Initial results with [18F]FAPI-74 PET/CT in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis. 68Ga-labeled FAP ligands exhibited highly promising results due to the crucial role of activated fibroblasts in fibrosis imaging of the lung. However, 18F-labeled FAP ligands might provide qualitatively much higher imaging results with accompanying economic benefits due to large-scale production. Thus, we sought to investigate the potential of [18F]FAPI-74 prospectively in a small patient cohort. METHODS: Eight patients underwent both [18F]FAPI-74-PET/CT and HRCT scans and were then compared with a control group without any fibrosing pulmonary disease. The tracer uptake of fibrotic lung areas was analyzed in synopsis with radiological and clinical parameters. RESULTS: We observed a positive correlation between the fibrotic active volume, the Hounsfield scale, as well as the vital and diffusing capacity of the lung. CONCLUSION: The initial results confirm our assumption that [18F]FAPI-74 offers a viable non-invasive assessment method for pulmonary fibrotic changes in patients with IPF.

Head-to-Head Intra-Individual Comparison of Biodistribution and Tumor Uptake of [18F]FAPI-74 with [18F]FDG in Patients with PDAC: A Prospective Exploratory Study.

BACKGROUND: Radiolabeled fibroblast activation protein (FAP) ligands, a novel class of tracers for PET/CT imaging, have demonstrated very promising results in various oncological, as well as in some benign, diseases with long-term potential to supplant the current pan-cancer agent [18F]FDG in some cancer types. Pancreatic ductal carcinoma (PDAC) belongs to the group of epithelial malignancies with a strong so-called "desmoplastic reaction", leading to a prominent tumor stroma with cancer-associated fibroblasts that exhibit a marked overexpression of fibroblast activation protein (FAP). The first clinical experiences in PDAC with 68Ga-labeled FAP ligands suggested superior sensitivity to [18F]FDG. However, there is limited data with 18F-labeled FAP derivatives, i.e. [18F]FAPI-74, yet prospective single- and multicenter trials are already ongoing. In this proof-of-concept study, we sought to evaluate the biodistribution, tumor uptake, and lesion detectability in patients with PDAC using [18F]FAPI-74 PET/CT as compared to [18F]FDG PET/CT scans for staging. METHODS: This study includes 7 patients (median age 69) who underwent both [18F]FDG PET/CT with contrast-enhancement and [18F]FAPI-74 PET with low-dose CT for primary staging (n = 3) and therapy response control after neoadjuvant (n = 1) or re-staging after palliative therapy (n = 3). The mean interval between PET scans was 11 ± 4 days (range 1-15 days). The [18F]FDG and [18F]FAPI-74 PET/CT scans were acquired at 64 ± 4.1 min (range 61-91 min) and 66.4 ± 6.3 min (range 60-76 min), respectively, after administration of 200 ± 94 MBq (range 79-318 MBq) and 235 ± 88 MBq (range 90-321 MBq), respectively. Quantification of tracer uptake was determined with SUVmax and SUVmean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUVmax of tumor lesions by the SUVmax of adipose tissue, skeletal muscle, and blood pool. RESULTS: Overall, 32 lesions were detected in 7 patients including primary (n = 7), lung (n = 7), bone (n = 3), lymph node (n = 13), and peritoneal metastases (n = 2). [18F]FAPI-74 detected 22% more lesions compared with [18F]FDG with a better TBR and visual lesion delineation. In one patient the primary lesion could be detected unequivocally with [18F]FAPI-74 but was missed by [18F]FDG imaging. Altogether, most of the lesions demonstrated markedly elevated uptake of [18F]FAPI-74 with a simultaneous lower uptake in the background, providing a very high visual contrast. CONCLUSION: To the best of our knowledge, this is the first, prospective, intra-individual investigation comparing [18F]FAPI-74 with [18F]FDG imaging in PDAC with encouraging results. These pivotalresults supporta larger, multicentric, prospective study to determine the value of [18F]FAPI-74 in detecting and staging PDAC in comparison with current standard of care imaging.

