Ventral Tegmental Area Amylin Receptor Activation Differentially Modulates Mesolimbic Dopamine Signaling in Response to Fat versus Sugar.

Amylin, a pancreatic hormone that is cosecreted with insulin, has been highlighted as a potential treatment target for obesity. Amylin receptors are distributed widely throughout the brain and are coexpressed on mesolimbic dopamine neurons. Activation of amylin receptors is known to reduce food intake, but the neurochemical mechanisms behind this remain to be elucidated. Amylin receptor activation in the ventral tegmental area (VTA), a key dopaminergic nucleus in the mesolimbic reward system, has a potent ability to suppress intake of palatable fat and sugar solutions. Although previous work has demonstrated that VTA amylin receptor activation can dampen mesolimbic dopamine signaling elicited by random delivery of sucrose, whether this is also the case for fat remains unknown. Herein we tested the hypothesis that amylin receptor activation in the VTA of male rats would attenuate dopamine signaling in the nucleus accumbens core in response to random intraoral delivery of either fat or sugar solutions. Results show that fat solution produces a greater potentiation of accumbens dopamine than an isocaloric sucrose solution. Moreover, activation of VTA amylin receptors elicits a more robust suppression of accumbens dopamine signaling in response to fat solution than to sucrose. Taken together these results shed new light on the amylin system as a therapeutic target for obesity and emphasize the reinforcing nature of high-fat/high-sugar diets.

3D kinematics of tibiotalar motion in patients with mobile bearing and fixed bearing total ankle arthroplasty: In vivo videofluoroscopic feasibility study.

BACKGROUND: As total ankle arthroplasty (TAA) is an increasingly common surgical intervention for patients with end-stage ankle arthritis, there is a need to better understand the dynamic performance of prosthetic implants during activities of daily living. Our purpose was to quantify and compare relative tibiotalar motion during gait in persons with a fixed-bearing (FB) and mobile-bearing (MB) total ankle arthroplasty. We hypothesized a FB prosthesis would have lower tibiotalar range of motion (ROM). METHODS: Patients at least 12 months postoperative with either a FB (n=5) or MB (n=3) total ankle arthroplasty were tested. We used high-speed biplanar videoradiography to quantify tibiotalar kinematics during self-selected gait. Angular and linear ROM in three axes were compared between the groups. RESULTS: ROM for dorsiflexion-plantarflexion, internal-external rotation, and inversion-eversion angles in FB subjects averaged 7.47±4.05°, 7.39±3.63°, and 4.51±2.13°, respectively. ROM in MB subjects averaged 6.74±2.04°, 6.28±4.51°, and 5.68±2.81°, respectively. Linear ROM along anteroposterior, mediolateral, and superior-inferior axes in FB subjects averaged 1.47±2.07 mm, 1.13±1.49 mm, and 0.28±0.30 mm, respectively. Linear ROM in MB subjects averaged 0.68±1.44 mm, 0.60±1.41 mm, and 0.20±0.13 mm, respectively. We found no significant difference between the two groups for any of these ROM parameters (p>0.05). CONCLUSION: Total ankle arthroplasty using either FB or MB design appears to confer similar ankle motion during the gait cycle in this biplanar fluoroscopic model. LEVEL OF EVIDENCE: Level IV, case series.

Automation improves the efficiency of weightbearing CT scan 3D volumetric assessments of the syndesmosis.

BACKGROUND: Weight-bearing CT (WBCT) 3D volumetric measurement has shown promising accuracy for the diagnosis of syndesmotic instability. However, these measurements are rather complex and time-consuming, rendering them a clinically unfavorable option. We hypothesized that automatized measurements would be more accurate and time-efficient than manual ones. METHODS: Thirty cases of intraoperatively confirmed syndesmotic instability along with thirty individuals with no injuries to the ankle joint were recruited as cases and controls, retrospectively. Two observers conducted the manual volumetric measurements two times, at a one-week interval. An automated algorithm for 3D WBCT measurements was developed to conduct the measurements on the axial images. The time spent on each method was recorded. Mann-Whitney U test was used to compare the values between human raters and computers. Inter- and intra-class reliability were calculated. RESULTS: The intra-class correlation coefficient was found to be "excellent" for the automated measurements (0.97) and "good" for the observers (0.75). Similarly, the Cronbach's alpha was shown to be higher for the computer (0.88) than the observers (0.60 and 0.62). The mean time spent on the measurements was different between human raters and the computer-assisted method (p < 0.001). CONCLUSION: Automated volumetric assessment of syndesmosis seems to be a faster and more reliable option than the manual one. We suggest future larger-scale prospective studies conducted under actual clinical circumstances for more definitive conclusions. LEVEL OF EVIDENCE: Retrospective case-control study - Level 3.

Radiographic Landmark Measurements for the Femoral Footprint of the Medial Patellofemoral Complex May Be Affected by Visible Femoral Shaft Length on Lateral Knee Radiographs.

