Evaluation of soft tissue profile changes around the nose and upper lip following maxillary anterior alveolar osteotomy with Wassmund and Wunderer technique in Japanese.

PURPOSE: The extent to which maxillary anterior alveolar osteotomy alters the facial profile remains unclear. The present study retrospectively analyzed and evaluated changes in maxillary anterior fragments and soft tissue from the nose to upper lip from pre- to postoperatively in patients who underwent the Wassmund and Wunderer (WW) technique. METHODS: Thirty-seven Japanese patients with maxillary prognathism underwent orthognathic surgery with the WW technique were retrospectively included in the present study. Changes in both hard- and soft-tissue landmarks and correlations between both tissues were evaluated using lateral cephalograms taken immediately before and ≥6 months after orthognathic surgery. RESULTS: The maxillary anterior segment showed predominantly posterior movement, with only slight upward movement. Posterior shift and lingual inclination of the maxillary anterior teeth were prominent. As for soft tissues, the change in the nasal tip was small and posterior change was large in the subnasal and upper lip areas. Nasolabial angle, nasal height, and inclination of nasal tip increased, while upper lip protrusion, nasal tip angle, and philtrum length decreased. Correlations were found between posterior changes in hard tissues and posterior changes in soft tissues. Among these, posterior changes and lingual inclination of the maxillary anterior teeth strongly correlate with posterior changes of the upper lip. CONCLUSION: Posterior shift of the maxillary anterior segment using the WW technique is useful because it can greatly improve the protrusion of the upper lip while minimizing nasal morphological changes, and the positioning of the maxillary anterior teeth may be an important key factor.

Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry.

OBJECTIVE: We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates, and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study. METHODS: Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure (VEXASCAF) assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels, and treatments were also recorded at enrolment and 3 months after enrolment. All exons of UBA1 were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients. RESULTS: Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including 3 deaths, 4 malignancies from two cases, 2 thromboses, and 13 infections (including 4 mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling, and pain) were the most common AEs. CONCLUSIONS: Patients with VEXAS syndrome required high-dose glucocorticoids to achieve remission, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.

Environmental Geomarker to Assess Impact on Hospitalization.

By linking medical real-world data with geographic information, it is possible to evaluate the impact on hospitalization based on these characteristics, such as patient residence information and disease and medical information. In this study, environmental exposure to air pollutants was reported as a risk factor, and predictive models were used to examine factors affecting health. The importance of the characteristics appeared according to the disease, and overall, the patient profile at the time of admission, such as ADL, was shown to be high, but for respiratory diseases, the cumulative concentration of air pollutants NO2, SPM, and NOx for one year before the onset of admission was the top risk factor for long-term hospitalization, suggesting the influence of exposure due to environmental factors.

Cholecystokinin receptor type A are involved in the circadian rhythm of the mouse retina.

The retina is the only organ projecting external light to the suprachiasmatic nucleus. Cholecystokinin receptor type A (Cckar/Cckar) is one of the essential factors for light reception in retinal cells. As there was a lack of literature on the matter, we aimed to elucidate the cause of the time-dependent phase change in clock gene expression. We found that Cckar mRNA expression in retinal cells exhibited diurnal variations. The rhythm of expression of the clock gene Per1/Per2 in retinal cells was altered in Cckar -/- mice. The light sensitivity of retinal cells was evaluated in wild-type mice, which showed c-Fos was activated in the ganglion cell layer more than in the inner granular layer. This increase in the number of c-Fos-positive cells was suppressed by lorglumide, a Cckar antagonist. Treatment of rat retina primary cells with lorglumide suppressed Per2 transcription, which was altered in a time-dependent manner relative to the Per2 expression. Light irradiation studies in Cckar -/- mice did not exhibit an increase in Period expression in the suprachiasmatic nucleus. These results indicate that Cckar is among the factors that regulate the cycle of clock genes on the retina. Cckar knockout attenuates the light responsiveness of suprachiasmatic nucleus and reduces the expression amplitude of Period genes in the retina. Thus, Cckar may contribute to entrainment of the light environment and maintenance of the expression cycle of Period gene, which is one of the core clock genes.

