Effect of dynamic humeral centring (DHC) treatment on painful active elevation of the arm in subacromial impingement syndrome. Secondary analysis of data from an RCT.

BACKGROUND: The physiotherapy dynamic humeral centring (DHC) aims to prevent subacromial impingement of rotator cuff tendons during elevation of the arm. The objective of the study was to determine whether DHC acts via an effect on subacromial impingement mechanism by assessing its effect on painful elevation of the arm in subacromial impingement syndrome. METHODS: This is a secondary analysis of results of a randomised controlled trial of the effectiveness of DHC. Sixty-nine patients with subacromial impingement syndrome were prospectively included. Patients and the assessor were blinded to the study hypothesis and treatment, respectively. Patients underwent DHC or non-specific mobilisation as a control for 6 weeks in 15 supervised individual outpatient sessions with home exercises. Outcomes were pain-free range of motion and presence of painful arc of the shoulder, both in active flexion and abduction of the arm at 3 months. RESULTS: At 3 months, pain-free range of motion, both flexion and abduction, was greater in the DHC group than in the mobilisation group. The number of patients with painful arc during flexion was decreased in the DHC group. CONCLUSIONS: DHC improves painful active elevation of the arm. We suggest that DHC may act via a specific effect on subacromial impingement mechanism.

ESM-1 expression in stromal cells is predictive of recurrence after radiofrequency ablation in early hepatocellular carcinoma.

BACKGROUND & AIMS: The prognosis of hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA) is mainly linked to tumor recurrence. So far, no tissue biomarker of recurrence has been validated in biopsy samples. We aimed at investigating the prognostic value of tissue biomarkers in HCC biopsy samples of patients treated with RFA. METHODS: All consecutive naive patients from 3 university hospitals, with compensated cirrhosis, early-stage (BCLC 0/A) uninodular HCC treated with RFA, and available tumor biopsy, were included. Edmondson's grade, and the expression of cytokeratin 19, glutamine synthase, beta-catenin, epithelial cell adhesion molecule (EpCAM), and endothelial cell-specific molecule 1 (ESM-1) were assessed. Main clinical end points were overall and early recurrence. Statistical analyses were performed using Kaplan Meier, Log-rank test, and Cox models. RESULTS: 150 patients were included. Recurrence, death or liver transplantation occurred in 85, 51, and 12 patients, respectively. Median follow-up was 27months. ESM-1 expression by HCC stromal endothelial cells was observed in 58 patients (40%) and was associated with higher serum AFP levels, larger tumor, and more frequent expression of EpCAM and surrogate markers of activation of the Wnt-ß-catenin pathway. The 2 independent predictive factors of overall recurrence were serum AFP (HR 1.11 [1.002; 1.22], p=0.045) and ESM-1 expression (HR 1.56 [1.004; 2.43], p=0.048). ESM-1 expression was also an independent predictive factor of early recurrence (HR 1.81 [1.02; 3.21], p=0.042). CONCLUSIONS: ESM-1 expression by stromal endothelial cells, in tumor biopsy samples, has an independent predictive value of early recurrence after RFA.

Helical CT-enteroclysis in the detection of small-bowel tumours: a meta-analysis.

OBJECTIVE: To perform a meta-analysis to determine sensitivity and specificity estimates of helical CT-enteroclysis in the detection of small-bowel tumours. METHODS: A search for relevant articles published from January 1992 to November 2010 was performed. Study design, patient characteristics and 2 × 2 contingency tables were recorded for eligible studies. Heterogeneity was assessed with the I (2) statistic. A bivariate generalised linear random-effects model was used to summarise sensitivity and specificity estimates for small-bowel tumour detection on a per-patient basis. Sensitivity and specificity estimates were compared in different subgroups. RESULTS: Twelve studies (696 patients) were eligible. The mean small-bowel tumour prevalence was 22.6 % (range 7.7-45.8 %). Inter-study heterogeneity was substantial for sensitivity (I (2) = 66.9 %; 95 % CI 28.7-88.5 %) and low for specificity (I (2) = 10.6 %; 95 % CI 0.0-55.0 %). On a per-patient basis, pooled sensitivity was 92.8 % (95 % CI 71.3-98.5 %) and pooled specificity 99.2 % (95 % CI 94.2-99.9 %) for the diagnosis of small-bowel tumour. Subgroup analysis revealed that small-bowel preparation, more than one imaging pass and large volumes (≥2 L) of enteral contrast agent did not improve tumour detection. CONCLUSION: Our meta-analysis confirms that helical CT-enteroclysis has high degrees of sensitivity and specificity for small-bowel tumour detection. However, our findings reinforce the need for more standardised individual studies.

