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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-1β 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-1β 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-1β-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1β 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.

Chronic kidney disease (CKD) refers to the phenomenon of progressive decline in the glomerular filtration rate accompanied by adverse consequences, including fluid retention, electrolyte imbalance, and an increased cardiovascular risk compared to those with normal renal function. The triggers for the irreversible renal function deterioration are multifactorial, and diabetes mellitus serves as a major contributor to the development of CKD, namely diabetic kidney disease (DKD). Recently, epigenetic dysregulation emerged as a pivotal player steering the progression of DKD, partly resulting from hyperglycemia-associated metabolic disturbances, rising oxidative stress, and/or uncontrolled inflammation. In this review, we describe the major epigenetic molecular mechanisms, followed by summarizing current understandings of the epigenetic alterations pertaining to DKD. We highlight the epigenetic regulatory processes involved in several crucial renal cell types: Mesangial cells, podocytes, tubular epithelia, and glomerular endothelial cells. Finally, we highlight epigenetic biomarkers and related therapeutic candidates that hold promising potential for the early detection of DKD and the amelioration of its progression.

The aim of this prospective study was to use direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to rapidly diagnose periprosthetic joint infections (PJIs). Synovial fluid was taken from 77 patients (80 joints, 41 hips and 39 knees) who met the International Consensus Meeting criteria for PJI, and inoculated into blood culture bottles (BCBs) and onto conventional swabs. Positive blood cultures were analyzed using either direct or routine MALDI-TOF MS. Pathogen identification and the time to identification was recorded. Differences between groups were analyzed using the Kruskal-Wallis test and Bonferroni's post-hoc test. Direct and routine MALDI-TOF MS both detected 64 positive results (80%), compared to 47 (59%) by conventional swabs (p = 0.002). Direct MALDI-TOF MS identified 85.3% of the gram-positive organisms and 92.3% of the gram-negative organisms. No fungi were identified by direct MALDI-TOF MS. In 17 BCBs that were flagged positive, identification by direct MALDI-TOF MS failed. Among the positive results in the direct MALDI-TOF MS group, Staphylococcus aureus accounted for 47%, followed by Staphylococcus epidermidis (17%), Escherichia coli (9%) and Klebsiella pneumoniae (9%). The median time to microorganism identification was significantly shorter with direct MALDI-TOF MS (12.7 h, IQR: 8.9-19.6 h) than with routine MALDI-TOF MS (39.5 h, IQR: 22.8-46.0 h) or swabs (44.4 h, IQR: 27.2-72.6 h) (p < 0.0001). In pairwise comparisons, there were significant differences in the time of microorganism identification between direct MALDI-TOF MS and routine MALDI-TOF MS (p < 0.0001) or swab culture (p < 0.0001). There was no significant difference between routine MALDI-TOF MS and swab culture (p = 0.0268). Compared with current laboratory practice, direct MALDI-TOF MS shortened the time to microorganism identification and had superior results compared to conventional swabs, except for fungi. Further studies should investigate whether the earlier administration of appropriate antimicrobial agents can improve the treatment outcomes of PJIs.

Background This study aimed to conduct a systematic review and meta-analysis to assess the impact of extended postoperative oral antibiotic prophylaxis (EPOAP) on the risk of reinfection following two-stage exchange arthroplasty for hip and knee periprosthetic joint infection (PJI). Methods A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted on January 11, 2025. Studies reporting reinfection rates in patients receiving EPOAP after two-stage exchange arthroplasty, compared to those who did not, were included. A random-effects model was used to calculate pooled risk ratios (RRs) and subgroup analyses were performed based on the duration of EPOAP use (> 2 weeks vs. ≤2 weeks) and the joint site (hip or knee). Results Five studies, including four retrospective cohort studies and one randomized controlled trial, with a total of 486 knees and 444 hips, were included. The meta-analysis demonstrated that EPOAP significantly reduced the risk of reinfection following two-stage exchange arthroplasty (pooled RR: 0.52; 95% confidence interval [CI]: 0.35, 0.75; p  = 0.0006). Subgroup analyses yielded similar findings, with significant reductions in reinfection risk for EPOAP duration > 2 weeks (pooled RR: 0.51; 95% CI: 0.34, 0.78; p  = 0.002), hip arthroplasty (pooled RR: 0.37; 95% CI: 0.20, 0.70; p  = 0.002), while knee arthroplasty showed a borderline nonsignificant reduction (pooled RR: 0.64; 95% CI: 0.39, 1.04; p  = 0.07). Only one cohort study reported a decreased risk of reinfection with EPOAP use ≤ 2 weeks. Two studies assessed adverse events related to EPOAP. No complications were observed among 22 patients in one cohort study, whereas 6 of 22 patients (27%) in an RCT experienced mild gastrointestinal or dermatologic reactions that led to treatment discontinuation. Additionally, another cohort study reported that 16 of 24 reinfection cases (67%) involved organisms resistant to EPOAP. Conclusions This meta-analysis suggests that EPOAP is associated with a reduced risk of reinfection following two-stage exchange arthroplasty for hip arthroplasty, while further research is warranted for knee cases. This approach may improve patient outcomes and help optimize post-operative antibiotic management.

