Infliximab biosimilar GP1111: a review of 5 years' post-approval experience.

INTRODUCTION: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha, and GP1111 (Zessly®, Sandoz) is the most recently approved infliximab biosimilar in Europe. We reviewed the approval process and key evidence for GP1111, focusing primarily on the indications of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). AREAS COVERED: This narrative review discusses preclinical, clinical, and real-world data for GP1111. EXPERT OPINION: Results from the Phase III REFLECTIONS trial in patients with moderate-to-severe active RA despite methotrexate therapy confirmed the similarity in efficacy and safety between GP1111 and reference infliximab. Switching from reference infliximab to GP1111 in REFLECTIONS had no impact on efficacy or safety. Since the European approval of GP1111 in March 2018, real-world data have also confirmed the efficacy and safety of switching from another infliximab biosimilar to GP1111 in patients with RA and IBD. In addition, budget impact analysis of various sequential targeted treatments in patients with RA found that GP1111 was cost-effective when used early after failure of conventional synthetic disease-modifying antirheumatic drugs. Therefore, 5 years' post-approval experience with GP1111 in RA and IBD, and key clinical and real-world evidence, support the safety and efficacy of continued use of GP1111 in all infliximab-approved indications.

Magnon-phonon Fermi resonance in antiferromagnetic CoF2.

Understanding spin-lattice interactions in antiferromagnets is a critical element of the fields of antiferromagnetic spintronics and magnonics. Recently, coherent nonlinear phonon dynamics mediated by a magnon state were discovered in an antiferromagnet. Here, we suggest that a strongly coupled two-magnon-one phonon state in this prototypical system opens a novel pathway to coherently control magnon-phonon dynamics. Utilizing intense narrow-band terahertz (THz) pulses and tunable magnetic fields up to µ0Hext = 7 T, we experimentally realize the conditions of magnon-phonon Fermi resonance in antiferromagnetic CoF2. These conditions imply that both the spin and the lattice anharmonicities harvest energy from the transfer between the subsystems if the magnon eigenfrequency fm is half the frequency of the phonon 2fm = fph. Performing THz pump-infrared probe spectroscopy in conjunction with simulations, we explore the coupled magnon-phonon dynamics in the vicinity of the Fermi-resonance and reveal the corresponding fingerprints of nonlinear interaction facilitating energy exchange between these subsystems.

Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .

Occurrence of injuries and illnesses in athletes with a physical impairment; a forty-week prospective cohort study.

OBJECTIVES: Currently, the knowledge about the epidemiology of sport-related health problems of athletes with a physical impairment is limited. Therefore, this study aims to describe the prevalence, incidence and severity of sport-related health problems of athletes with a physical impairment in the Netherlands over a one sport season. DESIGN: Prospective cohort study. METHODS: Athletes (n = 99) with a physical impairment participated in this study. After completing a baseline questionnaire, athletes started a 40-week health monitoring period, during which they completed the Dutch translation of the OSTRC Questionnaire on Health Problems every week. Based on the reported information, injury and illness prevalence, incidence, weekly cumulative severity score, weekly time loss from sport and the total burden were calculated. RESULTS: A total of 368 health problems were reported by 95 athletes. These health problems consisted of 258 injuries and 110 illnesses. The average weekly prevalence of health problems was 48.0 %; for injuries 34.6 %, and illnesses 13.4 %. Differences were found when considering injury severity, with the highest severity scores for athletes with a limb deficiency. Furthermore, recreational athletes reported the highest injury severity scores, followed by athletes who competed nationally and athletes who competed internationally. CONCLUSIONS: Data from this study show a high average weekly prevalence of health problems, and differences amongst various impairment categories and sport levels when considering the severity of injuries. These results add to the knowledge regarding sport-related health problem epidemiology in this population, indicating that impairment category and sport level should be taken into account when developing injury prevention strategies.

The Effect of Mindset and Breathing Exercises on Physical and Mental Health in Persons with Spinal Cord Injury-A Pilot Feasibility Study.

