The Genetic Basis Underpinning Sexually Selected Traits across Different Animal Lineages: Are There Genetic Mechanisms in Common?

Sexual selection involving female choice or female preference ('inter-sexual' selection) and/or male-male competition ('intra-sexual' selection) is one of the key mechanisms for evolutionary diversification and speciation. In particular, sexual selection is recently suggested to be an important mode to drive the evolution of the "novel" phenotype (i.e., "evolutionary novelty"). Despite extensive studies performed on sexually selected traits or male-specific ornaments (or weapon-like structures) with respect to their evolutionary origin, history and fitness benefits, relatively little is known about the molecular genetic mechanisms underlying their developmental process. However, with advances in genomic technologies (including whole transcriptome analysis using Next Generation Sequencing [NGS] techniques; RNA-Seq), progress has been made to unveil the genetic background underpinning diverse sexually selected traits in different animal taxa. In the present review, empirical data on the genes, genetic mechanisms, or regulatory pathways underlying various sexually selected traits were compiled to explore whether "common" genetic architectures shape the development and evolution of these traits across evolutionarily distant animal lineages. It is shown that the recruitment of the pre-existing genetic network for a new purpose (i.e., gene network "co-option") is rather widespread in the development and evolution of sexually selected traits, indicating that particular genes or gene sets are repeatedly involved in different sexually selected traits. Information on genes or genetic mechanisms regulating the development of sexually selected traits is an essential piece to complete a whole picture of the origin and evolution of sexually selected traits.

Elevated triglyceride levels are associated with increased risk for major adverse cardiovascular events in statin-naïve rheumatoid arthritis patients: A nationwide cohort study.

OBJECTIVES: To investigate the association between the four components of the lipid profile (total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) at baseline and composite major adverse cardiovascular events (MACEs) in statin-naïve rheumatoid arthritis (RA) patients with no previous history of cardiovascular events. METHODS: This nationwide population-based cohort study was performed on a total of 15,216 statin-naïve RA patients. The end point was a composite of clinical events, including myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death. We compared the incidence of and risk for clinical events according to each lipid variable. RESULTS: During follow-up (median 4.70 years), the incidence of MACE per 1000 person-years was 7.27. Among the four lipid components, only higher baseline TG levels were significantly associated with increased risk for composite MACE in RA subjects. The risk for composite MACE was significantly higher in the third (adjusted hazard ratio (HR), 1.35 [95% confidence interval (CI), 1.03-1.78]) and highest quartiles (adjusted HR, 1.74 [95%CI, 1.33-2.28]) of baseline TG level versus the lowest quartile. CONCLUSIONS: In statin-naïve RA patients, increased TG level is associated with increased risk for MACE. Therefore, screening and intervention for increased TG level may be clinically beneficial in this population.

Effects of light-emitting diode therapy on hand stiffness and pain in non-steroidal anti-inflammatory drug-refractory patients with tenosynovitis.

Objective: The objective of this study was to evaluate the safety and efficacy of light-emitting diode therapy (LEDT) in the management of pain and stiffness in patients with refractory hand tenosynovitis to non-steroidal anti-inflammatory drugs. Methods: A total of 12 patients were enrolled in the study and received LEDT twice a week for four weeks. Sociodemographic, clinical, and laboratory data were collected, and the visual analog scale (VAS) pain and stiffness scores of each hand were assessed every two weeks. The thickness of the flexor tendon in the patients' hand was evaluated using ultrasonography. To investigate the molecular effects of LEDT, we measured the expression levels of type III collagen in tendon cells, with and without LEDT treatment. Results: After undergoing LEDT, participants showed clinically significant improvements in VAS pain scores at weeks 2, 4, and 8 compared to their baseline, and in VAS stiffness scores at weeks 4 and 8. According to the ultrasonography results, there was a decreasing tendency in tendon thickness for each finger in week 8 compared to the baseline, but the difference was not statistically significant. No adverse events were reported. Additionally, our results indicated a significant increase in type III collagen levels in the LEDT group compared to the control group (1.48±0.18 vs. 0.99±0.02, p=0.031), indicating a potential molecular mechanism for the observed clinical improvements. Conclusion: LEDT may provide a viable alternative to pharmacological treatments in the future, due to its simple and easy method of administration.

