METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147.

FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients.

INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma.

METHODS: From April 2014 to December 2015, a total of 72 knees in 64 patients that underwent OWHTO, second-look arthroscopy, and magnetic resonance imaging (MRI) assessment, were enrolled. Preoperative and postoperative coronal and sagittal translation, joint line orientation angle, the distance between medial femoral notch marginal line and medial tibial spine, and PTS were evaluated. ACL status was arthroscopically graded from grade 1 (best) to 4 (worst). The MRI signal of the graft in three portions (proximal, middle, and distal) was graded from grade 1 (best) to 4 (worst).

RESULTS: High grade (3: partial, and 4: complete rupture) was noted in 28 cases (38.9%) at the second-look arthroscopy compared with 10 cases (13.9%) at index arthroscopy. The MRI signal grade significantly increased at follow up MRI compared with preoperative MRI (P<0.01). An increased signal was commonly noted in the middle and distal portions of the graft.

CONCLUSIONS: Geometric changes after OWHTO were related to ACL deterioration. The ACL was commonly affected at the middle and distal portions and rarely at the proximal portion. There is a possibility of impingement because of the geometric changes.

METHODS: This was a retrospective review of 270 consecutive patients (397 knees) who underwent primary TKA with an AR or PR system. Selection of implant size, mediolateral and anteroposterior alignment of the femoral component, as well as gaps were compared between groups.

RESULTS: In the AR group, more patients had femoral components which were upsized or downsized compared to those in the PR group (29.5% vs 12.0% respectively) and in patients who underwent bilateral TKA, 49.4% of those in the AR group had femur component size asymmetry. The AR group had better medio-lateral (ML) fit over the distal cutting surface area, smaller change in anterior offset but higher incidence of anterior notching when compared to the PR group. Posterior condylar offset (PCO) was restored in both groups and gap differences in flexion-extension and ML were comparable. There was also no difference in clinical scores and ROM between groups at 2-years follow-up.

METHODS: Postoperative CT scans of 200 propensity score-matched patients who underwent TKA with either an anatomic (ATC) or symmetrical tibia component (STC) were analyzed. Rotation was measured using four axes: surgical transepicondylar axis (sTEA), Berger's protocol, medio-lateral (ML) axis and posterior borders of the tibial plateau, while coverage was assessed by measuring fit and surface area. The relationship between coronal deformity, tibial torsion, rotation, and coverage was investigated.

RESULTS: Overall, STCs had more internal rotation when measured using the sTEA (-0.6° ± 3.5 vs 0.5° ± 3.6, p = 0.03), Berger's protocol (-21.6° ± 7.1 vs -17.9° ± 6.2, p = 0.000) and ML axes (2.9° ± 3.9 vs 8.1° ± 5.1, p = 0.000) compared to ATCs. STCs also had more posteromedial underhang (-3.3 mm ± 2.4 mm vs -1.7 mm ± 2.5 mm, p = 0.000) but smaller change in tibial torsion postoperatively (-18.4° ± 9.9° vs -13.1° ± 9.4°, p = 0.000). Tibial torsion was more pronounced in valgus than varus knees both preoperative (-25.4° ± 6.5° vs -20.2° ± 9.3°, p = 0.02) and postoperatively (-19.7° ± 7.2° vs -14.7° ± 10.3°, p = 0.04), but there was no difference in postoperative tibial torsion between ATCs and STCs in this subgroup.

OBJECTIVE: We examined whether adipocytokines might explain the ethnic differences in the relationship between obesity and insulin resistance among the three major ethnic groups in Singapore.

DESIGN AND PARTICIPANTS: This was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men. Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified using magnetic resonance imaging.

MAIN OUTCOME MEASURES: Plasma total and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were measured using enzyme-linked immunoassays.

RESULTS: Principle component (PC) analysis on the adipocytokines identified three PCs, which explained 49.5% of the total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was negatively associated with ISI in all ethnic groups. In the path analysis, SAT and VAT were negatively associated with ISI in Chinese and Malays without significant mediatory role of PC1. In South Asians, the relationship between VAT and ISI was mediated partly through PC1, whereas the relationship between SAT and ISI was mediated mainly through PC1.

METHODS: A total of 137 patients with 212 consecutive knees who underwent TKAs with or without functional stepwise MNP of superficial medial collateral ligament was recruited in this prospective cohort. Eighty-one patients with 129 knees who performed serial stress radiographs were enrolled in the final assessment. Superficial medial collateral ligament was punctured selectively (anteriorly or posteriorly or both) and sequentially depending on the site and degree of tightness. Mediolateral stability was assessed using serial stress radiographs and comparison was performed between the MNP and the non-MNP groups at postoperative 6 months and 1 year. Clinical outcomes were also evaluated between 2 groups.

