Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: results from the IORRA cohort.

OBJECTIVES: We aimed to examine the impact of concomitant interstitial lung disease (ILD) on achieving clinical remission and the occurrence of unfavourable clinical events in patients with RA. METHODS: Among the participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from 2011 to 2012, patients not achieving remission of 28-joint disease activity score (DAS28) at baseline and those with chest CT images were enrolled. Based on the chest CT images, the patients were divided into two groups: the ILD group and non-ILD group. The associations among the presence of ILD with time to achieving DAS28 remission and development of death, hospitalized infection, major adverse cardiac events (MACE), or malignancy within 5 years were evaluated using time-dependent Cox regression models. RESULTS: We enrolled 287 patients in the ILD group and 1235 in the non-ILD group. DAS28 remission was achieved at least once in 55.7% and 75.0% of the ILD and non-ILD groups within 5 years, respectively. Presence of ILD was significantly associated with failure to achieve DAS28 remission (adjusted hazard ratio [aHR]: 0.71; 95% CI: 0.58, 0.89). ILD was also a significant factor associated with death (aHR: 3.24; 95% CI: 2.08, 5.03), hospitalized infection (aHR 2.60; 95% CI: 1.77, 3.83), MACE (aHR: 3.40; 95% CI: 1.76, 6.58), and lung cancer (aHR: 16.0; 95% CI: 3.22, 79.2), but not with malignant lymphoma (aHR: 2.27; 95% CI: 0.59, 8.81). CONCLUSION: Concomitant ILD was a significant factor associated with failure to achieve clinical remission and the occurrence of the unfavourable clinical events in patients with RA.

Unincreased mortality of patients with early rheumatoid arthritis compared to the general population in the past 17 years: Analyses from the IORRA cohort.

OBJECTIVES: The aim of this article is to investigate the mortality rate of patients with early rheumatoid arthritis (RA) over the past 17 years. METHODS: Japanese patients with early RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2001 to 2012 were classified into Groups A (2001-06) and B (2007-12). The standardized mortality ratio (SMR) and 5-year survival rate were calculated. RESULTS: Groups A and B had 1609 and 1608 patients, of which 167 and 178 patients were lost during follow-up and 47 and 45 deaths were confirmed, respectively. The SMR (95% confidence intervals) for Groups A and B were 0.81 (0.59-1.08) and 0.78 (0.57-1.04), respectively, with the condition that all untraceable patients were alive. Assuming that the mortality rate of untraceable patients was twice as high as that of the general population, the SMR was 0.90 (0.68-1.19) for Group A and 0.92 (0.68-1.23) for Group B. The 5-year survival rates were 96.9% and 97.0% for Groups A and B, respectively. CONCLUSIONS: The 5-year mortality of patients with early RA has been comparable to that of the general Japanese population. The 5-year survival rate has been stable over the past 17 years.

Impact of craniotomy area on improvement of cerebral blood flow in combined revascularization surgery for moyamoya disease.

OBJECTIVE: To investigate factors associated with improvements in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) after combined revascularization surgery for moyamoya disease, with special attention to the size of craniotomy. METHODS: We retrospectively analyzed 35 hemispheres in 27 patients with adult and older pediatric moyamoya disease. CBF and CVR were measured separately in the MCA and ACA territories from acetazolamide-challenged single-photon emission computed tomography before and after 6 months postoperatively, and associations with various factors were analyzed. RESULTS: Postoperative CBF improved in patients with lower preoperative blood flow in both ACA and MCA territories. Postoperative CVR improved in 32 of 35 patients (91.4%) in the MCA territory and in 30 of 35 patients (85.7%) in the ACA territory, with more prominent improvement in the MCA territory than in the ACA territory (MCA territory 29.7% vs ACA territory 21.1%, p = 0.015). Craniotomy area did not correlate with postoperative CBF and only MCA territory was associated with good (≥30%) CVR improvement (odds ratio 9.33, 95% confidence interval 1.91-45.6, p = 0.003). CONCLUSIONS: Postoperative CBF improved in adult and older pediatric cases, reflecting preoperative CBF. Postoperative CVR improved in most cases, although the degree of improvement was more prominent in the MCA territory than in the ACA territory, suggesting a contribution of the temporal muscle. Large craniotomy area was not associated with improved blood flow in the ACA territory and should be applied prudently.

