Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.

BACKGROUND: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. METHODS: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). RESULTS: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased ß-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001). CONCLUSIONS: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.

The Association between Iron-Deficiency Anemia (IDA) and Septic Arthritis (SA): The Real-World Data.

Background and Objectives: Iron-deficiency anemia (IDA) could predispose the afflicted individuals to various infections and musculoskeletal disorders. This study attempted to investigate the association between IDA and septic arthritis (SA), a musculoskeletal disease. Materials and Methods: We investigated all the eligible subjects in the Taiwanese longitudinal health insurance database (LHID) between 2000 and 2012. Subjects with the diagnosis of IDA (International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM): 280) were allocated to the IDA cohort. The control subjects were randomly matched to every subject with IDA coding by age and sex at the 1:4 ratio. All of the recruited subjects were followed since the index date to the onset of SA (ICD-9-CM: 711.0), withdrawal from the insurance (including death), or 31 December 2013. Results: The cumulative incidence of SA was assessed. We showed that the cumulative incidence of SA was higher in the IDA cohort than in the control cohort (p-value < 0.0001). After adjustment of the comorbidities, the IDA patients had a 2.53-fold risk of SA compared to control subjects (aHR = 2.53, 95% CI = 1.89−3.38). Conclusions: IDA was associated with an increased risk of SA.

Incidence of Hip Fractures among Patients with Chronic Otitis Media: The Real-World Data.

Chronic otitis media (COM) has been considered as a localized disease, and its systemic impact is poorly understood. Whether COM-induced inflammation could be associated with systemic bone loss and hip fracture is unknown at present. Our study tried to determine the risk of hip fracture among COM patients. We selected the comparison individuals without the COM coding and paired the controls with COM patients by gender, age, and comorbidities (including osteoporosis) by about a one-to-two ratio. Our study showed that the incidence of hip fracture was 4.48 and 3.92 per 1000 person-years for comparison and COM cohorts respectively. The cumulative incidence of hip fracture is higher in the COM cohort (p < 0.001). After adjustment for gender, age, and comorbidities, the COM patients had a 1.11-fold (aHR = 1.11; 95% CI = 1.05−1.17) risk of hip fracture than the control subjects. Among COM patients, a history of hearing loss is associated with higher (aHR = 1.21; 95% CI = 1.20−1.42) fracture risk. Our study showed that COM patients, especially those with hearing loss, are susceptible to a higher risk for hip fracture.

Resistin enhances IL-1ß and TNF-α expression in human osteoarthritis synovial fibroblasts by inhibiting miR-149 expression via the MEK and ERK pathways.

Resistin is a cysteine-rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), which are critical pro-inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL-1ß, and TNF-α expression in OA knee synovial tissue compared with that from non-OA knees. Resistin-induced enhancement of IL-1ß and TNF-α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF-α and IL-1ß in OASFs by inhibiting miR-149 expression via MEK and ERK signaling. Our findings elucidate the inter-relationships between resistin and pro-inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium-targeted therapy in OA.

Systemic effects of platelet-rich plasma local injection on serum and urinary anabolic metabolites: A prospective randomized study.

Platelet-rich plasma (PRP) is widely utilized in the treatment of sports injuries. However, potential systemic effects after localized PRP injection are unclear at present. In this prospective randomized study, 24 Taiwanese male athletes with tendinopathy were randomized into a PRP group (n = 13) or a saline group (n = 11). The concentrations of serum and urine biomarkers were quantified by enzyme-linked immunosorbent assay assessment as well as gas chromatographic and mass spectrometric analysis, respectively. The results showed no significant differences in serum levels of growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein 3, vascular endothelial growth factor, platelet-derived growth factor-BB, or serum substance P(SP) between the two groups before intervention, nor at 1, 2, or 7 days after intervention. However, a significant decrease in the serum SP level 1 and 7 days after PRP injection was observed. Regarding urinary concentrations of metabolites of anabolic androgenic steroids (AAS), no between-group differences before intervention, nor at 1, 2, or 7 days after intervention, were observed. Our study failed to observe significant surge of serum anabolic molecules and urinary excretion of anabolic AAS metabolites after PRP injection.

