Use of Deep Learning to Evaluate Tumor Microenvironmental Features for Prediction of Colon Cancer Recurrence.

Deep learning may detect biologically important signals embedded in tumor morphologic features that confer distinct prognoses. Tumor morphologic features were quantified to enhance patient risk stratification within DNA mismatch repair (MMR) groups using deep learning. Using a quantitative segmentation algorithm (QuantCRC) that identifies 15 distinct morphologic features, we analyzed 402 resected stage III colon carcinomas [191 deficient (d)-MMR; 189 proficient (p)-MMR] from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy. Results were validated in an independent cohort (176 d-MMR; 1,094 p-MMR). Association of morphologic features with clinicopathologic variables, MMR, KRAS, BRAFV600E, and time-to-recurrence (TTR) was determined. Multivariable Cox proportional hazards models were developed to predict TTR. Tumor morphologic features differed significantly by MMR status. Cancers with p-MMR had more immature desmoplastic stroma. Tumors with d-MMR had increased inflammatory stroma, epithelial tumor-infiltrating lymphocytes (TIL), high-grade histology, mucin, and signet ring cells. Stromal subtype did not differ by BRAFV600E or KRAS status. In p-MMR tumors, multivariable analysis identified tumor-stroma ratio (TSR) as the strongest feature associated with TTR [HRadj 2.02; 95% confidence interval (CI), 1.14-3.57; P = 0.018; 3-year recurrence: 40.2% vs. 20.4%; Q1 vs. Q2-4]. Among d-MMR tumors, extent of inflammatory stroma (continuous HRadj 0.98; 95% CI, 0.96-0.99; P = 0.028; 3-year recurrence: 13.3% vs. 33.4%, Q4 vs. Q1) and N stage were the most robust prognostically. Association of TSR with TTR was independently validated. In conclusion, QuantCRC can quantify morphologic differences within MMR groups in routine tumor sections to determine their relative contributions to patient prognosis, and may elucidate relevant pathophysiologic mechanisms driving prognosis. SIGNIFICANCE: A deep learning algorithm can quantify tumor morphologic features that may reflect underlying mechanisms driving prognosis within MMR groups. TSR was the most robust morphologic feature associated with TTR in p-MMR colon cancers. Extent of inflammatory stroma and N stage were the strongest prognostic features in d-MMR tumors. TIL density was not independently prognostic in either MMR group.

Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas.

PURPOSE: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered. METHODS AND MATERIALS: SBRT (6.6 Gy × 5) was intended but hypofractionated RT (5 Gy × 5) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, or 3) based on adequacy. A score of 1 indicated no deviation, 2 indicated minor deviation, and 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score. RESULTS: Forty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic and 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets and 4 for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT and 7 (17.9%) with hypofractionated RT. Five cases (13%) required revision before treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2, and 11 (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded. CONCLUSIONS: Despite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. Although clinical outcomes did not appear to have been affected, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements.

Valor predictivo prequirúrgico del EuroSCORE I, EuroSCORE II y STS score en pacientes sometidos a cirugía cardíaca: informe preliminar / Pre-surgical predictive value of the EuroSCORE I, EuroSCORE II and STS score in patients undergoing cardiac surgery: preliminary report

RESUMEN Introducción: en cirugía cardiovascular, el EuroSCORE I, EuroSCORE II y STS score son herramientas que brindan pronóstico e información para la toma de decisiones. Es imperativo evaluar el valor predictivo real de los mismos en nuestro medio. Objetivo: evaluar el valor predictivo de los citados scores en pacientes sometidos a cirugía cardíaca en el área de cardiología del Hospital Nacional. Metodología: estudio de cohortes, retrospectivo, con muestreo no probabilístico de casos consecutivos. La población estuvo constituida por pacientes sometidos a cirugía cardiaca en el periodo comprendido entre enero 2020 a julio 2021. Fueron evaluadas 60 historias clínicas, excluidas 6, quedando finalmente 54 expedientes. Resultado: predominó el sexo masculino 57,14 %, la edad media fue de 60 ± 12 años (rango 26 - 82 años). El EuroSCORE II presentó un riesgo relativo de 10 (IC 95 % 1,3 ­ 90), p=0,004, sensibilidad 80 %, especificidad 78,43 %, VPP 26,67 % (IC 95 % 0,95 a 52,38) y VPN 97,56 % (IC 95 % 91,62 a 100 %). El EuroSCORE I presentó riesgo relativo de 1,6 (IC 95 % 0,2 ­ 10,9) p=0,50, sensibilidad 60 %, especificidad 52,94 %, VPP 11,11 % (IC 95 % 0,00 a 24,82) y VPN 93,10 % (IC 95 % 82,16 a 100 %). El STS score arrojó un riesgo relativo de 3,5 (IC 95 % 0,07 ­ 35), p=0,10, sensibilidad del 20 %, especificidad 93,33 %, valor predictivo positivo del 25 % (IC 95 % 0,00 a 79,93) y valor predictivo negativo 91,30 % (IC 95 % 82,07 a 100 %). La mortalidad global fue 8,93 % y morbilidad 93 %. Conclusión: se demostró un alto valor predictivo negativo en los scores, lo que determinó que pacientes con riesgo bajo e intermedio tuvieran una mortalidad baja.

