Rate of non-invasive follicular thyroid neoplasms with papillary-like nuclear features depends on pathologist's criteria: a multicentre retrospective Southern European study with prolonged follow-up.

PURPOSE: To determine the rate of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in a multi-institutional series from the Iberian Peninsula and describing this NIFTP cohort. METHODS: Retrospective study of papillary thyroid carcinoma (PTC) or well-differentiated tumours of uncertain malignant potential (WDT-UMP) diagnosed between 2005 and 2015 and measuring ≥5 mm in adult patients from 17 hospitals. Pathological reports were reviewed to determine the cases that fulfil the original criteria of NIFTP and histology was reassessed. Rates were correlated with the number of PTC and its follicular variant (FVPTC) of each institution. Demographic data, histology, management, and follow-up of the reclassified NIFTP cohort were recorded. RESULTS: A total of 182 cases with NIFTP criteria were identified: 174/3372 PTC (rate: 5.2%; range: 0-12.1%) and 8/19 WDT-UMP (42.1%). NIFTP rate showed linear correlation with total PTC (p: 0.03) and FVPTC (p: 0.007) identified at each centre. Ultrasound findings were non-suspicious in 60.1%. Fine-needle cytology or core biopsy diagnoses were undetermined in 49.7%. Most patients were treated with total thyroidectomy. No case had nodal disease. Among patients with total thyroidectomy, 89.7% had an excellent response evaluated 1 year after surgery. There were no structural persistence or relapses. Five patients showed residual thyroglobulin after 90 months of mean follow-up. CONCLUSIONS: NIFTP rate is low but highly variable in neighbouring institutions of the Iberian Peninsula. This study suggests pathologist's interpretation of nuclear alterations as the main cause of these differences. Patients disclosed an excellent outcome, even without using the strictest criteria.

Circulating biomarkers of collagen metabolism in arterial hypertension: relevance of target organ damage.

OBJECTIVE: Increasing experimental evidence indicates that alterations in the extracellular matrix are implicated in hypertension and its chronic complications. Selected markers of extracellular matrix metabolism were investigated as potential biomarkers for hypertensive remodelling and correlated with the severity and extent of target organ damage (TOD) in patients with essential hypertension. METHODS: We studied 159 consecutive patients being treated for essential hypertension. An exhaustive evaluation of the heart, kidney and blood vessel damage was performed, and plasma levels of plasma procollagen type I (PICP), matrix metalloproteinase-1 (MMP-1) and its inhibitor (tissue inhibitor metalloproteinase-1, TIMP-1) were determined. Patients were categorized into four groups: no TOD (33 patients), level 1 TOD (52 patients), level 2 TOD (44 patients) and level 3 TOD (30 patients). RESULTS: The serum levels of MMP-1 and TIMP-1 were higher in patients with TOD than in hypertensive patients without TOD. Increasing levels of these molecules were progressively associated with an increase in the number of organs damaged, with highest levels of markers in patients with level 3 TOD (heart, kidney and blood vessels). There were no differences in PICP levels between groups. We found a slight but significant correlation between TIMP-1 and all hypertensive organ damage. Logistic regression analysis showed that age, smoking, diabetes mellitus, abdominal perimeter, MMP-1 and TIMP-1 were independently related to the level of TOD. CONCLUSION: Circulating concentration of MMP-1 and TIMP-1 is associated with an extended hypertensive disease, with more TOD. TIMP-1 may have a role as a biomarker of total remodelling burden in hypertensive patients.

Inflammation and apoptosis in hypertension. Relevance of the extent of target organ damage.

INTRODUCTION AND OBJECTIVES: To investigate the relationship between inflammatory and apoptotic parameters and the severity and extent of target organ damage in patients with essential hypertension. METHODS: We studied 159 consecutive patients with treated essential hypertension. An exhaustive evaluation of damage to heart, kidney, and blood vessels was performed and plasma levels of inflammatory (interleukin 6 and soluble receptor of tumor necrosis factor-alpha type 2) and apoptotic markers (soluble receptor of tumor necrosis factor-alpha type 1 and soluble Fas receptor) were determined. Patients were categorized into four groups: a) no organ damage (33 patients); b) 1 organ damaged (52 patients); c) 2 organs damaged (44 patients), and d) 3 organs damaged (30 patients). RESULTS: Serum levels of interleukin 6, soluble receptor of tumor necrosis factor-alpha type 1 and soluble receptor of tumor necrosis factor-alpha type 2 were higher in patients with target organ damage than in hypertensive patients without organ damage. Increasing levels of these molecules were progressively associated with an increase in the number of organs damaged, and the highest levels were observed in the group with damage to 3 organs (heart, kidney, and blood vessels). There were no differences in soluble Fas receptor levels between groups. Logistic regression analysis showed that age, smoking, diabetes mellitus, abdominal circumference, interleukin 6, and soluble receptor of tumor necrosis factor-alpha type 1 were independently related to the number of target organs damaged. CONCLUSIONS: Extensive hypertensive disease with involvement of more target organs was associated with greater inflammatory and apoptotic activation in these hypertensive patients.

[Myocardial remodeling and immunologic activation in patients with heart failure]. / Remodelado miocárdico y activación inmunitaria en pacientes con insuficiencia cardiaca.

INTRODUCTION AND OBJECTIVES: Immune response-mediated regulation of myocardial collagen remains poorly understood. Our objective was to investigate the relationship between ventricular remodeling and immunologic activation in patients with heart failure (HF) by comparing dilated and ischemic cardiomyopathy. METHODS: We studied 94 patients with HF and dilated cardiomyopathy (n=46) or ischemic cardiomyopathy (n=48). We recorded left ventricular (LV) volumes, E/A ratio, and ejection fraction. Plasma concentrations of tumor necrosis factor alpha (TNFalpha), soluble TNFa receptor I (sTNF-RI), sTNF-RII, interleukin-6 (IL-6) and IL-10 were measured. The serum procollagen type-III amino-terminal propeptide (PIIINP) level was also obtained. RESULTS: Ventricular volumes were greater in the dilated cardiomyopathy than in the ischemic cardiomyopathy group (P< .05). However, sTNF-RI, sTNF-RII and PIIINP levels were higher in the ischemic group (P< .05). In this group, there were significant correlations between ventricular volumes and IL-10 and sTNF-RII levels. There was also a significant correlation between PIIINP and sTNF-RII levels (r=0.30; P< .05). In the dilated cardiomyopathy group, there was a significant correlation between ventricular volumes and IL-10 level, and between PIIINP level and IL-6 (r=0.32; P< .05) and sTNF-RII levels (r=0.32; P< .05). Multiple linear regression analysis, which included cytokine levels, age, sex and ventricular function, showed that the sTNF-RII level was an independent predictor of the PIIINP level (adjusted r(2)=0.16; P< .0001) and of ventricular volumes (LV end-systolic volume index, adjusted r(2)=0.034; P< .05; and LV end-diastolic volume index, adjusted r(2)=.048; P< .05) in both groups. CONCLUSIONS: In HF, there is an interaction between proinflammatory cytokines and the extracellular matrix. Immunologic implications vary according to disease etiology. The elevation in proinflammatory cytokine and PIIINP levels is greater in patients with ischemic cardiomyopathy. Multiple regression analysis showed that the sTNF-RII level was an independent predictor of ventricular remodeling.