Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

Risk of post-contrast acute kidney injury in emergency department patients with sepsis.

INTRODUCTION: Although computed tomography (CT) is a useful tool for exploring occult infection in patients with sepsis in the emergency department, the potential nephrotoxicity of contrast media is a major concern. Our study aimed to investigate the association between use of contrast-enhanced CT and the risks of acute kidney injury and other adverse outcomes in patients with sepsis. METHODS: In total, 587 patients with sepsis who underwent CT scan (enhanced CT group: 105, non-enhanced CT group: 482) from January 2012 to December 2016 at a tertiary referral centre were enrolled in this retrospective analysis, and propensity score matching was performed to minimise the selection bias. The length of stay, incidences of acute kidney injury and emergent dialysis, and short-term mortality were compared between the two groups. RESULTS: Compared with patients in the non-enhanced CT group, patients in the contrast-enhanced CT group did not have increased risks of acute kidney injury (odds ratio [OR]=1.38, 95% confidence interval [CI]=0.55-3.43; P=0.489), emergent dialysis (OR=1.31, 95% CI=0.47-3.68; P=0.602), or short-term mortality (OR=0.90, 95% CI=0.48-1.69; P=0.751). In addition, there was no significant difference in the median length of hospital stay between survivors in the two groups (20 vs 19 days, P=0.742). CONCLUSIONS: Intravenous contrast administration during CT scanning was not associated with prolonged length of hospital stay in patients with sepsis in an emergency setting. Moreover, the use of contrast-enhanced CT was not associated with increased risks of acute kidney injury, emergent dialysis, or short-term mortality.

The incidence and predictors of HBV relapse after cessation of tenofovir therapy in chronic hepatitis B patients.

This study investigates the incidences and predictors of hepatitis B virus (HBV) relapse after tenofovir disoproxil fumarate (TDF) therapy in hepatitis B e antigen (HBeAg)-positive and -negative patients. We retrospectively recruited 143 chronic hepatitis B (CHB) patients without cirrhosis (39 HBeAg-positive and 104 HBeAg-negative patients) who were previously treated with TDF and had post-treatment follow-up for at least 6 months (median: 55, IQR 36-85 weeks). All the patients fulfilled the stopping criteria of APASL 2012. The virological and clinical relapse rates at 104 weeks in HBeAg-positive patients were 66.6% and 59.1%, while they were 72.3% and 55.9%, respectively, in HBeAg-negative patients. Cox regression analysis revealed that the higher end-of-treatment HBsAg levels were an independent factor of virological relapse in HBeAg-positive and HBeAg-negative patients. The end-of-treatment HBsAg levels of 200 (area under the receiver operating characteristic (AUROC): 0.624) and 80 IU/mL (AUROC: 0.959) were the optimal values for predicting HBV relapse in HBeAg-positive and HBeAg-negative patients, respectively. The virological relapse rate at 78 weeks was 14.3% and 19.6% in HBeAg-positive and HBeAg-negative patients who achieved HBsAg ≤200 IU/mL and HBsAg ≤80 IU/mL, respectively. Two patients experienced hepatic decompensation upon hepatitis flares, and no patient died after timely retreatment. Seven patients experienced off-therapy HBsAg loss. The cumulative rates of HBsAg loss at 104 weeks were 45.5% and 59.3% in patients with end-of-treatment HBsAg ≤80 IU/mL and ≤50 IU/mL, respectively. In conclusions, the end-of-treatment HBsAg levels were a useful marker for predicting HBV relapse in HBeAg-positive and HBeAg-negative CHB patients.

Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. DESIGN: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. RESULTS: We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05). CONCLUSION: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.

Abnormal perfusion in patellofemoral subchondral bone marrow in the rat anterior cruciate ligament transection model of post-traumatic osteoarthritis: a dynamic contrast-enhanced magnetic resonance imaging study.

