Seasonal variability of ocean circulation near the Dotson Ice Shelf, Antarctica.

Recent rapid thinning of West Antarctic ice shelves are believed to be caused by intrusions of warm deep water that induce basal melting and seaward meltwater export. This study uses data from three bottom-mounted mooring arrays to show seasonal variability and local forcing for the currents moving into and out of the Dotson ice shelf cavity. A southward flow of warm, salty water had maximum current velocities along the eastern channel slope, while northward outflows of freshened ice shelf meltwater spread at intermediate depth above the western slope. The inflow correlated with the local ocean surface stress curl. At the western slope, meltwater outflows followed the warm influx along the eastern slope with a ~2-3 month delay. Ocean circulation near Dotson Ice Shelf, affected by sea ice distribution and wind, appears to significantly control the inflow of warm water and subsequent ice shelf melting on seasonal time-scales.

Adaptive architecture and mechanoresponse of epithelial cells on a torus.

Curvature is a geometric feature widely observed in the epithelia and critical to the performance of fundamental biological functions. Understanding curvature-related biophysical phenomena remains challenging partly owing to the difficulty of quantitatively tuning and measuring curvatures of interfacing individual cells. In this study, we prepared confluent wild-type Madin-Darby canine kidney cells on a torus structure presenting positive, zero, and negative Gaussian curvatures with a tubule diameter of 2-7 cells and quantified the mechanobiological characteristics of individual cells. Cells on the torus surface exhibited topological sensing ability both as an individual cell and collective cell organization. Both cell bodies and nuclei, adapted on the torus, exhibited local Gaussian curvature-dependent preferential orientation. The cells on the torus demonstrated significant adjustment in the nuclear area and exhibited asymmetric nuclear position depending on the local Gaussian curvature. Moreover, cells on top of the torus, where local Gaussian curvature is near zero, exhibited more sensitive morphological adaptations than the nuclei depending on the Gaussian curvature gradient. Furthermore, the spatial heterogeneity of intermediate filament proteins related to mechanoresponsive expression of the cell body and nucleus, vimentin, keratin and lamin A, revealed local Gaussian curvature as a key factor of cellular adaptation on curved surfaces.

Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors in the treatment of type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: This review evaluated the efficacy and safety of a combination therapy comprising a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) in type 2 diabetes. METHODS: A literature search through to May 2017 was carried out of PubMed, Embase and the Cochrane Central Register of Controlled Trials. Studies were eligible if they were randomized controlled trials (RCTs) comparing SGLT2i plus DPP4i (SGLT2i/DPP4i) against DPP4i±placebo or SGLT2i±placebo and published in English. The primary outcome was change in HbA1c from baseline. RESULTS: Eight RCTs comparing SGLT2i/DPP4i and DPP4i, and five RCTs comparing SGLT2i/DPP4i and SGLT2i, with three RCTs involving both comparisons, were included in the present review. SGLT2i/DPP4i resulted in a greater mean HbA1c reduction [weighted mean difference (WMD]): -0.62%] than did DPP4i alone, which was a much less marked reduction (WMD: -0.35%) than with SGLT2i alone. Also, significant differences in body weight loss from baseline were observed only with SGLT2i/DPP4i vs. DPP4i, but not vs. SGLT2i. The risk of hypoglycaemic events was low and similar between treatment groups. When subjects were stratified based on baseline HbA1c, any reduction by SGLT2i/DPP4i in relation to DPP4i was proportional to baseline HbA1c levels. However, compared with SGLT2i, HbA1c reductions with SGLT2i/DPP4i were modest regardless of baseline HbA1c. CONCLUSION: Combination therapy with SGLT2i and DPP4i is both efficacious and safe. In particular, a marked additional glucose-lowering effect is evident when SGLT2i is combined with or added to DPP4i, and not vice versa. However, baseline HbA1c determined the additional glucose-lowering effects of SGLT2i in combined treatment with DPP4i.

CUT-PCR: CRISPR-mediated, ultrasensitive detection of target DNA using PCR.

