Citations

Significance Noninvasive brain imaging holds great promise for expanding our capabilities of treating human neurologic and psychiatric disorders. However, key limitations exist in human-only studies, and the ability to use animal models would greatly advance our understanding of human brain function. Mice offer sophisticated genetic and molecular methodology, but correlating these data to functional brain imaging in the mouse brain has remained a major hurdle. This study is the first, to our knowledge, to use whole-brain functional imaging to show large-scale functional architecture with structural correlates in the mouse. Perhaps more important is the finding of conservation in brain topology and default network among rodents and primates, thereby clearing the way for a bridge measurement between human and mouse models.

Background— Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. Methods and Results— The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P =0.0003) and mechanical valve replacements (9.6% versus 2.4%; P <0.0001); however, there was no difference in CHA 2 DS 2 -VASc scores (scores ≥2 in 94% versus 95%; P =0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84; P <0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94; P =0.0001). Conclusions— Bridging anticoagulation is used in one quarter of anticoagulation interruptions and is associated with higher risk for bleeding and adverse events. These data do not support the use of routine bridging, and additional data are needed to identify best practices concerning anticoagulation interruptions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Abstract Deep brain stimulation (DBS) may improve disabling tics in severely affected medication and behaviorally resistant Tourette syndrome (TS). Here we review all reported cases of TS DBS and provide updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience. Candidates should have a Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM V) diagnosis of TS with severe motor and vocal tics, which despite exhaustive medical and behavioral treatment trials result in significant impairment. Deep brain stimulation should be offered to patients only by experienced DBS centers after evaluation by a multidisciplinary team. Rigorous preoperative and postoperative outcome measures of tics and associated comorbidities should be used. Tics and comorbid neuropsychiatric conditions should be optimally treated per current expert standards, and tics should be the major cause of disability. Psychogenic tics, embellishment, and malingering should be recognized and addressed. We have removed the previously suggested 25‐year‐old age limit, with the specification that a multidisciplinary team approach for screening is employed. A local ethics committee or institutional review board should be consulted for consideration of cases involving persons younger than 18 years of age, as well as in cases with urgent indications. Tourette syndrome patients represent a unique and complex population, and studies reveal a higher risk for post‐DBS complications. Successes and failures have been reported for multiple brain targets; however, the optimal surgical approach remains unknown. Tourette syndrome DBS, though still evolving, is a promising approach for a subset of medication refractory and severely affected patients. © 2014 International Parkinson and Movement Disorder Society

Purpose Distinguishing independent primary tumors from intrapulmonary metastases in non–small-cell carcinoma remains a clinical dilemma with significant clinical implications. Using next-generation DNA sequencing, we developed a chromosomal rearrangement–based approach to differentiate multiple primary tumors from metastasis. Methods Tumor specimens from patients with known independent primary tumors and metastatic lesions were used for lineage test development, which was then applied to multifocal tumors. Laser capture microdissection was performed separately for each tumor. Genomic DNA was isolated using direct in situ whole-genome amplification methodology, and next-generation sequencing was performed using an Illumina mate-pair library protocol. Sequence reads were mapped to the human genome, and primers spanning the fusion junctions were used for validation polymerase chain reaction. Results A total of 41 tumor samples were sequenced (33 adenocarcinomas [ADs] and eight squamous cell carcinomas [SQCCs]), with a range of three to 276 breakpoints per tumor identified. Lung tumors predicted to be independent primary tumors based on different histologic subtype did not share any genomic rearrangements. In patients with lung primary tumors and paired distant metastases, shared rearrangements were identified in all tumor pairs, emphasizing the patient specificity of identified breakpoints. Multifocal AD and SQCC samples were reviewed independently by two pulmonary pathologists. Concordance between histology and genomic data occurred in the majority of samples. Discrepant tumor samples were resolved by genome sequencing. Conclusion A diagnostic lineage test based on genomic rearrangements from mate-pair sequencing demonstrates promise for distinguishing independent primary from metastatic disease in lung cancer.