This study investigated the feasibility and efficacy of mindset and breathing exercises (Wim Hof Method (WHM)) on physical and mental health in persons with spinal cord injury (SCI). Ten individuals with SCI participated in this pilot study. These ten participants followed a 4-week WHM intervention, with one weekly group session in the rehabilitation center and daily practice at home using the WHM app. An in-person exit-interview was conducted post-intervention to collect qualitative information on participants' experiences, regarding the feasibility and effects of the intervention. Furthermore, tests and questionnaires were administered pre- and post-intervention to assess physical and mental health outcomes. Adherence to the weekly in-person meetings was excellent and no adverse events occurred. Physical and mental health outcomes in this small sample size showed some pre-post differences. This pilot feasibility study provides preliminary evidence supporting the feasibility and efficacy of the WHM, including mindset and breathing exercises, on physical and mental health of people with SCI. These results warrant a randomized-controlled trial, including cold exposure, of this novel intervention in people with SCI.

The impact of lower-limb function on upper-limb pull and push strength in elite handcycling athletes.

This study investigated the impact of performing a closed kinetic chain with the lower limbs on isometric upper-limb pull and push strength. Sixty-two elite handcyclists were assessed with the Manual Muscle Test and allocated to groups with partial to normal (LLF) or no lower-limb (no-LLF) function. Both groups performed upper-limb strength measurements under two kinetic-chain conditions. During the closed-chain condition, the lower limbs were attached to two footrests, providing horizontal and vertical support. During the open-chain condition, the footrests were removed and the limbs were supported vertically by a horizontal plate. Repeated-measures ANOVA were conducted to investigate main effects (open vs. closed chain, LLF vs. no-LLF) and their interaction. During pull, LLF performed better (p < 0.001, +11%) by pushing against the footrests. However, this increase in pulling strength during a closed-chain condition was not observed in the no-LLF. Therefore, findings suggest an advantage for the least impaired athletes by being able to perform lower-limb closed chains during pulling. Handcyclists with LLF can maximise pulling performance by adjusting the footrests. The classification system should consider the implications of these findings on the allocation of athletes with different levels of LLF and/or on the equipment regulation.

Upper-Body versus Lower-Body Cooling in Individuals with Paraplegia during Arm-Crank Exercise in the Heat.

PURPOSE: For wheelchair users with a spinal cord injury, the lower body may be a more convenient cooling site than the upper body. However, it remains unknown if leg cooling reduces thermal strain in these individuals. We compared the impact of upper-body versus lower-body cooling on physiological and perceptual outcomes during submaximal arm-crank exercise under heat stress in individuals with paraplegia. METHODS: Twelve male participants with paraplegia (T4-L2, 50% complete lesion) performed a maximal exercise test in temperate conditions, and three heat stress tests (32°C, 40% relative humidity) in which they received upper-body cooling (COOL-UB), lower-body cooling (COOL-LB), or no cooling (CON) in a randomized counterbalanced order. Each heat stress test consisted of four exercise blocks of 15 min at 50% of peak power output, with 3 min of rest in between. Cooling was applied using water-perfused pads, with 14.8-m tubing in both COOL-UB and COOL-LB. RESULTS: Gastrointestinal temperature was 0.2°C (95% confidence interval (CI), 0.1°C to 0.3°C) lower during exercise in COOL-UB versus CON (37.5°C ± 0.4°C vs 37.7°C ± 0.3°C, P = 0.009), with no difference between COOL-LB and CON ( P = 1.0). Heart rate was lower in both COOL-UB (-7 bpm; 95% CI, -11 to -3 bpm; P = 0.01) and COOL-LB (-5 bpm; 95% CI, -9 to -1 bpm; P = 0.049) compared with CON. The skin temperature reduction at the cooled skin sites was larger in COOL-LB (-10.8°C ± 1.1°C) than in COOL-UB (-6.7°C ± 1.4°C, P < 0.001), which limited the cooling capacity in COOL-LB. Thermal sensation of the cooled skin sites was improved and overall thermal discomfort was lower in COOL-UB ( P = 0.01 and P = 0.04) but not in COOL-LB ( P = 0.17 and P = 0.59) compared with CON. CONCLUSIONS: Upper-body cooling more effectively reduced thermal strain than lower-body cooling in individuals with paraplegia, as it induced greater thermophysiological and perceptual benefits.

