[Napping in the emergency department at Evreux hospital in Normandy]. / La sieste aux urgences à l'hôpital d'Évreux en Normandie.

Seeking to improve the working conditions in the reception of the emergency department, a hospital team has implemented a protocol aiming to promote and encourage the practice of napping for all medical and paramedical staff. Under less stress, even if successive 24- or 12-hour on-call shifts remain difficult, the professionals perceive a benefit in terms of quality of working life. This helps them make lucid decisions and perform procedures with dexterity, at any time of the day or night.

Artificial Intelligence for Detecting Acute Fractures in Patients Admitted to an Emergency Department: Real-Life Performance of Three Commercial Algorithms.

RATIONALE AND OBJECTIVES: Interpreting radiographs in emergency settings is stressful and a burden for radiologists. The main objective was to assess the performance of three commercially available artificial intelligence (AI) algorithms for detecting acute peripheral fractures on radiographs in daily emergency practice. MATERIALS AND METHODS: Radiographs were collected from consecutive patients admitted for skeletal trauma at our emergency department over a period of 2 months. Three AI algorithms-SmartUrgence, Rayvolve, and BoneView-were used to analyze 13 body regions. Four musculoskeletal radiologists determined the ground truth from radiographs. The diagnostic performance of the three AI algorithms was calculated at the level of the radiography set. Accuracies, sensitivities, and specificities for each algorithm and two-by-two comparisons between algorithms were obtained. Analyses were performed for the whole population and for subgroups of interest (sex, age, body region). RESULTS: A total of 1210 patients were included (mean age 41.3 ± 18.5 years; 742 [61.3%] men), corresponding to 1500 radiography sets. The fracture prevalence among the radiography sets was 23.7% (356/1500). Accuracy was 90.1%, 71.0%, and 88.8% for SmartUrgence, Rayvolve, and BoneView, respectively; sensitivity 90.2%, 92.6%, and 91.3%, with specificity 92.5%, 70.4%, and 90.5%. Accuracy and specificity were significantly higher for SmartUrgence and BoneView than Rayvolve for the whole population (P < .0001) and for subgroups. The three algorithms did not differ in sensitivity (P = .27). For SmartUrgence, subgroups did not significantly differ in accuracy, specificity, or sensitivity. For Rayvolve, accuracy and specificity were significantly higher with age 27-36 than ≥53 years (P = .0029 and P = .0019). Specificity was higher for the subgroup knee than foot (P = .0149). For BoneView, accuracy was significantly higher for the subgroups knee than foot (P = .0006) and knee than wrist/hand (P = .0228). Specificity was significantly higher for the subgroups knee than foot (P = .0003) and ankle than foot (P = .0195). CONCLUSION: The performance of AI detection of acute peripheral fractures in daily radiological practice in an emergency department was good to high and was related to the AI algorithm, patient age, and body region examined.

Umbilical cord blood T cells respond against the Melan-A/MART-1 tumor antigen and exhibit reduced alloreactivity as compared with adult blood-derived T cells.

Umbilical cord blood (UCB) is increasingly used as a source of hematopoietic progenitor cells to treat a variety of disorders. UCB transplant is associated with comparatively reduced incidence of graft-versus-host disease, robust graft versus leukemia effect, and relatively high incidence of opportunistic infections, three processes in which donor-derived T lymphocytes are known to be predominantly involved. To examine the differential functionality of UCB T cells, CD8(+) T cells specific for the melanoma-associated HLA-A2-restricted Melan-A(26-35) A27L peptide were isolated from HLA-A2(+) and HLA-A2(-) UCB samples and HLA-A2(+) and HLA-A2(-) adult peripheral blood using A2/Melan-A tetramers. In UCB samples, A2/Melan-A(+) CD8(+) T cells were detected at a frequency of 0.04%, were more frequent in HLA-A2(+) UCB, and were polyclonal and mostly naive. Consistent with Ag-driven expansion, the frequency of A2/Melan-A(+) CD8(+) T cells was increased following stimulation with cognate peptide or polyclonal activation, they acquired cell-surface markers reflective of effector/memory differentiation, their TCR repertoire became oligoclonal, and they expressed cytolytic activity and produced IFN-gamma. Although functional properties of A2/Melan-A(+) CD8(+) T cells derived from HLA-A2(+) UCB resembled those of HLA-A2(+) adult peripheral blood, they were more likely to reach terminal differentiation following polyclonal stimulation and produced less IFN-gamma in response to cognate peptide. A2/Melan-A(+) CD8(+) T cells from HLA-A2(-) UCB were poorly cytolytic, produced little IFN-gamma, and were predominantly monofunctional or nonfunctional. These properties of UCB-derived CD8(+) T cells could contribute to the reduced incidence of graft-versus-host disease and heightened incidence of opportunistic infections observed following UCB transplant.