PURPOSE: To assess the effect of visible femoral shaft length on the accuracy of radiographic landmarks of the medial patellofemoral complex (MPFC). METHODS: In 9 cadaveric knees, the MPFC footprint was exposed on the medial femur, and its proximal and distal boundaries were marked. Lateral fluoroscopic images of the knee were assessed in 1-cm length increments, beginning 1 cm proximal to the medial condyle and continuing proximally to 8 cm. The MPFC midpoint was described on each image relative to the posterior cortical line of the femur and a line perpendicular to this line through the proximal margin of the medial condyle. In addition, the MPFC midpoint was assessed relative to a line from the proximal posterior cortex to the midpoint of Blumensaat line. RESULTS: Using the posterior cortical line as a reference, the MPFC radiographic landmark moved anteriorly with decreasing visible femoral shaft on radiographs, particularly at 4 cm and less. However, no proximal-distal change was noted. Linear regression analysis demonstrated a relationship between visible femoral shaft and MPFC position on radiographs (R = 0.461, R2 = 0.212, B = -0.636, P < .001). For every centimeter decrease in the visible femoral shaft, the radiographic MPFC footprint moved anteriorly by 0.636 mm. Receiver operating characteristic curve analysis revealed that a minimum of 4 cm of femoral shaft on lateral radiographs is required for accurate MPFC footprint localization (area under the curve = 0.80; sensitivity = 76.7%; specificity = 69.0%; P < .001). In contrast, no anterior-posterior change was seen when referencing a line from the proximal posterior cortex to the midpoint of Blumensaat line. CONCLUSIONS: When using the posterior cortical line to identify the midpoint of the MPFC, at least 4 cm of femoral shaft should be visible for accurate assessment. If less than 4 cm of shaft is visible, a line through the midpoint of Blumensaat line and the proximal posterior cortex can be used as an alternative method to estimate the position of the femoral footprint. CLINICAL RELEVANCE: As fluoroscopy is frequently used intraoperatively for MPFC reconstruction, our findings may serve as a guide when assessing femoral tunnel placement on fluoroscopy.

The use of deep learning enables high diagnostic accuracy in detecting syndesmotic instability on weight-bearing CT scanning.

PURPOSE: Delayed diagnosis of syndesmosis instability can lead to significant morbidity and accelerated arthritic change in the ankle joint. Weight-bearing computed tomography (WBCT) has shown promising potential for early and reliable detection of isolated syndesmotic instability using 3D volumetric measurements. While these measurements have been reported to be highly accurate, they are also experience-dependent, time-consuming, and need a particular 3D measurement software tool that leads the clinicians to still show more interest in the conventional diagnostic methods for syndesmotic instability. The purpose of this study was to increase accuracy, accelerate analysis time, and reduce interobserver bias by automating 3D volume assessment of syndesmosis anatomy using WBCT scans. METHODS: A retrospective study was conducted using previously collected WBCT scans of patients with unilateral syndesmotic instability. One-hundred and forty-four bilateral ankle WBCT scans were evaluated (48 unstable, 96 control). We developed three deep learning models for analyzing WBCT scans to recognize syndesmosis instability. These three models included two state-of-the-art models (Model 1-3D Convolutional Neural Network [CNN], and Model 2-CNN with long short-term memory [LSTM]), and a new model (Model 3-differential CNN LSTM) that we introduced in this study. RESULTS: Model 1 failed to analyze the WBCT scans (F1 score = 0). Model 2 only misclassified two cases (F1 score = 0.80). Model 3 outperformed Model 2 and achieved a nearly perfect performance, misclassifying only one case (F1 score = 0.91) in the control group as unstable while being faster than Model 2. CONCLUSIONS: In this study, a deep learning model for 3D WBCT syndesmosis assessment was developed that achieved very high accuracy and accelerated analytics. This deep learning model shows promise for use by clinicians to improve diagnostic accuracy, reduce measurement bias, and save both time and expenditure for the healthcare system. LEVEL OF EVIDENCE: II.

Distinct Effects of Methamphetamine Isomers on Limbic Norepinephrine and Dopamine Transmission in the Rat Brain.

Methamphetamine (METH) is a psychostimulant that primarily exerts its effects on the catecholamine (dopamine (DA) and norepinephrine (NE)) systems, which are implicated in drug addiction. METH exists as two distinct enantiomers, dextrorotatory (d) and levorotatory (l). In contrast to d-METH, the major component of illicit METH used to induce states of euphoria and alertness, l-METH is available without prescription as a nasal decongestant and has been highlighted as a potential agonist replacement therapy to treat stimulant use disorder. However, little is known regarding l-METH's effects on central catecholamine transmission and behavior. In this study, we used fast-scan cyclic voltammetry to elucidate how METH isomers impact NE and DA transmission in two limbic structures, the ventral bed nucleus of the stria terminalis (vBNST) and nucleus accumbens (NAc), respectively, of anesthetized rats. In addition, the dose-dependent effects of METH isomers on locomotion were characterized. d-METH (0.5, 2.0, 5.0 mg/kg) enhanced both electrically evoked vBNST-NE and NAc-DA concentrations and locomotion. Alternatively, l-METH increased electrically evoked NE concentration with minimal effects on DA regulation (release and clearance) and locomotion at lower doses (0.5 and 2.0 mg/kg). Furthermore, a high dose (5.0 mg/kg) of d-METH but not l-METH elevated baseline NE and DA concentrations. These results suggest mechanistic differences between NE and DA regulation by the METH isomers. Moreover, l-METH's asymmetric regulation of NE relative to DA may have distinct implications in behaviors and addiction, which will set the neurochemical framework for future studies examining l-METH as a potential treatment for stimulant use disorders.