Comparación del consumo alimentario y calidad de vida relacionada con la salud entre baloncestistas de distinto nivel competitivo / Comparison of food consumption and health-related quality of life amongbasketball players of different competitive levels

Introducción: Los hábitos alimentarios y la salud mental son aspectos fundamentales para optimizar la preparación y el rendimiento deportivo de los baloncestistas.Objetivo: Comparar la frecuencia en el consumo de alimentos y la calidad de vida relacionada con la salud (CVRS)entre baloncestistas de distinto nivel competitivo (profesional,universitario y amateur). Material y métodos: Estudio transversal que evaluó 122baloncestistas masculinos (edad media de 30,60 ± 10,79años), distribuidos en jugadores de baloncesto profesional(JBP; n=25), universitario (JBU; n=26) y amateur (JBA;n=71). Las variables de estudio se evaluaron a través de encuestas en línea referentes a la frecuencia en el consumo de alimentos y CVRS (SF-36). Resultados: Los JBP ostentan un consumo significativamente mayor de cena (F= 5,007; p= 0,020) comparados conlos JBU, y de frutas (F= 5,857; p= 0,012), verduras (F= 3,756; p= 0,020) y cena (F= 5,007; p= 0,011) respecto a losJBA. Mientras que los JBU presentan un consumo significativamente mayor de frutas (F= 5,857; p= 0,035) que los JBA.Además, los JBU presentaron un consumo significativamente mayor de bebidas azucaradas (F= 9,293; p= 0,004) respecto a los JBP y JBA. La CVRS no presentó diferencias significativas entre los grupos. Conclusión: Los JBP presentan mayor frecuencia en el consumo de alimentos saludables al compararlos con JBU yJBA. Además, los JBU reportan mayor frecuencia en el consumo de bebidas azucaradas respecto a JBP y JBA. Mientras que, la CVRS es positiva independiente al nivel competitivo delos baloncestistas.(AU)

Introduction: Eating habits and mental health are fundamental aspects to optimize the preparation and sports performance of basketball players.Aim: To compare the frequency of food consumption andhealth-related quality of life (HRQoL) among basketball players of different competitive levels (professional, university,and amateur).Material and methods: Cross-sectional study that evaluated 122 male basketball players (mean age of 30.60 ± 10.79years), divided into professional (JBP; n=25), university (JBU;n=26) and amateur (JBA; n=71). The study variables wereevaluated through online surveys regarding the frequency offood consumption and HRQoL (SF-36). Results: The JBP show a significantly higher consumption of dinner (F= 5,007; p= 0,020) compared to the JBU,and of fruits (F= 5,857; p= 0,012), vegetables (F= 3,756;p= 0,020) and dinner (F= 5,007; p= 0,011) compared tothe JBA. While the JBU present a significantly higher con-sumption of fruits (F= 5,857; p= 0,035) than the JBA. In addition, the JBU had a significantly higher consumption ofsugary drinks (F= 9,293; p= 0,004) compared to the JBPand JBA. The HRQoL did not present significant differencesbetween the groups.Conclusion: The JBP have a higher frequency in the consumption of healthy foods when compared to JBU and JBA. Inaddition, the JBU report a higher frequency in the consumption of sugary drinks compared to the JBP and JBA. While, theHRQoL is positive regardless of the competitive level of thebasketball players.

Al[18F]F-NOTA-Octreotide Is Comparable to [68Ga]Ga-DOTA-TATE for PET/CT Imaging of Neuroendocrine Tumours in the Latin-American Population.

PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [68Ga]Ga-DOTA-TATE. Al[18F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [68Ga]Ga-DOTA-TATE and Al[18F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [68Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[18F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all p < 0.001), pancreatic uncinated process, kidneys, and small intestine (all p < 0.05). Nevertheless, despite the lower background uptake of Al[18F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [68Ga]Ga-DOTA-TATE but not by Al[18F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[18F]F-NOTA-Octreotide but not by [68Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[18F]F-NOTA-Octreotide is comparable to [68Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[18F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE.

Imaging GRPr Expression in Metastatic Castration-Resistant Prostate Cancer with [68Ga]Ga-RM2-A Head-to-Head Pilot Comparison with [68Ga]Ga-PSMA-11.

BACKGROUND: The gastrin-releasing peptide receptor (GRPr) is highly overexpressed in several solid tumors, including treatment-naïve and recurrent prostate cancer. [68Ga]Ga-RM2 is a well-established radiotracer for PET imaging of GRPr, and [177Lu]Lu-RM2 has been proposed as a therapeutic alternative for patients with heterogeneous and/or low expression of PSMA. In this study, we aimed to evaluate the expression of GRPr and PSMA in a group of patients diagnosed with castration-resistant prostate cancer (mCRPC) by means of PET imaging. METHODS: Seventeen mCRPC patients referred for radio-ligand therapy (RLT) were enrolled and underwent [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 PET/CT imaging, 8.8 ± 8.6 days apart, to compare the biodistribution of each tracer. Uptake in healthy organs and tumor lesions was assessed by SUV values, and tumor-to-background ratios were analyzed. RESULTS: [68Ga]Ga-PSMA-11 showed significantly higher uptake in tumor lesions in bone, lymph nodes, prostate, and soft tissues and detected 23% more lesions compared to [68Ga]Ga-RM2. In 4/17 patients (23.5%), the biodistribution of both tracers was comparable. CONCLUSIONS: Our results show that in our cohort of mCRPC patients, PSMA expression was higher compared to GRPr. Nevertheless, RLT with [177Lu]Lu-RM2 may be an alternative treatment option for selected patients or patients in earlier disease stages, such as biochemical recurrence.

