Feras Zaiem

Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast–enhanced MRI, and gadoxetate‐enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow‐up with the same versus alternative imaging is best for CT‐indeterminate or MRI‐indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast–enhanced MRI or gadoxetate‐enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs <1 cm. No studies examined whether adults with cirrhosis and an indeterminate nodule are best evaluated using biopsy, repeated imaging, or alternative imaging. Concerns about publication bias, inconsistent study results, increased risk of bias, and clinical factors precluded support for exclusive use of either gadoxetate‐enhanced or extracellular contrast–enhanced MRI over CT. Conclusion: CT, extracellular contrast–enhanced MRI, or gadoxetate‐enhanced MRI could not be definitively preferred for HCC diagnosis in patients with cirrhosis; in patients with cirrhosis and an indeterminate mass, there were insufficient data comparing biopsy to repeat cross‐sectional imaging or alternative imaging. (Hepatology 2018;67:401‐421).

Therapies for Advanced Stage Hepatocellular Carcinoma with Macrovascular invasion or Metastatic Disease: a Systematic Review and Meta‐analysis

Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades, there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors, such as macrovascular invasion and extrahepatic spread (EHS). We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics, including patients with both Child‐Pugh (CP) scores of A and B. A comprehensive search of several databases from each database inception to February 15, 2016 any language was conducted. We included 14 studies (three randomized controlled studies [RCTs] and 11 observational studies). We included studies that compared sorafenib, transarterial bland embolization/transarterial chemoembolization, yttrium‐90/radiation therapy, ablation (or combination), and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in overall survival (OS) for patients with advanced HCC and metastatic vascular invasion (MVI) and/or EHS and CP A liver disease (hazard ratio, 0.66 [95% confidence interval, 0.51‐0.87]; I2 = 0%). Several observational studies evaluated locoregional therapies alone or in combination with other treatments and were limited by very‐low‐quality of evidence. This was true for both patients with EHS and MVI. Conclusion: In patients with advanced HCC and CP A liver function, sorafenib is the only treatment that has been shown to improve OS in randomized studies. High‐quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease, are lacking. (Hepatology 2018;67:422‐435)

Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta‐analysis

Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down‐staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow‐up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06‐1.85; I2 = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060‐2.370; I2 = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down‐staging therapy versus no downstaging, and this showed a significant increase in 1‐year (two studies, RR, 1.11; 95% CI, 1.01‐1.23) and 5‐year (1 study, RR, 1.17; 95% CI, 1.03‐1.32) post‐LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision. Conclusion: In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (Hepatology 2018;67:381‐400).

Comparative Effectiveness and Safety of Cognitive Behavioral Therapy and Pharmacotherapy for Childhood Anxiety Disorders: A Systematic Review and Meta-analysis

Importance Childhood anxiety is common. Multiple treatment options are available, but existing guidelines provide inconsistent advice on which treatment to use. Objectives To evaluate the comparative effectiveness and adverse events of cognitive behavioral therapy (CBT) and pharmacotherapy for childhood anxiety disorders. Data Sources We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus from database inception through February 1, 2017. Study Selection Randomized and nonrandomized comparative studies that enrolled children and adolescents with confirmed diagnoses of panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety and who received CBT, pharmacotherapy, or the combination. Data Extraction and Synthesis Independent reviewers selected studies and extracted data. Random-effects meta-analysis was used to pool data. Main Outcomes and Measures Primary anxiety symptoms (measured by child, parent, or clinician), remission, response, and adverse events. Results A total of 7719 patients were included from 115 studies. Of these, 4290 (55.6%) were female, and the mean (range) age was 9.2 (5.4-16.1) years. Compared with pill placebo, selective serotonin reuptake inhibitors (SSRIs) significantly reduced primary anxiety symptoms and increased remission (relative risk, 2.04; 95% CI, 1.37-3.04) and response (relative risk, 1.96; 95% CI, 1.60-2.40). Serotonin-norepinephrine reuptake inhibitors (SNRIs) significantly reduced clinician-reported primary anxiety symptoms. Benzodiazepines and tricyclics were not found to significantly reduce anxiety symptoms. When CBT was compared with wait-listing/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Cognitive behavioral therapy reduced primary anxiety symptoms more than fluoxetine and improved remission more than sertraline. The combination of sertraline and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone. Head-to-head comparisons were sparse, and network meta-analysis estimates were imprecise. Adverse events were common with medications but not with CBT and were not severe. Studies were too small or too short to assess suicidality with SSRIs or SNRIs. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine. Cognitive behavioral therapy was associated with fewer dropouts than pill placebo or medications. Conclusions and Relevance Evidence supports the effectiveness of CBT and SSRIs for reducing childhood anxiety symptoms. Serotonin-norepinephrine reuptake inhibitors also appear to be effective based on less consistent evidence. Head-to-head comparisons between various medications and comparisons with CBT represent a need for research in the field.