Circulating tumor DNA (ctDNA) has emerged as a tumor-specific biomarker for the early detection of various cancers. To date, several techniques have been devised to enrich the extremely small amounts of ctDNA present in plasma, but they are still insufficient for cancer diagnosis, especially at the early stage. Here, we developed a novel method, CUT (CRISPR-mediated, Ultrasensitive detection of Target DNA)-PCR, which uses CRISPR endonucleases to enrich and detect the extremely small amounts of tumor DNA fragments among the much more abundant wild-type DNA fragments by specifically eliminating the wild-type sequences. We computed that by using various orthologonal CRISPR endonucleases such as SpCas9 and FnCpf1, the CUT-PCR method would be applicable to 80% of known cancer-linked substitution mutations registered in the COSMIC database. We further verified that CUT-PCR together with targeted deep sequencing enables detection of a broad range of oncogenes with high sensitivity (<0.01%) and accuracy, which is superior to conventional targeted deep sequencing. In the end, we successfully applied CUT-PCR to detect sequences with oncogenic mutations in the ctDNA of colorectal cancer patients' blood, suggesting that our technique could be adopted for diagnosing various types of cancer at early stages.

The 100 Most-Cited Articles Focused on Ultrasound Imaging: A Bibliometric Analysis.

Purpose The number of citations that an article has received reflects its impact on a particular research area. The aim of this study was to identify the 100 most-cited articles focused on ultrasound (US) imaging and to analyze the characteristics of these articles. Methods We determined the 100 most-cited articles on US imaging via the Web of Science database, using the search term. The following parameters were used to analyze the characteristics of the 100 most-cited articles: publication year, journal, journal impact factor, number of citations and annual citations, authors, department, institution, country, type of article, and topic. Results The number of citations for the 100 most-cited articles ranged from 1849 to 341 (median: 442.0) and the number of annual citations ranged from 108.0 to 8.1 (median: 22.1). The majority of articles were published in 1990 - 1999 (39 %), published in radiology journals (20 %), originated in the United States (45 %), were clinical observation studies (67 %), and dealt with the vessels (35 %). The Department of Internal Medicine at the University of California and the Research Institute of Public Health at the University of Kuopio (n = 4 each) were the leading institutions and Salonen JT and Salonen R (n = 4 each) were the most prolific authors. Conclusion Our study presents a detailed list and analysis of the 100 most-cited US articles, which provides a unique insight into the historical development in this field.

Associations of High-Dose Melphalan Pharmacokinetics and Outcomes in the Setting of a Randomized Cryotherapy Trial.

High-dose melphalan followed by autologous stem cell transplantation remains the standard of care for eligible patients with multiple myeloma, but disease response and toxicity, including severe mucositis, varies among patients. Our randomized trial investigated duration of cryotherapy (2 and 6 h) for reduction of mucositis prevalence and severity and explored factors associated with variability in pharmacokinetics and outcomes from melphalan therapy. The results demonstrate that 2-h is at least as effective as 6-h cryotherapy in decreasing severe mucositis. From a population pharmacokinetic model, we identified that fat-free mass, hematocrit, and creatinine clearance were significant covariates, as reported previously. Furthermore, we observed the rs4240803 SLC7A5 polymorphism was significantly associated with pharmacokinetic variability, and pharmacokinetics was associated with both mucositis and neutropenia. However, melphalan exposure was not associated with progression-free or overall survival in our dataset. These findings contribute to ongoing efforts to personalize melphalan dosing in transplant patients.

Percutaneous radiofrequency ablation for symptomatic uterine leiomyomas: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) in the treatment of uterine leiomyomas. MATERIALS AND METHODS: Medline, Embase, and Cochrane databases were searched through August 2014 for all relevant studies on RFA for uterine leiomyomas. The efficacy and safety of RFA were assessed using the outcome measures of tumor volume, symptom severity score, health-related quality of life (HRQL) score, procedure-related complications, and reintervention. The authors calculated pooled event rates with 95% confidence intervals using random-effects model to assess the effects of RFA. RESULTS: Eight observational studies were identified as eligible for inclusion in this meta-analysis and included 370 patients. All analyzed outcomes showed statistically significant improvements from baseline to final follow-up. Twenty-seven complications were identified and five of them qualified as major complications. Five patients required reintervention after RFA. CONCLUSIONS: Percutaneous RFA is an effective and safe treatment for patients with uterine leiomyomas.

Long-term follow up of HIV-1-infected Korean haemophiliacs, after infection from a common source of virus.