CCL20 inhibition for treating inflammation in ankylosing spondylitis.

OBJECTIVES: Th17 cells are known to play a significant role in AS. C-C motif chemokine ligand 20 (CCL20) binds to C-C chemokine receptor 6 (CCR6) on Th17 cells, promoting their migration to inflammation sites. The aim of this research is to examine the effectiveness of CCL20 inhibition in treating inflammation in AS. METHODS: Mononuclear cells from peripheral blood (PBMC) and SF (SFMC) were collected from healthy individuals and AS. Flow cytometry was used to analyse cells producing inflammatory cytokines. CCL20 levels were determined using ELISA. The impact of CCL20 on Th17 cell migration was verified using a Trans-well migration assay. The in vivo efficacy of CCL20 inhibition was evaluated using an SKG mouse model. RESULTS: The presence of Th17 cells and CCL20 expressing cells was higher in SFMCs from AS patients compared with their PBMCs. The CCL20 level in AS SF was significantly higher than in OA patients. The percentage of Th17 cells in PBMCs from AS patients increased when exposed to CCL20, whereas the percentage of Th17 cells in SFMCs from AS patients decreased when treated with CCL20 inhibitor. The migration of Th17 cells was found to be influenced by CCL20, and this effect was counteracted by the CCL20 inhibitor. In the SKG mouse model, the use of CCL20 inhibitor significantly reduced joint inflammation. CONCLUSION: This research validates the critical role of CCL20 in AS and suggests that targeting CCL20 inhibition could serve as a novel therapeutic approach for AS treatment.

Subtherapeutic hydroxychloroquine concentration is associated with increased disease activity and greater organ damage in lupus.

OBJECTIVE: To investigate the effects of the serum hydroxychloroquine (HCQ) concentration on clinical manifestations, disease activity, and organ damage in a longitudinal cohort of systemic lupus erythematosus (SLE) patients. METHODS: The 338 SLE patients were assessed with respect to their demographic data, clinical and laboratory findings, PGA, adjusted mean SLEDAI-2000 (AMS), and SLICC damage index annually for 5 consecutive years. Patients were divided into two groups according to their serum HCQ concentration at baseline: subtherapeutic (< 500 ng/mL) and therapeutic groups (≥ 500 ng/mL). The impact of the HCQ concentration on the clinical outcomes was evaluated in a longitudinal analysis using a generalized estimating equation (GEE). RESULTS: Of the 338 patients, 287 (84.9%) were in the subtherapeutic group at baseline. This group had a higher incidence of newly developed lupus nephritis (LN) (P = 0.036) and had been prescribed higher mean and cumulative doses of prednisolone (P = 0.003 and P = 0.013, respectively) than the therapeutic group. In multivariable analyses based on GEE, the subtherapeutic group had a higher AMS score (ß = 1.398, 95% confidence interval [CI]: 0.607-2.189, P < 0.001), higher PGA score (ß = 0.328, 95% CI: 0.215-0.441, P < 0.001), and higher SDI score (ß = 0.366, 95% CI: 0.061-0.671, P = 0.019) across all 5 years. CONCLUSION: The subtherapeutic HCQ concentration was associated with the development of new-onset LN, and had significant associations with disease activity and cumulative organ damage in SLE patients over time.

Significance of co-positivity for anti-dsDNA, -nucleosome, and -histone antibodies in patients with lupus nephritis.

