Wungrak Choi

Total ankle replacement in moderate to severe varus deformity of the ankle

Our study describes the clinical outcome of total ankle replacement (TAR) performed in patients with moderate to severe varus deformity. Between September 2004 and September 2007, 23 ankles with a varus deformity > or = 10 degrees and 22 with neutral alignment received a TAR. Following specific algorithms according to joint congruency, the varus ankles were managed by various additional procedures simultaneously with TAR. After a mean follow-up of 27 months (12 to 47), the varus ankles improved significantly in all clinical measures (p < 0.0001 for visual analogue scale and American Orthopaedic Foot and Ankle Society score, p = 0.001 for range of movement). No significant differences were found between the varus and neutral groups regarding the clinical (p = 0.766 for visual analogue scale, p = 0.502 for American Orthopaedic Foot and Ankle Society score, p = 0.773 for range of movement) and radiological outcome (p = 0.339 for heterotopic ossification, p = 0.544 for medial cortical reaction, p = 0.128 for posterior focal osteolysis). Failure of the TAR with conversion to an arthrodesis occurred in one case in each group. The clinical outcome of TAR performed in ankles with pre-operative varus alignment > or = 10 degrees is comparable with that of neutrally aligned ankles when appropriate additional procedures to correct the deformity are carried out simultaneously with TAR.

NFAT5 Induction and Its Role in Hyperosmolar Stressed Human Limbal Epithelial Cells

PURPOSE To introduce a tonicity response gene regulator, NFAT (nuclear factor of activated T-cell)-5 and determine its expression mechanism and specific roles in human limbal epithelial cell (HLECs) subjected to hyperosmolar stress. METHODS NFAT5 expression was determined in various hyperosmolar conditions in HLECs by RT-PCR and Western immunoblot analyses. NFAT5 translocation during hyperosmolar stress was observed by immunocytochemistry. NFAT5-related signal transduction activity was measured on the basis of inhibition of NF-kappaB (nuclear factor-kappaB), and MAPK activity. TNF-alpha and IL-1beta, -6, and -8 levels were determined after inhibition of NFAT5 and/or NF-kappaB. Hyperosmotic apoptotic cell death, with or without inhibition of NFAT5, was measured by flow cytometry. RESULTS NFAT5 was induced and translocated to the nucleus under conditions of hyperosmolar stress. It was inhibited by SB239063, a p38 MAPK inhibitor. Among the inflammatory cytokines induced in hyperosmolar stress conditions, IL-1beta and TNF-alpha levels were significantly reduced after inhibition of NFAT5. Of interest, even after 48 hours of hyperosmolar stress, 45% of HLECs survived. HLEC apoptosis increased markedly as a result of NFAT5 suppression. Moreover, most of the HLECs underwent cell death on dual inhibition of NF-kappaB and NFAT5. CONCLUSIONS NFAT5 is induced and translocates to the nucleus in HLECs undergoing hyperosmolar stress through activation of p38. IL-1 beta and TNF-alpha are induced via NFAT5 activation. Our data collectively indicate that NFAT5 may be an important gene regulator and survival factor in hyperosmolar stressed HLECs.

Heterotopic ossification after total ankle arthroplasty

We evaluated the incidence of heterotopic ossification following total ankle replacement to determine whether the degree of ossification was associated with the clinical outcome. We evaluated 90 ankles in 81 consecutive patients who underwent total ankle replacement, and heterotopic ossification was assessed according to proportional involvement of the ankle joint. Correlation analysis was used to investigate the association between heterotopic ossification and outcome. No significant association was found between the formation of heterotopic ossification and the clinical outcome. The degree of heterotopic ossification in the posterior ankle joint was not significantly correlated with posterior ankle pain (p = 0.929), the American Orthopaedic Foot and Ankle Society score (p = 0.454) or range of movement (p = 0.283). This study indicates that caution should be observed in attributing symptoms and functional limitation to the presence of heterotopic ossification in the posterior ankle joint when considering excision of heterotopic bone after total ankle replacement.

Residual pain due to soft-tissue impingement after uncomplicated total ankle replacement

We report the incidence and intensity of persistent pain in patients with an otherwise uncomplicated total ankle replacement (TAR). Arthroscopic debridement was performed in selected cases and the clinical outcome was analysed. Among 120 uncomplicated TARs, there was persistent pain with a mean visual analogue scale (VAS) of 2.7 (0 to 8). The intensity of pain decreased in 115 ankles (95.8%). Exercise or walking for more than 30 minutes was the most common aggravating factor (62 ankles, 68.1%). The character of the pain was most commonly described as dull (50 ankles, 54.9%) and located on the medial aspect of the joint (43 ankles, 47.3%). A total of seven ankles (5.8%) underwent subsequent arthroscopy. These patients had local symptoms and a VAS for pain ≥ 7 on exertion. Impingement with fibrosis and synovitis was confirmed. After debridement, the median VAS decreased from 7 to 3 and six patients were satisfied. The median VAS for pain and the American Orthopaedic Foot and Ankle Society score of the ankles after debridement was similar to that of the uncomplicated TARs (p = 0.496 and p = 0.066, respectively). Although TAR reduces the intensity of pain, residual pain is not infrequent even in otherwise uncomplicated TARs and soft-tissue impingement is the possible cause.

