Detection of Pancreatitis and Protein-Losing Gastroenteropathy Associated With Systemic Lupus Erythematosus by Protein Leakage Scintigraphy.

Systemic lupus erythematosus (SLE) rarely causes pancreatitis and/or protein-leakage gastroenteropathy as a gastrointestinal (GI) manifestation. Here, we describe the incidental detection of SLE-associated pancreatitis by protein leakage scintigraphy.

Nanopore DNA Sequencing Detected Chromothripsis-Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma.

An aneurysmal bone cyst (ABC) is a benign bone neoplasm that typically occurs during the first and second decades of life. ABC usually presents as a rapidly growing intramedullary expansile mass with multiple blood-filled cysts in the metaphysis of the long tubular bones. Here, we report a case of a periosteal solid ABC that was initially diagnosed as a high-grade surface osteosarcoma. A 10-year-old male was referred to our hospital for swelling and tenderness of the left upper arm. Radiography revealed periosteal mass without fluid-fluid levels. On performing open biopsy, the tumor showed hypercellular proliferation of uniform spindle to epithelioid cells with brisk mitotic activity (up to 12/2 mm2) and lace-like osteoid formation, which was diagnosed as a high-grade surface osteosarcoma. After one course of chemotherapy using adriamycin and cisplatin, peripheral sclerosis was conspicuous, which led to pathological review and revision of diagnosis as "possibly osteoblastoma." The patient was disease-free for 4 years after marginal resection and curettage. Retrospective nanopore DNA sequencing unexpectedly detected a PAFAH1B1::USP6 rearrangement. The fusion gene was further validated using reverse transcription-polymerase chain reaction and the diagnosis was revised to ABC. Chromothripsis involving chromosome 17 has also been identified. Methylation analysis classified the present tumor as an ABC or non-ossifying fibroma using t-distributed stochastic neighbor embedding and unsupervised hierarchical clustering. This case report highlights the utility of nanopore DNA sequencing for soft tissue and bone tumor diagnosis.

Fluorescence in situ hybridization-negative intra-articular myxoid liposarcoma with complex rearrangements involving EWSR1::DDIT3 detected using nanopore sequencing.

Myxoid liposarcoma (MLPS) is a rare sarcoma, typically arising in deep soft tissues during the fourth to fifth decades of life. Histologically, MLPS is composed of uniform oval cells within a background of myxoid stroma and chicken-wire capillaries. Genetically, MLPS is characterized by the FUS/EWSR1::DDIT3 fusion gene, which generally results from balanced interchromosomal translocation and is detectable via DDIT3 break-apart fluorescence in situ hybridization (FISH). Here, we report an unusual intra-articular MLPS case, negative for DDIT3 break-apart FISH but positive for EWSR1::DDIT3. An 18-year-old female was referred to our hospital complaining of an intra-articular mass in the right knee joint. Histologically, the tumor was mainly composed of mature adipocytes, brown fat-like cells, and lipoblasts. Nanopore sequencing detected DNA rearrangements between EWSR1 and DDIT3 and clustered complex rearrangements involving multiple chromosomes, suggesting chromoplexy. Methylation classification using random forest, t-distributed stochastic neighbor embedding, and unsupervised hierarchical clustering correctly classified the tumor as MLPS. The copy number was almost flat. The TERT promoter C-124T was also detected. This report highlights, for the first time, the potential value of a fast and low-cost nanopore sequencer for diagnosing sarcomas.

A Case of Systemic Chemotherapy With Paclitaxel/Cisplatin Followed by Wide Local Vulvectomy in Pelvic Lymph Nodes-Related Stage IVB Vulvar Cancer.

Multimodality treatments, including chemotherapy, radiation, and surgery, have been evaluated to reduce the extent of resection and morbidity in patients with advanced vulvar cancer. Here, we report the case of a 55-year-old woman diagnosed with advanced vulvar cancer with inguinal and pelvic lymph node metastasis. She exhibited cancerous labia, which were entirely covered with ulcerated and exophytic lesions of squamous cell carcinoma, and underwent systemic chemotherapy consisting of combined paclitaxel-cisplatin. After eight cycles of this regimen, the tumors had nearly regressed, and we performed a wide local vulvectomy with a plastic musculocutaneous flap. Pathological examination revealed no residual carcinoma in the excised labia, indicating that the chemotherapy elicited a pathological complete response. The paclitaxel-cisplatin regimen may provide sufficient efficacy for selected patients with stage IVB vulvar cancer. In addition, surgical strategies should be tailored to avoid complications associated with extensive surgery and more emphasis should be placed on the patient's expected quality of life.

Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing.

Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast-like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton-type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26-year-old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography-computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31-positive atypical spindle cells proliferated in slit-like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide-resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected CD63::PRKCD fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.

Calcium pyrophosphate crystal arthritis associated with immune checkpoint inhibitor successfully treated with intra-articular glucocorticoid: A case report.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated cystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.

The diagnostic utility of cytology specimen in a case of EWSR1::NFATC2 sarcoma.

EWSR1::NFATC2 sarcoma, a rare round cell sarcoma constituting the majority of EWSR1::non-ETS sarcomas, has recently been defined in the latest WHO classification. To date, the cytological findings of EWSR1::NFATC2 sarcoma remain undocumented. We present the case of a 25-year-old man with a history of polyostotic fibrous dysplasia in the right leg, referred to our hospital with left thigh pain. Cytological findings included metachromasia, minimally pleomorphic round cells, and eosinophilic infiltration. There was no precursor fibrous dysplasia and the initial diagnosis was undifferentiated pleomorphic sarcoma. Following histologic review, we successfully performed immunocytochemistry and fluorescence in situ hybridization (FISH) on archival cytology specimens. The tumor cells were positive for NKX2-2, NKX3-1, and PAX7 and showed amplified 5' single signals of EWSR1 gene. Reverse transcriptase-polymerase chain reaction revealed an in-frame fusion of EWSR1 and NFATC2. This report describes the cytological features of EWSR1::NFATC2 sarcoma and highlights the diagnostic utility of archival cytology specimens.

Single-cell RNA sequencing of submandibular gland reveals collagen type XV-positive fibroblasts as a disease-characterizing cell population of IgG4-related disease.

OBJECTIVES: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with an unknown etiology, affecting single/multiple organ(s). Pathological findings include the infiltration of IgG4-producing plasma cells, obliterative phlebitis, and storiform fibrosis. Although immunological studies have shed light on the dysregulation of lymphocytes in IgG4-RD pathogenesis, the role of non-immune cells remains unclear. This study aimed to investigate the demographics and characteristics of non-immune cells in IgG4-RD and explore potential biomarkers derived from non-immune cells in the sera. METHODS: We conducted single-cell RNA sequence (scRNA-seq) on non-immune cells isolated from submandibular glands of IgG4-RD patients. We focused on fibroblasts expressing collagen type XV and confirmed the presence of those fibroblasts using immunohistochemistry. Additionally, we measured the levels of collagen type XV in the sera of IgG4-RD patients. RESULTS: The scRNA-seq analysis revealed several distinct clusters consisting of fibroblasts, endothelial cells, ductal cells, and muscle cells. Differential gene expression analysis showed upregulation of COL15A1 in IgG4-RD fibroblasts compared to control subjects. Notably, COL15A1-positive fibroblasts exhibited a distinct transcriptome compared to COL15A1-negative counterparts. Immunohistochemical analysis confirmed a significant presence of collagen type XV-positive fibroblasts in IgG4-RD patients. Furthermore, immune-suppressive therapy in active IgG4-RD patients resulted in decreased serum levels of collagen type XV. CONCLUSIONS: Our findings suggest that collagen type XV-producing fibroblasts may represent a disease-characterizing non-immune cell population in IgG4-RD and hold potential as a disease-monitoring marker.

Molecular and Morphological Assessment of Juvenile and Adult Forms in the Giant Worm Eunice Cf. Aphroditois (Annelida: Eunicidae) and Its Phylogenetic Position in the Family.

