Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals

IntroductionThe aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents.Patients and methodsThis cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness–spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed.ResultsNinety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p = 0.02), spleen stiffness measurement (39.4 vs 46.05; p = 0.04), liver stiffness–spleen diameter to platelet ratio score (1.21 vs 2.02; p = 0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p = 0.04) and variceal risk index (?3.4 vs ?1.02; p = 0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3 kPa for liver stiffness measurement and 27 kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance.DiscussionLiver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.     

Left ventricular eccentric remodeling and matrix loss are mediated by bradykinin and precede cardiomyocyte elongation in rats with volume overload.

OBJECTIVES: We hypothesized that left ventricular (LV) remodeling and matrix loss in volume overload (VO) are mediated by bradykinin (BK) and exacerbated by chronic angiotensin-converting enzyme (ACE) inhibition. BACKGROUND: Chronic ACE inhibition increases anti-fibrotic BK and does not attenuate LV remodeling in pure VO. The relative contribution of changes in extracellular matrix versus cardiomyocyte elongation in acute and chronic LV chamber remodeling during VO is unknown. METHODS: Echocardiography, LV collagen content, and isolated cardiomyocytes were studied in rats after aortocaval fistula (ACF) of 12 h, 2 and 5 days, and 4, 8, and 15 weeks. We also studied ACF rats after BK2 receptor (BK2R) blockade (2 days) or ACE inhibition (4 weeks). RESULTS: At 2 days after ACF, LV end-diastolic dimension (LVEDD)/wall thickness was increased, and LV interstitial collagen was decreased by 50% without cardiomyocyte elongation. The BK2R blockade prevented collagen loss and normalized LVEDD/wall thickness. From 4 to 15 weeks after ACF, interstitial collagen decreased by 30% and left ventricular end-systolic (LVES) dimension increased despite normal LVES pressure and isolated cardiomyocyte function. The ACE inhibition did not decrease LVEDD/wall thickness, further decreased LV interstitial collagen, and did not improve LV fractional shortening despite decreased LVES pressure. CONCLUSIONS: Immediately after ACF induction, eccentric LV remodeling is mediated by interstitial collagen loss without cardiomyocyte elongation. Acute BK2R blockade prevents eccentric LV remodeling and improves function. Chronic ACE inhibition does not prevent eccentric LV remodeling or improve function. These findings suggest that ACE inhibitor-mediated increase in LV BK exacerbates matrix loss and explains why ACE inhibition is ineffective in VO.     

The number of deformed joints as a surrogate measure of damage in rheumatoid arthritis

OBJECTIVE: To evaluate the reliability and validity of the number of deformed joints (NDJ) as a surrogate measure of joint damage in rheumatoid arthritis (RA). METHODS: We tested interrater reliability and validity in determining the NDJ as a surrogate for joint damage in consecutive patients with RA. We rated each of 48 joints as normal or abnormal in terms of alignment and range of motion, and expressed the results as the total number of deformed joints. We compared the NDJ with the severity of damage on a plain radiograph of the hands, scored using Sharp's technique, as the gold standard measure of joint damage. We also compared the correlation between the NDJ and radiographic joint damage, on the one hand, and disease duration, performance-based measures of physical function, and the self-reported level of disability. RESULTS: The interrater reliability of the NDJ was excellent, with an intraclass correlation among four examiners of 0.94. To assess validity of the NDJ, we studied 273 RA patients from 5 clinical settings. Their average NDJ was 14 (range 0-43), and their average Sharp's score for joint space narrowing and erosions combined was 106 (range 4-309). The NDJ and the total Sharp's score were highly correlated (r = 0.83). Both measures were correlated to a similar degree with disease duration (r = 0.51 for each measure), grip strength (r = -0.49 for NDJ, and r = -0.51 for Sharp's score), walking velocity (r = -0.44 for NDJ, and r = -0.45 for Sharp's score), the timed button test (r = -0.62 for NDJ, and r = -0.57 for Sharp's score), and the Modified Health Assessment Questionnaire (r = 0.38 for NDJ, and r = 0.38 for Sharp's score). Both the Sharp's score and the NDJ worsened significantly in 38 patients for whom 1-2 year followup data were available. CONCLUSION: The NDJ is reliable and is strongly associated with the standard measure of joint damage in RA. Because it is easily performed in a clinical setting, it could be used as an economical surrogate of joint damage in studies of the long-term outcome of RA.     

