Experiences and perspectives related to shared decision-making among outpatients with degenerative joint disease in Taiwan: a qualitative study.

OBJECTIVES: Various treatment options are available for degenerative joint disease (DJD). During clinical visits, patients and clinicians collaboratively make decisions regarding the optimal treatment for DJD; this is the essence of shared decision-making (SDM). Here, we collated and assessed the SDM-related experiences and perspectives of outpatients with DJD in Taiwan. DESIGN: In-depth interviews and thematic analysis. SETTING: Primary care clinics of a regional teaching hospital in Taiwan, October 2021-May 2022. PARTICIPANTS: 21 outpatients with at least three visits for DJD and who were aware of SDM. RESULTS: Four main themes emerged in this study: first, equipping themselves with knowledge: outpatients obtained disease-related and treatment-related knowledge in various ways-seeking relevant information online, discussing with family and friends, learning from their own experiences or learning from professionals. Second, shared or not shared: physicians had different patterns for communicating with patients, particularly when demonstrating authority, performing mutual discussion, respecting patient preferences or responding perfunctorily. Third, seldom saying no to physician-prescribed treatment plans during clinical visits: most patients respected physicians' professionalism; however, some patients rejected physicians' recommendations indirectly, whereas some responded depending on their disease prognosis. Fourth, whose call?-participants decided to accept or reject a treatment plan independently or by discussing it with their families or by obeying their physicians' recommendations. CONCLUSIONS: In general, patients with DJD sought reliable medical information from various sources before visiting doctors; however, when having a conversation with patients, physicians dominated the discussion on treatment options. The patient-physician interaction dynamics during the SDM process determined the final medical decision, which was in accordance with either patients' original autonomy or physicians' recommendations. To alleviate medical paternalism and physician dominance, patients should be empowered to engage in medical decision-making and share their opinions or concerns with their physicians. Family members should also be included in SDM.

Attenuative effects of collagen peptide from milkfish (Chanos chanos) scales on ovariectomy-induced osteoporosis.

Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.

The Value of 18F-FDG PET/MRI in Detecting Lumbar Radiculopathy for Selective Percutaneous Endoscopic Discectomy: a Case Report.

Magnetic resonance imaging (MRI) is the most popular imaging modality for investigating intervertebral disc herniation. However, it has a high chance for identifying incidental findings that are morphologically or structurally abnormal but not responsible for patients' symptoms. Although a previous study suggested that 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) may help identify neuroinflammation in lumbar radiculopathy, there is currently no direct evidence obtained from surgery. Here, we describe the case of a 32-year-old man with low back pain and right leg paresthesia for 7 months. MRI demonstrated disc herniation at the L3-L4, L4-L5 and L5-S1 levels, causing bilateral L5 and left S1 root compression. 18F-FDG PET/MRI demonstrated increased 18F-FDG uptake at the right L5 root, which was compatible with the patient's symptoms. Transforaminal percutaneous endoscopic lumbar discectomy (PELD) was performed. Intraoperative images revealed a swollen nerve root at the right L5 after removal of the herniated disc. After surgery, the patient experienced immediate pain relief and had no recurrence at the 6-month follow-up. When performing PELD in patients with multilevel radiculopathy identified on MRI, the use of 18F-FDG PET/MRI can help in accurate localization of the symptomatic roots and minimize surgical incision and soft-tissue injury.

Effectiveness of question prompt lists in patients with breast cancer: A randomized controlled trial.