Survival after radiofrequency ablation and salvage transplantation in patients with hepatocellular carcinoma and Child-Pugh A cirrhosis.

BACKGROUND & AIMS: In patients with hepatocellular carcinoma (HCC) within the Milan criteria, liver transplantation (LT) may be the best therapeutic option. However, the shortage of grafts, leads to attempt liver resection (LR) or radiofrequency ablation (RFA) as a first-line treatment for patients with Child-Pugh A cirrhosis. METHODS: We report results, obtained between 2000 and 2007 from a single center, involving 67 patients (mean age: 57 years) eligible for LT, who were treated with RFA, followed by LT if there was recurrence or liver failure. RESULTS: Eighty three tumors were treated (mean size: 29±9 mm; 16 binodular forms). RFA achieved complete ablation in 96% of nodules. No mortality occurred. During a post-RFA median follow-up of 48 months, 38 patients experienced recurrence, corresponding to a 5-year recurrence rate of 58%. Of these, 14 patients did not receive a transplant because they fell outside the Milan criteria, 21 were transplanted, and 3 were treated by RFA after refusing LT. Binodularity (95% CI HR=2, 1.0-4.0; p=0.049) was the unique risk factor for recurrence. By the study's end-point, 24 patients had undergone LT (21 for HCC recurrence and three for liver failure). No HCC recurrence occurred after LT. Among the 43 non-transplant patients, 12 died due to HCC progression, and 27 were alive without detectable viable tumor. The probability rates for 5-year overall and tumor-free survival were 74% and 69%, respectively. CONCLUSIONS: First line RFA followed by salvage LT allows survival figures that are at least as good as a first-line LT, while limiting the number of grafts.

Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial.

BACKGROUND: Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction has traditionally been supported by unfractionated heparin, which has never been directly compared with a new anticoagulant using consistent anticoagulation and similar antiplatelet strategies in both groups. We compared traditional heparin treatment with intravenous enoxaparin in primary PCI. METHODS: In a randomised open-label trial, patients presenting with ST-elevation myocardial infarction were randomly assigned (1:1) to receive an intravenous bolus of 0·5 mg/kg of enoxaparin or unfractionated heparin before primary PCI. Wherever possible, medical teams travelling in mobile intensive care units (ambulances) selected, randomly assigned (using an interactive voice response system at the central randomisation centre), and treated patients. Patients who had received any anticoagulant before randomisation were excluded. Patients and caregivers were not masked to treatment allocation. The primary endpoint was 30-day incidence of death, complication of myocardial infarction, procedure failure, or major bleeding. The main secondary endpoint was the composite of death, recurrent acute coronary syndrome, or urgent revascularisation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00718471. FINDINGS: 910 patients were assigned to treatment with enoxaparin (n=450) or unfractionated heparin (n=460). The primary endpoint occurred in 126 (28%) patients after anticoagulation with enoxaparin versus 155 (34%) patients on unfractionated heparin (relative risk [RR] 0·83, 95% CI 0·68-1·01, p=0·06). The incidence of death (enoxaparin, 17 [4%] vs heparin, 29 [6%] patients; p=0·08), complication of myocardial infarction (20 [4%] vs 29 [6%]; p=0·21), procedure failure (100 [26%] vs 109 [28%]; p=0·61), and major bleeding (20 [5%] vs 22 [5%]; p=0·79) did not differ between groups. Enoxaparin resulted in a significantly reduced rate of the main secondary endpoint (30 [7%] vs 52 [11%] patients; RR 0·59, 95% CI 0·38-0·91, p=0·015). Death, complication of myocardial infarction, or major bleeding (46 [10%] vs 69 [15%] patients; p=0·03), death or complication of myocardial infarction (35 [8%] vs 57 [12%]; p=0·02), and death, recurrent myocardial infarction, or urgent revascularisation (23 [5%] vs 39 [8%]; p=0·04) were all reduced with enoxaparin. INTERPRETATION: Intravenous enoxaparin compared with unfractionated heparin significantly reduced clinical ischaemic outcomes without differences in bleeding and procedural success. Therefore, enoxaparin provided an improvement in net clinical benefit in patients undergoing primary PCI. FUNDING: Direction de la Recherche Clinique, Assistance Publique-Hôpitaux de Paris; Sanofi-Aventis.

Atorvastatin decreases computed tomography and S100-assessed brain ischemia after subarachnoid aneurysmal hemorrhage: a comparative study.

