A retrospective record review of tuberculous infections in rheumatoid arthritis patients on biologics in Malaysia.

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.

Manipulation under Anaesthesia for Patient Reported Stiffness after Total Knee Arthroplasty in an Asian Population.

INTRODUCTION: Stiffness after Total Knee Arthroplasty (TKA) is a complication that decreases patient satisfaction. Patients in an Asian population have potentially different requirements of knee range of motion. The authors have encountered patients who complain of subjective stiffness post TKA who do not have a severely restricting range of motion (ROM). Some patients have persistent subjective stiffness and undergone Manipulation Under Anaesthesia (MUA). We look at their functional outcomes post MUA. MATERIALS AND METHODS: This is a retrospective study, including 48 patients from a single institution who underwent MUA for stiffness, separated into objective and subjective knee stiffness. Patients with subjective knee stiffness who underwent MUA had failed conservative management. ROM, Oxford Knee Scores (OKS), Knee Society Scores (KSS) and Short Form 36 (SF36) scores were compared at two years post MUA. RESULTS: The demographics of the two patient groups were similar. The time interval between index TKA and MUA was higher in the subjective knee stiffness group. Pre-MUA OKS, KS Function Score, KSS and SF36 scores were similar in both patient subgroups. There was no significant difference in the OKS, KSS or SF36 at two year follow-up. The proportion of patients in each group who achieved the Minimum Clinically Important Difference (MCID) improvement in the scores was also similar. CONCLUSIONS: Patients with subjective knee stiffness can achieve similar functional outcome improvements in Oxford and Knee Society Scores with MUA at two years follow-up.

Laminar flow does not affect risk of prosthetic joint infection after primary total knee replacement in Asian patients.

BACKGROUND: The role of laminar flow (LAF) is contradictory with several studies failing to replicate risk reduction. The 2016 World Health Organization guidelines identified this lack of good comparative studies. AIM: To analyse the use of LAF and the incidence of prosthetic joint infections (PJIs) in Asian patients undergoing total knee replacement (TKR). METHODS: Patients who underwent standard cemented posterior-stabilized TKR from 2004 to 2014 were reviewed from a prospectively collected single-surgeon database. Revision, traumatic and/or inflammatory cases were excluded. The type of airflow used was identified. The technique and surgical protocol for all procedures were similar. Tourniquets and inserted drains were routinely used. Patellar resurfacing was not performed. Patients were followed up at the outpatient clinics at regular intervals up to two years. At each visit, the patient was assessed for the occurrence of PJI. FINDINGS: Of the 1028 procedures, 453 (44.1%) were performed in an LAF operating theatre (OT) whereas 575 (55.9%) were performed in a non-LAF OT. There were no significant differences between the two groups in terms of age, gender, or side of procedure. The overall incidence of PJI was 0.6% (N = 6). Three (50%) occurred in an LAF OT whereas three (50%) occurred in a non-LAF OT. This was not statistically significant. CONCLUSION: Laminar flow systems are costly to procure and maintain. With modern aseptic techniques, patient optimization, and use of prophylactic antibiotics, laminar flow does not appear to further reduce risk of PJI in Asian patients after TKR.

Pre-operative pressure pain thresholds do not meaningfully explain satisfaction or improvement in pain after knee replacement: a cohort study.

OBJECTIVES: Pain sensitization could be a risk factor for poor outcomes after knee replacement surgery (KR) for knee osteoarthritis (KOA). We aimed to evaluate the association between pre-operative central and peripheral pain sensitization measured using a digital pressure algometer and KR outcomes. METHODS: Consecutive patients with severe KOA listed for KR were recruited. Sociodemographic and symptoms data were collected prior to surgery. Pre-operative pressure pain thresholds (PPTs) were measured using a digital pressure algometer at the index knee and forearm. Patient satisfaction at 6 and 12 months after KR was assessed using a 4-point Likert scale, and dichotomized to satisfied and dissatisfied to KR. Western Ontario and McMaster Universities Index (WOMAC) Pain and function was assessed. The associations between pre-operative PPTs with KR outcomes at 6 and 12 months were evaluated. RESULTS: Of the 243 patients recruited, response rate at 6 and 12 months were 95.5% and 96.7%. The dissatisfaction rates were 8.2% and 5.1% at 6 and 12 months. There was no statistically significant association between pre-operative index knee or forearm PPTs and patient satisfaction. PPTs measured at the knee, but not the forearm, were weakly associated with change in the WOMAC pain score at 12 months, after adjustment for confounding factors. CONCLUSION: Pre-operative central sensitization, measured by handheld digital algometry, was not statistically significantly associated with satisfaction or change in pain after KR. Pre-operative peripheral sensitization was associated with change in pain symptoms after KR; however, this association was weak and unlikely to be a meaningful predictor of KR outcome in clinical practice.

