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Purpose: The Stickler syndromes are a group of connective tissue disorders characterised by congenital myopia, giant retinal tear and retinal detachment, cleft palate, hearing loss and premature arthropathy. Patients with Stickler syndrome are also susceptible to abnormalities of the crystalline lens. Since neither type II or type XI collagen (those typically affected in the vast majority of Stickler patients) are highly expressed in the lens, this observational cohort study explores potential alternative mechanisms to explain why patients frequently exhibit such unusual but characteristic types of cataract., Methods: Author observations drawn from a cohort of over 1800 patients with genetically confirmed Stickler syndrome., Results: 3 distinct lens pathologies were identified. Firstly, a congenital quadrantic lamellar opacity. This can be present in both type 1 (COL2A1) and type 2 (COL11A1) Stickler syndrome. Secondly, early onset Pantone 557 C blue-green nuclear cataract. Thirdly, congenital lens coloboma associated with localised zonule deficiency., Conclusions: The characteristic quadrantic lamellar lens opacity can be helpful in alerting to the possible diagnosis, particularly in sub-groups with an ocular-only phenotype. Temporal and spatial signalling pathways shared embryologically by both the developing vitreous body and crystalline lens suggest an ancillary role of the fibrillar collagens in cell signalling beyond their basic structural function. A common pathway of TGFβ/BMP super-family dysregulation may be shared with allied disorders associated with both retinal detachment and cataract as well as the pathobiology linking retinal detachment and cataract in the population at large. Congenital lens coloboma associated with localised zonule deficiency can increase the difficulty and risks of cataract surgery. Strategies to mitigate such risks are presented., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Diseases of joints are among the most frequent causes of chronic pain. In the course of joint diseases, the peripheral and the central nociceptive system develop persistent hyperexcitability (peripheral and central sensitization). This review addresses the mechanisms of spinal sensitization evoked by arthritis. Electrophysiological recordings in anesthetized rats from spinal cord neurons with knee input in a model of acute arthritis showed that acute spinal sensitization is dependent on spinal glutamate receptors (AMPA, NMDA, and metabotropic glutamate receptors) and supported by spinal actions of neuropeptides such as neurokinins and CGRP, by prostaglandins, and by proinflammatory cytokines. In several chronic arthritis models (including immune-mediated arthritis and osteoarthritis) spinal glia activation was observed to be coincident with behavioral mechanical hyperalgesia which was attenuated or prevented by intrathecal application of minocycline, fluorocitrate, and pentoxyfylline. Some studies identified specific pathways of micro- and astroglia activation such as the purinoceptor- (P 2 X 7 -) cathepsin S/CX 3 CR1 pathway, the mobility group box-1 protein (HMGB1), and toll-like receptor 4 (TLR4) activation, spinal NFκB/p65 activation and others. The spinal cytokines TNF, interleukin-6, interleukin-1β, and others form a functional spinal network characterized by an interaction between neurons and glia cells which is required for spinal sensitization. Neutralization of spinal cytokines by intrathecal interventions attenuates mechanical hyperalgesia. This effect may in part result from local suppression of spinal sensitization and in part from efferent effects which attenuate the inflammatory process in the joint. In summary, arthritis evokes significant spinal hyperexcitability which is likely to contribute to the phenotype of arthritis pain in patients., (© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Purpose: To document the long-term visual outcomes in patients with Blau syndrome., Methods: A retrospective institutional cohort study was conducted, and 13 patients with genetically confirmed Blau syndrome were included. Demographic and clinical data were collected from standardised medical charts. Baseline was defined as the first detected uveitis and data were recorded onwards at intervals of 1, 3, 5, 10, 15 and 20 years., Results: Anterior uveitis was the most common classification at baseline (57.1%). Among patients with documented uveitis lasting 10 years or more, all of them developed panuveitis. Median logMAR visual acuity at baseline was 0 (range -0.5; 0.7), 0.19 (range 0; 1.5) at year 5, and 0.7 (range 0.1 - no perception of light) at year 20, as recorded in 13, 16, and 10 eyes, respectively. All patients received treatment with topical and oral steroids, and multiple systemic immunosuppressants including biologics. Disease control, defined as having cells <1+ in both eyes and using topical steroid eye drops less than twice daily, was achieved in 14.3% to 37.5% of patients at the different time points. Cataract surgery was performed in 12 eyes of 8 patients, 3 eyes of 3 patients necessitated glaucoma surgery, and 4 eyes of 4 patients required surgery for retinal detachment., Conclusion: Uveitis associated with Blau syndrome commonly leads to severe, chronic panuveitis, requiring long-term systemic immunosuppression. Early diagnosis and timely initiation of biologics may prevent significant visual impairment.

Objectives: To examine the value of a novel high-resolution thermographic marker in the detection of joint inflammation compared to joint ultrasound (US) and to suggest thermographic cut-off values of joint inflammatory activity., Methods: Infrared thermographies were performed in patients with inflammatory arthritides and healthy controls. Patients were moreover examined clinically and by joint-US [Power-Doppler-(PDUS), Greyscale-US (GSUS)]. Regions of interest (ROIs) were defined for every joint and absolute temperature values within the ROIs were documented. The hottest areas ("hotspots") were identified by a clustering algorithm and the Hotspot/ROI-Ratio (HRR)-values were calculated. Subsequently, the HRR of patient-joints with different grades of hypervascularity (PDUS I°-III°) were compared among each other and with PDUS 0° control-joints. Diagnostic HRR-performance was tested by receiver-operating-characteristics., Results: 360 joints of 75 arthritis-patients and 1,808 joints of 70 controls were thermographically examined. HRR-values were statistically different between PDUS I-III vs. PDUS 0 and vs. healthy subjects for all four joint groups as well as in the majority of cases between patient-joints with different grades of hypervascularity (PDUS I°-III°; p<0.05). Taking joint-US as a reference, the best performance of HRR was found at the level of the wrist-joints by an area under the curve (AUC) of 0.91 (95%CI 0.84-0.98) with a sensitivity of 0.83 and specificity of 0.88., Conclusions: HRR showed an excellent performance in the differentiation of joints with US inflammatory activity from non-inflamed joints. Moreover, HRR was able to differentiate between joints with different grades of hypervascularity, making HRR a promising tool to assist disease activity monitoring.

