Acromial fractures following reverse shoulder arthroplasty: the role of the acromial morphology and a comparison of clinical outcomes.

BACKGROUND: The purpose was to evaluate the relationship between acromial morphology and the location of acromial fractures following reverse shoulder arthroplasty and determine whether fracture location and displacement impact clinical outcomes. METHODS: We performed a multicenter retrospective review of reverse shoulder arthroplasties complicated by acromial fractures. Radiographs were compared to determine the differences in acromial morphology, as well as fracture orientation and pattern, between patients with Levy type I (n = 17) and Levy type II (n = 25) fractures. Patients with a minimum of 2 years' follow-up were selected to examine the association between clinical outcomes and fracture location and displacement. Twenty-two patients were stratified based on whether they achieved the minimal clinically important difference (MCID) in the American Shoulder and Elbow Surgeons score (20 points). The groups were then compared regarding fracture location and displacement using measurements such as the acromiohumeral distance. RESULTS: The Levy type I group had a higher acromial slope than the Levy type II group (127° vs. 117°, P < .001). Levy type I fractures had a transverse pattern occurring in the coronal plane, whereas Levy type II fractures had an oblique pattern occurring in the sagittal plane (P < .001). At final follow-up, 12 of 22 patients (55%) achieved the MCID. Those who did not achieve the MCID had more displaced fractures including a lower acromiohumeral distance (8 mm vs. 20 mm, P = .007). There was no difference in the distribution of Levy type I and type II fractures based on the MCID cutoff (P = .093). CONCLUSION: An increased acromial slope is associated with transverse fractures in the Levy I region, whereas a lower acromial slope is associated with oblique fractures in the Levy II region. Overall, 55% of patients achieved the MCID at mid-term follow-up. The outcomes of those who did not achieve the MCID became worse postoperatively, and this was associated with increased fracture displacement.

Rabies is still a fatal but neglected disease: a case report.

BACKGROUND: Rabies, caused by a lyssavirus, is a viral zoonosis that affects people in many parts of the world, especially those in low income countries. Contact with domestic animals, especially dogs, is the main source of human infections. Humans may present with the disease only after a long period of exposure. Nearly half of rabies cases occur in children <15 years old. We report on a fatal case of rabies in a Ghanaian school child 5 years after the exposure incident, and the vital role of molecular tools in the confirmation of the diagnosis. CASE PRESENTATION: The patient, an 11-year-old junior high school Ghanaian student from the Obuasi Municipality in Ghana, presented with aggressive behavior, which rapidly progressed to confusion and loss of consciousness within a day of onset. Her parents reported that the patient had experienced a bite from a stray dog on her right leg 5 years prior to presentation, for which no antirabies prophylaxis was given. The patient died within minutes of arrival in hospital (within 24 hours of symptom onset). Real-time polymerase chain reaction testing of cerebrospinal fluid obtained after her death confirmed the diagnosis of rabies. Subsequent phylogenetic analysis showed the virus to belong to the Africa 2 lineage of rabies viruses, which is one of the predominant circulating lineages in Ghana. CONCLUSION: The incubation period of rabies is highly variable so patients may only present with symptoms long after the exposure incident. Appropriate molecular testing tools, when available as part of rabies control programmes, are vital in confirming cases of rabies.

A Weaving Rip-Stop Technique Leads to a Significantly Increased Load to Failure and Reduction in Suture-Tendon Cut-Through in a Biomechanical Model of Rotator Cuff Repair.

