Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.

Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.

Glycation promotes pulp calcification in Type 2 diabetes rat model.

OBJECTIVES: Intrapulpal calcifications can occur in the dental pulp of patients with diabetes. We focused on the association between ectopic calcifications in the dental pulp and advanced glycation end products (AGEs) in Spontaneously Diabetic Torii (SDT)-fatty rats, an obese type 2 diabetic rat model, to determine the mechanism of calcification with pulp stone in the dental pulp. MATERIALS AND METHODS: Pathologic calcification in the dental pulp of SDT-fatty rats was observed using electron microscopy and immunohistochemical analysis. Moreover, mechanical analysis of periapical region of molar tooth against occlusal force was performed. RESULTS: In SDT-fatty rats, pathogenic pulpal calcifications occurred during blood glucose elevation after 6 weeks, and granular calcification was observed in the dental pulp after 11 weeks. Pentosidine, a major AGE, and the receptor for AGEs were strongly expressed in the dental pulp of SDT-fatty rats. S100A8, TNF-α, and IL-6 also showed positive response in the dental pulp of the SDT-fatty rat, which indicated pulpal inflammation. Blood flow disorder and hypoxic dental pulp cells were also observed. In silico simulation, strain from occlusal force concentrates on the root apex. CONCLUSIONS: Glycation makes blood vessels fragile, and occlusal forces damage the vessels mechanically. These are factors for intrapulpal calcification of diabetes.

Clinical Significance of Coronary Healed Plaques in Stable Angina Pectoris Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Coronary healed plaques (HPs) reportedly have high vulnerability or show advanced atherosclerosis and a risk of rapid plaque progression. However, the prognosis of stable angina pectoris (SAP) patients with HPs undergoing percutaneous coronary intervention (PCI) remains under-investigated.Methods and Results: We analyzed 417 consecutive lesions from SAP patients undergoing pre- and post-intervention optical coherence tomography (OCT) for which HPs were defined as having a layered appearance. We investigated the differences in clinical and lesion characteristics, and post-PCI outcomes between HPs and non-HPs. To account for differences in clinical characteristics, propensity score matching was performed between the groups. HPs were observed in 216 lesions (51.8%) in the total cohort. In the propensity-matched cohort (n=294), HPs had higher rates of angiographic-B2/C lesions (77.6% vs. 59.2%, P<0.001), OCT-lipid-rich plaques (40.8% vs. 25.9%, P=0.007), macrophages (78.2% vs. 44.2%, P<0.001), greater luminal area stenosis (73.5±11.0% vs. 71.5±10.3%, P=0.002), and a higher prevalence of post-stenting irregular tissue protrusion (45.1% vs. 14.7%, P<0.001) than non-HPs. In the total cohort, target lesion revascularization (TLR)-free survival was poorer for HPs (log-rank test 7.66; P=0.006), and Cox proportional hazards analysis showed HP as an independent predictor of TLR (hazard ratio, 5.98; 95% confidence interval, 1.72-20.82; P=0.005). CONCLUSIONS: In SAP patients, HPs had greater complexity of lesions and higher vulnerability, which may have contributed to the poorer post-PCI outcomes.

Effects of advanced glycation end products on dental pulp calcification.

OBJECTIVE: The main aim of this study was to elucidate the effects of advanced glycation end products (AGEs) on the calcification of cultured rat dental pulp cells (RDPCs) and to investigate the crystallisation ability of glycated collagen. MATERIALS AND METHODS: AGEs were prepared via non-enzymatic glycation of a dish coated with type I collagen using dl-glyceraldehyde. To investigate the effects of AGEs on RDPCs, we performed WST-1 and lactate dehydrogenase assays; alkaline phosphatase, Alizarin Red S and immunohistochemical staining; and real-time quantitative reverse transcription PCR. In addition, we performed crystallisation experiments on glycated collagen. All microstructures were analysed using scanning electron microscopy/energy-dispersive X-ray spectroscopy and transmission electron microscopy/diffraction pattern analysis. RESULTS: AGEs did not affect the proliferation or differentiation of RDPCs, but enhanced the calcification rate and cytotoxicity. No major calcification-related genes or proteins were involved in these calcifications, and glycated collagen was found to exhibit a negative polarity and form calcium phosphate crystals. Cytotoxicity due to drastic changes in the concentration of pericellular ions led to dystrophic calcification, assumed to represent an aspect of diabetic pulp calcifications. CONCLUSION: Glycated collagen-containing AGEs provide a nurturing environment for crystallisation and have a significant effect on the early calcification of RDPCs.