RESULTS: Fifty-five TKAs required additional stepwise MNP (anterior needling 19, posterior needling 3, both anterior and posterior needling 33). Preoperative hip-knee-ankle angle and the difference in varus-valgus stress angle showed significant difference between the MNP and the non-MNP groups, respectively (P = .009, P = .037). However, there was no significant difference when comparing the varus-valgus stress angle between the MNP and the non-MNP groups during serial assessment. Clinical outcomes including range of motion also showed no significant differences between the 2 groups.

CONCLUSION: Functional medial ligament balancing with stepwise MNP can provide sufficient medial release with safety in TKA with varus aligned knee without clinical deterioration or complication such as instability.

METHODS: This single-blind, prospective, randomized, controlled trial involved intraoperative measurements for 271 femoral component implantations from 3 contemporary TKA systems, with 2 systems offering narrow sizing options. The difference between femoral component dimensions and the resected surface of distal femur was measured in millimeters at 5 distinct zones.

RESULTS: Overhang of standard femoral component was common in the anterior-medial condyle and anterior-lateral condyle ranging from 50.8% to 99.0% and 21.5% to 88.0%, respectively. With narrow femoral components, the rate of overhang reduced to 21.5%-30.2% and 9.2%-32.1%. Conversely, underhang rates were higher over the anterior flange width, middle medial-lateral and posterior medial-lateral zones. Standard components displayed higher underhang rates at these zones compared to narrow components. The good fit rate for femoral component was low among the 3 systems ranging from 1.0% to 56.0%. System with narrow option sizing increases the underhang rates in males, while improving the component fit among females at similar zones with rate ranging from 5.2% to 52.9%.

OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR.

METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia.

RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1).

METHODS: Eighty consecutive muscle biopsies in the Department of Pathology, National University of Singapore, in the period 1978-2000, in which a clinical diagnosis of floppy or hypotonic infant was made, were reviewed.

RESULTS: The commonest cause of severe hypotonia in infancy was spinal muscular atrophy, which accounted for 33% of cases followed by congenital muscular dystrophy (13%). Eight cases (10%) of infantile type II glycogenosis (Pompe's disease) were encountered. There were seven cases of congenital myopathy, of which four were centronuclear myopathy, and one each of central core myopathy, nemaline myopathy and congenital fibre type disproportion. One case of centronuclear myopathy was associated with type I fibre smallness. Type II atrophy, which is generally considered a non-specific change, was encountered in five cases. Of interest is the relatively large number of muscle biopsies (29%) in which no significant pathological features were encountered at the light microscopic, histochemical as well as ultra-structural level.

METHODS: In this non-interventional study involving 49 sites across five countries in Southeast Asia and South Korea, 379 stable NVAF patients who switched from VKA therapy to dabigatran during routine clinical practice were recruited and followed up for 6 months. Treatment convenience and satisfaction were evaluated using Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2). Through post hoc analysis, factors associated with improved treatment convenience scores at visit 2 were described.

RESULTS: Treatment convenience and satisfaction significantly improved after switching from VKAs to dabigatran at visit 2 and visit 3 (convenience: p<0.001 each vs baseline; satisfaction: p=0.0174 (visit 2), p=0.0004 (visit 3) compared with baseline). Factors predictive of higher (>80th percentile) response on treatment convenience were female sex, younger age (<75 years), higher baseline stroke risk, higher creatinine clearance and absence of concomitant hypertension, stroke or gastrointestinal diseases.

PATIENTS AND METHODS: This was a multinational, multicentre, non-interventional study involving 49 sites across 5 countries in South East Asia and South Korea where 934 patients newly diagnosed with NVAF were initiated on either dabigatran (N=591) or VKA (N=343). Data were collected at baseline and over two follow-up visits across 6 months. Treatment satisfaction and patient convenience were evaluated using the Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2).

RESULTS: The mean age of the patients was 65.9±10.4 years, and 64.2% were male. Mean CHA2DS2-VASc score was 2.4±1.5, and mean HAS-BLED score was 1.2±0.9. At baseline, patients initiated on dabigatran had higher stroke risk, bleeding risk, creatinine clearance and proportion of patients with concomitant illnesses compared with patients initiated on VKAs. Treatment convenience was perceived to be significantly better with dabigatran versus VKAs at visits 2 and 3 (p=0.0423 and 0.0287, respectively). Treatment satisfaction was significantly better with dabigatran compared with VKAs at visit 3 (p=0.0300).

CONCLUSION: In this study, dabigatran is associated with better patient perception in terms of treatment convenience and satisfaction compared with VKAs when used for stroke prevention in newly diagnosed NVAF patients from South East Asia and South Korea.

TRIAL REGISTRATION NUMBER: NCT02849509.