Self-reported symptoms of depression, anxiety and stress among patients with Rheumatoid Arthritis in a Malaysian rheumatology centre - prevalence and correlates.

OBJECTIVE: To determine the prevalence, correlates and independent predictors of self-reported depression, anxiety and stress in Rheumatoid arthritis (RA) patients in Hospital Melaka. METHODS: This was a cross-sectional survey using convenient sampling of 192 RA patients who attended the Rheumatology Clinic outpatient appointment, Hospital Melaka from June 2013 to December 2013. Depression, Anxiety and Stress Scale (DASS21) questionnaire was used to evaluate symptoms of depression, anxiety and stress. RA disease activity was assessed using the DAS28-ESR formula. Functional status was assessed via the Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Out of 189 completed questionnaires, 46%(n=86) patients reported psychological distress symptoms, and 25%(n=48) experienced more than one negative emotional states. The prevalence of depression, anxiety and stress among our patients were 23.3%(n=44), 42.3%(n=80) and 20.1%(n=38) respectively. There were significant positive correlations (p<0.05) between these psychological symptoms with disease activity, number of tender joints, general health, pain and HAQ score. Age was inversely correlated with depression, anxiety and stress. Higher number of swollen joints correlated positively with depression but not with anxiety and stress. HAQ was the only independent predictor for depression (Odds Ratio [OR]=2.07; 95%CI: 1.19 to 3.61) and anxiety (OR=1.81; 95%CI: 1.1 to 3.0) whilst pain was found to be independent predictor for stress (OR=1.04; 95%CI: 1.0 to 1.1). CONCLUSION: The incidence of depression and anxiety in our Malaysian sample of RA patient was comparable to that observed in Caucasian populations. Functional status was an independent predictor of depression and anxiety, whereas pain was an independent predictor of stress.

Targeting nuclear receptors in cancer-associated fibroblasts as concurrent therapy to inhibit development of chemoresistant tumors.

Most anticancer therapies to date focus on druggable features of tumor epithelia. Despite the increasing repertoire of treatment options, patient responses remain varied. Moreover, tumor resistance and relapse remain persistent clinical challenges. These observations imply an incomplete understanding of tumor heterogeneity. The tumor microenvironment is a major determinant of disease progression and therapy outcome. Cancer-associated fibroblasts (CAFs) are the dominant cell type within the reactive stroma of tumors. They orchestrate paracrine pro-tumorigenic signaling with adjacent tumor cells, thus exacerbating the hallmarks of cancer and accelerating tumor malignancy. Although CAF-derived soluble factors have been investigated for tumor stroma-directed therapy, the underlying transcriptional programs that enable the oncogenic functions of CAFs remain poorly understood. Nuclear receptors (NRs), a large family of ligand-responsive transcription factors, are pharmacologically viable targets for the suppression of CAF-facilitated oncogenesis. In this study, we defined the expression profiles of NRs in CAFs from clinical cutaneous squamous cell carcinoma (SCC) biopsies. We further identified a cluster of driver NRs in CAFs as important modifiers of CAF function with profound influence on cancer cell invasiveness, proliferation, drug resistance, energy metabolism and oxidative stress status. Importantly, guided by the NR profile of CAFs, retinoic acid receptor ß and androgen receptor antagonists were identified for concurrent therapy with cisplatin, resulting in the inhibition of chemoresistance in recurred SCC:CAF xenografts. Our work demonstrates that treatments targeting both the tumor epithelia and the surrounding CAFs can extend the efficacy of conventional chemotherapy.

Revision total knee arthroplasty for failed high tibial osteotomy and unicompartmental knee arthroplasty have similar patient-reported outcome measures in a two-year follow-up study.

