Adverse events (AEs) seriously affect patient safety and quality of care, and remain a pressing global issue. This study had three objectives: (1) to describe the proportions of patients affected by in-hospital AEs; (2) to explore the types and consequences of observed AEs; and (3) to estimate the preventability of in-hospital AEs. We applied a scoping review method and concluded a comprehensive literature search in PubMed and CINAHL in May 2017 and in February 2018. Our target was retrospective medical record review studies applying the Harvard method–or similar methods using screening criteria–conducted in acute care hospital settings on adult patients (≥18 years). We included a total of 25 studies conducted in 27 countries across six continents. Overall, a median of 10% patients were affected by at least one AE (range: 2.9–21.9%), with a median of 7.3% (range: 0.6–30%) of AEs being fatal. Between 34.3 and 83% of AEs were considered preventable (median: 51.2%). The three most common types of AEs reported in the included studies were operative/surgical related, medication or drug/fluid related, and healthcare-associated infections. Evidence regarding the occurrence of AEs confirms earlier estimates that a tenth of inpatient stays include adverse events, half of which are preventable. However, the incidence of in-hospital AEs varied considerably across studies, indicating methodological and contextual variations regarding this type of retrospective chart review across health care systems. For the future, automated methods for identifying AE using electronic health records have the potential to overcome various methodological issues and biases related to retrospective medical record review studies and to provide accurate data on their occurrence.

The loss of expression of chondrogenic markers during monolayer expansion remains a stumbling block for cell-based treatment of cartilage lesions. Here, we introduce sulfated alginate hydrogels as a cartilage biomimetic biomaterial that induces cell proliferation while maintaining the chondrogenic phenotype of encapsulated chondrocytes. Hydroxyl groups of alginate were converted to sulfates by incubation with sulfur trioxide-pyridine complex (SO3/pyridine), yielding a sulfated material cross-linkable with calcium chloride. Passage 3 bovine chondrocytes were encapsulated in alginate and alginate sulfate hydrogels for up to 35 days. Cell proliferation was five-fold higher in alginate sulfate compared with alginate (p=0.038). Blocking beta1 integrins in chondrocytes within alginate sulfate hydrogels significantly inhibited proliferation (p=0.002). Sulfated alginate increased the RhoA activity of chondrocytes compared with unmodified alginate, an increase that was blocked by β1 blocking antibodies (p=0.017). Expression and synthesis of type II collagen, type I collagen, and proteoglycan was not significantly affected by the encapsulation material evidenced by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Alginate sulfate constructs showed an opaque appearance in culture, whereas the unmodified alginate samples remained translucent. In conclusion, alginate sulfate provides a three dimensional microenvironment that promotes both chondrocyte proliferation and maintenance of the chondrogenic phenotype and represents an important advance for chondrocyte-based cartilage repair therapies providing a material in which cell expansion can be done in situ.

The cellular microenvironment plays a crucial role in directing proliferation and differentiation of stem cells. Cells interact with their microenvironment via integrins that recognize certain peptide sequences of extracellular matrix proteins. This receptor-ligand binding has profound impact on cell fate. Interactions of human bone marrow mesenchymal stem cells (hMSCs) with the triple helical collagen mimetic, GPC(GPP)5-GFOGER-(GPP)5GPC-NH2, and the fibronectin adhesion peptide, RGD, were studied in degradable or nondegradable polyethylene glycol (PEG) gels formed by Michael-type addition chemistry. Proliferation, cytoskeletal morphology, and chondrogenic differentiation of encapsulated hMSCs were evaluated. The hMSCs adopted a highly spread morphology within the GFOGER-modified gels, whereas RGD induced a star-like spreading of the cells. hMSCs within GFOGER-modified degradable gels had a high proliferation rate compared with cells in peptide-free gels ( p =0.017). Gene expression of type II collagen was highest in GFOGER-modified degradable gels after 21 days. Peptide incorporation increased GAG production in degradable gels after 7 and 21 days and GFOGER-modified degradable hydrogels had on average the highest GAG content, a finding that was confirmed by Alcian blue staining. In conclusion, the GFOGER peptide enhances proliferation in degradable PEG gels and provides a better chondrogenic microenvironment compared with the RGD peptide.