Hip osteoarthritis often coexists with adult spinal deformity, an abnormality in which sagittal spinopelvic malalignment is present. Debate exists whether to perform spinal realignment correction or ...total hip arthroplasty first. Hip extension and pelvic tilt are important compensatory mechanisms in the setting of sagittal spinopelvic malalignment and change after spinal realignment. We performed this study to evaluate the effect that the spinal realignment surgical procedure has on acetabular anteversion.
This study is a retrospective review of a multicenter, prospective, consecutive database of patients with adult spinal deformity who underwent surgical spinal realignment. Only patients who already had undergone a total hip arthroplasty prior to the spinal realignment procedure were retained for analysis. Patients were excluded if they had insufficient imaging or large-head, metal-on-metal bearings or they had undergone revision total hip arthroplasty in the study period. Acetabular anteversion was calculated via the ellipse method on a standing, posterior-anterior, 90-cm radiograph with a well-centered pelvis. Anteversion was measured preoperatively and at six weeks or three months after the spinal realignment procedure. Spinopelvic parameters measured included pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, T1 pelvic angle, sagittal vertical axis, T1-spinopelvic inclination, and thoracic kyphosis.
Forty-one hips (thirty-three patients) were identified. Acetabular anteversion significantly reduced (p < 0.001) after spinal correction by mean change of -4.96° (range, -22.32° to +2.36°). The change in anteversion correlated with the changes in sagittal pelvic orientation (0.828 for the pelvic tilt, -0.757 for the sacral slope, and -0.691 for the lumbar lordosis) and global spinopelvic alignment (0.579 for the sagittal vertical axis and 0.585 for the T1 pelvic angle). Regression analysis revealed that anteversion decreased by 1° for each of the following spinopelvic parameter changes (p < 0.001): 1.105° for spinopelvic tilt, 1.032° for sacral slope, and 3.163° for lumbar lordosis.
Patients with spinopelvic malalignment had a high prevalence of excessively anteverted acetabular components. Sagittal spinal correction following total hip arthroplasty resulted in reduced acetabular anteversion, which may have implications for stability. Changes in anteversion are most closely related to changes in pelvic tilt in an almost one-to-one ratio.
Abstract Background Lumbar-pelvic fusion reduces the variation in pelvic tilt in functional situations by reducing lumbar spine flexibility, which is thought to be important in maintaining stability ...of a total hip arthroplasty (THA). We compared dislocation and revision rates for patients with lumbar fusion and subsequent THA to a matched comparison cohort with hip and spine degenerative changes undergoing only THA. Methods We identified patients in New York State who underwent primary elective lumbar fusion for degenerative disc disease pathology and subsequent THA between January 2005 and December 2012. A propensity score match was performed to compare 934 patients with prior lumbar fusion to 934 patients with only THA according to age, gender, race, Deyo comorbidity score, year of surgery, and surgeon volume. Revision and dislocation rates were assessed at 3, 6, and 12 months post-THA. Results At 12 months, patients with prior lumbar fusion had significantly increased rates of THA dislocation (control: 0.4%; fusion: 3.0%; P < .001) and revision (control: 0.9%; fusion: 3.9%; P < .001). At 12 months, fusion patients were 7.19 times more likely to dislocate their THA ( P < .001) and 4.64 times more likely to undergo revision ( P < .001). Conclusion Patients undergoing lumbar fusion and subsequent THA have significantly higher risks of dislocation and revision of their hip arthroplasty than a matched cohort of patients with similar hip and spine pathology but only undergoing THA. During preoperative consultation for patients with prior lumbar fusion, orthopedic surgeons must educate the patient and family about the increased risk of dislocation and revision.
Summary
This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients ...encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well‐established registry.
Since our first report in 2013, the number of patients entered into the UKPID registry has more than doubled to 4758 encompassing 97% of immunology centers within the United Kingdom. We believe this registry now represents virtually all patients with primary immunodeficiency within the UK. As such, this dataset continues to provide valuable information to clinicians, researchers, service commissioners and industry alike on PID within the UK, which may not otherwise be available without the existence of a well‐established registry.
Abstract
Millions of individuals are exposed to repetitive head impacts (RHI) each year through contact sports, military blast, and interpersonal violence. RHI is the major risk factor for developing ...chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. Recent consensus criteria defined the pathognomonic lesion in CTE as perivascular, hyperphosphorylated tau (p-tau) in neuronal aggregates. Astroglial p-tau is an inconsistent supporting feature and not in itself diagnostic of CTE. This study quantitated the spatial and cellular distribution of p-tau pathology in postmortem dorsolateral frontal cortex of 150 individuals with CTE, from ages 21 to 80 years old, without comorbid pathology. p-Tau-immunoreactive cells were quantitated in the gray matter sulcus, crest, subpial region, and within pathognomonic CTE lesions. Significantly more neuronal p-tau than astrocytic p-tau was found across all cortical regions (p < 0.0001). Sulcal astrocytic p-tau was primarily (75%, p < 0.0001) localized to subpial regions as thorn-shaped astrocytes, a form of age-related tau astrogliopathy. Neuronal p-tau was significantly associated with age, years of RHI exposure, and CTE severity; astrocytic p-tau pathology was only significantly associated with age. These findings strongly support neuronal degeneration as a driving feature of CTE and will help inform future research and the development of fluid biomarkers for the detection of neuronal degeneration in CTE.
