Facultad de Medicina
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Examinando Facultad de Medicina por Autor "Aedo, Sócrates"
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Ítem The CAPRA-S Score and Immune Dysfunction as a Guide to Outcome in Men Treated with Prostatectomy Radical as Mono-Therapy for Prostate Cancer(Archivos Españoles de Urología, 2022-08) Murray, Nigel P.; Aedo, Sócrates; Fuentealba, Cynthia; Reyes, Eduardo; Salazar, AníbalObjective: Incorporate the immune function as determined by the absolute lymphocyte count (ALC) into the CAPRA-S risk stratification score to determine if predictive values could be improved. Materials and Methods: The clinical pathological findings in the surgical specimen and total PSA were used to define the three CAPRA-S risk groups. One month after surgery and at each follow up total PSA and the ALC were determined, until biochemical failure (BF) or the end of the study period. A cut off value of<1,000 lymphocytes/mm3 was used to define lymphocytopenia (LCP). Each CAPRA-S group was sub- ivided based on the presence or absence of LCP. Kaplan-Meier biochemical failure free survival (BFFS) curves and restricted mean biochemical failure free survival times were calculated for each group. Results: 404 patients participated of whom 103 (25.5%) underwent BF. 270 men were CAPRA-S low risk (LR), 89 intermediate risk (IR) and 45 high risk (HR), of whom LCP was found in 22 (8%) of low risk, 24 (27%) of intermediate risk and 17 (38%) of high risk men. LCP was significantly associated with a higher PSA, higher Gleason and CAPRA-S scores and BF. HRs were 1.76 for IR, 2.49 for HR and 1.29 for LCP. Five-year BFFS for men without LCP, LR 93.5%, IR 61% and HR 36%, for those with LCP, LR 55%, IR 25% and HR 6%. All patients with LCP and IR or HR scores relapsed within 6 years. 10 year BFFS for men without LCP were 71% LR, 43% IR and 23% HR, LR with LCP 16%. Men with BF had increasing LCP approximately 18 months before BF. Conclusions: The incorporation of the ALC taken one month after surgery with the CAPRA-S improves risk stratification; decreases in the ALC suggest that BF is occuring. These results need to be confirmed with larger studies.Ítem Health screening of middle-aged women: what factors impact longevity?(The North American Menopause Society, 2022-08) Blumel, Juan E.; Aedo, Sócrates; Murray, Nigel P.; Vallejo, María S.Objective The aim of this study was to measure the impact of different risk factors in middle-aged women on longevity evaluated after three decades of an initial health screening. Methods Women who received an annual check-up between 1990 and 1993 were recruited. Anamnesis and physical examination were recorded. Blood samples for the measurement of glycemia and lipids were taken. Data are reported as of December 2021. Results A total of 1,158 women aged 40 to 60 were studied. At 30.9 years of follow-up, the Kaplan-Meier overall survival was 75.6% (95% confidence interval, 72.6-78.3). The main causes of the 260 deaths observed were the following: cancer (n = 88; 33.8%), cardiovascular disease (n = 55; 21.2%), and infectious disease (n = 41; 15.8%). The following hazard ratios were found with the flexible parametric survival model: personal history of fracture (hazard ratio, 2.55; 95% confidence interval, 1.29-5.02; P = 0.007), type 2 diabetes mellitus (2.14; 1.18-3.88; P = 0.012), personal history of heart disease (1.85; 1.09-3.13; P = 0.022), chronic arterial hypertension (1.65; 1.25-2.17; P < 0.001), postmenopausal status (1.60; 1.13-2.26; P = 0.008), unskilled jobs (1.56; 1.17-2.07; P = 0.002), cigarette smoking (1.51; 1.17-1.94; P = 0.002), age (1.06; 1.03-1.09; P < 0.001), body mass index (1.04; 1.01-1.07; P = 0.004), multiparous (0.72; 0.56-0.93; P = 0.012), and active sexual intercourse (0.68; 0.52-0.87; P = 0.003). Lipid disorders did not reach statistical significance as a risk factor. Conclusions In this cohort, it was observed that most of the classic risk factors for mortality were present. However, a history of fracture appears in middle-aged women as a strong predictor of mortality, surpassing diabetes and arterial hypertension. Multiparity, on the other hand, was a protective factor.