Incidence and clinical course of femoral localized periosteal thickening and atypical femoral fracture over a 10-year period in patients with autoimmune inflammatory rheumatic disease.

Atypical femoral fracture (AFF) is generally a rare complication of long-term use of bisphosphonate (BP); glucocorticoid (GC) use and Asian race are also risk factors. Femoral localized periosteal thickening (LPT, also termed "beaking") of the lateral cortex often precedes AFF. This cohort study investigated the incidence of LPT and AFF and their clinical courses over 10 yr in patients with autoimmune inflammatory rheumatic diseases (AIRDs) treated with BP and GC. The study population consisted of 121 patients with AIRDs taking BP and GC. LPT was screened by X-ray, and the LPT shape was evaluated. Prednisolone (PSL) dose was 10 (8-12) mg/d at enrollment and 9 (6-10) mg/d at the last observation. LPT was evident in 10 patients at enrollment and increased linearly to 31 patients (26%) at the last observation. AFF occurred in 9 femurs of 5 patients with LPT. All patients with AFF had bilateral LPT, and the prevalence of pointed type and LPT height were higher in the AFF-positive group than in the AFF-negative group. AFF occurred before BP discontinuation in 2 patients, 1 yr after BP discontinuation in 1, after BP discontinuation followed by 7 yr of alfacalcidol use in 1, and after switching from alfacalcidol to denosumab in 1. The prevalence rates of AFF and LPT associated with long-term BP use with concomitant use of GC (mostly PSL ≥ 6 mg/d) in Japanese patients with AIRD increased over time. The selection of long-term osteoporosis treatment for LPT-positive patients is difficult in some cases.

The Impact of Dose Calibration Point Differences Between the Treatment Plan and Patient-specific Quality Assurance in Passive Scattering Proton Beam Therapy.

BACKGROUND/AIM: Passive scattering proton beam therapy (PSPT) is performed by taking actual measurements of all pre-designated fields in a treatment plan followed by appropriate adjustments to the prescribed dose. For this reason, it is necessary to ensure precision management of the measurements (patient-specific calibration) in the administration of a planned dose. Therefore, this study investigated the impact on dose distribution in treatment planning when the patient calibration point differs from the normalized point in a treatment plan. PATIENTS AND METHODS: A total of 16 cases were selected, where the patient calibration point and normalized point did not match, and the normalized point used in the treatment plan was changed to the patient calibration point using a treatment planning system (VQA ver. 2.01, HITACHI). At this point, the displacement of the relative dose at the isocenter was estimated as an error owing to the difference compared to the patient calibration point. RESULTS: Overall, the error was within the range of ±1.5%, with the exception of orbit cases. Calibrated points also tended to be lower than the normalized points in the treatment plan. In terms of treatment sites, a greater deviation was observed for head cases. Cases with a large deviation in sites other than the head were attributed to poor flatness within the radiation field owing to a narrower opening of the patient collimator. CONCLUSION: Dose measurement errors in PSPT due to differing calibration points were generally within ±1.5%, with higher deviations observed in head treatments because of complex structures and narrow collimator openings. A γ analysis for significant deviations showed a 98.7% passing rate, suggesting limited overall impact. It is important to select stable calibration points in dosimetry to ensure high precision in dose administration, particularly in complex treatment areas.

Plasma Venetoclax Concentrations in Patients with Acute Myeloid Leukemia Treated with CYP3A4 Inhibitors.

Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML simultaneously administered VEN and CYP3A4 inhibitors require a more appropriate management of drug-drug interactions (DDIs). Here, we report two cases of patients with AML (54-year-old man and 22-year-old woman) administrated VEN and CYP3A4 inhibitors, such as posaconazole, cyclosporine, or danazol. In the first case, we evaluated the appropriateness of timing for adjusting VEN dosage subsequent to the cessation of posaconazole. Consequently, modifying the VEN dosage in conjunction with the cessation of Posaconazole simultaneously may result in elevated plasma VEN levels. In the second case, plasma VEN concentrations were markedly elevated when co-administered with several CYP3A4 inhibitors. Additionally, in vitro assays were conducted for reverse translational studies to analyze CYP3A4 inhibition. CYP3A4 inhibition by combinatorial administration of cyclosporine A and danazol was demonstrated in vitro, which potentially explains the increasing plasma VEN concentrations observed in clinical settings. Although the acquisition of therapeutic effects is a major priority for patients, frequent therapeutic drug monitoring and dosage adjustments considering DDIs would be important factors in chemotherapy.

Development of a simultaneous LC-MS/MS analytical method for plasma: 16 antipsychotics approved in Japan and 4 drug metabolites.

The increased risk of adverse drug reactions due to the concomitant use of antipsychotics is problematic in the treatment of schizophrenia. Therefore, the simultaneous analysis of their plasma concentrations is required. In this study, we developed a simultaneous liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for analyzing plasma antipsychotics approved in Japan for therapeutic drug monitoring (TDM) applications. First, we counted the prescriptions for 16 antipsychotics and concomitant drugs used at the Tohoku University Hospital. LC-MS/MS was used for the simultaneous analysis of 16 antipsychotics and four drug metabolites. This analysis was conducted using a combination of selected reaction monitoring mode and reversed-phase chromatography. Following the examination of the MS/MS and LC conditions, an analytical method validation test was conducted. The developed method was used to analyze plasma antipsychotic levels in patients with schizophrenia. One-third of the patients received treatment with multiple antipsychotics. Under LC-MS/MS conditions, LC separation was performed using a combination of a C18 column and ammonium formate-based mobile phases with a gradient flow. The calibration curves were optimized by adjusting the ion abundance, and 11 compounds met the criteria for intra- and inter-day reproducibility tests. Some stability test results did not meet these criteria; therefore, further investigation is required. The developed method permitted the measurement of all the plasma parameters, including concentrations above the therapeutic range. Therefore, this method may be useful in the daily TDM practice of antipsychotics.

Detection of novel coltivirus-related sequences in Haemaphysalis megaspinosa ticks collected from Kanagawa Prefecture, Japan.

Coltiviruses, belonging to the genus Coltivirus within the family Spinareoviridae, are predominantly tick-borne viruses. Some of these species have been implicated in human diseases; however, their diversity, geographical distribution, and evolutionary dynamics remain inadequately. Therefore, this study was undertaken to explore the phylogenetic evolution of coltiviruses and related viruses. Our results revealed the detection of novel coltivirus-related sequences in adult female Haemaphysalis megaspinosa ticks collected from Kanagawa Prefecture, Japan. Molecular phylogenetic analysis revealed a close association between the sequences and the genome sequences of known coltivirus-related viruses, namely Qinghe tick reovirus and Fennes virus. The putative coltivirus-related virus was tentatively designated the Nakatsu tick virus. This study provides insights into the phylogenetic evolution of coltiviruses and related viruses.

Interstitial Lung Disease With Respiratory Failure After COVID-19 mRNA Vaccination.

A septuagenarian woman developed dyspnea on the day following a fifth vaccination. Just before vaccination, a chest X-ray showed no abnormalities, but after the fifth vaccination, bilateral diffuse ground-glass opacities were detected. Bronchoalveolar lavage revealed a lymphocyte predominance and transbronchial lung biopsy revealed growth of the alveolar epithelium, along with organized polypoid granulation tissues in the alveolar ducts and bronchioles. Despite the administration of corticosteroids, imaging revealed persistent fibrosis, and she required long-term oxygen therapy. Although recent reports indicated that corticosteroids are effective for drug-induced interstitial lung disease related to COVID-19 mRNA vaccination, this case presented a somewhat different clinical manifestation.

