The Relationship Between Canal Diameter and the Dorr Classification.

BACKGROUND: Particularly in broach-only uncemented total hip arthroplasty, a narrow femoral canal presents a technical challenge. Traditionally such femurs have been considered to be Dorr A. To our knowledge, however, no study has reported on the relationship between isthmus width and the Dorr classification. METHODS: We reviewed 500 high-quality, hard copy radiographs. Dorr classification and isthmus canal width were measured using an electronic caliper by 5 independent observers with intraobserver and interobserver error calculated. For this study, we defined a narrow canal as being ≤10 mm at its narrowest point (isthmus). RESULTS: Eight percent (40) were Dorr A, 85% (424) Dorr B, and 7% (36) Dorr C. With respect to isthmus width for Dorr A, 63% (25) were ≤10 mm compared to just 13% (55) of Dorr B. However, overall because there were more Dorr B femurs, 69% of those with an isthmus of ≤10 mm were Dorr B. CONCLUSION: In this population, almost 70% of patients with an isthmus ≤10 mm were Dorr B, with only 30% being Dorr A. When using a broach-only technique, isthmus width should be routinely measured on the preoperative anteroposterior radiographs so as to alert the surgeon to potential problems.

Falling age-related incidence of hip fractures in women, but not men, in Northern Ireland: 2001-2011.

Hip fractures place a large burden on healthcare and determining the variation in incidence is important to plan resources. We found, in Northern Ireland, that the age-related incidence for women is declining but the incidence for men and the total number of fractures remains static as the elderly population increases. INTRODUCTION: Hip fractures place a significant burden on healthcare systems throughout the world. Recent studies have shown that the incidence is starting to decline or plateau. We aimed to study the incidence of hip fractures in 2001 and 2011 within Northern Ireland and hope to guide further service provision. METHODS: The years 2001 and 2011 were selected as accurate census population data was available. The Hospital Inpatient System (HIS) database was used to collect the data and the search was carried out by a statistician using ICD codes S72.0 and S72.1. RESULTS: The total incidence of hip fractures in the population aged 50 and over fell from 358 per 100,000 to 274 per 100,000. In females, the incidence fell from 513 to 412 per 100,000. In males, the incidence increased from 172 to 178 per 100,000. The total number of hip fractures remained static (1737 in 2001 and 1739 in 2011) as a result of an increase in the elderly population. Incidence and total number of femoral neck fractures (S72.0) declined while the incidence and total number of pertrochanteric fractures (S72.1) increased. CONCLUSIONS: Our results are in keeping with the declining trend in hip fracture incidence in many Western countries, though we found that this is only true for women. The exact reasons for this remain unclear but are likely to be multifactorial. In the future, the number of fractures may increase further given the increasingly elderly population and further provision particularly for patients with pertrochanteric fractures will be required. Increased awareness, diagnosis and treatment of males with osteoporosis should be prioritised.

Treatment options beyond IFNα and NUCs for chronic HBV infection: expectations for tomorrow.

Chronic hepatitis B virus (HBV) infection may progress to cirrhosis, hepatocellular carcinoma (HCC) and end-stage liver failure with time. Interruption of this process can only be achieved through effective antiviral treatment. This approach has so far involved the use of immunomodulators such as pegylated interferon alpha (Peg-IFNα) for a finite period of up to a year and nucleos-(t)ide analogues (NUCs) for treatment over much longer periods of time. The latter act by suppressing HBV replication at the level of DNA synthesis by inhibiting the viral reverse transcriptase/DNA polymerase and causing premature termination of DNA synthesis. The ideal treatment end point is loss of HBsAg in both HBeAg+ve and HBeAg-ve patients following monotherapy. This, however, is only achievable in a minority of patients. Secondary outcomes are durable HBeAg loss and seroconversion to anti-HBe, which occur in about 18-30% of HBeAg+ve patients depending on the antiviral used, and sustained suppression of HBV-DNA accompanied by biochemical normalization and histological improvement in non-HBeAg+ve seroconverting and HBeAg-ve patients. There is therefore a need for additional direct-acting antivirals (DAAs) targeting different stages of the life cycle of the virus, as well as immunotherapeutic approaches. Such developments may pave the way for their use either alone or more likely in combination in the fight against chronic HBV infection. Such drugs or approaches, which are currently undergoing preclinical or clinical testing, are the subject of this review.

Effect of antiviral treatment on alfa-fetoprotein levels in HBV-related cirrhotic patients: early detection of hepatocellular carcinoma.

