Applicability and accuracy improvement of transient elastography using the M and XL probes by experienced operators.

Transient elastography (TE) is the reference method to obtain liver stiffness measurements (LSM), but no results are obtained in 3.1% and unreliable in 15.8%. We assessed the applicability and diagnostic accuracy of TE re-evaluation using M and XL probes. From March 2011 to April 2012 868 LSM were performed with the M probe by trained operators (50-500 studies) (LSM1). Measurements were categorized as inadequate (no values or ratio <60% and/or IQR/LSM >30%) or adequate. Inadequate LSM1 were re-evaluated by experienced operators (>500 explorations) (LSM2) and inadequate LSM2 using XL probe (LSMXL). Inadequate LSM1 were obtained in 187 (21.5%) patients, IQR/LSM >30% in 97 (51%), ratio <60% in 24 (13%) and TE failed to obtain a measurement in 67 (36%). LSM2 achieved adequate registers in 123 (70%) of 175 registers previously considered as inadequate. Independent variables (OR, 95%CI) related to inadequate LSM1 were body mass index (1.11, 1.04-1.18), abdominal circumference (1.03, 1.01-1.06) and age (1.03, 1.01-1.04) and to inadequate LSM2 were skin-capsule distance (1.21, 1.09-1.34) and abdominal circumference (1.05, 1.01-1.10). The diagnostic accuracy (AUROC) to identify significant fibrosis improved from 0.89 (LSM1) to 0.91 (LSM2) (P = 0.046) in 334 patients with liver biopsy or clinically significant portal hypertension. A third evaluation (LSMXL) obtained adequate registers in 41 (93%) of 44 patients with inadequate LSM2. Operator experience increases the applicability and diagnostic accuracy of TE. The XL probe may be recommended for patients with inadequate values obtained by experienced operators using the M probe. http://clinicaltrials.gov (NCT01900808).

Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis.

BACKGROUND AND AIMS: The stiffening of the extracellular matrix, and changes in its cellular and molecular composition, have been reported in the pathogenesis of fibrosis. We analyze the mechanisms that perpetuate ileal fibrosis in surgical resections of complicated Crohn's disease patients. METHODS: Ileal resections were obtained from affected and non-affected tissue of stenotic or penetrating Crohn's disease behavior. Ilea from non-IBD patients were used as control tissue. All samples underwent RNA sequencing. Human small intestinal fibroblasts were treated for 48 h with IL-1ß, TFGß1, PDGFB or TNF-α. Resistance to apoptosis was analysed by RT-PCR, western blot and immunohistochemistry in ileal tissue and by RT-PCR and FACS in cultured cells. RESULTS: Growth factor-driven signaling pathways and increased RAS GTPase activity were up-regulated in affected ilea in which we found expression of both the antiapoptotic molecule MCL1 and the transcription factor ETS1 in submucosal fibroblasts, and a senescence-associated secretory phenotype. In cultured intestinal fibroblasts, PDGFB induced an ETS1-mediated resistance to apoptosis that was associated with the induction of both of TGFB1 and IL1B, a cytokine that replicated the expression of SASP detected in ileal tissue. ETS1 drove fibroblast polarization between inflammatory and fibrogenic phenotypes in IL1ß-treated cells. CONCLUSIONS: Our data show resistance to apoptosis in complicated ileal CD, and demonstrate that PDGFB induce an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Results point to PDGFRB, IL1R1 or MCL1 as potential targets against ileal fibrosis.

Emotional prosody recognition enhances and progressively complexifies from childhood to adolescence.

Emotional prosody results from the dynamic variation of language's acoustic non-verbal aspects that allow people to convey and recognize emotions. The goal of this paper is to understand how this recognition develops from childhood to adolescence. We also aim to investigate how the ability to perceive multiple emotions in the voice matures over time. We tested 133 children and adolescents, aged between 6 and 17 years old, exposed to 4 kinds of linguistically meaningless emotional (anger, fear, happiness, and sadness) and neutral stimuli. Participants were asked to judge the type and intensity of perceived emotion on continuous scales, without a forced choice task. As predicted, a general linear mixed model analysis revealed a significant interaction effect between age and emotion. The ability to recognize emotions significantly increased with age for both emotional and neutral vocalizations. Girls recognized anger better than boys, who instead confused fear with neutral prosody more than girls. Across all ages, only marginally significant differences were found between anger, happiness, and neutral compared to sadness, which was more difficult to recognize. Finally, as age increased, participants were significantly more likely to attribute multiple emotions to emotional prosody, showing that the representation of emotional content becomes increasingly complex. The ability to identify basic emotions in prosody from linguistically meaningless stimuli develops from childhood to adolescence. Interestingly, this maturation was not only evidenced in the accuracy of emotion detection, but also in a complexification of emotion attribution in prosody.