OBJECTIVE: The aim of this study was to define the clinical, histopathologic, and prognostic features associated with simultaneous positivity for anti-dsDNA, -nucleosome, and -histone antibodies (3-pos) in Korean patients with biopsy-proven lupus nephritis (LN). METHODS: The 102 patients included in the study had undergone kidney biopsy prior to the start of induction treatment, were treated with immunosuppressives, and followed-up for >12 months. RESULTS: In total, 44 (43.1%) of the 102 LN patients were 3-pos. Patients with 3-pos had a higher SLEDAI-2K score (p = .002), lower lymphocyte count (p = .004), and higher rates of proteinuria > 3.5 g/24 h (p = .039) and positivity for urinary sediments (p = .005) at the time of renal biopsy than non-3-pos patients. 3-pos patients had a more proliferative form of LN (p = .045) in the renal histopathologic findings, and as co-positivity gradually increased from 0 to 3, the total activity score in the renal biopsy findings increased significantly (p = .033). In addition, 3-pos patients had a more rapid eGFR decline than non-3-pos patients after a follow-up of 83.2 months (p = .016). CONCLUSIONS: Our findings suggest that 3-pos is related to severe LN and that 3-pos patients are more likely to experience a rapid decline of renal function than non-3-pos patients.KEY MESSAGEPatients with co-positivity for anti-dsDNA, -nucleosome, and -histone antibodies (3-pos) had higher disease activity and a worse renal histopathology than those without co-positivity.3-pos patients had a more rapid decline of renal function than non-3-pos patients.

Population genetic structure of a recent insect invasion: a gall midge, Asynapta groverae (Diptera: Cecidomyiidae) in South Korea since the first outbreak in 2008.

Outbreaks of Asynapta groverae, an invasive mycophagous gall midge, in South Korea have been repeatedly reported since the first occurrence in 2008. This species is a nuisance to residents owing to its mass emergence from newly built and furnished apartments. Here, the levels of genetic diversity, divergence, and structure of invasive A. groverae populations were investigated to understand their ability to survive in novel locations. Population genetic analyses were performed on seven invasive populations, including the first outbreak, sporadically emerged, and two laboratory-isolated (quarantined) populations, using the mitochondrial COI sequences and the ten novel microsatellite markers developed in this study. Non-indigenous A. groverae managed to maintain their populations for 12 years despite decreased genetic polymorphisms resulting from multiple incidences of founder effects by a small number of colonists. Additionally, the advantageous sustainability of A. groverae in the particle boards from which they emerge suggests that human-mediated dispersal is plausible, which may allow for the successful spread or invasion of A. groverae to new locations. This study is one of the few examples to demonstrate that an insect species successfully invaded new regions despite exhibiting decreased genetic diversity that was maintained for a decade. These findings indicate that the high genetic diversity of the initial founding population and asexual reproduction would contribute to the successful invasion of A. groverae in novel environments.

Analysis of Single-Cell Transcriptome and Surface Protein Expression in Ankylosing Spondylitis Identifies OX40-Positive and Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Positive Pathogenic Th17 Cells.

OBJECTIVE: To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single-cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells. METHODS: This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single-cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid-induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan-injected SKG mice in which anti-GITR ligand and/or anti-OX40 ligand were used. RESULTS: We identified pathogenic Th17 cells as polyfunctional interleukin-17A (IL-17A)- and interferon-γ (IFNγ)-producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan-injected SKG mouse model. CONCLUSION: Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.

Polyarteritis nodosa presenting as leg pain with resolution of positron emission tomography-images: A case report.