Objective: This study aimed to assess dynamic stability in individuals with end-stage ankle arthritis compared to healthy controls by evaluating the margin of stability (MoS) during gait., Design: A cohort of 50 participants with end-stage ankle arthritis (AA) and 50 matched healthy controls (HC) were analyzed from an IRB approved database. Kinematic data were collected using an eight-camera motion analysis system, and MoS was calculated based on the extrapolated center of mass (XCoM) and the base of support (BoS). Statistical analysis was performed using a linear mixed effects model with gait speed as a covariate., Results: The analysis revealed a significant interaction between the group (AA vs. HC) and limb (arthritic vs. non-arthritic) at heel-strike and midstance. The non-arthritic limb demonstrated a significantly smaller AP MoS during heel-strike compared to the arthritic limb and either of the limbs of the HC group (p < 0.001). The arthritic limb demonstrated a significantly greater ML MoS during midstance compared to the non-arthritic limb and either of the limbs of the HC group (p < 0.001). AA group had significant slower gait speed (p < 0.001), smaller step length (p = 0.015) and smaller locomotor rehabilitation index (p < 0.001) than HC., Conclusion: Individuals with end-stage ankle arthritis exhibit altered dynamic stability during gait, with a significantly smaller AP MoS on the non-arthritic limb at heel-strike and greater ML MoS on the arthritic limb at midstance compared to healthy controls. Our results suggest that individuals with ankle arthritis are less stable when navigating single limb support of the arthritic limb. Further research should further examine the associations with fall risk in patients with ankle arthritis and evaluate the effectiveness of therapeutic interventions targeting these factors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Total ankle arthroplasty (TAA) is used to treat symptomatic end-stage ankle arthritis (AA). However, little is known about TAA's effects on gait symmetry., Research Question: Determine if symmetry changes from before surgery through two years following TAA utilizing the normalized symmetry index (NSI) and statistical parametric mapping (SPM)., Methods: 141 patients with end-stage unilateral AA were evaluated from a previously collected prospective database, where each participant was tested within two weeks of surgery (Pre-Op), one year and two years following TAA. Walking speed, hip extension angle and moment, hip flexion angle, ankle plantarflexion angle and moment, ankle dorsiflexion angle, weight acceptance (GRF1), and propulsive (GRF2) vertical ground reaction forces were calculated for each limb. Gait symmetry was assessed using the NSI. A linear mixed effects model with a single response for each gait symmetry variable was used to examine the fixed effect of follow-up time (Pre-Op, Post-1 yr, Post-2 yr) and the random effect of participant with gait speed as a covariate in the model. A one-dimensional repeated measures analysis of variance (ANOVA) statistical parameter mapping (SPM) was completed to examine differences in the time-series NSI to determine regions of significant differences between follow-up times., Results: Relative to Pre-Op values, GRF1, and GRF2 showed increased symmetry for discrete metrics and the time-series NSI across sessions. Hip extension moment had the largest symmetry improvement. Ankle plantarflexion angle was different between Pre-Op and Post-2 yr (p=0.010); and plantarflexion moment was different between Pre- Op and each post-operative session (p<0.001). The time-series Ankle Angle NSI was greater during the early stance phase in the Pre-Op session compared to Post-2 yr., Significance: Symmetry across most of the stance phase improved following TAA indicating that TAA successfully improves gait symmetry and future work should determine if these improvements restore symmetry to levels equivalent with health age-match controls., Competing Interests: Declaration of Competing Interest None of the authors declare any competing interests, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Despite recent developments in vitrectomy technology and instrumentation, rhegmatogenous retinal detachment in Stickler syndrome (RDS) remains a challenge for surgeons. RDSs are associated with a higher rate of complications and surgical failures than those not associated with Stickler syndrome. This study is a report about anatomic and visual outcomes of RDS surgery and describes the surgical techniques associated with the treatment of this specific condition., Methods: This is a retrospective, interventional, consecutive case series of patients with RDS undergoing retinal reattachment surgery from 1990 to 2020 at the Institute of Ocular Microsurgery (IMO) in Barcelona, Spain., Results: Twenty-four eyes of 18 patients with genetically confirmed Stickler syndrome were included in the study. Ten eyes (41.6%) presented a giant retinal tear. Retinal reattachment was achieved in all cases after an average of 1.21 (range 1-6) surgical interventions. Nineteen eyes (79%) required only one operation to achieve complete retinal reattachment. The most common first surgical procedure was a 4-mm scleral buckle with posterior pars plana vitrectomy and silicone oil endotamponade, performed on 16 (66.6%) of the eyes. The mean follow-up period was 10.2 years. Mean preoperative visual acuity LogMar was 1.10 (Snellen equivalent 20/252), which improved to 0.50 (Snellen equivalent 20/63) at final follow-up (p < 0.05)., Conclusion: In most RDS cases, anatomic success and visual acuity improvement can be achieved with the first surgical procedure, using a combination of silicone oil tamponade and a 4-mm scleral encircling band. In some early cases of RDS, other less invasive surgical techniques can be used., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: As total ankle arthroplasty (TAA) is an increasingly common surgical intervention for patients with end-stage ankle arthritis, there is a need to better understand the dynamic performance of prosthetic implants during activities of daily living. Our purpose was to quantify and compare relative tibiotalar motion during gait in persons with a fixed-bearing (FB) and mobile-bearing (MB) total ankle arthroplasty. We hypothesized a FB prosthesis would have lower tibiotalar range of motion (ROM)., Methods: Patients at least 12 months postoperative with either a FB (n=5) or MB (n=3) total ankle arthroplasty were tested. We used high-speed biplanar videoradiography to quantify tibiotalar kinematics during self-selected gait. Angular and linear ROM in three axes were compared between the groups., Results: ROM for dorsiflexion-plantarflexion, internal-external rotation, and inversion-eversion angles in FB subjects averaged 7.47±4.05°, 7.39±3.63°, and 4.51±2.13°, respectively. ROM in MB subjects averaged 6.74±2.04°, 6.28±4.51°, and 5.68±2.81°, respectively. Linear ROM along anteroposterior, mediolateral, and superior-inferior axes in FB subjects averaged 1.47±2.07 mm, 1.13±1.49 mm, and 0.28±0.30 mm, respectively. Linear ROM in MB subjects averaged 0.68±1.44 mm, 0.60±1.41 mm, and 0.20±0.13 mm, respectively. We found no significant difference between the two groups for any of these ROM parameters (p>0.05)., Conclusion: Total ankle arthroplasty using either FB or MB design appears to confer similar ankle motion during the gait cycle in this biplanar fluoroscopic model., Level of Evidence: Level IV, case series., Competing Interests: Declaration of Competing Interest This work was supported in part by Howmedica Osteonics Corp., also known as Stryker Orthopaedics., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The optimal management of primary glenohumeral arthritis (GHOA) in the elderly is an ongoing topic of debate. The purpose of this study was to compare functional outcomes and complications in patients aged 75 years or older treated with anatomic total shoulder arthroplasty (TSA) or reverse shoulder arthroplasty (RSA) for primary GHOA with an intact rotator cuff., Methods: A retrospective study was performed on a prospectively maintained database which was queried for patients 75 years of age or older who underwent TSA or RSA for primary GHOA with an intact rotator cuff at a single institution between 2012 and 2021 with minimum 2-year follow-up. Patient-reported outcomes (PROs), including Visual Analog Scale for pain, American Shoulder and Elbow Surgeons, and Subjective Shoulder Value, as well as active range of motion including forward flexion, external rotation, internal rotation, were collected preoperatively and postoperatively. Complications, reoperations, and satisfaction were also recorded. The percentage of patients achieving clinically significant improvement was evaluated with the minimally clinical important difference, substantial clinical benefit, and patient acceptable symptomatic state for each PRO., Results: One-hundred and 4 patients were available for analysis, including 67 TSA patients and 37 RSAs with a mean follow-up of 39.4 months. Preoperative baseline characteristics, PROs, and range of motion were similar between groups. RSA was more commonly performed for eccentric glenoid wear (Walch B2/B3, 62% vs. 22%; P < .001). While clinical outcomes improved comparably in both groups, the TSA cohort showed significantly greater improvement in external rotation (36° vs. 26°; P = .013). Both cohorts had low revision (3% for TSA vs. 0% for RSA) and complication (7% for TSA vs. 5% for RSA; P = .677) rates. Satisfaction was similar in both groups (93% for TSA vs. 92% for RSA; P = .900). Clinically significant improvement was comparable between groups based on the American Shoulder and Elbow Surgeons score (minimally clinical important difference, 93% for TSA vs. 100% for RSA; substantial clinical benefit, 82% vs. 95%; patient acceptable symptomatic state, 67% vs. 78%; P > .05)., Conclusion: In this retrospective small sample size comparison study, TSA and RSA provide similar short-term clinical outcomes for patients 75 years and older with primary GHOA and an intact rotator cuff. Complication and revision rates are comparably low at short-term follow-up. Our data suggests that advanced age alone should not be used as a decision-making tool for TSA vs. RSA in the setting of primary GHOA with an intact rotator cuff., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request.