3D-printed protected face shields for health care workers in Covid-19 pandemic.

The coronavirus pandemic resulted in a shortage of protective equipment. To meet the request of eye-protecting devices, an interdisciplinary consortium involving practitioners, researchers, engineers and technicians developed and manufactured thousands of inexpensive 3D-printed face shields, inside hospital setting. This action leads to the concept of "concurrent, agile, and rapid engineering".

Endothelial dysfunction in systemic lupus patients with low disease activity: evaluation by quantification and characterization of circulating endothelial microparticles, role of anti-endothelial cell antibodies.

OBJECTIVE: We attempted to evaluate endothelial dysfunction and the role of AECAs in systemic lupus (SL) with low disease activity. We quantified endothelial microparticles (EMps) and attempted to find the best flow cytometry method for that purpose. METHODS: CD105, CD144 and CD146 were tested, individually or in combination, on EMp-enriched plasma. Twenty-three healthy blood donors and 27 SL patients were evaluated. SL patients with a SLEDAI <10 (median 2.6) were evaluated in our outpatient clinic. For each patient, EMps (CD105-CD146(+), CD45(-)) and AECAs were quantified and characterized. RESULTS: The monochrome composite marker CD105-CD146 appeared to be the most efficient in detecting EMps. SL patients had more circulating EMps than healthy donors: respective median values were 2575 and 130 EMps/microl (P < 0.001). SL patients had more CD54(+) and CD54(-) EMps than healthy donors (496 vs 34 EMps CD54(+)/microl, P < 0.0001; 1875 vs 89 EMps CD54(-)/microl, P < 0.0001). The ratio CD54(+) EMps/total EMps was lower for lupus patients than for healthy individuals (20.3 vs 33.7%, P = 0.03). Twenty-four patients (89%) were positive for AECAs. EMp counts were not significantly higher for patients with AECAs. CONCLUSION: Monochrome composite marker is efficient in detecting the whole population of EMps using flow cytometry. SL patients with low disease activity have a marked endothelial dysfunction. EMps released from the endothelium originate from activated and non-activated cells. AECAs do not seem to be the main cause of endothelial dysfunction in this population.

Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is associated with an increased risk of thrombosis through unknown mechanisms. DESIGN AND METHODS: We studied 23 patients with PNH, before and after five and 11 weeks of treatment with eculizumab. We examined markers of thrombin generation and reactional fibrinolysis (prothrombin fragment 1+2 (F1+2), D-dimers, and plasmin antiplasmin complexes (P-AP), and endothelial dysfunction tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), soluble thrombomodulin (sTM), intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule (sVCAM-1), endothelial microparticles (EMPs), and tissue factor pathway inhibitor (TFPI). RESULTS: At baseline, vWF, sVCAM-1, the EMP count, and F1+2 and D-dimer levels were significantly elevated in the patients, including those with no history of clinical thrombosis. Treatment with eculizumab was associated with significant decreases in plasma markers of coagulation activation (F1+2, P=0.012, and D-dimers, P=0.01), and reactional fibrinolysis (P-AP, P=0.0002). Eculizumab treatment also significantly reduced plasma markers of endothelial cell activation (t-PA, P=0.0005, sVCAM-1, P<0.0001, and vWF, P=0.0047) and total (P=0.0008) and free (P=0.0013) TFPI plasma levels. CONCLUSIONS: Our results suggest a new understanding of the contribution of endothelial cell activation to the pathogenesis of thrombosis in PNH. The terminal complement inhibitor, eculizumab, induced a significant and sustained decrease in the activation of both the plasma hemostatic system and the vascular endothelium, likely contributing to the protective effect of eculizumab on thrombosis in this setting.

