Mechanistic Rationale for Ketene Formation during Dabbing and Vaping.

Ketene is one of the most toxic vaping emissions identified to date. However, its high reactivity renders it relatively challenging to identify. In addition, certain theoretical studies have shown that realistic vaping temperature settings may betoo low to produce ketene. Each of these issues is addressed herein. First, an isotopically labeled acetate precursor is used for the identification of ketene with enhanced rigor in vaped aerosols. Second, discrepancies between theoretical and experimental findings are explained by accounting for the effects of aerobic (experimental) versus anaerobic (simulated and theoretical) pyrolysis conditions. This finding is also relevant to explaining the relatively low-temperature production of aerosol toxicants beyond ketene. Moreover, the study presented herein shows that ketene formation during vaping is not limited to molecules possessing a phenyl acetate substructure. This means that ketene emission during vaping, including from popular flavorants such as ethyl acetate, may be more prevalent than is currently known.

Comparison of Intubating Conditions with Succinylcholine Versus Rocuronium in the Prehospital Setting.

OBJECTIVE: Rapid sequence intubation (RSI) is frequently performed by emergency medical services (EMS). We investigated the relationship between succinylcholine and rocuronium use and time until first laryngoscopy attempt, first-pass success, and Cormack-Lehane (CL) grades. METHODS: We included adult patients for whom prehospital RSI was attempted from July 2015 through June 2022 in a retrospective, observational study with pre-post analysis. Timing was verified using recorded defibrillator audio in addition to review of continuous ECG, pulse oximetry, and end-tidal carbon dioxide waveforms. Our primary exposure was neuromuscular blocking agent (NMBA) used, either rocuronium or succinylcholine. Our prespecified primary outcome was the first attempt Cormack-Lehane view. Key secondary outcomes were first laryngoscopy attempt success rate, timing from NMBA administration to first attempt, number of attempts, and hypoxemic events. RESULTS: Of 5,179 patients in the EMS airway registry, 1,475 adults received an NMBA while not in cardiac arrest. Cormack-Lehane grades for succinylcholine and rocuronium were similar: grade I (64%, 59% [95% CI 0.64-1.09]), grade II (16%, 21%), grade III (18%, 16%), grade IV (3%, 3%). The median interval from NMBA administration to start of the first attempt was 57 s for succinylcholine and 83 s for rocuronium (mean difference 28 [95% CI 20-36] seconds). First attempt success was 84% for succinylcholine and 83% for rocuronium. Hypoxemic events were present in 25% of succinylcholine cases and 23% of rocuronium cases. CONCLUSIONS: Prehospital use of either rocuronium or succinylcholine is associated with similar Cormack-Lehane grades, first-pass success rates, and rates of peri-intubation hypoxemia.

CD8+ Lymphocytes from Healthy Blood Donors Secrete Antiviral Levels of Interferon-Alpha.

The adaptive immune response to viral infections features the antigen-driven expansion of CD8+ T cells. These cells are widely recognized for their cytolytic activity that is mediated through the secretion of cytokines such as perforin and granzymes. Less appreciated is their ability to secrete soluble factors that restrict virus replication without killing the infected cells. In this study we measured the ability of primary anti-CD3/28-stimulated CD8+ T cells from healthy blood donors to secrete interferon-alpha. Supernatants collected from CD8+ T cell cultures were screened for their ability to suppress HIV-1 replication in vitro and their interferon-alpha concentrations were measured by ELISA. Interferon-alpha concentrations in the CD8+ T cell culture supernatants ranged from undetectable to 28.6 pg/mL. The anti-HIV-1 activity of the cell culture supernatants was observed to be dependent on the presence of interferon-alpha. Appreciable increases in the expression levels of type 1 interferon transcripts were observed following T cell receptor stimulation, suggesting that the secretion of interferon-alpha by CD8+ T cells is an antigen-driven response. In 42-plex cytokine assays, the cultures containing interferon-alpha were also found to contain elevated levels of GM-CSF, IL-10, IL-13, and TNF-alpha. Together, these results demonstrate that the secretion of anti-viral levels of interferon-alpha is a common function of CD8+ T cells. Furthermore, this CD8+ T cell function likely plays broader roles in health and disease.

Anti-infective DNase I coatings on polydopamine functionalized titanium surfaces by alternating current electrophoretic deposition.

