Associations between non-motor symptoms and patient characteristics in Parkinson’s disease: a multicenter cross-sectional study

ObjectiveParkinson’s disease (PD) is characterized by various non-motor symptoms (NMS), such as constipation, olfactory disturbance, sleep disturbance, mental disorders, and motor symptoms. This study aimed to investigate factors associated with NMS in patients with PD.MethodsSymptoms of PD were evaluated using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Parts I–IV. NMS was assessed using the MDS-UPDRS Part I (self-assessment of NMS) and rapid eye movement sleep behavior disorder (RBD) questionnaires. Patients were categorized by age into <70 years and ≥ 70 years (older adults) groups, according to disease duration into early-stage and advanced-stage groups with a cut-off value of 5 years for motor symptoms, and by sex into male and female groups.ResultsA total of 431 patients with PD (202 males and 229 females) with a mean age of 67.7 years, a mean disease duration of 6.4 years, and a mean Part I total score of 9.9 participated in this study. The Part I total score was significantly positively correlated (p < 0.01) with disease duration and Part II, III, and IV scores. For Part I sub-item scores, the older group had significantly higher scores for cognitive impairment, hallucinations, sleep problems, urinary problems, and constipation than the <70 years group, whereas the advanced-stage group had significantly higher scores for hallucinations, sleep problems, daytime sleepiness, pain, urinary problems, and constipation (p < 0.05) than the early-stage group. Anxiety was higher in female patients than in male patients, whereas daytime sleepiness, urinary problems, and RBD were higher in male patients than in female patients (p < 0.05). Factors affecting Part I included disease duration, Part II total scores, Part IV total scores, and RBD.ConclusionAccording to the self-questionnaire assessment, NMS was highly severe in older adult patients, those with longer illness duration, subjective and objective motor function impairments, and RBD. Sex-based differences were also observed

Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in combination is a useful diagnostic biomarker to distinguish familial Mediterranean fever from sepsis

Objective: To identify potential biomarkers to distinguish familial Mediterranean fever (FMF) from sepsis.Method: We recruited 28 patients diagnosed with typical FMF (according to the Tel Hashomer criteria), 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the FMF and sepsis groups in order to identify specific molecular networks. Multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by importance and determine specific biomarkers for distinguishing FMF from sepsis.Results: Fifteen of the 40 cytokines were found to be suitable for further analysis. Levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor 2, vascular endothelial growth factor, macrophage inflammatory protein-1b, and interleukin-17 were significantly elevated, whereas tumor necrosis factor-α (TNF-α) was significantly lower in patients with FMF compared with those with sepsis. Cytokine clustering patterns differed between the two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both GM-CSF and TNF-α could distinguish FMF from sepsis with high accuracy (cut-off values for GM-CSF = 8.3 pg/mL; TNF-α = 16.3 pg/mL; sensitivity, 92.9%; specificity, 94.4%; accuracy, 93.4%).Conclusion: Determination of GM-CSF and TNF-α levels in combination may represent a biomarker for the differential diagnosis of FMF from sepsis, based on measurement of multiple cytokines

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study

ABSTRACT: We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs

Clinical Analysis of Ten Cases of Neuralgic Amyotrophy

Background: Neuralgic amyotrophy (NA) typically develops with neuralgia in the upper limbs and causes localized muscle atrophy after pain subsides. NA is not well known; thus, many patients face delayed diagnosis and treatment. Methods: We evaluated the initial symptoms, symptom duration, neurological findings, impaired nerves, treatment, and sequelae in patients with NA in our department between 2010 and 2020. Results: Ten patients had upper-limb NA. The suprascapular nerve was the most commonly affected nerve (n = 9). Needle electromyography revealed abnormal findings in all patients, and fibrillations/positive sharp waves at rest were observed in seven patients. Nerve conduction studies showed reduced motor or sensory nerve action potential amplitudes in six patients. Brachial plexus magnetic resonance imaging (MRI) revealed abnormalities in five patients. The mean duration from symptom onset to diagnosis was 142 days (median: 130 days), and the mean duration from the first visit to our department to diagnosis was 41 days (median: 20 days). Sequelae were observed in patients diagnosed 200 days after symptom onset. Conclusion: A combination of needle electromyography of the affected muscles, nerve conduction studies, and a special MRI technique (short tau inversion recovery MRI) may support the diagnosis of NA lesions, even in the subacute to chronic phase

Switching from originator infliximab to biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving clinical remission (the IFX-SIRIUS study I)

BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) into clinical practice has dramatically improve the clinical outcomes of individuals with rheumatoid arthritis (RA). However, bDMARDs are associated with high costs, which has resulted in restricted treatment access and a burden on medical insurance finances. Although biosimilars offer cost-saving, their effectiveness and safety must be established in Post-Marketing Surveillance (PMS). Infliximab (IFX), a chimeric monoclonal antibody to TNF-alpha, is the first bDMARD; its biosimilar, CT-P13, is the first biosimilar DMARD approved for RA treatment in Japan. We will evaluate whether switching from originator IFX to CT-P13 is not inferior for maintaining non-clinical relapse to continued treatment with originator IFX in RA patients achieving clinical remission. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm against historical control and noninferiority clinical trial with a 24-week follow-up. Eighty RA patients who are treated by originator IFX for ?24 weeks and are achieving clinical remission will be included. Patients will be switched to CT-P13 with the unchanged dosing regimen. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the ratio of patients who experience a nonclinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of many biomarkers such as cytokines and chemokines.DISCUSSION: The study results are expected to show the noninferiority of switching to CT-P13 over the continuation of originator IFX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices but also MSUS to accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will explore whether parameters at baseline can predict a nonclinical relapse after switching from originator IFX to CT-P13 by integrating multilateral assessments, i.e., clinical disease activity indices, MSUS findings, and serum biomarkers. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on October 11, 2019 as jRCTs071190030

