An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40 mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD.

Clinical importance of anti-Ro52 antibody for polymyositis and dermatomyositis.

OBJECTIVES: To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM). PATIENTS AND METHODS: We retrospectively examined clinical features and status of anti-Ro52 Ab in patients with PM/DM admitted at the University of Tsukuba Hospital between January 2019 and February 2023. We compared anti-Ro52 Ab-positive and -negative groups. RESULTS: A total of 40 patients were selected and analyzed. Median age at diagnosis was 61.5 (48.8-69.3) years and 34 cases were female. Twenty-three cases were PM and 17 cases were DM (including 6 clinically amyopathic dermatomyositis: CADM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease (ILD) was detected in 29 cases, 9 of which were rapidly progressive. Glucocorticoid (GC)-resistant cardiomyopathy was detected in 6 cases, malignancy in 3 cases, and Sjögren's syndrome (SS) in 4 cases. Of the 22 anti-Ro52 Ab positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and -negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), ILD (95.5% vs. 44.4%), GC-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein (CRP) were significantly higher in the anti-Ro52 Ab-positive group (p<0.05). The frequencies of PM/DM, positivity of anti-MDA5 Ab, malignancies, and SS were comparable between groups. CONCLUSION: Anti-Ro52 Ab were frequently positive in PM/DM and anti-Ro52 Ab-positive patients showed significantly higher rates of anti-ARS Ab positivity and ILD, GC-resistant cardiomyopathy, concomitant use of immunosuppressants, and higher levels of CRP. Anti-Ro52 Ab may be useful as a severity marker in PM/DM.

Comparative analysis of low-field magnetic resonance imaging in patients with rheumatoid arthritis treated with certolizumab pegol or infliximab.

OBJECTIVES: The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). METHODS: The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. RESULTS: Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug-naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. CONCLUSIONS: The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX.

Long-term outcomes following surgical repair of coronary artery fistula in adults.

BACKGROUND AND AIM OF THE STUDY: Coronary artery fistula (CAF) is a relatively rare cardiac anomaly. We investigated long-term outcomes following surgical repair of CAF in adults. METHODS: We retrospectively investigated 13 consecutive patients undergoing surgical repair of CAF in our institution between 2008 and 2019 (67.3 ± 10.4 years old, 38% male). CAF types were coronary artery-pulmonary artery fistula (77%), coronary artery-coronary sinus fistula (15%), and both (8%). CAFs originated from the left coronary artery (38%), right coronary artery (8%), and bilateral coronary arteries (38%). Pulmonary and systemic flow (Qp/Qs) was measured in seven patients (54%), with a mean value of 1.52. Seven patients underwent surgery for CAFs alone, and others simultaneously underwent surgery for comorbid cardiac diseases. RESULTS: All procedures were conducted under cardiopulmonary bypass. Surgical procedures were direct epicardial ligation of fistula (92%), direct closure of CAF through pulmonary artery incision (38%), direct closure of CAF through coronary sinus incision (8%), or patch closure of CAF through coronary artery incision (8%). Myocardial perfusion scintigraphy showed asymptomatic myocardial ischemia in the right coronary area after surgery in one patient. There were no deaths perioperatively or during follow-up (mean: 66.6 months). There were no coronary or other CAF-related events. CONCLUSIONS: Several anatomical variations in CAF were observed which coexist with cardiac disease. Long-term outcomes following surgical repair were satisfactory, and the concurrent intervention of CAFs during surgery for comorbid cardiac disease is useful to prevent future complications related CAFs in adults.

Highly Efficient Aggregation-Induced Room-Temperature Phosphorescence with Extremely Large Stokes Shift Emitted from Trinuclear Gold(I) Complex Crystals.

Highly efficient (≈75% quantum yield), aggregation-induced phosphorescence is reported. The phosphorescence is emitted at room temperature and in the presence of air from crystals of trinuclear Au(I) complexes, accompanied by an extremely large Stokes shift of 2.2 × 104 cm-1 (450 nm). The mechanism of the aggregation-induced room-temperature phosphorescence from the Au complex crystals was investigated in terms of the crystal packing structure and the primary structure of the molecules. It was found that two kinds of intermolecular interactions occurred in the crystals, and that these multiple dual-mode intermolecular interactions in the crystals play a crucial role in the in-air room-temperature phosphorescence of the trinuclear Au(I) complexes.

[Tricuspid Valve Repair in a Patient with Isolated Tricuspid Valve Infective Endocarditis with Pulmonary Embolism;Report of a Case].

We report a case of 39-year-old man who developed tricuspid valve infective endocarditis with a complication of pulmonary embolism. He was transferred to our institution because of intermittent fever and enlargement of the vegetation of the tricuspid valve in spite of optimal antibiotics treatment. Computed tomography revealed pulmonary embolism, and transesophageal echocardiography showed a large and mobile vegetation (22×10 mm) on the tricuspid valve with moderate regurgitation. In addition, Streptococcus agalactiae was identified in blood cultures. The patient underwent surgical resection of the vegetation followed by tricuspid valve repair including De Vega's annuloplasty. Antibiotic therapy was continued for 4 weeks after surgery, and he was discharged on the 31st postoperative day. No endocarditis nor tricuspid valve dysfunction has re-occurred.

