Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

OBJECTIVES: To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). METHODS: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. RESULTS: Of these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 2.47) was linked to increased discontinuation due to toxic adverse events. CONCLUSION: Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors-A 2023 Update.

With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such malignancies often interfere with RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for a variety of malignancies. In parallel, evidence has accumulated that ICIs are associated with numerous immune-related adverse events (irAEs), such as hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, ICIs not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease-like symptoms, such as arthritis, myositis, and vasculitis, which are currently termed rheumatic irAEs. Rheumatic irAEs differ from classical rheumatic diseases in multiple aspects, and treatment should be individualized based on the severity. Close collaboration with oncologists is critical for preventing irreversible organ damage. This review summarizes the current evidence regarding the mechanisms and management of rheumatic irAEs with focus on arthritis, myositis, and vasculitis. Based on these findings, potential therapeutic strategies against rheumatic irAEs are discussed.

Influence of concomitant methotrexate use on the clinical effectiveness, retention, and safety of abatacept in biologic-naïve patients with rheumatoid arthritis: Post-hoc subgroup analysis of the ORIGAMI study.

OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.

Bexarotene-induced central hypothyroidism assessed by TRH stimulation test in cutaneous T-cell lymphoma patients.

Bexarotene-induced central hypothyroidism (CH), for which levothyroxine (LT4) replacement is recommended, has been shown to be caused by pituitary but not hypothalamic disorder experimentally, though the underlying mechanism in humans remains unclear. Here, the pathophysiology of bexarotene-induced CH was examined using a TRH stimulation test in cutaneous T-cell lymphoma (CTCL) patients. In this retrospective longitudinal observational study, serum TSH and free T4 (F-T4) levels were measured in 10 euthyroid patients with CTCL during 24 weeks of bexarotene treatment. TRH stimulation testing was performed following CH diagnosis, with LT4 replacement dosage adjusted to maintain F-T4 at the pre-treatment level. After one week of bexarotene administration, all 10 patients developed CH, based on combined findings of low or low-normal F-T4 with low or normal TSH levels. TSH peak response after a stimulation test at one week was reached at 30 minutes. However, that was <4 µIU/mL in all patients, indicating a blunted though not exaggerated and delayed TSH response. In eight who continued bexarotene for 24 weeks, median LT4 replacement dosage was 125 (range, 75-150) µg/day. TSH level at 30 as well as 15, 60, 90, and 120 minutes after TRH stimulation was significantly correlated with LT4 replacement dosage (ρ = -0.913, p = 0.002), whereas TSH and F-T4 basal levels at one week were not. These results suggest that pituitary hypothyroidism is responsible for bexarotene-induced CH, while TSH levels after TRH stimulation precisely reflect residual pituitary-thyroid function in patients receiving bexarotene.

Functional Outcomes of Microsurgical Resection for Cavernous Malformations of the Brainstem.

Long-term functional outcomes of microsurgical resection for cavernous malformations of the brainstem (CMB) have been largely unknown. Favorable outcomes after CMB surgery might be related to the achievement of complete resection and mRS at 1 month after the surgery. Preoperative sensory, cerebellar, trigeminal nerve, and lower cranial nerve symptoms tended to improve after surgery.We evaluated 25 consecutive patients with CMB surgically treated at our center between 2006 and 2021. The subjects included 11 men and 14 women, with ages ranging from 13 to 61 years (mean ± SD = 37 ± 12 years). Modified Rankin Scale (mRS) scores and neurological symptoms of the patients were evaluated before surgery, 1 month after surgery, and at the final follow-up at the outpatient clinic. The mean number of previous hemorrhages was 7 ± 1.0 and the mean lesion size was 21 ± 8 mm. The mRS scores on admission and at the final follow-up were 2.9 points and 1.7 points, respectively. The mRS scores at the final follow-up were significantly improved compared to those on admission. There was no statistical difference between the preoperative mRS and mRS at 1 month after the operation. Multivariable analysis indicated that mRS scores at 1 month after surgery were the most significant predictive factors for favorable outcomes. Complete resection was achieved in 24 of 33 operations. Incomplete resection was significantly related to the frequency of subsequent recurrent hemorrhage and high mRS scores at the final follow-up. Preoperative sensory, cerebellar, trigeminal nerve, and lower cranial nerve symptoms improved significantly after surgery.

Factors affecting global neurocognitive status and frontal executive functions in the early stage after surgical clipping of unruptured anterior circulation aneurysms with respect to keyhole clipping and conventional clipping.