Arthroscopic assessment of syndesmotic instability: Are we pulling correctly in the coronal plane?

BACKGROUND: While the lateral hook test (LHT) has been widely used to arthroscopically evaluate syndesmotic instability in the coronal plane, it is unclear whether the angulation of the applied force has any impact on the degree of instability. We aimed to determine if changing the direction of the force applied while performing the LHT impacts the amount of coronal diastasis observed in subtle syndesmotic injuries. METHODS: In 10 cadaveric specimens, arthroscopic evaluation of the syndesmotic joint was performed by measuring anterior and posterior-third coronal plane diastasis in the intact state, and repeated after sequential transection of the 1) anterior inferior tibiofibular ligament (AITFL), 2) interosseous ligament (IOL), and 3) posterior inferior tibiofibular ligament (PITFL). In all scenarios, LHT was performed under 100 N of laterally directed force. Additionally, LHT was also performed under: 1) anterior inclination of 15 degrees and 2) posterior inclination of 15 degrees in intact and AITFL+IOL deficient state. RESULTS: Compared to the intact state, the syndesmosis became unstable after AITFL +IOL transection under laterally directed force with no angulation (p = 0.029 and 0.025 for anterior and posterior-third diastasis, respectively), which worsened with subsequent PITFL transection (p = <0.001). Moreover, there was no statistical difference in anterior and posterior-third coronal diastasis in both intact and AITFL+IOL deficient states under neutral, anterior, and posteriorly directed force (p-values ranging from 0.816 to 0.993 and 0.396-0.80, respectively). However, in AITFL+IOL transected state, posteriorly directed forces resulted in greater diastasis than neutral or anteriorly directed forces. CONCLUSIONS: Angulation of the applied force ranging from 15 degrees anteriorly to 15 degrees posteriorly during intraoperative LHT has no effect on coronal plane measurements in patients with subtle syndesmotic instability. On the other hand, posteriorly directed forces result in more sizable diastasis, potentially increasing their sensitivity. CLINICAL RELEVANCE: When arthroscopically evaluating subtle syndesmotic instability, clinicians should assess coronal diastasis with the hook angled 15 degrees posteriorly.

Dynamic Ultrasound Can Accurately Quantify Severity of Medial Knee Injury: A Cadaveric Study.

Purpose: To quantify the severity of medial knee injuries based on medial compartment gapping as measured by stress ultrasonography. Methods: In 8 cadaveric knees, the distance between the medial tibial and femoral condyles was measured using ultrasonography. These measurements were obtained in the intact state and repeated after open sequential transection of the superficial medial collateral ligament (sMCL), deep medial collateral ligament (dMCL), posterior oblique ligament (POL), and arthroscopic transection of the anterior cruciate ligament (ACL). Knees were evaluated at 0° and 20° of knee flexion using the Telos device under 0 N and 100 N of valgus force. Receiver operating characteristic curve analysis and the DeLong test were used to determine whether measurements could distinguish between successive severity of MCL injury after identifying the optimal cutoff value for each injury state. Results: Of the 8 cadaveric knees included in this study, 3 were male and 5 were female. The mean age was 58 ± 11 years (range 48-82 years). When measured using ultrasonography at 20° knee flexion with valgus load, the medial tibiofemoral distance significantly increased with increasing severity of medial knee injury (P values ranging from .049 to <.001). The optimal cutoff values for distinguishing between an intact knee and sMCL injury were 8.3 mm (area under the curve [AUC] = 0.98), between sMCL and dMCL injury 9.9 mm (AUC = 0.89), dMCL and POL 16.7 mm (AUC = 0.88), and POL and ACL 18.6 mm (AUC = 0.84). When we compared combined intact and sMCL-transected stages with dMCL-transected stage, the optimal cut-off point to differentiate stable from unstable injuries was equal to 13.8 mm of medial tibiofemoral distance (AUC = 0.97; sensitivity = 100%; specificity = 94.1%). Conclusions: Dynamic ultrasonographic assessment can accurately quantify the severity of medial knee ligament injury based on medial compartment gapping. In our study, we found medial tibiofemoral distance >13.8 mm at 20° knee flexion under valgus force indicates the presence of dMCL injury with a diagnostic accuracy of 0.97. Clinical Relevance: Dynamic ultrasonography can quantify severity of medial knee injury without radiation and at point of care in multiple clinical settings.