Morbidity and mortality of infective endocarditis in a hospital system in New York City serving a diverse urban population

Infective endocarditis (IE) is a severe illness associated with significant morbidity and mortality. The primary purpose of this study was to evaluate morbidity and mortality of IE in a hospital serving the most diverse area in New York City. An analysis of 209 patients admitted to the hospital from 2000 to 2012 who were found to have IE based on modified Duke criteria. Among the 209 patients with IE, 188 (88.8%) had native heart valves and 21 (11.2%) had prosthetic valves. Of the patients with native heart valves, 3.7% had coronary artery bypass graft, 4.3% were active drug users, 6.3% had permanent pacemakers, 12.2% had a history of IE, 25.7% were diabetic, 17% had end-stage renal disease (ESRD), 9% had congestive heart failure, 8% had abnormal heart valves, and 13.8% had an unknown etiology. Mortality rates of the patients with prosthetic heart valves were 27.7% compared to 8.11% in patients with native heart valves (OR 3, p<0.0001). Since we identified diabetes mellitus and ESRD to be significant risk factors in our population, we isolated and compared characteristics of patients with and without IE. IE among patients with diabetes mellitus was 23% compared with 13.8% in the control group (p=0.016). Cases of IE in patients with ESRD were 15.3%, compared with 4% in the control group (p<0.0001). We identified an overall mortality rate of 20.1% in patients with IE, a readmission rate within 30 days of discharge of 21.5%, and an average age of 59 years. Among 209 patients, 107 were males and 102 females. The most common organisms identified were Staphylococcus aureus (43.7%), viridans streptococci (17%) followed by Enterococcus (14.7%). Despite appropriate treatment, high rates of morbidity and mortality remained, with a higher impact in patients greater than 50 years of age. Such discoveries raise the importance of controlling and monitoring risk factors for IE.

Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study

Objective: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. Methods: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta‐analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. Results: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5‐48] RCTs per MA) with average follow‐up of 24 (range, 1‐168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12‐3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow‐up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow‐up or the test for publication bias. Conclusion: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution.

Cardiac amyloidosis: pathogenesis, clinical context, diagnosis and management options

Abstract Amyloidosis covers a group of disorders that can manifest in virtually any organ system in the body and is thought to be secondary to misfolding of extracellular proteins with subsequent deposition in tissues. The precursor protein that is produced in excess defines the specific amyloid type. This requires histopathological confirmation using Congo-red dye with its characteristic demonstration of green birefringence under cross-polarized light. There are three main types of amyloidosis associated with cardiac involvement: light-chain (AL), familial or senile (ATTR), and secondary (AA) amyloidosis. The frequency of cardiac involvement and prognosis varies among each type. Amyloid cardiomyopathy commonly manifests as heart failure and the presenting features are usually dyspnoea, oedema, angina, pre-syncope and syncope. The diagnosis of cardiac amyloidosis is very hard and can easily be misdiagnosed. Although the imaging studies (such as echocardiography and cardiovascular magnetic resonance) may guide the diagnosis, tissue biopsy is needed for confirmation. Management of cardiac amyloidosis initially is to treat the underlying heart failure. Pacemaker implantation is usually required in patients with any conduction abnormalities. Transplantation is the next step with worsening heart failure. However, the aim of any treatment in amyloidosis, irrespective of type, is to prevent further deposition of amyloid while managing concurrent symptoms. In this manuscript, we will discuss the pathogenesis of cardiac amyloidosis, diagnostic methods and management options.

