Impact of the complement cascade on posttraumatic cartilage inflammation and degradation

The limited ability of articular cartilage to recover from injury, remains an unsolved clinical challenge in orthopaedic surgery. Persistent injury of the articular surface can lead to the development of posttraumatic osteoarthritis. The local inflammatory response contributes to the pathogenesis of osteoarthritis by inducing chondrocyte apoptosis and the de-regulation of chondrocyte matrix remodelling. The role of the complement system in contributing to secondary inflammation-mediated cartilage degradation represents a newer field of investigation. The purpose of this review article is to summarize the known complementmediated actions in cartilage homeostasis and injury. This article focuses on the known effects of complement on secondary chondrocyte apoptosis, and the interplay of the complement system with pro-inflammatory cytokines. Pharmacological therapies related to complement inhibition will be discussed as they potentially represent a new avenue for attenuating the effect of the complement system on cartilage repair

Immunohistochemical characterization of Fas (CD95) and Fas Ligand (FasL-CD95L) expression in the injured brain: Relationship with neuronal cell death and inflammatory mediators

Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas (CD95) and Fas ligand (FasL/CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/lymphotoxin-a knockout (–/–) and interleukin-6–/– mice were subjected to closed head injury (CHI) and sacrificed at 24 hours or 7 days postinjury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick end-labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co-localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine–/– and wild-type mice

The new timing in acute care surgery (new TACS) classification: a WSES Delphi consensus study.

BACKGROUND: Timely access to the operating room for emergency general surgery (EGS) indications remains a challenge across the globe, largely driven by operating room availability and staffing constraints. The "timing in acute care surgery" (TACS) classification was previously published to introduce a new tool to triage the timely and appropriate access of EGS patients to the operating room. However, the clinical and operational effectiveness of the TACS classification has not been investigated in subsequent validation studies. This study aimed to improve the TACS classification and provide further consensus around the appropriate use of the new TACS classification through a standardized Delphi approach with international experts. METHODS: This is a validation study of the new TACS by a selected international panel of experts using the Delphi method. The TACS questionnaire was designed as a web-based survey. The consensus agreement level was established to be ≥ 75%. The collective consensus agreement was defined as the sum of the percentage of the highest Likert scale levels (4-5) out of all participants. Surgical emergency diseases and correlated clinical scenarios were defined for each of the proposed classes. Subsequent rounds were carried out until a definitive level of consensus was reached. Frequencies and percentages were calculated to determine the degree of agreement for each surgical disease. RESULTS: Four polling rounds were carried out. The new TACS classification provides 6 colour-code classes correlated to a precise timing to surgery, defined scenarios and surgical condition. The WHITE colour-code class was introduced to rapidly (within a week) reschedule cancelled or postponed surgical procedures. Haemodynamic stability is the main tool to stratify patients for immediate surgery or not in the presence of sepsis/septic shock. Fifty-one surgical diseases were included in the different colour-code classes of priority. CONCLUSION: The new TACS classification is a comprehensive, simple, clear and reproducible triage system which can be used to assess the severity of the patient and the surgical disease, to reduce the time to access to the operating room, and to manage the emergency surgical patients within a "safe" timeframe. By including well-defined surgical diseases in the different colour-code classes of priority, validated through a Delphi consensus, the new TACS improves communication among surgeons, between surgeons and anaesthesiologists and decreases conflicts and waste and waiting time in accessing the operating room for emergency surgical patients