Objective: To investigate whether thermogenesis and the hypothalamus may be involved in the physiopathology of experimental arthritis (EA)., Methods: EA was induced in male Lewis rats by intradermal injection of Freund's complete adjuvant (CFA). Food intake, body weight, plasma cytokines, thermographic analysis, gene and protein expression of thermogenic markers in brown adipose tissue (BAT) and white adipose tissue (WAT), and hypothalamic AMP-activated protein kinase (AMPK) were analyzed. Virogenetic activation of hypothalamic AMPK was performed., Results: We first demonstrated that EA was associated with increased BAT thermogenesis and browning of subcutaneous WAT leading to elevated energy expenditure. Moreover, rats experiencing EA showed inhibition of hypothalamic AMPK, a canonical energy sensor modulating energy homeostasis at the central level. Notably, specific genetic activation of AMPK in the ventromedial nucleus of the hypothalamus (a key site modulating energy metabolism) reversed the effect of EA on energy balance, brown fat, and browning, as well as promoting amelioration of synovial inflammation in experimental arthritis., Conclusion: Overall, these data indicate that EA promotes a central catabolic state that can be targeted and reversed by the activation of hypothalamic AMPK. This might provide new therapeutic alternatives to treat rheumatoid arthritis (RA)-associated metabolic comorbidities, improving the overall prognosis in patients with RA., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The relationship between functional disability and magnetic resonance imaging (MRI) inflammation has been studied for the hands, but has not been well established for the feet, even though walking difficulties are common. Therefore, our objective was to study whether walking difficulties were associated with MRI inflammation at metatarsophalangeal (MTP) joints in early arthritis patients, at diagnosis and during 24 months of follow-up., Methods: A total of 532 consecutive patients presenting with early arthritis reported on the presence and severity of walking difficulties (Health Assessment Questionnaire question 4a, scale 0-3), and underwent unilateral contrast-enhanced MRI of MTP joints 1-5 at baseline. In total, 107 patients had clinical and MRI data at follow-up (4, 12, and 24 months). MRI inflammation (synovitis, tenosynovitis, and osteitis) was scored in line with the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system. At baseline, the association of walking disability with MRI inflammation was assessed using regression. Longitudinally, the association between a change in walking disability with a change in MRI inflammation was studied with linear mixed models., Results: At baseline, 81% of patients with walking disabilities had MRI inflammation at MTP joints, versus 68% without walking disabilities (P < 0.001). Total MRI inflammation (i.e., the sum of tenosynovitis, synovitis, and osteitis) was associated with severity of walking disability (β = 0.023, P < 0.001). Studying the MRI features separately, tenosynovitis, synovitis, and osteitis were all univariably associated with severity of walking disability (P < 0.001, P < 0.001, and P = 0.014, respectively). In multivariable analysis, the association was strongest for tenosynovitis. During follow-up, a decrease in MTP inflammation was associated with a decrease in walking disability (β = 0.029, P = 0.001); in multivariable analyses only, tenosynovitis was independently associated (β = 0.073, P = 0.049)., Conclusion: Of the different inflamed tissues in MTP joints, predominantly MRI-detected tenosynovitis was associated with walking disabilities. Likewise a reduction in tenosynovitis related to a decrease in walking disabilities. These results increase our understanding of the involvement of tenosynovitis in walking disabilities in early arthritis., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

To define the role of SETD2 in the WNT5a signaling in the context of osteoclastogenesis, we exploited two different models: in vitro osteoclast differentiation, and K/BxN serum-induced arthritis model. We found that SETD2 and WNT5a were upregulated during osteoclast differentiation and after induction of arthritis. Using gain- and loss-of-function approaches in the myeloid cell, we confirmed that SETD2 regulated the osteoclast markers, and WNT5a via modulating active histone marks by enriching H3K36me3, and by reducing repressive H3K27me3 mark. Additionally, during osteoclastic differentiation, the transcription of Wnt5a was also associated with the active histone H3K9 and H4K8 acetylations. Mechanistically, SETD2 directed induction of NF-κβ expression facilitated the recruitment of H3K9Ac and H4K8Ac around the TSS region of the Wnt5a gene, thereby, assisting osteoclast differentiation. Together these findings for the first time revealed that SETD2 mediated epigenetic regulation of Wnt5a plays a critical role in osteoclastogenesis and induced arthritis. Model for the Role of SETD2 dependent regulation of osteoclastic differentiation. A In monocyte cells SETD2-dependent H3K36 trimethylation help to create open chromatin region along with active enhancer mark, H3K27Ac. This chromatin state facilitated the loss of a suppressive H3K27me3 mark. B Additionally, SETD2 mediated induction of NF-κβ expression leads to the recruitment of histone acetyl transferases, P300/PCAF, to the Wnt5a gene and establish H3K9Ac and H4K8Ac marks. Along with other activation marks, these acetylation marks help in Wnt5a transcription which leads to osteoclastogenesis., (© 2021. The Author(s).)

Arthritis has been the most frequently reported main cause of disability among U.S. adults for >15 years (1), was responsible for >$300 billion in arthritis-attributable direct and indirect annual costs in the U.S. during 2013 (2), is linked to disproportionately high levels of anxiety and depression (3), and is projected to increase 49% in prevalence from 2010-2012 to 2040 (4). To update national prevalence estimates for arthritis and arthritis-attributable activity limitation (AAAL) among U.S. adults, CDC analyzed combined National Health Interview Survey (NHIS) data from 2016-2018. An estimated 58.5 million adults aged ≥18 years (23.7%) reported arthritis; 25.7 million (10.4% overall; 43.9% among those with arthritis) reported AAAL. Prevalence of both arthritis and AAAL was highest among adults with physical limitations, few economic opportunities, and poor overall health. Arthritis was reported by more than one half of respondents aged ≥65 years (50.4%), adults who were unable to work or disabled* (52.3%), or adults with fair/poor self-rated health (51.2%), joint symptoms in the past 30 days (52.2%), activities of daily living (ADL) † disability (54.8%), or instrumental activities of daily living (IADL) § disability (55.9%). More widespread dissemination of existing, evidence-based, community-delivered interventions, along with clinical coordination and attention to social determinants of health (e.g., improved social, economic, and mental health opportunities), can help reduce widespread arthritis prevalence and its adverse effects., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Stickler syndrome is a genetic disorder of connective tissue. One of the major symptoms associated with this disorder is an oro-facial malformation, which may cause a submucous cleft or a complete cleft of the hard palate. A 32-year-old man diagnosed with Stickler syndrome and a submucosal cleft palate (SMCP) visited our hospital with a chief complaint of excessive daytime sleepiness. The patient was diagnosed with severe obstructive sleep apnea (OSA), and administration of a polysomnography test revealed an apnea-hypopnea index (AHI) of 30.9 events/hour (h). Auto-titrating continuous positive airway pressure was initiated to control the OSA symptoms and subsequently the patient showed some improvement. However, due to continuous velopharyngeal insufficiency symptoms, intravelar veloplasty was performed. Three months after surgery, the AHI had decreased to 12.4 events/h. Recent studies have described a greater risk for OSA in individuals with cleft palate, than in the general population. The present case demonstrates surgical success in a patient with OSA and SMCP, suggesting that palatal surgery may be considered an optional surgical treatment for OSA patients with SMCP., (Copyright © 2020. Published by Elsevier B.V.)

Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance. The vasculature also provides local, often organ-specific, molecular signals that control the behaviour of other cell types in their vicinity during development, homeostasis and regeneration, and also in disease processes. In the skeletal system, the local vasculature is actively involved in both bone formation and resorption. In addition, blood vessels participate in inflammatory processes and contribute to the pathogenesis of diseases that affect the joints, such as rheumatoid arthritis and osteoarthritis. This Review summarizes the current understanding of the architecture, angiogenic growth and functional properties of the bone vasculature. The effects of ageing and pathological conditions, including arthritis and osteoporosis, are also discussed., (© 2021. Springer Nature Limited.)

Objective: Despite the joint pain and significant dysfunction that characterizes arthritis, many people with arthritis continue to carry out everyday duties and responsibilities. The objective of the present study was to describe participation in informal caregiving (unpaid assistance to someone with a health issue or limitation) among people with arthritis., Methods: Analysis of baseline data from the Canadian Longitudinal Study on Aging (CLSA), a nationally representative sample of people ages 45-85 years (n = 21,241), was performed. A questionnaire covering sociodemographic, health, and caregiving variables was completed by each study participant. Caregiving variables examined characteristics of the person who received the most care from the questionnaire respondent, as well as the types of caregiving (e.g., hands-on versus hands-off tasks) and amount of care provided (e.g., hours per week)., Results: There was no difference in the proportion of people with and without arthritis who provided informal care (46%). Individuals with arthritis reported worse health, but this did not affect the likelihood of providing care, nor the types or amount of care provided. Caregivers with and without arthritis were most likely to provide fewer than 7 hours per week of care, and the most common type of care was characterized as hands-off, particularly transportation assistance. Men were just as likely to provide care as women but were less likely to provide high intensity care or perform hands-on tasks., Conclusion: Despite reporting worse health on average, people with arthritis were just as likely as people without arthritis to provide informal care. The need to provide informal care among people with arthritis may impact their ability to engage in self-management activities for their arthritis., (© 2020, American College of Rheumatology.)

Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.

The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1β can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.

Objective: To determine whether patient global assessment of disease activity (PtGA) over the first year of disease course, as part of a Boolean-based definition of remission and considered individually, had a significant relationship with structural progression over 3 years in patients with early arthritis., Methods: We conducted a prospective, observational study using ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) cohort data. Remission states were defined as 1) 4-variable remission, which included a tender joint count in 28 joints, a swollen joint count in 28 joints (SJC28), a C-reactive protein (CRP; mg/dl) level, and PtGA (scored 0-10, all scores of ≤1); 2) PtGA near remission, which included the same parameters as 4-variable remission with only PtGA >1 (of a maximum possible score of 10); 3) 3-variable remission (sum of the proportion of patients in 4-variable remission and the proportion of patients in PtGA near remission); or 4) nonremission. The strictest status satisfied both at 6 and 12 months was considered. Radiographic progression was determined as a change of ≥5 points in the total Sharp/van der Heijde score (ΔSHS) from baseline to 3 years. The predictive capacities for radiographic damage of different remission definitions were assessed by odds ratio (OR). The association between each individual component of remission with ΔSHS was tested through multivariate linear regression analyses., Results: Among 520 patients, 7% achieved 4-variable remission and 12% achieved PtGA near remission. Radiographic progression was observed in 29% of patients who achieved 4-variable remission (OR versus nonremission; OR 0.32 [95% confidence interval (95% CI) 0.15, 0.68]) and in 45% of patients with PtGA near remission (OR 0.65 [95% CI 0.38, 1.11]); the comparison was not statistically different (OR 0.49 [95% CI 0.20, 1.18]). In 3-variable remission, radiographic progression was observed in 39%. Of the individual components, only the SJC28 and CRP level were associated with radiographic progression., Conclusion: All definitions of remission led to low structural degradation in early arthritis, and 4-variable remission led to less radiographic progression than PtGA near remission, but without a statistically significant difference. Both 4-variable remission and 3-variable remission appear to be useful targets when aiming for structural nonprogression., (© 2020, American College of Rheumatology.)

Background: This case study documents the first familial case of Blau syndrome (BS) in Palestine characterized with mutation in CARD15/NOD2., Case Presentation: Eighteen years old female was initially misdiagnosed with Juvenile idiopathic arthritis (JIA). The patient had been on steroids and methotrexate treatment for the last 16 years, but did not respond well to treatment. Initial examination at Saint John of Jerusalem Eye Hospital Group clinic showed bilateral intermediate uveitis with camptodactyly. The patient's sister (aged 19 years) had bilateral intermediate uveitis and camptodactyly. Both eyes of their father had signs of old posterior uveitis. Father's left eye showed 360 degrees posterior synechia, mature cataract with old Keratic precipitates (KPs). He also had camptodactyly. The patient was referred to pediatric rheumatologist to rule out sarcoidosis. Lung CT scan showed bronchiectasis, genetic consultation followed. Complete eye examination, full history, refraction, and Optical coherence tomography (oct) were done. Systemic and topical steroid therapy could not control the ocular inflammation. The family then was referred to a geneticist. Genetic analyses showed that the proband and all three family members had an R334q mutation in the CARD15/Nod2 gene., Conclusions: BS should be considered in the differential diagnosis of childhood uveitis, especially in low and middle income countries where it is misdiagnosed in many cases, which delay appropriate diagnosis and thus control. Genetic analysis of the CARD15/Nod2 gene is helpful in the diagnosis. Steroids alone are not enough to control the disease, other immunosuppressants and biologics are needed., (© 2021. The Author(s).)

