Discrepancies between actual weight, weight perception and weight loss intention amongst persons with NAFLD.

BACKGROUND: Currently, weight loss remains the main management strategy for NAFLD, but the weight loss intention and methods remain poorly characterized. METHODS: We analysed data about the perception of weight status, intention and methods to lose weight amongst 3,822 persons with NAFLD (United States Fatty Liver Index ≥ 30) from the National Health and Nutrition Examination Survey, 2001-2014. RESULTS: Only 53.9% of people with NAFLD intended to lose weight, 91.8% with perception of overweight and 8.2% with normal weight perception. Persons with perception of overweight or overweight/obese status were four times more likely to try to lose weight (adjusted odds ratios 3.9 and 4.2, respectively, both P < 0.0001). Younger age, women, higher educational level, Hispanic and blacks (versus whites) were significant independent factors associated with weight loss intention. Notably, ≤10% attended weight loss programme. Metabolic equivalent of task hours per week was significantly higher in whites who exercised to lose weight (vs. no exercise, P = 0.003) but not in other racial/ethnic groups. Interestingly, calorie intake was similar between those who dieted versus not (2056 vs. 1970 kcal/day, P = 0.11). About 30% reported ≥ 10-lb weight loss, with 50% higher odds of success for men but there was no difference by race/ethnicity. CONCLUSION: Overweight or obese perception was a key driver in weight loss activities but was inconsistent with actual weight status and varied by race/ethnicity and other sociodemographic factors. Weight loss programme is under-utilized and should take in account of weight perception training and culturally appropriate approach.

Systematic review with meta-analysis: effectiveness and tolerability of interferon-free direct-acting antiviral regimens for chronic hepatitis C genotype 1 in routine clinical practice in Asia.

BACKGROUND: Direct-acting antiviral (DAA) regimens have shown high efficacy and tolerability for patients with HCV genotype 1/1b (GT1/1b) in clinical trials. However, robust real-world evidence of interferon (IFN)-free DAA treatment for HCV GT1-infected patients in Asia is still lacking. AIM: To systematically review and meta-analyse the effectiveness and tolerability of IFN-free DAA therapy for HCV GT1 infection in Asia. METHODS: We included studies that enrolled adult patients with HCV GT1 infection in routine clinical practice in Asia, using IFN-free DAA regimens, and reported sustained virological response (SVR) after 12/24 weeks end-of-treatment by 31 May 2017. The pooled SVR rates were computed with a random-effects model. Subgroup analysis and meta-regression as previously registered in PROSPERO were performed to determine how pre-planned variables might have affected the pooled estimates. RESULTS: We included 41 studies from eight countries and regions, comprising of 8574 individuals. The pooled SVR rates for GT1 were 89.9% (95% CI 88.6-91.1, I2  = 55.1%) with daclatasvir/asunaprevir (DCV/ASV) and 98.1% (95% CI 97.0-99.0, I2  = 41.0%) with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV). Baseline cirrhosis but not prior treatment history and age, attenuated the effectiveness of both regimens. Baseline resistance associated substitutions (RASs) severely attenuated SVR of DCV/ASV (65.4% vs 94.3%, P < 0.001) and only minimally with LDV/SOF ± RBV (94.5% vs 99.2%, P = 0.003). Patients with renal dysfunction treated with DCV/ASV showed a higher SVR rate (93.9% vs 89.8%, P = 0.046). Patients with hepatocellular carcinoma (HCC) LDV/SOF ± RBV achieved a lower SVR than those without HCC (94.1% vs 98.7%, P = 0.001). CONCLUSION: All oral DAA treatment of HCV GT1 resulted in high cure rates in Asian patients in routine clinical practice setting including elderly patients and those with end-stage renal disease.

Life-threatening Torsades de Pointes resulting from "natural" cancer treatment.