Glucose tolerance, insulin secretion, insulin sensitivity and glucose effectiveness in normal and overweight hyperthyroid women

OBJECTIVE Inter-relationships between insulin sensi-tivity and body weight in patients with hyperthyroidism remain incompletely understood. We have examined whether a mild excess of body weight exacerbates the metabolic abnormalities of spontaneous hyperthyroidism. DESIGN AND PATIENTS Insulin-modified intravenous glucose tolerance tests were performed on 14 hyperthy-roid women with body mass indices (BMI) ranging from 21 to 31 kg/m². A control group of 19 healthy women matched for age and BMI was also studied. MEASUREMENTS Intravenous glucose tolerance (KG), first and second-phase integrated insulin responses to glucose, the integrated glucose area under the curve (AUC), and minimal model parameters of insulin sensitivity (SI) and glucose effectiveness (SG) were determined. RESULTS Hyperthyroid women had mean KG, glucose-induced insulin secretion and SG values similar to those in control women. The mean glucose AUC was higher in hyperthyroid patients (P<0.05). Lower insulin sensitivity was observed in hyperthyroid patients than in control women (SI=0.38±0.07 vs 0.59±0.07 l/min pmol 10⁴ (mean±SEM), P<0.05). A steeper decline in insulin sensitivity with increase in body mass index was found in hyperthyroid women when compared with the control group, after adjusting for age. When groups were compared according to their BMI, hyperthyroid women with normal weight (BMI≤25 kg/m², n=8) had mean KG, insulin response to glucose, glucose AUC, SG and SI values similar to those in normal weight control women (n=11). Overweight hyperthyroid patients (BMI>25 kg/m², n=6) had a higher (P<0.05) second-phase insulin response to glucose than normal weight patients, a higher glucose AUC (P<0.05) than normal weight patients and overweight controls (n=8), and a lower SI (P<0.05) than normal weight patients and overweight controls. SG was not influenced by BMI in hyperthyroid patients. CONCLUSIONS These results suggest that overall glucose tolerance was not significantly affected in normal weight hyperthyroid women. However, when a moderate excess of weight is also present, a state of clear insulin resistance occurs.     

Intratesticular delivery of tumor necrosis factor-alpha and ceramide directly abrogates steroidogenic acute regulatory protein expression and Leydig cell steroidogenesis in adult rats

Systemic or intratesticular release of TNF alpha and IL1 beta have been implicated in the reduced testosterone biosynthesis and impaired production of competent spermatozoa found in human patients suffering from sepsis or chronic inflammation. Although in vitro and in vivo studies have demonstrated that TNF alpha and IL1 beta intercept the hypothalamic-pituitary testis axis at different levels, the site(s) of action and relative contribution of each cytokine to the overall testicular failure associated to systemic inflammatory processes remains poorly defined. In this study we show that intratesticular delivery of TNF alpha induced a rapid (4 h) and sustained (up to 24 h) reduction in steroidogenic acute regulatory (StAR) protein expression and testosterone biosynthesis in nonstimulated or human chorionic gonadotropin-treated intact or hypophysectomized rats. Bilateral treatment with cell-permeant short-chain ceramides (C2-cer or C6-cer) reproduced the early (4 h) inhibitory action of TNFalpha on testosterone biosynthesis and testicular StAR expression. The inhibitory action of C2-cer or C6-cer was not observed in animals treated with inactive analogs (dihydroceramide), phosphorylcholine, sphingosine, or sphingosine-1P. In sharp contrast to the previously described ability of IL1 beta to prevent human chorionic gonadotropin-stimulated Leydig cell steroidogenesis in vitro, serum testosterone and testicular StAR protein expression remained unchanged in animals bilaterally injected with this cytokine. These data support the concept that TNF alpha triggers different effector mechanisms to directly inhibit Leydig cell StAR expression and steroidogenesis, which ultimately contribute to the global reproductive failure associated with chronic inflammation and sepsis.