Alpha-fetoprotein (AFP) is a marker of the presence of hepatocellular carcinoma (HCC), but is also elevated in advanced chronic hepatitis B. The detection and usage of AFP tests need to be improved. A cohort of 101 patients with advanced chronic hepatitis B and elevated AFP values was treated with entecavir (ETV) or peginterferon-alpha2a. ETV was more effective in reducing AFP levels; mean time to AFP normalization was 11.9 weeks after ETV treatment initiation vs 22.3 weeks in peginterferon treated patients (P = 0.000). An additional cohort of 93 hepatitis B virus (HBV) cirrhotic patients with elevated AFP were treated with ETV prospectively and maintained under intensive surveillance. HCC developed in 16 (17.2%) patients in whom the strongest independent predictor was a continued AFP rise in spite of ongoing treatment. In this context, nodules of sizes 10-14 mm and 15-20 mm were detected in 40% of patients each. In conclusion, HBV cirrhotic patients with rising AFP levels were at very high risk of HCC development. Early detection of minute lesions may be possible by monitoring AFP levels, whilst patients are on treatment in conjunction with enhanced computed tomography examination.

Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent.

An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.

Tailored regimen of interferon alpha for HBeAg-positive chronic hepatitis B: a prospective controlled study.

The response to interferon-alpha treatment of patients with chronic hepatitis B under the current protocol is not satisfactory. The aim of this study was to try an alternative approach to improve treatment outcome. Of 374 HBeAg-positive patients, 127 of them received 5 million units of interferon-alpha thrice weekly for 6 months and constituted the control group, while 247 in the study group received the same dosage but the duration of treatment was tailored. The study protocol provided for continuation of treatment if HBV DNA levels were continuously decreasing. The treatment ended when viral, antigenic and biochemical endpoints were reached or when HBV DNA levels were no longer decreasing. The median length of tailored treatment was 10 (range 6-24) months. The end-of-treatment response rates were 39.3% and 23.6% (P = 0.002), and after 12-month, follow-up, the sustained response rates were 40.5% and 28.3% (P = 0.013) in the study and control groups, respectively. Excluding the patients who dropped out, 228 and 115 completed a median of 40- and 44-month-long follow-up; the long-term response was thus 45.3% and 33.1% (P = 0.014) in the respective groups. Interferon-alpha treatment tailored in length demonstrated significantly increased efficacy in patients with chronic hepatitis B.

CT pulmonary angiography in lower limb arthroplasty: A retrospective review of 11 249 patients over 11 years.

Aims: The aims of this study were to determine the indications and frequency of ordering a CT pulmonary angiography (CTPA) following primary arthroplasty of the hip and knee, and to determine the number of positive scans in these patients, the location of emboli and the outcome for patients undergoing CTPA. Patients and Methods: We analyzed the use of CTPA, as an inpatient and up to 90 days as an outpatient, in a cohort of patients and reviewed the medical records and imaging for each patient undergoing CTPA. Results: Out of 11 249 patients, scans were requested in 229 (2.04%) and 86 (38%) were positive. No patient undergoing CTPA died within 90 days. The rate of mortality from pulmonary embolism (PE) overall was 0.08%. CTPA was performed twice as often following total knee arthroplasty (TKA) compared with total hip arthroplasty (THA), and when performed was twice as likely to be positive. Hypoxia was the main indication for a scan, being the indication in 149 scans (65%); and in 23% (11 of 47), the PE was peripheral and unilateral. Three patients suffered complications resulting from therapeutic anticoagulation for possible PE, two of whom had a negative CTPA. Conclusion: CTPA is more likely to be performed following TKA compared with THA. Hypoxia was the main presenting feature of PE. A quarter of PEs which were diagnosed were unilateral and peripheral. Further study may indicate which patients who have a PE after lower limb arthroplasty require treatment, and which can avoid the complications associated with anticoagulation. Cite this article: Bone Joint J 2018;100-B:938-44.

Hepatitis B virus: virology, molecular biology, life cycle and intrahepatic spread.

Hepatitis B virus is a member of the Hepadnaviridae family and responsible for causing acute and chronic hepatitis in humans. The current estimates of people chronically infected with the virus are put at 250 million worldwide. Immune-mediated liver damage in these individuals may lead to the development of cirrhosis and hepatocellular carcinoma later in life. This review deals with our current understanding of the virology, molecular biology, life cycle and cell-to-cell spread of this very important pathogen, all of which are considered essential for current and future approaches to antiviral treatment.

Interferon-alpha therapy in HBeAg-negative chronic hepatitis B: a long-term prospective study from north-western Greece.

