High-resolution MRI and micro-CT in an ex vivo rabbit anterior cruciate ligament transection model of osteoarthritis

OBJECTIVE: The aim of this study was to investigate the potential of using non-invasive, multi-modality imaging techniques to quantify disease progression in a rabbit model of experimentally induced osteoarthritis (OA). METHODS: High-resolution 4-T magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) techniques were implemented and validated in an ex vivo rabbit anterior cruciate ligament transection (ACLT) model of OA. A three-dimensional (3-D) rigid body registration technique was executed and evaluated to allow combined MR-CT analysis in co-registered image volumes of the knee. RESULTS: The 3-D MRI and micro-CT data formats made it possible to quantify cartilage damage, joint-space, and osseous changes in the rabbit ACLT model of OA. Spoiled gradient-recalled echo and fast-spin echo (FSE) sequences were jointly used to evaluate femorotibial cartilage and determine the sensitivity (78.3%) and specificity (95.3%) of 4-T MRI to detect clinically significant cartilage lesions. Overall precision error of the micro-CT technique for analysis of joint-space, volumetric bone mineral density (vBMD), and bone volume fraction (BV/TV) was 1.8%, 1.2%, and 2.0%, respectively. Co-registration of the 3-D data sets was achieved to within 0.36 mm for completed intermodality registrations, 0.22 mm for extrapolated intramodality registrations, and 0.50mm for extrapolated intermodality registrations. CONCLUSIONS: These results indicate that high-resolution 4-T MRI and micro-CT can be used to accurately quantify cartilage damage and calcified tissue changes in the rabbit ACLT model of OA. In addition, image volumes can be successfully co-registered to facilitate a comprehensive multi-modality examination of localized changes in both soft tissue and bone within the rabbit femorotibial joint.     

Reduced variability of acetabular cup positioning with use of an imageless navigation system

Positioning the acetabular component is one of the most important steps in total hip arthroplasty; malpositioned components can result in dislocations, impingement, limited range of motion, and increased polyethylene wear. Conventional surgery makes use of specialized alignment guides provided by the manufacturers of the implants. The use of mechanical guides has been shown to result in large variations of cup inclination and version. We investigated acetabular cup alignment with the nonimage-based hip navigation system compared with a conventional mechanically guided procedure in 12 human cadavers. Postoperative cup position relative to the pelvic reference plane was assessed in both groups with the use of a three-dimensional digitizing arm. In the navigated group, a median inclination of 45.5 degrees and a median anteversion of 21.9 degrees (goals, 45 degrees and 20 degrees) were reached. In the control group, the median inclination was 41.8 degrees and the median anteversion was 24.6 degrees. The ninetieth percentile showed a much wider range for the control group (36.1 degrees-51.8 degrees inclination, 15 degrees-33.5 degrees anteversion) than for the navigated group (43.9 degrees-48.2 degrees inclination, 18.3 degrees-25.4 degrees anteversion). This cadaver study shows that computer-assisted cup positioning using a nonimage-based hip navigation system allowed for more consistent placement of the acetabular component.     

Surgical versus non-surgical management of patients soon after acute myocardial infarction

Of 510 patients admitted to hospital with acute myocardial infarction, 34 had coronary artery bypass grafting before discharge (6-43 days (median 20) after infarction). The patients who were given grafts generally had a smaller infarction with less functional impairment than the 476 patients who were not. The outcome of coronary artery bypass grafting was investigated in a retrospective matched pair study. Patients were matched on the basis of the presence of postinfarction angina, left ventricular ejection fraction, location of the infarction, peak creatine kinase activity, Killip clinical class, and severity of coronary disease with 34 patients who were given medical treatment only. At one year follow up fewer of the operated patients had symptoms than did the matched non-operated patients. Survival at one year in the operated and non-operated groups respectively was 94% vs 91%; angina within one year occurred in 3% vs 68%; congestive heart failure in 3% vs 6%; and 0% vs 32% were referred for later bypass grafting or coronary angioplasty. It is concluded that coronary artery bypass grafting can be performed safely soon after myocardial infarction provided that left ventricular function is not seriously compromised. Such treatment is more effective than medical treatment for relief of angina during the first year after infarction.     

