Exploring the role of anticipatory postural adjustment duration within APA2 subphase as a potential mediator between clinical disease severity and fall risk in Parkinson's disease.

Introduction: People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. Methods: We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Results: Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). Conclusion: APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk.

Longitudinal artificial intelligence-based deep learning models for diagnosis and prediction of the future occurrence of polyneuropathy in diabetes and prediabetes.

OBJECTIVE: The objective of this study was to develop artificial intelligence-based deep learning models and assess their potential utility and accuracy in diagnosing and predicting the future occurrence of diabetic distal sensorimotor polyneuropathy (DSPN) among individuals with type 2 diabetes mellitus (T2DM) and prediabetes. METHODS: In 394 patients (T2DM=300, Prediabetes=94), we developed a DSPN diagnostic and predictive model using Random Forest (RF)-based variable selection techniques, specifically incorporating the combined capabilities of the Clinical Toronto Neuropathy Score (TCNS) and nerve conduction study (NCS) to identify relevant variables. These important variables were then integrated into a deep learning framework comprising Convolutional Neural Networks (CNNs) and Long Short-Term Memory (LSTM) networks. To evaluate temporal predictive efficacy, patients were assessed at enrollment and one-year follow-up. RESULTS: RF-based variable selection identified key factors for diagnosing DSPN. Numbness scores, sensory test results (vibration), reflexes (knee, ankle), sural nerve attributes (sensory nerve action potential [SNAP] amplitude, nerve conduction velocity [NCV], latency), and peroneal/tibial motor NCV were candidate variables at baseline and over one year. Tibial compound motor action potential amplitudes were used for initial diagnosis, and ulnar SNAP amplitude for subsequent diagnoses. CNNs and LSTMs achieved impressive AUC values of 0.98 for DSPN diagnosis prediction, and 0.93 and 0.89 respectively for predicting the future occurrence of DSPN. RF techniques combined with two deep learning algorithms exhibited outstanding performance in diagnosing and predicting the future occurrence of DSPN. These algorithms have the potential to serve as surrogate measures, aiding clinicians in accurate diagnosis and future prediction of DSPN.

Baroreflex Sensitivity as a Surrogate Biomarker for Concurrently Assessing the Severity of Arterial Stiffness and Cardiovascular Autonomic Neuropathy in Individuals with Type 2 Diabetes.

This study aimed to investigate whether baroreflex sensitivity (BRS) could serve as a reliable metric for assessing cardiovascular autonomic neuropathy (CAN) and concurrently act as a surrogate biomarker for evaluating the severity of arterial stiffness and CAN in individuals diagnosed with type 2 diabetes mellitus (T2DM). Participants underwent brachial-ankle pulse wave velocity (baPWV) as well as autonomic function evaluations encompassing the Sudoscan-based modified composite autonomic scoring scale (CASS), baroreflex sensitivity, and heart rate variability in time domains and frequency domains. Linear regression analysis was performed to evaluate the influence of independent variables on baPWV and modified CASS. Participants with higher baPWV values were older, with longer diabetes duration, lower body weight, body mass index, waist circumference, elevated systolic and diastolic blood pressure, and mean arterial blood pressure. They also exhibited a higher prevalence of retinopathy as the underlying disease and reduced estimated glomerular filtration rate. Multiple linear regression analysis revealed that age and BRS were significantly associated with baPWV while diabetes duration, UACR, and BRS were significantly associated with modified CASS. Our study confirms the significant association of BRS with baPWV and modified CASS in T2DM, highlighting its pivotal role in linking microvascular and macrovascular complications. This supports BRS as a surrogate marker for assessing both the severity of arterial stiffness and cardiovascular autonomic neuropathy in T2DM, enabling the early identification of complications.

Development and Comparison of Treatment Decision Tools for Glucocorticoid-Induced Osteoporosis.

