HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation

APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1

Usefulness of a wearable cardioverter defibrillator combined with catheter ablation for ventricular tachyarrhythmia storms after a myocardial infarction: A case report

We report a case of a 60-year-old man with recurrent poly- and monomorphic ventricular tachycardia related to a recent myocardial infarction. Due to drug-refractory ventricular tachycardia despite complete revascularization, he underwent catheter ablation. Afterwards, he was fitted with a wearable cardioverter defibrillator. Three months later, no ventricular tachycardia had been recorded and an electrophysiologic study failed to induce an episode. Thus, wearable cardioverter defibrillators are useful bridging devices pending a final decision to implant a cardioverter defibrillator

Evaluation of articular cartilage injury using computed tomography with axial traction in ankle joint

Category: Ankle Introduction/Purpose: Although chondral or osteochondral injuries are usually assessed by MRI, its accuracy is reportedly low because of the relatively thin cartilage layer and its close apposition to the cartilage talus and tibial plafond. The subchondral bone plays a role in cartilage metabolism, therefore the evaluation of subchondral bone is crucial for cartilage treatment. A method which enables the simultaneous evaluation of cartilage and subchondral bone is useful for the treatment of cartilage injury. The purpose of this study was to assess the feasibility of CT imaging with axial traction for the diagnosis of articular cartilage injuries. Methods: Chondral lesion in 18 ankles of 17 patients were evaluated. These 18 ankles consisted of 11 ankles of osteochondral lesion of the talar dome (OLT), 5 ankles of osteoarthritis of ankle joints and 2 ankles of anterior impingement syndrome. Twelve males and 5 women were included, with a mean age of 33.7 years (range, 15 -70 years). An ankle distractor foot strap was placed on the ankle with 30 degrees flexion of the knee joint, and a traction force of 80 N was applied during CT scanning. Gray scale CT images were allocated colors to make it easier to evaluate the cartilage layer. The international Cartilage Repair Society (ICRS) grades on CT were compared with those in arthroscopic findings. Results: The respective sensitivity and specificity of CT imaging with traction compared to ICRS grading were 74.4%, and 96.3%. The level of agreement of the ICRS grading between CT images and arthroscopic findings showed moderate (kappa coefficient; 0.547). The diagnosis of grade 3 or 4 lesions had 80.0% sensitivity. Axial traction to CT enabled the delineation of the cartilage surface including chondral thinning, defect and cartilage separation more visible (Figure 1). Conclusion: CT with axial traction could obtain acceptable levels of sensitivity and specificity for the evaluation of articular cartilage injuries in addition to the assessment of subchondral bone

Morphological change of OLT after excision of osteochondral fragment with microfracture on MRI

Category: Ankle Introduction/Purpose: Osteochondral lesion of talus (OLT) is treated by several procedures such as bone marrow stimulation technique, cartilage fragment fixation, or autologous osteochondoral bone implantation. The choice of surgical methods depends on the size of lesion and cartilage condition. For unstable small lesion, excision of osteochondral fragment is usually performed. Good clinical results after this procedure is reported, but it is unclear that the morphological repair of subchondral bone and cartilage like tissue at the lesion. The purpose of this study is to evaluate the restoration of subchondral bone and cartilage like tissue after arthroscopic microfracture with excision of osteochondral fragment, and to investigate the clinical outcomes of this operation for the athletes. Methods: From 2005 to 2015, 11 patients (6 men and 5 women) were performed arthroscopic microfracture with excision of osteochondral fragment for OLT. Average age was 28.6 years old (17 - 59 years old). The site of OLT was 10 medial and 1 lateral. The cases of athletes were 7 of 11 cases. The size of preoperative OLT by MRI, measure the depth of the resected site on 3-month postoperative MRI. And we evaluated the appearance of the repair site on 1 year postoperative MRI, clinical outcome using American Orthopaedic Foot and Ankle Society Clinical Rating System (AOFAS), return rate to sports, and period of return to the sports. Results: Preoperative size of lesion on MRI was 9.8 mm in sagittal view, and 6.0 mm in coronal view. Depth of the resected site in 3 months postoperative MRI was 3.1 mm. On one year postoperative MRI, the resected site was filled with cartilage like tissue, and the shape of restored site was good that mimicked the original shape (Figure 1). As for clinical outcome, AOFAS score was 65.4 points preoperatively, and it improved to 93.4 points 1 year postoperatively. In clinical outcomes of the athletes, all cases could return to sports. Average period to return sports was 5.6 months. Only in 1 case, mild pain during sports activity was remained. Preoperative AOFAS score of athletes was 71.4 points and it improved to 98.5 points postoperatively. Conclusion: According to this study, even if a symptom is mild, an early operation will be more likely to result in the early return to sports and good outcomes. In addition, these good outcomes and good congruency on 1 year postoperative MRI suggest that the restored cartilage like tissue is enough for the high activities. The cartilage is repaired with maintaining original shape of talus cartilage. And this method was effective for athletes and was able to get them return to sports with good outcome

