Ameliorative effects of Wikstroemia trichotoma 95% EtOH extract on a mouse model of DNCB-induced atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD). AIM OF THE STUDY: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA). MATERIALS AND METHODS: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured. RESULTS: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited ß-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-ß-apiofuranosyl (1 â†’ 6)-ß-glucopyranoside. CONCLUSIONS: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.

Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review.

BACKGROUND: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage. METHODS: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method. RESULTS: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias. CONCLUSIONS: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Cutaneous Calcified Mass of Foot in Pseudohypoparathyoidism: Case Report.

Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause to suggesting an underlying systemic condition. Because calcifications like these can arise from various causes, an accurate differential diagnosis is crucial. Differential diagnosis entails a methodical assessment of the patient, encompassing clinical presentation, medical history, radiological and pathological findings, and other pertinent factors. Through scrutiny of the patient's medical and trauma history, we can refine potential causes of calcification to vascular, metabolic, autoimmune, neoplastic, or traumatic origins. Furthermore, routine laboratory assessments, including serum levels of calcium, phosphorus, ionized calcium, vitamin D metabolites, and parathyroid hormone (PTH), aid in identifying metabolic etiologies. We describe a rare occurrence of osteoma cutis in a 15-year-old female patient with a history of pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). The patient presented with a painful mass on the lateral side of her left foot. The diagnosis was based on medical history, laboratory tests, and imaging, leading to an excisional biopsy and complete pain relief post-surgery. Understanding such rare occurrences and related conditions is crucial for accurate diagnosis and management.

RORα-GABP-TFAM axis alleviates myosteatosis with fatty atrophy through reinforcement of mitochondrial capacity.

BACKGROUND: Fat infiltration in muscle, called 'myosteatosis', precedes muscle atrophy, which subsequently results in sarcopenia. Myosteatosis is frequently observed in patients with nonalcoholic fatty liver disease (NAFLD). We have previously reported that retinoic acid receptor-related orphan receptor-α (RORα) regulates mitochondrial dynamics and mitophagy in hepatocytes, resulting in an alleviation of NAFLD. In this study, we aimed to investigate the role of RORα in skeletal muscle and to understand molecular mechanisms by which RORα controls mitochondrial capacity, using an NAFLD-associated myosteatosis mouse model. METHODS: To establish a myosteatosis model, 7-week-old C57BL/6N mice were fed with high-fat diet (HFD). After 15 weeks of diet feeding, an adeno-associated virus vector encoding RORα (AAV-RORα) was injected to gastrocnemius (GA) muscles, or after 7 weeks of HFD feeding, JC1-40, an RORα agonistic ligand, was administered daily at a dose of 5 mg/kg/day by oral gavage for 5 weeks. Histological, biochemical and molecular analyses in various in vivo and in vitro experiments were performed. RESULTS: First, the number of oxidative MyHC2a fibres with intensive lipid infiltration increased by 3.8-fold in the red region of the GA of mice with myosteatosis (P < 0.001). RORα was expressed around MyHC2a fibres, and its level increased by 2.7-fold after HFD feeding (P < 0.01). Second, treatment of RORα ligands in C2C12 myoblasts, such as cholesterol sulfate and JC1-40, enhanced the number of oxidative fibres stained for MyHC1 and MyHC2a by two-fold to four-fold (P < 0.01), while it reduced the lipid levels in MyHC2a fibres by 20-50% (P < 0.001) in the presence of palmitic acids. Third, mitochondrial membrane potential (P < 0.01) and total area of mitochondria (P < 0.01) were enhanced by treatment of these ligands. Chromatin immunoprecipitation analysis showed that RORα bound the promoter of GA-binding protein α subunit gene that led to activation of mitochondrial transcription factor A (TFAM) in C2C12 myoblasts (P < 0.05). Finally, intramuscular transduction of AAV-RORα alleviated the HFD-induced myosteatosis with fatty atrophy; lipid contents in MyHC2a fibres decreased by 48% (P < 0.001), whereas the number of MyHC2b fibre increased by 22% (P < 0.001). Also, administration of JC1-40 improved the signs of myosteatosis in that it decreased the level of adipose differentiation-related protein (P < 0.01) but increased mitochondrial proteins such as cytochrome c oxidase 4 and TFAM in GA muscle (P < 0.01). CONCLUSIONS: RORα plays a versatile role in regulating the quantity of mitochondria and the oxidative capacity, ultimately leading to an improvement in myosteatosis symptoms.

