To evaluate treatment satisfaction, disease outcomes, and perspectives of patients with poorly controlled rheumatoid arthritis (RA) treated with conventional synthetic, targeted synthetic, or ...biologic disease-modifying antirheumatic drugs (DMARDs), we conducted a subgroup (post hoc) analysis of Japanese patients participating in the SENSE study.
Data for Japanese patients (n/N = 118/1629) from the global, multicenter, cross-sectional, observational SENSE study were analyzed. The primary endpoint was the global satisfaction subscore assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4. Other patient-reported outcomes included self-reported RA medication adherence and Work Productivity and Activity Impairment-RA. Patient perspectives included patients' expectations and preference of pharmacologic treatment.
Median (range) age and RA disease duration were 67.0 (18.0-87.0) years and 8 (0.0-54) years, respectively; 81.4% of patients were female. Mean (SD) TSQM global satisfaction subscore was 56.8 (17.5), and only 5.9% of patients reported good satisfaction with treatment (TSQM global ≥80). Mean (SD) self-reported treatment adherence using VAS was high (93.5% 13.8%). Mean (SD) total work productivity impairment was 45.6% (32.0%); presenteeism contributed toward more total work productivity impairment (43.9% 30.4%) than absenteeism (8.3% 24.4%). Patients expected improvement in all parameters from their treatment, especially improvement in joint symptoms. Most patients (80.7%) preferred oral medication and 18.7% preferred monotherapy. Patient acceptability of potentially manageable side effects was high (7.5%-34.0%). Although most patients (81.3%) found combination therapy acceptable, 43.2% were receiving DMARD monotherapy.
Although most Japanese patients with RA with moderate-to-high disease activity were dissatisfied with their current DMARD treatment, high treatment adherence, high acceptability of combination therapy, high acceptability of manageable potential side effects, and preference for oral medication were reported. Data support the development of a more individualized and patient-centric approach for RA treatment.
The purpose of this study was to characterize the Bayesian penalized likelihood (BPL) reconstruction algorithm in comparison with an ordered subset expectation maximization (OSEM) reconstruction ...algorithm and to determine its optimal penalization factor (expressed as a beta value) for clinical use.
FDG PET/CT scans of 46 patients with lung cancer were reconstructed using OSEM and BPL with beta values of 200, 300, 400, 500, and 1000. The liver signal-to-noise ratio, mean standardized uptake value (SUV
) of the liver, and maximum standardized uptake value (SUV
) and SUV
of the cancers were measured. Tumors were categorized into three size groups, and the percentage difference in the tumor SUV
between OSEM and BPL with a beta value of 200 as well as the percentage difference in the SUV
between BPL with a beta value of 200 and BPL with a beta value of 1000 were calculated. Image quality was assessed by visual scoring.
BPL showed a significantly higher liver signal-to-noise ratio than OSEM, except for BPL with a beta value of 200. The liver SUV
showed no statistical difference among all algorithms. The SUV
and SUV
of tumors decreased as the beta value increased. BPL with a beta value of 200 produced a significantly higher tumor SUV
than did OSEM (
< 0.01), and BPL with a beta value of 400, 500, or 1000 produced a significantly lower tumor SUV
than did OSEM (
< 0.01). Visual analysis showed the highest and lowest scores for BPL with beta values of 500 and 200, respectively. In the small size group, the percentage difference in the SUV
between OSEM and BPL with a beta value of 200 and the percentage difference in the SUV
between BPL with a beta value of 200 and BPL with a beta value of 1000 were significantly larger than that in the other size groups (
< 0.01).
The BPL algorithm improves image quality without compromising image quantification. A beta value of 500 appeared to be optimal in this study. Smaller tumors were more influenced by BPL.
This study was conducted to assess the real-world safety and effectiveness of adalimumab in patients with juvenile idiopathic arthritis (JIA).
In this all-case, postmarketing surveillance study ...(NCT01412021) conducted in Japan, patients receiving adalimumab for JIA affecting multiple joints were observed for 24 weeks. The safety (adverse drug reactions ADRs/serious ADRs) and effectiveness (4-variable Disease Activity Score in 28 joints using erythrocyte sedimentation rate DAS28-4/ESR remission rate) were assessed.