Fluoroscopic Evaluation of the Role of Syndesmotic Injury in Lateral Ankle Instability in a Cadaver Model.

BACKGROUND: There is a high prevalence of concomitant lateral ankle ligament injuries and syndesmotic ligamentous injuries. However, it is unclear whether syndesmotic ligaments directly contribute toward the stability of the lateral ankle. Therefore, the aim of this study was to fluoroscopically evaluate the role of the syndesmotic ligaments in stabilizing the lateral ankle. METHODS: Twenty-four cadaveric specimens were divided into 3 groups and fluoroscopically evaluated for lateral ankle stability with all syndesmotic and ankle ligaments intact and then following serial differential ligamentous transection. Group 1: (1) anterior talofibular ligament (ATFL), (2) calcaneofibular ligament (CFL), and (3) posterior talofibular ligament (PTFL). Group 2: (1) anterior inferior tibiofibular ligament (AITFL), (2) interosseous ligament (IOL), (3) posterior inferior tibiofibular ligament (PITFL), (4) ATFL, (5) CFL, and (6) PTFL. Group 3: (1) AITFL, (2) ATFL, (3) CFL, (4) IOL, (5) PTFL, and (6) PITFL. At each transection state, 3 loading conditions were used: (1) anterior drawer test performed using 50 and 80 N of direct force, (2) talar tilt <1.7 Nm torque, and (2) lateral clear space (LCS) <1.7 Nm torque. These measurements were in turn compared with those of the stressed intact ligamentous state. Wilcoxon rank-sum test was used to compare the findings of each ligamentous transection state to the intact state. A P value <.05 was considered statistically significant. RESULTS: The lateral ankle remained stable after transection of all syndesmotic ligaments (AITFL, IOL, PITFL). However, after additional transection of the ATFL, the lateral ankle became unstable in varus and anterior drawer testing conditions (P values ranging from .036 to .012). Lateral ankle instability was also observed after transection of the ATFL and AITFL in varus and anterior drawer testing conditions (P values ranging from .036 to .012). Subsequent transection of the CFL and PTFL worsened the lateral ankle instability. CONCLUSION: Our findings suggest that isolated syndesmosis disruption does not result in lateral ankle instability. However, the lateral ankle became unstable when the syndesmosis was injured along with ATFL disruption. CLINICAL RELEVANCE: When combined with ATFL release, disruption of the syndesmosis appeared to destabilize the lateral ankle.

Utility of Diagnostic Ultrasound in the Assessment of Patellar Instability.

Background: The use of imaging to diagnose patellofemoral instability is often limited by the inability to dynamically load the joint during assessment. Therefore, the diagnosis is typically based on physical examination using the glide test to assess and quantify lateral patellar translation. However, precise quantification with this technique remains difficult. Purpose: To quantify patellar position using ultrasound imaging under dynamic loading conditions to distinguish between knees with and without medial patellofemoral complex (MPFC) injury. Study Design: Controlled laboratory study. Methods: In 10 cadaveric knees, the medial patellofemoral distance was measured to quantify patellar position from 0° to 40° of knee flexion at 10° increments. Knees were evaluated at each flexion angle under unloaded conditions and with 20 N of laterally directed force on the patella to mimic the glide test. Patellar position measurements were made on ultrasound images obtained before and after MPFC transection and compared for significant differences. To determine the ability of medial patellofemoral measurements to differentiate between MPFC-intact and MPFC-deficient states, area under the receiver operating characteristic (ROC) curve analysis and the Delong test were used. The optimal cutoff value to distinguish between the deficient and intact states was determined using the Youden J statistic. Results: A significant increase in medial patellofemoral distance was observed in the MPFC-deficient state as compared with the intact state at all flexion angles (P = .005 to P < .001). When compared with the intact state, MPFC deficiency increased medial patellofemoral distance by 32.8% (6 mm) at 20° of knee flexion under 20-N load. Based on ROC analysis and the J statistic, the optimal threshold for identifying MPFC injury was 19.2 mm of medial patellofemoral distance at 20° of flexion under dynamic loading conditions (area under the ROC curve = 0.93, sensitivity = 77.8%, specificity = 100%, accuracy = 88.9%). Conclusion: Using dynamic ultrasound assessment, we found that medial patellofemoral distance significantly increases with disruption of the MPFC. Clinical Relevance: Dynamic ultrasound measurements can be used to accurately detect the presence of complete MPFC injury.

Detection of ankle fractures using deep learning algorithms.