The Clinical Outcomes of Syndesmotic Flexible Fixation for Syndesmotic Injury With Ankle Fracture.

BACKGROUND: We evaluated whether the quality of syndesmotic reduction affects the short-term clinical outcomes of flexible fixation in patients with a rotational ankle fracture. METHODS: This study included 59 patients (32 men and 27 women) who underwent syndesmotic flexible fixation. The degree of syndesmotic reduction was evaluated on computed tomography (CT) images acquired within 3 days after surgery. We measured the divergence between anterior and posterior incisura at 1 cm above the distal tibial articular joint, then evaluated the degree of fibular rotation relative to the tibia. At 1 year after surgery, an objective clinical evaluation was performed using the American Orthopaedic Foot & Ankle Society (AOFAS) score, the visual analog scale (VAS), and the Foot and Ankle Outcome Score (FAOS). Additionally, repeat arthroscopy was performed during routine implant removal at nearly 1 year postoperatively. RESULTS: Among 59 patients who underwent syndesmotic flexible fixation, 56 patients had syndesmotic stability on repeat arthroscopy. At 1 year postoperation, AOFAS, VAS, and FAOS scores were, respectively, 90, 2.0, and 94 in the accurate reduction group (n = 24) and 90, 1.0, and 94.5 in the malreduction group (n = 35). CONCLUSION: Reduction quality after syndesmotic injury with flexible fixation, as determined by early postoperative CT imaging, did not affect patient prognosis. In this cohort, syndesmotic reduction and flexible fixation may produce good clinical outcomes in patients with syndesmotic injury and ankle fracture. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Nailfold capillaroscopy findings of interstitial pneumonia with autoimmune features.

BACKGROUND/AIMS: We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP). METHODS: Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (scleroderma/non-scleroderma patterns) were determined. RESULTS: A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern. CONCLUSION: NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.

Effect of music on colonoscopy performance: A propensity score-matched analysis.

BACKGROUND: Music has been used to reduce stress and improve task performance during medical therapy. AIM: To assess the effects of music on colonoscopy performance outcomes. METHODS: We retrospectively reviewed patients who underwent colonoscopy performed by four endoscopists with popular music. Colonoscopy performance outcomes, such as insertion time, adenoma detection rate (ADR), and polyp detection rate (PDR), were compared between the music and non-music groups. To reduce selection bias, propensity score matching was used. RESULTS: After one-to-one propensity score matching, 169 colonoscopies were selected from each group. No significant differences in insertion time (4.97 vs 5.17 min, P = 0.795) and ADR (39.1% vs 46.2%, P = 0.226) were found between the two groups. Subgroup analysis showed that the insertion time (3.6 vs 3.8 min, P = 0.852) and ADR (51.1% vs 44.7%, P = 0.488) did not significantly differ between the two groups in experts. However, in trainees, PDR (46.9% vs 66.7%, P = 0.016) and ADR (25.9% vs 47.6%, P = 0.006) were significantly lower in the music than in the non-music group. CONCLUSION: The current study found that listening to music during colonoscopy did not affect procedure performance. Moreover, it suggested that music may distract trainees from appropriately detecting adenomas and polyps.

Risk of cancer, cardiovascular disease, thromboembolism, and mortality in patients with rheumatoid arthritis receiving Janus kinase inhibitors: a real-world retrospective observational study using Korean health insurance data.