PURPOSE: To present an alternative arthroscopic rip-stop technique with a single suture tape weaved through the tendon from anterior to posterior and to biomechanically test its strength against a control technique consisting of a single-row repair with simple sutures. METHODS: This was a controlled biomechanical study. Dissection and harvesting of the supraspinatus muscle-tendon unit were performed along the cable in 9 matched-pair cadaveric shoulders. Samples were divided into 2 groups: simple suture repair only (SSR) and simple suture repair with rip-stop (SSPR). Biomechanical testing was performed with an initial preload, followed by cyclic loading and then ramp to failure. Peak-to-peak displacement, stiffness (in newtons per millimeter), load at failure (in newtons), and failure mechanism were recorded. Data were compared using the paired-sample t test. RESULTS: The average peak-to-peak displacement for SSR samples was not significantly different from that of SSPR samples (P = .96). Similarly, elongation in the SSR and SSPR groups was not significantly different (P = .82). Stiffness was significantly different between the SSR and SSPR groups (P = .0054): SSR samples were less stiff than SSPR samples. Moreover, SSR samples failed at significantly lower forces than did SSPR samples (P = .028). A larger percentage of failures occurred due to tendon cut-through among SSR samples versus suture breakage among SSPR samples. CONCLUSIONS: An alternative rip-stop technique is presented in this biomechanical model that may assist surgeons to better deal with difficult rotator cuff repairs. Weaving a suture tape as a rip-stop can increase stiffness, achieve higher failure loads when compared with simple suture repair with no rip-stop, and reduce tendon cut-through. CLINICAL RELEVANCE: This study provides insight into a variation of rip-stop stitch techniques that may help solve the clinical problem of failure occurring at the suture-tendon interface, specifically tendon cut-through.

Alterations in Intracardiac Flow Patterns Affect Mitral Leaflets Dynamics in a Model of Ischemic Mitral Regurgitation.

PURPOSE: This study was to evaluate the effects of ischemic mitral regurgitation (IMR) on vortex formation and leaflet dynamics using an established porcine infarct model of IMR. METHODS: Using direct coronary ligation, five animals were subjected to a posterolateral myocardial infarction (MI) followed by an MRI at 12-weeks post MI. MR imaging consisted of 4D time-resolved left ventricular (LV) flow, full coverage 2D LV cine, and high resolution 2D cine of mitral valve dynamics. Five additional naïve animals underwent identical imaging protocols to serve as controls. Image analysis was performed to obtain mitral transvalvular flows as well as LV volumes throughout the cardiac cycle. In addition, anterior to posterior mid-leaflet tip distances were measured throughout the cardiac cycle for determination of temporal leaflet dynamics. RESULTS: It was found IMR caused asymmetric vortex ring formation with the anterior vortex having a lower vorticity relative to its posterior counterpart. In contrast, normal ventricles create symmetric and tightly curled vortices in the basal chamber just underneath the mitral leaflets which conserve kinetic energy and aid in effective ejection. IMR animals were also evaluated for leaflet separation and were found to have a greater leaflet opening and achieved peak vorticity and peak leaflet opening later than control animals. CONCLUSION: In conclusion, this study shows the effects that altered vortex formation, due to IMR, can have on ventricular filling and leaflet dynamics. These findings have important implications for understanding blood flow through the dilated heart and how ring annuloplasty and volume reduction interventions may influence mitral valve dynamics.

In Vivo Image-Based 4D Modeling of Competent and Regurgitant Mitral Valve Dynamics.

BACKGROUND: In vivo characterization of mitral valve dynamics relies on image analysis algorithms that accurately reconstruct valve morphology and motion from clinical images. The goal of such algorithms is to provide patient-specific descriptions of both competent and regurgitant mitral valves, which can be used as input to biomechanical analyses and provide insights into the pathophysiology of diseases like ischemic mitral regurgitation (IMR). OBJECTIVE: The goal is to generate accurate image-based representations of valve dynamics that visually and quantitatively capture normal and pathological valve function. METHODS: We present a novel framework for 4D segmentation and geometric modeling of the mitral valve in real-time 3D echocardiography (rt-3DE), an imaging modality used for pre-operative surgical planning of mitral interventions. The framework integrates groupwise multi-atlas label fusion and template-based medial modeling with Kalman filtering to generate quantitatively descriptive and temporally consistent models of valve dynamics. RESULTS: The algorithm is evaluated on rt-3DE data series from 28 patients: 14 with normal mitral valve morphology and 14 with severe IMR. In these 28 data series that total 613 individual 3DE images, each 3D mitral valve segmentation is validated against manual tracing, and temporal consistency between segmentations is demonstrated. CONCLUSIONS: Automated 4D image analysis allows for reliable non-invasive modeling of the mitral valve over the cardiac cycle for comparison of annular and leaflet dynamics in pathological and normal mitral valves. Future studies can apply this algorithm to cardiovascular mechanics applications, including patient-specific strain estimation, fluid dynamics simulation, inverse finite element analysis, and risk stratification for surgical treatment.