INTRODUCTION: Nonradioactive cesium chloride (CsCl) is used by some alternative medicine advocates as a treatment for cancer. The therapy was proven to be neither safe nor effective. Chronic use of CsCl has resulted in cases with severe cardiotoxicity. CASE REPORT: A 65-year-old lady presented to our hospital's accident and emergency department with recurrent syncope attacks. Electrocardiogram monitoring showed QT prolongation and transient Torsades de Pointes (TDP) ventricular tachycardia. She was taking anticancer naturopathic drugs for 6 weeks before admission. One of her naturopathic drugs was subsequently confirmed containing 89% CsCl by weight. Besides conventional treatment of QT prolongation and TDP, the patient was given a 4-week course of oral Prussian blue to enhance gastrointestinal elimination of cesium. The serum half-life of cesium was reduced from 61.7 to 29.4 days after the use of Prussian blue. QT prolongation was normalized in 27 days. DISCUSSION: To our knowledge, this is the first published case of nonradioactive cesium poisoning treated with Prussian blue. A transient rise in serum cesium level was observed during Prussian blue therapy. Possible explanations for this observation include poor drug compliance during outpatient treatment and redistribution of cesium from body stores. CONCLUSION: Nonradioactive CsCl poisoning can result in severe cardiotoxicity with QT prolongation and TDP ventricular tachycardia. The key points in the management of nonradioactive cesium poisoning include cessation of cesium exposure, vigorous electrolytes replacement, and oral Prussian blue therapy.

Monitoring of epithelial cell caspase activation via detection of durable keratin fragment formation.

Keratins 18 and 19 (K18/K19) are epithelial-specific intermediate filament proteins. Apoptosis induces caspase cleavage at the highly conserved K18 or K19 Asp237, which in K18 is preceded by cleavage at Asp396. We characterized the keratin N-terminal fragments that are generated upon caspase digestion of K18/K19 at Asp237 in order to study keratin dynamics during apoptosis. This was carried out by generating and characterizing antibodies selective to K18/K19 Asp237. K18 or K19 peptides that expose Asp237 in 234VEVD were used for rabbit immunization. The generated antibodies recognized cleaved but not intact K18/K19, exclusively, as determined by blotting or immunofluorescence staining of apoptotic human HT29 cells or livers isolated from Fas-Ab-injected mice. Antibodies to K18/K19 Asp237 recognized the common VEVD-motif as determined by immunoblotting of cells transfected with K18, K19 or K20. The K18/K19 VEVD-directed antibodies demonstrated sequential Asp396 then Asp237 K18 cleavage during apoptosis. Specific-keratin selectivity of the anti-Asp237 antibodies was confirmed by their inability to recognize K14 after UV-induced apoptosis in transfected cells. The Asp237-containing apoptotic keratin fragments are secreted into the medium of cultured HT29 cells and are stable up to 96 h after inducing apoptosis. Furthermore, the generated antibodies recognize keratin apoptotic fragments in sera of mice undergoing hepatocyte apoptosis and sera of patients with cirrhosis, and also recognize apoptotic cells in various epithelial human tumours. Therefore, the N-terminal caspase-generated K18 fragment is stable in tissues and biological fluids. The Asp237-directed antibodies provide a powerful tool to study apoptosis in human and mouse tissues, cells and serum, using a broad range of detection modalities.

Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of interferon and ribavirin*.

In previous hepatitis C virus (HCV) treatment studies, Black patients not only had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV) than non-Black patients but also a higher frequency of HCV genotype 1 (GT-1) infection. The aim of this community-based study was to determine whether Black patients have a lower SVR rate independent of genotype. We prospectively enrolled 785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon alpha-2b 3 MU three times weekly + RBV 1000-1200 mg/day for 24 weeks (GT-2/3) or 48 weeks (GT-1). Black patients were more commonly infected with GT-1 (86.8%vs 64.8%, P < 0.001) and less frequently had an SVR compared with non-Black patients (8.4%vs 21.6%, P < 0.001). Within GT-1, Black patients had a lower SVR rate than non-Black patients (6.1%vs 14.1%, P = 0.004) but not within GT-2/3 (50.0%vs 36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs 15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm(3), P < 0.001) and required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P < 0.001). Independent predictors of SVR were GT-1 [odds ratio (OR) 0.33; 95% confidence interval (CI) 0.20-0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22-0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31-0.92; P = 0.023). In conclusion, Black patients infected with HCV GT-1 (but not GT-2/3) have a lower SVR rate than non-Black patients. This is not explained by their lower baseline haemoglobin levels and neutrophil counts that lead to higher rates of ribavirin and interferon dose reductions.

Amantadine in treatment of chronic hepatitis C virus infection?

