Browsing by Author "Carlos E Fardella"
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- ItemChanges in Clinical Presentation and Perioperative Management of Pheochromocytomas and Paragangliomas: A Four-Decade Experience in a Academic Center(2021) Thomas Uslar; Ignacio San Francisco; Roberto Ignacio Olmos; Stefano Pietro Macchiavello; Alvaro Zuñiga; Pablo Rojas; Marcelo Garrido; Alvaro Huete; Gonzalo Medez; Joaquin Cifuentes; Fernando Castro; Jose Tomas Zemelman; Daniela Olivari; Carlos E Fardella; Eugenio Arteaga; Jose Miguel Dominguez Ruiz-Tagle; Gloria Valdes; Rodrigo Tagle; Rene BaudrandObjective: Latin American reports on pheochromocytomas and paragangliomas (PPGL) are scarce. Recent studies have shown changes in both clinical presentation and management of these patients. We aimed to assess the main characteristics of PPGL patients in a single academic center over the last four decades. Experimental design: Cohort study. Patients and methods: Demographic, clinical, biochemical, genetic and perioperative data from 105 PPGL patients were retrospectively and prospectively collected over the 1980–2019 period. Patients were categorized into four groups (14 patients in the 1st, 25 patients in the 2nd, 27 patients in the 3th and 39 patients in the 4th decade) according to the date of diagnosis. Results: The mean age at diagnosis was 46±19 years, and the tumor size was 5.3±2.2 cm, female gender was 63%, bilateral tumor of 15%, paragangliomas 9% and metastatic disease in 15%. The aforementioned parameters remained stable across the four decades. During the study period we observed significant increases in doxazosin dosing (2.7±2.6 mg vs. 8.0±4.5 p<0.003) and laparoscopic procedures (28% vs. 84% p<0.001) along with a decrease in the length of hospital stay (10.0±8.9 vs. 3.8±1.7 days p=0.007). Among the 24 genetic tests performed, we identified 59% germline mutations. The most frequent mutations were RET (18%) and SDHX (18%), followed by VHL (14%), MAX (5%) and NF1 (4%). Notably, in the last decade we observed a dramatic increase in the proportion of incidental PPGL diagnosis (0% vs. 53% p<0.001) and genetic testing analyses (0 vs. 19 p<0.001). When comparing incidental diagnosis (n=25) versus clinically suspicious cases(n=50), incidentalomas had fewer adrenergic symptoms (38 vs. 62%; p<0.001), and lower rates of hypertension (64 vs. 80%; p=0.01), hypertension crises (28 vs. 44%; p=0.02), functionality (79 vs. 100%; p=0.01) and total catecholamines and/or metanephrine levels (8.4 vs. 12.5 fold above the upper normal limit; p=0.04). Conclusions: The implementation of a multidisciplinary program increased diagnosis and genetic testing and also optimized anesthesia and surgical procedure, translating into a notorious improvement in perioperative outcomes. In addition, we observed a change in the clinical presentation of PPGL in recent decades with a marked increase in incidental cases, which highlights the importance of early diagnosis and treatment.
- ItemRelationship Between Metabolic Syndrome Components and Proinflammatory Molecules(2021) Andrea Vecchiola; Killen Garcia; Luis-Martin González-Gómez; Alejandra Tapia-Castillo; Rocio Artigas; Rene Baudrand; Alexis M Kalergis; Cristian A Carvajal; Carlos E FardellaWe aimed to study the associations of 5 adipocytokines, two endothelial damage markers, and hs-CRP with the MetS components to distinguish the most significant cytokines likely related to distinct metabolic profiles. Methods: Cross-sectional study with 202 Chilean subjects (18–65 years old), categorized by MetS, and No-MetS according to Harmonizing ATP III. Adipocytokines profiling included adiponectin, leptin, hs-CRP, CTRP-1, PAI-1, FABP4, and metalloproteinase (MMP)-9 and MMP-2 activity. Results: Subjects with MetS showed higher levels of the most proinflammatories molecules but significantly lower adiponectin than subjects with No-MetS. Among the studied adipocytokines, PAI-1 and adiponectin showed the strongest associations with most of MetS components. PAI-1 was associate with MetS OR 1.107 [1.065–1.151], p< 0.0001, and adiponectin inversely associated with MetS OR 0.710 [0.610 -0.825], p< 0.0001). Following adjustment by sex, age, BMI, and 24 h sodium urinary excretion in a multivariate analysis, the association of PAI-1 OR 1.090 [1.044–1.137], p< 0.0001) and adiponectin OR 0.634 [0.519 - 0.775], p < 0.0001) with MetS remained significant. Multivariate analyses support a model where PAI-1associate to waist_hip, SBP, DBP, and glucose (all p< 0.0001) and adiponectin associate to TG (p=0.03) and HDL-cholesterol (p=0.0001). Conclusion: PAI-1 and Adiponectin rendered the most robust associations with MetS components in a general population, indicating that unfavourable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses should allow establishing whether these adipocytokines can anticipate the progress of MetS and cardiovascular risk. Conflict of interest: The authors declared no conflict of interest. Funding: This work was supported by Chilean grants CONICYT Fondo Nacional de Desarrollo Científico y Tecnológico, (FONDECYT) 1160695(CEF) and 1190419(RB); FONDECYT Post-doctorado 3200646(ATC); Millenium Institute of Immunology and Immunotherapy - ICM (P09/16-F)(AK-CEF).