A cohort comparison of humeral implant designs in reverse shoulder arthroplasty: does implant design lead to lower rates of complications and revision?

INTRODUCTION: The purpose of this study was to evaluate the outcomes, revisions, and complications between a first-generation cemented modular humeral implant and a second-generation monolithic, primarily uncemented humeral implant in reverse total shoulder arthroplasty with 135° neck-shaft angle and varying degrees of metallic glenosphere offsets. METHODS: We retrospectively evaluated patients undergoing reverse total shoulder arthroplasty from 2004 to 2014 with a first-generation cemented modular humeral implant (400 patients) or second-generation monolithic humeral stem (231 patients), who had at minimum 2-year clinical and radiographic follow-up. RESULTS: Both groups of patients had similar improvement of clinical outcomes (American Shoulder and Elbow Surgeons +30 points vs. +34 points, respectively) with improvements in all planes of motion (forward flexion +70° vs. +75°, abduction +61° vs. +71°, external rotation +23° vs. +22°, and internal rotation +1.6 vs. +1.5 level improvement, respectively). The incidence of humeral loosening for the cemented group was 3.6%, whereas in the uncemented group it was 0.4% (P = .01). A total of 28 shoulders treated with the cementing technique (4.0%) and 6 patients treated with the press-fit technique (1.5%) were revised (P = .028). The rate of postoperative acromial fractures within the first year was 3.4% in the cemented group and 1.8% in the uncemented group (P = .177). CONCLUSIONS: Both the first-generation cemented modular humeral stem implant and the second-generation monolithic humeral stem implant had equivalent clinical outcomes. In addition, with the monolithic stem primarily using press-fit fixation, there was a significant reduction in the incidence of radiographic loosening and the need for revision compared with a cemented stem.

Randomized prospective evaluation of the use of tranexamic acid and effects on blood loss for proximal humeral fracture surgery.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent that has been used to reduce blood loss in orthopedic surgery. It has been shown to decrease blood loss in upper- and lower-extremity arthroplasty, as well as lower-extremity fracture surgery. The use of TXA for proximal humeral fracture surgery has yet to be evaluated. The purpose of this study was to examine the effects of TXA on blood loss in patients undergoing open reduction-internal fixation (ORIF) or arthroplasty for the treatment of proximal humeral fractures. MATERIALS AND METHODS: A total of 101 patients were randomized to receive either a single preoperative dose of intravenous TXA (53 patients) or a control dose of saline solution (48 patients) at the time of proximal humeral fracture surgery. On the basis of patient age and fracture pattern, ORIF was performed in 57 patients (30 TXA and 27 control patients) and reverse shoulder arthroplasty (RSA) was performed in the other 44 patients (23 TXA and 21 control patients). Intraoperative blood loss plus 24-hour drain output was used to calculate total blood loss for each procedure. The preoperative-to-postoperative change in hemoglobin level was also evaluated for each patient. Further stratification of blood loss and change in hemoglobin level based on procedure (ORIF or RSA) was performed as well. RESULTS: Compared with the control group, the TXA group had less average intraoperative blood loss (178 mL vs. 129 mL, P < .0001), less postoperative drain output (103 mL vs. 62 mL, P < .0001), and less total blood loss (280 mL vs. 188 mL, P < .0001). Compared with the control group, the TXA group had a smaller average preoperative-to-postoperative change in hemoglobin level (-2.6 g/dL vs. -1.5 g/dL, P < .0001). Further stratification based on procedure showed that among patients undergoing ORIF and patients undergoing RSA, those receiving TXA had less average total blood loss and a smaller decrease in hemoglobin level than the control group. No identifiable intraoperative or postoperative complications associated with the use of TXA occurred in any patient. CONCLUSION: TXA was effective in reducing total blood loss and led to a smaller preoperative-to-postoperative decrease in hemoglobin level compared with control in patients undergoing surgery for proximal humeral fractures. This effect was consistent in patients treated with either ORIF or arthroplasty as the surgical procedure. TXA can be used to decrease blood loss in the surgical treatment of proximal humeral fractures.