OBJECTIVES: This study investigated whether Janus kinase inhibitors (JAKis) raise the risk of cardiovascular disease (CVD), venous thromboembolism (VTE), and cancer in patients with rheumatoid arthritis (RA). METHODS: We conducted a real-world retrospective observational study using data obtained from the Korean National Health Insurance Service database. Two data sets were analyzed: tumor necrosis factor inhibitor (TNFi)/JAKi-naive RA patients (set 1) and all RA patients who used TNFis or JAKis (set 2). The incidence rate ratios (IRRs) and hazard ratios (HRs) for acute myocardial infarction (AMI), stroke, cardiovascular (CV)-related mortality, major adverse cardiovascular events (MACE), VTE, arterial thromboembolism (ATE), cancer, and all-cause mortality were compared between the JAKi and TNFi groups. RESULTS: Set 1 included 1,596 RA patients (JAKi group: 645; TNFi group: 951), and set 2 included 11,765 RA patients (JAKi group: 2,498; TNFi group: 9,267). No adverse events (AEs) showed significantly higher IRRs in the JAKi groups than in the TNFi groups of sets 1 and 2. The HRs for MACE in the JAKi groups of sets 1 and 2 were 0.59 (95% confidence [CI], 0.35 to 0.99) and 0.80 (95% CI, 0.67 to 0.97), respectively. The JAKi group of set 2 showed a significantly higher risk of all-cause mortality (HR, 1.71; 95% CI, 1.32 to 2.20), but the other AEs did not demonstrate increased risks in the JAKi groups. CONCLUSIONS: In this study, JAKis did not increase the risk of AMI, stroke, CV-related mortality, MACE, VTE, ATE, or cancer in Korean RA patients relative to TNFis.

Clinical outcomes and risk factors associated with poor prognosis after endoscopic resection of 10-20 mm rectal neuroendocrine tumors: a multicenter, retrospective study of 10-year experience.

BACKGROUND: The efficacy of endoscopic resection for of 10-20 mm rectal neuroendocrine tumor (NET) remains controversial. We aimed to evaluate the clinical outcomes and risk factors associated with poor prognosis after endoscopic resection of 10-20 mm rectal NET and to determine the optimal treatment. METHODS: Patients who underwent endoscopic resection for rectal NET in four tertiary hospitals were enrolled, and data on with the clinical outcomes and risk factors related to poor prognosis were retrospectively analyzed. RESULTS: A total of 105 patients who underwent endoscopic submucosal resection (ESD; n = 65, 61.9%), modified endoscopic mucosal resection (mEMR; n = 31, 29.5%), and conventional EMR (cEMR; n = 9, 8.6%) were enrolled. The mean follow-up period was 41.2 ± 21.9 months. In the morphologic findings, the mean diameter was 11.6 mm (range 10-19); the shape was sessile (50.5%) and mixed type (49.5%), and surface depression was observed in 41.9% of patients. In the histologic findings, 87.6% of patients had G1 and 12.4% G2 tumor grade, and 3.8% of patients had lymphovascular invasion. The overall en bloc and histologically complete (R0) resections were 99.1% and 76.2%, respectively. cEMR was a less-frequently developed R0 resection. In the univariate and multivariate analyses for R0 resection, only surface depression was significantly associated. Regional or distant organs metastasis during follow-up developed in three patients (2.9%) and was significantly associated with female sex, redness, G2 tumor grade, and non-ESD methods. CONCLUSION: Patients who underwent endoscopic resection of 10-20 mm rectal NET had good prognosis; therefore, endoscopic resection can be considered as the first-line treatment, particularly for 10-14 mm rectal NET. However, the risk factors, such as female sex, redness, G2 tumor grade and non-ESD methods, were associated with regional or distant metastases during follow-up. Therefore, patients with these risk factors should be carefully monitored.

Clinical efficacy of alternative TNF inhibitor and secukinumab between primary non-responder and secondary non-responder of prior TNF inhibitor in ankylosing spondylitis.