Coronary Artery Disease in Young Adults

Abstract:Coronary heart disease (CHD) sustains a significant negative impact on hospital admissions and deaths worldwide. The prevalence of CHD in young adults is difficult to establish accurately, as these asymptomatic patients typically do not undergo diagnostic studies. In this article, the authors will focus on young adults with CHD emphasizing common and uncommon risk factors, current management and review of previous studies.

A systematic review of surveillance after endovascular aortic repair

Objective The objective of this systematic review and meta‐analysis was to evaluate the optimal modality and frequency of surveillance after endovascular aortic repair (EVAR) in adult patients with abdominal aortic aneurysms. Methods We searched for studies of post‐EVAR surveillance in MEDLINE In‐Process & Other Non‐Indexed Citations, MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Scopus through May 10, 2016. The outcomes of interest were endoleaks, mortality, limb ischemia, renal complications, late rupture, and aneurysm‐related mortality. Outcomes were pooled using a random‐effects model and were reported as incidence rate and 95% confidence interval. Results Of 1099 candidate references, we included 6 meta‐analyses and 52 observational studies. Complication rates were common after EVAR, particularly in the first year. Magnetic resonance imaging had a higher detection rate of endoleaks than computed tomography angiography. Doppler ultrasound had lower diagnostic accuracy, whereas contrast‐enhanced ultrasound was likely to be as sensitive as computed tomography angiography. The highest endoleak detection rates were in surveillance approaches that used combined tests. There were no studies that compared different surveillance intervals to determine optimal intervals; however, most studies reported detection rates of patient‐important outcomes at 1, 6, 12, 24, 36, 48, and 60 months. Data were insufficient to provide comparative inferences about the best strategy to reduce the risk of patient‐important outcomes, such as mortality, limb ischemia, rupture, and renal complications. Conclusions Several tests with reasonable diagnostic accuracy are available for surveillance after EVAR. The available evidence suggests a high complication rate, particularly in the first year, and provides a rationale for surveillance.

Muscle complex saving posterior sagittal anorectoplasty

INTRODUCTION Posterior sagittal anorectoplasty (PSARP) published by DeVries and Peña in 1982 had become the preferred surgical technique for the management of anorectal malformations (ARM). The original technique is based upon complete exposure of the anorectal region by means of a median sagittal incision that runs from the sacrum to the anal dimple, cutting through all muscle structures behind the rectum by dividing the levator muscle and the muscle complex. Then, the rectum is located in front of the levator and within the limits of the muscle complex. In this review, we described Muscle Complex Saving-Posterior Sagittal Anorectoplasty (MCS-PSARP), which is a less invasive technique that consists of keeping this funnel-shaped muscle complex completely intact and not divided, and pulling the rectum through this funnel, toward fixing the new anus to the skin. This technique aimed both to respect the lower part of the sphincter mechanism consisting of the muscle complex, and to avoid the disturbance of this important structure by dividing and resuturing it. METHODS We presented six cases of male patients who were born with anorectal malformation (ARM) and underwent MCS-PSARP. The surgical technique proved to be feasible to achieve the dissection of the rectal pouch and the division of the rectourethral fistula in all patients, by opening only the upper part of the sphincter mechanism, the levator muscle, and keeping the lower part consisting of intact muscle complex. RESULTS The early results in our series are encouraging; however, long-term functional outcomes of these patients are awaited. The surgical tips were also discussed. CONCLUSIONS This proposed approach in the management of anorectal malformation cases provides an opportunity to maximize preservation of the existing continence mechanisms. It preserves the muscle complex components of the levator muscle intact, allowing a better function of the continence mechanism.