Persistence of antibody to Hepatitis A virus 20 years after receipt of Hepatitis A vaccine in Alaska.

Hepatitis A vaccine is recommended for children ≥1 year old to prevent hepatitis A virus (HAV) infection. However, the duration of vaccine-induced immunity is unknown. We evaluated a cohort of Alaska Native persons 20 years after HAV vaccination. Children aged 3-6 years had been previously randomized to receive three doses of HAV vaccine (360 ELISA units/dose) at: (i) 0,1,2 months; (ii) 0,1,6 months; and (iii) 0,1,12 months. We measured anti-HAV antibody concentrations every 2-3 years; described geometric mean concentrations (GMC) and the proportion with protective antibody (≥20 mIU mL-1 ) over time; and modelled the change in GMC using fractional polynomial regression. Of the 144 participants, after 20 years 52 (36.1%) were available for the follow-up (17, 18, 17 children in Groups A, B and C, respectively). Overall, 46 (88.5%) of 52 available participants had anti-HAV antibody concentrations ≥20 mIU mL-1 , and overall GMC was 107 mIU mL-1 . Although GMC levels were lower in Group A (60; CI 34-104) than in Group B (110; CI 68-177) or Group C (184; CI 98-345) (B vs C: P=.168; A vs B/C: P=.011), there was no difference between groups after adjusting for peak antibody levels post-vaccination (P=.579). Models predicted geometric mean concentrations of 124 mIU mL-1 after 25 years, and 106 mIU mL-1 after 30 years. HAV vaccine provides protective antibody levels 20 years after childhood vaccination. Lower antibody levels in Group A may be explained by a lower initial peak response. Our results suggest a booster vaccine dose is unnecessary for at least 25-30 years.

The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary.

Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to 'test and treat' those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment of H. pylori in high-prevalence countries. They concluded that in Arctic countries where H. pylori prevalence exceeds 60%, treatment of persons with H. pylori infection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.

Esophagogastric junction distensibility in hiatus hernia.

Hiatus hernia is known to be an important risk factor for developing gastroesophageal reflux disease. We aimed to use the endoscopic functional lumen imaging probe (EndoFLIP) to evaluate the functional properties of the esophagogastric junction. EndoFLIP assessments were made in 30 patients with hiatus hernia and Barrett's esophagus, and in 14 healthy controls. The EndoFLIP was placed straddling the esophagogastric junction and the bag distended stepwise to 50 mL. Cross-sectional areas of the bag and intra-bag pressures were recorded continuously. Measurements were made in the separate sphincter components and hiatus hernia cavity. EndoFLIP measured functional aspects such as sphincter distensibility and pressure of all esophagogastric junction components and visualized all hiatus hernia present at endoscopy. The lower esophageal sphincter in hiatus hernia patients had a lower pressure (e.g. 47.7 ± 13.0 vs. 61.4 ± 19.2 mm Hg at 50-mL distension volume) and was more distensible (all P < 0.001) than the common esophagogastric junction in controls. In hiatus hernia patients, the crural diaphragm had a lower pressure (e.g. 29.6 ± 10.1 vs. 47.7 ± 13.0 mm Hg at 50-mL distension volume) and was more distensible (all P < 0.001) than the lower esophageal sphincter. There was a significant association between symptom scores in patients and EndoFLIP assessment. Conclusively, EndoFLIP was a useful tool. To evaluate the presence of a hiatus hernia and to measure the functional properties of the esophagogastric junction. Furthermore, EndoFLIP distinguished the separate esophagogastric junction components in hiatus hernia patients, and may help us understand the biomechanics of the esophagogastric junction and the mechanisms behind hiatal herniation.

Reinfection after successful eradication of Helicobacter pylori in three different populations in Alaska.

We performed a study to determine rates of reinfection in three groups followed for 2 years after successful treatment: American Indian/Alaska Native (AI/AN) persons living in urban (group 1) and rural (group 2) communities, and urban Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori infection based on a positive urea breath test (13C-UBT). After successful treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6, 12 and 24 months. At each visit, participants were asked about medication use, illnesses and risk factors for reinfection. We followed 229 persons for 2 years or until they became reinfected. H. pylori reinfection occurred in 36 persons; cumulative reinfection rates were 14·5%, 22·1%, and 12·0% for groups 1, 2, and 3, respectively. Study participants who became reinfected were more likely to have peptic ulcer disease (P = 0·02), low education level (P = 0·04), or have a higher proportion of household members infected with H. pylori compared to participants who did not become reinfected (P = 0·03). Among all three groups, reinfection occurred at rates higher than those reported for other US populations (<5% at 2 years); rural AI/AN individuals appear to be at highest risk for reinfection.

