Good manufacturing practices in autologous chondrocyte implantation: the experience in a public hospital

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Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Etravirine concentrations in seminal plasma in HIV-infected patients

Purpose of the study: Good penetration of antiretroviral drugs to the seminal plasma may be associated with a decrease in viral replication and play an important role in the prevention of sexual transmission of HIV. We present data from a series of HIV-infected ARV-experienced patients receiving etravirine-containing regimens, in whom etravirine concentrations and viral loads were determined in blood plasma and seminal plasma. The objective was to determine etravirine concentrations and HIV-1 viral load (VL) in blood plasma (BP) and seminal plasma (SP) of HIV-infected patients. Methods: Ten HIV-1 adult antiretroviral-experienced patients receiving an etravirine-containing regimen for at least 1 month were enrolled. Semen and blood samples were both collected around 12–24 h after the last etravirine dose, depending on once-daily or twice-daily dosing, respectively. HPLC/MS/MS was used to determine etravirine concentrations, and HIV-1 VL was determined by real-time PCR (limit of detection, VL 40 copies/mL). Results: Ten blood and twenty semen samples were collected. Median (range) CD4 count was 502 cells/mm3 (252–817) and median (range) BP VL was<40 copies/mL (40–362). Median (range) time on etravirine was 52 weeks (12–124). Median (range) BP etravirine concentration was 452.5 ng/mL (258–751). Median (range) SP etravirine concentration was 62.9 ng/mL (31.2–166), and values were above the protein-free IC50 range (0.39–2.4 ng/mL) in all cases. Median (range) etravirine SP:BP ratio was 0.16 (0.07–0.26). SP VL was<40 copies/mL in all patients, whereas BP VL was detectable in one patient with poor adherence to treatment. Conclusions: Total etravirine concentrations in male genital secretion are modest, reaching only 16% of the BP concentration, but nevertheless, more than 10 times above the wild type IC50 range

A novel DNA profiling application for the monitoring of cross-contamination in autologous chondrocyte implantation.

Abstract. \u2013 BACKGROUND: Autologous chondrocyte implantation (ACI) is a cell-based treatment that can be used to regenerate chondral defects. European legislation specifically classifies such produced chondrocytes as \u201cmedicinal for advanced cell therapy\u201d that have to be manufactured in pharmaceutical factories according to specific rules, named Good Manufacturing Practices (GMPs). One main requirement of cell manipulation in advanced therapy is to prevent the risk of any contamination. AIM: The aim of this study was to verify if chondrocyte cultures suitable for ACI were free of cross-contamination by means of DNA profiling techniques. MATERIALS AND METHODS: Cell cultures were carried on in a Hospital Cell Factory in compliance with European current Good Manufacturing Practices. DNA profiling, by means of Short Tandem Repeats and miniShort Tandem Repeats analyses, was performed on expanded chondrocytes and their related control blood samples. Mitochondrial DNA was analysed to further confirm the results and to evaluate possible mutations occurred in the samples. RESULTS: Our findings demonstrated the absence of cross-contamination between chondrocyte cultures and, thus, their identity maintenance until the end of the manipulation. CONCLUSIONS: DNA profiling technique can be a suitable test for quality control not only for chondrocyte manipulation, but for cell therapy in general