Sports-Related Health Problems in Para-Sports: A Systematic Review With Quality Assessment.

CONTEXT: Participation in sports is associated with a risk of sports-related health problems. For athletes with an impairment, sports-related health problems further burden an already restricted lifestyle, underlining the importance of prevention strategies in para-sports. OBJECTIVE: To provide a comprehensive overview with quality assessment of the literature on sports-related health problems, their etiology, and available preventive measures in para-sports following the steps of the Sequence of Prevention. DATA SOURCES: A literature search (in PubMed, Embase, SPORTDiscus, CINAHL and the Cochrane Library) was performed up to December 8, 2021, in collaboration with a medical information specialist. STUDY SELECTION: The search yielded 3006 articles, of which 64 met all inclusion criteria. STUDY DESIGN: Systematic review with quality assessment. LEVEL OF EVIDENCE: Level 3. DATA EXTRACTION: Two independent researchers carried out the screening process and quality assessment. One researcher extracted data, and the Sequence of Prevention categorized evidence. RESULTS: A total of 64 studies were included, of which 61 reported on the magnitude and risk factors of sports-related health problems, while only 3 reported on the effectiveness of preventive measures. Of these, 30 studies were of high quality. Most studies (84%) included elite-level athletes. The reported injury incidence varied widely between sports (0-91 per 1000 athlete days) and impairment categories (1-50 per 1000 athlete days). The same applies to illness incidence with regard to different sports (3-49 per 1000 athlete days) and impairment categories (6-14 per 1000 athlete days). CONCLUSION: This review shows the current vast range of reported sport-related health problems in para-sports. There is limited evidence concerning the severity of these sports-related health problems and inconclusive evidence on the risk factors. Lastly, the evidence regarding the development and effectiveness of preventive measures for para-athletes is sparse.

Heat preparedness and exertional heat illness in Paralympic athletes: A Tokyo 2020 survey.

Paralympic athletes may be at increased risk for exertional heat illness (EHI) due to reduced thermoregulatory ability as a consequence of their impairment. This study investigated the occurrence of heat-stress related symptoms and EHI, and the use of heat mitigation strategies in Paralympic athletes, both in relation to the Tokyo 2020 Paralympic Games and previous events. Paralympic athletes competing in Tokyo 2020 were invited to complete an online survey five weeks prior to the Paralympics and up to eight weeks after the Games. 107 athletes (30 [24-38] years, 52% female, 20 nationalities, 21 sports) completed the survey. 57% of respondents had previously experienced heat-stress related symptoms, while 9% had been medically diagnosed with EHI. In Tokyo, 21% experienced at least one heat-stress related symptom, while none reported an EHI. The most common symptom and EHI were, respectively, dizziness and dehydration. In preparation for Tokyo, 58% of respondents used a heat acclimation strategy, most commonly heat acclimatization, which was more than in preparation for previous events (45%; P = 0.007). Cooling strategies were used by 77% of athletes in Tokyo, compared to 66% during past events (P = 0.18). Cold towels and packs were used most commonly. Respondents reported no medically-diagnosed EHIs during the Tokyo 2020 Paralympic Games, despite the hot and humid conditions in the first seven days of competition. Heat acclimation and cooling strategies were used by the majority of athletes, with heat acclimation being adopted more often than for previous competitions.

Humid Heat Equally Impairs Maximal Exercise Performance in Elite Para-Athletes and Able-Bodied Athletes.