'Endoflip® evaluation of pharyngo-oesophageal segment tone and swallowing in a clinical population: a total laryngectomy case series'.

OBJECTIVES: To evaluate safety of positioning and distending the functional lumen imaging probe in the pharyngo-oesophageal segment in adults with known pharyngo-oesophageal segment dysfunction and to obtain preliminary measurements of pharyngo-oesophageal segment distensibility and opening during swallowing in a clinical group. METHODS: Prospective case series of ten adults post total laryngectomy (61-75 years) recruited from an outpatient ENT clinic. Functional lumen imaging probe was inserted trans-nasally, and the balloon was positioned in the pharyngo-oesophageal segment. Two 20-mL ramp distensions were completed, and subjects performed two dry and two 5-mL and 10-mL liquid swallows at a 12-mL balloon volume. Pharyngo-oesophageal segment distensibility was calculated from cross-sectional area (mm(2) ) and intraballoon pressure (mmHg) measures. During swallowing, extent (mm) and duration (secs) of pharyngo-oesophageal segment opening and intraballoon pressure drop (mmHg) were evaluated. RESULTS: Functional lumen imaging probe could be passed through the pharyngo-oesophageal segment in seven subjects, all of whom completed the protocol. During distensions, pharyngo-oesophageal segment cross-sectional area increased significantly (19.47-148.3 mm(2) , P < 0.001), and intraballoon pressure increased significantly (15- to 20-mL balloon volume, P = 0.005). Pharyngo-oesophageal segment diameter (5.1 mm) increased during dry (7.4 mm), 5-mL (7.3 mm) and 10-mL (7.7 mm) liquid swallows (P = 0.018). Pharyngo-oesophageal segment opening duration varied across dry (1 s), 5-mL (0.8 s) and 10-mL (1.6 s) liquid swallows. Resting intraballoon pressure (25.5 mmHg) did not alter significantly during swallowing (P = 0.656). CONCLUSION: Functional lumen imaging probe provides novel quantitative information regarding pharyngo-oesophageal segment distensibility and opening during swallowing in adults post total laryngectomy. No adverse events were observed in this first clinical study. Data were easy to acquire, and measures may direct candidacy for and establish effectiveness of interventions to alter pharyngo-oesophageal segment tone.

Genetic diversity of hepatitis B virus genotypes B6, D and F among circumpolar indigenous individuals.

Hepatitis B virus (HBV) infection is highly prevalent in circumpolar indigenous peoples. However, the clinical outcome is extremely variable, such that while hepatocellular carcinoma (HCC) is uncommon in Canadian Inuit, the incidence of HCC is slightly higher in Greenlanders than in Danes, and it is especially high in Alaskan Native people infected with HBV genotypes F (HBV/F) and C (HBV/C). These differences may be associated with the genomic variability of the predominant HBV genotype in each group. The purpose of this study was to determine the rate, nature and regional susceptibility of HBV genomic mutations among circumpolar indigenous individuals. Paired serum samples, separated by 5-6 years, were analysed from Canadian and Greenlandic Inuit infected with HBV genotype B6 (HBV/B6) and HBV/D, respectively, and from Alaskan Native people infected with HBV/F, each having subsequently developed HCC. Phylogenetic and mutational analyses were performed on full-genome sequences, and the dynamic evolution within the quasispecies population of each patient group was determined by clonal analysis of the non-overlapping core coding region. Mutations associated with severe outcomes predominated in HBV/F, mostly within the precore/core and PreS1 region. HBV/B6 genomes exhibited higher diversity compared to HBV/D and HBV/F, particularly within the core coding region. Thus, differing mutational profiles and genetic variability were observed among different HBV genotypes predominating in circumpolar indigenous patients. The unusual observation of persistently high genetic variability with HBV/B6 despite clinical inactivity could be due to the evolution of a host-pathogen balance, but other possible factors also need to be explored.

Incidence of diabetes mellitus in a population-based cohort of persons with chronic hepatitis B virus infection.