BACKGROUND: Although fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is widely used for diagnosis and follow-up of large sized vessel vasculitis, it is still not widely used for small to medium sized vessel vasculitis. CASE SUMMARY: This is the case of a 68-year-old male who presented at the emergency department complaining of fever, myalgia, and bilateral leg pain of over two weeks duration, with elevated levels of C-reactive protein. He was subsequently admitted and despite the absence of clinically significant findings, the patient continued to exhibit recurrent fever. A fever of unknown origin workup, which included imaging studies using FDG-PET/CT, revealed vasculitis involving small to medium-sized vessels of both lower extremities, demonstrated by linear hypermetabolism throughout the leg muscles. The patient was treated with methylprednisolone and methotrexate after diagnosis leading to the gradual resolution of the patient's symptoms. Three weeks later, a follow-up FDG-PET/CT was performed. Previously hypermetabolic vessels were markedly improved. CONCLUSION: Our case report demonstrated that FDG-PET/CT has tremendous potential to detect medium-sized vessel inflammation; it can also play a crucial role in prognosticating outcomes and monitoring therapeutic efficacy.

THE INITIAL ION SHIFT INDEX AS A PROGNOSTIC INDICATOR TO PREDICT PATIENT SURVIVAL IN TRAUMATIC DAMAGE CONTROL LAPAROTOMY PATIENTS.

ABSTRACT: Objective: The ion shift index (ISI), which considers extracellular fluid ions such as phosphate, calcium, and magnesium, represents the ion shift following ischemia; concentrations of these ions are maintained within narrow normal ranges by adenosine triphosphate-dependent homeostasis. The ISI is defined as follows: {potassium (mmol/L-1) + phosphate (mmol/L-1) + Mg (mmol/L-1)}/calcium (mmol/L-1). This study investigated the possibility of predicting the 30-day survival rate of patients who underwent traumatic damage control laparotomy by comparing ISI and other laboratory findings, as well as the initial Trauma and Injury Severity Score (TRISS) and shock indices. Methods: Among the 134 patients who underwent damage control surgery between November 2012 and December 2021, 115 patients were enrolled in this study. Data regarding injury mechanism, age, sex, laboratory findings, vital signs, Glasgow Coma Scale score, Injury Severity Score, Abbreviated Injury Scale score, blood component transfusion, type of surgery, postoperative laboratory outcomes, morbidity, mortality rates, fluids administered, and volume of transfusions were collected and analyzed. Results: In univariate analysis, the odds ratio of the initial ISI was 2.875 (95% confidence interval, 1.52-5.43; P = 0.04), which showed a higher correlation with mortality compared with other indices. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were derived from different multivariable logistic regression models. The initial ISI had high sensitivity and specificity in predicting patient mortality (AUC, 0.7378). In addition, in the model combining the initial ISI, crystalloids, and TRISS, the AUC showed a high value (AUC, 0.8227). Conclusion: The ISI evaluated using electrolytes immediately after admission in patients undergoing traumatic damage control surgery may be a predictor of patient mortality.

Folate deficiency is associated with increased radiographic severity of osteoarthritis in knee joints but not in hand joints.

OBJECTIVES: No previous studies have explored the effect of folate deficiency on the severity of osteoarthritis (OA). Therefore, we investigated the relationship between folate level and features on knee and hand radiographs in a large, population-based OA cohort. METHODS: Among 9,260 subjects enrolled in the Dong-gu study, 2,489 who had knee and hand joint radiographs were included. Of these, subjects with a history of amputation or total knee replacement were excluded. Serum folate levels were measured using blood samples collected at the time of enrolment and stored. A semi-quantitative system was used to grade the severity of hand and knee x-ray changes. Linear regression was performed to assess relationships between serum folate levels and knee and hand radiographic scores after adjusting for age, sex, body mass index, smoking, alcohol consumption, education, physical activity, occupation, vitamin D, and ferritin. RESULTS: A total of 2,322 subjects were recruited. After adjusting for confounders, participants with folate deficiency (<4 ng/mL) had higher total (p<0.001), osteophyte (p<0.001), joint space narrowing (p=0.002), tibial attrition (p<0.001), and sclerosis (p=0.005) scores for knee joint radiographs compared to participants with a normal folate level. After adjusting for confounders, the radiographic scores for hand joints did not differ between the groups. CONCLUSIONS: Folate deficiency is associated with increased radiographic severity of OA in knee joints, but not in hand joints. Further studies are needed to explore the differential effects of folate on the severity of knee and hand OA.

