Citations

We performed a Bayesian network meta‐analysis combining direct and indirect treatment comparisons to assess the comparative effectiveness of pharmacological agents for the treatment of nonalcoholic steatohepatitis (NASH). Through systematic literature review, we identified nine randomized, controlled trials (RCTs) including 964 patients with biopsy‐proven NASH, comparing vitamin E, thiazolidinediones (TZDs), pentoxifylline, or obeticholic acid to one another or placebo. The primary outcome was improvement in fibrosis stage; secondary outcomes were improvement in ballooning degeneration, lobular inflammation, and steatosis. We reported relative risks (RRs) and 95% confidence intervals (CIs) from direct meta‐analysis and 95% credible intervals (CrIs) from Bayesian network meta‐analysis, and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to appraise quality of evidence. Moderate‐quality evidence supports the use of pentoxifylline (RR, 0.26; 95% CrI: 0.05‐1.00) and obeticholic acid (RR, 0.81; 95% CI: 0.70‐0.95) over placebo in improving fibrosis. High‐quality evidence supports the effect of vitamin E, TZDs, and obeticholic acid over placebo in improving ballooning degeneration. All four interventions seemed to have at least moderate‐quality evidence over placebo to improve steatosis. Moderate‐quality evidence supports that TZDs, pentoxifylline, and obeticholic acid decrease lobular inflammation. All the head‐to‐head comparisons were supported by very‐low‐quality evidence except for superiority of TZDs over vitamin E on improving steatosis and lobular inflammation, which had moderate‐quality evidence. Conclusions : Based on direct and network meta‐analysis, pentoxifylline and obeticholic acid improve fibrosis, and vitamin E, TZDs, and obeticholic acid improve ballooning degeneration in patients with NASH. Future comparative trials of combination therapies targeting distinct histological features are warranted. (H epatology 2015;62:1417–1432)

Obstructive and central sleep apnea have been associated with increased risk of adverse cardiovascular events and mortality. Sympathetic dysregulation occurring as a result of the respiratory disturbance is thought to play a role in this increased risk. Sleep apnea increases the risk of arrhythmias, myocardial ischemia/infarction, stroke, and heart failure, all of which may increase mortality risk. A higher incidence of nocturnal arrhythmias, cardiac ischemia, and sudden death has been noted in subjects with sleep-disordered breathing (SDB). In this review, the association between SDB and each of these conditions is discussed, as well as the potential mechanisms underlying these risks and the effects of treatment of SDB. Particular emphasis is placed on the relationship between SDB and nocturnal atrial and ventricular arrhythmias, myocardial ischemia/infarction and sudden death.

Abstract Purpose: To determine the frequency and prognostic association of molecular markers by anatomic tumor site in patients with stage III colon carcinomas. Experimental Design: In a randomized trial of adjuvant FOLFOX ± cetuximab, BRAFV600E and KRAS (exon 2) mutations and DNA mismatch repair (MMR) proteins were analyzed in tumors (N = 3,018) in relationship to tumor location, including subsite. Cox models were used to assess clinical outcome, including overall survival (OS). Results: KRAS codon 12 mutations were most frequent at the splenic flexure and cecum; codon 13 mutations were evenly distributed. BRAF mutation frequency sharply increased from transverse colon to cecum in parallel with deficient (d) MMR. Nonmutated BRAF and KRAS tumors progressively decreased from sigmoid to transverse (all P < 0.0001). Significantly, poorer OS was found for mutant KRAS in distal [HR, 1.98; 95% confidence interval (CI), 1.49–2.63; P < 0.0001] versus proximal (1.25; 95% CI, 0.97–1.60; P = 0.079) cancers. BRAF status and outcome were not significantly associated with tumor site. Proximal versus distal dMMR tumors had significantly better outcome. An interaction test was significant for tumor site by KRAS (Padjusted = 0.043) and MMR (Padjusted = 0.010) for OS. Significant prognostic differences for biomarkers by tumor site were maintained in the FOLFOX arm. Tumor site was independently prognostic with a stepwise improvement from cecum to sigmoid (OS: Padjusted = 0.001). Conclusions: Mutation in BRAF or KRAS codon 12 was enriched in proximal cancers whereas nonmutated BRAF/KRAS was increased in distal tumors. Significant differences in outcome for KRAS mutations and dMMR were found by tumor site, indicating that their interpretation should occur in the context of tumor location. Clin Cancer Res; 21(23); 5294–304. ©2015 AACR.

Neoadjuvant treatment may result in better quality of life and functional status 1 year after diagnosis.

In this study, academic practice status and treatment year predicted use of adjuvant cisplatin-based chemotherapy.

Purpose: To report the use of an investigational stent-graft to treat an ascending aortic aneurysm in a patient with a heart transplant. Case Report: A 48-year-old man presented with a 3.5×1.5-cm saccular aneurysm in the mid anterior ascending aorta, abutting the sternum. The patient’s history was notable for placement of a left ventricular assist device followed by orthotopic heart transplantation 2 years prior to treat end-stage familial dilated cardiomyopathy. Under compassionate use, a custom-designed ascending aortic stent-graft (Zenith Ascend) was successfully delivered via an 18-F system and deployed just distal to the origin of the left main coronary artery under pulmonary artery catheter–guided rapid ventricular pacing. The patient was discharged the next day, and 6-month follow-up was unremarkable. Imaging at 5 months showed an excluded aneurysm sac with no endoleak or migration. Conclusion: The ideal ascending aortic stent-graft should be low profile, conformable to the arch anatomy, with short tip delivery system and a stepwise deployment mechanism that allows precise placement relative to the ostia of the coronary arteries and the innominate artery. This case illustrates the advancement of endovascular techniques to the most challenging segment of the aorta to decrease morbidity and mortality in high-risk patients.