Eunice aphroditois (Pallas, 1788) is a large polychaete worm (up to 3 m in length) and the type species of the genus. In Japan, a similar but potentially different species, Eunice cf. aphroditois, is distributed mainly in the rocky shores of the temperate and warm Pacific coasts. Juveniles and adults were suggested to be distinguished by their body color. The juvenile form was previously regarded as distinct species, Eunice flavopicta Izuka, 1912 and Eunice ovalifera Fauvel, 1936, although they are now considered synonymous with E. aphroditois. In this study, we revisited the validity of the present taxonomy based on morphological observations including SEM and microCT, and three molecular markers (cytochrome c oxidase subunit I [COI], 16S rRNA, and histone H3 genes) and investigated the phylogenetic position of E. cf. aphroditois in the family Eunicidae using the combined dataset of three genes (COI + 16S rRNA + 18S rRNA). The adult and juvenile forms were different in body size, color, the distribution of the branchiae and subacicular hooks, and maxillae shape, but not in other characteristics. One individual showed an intermediate body color between the two forms. The adult and juvenile forms shared major haplotypes and the maximum K2P genetic distance of COI was 1.7%, which can be considered within intraspecific variation. In the phylogenetic tree based on the combined gene dataset, E. cf. aphroditois was closely related to Eunice roussaei Quatrefages, 1866 and Eunice cf. violaceomaculata Ehlers, 1887, which are large species from the Mediterranean Sea and the Caribbean Sea, respectively.

Multi-focusing surface-emitting lasers.

Complete control of a beam pattern requires not only projecting a two-dimensional (2D) pattern but also focusing on a three-dimensional (3D) point cloud, which is typically achieved utilizing holography under the framework of diffraction. We previously reported direct focusing from on-chip size surface-emitting lasers that utilize a holographically modulated photonic crystal cavity based on 3D holography. However, this demonstration was of the simplest 3D hologram with a single point and single focal length, and the more typical 3D hologram with multiple points and multiple focal lengths has not yet been examined. Toward direct generation of a 3D hologram from the on-chip size surface-emitting laser, we here examined a simple 3D hologram featuring two different focal lengths with a single off-axis point in each to reveal the fundamental physics. Two types of holography, one based on superimposition and the other on random tiling, successfully demonstrated the desired focusing profiles. However, both types caused a spot noise beam in the far field plane due to interference between focusing beams with different focal lengths, especially in the case of the superimposing method. We also found that the 3D hologram based on the superimposing method consisted of higher order beams including the original hologram due to the manner of the holography. Secondly, we demonstrated a typical 3D hologram with multiple points and focal lengths and successfully showed the desired focusing profiles by both methods. We believe our findings will bring innovation to mobile optical systems and pave the way to developing compact optical systems in areas such as material processing, micro fluidics, optical tweezers, and endoscopy.

1.5†µm wavelength NPN-type photonic-crystal surface-emitting laser exceeding 100 mW.

A 1.5 µm laser diode has applications in eye-safe light detection and ranging (LiDAR) and optical communications via photonic integrated circuits. Photonic-crystal surface-emitting lasers (PCSELs) have lens-free applications in compact optical systems because of narrow beam divergences (<1 degree). However, the output power has still been less than 1 mW for 1.5 µm PCSELs. For higher output power, one approach is suppression of p-dopant Zn diffusion in the photonic crystal layer. Therefore, n-type doping was used for the upper crystal layer. Moreover, an NPN-type PCSEL structure was proposed to reduce intervalence band absorption in the p-InP layer. Here, we demonstrate a 1.5 µm PCSEL with 100 mW output power, which exceeds previous reported values by two orders of magnitude.

On-chip size, low-noise fringe pattern projector offering highly accurate 3D measurement.

Fringe pattern projectors are quite useful for highly accurate three-dimensional (3D) measurement when a projector or LED array is used for illumination. We have fabricated a 0.2 mm × 0.2 mm structured light source, which was an on-chip size surface-emitting laser that utilized a holographically modulated two-dimensional (2D) photonic crystal (PC). This will make possible an extremely compact 3D measurement system that will positively impact mobile systems. However, the fringe pattern tends to cause speckle-like noise that leads to severe positional error in 3D measurement. Here we present a simple approach to projecting a low-noise fringe pattern from our surface-emitting lasers by using a one-dimensional (1D) focusing hologram. This method improves the flatness of the fringe pattern by around four times.

Proportion of subsequent clinic visits among persons without regular clinic visits who were screened as having hyperglycemia: A retrospective cohort study.