AIMS: To determine the long-term response to interferon-alpha therapy in patients with hepatitis B e antigen-negative chronic hepatitis B, and the factors independently associated with response and survival. METHODS: Sixty-three patients with documented hepatitis B e antigen-negative chronic hepatitis B treated with interferon-alpha for a year were followed-up for a period of 6 years. RESULTS: Sustained biochemical and virological response was seen in 34.91% and 33.33% of patients at 6 and 12 months of follow-up, respectively, and histological improvement in 54.5% of sustained responders compared with non-responders (7.1%, P = 0.004, chi-squared test), at 6 months of follow-up. Multivariate analysis showed that patients with hepatitis B virus-DNA levels at 6 months of treatment <10,000 copies/mL had a low probability of relapse, compared with those with levels >10 000 copies/mL (P = 0.032). Age (>65 years) and hepatitis B virus-DNA level at 6 months of treatment (>10,000 copies/mL) were the independent factors for disease progression and survival (P = 0.041 and P = 0.044 respectively). At 6 years, a sustained response was still present in 19.04% of patients and 4.8% of them had developed anti-HBs. CONCLUSION: Hepatitis B virus-DNA monitoring by quantitative polymerase chain reaction at 6 months of treatment may allow for early prediction of response to interferon-alpha, and may serve as an indicator of disease progression in the future.

Hepatitis D virus.

The hepatitis D virus (HDV) relies on the helper hepatitis B virus (HBV) for the provision of its envelope, which consists of hepatitis B surface antigen (HBsAg). The RNA genome of HDV is a circular rod-like structure due to its extensive intramolecular base-pairing. HDV-RNA has ribozyme activity which includes autocatalytic cleavage and self-ligation properties, essential in virus replication via the rolling circle mechanism. Replication of the RNA is thought to be effected by cellular RNA polymerase II. Hepatitis D antigen (HDAg) is the only protein encoded by HDV-RNA and its long and short forms have a regulatory role in the replication and morphogenesis of the virus. Superinfected HBV carriers who become chronically infected with HDV are at increased risk of developing cirrhosis. Attempts to treat such carriers with interferon have not been particularly successful. In recent years the epidemiology of HDV has changed primarily due to the impact of HBV vaccination in preventing an increase in the pool of susceptible individuals. Copyright 1998 John Wiley & Sons, Ltd.

Short report: prednisolone withdrawal followed by lymphoblastoid interferon in the therapy of adult patients with presumed childhood-acquired chronic hepatitis B virus infection.

Eighteen patients with presumed childhood acquisition of chronic hepatitis B virus infection were initially entered into this randomized controlled trial. Twelve were treated with prednisolone for 4 weeks followed, after a 2-week gap, by thrice weekly lymphoblastoid alpha-interferon for 12 weeks. Two of these had previously acted as untreated controls. Three of the 12 patients (25%) [who were initially hepatitis B virus (HBV) surface antigen (HBsAg), 'e' antigen (HBeAg) and HBV-DNA positive] became HBeAg and HBV-DNA negative during therapy and remained so after 12 months post-therapy follow-up. One of these also lost HBsAg. A further two patients lost HBeAg and HBV-DNA during therapy but relapsed 6 and 9 months later. Two additional patients were HBV-DNA negative but HBeAg positive at the end of follow-up. None of the eight untreated control patients seroconverted during an identical follow-up period. Two further patients were HBsAg and HBeAg positive but HBV-DNA negative at the start of therapy. These were omitted from the final analysis: both subsequently lost HBeAg. The treatment response was associated with a rise in aspartate aminotransferase, peaking 2-6 weeks after prednisolone withdrawal, loss of HBV-DNA 0-8 weeks later and subsequent normalization of liver function tests. Treatment was well tolerated.

Non-invasive investigation of liver disease in haemophilic patients.

Liver biopsy specimens previously taken from 16 haemophilic patients with chronic non-A, non-B hepatitis were reviewed. The degree of fibrosis correlated with serum procollagen III peptide (sPIIIP) concentrations, measured both at the time of biopsy and 4.25 years later. Two patients with extremely high sPIIIP concentrations had collateral veins on computed tomography, suggesting portal hypertension. Twenty eight of 47 patients (60%) had splenomegaly on computed tomography, and of 28 patients in whom intravenous contrast medium was used, seven (25%) had collateral oesophageal veins. Serum procollagen III peptide estimations and computed tomography, both non-invasive investigations, indicated that hepatic fibrosis and portal hypertension had developed in a proportion of haemophilic patients with non-A, non-B hepatitis. Infection with the human immunodeficiency virus (HIV) may modify the course of this presumably cytopathic virus infection of the liver.

Use of biotinylated probes in serum hepatitis B virus DNA detection.

A dot-blot hybridisation assay for serum HBV DNA is described using a non-radioactive (biotinylated) DNA probe. The assay is both sensitive (1 pg of HBV DNA) and reproducible, and shows several advantages over similar assays which use 32P-labelled probes for the routine detection of infectious virus particles both in blood and in other biological fluids.