Evaluation of the ankle position sense in the fatigue foot

Category: Ankle Introduction/Purpose: Previous studies have described the damage of sensori-motor control in ankle sprain as being a possible cause of functional instability. The methods to demonstrate the functional instability, have included the postural balance test, peroneal muscle reaction time to sudden ankle inversion, peroneal nerve conduction velocity, and joint position sense of the ankle. On the other hand, isokinetic fatigue of ankle plantar flexion and dorsiflexion exhibits the correlation with postural instability. We hypothesize muscle fatigue around ankle joint causes abnormality of joint position sense, especially inversion at ankle joint, and it will be one of the causes of the ankle sprain. The aim of this study was to evaluate the inversion angle replication errors of before fatigue and after fatigue. Methods: 11 subjects were included in this study. The subjects were placed in a sitting position with the knee flexed at 70°. Each subject placed the foot on a goniometer footplate with the ankle at 20° planter flexion. Subjects were blindfolded to eliminate visual input and to facilitate concentration during testing. The foot was passively rotated internally at random to one of six positions (5°to 30°), always starting from 0°. The footplate was rotated manually to the index angle in approximately 1 s, and held in position for 5 s. Then the ankle was returned to the 0° position. After that, the subjects moved their ankle to match the previous test angle actively. The difference between the index angle and replication angle was measured. Ankles were enforced planter and dorsiflexion according to previous reports, and replication error was measured before and after fatigue. Results: The side-to-side difference of the replication errors was 1.9±1.7° in the before-fatigue group and 2.6±1.8° in the after-fatigue group. There was a statistically significant difference between both the groups (p<0.05). In each inversion angle, there were significant differences of the side-to-side differences of the replication errors at 5°and 10°inversion angles (0.8±0.9°, 1.5±1.4° in the before-fatigue group and 2.2±1.7°, 2.6±1.5° in the after-fatigue group respectively). Conclusion: This study revealed the deficit of joint position sense in ankle inversion induced by fatigue. Fatigue may be one of the risk factor of ankle sprain through the deficit of joint position sense in inversion angle during sports activity

Outcome of Autologous Bone Grafting with Preservation of Articular Cartilage to Treat Osteochondral Lesions of the Talus with Large Subchondral Cysts

Category: Ankle Introduction/Purpose: Treatment options for osteochondral lesion of the talus (OLT) have substantially increased over the last decade. There are a wide variety of surgical treatments for OLT, and good clinical results have been reported. However, treatment for OLT with large subchondral bone cysts remains under discussion. The combination of autologous bone grafting for subchondral bone cyst with fixation of articular cartilage would be the desirable procedure for the repair of the large subchondral cyst preserving the original cartilage with native structure and geometry. The purpose of this study is to evaluate the clinical outcome of autologous cancellous bone graft and fixation of cartilage fragment for OLT with large subchondral cysts. Methods: Patients comprised seven men and five women, aged 14–70 (mean 35.9) years. All OLTs included full-thickness articular cartilage, extended through subchondral bone and were associated with subchondral cysts. The mean size of the cysts was 9 ×8.6 ×12.3 mm on preoperative CT. Medial lesions were exposed through an oblique medial malleolar osteotomy; lateral lesions through expansion of an anterolateral arthroscopic portal. After refreshed the subchondral cyst, it was grafted with autologous cancellous bone from the distal tibial metaphysis, then cartilage fragments were fixed with nylon suture to surrounding cartilage. Postoperative MRI and CT scans were acquired for all patients at one year after surgery. Seven patients requested screw removal although none had symptoms. The screws were removed and simultaneous arthroscopic examination was performed at 1.5–2 years after surgery with the patients’ permission. The cartilage repair was assessed according to the criteria of the International Cartilage Repair Society (ICRS). Results: Functional outcome was evaluated at 25.3 (15–50) months after surgery. Mean American Orthopedic Foot and Ankle Society ankle-hindfoot outcome score improved from 65.7 to 92 (90–100) postoperatively, with 100% patient satisfaction. All follow-up CT scans showed that the grafts were well consolidated with the surrounding subchondral bone. On MRI one year after surgery, no scans showed any signs of osteochondral graft instability. The mean ICRS arthroscopic score from follow-up arthroscopy was 11.1 (8–12) points, and represented nearly normal cartilage. Conclusion: Our study demonstrated good results of autologous bone grafting in preserving articular cartilage in cases of symptomatic OLT with subchondral cysts. In seven cases, we performed follow-up arthroscopy at 1.5–2 years after primary operation and the chondral fragment showed a smooth surface and good stability. The technique of autologous bone grafting with chondral fragment fixation could be a promising option for treatment of OLT with subchondral cysts

Relationship between osteophyte and arthroscopic findings in osteoarthritis of ankle

