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Arthritis & Rheumatology (Hoboken, N.J.) Jun 2024To evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH)-associated genes among patients with systemic juvenile...
OBJECTIVE
To evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH)-associated genes among patients with systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS).
METHODS
Targeted sequencing of HLH genes (LYST, PRF1, RAB27A, STX11, STXBP2, UNC13D) was performed in sJIA subjects from an established cohort. Sequence data from control subjects were obtained in silico (dbGaP:phs000280.v8.p2). Rare variant association testing (RVT) was performed with sequence kernel association test (SKAT) package. Significance was defined as p < 0.05 after 100,000 permutations.
RESULTS
Sequencing data from 524 sJIA cases were jointly called and harmonized with exome-derived target data from 3000 controls. Quality control operations produced a set of 480 cases and 2924 ancestrally-matched control subjects. RVT of cases and controls revealed a significant association with rare protein-altering variants (minor allele frequency [MAF] < 0.01) of STXBP2 (p = 0.020), and ultra-rare variants (MAF < 0.001) of STXBP2 (p = 0.006) and UNC13D (p = 0.046). A sub-analysis of 32 cases with known MAS and 90 without revealed a significant difference in the distribution of rare UNC13D variants (p = 0.0047) between the groups. Additionally, sJIA patients more often carried ≥ 2 HLH variants than did controls (p = 0.007), driven largely by digenic combinations involving LYST.
CONCLUSION
We identified an enrichment of rare HLH variants in sJIA patients compared with controls, driven by STXBP2 and UNC13D. Biallelic variation in HLH genes was associated with sJIA, driven by LYST. Only UNC13D displayed enrichment in patients with MAS. This suggests that HLH variants may contribute to the pathophysiology of sJIA, even without MAS.
PubMed: 38937141
DOI: 10.1002/art.42938 -
Arthritis Care & Research Jun 2024The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic...
OBJECTIVE
The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease-modifying antirheumatic drugs (bDMARDs).
METHODS
The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Research Committee used case-based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM.
RESULTS
Four bDMARD CTPs were proposed: TNF-alpha inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67/72]) as well as for patient characteristics, assessments, outcome measures, and follow up. By weighted average, respondents indicated that they would most likely use rituximab followed by abatacept, TNF-alpha inhibitor, and tocilizumab.
CONCLUSION
CTPs for the use of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry-based prospective comparative effectiveness studies.
PubMed: 38937134
DOI: 10.1002/acr.25393 -
BMJ (Clinical Research Ed.) Jun 2024
Review
Topics: Humans; Low Back Pain; Analgesia; Analgesics
PubMed: 38936847
DOI: 10.1136/bmj-2024-080064 -
Brazilian Journal of Physical Therapy Jun 2024Migraine may be accompanied by several cervical musculoskeletal dysfunctions, for example an altered performance on the Craniocervical Flexion Test (CCFT). However, CCFT...
BACKGROUND
Migraine may be accompanied by several cervical musculoskeletal dysfunctions, for example an altered performance on the Craniocervical Flexion Test (CCFT). However, CCFT measurement properties are still unclear in patients with migraine.
OBJECTIVES
To determine intra- and inter-examiner reliability, construct validity, standard measurement error (SEM), and minimal detectable change (MDC) of the CCFT in patients with migraine.
METHODS
Women diagnosed with migraine were considered eligible for this study. Participants were assessed by two examiners for the inter-examiner reliability, and with 7-10 days interval for the intra-examiner reliability. Construct validity was assessed considering headache and neck pain frequency and intensity, and self-reported questionnaires, including the Headache Impact Test - 6 items (HIT-6), the 12-item Allodynia Symptom Checklist/Brazil (ASC-12), and the Neck Disability Index (NDI). In addition, participants performed cervical endurance and maximal voluntary isometric contraction of the cervical flexors.
RESULTS
A total of 103 women with migraine were recruited. The intra-examiner reliability was rated as good (ICC= 0.81, 95% CI: 0.73, 0.87), while the inter-examiner reliability was rated as moderate (ICC= 0.55, 95% CI: 0.40, 0.67). The intra and inter-examiner SEM were 1.31 and 1.36 mmHg respectively, and MDC were 3.63 and 3.77 mmHg. The HIT-6 and the cervical endurance flexion test were associated with the CCFT in a multiple linear regression model (p = 0.004, R = 0.35).
CONCLUSION
The CCFT presents adequate intra- and inter-examiner reliability. Better performance on the CCFT test was associated with better HIT-6 scores and greater cervical endurance time, which was not influenced by the presence of neck pain.
