Multiscale analysis of SRY-positive 46,XX testicular disorder of sex development: Presentation of nine cases

46,XX testicular disorder of sex development (46,XX TDSD) is a relatively rare condition characterised by the presence of testicular tissue with 46,XX karyotype. The present study aims to reveal the phenotype to genotype correlation in a series of sex-determining region Y (SRY)-positive 46,XX TDSD cases. We present the clinical findings, hormone profiles and genetic test results of six patients with SRY-positive 46,XX TDSD and give the details and follow-up findings of our three of previously published patients. All patients presented common characteristics such as azoospermia, hypergonadotropic hypogonadism and an SRY gene translocated on the terminal part of the short arm of one of the X chromosomes. Mean ± standard deviation (SD) height of the patients was 164.78 ± 8.0 cm. Five patients had decreased secondary sexual characteristics, and three patients had gynaecomastia with varying degrees. Five of the seven patients revealed a translocation between protein kinase X (PRKX) and inverted protein kinase Y (PRKY) genes, and the remaining two patients showed a translocation between the pseudoautosomal region 1 (PAR1) of X chromosome and the differential region of Y chromosome. X chromosome inactivation (XCI) analysis results demonstrated random and skewed XCI in 5 cases and 1 case, respectively. In brief, we delineate the phenotypic spectrum of patients with SRY-positive 46,XX TDSD and the underlying mechanisms of Xp;Yp translocations.     

Noncirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and treatment

The Asian Pacific Association for the Study of the Liver (APASL) Working Party on Portal Hypertension has developed consensus guidelines on the disease profile, diagnosis, and management of noncirrhotic portal fibrosis and idiopathic portal hypertension. The consensus statements, prepared and deliberated at length by the experts in this field, were presented at the annual meeting of the APASL at Kyoto in March 2007. This article includes the statements approved by the APASL along with brief backgrounds of various aspects of the disease.     

Gastric emptying time and the effect of cisapride in cirrhotic patients with autonomic neuropathy

GOALS To investigate the relationships between gastric emptying and autonomic dysfunction in hepatic cirrhosis and to assess the effects of cisapride on gastric emptying in cirrhotic patients.STUDY Twenty-four cirrhotic patients (8 patients in each Child-Pugh classification) and 25 healthy controls were enrolled. All the patients had viral (B or C) hepatitis. Patients with DM, alcoholic cirrhosis, active peptic ulcer, gastric malignancy and pyloric obstruction were excluded by esophagogastroduodenoscopy. Parasympathetic and sympathetic functions were assessed by the criteria set forth by Ewing and Clark. Drugs affecting GI motility and smoking were discontinued 48 hours and 12 hours prior to the study respectively. A solid-phase of gastric emptying study was conducted by scintigraphic method for the calculation of gastric half-emptying time (GET1/2). RESULTS The study revealed that 9 patients with Child-Pugh B and C cirrhosis had autonomic neuropathy and none of Child-Pugh A cirrhosis had autonomic neuropathy. Prolonged GET1/2 was noted in cirrhotics compared with the control group (p < 0.05). However, there was significant difference between 9 patients (Child B-C) with autonomic neuropathy compared with patients 15 patients without autonomic neuropathy. Again there was a significant difference in GET1/2 between Child A cirrhotic and Child B-C cirrhotic whether they had autonomic neuropathy or not. Cisapride decreased GET1/2 significantly in cirrhotic patients (Child B-C cirrhotic). Clearly, patients with autonomic neuropathy in Child B-C cirrhosis had significantly reduced GET1/2 after cisapride administration. Even though cisapride decreased GET1/2 in patients with Child B-C cirrhosis without autonomic neuropathy, this was not significant. CONCLUSION Autonomic neuropathy in advanced cirrhosis from viral hepatitis may cause prolonged gastric emptying. Cisapride can shorten gastric emptying time in such patients.     

Calcium pyrophosphate dihydrate and hydroxyapatite crystal deposition in the joint: New developments relevant to the clinician

The major types of crystals containing calcium, which causes arthropathy and periarticular disease, are calcium pyrophosphate dihydrate and basic calcium phosphates, including hydroxyapatite. Exciting advances include the identification of mutations in the gene ANKH associated with disordered inorganic pyrophosphate (PPi) transport in some kindred with familial chondrocalcinosis linked to chromosome 5p. In addition, central basic mechanisms governing cartilage calcification and their relationship to aging and osteoarthritis have now been elucidated. These include the role of plasma cell glycoprotein-1, the PPi-generating ecto-enzyme, in chondrocalcinosis and the linkage of low-grade inflammation to expression and activation of two cartilage-expressed transglutaminase isoenzymes with direct calcification-stimulating activity. This review discusses clinically pertinent new information on pathogenesis. The authors also address, in detail, current diagnostic and therapeutic issues pertaining to calcium pyrophosphate dihydrate and hydroxyapatite crystal deposition in the joint, as well as possible therapeutic directions for the future.     

Endoscopic management of gastric band erosions: a 7-year series of 14 patients

Background

Intragastric band migration is an unusual but major complication of gastric banding. We review our experience with endoscopic removal of eroded gastric bands.

