Persistent Joint Research Articles

Customizable interdental splinting for repair of pediatric mandibular fractures in children with mixed dentition: A novel technique

ObjectiveRepair of pediatric mandibular fractures (PMFs) can be challenging due to the lack of permanent dentition for immobilization, and the presence of unerupted teeth and growth plates in the mandible limiting the space for fixation. Interdental splinting (IDS) has been advocated to provide temporary fixation without the need for mandibular plating; however, there is sparse description of the surgical methodology, and data on long term outcomes are even more limited. The aim of this study is to present our technique and outcomes using a novel technique for IDS repair of pediatric mandible fractures. Study designObservational retrospective chart review. SettingTertiary care pediatric hospital. Subjects and methodsPediatric patients requiring operative repair for mandibular fracture at our tertiary care institution between 2004 and 2021 were included. Patients over 18 years of age, those who died due to associated injuries, or those who underwent non-IDS repairs were excluded. Subjects with at least 3 months of follow-up were assessed for efficacy of surgical repair and short-term adverse outcomes, and at least 1 year for long-term adverse events. Descriptive statistics were obtained. ResultsTwenty-three children were included in the study with an average age of 7.4 years (range 2–17 years). Fifty-two percent (52.2%) were female. The most common fracture site was the condyle, occurring in 16 children (70%). The indication for operative repair in all cases was malocclusion. The average duration of maxillomandibular fixation (MMF) with the novel IDS was 21 days (range 12–42 days). The average length of follow up was 1.6 years (range 3 months–11 years). All children had restored, functional occlusion at follow up with none requiring further orthodontic or dental intervention. Three children of the total cohort (13.0%) had prolonged hospitalization beyond 48 h for poor oral intake. Five children (21.7%) experienced minor long-term complications including persistent temporomandibular joint pain (n = 1, 4.3%), infection (n = 2, 8.7%), hypertrophic scar (n = 1, 4.3%) and exposure of hardware (n = 1, 4.3%). ConclusionPMFs resulting in malocclusion are safely and effectively managed with operative repair utilizing a customizable IDS, with few observed short- and long-term complications.

Chaenomeles Fructus (CF), the Fruit of Chaenomeles sinensis Alleviates IL-1β Induced Cartilage Degradation in Rat Articular Chondrocytes

Osteoarthritis (OA) causes persistent pain, joint dysfunction, and physical disability. It is the most prevalent type of degenerative arthritis, affecting millions of people worldwide. OA is currently treated with a focus on pain relief, inflammation control, and artificial joint surgery. Hence, a therapeutic agent capable of preventing or delaying the progression of OA is needed. OA is strongly associated with the degeneration of the articular cartilage and changes in the ECM, which are primarily associated with a decrease in proteoglycan and collagen. In the progress of articular cartilage degradation, catabolic enzymes, such as matrix metalloproteinases (MMPs), are activated by IL-1β stimulation. Given the tight relationship between IL-1β and ECM (extra-cellular matrix) degradation, this study examined the effects of Chaenomeles Fructus (CF) on IL-1β-induced OA in rat chondrocytes. The CF treatment reduced IL-1β-induced MMP3/13 and ADAMTS-5 production at the mRNA and protein levels. Similarly, CF enhanced col2a and aggrecan accumulation and chondrocyte proliferation. CF inhibited NF-κB (nuclear factor kappa B) activation, nuclear translocation induced by IL-1β, reactive oxygen species (ROS) production, and ERK phosphorylation. CF demonstrated anti-OA and articular regeneration effects on rat chondrocytes, thus, suggesting that CF is a viable and fundamental therapeutic option for OA.

Thumb Carpometacarpal joint dislocation: Case report and short review

Thumb carpometacarpal (CMC) joint dislocation is rare, and the treatment options may vary from conservatives’ strategies to open reduction and fixation. In face of pain and joint instability persistence, surgical intervention is required. We present the case of a 67-year-old male that was referred to our hospital with pain and edema of the left hand, after the failure of a conservative treatment. After initial refusal of open surgery, due to the persistent joint instability, open reduction of the CMC joint dislocation was performed, and stabilized using two percutaneous Kirschner wires after repairing the joint capsule and dorsoradial ligament. Immobilization was required for 4 weeks. After that, the Kirschner wires were removed. Along with physiotherapy, the follow-up showed no pain persistence nor CMC joint luxation reoccurrence while the joint recovered its mobility. Further studies are required in order to determine the optimal therapy for such cases and to provide standardized recommendations, taking into account that the restoration of thumb CMC joint mobility is one of the most important goals in hand surgery.