Evaluation of RABBIT risk score in Japanese patients with rheumatoid arthritis starting first bDMARDs: a validation study using the IORRA cohort data.

OBJECTIVE: To examine the ability of the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk score to predict the occurrence of serious infections in Japanese patients with rheumatoid arthritis (RA), after initiating their first biologic disease-modifying antirheumatic drug (bDMARD). METHODS: We used data from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from 2008 to 2020. Patients with RA who were started on their first bDMARDs were included. Those with missing data required to calculate the score were excluded. A receiver operating characteristic (ROC) curve was used to evaluate the discriminatory ability of the RABBIT score. RESULTS: A total of 1,081 patients were enrolled. During the one-year observational period, 23 (1.7%) patients had serious infections; the most frequent one was bacterial pneumonia (n=11, 44%). The median RABBIT score in the serious infection group was significantly higher than that in the non-serious infection group (2.3 [1.5-5.4] vs 1.6 [1.2-2.5], p<0.001). The area under the ROC curve for the occurrence of serious infections was 0.67 (95% confidence interval 0.52-0.79), suggesting that the score had low accuracy. CONCLUSION: Our present study revealed that the RABBIT risk score did not have sufficient discriminatory ability for predicting the development of severe infections in Japanese patients with rheumatoid arthritis after initiating their first bDMARD.

Trends in risks of malignancies in Japanese patients with rheumatoid arthritis: Analyses from a 14-year observation of the IORRA cohort.

OBJECTIVES: The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA). METHODS: Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000-04; early biologics, 2005-09; and recent biologics, 2010-13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models. RESULTS: Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80-1.14) in the pre-biologics period, 0.95 (0.82-1.09) in the early biologics period, and 0.87 (0.75-1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58-5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer. CONCLUSIONS: Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA.

Impact of concomitant chronic kidney disease on hospitalised infections and remission in patients with rheumatoid arthritis: results from the IORRA cohort.

OBJECTIVES: To investigate the impact of concomitant chronic kidney disease (CKD) on unfavourable clinical events and remission in Japanese patients with rheumatoid arthritis (RA). METHODS: We included 5103 patients with RA and CKD from the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort in 2012. CKD stages were classified into four groups: CKD with normal eGFR ≥60 ml/min/1.73 m2 and proteinuria; mild CKD, eGFR ≥45 to < 60; moderate CKD, eGFR ≥30 to < 45; and severe CKD, eGFR <30. We assessed the association between concomitant CKD and the occurrence of unfavourable clinical events or achieving remission during a 5-year observational period. RESULTS: Of the 5103 patients with RA, 686 (86.6%) had CKD. Concomitant CKD was associated with hospitalised infections [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.07-2.13, p = .02], especially in the moderate to severe CKD group (aHR 1.93, 95% CI 1.12-3.13, p = .02). Of all subjects, 2407 (47.2%) had active RA at baseline and 401 (16.7%) had CKD. Concomitant CKD was also associated with the failure of achieving remission (aHR 0.82, 95% CI 0.68-0.99, p = .04). CONCLUSIONS: Concomitant CKD was a risk factor for hospitalised infections in Japanese patients with RA and failure of achieving remission in patients with active RA.

Differences in patients' population and efficacy/effectiveness of biologic disease-modifying antirheumatic drugs between randomized controlled trials and real-world settings in patients with rheumatoid arthritis - using the IORRA cohort.