PURPOSE: This study investigated the most significant factor for the preservation of the global neurocognitive status and frontal executive functions in the surgical clipping of unruptured anterior circulation aneurysms, specifically in keyhole and conventional clipping procedures. METHODS: The prospective study that was performed to examine the effects of aneurysm surgery on the patient's global neurocognitive status and frontal executive functions started on April 2016. After exclusion posterior circulation aneurysms, anterior communicating aneurysms treated by interhemispheric approach, giant aneurysms, and paraclinoid aneurysms, 23 patients who were enrolled before May 2017 were treated by conventional clipping, and 18 patients who were enrolled after June 2017 were treated by keyhole clipping. Two patients were excluded from each group due to missing data. Finally, 21 and 16 patients in each group were analyzed, respectively. Three-tesla magnetic resonance imaging was performed before and after surgery to detect the presence of perioperative cerebral infarctions and brain edema. The Mini-Mental State Examination, Frontal Assessment Battery, and Self-Rating Depression Scale scores were obtained before and 1 month after surgery. RESULTS: Logistic regression analyses indicated that anterior communicating and internal carotid artery aneurysms were the most significant factors for poor outcomes and that keyhole clipping for these two types of aneurysm was the most significant factor for the preservation of patient global neurocognitive status. Keyhole clipping was also the most significant factor for the preservation of frontal executive functions in patients. CONCLUSIONS: Keyhole clipping may be more favorable than conventional clipping for the preservation of the global neurocognitive status and frontal executive functions. Moreover, it may be the most effective factor for preservation of global neurocognitive status when it is indicated for anterior communicating or internal carotid artery aneurysms.

Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study.

INTRODUCTION: Romosozumab reportedly increases bone mineral density (BMD) potently but might adversely affect cardiovascular disease (CVD). We evaluated the efficacy of romosozumab in osteoporotic HD patients with a high risk of fracture. MATERIALS AND METHODS: This was a single-center 1-year study in Japanese HD patients. Among 96 HD romosozumab-treated HD patients with high risk of fracture, 76 HD patients completed 1 year of subcutaneous administration of romosozumab (210 mg/4 weeks) for 1 year. Romosozumab-untreated HD patients (n = 55) were also included. Changes in BMD and serum markers, together with fracture occurrence, and CVD events, were monitored. RESULTS: During romosozumab treatment of 76 HD patients, BMD time-dependently increased significantly by 15.3% ± 12.9% at the lumbar spine (L1-4), and 7.2% ± 8.3% at the femoral neck at 1 year. Serum BAP and total P1NP increased significantly and serum TRACP-5b decreased at 4 weeks. Fragility fractures occurred in three (3.8%) patients. Hypocalcemia occurred at 4-48 weeks despite the increased dosing of active vitamin-D derivatives, but without any symptom. New CVD events occurred in 5.2% of romosozumab-treated HD patients and10.9% in romosozumab-untreated HD patients. CONCLUSIONS: BMD was increased significantly during romosozumab treatment at the lumbar spine, and the femoral neck, respectively, at 1 year in HD patients. Hypocalcemia occurred but without any intolerable event. There was no apparent increase in CVD events during 1 year of study, suggesting romosozumab as a promising agent for HD patients with severe osteoporosis.

Evaluation of myostatin as a possible regulator and marker of skeletal muscle-cortical bone interaction in adults.

INTRODUCTION: Bone mass was recently reported to be related to skeletal muscle mass in humans, and a decrease in cortical bone is a risk factor for osteoporosis. Because circulating myostatin is a factor that primarily controls muscle metabolism, this study examined the role of myostatin in bone mass-skeletal muscle mass interactions. METHODS: The subjects were 375 middle-aged community residents with no history of osteoporosis or sarcopenia who participated in a health check-up. Cortical bone thickness and cancellous bone density were measured by ultrasonic bone densitometry in a health check-up survey. The subjects were divided into those with low cortical bone thickness (LCT) or low cancellous bone density (LBD) and those with normal values (NCT/NBD). Bone metabolism markers (TRACP-5b, etc.), skeletal muscle mass, serum myostatin levels, and lifestyle were then compared between the groups. RESULTS: The percentage of diabetic participants, TRACP-5b, and myostatin levels were significantly higher, and the frequency of physical activity, skeletal muscle mass, grip strength, and leg strength were significantly lower in the LCT group than in the NCT group. The odds ratio (OR) of high myostatin levels in the LCT group compared with the NCT group was significant (OR 2.17) even after adjusting for related factors. Between the low cancellous bone density (LBD) and normal cancellous bone density (NBD) groups, significant differences were observed in the same items as between the LCT and NCT groups, but no significant differences were observed in skeletal muscle mass and blood myostatin levels. The myostatin level was significantly negatively correlated with cortical bone thickness and skeletal muscle mass. CONCLUSIONS: A decrease in cortical bone thickness was associated with a decrease in skeletal muscle mass accompanied by an increase in the blood myostatin level. Blood myostatin may regulate the bone-skeletal muscle relationship and serve as a surrogate marker of bone metabolism, potentially linking muscle mass to bone structure.

Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease.

INTRODUCTION: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated. METHODS: In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57-75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry. RESULTS: Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated with plasma ln-XOR activity after adjusting for several confounders. Plasma XOR activity was significantly higher in CKD patients with (n = 26) than in those without (n = 92) DM (62.7 [32.3-122] vs. 25.7 [13.4-45.8] pmol/h/mL, p < 0.001). A total of 38 patients were taking uric acid-lowering drugs. Multiple regression analysis of CKD patients not administered uric acid-lowering drugs (n = 80) showed no significant association between eGFR and plasma ln-XOR activity. In contrast, association between glycemic control and plasma ln-XOR activity was significant even in CKD patients without uric acid-lowering drug treatment. CONCLUSIONS: These results indicate the importance of glycemic control in CKD patients in regard to decreased XOR, possibly leading to a decrease in CVD events.

Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry: MedCity21 health examination registry.

Background We developed a novel high-sensitive assay for plasma xanthine oxidoreductase (XOR) activity that is not affected by the original serum uric acid level. However, the association of plasma XOR activity with that level has not been fully examined. Methods This cross-sectional study included 191 subjects (91 males, 100 females) registered in the MedCity21 health examination registry. Plasma XOR activity was determined using our assay for plasma XOR activity with [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Serum levels of uric acid and adiponectin, and visceral fat area (VFA) obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index. Results The median values for uric acid and plasma XOR activity were 333 µmol/L and 26.1 pmol/h/mL, respectively. Multivariable linear regression analysis showed a significant and positive association of serum uric acid level (coefficient: 26.503; 95% confidence interval: 2.06, 50.945; p = 0.035) with plasma XOR activity independent of VFA and HOMA-IR, and also age, gender, alcohol drinking habit, systolic blood pressure, estimated glomerular filtration rate (eGFR), glycated hemoglobin A1c, triglyceride, and adiponectin levels. The "gender*XOR activity" interaction was not significant (p = 0.91), providing no evidence that gender modifies the relationship between plasma XOR activity and serum uric acid level. Conclusions Plasma XOR activity was found to be positively associated with serum uric acid level independent of other known confounding factors affecting that level, including gender difference, eGFR, adiponectin level, VFA, and HOMA-IR.

Association of higher arterial ketone body ratio (acetoacetate/ß-hydroxybutyrate) with relevant nutritional marker in hemodialysis patients.

BACKGROUND: An association of higher levels of ß-hydroxybutyrate (ß-HB) in serum with greater mortality in hemodialysis (HD) patients has been reported. This study examined the significance of arterial ketone body ratio (AcAc/ß-HB), a relevant marker of energy state, in HD patients. METHODS: The levels of arterial AcAc and ß-HB, and AcAc/ß-HB ratio were determined in 49 HD patients just before undergoing an HD session. Additionally, changes in those levels during the session were examined to investigate their associations with clinical nutritional markers. RESULTS: Arterial ß-HB, but not AcAc, was significantly higher at the baseline in 25 patients with type 2 diabetes mellitus (T2DM) as compared to 24 non-DM patients, with a significant reduction in arterial AcAc/ß-HB ratio seen in those with DM. Although the arterial AcAc/ß-HB ratio before the HD session was significantly higher in the non-DM group, it did not differ significantly after the session between the groups, indicating a faster rate of ß-HB disappearance from circulation in non-DM HD patients during the interdialytic period. Multiple regression analysis, which included age, gender, presence/absence of DM, log HD duration, log ß-HB, and log AcAc/ß-HB ratio as independent variables, revealed an independent and significant association of log AcAc/ ß-HB ratio, but not log ß-HB, with serum albumin and uric acid. CONCLUSION: We found that a decreased AcAc/ß-HB ratio resulting from increased ß-HB, but not increased ß-HB itself, was a significant factor independently associated with decreased levels of serum albumin and uric acid, known to be related to higher mortality in HD patients. Furthermore, it is possible that higher mortality in DM HD patients can be explained by reduced arterial AcAc/ß-HB ratio.

