Positron Emission Tomography with [18F]ROStrace Reveals Progressive Elevations in Oxidative Stress in a Mouse Model of Alpha-Synucleinopathy.

The synucleinopathies are a diverse group of neurodegenerative disorders characterized by the accumulation of aggregated alpha-synuclein (aSyn) in vulnerable populations of brain cells. Oxidative stress is both a cause and a consequence of aSyn aggregation in the synucleinopathies; however, noninvasive methods for detecting oxidative stress in living animals have proven elusive. In this study, we used the reactive oxygen species (ROS)-sensitive positron emission tomography (PET) radiotracer [18F]ROStrace to detect increases in oxidative stress in the widely-used A53T mouse model of synucleinopathy. A53T-specific elevations in [18F]ROStrace signal emerged at a relatively early age (6-8 months) and became more widespread within the brain over time, a pattern which paralleled the progressive development of aSyn pathology and oxidative damage in A53T brain tissue. Systemic administration of lipopolysaccharide (LPS) also caused rapid and long-lasting elevations in [18F]ROStrace signal in A53T mice, suggesting that chronic, aSyn-associated oxidative stress may render these animals more vulnerable to further inflammatory insult. Collectively, these results provide novel evidence that oxidative stress is an early and chronic process during the development of synucleinopathy and suggest that PET imaging with [18F]ROStrace holds promise as a means of detecting aSyn-associated oxidative stress noninvasively.

Variable methodological quality and use found in systematic reviews referenced in STEMI clinical practice guidelines.

BACKGROUND: The objective of this study was to assess the methodological quality and clarity of reporting of the systematic reviews (SRs) supporting clinical practice guideline (CPG) recommendations in the management of ST-elevation myocardial infarction (STEMI) across international CPGs. METHODS: We searched 13 guideline clearinghouses including the National Guideline Clearinghouse and Guidelines International Network (GIN). To meet inclusion criteria CPGs must be pertinent to the management of STEMI, endorsed by a governing body or national organization, and written in English. We retrieved SRs from the reference sections using a combination of keywords and hand searching. Two investigators scored eligible SRs using AMSTAR and PRISMA. RESULTS: We included four CPGs. We extracted 71 unique SRs. These SRs received AMSTAR scores ranging from 1 (low) to 9 (high) on an 11-point scale. All CPGs consistently underperformed in areas including disclosure of funding sources, risk of bias, and publication bias according to AMSTAR. PRISMA checklist completeness ranged from 44% to 96%. The PRISMA scores indicated that SRs did not provide a full search strategy, study protocol and registration, assessment of publication bias or report funding sources. Only one SR was referenced in all four CPGs. All CPGs omitted a large subset of available SRs cited by other guidelines. CONCLUSIONS: Our study demonstrates the variable quality of SRs used to establish recommendations within guidelines included in our sample. Although guideline developers have acknowledged this variability, it remains a significant finding that needs to be addressed further. FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Evaluation of Fetal First and Second Cervical Vertebrae: Normal or Abnormal?

OBJECTIVES: To use 3-dimensional sonographic volumes to evaluate the variable appearance of the normal fetal cervical spine and craniocervical junction, which if unrecognized may lead to misdiagnosis of malalignment at the first and second cervical vertebrae (C1 and C2). METHODS: Three-dimensional sonographic volumes of the fetal cervical spine were obtained from 24 fetuses at gestational ages between 12 weeks 6 days and 35 weeks 1 day. The volumes were reviewed on 4-dimensional software, and the vertebral level was determined by labeling the first rib-bearing vertebra as the first thoracic vertebra. The ossification centers of the cervical spine and occipital condyles were then labeled accordingly and evaluated for alignment and structure by rotating the volumes in oblique planes. The appearance on multiplanar images was assessed for possible perceived anomalies, including malalignment, particularly at the C1 and C2 levels. Evidence of head rotation was correlated with the presence of possible malalignment at C1-C2. Head rotation was identified in the axial plane by measuring the angle of the anteroposterior axis of C1 to the anteroposterior axis of C2. RESULTS: Of the 24 fetuses, 16 had adequate quality to assess the entire cervical spine and craniocervical junction. All 16 cases showed an osseous component of C1 that did not align directly with C2 on some of the multiplanar images when the volumes were rotated, which could lead to suspected diagnosis of spinal malalignment or a segmental abnormality, as occurred in 2 clinical cases in our practice. All 16 cases showed at least some degree of head rotation, ranging from 2° to 36°, which may possibly explain the apparent malalignment. The lateral offset from C1 to C2 ranged from 0.0 to 3.3 mm. CONCLUSIONS: The normal C1 and C2 ossification centers may appear to be malaligned due to normal offsetting (lateral displacement) of C1 on C2. An understanding of the normal development of the cervical spine is important in assessing spinal anatomy.