OBJECTIVE: Although anterior cruciate ligament (ACL) injury is a well-recognized risk factor for developing knee post-traumatic osteoarthritis (PTOA), the process in the patellofemoral (PF) joint after ACL injury is still under-researched. Our aim was to investigate the perfusion changes in PF subchondral bone marrow in the rat ACL transection (ACLX) model of PTOA using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DESIGN: Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group): a normal control group and groups receiving ACLX and sham-surgery, respectively, in the right knee. Perfusion parameters in the patellar and femoral subchondral bone marrows of all rats were measured on DCE-MRI at 0, 4, 8, and 16 weeks after respective treatment. After the last MRI at week 16, the rats were sacrificed and their right knees were harvested for histologic examination. In addition, to observe the long-term histologic change in PF joints, 9 additional rats (n = 3 in each group) were included and sacrificed at week 32 for histologic examination. RESULTS: In the ACLX group vs the sham and control groups, the perfusion parameters were significantly changed in both patellar and femoral subchondral bone marrows at week 16. Histologic examination revealed cartilage defects in ACLX rats at 32 weeks after surgery. CONCLUSIONS: These data point to a possible functional relationship between subchondral bone marrow perfusion abnormalities and cartilage breakdown in PTOA. Moreover, the perfusion parameters derived from DCE-MRI can potentially serve as biomarkers of early OA.

Targeting post-translational modifications of histones for cancer therapy.

Post-translational modifications (PTMs) on histones including acetylation, methylation, phosphorylation, citrullination, ubiquitination, ADP ribosylation, and sumoylation, play important roles in different biological events including chromatin dynamics, DNA replication, and transcriptional regulation. Aberrant histones PTMs leads to abnormal gene expression and uncontrolled cell proliferation, followed by development of cancers. Therefore, targeting the enzymes required for specific histone PTMs holds a lot of potential for cancer treatment. In this review article, we retrospect the latest studies in the regulations of acetylation, methylation, and phosphorylation of histones. We also summarize inhibitors/drugs that target these modifications for cancer treatment.

Saturated fatty acid induces cancer stem cell-like properties in human hepatoma cells.

Hepatic steatosis has been reported to be a risk factor for the development of liver cancer. The underlying mechanism for carcinogenesis remains to be elucidated. It has been postulated that cancer stem cells (CSCs) within tumor tissues are a subset of cells with stem cell properties of self-renewal and undifferentiation. The purpose of this study was to investigate the effects of a saturated fatty acid, palmitate (PA), on CSC-like properties of human hepatoma HepG2 cells. We investigated the effects of PA on HepG2 cells and primary rat hepatocytes (PRH) by exposing them to PA to induce lipid accumulation. Significant fat accumulation was observed by Oil Red O staining in cells exposed to PA, and it was accompanied by significant increase in NFκB (p65) nuclear translocation in HepG2 cells. Notably, PA significantly enhanced the sphere forming ability of HepG2 cells, but not PRH. Furthermore, PA significantly increased stemness gene expressions of Sox2 and Oct4, and sonic hedgehog (Shh) production. Notably, NFκB inhibitors, N-Acetyl-L-cysteine and pyrollidine dithiocarbamate, and a NOX inhibitor, diphenyleneiodonium, significantly attenuated PA-induced sphere forming ability of HepG2 cells. Our results suggest that lipid accumulation may not only induce pro-inflammatory responses in hepatocytes but may also activate CSC-like properties of hepatoma cells through NFκB activation.

Multidrug overdose-induced myoclonus complicated by rhabdomyolysis: possible role and mechanism of muscle toxicity of risperidone.

WHAT IS KNOWN AND OBJECTIVE: Atypical antipsychotics are considered safe for treating schizophrenia and are rarely reported to induce rhabdomyolysis. CASE SUMMARY: Here is a case of a woman with schizophrenia who developed rhabdomyolysis following overdose of risperidone, trihexyphenidyl and benzodiazepines. There was no recurrence of rhabdomyolysis when above medication was resumed with therapeutic dose. WHAT IS NEW AND CONCLUSION: Multidrug overdose are common but are rarely reported to induce rhabdomyolysis. Overdose risperidone may increase the risk of rhabdomyolysis and need to be kept in mind.

Streptococcus agalactiae infective endocarditis with large vegetation in a patient with underlying protein S deficiency.