A Rare Case of Sphenoid Sinus Hemangioma With Intrasellar and Cavernous Sinus Extension.

Sphenoid sinus hemangiomas are uncommon and pose significant diagnostic challenges due to their rarity and the complex symptoms associated with their critical anatomical location. This report discusses a woman in her 40s who presented with worsening headaches, diplopia, and a sensation of pressure behind her eyes. Diagnostic imaging revealed a lobulated mass in the sphenoid sinus extending into the cavernous sinus and sella, initially mimicking an aggressive neoplastic pathology. However, histopathological examination following endovascular embolization and partial surgical resection confirmed the diagnosis of a cavernous hemangioma. This case highlights the importance of considering hemangiomas in the differential diagnosis of sphenoid sinus masses, especially when patients present with atypical symptoms and imaging shows features such as high vascularity and bone remodeling. The findings emphasize the need for careful diagnostic and therapeutic approaches to effectively manage such cases and differentiate them from more aggressive pathologies.

Acto3D: an open-source user-friendly volume rendering software for high-resolution 3D fluorescence imaging in biology.

Advances in fluorescence microscopy and tissue-clearing have revolutionised 3D imaging of fluorescently labelled tissues, organs and embryos. However, the complexity and high cost of existing software and computing solutions limit their widespread adoption, especially by researchers with limited resources. Here, we present Acto3D, an open-source software, designed to streamline the generation and analysis of high-resolution 3D images of targets labelled with multiple fluorescent probes. Acto3D provides an intuitive interface for easy 3D data import and visualisation. Although Acto3D offers straightforward 3D viewing, it performs all computations explicitly, giving users detailed control over the displayed images. Leveraging an integrated graphics processing unit, Acto3D deploys all pixel data to system memory, reducing visualisation latency. This approach facilitates accurate image reconstruction and efficient data processing in 3D, eliminating the need for expensive high-performance computers and dedicated graphics processing units. We have also introduced a method for efficiently extracting lumen structures in 3D. We have validated Acto3D by imaging mouse embryonic structures and by performing 3D reconstruction of pharyngeal arch arteries while preserving fluorescence information. Acto3D is a cost-effective and efficient platform for biological research.

Association of high disease activity and serum IL-6 levels with the incidence of inflammatory major organ events in Behçet disease: a prospective registry study.

Background: Little is known about the relationship between the disease activity of Behçet disease (BD) and the incidence of inflammatory major organ events. Objectives: In this prospective registry study, we investigated the association between the Behçet Disease Current Activity Form (BDCAF) and incidence of inflammatory major organ events, defined as the inflammation of the ocular, central nervous, intestinal, and vascular systems in BD. Methods: We enrolled participants from Japanese multicenter prospective cohorts. The BDCAF was evaluated annually. BD-related symptoms, including inflammatory major organ events, were monitored. The association between BDCAF and inflammatory major organ events was analyzed by time-to-event analysis. An unsupervised clustering of the participants' BDCAF, therapeutic agents, and multiple serum cytokines was also performed to examine their association with inflammatory major organ events. Results: A total of 260 patients were included. The patients had a median BDCAF score of 2 [Interquartile range, 1-3] at the enrolment and remained disease active at 1- and 2-year follow-ups, indicating residual disease activity in BD. Patients with a BDCAF score of 0 had a longer inflammatory major organ event-free survival at 52 weeks than those with a score of 1 or higher (p=2.2 x 10-4). Clustering analysis revealed that patients who did not achieve remission despite treatment with tumor necrosis factor inhibitors had high serum inflammatory cytokine levels and incidences of inflammatory major organ events. Among the elevated cytokines, IL-6 was associated with inflammatory major organ events. Conclusion: This study suggests that treatment strategies targeting overall disease activity and monitoring residual serum IL-6 may help prevent inflammatory major organ events in BD.

Identification and epidemiological study of an uncultured flavivirus from ticks using viral metagenomics and pseudoinfectious viral particles.

