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.     

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.     

Development of remineralizing, antibacterial dental materials

Light curable methacrylate dental monomers containing reactive calcium phosphate filler (monocalcium phosphate monohydrate (MCPM) with particle diameter of 29 or 90 μm) and β-tricalcium phosphate (β-TCP) at 1:1 weight ratio in a powder:liquid ratio (PLR) of 1:1 or 3:1 and chlorhexidine diacetate (0 or 5 wt.%), were investigated. Upon light exposure, approximately 90% monomer conversion was gained irrespective of the formulation. Increasing the PLR promoted water sorption by the set material, induced expansion and enhanced calcium, phosphate and chlorhexidine release. Concomitantly, a decline in compressive and biaxial flexural strengths occurred. With a reduction in MCPM particle diameter, however, calcium and phosphate release was reduced and less deterioration in strength observed. After 24 h, the remaining MCPM had reacted with water and β-TCP, forming, within the set materials, brushite of lower solubility. This provided a novel means to control water sorption, component release and strength properties. Measurable chlorhexidine release was observed for 6 weeks. Both diffusion rate and total percentage of chlorhexidine release decreased with lowering PLR or by adding buffer to the storage solutions. Higher chlorhexidine release was associated with reduced bacterial growth on agar plates and in a biofilm fermenter. In cell growth media, brushite and hydroxyapatite crystals precipitated on the composite material surfaces. Cells spread on both these crystals and the exposed polymer composite surfaces, indicating their cell compatibility. These formulations could be suitable antibacterial, biocompatible and remineralizing dental adhesives/liners.     

The effect of pulsed ultrasound on the survival of Drosophila

There are reports in the literature that the temporal peak intensity of pulsed ultrasound may be a better predictor of biological damage than is average intensity. The effects of temporal peak intensity on the survival of Drosophila melanogaster pupae exposed to pulsed ultrasound were investigated. Pulse average intensity and pulse repetition frequency were varied, while temporal average intensity and exposure duration were held constant. Thus, the total energy delivered was held constant. Survival was found to be directly dependent on pulse average intensity. We observed decreased survival at spatial average pulse average intensities as low as 0.5 W/cm2.     

Ancient nigella seeds from Boyalı Höyük in north-central Turkey

Aim of the study

The seeds of nigella (black cumin) (Nigella sativa L.) have been widely used as a natural remedy, either alone or in combination with bee products, for the treatment of many acute as well as chronic conditions for centuries, especially in the Middle East and Southeast Asia. In consideration of potential utilization, in recent years the seeds have been extensively studied in terms of pharmacological effects. It has been shown that the seeds have significant effects on multiple biological systems. In addition, the protective roles of the seeds with bee products (honey and wax) have been recently proved.This study reports the palaeoethnobotanical find of nigella seeds recovered in a pilgrim flask from the Old Hittite Period level of Boyal? Höyük (Mound), dating from around 1650 BC, in north-central Turkey. The study also deals with a comparison between the chemical properties of the Boyal? Höyük nigella seeds (ancient seeds) and those of modern nigella seeds. The results of chemical analysis of the debris found in the pilgrim flask to test the presence of bee product are also presented here.

Materials and methods

All macro-remains found in the pilgrim flask were first examined under a zoom stereomicroscope for specific determination and all were identified as nigella seeds using the reference collection of modern seeds. Ethyl alcohol and dichloromethane (Aldrich, Buch-Switzerland) were used for the extraction of the ancient seeds and modern nigella seeds to trace both polar and non-polar chemical compounds by a Gas Chromatography–Mass Spectrometer (GC–MS) system. Characterization of the chemical compounds in propolis extracts was also made by GC–MS.

Results

The GC–MS chromatograms showed that the ancient and modern seed samples were similar in essential oil acids. Many organic compounds of bee products, such as wax and phenolic antioxidants, were also detected in the container.

Conclusion

The results of this study indicated that the Hittite pilgrim flask contained a pure cache of nigella seeds mixed with bee products, wax and propolis. There has been no direct archaeological evidence for medicinal use of nigella seeds with bee products by the inhabitants of Boyal? Höyük or the Hittities so far. However, in view of the folkloric use of nigella seeds in combination with bee products for treatments of disorders and promotion of health, it is thought that the Boyal? Höyük material would represent a remedy used by the Hittites in Anatolia about 3600 years ago.