Long-term Glucocorticoid (GC) use results in compromised bone strength and fractures, and several treatment recommendations have been developed to prevent fractures, but none have been validated in a real-world setting. This study aims to create a treatment decision tool and compares this tool to the treatment suggestions from the American College of Rheumatology (ACR), International Osteoporosis Foundation and European Calcified Tissue Society (IOF-ECTS), and GC-adjusted Fracture Risk Assessment Tool (GC-FRAX), above the intervention threshold. We utilized registry data gathered at Chang Gung Memorial Hospital at Kaohsiung, Taiwan, between September 2014 and April 2021. This research is a single-center, observational, and case-controlled study. We recruited participants using prednisone for at least 2.5 mg/day or the equivalent dose for over 3 months, excluding those younger than 40, those with malignancies, or those currently undergoing anti-osteoporosis therapy. The primary endpoint was new fragility fractures within 3 years, including morphometric vertebral fractures detected at baseline and with a follow-up thoracic-lumbar spine X-ray. Participants were randomly allocated into derivation and validation sets. We developed the Steroid-Associated Fracture Evaluation (SAFE) tool in the derivation cohort by assessing the weights of exploratory variables via logistic regression. Prediction performance was compared in the validation set by the receiver operating characteristic (ROC) curve, the area under the curve (AUC), and sensitivity and specificity. A total of 424 treatment-naïve subjects were enrolled, and 83 (19.6%) experienced new fractures within 3 years. The final formula of the SAFE tool includes osteoporosis (1 point), an accumulated GC dose ≥ 750 mg within 6 months (or equivalent prednisolone of ≥4.5 mg/day for 6 months) (1 point), a BMI ≥ 23.5 (1 point), previous fractures (1 point), and elderliness of ≥70 years (2 points). In the validation set, a treatment decision based on the SAFE ≥ 2 points demonstrated an AUC of 0.65, with a sensitivity/specificity/accuracy of 75.9/54.0/58.9, with an ACR of 0.56 (100.0/11.0/31.0), IOF-ECTS 0.61 (75.9/46.0/52.7), and GC-FRAX 0.62 (82.8/42.0/51.2). Among current GIOP recommendations, the SAFE score serves as an appropriate treatment decision tool with increased accuracy and specificity.

Predictive value of heart rate variability and electrochemical skin conductance measurements for cardiovascular autonomic neuropathy persistence in type 2 diabetes and prediabetes: A 3-year follow-up study.

OBJECTIVE: The study aimed to explore risk stratification approaches for cardiovascular autonomic neuropathy (CAN) in individuals with prediabetes and type 2 diabetes (T2DM) over a three-year follow-up period. METHODS: Participants underwent evaluations of autonomic function encompassing cardiovascular autonomic reflex tests (CARTs), baroreflex sensitivity (BRS), heart rate variability (HRV) in time domains (standard deviation of all normal RR intervals (SDNN)) and frequency domains (high frequency/low frequency ratio), and electrochemical skin conductance (ESC). The diagnosis of CAN relied on abnormal CART results. Subjects were categorized into 4 groups, based on their assessment of cardiac autonomic function at 3-year follow-up, relative to the presence or absence of CAN at baseline assessment: Persistent absence of CAN; Resolution of CAN; Progression to CAN; and Persistent CAN. RESULTS: Participants with T2DM/prediabetes (n = 91/7) were categorized as: Persistent absence of CAN (n = 25), Resolution of CAN (n = 10), Progression to CAN (n = 18), and Persistent CAN (n = 45) groups. The Persistent absence of CAN group showed significant associations with SDNN. The Resolution of CAN group exhibited notable associations with mean HbA1C (follow-up), while the Progression to CAN group displayed a significant link with baseline estimated glomerular filtration rate. The Persistent CAN group demonstrated significant associations with SDNN and Sudoscan CAN risk score. Screening recommendations involve biennial to annual assessments based on risk levels, aiding in CAN detection and subsequent comprehensive and time-intensive autonomic function tests for confirmation. The study's findings offer improved risk categorization approaches for detecting CAN, which has relevance for shaping public health strategies.

Prognostic value of longitudinal HbA1c variability in predicting the development of diabetic sensorimotor polyneuropathy among patients with type 2 diabetes mellitus: A prospective cohort observational study.