Left ventricular end-systolic contractile entropy can predict cardiac prognosis in patients with complete left bundle branch block.

BACKGROUND: Several patients with complete left bundle branch block (CLBBB) show left ventricular (LV) dyssynchrony and poor cardiac prognosis. However, the prognostic value of LV end-systolic contractile entropy which was measured by single-photon emission computer tomography (SPECT) has not been elucidated in patients with CLBBB. METHODS AND RESULTS: We recruited consecutive 115 sinus-rhythm patients with CLBBB who underwent ECG-gated 201TlCl-SPECT. After 30 days of observation, finally 102 patients (75.2 ± 9.5 years, 62 male) were enrolled and observed retrospectively for a median of 671 days. Twenty-five patients fell into major cardiac events. Multivariate Cox regression analysis showed estimated glomerular filtration rate (eGFR) ≤ 39.35 mL/min and entropy ≥ 79% were significant and independent predictors for major cardiac events (hazard ratio: 4.256 and 7.587, P value = 0.006 and < 0.001, respectively). Machine learning (Random Forest method) revealed eGFR and entropy had higher feature importance than other predictors (0.140 and 0.138, respectively). Kaplan-Meyer curve analysis demonstrated that the group with entropy ≥ 79% and eGFR ≤ 39.36 mL/min had the worst cardiac prognosis (Logrank: P = 0.002). CONCLUSIONS: Left ventricular end-systolic contractile entropy predicts poor cardiac prognosis in patients with CLBBB, which may be more valuable than the other parameters of SPECT.

Neuroleptic malignant syndrome in patients with COVID-19.

We report the first two cases of Coronavirus Disease 2019 (COVID-19) who were receiving intensive care including favipiravir, and were clinically diagnosed with neuroleptic malignant syndrome (NMS) to focus attention on NMS in COVID-19 management. Case 1: A 46-year-old-man with acute respiratory distress syndrome (ARDS) caused by COVID-19 infection was being administered favipiravir. Fentanyl, propofol, and rocuronium were also given. On day 3, midazolam administration was initiated for deep sedation. On day 5, his high body temperature increased to 41.2 °C, creatine kinase level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS was suspected, and supportive therapy was initiated. High-grade fever persisted for 4 days and subsided on day 9. Case 2: A 44-year-old-man with ARDS caused by COVID-19 infection was being treated with favipiravir. On day 5, risperidone was started for delirium. On day 7, his body temperature suddenly increased to 40.8 °C, his CK level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS diagnosis was confirmed, and both, favipiravir and risperidone were discontinued on day 8. On the same day, his CK levels decreased, and his body temperature normalized on day 9. Patients with COVID-19 infection frequently require deep sedation and develop delirium; therefore, more attention should be paid to the development of NMS in patients who are being administered such causative agents. The mechanism underlying the occurrence of NMS in COVID-19 patients treated with favipiravir remains unknown. Therefore, careful consideration of NMS development is necessary in the management of COVID-19 patients.

An endoscopic dilation method using the rendezvous approach for the treatment of severe anastomotic stenosis after rectal cancer surgery: a case report.