Community-based entomological surveillance in three Chagas disease-endemic regions in sub-Andean Bolivia.

BACKGROUND: Chagas disease is endemic throughout most of Bolivia, with prevalence rates of 25% observed in some geographic areas located mainly in the sub-Andean region. METHODS: Community-based entomological surveillance was carried out in the sub-Andean departments of Cochabamba (municipalities of Cochabamba, Punata and Sacaba), Tarija (municipality of Tarija) and Chuquisaca (municipality of Sucre). The surveillance parameters evaluated were: (i) the proportion of cards with the presence of triatomines; (ii) the distribution of positive cards by area; and (iii) the proportion of cards with the presence of infected triatomines. RESULTS: Of the cards returned, in 852 (3.1%) there was a mention of the presence of triatomines. The species Triatoma infestans, Triatoma sordida and Triatoma guasayana were identified in 812 (95.3%), 39 (4.6%) and 1 (0.1%), respectively. The median monthly positivity rate of the cards during 2011-2018 was higher in Punata (9.1%; IQR=3.2-15.4%). The median monthly rate was highest in 2012 (2.7%; IQR=0-5.6%). Fifty positive cards (5.8%) presented insects that were positive for trypanosomatids, mainly in Cochabamba and Punata. CONCLUSIONS: The report of triatomines foci by inhabitants represents an effective surveillance system coordinated by a network of specialized and multidisciplinary health centers. These strategies, which should be included in the health policies of endemic countries, enable extending and deepening the dialogue among technicians, communities and their local authorities.

Evaluation of Safety and Dosimetry of 177Lu-DOTA-ZOL for Therapy of Bone Metastases.

Palliative treatment of bone metastasis using radiolabeled bisphosphonates is a well-known concept proven to be safe and effective. A new therapeutic radiopharmaceutical for bone metastasis is 177Lu-DOTA-zoledronic acid (177Lu-DOTA-ZOL). In this study, the safety and dosimetry of a single therapeutic dose of 177Lu-DOTA-ZOL were evaluated on the basis of a series of SPECT/CT images and blood samples. Methods: Nine patients with exclusive bone metastases from metastatic castration-resistant prostate cancer (mCRPC) (70.8 ± 8.4 y) and progression under conventional therapies participated in this prospective study. After receiving 5,780 ± 329 MBq 177Lu-DOTA-ZOL, patients underwent 3-dimensional whole-body SPECT/CT imaging and venous blood sampling over 7 d. Dosimetric evaluation was performed for main organs and tumor lesions. Safety was assessed by blood biomarkers. Results:177Lu-DOTA-ZOL showed fast uptake and high retention in bone lesions and fast clearance from the bloodstream in all patients. The average retention in tumor lesions was 0.02% injected activity per gram at 6 h after injection and approximately 0.01% at 170 h after injection. In this cohort, the average absorbed doses in bone tumor lesions, kidneys, red bone marrow, and bone surfaces were 4.21, 0.17, 0.36, and 1.19 Gy/GBq, respectively. The red marrow was found to be the dose-limiting organ for all patients. A median maximum tolerated injected activity of 6.0 GBq may exceed the defined threshold of 2 Gy for the red bone marrow in individual patients (4/8). Conclusion:177Lu-DOTA-ZOL is safe and has a favorable therapeutic index compared with other radiopharmaceuticals used in the treatment of osteoblastic bone metastases. Personalized dosimetry, however, should be considered to avoid severe hematotoxicity for individual patients.

Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC.

INTRODUCTION: PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties. METHODS: Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120-160 µg) [177Lu]Lu-PSMA-ALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers. RESULTS: [177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased. CONCLUSION: Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer.

Diagnostic Accuracy of 18F-PSMA-1007 PET/CT Imaging for Lymph Node Staging of Prostate Carcinoma in Primary and Biochemical Recurrence.