The risk of postoperative scapular spine fracture following reverse shoulder arthroplasty is increased with an onlay humeral stem.

BACKGROUND: The purpose of this study was to assess the effects of lateralization and distalization on scapular spine fracture (SSF) after reverse shoulder arthroplasty (RSA). The hypothesis was that postoperative distalization would increase the risk of SSF, whereas lateralization would not. METHODS: A multicenter retrospective review was performed at a minimum of 1 year postoperatively on primary RSAs with 3 different implants, 2 with an inlay design (n = 342) and 1 with an onlay design (n = 84). Functional outcome, range of motion, stem design, and radiographic measurements, including acromiohumeral distance and lateralization, were compared between groups with and without fracture. RESULTS: The incidence of SSF in the onlay group (11.9%) was significantly higher compared with the inlay group (4.7%; P = .043). Postoperative acromiohumeral distance was approximately 4 mm higher in the SSF group (37.5 mm) compared with the control group (33.7 mm; P = .042), whereas lateralization was similar between the 2 groups (52.8 mm vs. 53.9 mm; P = .362). Higher return to activity (92.1% vs. 71.4%; P < .001) as well as postoperative forward flexion was observed in the group without fracture (135° vs. 120°; P = .009). CONCLUSION: Increased postoperative distalization is associated with an increased risk of SSF after RSA. An onlay stem resulted in a 10 mm increase in distalization compared with an inlay stem, and a 2.5 times increased risk of SSF. Lateralization, however, does not appear to increase the risk of SSF.

Optimizing humeral stem fixation in revision reverse shoulder arthroplasty with the cement-within-cement technique.

BACKGROUND: The purpose of this study was to report on the clinical outcomes of patients undergoing revision reverse shoulder arthroplasty (RSA) by the cement-within-cement technique, as well as to identify whether surgical technique can affect subsequent humeral loosening. METHODS: In 98 patients, cemented humeral components that were revised to RSA using the cement-within-cement technique were identified and included in this study. We compared 8 patients in whom humeral stem loosening developed with 90 patients whose stem remained fixed. Preoperative and postoperative radiographs of each patient were downloaded in DICOM (Digital Imaging and Communications in Medicine) format and analyzed in Mimics. The total area of the cement mantle (in square millimeters) and of the stem (in square millimeters), as visualized on 2-dimensional plain films, was measured in each subject on both preoperative and postoperative radiographs. Outcomes at a minimum of 2 years of follow-up were analyzed. RESULTS: Clinical outcomes were available in 57 patients, with a mean follow-up period of 54 months (range, 21-156 months). Patients demonstrated significantly improved functional outcome scores and shoulder range of motion. In the group without loosening, the mean increase in the cement mantle area was 4380 ± 12701 mm2 (P < .0001). In the group with loosening, the mean increase in the cement mantle area was only 811 ± 4014 mm2 (P = .484). CONCLUSIONS: Use of the cement-within-cement technique for fixation of the humeral component in revision RSA is effective in improving functional outcome scores and shoulder range of motion. Furthermore, these findings suggest that efforts to maximize the cement volume during reimplantation may lessen the chance of humeral stem loosening requiring additional revision.

Defining the younger patient: age as a predictive factor for outcomes in shoulder arthroplasty.

