Left main stem stenosis angioplasty with intravascular ultrasound optimisation criteria guidance using a new generation everolimus drug-eluting stent.

INTRODUCTION: Intravascular ultrasound (IVUS) is recommended in the use of left main stem (LMS) percutaneous coronary intervention (PCI). Since the LMS diameter is usually larger than other coronary arteries, a new generation everolimus drug-eluting stent (DES), Synergy Megatron DES (Boston Scientific) has better axial and radial strength allowing more post implant overexpansion and consequently better suited for LMS lesions. We performed a study to evaluate the clinical outcomes of PCI using 1) an improved IVUS protocol with optimisation targets and 2) the use of Megatron stents. MATERIALS AND METHODS: This was a study involving LMS PCI coronary lesions using the Synergy Megatron DES. An IVUS protocol using predefined optimisation targets to evaluate for stent malapposition, longitudinal stent deformation, optimal stent expansion >90% of reference lumen and appropriate distal landing zone was used in all cases. The primary end-point was procedural success, defined by successful stent implantation with <30% residual stenosis. The secondary end-point was in-hospital and 30-day major adverse cardiovascular event (MACE). RESULTS: Eight patients with significant LMS stenosis were successfully treated with the Megatron stent. The primary end-point was achieved in all patients. There were no cases of stent malapposition or longitudinal stent deformation, one case did not have optimal LMS stent expansion and one case did not have an appropriate distal landing zone. IVUS optimisation criteria were met in 6 (75%) cases. There were no complications of coronary dissection, slow or no reflow, stent thrombosis or vessel perforation. None of the patients suffered in-hospital or 30-day MACE. The average LMS MLD at baseline was 2.1 ± 0.1mm and the post-PCI LMS MLD was 4.0 ± 0.5mm, with a significant acute luminal gain of 1.9 ± 0.7mm (p<0.01). A post-PCI MSA of 17 ± 3.9 mm2 was numerically superior compared to those documented in other LMS PCI trials. CONCLUSION: This study demonstrates low rates of shortterm major adverse cardiovascular events among patients with LMS PCI using the Megatron stents. It highlights the usefulness of IVUS-guided optimisation in LMS PCI. With the use of intravascular imaging, the new generation stent technology can improve the treatment of large proximal vessels and PCI of LMS lesions.

Intravascular imaging-guided treatment of severe coronary artery calcification with orbital atherectomy: A prospective single-centre registry.

INTRODUCTION: Coronary artery calcification can lead to suboptimal results when performing coronary angioplasty with conventional techniques. The presence of severe coronary artery calcium increases the complications of percutaneous coronary intervention as it may impede stent delivery and optimal stent expansion. The purpose of this study was to determine the procedural success and safety of orbital atherectomy (OA) in calcified lesions. MATERIALS AND METHODS: This was a prospective single-centre study regarding the utility of OA in the treatment of calcified coronaries. Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was used in all cases to characterise the severity of calcium pre-procedure, guide vessel sizing and assess procedural success. The primary endpoint was procedural success, defined by successful stent implantation following OA treatment. The secondary endpoint was in-hospital and 30-day major adverse cardiovascular event (MACE). RESULTS: Ten patients with severely calcified lesions were successfully treated with OA. The primary endpoint was achieved in all patients. All of the lesions were severely calcified with concentric calcium. None of the patients suffered in-hospital or 30-day MACE. The average minimal luminal diameter at baseline was 1.7 ± 0.3 mm and the post- PCI luminal diameter was 3.0 ± 0.3 mm, with a significant luminal gain of 1.3 ± 0.3 mm (p < 0.01). Slow flow during procedure occurred in 2 (20%) cases and dissection occurred in 1 (10%) case during procedure. These were successfully treated with stent delivery to achieve TIMI III flow. There were no cases of stent thrombosis or vessel perforation. CONCLUSION: Our experience demonstrates the feasibility and safety of OA in the management of calcified coronary stenosis. Intravascular imaging is an important adjunct to the use of OA to assess the severity of calcified coronary lesions, success of OA treatment and to aid sizing of the vessel for stent implantation. OA is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with good success rate and low rate of complications.

Treatment of severe coronary artery calcification with intravascular lithotripsy: Initial experience of a prospective single centre registry.