AIMS/INTRODUCTION: This prospective cohort study aims to identify the optimal measure of glycated hemoglobin (HbA1c) variability and to explore its relationship with the development of new diabetic sensorimotor polyneuropathy (DSPN) in individuals with type 2 diabetes mellitus, building upon previous cross-sectional studies that highlighted a significant association between HbA1c visit-to-visit variability and DSPN. MATERIALS AND METHODS: In a prospective study, 321 participants diagnosed with type 2 diabetes mellitus underwent comprehensive clinical assessments, neurophysiologic studies, and laboratory evaluations at enrollment and follow-up. Various indices, including HbA1c standard deviation (HbA1c SD), coefficient of variation (HbA1c CV), HbA1c change score (HbA1c HVS), and average real variability (HbA1c ARV), were employed to calculate the visit-to-visit variability HbA1c based on 3 month intervals. The investigation focused on examining the associations between these indices and the development of new DSPN. RESULTS: The average follow-up duration was 16.9 ± 6.9 months. The Cox proportional hazards model identified age (P = 0.001), diabetes duration (P = 0.024), and HbA1C ARV (P = 0.031) as the sole factors associated with the development of new DSPN. Furthermore, the cumulative risk of developing DSPN over 1 year demonstrated a significant association with HbA1C ARV (P = 0.03, log-rank test). CONCLUSIONS: Apart from age and diabetes duration, HbA1c variability emerged as a robust predictor for the occurrence of new DSPN. Among the various measures of HbA1c variability evaluated, HbA1c ARV demonstrated the highest potential as a reliable indicator for anticipating the onset of new DSPN.

Sudoscan as substitute for quantitative sudomotor axon reflex test in composite autonomic scoring scale and its correlation with composite autonomic symptom scale 31 in type 2 diabetes.

OBJECTIVE: This study aims to evaluate the feasibility of substituting electrochemical skin conductance measurement using SUDOSCAN for sudomotor function testing in the Composite Autonomic Scoring Scale (CASS) and to correlate the results with the Composite Autonomic Symptom Scale 31 (COMPASS 31) among patients with type 2 diabetes mellitus (T2DM). METHODS: Fifty patients with T2DM underwent cardiovascular autonomic function testing and the SUDOSCAN test and completed the COMPASS 31 questionnaire. We developed a SUDOSCAN-based sudomotor subscore as a substitute for the original sudomotor subscore (based on the quantitative sudomotor axon reflex test [QSART]). The modified CASS score (SUDOSCAN-based sudomotor subscore combined with the adrenergic and cardiovagal subscores) and the original CASS score without suomotor assessment (sum of the adrenergic and cardiovagal subscores) were obtained according to the results of the cardiovascular autonomic function and SUDOSCAN tests. RESULTS: The total COMPASS 31 score was significantly correlated with the modified CASS score (p = 0.019 and 0.037 for the raw and weighted scores, respectively) but not with the CASS score without sudomotor assessment. After adding the SUDOSCAN-based sudomotor subscore, the number of patients identified as having diabetic autonomic neuropathy (DAN) increased from 24 (48 %, based on the CASS score without sudomotor assessment) to 35 (70 %, based on the modified CASS score). The modified CASS score enhances the accuracy of assessing autonomic function and improves the diagnosis of diabetic autonomic neuropathy (DAN) among patients with T2DM. In medical settings where QSART is not accessible, SUDOSCAN testing offers a practical and efficient alternative.

Impacts of Chemerin Levels and Antioxidant Capacity on the Severity of Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes and Prediabetes.

Existing evidence supports an association between chemerin levels and cardiovascular risk, while reduced thiol levels are linked to diabetes mellitus. It is hypothesized that chemerin may contribute to autonomic dysfunction and cardiovascular risk in type 2 diabetes mellitus (T2DM), potentially mediated by the antioxidant capacity of patients with well-controlled T2DM and prediabetes. Comprehensive cardiovascular autonomic testing and biomarker assessments were conducted for all participants. The severity of cardiovascular autonomic neuropathy (CAN) was evaluated using the composite autonomic scoring scale (CASS). A mediation model was employed to explore the potential relationships among chemerin levels, antioxidant capacity (indicated by thiol levels), and CAN severity (indicated by CASS values). A total of 184 participants were enrolled in this study, comprising 143 individuals with T2DM and 40 individuals with prediabetes. The findings reveal a significant negative association between thiols levels (r = -0.38, p < 0.0001) and the CASS values, while a positive association is observed between chemerin levels (r = 0.47, p < 0.0001) and the CASS values. Linear regression analysis identified chemerin and thiols as independent variables significantly associated with CASS values. Subsequent mediation analysis elucidated that thiols levels act as mediators in the relationship between elevated chemerin levels and an increased CASS value. This study shows that poor cardiovascular function, higher chemerin levels, and reduced antioxidant capacity coexist in individuals with T2DM and prediabetes. Mediation analysis suggests a pathophysiological link between high chemerin levels and low antioxidant capacity, adversely impacting CAN severity.