Association of cystatin C- and creatinine-based eGFR with osteoporotic fracture in Japanese postmenopausal women with osteoporosis: sarcopenia as risk for fracture.

Coexistence of chronic kidney disease (CKD) is regarded as a risk for osteoporotic fracture particularly in postmenopausal women, not only because of increased parathyroid hormone level but also uremic sarcopenia. We examined the relationships of cystatin C-based glomerular filtration rate (eGFRcys) and creatinine-based GFR (eGFRcr), as well as their ratio with occurrence of osteoporotic fracture in postmenopausal osteoporotic women. This cross-sectional study included 555 postmenopausal women with osteoporosis. eGFRcr and eGFRcys were simultaneously measured, while occurrence of osteoporotic fracture was obtained by a medical chart review. Patients with osteoporotic fractures (n = 211) exhibited significantly lower levels of physical activity, eGFRcr, eGFRcys, and eGFRcys/eGFRcr ratios, while a higher percentage was CKD stage 3 or more, estimated by eGFRcr or eGFRcys (CKDcys), than those without (n = 344). Lower eGFRcys, but not lower eGFRcr, was independently associated with osteoporotic fracture in the entire cohort and that association was retained in CKDcys patients. Of great interest, higher eGFRcr was associated with osteoporotic fracture independent of eGFRcys in CKDcys patients. Furthermore, lower eGFRcys/eGFRcr ratio was independently associated with osteoporotic fracture in both CKDcys patients and the entire cohort. eGFRcys reduction might be associated with osteoporotic fracture in postmenopausal osteoporotic women, indicating the involvement of renal osteopathy in its occurrence. Furthermore, the association of higher, but not lower, eGFRcr with osteoporotic fracture in CKDcys cases might be explained by underestimation of renal dysfunction by eGFRcr resulting from decreased muscle mass and quality in those patients.

Thyroid blood flow in inferior thyroid artery as predictor for increase in levothyroxine dosage during pregnancy in women with Hashimoto's thyroiditis - a retrospective study.

BACKGROUND: We examined whether inferior thyroid artery peak systolic velocity (ITA-PSV) predicts an increase in levothyroxine (LT4) dosage in pregnant women with Hashimoto's thyroiditis. METHODS: Twenty-two women with Hashimoto's thyroiditis who were planning and later achieved pregnancy or confirmed as pregnant were enrolled in this retrospective longitudinal observational study. ITA-PSV and thyroid volume were measured using ultrasonography. Serum concentrations of free thyroxine (F-T4), free triiodothyronine (F-T3), and thyroid stimulating hormone (TSH) were simultaneously determined. We adjusted LT4 dosage to maintain serum TSH at < 2.5 µIU/mL (1st trimester) and later at < 3 µIU/mL (2nd, 3rd trimester). RESULTS: Eighteen patients (81.8%) required an increase in LT4 dosage during pregnancy, of whom 7 (31.8%) required an increase ≥50 µg. Multivariable regression analysis showed that TSH (ß = 0.507, p = 0.008) and ITA-PSV (ß = - 0.362, p = 0.047), but not thyroid volume, F-T4, or F-T3, were independently associated with increased LT4 dosage. Receiver-operating characteristic analysis for predicting an increase in LT4 ≥ 50 µg/day showed that the area under the curve (0.905) for ITA-PSV with TSH was not significantly increased (p = 0.123) as compared to that (0.743) for TSH alone, whereas integrated discrimination improvement was significantly increased (27.9%, p = 0.009). CONCLUSIONS: In pregnant patients with Hashimoto's thyroiditis, ITA-PSV was a significant predictor of increase in LT4 dosage independent of TSH level, while ITA-PSV plus TSH showed significantly improved predictability as compared to TSH alone. These results suggest that ITA-PSV reflects residual thyroid function and is useful for evaluating the need for increased thyroid hormone production in pregnant patients with Hashimoto's thyroiditis.

[Osteoporosis as a risk factor for cardiovascular disease.]

