Joint infection after knee arthroscopy: Medicolegal aspects

SummaryIntroductionSeptic knee arthritis following arthroscopy is a rare but dreaded complication: it might compromise patients’ functional prognosis and engage surgeon's liability. This study analyzes the context of such infection occurrences, their management as well as their medicolegal consequences.Patients and methodsTwenty-two cases of knee septic arthritis following arthroscopy were examined during the medicolegal litigation process and collected for assessment from a medical liability specialised insurer. Half of the patients were manual workers who worked on their knees, and seven knees had a previous surgical history. The procedures performed at arthroscopy included seven ligamentoplasties, nine meniscotomies, three arthroscopic lavages, one arthrolysis, one chondroma removal and one plica resection. Seven patients, to some point, received corticosteroids: three preoperative joint injections, three intraoperative injections, and one oral corticotherapy.ResultsClinical signs of septic arthritis appeared after a median interval of 8 days (0–37), twice after a hemarthrosis and once after an articular burn. The median delay before treatment initiation was 4.2 days, and in 10 cases this therapeutic delay exceeded 3 days. On average, 3.5 additional procedures (1–9) were required to treat the infection and its residual sequels. Two total knee prostheses were implanted. Only two patients were free of disabling sequellae, and in five patients these sequels affected their livelihood. The medicolegal consequences were a partially permanent disability averaging 5% (0–20), a total temporary work incapacity of 120 days (40–790), a suffering burden averaging 3 out of 7 (0–4,5) points on the scale conventionally used in France. Twelve of these legal claims led to court ordered patient compensation.DiscussionSome risk factors of articular infection are known and well-identified. They can be linked to the patient's condition (addiction to smoking, surgical history, professional activity) or to medical management (intra-articular corticoid injections, interventions under oral anticoagulants, inadvertently overheated irrigation fluid). When infection is suspected, it is often the needle-aspirated fluid's inappropriate handling (such as absence of bacteriological testing or defective waiting time for the results), which delays the diagnostic or therapeutic management of this complication. All failures of infection diagnosis or treatment heavily contribute to malpractice claims against the surgeon. Early and appropriate management of postoperative infections helps limiting the risk of functional sequellae for the patient and reduces the risk of malpractice litigation for the practitioner.Level of evidenceLevel IV; economic and decision analysis, retrospective study

CCL2 nitration is a negative regulator of chemokine-mediated inflammation.

Chemokines promote leukocyte recruitment during inflammation. The oxidative burst is an important effector mechanism, this leads to the generation of reactive nitrogen species (RNS), including peroxynitrite (ONOO). The current study was performed to determine the potential for nitration to alter the chemical and biological properties of the prototypical CC chemokine, CCL2. Immunofluorescence was performed to assess the presence of RNS in kidney biopsies. Co-localisation was observed between RNS-modified tyrosine residues and the chemokine CCL2 in diseased kidneys. Nitration reduced the potential of CCL2 to stimulate monocyte migration in diffusion gradient chemotaxis assays (p < 0.05). This was consistent with a trend towards reduced affinity of the nitrated chemokine for its cognate receptor CCR2b. The nitrated chemokine was unable to induce transendothelial monocyte migration in vitro and failed to promote leukocyte recruitment when added to murine air pouches (p < 0.05). This could potentially be attributed to reduced glycosaminoglycan binding ability, as surface plasmon resonance spectroscopy showed that nitration reduced heparan sulphate binding by CCL2. Importantly, intravenous administration of nitrated CCL2 also inhibited the normal recruitment of leukocytes to murine air pouches filled with unmodified CCL2. Together these data suggest that nitration of CCL2 during inflammation provides a mechanism to limit and resolve acute inflammation

Liver Resection for Primary Hepatic Neoplasms.

Subtotal hepatic resection was performed in 356 patients; 87 had primary hepatic malignancies, 108 had metastatic tumors, and 161 had benign lesions including 8 traumatic injuries. The global mortality was 4.2%. The experience has elucidated the role of subtotal hepatic resection both for benign and malignant neoplasms

Malformations ano-rectales

Anorectal malformations (ARM) are the result of an abnormal development of the terminal part of the digestive tract interesting anus and/or rectum that occur early between the sixth and tenth week of embryonic development. They carry a malformation spectrum of severity depending on the level of disruption of the anorectal canal and of the associated caudal malformations (sacrum and spine). ARM are associated in over half the cases with other malformations that can be integrated in some cases in known syndromes. If surgical treatment to restore anatomy as normal as possible is indispensable, post-operative care is essential for these patients whose defecation mechanisms are altered, to reach if not continence, at least a socially acceptable cleanliness

OA011-03. Clusterin, a natural ligand of DC-SIGN present in human semen inhibits HIV capture and transmission by dendritic cells

International audiencen.

Hijacking of the Pleiotropic Cytokine Interferon-γ by the Type III Secretion System of Yersinia pestis

Yersinia pestis, the causative agent of bubonic plague, employs its type III secretion system to inject toxins into target cells, a crucial step in infection establishment. LcrV is an essential component of the T3SS of Yersinia spp, and is able to associate at the tip of the secretion needle and take part in the translocation of anti-host effector proteins into the eukaryotic cell cytoplasm. Upon cell contact, LcrV is also released into the surrounding medium where it has been shown to block the normal inflammatory response, although details of this mechanism have remained elusive. In this work, we reveal a key aspect of the immunomodulatory function of LcrV by showing that it interacts directly and with nanomolar affinity with the inflammatory cytokine IFNγ. In addition, we generate specific IFNγ mutants that show decreased interaction capabilities towards LcrV, enabling us to map the interaction region to two basic C-terminal clusters of IFNγ. Lastly, we show that the LcrV-IFNγ interaction can be disrupted by a number of inhibitors, some of which display nanomolar affinity. This study thus not only identifies novel potential inhibitors that could be developed for the control of Yersinia-induced infection, but also highlights the diversity of the strategies used by Y. pestis to evade the immune system, with the hijacking of pleiotropic cytokines being a long-range mechanism that potentially plays a key role in the severity of plague

IFNγ binding to extracellular matrix prevents fatal systemic toxicity

Interferon-γ (IFNγ) is an important mediator of cellular immune responses, but high systemic levels of this cytokine are associated with immunopathology. IFNγ binds to its receptor (IFNγR) and to extracellular matrix (ECM) via four positively charged C-terminal amino acids (KRKR), the ECM-binding domain (EBD). Across evolution, IFNγ is not well conserved, but the EBD is highly conserved, suggesting a critical function. Here, we show that IFNγ lacking the EBD (IFNγ(ΔKRKR)) does not bind to ECM but still binds to the IFNγR and retains bioactivity. Overexpression of IFNγ(ΔKRKR) in tumors reduced local ECM binding, increased systemic levels and induced sickness behavior, weight loss and toxicity. To analyze the function of the EBD during infection, we generated IFNγ(ΔKRKR) mice lacking the EBD by using CRISPR–Cas9. Infection with lymphocytic choriomeningitis virus resulted in higher systemic IFNγ(ΔKRKR) levels, enhanced sickness behavior, weight loss and fatal toxicity. We conclude that local retention of IFNγ is a pivotal mechanism to protect the organism from systemic toxicity during prolonged immune stimulation