We present a case of a patient with underlying protein S deficiency who suffered from infective endocarditis with a large anterior mitral leaflet (AML) mass of approximately 4.5 cm in length. Intraoperative transesophageal echocardiography (TEE) revealed the mass at the AML base and a rupture of the posterior mitral leaflet chordae tendinae. The vegetation's large size may have been caused by one or more of three factors: location, underlying disease, and the microorganism causing infection. Patients with protein S deficiency are prone to thromboembolic events during cardiac surgery. Infective endocarditis caused by Streptococcus agalactiae usually has a poor prognosis, and, thus, early surgery is recommended.

Assessment of cam-type femoroacetabular impingement by ultrasonography: value of anterior femoral distance measurements.

PURPOSE: To retrospectively determine the reproducibility and performance of a quantitative measurement for cam-type femoroacetabular impingement (FAI) designated as the anterior femoral distance (AFD) of the femoral head-neck junction identified at ultrasonography (US). MATERIALS AND METHODS: 72 patients with clinically suspected FAI were retrospectively evaluated, and US studies were performed during a 20-month period. Of these, we selected 53 patients who underwent subsequent magnetic resonance (MR) arthrography and had adequate recorded US images. All the longitudinal US images of the anterior and anterosuperior contours of the femoral head-neck junction were recorded by a radiologist. 33 of these US images were also recorded by a technician. An alpha angle of > 55° on MR arthrography was indicative of cam-type FAI. Two independent radiology residents blinded to the clinical data and MR arthrography measured the maximal femoral head-neck overgrowth defined as the AFD on US (AFD-US). Reproducibility was assessed using intra-class correlation coefficients (ICCs) and Bland-Altman plots, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. RESULTS: AFD-US showed high intra- and inter-rater agreement (ICC = 0.913 - 0.968) in all measurements and good reproducibility among different operators in the anterior contour measurements (ICC = 0.881) but not in the anterosuperior contour measurements (ICC = 0.196). An AFD-US cut-off value of 4.0 mm in the anterior contour yielded the greatest sensitivity (80.9 %) and specificity (87.5 %) for the diagnosis of cam-type FAI by ROC analysis. CONCLUSION: AFD-US of the anterior contour of the femoral head-neck junction is helpful in diagnosing cam-type FAI.

Changes in physicochemical properties of egg white and yolk proteins from duck shell eggs due to hydrostatic pressure treatment.

The shell of the duck egg did not crack after pressure treatments (300 to 500 MPa; 25 degrees C; 10 min) in this study; therefore, the changes of physicochemical properties of egg white and yolk proteins from the intact shell egg by pressure treatment were first investigated and compared with those of pressurized hen liquid eggs. Although the proximate compositions of duck eggs and hen eggs were similar, the moisture and protein contents of hen whole eggs were higher than those of duck whole eggs. The protein contents of duck egg white and yolk were slightly lower than those of hen eggs, and the moisture content of duck egg white was equal to that of hen egg white, whereas that of duck egg yolk was lower than that of hen egg yolk. After pressure treatment at 500 MPa, the results of solubility, sulfhydryl content, surface hydrophobicity, and residual denaturation enthalpy showed that egg white proteins underwent slight but significant unfolding and aggregation, whereas pressure treatments below 500 MPa induced insignificant changes in the physicochemical properties. On the other hand, pressure treatments at 400 and 500 MPa significantly reduced the solubility and residual denaturation enthalpy of egg yolk proteins. However, the native PAGE result showed that pressure treatment up to 500 MPa did not affect the protein components of egg white and yolk. The results showed that the application of pressure treatment on duck shell egg may induce reversible denaturation of both egg white and yolk proteins. The egg white and yolk proteins may be prevented from denaturation after pressure treatment in the presence of the eggshell compared with the absence of the eggshell. As reported in the literature, pressure treatments at 300 to 500 MPa and 25 degrees C would be efficient for decontamination of duck shell eggs. Therefore, based on the consideration for food safety and functional properties, pressure processing can be a good preservation technique for duck shell eggs.

Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer.

BACKGROUND: Mutations of the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients predict the patients who will respond to EGFR tyrosine kinase inhibitor (TKI) treatment. A recent study has suggested that 33% of NSCLC showed primary tumor/metastasis discordance of EGFR expression by immunohistochemistry analysis. We intended to find out whether the EGFR mutations of primary lung cancers are concordant to that of corresponding metastatic tumors. MATERIALS AND METHODS: We analyzed EGFR exons 18-21 from paired primary and metastatic tumors in 67 lung cancer patients who had not received TKI before tissues were sampled. RESULTS: Using the direct sequencing method, 9 of 18 (50%) patients with EGFR mutation-positive primary lung tumors had lost the mutations in metastases. For 26 patients who were EGFR mutation positive in the metastatic tumors, 17 (65%) were negative in the primary tumors. We analyzed these paired tissues with discrepant EGFR mutations by the Scorpion Amplified Refractory Mutation System assay. Finally, the discordant rate reached 27% (18 of 67 cases). CONCLUSION: EGFR mutations in primary lung tumors do not always reflect the same situation in metastases. Analysis of EGFR mutations in the primary lung tumor would be inadequate for planning the use of TKI for advanced NSCLC.

Development of mouse embryos in vitro: preimplantation to the limb bud stage.

Mouse embryos were grown successfully in vitro from the blastocyst stage to the limb bud stage. Mouse blastocysts grown in vitro for 10 days showed blood circulation in the yilk sac, forelimb buds, and the primordia of liver, pancreas, and lungs. These characteristics are indicative of a developmental stage equivalent to one-half of the total gestation period in utero. Improvements in culture conditions from days 7 to 9 have made it feasible to culture mouse blastocysts beyond the early somite stage.

Monozygotic twin formation in mouse embryos in vitro.

Monozygotic twins developed from cultured murine blastocysts at the ratio of approximately 1:100. The locus at which the denuded blastocysts attached to the culture dish was usually a random section of their mural trophoblasts, in which case single egg cylinders developed unilaterally. However, in those few blastocysts attaching with their antipolar mural trophoblasts, the inner cell mass became subdivided into two parts because of restrictions imposed on its growth by the apically situated polar trophoblasts and the plastic substrate. Each subdivision apparently incorporated totipotent cells, resulting in the bilateral formation of two egg cylinders sharing the same ectoplacental cone.

Hoffa fracture: should precautions be taken during fixation and rehabilitation?

A coronal fracture of a femoral condyle (Hoffa fracture) is an unusual injury and there are only a handful of reports discussing it. We report a case of a 52-year-old worker who fell from a height, suffering lower limb injuries, including a Hoffa fracture with comminution, and had problems with malunion during the postoperative period. Clinicians should be aware that rehabilitation programmes need to be tailored to the method of fixation used to manage this uncommon fracture pattern.

Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma.

Malignant pleural effusions (MPEs) are often observed in lung cancer, especially adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in lung adenocarcinoma. The purpose of the present study was to investigate the EGFR mutation rate in MPEs of lung adenocarcinoma. Between June 2005 and December 2006, 136 MPEs from lung adenocarcinoma were collected for EGFR mutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of lung adenocarcinoma from patients without MPEs were assessed for EGFR mutation. The EGFR mutation rate was significantly higher in the patients with MPEs than in the patients without (68.4% versus 50.5%). The EGFR mutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0-1, and EGFR mutation were significantly associated with a longer overall survival for lung adenocarcinoma patients with MPEs. The patients with malignant pleural effusions related to lung adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for lung adenocarcinoma with malignant pleural effusions in east Asia.

Rat liver ischemia/reperfusion induced proinflammatory mediator and antioxidant expressions analyzed by gene chips and real-time polymerase chain reactions.