Amphiregulin Promotes Vascular Endothelial Growth Factor-C Expression and Lymphangiogenesis through STAT3 Activation in Human Chondrosarcoma Cells.

BACKGROUND/AIMS: Chondrosarcoma is the second most common primary malignancy of bone, characterized by a high metastatic potential. Increasing clinical data highlight the important role played by lymphangiogenesis in cancer metastasis. Amphiregulin (AR) has been implicated in tumor metastasis and lymphangiogenesis, but its association with vascular endothelial growth factor-C (VEGF-C) expression and lymphangiogenesis in chondrosarcoma is unclear. METHODS: We used qPCR, ELISA and Western blotting to detect AR-induced VEGF-C expression in chondrosarcoma cells. Lymphangiogenesis was investigated by lymphatic endothelial cells (LECs) migration and tube formation. An in vivo experiment examined AR expression in tumor-associated lymphangiogenesis. RESULTS: In this study, we found that both AR and VEGF-C expression correlated with tumor stage and were significantly higher than levels found in normal cartilage. Exogenous AR promoted VEGF-C expression in chondrosarcoma cells in a time- and dose-dependent manner and subsequently increased migration and tube formation of LECs. AR also increased VEGF-C expression and lymphangiogenesis through the Src/MEK/ERK/STAT3 signaling pathway. However, it is unclear as to how an EGFR ligand (AR) induces activation of the Src kinase. Knockdown of AR decreased VEGF-C expression in chondrosarcoma cells. Similarly, lymphangiogenesis was abolished in AR knockdown cells in an in vivo model of chondrosarcoma. CONCLUSION: These results indicate that AR occurs through the Src/MEK/ERK/STAT-3 pathway, activating VEGF-C expression and contributing to lymphangiogenesis in human chondrosarcoma. Thus, AR could be a therapeutic target in metastasis and lymphangiogenesis of chondrosarcoma.

Effects of computer-assisted navigation versus the conventional technique for total knee arthroplasty on levels of plasma thrombotic markers: a prospective study.

BACKGROUND: Venous thromboembolism (VTE) is a major sequela after total knee arthroplasty (TKA). We prospectively compared the differences in the perioperative plasma D-dimer and fibrinogen levels between the individuals undergoing TKA via computer-assisted navigation and via a conventional method as the surrogate comparison for VTE. There were 174 patients fulfilling the inclusion criteria and providing valid informed consent between September 2011 and November 2013. There were 69 females and 20 males in the navigation-assisted group (median age: 71.00 years), while the conventional group was composed of 59 females and 26 males (median age: 69.00 years). Blood samples were obtained prior to and at 24 and 72 h after surgery for measurement of the levels of plasma D-dimer and fibrinogen. RESULTS: A significantly lower plasma D-dimer level 24 h after TKA (p = 0.001) and a milder postoperative surge 24 h after TKA (p = 0.002) were observed in patients undergoing navigation-assisted TKA. The proportions of subjects exceeding the plasma D-dimer cut-off values of 7.5, 8.6 and 10 mg/L 24 h after TKA were all significantly higher in the conventional group than in the navigation-assisted group (p = 0.024, 0.004, and 0.004, respectively). CONCLUSIONS: A lower plasma D-dimer level and a milder surge in the plasma D-dimer level were observed in patients undergoing navigation-assisted TKA in comparison with patients undergoing conventional TKA 24 h after surgery. These findings may supplement the known advantages of navigation-assisted TKA.

Correlation between genetic polymorphism of angiopoietin-2 gene and clinical aspects of rheumatoid arthritis.