AIMS: Little is known about the relative outcomes of revision of unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) to total knee arthroplasty (TKA). The aim of this study is to compare the outcomes of revision surgery for the two procedures in terms of complications, re-revision and patient-reported outcome measures (PROMs) at a minimum of two years follow-up. PATIENTS AND METHODS: This study was a retrospective review of data from an institutional arthroplasty registry for cases performed between 2001 and 2014. A total of 292 patients were identified, of which 217 had a revision of HTO to TKA, and 75 had revision of UKA to TKA. While mean follow-up was longer for the HTO group compared with the UKA group, patient demographics (age, body mass index and Charlson co-morbidity index) and PROMs (Short Form-36, Oxford Knee Score, Knee Society Score, both objective and functional) were similar in the two groups prior to revision surgery. Outcomes included the rate of complications and re-operation, PROMS and patient-reported satisfaction at six months and two years post-operatively. We also compared the duration of surgery and the need for revision implants in the two groups. RESULTS: At two-year follow-up, both groups of patients had made significant improvement in terms of PROMs compared with pre-operative scores. PROMs and satisfaction rates were similar in the two groups. Complications requiring re-operation were significantly more frequent in the HTO group whilst more revision implants were used in the UKA group, resulting in a longer operative duration. CONCLUSION: Revision of HTO and UKA achieve similar post-operative PROMs and satisfaction. Revision of UKA more frequently requires revision components with increased operation duration but fewer complications requiring re-operation compared with revision of HTO. Cite this article: Bone Joint J 2017;99-B:1329-34.

Standing balance post total knee arthroplasty: sensitivity to change analysis from four to twelve weeks in 466 patients.

OBJECTIVE: Little is known about how static standing balance changes post total knee arthroplasty (TKA). The primary aim of this study was to examine the sensitivity to change and redundancy of center of pressure (COP) variables post-TKA. The secondary aim was to compare the sensitivity of these measures to standard clinical assessments of one repetition maximum knee extension strength and fast pace gait speed. DESIGN: 466 participants performed instrumented double-limb standing balance tests with eyes open at 4 and 12 weeks post-TKA. Measures of COP standard deviation, amplitude, root mean square (RMS), path length, detrended fluctuation analysis (DFA) and signal frequency content for the medial-lateral (ML) and anterior-posterior (AP) axes were examined. RESULTS: Significant decreases in total path length, ML variables related to sway velocity and AP signal complexity and frequency were observed. Inter-session Cohen's d effect size (ES) revealed the strongest effect was for high velocity ML path length, with a 12% decrease in this rapid sway. This variable, along with AP mean instantaneous frequency and AP DFA, were the only ones significantly different with effect sizes >0.20 and non-redundant (Spearman's rho <0.75). The ES of COP-derived variables (maximum = 0.45) were lower than gait speed (1.40) and knee extensor strength (1.54). CONCLUSION: Increased high velocity ML sway is present at four compared to 12 weeks post-TKA. This augmented rapid sway may provide increased challenges to the postural control system at a time coinciding with reduced strength levels, which could have implications for physical function during activities of daily living.

Outcomes and survivorship of unicondylar knee arthroplasty in patients with severe deformity.

Purpose Patients with severe deformity beyond the standard indications for unicompartmental knee arthroplasty (UKA) may be suitable and benefit from UKA. This study investigated their outcomes to determine whether good function and quality of life (QOL) can be achieved. MATERIALS AND METHODS: Fifty-three patients with severe deformity (40 patients with FFD ≥15° and 13 patients with varus deformity ≥15°, Group A) were matched with 53 patients with less severe deformities who underwent UKA (Group B/controls) in terms of age, sex, BMI and duration of follow-up. Their flexion range, Knee Society scores (KSS), Oxford knee scores (OKS) and SF-36 QOL scores were analysed pre-operatively and at 2 years. RESULTS: Group A patients were largely similar to Group B patients pre-operatively in terms of maximum flexion angle, OKS and SF-36 scores except for knee score and mental health component of SF-36. At 2 years, Group A reported largely similar results compared with Group B in all outcome scores (OKS, KSS, SF-36) and flexion angle. Post-operative mechanical alignment was better for the control group though it is not statistically significant. There were no revisions in the patients with severe pre-operative deformity at 5 years post-operatively. (Survivorship 100 % at 5 years). CONCLUSION: Selected patients with severe deformity can achieve good function and QOL with UKA if satisfactory mechanical alignment is restored. This study supports a broadening of the indications of UKA; however, further follow-up is needed to assess the longer-term durability of the operation. LEVEL OF EVIDENCE: IV.