BACKGROUND: Early and accurate detection of ankle fractures are crucial for optimizing treatment and thus reducing future complications. Radiographs are the most abundant imaging techniques for assessing fractures. Deep learning (DL) methods, through adequately trained deep convolutional neural networks (DCNNs), have been previously shown to faster and accurately analyze radiographic images without human intervention. Herein, we aimed to assess the performance of two different DCNNs in detecting ankle fractures using radiographs compared to the ground truth. METHODS: In this retrospective case-control study, our DCNNs were trained using radiographs obtained from 1050 patients with ankle fracture and the same number of individuals with otherwise healthy ankles. Inception V3 and Renet-50 pretrained models were used in our algorithms. Danis-Weber classification method was used. Out of 1050, 72 individuals were labeled as occult fractures as they were not detected in the primary radiographic assessment. Single-view (anteroposterior) radiographs was compared with 3-views (anteroposterior, mortise, lateral) for training the DCNNs. RESULTS: Our DCNNs showed a better performance using 3-views images versus single-view based on greater values for accuracy, F-score, and area under the curve (AUC). The highest sensitivity was 98.7 % and specificity was 98.6 % in detection of ankle fractures using 3-views using inception V3. This model missed only one fracture on radiographs. CONCLUSION: The performance of our DCNNs showed that it can be used for developing the currently used image interpretation programs or as a separate assistant solution for the clinicians to detect ankle fractures faster and more precisely. LEVEL OF EVIDENCE: III.

Isolated injuries to the lateral ankle ligaments have no direct effect on syndesmotic stability.

PURPOSE: This study aim was to detect the impact of lateral ankle ligaments injury on syndesmotic laxity when evaluated arthroscopically in a cadaveric model. The null hypothesis was that lateral ankle ligament injury does not affect the stability of syndesmosis. METHODS: Sixteen fresh-frozen above-knee amputated cadaveric specimens were divided into two groups of eight specimens that underwent arthroscopic evaluation of the distal tibiofibular joint. In both the groups, the assessment was first done with all syndesmotic and ankle ligaments intact. Thereafter, Group 1 underwent sequential transection of the three lateral ankle ligaments first to identify the effects of lateral ligament injury: (1) anterior talofibular ligament (ATFL), (2) calcaneofibular ligament (CFL), (3) posterior talofibular ligament (PTFL), then followed by the syndesmotic ligaments, (4) AITFL, (5) Interosseous ligament (IOL), and (6) PITFL. Group 2 underwent sequential transection of the (1) AITFL, (2) ATFL, (3) CFL, (4) IOL, (5) PTFL, and (6) PITFL, which represent the most commonly injured pattern in ankle sprain. In all scenarios, four loading conditions were considered under 100 N of direct force: (1) unstressed, (2) a lateral fibular hook test, (3) anterior to posterior (AP) fibular translation test, and (4) posterior to anterior (PA) fibular translation test. Distal tibiofibular coronal plane diastasis at the anterior and posterior third of syndesmosis, as well as AP and PA sagittal plane translation, were arthroscopically measured. RESULTS: The distal tibiofibular joint remained stable after transection of all lateral ankle ligaments (ATFL, CFL, and PTFL) as well as the AITFL. However, after additional transection of the IOL, the syndesmosis became unstable in both the coronal and sagittal plane. Syndesmosis laxity in the coronal plane was also observed after transection of the ATFL, CFL, AITFL, and IOL. Subsequent transection of the PITFL precipitated syndesmosis laxity in the sagittal plane, as well. CONCLUSIONS: The findings from the present study suggest that lateral ankle ligament injuries itself do not directly affect the stability of syndesmosis. However, if it combines with IOL injuries, even partial injuries cause syndesmotic laxity. As a clinical relevance, accurate diagnosis is the key for surgeons to determine syndesmosis fixation whether there is only AITFL injury or combined IOL injury in concomitant acute syndesmotic and lateral ligament injury.

Deep Learning Algorithms Improve the Detection of Subtle Lisfranc Malalignments on Weightbearing Radiographs.

BACKGROUND: Detection of Lisfranc malalignment leading to the instability of the joint, particularly in subtle cases, has been a concern for foot and ankle care providers. X-ray radiographs are the mainstay in the diagnosis of these injuries; thus, improving the performance of clinicians in interpreting radiographs can noticeably affect the quality of health care in these patients. Here we assessed the performance of deep learning algorithms on weightbearing radiographs for detection of Lisfranc joint malalignment in patients with Lisfranc instability. METHODS: In a retrospective study, 640 patients with Lisfranc malalignment leading to instability were recruited plus 640 individuals with uninjured feet and healthy Lisfranc joint as the control group. All radiographs were screened by orthopaedic surgeons. Two deep learning models were trained, validated, and tested (in a ratio 80:10:10) using a single-view (anteroposterior) and 3-view (anteroposterior, lateral, oblique) radiographs. The performances of the models were reported as sensitivity, specificity, positive and negative predictive values, accuracy, F score, and area under the curve (AUC). RESULTS: No significant differences were observed between the patients and the controls regarding age, gender, race, and body mass index. The best deep learning algorithm outperformed our human interpreters (<1% vs ~10% misdiagnosis), 94.8% sensitivity, 96.9% specificity, 98.6% accuracy, 95.8% F score, and 99.4% AUC. CONCLUSION: Deep learning methods have shown promising potential in acting as an assistant interpreter of radiographic images in patients with Lisfranc malalignment. Developing these algorithms can hasten and improve the accuracy of diagnosis and reduce further costs and burdens on the patients and health care system. LEVEL OF EVIDENCE: Level III, case-control Machine Learning study.