To investigate the effect of hepatitis B virus (HBV) infection on the development of diabetes mellitus (DM), we compared DM incidence and characteristics of Alaska Native persons with and without HBV infection. From 1990 to 2010, there were 52 incident DM cases among 1309 persons with infection vs 4557 DM cases among 85 698 persons without infection (log-rank test, P = 0.20). Compared to infected persons without DM, those with DM were significantly older (57.0 vs 47.4 years, P < 0.001) and had higher body mass index (34.5 vs 28.4 kg/m(2) , P < 0.001). Genotype, immune active disease and the presence of cirrhosis were not associated with DM. In this population-based cohort with over 20 years of follow-up, there was no effect of HBV infection on DM development.

A new evaluation of the upper esophageal sphincter using the functional lumen imaging probe: a preliminary report.

Objective and reliable evaluation of upper esophageal sphincter (UES) opening during swallowing based on videofluoroscopy and pharyngeal manometry challenges dysphagia clinicians. The functional lumen imaging probe (FLIP) is a portable tool based on impedance planimetry originally designed to measure esophogastric junction compliance. It is hypothesized that FLIP can evaluate UES distensibility, and can provide UES diameter and pressure measurements at rest, during swallowing, and during voluntary maneuvers. Eleven healthy adult subjects consented to FLIP evaluation. The probe was inserted transorally, and the balloon was positioned across the UES. Two 20-mL ramp distensions were completed. Changes in UES diameter and intraballoon pressure were measured during dry and 5-mL liquid swallows, and during voluntary swallow postures and maneuvers employed in clinical practice. The protocol was completed by 10 of 11 healthy subjects. Mean intraballoon pressure increased throughout 5-mL (5.8 mmHg; -4.5-18.6 mmHg), 10-mL (8.7 mmHg; 2.3-28.5 mmHg), 15-mL (17.3 mmHg; 9.5-34.8 mmHg), and 20-mL (31.2 mmHg; 16-46.3 mmHg) balloon volumes. Mean resting UES diameter (4.9 mm) increased during dry swallows (9.2 mm) and 5-mL liquid swallows (7.7 mm). Mean UES diameter increased during 5-mL liquid swallows with head turn to right (8.1 mm) and left (8.3 mm), chin tuck (8.4 mm), effortful swallow (8.5 mm), Mendelsohn maneuver (8.1 mm), and supraglottic swallow (7.8 mm). FLIP was safely inserted and distended in the UES, and provided useful quantitative data regarding UES distensibility and UES diameter changes during swallowing maneuvers. Further research is being conducted to explore the role of FLIP in UES evaluation.

Is chronic hepatitis B being undertreated in the United States?

Chronic infection with the hepatitis B virus (HBV) is a major risk factor for development of end-stage liver disease, including cirrhosis, liver failure and primary liver cancer. There are now seven antiviral agents approved by the United States Food and Drug Administration (FDA) for the management of chronic HBV infection. Despite the fact that there are between 1.4 and 2 million chronic HBV infections in the United States, fewer than 50,000 people per year receive prescriptions for HBV antiviral medications. This report discusses possible explanations for the disparity between the number of people who are chronically infected and the number of people who receive treatment. Explanations for this incongruence include the potentially large number of infected persons who are unscreened and thus remain undiagnosed, and lack of access, including insurance, education and referral to appropriate medical care, particularly for disproportionately infected populations.

Hepatitis D outbreak among children in a hepatitis B hyper-endemic settlement in Greenland.

Hepatitis B virus (HBV) infection is endemic in Greenland with 5-10% of the population being HBsAg-positive (chronic carriers). Surprisingly, despite of the high prevalence of HBV infection, acute and chronic hepatitis B, liver cirrhosis and primary hepatocellular carcinoma appear much less frequently than expected. The reasons for the low frequencies are unknown, but as a consequence implementation of a childhood HBV vaccination programme, though debated for years, has never been instituted. We describe an outbreak of hepatitis D (HDV) infection among children in a hepatitis B hyper-endemic settlement of 133 inhabitants on the west coast of Greenland. In 2006 a total of 27% of the inhabitants were HBsAg-positive (chronic carriers) and 83% were HBcAb-positive (previously exposed). Forty-six percent of the HBsAg-positive persons were below 20 years of age. On follow-up 1 year later a total of 68% of the HBsAg-positive persons were HDV-IgG positive. Five children, who were HBsAg-positive in 2006, had HDV-seroconverted from 2006 to 2007, indicating a HDV-super-infection. Most of the HDV-IgG positive children had markedly elevated liver enzymes. In the multivariate analysis, among the HBV and HDV markers, presence of HDV-IgG was most strongly associated with elevation of liver enzymes. In conclusion, the HBV-HDV super-infection and presumed HDV outbreak in this settlement challenges the notion that HBV infection may not be as harmless in Greenland as previously anticipated. The findings strongly suggest that HBV vaccination should be included in the child-immunization program in Greenland.