Association between rehabilitation attendance and physical function following discharge after total knee arthroplasty: prospective cohort study.

BACKGROUND: Rehabilitation is widely advocated and provided as a standard of care for patients with total knee arthroplasty (TKA) but its effects on intermediate- to longer-term physical function is unclear. Also unknown is the relationship between the number of rehabilitation sessions attended and functional outcomes. METHODS: We conducted a prospective cohort study of 1540 patients who had undergone TKA and were referred for rehabilitation. Physical function was indexed by the Short-Form 36 (SF-36) physical function score at 6 months post-TKA. We used multivariable linear regression to assess the association between rehabilitation attendance and Month-6 physical function. Among patients who attended rehabilitation, multivariable linear regression was used to examine the dose-response association between the number of sessions attended and Month-6 physical function. RESULTS: Of the 1540 patients, 68 patients did not attend rehabilitation, 86 patients attended one session, and 1386 patients attended two or more sessions. Adjusted for the propensity to attend rehabilitation, rehabilitation attendance was independently associated with better Month-6 SF-36 physical function (point estimate, 5.0 points; 95% CI, 0.5-9.5; P = 0.028 compared with patients with no rehabilitation). Among patients who attended rehabilitation, attending five sessions was associated with a 3.6-point increase in SF-36 scores (95% CI, 0.8-6.5; P = 0.01) relative to patients who attended one session. CONCLUSIONS: Rehabilitation attendance post-TKA is associated with an increase in self-report physical function. Among patients who attended rehabilitation, a modest dose-response relationship was observed between the number of sessions and functional outcomes.

Predictors for rehabilitation outcome in Asian geriatric hip fracture patients.

PURPOSE: To identify predictors for rehabilitation outcome in Asian geriatric hip fracture patients. METHODS: Records of 153 consecutive Asian patients aged 61 to 99 years who underwent surgery for hip fracture and were followed up for at least one year were reviewed. They were stratified into 4 agegroups: 60-69 years (n=27), 70-79 years (n=70), 80-89 years (n=50), and ≥90 years (n=6). Any comorbidity, regardless of severity, was recorded. Pre-injury and postoperative functional status was evaluated using the 36-item Short Form Health Survey. Relative functional gain (RFG) is equal to absolute functional gain (physical component summary [PCS] score at one year minus PCS score at 6 weeks) divided by the maximum potential gain (maximum PCS score minus PCS score at 6 weeks). RFG of <0.5 and ≥0.5 is defined as poor and good rehabilitation outcome, respectively. RESULTS: In univariate analysis, age 80-89 years (p=0.026), arthritis (p=0.082), and hypercholesterolaemia (p=0.014) were predictors for RFG. In multivariate analysis, age 80-89 years (p=0.016) remained a predictor for poor RFG, and hypercholesterolaemia remained a predictor for good RFG. CONCLUSION: Poor rehabilitation outcome was associated with patient age of 80-89 years; an orthogeriatric approach may be beneficial in optimising rehabilitation outcome in elderly hip fracture patients.

The influence of body mass index on functional outcome and quality of life after total knee arthroplasty.

