Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. METHODS: This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age- and sex-matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. RESULTS: Forty-two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = -0.73, p < .0001) in patients with non-IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = -0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non-IBM group (r = 0.56, p = .017), but not in the IBM group. DISCUSSION: Muscle EI may be useful as a surrogate marker of muscle inflammation in non-IBM IIM. Increased muscle EI may be difficult to interpret in patients with long-standing IBM, which has advanced and complex histopathology.

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.

Ultrasound assessment of sarcopenia in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the efficacy of ultrasound (US) as a diagnostic tool for sarcopenia in patients with rheumatoid arthritis (RA). METHODS: Female RA patients aged >50 years and matched controls were cross-sectionally assessed. Sarcopenia was diagnosed based on the 2019-updated Asian Working Group for Sarcopenia definition. The cross-sectional area (CSA) and echo intensity (EI) of the biceps brachii, rectus femoris, and EI of the vastus lateralis were examined bilaterally. Correction for subcutaneous fat and calculation of the recorrected EI (rcEI) were performed. We performed logistic regression using both muscle rcEI and CSA with receiver operating curve analysis to evaluate the discriminative performance per muscle group. RESULTS: Seventy-eight consecutive RA patients and 15 age-and sex-matched controls were assessed. Sarcopenia was diagnosed in 34 RA patients (43.6%). The rcEI of examined muscles were significantly higher, whereas CSA were significantly lower in sarcopenic RA patients than in non-sarcopenic patients and matched controls. The combined discriminative performance of rcEI and CSA was superior to those of rcEI or CSA alone. CONCLUSIONS: This study suggests the use of US for the diagnosis of sarcopenia in RA patients. The diagnostic performance increases when both echogenicity and CSA are considered together rather than individually.

Detection of nerve enlargement with ultrasound and correlation with skin biopsy findings in painful sensory neuropathy associated with Sjögren's syndrome.

OBJECTIVES: We evaluated usefulness of peripheral nerve ultrasound (US) in detecting abnormality in painful sensory neuropathy (PSN) associated with primary Sjögren's syndrome (pSS), and associations among various clinical factors, US findings, and intraepidermal nerve fiber density (IENFD). METHODS: We conducted a retrospective, single-center, observational study of patients with pSS-PSN. US image was obtained to measure cross sectional area (CSA) of peripheral nerves and compared with matched pSS control. RESULTS: We included 11 patients with pSS-PSN (10 women; age 70.5 ± 5.66) and 17 pSS controls (15 women; age 62.5 ± 16.7). Sural nerve CSA were significantly increased in pSS-PSN group (3.48 ± 1.0 mm2 vs 2.05 ± 0.65 mm2, p = .001). US of sural nerve showed the area under the ROC curve of 0.872 (95% CI, 0.732 - 1). Sural nerve CSA and IENFD of lower leg showed positive correlation. Compared with pSS-PSN patients with abnormal IENFD, those with normal IENFD showed significantly larger sural nerve CSA, and trends toward less systemic disease activity and small fiber impairment with sparing of large fibers. CONCLUSION: US was useful in discriminating pSS patients with PSN from those without. Additionally, US may disclose distinct subsets of pSS-PSN with different clinical findings and IENFD.

Abatacept may be effective and safe in patients with amyloid A amyloidosis secondary to rheumatoid arthritis.