OBJECTIVES: To evaluate the effectiveness of a question prompt list (QPL) in decision self-efficacy, decision-making participation, patient-physician communication, decisional conflict or regret, and health status in patients with breast cancer. METHODS: A total of 240 patients with breast cancer were randomly assigned to a QPL group or control group (n = 120 each). The intervention and control groups received an additional educational QPL booklet and routine care, respectively. RESULTS: The intervention group exhibited significant improvements in decision self-efficacy, perceived patient-physician interactions, and patient-physician communication compared with the control group. Multilevel modeling analyses revealed significant group-time interaction effects on decision self-efficacy (ß = 9.99, P < 0.01), perceived patient-physician interactions (ß = 8.10, P < 0.01), patient-physician communication (ß = 5.02, P < 0.01), and anxiety status (ß = -3.78, P < 0.05). The QPL intervention exerted more favorable effects than routine care, with repeated measurements of the same patients and the data of patients under the care of the same surgeons accounted for. CONCLUSIONS: The QPL intervention exerted multidimensional effects on decision-making outcomes among patients with breast cancer. PRACTICAL IMPLICATIONS: Clinicians can integrate a QPL into routine care for patients with breast cancer.

Utility of magnetic resonance spectroscopy and diffusion-weighted imaging for detecting changes in the femoral head in divers with hip pain at risk for dysbaric osteonecrosis.

BACKGROUND: Ischemia before the development of dysbaric osteonecrosis (DON) in femoral heads has never been investigated. We assessed whether quantitative magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) could detect dysbaric changes in divers with hip pain. METHODS: This IRB-approved exploratory study recruited 17 divers [9 with hip pain (Group 1); 8 asymptomatic (Group 2)] with normal findings on radiographs and conventional magnetic resonance imaging scans were age-, gender- and body-mass-index matched to 17 non-divers as controls (Group 1C, 2C). Apparent diffusion coefficients (ADCs) and MRS spectra were obtained from regions/voxels of interest on the femoral heads of all subjects. LCModel was used to determine water content, lipid composition, and the unsaturation index in bone marrow. Mann-Whitney non-parametric test was used to compare results of quantitative MRS and ADCs of ipsilateral femoral heads between divers and controls. RESULTS: MRS of the ipsilateral femoral heads revealed higher water (peak: 4.7 ppm) content, lower total lipid fraction (TLF), and higher unsaturation index (UI) of lipids in Group 1 than in Group 2 (water: P=0.040; UI: P=0.022) and Group 1C (water: P=0.027; TLF: P=0.039; UI: P=0.009). In contrast, femoral head ADCs were comparable between divers and controls. Five out of nine symptomatic divers were contacted for follow-up MRS and DWI studies, and the mean difference in water content in the femoral heads of patients with osteonecrosis was also higher than that in patients with symptom relief (osteonecrosis: 0.077±0.130 vs. symptom relief: 0.003±0.010). CONCLUSIONS: Dysbaric change in the femoral heads of divers with hip pain can be detected using quantitative MRS, which reveals increases in water content and UI of lipids, and a decrease in TLF.

Generation of human induced pluripotent stem cells from cystic fibrosis patient carrying nonsense mutation (p.S308X) in CFTR gene.

Cystic fibrosis (CF) is a genetic disease affects CFTR channel synthesis. While 90 percent of the CF patients now benefit from small molecule target therapies, this treatment has yet to extend to those bearing nonsense mutations. Studies of these rare mutations using cell lines with native pathological signatures of the disease may lead to breakthroughs in therapeutic development. Here, we report the generation of CF patient-derived induced pluripotent stem cells (iPSCs) carrying a nonsense mutation at position 308 (S308X). The pluripotency and genomic profile of the iPSC line was validated as a resource that can enable future research for CF.

Implantation of monocusp valve prolongs the duration of chest tube drainage in children with tetralogy of fallot after corrective surgery.