BACKGROUND: The purpose of this study was to define an age cutoff at which clinical outcomes and revision rates differ for patients undergoing primary anatomic total shoulder arthroplasty (TSA) and patients undergoing primary reverse shoulder arthroplasty (RSA). METHODS: This retrospective cohort study included 1250 primary shoulder arthroplasties (1131 patients) with minimum 2-year clinical follow-up (mean, 50 months [range, 24-146 months]). TSA (n = 518; mean age, 68.1 years [range, 28-90 years]) was performed for osteoarthritis in most cases (99%), whereas the primary diagnoses for RSA (n = 732; mean age, 70.8 years [range, 22-91 years]) included rotator cuff arthropathy (35%), massive cuff tear without osteoarthritis (29.8%), and osteoarthritis (20.5%). Outcomes included range of motion, the American Shoulder and Elbow Surgeons (ASES) score, and the revision rate. The relationship between age at the time of surgery in 5-year increments (46-50 years, 51-55 years, and so on) and the revision rate was examined to identify the age cutoff; this was then used to assess clinical outcomes. RESULTS: In patients younger than 65 years, TSA was associated with a 3.4-fold increased risk of revision (P = .01). RSA performed in patients younger than 60 years was associated with a 4.8-fold increased risk of revision (P < .001). TSA patients aged 65 years or older and RSA patients aged 60 years or older had better total ASES scores (82 vs. 77 [P = .03] and 72 vs. 62 [P = .002], respectively) and better internal rotation (interquartile range, TSA 5-6 vs. 4-5 [P = .002] and RSA 4-5 vs 3-4 [P = .04])-where 6 represents T4 to T6 and 4 represents T11 to L1-than their younger counterparts. CONCLUSION: Age at index arthroplasty affects outcomes and the risk of revision. Primary TSA patients younger than 65 years and RSA patients younger than 60 years have a significantly increased revision risk. These age cutoffs are also correlated with differences in ASES scores and internal rotation.

Acute surgical management of proximal humerus fractures: ORIF vs. hemiarthroplasty vs. reverse shoulder arthroplasty.

BACKGROUND: Proximal humerus fracture treatment varies by surgeon preference and patient factors. This study compares patient and fracture characteristics, with outcomes between current surgical treatment options. METHODS: Between 1999 and 2018, 425 proximal humerus fractures underwent acute surgical management: open reduction internal fixation (ORIF, n = 211), hemiarthroplasty (HA, n = 108), or reverse shoulder arthroplasty (RSA, n = 106). Patient and fracture characteristics included age, American Society of Anesthesiologists physical status classification (ASA), and fracture classification. Postoperative motion at 3, 6, and minimum 12 months (avg 20 ± 21 months), radiographic outcomes, and postoperative falls were analyzed. RESULTS: Average age for treatment groups was 65 ± 13 years (range: 18-93 years). Fractures were classified as 2- (11%), 3- (41%), or 4-part (48%). Age, ASA, and fracture classification were associated with selected surgical management (P < .0001, =.001, <.0001, respectively). Outcomes showed a significant improvement in forward flexion from 3 months to 6 months in all groups (P < .0001). No difference in final motion was seen between groups. Radiographic union was higher in ORIF (89%), and similar between HA (79%) and RSA (77%, P = .005). Rate of reoperation was RSA 6.6%, ORIF 17.5%, and hemiarthroplasty 15.7% (P = .029). Postoperatively, 23% patients had at least 1 fall, of which 73% resulted in fractures. CONCLUSION: Older patients with high ASA were treated with arthroplasty, and younger patients with lower ASA were treated with ORIF. All groups showed improvements in motion. At minimum 1 year of follow-up, there was no difference in motion between groups. ORIF and HA showed significantly more reoperations compared with RSA. Patients should be counseled about reoperation, fall risk, and prevention.

Effect of Nail Size, Insertion, and Δ Canal-Nail on the Development of a Nonunion After Intramedullary Nailing of Femoral Shaft Fractures.