Atypical presentation of adult T-cell leukaemia/lymphoma due to HTLV-1: prurigo nodularis lasting twelve years followed by an acute micropapular eruption.

Prurigo nodularis is a pruritic dermatosis of unknown origin. Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukaemia/lymphoma. HTLV-1 is not considered to be a cause of prurigo nodularis. A 52-year-old black man, from the French West Indies, who had had prurigo nodularis for 12 years, presented with a distinct micropapular eruption with the typical pathological picture of epidermotropic T-cell lymphoma. Based on HTLV-1-positive serology and monoclonal integration of HTLV-1 we diagnosed smouldering adult T-cell leukaemia/lymphoma. Re-examination of previous skin biopsies revealed that the disease had been evolving for 12 years. Treatment with alpha-interferon, 3 x 106 units three times a week, associated with zidovudine, 1 g daily, resulted in complete remission within 4 months. When investigating a prurigo nodularis, we therefore recommend: (i) performing HTLV-1 serology if the patient comes from an endemic area; (ii) if positive, performing CD25 staining and looking for a HTLV-1 clonal integration; and (iii) if positive, using a treatment targeting HTLV-1.

Livedo, dementia, thrombocytopenia, and endotheliitis without antiphospholipid antibodies: seronegative antiphospholipid-like syndrome.

We report a 51-year-old woman who presented with dementia, livedo racemosa, polyarthralgia, mild renal insufficiency, proteinuria, and thrombocytopenia. Cutaneous and renal biopsy specimens both showed an identical specific occlusive arteriolopathy consistent with Sneddon syndrome and antiphospholipid syndrome. However, no antiphospholipid antibodies were detected and we, therefore, diagnosed seronegative antiphospholipid-like syndrome. We discuss the nosology of this entity and its association with non-antiphospholipid antibody-related Sneddon syndrome. The common denominator of Sneddon syndrome and antiphospholipid syndrome with or without antiphospholipid antibodies seems to be the endothelial damage and occlusive arteriolopathy. Skin biopsy is useful to confirm the diagnosis of seronegative antiphospholipid-like syndrome.

Stem cells increase in numbers in perinecrotic areas in human renal cancer.

PURPOSE: Developing strategies to overcome resistance to sunitinib is a major challenge in human renal cell carcinoma (RCC). We hypothesized that sunitinib-induced tumor necrosis-associated hypoxia could interact with renal cancer stem cells in patients with metastatic RCC. EXPERIMENTAL DESIGN: We studied tissue samples from 7 patients with primary metastatic RCC, before and after sunitinib treatment, and from six xenograft models derived from human RCC. Two xenograft models were responders to sunitinib, the four others were nonresponders. CD133/CXCR4-coexpressing cells derived from the two responder xenograft models were used for in vitro studies. RESULTS: In the seven primary RCCs, we identified a significantly larger number of CD133/CXCR4-coexpressing cells in perinecrotic versus perivascular areas. Their numbers also significantly increased after treatment, in perinecrotic areas. We reproduced these clinical and pathologic results in all six RCC xenograft models with again a preferential perinecrotic distribution of CD133-expressing cells. Necrosis occurred at day 7 in the two responder models treated with sunitinib, whereas it occurred at day 21 in the untreated controls and in the four nonresponder models. Strikingly, when we studied the six RCC xenograft models at the time necrosis, whether spontaneous or sunitinib-induced, occurred, necrosis area correlated with stem-cell number in all 120 xenografted RCCs. When studied under experimental hypoxia, the number of CD133/CXCR4-coexpressing cells and their tumorigenic potency increased whereas their sensitivity to sunitinib decreased. CONCLUSIONS: In human RCC, sunitinib was able to generate resistance to its own therapeutic effect via induced hypoxia in perinecrotic areas where cancer stem cells were found in increased numbers.