BACKGROUND: Right ventricular outflow tract obstruction relief is one of the major procedures during the total correction of tetralogy of Fallot (TOF). Pulmonary insufficiency (PI) is usually inevitable after a transannular incision with a patch repair is performed. Therefore, some surgeons advocate to place a monocusp valve within the transannular patch (TAP) in order to decrease the severity of the PI. However, the monocusp valve seemed not be very effective in some patients who underwent the complete TOF repair. METHODS: Patients who had the classic form of TOF between January 2009 and January 2017 and underwent the corrective surgery with a TAP by the same cardiovascular surgeon were identified for further analysis. Clinical information including demographics at operation, perioperative data, and postoperative outcome were collected retrospectively and compared between the group with and without a monocusp valve. RESULTS: A total of 24 TOF cases were included in the final analysis, and 16 (66.7%) patients received a monocusp valve placement. The patients' characteristics before and during the surgery were similar between the two groups. The median duration of chest tube drainage after the total correction in the monocusp group was longer than those without the valve (p = 0.04). There was no difference in the immediate postoperative data, including the inflammation/infection status, the duration of mechanical ventilation, and the length of ICU and hospital stay. CONCLUSION: Implantation of a monocusp valve during the total TOF correction using a TAP did not bring benefit to improve the immediate postoperative outcomes, especially the duration of the pleural drainage. Further study with a prospective design and a larger number of cases is needed.

Genetic association between TNF-α G-308A and osteoarthritis in Asians: A case-control study and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is an important health issue in elderly people. Many studies have suggested that genetic factors are important risk factors for OA, of which tumor necrosis factor-α (TNF-α) is one of the most examined genes. Moreover, several studies have investigated the relationship between TNF-α G-308A polymorphisms and OA risk, but consistent results have not been obtained. OBJECTIVE: This study examines the association between TNF-α G-308A polymorphisms and knee OA. Moreover, meta-analysis and trial sequential analysis (TSA) was used to determine whether this is a susceptibility gene for knee OA. METHODS: Between 2015 and 2019, 591 knee OA cases and 536 healthy controls were recruited. The Kellgren-Lawrence grading system was used to identify the knee OA cases. A meta-analysis was conducted including related studies published until 2020 from PubMed, Embase, and previous meta-analysis to improve the evidence level of the current study. The results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) to evaluate the effect of this polymorphism on knee OA risk. The TSA was used to estimate the sample sizes required in this issue. RESULTS: A nonsignificant association was found between the AA genotype and knee OA [adjusted OR, 0.84; 95% CI, 0.62-1.15) in the recessive model] in the present case-control study, and analysis of other genetic models showed a similar trend. After adding the critical case-control samples for Asians, the TNF-α G-308A, AA genotype exhibited 2.57 times more risk of developing arthritis when compared with the GG + GA genotype (95% CI, 1.56-4.23), and the cumulative samples for TSA (n = 2182) were sufficient to obtain a definite conclusion. CONCLUSIONS: The results of this meta-analysis revealed that the TNF-α G-308A, AA genotype is a susceptible genotype for OA in the Asian population. This study integrated all current evidence to arrive at this conclusion, suggesting that future studies on Asians are not required.

High-Molecular-Weight Hyaluronic Acid Inhibits IL-1ß-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway.

Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1ß to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1ß increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1ß-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1ß culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.

Interleukin-26 Has Synergistic Catabolic Effects with Palmitate in Human Articular Chondrocytes via the TLR4-ERK1/2-c-Jun Signaling Pathway.

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

Cardamonin Attenuates Inflammation and Oxidative Stress in Interleukin-1ß-Stimulated Osteoarthritis Chondrocyte through the Nrf2 Pathway.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the deterioration of articular cartilage. The progression of OA leads to an increase in inflammatory mediators in the joints, thereby promoting the destruction of the cartilage matrix. Recent studies have reported on the anti-inflammatory and antioxidant properties of cardamonin, which also appears to interact with cellular targets, such as nuclear erythroid 2-related factor 2 (Nrf2), extracellular signal-regulated kinase (ERK), and mammalian target of rapamycin (mTOR) during the progression of tumors. To date, few studies have investigated the effects of cardamonin on chondrocyte inflammation. In the current study, we determined that treating interleukin-1 beta (IL-1ß-stimulated chondrocyte cells) with cardamonin significantly reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) and significantly inhibited the expression of pro-inflammatory proteins, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Cardamonin was also shown to: (1) inhibit the activation and production of matrix metalloproteinases (MMPs), (2) suppress the nuclear factor-κB (NF-κB) signaling pathway, (3) suppress the expression of toll-like receptor proteins, (4) activate the Nrf2 signaling pathway, and (5) increase the levels of antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). The increase in antioxidant proteins led to corresponding antioxidant effects (which were abolished by Nrf2 siRNA). Our findings identify cardamonin as a candidate Nrf2 activator for the treatment and prevention of OA related to inflammation and oxidative stress.