Prostate-specific membrane antigen (PSMA)-ligand PET/CT is performed on patients with prostate cancer to stage the disease initially or to identify sites of recurrence after definitive therapy. On the basis of clinical results, 18F-PSMA-1007 is a promising PSMA PET tracer, but detailed histologic confirmation has been lacking. Methods: Ninety-six patients with prostate cancer underwent 18F-PSMA-1007 PET/CT followed by either radical prostatectomy with lymphadenectomy or salvage lymphadenectomy. The histologic findings of PSMA PET-positive nodes were analyzed retrospectively. A lesion-based and patient-based analysis was performed comparing all positive lesions and only lesions larger than 3 mm on histopathology. Results: Of the patients, 90.6% received 18F-PSMA-1007 PET/CT for staging before the primary treatment, whereas 9.4% underwent imaging for biochemical recurrence. In 34.4% of the cohort, positive lymph nodes were present on imaging. In total, 1,746 lymph nodes were dissected in 96 patients. 18F-PSMA-1007 PET had a lesion-based sensitivity of 81.7%, a specificity of 99.6%, a positive predictive value of 92.4%, and a negative predictive value of 98.9% for detecting positive lymph nodes larger than 3 mm. In the analysis of all malignant nodes regardless of size, the overall sensitivity, specificity, positive predictive value, and negative predictive value on lesion-based analysis were 71.2%, 99.5%, 91.3%, and 97.9%, respectively. The patient-based analysis showed a sensitivity of 85.9% and a specificity of 99.5% for lymph nodes larger than 3 mm. Conclusion:18F-PSMA-1007 PET/CT reliably detects malignant lymph nodes and has an exceptional specificity of more than 99% for nodal metastases.

Registro de emisiones otoacústicas transientes basado en microcontroladores de alto rendimiento / Transient Otoacoustic Emissions Register based on High Performance Microcontrollers

La hipoacusia tiene una incidencia notable entre los recién nacidos. Una intervención temprana durante el período de maduración auditiva permite minimizar los efectos en el desarrollo intelectual del infante. Se propone el desarrollo de un Registrador de Emisiones Otoacústicas Transientes como parte de un sistema de cribado neonatal basado en microcontroladores de alto rendimiento. La prueba consiste en aplicar periódicamente un estímulo tipo chasquido para obtener la respuesta coclear. Se promedian las señales adquiridas y se aplica la Transformada Rápida de Fourier. El espectro obtenido es dividido en bandas de media octava para analizar la correlación y la relación señal-ruido. Si estos parámetros son mayores que los umbrales de referencia en la mayoría de las bandas, se considera al paciente apto para el desarrollo normal. El firmware fue implementado sobre el procesador STM32F405 y evaluado con el simulador Baby Isao; obteniéndose una sensibilidad del 87.5 por ciento y una especificidad del 93.75 por ciento(AU)

Hearing loss is highly incident among newborns. Early intervention during the period of auditory maturation allows adequate levels of intellectual development to be achieved. The development of a Transient Otoacoustic Emissions Recorder is proposed as part of a neonatal screening system based on high-performance microcontrollers. The test consists of periodically applying a click stimulus to obtain the cochlear response. The acquired signals are averaged and the Fast Fourier Transform is applied. The spectrum obtained is divided into half-octave bands to assess the correlation as well as the signal-noise ratio. If these parameters are greater than the reference thresholds in most of the bands, the patient is considered suitable for normal cognitive development. The firmware was implemented on the STM32F405 processor and evaluated with the Baby Isao simulator; obtaining a sensitivity of 87.5 percent and a specificity of 93.75 percent(AU)

La relación de la edad con los componentes espectrales de las realizaciones sin ruido de señales fotopletismográficas: resultados de un enfoque de identificación no lineal / Relationship of Age with Spectral Components of Noise-Free Realizations of Photoplethysmographic Signals: Outcomes of a Nonlinear Identification Approach

Background: Age-related changes in the vascular network have been widely documented, however, nonlinear identification has been poorly applied to the analysis of cardiovascular signals. Objective: To determine the impact of age on spectral components of Noise-free realizations (NFR) obtained from photoplethysmographic signals, summarized in the Kernel Complexity Regressive Index (KCRIndex). Methods: With 190 apparently healthy participants (9 to 89 years) from Orense, Spain, Photoplethysmographic signals were recorded during 5 minutes in supine position using Nellcor-395 pulse oximeter; signals were digitized at 1000 Hz, and furtherly submitted to nonlinear identification via a kernel nonlinear autoregressive estimator. KCRIndex is defined as the average of at least three negative slope values at the NFR log-log spectrum in the 9 to 25 Hz frequency region. Results: KCRIndex decreased with age in a linear fashion and did not differ between genders. The regression line obtained was KCRIndex=-0.025*age+6.868 (r=-0.751). Conclusions: KCRIndex, is strongly correlated with age, thus opening up new possibilities for cardiovascular exploration at primary health care settings and even on open field conditions(AU)