PubMed: 38936314
DOI: 10.1016/j.bjpt.2024.101085 -
Musculoskeletal Science & Practice Jun 2024Many physiotherapists do not feel adequately equipped to address psychosocial risk factors in people with complex pain states. Hence, a biopsychosocial blended...
BACKGROUND
Many physiotherapists do not feel adequately equipped to address psychosocial risk factors in people with complex pain states. Hence, a biopsychosocial blended intervention (Back2Action) was developed to assist physiotherapists to manage people with persistent spinal pain and coexisting psychosocial risk factors associated with the development or maintenance of persistent pain.
OBJECTIVE
This study aimed to gain insight into the experiences of physiotherapists with this blended psychosocial intervention.
DESIGN
and methods: This was an interpretative qualitative study with a reflexive thematic analysis of semi-structured interviews with physiotherapists (N = 15) who delivered Back2Action. The interview started with the grand-tour question: "What was your experience in using Back2Action?" Physiotherapist were encouraged to provide examples, and follow-up questions were posed to ensure a deeper understanding could be reached.
RESULTS
Four themes were constructed: Physiotherapists became increasingly aware of (1) their own implicit expectations, biases and skills, and underlying treatment paradigms, and (2) the implicit expectations from their patients towards them. This led to (3) creating a deeper and stronger therapeutic alliance with the patient, but also (4) an understanding that implementation of a true biopsychosocial intervention - even if offered in a blended form - requires more practice, confidence and resources.
CONCLUSIONS
Back2Action is considered a valuable treatment to deliver a biopsychosocial intervention in primary care. Considering the high level of knowledge, skills and competency of the participating physiotherapists, the perceived barriers may be more difficult to overcome for more junior physiotherapists.
PubMed: 38936263
DOI: 10.1016/j.msksp.2024.103121 -
Physical Therapy in Sport : Official... Jun 2024To evaluate non-contact injury prevention strategies of professional men's soccer clubs in elite North American league soccer. To understand the application, perceived...
OBJECTIVE
To evaluate non-contact injury prevention strategies of professional men's soccer clubs in elite North American league soccer. To understand the application, perceived effectiveness and barriers to implementation.
DESIGN
Online cross-Sectional Study.
SETTING
North American elite soccer teams.
PARTICIPANTS
96 medical and performance support staff of elite North American teams.
MAIN OUTCOME MEASURE
The survey consisted of 20 questions and captured 1) practitioners' demographics; 2) perceptions of risk factors; 3) the use of assessment and monitoring strategies; and 4) perceptions of the implementation of injury prevention programmes'.
RESULTS
Injury prevention programmes were perceived as 'effective' (Median 4, Interquartile range 4-4) and reduced injury rates (n = 94, 98%, 95 CI% 93 to 99). A range of potential risk factors were rated as "very important" (4.58 ± 0.52 Likert scale points; mean ± standard deviation). A multi-disciplinary approach to the design, application and monitoring of programmes was generally adopted. Competing training priorities (n = 75, 78%, 95 CI% 69 to 85) and game schedules (n = 71, 74%, 95 CI% 64 to 82) were the most prevalent barriers to injury prevention implementation.
CONCLUSIONS
Injury prevention programmes were perceived as effective in reducing non-contact injuries. Managing the conflicting priorities between scheduling training, tactical and conditioning goals were considered the key barriers to desired implementation.
PubMed: 38935993
DOI: 10.1016/j.ptsp.2024.06.003 -
Radiographics : a Review Publication of... Jul 2024Congenital talipes equinovarus (CTEV), also known as clubfoot, is a common musculoskeletal entity that affects one to two per 1000 live births worldwide. Imaging... (Review)
Review
Congenital talipes equinovarus (CTEV), also known as clubfoot, is a common musculoskeletal entity that affects one to two per 1000 live births worldwide. Imaging modalities including radiography, US, and MRI have emerged as valuable tools for the diagnosis, treatment, and monitoring of CTEV. The deformity is characterized by midfoot cavus, forefoot adductus, and hindfoot varus and equinus. The Ponseti method of manipulation and serial casting is the standard treatment of CTEV. Radiography shows the anatomy, position, and relationships of the different bones of the foot. US allows accurate assessment of cartilaginous and bony structures, in addition to its inherent advantages such as absence of ionizing radiation exposure. One of the indications for US is to monitor the response to Ponseti method treatment. MRI enables visualization of bones, cartilage, and soft tissues and allows multiplanar evaluation of deformities, providing a comprehensive imaging analysis of CTEV. An integrated approach that combines clinical examination and imaging findings is essential for effective management of CTEV. The authors provide a comprehensive overview of CTEV with a review of imaging modalities to help evaluate CTEV, focusing on radiography, US, and MRI. Using this article as a guide, radiologists involved in the assessment and treatment of CTEV can contribute to the management of the condition. RSNA, 2024 Supplemental material is available for this article.