Surgical versus non-surgical management of patients soon after acute myocardial infarction.

Of 510 patients admitted to hospital with acute myocardial infarction, 34 had coronary artery bypass grafting before discharge (6-43 days (median 20) after infarction). The patients who were given grafts generally had a smaller infarction with less functional impairment than the 476 patients who were not. The outcome of coronary artery bypass grafting was investigated in a retrospective matched pair study. Patients were matched on the basis of the presence of postinfarction angina, left ventricular ejection fraction, location of the infarction, peak creatine kinase activity, Killip clinical class, and severity of coronary disease with 34 patients who were given medical treatment only. At one year follow up fewer of the operated patients had symptoms than did the matched non-operated patients. Survival at one year in the operated and non-operated groups respectively was 94% vs 91%; angina within one year occurred in 3% vs 68%; congestive heart failure in 3% vs 6%; and 0% vs 32% were referred for later bypass grafting or coronary angioplasty. It is concluded that coronary artery bypass grafting can be performed safely soon after myocardial infarction provided that left ventricular function is not seriously compromised. Such treatment is more effective than medical treatment for relief of angina during the first year after infarction.     

Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta‐analysis

Schwannomatosis is a genetic disorder characterized by the occurrence of multiple peripheral schwannomas. Segmental schwannomatosis is diagnosed when schwannomas are restricted to 1 extremity and is thought to be caused by genetic mosaicism. We studied 5 patients with segmental schwannomatosis through microstructural magnetic resonance neurography and mutation analysis of NF2, SMARCB1, and LZTR1. In 4 of 5 patients, subtle fascicular nerve lesions were detected in clinically unaffected extremities. Two patients exhibited LZTR1 germline mutations. This appears contrary to a simple concept of genetic mosaicism and suggests more complex and heterogeneous mechanisms underlying the phenotype of segmental schwannomatosis than previously thought. Ann Neurol 2016;80:625–628     

Four of the six Drosophila rhodopsin‐expressing photoreceptors can mediate circadian entrainment in low light

Light is the major stimulus for the synchronization of circadian clocks with day–night cycles. The light‐driven entrainment of the clock that controls rest–activity rhythms in Drosophila relies on different photoreceptive molecules. Cryptochrome (CRY) is expressed in most brain clock neurons, whereas six different rhodopsins (RH) are present in the light‐sensing organs. The compound eye includes outer photoreceptors that express RH1 and inner photoreceptors that each express one of the four rhodopsins RH3–RH6. RH6 is also expressed in the extraretinal Hofbauer–Buchner eyelet, whereas RH2 is only found in the ocelli. In low light, the synchronization of behavioral rhythms relies on either CRY or the canonical rhodopsin phototransduction pathway, which requires the phospholipase C‐β encoded by norpA (no receptor potential A). We used norpA^P24 cry⁰² double mutants that are circadianly blind in low light and restored NORPA function in each of the six types of photoreceptors, defined as expressing a particular rhodopsin. We first show that the NORPA pathway is less efficient than CRY for synchronizing rest–activity rhythms with delayed light–dark cycles but is important for proper phasing, whereas the two light‐sensing pathways can mediate efficient adjustments to phase advances. Four of the six rhodopsin‐expressing photoreceptors can mediate circadian entrainment, and all are more efficient for advancing than for delaying the behavioral clock. In contrast, neither RH5‐expressing retinal photoreceptors nor RH2‐expressing ocellar photoreceptors are sufficient to mediate synchronization through the NORPA pathway. Our results thus reveal different contributions of rhodopsin‐expressing photoreceptors and suggest the existence of several circuits for rhodopsin‐dependent circadian entrainment. J. Comp. Neurol. 524:2828–2844, 2016. © 2016 Wiley Periodicals, Inc.     

A preliminary study of the effects of working memory training on brain function

Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (Cogmed?) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts.     