Radiographic Landmarks for the Femoral Attachment of the Medial Patellofemoral Complex: A Cadaveric Study.

PURPOSE: To report the radiographic landmarks for the medial patellofemoral complex (MPFC) footprint on the medial femur and describe the difference between the radiographic positions corresponding to the medial quadriceps tendon femoral ligament (MQTFL) and medial patellofemoral ligament (MPFL) fibers. METHODS: In 8 unpaired cadaveric knees, the MPFC footprint was exposed on the medial femur, and the proximal and distal boundaries of the footprint were marked. Lateral fluoroscopic images of the knee were obtained and analyzed using Image J. The proximal boundary corresponding to the MQTFL, the MPFC midpoint, and distal boundary corresponding to the MPFL were described radiographically and compared for differences in position. RESULTS: The proximal MQTFL footprint was 0.8 ± 0.6 mm anterior (P = .013) and 5.2 ± 1.8 mm proximal to the MPFC midpoint (P <.001), whereas the distal MPFL footprint was 0.8 ± 0.7 mm posterior (P = .012) and 5.9 ± 1.1 mm distal to the radiographic MPFC midpoint (P <.001). The radiographic point corresponding to the distal MPFL footprint was 0.8 ± 0.9 mm posterior (P = .011) and 11.1 ± 2.3 mm distal to the radiographic point of the proximal MQTFL footprint (P <.001). When using the point of intersection of the posterior cortical line and the proximal posterior condyle as a reference, 91.6% of all points correlating to the MQTFL, MPFC midpoint and MPFL, were within 10 mm in any direction from this radiographic landmark. CONCLUSIONS: On fluoroscopic imaging, the proximal MQTFL and distal MPFL fibers had significantly different radiographic positions from the MPFC midpoint on the femur. These findings should be considered when reconstructing specific components of the MPFC. CLINICAL RELEVANCE: As fluoroscopy is often used intraoperatively to guide graft placement, our findings may serve as a reference when differentiating the locations of the MPFL vs MQTFL on the femur for anatomic reconstruction.

Distinct limbic dopamine regulation across olfactory-tubercle subregions through integration of in vivo fast-scan cyclic voltammetry and optogenetics.

The olfactory tubercle (OT), an important component of the ventral striatum and limbic system, is involved in multi-sensory integration of reward-related information in the brain. However, its functional roles are often overshadowed by the neighboring nucleus accumbens. Increasing evidence has highlighted that dense dopamine (DA) innervation of the OT from the ventral tegmental area (VTA) is implicated in encoding reward, natural reinforcers, and motivated behaviors. Recent studies have further suggested that OT subregions may have distinct roles in these processes due to their heterogeneous DA transmission. Currently, very little is known about regulation (release and clearance) of extracellular DA across OT subregions due to its limited anatomical accessibility and proximity to other DA-rich brain regions, making it difficult to isolate VTA-DA signaling in the OT with conventional methods. Herein, we characterized heterogeneous VTA-DA regulation in the medial (m) and lateral (l) OT in "wild-type," urethane-anesthetized rats by integrating in vivo fast-scan cyclic voltammetry with cell-type specific optogenetics to stimulate VTA-DA neurons. Channelrhodopsin-2 was selectively expressed in the VTA-DA neurons of wild-type rats and optical stimulating parameters were optimized to determine VTA-DA transmission across the OT. Our anatomical, neurochemical, and pharmacological results show that VTA-DA regulation in the mOT is less dependent on DA transporters and has greater DA transmission than the lOT. These findings establish the OT as a unique, compartmentalized structure and will aid in future behavioral characterization of the roles of VTA-DA signaling in the OT subregions in reward, drug addiction, and encoding behavioral outputs necessary for survival.

Use of portable ultrasonography for the diagnosis of lateral ankle instability.