Objectives: To compare patient-reported outcome (PRO) domains between three arthritis phenotypes [undifferentiated arthritis (UA), autoantibody-negative RA (RA-) and autoantibody-positive RA (RA+)] at diagnosis, after 2 years and over time., Methods: All UA (n = 130), RA- (n = 176) and RA+ (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. PRO comparisons between phenotypes at baseline and after 2 years were performed with analysis of variance, while a linear mixed model compared them over time. Effect sizes were weighted against the minimal clinically important differences (MCIDs) for each PRO., Results: RA- patients had a higher disease burden compared with RA+ and UA. At baseline and after 2 years, RA- patients had more functional impairment and a poorer Physical Component Summary (PCS) compared with the other phenotypes, while they only scored worse for general health and morning stiffness duration at baseline. The MCIDs were exceeded at baseline, except for functional ability between RA+ and UA, while after 2 years only the MCID of the PCS was exceeded by RA- compared with UA and RA. After 2 years the PROs of all phenotypes improved, but PROs measuring functioning were still worse compared with the general population, even when patients had low disease activity., Conclusion: RA- patients had the highest disease burden of all phenotypes. Although most patients have low disease activity after treatment, all clinical phenotypes still have a similar significant impact on patients' lives, which is mainly physical. Therefore it is important to assess and address PROs in daily practice because of persistent disease burden despite low disease activity., Trial Registration: ISRCTN26791028., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Aims: The aim of this study was to assess arthritis of the basal joint of the thumb quantitatively using bone single-photon emission CT/CT (SPECT/CT) and evaluate its relationship with patients' pain and function., Methods: We retrospectively reviewed 30 patients (53 hands) with symptomatic basal joint arthritis of the thumb between April 2019 and March 2020. Visual analogue scale (VAS) scores for pain, grip strength, and pinch power of both hands and Patient-Rated Wrist/Hand Evaluation (PRWHE) scores were recorded for all patients. Basal joint arthritis was classified according to the modified Eaton-Glickel stage using routine radiographs and the CT scans of SPECT/CT, respectively. The maximum standardized uptake value (SUVmax) from SPECT/CT was measured in the four peritrapezial joints and the highest uptake was used for analysis., Results: According to Eaton-Glickel classification, 11, 17, 17, and eight hands were stage 0 to I, II, III, and IV, respectively. The interobserver reliability for determining the stage of arthritis was moderate for radiographs (k = 0.41) and substantial for CT scans (k = 0.67). In a binary categorical analysis using SUVmax, pain (p < 0.001) and PRWHE scores (p = 0.004) were significantly higher in hands with higher SUVmax. Using multivariate linear regression to estimate the pain VAS, only SUVmax (B 0.172 (95% confidence interval (CI) 0.065 to 0.279; p = 0.002) showed a significant association. Estimating the variation of PRWHE scores using the same model, only SUVmax (B 1.378 (95% CI, 0.082 to 2.674); p = 0.038) showed a significant association., Conclusion: The CT scans of SPECT/CT provided better interobserver reliability than routine radiographs for evaluating the severity of arthritis. A higher SUVmax in SPECT/CT was associated with more pain and functional disabilities of basal joint arthritis of the thumb. This approach could be used to complement radiographs for the evaluation of patients with this condition. Cite this article: Bone Joint J  2021;103-B(8):1380-1385.

Objective: Shared decision-making (SDM) is a strongly endorsed approach by which patients and clinicians work together to formulate a sensible care plan. The present study was undertaken to conduct a systematic review of SDM trials in patients considering knee arthroplasty (KA) to characterize how SDM was supported and the impact on care received., Methods: We searched multiple bibliographic databases from inception to December 31, 2019. A pair of reviewers working independently selected studies for inclusion, extracted data, and evaluated each trial's risk of bias., Results: We found 6 eligible randomized trials (4 included KA and hip arthroplasty), all of which tested the same proprietary decision aid (DA) (Treatment Choices for Hip or Knee Osteoarthritis), with some adding other materials to support SDM. These trials, all of which had moderate-to-high risk of bias, focused on assessing the effect of the DA on patient knowledge about the options while not explicitly supporting other aspects of SDM, such as choice awareness, deliberation, or decision-making. One trial found an increase in the number of African American patients undergoing KA in the 12 months following the intervention. No other trials found that SDM impacts clinical outcomes., Conclusion: Evidence for SDM in patients considering KA is mostly limited to a single DA. While use of this DA improves patient knowledge about their treatment options, this tool has not been shown to promote SDM, impact treatment decisions, or satisfaction with care. Future work should seek to support SDM directly and assess effects on treatment decisions, functional outcomes, and satisfaction., (© 2020, American College of Rheumatology.)

Rationale: Cryptococcal infection has been documented in immunocompromised patients. AIDS and renal transplant recipients account for majority of the cases. Most cases present with central nervous system or disseminated disease, with only few presenting soft tissue, bone, and joint manifestations., Patient Concerns: We present a case of soft tissue mass in a 66-year-old female renal transplant recipient and that of arthritis in a 64-year-old immunocompetent man who presented pseudogout arthropathy. Chest radiographies of both cases were negative. Biopsy revealed cryptococcal organisms. Blood culture or cerebrospinal fluid sampling indicated positive results for cryptococcal antigen., Diagnosis: Cryptococcus neoformans was recovered in the wound culture., Interventions: The patients received intravenous fluconazole and flucytosine, followed by oral fluconazole administration., Outcomes: Symptomatic improvements were achieved and no subsequent relapses were observed., Lessons: The authors experienced 2 cases of cryptococcosis with very unusual clinical presentation. Early clinical suspicion and serum cryptococcal antigen testing can help in rapid appropriate diagnosis in immunocompetent as well as immunocompromised patients even in the absence of pulmonary involvement., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: First metatarsophalangeal joint (MTPJ) fusion is the most effective technique for the treatment of MTPJ primary arthritis, severe hallux valgus and failure of primary corrective surgery of these conditions. It can be achieved through different techniques. We evaluated the outcomes in a cohort of patients treated with dorsal plate arthrodesis., Materials and Methods: We treated 30 feet for 28 patients; the mean follow-up was 35 months. For each foot, we collected radiological and clinical assessment, with the visual analogue scale (VAS) for pain and the Manchester and Oxford Foot questionnaire (MOFQ). The technique consisted in a cup and cone arthrodesis with the application of a low profile dorsal plate. Patients were allowed for immediate weight bearing., Results: Consolidation was achieved in all cases; in 29 cases, radiographic union was recorded within 6 months from surgery, in one case after 9 months. Comparison between the preoperative and postoperative of VAS and MOXFQ values showed a statistically significant difference (p < 0.05). Only one case developed wound dehiscence as complication., Conclusions: Even if there is still a debate regarding the best system for MTPJ fusion, we believe cup and cone fusion with dorsal plating is an effective method. Moreover, the stability of the osteosynthesis obtained allows for immediate post-operative weight bearing, making patients able to return soon to their normal life., Trial Registration: We present a retrospective study; all patients enrolled were retrospectively registered.

MicroRNA-128 (miR-128) is associated with cell proliferation, differentiation, migration, apoptosis, and survival. Genetic analysis studies have demonstrated that miR-128 participates in bone metabolism, which involves bone marrow-derived mesenchymal stem cells, osteoblasts, osteoclasts, and adipocytes. miR-128 also participates in regeneration of skeletal muscles by targeting myoblast-associated proteins. The deregulation of miR-128 could lead to a series of musculoskeletal diseases. In this review, we discuss recent findings of miR-128 in relation to bone metabolism and muscle regeneration to determine its potential therapeutic effects in musculoskeletal diseases, and to propose directions for future research in this significant field., (© 2020 Wiley Periodicals LLC.)