Sarcopenia and muscle weakness in elderly are contributed burden of public health and impact on quality of life. Weak grip strength was key role in diagnosis of sarcopenia and reported increased mortality, function declined in elderly. This study evaluated the association between GS and each common anthropometric characteristic in community-dwelling elderly. From 2017 to 2019, we conducted a community-based health survey among the elderly in Chiayi county, Taiwan. Participants were 65 years old or older, and total of 3,739 elderly subjects (1,600 males and 2,139 females) with a mean age of 76 years (range 65-85 years old) were recruited. General demographic data and lifestyle patterns were measured using a standard questionnaire. Anthropometric characteristics such as body height, body weight, body mass index (BMI), body waist and hip circumference, and body fat were measured by standard methods. GS was measured using a digital dynamometers (TKK5101) method. The mean GS was 32.8 ± 7.1 kg for males and 21.6 ± 4.8 kg for females (p < 0.001). For both sexes, elderly subjects with the same body weight but smaller body waist circumference had greater GS. The subjects with the same body waist size but heavier weight had greater GS. Furthermore, after adjusting for age, lifestyles, disease status, and potential anthropometric variable, multivariate regression analyses indicated that BMI was positively associated with GS (for males, beta = 0.310 and for females beta = 0.143, both p < 0.001) and body waist was negatively associated with GS (for males, beta = -0.108, p < 0.001; for females, beta = -0.030, p = 0.061). This study suggested that old adults with higher waist circumstance had weaker GS. Waist circumstance was negatively associated with GS, body weight was positively associated with GS in contrast. It may implies that central obesity was more important than overweight for GS in elderly.

Background Fracture-related infection (FRI) and subsequent persistent infections significantly affect fracture surgeries. We aimed to develop a precise, personalized risk calculator to assist orthopedic surgeons in evaluating perioperative FRI risk. Methods Data from 36,087 patients across two medical centers and four regional hospitals were analyzed. We assessed 29 risk factors, including patient characteristics, comorbidities, fracture location, and surgical variables using multivariable logistic regression. Each factor was weighted based on its regression coefficient. Discrimination and calibration were assessed with optimism-corrected AUC and Brier scores (1 000-fold bootstrap) and calibration plots. Results FRI occurred in 2396 patients (6.64%), and 453 patients (1.26%) experienced persistent infections. The top 10 risk factors included male sex, open fractures, tibiofibular fractures, ankle/foot fractures, operative time, hospital stay, peripheral vascular disease, diabetes, chronic kidney disease, and psychotic disorders. Optimism-corrected AUCs for predicting FRI and persistent infections were 0.781 [ p  < 0.001, 95% confidence interval (CI) 0.772–0.791] and 0.801 ( p  < 0.001, 95% CI 0.779–0.823), respectively. Optimal cutoff scores for predicting FRI and persistent infections were 213 (sensitivity 0.638, specificity 0.796) and 232 (sensitivity 0.658, specificity 0.821). Calibration plots demonstrated good predictive performance (mean absolute errors: FRI 0.006, persistent infection 0.006). Brier scores were 0.055 (FRI) and 0.012 (persistent infections), indicating good accuracy. Conclusions The FRI risk calculator showed good predictive abilities, with optimized cutoff points aiding perioperative planning and preventive measures. Patient engagement in understanding of infection risk can improve treatment outcomes. Limitations include participant biases and retrospective design; prospective external validation is recommended.