INTRODUCTION: Coronary artery calcification can lead to suboptimal results when performing coronary angioplasty with conventional techniques. Shockwave intravascular lithotripsy (IVL) has recently been introduced as a new modality to treat heavily calcified coronary arteries. The purpose of this study was to determine the procedural success and safety of IVL in calcified lesions. MATERIALS AND METHODS: This was a prospective single-centre study regarding the utility of IVL in treatment of calcified coronary arteries. Intravascular ultrasound (IVUS) was used in all cases to characterise the lesions pre procedure and to assess procedural success post procedure. The primary end point was procedural success, defined by IVL treatment and successful stent implantation. The secondary end point was in-hospital and 30-day major adverse cardiovascular event (MACE). RESULTS: Five patients with severely calcified lesions were successfully treated with IVL. The primary end point was achieved in all patients. All of the lesions were severely calcified with concentric calcium. Multiple calcium fractures were identified on IVUS after IVL in all cases. None of the patients suffered in-hospital or 30-day MACE. The average diameter stenosis at baseline was 1.8±0.4mm and the post PCI diameter stenosis was 2.9±0.1mm, with significant acute luminal gain of 1.2±0.3mm (p<0.01). There were no complications of coronary dissection, slow or no reflow, stent thrombosis, or vessel perforation. CONCLUSION: Our initial experience demonstrates the feasibility and safety of IVL in the management of calcified coronary stenosis. The shockwave IVL is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with a good success rate and low rate of complications.

Smartphone electrocardiogram for QT interval monitoring in Coronavirus Disease 2019 (COVID-19) patients treated with Hydroxychloroquine.

INTRODUCTION: The global pandemic of Corona Virus Disease 2019 (COVID-19) has led to the re-purposing of medications, such as hydroxychloroquine and lopinavir-ritonavir in the treatment of the earlier phase of COVID-19 before the recognized benefit of steroids and antiviral. We aim to explore the corrected QT (QTc) interval and 'torsadogenic' potential of hydroxychloroquine and lopinavir-ritonavir utilising a combination of smartphone electrocardiogram and 12-lead electrocardiogram monitoring. MATERIALS AND METHODS: Between 16-April-2020 to 30-April- 2020, patients with suspected or confirmed for COVID-19 indicated for in-patient treatment with hydroxychloroquine with or without lopinavir-ritonavir to the Sarawak General Hospital were monitored with KardiaMobile smartphone electrocardiogram (AliveCor®, Mountain View, CA) or standard 12-lead electrocardiogram. The baseline and serial QTc intervals were monitored till the last dose of medications or until the normalization of the QTc interval. RESULTS: Thirty patients were treated with hydroxychloroquine, and 20 (66.7%) patients received a combination of hydroxychloroquine and lopinavir-ritonavir therapy. The maximum QTc interval was significantly prolonged compared to baseline (434.6±28.2msec vs. 458.6±47.1msec, p=0.001). The maximum QTc interval (456.1±45.7msec vs. 464.6±45.2msec, p=0.635) and the delta QTc (32.6±38.5msec vs. 26.3±35.8msec, p=0.658) were not significantly different between patients on hydroxychloroquine or a combination of hydroxychloroquine and lopinavir-ritonavir. Five (16.7%) patients had QTc of 500msec or more. Four (13.3%) patients required discontinuation of hydroxychloroquine and 3 (10.0%) patients required discontinuation of lopinavirritonavir due to QTc prolongation. However, no torsade de pointes was observed. CONCLUSIONS: QTc monitoring using smartphone electrocardiogram was feasible in COVID-19 patients treated with hydroxychloroquine with or without lopinavir-ritonavir. The usage of hydroxychloroquine and lopinavir-ritonavir resulted in QTc prolongation, but no torsade de pointes or arrhythmogenic death was observed.

Paradoxical worsening of chest radiographs secondary to immune reconstitution syndrome (IRIS) in a patient with advanced HIV infection and Rhodococcus pneumonia.

We present a rare case of post-antiretroviral therapy (ART) paradoxically worsening of radiological findings in a patient with advanced HIV-infection on treatment for Rhodococcus pneumonia who was misdiagnosed with pulmonary tuberculosis. Despite clinical improvement, serial chest radiographs showed deteriorations a month after starting ART. This was attributed to Immune Reconstitution Inflammatory Syndrome (IRIS) which spontaneously resolved without any treatment.

Intraobserver and interobserver reliability of the computed tomography-based radiographic classification of primary elbow osteoarthritis: comparison with plain radiograph-based classification and clinical assessment.