Portable ultrasonography is increasingly used to evaluate ankle stability at the point of care. This study aims to determine the correlation of portable-ultrasonographic and fluoroscopic measurements of ankle laxity in a cadaveric ligament transection model of ankle ligament injury. We hypothesize that there is an association between portable-ultrasonographic and fluoroscopic measurements when performing stress evaluation of lateral ankle instability. Eight fresh-frozen below-knee amputated cadaveric specimens with intact proximal fibula underwent ultrasound and fluoroscopic evaluation of the ankle during anterior drawer and talar tilt testing. The assessment was first performed with all lateral ankle ligaments intact and thereafter with sequential transection of the anterior talofibular ligament, calcaneofibular ligament, and posterior talofibular ligament. The anterior drawer test was performed with both 50N and 80N of force, and talar tilt test was performed with 1.7 Nm of torque. Correlations between (1) portable-ultrasonographic and fluoroscopic measurements and (2) sequential transection of lateral ankle ligaments were evaluated using Spearman's rank correlations. The same statistical test was used to investigate the correlation between the ultrasonographic and the fluoroscopic measurements. The inter- and intra-observer agreement was assessed using the intraclass correlation coefficient through a two-way mixed-effects model with absolute agreement. Portable-ultrasonographic and fluoroscopic measurements increased as additional ligaments of the lateral ankle were transected (Spearman's rank correlation ranged from 0.74 to 0.81, 0.74 to 0.81, p-values < 0.001). Strong positive correlations between ultrasonographic and fluoroscopic measurements were found during the lateral ankle stability evaluation using anterior drawer and talar tilt testing (Spearman's rank correlation ranged from 0.81 to 0.85, 0.81 to 0.85, p-values < 0.001). Inter-rater (0.99, 95% CI: 0.98-0.99) and intra-rater reliability (0.97, 95% CI: 0.95-0.99) for the ultrasonographic measurements were substantial. In conclusion, there was a strong correlation found between ultrasonographic and fluoroscopic values measured during simulated anterior drawer and talar tilt test in a cadaveric ligament transection model. In this model, the portable-ultrasonographic measurement was found to be reliable for repeated measurements of the talar translation and the lateral clear space distance. Based on these data, ultrasonography is likely to become a valuable point of care diagnostic tool due to its ability to readily and dynamically evaluate suspected lateral ankle instability. Clinical Significance: The use of dynamic stress ultrasound to assess the anterior translation of the talus and the lateral clear space distance appears to be a reliable and repeatable technique to evaluate lateral ankle stability with a radiation-free, noninvasive, and low-cost manner.

Volume measurements on weightbearing computed tomography can detect subtle syndesmotic instability.

While weightbearing computed tomography (WBCT) allows three-dimensional (3D) visualization of the distal syndesmosis, image interpretation has largely relied on one-dimensional (1D) distance and, more recently, two-dimensional (2D) area measurements. This study aimed to (1) determine the sensitivity and specificity of 2D area and 3D volume WBCT measurements towards detecting subtle syndesmotic instability, (2) evaluate whether the patterns of changes in the 3D shape of the syndesmosis can be attributed to the type of ligament injury. A total of 24 patients with unilateral subtle syndesmotic instability and 24 individuals with uninjured ankles (controls) with bilateral ankle WBCT were assessed retrospectively. First, 2D areas at 0, 1, 3, 5, and 10 cm, and 3D volumes at 1, 3, 5, and 10 cm above the tibial plafond were measured bilaterally. Secondly, the 3D model of the distal tibiofibular space was created based on WBCT in a subset of 8 out of 24 patients in whom the type of ligament injury was recognized via magnetic resonance imaging. The 3D model of the injured side was superimposed on the uninjured contralateral side to visualize the pattern of changes in different planes. Volume measurement up to 5 cm above the tibial plafond showed the lowest p-value (<0.001 vs. other methods), higher sensitivity (95.8%, 95% confidence interval [CI]: 87.8-100), and specificity (83.3%, 95% CI: 68.4-98.2) for detection of syndesmotic instability. No specific pattern of changes in the 3D shape could be attributed to a type of ligament rupture. We suggest 3D volume measurements, best measured up to 5 cm proximal to the plafond, as a promising means of diagnosing syndesmotic instability, particularly for subtle cases that are hard to detect. Clinical significance: The ability to compare the ankle joints bilaterally in a 3D manner under physiologic weight provided by weightbearing CT has led to a more accurate diagnostic method. Using volumetric measurement up to 5 cm above the tibial plafond showed higher sensitivity and specificity for recognizing an unstable syndesmosis, especially in subtle cases. However, our preliminary investigations showed that the pattern of 3D alterations in the distal tibiofibular joint space based on WBCT images does not indicate the type of syndesmotic ligamentous injury. Our results can also help image viewing programs to improve their measurement tools to facilitate 3D measurement for the syndesmosis as well as other conditions that may benefit from 3D evaluation of the clinical images.

Arthroscopic Patellofemoral Measurements Can Reliably Assess Patellar Instability.