Factors associated with subclinical inflammation of wrist joints in rheumatoid arthritis patients with low or no disease activity- a RA ultrasound registry study.

BACKGROUND: To evaluate the factors to predict subclinical inflammation of wrist joints in patients with RA who are in clinical remission or low disease activity. METHODS: Gray scale and power Doppler ultrasound were performed on the dorsal radio-lunate of both wrists. The presence of synovitis, comorbidities, and use of disease modifying anti-rheumatic drugs were recorded. A Multivariable forward logistical regression model was used to identify factors associated with subclinical inflammation. RESULTS: There were 1248 patients (1010 females, 238 males; mean age: 60.0 ± 10.5 years ). 57.4% of patients in complete remission and low disease activity had sonographic inflammation. Multivariable forward logistic regression analysis indicated that male sex, smoking are positively associated with inflammation and that age, alcohol consumption, and use of methotrexate, glucocorticoid, or a biological therapy are negatively associated with inflammation. Use of biological agents decreased the risk of inflammation by 40.9%. CONCLUSIONS: There was evidence of subclinical inflammation in most patients who were in low or no disease activity, those with biological therapy had lower risk of subclinical inflammation.

Quantitative thermal testing as a screening and follow-up tool for diabetic sensorimotor polyneuropathy in patients with type 2 diabetes and prediabetes.

Introduction: The diagnosis and assessment of neuropathy severity of diabetic sensorimotor polyneuropathy (DSPN) are mainly based on clinical neuropathy scores and electrophysiologic studies. This study aimed to determine whether quantitative thermal testing (QTT) can be used as a screening and follow-up tool for DSPN of prediabetes and type 2 diabetes at baseline and at 1-year follow-up. Methods: All patients were assessed using the Toronto Clinical Neuropathy Score (TCNS) and underwent electrophysiological testing, including a nerve conduction study (NCS) and QTT, at baseline and at a 1-year follow-up. The TCNS and the composite scores of nerve conduction were used to assess the severity of DSPN. The DSPN status at the 1-year follow-up was classified as remaining no DSPN, remaining DSPN, regression to no DSPN, or progression to DSPN. Results: Diabetic sensorimotor polyneuropathy was initially diagnosed in 89 patients with prediabetes and type 2 diabetes (22%). The regressed to no DSPN in 29 patients and progressed to DSPN in 20 patients at the 1-year follow-up. TCNS was significantly correlated with composite scores of nerve conduction, hand cold detection threshold (CDT), hand warm detection threshold (WDT), foot CDT, and foot WDT. Stepwise logistic regression demonstrated that the foot CDT (p < 0.0001) was independently associated with the presence of DSPN. The TCNS, composite scores of the nerve conduction, hand WDT, hand CDT, foot WDT, and foot CDT were all statistically significant among the four different DSPN status groups at two different time periods (baseline and the 1-year follow-up). Conclusion: The foot CDT can be used as an initial screening tool for DSPN alternatively. The characteristics of nerve damage after 1 year of DSPN can be progressive or reversible, and the neurological functions of large and small fibers have a parallel trend, which can be objectively measured by NCS and QTT.

Effectiveness of Center of Pressure Trajectory as Anticipatory Postural Adjustment Measurement in Parkinson's Disease With Freezing of Gait History.

BACKGROUND: Evidence showed that patients with Parkinson's disease (PD) who have a history of freezing of gait (FOG) have hypometric anticipatory postural adjustment (APA) during gait initiation (GI) compared to PD without FOG. OBJECTIVES: This study aimed to test the feasibility of center of pressure (COP) displacement during GI as the measure of APA in PD with and without a history of FOG. METHODS: Patients with PD underwent COP trajectory measurements, including duration, length, velocity, and acceleration in different phases of APA (APA1, APA2a, APA2, and LOC), as well as evaluation of New Freezing of Gait Questionnaire (NFOG-Q), Tinetti balance and gait score, and Postural Instability and Gait Difficulty (PIGD) score in the on and off medication states. RESULTS: The duration (seconds) of APA2a, APA2b, and LOC were highest while velocity in mediolateral direction (X) (m/s), including APA1, APA2a, APA2b, and LOC showed lowest in PD with FOG. Velocity in the mediolateral direction in different phases of APA increased in patients with FOG after dopaminergic therapy. APA2a (seconds) and APA2b (X) (m/s) were significantly associated with NFOG-Q part II, APA2b (X) (m/s) was significantly associated with NFOG-Q part III, and APA2a (seconds) was significantly associated with Tinetti balance and gait and PIGD score. CONCLUSIONS: PD with FOG history showed a favorable response of APAs to dopaminergic replacement. The APA parameters by COP trajectory, especially lateral COP shift toward the stance foot (APA2b (X) (m/s) and APA2a (seconds)) are surrogate markers to assess PD with FOG history.

