Impact of pretransplant donor‐specific antibodies on kidney allograft recipients with negative flow cytometry cross‐matches

The Luminex test can detect low levels of donor‐specific antibody (DSA) that cannot be detected by flow‐cytometric cross‐matching (FCXM) in kidney transplantation (KT). This study evaluated the impact of DSA on clinical outcomes in KT recipients negative on FCXM. Of 575 consecutive patients who underwent living donor KT between January 2013 and July 2016, 494 (85.9%) were DSA‐negative and 81 (14.1%) were DSA‐positive. Although rates of acute cellular rejection (ACR) at 1 year were similar in the 2 groups (P = .54), the incidence of antibody‐mediated rejection (ABMR) was significantly higher in the DSA‐positive group (P < .01). There was no statistically significant association between rejection‐free graft survival (RFGS) rates and pretransplant class I DSA. However, evaluation of pretransplant class II DSA showed that RFGS rates were significantly lower in patients with mean fluorescence intensity (MFI) >3000 than in patients with DSA‐negative (P < .01). On multivariate analyses, class II DSA MFI ≥5000 was a significant risk factor for acute rejection (hazard ratio, 7.48; P < .01). These findings suggested that pretransplant DSA alone did not affect graft survival in KT recipients without desensitization. However, class II DSA MFI >5000 was an independent predictor of acute rejection in DSA‐positive patients.     

Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Aerosol gene delivery may provide the alternative for safe and effective treatment for lung cancer. Therefore, current study was performed to elucidate the potential effects of C-terminal modulator protein (CTMP) via aerosol on lung tumorigenesis. Lentiviral vector-CTMP was delivered into K-ras null lung cancer mice through the nose-only inhalation system for 30 min. After 48 h, the potential effects of CTMP on Akt1-related signals and cell cycle regulation in the lungs were evaluated by western blot, immunohistochemistry and zymography. Lentivirus-based CTMP delivery inhibited the Akt1 activity through selective suppression of Akt1 phosphorylation at Ser473. Aerosol delivery of CTMP inhibited proteins important for Akt1 signals, cell cycle and tumor metastasis in lungs of K-ras null mice. Together, our results suggest that lentivirus-mediated aerosol delivery of CTMP may be compatible with noninvasive in vivo gene therapy. Our results emphasize the importance of noninvasive-targeted delivery of CTMP for lung cancer therapy in the future. While the studies are conducted in mice, it is envisioned that noninvasive targeting the specific genes responsible for cancer progression is an attractive strategy for effective anticancer therapeutics.     

Plasma nitroglycerin concentrations and hemodynamic effects of sublingual, ointment, and controlled-release forms of nitroglycerin

After a sublingual test dose, 12 healthy men aged 21 to 29 yr were treated with controlled-release transdermal nitroglycerin skin patches designed to deliver 10 mg/day nitroglycerin and with nitroglycerin ointment (2%) (1-in amount from the tube spread over 50 cm2) for 24 hr in a double-blind crossover study. Assessment was by measurement of nitroglycerin in plasma, blood pressure, and pulse rate. The mean plasma concentration of nitroglycerin during ointment dosing was approximately 200% to 400% that during skin patch dosing. Levels during ointment dosing were closer to those from sublingual dosing than were those during skin patch dosing. Blood pressure and pulse rate changes were much the same during both transdermal treatments. Calculations showed that delivery of nitroglycerin from the skin patches would have to be over 40 to 80 cm2 of the skin to achieve nitroglycerin exposure of the order of that induced by 1 in of ointment spread over 50 cm2 or from sublingual dosing.     

The use of vacuum-assisted closure in spinal wound infections with or without exposed dura

Introduction

The treatment of postoperative deep spinal wound infection involves debridement and intravenous antibiotics. Authors have previously reported success in a small series of patients treated with vacuum-assisted closure (VAC) therapy, but its use over exposed dura is controversial and the outcome has not been reported in large series.

Purpose

To review the outcomes following the treatment of postoperative spinal infections with VAC therapy, particularly those with exposed dura.

Methods

This is a review of prospectively collected data in 42 patients, all of whom had deep postoperative spinal infections. 30 of these patients had exposed dura. All patients had an initial debridement followed by application of VAC Whitefoam (with exposed dura) or grey Granufoam (where no dura was exposed). Pressure was set at 50 mmHg with exposed dura or 125 mmHg where no dura was exposed. All patients underwent a minimum 6 week course of antibiotics. We report on the number of visits to theatre required for dressing changes and debridement and the eventual outcomes.

Results

Five patients required a flap reconstruction. Two patients died before definitive final closure due to other complications (pneumonia and stroke). In all the other patients, their wounds healed fully. A mean of 2.3 infection surgeries were required to eradicate infection and achieve wound closure.

Conclusions

This is one of the largest studies which confirms the safety and efficacy of VAC dressings in patients with spinal wound infections, even when the dura is exposed.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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Evaluation of Denka-Seiken turbidimetric high-sensitivity C-reactive protein assay.

C-reactive protein measured with a high sensitivity method (hsCRP) is an important prognostic indicator in patients with an acute coronary syndrome. We evaluated hsCRP measurement with regard to its precision, functional sensitivity, linearity, and interferences using Denka-Seiken CRP II Latex X2 turbidimetric method on two chemistry autoanalyzers: Olympus AU 640 and Hitachi 747. The coefficients of variation (CV) for within-run and between-run precision of hsCRP were satisfactory on both autoanalyzers. Functional sensitivities, expressed as concentrations associated with 10% total interassay CV, were 0.19 mg/l for the Hitachi 747 analyzer and 0.41 mg/l for the Olympus AU 640. The assay was linear up to 300 mg/l with a wide measuring range, which suggested the possibility of using this hsCRP measurement as an inflammation marker and as a risk marker for coronary heart disease (CHD). No significant interference was observed up to a triglyceride concentration of 34 mmol/l, and up to hemoglobin concentration of 4 g/l. The determination of hsCRP by turbidimetric method was satisfactory and acceptable for CHD risk assessment, as well as for use as a marker of inflammation.     

Enhancement of T helper type 1 immune responses against hepatitis B virus core antigen by PLGA nanoparticle vaccine delivery.

Currently, there is a need for therapeutic vaccines that are effective in inducing robust T helper type 1 (Th1) immune responses capable of mediating viral clearance in chronic hepatitis B infection. Hepatitis B therapeutic vaccines were designed and formulated by loading the hepatitis B core antigen (HBcAg) into poly(D,L-lactic-acid-co-glycolic acid) (PLGA) nanoparticles with or without monophospholipid A (MPLA), a Th1-favoring immunomodulator. These particles were around 300 nm in diameter, spherical in shape and had approximately 50% HBcAg encapsulation efficiency. A single immunization with a vaccine formulation containing (MPLA+HBcAg) coformulated in PLGA nanoparticles induced a stronger Th1 cellular immune response with a predominant interferon-gamma (IFN-gamma) profile than those induced by HBcAg alone, free (HBcAg+MPLA) simple mixture or HBcAg-loaded nanoparticles in a murine model. More importantly, the level of HBcAg-specific IFN-gamma production could be increased further significantly by a booster immunization with the (HBcAg+MPLA)-loaded nanoparticles. In summary, these results demonstrated that codelivery of HBcAg and MPLA in PLGA nanoparticles promoted HBcAg-specific Th1 immune responses with IFN-gamma production. These findings suggest that appropriate design of the vaccine formulation and careful planning of the immunization schedule are important in the successful development of effective HBV therapeutic vaccines.