In the early 1990s, 20 haemophiliacs (HPs) were infected with a common source of HIV-1 viruses through the contaminated clotting factor IX. The aim of this study is to review 20 HPs infected with a common source of virus. The enrolled patients have been consecutively treated with Korean red ginseng (KRG), zidovudine (ZDV) or two-drug therapy and highly active antiretroviral therapy (HAART). We determined full-length pol gene over 20 years and human leukocyte antigen (HLA) class I with peripheral blood mononuclear cells and reviewed medical records. Eighteen HPs experienced various opportunistic infections or clinical manifestations. There were significant inverse correlations between the HLA prognostic score and the annual decrease in CD4+ T-cell counts prior to HAART (AD) (P < 0.05) and the amount of KRG and the AD (P < 0.01). From 1998, the HPs had been treated with HAART. Each of the two patients died without and with HAART regimen respectively. At present, 16 HPs have been alive with HAART. Among the 16 HPs, 12 and 4 are on HAART-plus-KRG and HAART only respectively. Eleven HPs including 2 HPs with G-to-A hypermutations had revealed resistance mutations. Ten and two HPs have shown poor adherence and incomplete viral suppres-sion on HAART respectively. Virological failure based on WHO guidelines was not observed on KRG-plus-HAART. Two HPs revealed additional resistance mutations against two classes on KRG-plus-HAART. As a nationwide study, we first report overall features on clinical course of Korean haemophiliacs. Further education on the importance of drug adherence is needed.

Staging accuracy of endoscopic ultrasound performed by nonexpert endosonographers in patients with resectable esophageal squamous cell carcinoma: is it possible?

The accuracy of endoscopic ultrasound (EUS) is operator-dependent. According to learning curve study, the accuracy of EUS T-staging for esophageal cancer has been reported to be greater in an investigator who had performed at least 100 EUS examinations. We determined comparative study regarding T-staging accuracy of EUS for esophageal squamous cell carcinoma between expert and nonexpert endoscopic ultrasonographers. We retrospectively identified 73 consecutive patients with esophageal squamous cell carcinoma who underwent EUS and endoscopic mucosal resection, endoscopic submucosal dissection, or surgery. EUS was performed by expert (Group 1) and nonexpert (Group 2) endoscopic ultrasonographers in multitertiary hospitals. Groups 1 and 2 were 37 and 36 patients during 2005-2011, respectively. Forty-two patients (57.5%) of the overall patients underwent surgical exploration. Correct endoscopic ultrasonographic T-staging of Group 1 was observed in 34 (91.9%) patients, while that of Group 2 was observed in 26 (72.2%) patients. And there was significant difference in correct endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.035). The incorrect endoscopic ultrasonographic T-staging of Group 1 were three cases that were overstaging (8.1%), but in Group 2 there were seven overstaging (19.4%) and three understaging (8.3%). There was no significant difference in overstaging or understaging of incorrect endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.528). This study first provides evidence that endoscopic ultrasonographic T-staging of nonexpert endoscopic ultrasonographers was inferior to be correct, compared with that of expert endoscopic ultrasonographers. EUS staging for esophageal cancer should be performed by expert endoscopic ultrasonographers to provide appropriate management strategy.

EFFECTS OF RESISTANCE EXERCISES AND COMPLEX DECONGESTIVE THERAPY ON ARM FUNCTION AND MUSCULAR STRENGTH IN BREAST CANCER RELATED LYMPHEDEMA.

The incorporation of resistance exercises into the lifestyle of patients with lymphedema is understudied and an emerging interest. We investigated the effectiveness and results of adding a moderate intensity resistance exercise program for 8 weeks in conjunction with intensive CDT for 1 or 2 weeks (depending on severity) on arm volume, arm function, QOL, and muscular strength in patients with breast cancer-related lymphedema. This prospective, pilot trial included forty-four patients with a history of breast cancer who were beginning complex decongestive therapy for lymphedema. They were assigned to either the intervention (n = 22) or control (n = 22). groups. The intervention comprised of resis- tance band exercises 5 times a week for 8 weeks. These were initially supervised during the intensive lymphedema treatment, but performed independently during the study period. Limb volume, muscular strength, and the European Organization for Research and Treatment of Cancer QOL Questionnaire C30 (EORTC QLQ-C30), EORTC-Breast Cancer-Specific QOL Questionnaire (EORTC QLQ-BR23), and Disabilities of Arm, Shoulder, and Hand (DASH) questionnaires were assessed at baseline and at 8 weeks. After 8 weeks, the intervention group demonstrated statistically significant differences (p < 0.05) in the DASH score and muscular strength compared to the control group. Our results indicate that upper body resistance exercise demonstrates a positive effect on arm function and muscular strength without increasing arm volume in breast cancer related lymphedema during and shortly post intensive CDT lymphedema treatment.