Antecedentes: los cambios relacionados con la edad en la red vascular se han documentado ampliamente, sin embargo, la identificación no lineal solo se ha aplicado de manera esporádica al análisis de las señales cardiovasculares. Objetivo: determinar los cambios con la edad en los componentes espectrales de las realizaciones sin ruido (NFR) obtenidas a partir de señales fotopletismográficas, resumidas en el índice regresivo de la complejidad por núcleos (KCRIndex). Métodos: Con 190 participantes aparentemente sanos (de 9 a 89 años) residentes en Orense, España, se registraron señales fotopletismográficas durante 5 minutos en posición supina usando un oxímetro de pulso Nellcor-395; las señales se digitalizaron a 1000 Hz, y se sometieron a identificación no lineal a través de un estimador autorregresivo no lineal por núcleos. El KCRIndex se define como el promedio de al menos tres valores de pendiente negativos en el espectro log-log de NFR en la región de frecuencia de 9 a 25 Hz. Resultados: KCRIndex disminuyó con la edad de forma lineal y no difirió entre géneros. La línea de regresión obtenida fue KCRIndex = -0.025 * edad + 6.868 (r = -0.751). Conclusiones: Este índice propuesto está fuertemente correlacionado con la edad, lo que abre nuevas posibilidades para la exploración cardiovascular en entornos de atención primaria de salud e incluso en condiciones de campo(AU)

[Predictive value of dipyridamole myocardial perfusion tomography on survival]. / Estratificación de riesgo de muerte a mediano plazo de pacientes evaluados por enfermedad coronaria con SPECT de perfusión miocárdica bajo efecto de dipiridamol.

BACKGROUND: Dipyridamole (DIP) is the most commonly employed pharmacological stressor for myocardial perfusion tomography (SPECT) in patients unable to reach an adequate work load. AIM: To assess the predictive capacity of DIP SPECT on survival. MATERIAL AND METHODS: We included 985 adults aged 66 ±11 years (45% women) with rest and DIP-SPECT. The main indications for the procedure were coronary artery disease (CAD) screening in 66% and known CAD in 33%. Participants were followed up for a median of 65 months (interquartile range 54 to 86 months). During the follow up, 261 deaths were recorded and 98% had a specified cause in their death certificate. RESULTS: Myocardial SPECT was abnormal in 44% of participants. Transient ischemic defects were observed in 34%, fixed defects concordant with infarction in 27% and post-stress systolic dysfunction in 23%. Twenty five percent of deaths were attributable to cardiac or ischemic cause and 22% to cancer. In a bivariate analysis, the hazard ratio (HR) of death of any cause was lower in females and higher in the presence of CAD. The multivariate analysis showed that being older than 46 years increased the HR of death of any cause. In a bivariate analysis, the HR for cardiac death was higher when the myocardial SPECT showed ischemia, necrosis or left ventricular dilation. In the multivariate analysis, post-stress left ventricular systolic function was associated with a lower risk of cardiac death. CONCLUSIONS: An abnormal myocardial SPECT, perfusion abnormalities, left ventricular systolic function or dilation are independent predictors of cardiac death in these participants.

Efecto de la terapia de resincronización ventricular en los parámetros de disfunción endotelial y función sistólica izquierda en pacientes con insuficiencia cardíaca crónica y bloqueo completo de rama izquierda / Endothelial dysfunction, left ventricular function, and chronic heart failure with complete left bundle branch block: effect of resynchronization therapy