Immunogenicity of the hepatitis A vaccine 20 years after infant immunization.

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.

Kiaman magnetic interval in the Western United States.

Late-Paleozoic red beds in the western United States indicate that Earth's magnetic field was reversed for a period of the order of 50 x 10(6) years. This finding agrees with similar results from igneous rocks in Australia, indicating, that the long period of reversal in the magnetic field was worldwide. The rocks on the two continents appear to be essentially equivalent in time, suggesting early magnetization of the red beds. The time spectrum of reversals is irregular in geologic time, but present evidence suggests reversals characterized by time scales of 10(4) or 10(5), 10(6), and 50 x 10(6) years. The 50 x 10(6) year period of steady reversed field is found in the late Paleozoic and is termed the Kiaman magnetic interval.

Stable magnetic remanence in antiferromagnetic goethite.

Goethite, known to be antiferromagnetic, acquires thermoremanent magnetization at its Neel temperature of 120 degrees C. This remanence, extremely stable, is due to the presence of unbalanced spins in the antiferromagnetic structure; the spins may result from grain size, imperfections, or impurities.

Stepwise radiofrequency ablation of Barrett's esophagus preserves esophageal inner diameter, compliance, and motility.

BACKGROUND AND AIM: Stepwise endoscopic circumferential and focal radiofrequency ablation is safe and effective for the eradication of Barrett's esophagus. In contrast to other techniques, radiofrequency ablation appears to avoid significant esophageal scarring or stenosis. Our aim was to evaluate whether radiofrequency ablation has an adverse effect on esophageal function in patients treated for Barrett's esophagus containing intramucosal cancer and/or high-grade dysplasia. METHODS: Twelve patients with Barrett's esophagus containing intramucosal cancer or high-grade dysplasia were included in the study. After endoscopic resection of visible abnormalities, stepwise circumferential and focal ablation were performed every 2 months up to a maximum of five sessions. Measurement of the inner diameter was performed at 1-cm intervals in the distal esophagus. Manometry was performed using a water-perfused sleeve catheter. Compliance was evaluated using the functional lumen imaging probe (FLIP), measuring eight cross-sectional areas within a saline-filled bag with two pressure side holes, one proximal to and one inside the bag. Esophageal sizing, manometry, and compliance were recorded in patients at baseline and at least 2 months after the final ablation session. In addition, FLIP and manometry measurements were performed in 10 healthy volunteers. RESULTS: All patients achieved complete eradication of dysplasia and Barrett's esophagus, without severe complications or ablation-related stenoses. The esophageal diameter was unchanged by the ablation. Lower esophageal sphincter pressure and length and esophageal contraction amplitude before and after ablation were not significantly different. Baseline compliance was significantly different between healthy volunteers and Barrett's esophagus patients. Compliance was not, however, significantly changed by ablation. CONCLUSIONS: Stepwise circumferential and focal ablation of Barrett's esophagus is an effective and safe treatment modality for early Barrett's neoplasia that appears to preserve the functional characteristics of the esophagus.

The furosemide stress test for prediction of worsening acute kidney injury in critically ill patients: A multicenter, prospective, observational study.