During their blood-feeding process, ticks are known to transmit various viruses to vertebrates, including humans. Recent viral metagenomic analyses using next-generation sequencing (NGS) have revealed that blood-feeding arthropods like ticks harbor a large diversity of viruses. However, many of these viruses have not been isolated or cultured, and their basic characteristics remain unknown. This study aimed to present the identification of a difficult-to-culture virus in ticks using NGS and to understand its epidemic dynamics using molecular biology techniques. During routine tick-borne virus surveillance in Japan, an unknown flaviviral sequence was detected via virome analysis of host-questing ticks. Similar viral sequences have been detected in the sera of sika deer and wild boars in Japan, and this virus was tentatively named the Saruyama virus (SAYAV). Because SAYAV did not propagate in any cultured cells tested, single-round infectious virus particles (SRIP) were generated based on its structural protein gene sequence utilizing a yellow fever virus-based replicon system to understand its nationwide endemic status. Seroepidemiological studies using SRIP as antigens have demonstrated the presence of neutralizing antibodies against SAYAV in sika deer and wild boar captured at several locations in Japan, suggesting that SAYAV is endemic throughout Japan. Phylogenetic analyses have revealed that SAYAV forms a sister clade with the Orthoflavivirus genus, which includes important mosquito- and tick-borne pathogenic viruses. This shows that SAYAV evolved into a lineage independent of the known orthoflaviviruses. This study demonstrates a unique approach for understanding the epidemiology of uncultured viruses by combining viral metagenomics and pseudoinfectious viral particles.

Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of 11C-methionine in IDH-mutant astrocytoma.

PURPOSE: The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and 11C-methionine uptake in astrocytomas with IDH mutations. METHODS: We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent 11C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis. RESULTS: Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88 years vs. 6.80 years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23 years vs. 10.69 years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for 11C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012). CONCLUSION: Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.

Predictability of the National Psychological Stress Screening for Subsequent Long-Term Psychiatric Sick Leave Among Employees: A Multicenter Nested Case-Control Study.

OBJECTIVE: The aim of the study is to predict employees' long-term sick leave due to psychiatric disorders using the national psychological stress screening program. METHODS: University employees who took long-term psychiatric sick leave in 2016-2018 were assigned as cases. Those who were present at work and matched for sex, age, and occupation type were assigned as controls. Answers in a 57-item questionnaire were analyzed by multivariable regression, and a prediction model was developed. It was validated in cases and matched controls in 2019. RESULTS: Six items were identified as independent predictors by multivariable regression and included in a prediction model. The area under the receiver-operating characteristics curve was 0.768 (95% confidence interval: 0.723-0.813). This finding was similar to that in the validation sample. CONCLUSIONS: The performance of the prediction model was modest and the national Stress Check Program should be further refined.

Protocol of a phase II study investigating the efficacy and safety of trifluridine/tipiracil plus ramucirumab as a third-line or later treatment for advanced gastric cancer.

In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m2) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.

Screening and identification of persistent viruses in cell lines derived from medically important arthropods.

Arthropod-derived cell lines serve as crucial tools for studying arthropod-borne viruses (arboviruses). However, it has recently come to light that certain cell lines harbor persistent infections of arthropod-specific viruses, which do not cause any apparent cytopathic effects. Moreover, some of these persistent viral infections either inhibit or promote the growth of arboviruses. Therefore, it is of utmost importance to identify the presence of such persistent viruses and understand their impact on arboviral infections. In this study, we conducted a comprehensive virome analysis of several arthropod-derived cell lines, including mosquito-derived NIID-CTR, Ar-3, MSQ43, NIAS-AeAl-2, CCL-126 cells, and tick-derived IDE8 cells, along with flesh fly-derived NIH-Sape-4 cells. The aim was to determine if these cells were infected with persistent viruses. The results revealed the presence of 15 persistent viruses in NIID-CTR, Ar-3, MSQ43, NIAS-AeAl-2, and IDE8 cells. Among these, 11 were already known arthropod-specific viruses, while the remaining 4 were novel viruses belonging to Orthophasmavirus, Rhabdoviridae, Totiviridae, and Bunyavirales. In contrast, CCL-126 and NIH-Sape-4 cells appeared to be free of viral infections. This study provides valuable insights into the diversity and latency of arthropod-specific viruses within arthropod-derived cell lines. Further investigations are required to explore persistent viral infections in other arthropod-derived cell cultures and their effects on arbovirus replication. Understanding these factors will enhance the accuracy and reliability of experimental data obtained using these cell lines.