PURPOSE: This study aimed to compare the impact of hot-humid environmental conditions on performance outcomes, thermoregulatory responses, and thermal perception during exercise between elite para- and able-bodied (AB) athletes. METHODS: Twenty elite para-athletes (para-cycling and wheelchair tennis) and 20 elite AB athletes (road cycling, mountain biking, beach volleyball) performed an incremental exercise test in a temperate environment (mean ± SD, 15.2°C ± 1.2°C; relative humidity, 54% ± 7%) and a hot-humid environment (31.9°C ± 1.6°C, 72% ± 5%). Exercise tests started with a 20-min warm-up at 70% of maximal heart rate, after which power output increased by 5% every 3 min until volitional exhaustion. RESULTS: Time to exhaustion was shorter in hot-humid versus temperate conditions, with equal performance loss for para- and AB athletes (median (interquartile range), 26% (20%-31%) vs 27% (19%-32%); P = 0.80). AB athletes demonstrated larger exercise-induced increases in gastrointestinal temperature (T gi ) in hot-humid versus temperate conditions (2.2 ± 0.7 vs 1.7 ± 0.5, P < 0.001), whereas T gi responses in para-athletes were similar between conditions (1.3 ± 0.6 vs 1.3 ± 0.4, P = 0.74). Para- and AB athletes showed similar elevations in peak skin temperature ( P = 0.94), heart rate ( P = 0.67), and thermal sensation score ( P = 0.64) in hot-humid versus temperate conditions. CONCLUSIONS: Elite para-athletes and AB athletes demonstrated similar performance decrements during exercise in hot-humid versus temperate conditions, whereas T gi elevations were markedly lower in para-athletes. We observed large interindividual variation within both groups, suggesting that in both para- and AB athletes, personalized heat mitigation plans should be developed based on individual thermal testing.

The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study.

BACKGROUND: AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ 6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy. METHODS: During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate. Patients completing the IP who achieved SDAI remission (≤ 3.3) at weeks 40 and 52 entered a 48-week de-escalation (DE) period. Patients treated with abatacept + methotrexate were re-randomized to continue weekly abatacept + methotrexate, or de-escalate and then withdraw abatacept (after 24 weeks), or receive abatacept monotherapy. Proportions of patients achieving sustained SDAI and Boolean remission, and Disease Activity Score in 28 joints using C-reactive protein (DAS28 [CRP]) < 2.6, were assessed. For patients achieving early sustained SDAI remission at weeks 24/40/52, flow between disease activity categories and individual trajectories was evaluated; flow was also evaluated for later remitters (weeks 40/52 but not week 24). RESULTS: Among patients treated with abatacept + methotrexate (n/N = 451/752) at IP week 24, 22% achieved SDAI remission, 17% achieved Boolean remission, and 42% achieved DAS28 (CRP) < 2.6; of these, 56%, 58%, and 74%, respectively, sustained a response throughout IP weeks 40/52. Among patients with a sustained response at IP weeks 24/40/52, 82% (14/17) on weekly abatacept + methotrexate, 81% (13/16) on abatacept monotherapy, 63% (12/19) who de-escalated/withdrew abatacept, and 65% (11/17) on abatacept placebo + methotrexate were in SDAI remission at end of the DE period; rates were higher than for later remitters in all arms except abatacept placebo + methotrexate. CONCLUSIONS: A high proportion of individual patients achieving clinical endpoints at IP week 24 with abatacept + methotrexate sustained their responses through week 52. Of patients achieving early and sustained SDAI remission through 52 weeks, numerically more maintained remission during the DE period if weekly abatacept treatment continued. TRIAL REGISTRATION: NCT02504268 (ClinicalTrials.gov), registered July 21, 2015.

Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis.