AIMS/INTRODUCTION: We aimed to examine the proportion of subsequent clinic visits for persons screened as having hyperglycemia based on glycated hemoglobin (HbA1c) levels at screening and the presence/absence of hyperglycemia at health checkups before 1 year of the screening among those without previous diabetes-related medical care and attending regular clinic visits. MATERIALS AND METHODS: This retrospective cohort study used the 2016-2020 data of Japanese health checkups and claims. The study analyzed 8,834 adult beneficiaries aged 20-59 years without regular clinic visits who had never received diabetes-related medical care and whose recent health checkups showed hyperglycemia. The rates of 6-month subsequent clinic visits after health checkups were evaluated according to HbA1c levels and the presence/absence of hyperglycemia at checkups a year before. RESULTS: The overall clinic visit rate was 21.0%. The HbA1c-specific rates were 17.0, 26.7, 25.4 and 28.4% for <7.0, 7.0-7.4, 7.5-7.9 and ≥8.0% (64 mmol/mol), respectively. Persons with hyperglycemia at a previous screening had lower clinic visit rates than those without hyperglycemia, particularly in the HbA1c category of <7.0% (14.4% vs 18.5%; P < 0.001) and 7.0-7.4% (23.6% vs 35.1%; P < 0.001). CONCLUSIONS: The overall rate of subsequent clinic visits among those without previous regular clinic visits was <30%, including for participants with HbA1c ≥8.0%. Persons with previously detected hyperglycemia had lower clinic visit rates, despite requiring more health counseling. Our findings might be useful for designing a tailored approach to encourage high-risk individuals to seek diabetes care through clinic visits.

Relationship of systemic type I interferon activity with clinical phenotypes, disease activity, and damage accrual in systemic lupus erythematosus in treatment-naive patients: a retrospective longitudinal analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is heterogeneous in organ involvement and disease severity, presenting a broad clinical phenotype. Systemic type I interferon (IFN) activity has been shown to be associated with lupus nephritis, autoantibodies, and disease activity in treated SLE patients; however, these relationships are unknown in treatment-naive patients. We aimed to determine the relationship of systemic IFN activity with clinical phenotypes, disease activity, and damage accrual in treatment-naive SLE patients before and after induction and maintenance therapy. METHODS: Forty treatment-naive SLE patients were enrolled for this retrospective longitudinal observational study to examine the relationship between serum IFN activity and clinical manifestations of EULAR/ACR-2019 criteria domains, disease activity measures, and damage accrual. As controls, 59 other treatment-naive rheumatic disease patients and 33 healthy individuals were recruited. Serum IFN activity was measured by WISH bioassay and presented as an IFN activity score. RESULTS: Treatment-naive SLE patients had significantly higher serum IFN activity than other rheumatic disease patients (score: 97.6 and 0.0, respectively, p < 0.001). High serum IFN activity was significantly associated with fever, hematologic disorders (leukopenia), and mucocutaneous manifestations (acute cutaneous lupus and oral ulcer) of EULAR/ACR-2019 criteria domains in treatment-naive SLE patients. Serum IFN activity at baseline significantly correlated with SLEDAI-2K scores and decreased along with a decrease in SLEDAI-2K scores after induction and maintenance therapy (R2 = 0.112, p = 0.034). SLE patients who developed organ damage (SDI ≥ 1) had higher serum IFN activity at baseline than those who did not (SDI = 0) (150.0 versus 57.3, p= 0.018), but the multivariate analysis did not detect its independent significance (p = 0.132). CONCLUSIONS: Serum IFN activity is characteristically high and is linked to fever, hematologic disorders, and mucocutaneous manifestations in treatment-naive SLE patients. Serum IFN activity at baseline correlates with disease activity and decreases in parallel with a decrease in disease activity after induction and maintenance therapy. Our results suggest that IFN plays an important role in the pathophysiology of SLE and that serum IFN activity at baseline may be a potential biomarker for the disease activity in treatment-naive SLE patients.

