Citations

Abstract Background Guidelines recommend that all patients with upper gastrointestinal bleeding (UGIB) undergo endoscopy within 24 h. It is unclear whether a subgroup may benefit from an urgent intervention. We aimed to evaluate the influence of endoscopic hemostasis and urgent endoscopy on mortality in UGIB patients with high-risk stigmata (HRS). Methods Consecutive patients with suspected UGIB were enrolled in three Japanese hospitals with a policy to perform endoscopy within 24 h. The primary outcome was 30-day mortality. Endoscopic hemostasis and endoscopy timing (urgent, ≤6 h; early, >6 h) were evaluated in a regression model adjusting for age, systolic pressure, heart rate, hemoglobin, creatinine, and variceal bleeding in multivariate analysis. A propensity score of 1:1 matched sensitivity analysis was also performed. Results HRS were present in 886 of 1966 patients, and 35 of 886 (3.95%) patients perished. Median urgent-endoscopy time (n = 769) was 3.0 h (interquartile range [IQR], 2.0–4.0 h) and early endoscopy (n = 117) was 12.0 h (IQR, 8.5–19.0 h). Successful endoscopic hemostasis and urgent endoscopy were significantly associated with reduced mortality in multivariable analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09–0.52; P = 0.0006, and OR, 0.37; 95% CI, 0.16–0.87; P = 0.023, respectively). In a propensity-score-matched analysis of 115 pairs, adjusted comparisons showed significantly lower mortality of urgent vs early endoscopy (2.61% vs 7.83%, P < 0.001). Conclusions A subgroup of UGIB patients, namely those harboring HRS, may benefit from endoscopic hemostasis and urgent endoscopy rather than early endoscopy in reducing mortality. Implementing triage scores that predict the presence of such lesions is important.

Abstract BRCA1 plays an important roles in several biological events during the DNA damage response (DDR). Recently, some reports have indicated that BRCA1 dysfunction is involved in the pathogenesis of Alzheimer disease (AD). Furthermore, it has also been reported that BRCA1 accumulates within neurofibrillary tangles (NFTs) in the AD brain. In this study, we examined the immunohistochemical distribution of BRCA1 and another DDR protein, p53-Binding Protein 1 (53BP1), in AD, Pick disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration, and frontotemporal dementia with parkinsonism linked to chromosome 17. In control subjects, neither BRCA1 nor phosphorylated BRCA1 (pBRCA1; Ser1524) immunoreactivity was observed in neurons or glial cells; and that for pBRCA1 (Ser1423) and 53BP1 were slightly detected in neuronal nuclei. The immunoreactivity for both BRCA1 and pBRCA1 (Ser1423) was localized within phosphorylated tau inclusions in all tauopathies, whereas that for pBRCA1 (Ser1524) was mainly associated with Pick bodies in PiD and to a lesser extent with NFTs in AD. On the other hand, 53BP1-immunoreactive deposits tended to be increased in the nucleus of neurons in AD and PSP compared with those in control cases. Our results suggest that DDR dysfunction due to cytoplasmic sequestration of BRCA1 could be involved in the pathogenesis of tauopathies.

Abstract Aims To investigate valve sizing and the haemodynamic relevance of the predicted left ventricular outflow tract (LVOT) in patients with mitral annular calcification (MAC) undergoing transatrial transcatheter valve implantation (THV). Methods and results In total, 21 patients undergoing transatrial THV, multiplanar reconstruction (MPR), maximum intensity projection (MIP), and cubic spline interpolation (CSI) were compared for MA sizing during diastole. In addition, predicted neo-LVOT areas were measured in 18 patients and correlated with the post-procedural haemodynamic dimensions. The procedure was successful in all patients (100%). Concomitant aortic valve replacement was performed in eight patients (43%) (AVR group). Sizing using MPR and MIP yielded comparable results in terms of area, perimeter, and diameter, whereas the dimensions obtained with CSI were systematically smaller. The simulated mean systolic neo-LVOT area was 133.4 ± 64.2 mm2 with an anticipated relative LVOT area reduction (neo-LVOT area/LVOT area × 100) of 59.3 ± 14.7%. The systolic relative LVOT area reduction, but not the absolute neo-LVOT area, was found to predict the peak (r = 0.69; P = 0.002) and mean (r = 0.65; P = 0.004) post-operative aortic gradient in the overall population as well as separately in the AVR (peak: r = 0.91; P = 0.002/mean: r = 0.85; P = 0.002) and no-AVR (peak: r = 0.89; P = 0.003/mean: r = 0.72; P = 0.008) groups. Conclusion In patients with severe MAC undergoing transatrial transcatheter valve implantation, MPR, and MIP yielded comparable annular dimensions, while values obtained with CSI tended to be systematically smaller. Mitral annular area and the average annular diameter appear to be reliable parameters for valve selection. Simulated relative LVOT reduction was found to predict the post-procedural aortic gradients.