PURPOSE: To validate the furosemide stress test (FST) for predicting the progression of acute kidney injury (AKI). MATERIALS AND METHODS: We performed a multicenter, prospective, observational study in patients with stage I or II AKI. The FST (1 mg/kg for loop diuretic naïve patients and 1.5 mg/kg in patients previously exposed to loop diuretics) was administered. Subsequent urinary flow rate (UFR) recorded and predictive ability of urinary output was measured by the area under the curve receiver operatic characteristics (AuROC). Primary outcome was progression to Stage III AKI. Secondary outcomes included in-hospital mortality and adverse events. RESULTS: We studied 92 critically ill patients. 23 patients progressed to stage III AKI and had significantly lower UFR (p < 0.0001). The UFR during the first 2 h was most predictive of progression to stage III AKI (AuROC = 0.87), with an ideal cut-off of less than 200mls, with a sensitivity of 73.9% and specificity of 90.0%. CONCLUSION: In ICU patients without severe CKD with mild AKI, a UFR of less than 200mls in the first 2 h after an FST is predictive of progression to stage III AKI. Future studies should focus on incorporating a FST as part of a clinical decision tool for further management of critically ill patients with AKI.

Crystallographic publishing in the electronic age.

The journals of the International Union of Crystallography have grown in size and number over the past 60 years to match developments in scientific practice and technique. High quality of publication has always been at the forefront of editorial policy and ways in which this has been achieved are described. In particular, the development of standard exchange and archive formats for crystallographic data has allowed the editorial office to conduct automated analyses of structural data supporting articles submitted for publication and these analyses assist the scientific editors in careful and critical peer review. The new information technologies of the Internet age have allowed the IUCr journals to flourish and to provide a wide range of powerful services to authors, editors and readers alike. The integration of literature and supporting structural data is of particular importance. The new technologies have also brought fresh economic and cultural challenges, and offer completely new opportunities to disseminate the results of scientific research. The journals continue to respond to these challenges and take advantage of new opportunities in innovative ways.

Measurement of the axial force during primary peristalsis in the oesophagus using a novel electrical impedance technology.

The oesophagus serves to transport food and fluid from the pharynx to the stomach. Oesophageal function is usually evaluated by means of manometry which is a proxy of the force in the radial direction. However, force measurements in the axial direction will provide a better measure of oesophageal transport function. The aim of this study was to develop a probe based on electrical impedance measurements to quantify the axial force generated by oesophageal contractions, i.e. probe elongation was associated with the axial force. Calibration with weights up to 200 g was done. The dispersion, creep, temperature and bending dependence were studied at the bench. Subsequently, the probe was tested in vivo in a healthy human volunteer. The probe showed good reproducibility and the dispersion was <0.04. Some dependence on temperature, creep and bending was found. Interpolation of the calibration curves made it possible to compensate for temperature fluctuations. The maximum deviation was 6.1 +/- 3.7% at loads of 50 g. The influence of creep showed a maximum net creep of 6.1 g after 8 s. The swallowed bolus size correlated with the axial force measurements (P = 0.038) but not with manometric measurements. In conclusion, the new technique measures axial force in the oesophagus and may in the future provide valuable information about oesophageal function.

Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation.

Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested HBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, wild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.

Reinfection after successful eradication of Helicobacter pylori: a 2-year prospective study in Alaska Natives.

BACKGROUND: Limited information exists regarding risk factors for reinfection after cure of Helicobacter pylori infection. AIM: To determine the 2-year reinfection rate of H. pylori in a cohort of urban Alaska Natives. METHODS: Participants over 18 years of age undergoing oesophagogastroduodenoscopy had (13)C urea breath test, culture, CLOtest and histology performed. Those diagnosed with H. pylori who tested urea breath test-negative at 8 weeks after treatment were followed prospectively at 4 months, 6 months, 1 year and 2 years. Subjects experiencing H. pylori reinfection as defined by a positive urea breath test were compared with those who did not become reinfected using univariable and multivariable analysis. Risk of reinfection over time was estimated by the Kaplan-Meier method. RESULTS: Helicobacter pylori reinfection occurred in 14 of 98 subjects successfully treated. The cumulative reinfection rate was 5.1% (95% CI: 0.7%-9.5%) at 4 months, 7.2% (2.0-12.3%) at 6 months, 10.3% (4.2-16.3%) at 1-year and 14.5% (7.5-21.6%) at 2 years. In multivariable analysis, a history of previous peptic ulcer disease or presence of ulcer at time of study oesophagogastroduodenoscopy were the only risk factors associated with reinfection (P = 0.01). CONCLUSIONS: Based on the findings from our study, subjects with a history of or current peptic ulcer disease should be followed, after successful treatment for H. pylori, with periodic urea breath test to detect reinfection, as reinfection would put them at high risk for ulcer recurrence.