OBJECTIVES: To compare the drug retention times and clinical efficacy of alternative tumour necrosis factor inhibitors (TNFi) and secukinumab in primary and secondary non-responders with ankylosing spondylitis (AS). METHODS: AS patients treated with biologics and enrolled in the Korean College of Rheumatology Biologics registry were examined. Patients who did not respond to previous TNFi treatment were defined as primary and secondary non-responders. Data regarding drug discontinuation and clinical efficacy were collected after 1 year. Kaplan-Meier and Cox regression analyses were performed to compare drug survival and associated factors. Logistic regression analyses were conducted to compare the clinical efficacy secukinumab with that of alternative TNFi. RESULTS: In total, 124 patients (83 receiving alternative TNFi and 41 receiving secukinumab) had biologic changes due to clinical inefficacy. Drug retention rates in the alternative TNFi and secukinumab groups were similar (P = 0.096). However, subgroup analyses including only secondary non-responders revealed that secukinumab users showed a higher hazard ratio (HR) for drug discontinuation (HR = 3.77, P = 0.045). In addition, secukinumab was negatively associated with achieving BASDAI50 or a major improvement in the ASDAS. CONCLUSION: Alternative TNFi showed better drug retention and clinical efficacy in AS patients experiencing previous TNFi failure, in secondary non-responders. Therefore, alternative TNFi may be a more suitable treatment for secondary non-responders.

Gastric wall abscess after endoscopic submucosal dissection.

Gastric wall abscess, a localized form of phlegmonous gastritis, is a rare complication of endoscopic resection. We report the first case of gastric wall abscess developing after endoscopic submucosal dissection in Korea. A 72-year-old woman visited our clinic to receive treatment for gastric adenoma. The patient successfully underwent endoscopic submucosal dissection with no complications. The final diagnosis was well-differentiated tubular adenocarcinoma. We performed follow-up endoscopy 10 weeks later and found a large subepithelial lesion on the posterior wall of the gastric antrum. Abdominal computed tomography revealed hypodense wall thickening and a 5 cm heterogenous multilobular mass in the submucosal layer of the gastric antrum. Submucosal invasion with mucin-producing adenocarcinomas could therefore not be excluded. The patient agreed to undergo additional gastrectomy due to the possibility of a highly malignant lesion. The final diagnosis was acute suppurative inflammation with the formation of multiple abscesses in the mural layers and omentum. The patient was discharged with no complications.

Therapeutic Utility and Adverse Effects of Biologic Disease-Modifying Anti-Rheumatic Drugs in Inflammatory Arthritis.

Targeting specific pathologic pro-inflammatory cytokines or related molecules leads to excellent therapeutic effects in inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Most of these agents, known as biologic disease-modifying anti-rheumatic drugs (bDMARDs), are produced in live cell lines and are usually monoclonal antibodies. Several types of monoclonal antibodies target different pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-17A, IL-6, and IL-23/12. Some bDMARDs, such as rituximab and abatacept, target specific cell-surface molecules to control the inflammatory response. The therapeutic effects of these bDMARDs differ in different forms of inflammatory arthritis and are associated with different adverse events. In this article, we summarize the therapeutic utility and adverse effects of bDMARDs and suggest future research directions for developing bDMARDs.

Baseline bony erosions and time-averaged DAS28 predict discontinuation of TNF inhibitors in rheumatoid arthritis.

The present study evaluated the predictive role of baseline radiographic change and disease activity on drug retention and clinical response in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitor (TNFi). Korean Observational Study Network for Arthritis (KORONA) registry was evaluated to identify RA patients treated with a TNFi. Disease activity score-28 (DAS28) was evaluated at baseline and 1 year after TNFi initiation or at termination of TNFi due to inefficacy (within 1 year). The retention rate of TNFi was compared in patients with and without bony erosions. The hazard ratio (HR) for drug retention was evaluated by Cox regression analysis, as was the odds ratio (OR) for achieving remission (DAS28 < 2.6). This study included 109 RA patients, including 97 (89%) women and 30 (27.5%) with erosions, who were treated with a TNFi. Higher baseline DAS28 was negatively associated with achievement of remission (OR = 0.56, 95% CI 0.35-0.88). The TNFi retention rate was significantly lower in RA patients with than in those without erosions (p = 0.04). Factors significantly associated with drug discontinuation included the presence of erosions (HR = 2.45, 95% CI 1.08-5.51) and higher time-averaged DAS28 (HR = 2.17, 95% CI 1.47-3.20), whereas concomitant methotrexate was associated with lack of drug discontinuation (HR = 0.40, 95% CI 0.17-0.95). The presence of erosions and high time-averaged disease activity could predict poor retention of TNFi by RA patients. Higher baseline DAS28 was associated with a reduced clinical response in patients with RA.Trial registration Clinical Research Information Service of South Korea https://cris.nih.go.kr : KCT0000086, registered May 26, 2009.