Neutralization of Ocular Surface TNF-α Reduces Ocular Surface and Lacrimal Gland Inflammation Induced by In Vivo Dry Eye

PURPOSE The purpose of this study was to investigate the effectiveness of tumor necrosis factor (TNF)-α blocker for treatment of dry eye (DE)-induced inflammation and determine a more effective method to suppress lacrimal gland inflammation. Efficacy of topical versus systemic administration of TNF-α blockers was determined using a murine dry eye (DE) model. METHODS The TNF-α blocker HL036 was developed by modification of the TNF receptor I. Protein purity, binding affinity, and clearance of TNF-α was compared with etanercept. Using DE-induced C57BL/6 mice, corneal erosion and goblet cell counts were measured after subcutaneous or topical treatment with etanercept or HL036. Inflammatory cytokines in cornea and lacrimal glands were determined by quantitative RT-PCR and ELISA. RESULTS HL036 showed TNF-α binding affinity comparable to etanercept, as measured by surface plasmon resonance. HL036 concentration was significantly higher in cornea and anterior segment than etanercept and effectively eliminated TNF-α on ocular surfaces. Etanercept was preferentially concentrated in the posterior segment. Corneal erosion and goblet cell counts were improved only with topically applied etanercept and HL036. Ocular surface IFN-γ, IL-6, and IL-21 were significantly decreased by topical HL036. DE-induced lacrimal gland IFN-γ and IL-6 expression was effectively suppressed by topical etanercept and HL036. CONCLUSIONS Topical TNF-α blockers effectively suppressed lacrimal gland and corneal inflammation by suppressing IFN-γ, IL-21, and IL-6. Differences in TNF-α affinity, clearance, and local concentration of blockers may account for the anti-inflammatory effects in different ocular regions.

Ossicles associated with chronic pain around the malleoli of the ankle

We undertook a retrospective review of 24 arthroscopic procedures in patients with symptomatic ossicles around the malleoli of the ankle. Most of the patients had a history of injury and localised tenderness in the area coinciding with the radiological findings. Contrast-enhanced three-dimensional fast-spoiled gradient-echo MRI was performed and the results compared with the arthroscopic findings. An enhanced signal surrounding soft tissue corresponding to synovial inflammation and impingement was found in 20 patients (83%). The arthroscopic findings correlated well with those of our MRI technique and the sensitivity was estimated to be 91%. At a mean follow-up of 30.5 months (20 to 86) the mean American Orthopaedic Foot and Ankle Society score improved from 74.5 to 93 points (p < 0.001). Overall, the rate of patient satisfaction was 88%. Our results indicate that symptomatic ossicles of the malleoli respond well to arthroscopic treatment.

Association between skeletal muscle mass and radial augmentation index in an elderly Korean population

Increasing evidence supports the importance of maintaining skeletal muscle mass for cardiovascular health. However, there is limited data on the relationship between skeletal muscle mass and arterial stiffness targeting an elderly population. Thus, we investigated the association between skeletal muscle mass and arterial stiffness in an elderly Korean population. This study used data from the Korean Social Life, Health and Aging Project which started in 2011. In this cross-sectional study, 180 men (mean age 71.7) and 247 women (mean age 70.9) were included. Arm and leg muscle masses were measured by bioelectrical impedance analysis. Radial augmentation index, a noninvasive measure of arterial stiffness, was assessed by radial pulse wave analysis. The relationship between skeletal muscle mass and augmentation index was investigated by multiple linear regression analysis. In men, limb muscle mass was significantly and inversely associated with augmentation index (β=-1.07% per 1 kg muscle mass, p<0.001) when adjusted for age. This inverse association remained after additional adjustment for body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein-cholesterol, fasting glucose, insulin, smoking and alcohol intake (β=-0.69%, p=0.019). In women, the inverse association between limb muscle mass and augmentation index was less prominent (β=-0.59%, p=0.030), and the association disappeared when fully adjusted (β=-0.32%, p=0.304). However, limb muscle mass was not associated with resting blood pressure either in men or women. Our results suggest that decreased skeletal muscle mass may affect arterial wall elasticity.

Association between C reactive protein level and depressive symptoms in an elderly Korean population: Korean Social Life, Health and Aging Project

Objective The relationship between inflammatory markers and depressive symptoms has been reported inconsistently. Moreover, there were only a few studies conducted in an Asian population. The purpose of this study was to examine the association between C reactive protein (CRP) and depressive symptoms in an elderly Korean population. Design, setting and participants This study used data from the Korean Social Life, Health and Aging Project Health Examination Cohort, which started in 2011. Among participants aged 60 or over recruited from a rural community, 569 (224 men and 345 women) without a history of stroke, angina pectoris, myocardial infarction or CRP≥20 mg/L were employed for cross-sectional analyses. As a marker of systemic inflammation, CRP was measured. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple linear regression analysis was used to investigate the relationship between CRP and depressive symptoms. Results In men, CRP levels had significant associations with depressive symptoms before (β=0.420, p=0.010) and after (β=0.336, p=0.025) adjusting for age, body mass index, systolic blood pressure, number of comorbidities, smoking status, alcohol intake, marital status, education and sleep duration. However, in women, the association between CRP and depressive symptoms was not significant before (p=0.250) and after (p=0.256) adjustment. Conclusions Our findings suggest that elevated CRP levels are independently associated with the presence of depressive symptoms in elderly Korean men.

Additional surgical factors affecting the recurrence of hallux valgus after Ludloff osteotomy

We reviewed 91 patients (103 feet) who underwent a Ludloff osteotomy combined with additional procedures. According to the combined procedures performed, patients were divided into Group I (31 feet; first web space release), Group II (35 feet; Akin osteotomy and trans-articular release), or Group III (37 feet; Akin osteotomy, supplementary axial Kirschner (K-) wire fixation, and trans-articular release). Each group was then further subdivided into severe and moderate deformities. The mean hallux valgus angle correction of Group II was significantly greater than that of Group I (p = 0.001). The mean intermetatarsal angle correction of Group III was significantly greater than that of Group II (p < 0.001). In severe deformities, post-operative incongruity of the first metatarsophalangeal joint was least common in Group I (p = 0.026). Akin osteotomy significantly increased correction of the hallux valgus angle, while a supplementary K-wire significantly reduced the later loss of intermetatarsal angle correction. First web space release can be recommended for severe deformity. Additionally, K-wire fixation (odds ratio (OR) 5.05 (95% confidence interval (CI) 1.21 to 24.39); p = 0.032) and the pre-operative hallux valgus angle (OR 2.20 (95% CI 1.11 to 4.73); p = 0.001) were shown to be factors affecting recurrence of hallux valgus after Ludloff osteotomy.

Dry Eye-Induced CCR7+CD11b+ Cell Lymph Node Homing Is Induced by COX-2 Activities

PURPOSE We aimed to determine the role of CCR7+CD11b+ cell lymph node (LN) homing and T-cell differentiation in dry eye (DE)-induced immunopathogenesis and investigate the therapeutic effects of cyclooxygenase-2 (COX-2) and prostaglandin E2/eicosanoid-prostanoid (PGE2/EP) inhibitors against DE. METHODS Six-week-old female C57BL/6 mice were housed in a controlled-environment chamber and administered topical selective COX-2 inhibitors or EP2 antagonists. Expression of major histocompatibility complex (MHC)-IIhigh, CD11b+, CCR7+, IFN-γ+, IL-17+, and CD4+ in the corneas and draining LNs was evaluated using flow cytometry. Mixed lymphocyte reactions (MLRs) with carboxyfluorescein diacetate succinimidyl ester labeling and intracellular cytokine staining were used to verify DE-induced corneal dendritic cell function. mRNA expression of COX-2, EPs, and proinflammatory cytokines in ocular surface was evaluated using quantitative RT-PCR and immunohistochemical staining. RESULTS Dry eye significantly increased MHC-IIhighCD11b+ and CCR7+CD11b+ cells in the cornea and LNs, and MLR revealed CCR7+CD11b+ cells from DE corneas stimulated IL-17+CD4+ cell proliferation. mRNA levels of COX-2, EP2, IFN-γ, TNF-α, IL-6, and IL-17 were significantly higher in DE ocular surface but were suppressed by topical COX-2 inhibitors and EP2-specific blockers. Immunohistochemical staining showed COX-2 and matrix metalloproteinase expression in DE corneal epithelia that was diminished by both topical treatments. Furthermore, both topical treatments significantly reduced frequencies of MHC-IIhigh, CD11b+, and CCR7+CD11b+ cells in the corneas and LNs, but also IL-17+CD4+ cells in LNs. CONCLUSIONS Topical COX-2/EP2 treatment reduces CCR7+CD11b+ cells on the ocular surface with inhibition of cellular LN homing and suppresses Th17 immune response, suggesting the COX-2/PGE2/EP axis contributes to immuno-inflammatory pathogenesis on the ocular surface and may be a novel therapeutic target in DE.