OBJECTIVE: To determine whether intramedullary nail (IMN) diameter, antegrade versus retrograde insertion, or the difference between the canal and IMN diameter affect femoral shaft fracture healing. DESIGN: Retrospective analysis of a prospective database. SETTING: Level One Regional Trauma Center. PATIENTS/PARTICIPANTS: Seven hundred thirty-three femoral shaft fractures (OTA/AO 32) treated with an IMN between 1999 and 2017. After exclusion criteria, 484 fractures remained in the final analysis. INTERVENTION: Closed section, cannulated, interlocked, titanium alloy IMN using a reamed insertion technique. MAIN OUTCOME MEASUREMENTS: Nonunion, IMN size (10, 11.5, and 13 mm), antegrade versus retrograde insertion, Δ canal-nail diameter (ΔD) after reaming (<1, 1-2, or >2 mm). RESULTS: IMN diameters used were as follows: 314/10 mm (64%), 137/11.5 mm (28%), and 33/13 mm (8%). Forty-five percent were placed in antegrade versus 55% retrograde. Four hundred fifty-six fractures (94.2%) healed uneventfully. There were no IMN failures. 10/484 IMNs (2%) had broken interlocking screws; only 4 were associated with a NU. Average time to union was 23 weeks (12-119). Twenty-eight (5.8%) developed NU. There was no statistical correlation between (1) the NU rate and IMN diameter: 10 mm, 6.3%; 11.5 mm, 5.1%; 13 mm, 3% (P = 0.8, power = 0.85), (2) the NU rate and ΔD: 7.1% <1 mm, 5.6% 1-2 mm, 20% >2 mm (P = 0.36), (3) the NU rate and fracture location: Prox = 11%, Mid = 5%, Dist = 3% (P = 0.13), or (4) the NU rate and antegrade (7.2%) versus retrograde (4.2%) insertion (P = 0.24). CONCLUSION: Similar healing rates occurred regardless of IMN diameter, Δ canal-nail diameter after reaming, or insertion site. This indicates that a closed section, cannulated, interlocked, titanium alloy IMN with a diameter of 10 mm can be considered the standard diameter for the treatment of acute femoral shaft fractures, regardless of entry point. This should be associated with less reaming and therefore shorter operative times, and possibly less hospital implant inventories as well. Larger diameter IMN should be reserved for revision surgery. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Use of a modified Outerbridge-Kashiwagi procedure for the treatment of posttraumatic elbow sequelae.

BACKGROUND: To review our 10-year experience treating posttraumatic sequelae of the elbow using a modified Outerbridge-Kashiwagi (O-K) procedure. METHODS: Twenty-one patients with posttraumatic sequelae of the elbow treated using the technique were evaluated clinically using the Mayo Elbow Performance Score, range of motion testing, and pain level. We noted the presence of preoperative and postoperative ulnar nerve symptoms, complications, and reoperations. Open contracture release was selected to address either removal of hardware or ulnar nerve pathology. RESULTS: At a mean of 39 months (range, 12-116 months), the Mayo Elbow Performance Score improved from 52 to 84 (P < .0001) and the mean arc of motion improved from 44° to 98° (P < .0001). At the final follow-up, 90% of patients reported no pain or mild pain, and 81% of patients had a satisfactory objective result. In 15 of 21 cases (71%), it was necessary to mobilize the ulnar nerve. After contracture release, 1 patient developed new onset ulnar nerve symptoms. Three patients underwent reoperation: 2 for recalcitrant contracture and 1 for new onset ulnar nerve symptoms. CONCLUSIONS: The mini-open O-K procedure is safe and effective in restoring function in patients with retained hardware and posttraumatic contracture. Posttraumatic arthritic patients often require both removal of hardware and neurolysis of the ulnar nerve. The mini-open O-K procedure allows complete access to the elbow joint, which facilitates release for both intrinsic and extrinsic contracture.

Patient-specific CFD models for intraventricular flow analysis from 3D ultrasound imaging: Comparison of three clinical cases.

BACKGROUND: As the intracardiac flow field is affected by changes in shape and motility of the heart, intraventricular flow features can provide diagnostic indications. Ventricular flow patterns differ depending on the cardiac condition and the exploration of different clinical cases can provide insights into how flow fields alter in different pathologies. METHODS: In this study, we applied a patient-specific computational fluid dynamics model of the left ventricle and mitral valve, with prescribed moving boundaries based on transesophageal ultrasound images for three cardiac pathologies, to verify the abnormal flow patterns in impaired hearts. One case (P1) had normal ejection fraction but low stroke volume and cardiac output, P2 showed low stroke volume and reduced ejection fraction, P3 had a dilated ventricle and reduced ejection fraction. RESULTS: The shape of the ventricle and mitral valve, together with the pathology influence the flow field in the left ventricle, leading to distinct flow features. Of particular interest is the pattern of the vortex formation and evolution, influenced by the valvular orifice and the ventricular shape. The base-to-apex pressure difference of maximum 2mmHg is consistent with reported data. CONCLUSION: We used a CFD model with prescribed boundary motion to describe the intraventricular flow field in three patients with impaired diastolic function. The calculated intraventricular flow dynamics are consistent with the diagnostic patient records and highlight the differences between the different cases. The integration of clinical images and computational techniques, therefore, allows for a deeper investigation intraventricular hemodynamics in patho-physiology.