Osteoporosis(OP)is associated with high risk for cardiovascular disease(CVD). Concomitant occurrence of both OP and CVD seems to result from common pathological mechanisms between bone system and vascular system. It is expected that therapeutic agent for OP may be effective not only in normalization of bone metabolism but also in reducing vascular calcification. I give an outline with the relationship between bone metabolism and vascular calcification including epidemiology, outbreak mechanism, and effect on vascular calcification of OP treatment.

[Vestibular Schwannoma Surgery with Continuous Intraoperative Monitoring of Evoked Facial Nerve Electromyograms].

Preservation of facial nerve function is crucial during vestibular schwannoma surgery. Here, we report the utility of continuous intraoperative monitoring of evoked facial nerve electromyograms(EMGs)for preservation of facial nerve function during vestibular schwannoma surgery. A 64-year-old man presented with left ear hearing disturbance. CT and MRI revealed a tumor mass(4cm)with cyst formation in the left cerebellopontine angle. Microsurgical removal was performed with continuous intraoperative monitoring of evoked facial nerve EMGs. An electrode with Ag wire and absorbable gelatin sponge, which we developed, was used for continuous monitoring. It could be placed and fixed more easily on the root exit zone of the facial nerve than the previously reported electrodes and provide reliable information during surgery. The tumor mass could be removed safely without inducing facial nerve palsy. Continuous intraoperative monitoring of evoked facial nerve EMGs with this newly developed electrode could facilitate successful schwannoma surgery.

Effects of Teriparatide and Sequential Minodronate on Lumbar Spine Bone Mineral Density and Microarchitecture in Osteoporosis.

The trabecular bone score (TBS) is a new surrogate for trabecular bone microarchitecture assessment, independent of bone mineral density (BMD), calculated from pixel gray-level variations in the lumbar spine (LS) dual-energy X-ray absorptiometry (DXA) image. Although Teriparatide (TPTD) increased LS-BMD as well as TBS in 2 years, the precise time-course of these parameters was not well known. The aim of this study was to determine the changes in LS-BMD and the TBS in osteoporotic patients treated with TPTD, followed by minodronate (MINO). Primary osteoporotic patients with a low LS-BMD (T-score < -2.5) and/or at least one vertebral fracture were treated with TPTD subcutaneously at 20 µg/day for 12-24 months, followed by MINO (orally at 50 mg/once monthly) for 12 months. LS-BMD and the TBS were measured at 0, 3, 6, 12, and 24 months after the initiation of TPTD treatment, and 12 months after the initiation of MINO. The increments of LS-BMD, significant at 6 months, increased until 12 months, whereas the increments of TBS, significant at 3 months (0.035 ± 0.011; p = 0.045 vs. the baseline), stabilized until 12 months. TPTD treatment, followed by 12 months of MINO, maintained both BMD and the TBS. Comparing the increments of the TBS to those of LS-BMD, our results indicate that TPTD treatment improved trabecular microarchitecture faster than mineralization. TPTD treatment, followed by MINO, can maintain both BMD and the TBS.

[New methods for the evaluation of bone quality. Diseases Affecting Bone Quality.]

Impaired bone quality is associated with fragility bone fractures independently of bone mineral density. Lifestyle disease-induced osteoporosis, such as diabetes or chronic kidney disease, and glucocorticoid-induced osteoporosis are listed as the diseases affecting bone quality. TBS(trabecular bone score)developed recently will be able to evaluate the trabecular microarchitecture quickly and easily. Various clinical studies evaluated bone quality by TBS has performed. I give an outline about the diseases affecting bone quality.

Preparation of Microvolume Anion-Exchange Cartridge for Inductively Coupled Plasma Mass Spectrometry-Based Determination of (237)Np Content in Spent Nuclear Fuel.