The Angiopoietin-2 (Ang2) gene encodes angiogenic factor, and the polymorphisms of Ang2 gene predict risk of various human diseases. We want to investigate whether the single nucleotide polymorphisms (SNPs) of the Ang2 gene can predict the risk of rheumatoid arthritis (RA). Between 2016 and 2018, we recruited 335 RA patients and 700 control participants. Comparative genotyping for SNPs rs2442598, rs734701, rs1823375 and rs12674822 was performed. We found that when compared with the subjects with the A/A genotype of SNP rs2442598, the subjects with the T/T genotype were 1.78 times likely to develop RA. The subjects with C/C genotype of SNP rs734701 were 0.53 times likely to develop RA than the subjects with TT genotype, suggesting the protective effect. The subjects with G/G genotype of SNP rs1823375 were 1.77 times likely to develop RA than the subjects with C/C genotype. The subjects with A/C and C/C genotype of SNP rs11137037 were 1.65 and 2.04 times likely to develop RA than the subjects with A/A genotype. The subjects with G/T and T/T genotype of SNP rs12674822 were 2.42 and 2.25 times likely to develop RA than the subjects with G/G genotype. The T allele over rs734701 can lead to higher serum erythrocyte sedimentation rate level (p = 0.006). The A allele over rs11137037 was associated with longer duration between disease onset and blood sampling (p = 0.003). Our study suggested that Ang2 might be a diagnostic marker and therapeutic target for RA therapy. Therapeutic agents that directly or indirectly modulate the activity of Ang2 may be the promising modalities for RA treatment.

VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis.

Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; p = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; p = 0.01). Our findings suggest that VEGF-C gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the VEGF-C gene may be promising for RA treatment.

Associations between Adipokines in Arthritic Disease and Implications for Obesity.

Secretion from adipose tissue of adipokines or adipocytokines, comprising of bioactive peptides or proteins, immune molecules and inflammatory mediators, exert critical roles in inflammatory arthritis and obesity. This review considers the evidence generated over the last decade regarding the effects of several adipokines including leptin, adiponectin, visfatin, resistin, chemerin and apelin, in cartilage and bone homeostasis in the pathogenesis of rheumatoid arthritis and osteoarthritis, which has important implications for obesity.

Increased expression of type 1 cannabinoid (CB1) receptor among patients with rotator cuff lesions and shoulder stiffness.

BACKGROUND: Shoulder stiffness is a disease manifested by pain, limited range of motion, and functional disability. The inflammatory and fibrosis processes play a substantial role in the pathogenesis of shoulder stiffness. The CB1 receptor has been recognized to mediate the processes of pathologic fibrosis. This study investigated the role of the CB1 pathway in pathogenesis of rotator cuff lesions with shoulder stiffness. METHODS: All of the patients undergoing repair surgery for rotator cuff lesions were recruited and subcategorized into subjects with and without shoulder stiffness. Reverse transcription-polymerase chain reaction assay was used to evaluate the expression level of CB1 and interleukin 1ß (IL-1ß) in the subacromial bursae, and enzyme-linked immunosorbent assay was used to measure the concentration of CB1 and IL-1ß in the subacromial fluid. Tenocytes treated with CB1 agonists and antagonists were also studied for the relationship of CB1 and the inflammatory cytokine IL-1ß. RESULTS: The patients with shoulder stiffness had higher messenger RNA (mRNA) expression (P = .040) and immunohistochemistry staining (P < .001) of CB1 in the subacromial bursa and higher CB1 concentration in the subacromial fluid (P = .008). Tenocytes treated with the CB1 agonist WIN 55,212-2 and antagonist AM251 showed increased expression of IL-1ß mRNA (P = .049) and suppressed expression of IL-1ß mRNA (P = .001), respectively. DISCUSSION: The CB1 pathway is involved in the pathogenesis of shoulder stiffness. It may be a promising target for the treatment of rotator cuff lesions with shoulder stiffness.

Complement component C3: Serologic signature for osteogenesis imperfecta. Analysis of a comparative proteomic study.