Gastric CD56-negative Extranodal Natural Killer/T-cell Lymphoma: A Case Report.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL-NT) is the most common subtype of Epstein-Barr virus-associated NK/T-cell lymphomas. ENKTCL-NT occurs infrequently in the gastrointestinal tract. In particular, reports of ENKTCL-on NT arising from the stomach are extremely rare. Several clusters of differentiation (CDs) have been useful in recognizing NK-cells, T-cells, and tumor cells of NK/T-cell lymphomas. Among them, the CD56 antigen is considered the most sensitive marker for ENKTCL-NT and is expressed in almost all cases of ENKTCL-NT. Thus, the development of CD56-negative ENKTCL-NT is highly atypical. This paper reports a case of a young Asian female who presented with gastric ulcer bleeding. The patient was histologically diagnosed with ENKTCL-NT. No tumor cells for CD56 were observed, whereas no monoclonality of the T-cell receptor gamma gene rearrangement was detected in the tumor cells. The patient was scheduled for systemic chemotherapy six times and achieved complete remission. Peripheral blood-hematopoietic stem cell transplantation was performed later.

DJ-1 controls T cell differentiation and osteoclastogenesis in rheumatoid arthritis.

Herein, we investigated the effect of DJ-1 on helper T cell differentiation, fibroblast-like synoviocyte (FLS) activation, and osteoclastogenesis in rheumatoid arthritis (RA). Serum and synovial fluid (SF) of RA and osteoarthritis (OA) patients were collected, and DJ-1 and H2O2 levels were investigated. CD4+ cells from peripheral blood mononuclear cells (PBMCs) were cultured under type 17 helper T cell (Th17) polarization conditions, and CD4+ T cell differentiation, pro-inflammatory cytokine levels, and soluble receptor activator of nuclear factor kappa-Β ligand (RANKL) were assessed. RA-FLSs were stimulated with 50 µM H2O2, and DJ-1 (10, 50, 100 ng/mL) to evaluate MMP-9, VEGF, TNF-α, and sRANKL production, while RANKL+ FLSs were assessed using flow cytometry. Monocytes were cultured with RANKL or IL-17A with or without DJ-1 and H2O2-pretreated RA-FLS, and tartrate-resistant acid phosphatase (TRAP) staining and RT-qPCR of osteoclast-related genes were performed. The levels of DJ-1 and H2O2 in serum and SF of RA patients were higher than those of OA patients. Under Th17-polarizing conditions, CD4+RANKL+ and CD4+CCR4+CCR6+CXCR3- T cells decreased, whereas CD4+CD25highFoxp3+ T cell increased after DJ-1 administration. Additionally, IL-17A, TNF-α, and sRANKL levels decreased in DJ-1-treated groups. DJ-1 lowered MMP-9, VEGF, TNF-α, and sRANKL levels, and RANKL+ FLS in ROS-stimulated RA-FLS. Both RANKL and IL-17A stimulated osteoclast differentiation, DJ-1 decreased TRAP+ cell count, and the expression levels of TRAP, ATP6v0d2, NFATc1, and CTSK. These findings were also observed in in vitro osteoclastogenesis with DJ-1 pretreated RA-FLS. As DJ-1 regulates Th17/Treg imbalance, pro-inflammatory cytokine production, RA-FLS activation, and osteoclastogenesis, it holds potential for RA therapy.

Comparison between oxaliplatin therapy and capecitabine monotherapy for high-risk stage II - III elderly patients with colon cancer.