BACKGROUND: Postoperative anastomotic stenosis is a common complication in colorectal cancer patients (3-30%). Complete anastomotic stenosis is rare; however, when it occurs, almost all cases require surgical treatment. We herein report a case in which endoscopic dilation was effective for treating complete anastomotic stenosis after high anterior resection in a rectal cancer patient. CASE PRESENTATION: The patient was a 67-year-old man who underwent laparoscopic high anterior resection for rectal cancer (RS, T4a, N0, M0, Stage IIB (TNM Classification of Malignant Tumors)) in May 2018. The postoperative course was good and the patient was discharged on the 12th postoperative day. Subsequently adjuvant chemotherapy was initiated with oral uracil and tegafur plus leucovorin (UFT/LV); however, he complained of frequent defecation and melena after completion of the first course of chemotherapy. Thus, colonoscopy was performed, which revealed anastomotic stenosis. Endoscopic dilation was initially attempted, but failed. Thus, low anterior resection was performed with diverting colostomy. Four additional courses of chemotherapy were administered for 1 month after surgery. At 6 months after the second surgery, colonoscopy was performed, and complete anastomotic stenosis was pointed out again. The patient was successfully treated by endoscopic dilation using the rendezvous method. After this treatment, the lumen of the anastomotic site was observed to have narrowed again and endoscopic dilatation to treat anastomotic stenosis was repeated. In addition, he received local injection of steroids in anastomotic stenosis site. The lumen of anastomotic stenosis remained after the local injection of steroids and closure of colostomy was performed 9 months after the second operation. CONCLUSIONS: Endoscopic dilation using the rendezvous method was effective for treating anastomotic stenosis after colorectal surgery.

PR deviation as a risk marker for cardiac events in patients with Takotsubo syndrome.

BACKGROUND: PR segment deviation (PRD: defined as PR elevation in aVR and PR depression in lead II/III) on electrocardiography is frequently observed in patients with acute pericarditis; however, there have been few studies that explore the occurrence of PRD in patients with Takotsubo syndrome (TTS). The clinical significance of PRD in TTS is not clearly elucidated. METHODS & RESULTS: A total of 52 consecutive patients with TTS in sinus rhythm (73.9 ± 13.8 years, nine males) were enrolled in the study. The major cardiac events were defined as sustained ventricular tachycardia or ventricular fibrillation, Killip class 4 heart failure, and cardiac death within 30 days. PRD in the hyperacute phase (within 48 h from the onset of TTS) was observed in 15 patients (29%), and all PRDs disappeared or diminished at 1 week later. The PRD (+) group had a higher value of C-reactive protein level (median: 1.80 mg/dL [0.31-3.26] vs 0.20 mg/dL [0.06-0.81], P  =  0.013) and creatine kinase-muscle/brain isoenzyme (median: 60 IU/L [28-75] vs 17 IU/L [13-26], P < 0.001) and a lower level of left ventricular ejection fraction (42.7 ± 7.2% vs 48.8 ± 9.4%, P  =  0.041) than the PRD (-) group. Multivariate analysis showed that PRD was a significant and independent predictor for major cardiac events (odds ratio  =  21.0, 95% confidence interval  =  1.18-273). CONCLUSIONS: TTS patients with PRD in the hyperacute phase showed a high incidence of major cardiac events. Therefore, PRD may help to identify TTS patients at high risk for cardiac event.

Life-Threatening Ventricular Arrhythmia and Brugada-Type ST-Segment Elevation Associated With Acute Ischemia of the Right Ventricular Outflow Tract.

BACKGROUND: Brugada-type ECG (Br-ECG) is occasionally observed during acute myocardial ischemia of the right ventricular outflow tract (RVOT). No studies have explored, however, the association of ventricular tachyarrhythmia and development of Br-ECG due to acute ischemia of the RVOT.Methods and Results:The study included 13 consecutive patients with acute ischemia of the RVOT during coronary catheterization. Patients were divided into 2 groups: those with Br-ECG (group B) and those without (group N). The proportion of male patients was higher in group B than in group N (100% vs. 25%, P<0.01), and VT/VF developed in only patients with Br-ECG (group B). In group B, VT/VF was observed in patients without pre-existing organic change in the conus/right ventricular (RV) branch of the right coronary artery and no VT/VF was seen in patients with organic coronary stenosis despite Br-ECG. CONCLUSIONS: Acute myocardial ischemia of the RVOT caused Br-ECG predominantly in male patients and subsequent development of VT/VF in some patients. VT/VF was seen in patients without any obstructive lesion but arrhythmic events were not observed in RVOT ischemia in the case of pre-existing coronary occlusion or stenosis of the conus or RV branch, suggesting the effects of precondition.