OBJECT External ventricular drainage (EVD) after intraventricular hemorrhage (IVH) without symptomatic hydrocephalus is controversial. The object of this study was to examine indicators or the timeframe for hydrocephalus in patients not immediately treated with EVD after IVH. METHODS Records from 2007 to 2014 were searched for “intraventricular hemorrhage” or “IVH.” Inclusion criteria were IVH after intracerebral hemorrhage (ICH), trauma, tumor, or vascular anomalies. Exclusion criteria were IVH with more than minimal subarachnoid hemorrhage, catastrophic ICH, layering IVH only, or hydrocephalus treated immediately with EVD. IVH was measured with the modified Graeb Score (mGS). An mGS of 5 indicates a full ventricle with dilation. Statistics included chi-square, Student’s t-test, and Mann-Whitney tests; receiver operating characteristics; and uni- and multivariate logistic regression. RESULTS One hundred five patients met the criteria; of these, 30 (28.6%) required EVD. Panventricular IVH was the most common pattern (n = 49, 46.7%), with 25 of these patients (51%) requiring EVD. The median mGS was 18 ± 5.4 (range 12–29) and 9 ± 4.5 (range 2–21) in the EVD and No-EVD groups, respectively (p < 0.001). Factors associated with EVD were radiological hydrocephalus at presentation, midline shift > 5 mm, Glasgow Coma Scale (GCS) score < 8, mGS > 13, third ventricle mGS = 5, and fourth ventricle mGS = 5. On multivariate analysis, GCS score < 8 [4.02 (range 1.13–14.84), p = 0.032], mGS > 13 [3.83 (range 1.02–14.89), p = 0.046], and fourth ventricle mGS = 5 [5.01 (range 1.26–22.78), p = 0.022] remained significant. Most patients treated with EVD (n = 25, 83.3%) required it soon after presentation [6.4 ± 3.3 (range 1.5–14) hrs]. The remaining 5 patients (16.7%) had a delayed EVD requirement [70.7 ± 22.7 (range 50–104.5) hrs]. CONCLUSIONS In this study population, the risk for EVD was variable, but greater with mGS > 13, coma, and a dilated fourth ventricle. While the need for EVD occurs within the 1st day after IVH in most patients, a minority require EVD after 48 hours.

Abstract Background Hyposmia is common in Parkinson's disease (PD) and is also observed with normal aging. It can be ascertained through objective testing, but it is unclear whether patients are aware of deficits and whether this has implications for cognitive status. Methods Subjects in the Arizona Study of Aging and Neurodegenerative Disorders were studied with annual motor and cognitive testing with objective smell testing (University of Pennsylvania Smell Identification Test; UPSIT ) done every third year beginning in 2002. Those with a baseline UPSIT <25th percentile (hyposmia) were studied for presence of unawareness of hyposmia and cognitive status. Results There were 75 subjects with PD and 143 nonparkinsonian controls with hyposmia. Lack of awareness of hyposmia was present in 16% of PD subjects and 47% of those without PD . In PD , there was no increase in unawareness in PD with dementia. In non‐ PD controls, unawareness was correlated with presence of dementia. Unawareness of hyposmia correlated most strongly with the neuropsychiatric tests of learning and memory. In controls without dementia or PD , 48% were unaware. Conclusions Querying patients about anosmia might be useful in parkinsonian disorders without objective testing. However, in elderly controls, it should be followed by objective testing and lack of awareness has implications for worsened cognitive status.

PurposeTo describe how integrated gradient nonlinearity (GNL) correction can be used within noniterative partial Fourier (homodyne) and parallel (SENSE and GRAPPA) MR image reconstruction strategies, and demonstrate that performing GNL correction during, rather than after, these routines mitigates the image blurring and resolution loss caused by postreconstruction image domain based GNL correction.MethodsStarting from partial Fourier and parallel magnetic resonance imaging signal models that explicitly account for GNL, noniterative image reconstruction strategies for each accelerated acquisition technique are derived under the same core mathematical assumptions as their standard counterparts. A series of phantom and in vivo experiments on retrospectively undersampled data were performed to investigate the spatial resolution benefit of integrated GNL correction over conventional postreconstruction correction.ResultsPhantom and in vivo results demonstrate that the integrated GNL correction reduces the image blurring introduced by the conventional GNL correction, while still correcting GNL‐induced coarse‐scale geometrical distortion. Images generated from undersampled data using the proposed integrated GNL strategies offer superior depiction of fine image detail, for example, phantom resolution inserts and anatomical tissue boundaries.ConclusionNoniterative partial Fourier and parallel imaging reconstruction methods with integrated GNL correction reduce the resolution loss that occurs during conventional postreconstruction GNL correction while preserving the computational efficiency of standard reconstruction techniques. Magn Reson Med 75:2534–2544, 2016. © 2015 Wiley Periodicals, Inc.