BACKGROUND/PURPOSE: Osteogenesis imperfecta (OI) is a disease characterized by low bone mass and bony fragility. This study investigated the serum proteomic profiles and their correlation with bone density for OI cases. METHODS: Twenty OI patients and 20 control participants were included. Comparative serum proteomic profiles were analyzed by two-dimensional electrophoresis and tandem mass spectrometry. Serum protein levels were measured by enzyme-linked immunosorbent assay. Cutoff values and areas under the curve were estimated by the receiver operating characteristic curve. Bone mineral density data was obtained from all OI patients. RESULTS: Candidate proteins identified by electrophoresis were complement component C3 (C3), vitamin D-binding protein (DBP), and haptoglobin (HP). Enzyme-linked immunosorbent assay validation showed that OI patients had decreased C3 and DBP and increased HP. The results were not affected by age or bisphosphonate use. Serum C3 levels significantly correlated with bone mineral density of the lumbar spine and hip. C3 had the greatest areas under the curve to distinguish OI from healthy controls. CONCLUSION: Serum C3, DBP, and HP are emerging serologic signatures for OI. Concentrations of serum C3 correlated with the T score of OI patients. C3 had the greatest areas under the curve of the three proteins to distinguish OI from healthy controls.

Effects of Adding Extracorporeal Shockwave Therapy (ESWT) to Platelet-Rich Plasma (PRP) among Patients with Rotator Cuff Partial Tear: A Prospective Randomized Comparative Study.

A rotator cuff tear is a prevalent ailment affecting the shoulder joint. The clinical efficacy of combined therapy remains uncertain for partial rotator cuff tears. In this study, we integrated extracorporeal shockwave therapy (ESWT) with platelet-rich plasma (PRP) injection, juxtaposed with PRP in isolation. Both cohorts exhibited significant improvements in visual analogue scale (VAS), Constant-Murley score (CMS), degrees of forward flexion, abduction, internal rotation, and external rotation, and the sum of range of motion (SROM) over the six-month assessment period. The application of ESWT in conjunction with PRP exhibited notable additional enhancements in both forward flexion (p = 0.033) and abduction (p = 0.015) after one month. Furthermore, a substantial augmentation in the range of shoulder motion (SROM) (p < 0.001) was observed after six months. We employed isobaric tag for relative and absolute quantitation (iTRAQ) to analyze the differential plasma protein expression in serum samples procured from the two groups after one month. The concentrations of S100A8 (p = 0.042) and S100A9 (p = 0.034), known to modulate local inflammation, were both lower in the ESWT + PRP cohort. These findings not only underscore the advantages of combined therapy but also illuminate the associated molecular changes.

Cannabinoid receptor 1 mediates glucocorticoid-induced bone loss in rats by perturbing bone mineral acquisition and marrow adipogenesis.

OBJECTIVE: Prolonged glucocorticoid treatment increases the risk of osteopenic disorders. Bone loss and marrow fat accumulation are prominent features of glucocorticoid-induced skeletal destruction. Cannabinoid receptor 1 (CB(1) ) has been found to regulate energy expenditure and adipose tissue lipogenesis. We undertook this study to investigate whether CB(1) signaling regulates glucocorticoid-induced bone loss. METHODS: Rats were administered glucocorticoid, CB(1) antisense oligonucleotide, CB(1) sense oligonucleotide, or the CB(1) antagonist AM251. Bone mineral density, microstructure, biomechanical strength, and signaling transduction were assessed by dual x-ray absorptiometry, micro-computed tomography, material testing, and immunoblotting, respectively. Primary bone marrow stromal cells were isolated for assessment of ex vivo osteoblast and adipocyte differentiation. RESULTS: Glucocorticoid administration accelerated bone deterioration and fatty marrow formation in association with up-regulation of CB(1) expression. Genetic and pharmacologic blockade of CB(1) by CB(1) antisense oligonucleotide and AM251 attenuated the deleterious effects of glucocorticoid treatment on bone mineral density, trabecular microarchitecture, and mechanical properties. CB(1) antagonism improved osteoblast survival, osteoblast surface, and bone mineral acquisition, but abrogated marrow adiposity. Knockdown of CB(1) restored osteogenic differentiation capacity and attenuated the promoting effects of glucocorticoid on adipogenic differentiation in primary bone marrow mesenchymal cells. CB(1) signaling modulated ERK, JNK, and Akt activation as well as runt-related transcription factor 2 and peroxisome proliferator-activated receptor γ2 signaling. Adiponectin signaling was activated by CB(1) regulation of bone formation and fatty marrow. CONCLUSION: CB(1) mediates glucocorticoid-induced suppression of bone formation and marrow fat homeostasis. CB(1) antagonism reduces adipogenic and apoptotic reactions in bone microenvironments, thereby abrogating the deleterious effects of glucocorticoid treatment on bone integrity. Modulation of CB(1) signaling has therapeutic potential for preventing glucocorticoid-induced osteopenic disorders.

