Distal radius fluoroscopic skyline view: extension–supination versus flexion–supination

European Journal of Orthopaedic Surgery & Traumatology - The aim of our study was to compare the vertical fluoroscopic view of the wrist in extension and supination (ES) to the view in flexion...     

MRI‐Guided High‐Intensity Focused Ultrasound as an Emerging Therapy for Stroke: A Review

Stroke, either ischemic or hemorrhagic, accounts for significantly high morbidity and mortality rates around the globe effecting millions of lives annually. For the past few decades, ultrasound has been extensively investigated to promote clot lysis for the treatment of stroke, myocardial infarction, and acute peripheral arterial occlusions, with or without the use of tPA or contrast agents. In the age of modern minimal invasive techniques, magnetic resonance imaging‐guided high‐intensity focused ultrasound is a new emerging modality that seems to promise therapeutic utilities for both ischemic and hemorrhagic stroke. High‐intensity focused ultrasound causes thermal heating as the tissue absorbs the mechanical energy transmitted by the ultrasonic waves leading to tissue denaturation and coagulation. Several in‐vitro and in‐vivo studies have demonstrated the viability of this technology for sonothrombolysis in both types of stroke and have warranted clinical trials. Apart from safety and efficacy, initiation of trials would further enable answers regarding its practical application in a clinical setup. Though this technology has been under study for treatment of various brain diseases for some decades now, relatively very few neurologists and even neurosurgeons seem to be acquainted with it. The aim of this review is to provide basic understanding of this powerful technology and discuss its clinical application and potential role as an emerging viable therapeutic option for the future management of stroke.     

Increasing the Risk of Stroke by Opium Addiction

IntroductionStroke is among the leading causes of mortality and morbidity in the world. Besides the identified risk factor, Ischemic stroke evidence show drug use develops or exacerbates the atherosclerotic process. The current study aimed at comparing cerebrovascular ultrasounds’ changes in addicted and nonaddicted people who developed ischemic stroke.MethodsIn the current cross-sectional study, a total of 133 patients with ischemic stroke who were admitted to Vali-Asr hospital from June 2016 to April 2017 were enrolled. For obtaining the quantitative data, t test or Mann-Whitney test was employed to compare the addict or no-addict groups, as well as, categorical data testing was performed using chi-square test. Also, the multiple logistic regression was used for identifying the factors and the significance level was set at 5%.ResultsThe current study was performed on 133 patients, among them 41 patients (30.8%) were opium addicted, and 92 patients (69.2%) were nonaddict. The mean [IQR] number of atherosclerotic plaques were significantly higher in opium addicted group in comparison with the nonaddicted group (3.0 [1.0-4.0] versus 1.5 [0.0-3.0], P = .008). The possibility of increasing the number of plaques in addicted patients was 1.42 times higher than the nonaddicted patients (odds ratio (95% confidence interval): 1.42 (1.11-1.81), P = .005).ConclusionThe findings demonstrated a significant difference in the vessel stenosis pattern between the addict and nonaddict ischemic stroke groups. To investigate the possible effects of opium use and its associated parameters, ie, dosage, duration of use, and the way of opium use on ischemic stroke, further studies are required.     

Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies

Cancer immunotherapy centers on modulating the host's tumor-directed immune response. One promising approach involves augmentation of cell-mediated immunity by interrupting T-cell pathways responsible for immune down-regulation or tolerance. The discovery of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and its role as a key negative regulator for T cells has prompted efforts to target this signaling molecule to improve cancer therapy. Activation, or 'priming', of naive T cells in response to tumor-cell invasion comprises a dual-signaling mechanism. Signal 1 requires tumor-associated antigen recognition by the T-cell receptor, while signal 2 occurs through binding of CD80 or CD86 (B7.1 of 2) on the antigen presenting cell (APC) with CD28 on the T cell. Importantly, there is a final step responsible for naturally occurring immune regulation; this occurs in response to competitive binding of CD80/CD86 on the APC by CTLA-4 on the T cell. This 'immune checkpoint' interrupts signal 2 and inhibits the activated T cell. Targeting CTLA-4 as an anticancer strategy: Following proof-of-concept studies in animals, fully human anti-CTLA-4 antibodies were developed and 2 are undergoing clinical evaluation. Ipilimumab and tremelimumab have shown promising antitumor activity, initially in patients with advanced melanoma. Class-specific immune-related adverse events (irAEs) were common and mostly transient and/or manageable. These events are thought to be mechanism-of-action-related, indicating immune tolerance is broken; this relation may also explain the association between irAEs and response seen in several trials. Interruption of immune inhibitory pathways via CTLA-4 blockade appears to be a promising strategy for cancer immunotherapy.     