OBJECTIVES: To develop a staging system that could better reflect symptoms by the spurs quantification in the fossa and joint space narrowing using computed tomography (CT) for elbow arthritis and to evaluate its reproducibility with multiple readers. METHODS: This retrospective study evaluated 81 cases of primary elbow osteoarthritis using both plain radiography and CT. Qualitative and quantitative analyses were independently performed by four orthopedic surgeons using previous and newly proposed staging systems. The reproducibility of the new system was analyzed with intraclass correlation coefficients (ICC). Correlations between symptoms and radiologic classification were assessed using Pearson's correlation coefficient (PCC). RESULTS: The interobserver agreement (1) and intraobserver agreement (2) among the four evaluators was present by ICC. (1) The system of Hastings and Rettig [first observation, 0.544 (95% confidence interval (CI), 0.436-0.649); second observation, 0.582 (95% CI, 0.478-0.682)] and Broberg and Morrey's staging system [first observation, 0.620 (95% CI, 0.521-0.714); second observation, 0.656 (95% CI, 0.562-0.743)] showed substantial and moderate retrospective agreement, whereas the CT-based staging system showed almost perfect agreement [first observation, 0.867 (95% CI, 0.820-0.906); second observation, 0.909 (95% CI, 0.875-0.936)]. (2) The intraobserver agreement was almost perfect in the Brogerg and Morrey's and CT-based staging systems. CT-based staging showed high correlation with visual analogue scale (PCC 0.754, P < 0.001) and Mayo elbow performance score (PCC -0.614, P < 0.001) and moderate correlation with range of motion (PCC -0.458, P < 0.001). CONCLUSIONS: CT-based staging system was highly reproducible and clinically feasible than previous plain radiograph-based staging systems.

Structural optimization of cyclic peptides that efficiently detect denatured collagen.

To develop a facile method for detecting denatured collagen, we investigated the structure-activity relationship of cyclic collagen-mimetic peptides (cCMPs). Reported cCMP prototypes tend to self-assemble and they must be disassembled just before use. Introducing charge repulsion and a deformation in the peptide backbone structure enabled cCMPs to detect denatured collagen without a pre-treatment for disassembly. Using the optimized cCMP, types I-V collagen were detected by western blotting and denatured collagen fibrils were visualized in a cell culture system.

Demographic characteristics and outcomes of continuous ambulatory peritoneal dialysis related peritonitis in Miri General Hospital, Malaysia.

INTRODUCTION: Sarawak has a population that is geographically and characteristically widely varied. In this study we aimed to determine the demographic characteristics of our patient population who undergo continuous ambulatory peritoneal dialysis (CAPD) and to study the incidence, the microbiology and the outcome of CAPD peritonitis. METHODS: A retrospective record review of all CAPD patients on follow-up at the Miri Hospital, Sarawak, Malaysia from 2014 until 2017 was done. RESULTS AND DISCUSSION: During the 4-year period, the overall peritonitis rate was 0.184 episodes per patient-year. Gram-positive and gram-negative bacteria each constituted one-third of the peritonitis; fungi (2.6%), Mycobacterium tuberculosis (MTB) (5.3%), polymicrobial (2.6%) and sterile culture (26.3%). The most commonly isolated gram-positive bacteria were coagulase-negative Staphylococcus. Our peritonitis rate is comparable to that of other centres i.e., Japan 0.195 and Indonesia 0.25. In comparison, countries like India (0.41), Korea (0.40) and Singapore (0.59) had relatively higher rate of PD-associated peritonitis. Two tuberculosis peritonitis patients died. The rate of catheter removal was approximately 20%. Gram-negative bacteria and MTB have a higher risk of catheter loss. About one-fifth used rainwater to clean their CAPD exit site. Out of this group, 33% did not boil the rainwater prior to usage. CONCLUSION: Patient's characteristics and microbial susceptibility vary in different places of practice. The high rates of culture-negative peritonitis and high mortality risks associated with TB peritonitis warrant special attention. In patients with refractory peritonitis, early catheter removal is warranted in order to reduce mortality and minimize damage to peritoneal membrane.

Phenotypic variation among siblings with arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in broad disease spectrum. Three patterns of phenotypic expression have been described: (1) "classic" subtype, with predominant right ventricle involvement, (2) "left dominant" subtype, with early and dominant left ventricle involvement, and (3) "biventricular" subtype, with both ventricles equally affected. Genotypephenotype associations have been described, but there are other genetic and non-genetic factors that can affect disease expression. We describe two different phenotypic expressions of ARVC in a family.

Cyclic Peptides for Efficient Detection of Collagen.