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

BACKGROUND: This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. METHODS AND DESIGN: Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. DISCUSSION: The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. TRIAL REGISTRATION: UMIN000019081 ; Registration date: 2015/9/30.

Activation of human bitter taste receptors by polymethoxylated flavonoids.

Tangeretin and nobiletin are polymethoxylated flavonoids in citrus peel. Both tangeretin and nobiletin are bitter; however, their bitterness has not been evaluated using human bitter taste receptors (hTAS2Rs). We screened 25 kinds of hTAS2Rs and found that hTAS2R14 and hTAS2R46 received both compounds.

Multidrug-resistant IgA Vasculitis with Gastrointestinal Symptoms Successfully Treated with Intravenous Cyclophosphamide and Maintained with Mycophenolate Mofetil.

We present the case of a 17-year-old woman with IgA vasculitis (IgAV) who presented with relapsing gastrointestinal (GI) symptoms that were refractory to glucocorticoid and combination therapy with cyclosporine A, azathioprine or mycophenolate mofetil (MMF). The patient responded well to remission induction with intravenous cyclophosphamide (IVCY) and was successfully maintained with MMF. Remission induction with IVCY followed by maintenance therapy with MMF was effective in a patient with multidrug-resistant IgAV with GI lesions.

Improvement in Processability for Injection Molding of Bisphenol-A Polycarbonate by Addition of Low-Density Polyethylene.

The rheological properties and processability at injection molding were studied for bisphenol-A polycarbonate (PC) that was modified by low-density polyethylene (LDPE) having a low shear viscosity. The LDPE addition significantly decreased the steady-state shear viscosity, especially in the high shear rate region. The decrease did not originate from slippage on the die wall but due to interfacial slippage between the PC and dispersed LDPE droplets that deformed to the flow direction to a great extent. As a result of the viscosity decrease, injection pressure largely decreased from 150 to 110 MPa with the addition only 5 wt.% of LDPE. The enhanced flowability also reduced the warpage of the molded product significantly, demonstrating that the processability at injection molding was improved by the addition of LDPE.

Coevolution of Myoelectric Hand Control under the Tactile Interaction among Fingers and Objects.

The usability of a prosthetic hand differs significantly from that of a real hand. Moreover, the complexity of manipulation increases as the number of degrees of freedom to be controlled increases, making manipulation with biological signals extremely difficult. To overcome this problem, users need to select a grasping posture that is adaptive to the object and a stable grasping method that prevents the object from falling. In previous studies, these have been left to the operating skills of the user, which is extremely difficult to achieve. In this study, we demonstrate how stable and adaptive grasping can be achieved according to the object regardless of the user's operation technique. The required grasping technique is achieved by determining the correlation between the motor output and each sensor through the interaction between the prosthetic hand and the surrounding stimuli, such as myoelectricity, sense of touch, and grasping objects. The agents of the 16-DOF robot hand were trained with the myoelectric signals of six participants, including one child with a congenital forearm deficiency. Consequently, each agent could open and close the hand in response to the myoelectric stimuli and could accomplish the object pickup task. For the tasks, the agents successfully identified grasping patterns suitable for practical and stable positioning of the objects. In addition, the agents were able to pick up the object in a similar posture regardless of the participant, suggesting that the hand was optimized by evolutionary computation to a posture that prevents the object from being dropped.

Fluttering cord-like thrombus in the aortic arch.

BACKGROUND: The optimal treatment for aortic thrombus remains to be determined, but surgical treatment is indicated when there is a risk for thromboembolism. CASE PRESENTATION: A 47-year-old male presented with weakness in his left arm upon awakening. Contrast-enhanced computed tomography and transesophageal echocardiography revealed a mobile pedunculated object suggestive of a thrombus arising from the ascending aorta and extending to the left common carotid artery. It was removed under hypothermic circulatory arrest and direct cannulation of the left carotid artery to avoid carotid thromboembolism. Histopathological examination revealed that the object was a thrombus. The patient had an uneventful postoperative course and was discharged 9 days after surgery. CONCLUSION: When a thrombus in the aortic arch extends to the neck arteries, direct cannulation of the neck arteries with selective cerebral perfusion via cervical incision is a useful technique.

Clinical features and serum cytokine profiles of elderly-onset adult-onset Still's disease.