Thresholds of Etchable Track Formation and Chemical Damage Parameters in Poly(ethylene terephthalate), Bisphenol A polycarbonate,and Poly(allyl diglycol carbonate) Films at the Stopping Powers Ranging from 10 to 12,000 keV/MUm

The damage structure of latent tracks in poly(ethylene terephthalate) (PET) has been examined by Fourier transform infrared (FT-IR)measurements. Results are compared with those from previous studies on bisphenol A polycarbonate (PC) and poly(allyl diglycol carbonate)(PADC). These polymers are exposed to protons and heavy ions (He, C, Ne, Si, Ar, Fe, Kr, and Xe) in air with energies less than 6 MeV/n, as wellas gamma rays from an intense Co-60 source. Chemical damage parameters, namely, damage density, which is the number of losses ofconsidered functional groups per unit length of tracks, radial size of the track core, in which the considered chemical groups are lost, and radiationchemical yields (G values) for each group are evaluated as a function of the stopping power. It has been confirmed that latent tracks will beetchable when the radial track core size is larger than the distance between two adjacent breaking points of polymer chains. The predominantbreaking points are the C–O bonds in ether, ester, and carbonate ester bonds

Dependence of track core structure on the stopping powers ranging from 10 to 12,000 keV/MUm in PET, PC and PADC films

16th International Conference on Radiation Effects in Insulator

Clinical Management and Outcomes of Adrenal Hemorrhage Following Adrenal Vein Sampling in Primary Aldosteronism

Aldosterone-producing adenoma and bilateral adrenal hyperplasia account for >90% of all primary aldosteronism cases. Distinguishing between bilateral and unilateral disease is of fundamental importance because it allows targeted therapy. Adrenal vein sampling (AVS) is the only reliable means to preoperatively differentiate between unilateral and bilateral subtypes. A rare but serious complication of AVS is an adrenal hemorrhage (AH). We retrospectively examined in detail 24 cases of AH during AVS in 6 different referral hypertension centers. AH more often affected the right adrenal (n=18) than the left (n=5, P10 years) and less experienced radiologists. Of 9 patients who suffered AH in the gland contralateral to an aldosterone-producing adenoma and who underwent complete (n=6) or partial (n=3) unilateral adrenalectomy, only one required long-term corticosteroid replacement for adrenal insufficiency. No reduction in blood pressure or biochemical resolution of primary aldosteronism occurred in any of those patients who experienced AH in the gland ipsilateral to an aldosterone-producing adenoma (n=6) or who had bilateral adrenal hyperplasia (n=9). No patient required invasive treatments to control bleeding or blood transfusion. In conclusion, AH usually has a positive outcome causing either no or minor effects on adrenal function, and AVS should remain the best approach to primary aldosteronism subtype differentiation

Discontinuation of biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving sustained clinical remission or low disease activity during the IFX-SIRIUS STUDY I (the IFX-SIRIUS STUDY II)

BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs into clinical practice has dramatically improved the clinical outcomes of individuals with rheumatoid arthritis (RA). We are conducting the IFX-SIRIUS STUDY I that evaluates whether switching from originator infliximab (IFX) to its biosimilar, CT-P13, is not inferior in maintaining nonclinical relapse to continue treatment with originator IFX in patients with RA achieving clinical remission. It is the next great issue whether disease activity can be maintained in good condition after discontinuation of CT-P13 because no evidence is available regarding the clinical value of discontinuing biosimilars in patients with RA. Thus, we will evaluate whether a condition without clinical relapse will be maintained after discontinuation of CT-P13 in patients with RA, achieving clinical remission or low disease activity during the IFX-SIRIUS STUDY I. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. Patients with RA who are treated with CT-P13 and sustained nonclinical relapse during the IFX-SIRIUS STUDY I will be included. Patients will discontinue CT-P13 after the study period of the IFX-SIRIUS STUDY I. We will evaluate disease activity by clinical disease activity indices and musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who do not have clinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of multiple biomarkers, such as cytokines and chemokines. In addition, if a clinical relapse occurs in patients after the discontinuation of CT-P13, we will evaluate the effectiveness and safety of restarting CT-P13. DISCUSSION: The study results are expected to show the clinical benefit of the discontinuation of CT-P13 and effectiveness and safety of restarting CT-P13 after clinical relapse. The strength of this study is to prospectively evaluate the therapeutic effectiveness by not only clinical disease activity indices but also standardized MSUS findings in multiple centers. We will explore whether parameters at baseline can predict a nonclinical relapse after the discontinuation of CT-P13 by integrating multilateral assessments, that is, patient\u27s characteristics, clinical disease activity indices, MSUS findings, and serum biomarkers. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on April 20, 2020 as jRCTs071200007