OBJECTIVE: Statins, which improve the bioavailability of endogenous nitric oxide and upregulate endothelial nitric oxide synthase, have been used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage. The objective of this study was to determine whether statin therapy diminished vasospasm-induced ischemia as assessed using daily measurements of serum S100B, a biomarker for cerebral ischemia, and computed tomography measurement of ischemic lesion volume. DESIGN: Single-center study of cases and historical controls. SETTING: Neurointensive care unit in a university hospital. PATIENTS: Consecutive patients with aneurysmal subarachnoid hemorrhage treated with clipping or coiling within 96 hrs of symptom onset (n = 278) were included from April 2004 to October 2007. INTERVENTION: Oral atorvastatin, 40 mg/day for 21 days, was used routinely starting on December 1, 2005, in 142 patients, who were compared with the 136 patients managed earlier. MEASUREMENTS AND MAIN RESULTS: Ischemic lesion size was measured using computed tomography on the last available scan and serum S100B was assayed daily for 15 days after admission. Angiographic narrowing was semiquantitatively assessed in patients with vasospasm. In the overall population, cerebral vasospasm was significantly less common in the statin-treated group. Severity of vasospasm, as assessed on the most severe angiogram, was lowered with statin. Statins significantly reduced volume of ischemia in patients with vasospasm and an uncomplicated coiling procedure. S100B levels were significantly lower in statin-treated patients, and the decrease was greatest among high-grade patients (World Federation of Neurological Surgeons 3-5). No differences were found between statin-treated and untreated groups regarding rescue therapy intensity or 1-yr clinical outcomes. CONCLUSIONS: Atorvastatin reduces the incidence, the severity and the ischemic consequences of vasospasm as assessed on computed tomography. In high-grade World Federation of Neurological Surgeons patients, atorvastatin decreases serum levels of S100B, a biomarker of brain ischemia. Despite these positive effects on biomarkers, no improvement of outcome was seen in the overall population, although there was a tendency for a better clinical outcome in high-grade patients.

Prospective short-term evaluation of transurethral needle ablation procedure in an ambulatory setting.

OBJECTIVE: To assess the results of transurethral needle ablation (TUNA) (Prostiva®, Medtronic, France) performed in an ambulatory setting in men with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A multicenter open-label study was conducted. Short-term success was defined by ability to leave the hospital on the evening of the intervention, and absence of rehospitalization due to complications during the first postoperative month. Sexual and urinary functions were evaluated by validated questionnaires. RESULTS: The procedure was successful in 44/49 patients. Sexual and ejaculatory function was not affected or slightly improved in the majority of patients. Urinary parameters improved with a 32% decrease in the International Prostate Symptom Score. At 1 month postoperation, more than 80% of patients were satisfied, and 36/41 patients were prepared to undergo the procedure again if needed. Our study was limited by the short follow-up duration. CONCLUSIONS: TUNA can be successfully performed in an ambulatory setting under local and/or general anesthesia with a high level of patient satisfaction and a low short-term morbidity, especially on sexual function. Thus, the procedure is a suitable mini-invasive option for patients who cannot/do not want to take medical therapy or undergo invasive surgical procedures, or want to preserve their sexual function.

Tuberculosis in the intensive care unit: A retrospective descriptive cohort study with determination of a predictive fatality score.

BACKGROUND: Despite effective treatments, tuberculosis-related mortality remains high among patients requiring admission to the intensive care unit (ICU). OBJECTIVE: To determine prognostic factors of death in tuberculosis patients admitted to the ICU, and to develop a simple predictive scoring system. METHODS: A 10-year, retrospective study of 53 patients admitted consecutively to the Hôpitaux de Paris, Hôpital Lariboisière (Paris, France) ICU with confirmed tuberculosis, was conducted. A multivariate analysis was performed to identify risk factors for death. A predictive fatality score was determined. RESULTS: Diagnoses included pulmonary tuberculosis (96%) and tuberculous encephalomeningitis (26%). Patients required mechanical ventilation (45%) and vasopressor infusion (28%) on admission. Twenty patients (38%) died, related to direct tuberculosis-induced organ failure (n=5), pulmonary bacterial coinfections (n=14) and pulmonary embolism (n=1). Using a multivariate analysis, three independent factors on ICU admission were predictive of fatality: miliary pulmonary tuberculosis (OR 9.04 [95% CI 1.25 to 65.30]), mechanical ventilation (OR 11.36 [95% CI 1.55 to 83.48]) and vasopressor requirement (OR 8.45 [95% CI 1.29 to 55.18]). A score generated by summing these three independent variables was effective at predicting fatality with an area under the ROC curve of 0.92 (95% CI 0.85 to 0.98). CONCLUSIONS: Fatalities remain high in patients admitted to the ICU with tuberculosis. Miliary pulmonary tuberculosis, mechanical ventilation and vasopressor requirement on admission were predictive of death.

