Sub-angiographic peripheral emboli in high resolution DWI after endovascular recanalization

Journal of Neurology - To analyze the incidence of peripheral emboli after successful mechanical thrombectomy (MT) of intracranial large vessel occlusions (LVO). We performed a prospective analysis...     

Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation

Journal of Neurology - Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced...     

Pharmakotherapie und intensivmedizinische Aspekte des Status epilepticus: Update 2020/2021

Die Anaesthesiologie - Die gezielte Therapie epileptischer Ereignisse und im Speziellen des Status epilepticus (SE) setzt das sichere Erkennen der Krankheitsbilder voraus, wofür gerade bei...     

Effect of reverse total shoulder arthroplasty humeral inclination on glenohumeral range of motion,deltoid force,and glenoid strain: a biomechanical study

BackgroundReverse total shoulder arthroplasty (RSA) primarily varies between 2 implant design options: a 135 humeral stem inclination that closely resembles anatomic orientation, versus the Grammont-style 155 humeral stem inclination that further medializes and distalizes the center of rotation (COR). The purpose of this study was to compare deltoid force, glenoid strain, and simulated glenohumeral range of motion (ROM) between RSA 135 and RSA 155 designs, with a series of standardized permutations of glenosphere offset and rotator cuff pathology.MethodsTwelve fresh-frozen cadaveric shoulder specimens were studied using a shoulder simulator. Native shoulder motion profiles for reproducible abduction range of motion were established using a customized testing device. Optical 3-dimensional tracking and pressure sensors were used to accurately record glenohumeral range of motion (ROM), deltoid force, and glenoid strain for RSA 135 and RSA 155 designs. For each cohort, all combinations of glenosphere offsets and rotator cuff tendon involvement were evaluated.ResultsThere was no significant difference in the overall abduction ROM between the 155 and the 135 humeral stem implants (P = .75). Resting abduction angle and maximum abduction angle were significantly greater with a 155 + STD (standard offset) construct than with a 135 + STD construct (P < .001 and P = .01, respectively). Both stem inclinations decreased combined deltoid force requirements as compared the native shoulder with a massive cuff tear. Effective glenoid strain did not vary significantly between 135 + STD and 155 + STD constructs (P = .66).ConclusionOverall, range of motion between the 135 and the 155 humeral stem inclinations was not significantly different. The cumulative deltoid force was lower in RSA shoulders when compared to native shoulders with massive rotator cuff tears, highlighting the utility of both implant designs. The Grammont-style 155 stem coupled with a 2.5 mm inferior offset glenosphere required less deltoid force to reach maximum abduction than did the more anatomic, lateralized 135 stem coupled with a 4 mm lateral offset glenosphere.Level of EvidenceBasic Science, Biomechanics Controlled Laboratory Study     

Specific changes in the expression of imprinted genes in prostate cancer—implications for cancer progression and epigenetic regulation

Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation, enhancer of zeste homologue 2 (EZH2) overexpression and altered patterns of histone modifications is associated with the progression of prostate cancer. DNA methylation, EZH2 and histone modifications also ensure the parental-specific monoallelic expression of at least 62 imprinted genes. Although it is therefore tempting to speculate that epigenetic dysregulation may extend to imprinted genes, expression changes in cancerous prostates are only well documented for insulin-like growth factor 2 (IGF2). A literature and database survey on imprinted genes in prostate cancer suggests that the expression of most imprinted genes remains unchanged despite global disturbances in epigenetic mechanisms. Instead, selective genetic and epigenetic changes appear to lead to the inactivation of a sub-network of imprinted genes, which might function in the prostate to limit cell growth induced via the PI3K/Akt pathway, modulate androgen responses and regulate differentiation. Whereas dysregulation of IGF2 may constitute an early change in prostate carcinogenesis, inactivation of this imprinted gene network is rather associated with cancer progression.     

Circulating mitochondrial DNA in serum: A universal diagnostic biomarker for patients with urological malignancies

ObjectiveCell-free circulating mitochondrial DNA (mtDNA) has been proposed as universal diagnostic and prognostic biomarker in cancer patients.Patients and methodsCell-free DNA was isolated from 1 ml serum from patients with bladder cancer (BCA, n = 84), renal cell carcinoma (RCC, n = 33), and prostate cancer (CaP, n = 23), and compared with healthy individuals (n = 79). Quantitative real-time PCR was used to analyze the levels of a 79 bp (mtDNA-79), and 220 bp (mtDNA-220) fragment of the mitochondrial specific 16S-RNA. The mitochondrial DNA integrity (mtDNA-integrity) was defined as ratio of mtDNA-220 to mtDNA-79 fragments.ResultsIn healthy controls, mtDNA-79 levels were increased in male volunteers; mtDNA-230 levels and mtDNA-integrity were correlated with age. Neither mtDNA levels nor mtDNA-integrity were correlated with age or gender in cancer patients. Circulating mtDNA-79 (median 8.75 × 10⁶ vs. 0.43 × 10⁶ copies/ml) and mtDNA-230 (8.11 × 10⁶ vs. 0.27 × 10⁶ copies/ml) levels were significantly increased in cancer patients and allowed sensitive (84%) and specific (97%) discrimination from healthy controls. mtDNA levels were unequally distributed among the different cancer entities (mtDNA-79: BCA 9.54 × 10⁶ vs. RCC 6.69 × 10⁶ vs. CaP 4.48 × 10⁶ copies/ml; mtDNA-230: BCA 9.78 × 10⁶ vs. RCC 6.74 × 10⁶ vs. CaP 1.94 × 10⁶ copies/ml). The mtDNA-integrity was increased in RCC and BCA patients compared to control subjects and CaP patients. Serum mtDNA-integrity was correlated with pathological stage in RCC and with tumor grade in BCA patients.ConclusionCirculating mtDNA levels are associated with gender and age in healthy individuals, but not in cancer patients. Quantification of circulating mtDNA may help identify patients with urologic malignancies.