Peripheral changes in immune cell populations and soluble mediators after anti-PD-1 therapy in non-small cell lung cancer and renal cell carcinoma patients.

Patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) have shown benefit from anti-PD-1 therapies. However, not all patients experience tumor shrinkage, durable responses or prolonged survival, demonstrating the need to find response markers. In blood samples from NSCLC and RCC patients obtained before and after anti-PD-1 treatment, we studied leukocytes by complete blood cell count, lymphocyte subsets using flow cytometry and plasma concentration of nine soluble mediators, in order to find predictive biomarkers of response and to study changes produced after anti-PD-1 therapy. In baseline samples, discriminant analysis revealed a combination of four variables that helped differentiate stable disease-response (SD-R) from progressive disease (PD) patients: augmented frequency of central memory CD4+ T cells and leukocyte count was associated with response while increased percentage of PD-L1+ natural killer cells and naïve CD4+ T cells was associated with lack of response. After therapy, differential changes between responders and non-responders were found in leukocytes, T cells and TIM-3+ T cells. Patients with progressive disease showed an increase in the frequency of TIM-3 expressing CD4+ and CD8+ T cells, whereas SD-R patients showed a decrease in these subsets. Our findings indicate that a combination of immune variables from peripheral blood (PB) could be useful to distinguish response groups in NSCLC and RCC patients treated with anti-PD-1 therapy. Frequency of TIM-3+ T cells showed differential changes after treatment in PD vs SD-R patients, suggesting that it may be an interesting marker for monitoring progression during therapy.

Pulmonary neuroendocrine carcinoid tumors: Is there a predictive role to the Ki 67 index?

INTRODUCTION: There are several factors predicting evolution in carcinoid tumors (CT) to date including the Ki67 role. AIMS: The aim of this study is to identify a KI67 cut-off point for a population of CT and determine its prognostic implication in global and disease-free survival. METHODS: Hematoxylin-eosin slides of 102 CT were revised. The percentage of cells expressing Ki 67 was determined manually. STATISTICAL ANALYSIS: The variables were compared with the t-test or the Wilcoxon test according to their distribution, the categorical ones with Chi-square or Fisher's test. The best cut-off point was established by constructing receiver operating characteristic curves, then using that value as a dichotomous variable. RESULTS: 72 typical carcinoids (TC) and 30 atypical carcinoids (AC) were analyzed; 66% were female. Median age (TC 38 vs. AC 51, P = 0.001), Ki67 expression (TC 0.63 vs. AC 2, P = 0.003), tumor size (TC 2.5 vs. AC 2.6, P = 0.001), the percentage relapse (TC 3.4% vs. AC 23%, P = 0.006), and the number of deaths (TC 1 vs. AC 4, P = 0.042) were significantly higher in the AC subgroup. The best cut-off point for Ki 67 was 0.755 (area under the curve AUC 0.564, 95% confidence interval 0.270-0.857), with no significant differences found in the disease-free and overall survival curves when considering values < or ≥ at the established cut-off point. The best cut-off point of the Ki-67 when exclusively analyzing AC was 1.18. When using this value as a predictive variable, a marginal statistical association was observed between Ki-67 expression, mortality (P = 0.077), and the frequency of relapses (P = 0.054). CONCLUSIONS: Histological type is the best predictor of prognosis in the carcinoid tumor group. In the AC subgroup, the marginal association between mortality, frequency of relapses and Ki values 67 ≥ 1.18 has clinical relevance future analyses are required to determine the real predictive value of this variable.

Calcifilaxis en enfermedad renal crónica estadio IIIa. Presentación de un caso clínico / Calciphylaxis in chronic renal disease stage IIIa. Clinical case presentation

Se presenta un caso clínico de una paciente de 23 años con enfermedad renal crónica estadio IIIa (ERC EIIIa), secundaria a glomerulopatía focal y segmentaria, que evoluciona con lesiones ulceradas de fondo necrótico dolorosas con biopsia compatible con calcifilaxis. Se suspende tratamiento inmunosupresor, bloqueante cálcicos y calcitriol e inicia tratamiento antibiótico, con buena evolución. La calcifilaxis es una enfermedad que afecta principalmente a pacientes con enfermedad renal terminal. Debido a su alta mortalidad, se deben aumentar los esfuerzos en la prevención de los factores de riesgo modificables y en el reconocimiento temprano. Reportamos el caso de una paciente con un Clearance de Creatinina de 53.8 ml/min. por CKD-EPI y factores predisponentes no convencionales para el desarrollo de la enfermedad demostrando que la calcifilaxis no es una entidad exclusiva de pacientes con enfermedad renal estadio V en terapia de sustitución

Calciphylaxis is a disease that affects mainly end-stage renal disease patients. Due to its high mortality, every effort should be taken to prevent modifiable risk factors and to make an early diagnosis. We report the case of a 23 year old patient with chronic renal disease stage IIIa (CKD IIIa) secondary to focal segmental glomerulopathy and 53.8 ml/min glomerular filtration rate calculated with the CKD-EPI formula, with non-conventional predisposing risk factors for disease development. Immunosuppressive treatment, calcium blockers, and calcitriol were stopped and antibiotic treatment was applied with good evolution. This case shows that calciphylaxis in not an exclusive entity seen in patients with stage V CKD on renal replacement therapy.