Higher procoagulatory potential but lower DIC score in COVID-19 ARDS patients compared to non-COVID-19 ARDS patients.

BACKGROUND: COVID-19 is a novel viral disease. Severe courses may present as ARDS. Several publications report a high incidence of coagulation abnormalities in these patients. We aimed to compare coagulation and inflammation parameters in patients with ARDS due to SARS-CoV-2 infection versus patients with ARDS due to other causes. METHODS: This retrospective study included intubated patients admitted with the diagnosis of ARDS to the ICU at Munich university hospital. 22 patients had confirmed SARS-CoV2-infection (COVID-19 group), 14 patients had bacterial or other viral pneumonia (control group). Demographic, clinical parameters and laboratory tests including coagulation parameters and thromboelastometry were analysed. RESULTS: No differences were found in gender ratios, BMI, Horovitz quotients and haemoglobin values. The median SOFA score, serum lactate levels, renal function parameters (creatinine, urea) and all inflammation markers (IL-6, PCT, CRP) were lower in the COVID-19 group (all: p < 0.05). INR (p < 0.001) and antithrombin (p < 0.001) were higher in COVID-19 patients. D-dimer levels (p = 0.004) and consecutively the DIC score (p = 0.003) were lower in this group. In ExTEM®, Time-to-Twenty (TT20) was shorter in the COVID-19 group (p = 0.047), these patients also had higher FibTEM® MCF (p = 0.005). Further, these patients presented with elevated antigen and activity levels of von-Willebrand-Factor (VWF). CONCLUSION: COVID-19 patients presented with higher coagulatory potential (shortened global clotting tests, increased viscoelastic and VWF parameters), while DIC scores were lower. An intensified anticoagulation regimen based on an individual risk assessment is advisable to avoid thromboembolic complications.

Particle characterisation and cytokine expression in failed small-diameter metal-on-metal total hip arthroplasties.

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the 'biologically active area' of all metal wear particles may predict the type of peri-prosthetic tissue response. Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. These results suggest that the 'biologically active area' predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA.

[Rituximab in the treatment of acquired haemophilia A in a patient with polymyalgia rheumatica]. / Rituximab in der Behandlung der erworbenen Hämophilie A bei einem Patienten mit Polymyalgia rheumatica.

UNLABELLED: Acquired hemophilia A is a rare but potentially life-threatening bleeding disorder. It is caused by the development of autoantibodies directed against coagulation factor VIII in adults or elderly patients, who do not have a personal or family history of bleeding. CASE: A man (age: 76 years) on prednisone and leflunomide for polymyalgia rheumatica developed spontaneous severe haematomas. The patient was diagnosed with acquired factor VIII deficiency (FVIII activity 1.2%, FVIII inhibitor 31.7 BU). Due to the active bleeding diathesis, treatment was administered with activated prothrombin complex concentrates (FEIBA®, Baxter). Immunosuppressive treatment with a combination of oral prednisone (1 mg/kg daily) and cyclophosphamide (1,5 mg/kg daily) was administered to reduce the FVIII inhibitor. However, after two weeks of treatment, FVIII was only 3% and no clinical improvement was observed. Treatment with the anti CD20 monoclonal antibody rituximab intravenously at 375 mg/m2 once weekly for four consecutive weeks was started. The patient showed rapid clinical improvement following rituximab treatment. He achieved a complete remission defined as return to normal FVIII activity and undetectable FVIII inhibitor titer. After a follow-up of six months no relapse occurred. CONCLUSION: Rituximab appears an effective and well-tolerated treatment for patients with acquired haemophilia.

Rotator cuff tears: assessment with MR arthrography in 275 patients with arthroscopic correlation.

We assessed the diagnostic performance of magnetic resonance (MR) arthrography in the diagnosis of articular-sided partial-thickness and full-thickness rotator cuff tears in a large symptomatic population. MR arthrograms obtained in 275 patients including a study group of 139 patients with rotator cuff tears proved by arthroscopy and a control group of 136 patients with arthroscopically intact rotator cuff tendons were reviewed in random order. MR imaging was performed on a 1.0 T system (Magnetom Expert, Siemens). MR arthrograms were analyzed by two radiologists in consensus for articular-sided partial-thickness and full-thickness tears of the supraspinatus, infraspinatus, and subscapularis tendons. At arthroscopy, 197 rotator cuff tears were diagnosed, including 105 partial-thickness (93 supraspinatus, nine infraspinatus, three subscapularis) and 92 full-thickness (43 supraspinatus, 20 infraspinatus, 29 subscapularis) tendon tears. For full-thickness tears, sensitivity, specificity, and accuracy were 96%, 99%, and 98%, respectively, and for partial tears 80%, 97%, and 95%, respectively. False negative and positive assessments in the diagnosis of articular-sided partial-thickness tears were predominantly [78% (35/45)] observed with small articular-sided (Ellman grade1) tendon tears. MR arthrography is highly accurate in the diagnosis of full-thickness rotator cuff tears and is accurate in the diagnosis of articular-sided partial-thickness tears. Limitations in the diagnosis of partial-thickness tears are mainly restricted to small articular-sided tears (Ellman grade 1) due to difficulties in differentiation between fiber tearing, tendinitis, synovitic changes, and superficial fraying at tendon margins.