HISTORIQUE: Malgré des traitements efficaces, la mortalité liée à la tuberculose demeure élevée chez les patients qui doivent être hospitalisés à l'unité de soins intensifs (USI). OBJECTIF: Déterminer les facteurs pronostiques de décès chez les patients tuberculeux admis à l'USI et élaborer un système d'indice prédictif simple. MÉTHODOLOGIE: Les chercheurs ont mené une étude rétrospective d'une durée de dix ans auprès de 53 patients hospitalisés consécutivement à l'USI de l'Hôpital Lariboisière des Hôpitaux de Paris, en France, en raison d'une tuberculose confirmée. Ils ont procédé à une analyse multivariée pour déterminer les facteurs de risque de décès et ont établi un indice prédictif de fatalité. RÉSULTATS: Les diagnostics incluaient une tuberculose pulmonaire (96 %) et une encéphaloméningite tuberculeuse (26 %). Les patients avaient besoin d'une ventilation mécanique (45 %) et d'une perfusion de vasopresseur (28 %) à l'admission. Vingt patients (38 %) sont décédés en raison d'une insuffisance organique liée directement à la tuberculose (n=5), de co-infections bactériennes pulmonaires (n=14) et d'une embolie pulmonaire (n=1). Selon l'analyse multivariée, trois facteurs indépendants à l'admission à l'USI étaient prédictifs d'une fatalité : une tuberculose miliaire (RRR 9,04 [95 % IC 1,25 à 65,30]), une ventilation mécanique (RRR 11,36 [95 % IC 1,55 à 83,48]) et des besoins vasopressifs (RRR 8,45 [95 % IC 1,29 à 55,18]). Un indice conforme à la somme de ces trois variables indépendantes était efficace pour prévenir la fatalité, avec une zone sous la courbe ROC de 0,92 (95 % IC 0,85 à 0,98). CONCLUSIONS: Les décès demeurent élevés chez les patients tuberculeux admis à l'USI. La tuberculose miliaire, la ventilation mécanique et les besoins vasopressifs à l'admission sont prédictifs d'un décès.

Intermediate hepatobiliary cells predict an increased risk of hepatocarcinogenesis in patients with hepatitis C virus-related cirrhosis.

BACKGROUND & AIMS: The expression of biliary lineage markers such as cytokeratin (K) 7 by hepatocytes is thought to reflect an altered regeneration pathway recruiting a stem cell compartment, more prone to carcinogenesis. We aimed to investigate the presence of these so-called intermediate hepatobiliary cells (IHC) in liver biopsies of patients with hepatitis C-related cirrhosis and their potential influence on the subsequent occurrence of hepatocellular carcinoma (HCC). METHODS: From a cohort of patients with hepatitis C-related cirrhosis, prospectively screened for HCC, we retrospectively selected those with a liver biopsy performed for the initial diagnosis of cirrhosis. Presence of IHC was recorded when foci of K7-positive, intermediate-sized hepatocytes were detected. RESULTS: A total of 150 patients were included (87 men; mean age, 57 y; range, 19-84 y; body mass index, 25 kg/m(2)). After a median follow-up period of 4.85 years, HCC was diagnosed in 36 patients (24%). Baseline liver biopsy showed intermediate hepatobiliary cell foci in 61 patients (41%). Intermediate cells co-expressed both hepatocytes markers and the progenitor cell markers Ep-CAM and K19. The presence of intermediate hepatobiliary cells was associated independently with HCC occurrence (Fine and Gray model; hazard ratio, 2.48; 95% confidence interval, 1.24-4.96; P = .01). Other predictors of HCC were diabetes and low platelet count. The HCC annual incidence rate was significantly higher in patients with IHC compared with patients without (8.14% vs 3.12%, Gray's test, P = .003). CONCLUSIONS: The aberrant expression of biliary K by hepatocytes in patients with hepatitis C virus-related cirrhosis is related independently to HCC occurrence.

Assessment of dynamic humeral centering in shoulder pain with impingement syndrome: a randomised clinical trial.

OBJECTIVES: Treatment for degenerative rotator cuff disease of the shoulder includes physiotherapy. Dynamic humeral centering (DHC) aims at preventing subacromial impingement, which contributes to the disease. The goal of this study was to assess the effectiveness of DHC. METHOD: 69 patients with shoulder pain and impingement syndrome were prospectively included in a single-centre randomised trial with a 12-month follow-up. Patients and assessor were blinded to the study hypothesis and treatment, respectively. DHC and non-specific mobilisation as control were performed for 6 weeks, in 15 supervised individual outpatient sessions, and patients performed daily home exercises. The planned primary outcome was the Constant score including subscores for pain, activity, mobility and strength at 3 months. Secondary outcomes were the Constant score and subscores at 12 months, and medication use for pain at 3 and 12 months. RESULTS: The DHC group did not differ from the control group in the total Constant score at 3 months. However, the DHC group showed a higher Constant subscore for pain (12.2 (SD 2.8) vs 9.9 (2.9), least square means difference 2.1, 95% CI 0.7 to 3.5, p=0.004). At 3 months, the DHC group also showed a higher rate of no medication use (96.7% vs 71%, proportional difference 25.7, 95% CI 3.7 to 51.9, p=0.012). There was no other intergroup difference. CONCLUSIONS: There was no difference in the total Constant score between DHC and controls. However, pain was improved at 3 months after DHC. The differences found in subscores for pain should be explored in future studies. Trial registration clinicaltrials.gov Identifier: NCT 01022775.