Prevalence and prognosis after a first nontransmural myocardial infarction.

Prevalence, prognosis, and coronary anatomy associated with nontransmural myocardial infarction (MI) were prospectively assessed in 458 consecutive men admitted to our coronary care unit with a first MI. Cardiac catheterization was performed in 402 of the 436 survivors within 1 month of the acute event. Mean follow-up was 33 months (range 5 to 72). Nontransmural MI was diagnosed in 28 patients (6%). These patients were younger (46 +/- 10 versus 51 +/- 7 years, p less than 0.001) and had lower peak creatine kinase values (601 +/- 319 versus 1,141 +/- 923 U, p less than 0.01) and better ejection fraction (63 +/- 8 versus 46 +/- 14, p less than 0.001) than did their counterparts. Survivors of nontransmural MI also had fewer affected arteries (p less than 0.001) and a lower prevalence of total or subtotal occlusion (greater than 90%) in the involved artery (p less than 0.01). Mortality in the acute phase and long-term survival at 4 years (Kaplan-Meier) in patients with nontransmural MI (94%) were similar to those in patients with transmural MI (90%). The occurrence of new nonfatal coronary events was also similar in both groups of MI survivors. Thus, in the absence of symptoms, more aggressive management to improve survival does not seem warranted after nontransmural MI.

Significance of Q-wave regression after transmural acute myocardial infarction.

A total of 313 consecutive patients was studied to assess the prevalence and prognostic implications of Q-wave loss after transmural acute myocardial infarction. Heart catheterization, including single-plane left ventriculography and selective coronary arteriography, was performed before hospital discharge. After a mean follow-up of 65 (1 to 100) months, 34 patients (11%) lost their Q waves. The time interval from the acute event to the first electrocardiogram showing Q-wave disappearance was 14 (1 to 32) months. Peak creatine kinase value was significantly higher in patients who retained their Q waves than in those who lost them (1,121 +/- 813 vs 779 +/- 464 IU, respectively, p less than 0.05). Severity of coronary artery disease, as judged by the number of diseased arteries and the number of arteries with total or subtotal occlusion, was similar in both groups. However, patients showing Q-wave regression had lower left ventricular end-diastolic pressure, higher ejection fraction and fewer abnormally contracting segments than their counterparts (12 +/- 6 vs 15 +/- 7 mm Hg, p less than 0.05; 53 +/- 11 vs 44 +/- 14%, p less than 0.001; 1 +/- 1 vs 2 +/- 1 segments, p less than 0.001, respectively). In addition, no patient with normalized electrocardiogram presented with left ventricular aneurysm. Although differences in mortality, nonfatal reinfarction and new onset of angina between the 2 groups were not significant, congestive heart failure was prevalent among patients with permanent Q waves (23 vs 6%, p less than 0.05). Our findings suggest that Q-wave loss after AMI may be related to a smaller infarct size.

Natural history of severe left ventricular dysfunction after myocardial infarction.

The prevalence and prognosis of severe left ventricular dysfunction after infarction was prospectively analyzed in a series of 259 male patients aged 60 years or less surviving an acute myocardial infarction. All patients underwent coronary angiography 30 days after the acute event and were followed up for a mean period of 34 months (range, 15 to 55 months). Forty-five patients (17 percent) were found to have severe left ventricular dysfunction (ejection fraction less than or equal to 30 percent). Comparison of patients with and without severe impairment of left ventricular function showed the former to have a lower cardiac index (p less than 0.001), higher left ventricular end-diastolic volume index (p less than 0.001), and a higher prevalence of three-vessel disease (p less than 0.025) and of total or subtotal occlusion of at least one coronary artery (p less than 0.025). While the occurrence of congestive heart failure was higher in patients with severe left ventricular dysfunction (p less than 0.001), the probability of developing angina was similar in both groups. Cox's regression analysis showed ejection fraction to be the only independent predictor of survival in patients with severe impairment of left ventricular function. An ejection fraction of 20 percent or less identified a subset of patients with the highest mortality (62 percent at four years), significantly different from that of patients whose ejection fraction was between 21 and 30 percent (28 percent) (p less than 0.001).

Intraventricular meningiomas: MR imaging and MR spectroscopic findings in two cases.

CT, MR imaging, MR spectroscopy, and angiography were performed in two men (ages 21 and 48, respectively) with intraventricular meningioma. In both cases, CT and MR imaging showed large tumors located in the trigone of the right lateral ventricle that enhanced intensely after contrast administration. MR spectroscopy was helpful in supporting a preoperative diagnosis of meningioma in both cases.