OBJECTIVES: To examine the efficacy and safety of abatacept (ABT) in patients with amyloid A (AA) amyloidosis secondary to rheumatoid arthritis (RA), and to speculate about the immunologic association of ABT with AA amyloid deposit regression. METHODS: We administered ABT to 70- and 65-year-old Japanese women with RA and AA amyloidosis. We quantified serum cytokine concentrations and analysed regulatory T lymphocytes (Treg cells) via flow cytometry. We also studied AA amyloid deposits via histopathology and immunohistochemistry. RESULTS: ABT improved rheumatoid inflammation and AA amyloidosis, one case showing clinical remission and the other demonstrating incomplete recovery of nephrosis but stable kidney function. Serum levels of interleukin-6 and tumour necrosis factor α decreased to baseline in the first 6 months of treatment, but serum interleukin-2 concentrations did not change. CD4+CD25++FoxP3+ Treg cells gated on T lymphocytes and CD4+ T lymphocytes decreased to baseline in the first 3 treatment months. One case showed complete regression of AA amyloid fibrils in serial upper gastrointestinal biopsies, but the other case still had AA amyloid deposits despite ABT-induced normalised rheumatoid inflammation, with polymorphonuclear leukocytes and macrophages infiltrating tissues containing AA amyloid. CONCLUSIONS: ABT demonstrated efficacy and safety in AA amyloidosis secondary to RA and affected Treg cells and inflammatory cytokines. Because the gradual decrease in Treg cells population coincided with AA amyloid deposit regression during ABT therapy, AA amyloid fibril turnover in these patients may involve an immunologic mechanism. Phagocytes seemed to have an important role in AA amyloid fibril regression, which suggests an immunologic interaction.

PCR amplification and DNA sequence analysis of parasitic intestinal protozoa in specimens stained with Chlorazol Black E.

Chlorazol Black E (CBE) stain has been used for the detection and identification of intestinal parasitic protozoa. In recent years, genotyping of protozoa has been performed to examine pathogenicity and for epidemiologic analysis. In this study, protozoan DNA was amplified from preserved human fecal specimens stained with CBE that were positive for Giardia intestinalis (syn. G. lamblia and G. duodenalis), Chilomastix mesnili, Pentatrichomonas hominis, and Entamoeba histolytica. DNA was amplified from 11 of the 12 (91.6%) samples examined. DNA from CBE-stained smears of G. intestinalis, E. histolytica, and P. hominis was amplified, whereas any amplification product could not be obtained from one of three smears of C. mesnili. Storage term and protozoan number had no association with results of PCR amplification. In genotyping of G. intestinalis, four out of six (66.7%) samples were of genotype AI, while the remaining two (33.3%) samples were of genotype B. The amplified DNA sequences showed high similarity (>99%) with that of G. intestinalis in the GenBank database. These results suggest that DNA remains stable in CBE-stained smears for long term. The present study demonstrates that nuclear extracts from specimens stained with CBE can be amplified by PCR and suggests that specimens stored for extended periods could be applied to genetic and prospective epidemiologic analyses.

The human female heart incorporates glucose more efficiently than the male heart.

BACKGROUND: Oestrogen is known to play a cardioprotective role in cardiovascular diseases, as demonstrated in a number of animal studies. However, few human studies have investigated sex-based differences with regard to cardiac glucose uptake using (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). METHODS: Therefore, we evaluated healthy male and female subjects who underwent FDG-PET/CT examination to determine whether there was a sex-related difference in cardiac glucose uptake with age. RESULTS: In females, the prevalence of maximal FDG uptake (PET score 2) demonstrated a convex pattern with ageing, and it peaked at age 51-60 years in the females, gradually decreasing to a minimum at age >70 years. In contrast, the prevalence of maximal FDG uptake by age in males was a mirror image of that in females, i.e. it formed a concave pattern with a nadir at 61-70 years, followed by an increase in the prevalence. These findings suggest that female hearts depend more on glucose as an energy substrate as they age, however, efficient glucose uptake is attenuated with increasing age. In contrast, the male heart sustains its glucose uptake capacity at age >70 years. CONCLUSION: This characteristic sex-based difference in cardiac glucose uptake might be related to the female predominance of Takotsubo cardiomyopathy.

Imaging assessment of enthesitis in spondyloarthritis.