We report here a new class of collagen-binding peptides, cyclic collagen-mimetic peptides (cCMPs), that efficiently hybridize with the triple-helix-forming portions of collagen. cCMPs are composed of two parallel collagen-like (Xaa-Yaa-Gly)n strands with both termini tethered by covalent linkages. Enzyme-linked immunosorbent assays and western blotting analysis showed that cCMPs exhibit more potent affinity toward collagen than reported collagen-binding peptides and can specifically detect different collagen polypeptides in a mixture of proteins. Collagen secreted from cultured cells was detected by confocal microscopy with fluorescein-labeled cCMP. The cCMP is also shown to detect sensitively folding intermediates in the endoplasmic reticulum, something that was difficult to visualize with conventional collagen detectors. Molecular-dynamics simulations suggested that a cCMP forms a more stably hybridized product than its single-chain counterpart; this could explain why cCMP has higher affinity toward denatured collagen. These results indicate the usefulness of cCMPs as tools for detecting denatured collagen.

Interaction between NUDT15 and ABCC4 variants enhances intolerability of 6-mercaptopurine in Japanese patients with childhood acute lymphoblastic leukemia.

6-Mercaptopurine (6-MP) is a main component of childhood acute lymphoblastic leukemia (ALL) treatment. Some candidate gene variants are associated with its toxicities, but the major variants and effects of combined variants remain unclear. We used Cox regression analysis to evaluate the time-dependent association between candidate variants and the cumulative incidence of 6-MP intolerability in 95 Japanese patients. The major risk factors for severe leukopenia were ABCC4 rs3765534, NUDT15 rs116855232 and rs186364861 in multi-covariate analysis (P<0.05). NUDT15 intermediate activity variant, that is, heterozygous rs116855232 or rs186364861 variant, and the ABCC4 rs3765534 variant showed leukopenia more frequently than either variant alone. All patients with both the intermediate activity NUDT15 variant and the ABCC4 rs3765534 variant suffered from leukopenia, and 57.1% patients required 50% protocol dose by day 168. These data indicate that NUDT15 and ABCC4 are major factors for 6-MP intolerability and that the interaction between these variants enhances intolerability to 6-MP.

Study of low salt diet in hypertensive patients with chronic kidney disease.

INTRODUCTION: The efficacy of blood pressure (BP) reduction with salt restriction in CKD subjects and its sustainability is not well established. METHODS: We enrolled 75 hypertensive patients with CKD into one-month salt restricting diet. 24-hour urinary sodium and potassium was measured to verify their salt intake followed by 1½ year follow-up. RESULTS: Their creatinine clearance was 43 ± standard deviation 33ml/min/1.73m2. Urinary Na excretion (24HUNa) was 173±129mmol/day, reducing to 148±81 by 31±6 day. Mean, systolic and diastolic BP (MBP, SBP, DBP) were reduced from 102±9 to 97±11 (p<0.001), 148±10 to 139±16 (p<0.001), 78±12 to 75±12 mmHg (p=0.012) respectively. Moderate correlations were shown between reductions in 24-hour urinary Na and MBP, SBP, DBP: r=0.366, 0.260, 0.365; p=0.001, 0.025, 0.001; whereas 24-hour urinary Na-K ratio showed mild correlation. Subjects have some tendency to drift back to previous Na intake profile in follow-up and thus repetitive education is necessary. In subanalysis, 34 subjects with baseline 24HUNa >150 mmol/day, benefited significantly with MBP, SBP, DBP reduction from 102±9 to 95±9 (p=0.001), 146±10 to 135±14 mmHg (p=0.001), 80±11 to 75±11 mmHg (p=0.002) in line with 24HUNa reduction from 253±154 to 163±87mmol/day (p=0.004) and urinary protein-creation ratio reduction from geometric mean of 95 to 65 g/mol. Thirty five subjects with 24HUNa reduction of >20mmol/day have significant reduction in MBP, SBP, DBP: -8 vs -2, -15 vs -4, -5 vs -2 mmHg (p=0.027, 0.006, 0.218) and urinary protein-creatinine ratio: -82 vs 2g/mol (p=0.030) compared to the other forty subjects. CONCLUSION: Quantification of 24-hour urinary Na helps in predicting potential antihypertensive effect with dietary salt reduction of CKD subjects. Salt restriction reduces BP especially in patients with estimated daily sodium intake of >150mmol/day. Reduction in sodium intake beyond 20mmol/day reduced both BP and proteinuria.

