Radiation dose of digital radiography (DR) versus micro-dose x-ray (EOS) on patients with adolescent idiopathic scoliosis: 2016 SOSORT- IRSSD “John Sevastic Award” Winner in Imaging Research

Background

Patients with adolescent idiopathic scoliosis (AIS) frequently receive x-ray imaging at diagnosis and subsequent follow monitoring. The ionizing radiation exposure has accumulated through their development stage and the effect of radiation to this young vulnerable group of patients is uncertain. To achieve the ALARA (as low as reasonably achievable) concept of radiation dose in medical imaging, a slot-scanning x-ray technique by the EOS system has been adopted and the radiation dose using micro-dose protocol was compared with the standard digital radiography on patients with AIS.

Methods

Ninety-nine participants with AIS underwent micro-dose EOS and 33 underwent standard digital radiography (DR) for imaging of the whole spine. Entrance-skin dose was measured using thermoluminescent dosimeters (TLD) at three regions (i.e. dorsal sites at the level of sternal notch, nipple line, symphysis pubis). Effective dose and organ dose were calculated by simulation using PCXMC 2.0. Data from two x-ray systems were compared using independent-samples t-test and significance level at 0.05. All TLD measurements were conducted on PA projection only. Image quality was also assessed by two raters using Cobb angle measurement and a set of imaging parameters for optimization purposes.

Results

Entrance-skin dose from micro-dose EOS system was 5.9–27.0 times lower at various regions compared with standard DR. The calculated effective dose was 2.6?±?0.5 (μSv) and 67.5?±?23.3 (μSv) from micro-dose and standard DR, respectively. The reduction in the micro-dose was approximately 26 times. Organ doses at thyroid, lung and gonad regions were significantly lower in micro-dose (p?<?0.001). Data were further compared within the different gender groups. Females received significantly higher (p?<?0.001) organ dose at ovaries compared to the testes in males. Patients with AIS received approximately 16–34 times lesser organ dose from micro-dose x-ray as compared with the standard DR. There was no significant difference in overall rating of imaging quality between EOS and DR. Micro-dose protocol provided enough quality to perform consistent measurement on Cobb angle.

Conclusions

Entrance-skin dose, effective dose and organ dose were significantly reduced in micro-dose x-ray. The effective dose of a single micro-dose x-ray (2.6 μSv) was less than a day of background radiation. As AIS patients require periodic x-ray follow up for surveillance of curve progression, clinical use of micro-dose x-ray system is beneficial for these young patients to reduce the intake of ionizing radiation.

     

Comparison if the addition of multilevel vertebral augmentation to conventional therapy will improve the outcome of patients with multiple myeloma

Background

This was a prospective study to evaluate the effect of multilevel vertebral augmentation in addition to conventional therapy in multiple myeloma patients.

Methods

We treated 27 patients, whom were recently diagnosed to have multiple myeloma by two ways of treatment. Thirteen patients (group I) were treated with conventional therapy and 14 patients (group II) with adding vertebroplasty and kyphoplasty. Patients were evaluated pre-treatment and at half, one, two and 3-years post-treatment by using Oswestry Disability Index (ODI), the Stanford Score (SS) and the Spinal Instability Neoplastic Score (SINS).

Results

Mean values of ODI, SS and SINS were 31.9 (63.8%), 4.3 and 13.8 for group I and 33.2 (66.4%), 4.6 and 12.8 for group II before starting treatment. Group II showed improvement better than group I at all follow-up intervals with best results at first 6 months. P-values at the end of the study were ODI?=?0.047, SS?=?0.180 and SINS?=?0.002. Mortality rates were equal of both groups (four patients of each group).

Conclusion

Adding vertebral augmentation to conventional therapy improves multiple myeloma patients’ quality of life, but didn’t affect the mortality rate.

     

Doxorubicin chemotherapy affects intracellular and interstitial nitric oxide concentrations in skeletal muscle

The role of nitric oxide (NO) in doxorubicin (DOX; cancer chemotherapeutic)-induced cardiotoxicity is well established. In skeletal muscle (SM), NO regulation plays a critical role in health, biogenesis, and function. Despite the increasing evidence that indicates the negative impact of DOX on SM function, the effect of DOX on NO production in SM has yet to be examined. The purpose of the current study was to simultaneously examine intracellular and interstitial NO concentrations in the SM following the administration of DOX. A single dose of 1.5 or 4.5 mg/kg was administered intraperitoneally to male Sprague Dawley rats, and interstitial (IS) and intracellular (IC) NO was quantified every 24 up to 192 h post-injection. There was no significant difference in IC NO following the injection of 1.5 mg/kg DOX when compared to the control; however, the administration of 4.5 mg/kg DOX resulted in lower (P?<?0.05) concentrations of NO in the IC. Interestingly, a consistently higher (P?<?0.05) concentration of NO in the IS was established following the administration of 1.5 mg/kg compared to the control while no significant changes in IS NO resulted from the administration of the 4.5 mg/kg dose. The fluctuation of IS and IC NO was not a result of substrate availability as arginine concentrations remained stable throughout the experiment. By utilizing the microdialysis technique, we have simultaneously quantified for the first time the IS and IC concentrations of NO in SM following DOX administration. These data provide important insight in the possible mechanisms leading to DOX-related SM dysfunction.     

Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism

Serine proteases play an important role in inflammation via PARs. However, little is known of expression levels of PARs on monocytes of allergic patients, and influence of serine proteases and PARs on TNF-α secretion from monocytes. Using quantitative real-time PCR (qPCR) and flowcytometry techniques, we observed that the expression level of PAR-2 in monocytes of patients with allergic rhinitis and asthma was increased by 42.9 and 38.2 %. It was found that trypsin, thrombin, and tryptase induced up to 200, 320, and 310 % increase in TNF-α release from monocytes at 16 h, respectively. PAR-1 agonist peptide, SFLLR-NH₂, and PAR-2 agonist peptide tc-LIGRLO-NH₂ provoked up to 210 and 240 % increase in release of TNF-α. Since SCH 79797, a PAR-1 antagonist, and PD98059, an inhibitor of ERK inhibited thrombin- and SFLLR-NH₂-induced TNF-α release, the action of thrombin is most likely through a PAR-1- and ERK-mediated signaling mechanism. Similarly, because FSLLRN-NH₂, an inhibitor of PAR-2 diminished tryptase- and tc-LIGRLO-NH₂-induced TNF-α release, the action of tryptase appears PAR-2 dependent. Moreover, in vivo study showed that both recombinant cockroach major allergens Per a 1 and Per a 7 provoked upregulation of PAR-2 and PAR-1 expression on CD14+ cells in OVA-sensitized mouse peritoneum. In conclusion, increased expression of PAR-2 in monocytes of AR and asthma implicates that PAR-2 likely play a role in allergy. PAR-2- and PAR-1-mediated TNF-α release from monocytes suggests that these unique protease receptors are involved in the pathogenesis of inflammation.     

Extracellular ATP protects pancreatic duct epithelial cells from alcohol-induced damage through P2Y<Subscript>1</Subscript> receptor-cAMP signal pathway

Extracellular adenosine-5′-triphosphate (ATP) regulates cell death and survival of neighboring cells. The detailed effects are diverse depending on cell types and extracellular ATP concentration. We addressed the effect of ATP on ethanol-induced cytotoxicity in epithelial cells, the cell type that experiences the highest concentrations of alcohol. Using pancreatic duct epithelial cells (PDEC), we found that a micromolar range of ATP reverses all intracellular toxicity mechanisms triggered by exceptionally high doses of ethanol and, thus, improves cell viability dramatically. Out of the many purinergic receptors expressed in PDEC, the P2Y₁ receptor was identified to mediate the protective effect, based on pharmacological and siRNA assays. Activation of P2Y₁ receptors increased intracellular cyclic adenosine monophosphate (cAMP). The protective effect of ATP was mimicked by forskolin and 8-Br-cAMP but inhibited by a protein kinase A (PKA) inhibitor, H-89. Finally, ATP reverted leakiness of PDEC monolayers induced by ethanol and helped to maintain epithelial integrity. We suggest that purinergic receptors reduce extreme alcohol-induced cell damage via the cAMP signal pathway in PDEC and some other types of cells.     

Arsenic alters global histone modifications in lymphocytes in vitro and in vivo

Arsenic, an established carcinogen and toxicant, occurs in drinking water and food and affects millions of people worldwide. Arsenic appears to interfere with gene expression through epigenetic processes, such as DNA methylation and post-translational histone modifications. We investigated the effects of arsenic on histone residues in vivo as well as in vitro. Analysis of H3K9Ac and H3K9me3 in CD4+ and CD8+ sorted blood cells from individuals exposed to arsenic through drinking water in the Argentinean Andes showed a significant decrease in global H3K9me3 in CD4+ cells, but not CD8+ cells, with increasing arsenic exposure. In vitro studies of inorganic arsenic-treated T lymphocytes (Jurkat and CCRF-CEM, 0.1, 1, and 100 μg/L) showed arsenic-related modifications of H3K9Ac and changes in the levels of the histone deacetylating enzyme HDAC2 at very low arsenic concentrations. Further, in vitro exposure of kidney HEK293 cells to arsenic (1 and 5 μM) altered the protein levels of PCNA and DNMT1, parts of a gene expression repressor complex, as well as MAML1. MAML1 co-localized and interacted with components of this complex in HEK293 cells, and in silico studies indicated that MAML1 expression correlate with HDAC2 and DNMT1 expression in kidney cells. In conclusion, our data suggest that arsenic exposure may lead to changes in the global levels of H3K9me3 and H3K9Ac in lymphocytes. Also, we show that arsenic exposure affects the expression of PCNA and DNMT1—proteins that are part of a gene expression silencing complex.