Effects of Surgical Intervention for Bone Metastases on Survival in Patients with Advanced Cancer: A Nationwide Population-Based Cohort Study.

PURPOSE: With recent advances in surgical techniques and instruments, orthopedic surgeons are better equipped to treat metastatic bone disease. There has also been considerable progress in the non-surgical treatment of cancers, specifically in improving the survival rate of patients with advanced cancer. However, it remains unclear whether surgical resection of a metastatic bone lesion poses additional risk to the survival of patients with advanced cancer. PATIENTS AND METHODS: This study utilized data from the National Health Insurance Research Database (NHIRD) in Taiwan between 2000 and 2015. Patients aged ≥18 years, who had been recently diagnosed with bone metastases (BM), were enrolled and assigned to either the surgery or non-surgery groups. The demographic characteristics were analyzed, and the adjusted hazard ratios (aHR) of mortality were calculated using Cox regression analysis. RESULTS: Of the 4,549,226 individuals in the inpatient database of the NHIRD, 83,536 patients with BM were enrolled in this study. Among them, 8802 underwent surgical resection for skeletal metastatic lesion and 66,098 did not. Altogether, 28,691 patients died, including 2798 (31.8%) in the surgery group and 25,893 (39.2%) in the non-surgery group. The aHR for mortality was 0.7-fold lower in the surgery group (p < 0.001). CONCLUSION: This study demonstrates that surgical resection of metastatic bone lesions did not pose any additional risk to survival outcomes. Thus, we believe that surgery, if indicated, could have a competitive role in the management of metastatic bone disease.

The Decisive Case-Control Study Elaborates the Null Association between ESR1 XbaI and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis.

(1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor α (ERα) has been considered to play a key role due to a large gender difference in its expression. ERα is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case-control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren-Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78-1.20) and adjusted-OR: 0.90 (95% CI: 0.71-1.15) in allele model] in the present case-control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case-control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59-1.04)] with a high heterogeneity (I2: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56-1.95), I2: 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.

NKX6-1 mediates cancer stem-like properties and regulates sonic hedgehog signaling in leiomyosarcoma.

BACKGROUND: Leiomyosarcoma (LMS), the most common soft tissue sarcoma, exhibits heterogeneous and complex genetic karyotypes with severe chromosomal instability and rearrangement and poor prognosis. METHODS: Clinical variables associated with NKX6-1 were obtained from The Cancer Genome Atlas (TCGA). NKX6-1 mRNA expression was examined in 49 human uterine tissues. The in vitro effects of NXK6-1 in LMS cells were determined by reverse transcriptase PCR, western blotting, colony formation, spheroid formation, and cell viability assays. In vivo tumor growth was evaluated in nude mice. RESULTS: Using The Cancer Genome Atlas (TCGA) and human uterine tissue datasets, we observed that NKX6-1 expression was associated with poor prognosis and malignant potential in LMS. NKX6-1 enhanced in vitro tumor cell aggressiveness via upregulation of cell proliferation and anchorage-independent growth and promoted in vivo tumor growth. Moreover, overexpression and knockdown of NKX6-1 were associated with upregulation and downregulation, respectively, of stem cell transcription factors, including KLF8, MYC, and CD49F, and affected sphere formation, chemoresistance, NOTCH signaling and Sonic hedgehog (SHH) pathways in human sarcoma cells. Importantly, treatment with an SHH inhibitor (RU-SKI 43) but not a NOTCH inhibitor (DAPT) reduced cell survival in NKX6-1-expressing cancer cells, indicating that an SHH inhibitor could be useful in treating LMS. Finally, using the TCGA dataset, we demonstrated that LMS patients with high expression of NKX6-1 and HHAT, an SHH pathway acyltransferase, had poorer survival outcomes compared to those without. CONCLUSIONS: Our findings indicate that NKX6-1 and HHAT play critical roles in the pathogenesis of LMS and could be promising diagnostic and therapeutic targets for LMS patients.