ABSTRACT Introduction: in cardiovascular surgery, the EuroSCORE I, EuroSCORE II and STS score are tools that provide prognosis and information for decision making. It is imperative to evaluate their real predictive value in our environment. Objective: to evaluate the predictive value of the aforementioned scores in patients undergoing cardiac surgery in the Hospital Nacional cardiology area. Methodology: retrospective cohort study, with non-probabilistic sampling of consecutive cases. The population consisted of patients undergoing cardiac surgery in the period from January 2020 to July 2021. 60 medical records were evaluated, 6 excluded, finally leaving 54 records. Result: male sex predominated 57,14 %, the mean age was 60 ± 12 years (range 26 - 82 years old). The EuroSCORE II presented a relative risk of 10 (95 % CI 1.3 - 90), p = 0.004, sensitivity 80 %, specificity 78,43 %, PPV 26,67 % (95 % CI 0,95 to 52,38) and NPV 97,56 % (95 % CI 91,62 to 100 %). The EuroSCORE I presented a relative risk of 1.6 (95 % CI 0.2 - 10.9) p = 0.50, sensitivity 60 %, specificity 52,94 %, PPV 11,11 % (95 % CI 0.00 a 24,82) and NPV 93,10 % (95 % CI 82.16 to 100 %). The STS score yielded a relative risk of 3,5 (95 % CI 0.07 - 35), p = 0.10, sensitivity of 20 %, specificity 93,33 %, positive predictive value of 25 % (CI 95 % 0 .00 to 79.93) and negative predictive value 91,30 % (95 % CI 82.07 to 100 %). Overall mortality was 8,93 % and morbidity 93 %. Conclusion: a high negative predictive value was demonstrated in the scores, which determined that patients with low and intermediate risk had a low mortality.

Frecuencia de lesiones coronarias epicárdicas en pacientes con cardiopatía dilatada en un Departamento de Cardiología en el periodo 2015 - 2021 / Frequency of epicardial coronary lesions in patients with Dilated Heart Disease in a Department of Cardiology in the period from 2015 to 2021

RESUMEN Introducción: la cardiopatía dilatada definida como la dilatación de cavidades cardiacas de múltiples etiologías tiene una prevalencia en adultos de alrededor de 1/2.500 individuos. La ecocardiografía transtorácica determina la dilatación de cavidades y evalúa la función ventricular mientras que la cinecoronariografía permite identificar la etiología principalmente isquémica por afección de arterias coronarias epicárdicas. La utilización de la cinecoronariografía como primera línea para el diagnóstico etiológico, implica riesgos propios de un método invasivo con un alto costo en recursos económicos, por lo cual es imperioso determinar el posible resultado de dicho procedimiento. Objetivo: determinar la frecuencia de lesiones coronarias epicárdicas en pacientes con Cardiopatía Dilatada en un Departamento de Cardiología en el periodo del 2015 ­ 2021. Metodología: estudio observacional, descriptivo, retrospectivo y de corte transversal con muestreo no probabilístico por conveniencia, mediante la revisión en la base de datos en un Departamento de Cardiología. Resultados: este estudio incluyó a 88 pacientes, con disnea en clase funcional II-IV de la NYHA y cardiopatía dilatada por ecocardiografía, de etiología no filiada. De éste grupo, 66 % eran varones y 34 % mujeres, la media de edad fue de 56 ± 11,19 años. Al ser sometidos a cinecoronariografía diagnostica, se constató que el 23 % presentó lesiones coronarias epicárdicas, siendo la más frecuente la lesión de un vaso (55 %), predominando el sexo masculino en aquellos con o sin lesiones coronarias epicárdicas. Conclusiones: la frecuencia de lesiones coronarias epicárdicas en pacientes con cardiopatía dilatada, es baja.