Implant-associated infections (IAIs) can cause serious problems due to the difficult-to-treat nature of the biofilms formed on the implant surface. In mature biofilms, the matrix, which consists of polysaccharides, proteins, lipids and extracellular DNA (eDNA), forms a protective environment for the residing bacteria, shielding them from antibiotics and host defenses. Recently, the indirect prevention of biofilm growth through the degradation of eDNA using an enzyme, such as deoxyribonuclease (DNase) I, has gained attention and is regarded as a promising strategy in the battle against IAIs. In this study, coatings of DNase I were applied on titanium implant materials and their anti-infective properties were investigated. First, the effectiveness of alternating current electrophoretic deposition (AC-EPD) as a novel processing route to apply DNase I on titanium was examined and compared with the commonly applied diffusion methodology (i.e. classic dipping). For the same processing time, the use of AC-EPD in combination with a polydopamine (PDA) coupling chemistry on the titanium electrode surface significantly increased the protein deposition yield as compared to classic dipping, thereby yielding homogeneous coatings with a thickness of 12.8 nm and an average surface roughness, Sa, of ∼20 nm. X-ray photoelectron spectroscopy confirmed the presence of peptide bonds on all DNase-coated substrates. Time-of-flight secondary ion mass spectrometry detected a more dense DNase I layer in the case of AC-EPD for electrodes coupled as anode during the high-amplitude half cycle of the AC signal. The enzyme activity, release kinetics, and shelf life of DNase I coatings were monitored in real-time using a quantitative qDNase assay. The activity of DNase I coatings produced using AC-EPD was three time higher than for coatings prepared by classic dipping. For both deposition methods, a high initial burst release was observed within the first 2 h, while some activity was still retained at the surface after 7 days. This can be explained by the stable attachment of a small fraction of DNase to the surface through covalent bonding to the PDA layer, while superimposing DNase deposits were only loosely bound and therefore released rapidly upon immersion in the medium. Interestingly, coatings prepared with AC-EPD exhibited a prolonged, gradual release of DNase activity. The AC-EPD DNase coatings significantly reduced biofilm formation of both Staphylococcus epidermidis and Pseudomonas aeruginosa up to 20 h, whereas DNase coatings prepared by short classic dipping only reduce S. epidermidis biofilm formation, and this to a lesser extent as compared to AC-EPD DNase coatings. Overall, this study indicates that AC-EPD allows to rapidly concentrate DNase I on PDA-functionalized titanium, while maintaining the enzyme activity and anti-infective ability. This highlights the potential of AC-EPD as a time-efficient coating strategy (as opposed to the much slower dip-coating methodologies) for bioactive molecules in a wide variety of biomedical applications.

Acute compartment syndrome of the leg caused by cocaine use, creatine supplementation and vigorous exercise.

Delayed diagnosis of acute compartment syndrome (ACS) can be catastrophic. Reporting abnormal presentations to facilitate timely diagnosis and treatment is vital. We present a case of ACS in the deep posterior compartment of the leg with an unusual presentation and cause. The patient presented to the emergency department complaining of numbness on the plantar aspect of his left foot, and described a history of cocaine use, increased exercise and creatine supplementation. The patient was diagnosed with acute deep posterior compartment syndrome of the left leg and underwent a lower extremity fasciotomy. There are case reports demonstrating that strenuous activity, drug use and creatine supplementation cause increased compartment pressures and ACS. Rare in the literature is a case where these activities occur concurrently with the abnormal presentation of symptoms seen in this case. We hope this case brings awareness of atraumatic risk factors and uncommon presentations to the medical community.

["Long-haul COVID": An opportunity to address the complexity of post-infectious functional syndromes]. / « COVID long ¼ : une opportunité pour approcher la complexité des syndromes fonctionnels post-infectieux.

In this work, we address the issue of prolonged symptoms following an infection by SARS-CoV-2, labeled "long COVID". This clinically unspecific syndrome must be put in perspective with the post-infectious syndromes known for a long time but ultimately poorly understood and little studied, qualified, for lack of convincing arguments for a unambiguous pathophysiology and better terms, as functional somatic syndromes. The clinical implications for clinical care ("holistic" work-up and care of patients), for research (need for truly "bio-psycho-social" investigations), and the social implications of "long COVID" (social construction of the syndrome through the experiences of patients exposed on social networks, inequalities in the face of the disease and its socioeconomic consequences) are considered. "Long COVID" must be view, because of its expected prevalence, as an opportunity to address the complexity of post-infectious (functional) syndromes, their risk factors, and the biological, psychological and social mechanisms underlying them.

[Rituximab immunomonitoring in autoimmune diseases: a support tool in clinical practice?] / Immunomonitoring du rituximab appliqué aux maladies auto-immunes : une aide pour la pratique clinique ?

INTRODUCTION: Immune monitoring of monoclonal antibodies is a helpful tool in optimizing the management of patients treated with TNF blockers, especially in gastroenterology. In contrast, studies evaluating the interest of such monitoring are lacking for other monoclonal antibodies used in autoimmune diseases, including rituximab despite its widespread use in the field for almost 15 years. Hence, we conducted a study whose goal was to describe the clinical and biological characteristics of all patients who had a rituximab immune monitoring. METHODS: All the clinical, biological and therapeutic data attached to the demands (from 2015 onwards) we received for immune monitoring of rituximab (measurements of rituximab serum levels and anti-rituximab antibodies using the drug-sensitive assay LISA-TRACKER Duo Rituximab®), were retrospectively reviewed. Suspected cases of hypersensitivity and secondary non-response were included. RESULTS: Several medical specialities (nephrology, haematology, neurology, rheumatology, internal medicine) were represented among the 18 records included in the study (out of 23 demands), 10 being suspected cases of hypersensitivity and 8 secondary non-responders. All 6 patients whose symptoms were consistent with the classical presentation of serum sickness, as well as half of the secondary non-responders, were positive for antirituximab antibodies. CONCLUSION: This detailed real world case study illustrates the potential benefits of rituximab immune monitoring (especially anti-rituximab antibodies) in autoimmune diseases, suggesting it could be helpful in suspected cases of serum sickness, as well as secondary non-response (B-cell non-depletion being an early red flag). Larger and disease-specific studies are warranted to support these findings.

[Myelofibrosis: A review]. / Les myélofibroses.

Myelofibrosis is a BCR-ABL1-negative chronic myeloproliferative neoplasm that includes primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. It is characterized by stem cell-derived clonal proliferation that is often, but not always, accompanied by somatic mutations, which are classified into driver mutations (JAK2, CALR, or MPL), subclonal mutations and fibrosis on bone marrow biopsy. Myelofibrosis commonly demonstrates splenomegaly, constitutional symptoms, anemia, thrombocytosis, or thrombocytopenia. Patients may also be asymptomatic. Complications as thromboembolic or hemorrhagic events can reveal the disease. Primary myelofibrosis is the least common myeloproliferative neoplasm but is associated with poor survival and acute leukemic transformation. In contrast to the significant progress made in understanding the disease's pathogenesis, treatment for myelofibrosis remains largely palliative. The JAK2 inhibitor, ruxolitinib is not sufficient in eliminating the underlying myeloid progenitor clone, as disease inevitably returns with therapy discontinuation. Allogeneic hematopoietic stem cell transplantation is the only therapeutic option that offers potential cure. The development of novel treatment strategies aimed at slowing or even reversing disease progression, prolonging patient survival and preventing evolution to blast-phase are still lacking.

Comparative Effectiveness in Perioperative Outcomes of Robotic versus Open Radical Cystectomy: Results from a Multicenter Contemporary Retrospective Cohort Study.

BACKGROUND: The comparative effectiveness of robotic-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) in terms of perioperative outcomes is still a matter of debate affecting payors, physicians, and patients. OBJECTIVE: To evaluate comparative perioperative and longer-term morbidity of RARC versus ORC in a multicenter contemporary retrospective cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter study included patients with bladder cancer treated with radical cystectomy at 10 academic centers between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intraoperative outcomes including blood loss and operative time as well as postoperative outcomes including time to discharge, complication, readmission, reoperation, and mortality rates at 30 and 90 d were assessed. Multiple imputation and inverse probability of treatment weighting (IPTW) were used. IPTW-multivariable-adjusted regression and logistic analyses were performed to evaluate the associations of RARC versus ORC with perioperative outcomes at 30 and 90 d. RESULTS AND LIMITATIONS: Overall, 1887 patients (1197 RARC and 690 ORC) were included in the study. After IPTW-adjusted analysis, no differences between the groups in terms of preoperative characteristics were observed. RARC was associated with lower blood loss (p<0.001), shorter length of stay (p<0.001), and longer operative time (p=0.007). On IPTW-adjusted multivariable logistic regression analyses, no differences in terms of 30- and 90-d complications, reoperation, and mortality rates were observed. RARC was independently associated with a higher readmission rate at both 30 and 90 d. Limitations are mainly related to the retrospective nature of the study. CONCLUSIONS: While RARC was associated with less blood loss and shorter hospital stay, it also led to longer operation times and more readmissions. There were no differences in 30- and 90-d complications. Because there are no apparent differences in safety between ORC and RARC in expert centers, differences in oncologic and cost-effectiveness outcomes are likely to drive decision making regarding RARC utilization. PATIENT SUMMARY: In this study we investigated the differences between RARC and ORC in terms of perioperative outcomes. We found no difference in early and late complications. We concluded that, to date, differences in oncologic and cost-effectiveness outcomes should drive decision making regarding RARC utilization.

[First-episode psychosis as primary manifestation of medical disease: An update]. / Premier épisode psychotique révélant une affection médicale générale : mise au point pour l'interniste.

A huge variety of medical diseases may potentially present with isolated psychotic symptoms, and disease-specific treatment or management is available for a significant part of them. The initial medical work-up of a first-episode psychosis (FEP) is of crucial importance. This literature review aimed to identify medical conditions potentially revealed by FEP, to list the warning signs of secondary psychosis, and to discuss a screening strategy. Underlying organic conditions may be drugs and medications, neurologic diseases, infections, inflammatory and/or autoimmune pathologies, and metabolic disorders whether of hereditary origin. Each patient presenting with a first-episode psychosis should be evaluated with a precise anamnesis, a careful clinical examination, and routine laboratory tests. Brain imaging and tests (depending on the context) should be performed in the presence of atypical clinical features or "red flags", leading to suspect an organic disease.

Accurate prediction of progression to muscle-invasive disease in patients with pT1G3 bladder cancer: A clinical decision-making tool.

PURPOSE: To improve current prognostic models for the selection of patients with T1G3 urothelial bladder cancer who are more likely to fail intravesical therapy and progress to muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a retrospective analysis of 1,289 patients with pT1G3 urothelial bladder cancer who were treated with transurethral resection of the bladder (TURB) and adjuvant intravesical bacillus-Calmette-Guérin (BCG). Random-split sample data and competing-risk regression were used to identify the independent impact of lymphovascular invasion (LVI) and variant histology (VH) on progression to MIBC. We developed a nomogram for predicting patient-specific probability of disease progression at 2 and 5 years after TURB. Decision curve analysis (DCA) was performed to evaluate the clinical benefit associated with the use of our nomogram. RESULTS: In the development cohort, within a median follow-up of 51.6 months (IQR: 19.3-92.5), disease progression occurred in 89 patients (13.8%). A total of 84 (13%) patients were found to have VH and 57 (8.8%) with LVI at TURB. Both factors were independently associated with disease progression on multivariable competing-risk analysis (HR: 4.4; 95% CI: 2.8-6.9; P<0.001 and HR: 3.5; 95% CI: 2.1-5.8; P<0.001, respectively). DCA showed superior net benefits for the nomogram within a threshold probability of progression between 5% and 55%. Limitations are inherent to the retrospective design. CONCLUSIONS: We demonstrated the clinical value of the integration of LVI and VH in a prognostic model for the prediction of MIBC. Indeed, our tool provides superior individualized risk estimation of progression facilitating decision-making regarding early RC.

Novel endoscopic visualization techniques for bladder cancer detection: a review of the contemporary literature.

PURPOSE OF REVIEW: To describe the principles of photodynamic diagnosis (PDD), narrow-band imaging (NBI) and Storz Professional Image Enhancement System (SPIES) techniques for the endoscopic management of nonmuscle-invasive bladder cancer (BCa) and to report their impact on clinical practice. RECENT FINDINGS: PDD is associated with an increased sensitivity for detecting BCa specifically carcinoma in situ (CIS). Moreover, PDD has been shown to lower recurrence rate in comparison with white-light cystoscopy. The impact on progression-free survival is still unclear yet. NBI and, more recently, SPIES are two novel imaging techniques that do not require preoperative instillation of photosensitizing agents. NBI seems to be associated with lower recurrence rates. Nevertheless, further trials are necessary to confirm these results, in particular in high-risk lesions and CIS. Randomized clinical trials addressing the clinical impact of SPIES are ongoing. SUMMARY: Novel endoscopic imaging techniques are useful diagnostic tools for evaluating BCa during cystoscopic diagnostic surveillance as well as during transurethral resection of the bladder. Although the standard of care remains white-light cystoscopy, these techniques provide higher sensitivity in detecting BCa especially CIS. The continued evidence also suggests that this increased detection leads to lower recurrence rates. The impact on progression and the cost-efficacy as well as selection remains to be refined.

Analysis of the CD8+ T cell anti-HIV activity in heterologous cell co-cultures reveals the benefit of multiple HLA class I matches.

CD8+ T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4+ T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8+ T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4+ T cells. Altogether, CD8+ T cell anti-HIV activity was evaluated in more than 200 co-cultures. Marked heterogeneity in HIV-1 replication levels was observed among the co-cultures sharing a common CD8+ T cell source. The co-cultures that exhibited greater than 50% reduction in HIV production were found to have significantly increased numbers of matching HLA class I alleles (Yates chi-square = 54.21; p < 0.001). With CD8+ T cells from HIV controllers and asymptomatic viremic individuals, matching HLA-B and/or HLA-C alleles were more predictive of strong anti-HIV activity than matching HLA-A alleles. Overall, HLA class I genotype matches were more closely associated with CD8+ T cell anti-HIV activity than supertype pairings. Antibodies against HLA class I and CD3 reduced the CD8+ T cell anti-HIV activity. Stimulated CD8+ T cells exhibited increased anti-HIV activity and reduced dependency on HLA compatibility. These findings provide evidence that the maximal suppression of HIV replication by CD8+ T cells requires the recognition of multiple epitopes. These studies provide insight for HIV vaccine development, and the analytic approach can be useful for the functional characterization of HLA class I alleles and tentative HLA class I supertypes.

Recovery and assessment of leukocytes from LR Express filters.

Leukocytes, or white blood cells, are used for a variety of investigational purposes and they offer advantages over laboratory-adapted cell lines. Leukocytes that are typically discarded by blood banks during the collection of red blood cells, platelets, and plasma can often be obtained for research use. However, the available leukocytes are frequently contained within a blood filtration device, such as the Terumo LR Express (TLRE) filter. In this study, procedures were evaluated for the ability to elute viable leukocytes from TLRE filters. The recovered leukocytes were assessed for composition, growth, and functionality. The large majority (>70%) of leukocytes were eluted with a single reverse-elution procedure and the recovered cells contained representative populations of the major leukocyte subsets. Purified T cells exhibited diverse T cell receptor repertoires, characteristic growth upon mitogen stimulation, and CD4+ T cells were able to support HIV-1 propagation. Purified monocytes were able to be differentiated into phenotypically characteristic populations of macrophages and dendritic cells. Overall, TLRE filters offer an attractive source of primary human cells for research and possibly clinical purposes.

Pandemic (H1N1) 2009 influenza A virus infection associated with respiratory signs in sloth bears (Melursus ursinus).

In 2009, a pandemic influenza A virus (pH1N1) spread globally in humans and infected a broad range of captive animals with close human contact. In February 2014, a pH1N1 virus was isolated from a sloth bear with respiratory signs at a US zoo, demonstrating that recurring epidemics present an ongoing threat to animals, including threatened species. This is the first report of pH1N1 infection in sloth bears. To understand the sloth bear virus within the global context of pH1N1, phylogenetic trees were inferred including full-length sequences from available non-human, non-swine hosts, representing four families in the order Carnivora and one order of birds. A combination of phylogenetic and epidemiological evidence strongly suggests the sloth bear was infected with a human-origin pH1N1 virus, supporting the implementation of biosecurity measures to protect human and animal health.

Brief Report: Increased Expression of the Type I Interferon Receptor on CD4+ T Lymphocytes in HIV-1-Infected Individuals.

BACKGROUND: Type I interferons (IFN1s; eg, interferon-alpha and interferon-beta) are potent cytokines that inhibit the replication of human immunodeficiency virus-1 (HIV-1) and other viruses. The antiviral and immunoregulatory activities of IFN1 are mediated through ligand-receptor interactions with the IFN1 receptor complex (IFNAR). Variation in the cell-surface density of IFNAR could play a role in HIV-1 pathogenesis. METHODS: In this cross-sectional study of fresh whole blood, we used flow cytometry to evaluate the expression of IFNAR2 on lymphocyte subsets from HIV-1-infected (n = 33) and HIV-1-uninfected (n = 22) individuals. RESULTS: In comparison with healthy blood bank donors, we observed that the HIV-1-infected individuals, particularly those having advanced to disease, exhibited the increased expression of IFNAR2 on CD4 T cells (relative fluorescence intensity 6.9 vs. 9.0; P = 0.027). The CD4:CD4 T-cell IFNAR2 expression-level ratio provides an internally standardized measure of this alteration. The observed increased expression of IFNAR2 was largely restricted to CD4 T cells that expressed the chemokine receptor CXCR4 and lacked the expression of CCR5. CONCLUSIONS: HIV-1-infected individuals exhibit an increased expression of the IFN1 receptor on CD4 T cells. The level of IFNAR2 expression seems to increase with disease progression. These findings provide insight for the immunologic alterations associated with HIV-1 infection and possibly new therapeutic approaches.

Vaccine hesitancy among general practitioners: evaluation and comparison of their immunisation practice for themselves, their patients and their children.

To gain knowledge about vaccine hesitancy among general practitioners (GPs), we conducted a survey to compare their vaccination attitudes for themselves, their children and their patients. A questionnaire survey was sent to GPs working in private practice in the Rhône-Alpes region, France, between October 2013 and January 2014. GPs' immunisation practices for diphtheria-tetanus-poliomyelitis (DTP), measles-mumps-rubella (MMR), pneumococcal, pertussis, hepatitis B (hepB), human papillomavirus (HPV), seasonal and H1N1 influenza and meningococcal C (menC) vaccines were considered. Divergence was defined by the presence of at least one different immunisation practice between their patients and their children. A total of 693 GPs answered the questionnaire. When considering all investigated vaccines, 45.7 % of divergence was found. Individually, divergence was highest for the newest and more controversial, i.e. HPV (11.8 %), hepB (13.1 %), menC (23.7 %) and pneumococcal (19.8 %) vaccines. Only 73.9 % of GPs declared that they recommended HPV vaccine for their daughters. After multivariate analysis, older age was associated with higher risk of divergence. According to the French 2012 recommendations, GPs were insufficiently immunised, with 88 % for DTP and 72 % for pertussis. GPs declared to recommend vaccination against DTP, pertussis and MMR for their patients and their children in more than 95 % of cases. The declared rates of recommendation were lower than 90 % for other vaccines. These results bring new insight about vaccine hesitancy. GPs have divergent immunisation attitudes toward their relatives and their patients, especially when considering the newest and most controversial vaccines, with HPV vaccine being the main focus of controversies.

Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States.

A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented.

[Review of the current use of rituximab during 4 years in a French university hospital]. / Le rituximab dans la vraie vie: revue d'utilisation du rituximab de 2010 à 2013 au CHU de Saint-Étienne.

PURPOSE: Rituximab is a human/murine chimeric monoclonal antibody primarily used for treating non-Hodgkin's B-cell lymphoma. Recently, it has also been used in the treatment of several autoimmune diseases. PATIENTS AND METHODS: We conducted a retrospective analysis of patients treated at least once with rituximab between 2010 and 2013 in a French university hospital, to provide a panoramic view of rituximab use including FDA or off-labels uses, its efficacy and safety. RESULTS: Eighty-seven patients were included with 20 different indications: cryoglobulinemic vasculitis (16%) and anti-PLA2R idiopathic membranous nephropathy (13%) were the most frequent. Rituximab use was off-labels in 50% of cases. Eleven percent of patients experienced severe adverse events, mostly infections. After rituximab, 17% of patients were in complete response (CR), 41% in partial response (PR), and 39% non-responding (NR). Relapse was observed in 65% (33/51) of responding patients. CONCLUSION: Further investigation with randomized controlled trials will provide more insight into the specifics of the role of RTX in the overall management of each disease. Identifying clear objectives and strict outcome measures, associated with long term clinical and biological follow-up would help deciding when, how and in which therapeutic regimen will rituximab most benefit a disease or a patient.