Purpose The purpose of this prospective comparative study was to evaluate the effect of intraoperative platelet‐rich plasma (PRP) injection on the outcomes of patients undergoing hip arthroscopy for labral treatment. Methods During the period from November 2010 through March 2012, all patients undergoing hip arthroscopy for labral tears were considered for this study. The study group received intra‐articular PRP at the end of the operation, and the control group received an intra‐articular injection of 0.25% bupivacaine. Selection for the study group was based on the day of the week on which the patient underwent surgery. The protocol included administration of 4 hip‐specific patient‐reported outcome tools. Patients also reported their pain score on a visual analog scale from 0 to 10. Scores were recorded at the preoperative visit and at 3 months and 2 years postoperatively. Results A minimum of 2 years' follow‐up was available for 306 patients. Thirteen patients (4.2%) underwent conversion to total hip arthroplasty and 24 patients (7.8%) underwent revision hip arthroscopy, which left 91 patients in the study group and 180 patients in the control group. The study group had slightly higher pain scores than the control group (3.4 v 2.5) 2 years after surgery ( P = .005). No difference in pain scores was identified at 3 months postoperatively. The 2‐year modified Harris Hip Score was slightly lower in the study group (78.6) than in the control group (82.6) ( P = .049). No significant difference was observed for the Hip Outcome Score–Activities of Daily Living, Hip Outcome Score–Sport‐Specific Subscale, or Non‐Arthritic Hip Score at any time point. There was no significant difference between groups for conversion to total hip arthroplasty or revision surgery. Conclusions On the basis of the results of this study, intraoperative PRP injection does not appear to improve the clinical results of patients undergoing hip arthroscopy for labral treatment. Level of Evidence Level II, prospective comparative study.

Background: Ankle arthrodesis is considered to be a well-accepted technique for end-stage ankle arthritis. Our purpose was to evaluate outcomes of patients with bilateral ankle arthrodeses with attention to radiographic and functional outcomes. Methods: Medical records of 31 patients were reviewed from 1977 through 2007. All patients had 1 year of clinical follow-up after their contralateral ankle arthrodesis, with an average follow-up of 11.2 years following the initial arthrodesis. Pertinent patient demographics and information pertaining to the operative procedure, complications, and subsequent adjacent joint fusions was collected. Radiographs were reviewed for time to fusion and adjacent joint arthritis. Functional outcomes were measured using the Foot and Ankle Ability Measure (FAAM) and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle and Hindfoot scale. Results: Ten females and 21 males underwent bilateral ankle fusions at an average age of 57 years at the time of the initial fusion. The contralateral fusion occurred on average 3.1 years following the initial fusion. Radiographic fusion occurred 12 weeks following the initial fusion and 14 weeks following the contralateral fusion. There was a significant increase ( P = .0001) in the average AOFAS score postoperatively in both ankles. The average FAAM score at last follow-up was 70. Adjacent joint arthritis developed in the majority of patients; however, most of the patients were free from adjacent fusions and reported their function as “normal” or “nearly normal” at last follow-up. Conclusion: Bilateral ankle arthrodesis was an acceptable treatment option for patients with bilateral, end-stage ankle arthritis. Level of Evidence: Level IV, retrospective case series.

There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

HCV-specific neutralizing antibodies protect humanized mice from challenge and suppress established infections.

Purpose The purpose of this study was to investigate the influence of multiple demographic and radiographic findings on the size of labral tears identified at the time of hip arthroscopy. Methods Data were prospectively collected for patients treated with arthroscopic labral repair or debridement from February 2008 to August 2011. Preoperative radiographic and demographic data were collected for 392 patients during the study period. Exclusion criteria included revision surgery and previous hip conditions. An anteroposterior pelvic view, 45° Dunn view, and false‐profile view were used to measure Tönnis grade, neck‐shaft angle, alpha angle, lateral center edge angle (LCEA), anterior center edge angle (ACEA), acetabular inclination, and the extent of crossover sign when present. At the time of surgery, labral tear size and location were documented for all patients, using traditional acetabular clock face nomenclature for sizing. A multiple linear regression analysis was then performed to assess the correlation of radiographic and demographic findings with the size of the labral tear. Results Regression analysis displayed statistical significance for sex ( P < .0001), age ( P < .0001), and alpha angle ( P = .005) with labral tear size. For female patients, Tönnis grade ( P = .0004) and neck‐shaft angle ( P = .004) correlated with labral tear size. This model accounted for only 26% of variation in labral tear size. Conclusions Preoperative risk factors for the extent of labral tear size are male sex, increasing age, and increasing alpha angle. Labral tears were larger in female patients with higher Tönnis grades and lower neck‐shaft angles. Measurements of acetabular coverage and version showed no correlation with labral tear size. The majority of labral tear size variation was not accounted for in this model. Level of Evidence Level IV, therapeutic case series.