OBJECTIVES: To evaluate the differences in patients' population and efficacy/effectiveness of biological disease-modifying antirheumatic drugs (bDMARDs) between randomized controlled trials (RCTs) and clinical practice in patients with rheumatoid arthritis. METHODS: We reviewed inclusion criteria in Phase II or III RCTs of bDMARDs conducted in Japan. The Institute of Rheumatology, Rheumatoid Arthritis study participants during the period when each RCT was conducted (Cohort A) and new bDMARD users at our institute in 2016 (Cohort B) were assessed for the fulfilment of the inclusion criteria. The effectiveness of bDMARDs in our cohort and their efficacy in RCTs were compared using the inverse-variance method. RESULTS: Nineteen RCTs were selected. The mean proportions of patients fulfilling all inclusion criteria of each RCT in Cohorts A and B were 2.3% and 7.6%, respectively. The pooled proportion ratios (95% confidence interval) for achieving the American College of Rheumatology 20 (ACR20), ACR50, ACR70, and disease activity score 28 remission in non-eligible cases for eight RCTs versus all corresponding RCTs were 0.38 (0.30-0.51), 0.41 (0.30-0.57), 0.54 (0.35-0.82), and 1.28 (1.10-1.56), respectively. CONCLUSIONS: Few rheumatoid arthritis patients fulfilled the inclusion criteria of the RCTs in clinical settings. There was a difference in the efficacy/effectiveness of bDMARDs between RCTs and clinical practice.

Risk of herpes zoster in patients with rheumatoid arthritis in the biologics era from 2011 to 2015 and its association with methotrexate, biologics, and corticosteroids.

OBJECTIVES: To elucidate the incidence and risk factors of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) in the biologics era. METHODS: We determined the rate of HZ occurrence among the RA patients that participated in the Institute of Rheumatology, Rheumatoid Arthritis surveys from 2011 to 2015, by assessing medical records. The standardised incidence rate per 1000 patient-years with a 95% confidence interval (CI) was calculated, and risk factors for HZ were analysed using a time-dependent Cox regression analysis. RESULTS: Among 7815 patients (female, 84.7%) contributing to 25,863 patient-years of observation, 340 HZ events in 309 patients were confirmed. The standardised incidence rate (95% CI) per 1000 patient-years was 8.5 (6.9-10.5) in total, 6.0 (3.7-9.2) in men, and 11.0 (8.7-13.7) in women. Risk factors for HZ were age per 10 years (hazard ratio 1.14, 95% CI 1.03-1.26, p < .05), Japanese version of the Health Assessment Questionnaire (J-HAQ) score of 0.5-1.5 (versus J-HAQ = 0; 1.51, 1.09-2.10, p < .05), methotrexate use (1.58, 1.06-2.36, p < .05), and biologic use (1.88, 1.44-2.47, p < .01). CONCLUSIONS: In the era when biologics were frequently used and corticosteroid use and doses were decreasing, methotrexate and biologics increased the risk for HZ.

Effectiveness and safety of subcutaneous abatacept in biologic-naïve RA patients at Week 52: A Japanese multicentre investigational study (ORIGAMI study).

OBJECTIVES: To evaluate the effectiveness and safety of abatacept over 52 weeks in biologic-naïve rheumatoid arthritis (RA) patients with moderate disease activity in the prospective, 5-year, observational study (ORIGAMI study) in Japan. METHODS: Abatacept (125 mg) was administered subcutaneously once a week. Clinical outcomes included Simplified Disease Activity Index (SDAI) remission at Week 52 (primary endpoint), Japanese Health Assessment Questionnaire (J-HAQ), EuroQol 5-Dimension Questionnaire (EQ-5D), treatment retention, and safety. The results were compared with those of conventional synthetic disease-modifying antirheumatic drug (csDMARD) controls from the ongoing Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry. RESULTS: Overall, 325 patients were enrolled, with a mean age of 66.9 ± 12.7 years. The proportion of patients achieving SDAI remission (≤3.3) at Week 52 was 18.9% (95% CI: 14.3-23.6) and low disease activity (≤11) was 53.3% (95% CI: 47.4-59.1). A significant improvement was observed in J-HAQ and EQ-5D over 52 weeks in both the abatacept and csDMARD groups. The probability of abatacept treatment retention at Week 52 was 69.9% (95% CI: 64.7-75.5). Adverse events and serious adverse events were reported in 50.0% and 12.1% of patients, respectively. CONCLUSIONS: Abatacept significantly improved disease activity, physical disability, and quality of life for up to 52 weeks in RA patients in a real-world setting.