Clinical characteristics predicting early clinical failure after 72 h of antibiotic treatment in women with community-onset acute pyelonephritis: a prospective multicentre study.

In patients with community-onset acute pyelonephritis (CO-APN), assessing the risk factors for poor clinical response after 72 h of antibiotic treatment (early clinical failure) is important. The objectives of this study were to define those risk factors, and to assess whether early clinical failure influences mortality and treatment outcomes. We prospectively collected the clinical and microbiological data of women with CO-APN in South Korea from March 2010 to February 2012. The numbers of cases in the early clinical success and early clinical failure groups were 840 (79.1%) and 222 (20.9%), respectively. Final clinical failure and mortality were higher in the early clinical failure group than in the early clinical success group (14.9% vs 2.3%, p <0.001; 6.8% vs 0.1%, p 0.001, respectively). In a multiple logistic regression model, the risk factors for early clinical failure among the total 1062 patients were diabetes mellitus (OR 1.5; 95% CI 1.1-2.1), chronic liver diseases (OR 3.3; 95% CI 1.6-6.7), malignancy (OR 2.2; 95% CI 1.1-4.4), Pitt score ≥2 (OR 2.5; 95% CI 1.6-3.8), presence of azotaemia (OR 1.8; 95% CI 1.2-2.7), white blood cell count ≥20 000/mm(3) (OR 2.5; 95% CI 1.6-4.0), serum C-reactive protein level ≥20 mg/dL (OR 1.7; 95% CI 1.2-2.4), and history of antibiotic usage within the previous year (OR 1.5; 95% CI 1.1-2.2). Analysing the subgroup of 743 patients with CO-APN due to Enterobacteriaceae, fluoroquinolone resistance of the uropathogen was another factor associated with early clinical failure (OR 1.7; 95% CI 1.1-2.5). Simple variables of underlying diseases, previous antibiotic usage and initial laboratory test outcomes can be used to decide on the direction of treatment in CO-APN.

Regional long-term model of radioactivity dispersion and fate in the Northwestern Pacific and adjacent seas: application to the Fukushima Dai-ichi accident.

The compartment model POSEIDON-R was modified and applied to the Northwestern Pacific and adjacent seas to simulate the transport and fate of radioactivity in the period 1945-2010, and to perform a radiological assessment on the releases of radioactivity due to the Fukushima Dai-ichi accident for the period 2011-2040. The model predicts the dispersion of radioactivity in the water column and in sediments, the transfer of radionuclides throughout the marine food web, and subsequent doses to humans due to the consumption of marine products. A generic predictive dynamic food-chain model is used instead of the biological concentration factor (BCF) approach. The radionuclide uptake model for fish has as a central feature the accumulation of radionuclides in the target tissue. The three layer structure of the water column makes it possible to describe the vertical structure of radioactivity in deep waters. In total 175 compartments cover the Northwestern Pacific, the East China and Yellow Seas and the East/Japan Sea. The model was validated from (137)Cs data for the period 1945-2010. Calculated concentrations of (137)Cs in water, bottom sediments and marine organisms in the coastal compartment, before and after the accident, are in close agreement with measurements from the Japanese agencies. The agreement for water is achieved when an additional continuous flux of 3.6 TBq y(-1) is used for underground leakage of contaminated water from the Fukushima Dai-ichi NPP, during the three years following the accident. The dynamic food web model predicts that due to the delay of the transfer throughout the food web, the concentration of (137)Cs for piscivorous fishes returns to background level only in 2016. For the year 2011, the calculated individual dose rate for Fukushima Prefecture due to consumption of fishery products is 3.6 µSv y(-1). Following the Fukushima Dai-ichi accident the collective dose due to ingestion of marine products for Japan increased in 2011 by a factor of 6 in comparison with 2010.

Clinical characteristics of community-acquired acute pyelonephritis caused by ESBL-producing pathogens in South Korea.