Methods

We retrospectively evaluated the cases of 110 morbidly obese patients who underwent adjustable gastric banding between 2005 and 2012 to identify those who experienced band erosion. To remove the migrated band, we used an endoscopic approach with a Gastric Band Cutter.

Results

Band or tube erosion occurred in 14 patients (12.7%). The median time interval from the initial gastric band placement to the diagnosis of band erosion was 32 (range 18–52) months. Upper abdominal pain, port site infection, loss of restriction and weight regain were the most common symptoms. We used the Gastric Band Cutter to remove the band endoscopically. It was able to cut the band successfully in all but 1 patient, in whom twisting of the cutting wire required conversion from endoscopy to laparotomy. In 2 patients, the band, after being cut, was locked in the gastric wall and required laparotomic removal. In 1 patient, we performed surgery for intragastric penetration of the connecting tube broken close to the band.

Conclusion

The Gastric Band Cutter was successful in dividing the band in all but 1 patient, although we could not always complete the procedure endoscopically. Endoscopic removal seems to be effective and safe for band erosion.     

The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol

Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin–Frankfurt–Münster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan–Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged ≥6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of <20?×?10⁹/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23.2 months. Death occurred in 69 of 343 patients (20.1 %). The major causes of death were infection and relapse. None of the patients died of drug-related toxicity. The ALL-BFM 95 protocol was applied successfully in these two centers. In developing countries in which minimal residual disease cannot be monitored, this protocol can still be used with high survival rates.     

The oblique plane deformity in slipped capital femoral epiphysis

Background

Slipped capital femoral epiphysis (SCFE) is commonly treated with in situ pinning. However, a severe slip may not be suitable for in situ pinning because the required screw trajectory is such that it risks perforating the posterior cortex and damaging the remaining blood supply to the capital epiphysis. In such cases, an anteriorly placed screw may also cause impingement. It is also possible to underestimate the severity of the slip using conventional radiographs. The aim of this study was to describe and evaluate a novel method for calculating the true deformity in SCFE and to assess the interobserver and intraobserver reliability of this technique.

Methods

We selected 20 patients with varying severity of SCFE who presented to our institution. Cross-sectional imaging [either axial computed tomography (CT) scans or magnetic resonance imaging (MRI) scans] and anteroposterior (AP) pelvis radiographs were assessed by four reviewers with varying levels of experience on two occasions. The degree of slip on the axial image and on the AP pelvis radiographs were measured and, from this, the oblique plane deformity was calculated using the method as popularised by Paley. The intraclass correlation coefficient (ICC) was calculated to determine the interobserver and intraobserver reliabilities between and amongst the raters.

Results

The interobserver reliability for the calculated oblique plane deformity in SCFE ICC was 0.947 [95 % confidence interval (CI) 0.90–0.98] and the intraobserver reliability for the calculated oblique plane deformity of individual raters ranged from 0.81 to 0.94. The deformity in the oblique plane was always greater than the deformity measured in the axial or the coronal plane alone.

Conclusion

This method for calculating the true deformity in SCFE has excellent interobserver and intraobserver reliability and can be used to guide treatment options. This technique is a reliable and reproducible method for assessing the degree of deformity in SCFE. It may help orthopaedic surgeons with varying degrees of experience to identify which hips are suitable for in situ pinning and those which require surgical dislocation and anatomical reduction, given that plain radiographs in a single plane will underestimate the true deformity in the oblique plane.

Level of evidence

Level II diagnostic study.     

Advancing Biomarker Development Through Convergent Engagement: Summary Report of the 2nd International Danube Symposium on Biomarker Development,Molecular Imaging and Applied Diagnostics; March 14–16, 2018; Vienna,Austria

Molecular Imaging and Biology - Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During...     

What Is the Risk of Reactivation in Patients with Resolved and Past HBV Infection During Immunosuppressive Therapy If HBV-DNA Negative before Treatment?

BackgroundReactivation of Hepatitis B (HBVr) related to immunosuppressive drug therapy (ISDT) in patients with resolved and past infection is a challenging entity. The number of prospective long-term studies is limited.MethodsTwo groups of patients with resolved and past HBV infection were analyzed prospectively. The patients were further categorized as 266 patients receiving ISDT (group 1) and 246 patients receiving antineoplastic therapy (group 2).ResultsWe did not detect any cases of HBVr among 108 patients receiving rituximab (71 of which were anti-HBc positive only), 111 patients receiving tumor necrosis factor inhibitors (66 of which were anti-HBc positive only), and 42 patients receiving high-dose glucocorticoids for more than 4 weeks (24 of which were anti-HBc positive only) during a mean follow-up time of more than 24 months. Subgroup analysis of the anti-HBs (+) patients showed that in group A (anti-HBs >1000 mIU/mL) the antibody levels did not change; in group B (anti-HBs between 100 and 1000 mIU/mL) the antibody levels changed non-significantly (P = .25), and in Group C (anti-HBs between 0 and 100 mIU/mL) the antibody levels declined significantly (P = .002). Furthermore, 16 patients in Group C had an anti-HBs loss during follow-up, but no HBVr was detected.ConclusionThe risk of HBVr by immunosuppressive therapy in this group may be lower than that suspected in the literature and anti-HBs levels may not seem to correlate with the risk of reactivation.