PURPOSE: 45% of colon cancer patients are elderly, yet they are often deviated from standard cancer management. The MOSAIC trial favored FOLFOX over FL with superior oncologic outcomes; however, which regimen is most beneficial in elderly population remains unclear. This study aimed to compare the efficacy of oxaliplatin-added chemotherapy and capecitabine monotherapy in high-risk stage II/stage III elderly colon cancer patients. METHODS: Colon cancer patients ≥70 years of age who received adjuvant chemotherapy at Inje University Busan Paik Hospital between February 2009 to April 2016 were included. Patients were separated into the oxaliplatin-added group and capecitabine monotherapy group. The primary outcomes were CSS and OS. RESULTS: Of 74 patients, 45 received oxaliplatin-added chemotherapy and 29 received capecitabine monotherapy. There was no difference between the two groups in CSS or OS (p = 0.9670 and p = 0.6801, respectively). The N stage was significantly associated with CSS in both uni/multivariate analysis (p = 0.0565 and p = 0.0347, respectively). The oxaliplatin-added group had more stage III patients, so we performed a subgroup analysis of CSS and OS based on stage, which also showed no significant difference. CONCLUSIONS: Capecitabine monotherapy is an oncologically safe regimen compared to oxaliplatin-added regimens in elderly patients with high-risk stage II/stage III colon cancer.

Clinical Features and Prognosis of Patients with Primary Intestinal B-cell Lymphoma Treated with Chemotherapy with or without Surgery.

Background/Aims: This multicenter study reviewed the clinical features and prognosis according to the primary site of involvement and the treatment modality in patients with B-cell primary intestinal lymphoma (PIL). Methods: Among 125 consecutive patients diagnosed with PIL, 100 patients were analyzed. Results: The median age was 59 years, and the male to female ratio was 1.86:1. Diffuse large B-cell lymphoma (66/100, 66.0%) was the most common histological subtype. The estimated 5-year survival rate (5-YSR) was 48.5%. The 5-YSR was similar regardless of the type of primary treatment (chemotherapy alone vs. surgery/chemotherapy, 50.7 vs. 45.3%, p=0.582). A comparison of the survival according to the primary site of involvement revealed a 5-YSR of 32.5% (p=0.027), 64.3% (reference), 46.5% (p=0.113), and 49.8% (p=0.024) for the small intestine, ileocecal region, large intestine, and multiple sites, respectively. Multivariate analysis, however, revealed a low hemoglobin level, advanced Ann Arbor stage, and aggressive histological type to be independent prognostic factors for shorter survival but not ileocecal region involvement. Conclusions: The Ann Arbor stage, hemoglobin level, and histological type were independent prognostic factors for survival, while the primary site of involvement and treatment modality did not affect the prognosis in patients with B-cell PIL.

Effectiveness and drug retention of biologic disease modifying antirheumatic drugs in Korean patients with late onset ankylosing spondylitis.

The clinical data on the biologic disease-modifying antirheumatic drug (bDMARD) use in late-onset ankylosing spondylitis (LOAS) is limited. Thus, this study aimed to evaluate the drug efficacy and retention rate of bDMARDs in LOAS and compare it to young-onset ankylosing spondylitis (YOAS). Data of patients with AS receiving bDMARDs were extracted from the Korean College of Rheumatology Biologics and Targeted Therapy registry. Patients whose age of onset was > 50 years and ≤ 50 years were classified as having LOAS and YOAS, respectively. Their baseline characteristics and disease-associated parameters were evaluated. Drug efficacy [Ankylosing Spondylitis Disease Activity Score (ASDAS)-clinically important improvement (CII), ASDAS-major improvement (MI), Assessment of SpondyloArthritis International Society (ASAS) 20, and ASAS 40] at 1-year follow-up and drug retention rates were assessed. A total of 1708 patients (comprising 1472 patients with YOAS and 236 patients with LOAS) were included in this analysis. The LOAS group had a lower prevalence among males, lower HLA-B27 positivity and a higher prevalence of peripheral arthritis. Patients with LOAS were more likely to have higher disease-associated parameters (inflammatory reactants, patient global assessment, ASDAS-erythrocyte sedimentation rate, and ASDAS-C-reactive protein). LOAS was negatively associated with achieving ASDAS-CII, ASAS 20, and ASAS 40. The drug retention rate was lower in LOAS; however, the propensity score-matched and covariate-adjusted hazard ratios for bDMARD discontinuation were comparable to YOAS. There were no differences in the drug retention rates based on the type of bDMARD used in LOAS. Inferior clinical efficacy and shorter drug retention time were found in patients with LOAS receiving bDMARDs using real-world nationwide data. There were no differences among each bDMARD type.