OBJECTIVES: The aim of this study was to determine the risk factors and clinical characteristics of community-acquired acute pyelonephritis (CA-APN) caused by extended-spectrum ß-lactamase (ESBL)-producing organisms. METHODS: From March 2010 to February 2011, patients with CA-APN were recruited in 11 hospitals in South Korea. Clinical and microbiological data were collected prospectively, and the ESBLs and multilocus sequence types of the ESBL-producing Escherichia coli were characterized. Comparison between CA-APN caused by ESBL-producing Enterobacteriaceae and those by non-ESBL-producing organisms was performed. RESULTS: A total of 566 patients were recruited. Enterobacteriaceae were detected in 526 patients. Forty-six isolates (46/526, 8.7 %) were positive for ESBLs. Clinical and microbiological failure did not differ between the two groups, despite there being fewer patients with ESBL-positive isolates provided with appropriate antibiotics initially (19.6 vs. 93.8 %, p < 0.001). However, the duration of hospitalization was longer in the ESBL group (10.5 vs. 7.0 days, p = 0.012). In a logistic regression model, Charlson score ≥1 point [odds ratio (OR) 3.4, 95 % confidence interval (CI) 1.6-7.0, p = 0.001], antibiotics usage during the previous year (OR 3.1, 95 % CI 1.4-7.2, p = 0.008), and urinary catheterization during the previous month (OR 4.4, 95 % CI 1.1-17.6, p = 0.035) were associated with the risks of CA-APN by ESBL producers. CTX-M-15 (48 %) and CTX-M-14 (38 %) were the most common ESBLs. ST131 was the most common clone (7/24, 29.1 %), which was more frequently resistant to cefepime, fosfomycin, and temocillin. CONCLUSIONS: The risk factors for CA-APN by ESBL producers were Charlson score ≥1 point, antibiotics usage during the previous year, and urinary catheterization during the previous month.

The clinical characteristics of gastroesophageal reflux disease in patients with laryngeal symptoms who are referred to gastroenterology.

The prevalence of gastroesophageal reflux disease (GERD) has increased recently in Asia-Pacific countries. However, little is known about its prevalence and clinical characteristics in GERD patients with atypical symptoms in Asia. The aim of this study was to investigate the clinical characteristics of GERD in patients who had laryngeal symptoms in Korea. Data were gathered retrospectively from patients who presented with atypical symptoms, such as throat discomfort, globus pharyngeus, hoarseness, and chronic cough. They underwent a 24-hour ambulatory intraesophageal pH monitoring and filled in a validated reflux questionnaire. Overall, 128 patients (36 men and 92 women) with laryngeal symptoms were included. Of these 128, 43 patients (34%) had erosive esophagitis or pathological reflux from 24-hour ambulatory pH monitoring, and 24 (19%) had a positive Bernstein test or positive symptom index from 24-hour pH monitoring. Sixty-one patients (48%) had no evidence of reflux esophagitis on upper endoscopy and pathological acid reflux on 24-hour pH monitoring. Fifty-six patients (44%) had weekly heartburn or regurgitation. Typical symptoms and dyspepsia were significantly more common in patients with GERD who had laryngeal symptoms than non-GERD. Fifty-two percent of patients had laryngeal symptoms that were associated with GERD. The presence of typical reflux symptoms and dyspepsia are risk factors for GERD in patients who present with laryngeal symptoms.

Comparison of bolus transit patterns identified by esophageal impedance to barium esophagram in patients with dysphagia.