A comparison of dabigatran and warfarin for stroke prevention in elderly Asian population with nonvalvular atrial fibrillation: An audit of current practice in Malaysia.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with significant morbidity and mortality in relation to thromboembolic stroke. Our study aimed to evaluate the safety and efficacy of dabigatran in stroke prevention in elderly patient with nonvalvular AF with regard to the risk of ischemic stroke and intracranial haemorrhage (ICH) in real-world setting. METHODS: A retrospective cohort study of 200 patients on dabigatran and warfarin from January 2009 till September 2016 was carried out. Data were collected for 100 patients on dabigatran and 100 patients on warfarin. RESULTS: The mean follow-up period was 340.7±322.3 days for dabigatran group and 410.5±321.2 days for warfarin group. The mean time in therapeutic range (TTR) was 52±18.7%. The mean CHA2DS2 -VASc score for dabigatran group was 4.4±1.1 while 5.0±1.5 for warfarin group. None in dabigatran group experienced ischemic stroke compared to one patient in warfarin group (p=0.316). There was one patient in dabigatran group suffered from ICH compared to none in warfarin group (p=0.316). Four patients in warfarin group experienced minor bleeding, while none from dabigatran group (p=0.043). CONCLUSION: Overall bleeding events were significantly lower in dabigatran group compared to warfarin group. In the presence of suboptimal TTR rates and inconveniences with warfarin therapy, non-vitamin-K antagonist oral anticoagulants (NOAC) are the preferred agents for stroke prevention in elderly Asian patients for nonvalvular AF.

Missed opportunities for earlier HIV-testing in patients with HIV infection referred to a tertiary hospital, a cross-sectional study.

INTRODUCTION: In Malaysia, the prevalence of missed opportunities for HIV-testing is unknown. Missed opportunities have been linked to late diagnosis of HIV and poorer outcome for patients. We describe missed opportunities for earlier HIV-testing in newly-HIV-diagnosed patients. METHODS: Cross sectional study. Adult patients diagnosed with HIV infection and had at least one medical encounter in a primary healthcare setting during three years prior to diagnosis were included. We collected data on sociodemographic characteristics, patient characteristics at diagnosis, HIV-related conditions and whether they were subjected to risk assessment and offered HIV testing during the three years prior to HIV diagnosis. RESULTS: 65 newly HIV-diagnosed patients (male: 92.3%; Malays: 52.4%; single: 66.7%; heterosexual: 41%; homosexual 24.6%; CD4 <350 at diagnosis: 63%). 93.8% were unaware of their HIV status at diagnosis. Up to 56.9% had presented with HIV-related conditions at a primary healthcare facility during the three years prior to diagnosis. Slightly more than half were had risk assessment done and only 33.8% were offered HIV-testing. CONCLUSIONS: Missed opportunities for HIV-testing was unacceptably high with insufficient risk assessment and offering of HIV-testing. Risk assessment must be promoted and primary care physicians must be trained to recognize HIV-related conditions that will prompt them to offer HIVtesting.

Prevalence of type 5 familial hemophagocytic lymphohistiocytosis in Korea and novel mutations in STXBP2.

Familial hemophagocytic lymphohistiocytosis (F-HLH or FHL) is a potentially fatal immune dysregulation syndrome with a heterogeneous genetic background. Most recently, STXBP2 has been identified as the causative gene of type 5 FHL (FHL5) with a worldwide distribution. In this study, we investigated the prevalence of FHL5 in Korea. About 50 Korean pediatric patients with HLH who lacked pathogenic mutations in PRF1, UNC13D, or in STX11 from the previous series of 72 patients with HLH were analyzed for STXBP2 mutations by conventional sequencing analyses. As a result, we found one patient with two novel mutations of STXBP2: c.184A>G and c.577A>C. c.184A>G (p.Asn62Asp) was located within a highly conserved region of the STXBP2 protein and predicted to be deleterious. c.577A>C in exon 7 resulted in incomplete splicing mutation with exon 7 skipping concurrent with exon 7-retained transcript with p.Lys193Gln substitution. The frequency of FHL5 was ~1% (1/72) in Korean pediatric patients with HLH. This is the first study on FHL5 in Korea, and the data from a nationwide patient cohort provide another piece of genetic profiles of FHL.

A neuron-glia interaction involving GABA transaminase contributes to sleep loss in sleepless mutants.