Acute Endovascular Revascularization for Patients with Common Carotid Artery Occlusion Apparent on Cervical Magnetic Resonance Angiography.

OBJECTIVES: In the endovascular treatment of acute cerebral large-vessel occlusion, cervical magnetic resonance angiography (MRA) is a useful modality for assessing the access route. However, we sometimes encounter cases in which not only the internal carotid artery (ICA), but also the common carotid artery (CCA) is poorly visualized, leading to hesitation over which devices and techniques to choose for revascularization. We retrospectively evaluated such cases, focusing on image findings and treatment results. MATERIALS AND METHODS: Data from 96 patients who underwent acute endovascular revascularization from January 2016 to December 2019 were analyzed. We extracted patients with poor CCA visualization on cervical MRA from 35 cases with ICA occlusion, and examined angiographic findings, treatment methods, and outcomes. RESULTS: Poor visualization of the CCA in cervical MRA was observed in 8 cases. All cases displayed atrial fibrillation or sick sinus syndrome. Angiographic findings showed true CCA occlusion in 2 patients and ICA occlusion in 6 patients. Reasons for the inability to visualize the CCA on cervical MRA were speculated to be stenosis of the external carotid artery (ECA), presence of embolism in the ECA, or severe heart failure. In cases of true CCA occlusion, thrombus was aspirated using the balloon guide catheter and good recanalization was obtained. Seven of 8 patients displayed favorable recanalization, with good prognosis after 90 days in 5 patients. CONCLUSIONS: Poor CCA visualization on cervical MRA does not necessarily represent true CCA occlusion. Aspiration of thrombus from a balloon guide catheter is effective for true CCA occlusion.

Successful discontinuation of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis in real-world settings.

OBJECTIVES: To analyze the proportion of successful biological disease-modifying antirheumatic drugs (bDMARDs) discontinuation and related factors in patients with rheumatoid arthritis (RA) in clinical settings. METHODS: Among 1775 RA patients who started bDMARDs between 2003 and 2012, 43 patients with DAS28-ESR <3.2 at the time of bDMARD discontinuation were extracted. Patients were divided into two groups (bio-free success: BS and bio-free failure: BF groups) based on bDMARD usage and disease activity 1 year after discontinuation. We evaluated the proportion of bio-free success and assessed factors related to bio-free success. RESULTS: Twenty-five patients (58.1%: BS group) maintained discontinuation of bDMARDs and DAS28-ESR <3.2 at 1 year after discontinuation. The median DAS28-ESR at bDMARD initiation was lower in the BS group than in the BF group (3.95 vs 5.04; p = .04). The BS group experienced a larger decrease in average glucocorticoid (GC) dose during bDMARD use than the BF group (-3.0 mg/day vs 0 mg/day; p = .01). CONCLUSION: bDMARDs were discontinued without flare up of RA in 58.1% of patients with RA in clinical settings. A lower DAS28-ESR at initiation and reduction of GC dose before discontinuation of bDMARD were important factors associated with bio-free success.

Extended endoscopic endonasal resection of craniopharyngioma using intraoperative visual evoked potential monitoring: technical note.