Resumen: Introducción: La insuficiencia cardíaca crónica (ICC) es una condición compleja asociada a inflamación sistémica y a disfunción endotelial (DE) cuya patogénesis no es bien comprendida. Objetivo: Evaluar una posible relación entre marcadores de DE periférica con la respuesta a terapia de resincronización ventricular (TRV). Método: 20 pacientes con ICC, QRS ≥120ms y fracción de eyección ventricular izquierda (FEVI) ≤35% se estudiaron pre y 6 meses post-TRV con: Minnesota Living with Heart Failure Questionnaire (MLHFQ); test de marcha (TM-6min); Ecocardiografía-2D y SPECT de perfusión gatillado en reposo; proteína C-reactiva ultra sensible (us-PCR); péptido natriurético cerebral (pro-BNP); células endoteliales circulantes (CEC); moléculas de adhesión soluble vascular (sVCAM) e intercelular (sICAM); interleukina-6 (IL-6) y Factor von Willebrand (FvW). Se clasificaron como respondedores o no a TRV según criterios preestablecidos. Resultados: Promedios basales: pro-BNP 5.290pg/ml; us-PCR 1,7ug/mL; MLHFQ 72; TM-6min 391 metros. Las CEC y sICAM estaban sobre límites normales. Post-TRV, el 50% fue respondedor: 11/20 mejoraron ≥1 clase NYHA y ≥10% del TM-6min; ML-HFQ disminuyó (p<0.0001); FEVI mejoró (p=0.003); volumen final sistólico disminuyó (p=0.008) y también pro-BNP (p=0.03). En los respondedores, las CEC disminuyeron, persistiendo elevadas, sobre lo normal. Existieron correlaciones entre cambios de pro-BNP con TM-6min y entre us-PCR con MLHFQ y FvW (p≤0.004 en todas). Conclusiones: En ICC existe evidencia de significativa DE, expresada por sICAM y CEC, biomarcador periférico sensible. Estas disminuyeron 6 meses post-TRV, persistiendo sobre el límite normal. Otros parámetros funcionales e inflamatorios se correlacionaron en el grupo total, sin diferencias entre grupos respondedores y no respondedores.

Abstract: Introduction: Chronic heart failure (CHF) is a complex condition associated with systemic inflammation and endothelial dysfunction (ED) whose pathogenesis is not well understood. Objective: to evaluate a possible relationship between peripheral ED markers and response to cardiac resynchronization therapy (CRT). Method: 20 patients with CHF, QRS ≥120ms and left ventricular ejection fraction (LVEF) ≤35% were studied before and 6 months post-CRT. Minnesota Living with Heart Failure Questionnaire (MLHFQ); walking test (6min-WT); 2D-echocardiography and gated perfusion SPECT at rest; ultra-sensitive C-reactive protein (us-CRP); brain natriuretic peptide (pro-BNP); circulating endothelial cells (CEC); vascular soluble adhesion (sVCAM) and intercellular adhesion molecules (sICAM); interleukin-6 (IL-6) and von Willebrand Factor (vWF) were measured in all subjects. They were classified as responders or not to CRT, according to pre-established criteria. Results: Basal means: pro-BNP 5,290 pg / ml; us-CRP 1.7 ug/mL; MLHFQ 72; 6min-WT 391 meters. The CEC and IL-6 were above normal limits. Post-CRT, 50% were responders: 11/20 improved ≥1 NYHA class and ≥10% increase in 6min-WT; MLHFQ decreased (p <0.0001); LVEF improved (p = 0.003); final systolic volume decreased (p = 0.008) and also pro-BNP (p= 0.03). In responders CEC decreased, persisting over normal limits. There were correlations between changes of pro-BNP with TM-6min and between us-PCR with MLHFQ and vWF (p≤0.004 in all). Conclusions: In CHF there is evidence of significant ED, expressed by sICAM and CEC, a sensitive peripheral biomarker that decreased 6 months post-CRT although persisting above normal limits. Other functional and inflammatory parameters were correlated in the total group, without differences between responders and non-responders.

Evidence of response to pembrolizumab in a patient with Lynch syndrome-related metastatic colon cancer.

Patients with Lynch Syndrome (LS) are at high risk of developing colorectal cancer at an early age. Germline mutations in DNA mismatch repair genes and microsatellite instability are clear signatures of this autosomal dominant disorder. Here, we report the clinical history of a 38-year-old patient with LS-related metastatic colon cancer treated in Chile with immunotherapy (pembrolizumab). The patient exhibited a pathogenic deletion in Epithelial cell Adhesion Molecule (EPCAM) and mutS homolog 2 (MSH2) genes, and after diagnosis received 12 cycles of FOLFOX. The tumor mass, however, continued to grow, and a new metastatic mucinous adenocarcinoma of 13 mm appeared at the level of the 11th right dorsal vertebra. To treat these lesions, the patient received immunotherapy scheme with pembrolizumab (200 mg every 21 days). After only four cycles, the patient's symptoms improved and the lesions showed less metabolic activity. After 12 cycles with pembrolizumab, the patient started palliative radiation and systemic second-line treatment with FOLFIRI and Avastin. The immunotherapy scheme with pembrolizumab was capable of delaying the second-line treatment for at least 8 months, becoming a useful therapeutic option for this patient. Thus, our study highlights the importance of implementing immunotherapy treatment programs for LS-colorectal cancer patients in South American countries.