Bolus transit through the esophagus has not been validated by videoesophagram in patients with dysphagia and changes in impedance with abnormal barium transit have not been described in those patients. The aim of this study was to compare esophageal impedance findings with barium esophagram measurements in patients with dysphagia. The consecutive patients with dysphagia underwent conventional multichannel esophageal impedance manometry, after which a barium videoesophagram was performed simultaneously with multichannel esophageal impedance manometry using a mean of three swallows of barium. Esophageal emptying patterns shown in the esophagogram were classified by the degree of intraesophageal stasis and presence of intraesophageal reflux. Bolus transit patterns in impedance were classified as complete and incomplete transit. Sixteen patients (M : F = 8 : 8, mean age, 47 years) were enrolled. Their manometric diagnosis were normal (n= 6), ineffective esophageal motility (n= 1), diffuse esophageal spasm (DES; n= 2), and achalasia (n= 7). Sixty-three swallows were analyzed. According to impedance analysis, 21/22 swallows with normal barium emptying showed complete transit (96%) and 31/32 swallows with severe stasis showed incomplete transit (97%). Nine swallows with mild stasis showed either complete or incomplete transit patterns in impedance. Swallows with mild barium stasis and complete transit in impedance were observed in patients who had received treatment (two patients with achalasia with history of esophageal balloonplasty and a patient with DES after nifedipine administration). Impedance reflected severe stasis with retrograde barium movement and described typical bolus transit patterns in patients with achalasia and DES. In conclusion, impedance-barium esophagram concordance is high for swallows with normal esophageal emptying and for severe barium stasis in patients with dysphagia.

Molecular evidence of HIV-1 transmission in 20 Korean individuals with haemophilia: phylogenetic analysis of the vif gene.

To assess whether a genetic relationship exists between the viruses infecting HIV-positive patients with haemophilia and those infecting plasma donors, we determined the vif sequences in 169 individuals, including 20 haemophilia patients, 3 plasma donors, and 146 local controls. Twenty haemophilia patients were diagnosed with HIV-1 at 1-2 years after exposure to factor IX (FIX) manufactured in Korea, beginning in 1989-1990. Plasma samples from donors O and P were used to manufacture clotting factors including FIX used to treat the 20 haemophiliacs. The vif gene from frozen stored serum samples obtained 1-3 years after diagnosis was amplified by RT-PCR, and subjected to direct sequencing. Phylogenetic analysis revealed that vif sequences from 128 of the samples (including haemophilia patients and donors) belonged to the Korean subclade of HIV-1 subtype B (KSB). Sequences from 41 other participants were identified as subtype B, but outside the Korean subclade. Sequences of the vif gene from donors O and P plus the 20 individuals with haemophilia comprised two subclusters within KSB. In addition, signature pattern analysis disclosed the presence of conserved nucleotides at two positions in donors and haemophiliacs only. Together with information on KSB, dates of plasma donations and seroconversion of haemophilia patients, our results suggest that the haemophiliacs examined here became infected by viruses in the domestic clotting factor used for treatment.

Experimental lung collapse following deployment of a self-expandable bronchial occluder in a rabbit model.

OBJECTIVES: Closure of a bronchopleural fistula is required to prevent fatal empyema or aspiration pneumonia. The purpose of this study was to determine the feasibility and efficacy of bronchial occlusion with a self-expandable occluder to induce experimental lung collapse in a rabbit model. METHODS: 10 bronchial occluders (wine glass appearance; 8 mm in diameter and 15 mm in length) were implanted in the native left main bronchi of 10 rabbits via an endotracheal route. We analysed the following: (1) diameters and morphological changes of the bronchial occluders during follow-up; (2) percentage volume of the collapsed lung during follow-up; and (3) complications and gross pathology. 1-day and 2-week follow-up CT scans were routinely obtained. Rabbits were sacrificed 4 weeks after the experiment. RESULTS: In all 10 rabbits, the bronchial occluders were successfully implanted and were completely expanded within 2 weeks. Complete collapse of the left lung occurred in three rabbits on day 1 and in an additional two rabbits 2 weeks following implantation. Two other rabbits maintained the percentage volume of the collapsed lung between 51% and 99% during follow-up; the other three rabbits had <50% during follow-up. Pneumothoraces occurred in nine rabbits, but completely resolved at the 2-week follow-up. Right lung herniation across the midline progressed 2 weeks after occluder implantation. CONCLUSION: Placement of self-expandable occluders in a rabbit bronchus model was feasible and showed a potential to induce artificial lung collapse. While pneumothoraces were common, they resolved during follow-up.

Impact of non-alcoholic fatty liver disease on microalbuminuria in patients with prediabetes and diabetes.