Application of Intra-articular Corticosteroid Injection in Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is one of the common rheumatic diseases in pediatrics. Persistent synovitis and joint pain cause reduced range of motion, deformity and gait interruption, which are important reasons for children's disability and a decline in their quality of life. Rheumatology experts have explored good treatment strategies, among which intra-articular corticosteroid injections (IACIs) targeting joints can greatly reduce these systemic adverse reactions while still obtaining local anti-inflammatory effects. Local inhibition of synovitis by the use of steroid hormones in a joint cavity can avoid or reduce adverse reactions of systemic therapy, prevent or treat leg length variance and joint contracture, solve Baker's cyst, improve tenosynovitis, promote physical therapy and rehabilitation, make gait change smoothly, relieve pain, and restore joint function. Given the importance of IACIs in treating JIA, this paper reviewed the case selection, drug injection, dose selection, current anesthesia and injection techniques, the efficacy, recurrence, and influencing factors of IACIs, the management of physiotherapy intervention post-injection, the application of ultrasound guidance and the safety and complications of IACIs in children with JIA. This study aims to guide the use of IACIs for the best approach throughout the review.

Spontaneously reported persistent symptoms related to coronavirus disease 2019 one year after hospital discharge : Aretrospective cohort single-center study.

BackgroundThere are no outcome studies for coronavirus disease 2019 (COVID-19) survivors one year after hospital discharge in Germany.MethodsThis retrospective cohort study included all patients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalized in the departments of internal medicine of the Klinikum Saarbrücken, a tertiary care hospital, between March 15 and December 31, 2020. A telephone interview with survivors was conducted at least 12 months after discharge. The interview was initiated with an open-ended question whether the patient had fully recovered from the disease. In the event of a subjective incomplete recovery, the patient was prompted to report any continuous or frequent symptoms that had not occurred prior to COVID-19. Finally, independent of the open-ended question response, all patients were asked closed questions which addressed new symptom onset of persistent fatigue, cognitive dysfunction, headache, muscle and joint pain following COVID-19.ResultsIn all, 235 survivors were contacted and 162 could be included in the analysis. In 55 of 162 interviews (34.0%) at least one persistent COVID-19 symptom (PCS) was spontaneously reported. Four of 55 survivors with PCS reported five additional symptoms on the closed questions. One survivor, who responded positively to the open-ended question, reported new onset PCS in response to the closed questions. Physical fatigue (24.7%), cognitive dysfunction (14.8%), shortness of breath (8.6%), muscle and joint pain (6.8%) and headache (6.2%) were the most frequently reported PCS.ConclusionsDespite an interview technique aimed to reduce attribution bias by patients, one third of COVID-19 inpatient survivors report PCS one year after hospitalization.The complete article is written in English.

Causes of knee pain evaluated by arthroscopy after knee arthroplasty: a case series.

The origin of persistent pain and joint limitation after knee arthroplasty are controversial and difficult to diagnose. Knee arthroscopy is indicated when the results of routine evaluation tests are not clear. The purpose of this study was to determine through arthroscopy the cause of post-knee-arthroplasty pain symptoms in patients without a prior diagnosis of cause of pain. This prospective case series study described the outcomes of 34 patients (35 knees) with pain and limited function in the arthroplastic joint, who underwent diagnostic and therapeutic arthroscopy. Patients were clinically evaluated using range-of-motion tests and the Lysholm, Hospital for Special Surgery (HSS) and Knee Society Score (KSS) scales. The procedure found cyclops in 17 knees, synovitis in 9 knees, arthrofibrosis in 6 knees, polyethylene wear with debris in two knees, and polyethylene bouncing in one knee with unicompartmental arthroplasty with a mobile polyethylene platform. It was effective for the relief of pain symptoms, with excellent or good outcomes in 80% of cases; there was a poor outcome in 11.43%, which maintained the presentation of pain and underwent revision arthroplasty, and, in 8.57%, did not undergo another surgery despite symptom persistence. Post-arthroplasty knee arthroscopy seems beneficial in patients with pain and without a pre-established diagnosis and who had already undergone conservative treatment unsuccessfully.