Estratificación de riesgo de muerte a mediano plazo de pacientes evaluados por enfermedad coronaria con SPECT de perfusión miocárdica bajo efecto de dipiridamol / Predictive value of dipyridamole myocardial perfusion tomography on survival

Background: Dipyridamole (DIP) is the most commonly employed pharmacological stressor for myocardial perfusion tomography (SPECT) in patients unable to reach an adequate work load. Aim: To assess the predictive capacity of DIP SPECT on survival. Material and Methods: We included 985 adults aged 66 ±11 years (45% women) with rest and DIP-SPECT. The main indications for the procedure were coronary artery disease (CAD) screening in 66% and known CAD in 33%. Participants were followed up for a median of 65 months (interquartile range 54 to 86 months). During the follow up, 261 deaths were recorded and 98% had a specified cause in their death certificate. Results: Myocardial SPECT was abnormal in 44% of participants. Transient ischemic defects were observed in 34%, fixed defects concordant with infarction in 27% and post-stress systolic dysfunction in 23%. Twenty five percent of deaths were attributable to cardiac or ischemic cause and 22% to cancer. In a bivariate analysis, the hazard ratio (HR) of death of any cause was lower in females and higher in the presence of CAD. The multivariate analysis showed that being older than 46 years increased the HR of death of any cause. In a bivariate analysis, the HR for cardiac death was higher when the myocardial SPECT showed ischemia, necrosis or left ventricular dilation. In the multivariate analysis, post-stress left ventricular systolic function was associated with a lower risk of cardiac death. Conclusions: An abnormal myocardial SPECT, perfusion abnormalities, left ventricular systolic function or dilation are independent predictors of cardiac death in these participants.

ECGEstudio: Herramienta para el diagnóstico de enfermedades cardiovasculares / ECGEstudio: Tool for the diagnosis of cardiovascular diseases

El objetivo del siguiente trabajo es exponer el diseño y las principales características de un sistema desarrollado para el análisis del ECG de reposo. Este está compuesto por: un módulo que adquiere el ECG y lo transmite vía USB, una computadora personal y una aplicación desarrollada sobre la tecnología .NET. Se realizan estudios de tendencia, no encontrados en los electrocardiógrafos tradicionales, para analizar la evolución de la Hipertrofia Ventricular, la tendencia a la Muerte Súbita y la recuperación posterior a un infarto cardiaco. Para el diseño del sistema, se siguió una estructura por capas con niveles de abstracción que faciliten su mantenimiento y actualización. Microsoft Visual Studio 2010 fue el entorno de desarrollo y SQL Server Compact el gestor de base de datos. El sistema fue evaluado con señales simuladas y provenientes de voluntarios con frecuencias cardíacas entre 30 y 240 latidos por minutos, obteniéndose una sensibilidad superior al 99 por ciento en la detección de complejos QRS(AU)

The aim of this paper is to discuss the main features of a system developed for the resting ECG analysis. The proposed system is composed of an electronic ECG module for signal acquisition and transmission via USB, a personal computer and a Windows application developed on .NET technology. Trend studies, based on several ECGs from a patient, are made to analyze the evolution of ventricular hypertrophy, the propensity to sudden death and the recovering degree after suffering a heart attack; this kind of study is not available in traditional electrocardiographs. The proposed was designed as a layered structure with levels of abstraction to facilitate their continued maintenance and updating. Microsoft Visual Studio 2010 was selected as the development environment and SQL Server Compact as the database manager. The system was tested with simulated ECGs and signals from volunteers with heart rates between 30 and 240 beats per minute, giving sensitivity in QRS complex detection over 99 percent(AU)

ECGEstudio: Herramienta para el diagnóstico de enfermedades cardiovasculares / ECGEstudio: Tool for the diagnosis of cardiovascular diseases

El objetivo del siguiente trabajo es exponer el diseño y las principales características de un sistema desarrollado para el análisis del ECG de reposo. Este está compuesto por: un módulo que adquiere el ECG y lo transmite vía USB, una computadora personal y una aplicación desarrollada sobre la tecnología .NET. Se realizan estudios de tendencia, no encontrados en los electrocardiógrafos tradicionales, para analizar la evolución de la Hipertrofia Ventricular, la tendencia a la Muerte Súbita y la recuperación posterior a un infarto cardiaco. Para el diseño del sistema, se siguió una estructura por capas con niveles de abstracción que faciliten su mantenimiento y actualización. Microsoft Visual Studio 2010 fue el entorno de desarrollo y SQL Server Compact el gestor de base de datos. El sistema fue evaluado con señales simuladas y provenientes de voluntarios con frecuencias cardíacas entre 30 y 240 latidos por minutos, obteniéndose una sensibilidad superior al 99 por ciento en la detección de complejos QRS(AU)