Enthesitis, defined as the inflammation of the origin and insertion of ligaments, tendons, aponeuroses, annulus fibrosis, and joint capsules, is a hallmark of spondyloarthritis (SpA). New imaging techniques including magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography with computed tomography using 18F-fluorodeoxyglucose capable of detecting morphological and metabolic abnormalities and monitoring disease activity have improved the assessment and management of enthesitis of SpA.

Estrogen is involved in improvement of impaired cardiac glucose uptake in cancer patients.

We previously demonstrated that inflammatory stress impaired cardiac glucose uptake, using fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) by showing that a proportion of patients with subtle FDG signals was remarkably increased compared with that of normal subjects. The current study assessed the inhibitory effects of cancer-associated stress on cardiac glucose uptake in female cancer patients, and compared the results with those obtained for healthy female subjects. Cardiac glucose uptake was decreased in female cancer, as indicated by the significantly higher number of patients with poor FDG uptake and the lower number of patients with high FDG uptake, compared with the number of healthy subjects with poor and high FDG uptake, respectively. These results suggest that cancer-associated stress inhibited cardiac glucose utilization. From the 78 female cancer patients, 13 oophorectomized patients, who underwent repeated postoperative follow-up examinations by FDG-PET/CT before and after receiving hormone replacement therapy (HRT) with estrogen derivatives, were analyzed to determine the effects of estrogen on cardiac glucose uptake. HRT increased a proportion of patients with high FDG signals to comparable in healthy subjects with high FDG uptake, whereas that of patients with poor FDG uptake decreased. These results suggest that estrogen can improve cardiac glucose uptake in cancer-resected and oophorectomized patients. .

F-18 FDG PET/CT provides the earliest findings of enthesitis in reactive arthritis.

A 31-year-old woman developed polyarthralgia and extension disorder of the right elbow of 2 months' duration without abdominal symptom. Laboratory findings revealed C-reactive protein 2.7 mg/dL. Anti-nuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) antibody were negative. F-18 FDG PET/CT showed elevated pinpoint uptakes of FDG in the entheses. In contrast, MRI revealed no specific findings. Four months after PET/CT, she developed right lower abdominal pain. Colonoscopy showed abscess in ascending colon, which the initial PET/CT finding might mean early image of infective colitis. A diagnosis of early reactive arthritis was made. Treatment with antibiotics improved colitis, colonic abscess, and enthesitis after 2 months. Moreover, F-18 FDG PET/CT showed no accumulation in colon and entheses. These findings suggest that F-18 FDG PET/CT scanning allows enthesitis in the early stage of reactive arthritis, before the possible detection by the other procedures.

Neutrophil infiltration and oxidant-production in human atherosclerotic carotid plaques.

To clarify the clinical implications of neutrophils in vulnerable plaques we evaluated the function and activity of infiltrated neutrophils in an atherosclerotic plaque, focusing on oxidant production. A histopathological investigation was performed using carotid arterial samples obtained from seven patients. The atherosclerotic plaques were examined cytochemically for naphthol-ASD-chloroacetate esterase activity and oxidant-production, and immunohistochemically using N-formyl peptide receptor-like 1 (fPRL1)-, CD66b-, CD68- or p22phox-specific antibodies. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque was estimated using an activity index. Naphthol-ASD-chloroacetate esterase activity was found in cells located in the atherosclerotic plaque, indicating that the cells were neutrophils. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque decreased to approximately 60% of the intensity observed in the capillary vessels. Oxidant-production was also detected in the plaques, and both neutrophils and macrophages were observed at the corresponding oxidant-production sites. p22phox expression was also located in the same areas in which oxidant-production was observed in these plaques. We could not directly evaluate how much ROS generated from the infiltrated neutrophils contributed the plaque vulnerability followed by its rupture. However, the infiltrated neutrophils in the atherosclerotic plaques morphologically appeared activated and were actively generating oxidant, implying that neutrophils, together with macrophages, infiltrate into atherosclerotic plaques and contribute to plaque vulnerability.