Problem alcohol use in veterans with mild traumatic brain injury: Associations with cognitive performance and psychiatric symptoms

Introduction: Given that little is known about the associations between alcohol use, cognition, and psychiatric symptoms among veterans with a history of mild traumatic brain injury (mTBI), we aimed to (a) characterize how they differ from veteran controls on a measure of problem drinking; (b) investigate whether problem drinking is associated with demographic or mTBI characteristics; and (c) examine the associations between alcohol use, mTBI history, psychiatric functioning, and cognition. Method: We assessed 59 veterans (n = 32 with mTBI history; n = 27 military controls) for problem alcohol use (Alcohol Use Disorders Identification Test: AUDIT), psychiatric symptoms, and neuropsychological functioning. Results: Compared to controls, veterans with mTBI history were more likely to score above the AUDIT cutoff score of 8 (p = .016), suggesting a higher rate of problem drinking. Participants with mTBI history also showed elevated psychiatric symptoms (ps < .001) and lower cognitive scores (ps < .05 to < .001). Veterans with higher AUDIT scores were younger (p = .05) and had less education (p < .01) and more psychiatric symptoms (ps < .01), but mTBI characteristics did not differ. After controlling for combat and mTBI history (R² = .04, ns) and posttraumatic stress disorder (PTSD) symptoms (ΔR² = .08, p = .05), we found that higher AUDIT scores were associated with poorer attention/processing speed, F(9, 37) = 2.55, p = .022; ΔR² = .26, p = .03. Conclusions: This preliminary study suggested that veterans with mTBI history may be at increased risk for problem drinking. Problem alcohol use was primarily associated with more severe PTSD symptoms and poorer attention/processing speed, though not with combat or mTBI characteristics per se. Importantly, findings emphasize the importance of assessing for and treating problematic alcohol use and comorbid psychiatric symptoms among veterans, including those with a history of neurotrauma.     

Rapidly acquired valgus deformity of the knee after osteochondroma resection in multiple hereditary exostoses pediatric patients: A report of two cases

Patients with multiple hereditary exostoses (MHE) often develop leg length discrepancies and limb alignment deformity around the knee as part of the natural course of the disease. Limb alignment deformity occurring post-resection of an osteochondroma has been described in one case report and only pertaining to the proximal medial tibia location. Here we describe the case of 2 patients with MHE, a 7-year-old female who underwent resection of distal femur and proximal tibia osteochondromas and a 9-year-old female who had a distal femur osteochondroma resected. Both patients developed rapidly progressive valgus knee deformity requiring surgical intervention. Excision of osteochondromas near the physis of a skeletally immature patient can cause overgrowth from the involved side of the growth plate resulting in a rapidly progressing unilateral coronal plane deformity. Surgeons should be aware of this potential complication and closely follow growing patients with serial alignment radiographs and counsel the family regarding the potential of acquired limb deformity and subsequent surgeries.     

Disappointing short-term results with the DePuy ASR XL metal-on-metal total hip arthroplasty

Outcomes of ultralarge-diameter femoral heads used in metal-on-metal (MOM) total hip arthroplasty (THA) are relatively unknown. This study reports on early failures of the ASR XL (Depuy, Warsaw, Ind) and assesses whether a correlation with cup positioning exists. A retrospective review of 70 consecutive MOM THAs with ultralarge-diameter femoral head and monoblock acetabular component was conducted. Minimum follow-up was 24 months. Of 70 THAs, 12 (17.1%) required revision within 3 years for pain (7), loosening (3), and squeaking (2). Three additional THAs noted squeaking, 2 noted grinding, and 3 additional hips had persistent pain. In total, 20 (28.6%) of 70 demonstrated implant dysfunction. Acetabular components for all symptomatic hips were in acceptable range of cup abduction and anteversion. The failures noted with this design do not correlate to cup placement. The high rate of implant dysfunction at early follow-up suggests serious concerns with the concept of MOM THA with an ultralarge-diameter femoral head paired with a monoblock acetabular cup.