Invasion Pattern of Aedes aegypti in the Native Range of Ae. albopictus in Vietnam Revealed by Biogeographic and Population Genetic Analysis.

Since its introduction to Asia, Aedes aegypti has coexisted with the native species Ae. albopictus and has been reported to transmit several infectious diseases. However, the development of efficient disease prevention and vector control is hindered by the relatively poor understanding of the biogeography and the genetic diversity of Ae. aegypti in the region. This study aimed to determine the invasion patterns of Ae. aegypti by evaluating the distribution and abundance of Ae. aegypti and Ae. albopictus in different climatic regions (northern temperate and southern tropical regions) and habitats (domestic, peri-domestic, and natural). We further analyzed the genetic diversity and phylogenetic relationships of Ae. aegypti populations in Vietnam using mitochondrial COI gene sequences. Both Aedes species were observed at most of the study sites, but only Ae. albopictus thrived in northern mountainous areas. In sympatric ranges, the individual abundance of the species was influenced by regional climate and habitats. The tropical climate and availability of domestic containers facilitated the dominance of Ae. aegypti, whereas temperate climates and natural breeding sites facilitated that of Ae. albopictus. In addition, many genetic polymorphisms were detected in the Ae. aegypti populations, which formed two distinct genetic groups; however, this genetic diversity is unlikely to be relevant to the invasive success of Ae. aegypti. These findings provide insights into the mechanisms and patterns of Ae. Aegypti invasion, which depend on the climate and reproductive strategies in the native range of Ae. albopictus in Asia.

Low genetic diversity, local-scale structure, and distinct genetic integrity of Korean chum salmon (Oncorhynchus keta) at the species range margin suggest a priority for conservation efforts.

Chum salmon (Oncorhynchus keta) is an ecologically and economically important species widely distributed across the North Pacific Ocean. However, the population size of this fishery resource has declined globally. Identifying genetic integrity, diversity and structure, and phylogenetic relationships of wild populations of O. keta over an entire species' range is central for developing its effective conservation and management plans. Nevertheless, chum salmon from the Korean Peninsula, which are comprised of its southwestern range margins, have been overlooked. By using mtDNA control region and 10 microsatellite loci, we here assessed the genetic diversity and structure for 16 populations, including 10 wild and six hatchery populations, encompassing the species entire geographic range in South Korea. The analyses showed that genetic diversity is significantly higher for wild than for hatchery populations. Both marker sets revealed significant genetic differentiation between some local populations. Comparisons of six wild and their respective hatchery populations indicated that allele/haplotype frequencies considerably differ, perhaps due to a strong founder effect and/or homogenizing of hatchery populations for stocking practice. Despite its single admixed gene pool for the Korean chum salmon, some local populations housing their own unique lineages should be accorded with a high priority to safeguard their genetic integrities. The results of our comparative analyses of the Korean population with other North Pacific chum salmons (inhabiting regions of Japan, Russia, and North America) revealed a lower diversity but higher contribution to the overall species-level genetic diversity, and also its unique genetic integrity. These findings advocate for the evolutionary significance of the Korean population for species-level conservation.

DNA Barcoding of Chironomid Larvae (Diptera: Chironomidae) from Large Rivers in South Korea to Facilitate Freshwater Biomonitoring and Public Health Surveillance.

