The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection

BackgroundWe assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection.MethodsAmong 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay.ResultsHBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001.ConclusionHBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.     

Comparison of primary repair and repair with polyglycolic acid coated tube in recurrent laryngeal nerve cuts (an experimental study)

BackgroundRecurrent laryngeal nerve (RLN) injury is an important complication of thyroid surgery. In our study, we aimed to compare the effects of primary repair and polyglycolic acid (PGA) coated tube repair on nerve function and regeneration in RLN cuts in rats.MethodsTwenty seven rats were used for the study. Group-1 with only nerve cuts, group-2 with primary repair, and group-3 with conduit repair. The study was planned over two-stage surgery. In the first step, nerve defect formation and nerve repair were performed in the same session. In the second step, samples were taken from the subjects for histopathological.ResultsVocal cord mobility was proportionally higher in group-3 than other groups. However, there was no statistically significant difference between the groups (p < 0.239). The mean number of highest axons were detected the group-3.ConclusionsWe think that PGA coated conduit can provide a more accurate orientation of nerve fibers by creating an isolated environment when compared to the primary repair. And this may be the cause of functional improvement in the nerve.     

羟基磷灰石涂层—钛基牙种植体的动物植入实验

将５６枚等离子喷涂羟基磷灰石涂层－钛基牙种植体植入狗股骨干。分别在术后１、２、３、４个月时制取不脱钙标本切片，作组织学观察、显微Ｘ线摄影及计算机辅助植体－骨接触率测量。     

Outcomes of Long Tapered Hydroxyapatite-Coated Stems in Revision Total Hip Arthroplasty

The purpose of this study was to evaluate the outcome of femoral component revisions using a long tapered HA coated femoral revision stem. Between 2001 and 2008, 55 femoral component revisions were performed using this stem. Forty-one patients were available for follow up evaluation at average of 59 months. The clinical results were evaluated using the HHS and serial radiographs were evaluated for loosening. The mean HHS was 71 (range 22–100). Three hips required revision of KAR stem (1 aseptic loosening, 1 infection, 1 limb length discrepancy). Only one prosthesis demonstrated radiographic evidence of subsidence. Our study suggests that long tapered HA coated revision femoral components can provide stable fixation and in-growth in cases where there is good proximal femoral bone stock and favorable canal geometry.     

Long‐term outcomes in African American kidney transplant recipients under contemporary immunosuppression: a four‐yr analysis of the Mycophenolic acid Observational REnal transplant (MORE) study

Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four‐yr data on 904 patients receiving tacrolimus and enteric‐coated mycophenolate sodium (EC‐MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non‐AA (n = 686) patients. Mean tacrolimus dose was higher in AA vs. non‐AA patients but mean tacrolimus trough concentration was similar. Use of the recommended MPA dose in AA patients decreased from 78.9% at baseline to 33.1% at year 3. More AA patients received the recommended MPA dose with EC‐MPS than MMF at month 6 (56.2% vs. 35.7%, p = 0.016) and month 36 (46.6% vs. 16.7%, p = 0.029), with no safety penalty. Significantly, more AA patients received corticosteroids than non‐AA patients. Biopsy‐proven acute rejection was higher in AA vs. non‐AA patients (18.9% vs. 10.7%, p = 0.003), as was graft loss (10.9% vs. 4.4%, p = 0.003); differences were confirmed by Cox regression analysis. Patient survival was similar. Estimated GFR was comparable in AA vs. non‐AA patients. Kidney allograft survival remains lower for AA vs. non‐AA recipients even under the current standard of care.     