Microvolume anion-exchange porous polymer disk-packed cartridges were prepared for Am/Np separation, which is required prior to the measurement of Neptunium-237 ((237)Np) with inductively coupled plasma mass spectrometry (ICPMS). Disks with a volume of 0.08 cm(3) were cut out from porous sheets having anion-exchange-group-containing polymer chains densely attached on the pore surface. Four different amine-based groups, N,N-dimethylaminoethyl methacrylate, trimethylammonium, diethylamine, and triethylenediamine (TEDA), were selected as the anion-exchange groups to be introduced into the porous sheets. The separation performances of Am/Np were evaluated using a standard solution of (243)Am, which had the same activity as its daughter nuclide (239)Np in secular equilibrium. (239)Np recovery of close to 100% with practically no contamination of (243)Am was achieved using the TEDA-introduced disk-packed cartridge. The time to elute (239)Np from the cartridge was approximately 40 s. The TEDA-introduced disk-packed cartridge was applied to the separation of Np from a spent nuclear fuel sample to confirm its separation performance. A known amount of (243)Am ((239)Np) was added to the spent nuclear fuel sample solution to monitor the chemical yield of Np. The chemical yield of Np calculated from a measured concentration of (239)Np was 90.4%. Am leakage in the Np-eluted solution was less than 1 ppt, corresponding to 0.001% of the original Am concentration in the sample. This indicates that no additional (239)Np was produced by the decay of the (243)Am remaining in the Np-eluted solution, thus providing a reliable chemical yield. U, which can cause a serious spectral interference involving the peak tail from the mass spectrum of (238)U, was thoroughly removed with the TEDA cartridge, providing interference-free measurement of (237)Np. The concentration of (237)Np obtained by ICPMS was 718 ± 12 ng/mg-U, which agrees well with the theoretically calculated value. Compared with the conventional separation technique using commercially available anion-exchange resin columns, the time required to adsorb, wash, and elute Np using the TEDA- introduced disk-packed cartridge was reduced by 75%.

High Coronary Heart Disease Risk in Hemodialysis Patients with Central Sleep Apnea: A Pilot Study.

BACKGROUND: The high prevalence of sleep apnea is reported in hemodialysis patients despite the low prevalence of obesity. The present study compared the occurrence of central sleep apnea (CSA) in hemodialysis patients with that in non-hemodialysis patients, and its association with new-onset coronary heart disease (CHD) events. METHODS: Seventy-three hemodialysis and 444 non-hemodialysis patients were examined for CSA and obstructive sleep apnea (OSA) occurrence using polysomnography. Hemodialysis patients were monitored for the occurrence of new-onset CHD events. RESULTS: Hemodialysis patients had a significantly higher central apnea-hypopnea index (AHI; 0.7, range 0.2-3.1) than age-, sex- and obstructive AHI-matched non-hemodialysis patients (0.1, range 0-1.0; p < 0.001), in contrast with an insignificant difference for obstructive AHI. Furthermore, the prevalence of CSA was significantly higher in the hemodialysis (21.9%) than in the non-hemodialysis group (9.7%; p = 0.004). A significant and negative association existed between log (central AHI + 1) and Kt/V in hemodialysis patients. In the Kaplan-Meier analysis, hemodialysis patients with CSA had a significantly higher rate of new-onset CHD events than those without CSA. Cox proportional-hazards regression analysis identified CSA prevalence as an independent risk factor for the development of a new-onset CHD event, independent of OSA. CONCLUSIONS: The present study demonstrated that hemodialysis patients had a significantly higher CSA prevalence than non-hemodialysis patients despite similar obstructive AHI, and that hemodialysis patients with CSA had a significantly higher risk for new-onset CHD events than those without CSA independent of obstructive AHI, suggesting CSA as a potential CHD risk specifically in hemodialysis patients.

Clinicopathologic features of small cell glioblastomas.

Small cell glioblastoma (SCGBM) is a variant of glioblastomas characterized by a predominant population of small and monomorphic glial cells. The aim of the present study was to investigate clinical, neuroimaging, pathologic, and genetic features of SCGBM. The clinicopathologic and genetic features were evaluated in 14 patients with SCGBM. All cases were divided into multifocal and solitary type by MRI, and extent of microvascular proliferation, intratumoral necrosis, and perivascular lymphocytic accumulation were investigated. IDH1 mutations by immunohistochemistry (IDH1 R132H) and 1p 19q codeletion by fluorescence in situ hybridization were detected. Patients ranged from 23 to 92 years of age (median: 71 years), with three females and eleven males. The overall survival time of the patients ranged from 7 to 23 months (mean: 11 months). Nine patients (64%) were the multifocal type. Pathologic study revealed that the microvascular proliferation, necrosis, and lymphocytic infiltration were limited in SCGBM. Immunohistochemically, tumor cells were negative for IDH1 R132H in all patients. FISH analysis demonstrated that no SCGBM had 1p/19q codeletion in informative patients. Our investigation suggested that an elderly onset and multifocal lesions were characteristics of SCGBM associated with degradation of the immune response, infiltrative feature of tumor cells, and an unfavorable prognosis.