Chironomid larvae are among the dominant benthic macroinvertebrates in all types of water systems in South Korea. They may pass through pipes in rivers (raw water) and occur in drinking water, thus creating public health issues. However, little is known about the larval stages of chironomids in large South Korean rivers. Therefore, we examined larval-adult associations in chironomids inhabiting major rivers used as water sources. The larvae were collected in 2015 and 2016 from nine locations along the four largest rivers in South Korea using a Ponar grab. Cytochrome oxidase subunit I (COI) sequences were generated from the larval specimens, and the species were identified by comparing these sequences to those in a newly constructed DNA barcode library of Chironomidae in South Korea. The samples from the four rivers yielded 61 mitochondrial COI sequences belonging to 18 species, including Hydrobaenus kondoi Saether, 1989, which was reported for the first time in the Korean Peninsula. Further, morphological identification of the larvae was conducted, and a pictorial taxonomic key to Chironomidae species in large rivers in South Korea was developed to facilitate freshwater biomonitoring research. Finally, an action flow chart was created for the rapid identification of chironomid larvae in infested drinking water or water purification facilities.

Antiphospholipid syndrome with renal and splenic infarction after blunt trauma: A case report.

BACKGROUND: In trauma patients, bleeding is an immediate major concern. At the same time, there are few cases of acute vascular occlusion after blunt trauma, and it is unclear what assessment and diagnosis should be considered for these cases. Herein, we describe a patient diagnosed with antiphospholipid syndrome after a hypercoagulable workup for acute renal and splenic vascular occlusion due to blunt trauma. CASE SUMMARY: A 20-year-old man was admitted to the emergency department with abdominal pain after hitting a tree while riding a sled 10 h ago. He had no medical history. Radiological investigations revealed occlusion of the left renal artery with global infarction of the left kidney and occlusion of branches of the splenic artery with infarction of the central portion of the spleen. Attempted revascularization of the left renal artery occlusion through percutaneous transluminal angioplasty failed due to difficulty in passing the wire through the total occlusion. Considering the presence of acute multivascular occlusions in a young man with low cardiovascular risk, additional laboratory tests were performed to evaluate hypercoagulability. The results suggested a high possibility of antiphospholipid syndrome. Treatment with a subcutaneous injection of enoxaparin was started and changed to oral warfarin after two weeks. The diagnosis was confirmed, and he continued to visit the rheumatology outpatient clinic while taking warfarin. CONCLUSION: A hypercoagulable workup can be considered in trauma patients with acute multivascular occlusion, especially in young patients with low cardiovascular risk.

Diversity and DNA Barcode Analysis of Chironomids (Diptera: Chironomidae) from Large Rivers in South Korea.

Most large rivers in South Korea run through major cities, which often experience many environmental problems, including outbreaks of non-biting midges (Diptera: Chironomidae). However, chironomid species inhabiting large rivers have not been thoroughly investigated. We aimed to identify chironomid species collected from the four main large rivers in South Korea, construct a corresponding DNA barcode library, and examine the distribution and community structure of the identified riverine species. Adult chironomids were collected from nine sites along the rivers by using sweep nets and light traps during June and August 2015. Adults were morphologically identified, and COI nucleotide sequences were generated to verify the species identification and construct a DNA barcode library. The distribution and community structure of the identified species were also analyzed. A total of 124 COI sequences were established from 37 species belonging to 19 genera, and the resulting DNA barcode library effectively discriminated >90% of riverine Chironomidae in South Korea. Ten species, which are considered indicator species for large rivers, were collected from all four rivers. In addition, members of the subfamily Chironominae were collected more frequently than members of other subfamilies, with Tanytarsus tamagotoi being the most common and widespread chironomid species in South Korea. The DNA barcode library developed in this study will facilitate environmental studies of large rivers, such as biomonitoring chironomid larvae.

Comparison of the efficacy and risk of discontinuation between non-TNF-targeted treatment and a second TNF inhibitor in patients with rheumatoid arthritis after first TNF inhibitor failure.