The initial management of rheumatoid arthritis (RA) has a high impact on disease prognosis. Therefore, we need to select the most appropriate treatment as soon as possible. This goal requires biomarkers of disease severity and prognosis. One such biomarker may be the presence of anti-carbamylated protein antibodies (ACarPA) because it is associated with adverse long term outcomes as radiographic damage and mortality. Here, we have assessed the ACarPA as short-term prognostic biomarkers. The study was conducted in 978 prospective early arthritis (EA) patients that were followed for two years. Our results show the association of ACarPA with increased levels of all the disease activity measures in the first visit after arthritis onset. However, the associations were more significant with the high levels in local measures of inflammation and physician assessment than with the increases in systemic inflammation and patient-reported outcomes. More notably, disease activity was persistently increased in the ACarPA positive patients during the two years of follow-up. These differences were significant even after accounting for the presence of other RA autoantibodies. Therefore, the ACarPA could be considered short-term prognostic biomarkers of increased disease activity in the EA patients.

Background: Diseases of the pancreas may present with extrapancreatic symptoms, such as (poly)arthritis or necrosis of subcutaneous fat. A combination of pancreatitis, panniculitis and (poly)arthritis is referred to as the PPP syndrome, which is associated with acute and chronic pancreatitis, as well as pancreatic malignancies., Case Description: This article describes a patient which was admitted to our hospital with severe polyarthritis and panniculitis. A meticulous work-up revealed an underlying focal alcoholic pancreatitis. The clinical course in our patient illustrates the severity of the PPP syndrome and emphasizes the need of a multidisciplinary approach., Conclusion: Panniculitis and/or (poly)arthritis may be the first symptom of underlying pancreatic disease. Timely recognition and diagnosis is imperative for successful treatment and outcome. The multi-organ involvement in the PPP syndrome requires close collaboration across different medical departments.

Reasons of mon- and oligoarthritis are heterogeneous. The diagnostic approach includes a detailed medical anamnesis, physical examination and imaging (conventional X-ray, sonography, MRI and, CT). Analysis of the synovial fluid is required in suspected septic arthritis and frequently helps in diagnosis and differential diagnosis of crystal arthropathies. Dual-energy-CT (DECT) detects sodium urate crystals and can replace joint puncture in some cases. In addition to crystal arthropathies and septic arthritis, differential diagnosis of mon-/oligoarthritis includes reactive arthritis, arthrosis and monarthritic courses of SpA/PsA. A rheumatologist should be consulted particularly in the case of persistent monarthritides, in order to initiate a specific therapy to prevent secondary damage., Competing Interests: Frau Kernder wird zur Durchführung der LuLa-Studie von GSK und UCB Pharma unterstützt.Herr Sewerin: Forschungsförderung: Deutsche Forschungsgesellschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), AMGEN, AbbVie, BMS, Celgene, Chugai, Deutscher Psoriasis-Bund, Janssen-Cilag, Lilly, Novartis, Roche, Rheumazentrum-Rhein-Ruhr, UCB Pharma Referentenhonorar AXIOM Health, AMGEN, AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Chugai Pharma Marketing Ltd./Chugai Europe, Deutscher Psoriasis-Bund, Gilead Sciences, Hexal Pharma, Janssen-Cilag, Johnson & Johnson, Lilly/Lilly Europe/Lilly Global, medi-login, Mediri GmbH, Novartis Pharma, Onkowissen GmbH, Pfizer, Roche Pharma, Rheumazentrum Rhein-Ruhr, Sanofi-Genzyme, Spirit Medical Communication, Swedish Orphan Biovitrum, UCB Pharma., (Thieme. All rights reserved.)

Polyarthritis is defined by the palpable synovitic swelling of more than 4 joints. Polyarthritis is always due to a systemic disease and not a local process. Causes include a broad spectrum of rheumatic and infectious diseases with clearly different therapeutic options. It is also important to differentiate arthritis from osteoarthrosis. The objective of this paper is to give an overview on patient history, clinical presentation, diagnostic investigations and the differential diagnosis of the most common diseases that present as polyarthritis., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective: The aim of this review was to systematically identify, appraise and synthesise evidence on work-related outcomes experienced by younger to middle-aged adults (aged 16-50 years) with arthritis., Methods: Eligible studies were identified in Medline, PsycINFO, Embase and CINAHL in January 2020. Quantitative and qualitative studies containing self-reported data on work-related outcomes on younger/middle-aged adults with arthritis were included. Quality assessment was undertaken using validated quality appraisal tools from the Joanna Briggs Institute., Results: Thirty-four studies were identified for inclusion. Work outcomes were organised around five themes: (1) arthritis-related work productivity outcomes, (2) arthritis-related work participation outcomes, (3) other arthritis-related workplace outcomes, (4) barriers to work participation associated with arthritis and (5) enablers to work participation associated with arthritis. Arthritis was associated with work limitations on the Workplace Activity Limitations Scale (average scores ranging from 5.9 (indicating moderate workplace difficulty) to 9.8 (considerable workplace difficulty)), and higher work disability prevalence rates (range: 6%-80%) relative to healthy populations. Arthritis was not associated with decreased absenteeism on the Work Productivity and Activity Impairment Questionnaire (mean (SD) 7.9% (14.0%)), indicating low levels of absenteeism, similar to healthy populations. As work outcomes were commonly binary, person-centred (qualitative) perspectives on barriers and enablers augmented the quantitative findings., Conclusion: Arthritis is commonly associated with poorer work outcomes for younger/middle-aged adults relative to healthy populations. Additional research focusing solely on the workplace needs of younger/middle-aged population groups is required to inform tailored interventions and workplace support initiatives to maximise productive working years., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early life experience can cause long-term alterations in the nociceptive processes underlying chronic pain, but the consequences of early life arthritic joint inflammation upon the sensory innervation of the joint is not known. Here, we measure pain sensitivity and sensory innervation in a young, juvenile and adult rodent model of arthritic joints and test the consequences of joint inflammation in young animals upon adult arthritic pain and joint innervation., Methods: Unilateral ankle joint injections of complete Freund's adjuvant (CFA) (6-20 µl) were performed in young, postnatal day (P)8, adolescent (P21) and adult (P40) rats. A separate cohort of animals were injected at P8, and again at P40. Hindpaw mechanical sensitivity was assessed using von Frey monofilaments (vF) for 10 days. Nerve fibres were counted in sections through the ankle joint immunostained for calcitonin gene-related peptide (CGRP) and neurofilament 200 kDa (NF200)., Results: Ankle joint CFA injection increased capsular width at all ages. Significant mechanical pain hypersensitivity and increased number of joint CGRP + ve sensory fibres occurred in adolescent and adult, but not young, rats. Despite the lack of acute reaction, joint inflammation at a young age resulted in significantly increased pain hypersensitivity and CGRP + fibre counts when the rats were re-inflamed as adults., Conclusions: Joint inflammation increases the sensory nociceptive innervation and induces acute pain hypersensitivity in juvenile and adult, but not in young rats. However, early life joint inflammation 'primes' the joint such that adult inflammatory pain behaviour and nociceptive nerve endings in the joint are significantly increased. Early life joint inflammation may be an important factor in the generation and maintenance of chronic arthritic pain.

