMAP) and plasma samples from 349 patients were analyzed for levels of 750 miRNAs (miRCURY miRNA PCR). Tumor tissues from 7 responders and 10 patients who did not respond (progressors) were analyzed by next-generation sequencing (FoundationOne). Forty-six tumor tissues were analyzed for expression patterns of 770 genes involved in oncogenic and inflammatory pathways (PanCancer Immune Profiling). Associations between plasma levels of proteins and miRNAs and response to treatment (overall survival and time to progression) were evaluated using a Cox proportional hazards model. Results Decreased baseline plasma concentrations of 5 of 266 evaluable proteins (angiopoietin 1, cystatin B, the latency-associated peptide of transforming growth factor beta 1, oxidized low-density lipoprotein receptor 1, and C-C motif chemokine ligand 3; adjusted P ≤.05) were significantly associated with increased overall survival time after regorafenib treatment. Levels of these 5 proteins, which have roles in inflammation and/or HCC pathogenesis, were not associated with survival independently of treatment. Only 20 of 499 patients had high levels and a reduced survival time. Plasma levels of α-fetoprotein and c-MET were associated with poor outcome (overall survival) independently of regorafenib treatment only. We identified 9 plasma miRNAs (MIR30A, MIR122, MIR125B, MIR200A, MIR374B, MIR15B, MIR107, MIR320, and MIR645) whose levels significantly associated with overall survival time with regorafenib (adjusted P ≤.05). Functional analyses of these miRNAs indicated that their expression level associated with increased overall survival of patients with tumors of the Hoshida S3 subtype. Next-generation sequencing analyses of tumor tissues revealed 49 variants in 27 oncogenes or tumor suppressor genes. Mutations in CTNNB1 were detected in 3 of 10 progressors and VEGFA amplification in 1 of 7 responders. Conclusion We identified expression patterns of plasma proteins and miRNAs that associated with increased overall survival times of patients with HCC following treatment with regorafenib in the RESORCE trial. Levels of these circulating biomarkers and genetic features of tumors might be used to identify patients with HCC most likely to respond to regorafenib. ClinicalTrials.gov number NCT01774344. NCBI GEO accession numbers: mRNA data (NanoString): GSE119220 ; miRNA data (Exiqon): GSE119221 [ABSTRACT FROM AUTHOR]