The aim of this paper is to discuss the main features of a system developed for the resting ECG analysis. The proposed system is composed of an electronic ECG module for signal acquisition and transmission via USB, a personal computer and a Windows application developed on .NET technology. Trend studies, based on several ECGs from a patient, are made to analyze the evolution of ventricular hypertrophy, the propensity to sudden death and the recovering degree after suffering a heart attack; this kind of study is not available in traditional electrocardiographs. The proposed was designed as a layered structure with levels of abstraction to facilitate their continued maintenance and updating. Microsoft Visual Studio 2010 was selected as the development environment and SQL Server Compact as the database manager. The system was tested with simulated ECGs and signals from volunteers with heart rates between 30 and 240 beats per minute, giving sensitivity in QRS complex detection over 99 percen(AU)

Seguimiento clínico en pacientes con buena capacidad metabólica en la prueba de esfuerzo con SPECT miocárdico / Follow-up of patients with good exercise capacity in stress test with myocardial single-photon emission computed tomography (SPECT)

Background: The evaluation of coronary artery disease (CAD) can be performed with stress test and myocardial SPECT tomography. Aim: To assess the predictive value of myocardial SPECT using stress test for cardiovascular events in patients with good exercise capacity. Material and Methods: We included 102 males aged 56 ± 10 years and 19 females aged 52 ± 10 years, all able to achieve 10 METs and ≥ 85% of the theoretical maximum heart rate and at least 8 min in their stress test with gated 99mTc-sestamibi SPECT. Eighty two percent of patients were followed clinically for 33 ± 17 months. Results: Sixty seven percent of patients were studied for CAD screening and the rest for known disease assessment. Treadmill stress test was negative in 75.4%; 37% of patients with moderate to severe Duke Score presented ischemia. Normal myocardial perfusion SPECT was observed in 70.2%. Reversible defects appeared in 24.8% of cases, which were of moderate or severe degree (> 10% left ventricular extension) in 56.6%. Only seven cases had coronary events after the SPECT. Two major (myocardial infarction and emergency coronary revascularization) and 5 minor events (elective revascularization) ere observed in the follow-up. In a multivariate analysis, SPECT ischemia was the only statistically significant parameter that increased the probability of having a major or minor event. Conclusions: Nearly a quarter of our patients with good exercise capacity demonstrated reversible defects in their myocardial perfusion SPECT. In the intermediate-term follow-up, a low rate of cardiac events was observed, being the isotopic ischemia the only significant predictive parameter.

[Serum lipid levels in a group of cocaine dependent subjects in recent abstinence]. / Descripción de los hallazgos en el perfil lipídico y proteico de pacientes dependientes a cocaína, en abstinencia reciente.

BACKGROUND: Chronic cocaine users develop multiple potentially lethal ischemic vascular complications associated with accelerated atherosclerosis. AIM: To assess biochemical and lipid profiles among cocaine dependent subjects in recent abstinence. MATERIAL AND METHODS: A blood sample to measure blood count, biochemical and lipid profiles was obtained from 78 patients aged 19 to 53 years (78% males) who complied with DSM-IV criteria for cocaine dependency. Laboratory results were compared with a group of normal subjects. RESULTS: All cases had positive urinary cocaine, with a mean consumption lapse of 7.6 years. The frequency of smoking was higher in cases. Dependent males had higher body mass index than controls. Compared to controls, dependent females had significantly higher triglyceride (TG) levels and lower HDL cholesterol. Therefore the relation total/HDL cholesterol was higher (p = 0.0365). Dependent males had higher TG levels than their normal counterparts. Dependent subjects consuming cocaine base-paste had higher TG levels. Total proteins, albumin, urea and blood urea nitrogen were lower in dependent subjects. Among males, serum creatinine was lower and blood urea was positively correlated with the daily amount of cocaine use (p = 0.03). After a month of strict abstinence, lipid profile was repeated in 27 patients and remained unchanged. CONCLUSIONS: Chronic cocaine use was associated with higher TG in both genders and lower HDL cholesterol in women when compared with a group of healthy counterparts.