INTRODUCTION: One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA. METHODS: The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate. PRIMARY ENDPOINT: SDAI remission (≤ 3.3) at week 24. Pre-planned exploratory endpoint: maintenance of remission in patients with sustained remission (weeks 40 and 52) who, from week 56 for 48 weeks (DE period), (1) continued combination abatacept + methotrexate, (2) tapered abatacept to every other week (EOW) + methotrexate for 24 weeks with subsequent abatacept withdrawal (abatacept placebo + methotrexate), or (3) withdrew methotrexate (abatacept monotherapy). RESULTS: Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm achieved SDAI remission at week 24 (p = 0.2359). There were numerical differences favoring combination therapy in clinical assessments, patient-reported outcomes (PROs) and week 52 radiographic non-progression. After week 56, 147 patients in sustained remission with abatacept + methotrexate were randomized (combination, n = 50; DE/withdrawal, n = 50; abatacept monotherapy, n = 47) and entered DE. At DE week 48, SDAI remission (74%) and PRO improvements were mostly maintained with continued combination therapy; lower remission rates were observed with abatacept placebo + methotrexate (48.0%) and with abatacept monotherapy (57.4%). Before withdrawal, de-escalating to abatacept EOW + methotrexate preserved remission. CONCLUSIONS: The stringent primary endpoint was not met. However, in patients achieving sustained SDAI remission, numerically more maintained remission with continued abatacept + methotrexate versus abatacept monotherapy or withdrawal. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02504268. Video abstract (MP4 62241 KB).

Patients with rheumatoid arthritis (RA) experience inflamed and damaged joints. RA is an autoimmune disease in which proteins called autoantibodies, particularly anti-citrullinated protein autoantibodies, target the patient's own joint tissue and organs by mistake, leading to symptomatic inflammation. Successful treatment can decrease the disease's activity to a state known as remission. Patients in remission may experience little or no symptoms and it may be possible for some to then be able to decrease their treatment. Here, we report the results of a large, international study that looked at two treatments, abatacept and methotrexate, in patients with RA and anti-citrullinated protein autoantibodies. The study had two parts. Firstly, to see how many patients had success (remission) with weekly abatacept and/or methotrexate treatment, and secondly, to see if remission was maintained when treatment was either continued or decreased and stopped. The study showed that the number of patients in remission 6 months after treatment started was not greatly different between patients treated with both abatacept and methotrexate and those treated with just methotrexate. Those taking abatacept and methotrexate together had better remission rates 1 year later. More patients also stayed in remission when they continued to receive both abatacept and methotrexate compared with those who were just treated with abatacept or when their abatacept treatment was decreased and stopped. More patients stayed in remission when abatacept was decreased than when it was stopped. The results from this study may help determine possible future treatment reduction and/or withdrawal plans for some patients with RA.

Hypoxia-Driven TGFß Modulation of Side Population Cells in Breast Cancer: The Potential Role of ERα.

Epithelial-to-mesenchymal transition (EMT) is known to be important in regulating the behaviour of cancer cells enabling them to acquire stem cell characteristics or by enhancing the stem cell characteristics of cancer stem cells, resulting in these cells becoming more migratory and invasive. EMT can be driven by a number of mechanisms, including the TGF-ß1 signalling pathway and/or by hypoxia. However, these drivers of EMT differ in their actions in regulating side population (SP) cell behaviour, even within SPs isolated from the same tissue. In this study we examined CoCl2 exposure and TGF-ß driven EMT on SP cells of the MDA-MB-231 and MCF7 breast cancer cell lines. Both TGF-ß1 and CoCl2 treatment led to the depletion of MDA-MB-231 SP. Whilst TGF-ß1 treatment significantly reduced the MCF7 SP cells, CoCl2 exposure led to a significant increase. Single cell analysis revealed that CoCl2 exposure of MCF7 SP leads to increased expression of ABCG2 and HES1, both associated with multi-drug resistance. We also examined the mammosphere forming efficiency in response to CoCl2 exposure in these cell lines, and saw the same effect as seen with the SP cells. We suggest that these contrasting effects are due to ERα expression and the inversely correlated expression of TGFB-RII, which is almost absent in the MCF7 cells. Understanding the EMT-mediated mechanisms of the regulation of SP cells could enable the identification of new therapeutic targets in breast cancer.

Optimization of Protocols Using Neuromuscular Electrical Stimulation for Paralyzed Lower-Limb Muscles to Increase Energy Expenditure in People With Spinal Cord Injury.