Micro Ribonucleic Acid-29a (miR-29a) Antagonist Normalizes Bone Metabolism in Osteogenesis Imperfecta (OI) Mice Model.

Osteogenesis imperfecta (OI) is not curative nowadays. This study tried to unriddle the therapeutic potential of micro ribonucleic acid-29a (miR-29a) antagonist in treating OI in a mouse animal model (B6C3Fe a/a-Col1a2oim/J). We showed that the expression levels of miR-29a were higher in bone tissues obtained from the OI mice than from wild-type mice demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization assay. We established lentivirus-shuttled vector expressing miR-29a antisense oligonucleotide (miR-29a-AS) and miR-29a precursors (pre-miR-29a), showing that the inferior bony architecture in micro-computed tomography and pertinent morphometric parameters could be rescued by miR-29a-AS and deteriorated by pre-miR-29a. The decreased proliferating cell nuclear antigen (PCNA), increased Dickkopf-1 (DKK1), and decreased ß-catenin expression in OI mice could be accentuated by pre-miR-29a and normalized by miR-29a-AS. The decreased osteogenesis and increased osteoclastogenesis in OI mice could also be accentuated by pre-miR-29a and normalized by miR-29a-AS. miR-29a-AS did not seem to possess severe hepatic or renal toxicities.

Changes in Serum Bone Metabolism Markers after Living Donor Liver Transplantation (LDLT) and Their Association with Fracture Occurrences.

Living donor liver transplantation (LDLT) is lifesaving, but can lead to osteoporosis and fractures. In our 3-year study of 25 LDLT recipients, we observed significant reductions in lumbar spine and femoral neck T scores, along with bone resorption marker reductions and liver regeneration marker increases. Serum calcium levels increased, while osteoprotegerin (OPG) decreased and Dickkopf-related protein 1 (DKK-1) increased. Patients who suffered fractures within 3 years of LDLT had higher serum OPG, lower serum nuclear factor kappa B ligand (RANKL), a higher OPG/RANKL ratio and higher serum DKK-1 levels. OPG, RANKL, OPG/RANKL ratio and DKK-1 levels before LDLT predicted hip or spine fractures within three years after LDLT. Further research is necessary to determine the optimal level of osteoclastic activity for preventing fracture onset.

Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis.

BACKGROUND: Micro-ribonucleic acids (miRNAs) are involved in osteoarthritis (OA) pathogenesis and clock-controlled genes (CCGs) regulation. However, the interaction between miRNAs and CCGs remains unclear. METHODS: Human OA samples were used to assess CCGs expression. Cartilage-specific miR-128a knockout mouse model was established to investigate miR-128a's role in OA pathogenesis. Destabilization of the medial meniscus (DMM) model was employed to simulate OA. RESULTS: Transcription levels of nuclear receptor subfamily 1 group D member 2 (NR1D2) were lower in both human OA samples and wild-type mice undergoing DMM compared to non-OA counterparts. MiR-128a knockout mice showed reduced disturbances in micro-computed tomographic and kinematic parameters following DMM, as well as less severe histologic cartilage loss. Immunohistochemistry staining revealed a lesser decrease in NR1D2-positive chondrocytes after DMM in miR-128a knockout mice than in wild-type mice. NR1D2 agonist rescued the suppressed expression of cartilage anabolic factors and extracellular matrix deposition caused by miR-128a precursor. CONCLUSIONS: Cartilage-specific miR-128a knockout mice exhibited reduced severity, less disrupted kinematic parameters, and suppressed NR1D2 expression after DMM. NR1D2 enhanced the expression of cartilage anabolic factors and extracellular matrix deposition. These findings highlight the potential of employing miR-128a and CCG-targeted therapy for knee OA.

Exploring the Relationship between Periodontitis, Anti-Periodontitis Therapy, and Extra-Oral Cancer Risk: Findings from a Nationwide Population-Based Study.