A randomized controlled trial of alleviated positioning after small macular hole surgery.

OBJECTIVE: To establish whether the success rate of surgery for small idiopathic macular holes (diameter, ≤ 400 µm) is significantly reduced if facedown positioning is replaced by simply taking care to avoid the supine position. DESIGN: Randomized, controlled, parallel-assignment, open-label, interventional, multicenter clinical trial. PARTICIPANTS: Sixty-nine patients from 6 specialized vitreoretinal units, randomized into 2 parallel groups and followed up after surgery for 3 months. METHODS: All patients underwent pars plana vitrectomy, peeling of any epiretinal membrane, and 17% C2F6 gas filling. Patients then were advised randomly to observe either strict facedown positioning for 22 of 24 hours or simply to avoid the supine position for 10 days. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of anatomic closure 3 months after surgery. Main secondary measurements included Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, progression of cataract, and frequency of complications. RESULTS: The mean size of macular holes was approximately 300 µm in both groups. Closure rates were more than 90% in both groups: 32 (91.4%) of 34 eyes in the alleviated positioning group versus 32 (94.1%) of 35 eyes in the facedown positioning group (lower margin of 95% confidence interval of difference, -14.88%). The ETDRS scores at 3 months increased in both groups by 10.23 ± 14.64 and 10.52 ± 14.54 letters, respectively. Progression of cataract and the rate of other complications were not significantly different in the 2 groups. CONCLUSIONS: The success rate of surgery for idiopathic macular holes of 400 µm or smaller is not significantly reduced if facedown positioning is replaced by simply taking care to avoid the supine position. These macular holes can be treated by streamlined surgery, that is, with no internal limiting membrane peeling and no facedown positioning (only avoidance of the supine position) with a closure rate of more than 90% and a mean gain in visual acuity of more than 2 ETDRS lines at 3 months.

Carotid atherosclerotic markers in CADASIL.

PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations of the NOTCH3 gene. Marked variations in disease severity have raised the hypothesis that non-genetic factors may modulate the expressivity of the phenotype. The aim of the current study was to evaluate whether atherosclerosis, assessed by carotid duplex ultrasonography, is associated with variations in the clinical and MRI phenotype of CADASIL. METHODS: Data from 144 consecutive patients enrolled in an ongoing prospective cohort study were collected. Degree of disability was assessed by the modified Rankin Scale, that of cognitive impairment by the Mattis Dementia Rating Scale (MDRS). The total volume of the brain, of lacunar lesions and of white matter hyperintensities, the number of cerebral microhemorrhages, and parameters derived from histograms of apparent diffusion coefficient were measured on cerebral MRI. Atherosclerosis was evaluated by B-mode ultrasonography of carotid arteries. Both the carotid intima-media thickness (cIMT) and the presence of carotid plaques or stenosis were recorded. RESULTS: Higher cIMT was found to be independently associated with lower MDRS scores when this score was less than the quartile limit (p = 0.02). Only a trend for a positive association was detected between cIMT and the Rankin score (p = 0.06). There was no significant association between carotid markers and the occurrence of stroke or MRI parameters except for diffusion data. The mean and peak values of MRI diffusion histograms were found positively associated with the presence of plaques (p < 0.01). CONCLUSION: The results suggest that the severity of atherosclerosis may relate to cognitive decline in CADASIL and that this effect is possibly related to the degree of microstructural cerebral tissue lesions. Longitudinal studies are needed to confirm these results.

Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial.

