Risk factors for infectious complications after open fractures; a systematic review and meta-analysis

__Purpose__ The purpose of this study was to identify risk factors for the development of infection after open fracture fixation. __Methods__ A comprehensive search in all scientific literature of the last 30 years was performed in order to identify patient-, trauma-, diagnosis- and treatment-related risk f

Management of critical-sized bone defects in the treatment of fracture-related infection: a systematic review and pooled analysis

Purpose: This systematic review determined the reported treatment strategies, their individual success rates, and other outcome parameters in the management of critical-sized bone defects in fracture-related infection (FRI) patients between 1990 and 2018. Methods: A systematic literature search on treatment and outcome of critical-sized bone defects in FRI was performed. Treatment strategies identified were, autologous cancellous grafts, autologous cancellous grafts combined with local antibiotics, the induced membrane technique, vascularized grafts, Ilizarov bone transport, and bone transport combined with local antibiotics. Outcomes were bone healing and infection eradication after primary surgical protocol and recurrence of FRI and amputations at the end of study period. Results: Fifty studies were included, describing 1530 patients, the tibia was affected in 82%. Mean age was 40 years (range 6–80), with predominantly male subjects (79%). Mean duration of infection was 17 months (range 1–624) and mean follow-up 51 months (range 6–126). After initial protocolized treatment, FRI was cured in 83% (95% CI 79–87) of all cases, increasing to 94% (95% CI 92–96) at the end of each individual study. Recurrence of infection was seen in 8% (95% CI 6–11) and amputation in 3% (95% CI 2–3). Final outcomes overlapped across treatment strategies. Conclusion: Results should be interpreted with caution due to the retrospective and observational design of most studies, the lack of clear classification systems, incomplete data reports, potential underreporting of adverse outcomes, and heterogeneity in patient series. A consensus on classification, treatment protocols, and outcome is needed to improve reliability of future studies

Insights into treatment and outcome of fracture-related infection: a systematic literature review

Introduction: Standardized guidelines for treatment of fracture-related infection (FRI) are lacking. Worldwide many treatment protocols are used with variable success rates. Awareness on the need of standardized, evidence-based guidelines has increased in recent years. This systematic literature review gives an overview of available diagnostic criteria, classifications, treatment protocols, and related outcome measurements for surgically treated FRI patients. Methods: A comprehensive search was performed in all scientific literature since 1990. Studies

An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which may result in acute respiratory distress syndrome (ARDS), multiorg

Activin A Suppresses Osteoblast Mineralization Capacity by Altering Extracellular Matrix (ECM) Composition and Impairing Matrix Vesicle (MV) Production

During bone formation, osteoblasts deposit an extracellular matrix (ECM) that is mineralized via a process involving production and secretion of highly specialized matrix vesicles (MVs). Activin A, a transforming growth factor-beta (TGF-beta) superfamily member, was previously shown to have inhibitory effects in human bone formation models through unclear mechanisms. We investigated these mechanisms elicited by activin A during in vitro osteogenic differentiation of human mesenchymal stem cells (hMSC). Activin A inhibition of ECM mineralization coincided with a strong decline in alkaline phosphatase (ALP(1)) activity in extracellular compartments, ECM and matrix vesicles. SILAC-based quantitative proteomics disclosed intricate protein composition alterations in the activin A ECM, including changed expression of collagen XII, osteonectin and several cytoskeleton-binding proteins. Moreover, in activin A osteoblasts matrix vesicle production was deficient containing very low expression of annexin proteins. ECM enhanced human mesenchymal stem cell osteogenic development and mineralization. This osteogenic enhancement was significantly decreased when human mesenchymal stem cells were cultured on ECM produced under activin A treatment. These findings demonstrate that activin A targets the ECM maturation phase of osteoblast differentiation resulting ultimately in the inhibition of mineralization. ECM proteins modulated by activin A are not only determinant for bone mineralization but also possess osteoinductive properties that are relevant for bone tissue regeneration

In Vitro Elution of Gentamicin from CERAMENT® G Has an Antimicrobial Effect on Bacteria With Various Levels of Gentamicin Resistance Found in Fracture-related Infection

Background: Fracture-related infection is a serious complication after trauma. CERAMENT® G combines dead-space management with local release of gentamicin in a single-stage procedure. Bacterial resistance against antibiotics is increasing. The local effect of CERAMENT® G on bacteria resistant to systemically administered gentamicin is unknown. Questions/purposes:(1) What is the in vitro elution pattern of gentamicin from CERAMENT® G using a full washout model? (2) What is the in vitro antimicrobial activity (zone of inhibition) of CERAMENT® G against bacterial isolates found in fracture-related infection with different susceptibility levels toward gentamicin? Methods Elution of gentamicin from CERAMENT® G was determined in vitro over a period of 2 months. Elution experiments were performed in fivefold, with gentamicin being sampled in threefold at 19 different timepoints within 2 months. Antimicrobial activity was determined using the four most-frequently cultured bacterial species found in fracture-related infection: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Enterobacter cloacae. For each of the species, four different isolates with a different susceptibility to gentamicin were used. According to the European Committee on Antimicrobial Susceptibility Testing, the susceptibility of each isolate was classified into four different groups: fully susceptible (minimum inhibitory concentration 0.064 to 4 mg/L), minimally resistant (minimum inhibitory concentration 4 to 16 mg/L), moderately resistant (minimum inhibitory concentration 8 to 96 mg/L), and highly resistant (minimum inhibitory concentration 24 to 1024 mg/L), depending on each organism. The antimicrobial activity of CERAMENT® G was determined according to the European Committee on Antimicrobial Susceptibility Testing disk protocol. The experiment was performed in fivefold for each isolate. The zone of inhibition was compared between each bacterial isolate and within each of the four separate species. Nonlinear regression statistics were calculated between the zone of interest and logarithmic minimum inhibitory concentration for each bacterial species. Results:After 24 hours, 95% of all available gentamicin was eluted, and gentamicin was still detectable after 2 months. CERAMENT® G showed antimicrobial activity against all bacterial species; only Staphylococcus aureus (with a minimum inhibitory concentration &gt; 1024 mg/L) was not susceptible. The zone of interest of the different bacterial isolates was correlated with the logarithmic minimum inhibitory concentration. Conclusion:CERAMENT® G offers a bone substitute capable of releasing high levels of gentamicin within a short period of time. This study shows that CERAMENT® G has antimicrobial activity against bacterial isolates that are resistant to gentamicin when systemically administered. This finding raises the question of whether European Committee on Antimicrobial Susceptibility Testing cutoff points for systemic application are useful for the use of local CERAMENT® G. Standardized experiments to determine local antibiotic antimicrobial activity in fracture-related infection treatment are needed to form guidelines for the use of local antibiotics and ultimately improve fracture-related infection treatment. Clinical Relevance:Local concentrations of gentamicin with CERAMENT® G are much higher than when systemically administered. It seems effective against certain bacterial strains that are not affected by systemically reachable concentrations of gentamicin. CERAMENT® G might still be effective when bacteria that are resistant to systemically administered concentrations of gentamicin are occulated from patients with fracture-related infection.</p