Improved Renal Function in Initial Treatment Improves Patient Survival, Renal Outcomes, and Glucocorticoid-Related Complications in IgG4-Related Kidney Disease in Japan.

Introduction: We aimed to clarify long-term renal prognosis, complications of malignancy, glucocorticoid (GC) toxicity, and mortality in immunoglobulin G4 (IgG4)-related kidney disease (IgG4-RKD). Methods: Reviewing the medical records of 95 patients with IgG4-RKD, we investigated clinical and pathologic features at baseline, the course of renal function, complications of malignancy, GC toxicity, and mortality during follow-up (median 71 months). The standardized incidence ratio (SIR) of malignancy and standardized mortality ratio were calculated using national statistics. Factors related to outcomes were assessed by Cox regression analyses. Results: At diagnosis, the median estimated glomerular infiltration rate (eGFR) was 46 ml/min per 1.73 m2. GC achieved initial improvement. Additional renal function recovery within 3-months of initial treatment occurred in patients with highly elevated serum IgG and IgG4 levels and hypocomplementemia. During follow-up, 68%, 17%, and 3% of the patients had chronic kidney disease (CKD), >30% eGFR decline, and end-stage renal disease (ESRD), respectively. Age-adjusted and sex-adjusted Cox regression analyses indicated that eGFR (hazard ratio [HR], 0.71) and extensive fibrosis (HR, 2.58) at treatment initiation had a significant impact on the time to CKD. Ten patients died, and the standardized mortality ratio was 0.94. The SIR of malignancy was 1.52. The incidence rate (IR) of severe infection was 1.80/100 person-years. Cox regression analyses showed that the best eGFR within 3 months after treatment initiation were associated with lower mortality (HR 0.67) and fewer severe infections (HR 0.63). Conclusion: This study suggests that more renal function recovery through early treatment initiation may improve patient survival, renal outcomes, and some GC-related complications in IgG4-RKD.

A Case of Adult-Onset Still's Disease With Hypocomplementemia.

Adult-onset Still's disease (AOSD) causes fever, rash, pharyngalgia, and arthralgia through autoinflammation. Its complement titer has not previously received attention because this usually increases during the inflammatory process. Our female patient in her 60s was admitted to the hospital with fever, rash, arthralgia, and pharyngalgia. Her white blood cell count was 19,130/µL, hemoglobin was 11.0 g/dL, platelet count was 26.0 × 104/µL, and ferritin titer was 6,175 ng/mL. Anti-nuclear antibodies and anti-neutrophil cytoplasmic antibodies were negative. The presence of infectious diseases and malignancies was excluded. She was diagnosed with hypocomplementemia at the onset of AOSD because of her low complement component 4 (C4) titer (<5.0 mg/dL). Her complement component 3 (C3) titer was 104.5 mg/dL, which was within normal limits. There was no sign of thrombotic microangiopathy (TMA) or hemophagocytosis. She was treated with high-dose corticosteroids, including pulse methylprednisolone therapy, cyclosporine, methotrexate, and intravenous immunoglobulin, but was resistant to these, and her disease repeatedly flared up. Treatment with intravenous cyclophosphamide eventually led to remission. Post-treatment, her C4 titer increased to within the normal range. Although hypocomplementemia with TMA or hemophagocytosis has been reported in AOSD patients, our patient showed no sign of either at disease onset. Hypocomplementemia of AOSD may be a sign of high disease activity and could be a predictive marker for resistance to standard therapy.