Clinical Utility of Plantar Pressure Measurements as Screening in Patients With Parkinson Disease With and Without Freezing of Gait History.

OBJECTIVE: To test the feasibility of objective assessments using the TekScan MatScan pressure mat plantar pressure measurement as a time-effective screening service for Parkinson disease (PD) with and without freezing of gait (FOG) history. DESIGN: Prospective cross-sectional study. SETTING: Largest medical center in southern Taiwan. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Plantar pressure measurements including average peak pressure (PP), contact area (CA), and pressure-time integral (PTI) in static and dynamic conditions as well as clinical scores during off-medication states. PARTICIPANTS: A total of 103 patients with PD and 22 age- and sex-matched volunteers without PD (N=125). RESULTS: Plantar pressure assessment including PP, CA, and PTI on the total foot areas between participants with PD and controls without PD in the static conditions are similar. Patients with PD presented higher PTI on total foot areas as well as hallux, midfoot area, and medial and lateral heels during dynamic conditions than controls without PD. The PP, CA, and PTI during the static condition and CA during the dynamic condition on the hallux showed statistical significance between PD with and without FOG history. Stepwise logistic regression after controlling with age and body mass index showed only PTI on hallux (static conditions) was significantly associated with the presence of FOG. The receiver operating characteristic curve analysis in diagnostic accuracy for FOG in PTI was statistically significant (P=.002; area under the curve, 0.71). CONCLUSIONS: FOG screening using the TekScan MatScan pressure mat plantar pressure measurement could serve as a time-effective screening service at the outpatient clinic. Based on our study, PTI may be valuable in auxiliary diagnosis.

The Effects of Indoxyl Sulfate and Oxidative Stress on the Severity of Peripheral Nerve Dysfunction in Patients with Chronic Kidney Diseases.

Pieces of evidence support the view that the accumulation of uremic toxins enhances oxidative stress and downstream regulation of signaling pathways, contributing to both endothelial microangiography and cell dysfunction. This study is to address the impact of protein-binding uremic toxins on the severity of peripheral nerve function in patients with chronic kidney disease (CKD). Fifty-four patients with CKD were included in the Toronto Clinical Neuropathy Score (TCNS), nerve conduction study (NCS), and laboratory studies including protein-binding uremic toxin (indoxyl sulfate [IS] and p-cresyl sulfate [PCS]), oxidative stress (Thiol and thiobarbituric acid reacting substances [TBARS]), and endothelial dysfunction (serum intercellular adhesion molecule 1 [sICAM-1] and serum vascular adhesion molecule 1 [sVCAM-1]) at enrollment. We used composite amplitude scores (CAS) to analyze the severity of nerve conductions on peripheral nerve function. TCNS and CAS were higher in the diabetic CKD group (p = 0.02 and 0.01, respectively). The NCS revealed the compound muscle action potential of ulnar and peroneal nerves and the sensory nerve action potential of ulnar and sural nerves (p = 0.004, p = 0.004, p = 0.004, and p = 0.001, respectively), which was found to be significantly low in the diabetic group. CAS was significantly correlated with age (r = 0.27, p = 0.04), urine albumin-creatinine ratio (UACR) (r = 0.29, p = 0.046), free-form IS (r = 0.39, p = 0.009), sICAM-1 (r = 0.31, p = 0.02), sVCAM-1 (r = 0.44, p < 0.0001), TBARS (r = 0.35, p = 0.002), and thiols (r = −0.28, p = 0.045). Linear regression revealed that only TBARS and free-form IS were strongly associated with CAS. The mediation analysis shows that the sVCAM-1 level serves as the mediator between higher IS and higher CAS. IS and oxidative stress contribute to the severity of peripheral nerve dysfunction in patients with CKD, and chronic glycemic impairment can worsen the conditions.