Unsolved issues of treatment of adult patients with hemophilia A

Sufficient supply of coagulation factors products has significantly improved life quality and expectancy in patients with hemophilia. Certain difficulties, however, persist when it comes to the treatment of the disease. To analyze current therapeutic approaches and identify major unsolved issues in the treatment of patients with hemophilia A. An online survey of 100 adult patients with hemophilia A was held. More than a half of the surveyed sample (59%) are patients aged 19 to 40 with the severe form of the disease, 73% of respondents receive a replacement therapy with plasmatic factors, 42% of patients inject drugs 3 times a week or more. More than a half of all age groups with hemophilia have persistent pain and limited joint mobility, in 70% of the patients, bleeding into the joints occurred 4 or more times within the past year, 47% of the patients with hemophilia A are partially satisfied or dissatisfied with their state of health, 92% of the patients would like to improve their quality of life. At the same time, about 1/3 of the patients would like to reduce the frequency of drug administration. More than 40% of the respondents did not visit a hematologist during the year, 85% do not conduct regular laboratory monitoring. The survey results demonstrate numerous areas of potential change pertaining to the approaches towards therapy and to the innovative drugs for the treatment of patients with hemophilia.

Spacer exchange in persistent periprosthetic joint infection: microbiological evaluation and survivorship analysis.

The purposes of this study were to determine demographics and characteristics of patients who underwent spacer exchange for persistent infection in the setting of two-stage arthroplasty for periprosthetic joint infection, to describe the microbiology of pathogens involved, to analyze survivorship free from infection in these patients. The institutional prospectively collected database was reviewed to enroll patients with minimum 2 years follow-up. Patients who underwent two-stage procedure for septic arthritis were excluded, as were patients who had spacer fracture or dislocation. A total of 34 patients (41 procedures) were included. Mean age was 65.0 ± 12.8years. Mean follow-up was 53.4 ± 24.8months. Mean number of previous procedures was 3.6 ± 1.2. A total of 27 (79.4%) patients underwent final reimplantation. The most frequently isolated pathogen in spacer exchange was Staphylococcus epidermidis (10 cases, 28.6%). Polymicrobial cultures were obtained from 9 (25.71%) patients, 10 (28.6%) presented culture-negative infections. A total of 11 (32.4%) resistant pathogens were isolated, and 16 (47.0%) difficult to treat pathogens were detected. Eradication rate was 78.8%. Overall survivorship of implants after final reimplantation was 72.8% at 51.8months. Surgeons should be aware that subjects necessitating spacer exchange often present multiple comorbidities, previous staged revision failures, soft-tissue impairment and difficult to treat infection. In these patients, spacer exchange provides good clinical results and infection eradication, preventing arthrodesis or amputation.

Interplay Between Iron Overload and Osteoarthritis: Clinical Significance and Cellular Mechanisms.

There are multiple diseases or conditions such as hereditary hemochromatosis, hemophilia, thalassemia, sickle cell disease, aging, and estrogen deficiency that can cause iron overload in the human body. These diseases or conditions are frequently associated with osteoarthritic phenotypes, such as progressive cartilage degradation, alterations in the microarchitecture and biomechanics of the subchondral bone, persistent joint inflammation, proliferative synovitis, and synovial pannus. Growing evidences suggest that the conditions of pathological iron overload are associated with these osteoarthritic phenotypes. Osteoarthritis (OA) is an important complication in patients suffering from iron overload-related diseases and conditions. This review aims to summarize the findings and observations made in the field of iron overload-related OA while conducting clinical and basic research works. OA is a whole-joint disease that affects the articular cartilage lining surfaces of bones, subchondral bones, and synovial tissues in the joint cavity. Chondrocytes, osteoclasts, osteoblasts, and synovial-derived cells are involved in the disease. In this review, we will elucidate the cellular and molecular mechanisms associated with iron overload and the negative influence that iron overload has on joint homeostasis. The promising value of interrupting the pathologic effects of iron overload is also well discussed for the development of improved therapeutics that can be used in the field of OA.