Antiphospholipid antibody positivity and the thrombotic risk in Japanese patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: It has been reported that 21.0-51.7% of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) patients were antiphospholipid antibody (aPL)-positive. However, the clinical significance of aPL positivity in AAV is not fully understood. METHODS: We retrospectively assessed patients with AAV diagnosed from 2013 to 2020 at our hospital. Positivity of aPL was defined as positivity of anti-cardiolipin antibody, anti-cardiolipin ß2 glycoprotein 1 complex antibody, and/or lupus anticoagulant at least one time during the follow-up periods. The thrombotic risk of aPL positivity was examined by multivariate analyses with the Cox regression model. RESULTS: A total of 93 patients with a median age of 71.9 years were included in the study. The median follow-up period was 35.4 months. Thirty-one patients (33.3%) were aPL-positive. Twenty-two thrombotic events occurred in 17 patients (18.3%). Thrombotic events occurred more frequently in aPL-positive patients than in aPL-negative patients (P = 0.011). Multivariate analyses with two different models identified aPL positivity as a thrombotic risk factor (hazard ratios 4.302 and 5.956, 95% confidence intervals 1.546-11.968 and 1.940-18.281, respectively). CONCLUSIONS: The proportion of aPL-positive patients was 33.3%, and aPL positivity increased the thrombotic risk in Japanese patients with AAV.

Anti-RANKL Inhibits Thymic Function and Causes DRONJ in Mice.

Background: Denosumab, a human monoclonal antibody against receptor activator of nuclear factor-kappa B ligand (RANKL), is a novel bone antiresorptive agent used in patients with osteoporosis or metastatic bone cancer. Denosumab-related osteonecrosis of the jaw (DRONJ) has been recently reported in patients using denosumab. However, the mechanisms of DRONJ are not fully understood. Appropriate pathogenic mechanisms of DRONJ have yet to be established. Therefore, we investigated the pathogenesis of DRONJ in mice. Methods: Anti-mouse RANKL monoclonal antibody and melphalan were performed to create a mouse model of DRONJ-like lesions in female C57BL/6J mice. We examined the development of DRONJ-like lesions and immune function. Results: We showed that administration of anti-mouse RANKL monoclonal antibody and melphalan caused DRONJ-like lesions that recapitulated major clinical manifestations of the human disease, including the characteristic features of an open alveolar socket and exposed necrotic bone. In the analysis using a mouse model of DRONJ-like lesion, it was revealed that anti-mouse RANKL monoclonal antibody and melphalan suppress autoimmune regulator (AIRE) expression in the thymus and imbalanced T cell populations. Conclusion: This study suggests evidence of an immunity-based mechanism of DRONJ-like disease. This work may contribute to a better understanding of the pathogenesis of human DRONJ.

Direct-focusing surface-emitting laser.

Focusing is a fundamental optical technique that has been widely implemented via lenses. Here, we demonstrate direct focusing from a band-edge surface-emitting laser, whose emission area is 200 µm × 200 µm, without any lenses. To achieve this, a phase-modulating layer is incorporated into the laser cavity. This layer acts simultaneously as a lasing cavity similar to that of a photonic crystal laser and as a holographic spatial-phase modulator, which transforms the output beam into a focusing beam by slightly shifting the positions of holes from a periodic square lattice. Beam profiles along the surface normal clearly show that direct focusing occurs with a focal length and focal spot size of 310 µm and 6.1 µm, respectively. The focal length agrees well with the theoretical value, and the focal spot size is 2.0 times the diffraction-limited size, which indicates that the higher transverse modes are sufficiently suppressed. In addition, the power density at the focus is 540 times higher than that at the near-field plane. Interestingly, a focus pattern is also observed in the opposite direction at the near-field plane, which indicates that a converging beam and a diverging beam are simultaneously emitted because of the nature of the in-plane band-edge laser. The conventional beam patterns of semiconductor laser cavities are limited to the regime of two-dimensional projection based on a Fourier hologram. In contrast, we demonstrate the simplest form of a three-dimensional point cloud based on a Fresnel hologram, which is quite useful for micro-sensing applications such as microfluidics, flow cytometry, blood sensors, and endoscopy.