Development of a predictive in vitro dissolution for clarithromycin granular suspension based on in vitro-in vivo correlations

The objective of this study was to evaluate the in vitro behavior of different clarithromycin granular suspensions based on a developed in vitro-in vivo correlation model, using one reference and two test formulations. In vitro release rate data were obtained for each product using the USP apparatus II, operated at 50?rpm under different pH conditions. The dissolution efficiency was used to analyze the dissolution data. In vivo study was performed on six healthy male volunteers under fasting condition. Correlation was made between in vitro release and in vivo absorption. A linear model was developed using percent absorbed data versus percent dissolved data from the three products. Dissolution condition of 0.1N HCl for 1?h and then phosphate buffer at pH 6.8 was found to be the most discriminating dissolution method. Rate of absorption for the reference as estimated by Wagner-Nelson deconvolution was correlated with in vitro release with a correlation coefficient of 0.99. The in vivo results for the two test products were compared to the predicted values using the reference model with a correlation coefficient of 0.94. Furthermore, multiple level C correlations were obtained for some pharmacokinetic parameters with the corresponding in vitro kinetic parameters with correlation coefficients exceeding 0.90. Moreover, the interpretation of the in vitro and in vivo data with reference to formulations was discussed.     

Mycophenolate Fetal Toxicity and Risk Evaluation and Mitigation Strategies

The mycophenolic acid (MPA) preparations are one of the most commonly used immunosuppressants in the United States. However, these agents carry a black box warning regarding their use during pregnancy due to an association with increased risk of miscarriage and congenital defects. To ensure that the benefits of MPA outweigh the risks, the Food and Drug Administration (FDA) required all manufacturers of MPA products to propose risk evaluation and mitigation strategies (REMS). Four years after initially calling for proposals, the FDA approved a single shared REMS system in September 2012. The elements of the MPA REMS include a medication guide and elements to assure safe use (ETASU). The medication guide, which was previously FDA‐approved in 2008, should continue to be distributed to patients, and the ETASU requires physicians to complete training and obtain patient signatures on the “Patient‐Prescriber Acknowledgement Form.” A single, national, voluntary pregnancy registry is available, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA products among patients and possibly practitioners.     

Polysaccharides: a targeting strategy for colonic drug delivery

Introduction: Colon targeting has gained increasing importance for the topical treatment of diseases of the colon, such as Crohn's disease, ulcerative colitis, colorectal cancer and amebiasis. Various strategies used for targeting drugs to the colon include formation of a prodrug, coating with time or pH-dependent polymers, use of colon-specific biodegradable polymers, osmotic systems and pressure-controlled drug delivery systems. Among the different approaches used, polysaccharides that are precisely activated by the physiological conditions of the colon hold great promise, as they provide improved site specificity and meet the desired therapeutic needs.

Areas covered: This review aims to summarize the natural and modified properties of polysaccharides that are responsible for their colon targeting abilities. Emphasis is placed on describing formulation approaches that use polysaccharides as a strategy for targeting drugs to the colon.

Expert opinion: Polysaccharide-based colon-targeted drug delivery systems are effective when they are precisely activated by the physiological conditions of the colon. Absence of enzymes during colonic disorders might hinder the activation of the delivery system. To guarantee delivery of the drug to the colon, it is preferable to combine polysaccharides with enteric or cellulose polymers.     

Revision Hip Arthroplasty with A Modular Cementless Stem: Mid-Term Follow Up

Despite the increasing volume of revision total hip arthroplasty (THA) being performed in the United States, there are few studies reporting mid-term clinical and radiographic outcomes of modular fully porous-coated femoral stems. We retrospectively studied a consecutive series of patients who underwent revision THA with a modular extensively porous-coated femoral component at a single institution and by a single surgeon. The final study group included 54 hips (52 patients) followed for an average of 84 months. Ten-year survival rates with revision for any reason and revision for femoral loosening as endpoints were 94% and 100%, respectively. No complications regarding the modular junction were encountered. Of the 50 hips with adequate radiographs, all showed proximal ingrowth and 42 (84%) had both proximal and distal ingrowth. The modular, fully porous-coated femoral stem studied demonstrated excellent survivorship and bone ingrowth at mid-term follow up.