J.J.EarnshawR.H.S.GregsonPractical Peripheral Arterial Thrombolysis1994Butterworth Heinemann207 pages, £35

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A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity.

Signaling via the intracellular pathogen receptors nucleotide-binding oligomerization domain-containing proteins NOD1 and NOD2 requires receptor interacting kinase 2 (RIPK2), an adaptor kinase that can be targeted for the treatment of various inflammatory diseases. However, the molecular mechanisms of how RIPK2 contributes to NOD signaling are not completely understood. We generated FLAG-tagged RIPK2 knock-in mice using CRISPR/Cas9 technology to study NOD signaling mechanisms at the endogenous level. Using cells from these mice, we were able to generate a detailed map of post-translational modifications on RIPK2. Similar to other reports, we did not detect ubiquitination of RIPK2 lysine 209 during NOD2 signaling. However, using site-directed mutagenesis we identified a new regulatory region on RIPK2, which dictates the crucial interaction with the E3 ligase XIAP and downstream signaling outcomes. © 2020 The Authors

Occlusion of the common femoral artery by cement after total hip arthroplasty: a case report

The incidence of vascular injuries after total hip arthroplasty is extremely low. In this report we describe an unusual injury to the common femoral artery. A 59-year-old Caucasian woman presented with rest pain, numbness and cramps in the operated limb after hip replacement. Cement leakage under the transverse ligament had caused occlusion of the common femoral artery necessitating vascular reconstruction. She had a good functional recovery at follow-up. To the best of our knowledge, this is the first well-documented case reporting this pathomechanism of vascular lesion to the femoral artery. This case report highlights the potential risk of such a limb-threatening complication, and awareness should lead to prevention by meticulous surgical technique (correct technique of pressurization) or to early detection of the lesio

A rare case of arterial avulsion presenting with occult blood loss following total hip arthroplasty: a case report

INTRODUCTION: Iatrogenic arterial damage during total hip replacement is a rare but potentially life- or limb-threatening complication. To the best of our knowledge, this is the first reported case of an avulsion injury to a posterior branch of the profunda femoral artery during primary hip arthroplasty. CASE PRESENTATION: We describe the case of a 55-year-old Caucasian man who underwent a total hip replacement. The patient's hemoglobin levels dropped postoperatively, but there was no obvious bleeding, hemodynamic instability, pulsatile mass, or limb ischemia. The patient's hemoglobin levels continued to drop despite nine units of transfused blood. Three days after surgery, the patient underwent an angiography that showed an avulsion injury to a posterior branch of the profunda femoral artery. The avulsion was ligated and the hematoma was evacuated. CONCLUSION: Vascular damage may present in many ways including obvious bleeding, haemodynamic instability, a pulsatile mass, limb ischemia, and occult blood loss. Any of these signs in isolation or in combination could represent a vascular injury and an urgent angiogram should be considered

TAK1 Is Required for Survival of Mouse Fibroblasts Treated with TRAIL, and Does So by NF-κB Dependent Induction of cFLIPL

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known as a “death ligand”—a member of the TNF superfamily that binds to receptors bearing death domains. As well as causing apoptosis of certain types of tumor cells, TRAIL can activate both NF-κB and JNK signalling pathways. To determine the role of TGF-β-Activated Kinase-1 (TAK1) in TRAIL signalling, we analyzed the effects of adding TRAIL to mouse embryonic fibroblasts (MEFs) derived from TAK1 conditional knockout mice. TAK1−/− MEFs were significantly more sensitive to killing by TRAIL than wild-type MEFs, and failed to activate NF-κB or JNK. Overexpression of IKK2-EE, a constitutive activator of NF-κB, protected TAK1−/− MEFs against TRAIL killing, suggesting that TAK1 activation of NF-κB is critical for the viability of cells treated with TRAIL. Consistent with this model, TRAIL failed to induce the survival genes cIAP2 and cFlipL in the absence of TAK1, whereas activation of NF-κB by IKK2-EE restored the levels of both proteins. Moreover, ectopic expression of cFlipL, but not cIAP2, in TAK1−/− MEFs strongly inhibited TRAIL-induced cell death. These results indicate that cells that survive TRAIL treatment may do so by activation of a TAK1–NF-κB pathway that drives expression of cFlipL, and suggest that TAK1 may be a good target for overcoming TRAIL resistance

Autoimmune encephalomyelitis in NOD mice is not initially a progressive multiple sclerosis model.

OBJECTIVE: Despite progress in treating relapsing multiple sclerosis (MS), effective inhibition of nonrelapsing progressive MS is an urgent, unmet, clinical need. Animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), provide valuable tools to examine the mechanisms contributing to disease and may be important for developing rational therapeutic approaches for treatment of progressive MS. It has been suggested that myelin oligodendrocyte glycoprotein (MOG) peptide residues 35-55 (MOG35-55 )-induced EAE in nonobese diabetic (NOD) mice resembles secondary progressive MS. The objective was to determine whether the published data merits such claims. METHODS: Induction and monitoring of EAE in NOD mice and literature review. RESULTS: It is evident that the NOD mouse model lacks validity as a progressive MS model as the individual course seems to be an asynchronous, relapsing-remitting neurodegenerative disease, characterized by increasingly poor recovery from relapse. The seemingly progressive course seen in group means of clinical score is an artifact of data handling and interpretation. INTERPRETATION: Although MOG35-55 -induced EAE in NOD mice may provide some clues about approaches to block neurodegeneration associated with the inflammatory penumbra as lesions form, it should not be used to justify trials in people with nonactive, progressive MS. This adds further support to the view that drug studies in animals should universally adopt transparent raw data deposition as part of the publication process, such that claims can adequately be interrogated. This transparency is important if animal-based science is to remain a credible part of translational research in MS.Stichting MS ResearchWellcome TrustMedical Research CouncilNational Multiple Sclerosis Society. Grant Number: RG4132A5/

Prediction of outcome after abdominal aortic aneurysm rupture

BackgroundMost vascular surgeons practice a selective policy of operative intervention for patients with ruptured abdominal aortic aneurysm (AAA). The evidence on which to justify operative selection remains uncertain. This review examines the prediction of outcome after attempted open repair of ruptured AAA.MethodsThe Medline and EMBASE databases and Cochrane Database of Systematic Reviews were searched for clinical studies relating to the prediction of outcome after ruptured AAA. Reference lists of relevant articles were also reviewed.ResultsThe last 20 years has seen >60 publications considering variables predictive of outcome after AAA rupture. Four predictive scoring systems are reported: Hardman Index, Glasgow Aneurysm Score, Physiological and Operative Severity Score for Enumeration of Mortality and Morbidity (POSSUM), and the Vancouver Scoring System. No scoring system has been shown to have consistent or absolute validity. Of the remaining data, there are no individual or combination of variables that can accurately and consistently predict outcome.ConclusionsLittle robust evidence is available on which to base preoperative outcome prediction in patients with ruptured AAA. Experienced clinical judgement will remain of foremost importance in the selection of patients for ruptured AAA repair