Background Anemia and blood transfusions are recognized as risk factors for periprosthetic joint infections (PJI). Tranexamic acid (TXA) is established in reducing perioperative blood loss and transfusion requirements. Our study investigates the impact of perioperative TXA administration on the incidence of PJI in patients undergoing total joint arthroplasty (TJA) and evaluates the association of intravenous (IV) and topical applications with PJI occurrence. Methods A retrospective review was performed on 8042 patients who underwent primary total hip arthroplasty (THA) and knee arthroplasty (TKA) from January 2009 to December 2020, with a minimum one-year follow-up at our institution. We compared patients who received TXA ( n  = 3664, with 2345 receiving it IV and 1319 topically) to those who did not ( n  = 4378). 0.5–1.25 g of IV TXA was administered before skin incision, and 1.5–3 g of topical TXA was injected intra-articularly or into the drainage tube during surgery. The primary outcome was PJI development within one year, defined by the 2013 International Consensus Meeting criteria. Secondary outcomes included blood transfusion, hospital length of stay (LOS), venous thromboembolism (VTE), and 90-day readmission. We employed multivariate logistic regression and propensity score weighting to adjust for potential confounders and conducted subgroup analyses to assess PJI odds in TKA and THA patients treated with IV and topical TXA. Results The TXA group demonstrated a lower PJI occurrence (1.1% vs. 2.1%, p  < 0.001), less blood transfusion (14.4% vs. 22.7%, p  < 0.001) and shorter LOS (5.6 ± 1.6 vs. 6.5 ± 2.5, p  < 0.001) compared to those without TXA. There was no difference between the two groups with regards to VTE and 90-day readmission. Perioperative TXA administration demonstrated lower PJI in multivariate analysis (OR 0.54, 95% CI 0.36–0.80, p  = 0.002), and in propensity score weighting (OR 0.53, 95% CI 0.36–0.80, p  = 0.002). In the subgroup analysis, both IV and topical administration of TXA resulted in decreased PJI (IV group: OR 0.53, 95% CI, 0.33–0.84, p  = 0.007, topical group: OR 0.51, 95% CI, 0.29–0.89, p  = 0.018), especially in primary TKA (IV TXA, OR 0.49, 95% CI, 0.29–0.83, p  = 0.008; Topical TXA, OR, 0.56, 95% CI, 0.32–0.98, p  = 0.042). Conclusion Perioperative TXA administration in primary hip and knee arthroplasty is significantly associated with a reduced PJI occurrence. Both IV and topical TXA routes showed similar association with reduced PJI occurrence, with a notable correlation observed in primary TKA.

The use of extended antibiotic (EA) prophylaxis (> 24 h) remains controversial in aseptic revision arthroplasty. We sought to determine whether EA prophylaxis reduces the risk of periprosthetic joint infection (PJI) in aseptic revision hip and knee arthroplasty. A total of 2800 patients undergoing aseptic revision hip and knee arthroplasty at five institutional databases from 2008 to 2017 were evaluated. One to two nearest-neighbor propensity score matching analysis was conducted between patients who did and did not receive extended antibiotic prophylaxis. The matching elements included age, sex, body mass index, Charlson comorbidity index, hospital distribution, year of surgery, joint (hip or knee), surgical time, CRP, preoperative hemoglobin, albumin, and length of stay. The primary outcome was the development of PJI, which was assessed at 30 days, 90 days, and 1 year following revision and analyzed separately. A total of 2467 (88%) patients received EA prophylaxis, and 333 (12%) patients received standard antibiotic (SA) prophylaxis (≤ 24 h). In the propensity-matched analysis, there was no difference between patients who received EA prophylaxis and those who did not in terms of 30-day PJI (0.3% vs. 0.3%, p = 1.00), 90-day PJI (1.7% vs. 2.1%, p = 0.62) and 1- year PJI (3.8% vs. 6.0%, p = 0.109). For revision hip, the incidence of PJI was 0.2% vs 0% at 30 days (p = 0.482), 1.6% vs 1.4% at 90 days (p = 0.837), and 3.4% vs 5.1% at 1 year (p = 0.305) in the EA and SA group. For revision knee, the incidence of PJI was 0.4% vs 0.9% at 30 days (p = 0.63), 1.8% vs 3.4% at 90 days (p = 0.331), and 4.4% vs 7.8% at 1 year (p = 0.203) in the EA and SA group. A post hoc power analysis revealed an adequate sample size with a beta value of 83%. In addition, the risks of Clostridium difficile and resistant organism infection were not increased. This multi-institutional study demonstrated no difference in the rate of PJIs between patients who received extended antibiotic prophylaxis and those who did not in aseptic revision arthroplasty. The risk of C. difficile and resistant organism infection was not increased with prolonged antibiotic use.