Ítem Improvement in the neutrophil-lymphocyte ratio after combined FOLFOX chemotherapy for stage III colon cancer is associated with improved minimal resdiual disease and outcome(Asia Pacific Organization for Cancer Prevention (APOCP), 2022-02-19) Murray, Nigel P.; Villalon, Ricardo; Hartmann, Dan; Rodriguez, Patricia Maria; Aedo, SócratesIntroduction: Minimal residual disease (MRD) is the net result of the biological properties of disseminated tumour cells and the effect of the immune system and treatment to eliminate them. The aim of this study was to analyse the effect of combined chemotherapy on the immune function as determined by the neutrophil-lymphocyte ratio (NLR) and if it was associated with changes in the subtype of minimal residual disease and outcome in stage III colon cancer. Methods and Patients: A prospective, single centre observational study; the NLR was determined immediately prior to and one, two and three months after completing chemotherapy. Circulating tumour cells (CTCs) and bone marrow micro-metastasis (mM) using immunocytochemistry with anti-CEA were determined prior to and one month after chemotherapy. The association of changes in the NLR with MRD subtypes classified as Group I (negative for CTCs and mM), Group II (positive for mM) and Group III (positive for CTCs) as a result of chemotherapy and five-year disease free progression (DFS) analysed. Results: One hundred and eighty eight patients participated of whom 83 (44.9%) relapsed. In non-relapsing patients the NLR significantly increased and was higher after chemotherapy compared with relapsing patients. Significant increases in the NLR were associated with changes to a better MRD prognostic subtype and decreases with a worse MRD subtype. Neither baseline NLR nor MRD subtype predicted response to chemotherapy. DFS for MRD subgroups were 88%, 56% and 6% for Groups I to III respectively. Conclusions: Immune function as measured by the NLR is associated with MRD prognostic subtypes, improvements in the NLR are associated with improvements in MRD post chemotherapy but neither baseline NLR or MRD predicted outcome.Ítem Increasing immune dysfunction is associated with increasing matrix-metalloproteinase-2 expression and predicts biochemical failure in men with bone marrow micro-metastasis positive localized prostate cancer(Asian Pacific Organization for Cancer Prevention (APOCP), 2022-07) Murray, Nigel P.; Aedo, Sócrates; Fuentealba, Cynthia; Reyes, Eduardo; Salazar, AníbalIntroduction: To determine if there was an association of the ALC (absolute lymphocyte count) and LCP (lymphocytopenia) with the expression of MMP-2 in bone marrow micro-metastasis, the changes occurring during follow-up and association with biochemical failure. Methods and patients: One month after surgery blood and bone marrow samples were taken to determine the presence of micro-metastasis, the presence of circulating prostate cells (CPCs) and ALC. CPCs and micro-metastasis were detected using immunocytochemistry and MMP-2 expression determined in micrometastasis. Only men positive for micro-metastasis participated in the study. At end follow blood was taken for serum PSA, ALC and CPCs, if the ALC decreased by more than 10% bone marrow sampling was repeated and MMP-2 expression determined, similarly for men with BF. Men who had stable ALCs had an end of study evaluation of the bone marrow. Results: 402 men underwent radical prostatectomy, one month post surgery 79 men were positive for only bone marrow micro-metastasis and formed the study group; of whom 36/79 (45%) underwent BF. Clinical pathological findings were not significantly different between men with or without BF. In men with BF the ALC was significantly lower one-month post surgery. The 5 and 10 year Kaplan-Meier survival was 100% at 5-years and 65% at 10-years for the whole cohort. Men without BF had stable ALCs. A decrease of >10% in the ALC was associated with increasing MMP-2 expression in the micro-metastasis and surrounding stromal tissue, the appearance of CPCs 6-12 months later and BF. Conclusions: the immune host-tumour cell interaction in the microenvironment is dynamic and changes with time. A decreasing ALC may be a valuable marker in identifying men with high risk of BF and changes in immune mediated dormancy before the PSA rises.