AIMS: This study investigated the influence of body mass index (BMI) on the post-operative fall in the level of haemoglobin (Hb), length of hospital stay (LOS), 30-day re-admission rate, functional outcome and quality of life, two years after total knee arthroplasty (TKA). PATIENTS AND METHODS: A total of 7733 patients who underwent unilateral primary TKA between 2001 and 2010 were included. The mean age was 67 years (30 to 90). There were 1421 males and 6312 females. The patients were categorised into three groups: BMI < 25.0 kg/m(2) (normal); BMI between 25.0 and 39.9 kg/m(2) (obese); and BMI ≥ 40.0 kg/m(2) (morbidly obese). RESULTS: Compared with the normal and obese groups, the mean LOS was longer by one day (95% confidence interval (CI) 0 to 2) in the morbidly obese group (p = 0.003 and p = 0.001 respectively). The 30-day re-admisison rate was also higher in the morbidly obese group compared to the obese group (OR 2.323, 95% CI 1.101 to 4.900, p = 0.024); and showed a higher trend compared to the normal group (OR 1.850, 95% CI 0.893 to 3.831, p = 0.100). However, the morbidly obese group had a smaller drop in post-operative Hb level by a mean of 0.5 g/dl (0.3 to 0.6) and 0.3 g/dl (0.1 to 0.5), when compared with the normal and obese groups respectively (both p < 0.001). Furthermore, the mean improvement in Oxford Knee Score (OKS) and Knee Society Knee Score (KSKS) at two years follow-up was three points (two to four) and five points (two to seven) more in the morbidly obese group than in the normal group (both p < 0.001). The mean improvement in Knee Society Function Score, and Physical and Mental Component Scores of Short Form-36 were comparable between the three BMI groups (p = 0.736, p = 0.739 and p = 0.731 respectively). The ten-year rate of survival was 98.8% (98.0 to 99.3), 98.9% (98.5 to 99.2) and 98.0% (95.8 to 100), for the normal, obese and morbidly obese groups, respectively (p = 0.703). CONCLUSION: Although morbidly obese patients have a longer LOS and higher 30-day re-admission rate after TKA, they have a smaller drop in post-operative Hb level and larger improvement in OKS and KSKS at two years follow-up. The ten-year rate of survival of TKA was also comparable with those with a normal BMI. TAKE HOME MESSAGE: Morbidly obese patients should not be excluded from the benefits of TKA. Cite this article: Bone Joint J 2016;98-B:780-5.

Predicting discharge outcomes after total knee replacement using the Risk Assessment and Predictor Tool.

OBJECTIVE: To explore the use of the Risk Assessment and Predictor Tool (RAPT) as a pre-operative tool to predict postoperative discharge destination and length of stay for patients undergoing total knee replacement (TKR) in Singapore. PARTICIPANTS AND SETTING: A cohort of 569 patients undergoing primary TKR at the Singapore General Hospital were recruited prospectively from November 2009 to June 2010. INTERVENTION: All patients completed a modified RAPT questionnaire pre-operatively, and underwent standard clinical pathway guidelines for TKR throughout the study. MAIN OUTCOME MEASURES: Actual discharge destination (ADDest) and length of stay (LOS). DESIGN: Total RAPT score and preferred discharge destination (PDD) were recorded pre-operatively, while ADDest and LOS were obtained immediately after discharge. Multivariable logistic regression and multivariable regression analysis were used to determine whether the RAPT items and score could predict the discharge outcomes. RESULTS: Total RAPT score was a significant predictor of LOS for patients following TKR (R=0.24, P<0.001); the higher the RAPT score, the longer the LOS. Total RAPT score was also a significant predictor of actual discharge to home [odds ratio (OR) 2.32, 95% confidence interval (CI) 1.11 to 4.85]. PDD was a significant predictor for LOS (R=0.22, P<0.001) and ADDest (R=0.33, P<0.001). Patients who chose to be discharged home were more likely to be directly discharged home (OR 9.79, 95% CI 5.07 to 18.89, P<0.001). CONCLUSION: Total RAPT score and PDD were significant predictors of ADDest and LOS for patients following TKR in Singapore. The ability to predict discharge outcomes following TKR could assist caregivers, healthcare professionals and administrators in optimising care and resource allocations for patients.

Simultaneous versus staged bilateral unicompartmental knee replacement.

We prospectively followed 171 patients who underwent bilateral unicompartmental knee replacement (UKR) over a period of two years. Of these, 124 (72.5%) underwent a simultaneous bilateral procedure and 47 (27.5%) underwent a staged procedure. The mean cumulative operating time and length of hospital stay were both shorter in the simultaneous group, by 22.5 minutes (p < 0.001) and three days (p < 0.001), respectively. The mean reduction in haemoglobin level post-operatively was greater by 0.15 g/dl in the simultaneous group (p = 0.023), but this did not translate into a significant increase in the number of patients requiring blood transfusion (p = 1.000). The mean hospital cost was lower by $8892 in the simultaneous group (p < 0.001). There was no significant difference in the rate of complications between the groups, and at two-year follow-up there was no difference in the outcomes between the two groups. We conclude that simultaneous bilateral UKR can be recommended as an appropriate treatment for patients with bilateral medial compartment osteoarthritis of the knee.