SUMMARY: Treatment of chronic hepatitis C (CHC) continues to be an important and growing challenge. As the response rate to FDA-approved treatment improved over the past decade, we are facing increasing number of difficult-to-treat patients such as those who have failed prior anti-viral therapy. The role of amantadine in the treatment of CHC remains unclear. Studies thus far have produced conflicting results, and type II error could not be excluded. This review summarized results published in the literature from 1997 to 2003, and reviewed the existing questions and controversies regarding the use of amantadine. Current literature suggests that amantadine is ineffective as monotherapy. Amantadine increased the sustained virologic response of certain treatment naïve patients when used in combination with interferon, and may be effective as an adjunct to interferon-based combination therapy in some patients who have failed or relapsed on prior therapy. Factors such as small sample size, patient characteristics, and differences in treatment protocols including amantadine preparation and duration of therapy might explain the conflicting observations of various studies. Further investigations are needed to define optimal dosing and formulation of amantadine, and its appropriate role in management of CHC infection.

Compound odontoma associated with an unerupted and dilacerated maxillary primary central incisor in a young patient.

The occurrence of odontoma in the primary dentition is uncommon. There are very few reports of non-eruption of a dilacerated primary tooth in the literature. A rare case of compound odontoma in association with an unerupted dilacerated maxillary primary incisor in a young patient is reported. There was also a developing supernumerary tooth in the vicinity of the odontoma. The clinical features and management of these conditions are discussed. The relevant literature is reviewed. A possible causal relationship between odontoma and dilaceration is highlighted.

Electrospray ionisation mass spectrometry: principles and clinical applications.

This mini-review provides a general understanding of electrospray ionisation mass spectrometry (ESI-MS) which has become an increasingly important technique in the clinical laboratory for structural study or quantitative measurement of metabolites in a complex biological sample. The first part of the review explains the electrospray ionisation process, design of mass spectrometers with separation capability, characteristics of the mass spectrum, and practical considerations in quantitative analysis. The second part then focuses on some clinical applications. The capability of ESI-tandem-MS in measuring bio-molecules sharing similar molecular structures makes it particularly useful in screening for inborn errors of amino acid, fatty acid, purine, pyrimidine metabolism and diagnosis of galactosaemia and peroxisomal disorders. Electrospray ionisation is also efficient in generating cluster ions for structural elucidation of macromolecules. This has fostered a new and improved approach (vs electrophoresis) for identification and quantification of haemoglobin variants. With the understanding of glycohaemoglobin structure, an IFCC reference method for glycohaemoglobin assay has been established using ESI-MS. It represents a significant advancement for the standardisation of HbA1c in diabetic monitoring. With its other applications such as in therapeutic drug monitoring, ESI-MS will continue to exert an important influence in the future development and organisation of the clinical laboratory service.

Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis.

The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.

Delayed fatal hemorrhage from pseudoaneurysm of the hepatic artery after percutaneous liver biopsy.

Hemorrhage is the most common serious complication of percutaneous liver biopsy. Liver biopsy is usually done in an outpatient setting because most significant hemorrhage is evident within a few hours after biopsy. Delayed hemorrhage occurs much less frequently but carries a much higher mortality. We present a 41-yr-old man with chronic hepatitis C who underwent a percutaneous liver biopsy uneventfully but was found to have a pseudoaneurysm of the hepatic artery 5 days later. Shortly after admission, the patient experienced bleeding into the liver from the pseudoaneurysm, which was controlled initially by angiographic embolization. However, recurrent bleeding could not be controlled by repeat angiography and surgical intervention, and the patient expired. The diagnosis and management of pseudoaneurysm of the hepatic artery complicating liver biopsy is reviewed.

Endoscopic gastrointestinal manifestations of liver disease.

Esophageal and gastric varices are common manifestations of advanced chronic liver disease, but other endoscopic gastrointestinal manifestations of portal hypertension may occur. In the upper gastrointestinal tract, portal hypertensive gastropathy, particularly when severe, and gastric antral vascular ectasias are important alternative causes of gastrointestinal bleeding. Portal hypertensive enteropathy is an uncommon source of gastrointestinal bleeding, and its overall clinical significance remains unknown. In the lower gastrointestinal tract, portal hypertension may be associated with hemorrhoids, anorectal varices, and portal hypertensive colopathy, all of which are occasional causes of gastrointestinal bleeding.

Mercury intoxication presenting with tics.

