Tyrosine kinase inhibitors in iodine-refractory differentiated thyroid cancer: experience in clinical practice.

PURPOSE: The aim of this study is to describe our clinical experience with tyrosine kinase inhibitors (TKIs) and to evaluate their efficacy and tolerability in patients with iodine-refractory differentiated thyroid cancer (DTC). METHODS: There were 17 patients (47.1% women, mean age: 65.7) with DTC iodine-refractory (9 papillary, 2 follicular and 3 Hürthle cell), treated with TKIs: 16 with sorafenib and 1 with lenvatinib as first-line treatment; 7 required second-line treatment (4 lenvatinib and 3 axitinib). Primary endpoints were progression-free survival (PFS) and radiographic response (determinate at 3, 6, 12, 18, and 24 months after the initiation of treatment) and second endpoints were determining differences in baseline characteristics depending on clinical course and describing toxicities and tolerability. RESULTS: Median PFS was 18 months. During the first 24 months of treatment with TKIs PR rate was 35.3% (only 5.8% ≥ 6 months) and SD ≥ 6 months was observed in 58.8%. There were no significant differences in baseline characteristics between patients with good and poor evolution. Adverse events (AEs) were present in 100% of patients, but most of them were grade 1 and 2. CONCLUSIONS: In our population of patients with iodine-refractory DTC, treatment with sorafenib, lenvatinib, and axitinib allows the stabilization of the disease in a high percentage of cases, with acceptable tolerability.

Postpartum development of endothelial dysfunction and oxidative stress markers in women with previous gestational diabetes mellitus.

BACKGROUND: Relationships between adhesion molecules (AM), oxidative stress, gestational diabetes mellitus (GDM) and future development of type 2 diabetes mellitus are unclear. AIM: We investigated AM and oxidant/antioxidant markers in women with previous history of GDM. SUBJECTS AND METHODS: Postpartum women with GDM (cases; n = 41) and healthy women (controls; n = 21) had clinical and laboratory variables measured, including indicators of vascular damage (ICAM-1, VCAM-1 and E-selectin), oxidative stress (LPO, GSH and GST) and antioxidant markers (catalase, SOD, GPX and TAC). RESULTS: Previous GDM versus control women presented higher body mass index: 27.4 ± 5.6 versus 23.9 ± 3.6 (p = 0.013); waist circumference: 85.2 ± 12.9 versus 77.5 ± 9.0 (p = 0.017); MetS (WHO definition): 14.6 versus 0 % (p = 0.012); MetS (NCEP-ATPIII definition): 22 versus 0 % (p = 0.002); low HDL: 36.6 versus 9.5 % (p = 0.024); fasting glucose (mmol/L): 5.4 ± 0.6 versus 4.9 ± 0.2 (p < 0.001); glucose 120 min (mg/dL): 105.0 ± 30.2 versus 85.1 ± 14.2 (p = 0.007); fasting insulin (µU/mL): 13.4 ± 8.1 versus 8.4 ± 4.3 (p = 0.004); HOMA index: 3.3 ± 2.3 versus 1.8 ± 1.0 (p = 0.002); HbA1c (%/mmol/mol): 5.4 ± 0.2 versus 5.2 ± 0.2/36 ± 1.4 versus 33 ± 1.4 (p = 0.021); uric acid (mg/dL): 4.1 ± 1 versus 3.5 ± 0.6 (p = 0.009); catalase (nmol/min/mL): 38.7 ± 15.6 versus 28.9 ± 11.1 (p = 0.013). There were no significant differences in hypertension prevalence, lipid fractions, albumin/creatinine ratio and AM. CONCLUSIONS: Women with previous GDM have high catalase levels which correlate positively with glucose intolerance, indicating the potential effect of oxidative stress on postpartum dysglycemic status.

Impact of an outpatient cardiac rehabilitation program on clinical and analytical variables in cardiovascular disease.