Incidence of bone metastases in patients with organ-specific cancers: A nationwide population-based cohort study.

BACKGROUND: Bones are the third most common site of metastasis, although bone metastasis (BM) incidence varies widely. This study investigated the incidence of BM in the most common cancers in Taiwan to present the recent treatment landscape in patients with organ-specific cancers. METHODS: Data from the National Health Insurance Research Database of Taiwan were used to identify adult patients diagnosed with organ-specific cancers between January 1, 2000 and December 31, 2015. Kaplan-Meier analysis was used to quantify cumulative BM incidence at follow-up. BM incidences associated with different cancers were calculated comprehensively and stratified by sex, age group and follow-up periods, and age- and sex-adjusted hazard ratios (HRs) of BM were calculated using multivariate Cox regression analysis. RESULTS: Among 938 776 participants (mean follow-up, 9.2 years), liver (19.6%), colorectal (17.1%) and lung (15.1%) cancers were most commonly associated with BM. The mean interval between a primary cancer diagnosis and BM was 2 years. BM incidence varied widely among cancers; lung cancer (3213 per 105 person-years) was associated with the highest BM risk, followed by oesophageal, prostate and breast cancer. HRs of BM were significantly higher for lung cancer (HR = 8.1) than for other cancers. CONCLUSION: The estimated BM incidence provided insight into oncological clinical practice trends in the Asia-Pacific region. BM incidence may vary among populations. Understanding the principles of clinical evaluation in patients with cancer of unknown primary origin can facilitate appropriate treatment recommendations.

Astaxanthin attenuates joint inflammation induced by monosodium urate crystals.

Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction. This study investigated whether astaxanthin (AXT), which has documented anti-inflammatory and antioxidant properties, exhibits protective effects against monosodium urate (MSU) crystal-induced inflammation. Cell viability of J774A.1 murine macrophages was assessed by AXT dose-dependent incubation by MTT assays, and expression levels of iNOS and COX-2 proteins as well as secretion of IL-1ß were also analyzed under MSU crystals stimulation with or without AXT treatment. The production of inflammatory mediators was found to significantly decrease with AXT treatment, and the formation of the inflammasome complex was also attenuated when cells were co-stimulated with MSU crystals and AXT. Furthermore, we found that expression of the MAPK pathway was downregulated in J774A.1 cells. AXT also inhibited the induction of COX-2 and IL-6 in human chondrocytes and synovial fibroblasts by western blots. Finally, an MSU crystal intra-articular injection rat model for gouty arthritis was utilized in which treatment groups received 5-daily intraperitoneal injections of AXT prior to MSU crystal stimulation, or once intra-articular injections of AXT following MSU crystal stimulation for 6 hours. Results of synovitis score analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only. These results indicate that AXT attenuates the effects of MSU crystal-induced inflammation by suppressing the production of pro-inflammatory cytokines and inflammatory mediators. Our findings that the anti-inflammatory activities of AXT may be beneficial in the treatment of MSU crystal-induced arthritis.

Midshaft clavicle fracture following osteosynthesis with a hook plate: a retrospective case analysis.

