Objectives: To evaluate the diagnostic performance of seven rapid IgG/IgM tests and the Euroimmun IgA/ IgG ELISA for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients. Methods: Specificity was evaluated in 103 samples collected before January 2020. Sensitivity and time to seropositivity was evaluated in 167 samples from 94 patients with COVID-19 confirmed with RT-PCR on nasopharyngeal swab. Results: Specificity (confidence interval) of lateral flow assays (LFAs) was 91.3% (84.0e95.5) for IgM, 90.3% (82.9e94.8) for IgG, and 85.4% (77.2e91.1) for the combination IgM OR IgG. Specificity of the ELISA was 96.1% (90.1e98.8) for IgG and only 73.8% (64.5e81.4) for IgA. Sensitivity 14e25 days after the onset of symptoms was between 92.1% (78.5e98.0) and 100% (95.7e100) for IgG LFA compared to 89.5% (75.3e96.4) for IgG ELISA. Positivity of IgM OR IgG for LFA resulted in a decrease in specificity compared to IgG alone without a gain in diagnostic performance, except for VivaDiag. The results for IgM varied significantly between the LFAs with an average overall agreement of only 70% compared to 89% for IgG. The average dynamic trend to seropositivity for IgM was not shorter than for IgG. At the time of hospital admission the sensitivity of LFA was <60%. Conclusions: Sensitivity for the detection of IgG antibodies 14e25 days after the onset of symptoms was 92.1% for all seven LFAs compared to 89.5% for the IgG ELISA. The results for IgM varied significantly, and including IgM antibodies in addition to IgG for the interpretation of LFAs did not improve the diagnostic performance.

Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients' short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group. Level of evidence: Level V.

Objectives The aim was to determine the antibody response against SARS-CoV-2 spike protein and nucleoprotein using four automated immunoassays and three ELISAs for the detection of total Ig antibodies (Roche) or IgG (Abbott, Diasorin, Snibe, Euroimmun, Mikrogen) in COVID-19 patients. Methods Sensitivity and dynamic trend to seropositivity were evaluated in 233 samples from 114 patients with moderate, severe or critical COVID-19 confirmed with PCR on nasopharyngeal swab. Specificity was evaluated in 113 samples collected before January 2020, including 24 samples from patients with non-SARS coronavirus infection. Results Sensitivity for all assays was 100% (95% confidence interval 83.7–100) 3 weeks after onset of symptoms. Specificity varied between 94.7% (88.7–97.8) and 100% (96.1–100). Calculated at the cut-offs that corresponded to a specificity of 95% and 97.5%, Roche had the highest sensitivity (85.0% (79.8–89.0) and 81.1% (76.6–85.7), p < 0.05 except vs. Abbott). Seroconversion occurred on average 2 days earlier for Roche total Ig anti-N and the three IgG anti-N assays (Abbott, Mikrogen, Euroimmun) than for the two IgG anti-S assays (Diasorin, Euroimmun) (≥50% seroconversion day 9–10 vs. day 11–12 and p < 0.05 for percent seropositive patients day 9–10 to 17–18). There was no significant difference in the IgG antibody time to seroconversion between critical and non-critical patients. Discussion Seroconversion occurred within 3 weeks after onset of symptoms with all assays and on average 2 days earlier for assays detecting IgG or total Ig anti-N than for IgG anti-S. The specificity of assays detecting anti-N was comparable to anti-S and excellent in a challenging control population.

Background: Both fracture-related infections (FRIs) and periprosthetic joint infections (PJIs) include orthopaedic implant-associated infections. However, key aspects of management differ due to the bone and soft tissue damage in FRIs and the option of removing the implant after fracture healing. In contrast to PJIs, research and guidelines for diagnosis and treatment in FRIs are scarce. Objectives: This narrative review aims to update clinical microbiologists, infectious disease specialists and surgeons on the management of FRIs. Sources: A computerized search of PubMed was performed to identify relevant studies. Search terms included 'Fracture' and 'Infection'. The reference lists of all retrieved articles were checked for additional relevant references. In addition, when scientific evidence was lacking, recommendations are based on expert opinion. Content: Pathogenesis, prevention, diagnosis and treatment of FRIs are presented. Whenever available, specific data of patients with FRI are discussed. Implications: Management of patients with FRI should take into account FRI-specific features. Treatment pathways should implement a multidisciplinary approach to achieve a good outcome. Recently, international consensus guidelines were developed to improve the quality of care for patients suffering from this severe complication, which are highlighted in this review.

The avascular nature of cartilage makes it a unique tissue 1 – 4 , but whether and how the absence of nutrient supply regulates chondrogenesis remains unknown. Here, we show that obstruction of vascular invasion during bone healing favours chondrogenic over osteogenic differentiation of skeletal progenitor cells. Unexpectedly, this process is driven by a decreased availability of extracellular lipids. When lipids are scarce, skeletal progenitors activate FoxO transcription factors, which bind to the Sox9 promoter and increase its expression. Besides initiating chondrogenesis, SOX9 acts as a regulator of cellular metabolism by suppressing fatty acid oxidation, and thus adapts the cells to an avascular life. Our results define lipid scarcity as an important determinant of chondrogenic commitment, reveal a role for FoxOs during lipid starvation, and identify SOX9 as a critical metabolic mediator. These data highlight the importance of the nutritional microenvironment in the specification of skeletal cell fate.