Category: Ankle Introduction/Purpose: Mortise view weight-bearing radiograph is widely used for the diagnosis of osteoarthritis of ankle. Thickness of the articular cartilage cannot be accurately evaluated in the evaluation of joint space from weight-bearing radiograph, because lateral tibiotalar joint space is maintained in valgus type osteoarthritis in some cases. There are few reports on the relation between osteophyte and the articular cartilage injury. We considered that it might be possible to estimate the cartilage injury more accurately by examining osteophytes. The purpose of this study is to analyze the relationship between the location and grade of osteophytes in weight-bearing radiograph and cartilage injury in arthroscopic findings was analyzed. Methods: Twenty-one anklets of 21 patients consisted of 10 males and 10 females, with mean age of 61.4 years (31-79 years), who underwent arthroscopic surgery for osteoarthritis in our department were included. Weight-bearing radiograph were taken before surgery. Location and grade of osteophytes were evaluated using Ankle and Hindfoot Radiographic Osteoarthritis Scoring reported by Kraus et al. Arthroscopic findings were evaluated with International Cartilage Repair Society (ICRS) Grade at a total of 20 sites (9 areas of tibia and talar in tibiotalar joint, medial malleolus and lateral malleolus). The correlation between radiographic findings and arthroscopic findings were analyzed. Results: In Mortise view, strong correlations were found between lateral tibial osteophyte grade and ICRS grade of the center (talus R = 0.69, tibia R = 0.76), the central lateral (tibia R = 0.79), the posterior center (talus R = 0.72, tibia R = 0.74) and the posterior lateral of the tibiotalar joint (talus R = 0.63, tibia R = 0.76). There are moderate correlations between distal fibular osteophyte grade and ICRS grade of the medial inner (tibia R = 0.74) and the posterior medial of the tibiotalar joint (talus R = 0.61, tibia = 0.63). In lateral view, there are moderate correlations between posterior talar osteophyte grade and ICRS grade at the center of the tibiotalar joint (talus R = 0.61, tibia R = 0.60). Conclusion: From this study, there was a strong correlation between location and grade osteophyte and the articular cartilage injury. Osteoarthritis progression is caused by degeneration of the cartilage because of the joint instability, and osteophytes were formed by traction force or impaction. This study showed that local cartilage injury is thought to be related to osteophytes. By evaluating the location and size of osteophytes, the articular cartilage injury might be predicted accurately before arthroscopic surgery

Gait analysis using the Oxford Foot Model for ankle arthrodesis compared with normal control

Category: Ankle Arthritis Introduction/Purpose: Ankle arthrodesis is still the primary treatment for end-stage arthritis of the ankle that does not respond to conservative treatment. However, comparative studies demonstrated that the patients’ functional outcomes remain significantly lower than normal, progression of subtalar and midfoot arthritis and there could be measurable abnormalities in their gait parameters. Previous studies demonstrated gait analysis after ankle arthrodesis using 3D motion capture system. These studies used a single segment foot model, which had the limitation of detailed motion analysis. 3D multi-segmental foot model enables to perform detailed analysis segmentally such as fore foot and hind foot. The purpose of this study was to examine foot kinematics during walking after ankle arthrodesis using 3D multi-segment foot model as compared with a healthy control group. Methods: Between 2014 and 2016, nine patients who underwent an isolated ankle arthrodesis were followed for a mean 2 years after surgery, and five control subjects were included for comparison. Physical examination, radiographic examination and gait examination were performed. For gait analysis Vicon Nexus system with 16 MX-Cameras was used to capture foot kinematics during barefoot walking at self-selected speed along a 10 m walkway. Markers were placed according to the Oxford Foot Model (OFM). Patients completed preoperative and annual postoperative functional outcome scores including the Japanese Society for Surgery of the Foot (JSSF) scale. Results: JSSF scale was significantly improved from pre-operation to post-operation (50 points versus 85 points; p<0.05). The range of sagittal motion in hind foot during one gait cycle was significantly smaller in the arthrodesis group than in the healthy group (4.6 degrees versus 20 degrees; p<0.05). The range of coronal motion in hind foot was also significantly smaller in the arthrodesis group than that in the healthy group (3.7 degrees versus 15.1 degrees; p<0.05). There was no significant difference in the range of sagittal motion in forefoot between arthrodesis group and healthy group (20.2 degrees versus 16.6 degrees). However, there were significant differences at heel contact. Forefoot in arthrodesis group was significantly toward plantarflexion (6.1 degrees versus -2.0 degrees; p<0.05). Conclusion: In this study, detailed motion of foot after ankle arthrodesis could be analyzed by using OFM. Range of sagittal motion in hind foot in arthrodesis group during one gait cycle was significantly smaller than that in healthy group. However, no significant difference was observed in the forefoot. The same result was also obtained on the frontal plane. In arthrodesis group, forefoot tended to be more plantarflexion than healthy group in gait, especially there was significant difference at heel contact. These findings suggested to cause lower functional outcomes and the progression of subtalar and midfoot arthritis after ankle arthrodesis