Identify differential inflammatory cellular and serology pathways between children and adult patients in the lupus registry.

BACKGROUND: Age variances in systemic lupus erythematosus (SLE) may reflect different patterns and consequences. Monocyte differentiation is critical, and cytokine and chemokine milieu may be associated with long term outcome and treatment responses. This study aims to evaluate the inflammatory cellular and serology pathways associated with age in our lupus registry. METHODS: We included patients with SLE and divided them into 2 groups according to age, ≤18 or >18 years old. We performed flow cytometry analysis to define the peripheral blood monocyte differentiation pattern and phenotypes and used the multiplex method to detect cytokine and chemokine panels. The results were then compared between the 2 subgroups. RESULTS: In total, 47 SLE patients were included in this study. Of those, 23 patients were 18 years old or younger, and 24 patients were over the age of 18 years old. An increased distribution of circulating Type 2b macrophage (M2b) subsets was found in patients over 18 years old (P < 0.01), and we found the Type 1 macrophage (M1) to demonstrate a marked increase in those patients ≤18 years old (P = .05). Eotaxin values were significantly higher in patients >18 years old (P = .03), and Macrophage Inflammatory Protein (MIP)-1alpha, MIP-1beta, Interleukine (IL)-1Ra, Interferon (IFN)-alpha2, IL-12, IL-13, IL-17A, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-9, Monocyte Chemoattractant Protein (MCP)-3, Transforming Growth Factor (TGF)-alpha, and Tumor necrosis factor (TNF)-beta were significantly higher in patients ≤18 years old (all P < .05). CONCLUSIONS: We found significant M2b polarization in adult SLE patients, and several cytokines and chemokines were significantly higher in SLE patients ≤ 18 years old. Peripheral blood mononuclear cell differentiation and cytokine milieu could represent composite harm from both Type 2 helper T cells (Th2) and Type 17 helper T cells (Th17) pathways and may thus be a potential therapeutic target in younger SLE patients.

The Impact of Seropositivity on Systemic Bone Loss in Rheumatoid Arthritis-A 3-Year Interim Analysis of a Longitudinal Observational Cohort Study.

Objective: To explore the impact of seropositivity on systemic bone loss in rheumatoid arthritis (RA). Methods: We conducted an interim analysis of the RA registry. Patients were examined with dual-energy X-ray absorptiometry at baseline and again 3 years later. Participants were grouped into seropositive (SPRA) and seronegative (SNRA) based on the presence or absence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (ACPA). After matching (1:2) for age and sex, SNRA and SPRA patients were divided into groups A and B. Each matched group (A or B) was further subdivided according to the number of antibodies present (0, group I; 1, group II; 2, group III). Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict bone mineral density (BMD) change. Results: A total of 477 participants who completed a 3-year observation period were included. After matching, 312 participants were enrolled (group A, 104; group B, 208). Three years later, group B had significant BMD reduction in the femoral neck (FN) (p < 0.001), total hip (TH) (p = 0.001), and first through fourth lumbar vertebrae (L1-4) (p = 0.006), while group A had bone loss only at FN (p = 0.002). Groups I, II, and III included 104, 52, and 156 participants, respectively. Compared to baseline, BMD decreased significantly at FN (p = 0.002) in group I, FN (p < 0.001) in group II, and FN (p < 0.001), TH (p = 0.002), and L1-4 (p = 0.016) in group III. In terms of regression-adjusted percent change in BMD, more significantly negative changes were found at all measured sites in group B (p < 0.001, all) and at TH and L1-4 within groups I-III (p for trend < 0.001 and < 0.001, respectively). Regardless of antibodies, anti-osteoporotic therapy can preserve bone density in RA patients. Conclusion: After 3 years, SPRA patients lost more bone density than SNRA patients. More attention should be paid to SPRA patients, especially those with double-positive antibodies, including a vigorous evaluation of BMD and fracture risk. Anti-osteoporotic therapy can prevent BMD loss irrespective of autoantibodies.

Establishment of a preliminary FRAX®-based intervention threshold for rheumatoid arthritis-associated fragility fracture: a 3-year longitudinal, observational, cohort study.