Background Hip-spine syndrome (HSS) poses a diagnostic challenge because lumbar degenerative disease, sacro-iliac joint dysfunction, and hip osteoarthritis often produce overlapping symptoms. The suboptimal diagnostic pathways may contribute to adverse clinical outcomes. Earlier work suggested that orthopaedic surgeons more consistently obtain hip imaging than neurosurgeons when treating patients who ultimately require both lumbar and hip operations. Whether this observation holds in a tertiary-care electronic medical-record (EMR) setting remains unknown. Methods We queried the Chang Gung Research Database (CGRD), the largest multi-institutional EMR repository in Taiwan, for patients aged 50–85 years who underwent both hip arthroplasty and lumbar surgery within the same 12-month period between 2001 and 2024. Cohorts were categorised as hip-then-spine (HS, n  = 58), spine-then-hip (SH, n  = 223), or simultaneous procedures (Both, n  = 2). SH patients were stratified by the specialty of the spine surgeon: orthopaedic (OS, n  = 104) versus neurosurgical (NS, n  = 111). Primary outcomes were (1) pre-operative ordering of combined spine + pelvis/hip radiography and (2) documentation of hip pathology before spine surgery. Group differences were analysed with χ² or Student’s t tests (α = 0.05). Results Combined spine-and-hip imaging was obtained significantly more often by OS than by NS (73.1% vs. 51.4%; p  < 0.001; FDR q-value: 0.002). Hip osteoarthritis or osteonecrosis was recorded pre-operatively in 26.9% of OS cases versus 21.6% of NS cases, a non-significant difference attributable to limited sample size ( p  = 0.364). The SH:HS ratio showed approximately 4:1, indicating that spine surgery typically precedes hip arthroplasty in routine practice. Conclusions Within a tertiary-care EMR database, orthopaedic surgeons were more likely than neurosurgeons to order comprehensive spinopelvic imaging, thereby enhancing detection of hip pathology in patients with suspected HSS. These findings underscore the importance of mandated and standardized pre-operative hip/pelvic imaging before lumbar surgery and support efforts to harmonise diagnostic protocols across specialties.

The glucokinase regulator gene ( GCKR ) is located on chromosome 2p23. It plays a crucial role in maintaining plasma glucose homeostasis and metabolic traits. Recently, genome-wide association studies have revealed a positive association between hyperuricemia and GCKR variants in adults. This study investigated this genetic association in Taiwanese adolescents. Data were collected from our previous cross-sectional study (Taipei Children Heart Study). The frequencies of various genotypes (CC, CT, and TT) or alleles (C and T) of the GCKR intronic single-nucleotide polymorphism (SNP) rs780094 and the coding SNP rs1260326 (Pro446Leu, a common 1403C-T transition) were compared between a total of 968 Taiwanese adolescents (473 boys, 495 girls) with hyperuricemia or normal uric acid levels on the basis of gender differences. Logistic and linear regression analyses explored the role of GCKR in abnormal uric acid (UA) levels. Boys had higher UA levels than girls (6.68 ± 1.29 and 5.23 ± 0.95 mg/dl, respectively, p  < 0.001). The analysis of both SNPs in girls revealed that the T allele was more likely to appear in patients with hyperuricemia than the C allele. After adjusting for confounders, the odds ratio (OR) for hyperuricemia incidence in the TT genotype was 1.75 (95% confidence interval [CI] 1.02–3.00), which was higher than that in the C allele carriers in rs1260326 in the girl population. Similarly, the TT genotypes had a higher risk of hyperuricemia, with an OR of 2.29 (95% CI 1.11–4.73) for rs1260326 and 2.28 (95% CI 1.09–4.75) for rs780094, than the CC genotype in girl adolescents. The T (Leu446) allele of GCKR rs1260326 polymorphism is associated with higher UA levels in Taiwanese adolescent girls.