A 5 year old Chinese boy presented with recurrent oral ulceration followed by motor and vocal tics. The Chinese herbal spray he used for his mouth ulcers was found to have a high mercury content. His blood mercury concentration was raised. Isolated tics as the sole presentation of mercury intoxication has not previously been reported.

Management of gallstones and their complications.

The accurate differentiation of gallstone-induced biliary colic from other abdominal disease processes is the most crucial step in the successful management of gallstone disease. Despite the availability of many imaging techniques to demonstrate the presence of gallstones, clinical judgment ultimately determines the association of symptoms with cholelithiasis and its complications. Adult patients with silent or incidental gallstones should be observed and managed expectantly, with few exceptions. In symptomatic patients, the intervention varies with the type of gallstone-induced complication. In this article, we review the salient clinical features, diagnostic tests and therapeutic options employed in the management of gallstones and their complications.

Epidemiology of hepatitis C virus infection in American veterans.

OBJECTIVE: This study reports the findings of hepatitis C virus (HCV) infection in a large Department of Veterans Affairs Health Care System in suburban Northern California. METHODS: All veterans who had anti-HCV (EIA II) tested during a 6-yr period (7/92 to 6/98) were included in this study. To estimate the seroprevalence of anti-HCV among our population, 126 consecutive bloodborne pathogen exposure accidents were studied. RESULTS: Of 8558 veterans tested for anti-HCV (EIA II), 2985 (35%) veterans were positive with a mean age of 48.4 yr (range, 28-89 yr). Sixty percent were between the age of 41 and 50 yr. Risk factors for HCV infection identified in 409 consecutive veterans were intravenous drug abuse (81%), unknown (11%), blood transfusion (3%), sexual/household contact (2%), transfusion and intravenous drug use (2%), and tattoo (1%). Of 215 consecutive anti-HCV-positive veterans whose sera were tested by polymerase chain reaction, 96% were viremic. The most common HCV genotypes were 1a (50.5%), 1b (22.8%), 3a (12.1%), 2b (9.7%), 2a (1.9%), undetermined (1.9%), and mixed infection (1%). Veterans infected with genotype 1b were significantly older. Among 126 consecutive bloodborne pathogen exposure accidents, hepatitis C serology was available for 72 index veterans involved in the accidents and 18% were positive. CONCLUSIONS: We found the epidemiology of hepatitis C infection was different in the veteran population when compared to other published data on nonveterans. Hepatitis C infection was much more common among veteran, within a very narrow age distribution and intravenous drug use was the major risk factor.

Differential diagnosis of gallstone-induced complications.

Early recognition and prompt intervention are the most crucial steps in the management of gallstone-induced biliary disease. Many conditions can mimic the presentation of gallstone-induced complications. Therefore, participation of a clinically astute physician is essential in evaluating symptoms and interpreting diagnostic data in patients with symptomatic gallstones.

Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.

UNLABELLED: Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. BACKGROUND: In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients. METHODS: After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine). RESULTS: In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006). CONCLUSION: In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.

Long-term benzodiazepine users--characteristics, views and effectiveness of benzodiazepine reduction information leaflet.

OBJECTIVE: The authors looked at the clinical characteristics of long-term benzodiazepine users and how they viewed their use of benzodiazepine. We also examined the effectiveness of a self-help leaflet on reducing benzodiazepine use. METHOD: One hundred and nine long-term benzodiazepine users (daily use for more than 1 year) were assessed. Their perceived beneficial and undesirable effects of benzodiazepine and intention to reduce benzodiazepine use were studied and their history of benzodiazepine use was obtained. Psychiatric diagnosis and medical history were reviewed. A self-help leaflet was provided to 56 users whose anxiety symptoms were assessed to have been under control. We re-examined these 56 users 3 months later on their use of benzodiazepine and anxiety levels. RESULTS: The 109 long-term benzodiazepine users used a therapeutic dose of benzodiazepine (median: 10 mg diazepam equivalent) regularly for a median of 9 years (range: 1-40). Most of the users found benzodiazepine helpful and only 11% of them reported undesirable side effects. Half of the 109 subjects refused to reduce the dosage. Most of the subjects still experienced significant anxiety despite the use of benzodiazepine. Fourteen of the 56 subjects provided with a self-help leaflet were able to reduce a median of 2.5 mg of diazepam equivalent when re-examined after 3 months. CONCLUSION: The results are compared with previous studies in Western societies and are discussed in the light of clinical management of patients with anxiety disorders.