Objectives: Despite improved care for rheumatoid arthritis (RA) patients, many still experience treatment failure with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs [tsDMARDs; typically Janus kinase inhibitors (JAKi)], and eventually switch to other agents. We compared the efficacy of a second tumor necrosis factor inhibitor (TNFi) and non-TNF-targeted treatment as the second-line treatment in patients showing an insufficient response to the first TNFi. Methods: Patients were included if they had received at least one prescription for a TNFi, and at least one follow-up prescription for a second TNFi or non-TNF-targeted treatment after discontinuation of the first drug. In total, 209 patients were analyzed, including 69 with a second TNFi and 140 with a non-TNF-targeted treatment (106 non-TNFi biologics and 34 JAKi). Cox regression was used to estimate the hazard ratio (HR) for discontinuation. Results: The mean follow-up period after switching was 28.0 (range: 0-80) months and 24.4% of the 209 patients switched or discontinued the second drug. In multivariate Cox proportional hazard analysis, the non-TNF-targeted treatment group had a lower likelihood of discontinuing their treatment than the second TNFi group [HR = 0.326, 95% confidence interval (CI): 0.170-0.626, p = 0.001]. When analyzed separately, the risk of discontinuation was significantly lower in both the non-TNFi biologic (HR = 0.318, 95% CI: 0.160-0.633, p = 0.001) and JAKi (HR = 0.356, 95% CI: 0.129-0.980, p = 0.046) groups than in the second TNFi group. Conclusion: Our study supported switching to a non-TNF-targeted treatment instead of TNF cycling in patients with RA showing an inadequate response to initial TNFi.

Non-adherence to methotrexate was associated with high disease activity and poor health-related outcomes during a 4-year follow-up of rheumatoid arthritis patients.

OBJECTIVES: Although methotrexate (MTX) is the first-line drug for management of rheumatoid arthritis (RA), non-adherence to MTX is highly prevalent and under-recognised. Here, we investigated adherence to MTX and its impact on clinical outcomes during follow-up in patients with RA. METHODS: In total, 367 RA patients were included in this study, with patient visits conducted annually for 4 consecutive years. Adherence was defined by the medication possession ratio during the follow-up period. We divided the patients into two groups; patients who took ≥80% of their prescribed MTX doses and those who did not. In a prospective cohort, the generalised estimating equations were used to identify longitudinal associations between drug adherence and clinical outcomes including disease activity, physical function, and quality of life. RESULTS: Of the 367 RA patients, 8.7% were found to have taken MTX <80% during the period of follow up. After adjustment for confounders, non-adherence to MTX was significantly associated with higher DAS28-ESR during the follow-up period (coefficient ß=0.989, 95%; CI: 0.603-1.375; p<0.001). In addition, non-adherence to MTX was a significant predictor of RAPID3 (coefficient ß=1.847; 95% CI: 0.221-3.472; p=0.026) and EQ-5D (coefficient ß= -0.051; 95% CI: -0.090-0.012; p=0.010) after adjustment for confounding factors. CONCLUSIONS: Non-adherence to MTX was significantly associated with worse clinical outcomes, as evidenced by higher disease activity, poorer physical function, and lower health-related quality of life during a 4-year follow-up of RA patients.

Disentangling Diagnosis and Management of Fibromyalgia.

Fibromyalgia (FM) is a chronic pain condition characterized by widespread pain accompanied by symptoms such as fatigue, sleep disturbance, cognitive dysfunction, and mood disorder. The pathophysiology of FM has been unclear, leading to inconsistent diagnosis and ineffective management. Several diagnostic criteria for FM have been proposed in recent years, including the revised 2016 American College of Rheumatology (ACR) criteria, the criteria of the ACTTION-American Pain Society Pain Taxonomy (AAPT) group, and the modified 2019 Fibromyalgia Assessment Status (FAS) criteria. Despite the appearance of newer criteria for FM diagnosis, the 2016 ACR criteria demonstrate the best performance. Many randomized controlled studies and systematic reviews have shown the therapeutic efficacies of pharmacological and non-pharmacological treatments of FM. Nevertheless, further research is needed to develop better treatment options.