ABSTRACT Introduction: dilated heart disease defined as the dilation of cardiac cavities of multiple etiologies has a prevalence in adults of around 1/2.500 individuals. Transthoracic echocardiography determines chamber dilation and evaluates ventricular function, while coronary angiography can identify the mainly ischemic etiology due to involvement of the epicardial coronary arteries. The use of coronary angiography as the first line for the etiological diagnosis implies risks of an invasive method with a high cost in economic resources, for which it is imperative to determine the possible result of said procedure. Objective: to determine the frequency of epicardial coronary lesions in patients with Dilated Heart Disease in a Departmento de Cardiología in the period 2015-2021. Methodology: observational, descriptive, retrospective and cross-sectional study with non-probabilistic convenience sampling, by reviewing the database in a Departmento de Cardiología. Results: this study included 88 patients, with dyspnea in NYHA functional class II-IV and dilated heart disease by echocardiography, of unknown etiology. Out of this group, 66% were men and 34 % women, the mean age was 56 ± 11.19 years. When undergoing diagnostic cinecoronariography, it was found that 23 % had epicardial coronary lesions, the most frequent being a lesion of a vessel (55 %), with the male sex predominating in those with or without epicardial coronary lesions. Conclusions: the frequency of epicardial coronary lesions in patients with dilated heart disease is low.

Factores de riesgo en pacientes con cardiopatía isquémica internados en el Hospital de la Fundación Tesãi, Ciudad del Este, Paraguay / Risk factors in patients with ischemic heart disease admitted to the Hospital de la Fundación Tesãi, Ciudad del Este, Paraguay

RESUMEN Introducción: las enfermedades cardiovasculares ocupan el primer lugar de mortalidad a escala mundial, por lo que es importante conocer los factores de riesgo más frecuentes en pacientes con cardiopatía isquémica. Objetivo: describir la frecuencia de los factores de riesgo en pacientes con cardiopatía isquémica internados en el Hospital de la Fundación Tesãi, Ciudad del Este, Paraguay. Metodología: el diseño del estudio fue observacional, descriptivo, retrospectivo y de corte transversal, incluyó 61 pacientes mayores de 20 años internados en el Hospital de la Fundación Tesãi, Ciudad del Este, Paraguay, entre marzo de 2018 y marzo de 2019. Resultados: la edad representativa estuvo en el rango etario de 45 a 64 años en el grupo de hombres, y de 65 a 74 años en el grupo de mujeres, con predominio del sexo masculino. Los factores de riesgo más relevantes fueron la hipertensión arterial y la dislipidemia. Sin embargo, el tabaquismo fue el menos frecuente. Conclusión: la hipertensión arterial y dislipidemia son los factores de riesgo más frecuentes.

ABSTRACT Introduction: cardiovascular diseases occupy the first place of mortality worldwide, so it is important to know the most frequent risk factors in patients with ischemic heart disease. Objective: to describe the frequency of risk factors in patients with ischemic heart disease admitted to the Hospital de la Fundación Tesãi, Ciudad del Este, Paraguay. Methodology: the study design was observational, descriptive, retrospective and cross-sectional, it included 61 patients older than 20 years admitted to the Hospital de la Fundación Tesãi, Ciudad del Este, Paraguay, between March 2018 and March 2019. Results: the representative age was in the age range of 45 to 64 years in the group of men, and 65 to 74 years in the group of women, with a predominance of males. The most relevant risk factors were arterial hypertension and dyslipidemia. However, smoking was the least frequent. Conclusion: arterial hypertension and dyslipidemia are the most frequent risk factors.

Chronic right ventricular apical pacing: adverse effects and current therapeutic strategies to minimize them.

The permanent cardiac pacemaker is the only effective therapy for patients with symptomatic bradycardia and hundreds of millions are implanted worldwide every year. Despite its undisputed clinical benefits, the last two decades have drawn much attention to the negative effects associated with long-term pacing of the right ventricle (RV). Experimental and clinical studies have shown that RV pacing produces ventricular dyssynchrony, similar to that of left bundle branch block, with consequent detrimental effects on cardiac structure and function, with adverse clinical outcomes such as atrial fibrillation, heart failure and death. Although clinical evidence largely comes from subanalyses of pacemaker and implantable cardiac defibrillator studies, there is strong evidence that patients with reduced left ventricular function are at high risk of suffering from the detrimental effects of long-term RV pacing. Biventricular pacing in cardiac resynchronization therapy devices can prevent ventricular dyssynchrony and has emerged as an attractive option in this patient group with promising results and more clinical studies underway. Moreover, there is evidence that specific pacemaker algorithms that minimize RV pacing can reduce the negative effects of RV stimulation on cardiac function and may also prevent clinical deterioration. The extent of the long-term clinical effects of RV pacing in patients with normal ventricular function and how to prevent this are less clear and subject to future investigation.

Taquicardia antidrómica secundaria a ablación de vía accesoria / Antidromic Tachycardia Secondary to Accessory Pathway Ablation

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