OBJECTIVE: The aim of this study was to evaluate whether using surface neuromuscular electrical stimulation (NMES) for paralyzed lower-limb muscles results in an increase in energy expenditure and whether the number of activated muscles and duty cycle affect the potential increase. DESIGN: This was a cross-sectional study. RESULTS: Energy expenditure during all NMES protocols was significantly higher than the condition without NMES (1.2 ± 0.2 kcal/min), with the highest increase (+51%; +0.7 kcal/min, 95% confidence interval, 0.3-1.2) for the protocol with more muscles activated and the duty cycle with a shorter rest period. A significant decrease in muscle contraction size during NMES was found with a longer stimulation time, more muscles activated, or the duty cycle with a shorter rest period. CONCLUSION: Using NMES for paralyzed lower-limb muscles can significantly increase energy expenditure compared with sitting without NMES, with the highest increase for the protocol with more muscles activated and the duty cycle with a shorter rest period. Muscle fatigue occurred significantly with the more intense NMES protocols, which might cause a lower energy expenditure in a longer protocol. Future studies should further optimize the NMES parameters and investigate the long-term effects of NMES on weight management in people with SCI.

The Role of Genetics in Clinically Suspect Arthralgia and Rheumatoid Arthritis Development: A Large Cross-Sectional Study.

OBJECTIVE: To investigate whether established genetic predictors for rheumatoid arthritis (RA) differentiate healthy controls, patients with clinically suspect arthralgia (CSA), and RA patients. METHODS: Using analyses of variance, chi-square tests, and mean risk difference analyses, we investigated the association of an RA polygenic risk score (PRS) and HLA shared epitope (HLA-SE) with all participant groups, both unstratified and stratified for anti-citrullinated protein antibody (ACPA) status. We used 3 separate data sets sampled from the same Dutch population (1,015 healthy controls, 479 CSA patients, and 1,146 early classified RA patients). CSA patients were assessed for conversion to inflammatory arthritis over a period of 2 years, after which they were classified as either CSA converters (n = 84) or CSA nonconverters (n = 395). RESULTS: The PRS was increased in RA patients (mean ± SD PRS 1.31 ± 0.96) compared to the complete CSA group (1.07 ± 0.94) and compared to CSA converters (1.12 ± 0.94). In ACPA- strata, PRS distributions differed strongly when comparing the complete CSA group (mean ± SD PRS 1.05 ± 0.94) and CSA converters (0.97 ± 0.87) to RA patients (1.20 ± 0.94), while in the ACPA+ strata, the complete CSA group (1.25 ± 0.99) differed clearly from healthy controls (1.05 ± 0.94) and RA patients (1.41 ± 0.96). HLA-SE was more prevalent in the RA group (prevalence 0.64) than the complete CSA group (0.45), with small differences between RA patients and CSA converters (0.64 versus 0.60) and larger differences between CSA converters and CSA nonconverters (0.60 versus 0.42). HLA-SE prevalence differed more strongly within the ACPA+ strata as follows: healthy controls (prevalence 0.43), CSA nonconverters (0.48), complete CSA group (0.59), CSA converters (0.66), and RA patients (0.79). CONCLUSION: We observed that genetic predisposition increased across pre-RA participant groups. The RA PRS differed in early classified RA and inflammatory pre-disease stages, regardless of ACPA stratification. HLA-SE prevalence differed between arthritis patients, particularly ACPA+ patients, and healthy controls. Genetics seem to fulfill different etiologic roles.

Associations between meeting exercise guidelines, physical fitness, and health in people with spinal cord injury.