In the safety population (n = 356), 90.3% (65/72; weight, ≥15-<30 kg) of patients received adalimumab 20 mg every 2 weeks (q2w) and 98.3% (236/240; weight ≥30 kg) received 40 mg q2w. Incidence of ADRs and serious ADRs was 29.8% (106/356) and 3.4% (12/356), respectively. Incidence of ADRs was significantly higher in patients aged <15 years vs. ≥15 years (34.6% vs. 21.1%, p = .0072), those with comorbidities vs. without (38.3% vs. 25.7%, p = .0155), and those receiving dose <40 mg q2w vs. ≥40 mg q2w (38.8% vs. 26.9%, p = .0418). DAS28-4/ESR remission rate improved from 21.7% (36/166) at baseline to 74.7% (112/150) at week 24.
Adalimumab was well tolerated and had acceptable safety and effectiveness in patients with JIA in the real-world setting.
Sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed in various immune cells and most of them carry signaling functions. High-affinity synthetic sialoside ligands have been ...developed for various Siglecs. Therapeutic potentials of the nanoparticles and compounds that contain multiple numbers of these sialosides and other reagents such as toxins and antigens have been demonstrated. However, whether immune responses can be regulated by monomeric sialoside ligands has not yet been known. CD22 (also known as Siglec-2) is an inhibitory molecule preferentially expressed in B lymphocytes (B cells) and is constitutively bound and functionally regulated by α2,6 sialic acids expressed on the same cell (cis-ligands). Here, we developed synthetic sialosides GSC718 and GSC839 that bind to CD22 with high affinity (IC
~100 nM), and inhibit ligand binding of CD22. When B cells are activated by B cell antigen receptor (BCR) ligation, both GSC718 and GSC839 downregulate proliferation of B cells, and this regulation requires both CD22 and α2,6 sialic acids. This result suggests that these sialosides regulate BCR ligation-induced B cell activation by reversing endogenous ligand-mediated regulation of CD22. By contrast, GSC718 and GSC839 augment B cell proliferation induced by TLR ligands or CD40 ligation, and this augmentation requires CD22 but not α2,6 sialic acids. Thus, these sialosides appear to enhance B cell activation by directly suppressing the inhibitory function of CD22 independently of endogenous ligand-mediated regulation. Moreover, GSC839 augments B cell proliferation that depends on both BCR ligation and CD40 ligation as is the case for
B cell responses to antigens, and enhanced antibody production to the extent comparable to CpG oligonuleotides or a small amount of alum. Although these known adjuvants induce production of the inflammatory cytokines or accumulation of inflammatory cells, CD22-binding sialosides do not. Thus, synthetic sialosides that bind to CD22 with high-affinity modulate B cell activation through endogenous ligand-dependent and independent pathways, and carry an adjuvant activity without inducing inflammation.
Fetus in fetu (FIF) is a rare congenital anomaly resulting from abnormal embyogenesis in monochorionic diamniotic twins and appears as a cystic mass containing fetus-like structures mainly in the ...retroperitoneum of infants. Although there is a theory that FIF is a highly differentiated teratoma, it is commonly distinguished from teratoma as a mass containing a vertebral axis with appropriate arrangement of limbs or other organs around this axis. Here we present a case of FIF with aorta-like structure visualized by contrast-enhanced computed tomography. A 5-day-old girl was pointed out a cystic mass in the abdomen by ultrasound examination. Abdominal contrast-enhanced computed tomography revealed a retroperitoneal cystic mass with spine- and limb-like bone structures and blood vessel-like elongated structures and it was confirmed as FIF by surgery. The presence of major vascular structures along the skeletal axis is clearly different from teratoma and suggests that it occurred as an embryo and underwent some stage of development. Our findings strongly support the monozygotic twin theory.
A 69-year-old man was transferred to our hospital for massive hemorrhage from a right hepatic artery pseudoaneurysm 5 months after surgery for gastric cancer. Stent-graft placement was planned to ...avoid fatal hepatic infarction, and a guiding sheath was advanced deeply into the tortuous and stenotic right hepatic artery beyond the pseudoaneurysm for safe deployment of a stent-graft. However, this advancement caused arterial dissection of the right hepatic artery. After the guiding sheath was pulled back, a Viabahn stent-graft was successfully advanced over a guidewire to exclude the pseudoaneurysm. We consider that a Viabahn stent-graft is more flexible than a guiding sheath and that advancing a Viabahn stent-graft directly from a proximally placed guiding sheath is safer than advancing a guiding sheath into a tortuous and stenotic abdominal artery.