Sleep is an essential process and yet mechanisms underlying it are not well understood. Loss of the Drosophila quiver/sleepless (qvr/sss) gene increases neuronal excitability and diminishes daily sleep, providing an excellent model for exploring the underpinnings of sleep regulation. Here, we used a proteomic approach to identify proteins altered in sss brains. We report that loss of sleepless post-transcriptionally elevates the CG7433 protein, a mitochondrial γ-aminobutyric acid transaminase (GABAT), and reduces GABA in fly brains. Loss of GABAT increases daily sleep and improves sleep consolidation, indicating that GABAT promotes wakefulness. Importantly, disruption of the GABAT gene completely suppresses the sleep phenotype of sss mutants, demonstrating that GABAT is required for loss of sleep in sss mutants. While SSS acts in distinct populations of neurons, GABAT acts in glia to reduce sleep in sss flies. Our results identify a novel mechanism of interaction between neurons and glia that is important for the regulation of sleep.

The effect of the intensity of lipid-lowering medications on the LDL cholesterol treatment goals of Asian patients with dyslipidaemia in primary care.

WHAT IS KNOWN AND OBJECTIVE: Dyslipidaemia is the key risk factor for arthrosclerosis, leading to myocardial infarctions and strokes. Achieving LDL cholesterol (LDL-C) treatment goals using lipid-lowering therapy (LLT) mitigates such cardiovascular risks. This study aimed to determine the proportions and factors influencing patients with dyslipidaemia on LLT who achieved their recommended LDL-C treatment goals. METHODS: Adult Asian patients with dyslipidaemia, aged 31-80 years, were enrolled in a questionnaire survey. Using simplified Framingham risk scores, these patients were classified into low (LR), medium (MR) and high (HR) cardiovascular risk groups. Their lipid-lowering therapy was classified into low-intensity (LI), medium-intensity (MI) and high-intensity (HI) groups according to the 2013 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Data on their demographic, clinical, self-reported attitude and adherence to LLT were correlated with their latest lipid profiles from their electronic health records. These data were analysed using chi-square test, or independent t-test where appropriate for categorical variables and continuous data. Logistic regression was used to identify factors relating to LDL-C goal attainment. RESULTS AND DISCUSSION: Amongst the 917 patients treated with LLT, 60·9% were females and 56·2% aged >60 years. The commonest statins prescribed were simvastatin (77·7%), atorvastatin (15·3%), rosuvastatin (4·3%) and lovastatin (3·4%). Those who attained LDL-C treatment goals included 89·4%, 77·4% and 70% of the LR, MR and HR groups. Overall, 72·4% of the patients achieved LDL-C treatment goals. Despite 98·4% of them self-reported LLT adherence, only 85·5%, 69·5% and 50% of the LI, MI and HI subgroups attained the desired outcomes, respectively. WHAT IS NEW AND CONCLUSION: Overall, 27·6% of patients with dyslipidaemia, including 30% of the HR group, did not achieve LDL-C treatment goals, despite on LLT. Addressing their concerns and adjusting medication doses of their LLT are needed for better outcomes.

Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study.

The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.

Multidrug resistance protein 4 (MRP4) polymorphisms impact the 6-mercaptopurine dose tolerance during maintenance therapy in Japanese childhood acute lymphoblastic leukemia.

Multidrug resistance protein 4 (MRP4) is involved in the efflux of nucleoside derivatives and has a role in the determination of drug sensitivity. We investigated the relationship between MRP4 genetic polymorphisms and doses of the 6-mercaptopurine (6-MP) and methotrexate. Further, we evaluated the frequency of therapeutic interruption during maintenance therapy in Japanese children with acute lymphoblastic leukemia (ALL). Ninety-four patients received an initial 6-MP dose in the range of 30-50 mg m(-2) in this analysis. Patients with homozygous variant allele in any of MRP4 G2269A, C912A and G559T required high frequency of 6-MP dose reduction compared with non-homozygous individuals. Average 6-MP dose for patients with homozygous variant allele on either MRP4 or inosine triphosphate pyrophosphatase was significantly lower than that for patients with non-homozygous variant allele during maintenance therapy (30.5 versus 40.0 mg m(-2), P=0.024). Therefore, MRP4 genotyping may be useful for personalizing the therapeutic dose of 6-MP during the ALL maintenance therapy in Japanese.

Influence of hepatitis B virus reactivation on the recurrence of HBV-related hepatocellular carcinoma after curative resection in patients with low viral load.

It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B-related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV-related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre-operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV-related HCC after curative resection were investigated. Fifty-three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV-related HCC in patients with low viral load.