Cardiac function changes with switching from the supine to prone position: analysis by quantitative semiconductor gated single-photon emission computed tomography.

BACKGROUND: Prone positioning is required in certain operations such as spinal surgery. Changes in cardiac function in the prone position have been studied with various methodologies. Few studies have investigated changes in left ventricular diastolic function and rhythm in subjects turned prone. METHODS AND RESULTS: Cardiac function was evaluated in the supine and prone positions in 90 patients without atrial fibrillation who underwent (99m)Tc-tetrofosmin quantitative gated single-photon emission computed tomography. Three groups of 30 patients each were classified as "no history of myocardial ischemia or cardiomyopathy" (Group A), "history of myocardial infarction" (Group B), and "ischemic heart disease without myocardial infarction history" (Group C). Upon assuming the prone position, the cardiac index and any dyssynchrony worsened in all groups. Ejection fraction changes occurred only in Group B, and diastolic function changes occurred in Groups B and C, but not in Group A. The changes caused by prone positioning were more severe in the patients with poor cardiac function. CONCLUSIONS: Prone positioning induces significant changes in systolic and diastolic function, as well as dyssynchrony. The negative effects of prone positioning are more severe in patients with poor baseline cardiac function.

Effects of repetitive transcranial magnetic stimulation and intensive occupational therapy on motor neuron excitability in poststroke hemiparetic patients: a neurophysiological investigation using F-wave parameters.

BACKGROUND: The combination protocol of repetitive transcranial magnetic stimulation (RTMS) and intensive occupational therapy (OT) improves motor function of the paretic upper limb in poststroke patients. However, the effect of RTMS/OT on motor neuron excitability remains to be investigated. The purpose of this study was to determine the effect of 15-day application of RTMS/OT on motor neuron excitability in such patients using neurophysiological studies including F-wave parameter measurements. SUBJECTS AND METHODS: Ten poststroke patients with spastic upper limb hemiparesis were studied (mean age: 57.4 ± 8.1 years, ± SD). Patients were hospitalized for 15 days to receive RTMS/OT. One session of 40-min low-frequency RTMS and two sessions of 120-min intensive OT were provided daily. Neurophysiological studies including F-wave parameters measurements were performed on the days of admission/discharge. Motor function and spasticity of the affected upper limb were evaluated on the same time points. RESULTS: RTMS/OT significantly improved motor function of the affected upper limb. RTMS/OT decreased the modified Ashworth scale (MAS) in the affected upper limb (p < 0.05), but did not change F-wave frequency in either upper limb. However, both F-mean/M ratio and F-max/M ratio significantly decreased in the affected upper limb (all p < 0.05). CONCLUSIONS: The 15-day protocol of LF-RTMS/OT produced significant reduction of motor neuron excitability. RTMS/OT can potentially produce significant reduction in upper limb spasticity in the affected upper limb, although this finding should be confirmed in a larger number of patients.

Structural deterioration of finger joints with ultrasonographic synovitis in rheumatoid arthritis patients with clinical low disease activity.