Background: Low wall shear stress (LSS) is an established cause of pro-atherogenic endothelial pathophysiology, yet it has never been demonstrated in the cerebral circulation affected by intracranial atherosclerotic disease (ICAD). Noninvasive CT angiography (CTA) computational fluid dynamics (CFD) enables high-resolution investigation of detailed post-stenotic phenomena. We used all available CTA data in the SAMMPRIS trial of ICAD to detect and quantify post-stenotic LSS. Methods: CTA source images from SAMMPRIS were reconstructed in 3D followed by geometry refinements to generate a mesh of the diseased arterial lesion and adjacent segments. CFD was performed with Ansys (ICEM, Fluent), applying reference boundary conditions with k-omega turbulence and non-Newtonian modeling of the traversing blood viscosity. 3D CFD parameter maps illustrated velocity, velocity swirling and corresponding wall shear stress. Results: 144 subjects enrolled in SAMMPRIS had CTA at baseline, including 140 with CTA source images enabling CFD. Post-stenotic velocity profiles revealed vortices in all cases, quantified by swirling and turbulent kinetic energy. These luminal flow changes were adjacent to focal regions of LSS in the post-stenotic region (Figure). Conclusions: Low wall shear stress is associated with vortices of fluid flow in CTA CFD modeling of ICAD from SAMMPRIS. CTA source images may be used to noninvasively quantify LSS and model this pro-atherogenic factor in ICAD across a wide variety of lesions. Future studies should examine the related endothelial biology and potential link with plaque evolution.

Purpose To determine the feasibility of shear wave elastography (SWE) with B‐mode ultrasound in predicting the stiffness of the rotator cuff muscle before arthroscopic rotator cuff repair to evaluate the difficulty of the surgical procedure, as well as to compare SWE with the Goutallier stage on magnetic resonance imaging (MRI). Methods Thirty‐eight patients with a full‐thickness supraspinatus tear requiring arthroscopic rotator cuff repair participated. The Goutallier stage of fatty infiltration on MRI was measured before surgery, as was the SWE modulus of the anterior superficial, anterior deep, posterior superficial, and posterior deep (PD) regions of the supraspinatus muscle. To measure the stiffness of the supraspinatus musculotendinous unit during surgery, the supraspinatus tendon was axially stretched until the anatomic insertion site was reached, and force per deformation was recorded. The correlation between stiffness of the supraspinatus and SWE value in each region of the supraspinatus muscle or Goutallier stage was determined. In addition, patients were divided into 2 groups: (1) In the complete footprint coverage group, greater than 50% of the footprint was covered during the stiffness measurement, and (2) in the incomplete footprint coverage group, less than 50% of the footprint was covered during the stiffness measurement. Differences in SWE value and Goutallier stage were measured between the 2 groups. Results The best correlation of stiffness with the SWE modulus of the PD muscle of the supraspinatus was R = 0.69, and the correlation of stiffness with the Goutallier stage on MRI was R = 0.48. The SWE value of the PD region was greater in the incomplete footprint coverage group than in the complete footprint coverage group, although the Goutallier stage was not significantly different. Conclusions The highest correlation with stiffness of the supraspinatus musculotendinous unit was with the SWE modulus of the PD muscle, as compared with SWE evaluation of the other regions or the Goutallier stage on MRI. Ultrasound SWE can predict the stiffness of the supraspinatus musculotendinous unit best. Clinical Relevance Rotator cuff retraction adds difficulty to arthroscopic rotator cuff repair. Ultrasound SWE may be used for presurgical planning.

AimsThe human epidermal growth factor receptor family consists of four members that belong to the ErbB lineage of proteins (ErbB1‐4). Neuregulin‐1 (NRG1)/ErbB signalling regulates brain development and function. Abnormalities in this signalling have been implicated in the aetiology or development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. So, we aimed at investigating whether the expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy (PSP).MethodsThe brains of 10 PSP and six control patients were investigated by immunohistochemical analysis.ResultsWhereas C‐terminal ErbB4 immunoreacitivity was partially but distinctly present in the cytoplasm and/or in the nucleus of neurons in control patients, it was rarely observed in the neuronal nuclei in PSP patients. In contrast, neurofibrillary tangles, coiled bodies and threads were robustly immunoreactive for C‐terminal ErbB4 in PSP. Double immunofluorescence for C‐terminal ErbB4 and phospho‐tau revealed co‐localization of these proteins within neuronal and glial inclusions. To the contrary, there was no difference in the subcellular localization of NRG1, ErbB1, ErbB2, and N‐terminal ErbB4 between control and PSP patients. These proteins were localized in the cytoplasm of neurons.ConclusionsOur present results suggest that NRG1/ErbB4 signalling could be an important event in the pathogenesis of PSP.