The role of astrocytes is becoming increasingly important to understanding how glioblastoma (GBM) tumor cells diffusely invade the brain. Yet, little is known of the contribution of extracellular ...vesicle (EV) signaling in GBM/astrocyte interactions. We modeled GBM-EV signaling to normal astrocytes in vitro to assess whether this mode of intercellular communication could support GBM progression. EVs were isolated and characterized from three patient-derived GBM
stem
cells (NES
+
/CD133
+
) and their differentiated (
diff
) progeny cells (NES
−
/CD133
−
). Uptake of GBM-EVs by normal primary astrocytes was confirmed by fluorescence microscopy, and changes in astrocyte podosome formation and gelatin degradation were measured. Quantitative mass spectrometry-based proteomics was performed on GBM-EV stimulated astrocytes. Interaction networks were generated from common, differentially abundant proteins using Ingenuity® (Qiagen Bioinformatics) and predicted upstream regulators were tested by qPCR assays. Podosome formation and Cy3-gelatin degradation were induced in astrocytes following 24-h exposure to GBM-
stem
and -
diff
EVs, with EVs released by GBM-
stem
cells eliciting a greater effect. More than 1700 proteins were quantified, and bioinformatics predicted activations of MYC, NFE2L2, FN1, and TGFβ1 and inhibition of TP53 in GBM-EV stimulated astrocytes that were then confirmed by qPCR. Further qPCR studies identified significantly decreased Δ133p53 and increased p53
β
in astrocytes exposed to GBM-EVs that might indicate the acquisition of a pro-inflammatory, tumor-promoting senescence-associated secretory phenotype (SASP). Inhibition of TP53 and activation of MYC signaling pathways in normal astrocytes exposed to GBM-EVs may be a mechanism by which GBM manipulates astrocytes to acquire a phenotype that promotes tumor progression.
Abstract Background Context Patients with degenerative lumbar stenosis (DLS) adopt a forward flexed posture in an attempt to decompress neural elements. The relationship between sagittal alignment ...and severity of lumbar stenosis has not previously been studied. Purpose We hypothesized that patients with increasing radiological severity of lumbar stenosis will exhibit worsening sagittal alignment. Study Design This is a cross-sectional study. Patient Sample Our sample consists of patients who have DLS. Outcome Measures Standing pelvic, regional, lower extremity and global sagittal alignment, and health-related quality of life (HRQoL) were the outcome measures. Methods Patients with DLS were identified from a retrospective clinical database with corresponding full-body stereoradiographs. Exclusion criteria included coronal malalignment, prior spine surgery, spondylolisthesis>Grade 1, non-degenerative spinal pathology, or skeletal immaturity. Central stenosis severity was graded on axial T2-weighted magnetic resonance imaging (MRI) from L1–S1. Foraminal stenosis and supine lordosis was graded on sagittal T1-weighted images. Standing pelvic, regional, lower extremity, and global sagittal alignment were measured using validated software. The HRQoL measures were also analyzed in relation to severity of stenosis. Results A total of 125 patients were identified with DLS on appropriate imaging. As central stenosis grade increased, patients displayed significantly increasing standing T1 pelvic angle, pelvic tilt, sagittal vertical axis, and pelvic incidence-lumbar lordosis (p<.05). No significant difference wasfound in pelvic incidence, supine lordosis, thoracic kyphosis, or T1 spinopelvic inclination between central stenosis groups. Despite similar supine lordosis between stenosis groups, patients with Grades 2 and 3 stenosis had less standing lordosis, suggesting antalgic posturing. Upper lumbar (L1–L3) stenosis predicted worse alignment than lower lumbar (L4–S1) stenosis. Increasing severity of foraminal stenosis was associated with reduced lumbar lordosis; however, no significant postural difference in lordosis, thoracolumbar, or lower extremity compensatory mechanisms were noted between foraminal stenosis groups. Stenosis grading did not predict worsening HRQoLs in central or foraminal stenosis. Conclusions Severity of central lumbar stenosis as graded on MRI correlates with severity of sagittal malalignment. These findings support theories of sagittal malalignment as a compensatory mechanism for central lumbar stenosis.
Distance sampling is a popular statistical method to estimate the density of wild animal populations. Conventional distance sampling represents animals as fixed points in space that are detected with ...an unknown probability that depends on the distance between the observer and the animal. Animal movement can cause substantial bias in density estimation. Methods to correct for responsive animal movement exist, but none account for nonresponsive movement independent of the observer. Here, an explicit animal movement model is incorporated into distance sampling, combining distance sampling survey data with animal telemetry data. Detection probability depends on the entire unobserved path the animal travels. The intractable integration over all possible animal paths is approximated by a hidden Markov model. A simulation study shows the method to be negligibly biased (<5%) in scenarios where conventional distance sampling overestimates abundance by up to 100%. The method is applied to line transect surveys (1999-2006) of spotted dolphins (Stenella attenuata) in the eastern tropical Pacific where abundance is shown to be positively biased by 21% on average, which can have substantial impact on the population dynamics estimated from these abundance estimates and on the choice of statistical methodology applied to future surveys.
Supplementary materials
for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.
This paper presents the design of a front-end circuit for monolithic active pixel sensors. The circuit operates with a sensor featuring a small, low-capacitance (< 2 fF) collection electrode and is ...integrated in the DPTS chip, a proof-of-principle prototype of 1.5 mm × 1.5 mm including a matrix of 32 × 32 pixels with a pitch of 15 μm. The chip is implemented in the 65 nm imaging technology from the Tower Partners Semiconductor Co. foundry and was developed in the framework of the EP-R&D program at CERN to explore this technology for particle detection. The front-end circuit has an area of 42 μm 2 and can operate with a power consumption as low as 12 nW. Measurements on the prototype relevant to the front-end will be shown to support its design.
Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ...ischemia-reperfusion injury in solid organ transplantation.
A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups.
No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm (p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC.
RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation.
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