Neonatal subpial hemorrhage has been underrecognized until recently and its pathophysiology remains unclear. Advances in magnetic resonance imaging have facilitated the identification of hemorrhage ...within the subpial space and cohort studies recently reported its imaging and clinical features. We encountered two cases of neonatal subpial hemorrhage along the medial side of the temporal lobe. Case 1: A 1-day-old boy had repeated apneic attacks with cyanosis from 2 hours after birth at 39 weeks of gestation by vacuum extraction delivery. Computed tomography and magnetic resonance imaging showed subpial hemorrhage from the medial to caudal side of the right temporal lobe with T2 prolongation in the underlying cerebral parenchyma. Case 2: A 0-day-old boy had repeated apneic attacks with cyanosis from 3 hours after birth at 39 weeks of gestation by vaginal delivery. Subpial hemorrhage was observed from the anterior to medial side of the left temporal lobe on computed tomography and magnetic resonance imaging. On magnetic resonance imaging, the adjacent brain parenchyma showed a hyperintense signal on T2-weighted imaging. No abnormalities or signs of fetal distress were noted in the course of delivery. A mildly prolonged activated partial thromboplastin clotting time, an elevated D-dimer level, and low fibrinogen level were detected in a blood examination after birth in both cases. Both cases had subpial hemorrhage along the medial side of the temporal lobe, which suggested that an external mechanical force with fetal head molding during delivery caused subpial hemorrhage; however, other factors, including coagulopathy, may be involved in its pathophysiology.
Objectives: To assess the detectability of a low-signal-intensity line within adenomyosis lesions adjacent to the endometrium on apparent diffusion coefficient (ADC) maps, and to establish ...correlations between these lesions and their possible causes, and more particularly the hormonal changes and magnetic resonance (MR) factors. Materials and methods: MR images were obtained from 110 patients with adenomyosis (age 30–57 y.o.) using 3.0 T or 1.5 T MR units. Recognition of the low-signal-intensity line on ADC map was scored using confidence level. The correlation between recognition of the line and the following factors were examined: magnetic field strength, age group, menstrual cycle phases, history of delivery, and hormonal treatments. Presence of the structure corresponding to the low-signal-intensity line on ADC map was evaluated pathologically in the cases that underwent surgery. Results: The low-signal-intensity line visible on ADC map was recognized in 55/110 patients. The visibility of the line was not significantly related to hormonal status, age, history of delivery, or magnetic resonance imaging (MRI) magnet strength. There were no corresponding pathological structures. Conclusion: One half of the adenomyosis patients showed discrepant appearances in T2-weighted (T2WI) vs. ADC map, but no significant relationship with hormonal changes was found in this study. This result may suggest that the low-signal-intensity line within the junctional zone may be related to a functional phenomenon.
A 73-year-old man with lung cancer underwent bone scintigraphy for disease staging. Diffuse myocardial technetium hydroxymethylene diphosphonate (
Tc-HMDP) uptake was incidentally found. A diagnosis ...of amyloid transthyretin (ATTR) cardiac amyloidosis was suspected, although the patient had no symptoms at this time. Single-photon emission computed tomography (SPECT) showed particularly strong uptake in the ventricular septum. Cardiac magnetic resonance imaging (CMR) showed widespread subendocardial and partly transmural enhancement of the left ventricular myocardium on delayed postcontrast T1-weighted images. These findings were consistent with ATTR cardiac amyloidosis.
F-FDG uptake in the left ventricle wall was observed on PET/CT. He was finally diagnosed with ATTR by endomyocardial biopsy. There are two major subtypes of cardiac amyloidosis: ATTR amyloidosis and amyloid light-chain (AL) amyloidosis. Endomyocardial biopsy is the gold standard for diagnosis. Recently, however, several reports have shown that bone scintigraphy using a
Tc-labelled bone-seeking agent can detect ATTR cardiac amyloidosis and differentiate it from AL amyloidosis. Bone scintigraphy may play an important role in the detection and differentiation of ATTR cardiac amyloidosis.
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