A previously healthy 53-year-old man was hospitalised for 12 days due to COVID-19 with shortness of breath. A few days after discharge from hospital, the patient developed fever and severe pain in several joints in the lower extremities. The pain was so severe that the patient was unable to stand on his feet. Synovial fluid from the right-side knee contained a high number of polynuclear cells and a few mononuclear cells. Microscopy, culture and PCR tests for bacterial infection were all negative. Furthermore, the patient tested negative for rheumatoid factor, anti-cyclic citrullinated peptide and human leukocyte antigen (HLA)-B27. Thus, the condition was compatible with reactive arthritis. The condition improved markedly after a few days' treatment with non-steroid anti-inflammatory drugs and prednisolone., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the characteristics of fundus autofluorescence (FAF) images and visual functions in eyes with Stickler syndrome using ultra-widefield FAF images., Methods: Forty-six eyes of 26 patients with mutations in the COL2A1 gene underwent ultra-widefield FAF imaging. The eyes were categorized into three types; no signs of abnormal AF, predominantly hyperfluorescent AF (hyper-AF), and predominantly hypofluorescent AF (hypo-AF). Goldmann perimetry was performed on 34 eyes, and line-scan images of the abnormal AF lesions were obtained by swept-source optical coherence tomography in 4 eyes., Results: Abnormal AF lesions were found in 37 eyes of 21 (80.7%) of the 26 patients. Hyper-AF was found in 15 eyes and hypo-AF was found in 22 eyes. The FAF changes corresponded with the funduscopically observed radial paravascular retinal degeneration. The average age at the examination was significantly younger in patients who had eyes with hyper-AF or no abnormal AF than in those with hypo-AF (12.8 vs. 28.4 years; P = 0.009). Abnormal AF-associated visual field defects were found in 5/10 (50%) eyes with hyper-AF and 17/18 (94%) eyes with hypo-AF. Hyper-AF changes tended to appear before retinal changes were detectable by fluorescein angiography. An absence of the ellipsoid zone and the outer nuclear layer and a thinning of the overall retinal thickness were found corresponding to the hypo-AF lesions in the swept source optical coherence tomography images., Conclusion: Abnormal FAF is characteristic of eyes with Stickler syndrome. Age-related alterations of the FAF was associated with visual field defects and disruption of the photoreceptors and retinal pigment epithelial cells., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: The Timed Up and Go (TUG) test is used to assess a person's mobility and balance. We aimed to provide updated reference values for TUG performance for the community-dwelling older population according to age and sex, and according to the presence of arthritis and non-communicable diseases (NCDs)., Participants and Methods: Cross-sectional data from the seventh wave (2015-2016) of the population-based Norwegian Tromsø Study counting 5400 community-dwelling people (53% women), aged 60-84 years were used. Reference values were presented as percentiles and means for men and women by age at five-year intervals., Results: Median TUG score was stable during age 60-65 years, and after age 65 years median TUG score increased significantly with age (increase by 0.14 sec per 1 year higher age in both men and women, p<0.001). At the youngest ages (<65 years), in both men and women, there were no differences in TUG performance for those with NCD or arthritis compared to those without these diseases. After age 65 however, those without these diseases performed significantly better (p<0.05) in both men and women., Conclusion: The present study provided percentile reference values for TUG performance in community-dwelling older adults in Norway by age and sex, and in subgroups of those having arthritis and NCDs. TUG scores increased with age, and performance was significantly poorer among participants with arthritis or NCDs after age 65 years. The findings may guide clinical interventions for individuals with mobility and balance disabilities., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Svinøy et al.)

Background: Early-onset sarcoidosis (EOS) and Blau syndrome (BS) are systemic inflammatory granulomatous diseases without visible pulmonary involvement, and are distinguishable from their sporadic and familial forms. The diseases are characterized by a triad of skin rashes, symmetrical polyarthritis, and recurrent uveitis. The most common morbidity is ocular involvement, which is usually refractory to conventional treatment. A gain-of-function mutation in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been demonstrated in this disease; however, little is known about the relationship between the activation of NOD2 and the pathophysiology of EOS/BS. Here we describe EOS/BS with a novel mutation in the NOD2 gene, as well as detection of Propionibacterium acnes (P. acnes) in the granulomatous inflammation., Case Presentation: An 8-year-old Japanese girl presented with refractory bilateral granulomatous panuveitis. Although no joint involvement was evident, she exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis, and P. acnes was detected within the sarcoid granulomas by immunohistochemistry with P. acnes-specific monoclonal (PAB) antibody. Genetic analyses revealed that the patient had a NOD2 heterozygous D512V mutation that was novel and not present in either of her parents. The mutant NOD2 showed a similar activation pattern to EOS/BS, thus confirming her diagnosis. After starting oral prednisolone treatment, she experienced an anterior vitreous opacity relapse despite gradual prednisolone tapering; oral methotrexate was subsequently administered, and the patient responded positively., Conclusions: We presented a case of EOS/BS with a novel D512V mutation in the NOD2 gene. In refractory granulomatous panuveitis cases without any joint involvement, EOS/BS should be considered as a differential diagnosis; genetic analyses would lead to a definite diagnosis. Moreover, this is the first report of P. acnes demonstrated in granulomas of EOS/BS. Since intracellular P. acnes activates nuclear factor-kappa B in a NOD2-dependent manner, we hypothesized that the mechanism of granuloma formation in EOS/BS may be the result of NOD2 activity in the presence of the ligand muramyl dipeptide, which is a component of P. acnes. These results indicate that recognition of P. acnes through mutant NOD2 is the etiology in this patient with EOS/BS.

Objective: The biological mechanisms of cryotherapy for managing acute pain remain unclear. Additionally, it is unknown whether the effectiveness of cryotherapy depends on the applied temperature. This study aimed to clarify the biological effects of cryotherapy and to examine the therapeutic effects of cryotherapy applied at different temperatures in rats., Methods: This was an experimental study using a rat knee joint arthritis model. Thirty-five Wistar rats were randomly divided into arthritis (AR), arthritis with 5°C cryotherapy (CR-5), arthritis with 10°C cryotherapy (CR-10), and sham-arthritis control (CON) groups. Arthritis was induced by injecting a mixture of kaolin/carrageenan into the right knee joint. Cryotherapy was applied for 7 days starting the day after injection by immersing the right knee joint in 5°C or 10°C water. Joint transverse diameter, pressure pain threshold, and pain-related behaviors were assessed for 7 days. The number of CD68-positive cells in the knee joint and the expression of calcitonin gene-related peptide in the spinal dorsal horn 8 days after injection were analyzed by immunohistochemical staining., Results: Improvements in transverse diameter, pressure pain threshold, and pain-related behaviors were observed in the CR-5 and CR-10 groups on the 3rd day compared with the AR group. The number of CD68-positive cells and the expression of calcitonin gene-related peptide in the CR-5 and CR-10 groups were significantly decreased compared with the AR group. There were no significant differences in all results between the CR-5 and CR-10 groups., Conclusions: Cryotherapy can ameliorate inflammatory pain through reduction of synovium and central sensitization. Additionally, the effects of cryotherapy lower than 10°C are observed independent of applied temperature., Impact: Cryotherapy may be beneficial as a physical therapy modality for pain and swelling management in the acute phase of inflammation. Translational human study is needed to determine the effective cryotherapy temperature for the inflammatory pain., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In severe cases of ankle and subtalar arthritis, arthrodesis of the subtalar joint is performed in combination with ankle arthroplasty. In these special cases gait analysis reveals real motion at the replaced tibiotalar joint., Methods: Twenty-three patients affected by ankle and subtalar arthritis, treated either with a 3-component or a 2-component prosthesis in combination with subtalar arthrodesis, were clinically evaluated preoperatively and at a minimum of 1-year follow-up. Gait analysis was performed postoperatively using a multi-segment foot protocol. Foot kinematics were compared to corresponding data from a healthy control group., Results: Clinical scores significantly improved from preoperative to follow-up. The clinically measured passive ankle dorsiflexion/plantarflexion significantly improved at the follow-up. Patients' normalized walking speed and stride length were significantly lower than those in control. With exception of the ankle frontal-plane motion, sagittal-plane mobility of foot joints was about 50% than that in healthy joints., Conclusions: Improvement in clinical scores was found for both prostheses. Normal spatio-temporal parameters were not restored. In these patients, fusion of the subtalar joint appeared to be compensated by larger frontal-plane motion at the tibiotalar joint., Level of Evidence: Level III- retrospective comparative study. The study was approved by the local Ethics Committee as protocol MAT (protocol registration at clinicaltrials.gov NCT03356951)., (Copyright © 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Background: Prolonged social isolation as a result of the COVID-19 global pandemic has been a source of considerable psychological distress for many people. This can manifest in many ways and if left undetected can impact negatively on general health. It is essential to understand the impact of these conditions on inflammatory arthritis (IA) patients, especially axial spondyloarthropathy (axSpA)., Aim: To capture the level of psychological distress for patients with IA following prolonged social isolation., Methods: A survey was sent out to patients with a confirmed diagnosis of IA. This captured changes in sleep, mood, disease activity, employment and general health since the beginning of the social isolation period. A PHQ-4 (Patient Health Questionnaire) was included to determine level of psychological distress., Results: Females with IA reported significantly higher rates of decline in general health (40% vs 16%, p = 0.01), mood disturbance (43.4% vs 26%, p = 0.03) and increased disease activity (50% vs 16%, p = 0.01) compared to males. Evaluating the mean PHQ-4 scores, no significant difference was noted between genders (4.80 vs 3.44, p = 0.10). However, females demonstrated a non-significant trend toward increased rates of moderate to severe psychological distress (40% vs 30%, p = 0.13). Subanalysis of patients with axSpA found high rates of moderate to severe distress in both genders., Conclusions: Females with IA reported significantly higher rates of decline in general health, mood disturbance and increased disease activity during the period of social isolation. This was reflected in a trend towards greater levels of psychological distress.