BACKGROUND: To establish a FRAX®-based prediction model for rheumatoid arthritis (RA)-associated fragility fracture. METHODS: This study is a longitudinal, real-world, registry cohort study. Patients with RA were registered to start in September 2014. The baseline demographics, bone mineral density (BMD), and risk factors of osteoporosis or fragility fracture were recorded. Subsequent fragility fractures during the 3-year observation period were also recorded. We developed a fixed intervention threshold (FITD) to identify fractures by choosing an optimal cut-off point on the receiver operating characteristic (ROC) curve and FRAX®. Several models for intervention thresholds (IT), including fixed intervention threshold (Taiwan) (FITT), age-specific individual intervention threshold (IIT), and hybrid intervention threshold (HIT), were compared to evaluate which IT model will have better discriminative power. RESULTS: As of December 2020, a total of 493 RA participants have completed the 3-year observation study. The mean age of the participants was 59.3 ± 8.7, and 116 (23.5%) new fragility fractures were observed during the study period. In terms of pairwise comparisons of area under the curve (n, 95% confidence interval) in the ROC curve, the FITD (0.669, 0.610-0.727, p < 0.001) with a value of 22% in major osteoporotic fracture and FITT (0.640, 0.582-0.699, p < 0.001) is significantly better than reference, but not for IIT (0.543, 0.485-0.601, p = 0.165) and HIT (0.543, 0.485-0.601, p = 0.165). CONCLUSION: An optimal FIT is established for intervention decisions in RA-associated fragility fractures. This model can offer an easy and simple guide to aid RA caregivers to provide interventions to prevent fragility fractures in patients with RA.

Radiotherapy Is Associated with an Accelerated Risk of Carotid Atherosclerosis in Patients with Nasopharyngeal Carcinoma: A Nine-Year Prospective Follow-Up Study.

Radiation-related extracranial vasculopathy is a common late effect after radiation in patients with nasopharyngeal carcinoma (NPC). We proposed the hypothesis that radiation-related extracranial vasculopathy is a progressive process that can begin immediately after radiotherapy and persist for a longer period, and inflammation and oxidative stress may play a pivotal role in this process. Thirty-six newly diagnosed NPC patients were assessed with B-mode ultrasound for the common carotid artery (CCA) intima media thickness (IMT) measurement as well as surrogate markers at three different stages (baseline, immediately after concurrent chemoradiation therapy (CCRT), and 9 years after enrollment). A healthy control group was also recruited for comparison. Surrogate markers including a lipid profile, HbA1c, inflammation, oxidative stress, and platelet activation markers were assessed. The mean CCA IMT in the NPC group were increased immediately after CCRT (p = 0.043). The mean CCA IMT value after a 9-year follow-up also showed a significant increase in NPC and control group, respectively (p < 0.0001 and p < 0.0001, paired t test). The annual increase mean CCA IMT (mm) was 0.053 ± 0.025 and 0.014 ± 0.013 in NPC and control group, respectively (p < 0.0001). The baseline high sensitivity CRP (hs-CRP), thiol, TBARS, and CD63 level were significantly higher in the NPC group (hs-CRP, p = 0.001, thiol, p < 0.0001, TBARS, p = 0.05, and CD63 level, p = 0.04). The thiol and TBARS levels were significantly lower in NPC patients immediately after CCRT (thiol, p < 0.0001, and TBARS, p = 0.043). The CD62P level was significantly higher while the thiol level was significantly lower in the NPC group after a 9-year follow-up (CD62P level, p = 0.007; and thiol level, p = 0.004). Radiation-related extracranial vasculopathy is a progressive process that begins immediately after radiotherapy with significantly increased carotid IMT compared to the control group during the 9-year follow-up. Chronic inflammation and oxidative stress might serve to drive the process and also contribute to increased platelet activation.

Concurrent chemoradiation therapy is associated with an accelerated risk of cardiovascular autonomic dysfunction in patients with nasopharyngeal carcinoma: A 9-year prospective follow-up study.