Tumor paint: a chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci

Toward the goal of developing an optical imaging contrast agent that will enable surgeons to intraoperatively distinguish cancer foci from adjacent normal tissue, we developed a chlorotoxin:Cy5.5 (CTX:Cy5.5) bioconjugate that emits near-IR fluorescent signal. The probe delineates malignant glioma, medulloblastoma, prostate cancer, intestinal cancer, and sarcoma from adjacent non-neoplastic tissue in mouse models. Metastatic cancer foci as small as a few hundred cells were detected in lymph channels. Specific binding to cancer cells is facilitated by matrix metalloproteinase-2 (MMP-2) as evidenced by reduction of CTX:Cy5.5 binding in vitro and in vivo by a pharmacologic blocker of MMP-2 and induction of CTX:Cy5.5 binding in MCF-7 cells following transfection with a plasmid encoding MMP-2. Mouse studies revealed that CTX:Cy5.5 has favorable biodistribution and toxicity profiles. These studies show that CTX:Cy5.5 has the potential to fundamentally improve intraoperative detection and resection of malignancies.     

The Cardiac Effects of Prolonged Vitamin B12 and Folate Deficiency in Rats

In the recent past, hyperhomocysteinemia (HHCY) has been linked to chronic heart failure. Folate and vitamin B12 deficiencies are the common causes of HHCY. The impact of these vitamins on cardiac function and morphology has scarcely been investigated. The aim of this study was to conduct an analysis of the cardiac effect of folate and vitamin B12 deficiency in vivo. Two groups of rats, a control (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10), were fed for 12 weeks with a folate and vitamin B12-free diet or an equicaloric control diet. Plasma and tissue concentrations of HCY, S-adenosyl-homocysteine (SAH), S-adenosyl-methionine (SAM), and brain natriuretic peptide (BNP) were measured. Moreover, echocardiographic and histomorphometric analyses were performed. VitDef animals developed a significant HHCY (Co vs VitDef: 6.8 ± 2.7 vs 61.1 ± 12.8 μmol/l, P < 0.001). Fractional shortening, left ventricular dimension at end-diastole and end-systole, posterior wall thickness, perivascular collagen, mast cell number, and BNP tissue levels were comparable in VitDef and Co animals. Interstitial collagen (Co vs VitDef: 6.8 ± 3.0 vs 4.5 ± 2.1%, P < 0.05), plasma BNP (Co vs VitDef: 180 ± 80 vs 70 ± 60 ng/l, P < 0.05), and tissue HCY (Co vs VitDef: 0.13 ± 0.07 vs 0.07 ± 0.04 μmol/g protein, P < 0.05) were lower in VitDef animals. Folate and vitamin B₁₂ deficiency do not affect cardiac function and morphology.     

Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease

Among genetic factors that may contribute to the development and progression of Graves’ disease (GD) and its complications are polymorphisms in the genes encoding cytokines. The association between GD and the following polymorphisms in anti-inflammatory cytokines was studied in 107 patients with GD and 140 healthy controls: IL-4 (−1098T/G, −590T/C, −33C/T), IL-10 (−1082A/G, −819C/T, −592C/A) and TGF-β (+869T/C, +915G/C). The following alleles and genotypes were significantly (P < 0.01 after correction for multiple testing) more frequent among patients: the IL-4 −1098G allele and GG genotype (OR = 3.12 and 105.00, respectively), IL-4 −33T allele and TT genotype (OR = 2.52 and 118.83, respectively), IL-10 −1082G allele and GG genotype (OR = 2.16 and 6.40, respectively), IL-10 −819T allele, TC and TT genotype (OR = 2.60, 3.68 and 6.76, respectively), IL-10 −592A allele, AC and AA genotype (OR = 2.41, 2.89 and 5.68, respectively), TGF-β +869C allele and CC genotype (OR = 2.24 and 6.21, respectively), and TGF-β +915C allele, CG and CC genotype (OR = 7.81, 11.80 and 20.40, respectively). The only allele and genotype with a lower frequency in patients were IL-4 −590T allele and TC genotype (OR = 0.47 and 0.08, respectively; P < 0.01). In conclusion, this study highlighted the importance of anti-inflammatory cytokine gene polymorphisms in susceptibility to GD.