There is strong evidence showing that the activation of peripheral proteinase-activated receptors type 2 (PAR-2) can initiate hyperalgesic and inflammatory responses in the joint. However, to date, there is no report of functional spinal PAR-2 receptors in arthritis models. The primary aim of this study was to evaluate the activity of PAR-2 receptors at the spinal cord by using a potent agonist (FLIGRL) in naïve animals, and an antagonist (GB83) in different models of joint pain. Saline or FLIGRL (10 nmol) were injected intrathecally in naïve animals and nociceptive behaviour was evaluated over a 24 h time period by von Frey hair algesiometry. Paw withdrawal threshold decreased from 3 to 24 h and this allodynic effect was blocked by GB83 (90 nmol; i.p.). Acute inflammatory joint pain was induced by injecting 0.5 % kaolin/carrageenan (50 μL each) into the right knee joint of male Wistar rats (24 h recovery). Chronic inflammatory joint pain was modelled by intraarticular injection of Freund's complete adjuvant (FCA; 50 μL; 7 days recovery) or chronic osteoarthritis pain by sodium monoiodoacetate (MIA; 3 mg; 14 days recovery). Animals were then treated with either intrathecal vehicle or 10 nmol of GB83 (10 μL); joint pain was evaluated throughout the subsequent 3 h period. The acute inflammatory pain induced by kaolin/carrageenan was not affected by treatment with GB83. Conversely, both chronic arthritis models demonstrated increased hind paw withdrawal threshold after spinal injection of the PAR-2 antagonist. Based on these results, spinal PAR-2 receptors are involved in joint nociceptive processing in chronic but not acute arthritic conditions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The carpometacarpal joint of the thumb is one of the joints most commonly affected by arthritis. The dominant hand is involved in 60-65% of cases, with a higher prevalence among women. The condition results in significant disability of the hand, which affects activities of daily living. Management is dependent on both the clinical stage of the disease and patient expectations and demands., Objective: The aim of this article is to review the current non-operative and operative modalities in managing pain symptoms, and explore evidence for the use of these modalities., Discussion: Basal thumb arthritis is a very common condition encountered by the general practitioner. Treatment must focus on functional expectations and demands of the patient, and individualised treatment plans need to be tailored to the patient. Hand therapy in addition to patient education and use of an orthosis has been shown to be very effective in management of the early stages of basal thumb arthritis. With more advanced disease, surgical modalities provide better symptomatic control.

An unstable and osteoarthritic distal radioulnar joint presents with considerable functional impairment, pain, and weakness in gripping manipulation of objects. A wide variety of surgical alternatives have been described to address these concerns. Resection arthroplasties include different types of distal ulna resection and soft tissue procedures; good overall results have been described for these types of procedures, although they have shown limitations in achieving and maintaining pain relief and stability, especially in more active patients. Since the late 1980s, partial and total joint arthroplasties have emerged as good alternatives for treatment in young and more active patients., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The mycobacterium tuberculosis (TB) IFN-γ release assay (TB-IGRA) assesses peripheral blood cell release of IFN-γ upon ex vivo exposure to mitogen (IGRA-MT), TB antigen or a negative/nil control (IGRA-NL); IGRA-NL is a measure of spontaneous IFN-γ release (SIR). Here, we investigate the diagnostic associations of elevated SIR and the potential use of IGRA-NL as a novel biomarker in SLE., Methods: We analysed diagnostic code frequencies among 11 823 individuals undergoing TB-IGRA testing between 2010 and 2015 in a large urban US health-care system. To study the relationship between IGRA-NL and SLE, we identified 99 individuals with SLE and TB-IGRA test results then assessed correlations between IGRA-NL, normalized IGRA-NL (the quotient of IGRA-NL/IGRA-MT), disease manifestations and disease activity., Results: We identified a discovery cohort of 108 individuals with elevated SIR (>5 S.d. above median) that was significantly enriched for a limited set of diagnoses, including SLE, TB infection, haemophagocytic lymphohistiocytosis and HIV infection. In SLE patients undergoing TB-IGRA testing, normalized IGRA-NL correlated better with disease activity than did anti-dsDNA or complement levels. This relationship appeared to reflect interactions between normalized IGRA-NL and the presence of acute skin disease, hypocomplementemia, fever and thrombocytopenia., Conclusion: Elevated SIR appears to be associated with a limited number of disease processes, including SLE. The diagnostic utility of SIR remains to be determined. IFN-γ activation, as measured by the TB-IGRA test, may offer a readily available tool for assessing disease activity in patients with SLE., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

An unstable, arthritic elbow presents a therapeutic challenge. Patients may have painful, limited range of motion, often due to trauma or progressive joint destruction from rheumatologic disease. The options for management may be particularly challenging when treating young, active patients. While elbow arthroplasty usually provides predictable pain relief and joint range of motion, concerns exist regarding postoperative activity limitations and implant survival. Therefore, these procedures are limited to select subsets of patients, typically low-demand, elderly patients. Interposition arthroplasty is an option for the young, active patient with a painful arthritic elbow., Competing Interests: Disclosure The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial; payments or other benefits from any commercial entity related to the subject of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)