BACKGROUND: To avoid deterioration of visual function, extended endoscopic endonasal transsphenoidal surgery (TSS) for craniopharyngioma was performed with visual evoked potential (VEP) monitoring using light-emitting diodes (LEDs). METHODS: The position of the optic chiasm was carefully evaluated on the preoperative midsagittal magnetic resonance (MR) images. Intraoperatively, direct and sharp dissection of the tumor from the optic chiasm was performed under VEP monitoring with LEDs through extended endoscopic endonasal TSS. If the VEP finding changed and became unstable, the operator were informed and stopped the surgical manipulation for the optic chiasm to recover. After 5-10 min, recovery of VEP findings was checked and the procedure resumed. RESULTS: Extended endoscopic endonasal TSS with VEP monitoring was performed in consecutive 7 adult patients with newly diagnosed suprasellar craniopharyngiomas with maximum diameters of 25-41 mm (mean 33.7 mm). VEPs were stable throughout the surgery in 5 cases, but showed temporary instability and amplitude decrease in 2 cases, although the VEPs had recovered at the end of the surgery. Visual function, evaluated using visual impairment score, was improved after surgery in all patients. Gross total removal was achieved in 5 cases, and subtotal removal (90%) in 2 cases. CONCLUSIONS: Intraoperative VEP monitoring is the only way to test visual function during surgery, and may be important and helpful in extended endoscopic endonasal TSS, which requires direct dissection between the optic nerve and craniopharyngioma under the endoscope.

Combined supra-infrasellar approach to pituitary macroadenoma with oculomotor cistern extension: surgical strategy and experience.

BACKGROUND: Oculomotor cistern extension (OMCE) of pituitary adenoma through the oculomotor triangle may be one of the major characteristics of multi-lobulated adenoma. The OMCE may be hard to remove only through the endonasal approach. METHOD: We applied the simultaneous combined supra-infrasellar approach to remove pituitary adenoma with relatively large OMCE. Four (7.3%) of 55 consecutive patients with initially operated pituitary macroadenoma (> 10 mm) had OMCE. The combined supra-infrasellar approach was adopted in two cases with relatively large OMCE. RESULTS: The simultaneous combined supra-infrasellar approach was performed with the transcranial microscopic transsylvian anterior temporal approach and the nasal endoscopic approach. The medial main mass was removed through the nasal side. The lateral OMCE was also removed through the nasal side by pushing the tumor in the sellar direction from the transcranial side. The oculomotor nerve was confirmed with electrical nerve stimulation. The main medial mass and the OMCE were mostly removed in both cases. Remnant tumor in the cavernous sinus was treated by gamma knife radiosurgery. Endoscopic transsphenoidal removal was performed in the other two cases with relatively small OMCE. CONCLUSIONS: Pituitary macroadenomas with OMCE are a newly recognized form of progression with important implications for surgical strategy. The combined supra-infrasellar approach performed with the transcranial microscopic transsylvian anterior temporal approach using electrical nerve stimulation and the nasal endoscopic approach may be useful for this type of multi-lobulated pituitary adenoma.

Angiographical Jaggy Sign of Remnant M2 Occlusion during Acute Mechanical Thrombectomy.

BACKGROUND AND PURPOSE: During mechanical thrombectomy for acute main trunk occlusion, we sometimes encounter difficult situation; 1 M2 branch of the middle cerebral artery is successfully recanalized, while the other remains occluded. In this study, we focused on the angiographical findings of remnant occlusion. METHODS: Among 83 patients who underwent mechanical thrombectomy for the acute internal carotid artery or proximal middle cerebral artery (M1) occlusion, 25 patients (30%) intraoperatively exhibited the remnant M2 occlusion, in spite of the recanalization of the other M2. We classified the angiographical findings of the remnant M2 occlusion and examined the clinical features, prognosis, and complications, in relation to additional thrombectomy. RESULTS: The remnant M2 occlusion was classified into stump type (40%, 10 cases), round deficit type (28%, 7 cases), and jaggy type (32%, 8 cases). Multivariate analysis suggested that noncardioembolic stroke may lead to jaggy type remnant occlusion with marginal significance (P = .051). Additional thrombectomy for the remnant M2 occlusion resulted in failed recanalization in 6% in the nonjaggy (stump or round deficit) type, whereas in 50% in the jaggy type groups (P = .023). Symptomatic intracranial hemorrhage occurred in 6% in the nonjaggy and 38% in the jaggy groups (P = .081), and poor outcome at discharge in 29% and in 50%, respectively. CONCLUSIONS: Angiographical jaggy sign in the remnant M2 occlusion suggests the pre-existing or procedure-related pathology, such as atherosclerosis, vasospasm, or arterial dissection. Additional thrombectomy should be carefully determined, as which might lead to adverse events and poor outcomes.