This study aimed to evaluate the systemic impact of periodontitis, previously considered a local disease, on cancer occurrence. We enrolled 683,854 participants, comparing cancer incidence among those with and without periodontitis and assessing the impact of periodontal treatment on cancer risk. Regardless of gender, age, Charlson comorbidity index, or the use of non-steroidal anti-inflammatory drugs, periodontitis patients had a lower overall cancer risk than controls. However, men with periodontitis had a higher risk of prostate cancer (adjusted hazard ratio [aHR] = 1.22; 95% confidence interval [CI] = 1.10-1.35), and both men and women had a higher risk of thyroid cancer (women: aHR = 1.20, 95%CI = 1.04-1.38; men: aHR = 1.51, 95% CI = 1.15-1.99). Patients with periodontitis who received treatment showed a reduced cancer risk (aHR = 0.41; 95% CI = 0.38-0.44) compared to untreated patients. Proper treatment for periodontitis may lower an individual's cancer risk more than if they did not have the disease at all, suggesting that periodontitis is a modifiable risk factor for cancer.

The Impact of Chronic Pancreatitis on the Occurrences of Human Cancers: Real-World Data.

Chronic pancreatitis (CP) may induce systemic inflammation, potentially increasing cancer susceptibility. However, the link between CP and extra-pancreatic cancer remains underexplored. Employing Taiwanese National Health Insurance Database data from 2000 to 2017, we compared 5394 CP patients with 21,576 non-CP individuals through propensity score matching. CP patients exhibited a significantly higher cancer risk (adjusted hazard ratio (aHR) of 1.32 for females and 1.68 for males) and cumulative incidence (p < 0.001) compared to non-CP individuals. CP showed notable associations with pancreatic (aHR = 3.51), liver (aHR = 1.62), stomach (aHR = 2.01), and other cancers (aHR = 2.09). In terms of liver cancer, CP was significantly associated with patients without viral hepatitis, regardless of gender (aHR = 2.01 for women; aHR = 1.54 for men). No significant cancer occurrences were observed within the first year following CP diagnosis. Pancreatic or liver cancer developed in approximately half of CP patients within 2-3 years, while gastric cancer in male CP patients predominantly occurred around the fifth year after diagnosis. These findings inform potential cancer-screening plans for CP patients.

Avoidance of intramedullary violation in computer-assisted total knee arthroplasty lowers the incidence of periprosthetic joint infection compared with conventional total knee arthroplasty: A propensity score matching analysis of 5342 cases.

BACKGROUND: Conventional total knee arthroplasty (CONV-TKA) inevitably perturbs femoral medullary canal, disturbs medullary micro-architecture and increases blood loss and inflammatory responses. We hypothesized that avoidance of intramedullary violation may lower the incidence of periprosthetic joint infection (PJI). The aim of this study was to verify whether computer-assisted total knee arthroplasty (CAS-TKA) lowers the incidence of PJI as compared with CONV-TKA. METHODS: A propensity score matching study of 5342 patients who underwent CAS-TKA (n = 1085) or CONV-TKA (n = 4257) for primary osteoarthritis of the knee from 2007 to 2015 in our institute was performed. Patients who underwent CAS-TKA were matched to those who received CONV-TKA at a 1:2 ratio according to demographics and comorbidities. PJI was defined according to the Musculoskeletal Infection Society diagnostic criteria from the 2013 International Consensus Meeting. RESULTS: After controlling potential risk factors, the use of CAS-TKA resulted in a lower incidence of PJI as compared with CONV-TKA [adjusted hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.18-0.99]. The same trend in PJI reduction was observed with the usage of CAS-TKA under sensitivity testing [HR, 0.33; 95% CI, 0.12-0.95]. The cumulative incidence of PJI was lower in the CAS-TKA group than the CONV-TKA group (log-rank test, p = 0.013). CONCLUSION: Avoidance of intramedullary violation during TKA may play a pivotal role in lowering the incidence of PJI. The use of CAS-TKA can reduce the incidence of PJI, with a better survival rate in terms of being free of PJI, as compared with CONV-TKA.