The Relationship Between Cricket Participation, Health, and Wellbeing: A Systematic Scoping Review.

Summarising and synthesising the evidence on cricket health and wellbeing can help inform cricket stakeholders and navigate future research directions. The purpose of this study was to investigate the relationship between cricket participation, health and wellbeing at all ages and playing standards, and identify research gaps in the existing literature. A scoping review was performed from inception to March, 2020. Studies were included if they assessed a construct related to health and/or wellbeing in cricketers, available in English. 219 articles were eligible. Injury incidence per 1,000 player exposures ranged from 1.8-5.7 injuries. 48% of former cricketers experienced persistent joint pain. However, former cricketers reported greater physical activity levels and mental-components of quality of life compared to the general population. Heat injury/illness and skin cancer are concerns and require further research. Cricket participation is associated with an inherent injury risk, which may have negative implications for musculoskeletal health in later life. However, cricket participation is associated with high quality of life which can persist after retirement. Gaps in the literature include prospective studies on health and wellbeing of cricketers, female cricketers, injury prevention strategies, and the impact of cricket participation on metabolic health and lifetime physical activity.

Arthroscopic Foveal Repair of the Triangular Fibrocartilage Complex Improved the Clinical Outcomes in Patients With Persistent Symptomatic Distal Radio-Ulnar Joint Instability After Plate Fixation of Distal Radius Fractures: Minimum 2-Year Follow-Up

To investigate the longitudinal trend of symptomatic distal radioulnar joint (DRUJ) instability after plate fixation for distal radius fractures (DRFs), determine which factors are associated with persistent symptomatic DRUJ instability, and evaluate the postoperative outcomes of arthroscopic foveal repair of the triangular fibrocartilage complex (TFCC) in patients with persistent symptomatic DRUJ instability after plate fixation for DRF. All consecutive patients who underwent plate fixation for DRF between January 2014 and December 2017 and were followed up for a minimum of 1 year were included in this retrospective study. DRUJ instability was evaluated by subjective ulnar wrist pain and physical examination that included foveal sign and ballottement testing every 2 months after surgery. In patients with persistent symptomatic DRUJ instability lasting >6 months, arthroscopic transosseous foveal repair was performed with consent. Clinical outcomes were evaluated at a minimum of 2 years after surgery. The Generalized Estimating Equation model was used to analyze the incidence rate trend of symptomatic DRUJ instability. Overall, 204 patients were included. The incidence of symptomatic DRUJ instability decreased gradually with time after fixation for DRF until 6 months and was maintained thereafter. Thirty-four of 204 patients (16.6%) had persistent symptomatic DRUJ instability. In multivariable analysis, only high-energy injury was an independent risk factor for persistent symptomatic DRUJ instability (P= .003; odds ratio= 3.599). Seventeen patients underwent arthroscopic foveal repair. The mean follow-up period thereafter was 28.6 months. All clinical outcomes improved significantly compared with preoperative values, and no patient had residual DRUJ instability. In patients who had persistent symptomatic DRUJ instability for >6 months after plate fixation for DRFs, arthroscopic foveal repair of the TFCC is considered as a treatment option. Arthroscopic foveal repair of the TFCC to stabilize the DRUJ provided satisfactory clinical and functional outcomes and decreased ulnar-side pain. Level IV, retrospective case series.