PURPOSE: To arthroscopically describe patellar position based on lateralization, tilt, and engagement, and compare measurements in normal, medial patellofemoral complex-(MPFC) deficient, and MPFC-reconstructed knees. METHODS: In 10 cadaveric knees, arthroscopic patellar position was assessed by performing digital measurements on arthroscopic images obtained through a standard anterolateral portal. Lateralization was measured as millimeters overhang of the patella past the lateral edge of the lateral femoral condyle, viewing from the lateral gutter. Patellar tilt was calculated as the difference in medial and lateral distances from the patella to the trochlea, viewing from the sunrise view. Patellotrochlear distance was measured as the anteroposterior distance between the central trochlear groove and patella on the sunrise view. Measurements were obtained at 10° intervals of knee flexion from 0° to 90°, in intact knees (group 1), after arthroscopically transecting the MPFC fibers (group 2), and after MPFC reconstruction (group 3). Optimal cutoff values were identified to distinguish between intact versus MPFC-deficient states. RESULTS: When compared to group 1, group 2 demonstrated increased patellar lateralization by 22.5% at 0°-40° knee flexion (P = .006), which corrected to baseline in group 3 (P = .006). Patellar tilt measurements demonstrated no differences between groups. Patellotrochlear distance increased by 21.0% after MPFC transection (P = .031) at 0°-40° knee flexion, with correction to baseline after MPFC reconstruction (P = .031). More than 7 mm of lateral overhang at 20°-30° flexion and >6 mm of patellotrochlear distance at 10°-20° flexion were found to indicate MPFC deficiency. CONCLUSIONS: Utilizing standardized arthroscopic views, we identified significant increases in patellar lateralization and patellotrochlear distance in early knee flexion angles after MPFC transection, and these changes normalized after MPFC reconstruction. CLINICAL RELEVANCE: Arthroscopic assessments of patellar position may be useful in evaluating patellofemoral stability during patellar stabilization surgery.

Utility of WBCT to Diagnose Syndesmotic Instability in Patients With Weber B Lateral Malleolar Fractures.

BACKGROUND: Diagnosing syndesmotic instability accompanying Weber B ankle fractures can be challenging. This study aimed to evaluate the ability of weight-bearing computed tomography (WBCT) to diagnose syndesmotic instability using one-dimensional, two-dimensional, and three-dimensional measurements among patients with unilateral Weber B lateral malleolar fractures with symmetric medial clear space (MCS) on initial radiographs and yet demonstrated operatively confirmed syndesmotic instability. METHODS: The treatment group included 23 patients with unilateral surgically confirmed syndesmotic instability accompanying Weber B ankle fractures who underwent preoperative bilateral foot and ankle WBCT. The control group included 18 unilateral Weber B ankle fracture patients without syndesmotic instability who underwent bilateral WBCT. Measurements on WBCT images included the following: (1) syndesmotic area, (2) anterior, middle, and posterior distal tibiofibular distance, (3) fibular rotation, (4) distance from fibular tip to plafond, (5) fibular fracture displacement, and (6) MCS distance. In addition, the following volumetric measurements were calculated: (1) syndesmotic joint volume from the tibial plafond extending to 3 and 5 cm proximally, (2) MCS volume, and (3) lateral clear space volume. Area under the receiver operating characteristic curve analysis and Delong test were used, and optimal cutoff values to distinguish between stable and unstable syndesmosis were determined using Youden J statistic. RESULTS: Among patients with unilateral syndesmotic instability and Weber B ankle fractures, all WBCT measurements were significantly greater than uninjured side, except MCS distance, syndesmotic area, and anterior and posterior tibiofibular distances (P values <0.001 to 0.004). Moreover, syndesmosis volume spanning from the tibial plafond to 5 cm proximally had the largest area under the curve of 0.96 (sensitivity = 90%; specificity = 95%), followed by syndesmosis volume up to 3 cm proximally (area under the curve = 0.91; sensitivity = 90%; specificity = 90%). Except for MCS volume and distal fibular tip to tibial plafond distance, the control group showed no side-to-side difference in any parameter. CONCLUSION: Syndesmotic joint volume measurements seem to be best suited to diagnose syndesmotic instability among patients with Weber B ankle fractures, compared with other two-dimensional and three-dimensional WBCT measurements. LEVEL OF EVIDENCE: Level III, comparative diagnostic study.

The stability of total talar prosthesis-How stable to dislocation? Cadaveric study.

The aim of this study was to characterize ankle stability of total talar prosthesis (TTP) and to determine the effect of implant sizes on stability as well as the resistance to TTP dislocation. Twelve below-knee cadaveric specimens were divided into two groups. Group 1 received a size matched implant and Group 2 received downsized implant by 5%. The stability assessment under fluoroscopy was performed for each cadaver in its native state. Following TTP insertion process, each then underwent evaluation of the TTP ankle stability. The stability of pre- and post-TTP was compared. (1) Anterior drawer distance. (2) Talar tilt angle under varus and valgus stress. (3) Subtalar tilt angle under varus stress was measured. Finally, the dislocation test was performed using the aforementioned testing conditions, then the stress force was slowly increased from 0 to 350 N, during which time it was observed on fluoroscopy all the time. Compared to pre TTP ankles, varus and anterior drawer stress showed significant instability (p < 0.001-0.031). Only anterior drawer stress in smaller sized implants showed significant instability when compared to identical sized implants (p = 0.008). No dislocation was seen under varus, valgus, and subtalar stress. However, anterior dislocation was observed in all cases of smaller size implant group (p = 0.045). TTP implant was stable under valgus and subtalar stress. However, clinicians should pay attention to anterior instability. Notably, downsized implants should be considered carefully to minimize the chance of anterior dislocation.