Patient-specific CFD simulation of intraventricular haemodynamics based on 3D ultrasound imaging.

BACKGROUND: The goal of this paper is to present a computational fluid dynamic (CFD) model with moving boundaries to study the intraventricular flows in a patient-specific framework. Starting from the segmentation of real-time transesophageal echocardiographic images, a CFD model including the complete left ventricle and the moving 3D mitral valve was realized. Their motion, known as a function of time from the segmented ultrasound images, was imposed as a boundary condition in an Arbitrary Lagrangian-Eulerian framework. RESULTS: The model allowed for a realistic description of the displacement of the structures of interest and for an effective analysis of the intraventricular flows throughout the cardiac cycle. The model provides detailed intraventricular flow features, and highlights the importance of the 3D valve apparatus for the vortex dynamics and apical flow. CONCLUSIONS: The proposed method could describe the haemodynamics of the left ventricle during the cardiac cycle. The methodology might therefore be of particular importance in patient treatment planning to assess the impact of mitral valve treatment on intraventricular flow dynamics.

Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder.

While the neurobiological basis and developmental course of attention-deficit/hyperactivity disorder (ADHD) have not yet been fully established, an imbalance between inhibitory/excitatory neurotransmitters is thought to have an important role in the pathophysiology of ADHD. This study examined the changes in cerebral levels of GABA+, glutamate and glutamine in children and adults with ADHD using edited magnetic resonance spectroscopy. We studied 89 participants (16 children with ADHD, 19 control children, 16 adults with ADHD and 38 control adults) in a subcortical voxel (children and adults) and a frontal voxel (adults only). ADHD adults showed increased GABA+ levels relative to controls (P = 0.048), while ADHD children showed no difference in GABA+ in the subcortical voxel (P > 0.1), resulting in a significant age by disorder interaction (P = 0.026). Co-varying for age in an analysis of covariance model resulted in a nonsignificant age by disorder interaction (P = 0.06). Glutamine levels were increased in children with ADHD (P = 0.041), but there was no significant difference in adults (P > 0.1). Glutamate showed no difference between controls and ADHD patients but demonstrated a strong effect of age across both groups (P < 0.001). In conclusion, patients with ADHD show altered levels of GABA+ in a subcortical voxel which change with development. Further, we found increased glutamine levels in children with ADHD, but this difference normalized in adults. These observed imbalances in neurotransmitter levels are associated with ADHD symptomatology and lend new insight in the developmental trajectory and pathophysiology of ADHD.

Age dependent electroencephalographic changes in attention-deficit/hyperactivity disorder (ADHD).

OBJECTIVE: Objective biomarkers for attention-deficit/hyperactivity disorder (ADHD) could improve diagnostics or treatment monitoring of this psychiatric disorder. The resting electroencephalogram (EEG) provides non-invasive spectral markers of brain function and development. Their accuracy as ADHD markers is increasingly questioned but may improve with pattern classification. METHODS: This study provides an integrated analysis of ADHD and developmental effects in children and adults using regression analysis and support vector machine classification of spectral resting (eyes-closed) EEG biomarkers in order to clarify their diagnostic value. RESULTS: ADHD effects on EEG strongly depend on age and frequency. We observed typical non-linear developmental decreases in delta and theta power for both ADHD and control groups. However, for ADHD adults we found a slowing in alpha frequency combined with a higher power in alpha-1 (8-10Hz) and beta (13-30Hz). Support vector machine classification of ADHD adults versus controls yielded a notable cross validated sensitivity of 67% and specificity of 83% using power and central frequency from all frequency bands. ADHD children were not classified convincingly with these markers. CONCLUSIONS: Resting state electrophysiology is altered in ADHD, and these electrophysiological impairments persist into adulthood. SIGNIFICANCE: Spectral biomarkers may have both diagnostic and prognostic value.

Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study.

There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD-the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)-and one 'control' region-the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal 'control' region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate-glutamine levels are not explained by use of stimulant medication.

Physiological and psychological individual differences influence resting brain function measured by ASL perfusion.

Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity.