A Functional Polymorphism Downstream of Vitamin A Regulator Gene CYP26B1 Is Associated with Hand Osteoarthritis.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10-7-7.31 × 10-6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10-7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10-6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D' = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

Lunate dislocation with avulsed triquetral fracture: A case report.

BACKGROUND: Lunate dislocation is an uncommon traumatic wrist injury that require prompt surgical management. Misdiagnosis or delayed treatment often leads to a poor outcome. Open reduction and surgical repair of disrupted ligaments are done in most cases to prevent long-term joint dysfunction. However, this method has certain limitations that include partial functional improvement, which poses a high risk for degenerative arthritis and wrist instability. CASE SUMMARY: A 37-year-old man presented to the Emergency Department of our hospital following a motorcycle accident. Physical examination revealed swelling and tenderness of the right hand and wrist. The patient was initially misdiagnosed with a wrist contusion by an emergency physician, but was eventually diagnosed with lunate dislocation associated with a triquetral avulsed fracture, indicated for open reduction and ligament repair. We performed closed reduction and two Kirschner wire fixations following Tavernier's method. The injured hand was protected with a standard short-arm orthosis for one month. The patient returned to normal daily work without discomfort at five months postoperatively. Encouragingly, there was no lunate necrosis or arthritis in the latest radiologic examinations. CONCLUSION: This case provides evidence that the closed reduction technique for addressing such cases can reduce soft tissue destruction.

The association between gallstone disease (GSD) and hip fracture: a nationwide population-based study.

Objectives: Despite the high prevalence of gallstone disease (GSD), the shared risk factors of GSD and osteoporosis, and the known association between hip fracture and hepatobiliary diseases, the association between hip fracture and GSD is not currently clear. Therefore, we performed a nationwide population-based study to investigate the association between GSD and hip fracture to determine the impact of cholecystectomy on the risk of fracture.Methods: In this study, we assessed all subjects in the longitudinal health insurance database (LHID) between 2000 and 2011, excluding those subjects aged >20 years old and those with a previous history of hip fracture (ICD-9-CM 820). Among those that were included, subjects with at least two or more outpatient visits or with one record of hospitalization under the coding of GSD (ICD-9-CM code: 574) were allocated to the GSD cohort. The remaining subjects were designated to the control cohort. All participants were followed till the onset of hip fracture, withdrawal from the NHI, or the end of 2013.Results: We found that the cumulative incidence of hip fracture was higher in the GSD cohort than in the control cohort (log-rank test: p-value < 0.01). After adjustment, the GSD patients had a 1.21-fold risk of hip fracture compared to control subjects (aHR = 1.21, 95% CI = 1.21-1.30). Comparison between those subjects without GSD and those without cholecystectomy revealed that the risk of hip fracture was higher among GSD patients that had not undergone cholecystectomy (aHR = 1.17, 95% CI = 1.06-1.29) or those that had undergone cholecystectomy (aHR = 1.22, 95% CI = 1.06-1.41).Conclusion: Based upon these results, we concluded that GSD was associated with an increased risk of hip fracture regardless of whether the patient had undergone cholecystectomy.

Adjacent segment disease following Dynesys stabilization for lumbar disorders: A case series of mid- and long-term follow-ups.

BACKGROUND: Radiologic adjacent segment degeneration (ASDeg) can occur after spinal surgery. Adjacent segment disease (ASDis) is defined as the development of new clinical symptoms corresponding to radiographic changes adjacent to the level of previous spinal surgery. Greater pre-existing ASDeg is generally considered to result in more severe ASDis; nonetheless, whether the ASDeg status before index surgery influences the postoperative risk of revision surgery due to ASDis warrants investigation. AIM: To identify possible risk factors for ASDis and verify the concept that greater preexisting ASDeg leads to more severe ASDis. METHODS: Data from 212 patients who underwent posterior decompression with Dynesys stabilization from January 2006 to June 2016 were retrospectively analyzed. Patients who underwent surgery for ASDis were categorized as group A (n = 13), whereas those who did not were classified as group B (n = 199). Survival analysis and Cox proportional hazards models were used to compare the modified Pfirrmann grade, University of California-Los Angeles grade, body mass index, number of Dynesys-instrumented levels, and age. RESULTS: The mean time of reoperation was 7.22 (1.65-11.84) years in group A, and the mean follow-up period was 6.09 (0.10-12.76) years in group B. No significant difference in reoperation risk was observed: Modified Pfirrmann grade 3 vs 4 (P = 0.53) or 4 vs 5 (P = 0.46) for the upper adjacent disc, University of California-Los Angeles grade 2 vs 3 for the upper adjacent segment (P = 0.66), age of < 60 vs > 60 years (P = 0.9), body mass index < 25 vs > 25 kg/m2 (P = 0.3), and sex (P = 0.8). CONCLUSION: Greater preexisting upper ASDeg was not associated with a higher rate of reoperation for ASDis after Dynesys surgery. Being overweight tended to increase reoperation risk after Dynesys surgery for ASDis.

Integrin-linked kinase is involved in TNF-alpha-induced inducible nitric-oxide synthase expression in myoblasts.

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine produced by activated macrophages. Nitric oxide (NO) is a highly reactive nitrogen radical implicated in inflammatory responses. We investigated the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and NO production stimulated by TNF-alpha in cultured myoblasts. TNF-alpha stimulation caused iNOS expression and NO production in myoblasts (G7 cells). TNF-alpha-mediated iNOS expression was attenuated by integrin-linked kinase (ILK) inhibitor (KP392) and siRNA. Pretreatment with Akt inhibitor, mammalian target of rapamycin (mTOR) inhibitor (rapamycin), NF-kappaB inhibitor (PDTC), and IkappaB protease inhibitor (TPCK) also inhibited the potentiating action of TNF-alpha. Stimulation of cells with TNF-alpha increased ILK kinase activity. TNF-alpha also increased the Akt and mTOR phosphorylation. TNF-alpha mediated an increase of NF-kappaB-specific DNA-protein complex formation, p65 translocation into nucleus, NF-kappaB-luciferase activity was inhibited by KP392, Akt inhibitor, and rapamycin. Our results suggest that TNF-alpha increased iNOS expression and NO production in myoblasts via the ILK/Akt/mTOR and NF-kappaB signaling pathway.

The Predictive Value of Pre-/Postneoadjuvant Chemoradiotherapy MRI Characteristics for Patient Outcomes in Locally Advanced Rectal Cancer.

RATIONALE AND OBJECTIVES: This study aimed to investigate the predictive value of pre-/postneoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) characteristics for the long-term survival outcomes in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: We retrospectively evaluated pre- and post-nCRT MRI and clinicopathologic characteristics of LARC patients. The 3-year disease-free survival (DFS) was estimated using the Kaplan-Meier product-limit method. Associations between MRI variabilities and survival outcomes were assessed using Cox proportional hazards model. RESULTS: In total, 171 LARC patients (112 men and 59 women) with a median age of 55 years (range, 27-82 years) treated with nCRT were evaluated. The median follow-up was 47.6 months, and the 3-, 4-, and 5-year DFS in the overall cohort was 76.6%, 74.5%, and 73.7%, respectively. MRI assessment of extramural venous invasion (mrEMVI) positivity was a significant independent adverse factor of long-term survival (hazard ratio [HR] = 2.589, 95% confidence interval [CI] = 1.398-4.794, p = 0.002) on multivariate analysis. Patients with positive mrEMVI had significantly lower 3-year DFS than those with negative mrEMVI (52.6 months vs 65.1 months; p = 0.003). Moreover, the tumor regression grade on MRI (mrTRG) also significantly correlated with survival outcomes in patients with LARC. Patients with partial response on post-nCRT MRI (mrPR) showed short DFS than those with complete response (mrCR; HR = 4.914, 95% CI = 1.176-20.533, p = 0.029). The 3-year DFS of mrCR and mrPR patients were 74.3 months and 58.9 months, respectively (p = 0.011). CONCLUSION: The pre-/post-nCRT MRI characteristics may be used to long-term survival stratification in LARC patients. mrEMVI positivity was an independent adverse prognostic indicator for 3-year DFS. Further, mrTRG may also be a predictive factor for the prognosis of LARC patients. The pre-/post-nCRT MR imaging may offer more information for providing individualized treatment.

Treatment for ipsilateral fractures of femoral neck and shaft.

BACKGROUND: Concomitant ipsilateral femoral shaft and neck fractures present a challenge to the orthopaedic surgeon, and no consensus has yet emerged on the optimal treatment method. We report the results of a retrospective study of 43 patients with these complex fractures who were treated at a single Level 1 trauma centre. PATIENTS AND METHODS: The study participants consisted of 28 males and 15 females with a mean age of 43 years. The mean follow-up period was 48 months. Four different treatment methods were used: (1) antegrade reamed intramedullary nailing of the shaft with cancellous screw fixation of the neck, (2) dynamic hip screw (DHS) fixation of the neck and low-contact dynamic compression plate (LCDCP) fixation of the shaft, (3) cancellous screw fixation of the neck and LCDCP fixation of the shaft, and (4) reconstruction nailing of both shaft and neck. RESULTS: No statistically significant differences in amount of blood loss, duration of surgery, total complication rate, nor clinical results were found among the four treatment methods. For femoral neck fracture, however, the complication rate of cannulated screw with antegrade intramedullary nailing fixation was 11 times that of DHS with LCDCP fixation. CONCLUSIONS: Antegrade nail with screw fixation is not a recommended treatment method in patients with ipsilateral femoral shaft and neck fractures.