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin.

The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as ß-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.

Nox4-dependent ROS modulation by amino endoperoxides to induce apoptosis in cancer cells.

Tumor metastasis is the main cause of death in cancer patients. Anoikis resistance is one critical malefactor of metastatic cancer cells to resist current clinical chemotherapeutic treatments. Although endoperoxide-containing compounds have long been suggested as anticancer drugs, few have been clinically employed due to their instability, complex synthesis procedure or low tumor cell selectivity. Herein, we describe a one-pot strategy to synthesize novel amino endoperoxides and their derivatives with good yields and stabilities. In vitro cell-based assays revealed that 4 out of the 14 amino endoperoxides selectively induce metastatic breast carcinoma cells but not normal breast cells to undergo apoptosis, in a dose-dependent manner. Mechanistic studies showed that the most potent amino endoperoxide, 4-Me, is selective for cancer cells expressing a high level of Nox4. The anticancer effects are further shown to be associated with reduced O2(-):H2O2 ratio and increased ·OH level in the cancerous cells. Animal study showed that 4-Me impairs orthotopic breast tumor growth as well as tumor cell metastasis to lymph nodes. Altogether, our study suggests that anticancer strategies that focus on redox-based apoptosis induction in tumors are clinically viable.

Evaluation of the relationship between anteroposterior translation of a posterior cruciate ligament-retaining total knee replacement and functional outcome.

The success of total knee replacement (TKR) depends on optimal soft-tissue balancing, among many other factors. The objective of this study is to correlate post-operative anteroposterior (AP) translation of a posterior cruciate ligament-retaining TKR with clinical outcome at two years. In total 100 patients were divided into three groups based on their AP translation as measured by the KT-1000 arthrometer. Group 1 patients had AP translation < 5 mm, Group 2 had AP translation from 5 mm to 10 mm, and Group 3 had AP translation > 10 mm. Outcome assessment included range of movement of the knee, the presence of flexion contractures, hyperextension, knee mechanical axes and functional outcome using the Knee Society score, Oxford knee score and the Short-Form 36 questionnaire. At two years, patients in Group 2 reported significantly better Oxford knee scores than the other groups (p = 0.045). A positive correlation between range of movement and AP translation was noted, with patients in group 3 having the greatest range of movement (mean flexion: 117.9° (106° to 130°)) (p < 0.001). However, significantly more patients in Group 3 developed hyperextension > 10° (p = 0.01). In this study, the best outcome for cruciate-ligament retaining TKR was achieved in patients with an AP translation of 5 mm to 10 mm.

Getting 'Smad' about obesity and diabetes.

Recent findings on the role of transforming growth factor (TGF)-ß/Smad3 signaling in the pathogenesis of obesity and type 2 diabetes have underscored its importance in metabolism and adiposity. Indeed, elevated TGF-ß has been previously reported in human adipose tissue during morbid obesity and diabetic neuropathy. In this review, we discuss the pleiotropic effects of TGF-ß/Smad3 signaling on metabolism and energy homeostasis, all of which has an important part in the etiology and progression of obesity-linked diabetes; these include adipocyte differentiation, white to brown fat phenotypic transition, glucose and lipid metabolism, pancreatic function, insulin signaling, adipocytokine secretion, inflammation and reactive oxygen species production. We summarize the recent in vivo findings on the role of TGF-ß/Smad3 signaling in metabolism based on the studies using Smad3(-/-) mice. Based on the presence of a dual regulatory effect of Smad3 on peroxisome proliferator-activated receptor (PPAR)ß/δ and PPARγ2 promoters, we propose a unifying mechanism by which this signaling pathway contributes to obesity and its associated diabetes. We also discuss how the inhibition of this signaling pathway has been implicated in the amelioration of many facets of metabolic syndromes, thereby offering novel therapeutic avenues for these metabolic conditions.