Transcriptomic and proteomic patterns of systemic inflammation in on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) provides controlled operative conditions but induces a whole-body inflammatory response capable of initiating devastating morbidity and mortality. Although technically more demanding, deliberate avoidance of CPB in off-pump surgery attenuates the physiological insult associated with CABG. METHODS AND RESULTS: To systematically assess the molecular mechanisms underlying the better-preserved remote organ function, we studied gene expression patterns in leukocytes and plasma proteomic response to on-pump and off-pump CABG. Proteomic analysis confirmed (tumor necrosis factor-alpha, interleukin [IL]-6, IL-10) and expanded (eg, interferon [IFN]-gamma, granulocyte colony-stimulating factor [G-CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1beta) the mediators released on CPB, whereas blood leukocyte transcriptomics suggested that circulating leukocytes are not primarily responsible for this response. Interestingly, release of some cytokines (eg, IL-6, IFN-gamma, G-CSF) was observed on off-pump surgery to a similar extent but with delayed kinetics. A total of 45 of 4868 transcripts were identified to be significantly altered as a result of initiation of CPB. Systematic analysis of transcriptional activation by CPB revealed primarily genes involved in inflammation-related cell-cell communication (such as L-selectin or intercellular adhesion molecule-2) and signaling (such as IL-1, IL-8, or IL-18 receptors and toll-like receptors 4, 5, and 6), thus confirming a "primed" phenotype of circulating peripheral blood mononuclear cells. CONCLUSIONS: Gene array and multiplex protein analysis, only in concert, can illuminate the molecular mechanisms responsible for systemic sequelae of CPB and indicate that circulating leukocytes overexpress adhesion and signaling factors after contact with CPB, which potentially facilitates their trapping, eg, in the lungs and may promote a subsequent tissue-associated inflammatory response.

Comparison of multislice CT arthrography and MR arthrography for the detection of articular cartilage lesions of the elbow.

The objective of this study was to compare the value of multislice CT arthrography and MR arthrography in the assessment of cartilage lesions of the elbow joint. Twenty-six cadaveric elbow specimens were examined with the use of CT arthrography and MR arthrography prior to joint exploration and macroscopic inspection of articular cartilage. Findings at CT and MR arthrography were compared with macroscopic assessments in 104 cartilage areas. At macroscopic inspection, 45 cartilage lesions (six grade 2 lesions, 25 grade 3 lesions, 14 grade 4 lesions) and 59 areas of normal articular cartilage were observed. With macroscopic assessment as the gold standard CT and MR arthrography showed an overall sensitivity/specificity of 80/93% and 78/95% for the detection of cartilage lesions, respectively. Only two of six grade 2 lesions were detected by CT and MR arthrography. For the diagnosis of grade 3 and 4 lesions, the sensitivity/specificity was 87/94% with CT arthrography, and 85/95% with MR arthrography. In an experimental setting multislice CT arthrography and MR arthrography showed a similar performance in the detection of cartilage lesions. Both methods indicated limited value in the diagnosis of grade 2 articular cartilage lesions.

HMG-CoA reductase inhibitors reduce adhesion of human monocytes to endothelial cells.

HMG-CoA reductase inhibitors (statins) are believed to reduce coronary heart disease by mechanisms in addition to their well-known cholesterol-lowering effect. We studied the effect of these drugs on monocyte cell adhesion to endothelium. Pretreatment of monocytic cells (U937, THP-1, human CD14(+) monocytes) with 0.01-10 microM concentrations of atorvastatin, cerivastatin, or simvastatin significantly reduced cell adhesion to endothelium. In contrast, pretreatment of endothelium with statins did not affect adhesion of monocytes. Adhesion of monocytes to vascular cell adhesion molecule-1-coated dishes was reduced by these drugs. Cerivastatin also reduced PMA induction of NF-kappaB. Since monocyte adhesion to endothelium is an early event in atherogenesis, treatment with statins in prevention of coronary heart disease may have additional salutary effects to lowering of plasma LDL cholesterol. Our results indicate that the reduction of monocyte adhesion by HMG-CoA reductase inhibitors may be considered as a class effect.

Whole-body bone marrow MRI in patients with metastatic disease to the skeletal system.

PURPOSE: The purpose of this study was to evaluate the diagnostic potential of a whole-body bone marrow MR protocol in the detection of bone metastases. METHOD: Whole-body bone marrow MRI was performed in 18 patients with known malignant tumors and suspected bone metastases. The imaging protocol consisted of fast T1-weighted and STIR sequences applied in different anatomical positions covering the whole skeleton. MRI findings indicating bone metastases were compared with findings from bone scintigraphy. Metastatic lesions were confirmed by follow-up MR examinations, bone scintigraphy, radiography, or CT. RESULTS: A total number of 216 lesions were detected with MRI in comparison with 159 lesions detected with bone scintigraphy. Follow-up examinations confirmed 105 lesions. MRI detected 96 (91.4%) of the confirmed lesions, whereas bone scintigraphy detected 89 (84.8%). The entire examination, including patient positioning and changing of imaging coils, required 45 min of room time. CONCLUSION: Whole-body bone marrow MRI as used in this study is an effective method for evaluating the entire skeletal system in patients with suspected metastatic disease.