PURPOSE: (1) To estimate the proportion of Dutch wheelchair users with spinal cord injury (SCI) who meet different SCI exercise guidelines; (2) to evaluate which demographic and lesion characteristics are associated with meeting these guidelines; (3) whether meeting these guidelines is associated with physical fitness and health. MATERIALS AND METHODS: Based on the PASIPD questionnaire items, participants were allocated to meeting two SCI aerobic exercise guidelines, which differ in exercise load. Differences in personal, lesion, fitness, and health characteristics between groups were tested with a one-way ANOVA. Multiple regression analyses were performed to evaluate if meeting guidelines was associated with better fitness and health. Statistical significance was accepted at p < 0.05. RESULTS: Of the 358 included participants, 63.1% met at least one aerobic exercise guideline. Being female, older age, having tetraplegia, and lower educational level were associated with a lower likelihood to meet the aerobic exercise guidelines. Meeting aerobic exercise guidelines showed a positive association with all respiratory and exercise capacity parameters. Limited associations were found between meeting exercise guidelines and health. CONCLUSIONS: Meeting exercise guidelines was associated with better respiratory functions and exercise capacity with additional fitness and some body composition benefits in higher exercise activity levels.IMPLICATIONS FOR REHABILITATIONMeeting SCI exercise guidelines are associated with better respiratory functions and exercise capacity with additional fitness and body composition benefits when higher exercising at higher activity levels, emphasizing the value and importance of regular exercise in individuals with SCI.

Glycobiology of rheumatic diseases.

Glycosylation has a profound influence on protein activity and cell biology through a variety of mechanisms, such as protein stability, receptor interactions and signal transduction. In many rheumatic diseases, a shift in protein glycosylation occurs, and is associated with inflammatory processes and disease progression. For example, the Fc-glycan composition on (auto)antibodies is associated with disease activity, and the presence of additional glycans in the antigen-binding domains of some autoreactive B cell receptors can affect B cell activation. In addition, changes in synovial fibroblast cell-surface glycosylation can alter the synovial microenvironment and are associated with an altered inflammatory state and disease activity in rheumatoid arthritis. The development of our understanding of the role of glycosylation of plasma proteins (particularly (auto)antibodies), cells and tissues in rheumatic pathological conditions suggests that glycosylation-based interventions could be used in the treatment of these diseases.

Shoulder muscle activity after latissimus dorsi transfer in an active elevation.

Background: After latissimus dorsi transfer (LDT), an increase in scapulothoracic (ST) contribution in thoracohumeral (TH) elevation is observed when compared to the asymptomatic shoulder. It is not known which shoulder muscles contribute to this change in shoulder kinematics, and whether the timing of muscle recruitment has altered after LDT. The aim of the study was to identify which shoulder muscles and what timing of muscle recruitment are responsible for the increased ST contribution and shoulder elevation after LDT for a massive irreparable posterosuperior rotator cuff tear (MIRT). Methods: Thirteen patients with a preoperative pseudoparalysis and MIRT were recruited after LDT with a minimum follow-up of 1 year. Three-dimensional electromagnetic tracking was used to assess maximum active elevation of the shoulder (MAES) in both the LDT and the asymptomatic contralateral shoulder (ACS). Surface electromyography (EMG) tracked activation (% EMG max) and activation timing of the latissimus dorsi (LD), deltoid, teres major, trapezius (upper, middle and lower) and serratus anterior muscles were collected. MAES was studied in forward flexion, scapular abduction and abduction in the coronal plane. Results: In MAES, no difference in thoracohumeral motion was observed between the LDT and ACS, P = .300. However, the glenohumeral motion for MAES was significantly lower in LDT shoulders F(1,12) = 11.230, P = .006. The LD % EMG max did not differ between the LDT and ACS in MAES. A higher % EMG max was found for the deltoid F(1,12) = 17.241, P = .001, and upper trapezius F(1,10) = 13.612, P = .004 in the LDT shoulder during MAES. The middle trapezius only showed a higher significant difference in % EMG max for scapular abduction, P = .020 (LDT, 52.3 ± 19.4; ACS, 38.1 ± 19.7).The % EMG max of the lower trapezius, serratus anterior and teres major did not show any difference in all movement types between the LDT and ACS and no difference in timing of recruitment of all the shoulder muscles was observed. Conclusions: After LDT in patients with a MIRT and preoperative pseudoparalysis, the LD muscle did not alter its % EMG max during MAES when compared to the ACS. The cranial transfer of the LD tendon with its native %EMG max, together with the increased %EMG max of the deltoid, middle and upper trapezius muscles could be responsible for the increased ST contribution. The increased glenohumeral joint reaction force could in turn increase active elevation after LDT in a previous pseudoparalytic shoulder.