OBJECTIVE: In this study we investigated the relationship between synovial vascularity (SV) and structural alteration of finger joints in patients with RA and long-term sustained clinical low disease activity (CLDA). METHODS: RA patients with CLDA of >2 years (minimum 1 year of CLDA for study entry plus 1 year of observation) were analysed. Quantitative SV values were sequentially measured in each finger joint using power Doppler ultrasonography (0, 8, 20 and 52 weeks). Radiological progression of local finger joints was evaluated according to the Genant-modified Sharp score (0-52 weeks). RESULTS: Of the 25 patients enrolled, 15 patients were finally analysed after excluding 10 patients who failed to maintain CLDA during the observational period. Changes in radiological progression of MCP and PIP joints with positive SV were significantly greater than those in joints with negative SV. Joint space narrowing (JSN) was strongly related to structural alteration of finger joints. In joints with positive SV, changes in structural alteration did not relate to total SV values, which reflect total exposure to inflammation in an observational period. CONCLUSION: Even in patients with a long period of CLDA, finger joints with positive SV showed structural alteration, especially in the progression of JSN. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, http://www.umin.ac.jp/ctr/, UMIN000007305.

Unmasking Brugada-type electrocardiogram on deep inspiration.

BACKGROUND: Electrocardiogram (ECG) recorded at the upper intercostal lead positions is recommended as an additional diagnostic clue for Brugada syndrome (BrS), but similar recording conditions to unmask ECG signs have not been explored. METHODS AND RESULTS: We evaluated the diagnostic usefulness for unmasking ECG signs of BrS using recordings at the upper intercostal lead position, on deep inspiration and on standing. In 34 patients (mean age, 49±14 years; 30 male) with diagnosed and suspected BrS, ECG type and ST-elevation in leads V1-V3 recorded at a higher position by 1 rib from the standard position (3ICS), and at standard lead positions (4ICS) on deep inspiration (DI test) and on standing (Stand test) were compared with the conventional lead positions (baseline). While type 1 ECG had been documented in 17 of 34 patients on at least 1 occasion in the past, only 4 had the sign at baseline during the study. Twenty patients had type 1 on 3ICS recording, 18 on DI test, and 6 on Stand test. Among 17 patients without previous documentation of spontaneous type 1, 7 had type 1 on 3ICS recording, 6 on DI test, and 1 on Stand test. CONCLUSIONS: ECG recording on deep inspiration is useful to unmask diagnostic signs of BrS and has similar accuracy to 3ICS recording.

J wave and fragmented QRS formation during the hyperacute phase in Takotsubo cardiomyopathy.

BACKGROUND: The J wave and fragmented QRS (fQRS) on electrocardiography are suggested to be closely related to cardiac arrhythmogenesis. Takotsubo cardiomyopathy (TTC) occasionally causes fatal cardiac conditions including life-threatening ventricular arrhythmia. There has been, however, only 1 case report describing the J wave in TTC, and fQRS has not been reported thus far in relation to clinical courses and prognosis. METHODS AND RESULTS: J wave and fQRS formation were investigated in 31 consecutive patients with TTC. Nine patients (29%) had J waves and/or fQRS (group A), whereas the remaining 22 did not (group B). The J wave (4 patients), fQRS (4 patients), or both (1 patient) appeared transiently during the hyperacute phase. Left ventricular ejection fraction was significantly lower in group A. Summed defect score of single-photon emission computed tomography using iodine 123 beta-methyl-p-iodophenyl-pentadecanoic acid, and creatine kinase MB isozyme (CKMB) were significantly higher in group A. On multivariate analysis CKMB was a significant indicator of J wave or fQRS. Moreover, the J wave was a significant indicator for cardiac death and/or ventricular tachyarrhythmia (odds ratio, 11.5; P=0.026). CONCLUSIONS: Patients with TTC frequently had J waves and/or fQRS during the hyperacute phase, and which were associated with myocardial damage. J wave was also an indicator for cardiac death and/or ventricular tachyarrhythmia. J waves and fQRS may be useful markers for myocardial damage.

Local muscle injection of botulinum toxin type a synergistically improves the beneficial effects of repetitive transcranial magnetic stimulation and intensive occupational therapy in post-stroke patients with spastic upper limb hemiparesis.