Recent studies have suggested that the clinical features of elderly-onset adult-onset Still's disease (AOSD) differ from those of young and middle-aged-onset patients, whereas the details remain unclear, and cytokine profiles of elderly-onset AOSD have not been reported. To clarify the clinical features and cytokine profiles of elderly-onset AOSD, we examined patients with AOSD who developed the disease between January 2006 and September 2021. We divided the patients into the young and middle-aged-onset group (aged < 65 years) and the elderly-onset group (aged ≥ 65 years) and compared the groups in terms of patient characteristics, clinical symptoms, laboratory findings including serum interleukin (IL)-6 and IL-18, treatment, and prognosis. A total of 48 patients were examined (10 in the elderly-onset group). In the elderly-onset group, atypical rash was significantly more frequent, typical rash and splenomegaly were significantly less frequent, white blood cell count and neutrophil ratio were significantly higher and serum IL-6 levels were significantly lower. Serum IL-6 showed a significantly negative correlation with age at onset. Treatment and relapse were comparable between the 2 groups, whereas infections were significantly more frequent in the elderly-onset group. The clinical features and cytokine profiles of elderly-onset AOSD might differ from those of young and middle-aged-onset AOSD.

Impact of dialysis in patients undergoing bioprosthetic aortic valve replacement.

OBJECTIVES: To determine the incidence of bioprosthetic structural valve deterioration in dialysis patients undergoing aortic valve replacement compared to that in patients without dialysis. METHODS: This single-centre retrospective observational study included 1159 patients who underwent aortic valve replacement using bioprosthetic valves for aortic stenosis and/or regurgitation at our institution between 2007 and 2017 [patients with dialysis (group D, n = 134, 12%) or without dialysis (group N, n = 1025, 88%)]. To adjust for potential differences between groups in terms of initial preoperative characteristics or selection bias, a propensity score analysis was conducted. The final sample that was used in the comparison included 258 patients, as follows: 129 patients with dialysis (group D) and 129 patients without dialysis (group N). The cumulative incidences of all-cause death, cardiac death and moderate or severe structural valve deterioration were estimated using the Kaplan-Meier method. RESULTS: Operative mortality was significantly higher in group D than group N (9% vs 0%, P = 0.001). Kaplan-Meier analysis revealed that in group D, the incidence was significantly higher for all-cause death (P < 0.001, 50% vs 18% at 5 years), cardiac death (P = 0.001, 18% vs 5% at 5 years) and moderate or severe structural valve deterioration (P < 0.001, 29% vs 5% at 5 years) compared with group N. CONCLUSIONS: The incidence of structural valve deterioration in dialysis patients undergoing aortic valve replacement was higher than that in patients without dialysis. Bioprosthetic valves should be carefully selected in dialysis patients undergoing aortic valve replacement.

Observation of crystallisation dynamics by crystal-structure-sensitive room-temperature phosphorescence from Au(I) complexes.

The aggregation behaviour of Au(I) complexes in condensed phases can affect their emission properties. Herein, aggregation-induced room-temperature phosphorescence (RTP) is observed from the crystals of trinuclear Au(I) complexes. The RTP is highly sensitive to the crystal structure, with a slight difference in the alkyl side chains causing not only a change in the crystal structure but also a shift in the RTP maximum. Furthermore, in nanocrystals, reversible RTP colour changes are induced by phase transitions between crystal polymorphs during crystal growth from solution or the pulverisation of bulk crystals. The colour change mechanism is discussed in terms of intermolecular interactions in the crystal structure of the luminescent aggregates. The results suggest that the behaviour in nanocrystals may differ from that in bulk crystals. These insights will advance the fundamental understanding of crystallisation mechanisms and may aid in the discovery of new materials properties for solids with nano- to micrometre sizes.

¹°6Ruthenium plaque therapy (RPT) for retinoblastoma.

PURPOSE: To evaluate the effectiveness of episcleral ¹°6ruthenium plaque therapy (RPT) in the management of retinoblastoma. METHODS AND MATERIALS: One hundred one RPTs were retrospectively analyzed that were performed in 90 eyes of 85 patients with retinoblastoma at National Cancer Center Hospital between 1998 and 2008. Each RPT had a corresponding tumor and 101 tumors were considered in the analysis of local control. Median follow-up length was 72.8 months. Median patient age at the RPT was 28 months. Median prescribed doses at reference depth and outer surface of the sclera were 47.4 Gy and 162.3 Gy, respectively. RESULTS: Local control rate (LCR) and ocular retention rate (ORR) at 2 years were 33.7% and 58.7%, respectively. Unilateral disease, International Classification of Retinoblastoma group C or more advanced at the first presentation or at the time of RPT, vitreous and/or subretinal seeding, tumor size greater than 5 disc diameter (DD), reference depth greater than 5 mm, dose rate at reference depth lower than 0.7 Gy/hour, dose at the reference depth lower than 35 Gy, and (biologically effective dose with an α/ß ratio of 10 Gy) at the reference depth lower than 40 Gy(10) were associated with unfavorable LCR. Two patients died of metastatic disease. Radiation complications included retinal detachment in 12 eyes (13.3%), proliferative retinopathy in 6 (6.7%), rubeosis iris in 2 (2.2%), and posterior subcapsular cataract in 23 (25.6%). CONCLUSION: RPT is an effective eye-preserving treatment for retinoblastoma.