Topics: Clubfoot; Humans; Magnetic Resonance Imaging; Infant, Newborn; Infant
PubMed: 38935547
DOI: 10.1148/rg.230178 -
Cell Reports Jun 2024With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23),...
With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23), urine phosphate, and the muscle metabolite L-β-aminoisobutyric acid (L-BAIBA), suggesting that L-BAIBA may play a role in phosphate metabolism. Here, we show that L-BAIBA increases in serum with exercise and elevates Fgf23 in osteocytes. The D enantiomer, described to be elevated with exercise in humans, can also induce Fgf23 but through a delayed, indirect process via sclerostin. The two enantiomers both signal through the same receptor, Mas-related G-protein-coupled receptor type D, but activate distinct signaling pathways; L-BAIBA increases Fgf23 through Gαs/cAMP/PKA/CBP/β-catenin and Gαq/PKC/CREB, whereas D-BAIBA increases Fgf23 indirectly through sclerostin via Gαi/NF-κB. In vivo, both enantiomers increased Fgf23 in bone in parallel with elevated urinary phosphate excretion. Thus, exercise-induced increases in BAIBA and FGF23 work together to maintain phosphate homeostasis.
PubMed: 38935499
DOI: 10.1016/j.celrep.2024.114397 -
European Journal of Applied Physiology Jun 2024We tested the hypothesis that heat stress influences the closed-loop cardio-postural control by an increased blood pressure (BP) drop and postural sway.
PURPOSE
We tested the hypothesis that heat stress influences the closed-loop cardio-postural control by an increased blood pressure (BP) drop and postural sway.
METHODS
Fourteen healthy individuals (eight women) performed two orthostatic tests under thermal reference (TC; ~ 24 ºC) and HOT (~ 38 ºC) conditions. The center-of-pressure (COP) displacements and the electromyography (EMG) activity of the calf muscles (medial gastrocnemius and tibialis anterior) were recorded during the initial orthostasis (ORT onset) after the supine-to-stand challenge. At the same period, BP (beat-to-beat) was continuously monitored, and supine-to-stand variations (∆%) were calculated. Sublingual temperature (Tsl) was measured as a surrogate of internal temperature.
RESULTS
Tsl increased in HOT compared to TC (TC 36.5 ± 0.3 vs. HOT 36.7 ± 0.3 ºC; p < 0.01). COP distance was greater in HOT compared to TC condition (TC 596.6 ± 242.4 vs. HOT 680.2 ± 249.1 mm; p < 0.01). EMG activity of the gastrocnemius decreased in HOT compared to TC condition (TC 95.5 ± 19.8 vs. HOT 78.4 ± 22.8%mV; p = 0.02). EMG of tibialis did not change between TC and HOT (TC 83.5 ± 42.9 vs. HOT 66.1 ± 31.9% mV; p = 0.29). BP showed a greater fall in HOT compared to TC condition (∆%TC - 24.5 ± 13.2 vs. ∆%HOT - 33.2 ± 20.2%; p = 0.01).
CONCLUSION
Heat stress causes a greater fall in blood pressure and a reduction in musculoskeletal pump activity during orthostatic onset. These effects could be potential mechanisms that underlie augmented postural instability under a heated environment.
PubMed: 38935152
DOI: 10.1007/s00421-024-05546-8 -
Zeitschrift Fur Rheumatologie Jun 2024Patients with diseases of the musculoskeletal system are confronted with a large quantity of treatment offers based on methods of complementary medicine. Despite...
Patients with diseases of the musculoskeletal system are confronted with a large quantity of treatment offers based on methods of complementary medicine. Despite a considerable number of publications on this topic, the scientific evidence is still poor. This article focuses on Ayurvedic medicine (AM), traditional Chinese medicine (TCM), mind-body medicine and homeopathy. These procedures have a longstanding tradition of practice and each claims to have its own theoretical concept; however, the application in the field of rheumatology can only be recommended either for specific entities or, in the case of homeopathy, not at all. In addition, this article summarizes the evidence for dietary recommendations, nutritional supplements and herbal medicine in rheumatology. The latter topics are frequently discussed in the popular press and are a much-debated issue between physicians and patients; however, clear-cut recommendations for the application on a scientific basis are the exception and mainly consist of the endorsement to adhere to the principles of a Mediterranean diet.
PubMed: 38935116
DOI: 10.1007/s00393-024-01524-9