PURPOSE: The clavicle hook plate has been commonly used to treat distal clavicle fractures and acromioclavicular (AC) joint dislocations; however, midshaft clavicle fracture at the medial end of the hook plate remains an underestimated complication. We aimed to discover the risk factors for this complication and the influence of these risk factors on patients and to suggest preventive surgical techniques. METHODS: We retrospectively reviewed the records of 150 patients with acute distal clavicle fractures or acute AC joint dislocations treated by internal fixation with a clavicle hook plate. The patient demographics, the occurrence of midshaft clavicle fracture at the medial end of the hook plate, and functional outcomes were analyzed. The functional outcomes were evaluated with the American Shoulder and Elbow Surgeons (ASES) Shoulder Score and grading of the Constant shoulder score after the hook plate was removed. RESULTS: In total, 17 patients had complicating midshaft clavicle fractures at the medial end of the hook plate. Elderly patients had a higher risk of developing this complication than young patients. The odds ratio was 4.4 (p < 0.05). The average ASES score and grading of Constant score of these patients were 74.1 and 16.3 points, respectively, which were significantly inferior to those of patients without complications (p < 0.001). CONCLUSION: The incidence of midshaft clavicle fractures following osteosynthesis with a clavicle hook plate was not negligible, especially in elderly patients. This complication may impair shoulder function and quality of life. Awareness of this complication and the risk factors for this complication reminds us to perform such operations with caution.

Aberrant distribution and function of plasmacytoid dendritic cells in patients with ankylosing spondylitis are associated with unfolded protein response.

Although human leucocyte antigen (HLA)-B27 is strongly associated with ankylosing spondylitis (AS), the association of unfolded protein response (UPR) induced by HLA-B27 misfolding in AS remains controversial. Since dendritic cells (DCs) are crucial in induction of AS in HLA-B27-transgenic rats, and plasmacytoid DCs (pDCs) belong to one type of DCs, we here aim to study the relevance of pDCs and UPR in AS. Peripheral pDCs were isolated from 27 HLA-B27(+) AS patients and 37 controls. The bone marrow (BM) and synovium of inflamed hips from AS patients and controls were obtained. We found a significantly higher frequency of pDCs in the peripheral blood, BM, or inflamed synovium of hips, which is associated with the enhanced expression of pDC trafficking molecules, CCR6 and CCL20 in the synovium of AS patients. Functional analysis further revealed that several inflammatory cytokines, including TNFα, IL-6, and IL-23, secreted by pDCs were significantly increased in AS patients as compared with those in controls. Remarkably, protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway in UPR was up-regulated in pDCs of AS patients. Notably, PERK inhibitor treatment significantly inhibited the enhanced cytokine production by pDCs of AS patients. Further, the extent of PERK activation was significantly associated with the increased disease severity of AS patients. Our data uncover the aberrant distribution and function of pDCs in AS patients. The up-regulated PERK pathway in UPR of pDCs not only contributes to enhanced cytokine production of pDCs, but also is associated with increased disease activity of AS patients.

Staphylococcal phosphatidylinositol-specific phospholipase C potentiates lung injury via complement sensitisation.

Staphylococcus aureus is frequently isolated from patients with community-acquired pneumonia and acute respiratory distress syndrome (ARDS). ARDS is associated with staphylococcal phosphatidylinositol-specific phospholipase C (PI-PLC); however, the role of PI-PLC in the pathogenesis and progression of ARDS remains unknown. Here, we showed that recombinant staphylococcal PI-PLC possesses enzyme activity that causes shedding of glycosylphosphatidylinositol-anchored CD55 and CD59 from human umbilical vein endothelial cell surfaces and triggers cell lysis via complement activity. Intranasal infection with PI-PLC-positive S. aureus resulted in greater neutrophil infiltration and increased pulmonary oedema compared with a plc-isogenic mutant. Although indistinguishable proinflammatory genes were induced, the wild-type strain activated higher levels of C5a in lung tissue accompanied by elevated albumin instillation and increased lactate dehydrogenase release in bronchoalveolar lavage fluid compared with the plc- mutant. Following treatment with cobra venom factor to deplete complement, the wild-type strain with PI-PLC showed a reduced ability to trigger pulmonary permeability and tissue damage. PI-PLC-positive S. aureus induced the formation of membrane attack complex, mainly on type II pneumocytes, and reduced the level of CD55/CD59, indicating the importance of complement regulation in pulmonary injury. In conclusion, S. aureus PI-PLC sensitised tissue to complement activation leading to more severe tissue damage, increased pulmonary oedema, and ARDS progression.