Purification of woodchuck hepatitis surface antigen using a monoclonal antibody raised against the antigen.

Woodchuck hepatitis virus (WHV) is closely related to the human hepatitis B virus (HBV) and infection of woodchucks with WHV creates a useful model for studies of immunity, pathogenesis and therapy of HBV infection. To increase the usefulness of this model, monoclonal antibodies were raised to woodchuck hepatitis surface antigen (WHsAg) and one of these antibodies was used to purify the antigen by affinity chromatography from serum, a simpler and quicker method of purification than the current ultracentrifugation methods. The bands found by SDS-polyacrylamide gel electophoresis of WHsAg were the major 25 and 29 kilodalton (kDa) bands and a triplet of 45, 51 and 55 kDa which are thought to be the glycosylated and unglycosylated middle and large WHsAg. Both the antibody and the antigen are valuable reagents for the study of WHV infection.

Hepatitis C virus phylogeny: a useful clinical tool.

In order to type 45 recent isolates of Hepatitis C virus (HCV) originating from four different geographic regions of the world, we performed phylogenetic analysis of a 192 nucleotides (nts) long sequence from the 5'non-coding region (5'-NCR) of the virus genome and compared them with 55 HCV isolates/strains of known type. The results of this study showed that phylogenetic studies can assign an HCV isolate to the correct type in 100% and to the correct subtype in 98%. A comparison ofthis method with other methods using commercial kits revealed that it is appropriate for clinical use and is cost effective.

Randomised controlled trial of lymphoblastoid interferon alfa in Europid men with chronic hepatitis B virus infection.

OBJECTIVE: To confirm the findings of pilot studies that interferon alfa is an effective treatment of Europid men with chronic hepatitis B virus infection. DESIGN: Randomised controlled trial of three months treatment with interferon alfa followed by 12 months of observation. SETTING: Outpatient clinic of a tertiary referral centre. PATIENTS: 37 Treated men (six anti-HIV positive) and 34 untreated men (nine anti-HIV positive) who met the criteria for the trial. Four controls failed to complete follow up. INTERVENTIONS: The treated group received subcutaneous injections of 5-10 MU interferon alfa/m2 daily for five days, then 10 MU/m2 thrice weekly for 11 weeks. Follow up continued at monthly intervals for 12 months. Untreated controls were monitored over the same period. MAIN OUTCOME MEASURE: Hepatitis B e antigen and hepatitis B virus DNA state after 15 months of observation. RESULTS: 12 Of the 37 treated patients cleared hepatitis B e antigen and hepatitis B virus DNA, whereas only one of 30 untreated controls seroconverted over the same period--an increased response rate of 29% (95% confidence interval 13% to 45%). The life table estimate of response at 15 months was 35% in treated patients, an increase of 32% above controls (95% confidence interval 16% to 48%). The response rates in groups by predictive pretreatment variables were 12 of 31 anti-HIV negative patients (excess response 34%; 95% confidence interval 14% to 54%), 12 of 26 with chronic active hepatitis before treatment (excess response 46%; 27% to 65%), and 12 of 21 with a pretreatment serum aspartate aminotransferase activity greater than 70 IU/l (excess response 46%; 16% to 76%). The combination of these factors predicted response with a sensitivity of 100% and a specificity of 80%. Four of the 12 responders, who had all been infected for less than two years, also lost hepatitis B surface antigen. Treatment was well tolerated. CONCLUSIONS: Interferon alfa is effective in the treatment of a proportion of Europid men with chronic hepatitis B virus infection, who might be identified before treatment. Additional strategies are required to improve the rate of response.

[Subclasses of antibodies to hepatitis B core antigen in chronic HBV infections: changes during treatment with interferons and predictors of response].

Response to interferon therapy in chronic hepatitis B virus (HBV) carrier is preceded by the appearance of IgM class anti-HBc (antibody to hepatitis B core antigen). The temporal relationship and magnitude of the IgM anti-HBc response is variable, suggesting that the antibody is not directly involved in hepatocyte lysis, but is merely a marker of a changed state of immunity to the nucleocapsid proteins induced by interferon. IgG 1, 2, 3 and 4 did not change during therapy. IgG anti-HBc of all subclasses was absent in two Chinese HBV carriers. Lower than normal titres of anti-HBc (P less than 0.001) were detected in human immunodeficiency virus antibody positive (anti-HIV) carriers. These data indicate the presence of altered immunity to the nucleocapsid antigens in these two types of chronic HBV carrier that are known to respond poorly to antiviral therapy.