Cell death induced on cell cultures and nude mouse skin by non-thermal, nanosecond-pulsed generated plasma.

Non-thermal plasmas are gaseous mixtures of molecules, radicals, and excited species with a small proportion of ions and energetic electrons. Non-thermal plasmas can be generated with any high electro-magnetic field. We studied here the pathological effects, and in particular cell death, induced by nanosecond-pulsed high voltage generated plasmas homogeneously applied on cell cultures and nude mouse skin. In vitro, Jurkat cells and HMEC exhibited apoptosis and necrosis, in dose-dependent manner. In vivo, on nude mouse skin, cell death occurred for doses above 113 J/cm(2) for the epidermis, 281 J/cm(2) for the dermis, and 394 J/cm(2) for the hypodermis. Using electron microscopy, we characterized apoptosis for low doses and necrosis for high doses. We demonstrated that these effects were not related to thermal, photonic or pH variations, and were due to the production of free radicals. The ability of cold plasmas to generate apoptosis on cells in suspension and, without any sensitizer, on precise skin areas, opens new fields of application in dermatology for extracorporeal blood cell treatment and the eradication of superficial skin lesions.

Targeted Gene Addition of Microdystrophin in Mice Skeletal Muscle via Human Myoblast Transplantation.

Zinc finger nucleases (ZFN) can facilitate targeted gene addition to the genome while minimizing the risks of insertional mutagenesis. Here, we used a previously characterized ZFN pair targeting the chemokine (C-C motif) receptor 5 (CCR5) locus to introduce, as a proof of concept, the enhanced green fluorescent protein (eGFP) or the microdystrophin genes into human myoblasts. Using integrase-defective lentiviral vectors (IDLVs) and chimeric adenoviral vectors to transiently deliver template DNA and ZFN respectively, we achieved up to 40% targeted gene addition in human myoblasts. When the O(6)-methylguanine-DNA methyltransferase(P140K) gene was co-introduced with eGFP, the frequency of cells with targeted integration could be increased to over 90% after drug selection. Importantly, gene-targeted myoblasts retained their mitogenic activity and potential to form myotubes both in vitro and in vivo when injected into the tibialis anterior of immune-deficient mice. Altogether, our results could lead to the development of improved cell therapy transplantation protocols for muscular diseases.Molecular Therapy - Nucleic Acids (2013) 2, e68; doi:10.1038/mtna.2012.55; published online 29 January 2013.

A humanized mouse model of idiopathic nephrotic syndrome suggests a pathogenic role for immature cells.

Idiopathic nephrotic syndrome is characterized by glomerular proteinuria in the absence of infiltrating cells or immunoglobulin deposits. Although it is suspected that T cells secrete a circulating factor that leads to proteinuria by altering the permeability of the glomerular filtration barrier, the precise etiology of this syndrome is unknown. Because an animal model that mimics human idiopathic nephrotic syndrome does not exist, we developed a humanized mouse model of the disease by injecting CD34(+) stem cells or CD34(-) peripheral blood mononuclear cells from afflicted patients into immunocompromised mice. Even though both CD34(+) and CD34(-) cells induced the engraftment of human CD45(+) leukocytes in mice, only the injection of CD34(+) stem cells induced albuminuria. Ultrastructural analysis of glomeruli from the resulting proteinuric mice revealed effacement of podocyte foot processes, similar to the pathology observed in the human disease. Therefore, our data suggest that the cells responsible for the pathogenesis of idiopathic nephrotic syndrome are more likely to be immature differentiating cells rather than mature peripheral T cells.