Quasiparticle band structure, exciton, and optical properties of few-layer blue phosphorus

The evolution of quasiparticle electronic structure, exciton, and optical properties in the few-layer blue phosphorus has been studied with the many-body perturbation method. The quasiparticle band gap decreases gradually with increasing the layer number and the system will finally evolve to metallic state in the bulk form. In spite of the increasing thickness in these indirect-band-gap semiconductors, the exciton-dominated optical properties with large binding energies are still found in the few-layer systems. With increasing layer number, the overall dielectric screening gets enhanced. However, the persistent large joint density of states associated with the parallel band structure in blue phosphorus gives rise to a much larger binding energy than the value predicted in an effective screening model. Our studies have not only provided a deep understanding of excitons in 2D semiconductors but also provided solid data for further experimental exploration of the application of few-layer blue phosphorus in optoelectronics.

A Comparison of the Risk of Fracture in Rheumatoid Arthritis Patients with and without Receiving Chinese Herbal Medicine.

ObjectivePatients with rheumatoid arthritis (RA) often suffer from bone complications due to persistent joint inflammation, especially incident fracture. Nowadays, Chinese herbal medicines (CHMs) have provided safe and effective therapy for treating skeletal conditions, but it is unclear whether CHMs can prevent fracture onset among RA individuals. This study aimed to determine the association between the use of CHMs and the risk of fracture among them.MethodsThis retrospective, population-based study retrieved administrative health data from the Taiwan National Health Insurance (NHI) database to identify patients with newly diagnosed RA between 2000 and 2009. Of the 6178 incident RA patients, 2495 matched pairs of CHMs users and non-CHMs users were identified by propensity score matching. Enrollees with hip fractures prior to RA onset were excluded. Included subjects were followed until the end of 2013. Incidence and adjusted hazard ratios (HR) of new-onset bone fracture in the multivariable Cox proportional hazard model were measured with 95% confidence interval (CI).ResultsFracture incidence was lower in CHMs users than in the comparison cohort (26.91 vs 32.94 per 1000 person-years, respectively), with an adjusted HR of 0.82 (95% CI: 0.73–0.92). Subjects receiving CHMs for more than 2 years had a much lower risk of fracture onset by more than 50%. Some CHMs prescriptions (Yan Hu Suo, Bei Mu, Da Huang, Dang Shen, Fu-Zi, Shu-Jing-Huo-Xue-Tang, Dang-Gui-Nian-Tong-Tang, Jia-Wei-Xiao-Yao-San, Gan-Lu-Yin, and Gui-Zhi-Shao-Yao-Zhi-Mu-Tang) were associated with reduced fracture risk.ConclusionAdding CHMs to routine treatment was found to be related to lower fracture risk in RA patients.

Abstract 13685: Combined Genetic Defects of Sitosterolemia and Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) is an inherited disorder caused by mutations in the genes in the LDL receptor pathway, including LDLR , PCSK9 , APOB, and ARH . Defective uptake of LDL by the liver increases plasma LDL-cholesterol (LDL-C) levels, leading to an increased risk of coronary heart disease. The differential diagnosis of FH includes sitosterolemia which is a rare autosomal recessive disorder caused by mutations in ABCG5 or ABCG8 . Case presentation: Here we present a rare case of sitosterolemia with a genetic diagnosis of FH. A 64-years-old woman, clinically diagnosed as FH with Achilles tendon thickness (>18 mm on X-ray imaging), had been taking statins only intermittently due to muscle pains. The combinatorial therapy with ezetimibe decreased her plasma LDL-C levels to around 90-250 mg/dL with variable adherence to statins and dietary management. Further addition of a PCSK9 inhibitor (evolocumab) was largely ineffective with plasma LDL-C levels of 90-190 mg/dL. A systemic medical evaluation revealed persistent joint pains of unknown etiology and slightly decreased platelet count. These clinical features led us to suspect sitosterolemia. Biochemical and genetic analyses: Plasma concentration of sitosterol was elevated (16.8 mg/dL). Genetic testing was performed after obtaining informed consent. All procedures were subjected to approval by the human genome, gene analysis research ethics committee of the University of Tokyo. In addition to a heterozygous missense mutation in LDLR (p.Arg115His), a homozygous nonsense mutation in ABCG5 (p.Tyr188Ter) was identified. No rare variants were found in PCSK9 nor ABCG8 . Conclusions: To our knowledge, this is the first case of a combined genetic defect of sitosterolemia and FH. Atypical clinical manifestations such as large fluctuations of LDL-C levels, unresponsiveness to a PCSK9 inhibitor, arthralgia, and a reduced platelet count led to the genetic diagnosis. Our case is informative in the perspective of precision medicine, highlighting the importance of systemic medical evaluation to select patients who will be benefited more from genetic testing as well as the necessity of future drug development for this rare and intractable disease.

Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis

Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have primarily been characterized in the RA synovial membrane. Here we aim to phenotypically and functionally characterize cultured synovial fluid-derived FLS (sfRA-FLS). Paired peripheral blood mononuclear cells (PBMC) and sfRA-FLS from patients with RA were obtained and monocultures of sfRA-FLS and autologous co-cultures of sfRA-FLS and PBMC were established. The in situ activated sfRA-FLS were CD34-, CD45-, Podoplanin+, Thymocyte differentiation antigen-1+. SfRA-FLS expressed uniform levels of NFкB-related pathway proteins and secreted several pro-inflammatory cytokines dominated by IL-6 and MCP-1. In a co-culture model with autologous PBMC, the ICAM-1 and HLA-DR expression on sfRA-FLS and secretion of IL-1β, IL-6, and MCP-1 increased. In vivo, human sfRA-FLS were cartilage invasive both at ipsilateral and contralateral implantation site. We conclude that, sfRA-FLS closely resemble the pathological sublining layer FLS subset in terms of surface protein expression, cytokine production and leukocyte cross-talk potential. Further, sfRA-FLS are comparable to tissue-derived FLS in their capabilities to invade cartilage at implantation sites but also spread tissue destruction to a distant site. Collectively, sfRA-FLS can serve as a an easy-to-obtain source of pathological sublining FLS in RA.

Association between clusters of back and joint pain with opioid use in middle-aged community-based women: a prospective cohort study

BackgroundTo determine the relationship between clusters of back pain and joint pain and prescription opioid dispensing.MethodsOf 11,221 middle-aged participants from the Australian Longitudinal Study of Women’s Health, clusters of back pain and joint pain from 2001 to 2013 were identified using group-based trajectory modelling. Prescription opioid dispensing from 2003 to 2015 was identified by linking the cohort to Pharmaceutical Benefit Scheme dispensing data. Multinomial logistic regression was used to examine the association between back pain and joint pain clusters and dispensing of prescription opioids. The proportion of opioids dispensed in the population attributable to back and join pain was calculated.ResultsOver 12 years, 68.5 and 72.0% women reported frequent or persistent back pain and joint pain, respectively. There were three clusters (‘none or infrequent’, ‘frequent’ and ‘persistent’) for both back pain and joint pain. Those in the persistent back pain cluster had a 6.33 (95%CI 4.38-9.16) times increased risk of having > 50 opioid prescriptions and those in persistent joint pain cluster had a 6.19 (95%CI 4.18-9.16) times increased risk of having > 50 opioid prescriptions. Frequent and persistent back and joint pain clusters together explained 41.7% (95%CI 34.9-47.8%) of prescription opioid dispensing. Women in the frequent and persistent back pain and joint pain clusters were less educated and reported more depression and physical inactivity.ConclusionBack pain and joint pain are major contributors to opioid prescription dispensing in community-based middle-aged women. Additional approaches to reduce opioid use, targeted at those with frequent and persistent back pain and joint pain, will be important in order to reduce the use of opioids and their consequent harm in this population.