STUDY OBJECTIVE: The quality of endoscopy depends on the quality of upper gastrointestinal tract preparation. We determine whether in acute upper gastrointestinal bleeding the frequency of satisfactory stomach visualization was different after intravenous erythromycin, a nasogastric tube with gastric lavage, or both. METHODS: We performed a prospective, randomized, multicenter (6 emergency departments) study in patients with acute upper gastrointestinal bleeding presenting with hematemesis or melena. The patients were randomized into 3 groups: (1) intravenous erythromycin infusion without nasogastric tube placement (erythromycin group), (2) nasogastric tube placement without erythromycin (nasogastric group), and (3) intravenous erythromycin infusion combined with nasogastric tube placement (nasogastric-erythromycin group). The main outcome measure was the proportion of satisfactory stomach visualization. RESULTS: Two hundred fifty-three patients (181 men, mean age 61 years [SD 15 years], 84 with cirrhosis) were randomized: 84 (erythromycin group), 85 (nasogastric group), and 84 (nasogastric-erythromycin group). Overall, there was 85% satisfactory stomach visualization; between-group differences were not significant: -4% (95% confidence interval [CI] -15% to 6%) for the erythromycin group and nasogastric-erythromycin group, 2% (95% CI -14% to 9%) for the erythromycin group and nasogastric group, and -6.5% (95% CI -17% to 4%) for the nasogastric group and nasogastric-erythromycin group. The duration of the endoscopic procedure, rebleeding frequency, the need for a second endoscopy, the number of transfused blood units, and mortality at days 2, 7, and 30 did not differ significantly between groups. CONCLUSION: In acute upper gastrointestinal bleeding, administration of intravenous erythromycin provides satisfactory endoscopic conditions, without the need for a nasogastric tube and gastric lavage.

Insulin resistance, serum leptin, and adiponectin levels and outcomes of viral hepatitis C cirrhosis.

BACKGROUND & AIMS: Mechanisms linking obesity and unfavourable outcomes in patients with viral hepatitis C (HCV) cirrhosis are not well understood. Obesity is associated with insulin resistance, increased leptin, and decreased adiponectin serum levels. METHODS: We assessed the predictive value of those factors for the occurrence of hepatocellular carcinoma (HCC) and liver-related death or transplantation in a cohort of 248 patients (mean age 58 (12 years, BMI 25.4 ± 4.4 kg/m(2)) with compensated HCV cirrhosis and persistent infection prospectively followed and screened for HCC. RESULTS: The mean baseline serum levels of adiponectin and leptin were 16.8 ± 15 mg/L and 16.8 ± 19 ng/ml, respectively. The mean homeostasis model assessment of insulin resistance (HOMA) index was 3.8 ± 3; median 2.9. After a median follow-up of 72 months, 61 patients developed HCC, 58 died of liver causes, and 17 were transplanted. The incidences (Kaplan Meier) of HCC were 7%, 18%, and 27% at 5 years (p=0.017) and of liver-related death or transplantation 15%, 15% and 29% (p=0.002) according to the lowest, middle and highest tertile of HOMA, respectively. In multivariate analysis, the HOMA index was associated with HCC occurrence (HR=1.10, [1.01-1.21] p=0.026) and was a strong predictor of liver-related death or transplantation (HR=1.13, [1.07-1.21] p<0.0001). Serum levels of adiponectin and leptin were not associated with the outcome. CONCLUSIONS: In patients with compensated HCV cirrhosis, insulin resistance but not serum levels of adiponectin and leptin predicted the occurrence of HCC and of liver-related death or transplantation.

Suspected anastomotic recurrence of Crohn disease after ileocolic resection: evaluation with CT enteroclysis.

PURPOSE: To determine the utility of computed tomographic (CT) enteroclysis for characterization of the status of the anastomotic site in patients with Crohn disease who had previously undergone ileocolic resection. MATERIALS AND METHODS: Written informed consent was prospectively obtained from all patients, and the institutional review board approved the study protocol. CT enteroclysis findings in 40 patients with Crohn disease who had previously undergone ileocolic resection were evaluated independently by two readers. Endoscopic findings, histopathologic findings, and/or the Crohn disease activity index was the reference standard. Interobserver agreement between the two readers was calculated with kappa statistics. Associations between CT enteroclysis findings and anastomotic site status were assessed at univariate analysis. The sensitivity, specificity, and accuracy of CT enteroclysis, with corresponding 95% confidence intervals (CIs), for the diagnosis of normal versus abnormal anastomosis and the diagnosis of anastomotic recurrence versus fibrostenosis were estimated. RESULTS: Interobserver agreement regarding CT enteroclysis criteria was good to perfect (kappa = 0.72-1.00). At univariate analysis, stratification and anastomotic wall thickening were the two most discriminating variables in the differentiation between normal and abnormal anastomoses (P < .001). Stratification (P < .001) and the comb sign (P = .026) were the two most discriminating variables in the differentiation between anastomotic recurrence and fibrostenosis. In the diagnosis of anastomotic recurrence, severe anastomotic stenosis was the most sensitive finding (95% [20 of 21 patients]; 95% CI: 76.18%, 99.88%), both comb sign and stratification had 95% specificity (18 of 19 patients; 95% CI: 73.97%, 99.87%), and stratification was the most accurate finding (92% [37 of 40 patients]; 95% CI: 79.61%, 98.43%). In the diagnosis of fibrostenosis, both severe anastomotic stenosis and anastomotic wall thickening were 100% sensitive (eight of eight patients; 95% CI: 63.06%, 100.00%), and using an association among five categorical variables, including severe anastomotic stenosis, anastomotic wall thickening with normal or mild mucosal enhancement, absence of comb sign, and absence of fistula, yielded 88% sensitivity (seven of eight patients; 95% CI: 47.35%, 99.68%), 97% specificity (31 of 32 patients; 95% CI: 83.78%, 99.92%), and 95% accuracy (38 of 40 patients; 95% CI: 83.08%, 99.39%). CONCLUSION: CT enteroclysis yields objective and relatively specific morphologic criteria that help differentiate between recurrent disease and fibrostenosis at the anastomotic site after ileocolic resection for Crohn disease. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09091165/-/DC1.

Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis.

UNLABELLED: For the treatment of small hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) is in some centers considered a first-line therapeutic option. However, such a strategy is still under debate with regard to tumor and patient characteristics. In this single-center study we assessed the 5-year survival and prognosis factors in 235 consecutive patients with cirrhosis (Child-Pugh A/B: 205/30) who received RFA as first-line treatment for up to three HCC

Differentiation between true focal liver lesions and pseudolesions in patients with fatty liver: evaluation of helical CT criteria.

OBJECTIVE: To determine the potential of helical CT for differentiating true lesions from pseudolesions in patients with fatty liver. METHODS: Helical CT of 44 patients with diffuse fatty liver (22 with true lesions; 22 with pseudolesions) were reviewed by two observers with regard to morphological features of visible lesions. Univariate analysis was used to detect discriminating criteria for the diagnosis of true lesions. RESULTS: Interobserver agreement was excellent for 9/10 morphological criteria (kappa = 0.831-1). True lesions were more frequently distant from the liver capsule (50.00% vs. 4.55%), located in the right lobe (72.73% vs. 31.82%), round (86.36% vs. 54.55%), heterogeneous (27.27% vs. 0.00%) and had ill-defined margins (40.91% vs. 13.64%) compared with pseudolesions (P < 0.05). Using univariate analysis, a location distant from the liver capsule was the most discriminating variable to differentiate between true and pseudolesions (P = 0.0060). Hyperattenuating content and round shape were the most sensitive criteria (sensitivity = 90.91% and 86.36%, respectively) for the diagnosis of true lesions, and heterogeneity, vascular displacement and encapsulation were the three most specific ones (specificity = 100.00%). Best accuracy was obtained with an association of the three variables (accuracy = 86.36%). CONCLUSION: Helical CT provides objective and discriminating morphological criteria to differentiate between true lesions and pseudolesions in patients with fatty liver.

Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Phase 1 and Randomized Phase 2 Trial.

Importance: ERBB2 (HER2)-targeted therapy provides benefits in metastatic breast cancer (mBC) and gastric cancer, but additional treatments are needed to maximize efficacy and quality of life. Objective: To determine maximum tolerated doses (MTDs) of trastuzumab emtansine (T-DM1) plus capecitabine in patients with previously treated ERBB2-positive mBC and locally advanced/metastatic gastric cancer (LA/mGC) (phase 1) and the efficacy and safety of this combination vs T-DM1 alone in patients with mBC (phase 2). Design, Setting, and Participants: The MTD in phase 1 was assessed using a 3 + 3 design with capecitabine dose modification. Phase 2 was an open-label, randomized, international multicenter study of patients with mBC treated with T-DM1 plus capecitabine or T-DM1 alone. Eligible patients had previously treated ERBB2-positive mBC or LA/mGC with no prior chemotherapy treatment for advanced disease. Interventions: Patients in the phase 1 mBC cohort received capecitabine (750 mg/m2, 700 mg/m2, or 650 mg/m2 twice daily, days 1-14 of a 3-week cycle) plus T-DM1 3.6 mg/kg every 3 weeks. Patients with LA/mGC received capecitabine at the mBC phase 1 MTD, de-escalating as needed, plus T-DM1 2.4 mg/kg weekly. In phase 2, patients with mBC were randomized (1:1) to receive capecitabine (at the phase 1 MTD) plus T-DM1 or T-DM1 alone. Main Outcomes and Measures: The phase 1 primary objective was to identify the MTD of capecitabine plus T-DM1. The phase 2 primary outcome was investigator-assessed overall response rate (ORR). Results: In phase 1, the median (range) age was 54.0 (37-71) and 57.5 (53-70) years for patients with mBC and patients with LA/mGC, respectively. The capecitabine MTD was identified as 700 mg/m2 in 11 patients with mBC and 6 patients with LA/mGC evaluable for dose-limiting toxic effects. In phase 2, between October 2014 and April 2016, patients with mBC (median [range] age, 52.0 [28-80] years) were randomized to receive combination therapy (n = 81) or T-DM1 (n = 80). The ORR was 44% (36 of 81 patients) and 36% (29 of 80 patients) in the combination and T-DM1 groups, respectively (difference, 8.2%; 90% CI, -4.5 to 20.9; P = .34; clinical cutoff, May 31, 2017). Adverse events (AEs) were reported in 78 of 82 patients (95%) in the combination group, with 36 (44%) experiencing grade 3-4 AEs, and 69 of 78 patients (88%) in the T-DM1 group, with 32 (41%) experiencing grade 3-4 AEs. No grade 5 AEs were reported. Conclusions and Relevance: Adding capecitabine to T-DM1 did not statistically increase ORR associated with T-DM1 in patients with previously treated ERBB2-positive mBC. The combination group reported more AEs, but with no unexpected toxic effects. Trial Registration: ClinicalTrials.gov Identifier: NCT01702558.