Latent class analysis of 216 patients with adult-onset Still's disease.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease which encompasses patients with heterogenous presentation and a wide range of clinical courses. In this study, we aimed to identify potential subgroups of AOSD and reveal risk factors for relapse. METHODS: We included a total of 216 AOSD patients who received treatment in nine hospitals between 2000 and 2019. All patients fulfilled the Yamaguchi classification criteria. We retrospectively collected information about baseline characteristics, laboratory tests, treatment, relapse, and death. We performed latent class analysis and time-to-event analysis for relapse using the Cox proportional hazard model. RESULTS: The median age at disease onset was 51.6 years. The median follow-up period was 36.8 months. At disease onset, 22.3% of the patients had macrophage activation syndrome. The median white blood cell count was 12,600/µL, and the median serum ferritin level was 7230 ng/mL. Systemic corticosteroids were administered in all but three patients (98.6%) and the median initial dosage of prednisolone was 40mg/day. Ninety-six patients (44.4%) were treated with concomitant immunosuppressants, and 22 (10.2%) were treated with biologics. Latent class analysis revealed that AOSD patients were divided into two subgroups: the typical group (Class 1: 71.8%) and the elderly-onset group (Class 2: 28.2%). During the follow-up period, 13 of 216 patients (6.0%) died (12 infections and one senility), and 76 of 216 patients (35.1%) experienced relapses. Overall and relapse-free survival rates at 5 years were 94.9% and 57.3%, respectively, and those rates were not significantly different between Class 1 and 2 (p=0.30 and p=0.19). Time-to-event analysis suggested higher neutrophil count, lower hemoglobin, and age ≥65 years at disease onset as risk factors for death and age ≥65 years at disease onset as a risk factor for relapse. CONCLUSIONS: AOSD patients were divided into two subgroups: the typical group and the elderly-onset group. Although the survival of patients with AOSD was generally good, the patients often experienced relapses. Age ≥65 years at disease onset was the risk factor for relapse.

Associations of ultrasound-based inflammation patterns with peripheral innate lymphoid cell populations, serum cytokines/chemokines, and treatment response to methotrexate in rheumatoid arthritis and spondyloarthritis.

OBJECTIVES: We aimed to explore the associations of musculoskeletal inflammation patterns with peripheral blood innate lymphoid cell (ILC) populations, serum cytokines/chemokines, and treatment response to methotrexate in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We enrolled 100 patients with either RA or SpA and performed ultrasound to evaluate power Doppler signals for synovitis (52 joint regions), tenosynovitis (20 tendons), and enthesitis (44 sites). We performed clustering analysis using unsupervised random forest based on the multi-axis ultrasound information and classified the patients into groups. We identified and counted ILC1-3 populations in the peripheral blood by flow cytometry and also measured the serum levels of 20 cytokines/chemokines. We also determined ACR20 response at 3 months in 38 patients who began treatment with methotrexate after study assessment. RESULTS: Synovitis was more prevalent and severe in RA than in SpA, whereas tenosynovitis and enthesitis were comparable between RA and SpA. Patients were classified into two groups which represented synovitis-dominant and synovitis-nondominant inflammation patterns. While peripheral ILC counts were not significantly different between RA and SpA, they were significantly higher in the synovitis-nondominant group than in the synovitis-dominant group (ILC1-3: p = 0.0007, p = 0.0061, and p = 0.0002, respectively). On the other hand, clustering of patients based on serum cytokines/chemokines did not clearly correspond either to clinical diagnoses or to synovitis-dominant/nondominant patterns. The synovitis-dominant pattern was the most significant factor that predicted clinical response to methotrexate (p = 0.0065). CONCLUSIONS: Musculoskeletal inflammation patterns determined by ultrasound are associated with peripheral ILC counts and could predict treatment response to methotrexate.

A case of cervical clear cell carcinoma with serous component.

Cervical clear cell carcinoma (CCCC) is rare. This report describes the case of CCCC with a serous component. A 22-year-old woman presented with vaginal bleeding. A cervical tumor was discovered: pelvic magnetic resonance imaging revealed a tumor measuring 46 mm. Radical hysterectomy was performed based on the diagnosis of stage IB2 cervical cancer. After histological examination of the specimen revealed a coexisting invasive clear cell carcinoma (95%) and serous carcinoma (5%), five cycles of nedaplatin and irinotecan therapy were administered as postoperative adjuvant chemotherapy. Local recurrence in the vaginal vault was observed at 7 months after surgery. Radiation therapy and chemotherapy were administered. The patient is alive without evidence of recurrence at 26 months after surgery.