Pharmacoeconomic analysis of biological disease modifying antirheumatic drugs in patients with rheumatoid arthritis based on real-world data from the IORRA observational cohort study in Japan.

OBJECTIVES: To evaluate the cost-effectiveness of biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) in a real-world setting in Japan. METHODS: We used a state-transition model and parameters were determined from RA patients registered in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study on 421 patients who had failed at least one DMARD and started either 1 of 4 bDMARDs (bDMARD group; adalimumab, etanercept, infliximab, and tocilizumab) or methotrexate (control group). bDMARD group was evaluated as two groups: sequence of any 1 of 4 bDMARDs with and without tocilizumab. The incremental cost-effectiveness ratios (ICERs) for bDMARD group were estimated using base-case analysis, probabilistic sensitivity analysis (PSA) and scenario sensitivity analyses. RESULTS: ICERs of bDMARD group with or without tocilizumab were $38,179 and $48,855, respectively. By PSA, these sequences had respective probabilities of 86.8% and 75.1% of falling below the assumed cost-effectiveness threshold of $50,000 in Japan. Scenario sensitivity analyses showed that the best population for initiating bDMARD was RA patients less than 50 years old with Japanese version of HAQ between 1.1 and 1.6 and using tocilizumab as the bDMARD. CONCLUSION: bDMARDs were cost-effective for RA patients based on a real-world setting in Japan.

Assessment of the effectiveness of golimumab 50-mg and 100-mg regimens in patients with rheumatoid arthritis in daily practice.

OBJECTIVES: To assess the effectiveness of the golimumab (GLM) 50-mg and 100-mg regimens in patients with rheumatoid arthritis (RA) in daily practice. METHODS: We retrospectively analyzed RA patients who started GLM between September 2011 and July 2012. Patients were divided into three groups: a 50-mg group; a 50/100-mg group (had a dose increase to 100 mg); and a 100-mg group (started GLM at 100 mg). We assessed Disease Activity Score 28 (DAS28) and treatment continuation rate. Risk factors associated with time to discontinuation of the 50-mg regimen were determined with proportional hazards analysis. RESULTS: We analyzed 74 patients: 43 in the 50-mg group, 23 in the 50/100-mg group, and 8 in the 100-mg group. DAS28 improved from 4.0 ± 1.0, 4.8 ± 1.0, and 4.7 ± 1.9, respectively, at baseline to 2.4 ± 1.2, 3.3 ± 1.5, and 2.5 ± 0.7, respectively, at week 52. Treatment continuation rates at week 52 were 73.7%, 60.9%, and 87.5%, respectively. In the 50/100-mg group, the mean DAS28 improved significantly from 4.4 ± 1.2 before to 3.6 ± 1.3 12 weeks after the dose increase. Oral corticosteroid therapy ≥ 5 mg/day, previous use of two biologic agents, and DAS28 > 5.1 at initiation of GLM were significantly associated with discontinuation of the 50-mg regimen. CONCLUSIONS: Both GLM 50-mg and 100-mg regimens are effective in patients with RA in daily practice.

Factors associated with decreasing diffusion-weighted imaging-positive area volume after mechanical thrombectomy in patients with large early ischemic changes.