Failure in rock with intersecting rough joints under uniaxial compression

Uniaxial compressive tests were performed on Y-jointed granite specimens to explore how intersecting rough joints affect the strength, failure mode, and precursory damage characteristics of the jointed rock mass. The mechanical properties, joint dip angles, and joint roughness of the specimens were measured prior to the tests, then the loading stress, surface displacement fields, acoustic emission (AE) signals, and failure modes were recorded during the loading process. As the uniaxial compressive strength (σc) of the specimens increased, three different failure modes appeared: shear failure along the persistent joint with rock wedge falling, compressive failure with rock wedge ejection, and overall crushing accompanied with rock fragment splashing, the σc thresholds of the three failure modes are about 50 MPa and 90 MPa, respectively. The deformability of the specimens weakened gradually as σc increased. AE events spread from the joint surface to the interior of the rock block until final failure. For specimens that failed in shear mode, multiple sudden stress drops along with sharp displacement increases occurred during the tests but no entire failure occurred. Other specimens tended to present one eventual unstable failure. When the peak shear strength of the non-persistent joint was higher than or near to that of the persistent joint, the σc of a given Y-jointed specimen was mainly determined by the persistent joint. Otherwise, it was simultaneously controlled by the two joints. Both the joint dip angle and joint roughness were found to significantly influence the σc of the specimens. Each stress drop was accompanied by significant AE signal variations, though the AE indicators are difficult to effectively utilize for early warning of specimen failure.

Trajectories of opioid consumption from day of surgery to 28 days postoperatively: a prospective cohort study in patients undergoing abdominal, joint, or spine surgery

IntroductionDescriptions of opioid use trajectories and their association with postsurgical pain and opioid consumption are limited. We hypothesized that trajectories of opioid consumption in the first 28 days following surgery...

Responses of patients with juvenile idiopathic arthritis to methotrexate: a genomic outlook

ABSTRACT Introduction : Juvenile idiopathic arthritis (JIA) is a chronic disease characterized by persistent joint inflammation. JIA is the most common pediatric chronic rheumatic disease and no curative therapy is currently available. Methotrexate (MTX) is an important treatment for JIA even though a high inter-individual variability in response is observed in patients. Among the factors of this variability, genetics and epigenetics might play an important role. Areas covered : This review summarizes the results of pharmacogenetic and pharmacoepigenetic studies regarding MTX response in JIA. Studies considering epigenetic factors in JIA patients are still very limited, therefore this review includes also studies performed in adult patients with rheumatoid arthritis. Moreover, the relevance of biomarkers measured in blood or urine of JIA patients in relation to MTX treatment is discussed. Expert opinion : Nowadays, even though many pharmacogenomics studies have been published, a specific genetic marker predictor of MTX efficacy or adverse events has not yet been identified. Encouraging results are available and great expectations rely on the study of epigenetics. Future studies are needed in order to identify genetic and epigenetic biomarkers that can be implemented in the clinical practice.

Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis.

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by inflammatory cell infiltration, leading to persistent synovitis and joint destruction. The pathogenesis of RA remains unclear. This study aims to explore the immune molecular mechanism of RA through bioinformatics analysis.MethodsFive microarray datasets and a high throughput sequencing dataset were downloaded. CIBERSORT algorithm was performed to evaluate immune cell infiltration in synovial tissues between RA and healthy control (HC). Wilcoxon test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the significantly different infiltrates of immune cells. Differentially expressed genes (DEGs) were screened by “Batch correction” and “RobustRankAggreg” methods. Functional correlation of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Candidate biomarkers were identified by cytoHubba of Cytoscape, and their diagnostic effectiveness was predicted by Receiver Operator Characteristic Curve (ROC) analysis. The association of the identified biomarkers with infiltrating immune cells was explored using Spearman’s rank correlation analysis in R software.ResultsTen significantly different types of immune cells between RA and HC were identified. A total of 202 DEGs were obtained by intersection of DEGs screened by two methods. The function of DEGs were significantly associated with immune cells. Five hub genes (CXCR4, CCL5, CD8A, CD247, and GZMA) were screened by R package “UpSet”. CCL5+CXCR4 and GZMA+CD8A were verified to have the capability to diagnose RA and early RA with the most excellent specificity and sensitivity, respectively. The correlation between immune cells and biomarkers showed that CCL5 was positively correlated with M1 macrophages, CXCR4 was positively correlated with memory activated CD4+ T cells and follicular helper T (Tfh) cells, and GZMA was positively correlated with Tfh cells.ConclusionsCCL5, CXCR4, GZMA, and CD8A can be used as diagnostic biomarker for RA. GZMA-Tfh cells, CCL5-M1 macrophages, and CXCR4- memory activated CD4+ T cells/Tfh cells may participate in the occurrence and development of RA, especially GZMA-Tfh cells for the early pathogenesis of RA.