BACKGROUND: It is unknown whether microalbuminuria is associated with non-alcoholic fatty liver disease (NAFLD) among patients with prediabetes and type 2 diabetes mellitus (DM). This study investigated the association of NAFLD with microalbuminuria among patients with prediabetes and diabetes. METHODS: We evaluated 1361 subjects who had an abnormal oral glucose tolerance test (OGTT) on routine screening. All participants were divided into two groups, prediabetes and newly diagnosed type 2 DM, and the association of NAFLD with metabolic parameters on microalbuminuria was analysed. RESULTS: The patients with NAFLD had higher prevalence rates of microalbuminuria (6.3% vs 19%; P = 0.001 in prediabetes, 4.5% vs 32.6%; P < 0.001 in diabetes) and also had a greater albumin-to-creatinine ratio (14.6 +/- 52.0 microg/mg Cr vs 27.7 +/- 63.9 microg/mg Cr; P = 0.051 in prediabetes, 11.4 +/- 21.4 microg/mg Cr vs 44.7 +/- 76.4 microg/mg Cr; P < 0.001 in diabetes) than those without NAFLD. The logistic regression analysis showed that NAFLD was associated with increased rates of microalbuminuria (odds ratio 3.66; 95%confidence interval (CI) 1.31-10.20, P = 0.013 in prediabetes, odds ratio 5.47;95% CI 1.01-29.61, P = 0.048 in diabetes), independently of age, sex, body mass index, waist circumference, liver enzymes, lipid profiles, HbA1c, insulin resistance as estimated by homeostasis model assessment, hypertension,smoking status and the metabolic syndrome. CONCLUSIONS: The results of our study revealed a strong relationship between microalbuminuria and NAFLD in the patients with prediabetes and newly diagnosed diabetes. Further studies are required to confirm whether NAFLD is a predictor of the development of microalbuminuria in patients with prediabetes and diabetes.

Change of insulin sensitivity in hepatitis C patients with normal insulin sensitivity: a 5-year prospective follow-up study variation of insulin sensitivity in HCV patients.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with a high prevalence of diabetes mellitus (DM). Insulin resistance (IR) is known to play a crucial role in the development of DM in chronic hepatitis C (CHC) patients. We prospectively investigated changes of insulin sensitivity in CHC patients during a 5-year period and analysed the factors significantly associated with IR. METHODS: Sixty-two CHC patients with normal insulin sensitivity (CHC group), and a healthy control group of 172 subjects matched by age, gender, body mass index and lifestyles were studied. We compared the initial baseline insulin sensitivity, metabolic parameters and incidence of IR at the end of the follow-up period between the two groups. The changes in insulin sensitivity, metabolic parameters and the development of IR were analysed as well as factors associated with the development of IR. RESULTS: IR developed in 22.5% of 62 CHC patients and 5.2% of 172 normal individuals (P < 0.001). HCV infection per se and the genotype 1 were independent risk factors for the development of IR. The duration of infection > or = 120 months, initial fasting glucose 90-100 mg/dL, fasting insulin > or = 10 microIU/mL and the homeostasis model assessment (HOMA-IR) 2.3-2.7 were significantly associated with the development of IR in the CHC group. CONCLUSION: HCV infection was an independent risk factor for the development of IR. All CHC patients, even those with normal insulin sensitivity, require careful monitoring for the development of IR.

Pitfalls in the radiological and pathological correlation of tumour response rates of hepatocellular carcinoma following radiofrequency ablation.

According to the American Association for the Study of Liver Diseases (AASLD) guidelines, radiofrequency ablation (RFA) is a safe and effective treatment for patients with unresectable hepatocellular carcinoma (HCC). In most studies, the initial complete tumour response rates of small HCCs < or =3 cm following RFA have been reported as more than 90% or 95%, and local tumour progression rates have been reported as approximately 10% or 20%. Notwithstanding these promising clinical outcomes, the complete tumour response rates for HCC following RFA as determined by conventional histopathological diagnostic criteria have been reported to be less than 50% in many recent reports. While considering that most cases of local tumour progression of HCC are known to occur within two years following RFA, it may not be reasonable to assume that clinical and radiological examinations have significantly overestimated the tumour response rates. On the contrary, it is likely that the conventional histopathological examination techniques may have underestimated the tumour response rates. The apparent discrepancy between the histopathological and the radiological tumour response of radiofrequency ablation for hepatocellular carcinomas can be attributed to several histological features, such as thermal fixation or apoptosis, that were not included in the conventional histopathological diagnostic criteria. However, a robust conclusion cannot be derived because of lack of adequate controlled studies, and further well designed prospective multicentre trials will be helpful to solve this issue.