CT enteroclysis features of uncomplicated celiac disease: retrospective analysis of 44 patients.

PURPOSE: To describe the computed tomographic (CT) enteroclysis features of uncomplicated celiac disease (CD) and to determine the most indicative appearance of this condition by using a retrospective case-control study. MATERIALS AND METHODS: This study had institutional review board approval. The CT enteroclysis examinations of 44 consecutive patients with proved uncomplicated CD (21 men, 23 women; mean age, 44.45 years) were reviewed by two blinded readers and compared with those obtained in 44 control subjects (21 men, 23 women; mean age, 44.48 years), who were matched for sex and age. Comparisons were calculated by using univariate analysis. RESULTS: Reversed jejunoileal fold pattern had the highest specificity (100%; 44 of 44; 95% confidence interval [CI]: 91.96%, 100%) and was the most discriminating independent variable for the diagnosis of uncomplicated CD (odds ratio, 39.9; P < .0001) but had a sensitivity of 63.64% (28 of 44; 95% CI: 47.77%, 77.59%). Ileal fold thickening, vascular engorgement, and splenic atrophy were other variables that strongly correlated with the presence of uncomplicated CD. CONCLUSION: CT enteroclysis may help establish a diagnosis of uncomplicated CD and may clarify the cause of nonspecific gastrointestinal symptoms in patients with unknown CD. However, future prospective trials are needed to determine the actual value of CT enteroclysis in patients with CD and validate the clinical usefulness of CT enteroclysis in the detection of unknown uncomplicated CD.

Immediate vs delayed intervention for acute coronary syndromes: a randomized clinical trial.

CONTEXT: International guidelines recommend an early invasive strategy for patients with high-risk acute coronary syndromes without ST-segment elevation, but the optimal timing of intervention is uncertain. OBJECTIVE: To determine whether immediate intervention on admission can result in a reduction of myocardial infarction compared with a delayed intervention. DESIGN, SETTING, AND PATIENTS: The Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention (ABOARD) study, a randomized clinical trial that assigned, from August 2006 through September 2008 at 13 centers in France, 352 patients with acute coronary syndromes without ST-segment elevation and a Thrombolysis in Myocardial Infarction (TIMI) score of 3 or more to receive intervention either immediately or on the next working day (between 8 and 60 hours after enrollment). MAIN OUTCOME MEASURES: The primary end point was the peak troponin value during hospitalization; the key secondary end point was the composite of death, myocardial infarction, or urgent revascularization at 1-month follow-up. RESULTS: Time from randomization to sheath insertion was 70 minutes with immediate intervention vs 21 hours with delayed intervention. The primary end point did not differ between the 2 strategies (median [interquartile range] troponin I value, 2.1 [0.3-7.1] ng/mL vs 1.7 [0.3-7.2] ng/mL in the immediate and delayed intervention groups, respectively; P = .70). The key secondary end point was observed in 13.7% (95% confidence interval, 8.6%-18.8%) of the group assigned to receive immediate intervention and 10.2% (95% confidence interval, 5.7%-14.6%) of the group assigned to receive delayed intervention (P = .31). The other end points, as well as major bleeding, did not differ between the 2 strategies. CONCLUSION: In patients with acute coronary syndromes without ST-segment elevation, a strategy of immediate intervention compared with a strategy of intervention deferred to the next working day (mean, 21 hours) did not result in a difference in myocardial infarction as defined by peak troponin level. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00442949.