Unusual Concentration of Tc-99m methylendiphosphonate in Rhabdomyosarcoma.

Extraosseous accumulation of bone-seeking agents is rare, but has been previously reported in pediatric sarcomas and neuroblastomas. We present an unusual case of a 5-month-old male with an abdominal mass observed clinically by his parents and referring pediatrician. Contrast abdominal computerized tomography confirmed the presence of a large pelvic mass that was diagnosed pathologically as embryonal rhabdomyosarcoma. A bone scintigraphy that was performed for staging of the disease revealed accumulation of the radiopharmaceutical in the tumor. There was no evidence for skeletal metastatic disease. This case further demonstrates the nonspecificity of soft-tissue tumor uptake on bone scintigraphy.

Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients.

PURPOSE: Inflammatory processes have been implicated in the pathogenesis of both depression and cancer. Links between depressive symptoms, interleukin-6 (IL-6), and cortisol dysregulation have been demonstrated in cancer patients, but vegetative versus affective components of depression have been minimally examined. The objective of the current study was to examine associations between IL-6, diurnal cortisol rhythms, and facets of depression in epithelial ovarian cancer patients. PATIENTS AND METHODS: Patients awaiting surgery for a pelvic mass suspected for ovarian cancer completed questionnaires, collected salivary samples for 3 days presurgery, and gave a presurgical blood sample. Ascites was obtained during surgery. IL-6 was measured by enzyme-linked immunosorbent assay and cortisol by a chemiluminescence immunoassay. The final sample included 112 invasive ovarian cancer patients (86 advanced stage, 26 early stage) and 25 patients with tumors of low malignant potential (LMP). RESULTS: Advanced-stage ovarian cancer patients demonstrated elevations in vegetative and affective depressive symptoms, plasma IL-6, and the cortisol area under the curve (AUC) compared with patients with LMP tumors (all P < .05). Among invasive ovarian cancer patients, greater vegetative depression was related to elevated IL-6 in plasma (P = .008) and ascites (P = .024), but affective depression was unrelated to IL-6. Elevations in total depression (P = .026) and vegetative depression (P = .005) were also related to higher evening cortisol levels. Plasma IL-6 was related to greater afternoon and evening cortisol and cortisol AUC (all P values < .005). CONCLUSION: These results demonstrate significant relationships between IL-6, cortisol, and vegetative depression, and may have implications for treatment of depression in ovarian cancer patients.

Ligamentum teres maintenance and transfer as a stabilizer in open reduction for pediatric hip dislocation: surgical technique and early clinical results.

PURPOSE: The ligamentum teres has primarily been considered as an obstruction to reduction in children with developmental dislocation of the hip (DDH). In the early surgical descriptions of both the medial (Ludloff) approach and the anterior (Salter) approach to the hip, it was generally accepted that the ligamentum teres was an obstruction to reduction and was excised (similar to the discarding of menisci for knee surgery in our orthopedic history). Because of the known propensity for early re-dislocation following open reduction, we developed surgical methods for maintaining the ligamentum teres when performing open reduction for hip dislocation in young children. This study presents the surgical methods developed for ligament maintenance and transfer, and analyzes the early clinical and radiographic results in a study group. METHODS: The techniques for open reduction by both the medial Ludloff approach and the anterior open reduction were developed and refined. Twenty-one children (23 hips) had ligamentum teres shortening and transfer performed as part of either a medial Ludloff or anterior open reduction for hip dislocation. Complete pre-operative and post-operative clinical and radiographic analysis was performed. RESULTS: All patients had stable hips at follow-up. The transferred ligamentum teres appeared to provide additional stability to prevent repeat dislocation. We noted no apparent loss of hip motion or other adverse events. One patient had avascular necrosis (AVN). CONCLUSIONS: In this series of 23 hips, in which ligamentum teres transfer/tenodesis was utilized, we found no residual subluxation or dislocation in either the medial Ludloff or the anterior open reduction groups. Based on these early positive results, we recommend the method for children treated with the Ludloff open reduction procedure. Although we have less experience with it, the technique presented for ligamentum maintenance and transfer in anterior open reduction may provide similar added stability. This is an early follow-up study, and long-term follow-up will be required to confirm the ultimate femoral head and acetabular development.