BACKGROUND: Concurrent chemoradiation therapy (CCRT) is the mainstay treatment for patients with nasopharyngeal carcinoma (NPC). Baroreflex impairment can be a late sequela in patients after neck radiotherapy. We hypothesized that cardiovascular autonomic dysfunction is a progressive process that can begin after CCRT and persists for a longer period. METHODS: Cardiovascular autonomic function was assessed in 29 newly diagnosed patients with NPC using standardized measures including heart rate response to deep breathing (HRDB), Valsalva ratio (VR), baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV), biomarkers of oxidative stress, and inflammation at three different time points (baseline, immediately after CCRT, and 9 years after enrollment). A healthy control group was recruited for the comparison. RESULTS: Although there was an aging effect on autonomic parameters in both groups during the 9 years of follow-up, the between-group comparison showed that there was a significant decrease in HRDB, VR, and HRV at the 9th year of follow-up in the NPC group. Repeated measures ANOVA after controlling for age and sex showed that both HRDB and triangle index of HRV had statistically significant differences between the two groups. CONCLUSION: Based on our results, cardiovascular autonomic dysfunction after CCRT is a progressive and dynamic process. Cardiovagal impairment occurs in the early phase and persists in decline, while adrenergic dysfunction is significant only after a 9-year follow-up. In contrast to the current opinion, our study showed that both afferent and efferent baroreflex pathways can be involved after CCRT.

Feasibility of Combining Disease-Specific and Balance-Related Measures as Risk Predictors of Future Falls in Patients with Parkinson's Disease.

Evidence supports the view that postural sway in a quiet stance increases with clinical disease severity and dopaminergic therapy in idiopathic Parkinson's disease (PD), which, in turn, increases the risk of falling. This study evaluated the feasibility of combining disease-specific and balance-related measures as risk predictors for future falls in patients with PD. The patients with PD underwent postural sway measurements (area, length, and velocity traveled by the excursion of the center of pressure) and clinical functional scores (Parkinson's Disease Rating Scale [UPDRS] and Tinetti balance and gait score assessment) in both the on- and off-states of dopaminergic therapy. The outcome was defined as the development of a new fall. The sway area, velocity, and length increased after the medication administration. The Cox proportional hazards model showed that only previous fall history, Tinetti balance and gait score (on-state), and levodopa equivalent daily dose (LEDD) were associated with the development of future falls. The cumulative risk of fall development showed that the sway length and velocity were associated with future falls after more than six months. The combined LEDD, Tinetti balance and gait score (on-state), and velocity and length of postural sway (on-state) had the highest diagnostic accuracy (area under the curve = 0.9, p < 0.0001). Dopaminergic therapy can improve clinical functional scores but worsen balance-related measures. Increased sway length and velocity during the medication state are hallmarks of future falls, particularly in advanced PD. Combining disease-specific and balance-related measures can serve as an auxiliary diagnosis as risk predictors for future falls.

Risk factor analysis of fragility fractures in rheumatoid arthritis: A 3-year longitudinal, real-world, observational, cohort study.

OBJECTIVES: To explore the risk factors for fragility fractures in rheumatoid arthritis (RA) patients using a 3-year longitudinal, observational cohort study. METHODS: This RA registry study included consecutive RA patients in the outpatient clinic of Chang Gung Memorial Hospital since September 1, 2014. The demographics, clinical characteristics, lifestyle, evidence of previous fracture, risk factors according to the Fracture Risk Assessment Tool (FRAX®), and the FRAX score of each participant were recorded. The participants were categorized into the new incident fracture (group A) and no incident fracture (group B) groups based on evidence or absence of new incident fractures and propensity score matching (age and gender, 1:2). RESULTS: Overall, 477 participants completed the 3-year observation period. After matching, 103 and 206 participants were allocated to groups A and B, respectively. The non-adjusted model revealed, presented as hazard ratio (HR) (95% confidence interval [CI]), that the presence of co-morbidity (1.80 [1.17-2.78], p = 0.008), Health Assessment Questionnaire Disability Index (1.35 [1.07-1.69], p = 0.010), lower baseline hip bone mineral density (0.11 [0.02-0.48], p = 0.004), longer disease duration (1.02 [1.00-1.04], p = 0.026), higher FRAX score of major fracture (1.03 [1.02-1.04], p<0.001) or hip fracture (1.03 [1.02-1.04], p<0.001), and previous fracture history (2.65 [1.79-3.94], p<0.001) were associated with new incident fracture. After adjustment, it was disclosed that a previous fracture is an independent risk factor for fragility fractures in RA patients (2.17 [1.20-3.90], p = 0.010). CONCLUSIONS: In addition to aging and disease-related factors, previous fracture history is the most important risk factor for fragility fractures in RA patients.