OBJECTIVES: This study aimed to evaluate the factors associated with decreasing diffusion-weighted imaging (DWI) positive areas in patients with large early ischemic changes after mechanical thrombectomy (MT). MATERIALS AND METHODS: This retrospective single-center clinical study was conducted between January 2013 and December 2022. We included consecutive patients who underwent MT for acute large-vessel occlusion of the anterior circulation with low pretreatment DWI-Alberta Stroke Program Early Computed Tomography Scores (ASPECTS) (0-5), effective recanalization [thrombolysis in cerebral infarction (TICI) 2b or TICI3], and magnetic resonance imaging (MRI) acquired before and after MT. We measured the DWI-positive area volume before and after MT. The primary endpoint was the after/before-MT DWI-positive area-volume ratio. RESULTS: In total, 28 patients were included in this study. Eight patients (29%) had an after/before-MT DWI-positive area-volume ratio of <1. The median mean apparent diffusion coefficient (ADC) levels of the DWI-positive areas in the groups with a ratio of <1 or >1 were 717 × 106 mm2/s and 637 × 106 mm2/s, respectively (p = 0.011). Multivariate logistic regression analysis showed that ADC level (OR, 1.020 [95% confidence intervals (CIs), 1.001-1.040]; p = 0.040) was an independent predictor of a decreased DWI-positive area after MT. There was a negative correlation between the mean ADC level and the after/before-MT DWI-positive area-volume ratio (p < 0.001, |ρ| = 0.650), and the mean pretreatment ADC cutoff level was 649 × 106 mm2/s (area under the curve (AUC) = 0.806) for predicting a volume ratio of <1. CONCLUSIONS: The mean ADC level before-MT correlated with the after/before-MT DWI-positive area-volume ratio. A mean pretreatment ADC cutoff level of 649 × 106 mm2/s predicted a decreased DWI-positive area after MT.

Interstitial lung disease with prolonged fever that occurred during long-term administration of olaparib in a 74-year-old ovarian cancer patient: Radiological features and considerations for preventing delayed diagnosis.

A 74-year-old woman, who had been receiving olaparib for the treatment of ovarian cancer for more than a year, visited the emergency department complaining of a fever that had lasted for 1 month. She had been taking antipyretics and antibiotics for her fever, but without any effect. Although she had no symptoms other than fever, she had stopped taking olaparib for 1 week before her visit because she had developed anemia caused by myelosuppression from olaparib. After discontinuing olaparib, her maximum body temperature decreased. On admission, chest X-ray revealed no abnormalities, but chest CT showed diffuse ground-glass opacities. Chest CT taken 5 days later showed partial improvement; therefore, we diagnosed her with interstitial lung disease (ILD) associated with olaparib. After short-term steroid treatment, the ground-glass opacities disappeared, and the patient became afebrile. The CT scan taken for tumor evaluation 2 days before the onset of fever showed a few centrilobular nodular opacities and small patchy ground-glass opacities. These findings could indicate early lesions of ILD, but they seemed inconspicuous and nonspecific, and it might have been difficult to diagnose ILD then. To date, few cases of ILD associated with olaparib have been reported. However, based on previous reports, fever is often seen, and CT findings mainly comprise diffuse ground-glass opacities, and in some cases, centrilobular nodular shadows. Thus, in conjunction with the findings of the present case, these characteristics may be representative of olaparib-induced ILD.

Mitochondrial biogenesis in white adipose tissue mediated by JMJD1A-PGC-1 axis limits age-related metabolic disease.

Mitochondria play a vital role in non-shivering thermogenesis in both brown and subcutaneous white adipose tissues (BAT and scWAT, respectively). However, specific regulatory mechanisms driving mitochondrial function in these tissues have been unclear. Here we demonstrate that prolonged activation of ß-adrenergic signaling induces epigenetic modifications in scWAT, specifically targeting the enhancers for the mitochondria master regulator genes Pgc1a/b. This is mediated at least partially through JMJD1A, a histone demethylase that in response to ß-adrenergic signals, facilitates H3K9 demethylation of the Pgc1a/b enhancers, promoting mitochondrial biogenesis and the formation of beige adipocytes. Disruption of demethylation activity of JMJD1A in mice impairs activation of Pgc1a/b driven mitochondrial biogenesis and limits scWAT beiging, contributing to reduced energy expenditure, obesity, insulin resistance, and metabolic disorders. Notably, JMJD1A demethylase activity is not required for Pgc1a/b dependent thermogenic capacity of BAT especially during acute cold stress, emphasizing the importance of scWAT thermogenesis in overall energy metabolism.