OBJECTIVE: Ischemia/reperfusion (I/R) of the rat liver induces injury; however, few studies have investigated gene expressions associated with this phenomenon. In this study, gene chip and real-time polymerase chain reactions (PCR) were used to study the expressions of the proinflammatory mediators and antioxidants after I/R. MATERIALS AND METHODS: Ischemia was induced by clamping the common hepatic artery and portal vein for 40 minutes followed by 90 minutes reperfusion. Blood samples collected before ischemia and after reperfusion were analyzed for alanine amino transferase, lactic dehydrogenase, hydroxyl radicals, nitric oxide (NO), and tumor necrosis factor alpha (TNFalpha). Expressions of TNFalpha, interleukin 12 (IL12), cyclooxygenase II (COXII), and other inflammatory mediators were analyzed by gene chips. COXII, TNFalpha, and antioxidants of mitochondrial superoxide dismutase (SOD(Mn)), catalase, and heat shock protein 70 (HSP70) were double confirmed by real-time PCRs. RESULTS: This protocol resulted in elevations in the blood concentrations of NO, hydroxyl radicals, TNFalpha, ALT, and LDH (P < .01) in the I/R but not the sham-operated group. Reperfusion induced significant increases in the expressions of TNFalpha, IL12, COXII, SOD(Mn), catalase, and HSP70. Real-time PCR also demonstrated increases in mRNA expressions of the proinflammatory mediators and antioxidants. CONCLUSIONS: This protocol resulted in oxidative stress, nitrosative stress, and liver injury. The increases in expressions of both proinflammatory mediators and antioxidants suggested that an imbalance between inflammation and anti-inflammation could be the possible reason for the liver injury after I/R.

What happens after no contralateral exploration in total extraperitoneal (TEP) herniorrhaphy of clinical unilateral inguinal hernias?

BACKGROUND: While performing unilateral TEP herniorrhaphy, controversy still exists about whether to do contralateral exploration or not. Routine contralateral exploration has been proposed to prevent metachronous contralateral hernias by the repair of incidental contralateral occult hernias. Some surgeons have even proposed to do prophylactic bilateral TEP herniorrhaphy for unilateral hernia patients. To evaluate the appropriateness of not doing contralateral exploration in unilateral TEP herniorrhaphy, we reviewed our experiences under our practice of no contralateral exploration and we also reviewed other published literature. METHODS: A total of 305 patients who underwent 313 TEP herniorrhaphies for inguinal hernias by a single surgeon during August 2012-July 2016 at Chia-Yi Christian Hospital were enrolled in this retrospective study. Demographic, perioperative and follow-up data were obtained for analysis and review. RESULTS: Of the 305 patients, 261 patients had unilateral TEP herniorrhaphy and 44 patients had bilateral TEP herniorrhaphy. The mean operation time for the unilateral TEP herniorrhaphy group was 59.8 min, and for the bilateral TEP herniorrhaphy group it was 85.2 min (p < 0.001). Seven of 261 (2.7%) patients had metachronous contralateral hernia after unilateral TEP herniorrhaphy. There were no statistically significant differences in any of the outcome variables when comparing the sequential and simultaneous primary bilateral TEP herniorrhaphies. CONCLUSIONS: Without routine contralateral exploration, the incidence of metachronous contralateral hernia was 2.7% (7/261) in unilateral hernia patients. This is acceptable as metachronous hernia also occurred in 3.2% of patients with negative contralateral exploration according to our literature review. Sequential and simultaneous bilateral primary TEP herniorrhaphy outcomes were similar. We conclude that no exploration for the other groin is a justified decision for unilateral inguinal hernia patients.

Hemopoiesis of the cultured whole mouse embryo.

In vitro cultured murine embryos provide a valuable methodology for studying the ontogeny of hemopoiesis in mammalian embryos. Under improved conditions, 49% of mouse embryos cultured from the blastocyst stage reached the early somite stage. The development of the embryo was arrested at different stages by omitting human cord serum from the culture medium at specific times. These observations suggest the appearance and differentiation of the first hemopoietic cells in the mouse yolk sac to be independent of a normal embryo. In the yolk sac of all cultured mouse embryos, hemopoietic cell differentiated into a major cell type, erythroblasts, and minor cell types such as monocytes, macrophages, and granulocytic cells. A small number of hemopoietic cells remained undifferentiated.