PURPOSE: The aim of the study was to determine the effect of lifestyle changes in patients participating in a cardiac rehabilitation program. METHODS: Patients with cardiovascular disease (N = 59) were enrolled in cardiac rehabilitation, which included nutritional and exercise interventions. All patients completed the program, but only 44 attended the reassessment after 12 months because of work reasons or lack of time or interest. RESULTS: Ergometry before and after cardiac rehabilitation showed significant differences in exercise tolerance time (5.2 ± 1.8 minutes vs 7.1 ± 2.1 minutes; P< .001), metabolic equivalents (6.5 ± 1.8 vs 8.8 ± 2.2; P< .001), and the Börg rating of perceived exertion scale (12 ± 1.8 points vs 13.7 ± 1.6 points; P= .005). At the end of the intervention program, significant improvements were seen in body weight (82.6 ± 15.2 kg vs 80.8 ± 14.3 kg; P< .001), waist circumference (100.3 ± 12.4 cm vs 98.0 ± 11.0 cm; P= .002), and levels of fasting glucose (126.5 ± 44.6 mmol/L vs 109.6 ± 24.8 mmol/L; P< .001), low-density lipoprotein cholesterol (2.7 ± 0.9 mmol/L vs 2.5 ± 0.8 mmol/L; P= .033), and C-reactive protein (5.1 ± 8.7 µg/mL vs 4.1 ± 2.6 µg/mL; P= .008), as well as in adherence to a healthy diet as estimated by the Trichopoulou questionnaire score (7.9 ± 2.3 vs 10.6 ± 1.5; P< .001). Twelve months later, however, many of these benefits had either remained stable or worsened. CONCLUSIONS: Cardiac rehabilitation is an appropriate program for the improvement of clinical and analytical variables, such as functional capacity, carbohydrate and lipid metabolism, anthropometric measures, and diet. However, 12 months later, many of these benefits either remained stable or worsened.

Los anticuerpo frente a las formas modificadas de la LDL. Un tema por dilucidar / Antibodies against modified forms of low-density lipoprotein. An issue to be elucidated

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Influence of regular alcohol consumption on uricaemia in unselected healthy individuals.

We analysed serum uric acid concentrations in a group of healthy male and female volunteers in Córdoba (Spain) possessing varying nutritional habits, in order to correlate them with their usual alcohol intake as measured according to a protocolized, blind dietary questionnaire. There was no significant correlation between the serum uric acid and the amount of alcohol regularly drunk by either male or female individuals. These results suggest that a moderate alcohol intake has no effect on uricaemia in healthy individuals.

Renal excretion of urate by hyperuricaemic-hyperlipidemic patients.

We studied the renal urate excretory function in two groups of hyperuricaemic male patients composed of individuals with associated hyperlipidemia and hyperuricaemic-normolipidemic individuals, respectively. Both the hyperlipidemia and the hyperuricaemia were primary inasmuch as none of the patients studied was obese or had an above-normal alcohol intake or blood hypertension. The results obtained show that hyperuricaemic-hyperlipidemic patients have higher serum levels of uric acid and poorer urate excretion as reflected in smaller clearance and fractioned excretion of the metabolite than hyperuricaemic-normolipidemic patients. This, in turn, suggests the occurrence of differences in the extent of the urate handling anomalies between the two groups of patients.

[Diet and hypertriglyceridemia: influence of dietary modifications on plasma lipids, lipoproteins and apoproteins in patients with primary hypertriglyceridemia]. / Dieta e hipertrigliceridemia: influencia de las modificaciones dietéticas sobre los lípidos, lipoproteínas y apoproteínas plasmáticas en pacientes con hipertrigliceridemia primaria.

BACKGROUND: To investigate the influence of dietary changes on plasma lipoproteins and apoproteins in 10 patients with hypertriglyceridemia (plasma triglycerides greater than 1000 mg/dl). METHODS: A sequential study with three periods was designed: 1) Inclusion with uncontrolled free diet; 2) Two weeks of a diet with about 1000 calories/day, controlled with a daily survey; and 3) One week of "free" diet of about 2000 calories. At the end of the three periods the following were measured in each patient: weight, glycemia, plasma IRI and C-peptide, plasma, triglycerides, cholesterol, chylomicron, VLDL, LDL and HDL cholesterol. At the end of the second and third periods the caloric and immediate principles intake were individually considered. RESULTS: A reduction in plasma cholesterol and triglycerides was observed in all cases after the caloric reduction, and also a disappearance of chylomicrons. The reduction of triglycerides took place in all lipoproteins. By contrast, after the low-calorie diet only the VLDL-cholesterol was reduced, while LDL- and HDL-cholesterol increased. The apo C-III/apo C-II ratio was significantly reduced after the low-calorie diet. The plasma glycemia, IRI and C-peptide were negatively correlated with LDL-cholesterol and with the apo C-III/apo C-II ratio. The best model to explain the oscillations of plasma triglycerides depending on the diet was that including the three ingested immediate principles together with the total diet calories. CONCLUSIONS: During the caloric restriction there would be an increased catabolism of VLDL to LDL. This reduction would be mediated by C-III and C-II apoproteins, probably through the oscillations of plasma IRI.