BACKGROUND: The purpose of this study was to determine whether local injection of botulinum toxin type A (BoNT-A) into the spastic muscles has any added benefits to repetitive transcranial magnetic stimulation (RTMS)/occupational therapy (OT) in patients with spastic upper limb hemiparesis. METHODS: The study subjects of 80 post-stroke patients with spastic upper limb hemiparesis (age: 60.2 ± 13.0 years, time after stroke: 55.3 ± 43.0 months), were divided into the BoNT-A plus RTMS/OT group and RTMS/OT group. BoNT-A was injected into the spastic muscles (total dose: 240 units) before RTMS/OT. The latter included 12 sessions of 40 min RTMS over the non-lesional hemisphere and 240-min intensive OT daily over 15 days. Spasticity was evaluated by the modified Ashworth scale (MAS) and the motor function of the affected upper limb was evaluated serially with Fugl-Meyer Assessment and Wolf Motor Function Tests. RESULTS: Both groups showed significant improvements in spasticity and motor function. The addition of BoNT-A resulted in better improvement in FMA score and MAS of finger flexor muscles (p < 0.05). CONCLUSIONS: The triple-element protocol of local injection of BoNT-A into spastic finger muscles, RTMS and intensive OT, is a promising therapeutic program for post-stroke spastic upper limb hemiparesis, although its significance should be confirmed in randomized, placebo-controlled trials.

Crystal structures of complexes of vitamin D receptor ligand-binding domain with lithocholic acid derivatives.

The secondary bile acid lithocholic acid (LCA) and its derivatives act as selective modulators of the vitamin D receptor (VDR), although their structures fundamentally differ from that of the natural hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3)]. Here, we have determined the crystal structures of the ligand-binding domain of rat VDR (VDR-LBD) in ternary complexes with a synthetic partial peptide of the coactivator MED1 (mediator of RNA polymerase II transcription subunit 1) and four ligands, LCA, 3-keto LCA, LCA acetate, and LCA propionate, with the goal of elucidating their agonistic mechanism. LCA and its derivatives bind to the same ligand-binding pocket (LBP) of VDR-LBD that 1,25(OH)2D3 binds to, but in the opposite orientation; their A-ring is positioned at the top of the LBP, whereas their acyclic tail is located at the bottom of the LBP. However, most of the hydrophobic and hydrophilic interactions observed in the complex with 1,25(OH)2D3 are reproduced in the complexes with LCA and its derivatives. Additional interactions between VDR-LBD and the C-3 substituents of the A-ring are also observed in the complexes with LCA and its derivatives. These may result in the observed difference in the potency among the LCA-type ligands.

Positive synovial vascularity in patients with low disease activity indicates smouldering inflammation leading to joint damage in rheumatoid arthritis: time-integrated joint inflammation estimated by synovial vascularity in each finger joint.

OBJECTIVE: To investigate the relationship between synovial vascularity and joint damage progression in each finger joint of patients with RA under low disease activity during treatment with biologic agents. METHODS: We studied 310 MCP and 310 PIP joints of 31 patients with active RA who were administered adalimumab (ADA) or tocilizumab (TCZ). Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at weeks 8, 20 and 40. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and at week 50. RESULTS: Composite scores of the DAS with 28 joints and the Simplified Disease Activity Index (SDAI) were significantly decreased from baseline to week 8, being sustained at a low level by biologic agents during the observational period. MCP and PIP joints with positive synovial vascularity after week 8 showed more subsequent joint damage progression than joints without synovial vascularity throughout the follow-up. The changes in radiographic progression in these joints were independent of the sum of synovial vascularity from baseline to week 40 or the occasional occurrence of positive synovial vascularity. CONCLUSION: Smouldering inflammation reflected by positive synovial vascularity under low disease activity was linked to joint damage. The damage progressed irrespective of the severity of positive synovial vascularity. Even with a favourable overall therapeutic response, monitoring of synovial vascularity has the potential to provide useful joint information to tailor treatment strategies. Trial registration. University Hospital Medical Information Network Clinical Trials Registry; http://www.umin.ac.jp/ctr/; UMIN000004476.