Eustachian tube symptoms are frequent in chronic rhinosinusitis and respond well to endoscopic sinus surgery

BACKGROUND: Symptoms of Eustachian tube (ET) dysfunction are seldom assessed in patients with chronic rhinosinusitis (CRS). The Sino-Nasal Outcome Test (SNOT-22) quality-of-life tool includes two questions that specifically screen for symptoms of ET dysfunction (Ear Fullness; Ear Pain). OBJECTIVE: The purpose of this study was to determine the extent to which these ET symptoms were present in patients with CRS, and whether these symptoms respond to endoscopic sinus surgery (ESS). METHODOLOGY: SNOT-22 data collected prospectively at time of recruitment into IRB-approved clinical trials or case-control studies in CRS was pooled to provide a cross section of the frequency and severity of ET dysfunction. When applicable to the trials, the SNOT-22 was repeated at least 3 months following ESS. RESULTS: Five trials rendering 131 patients were available for assessment. The control group comprised of 251 participants from two case-control studies. Ear Fullness of equal/greather than 1 was reported in 80/131 CRS patients compared to 45/251 control patients. Ear Pain of equal/greather than 1 was reported in 39/131 CRS patients compared to 33/251 control patients. Following ESS, mean Ear Fullness and Ear Pain scores decreased to 1.17 and 0.73, respectively. CONCLUSION: Symptoms suggestive of ET dysfunction are frequent in CRS, and for most patients the symptoms will decrease post-ESS to a level comparable with a non-CRS population. Patients whose ET symptoms do not respond to ESS may represent a target population for emerging therapeutic options for ET dysfunction

Prevalence of Coxiella burnetii seropositivity and shedding in farm, pet and feral cats and associated risk factors in farm cats in Quebec, Canada

Cats represent a potential source of Coxiella burnetii, the aetiological agent of Q fever in humans. The prevalence and risk factors of C. burnetii infection in farm, pet and feral cats were studied in Quebec, Canada, using a cross-sectional study. Serum samples were tested using a specific enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies against C. burnetii, whereas rectal swabs were assayed using real-time quantitative polymerase chain reaction (qPCR) for the molecular detection of the bacteria. Potential risk factors for farm cats were investigated using clinical examinations, questionnaires and results from a concurrent study on C. burnetii farm status. A total of 184 cats were tested: 59 from ruminant farms, 73 pets and 52 feral cats. Among farm cats, 2/59 (3.4%) were ELISA-positive, 3/59 (5.1%) were ELISA-doubtful and 1/59 (1.7%) was qPCR-positive. All pets and feral cats were negative to C. burnetii ELISA and qPCR. Farm cat positivity was associated with a positive C. burnetii status on the ruminant farm (prevalence ratio = 7.6, P = 0.03). Our results suggest that although pet and feral cats do not seem to pose a great C. burnetii risk to public health, more active care should be taken when in contact with cats from ruminant farms

EUFOREA/EPOS2020 statement on the clinical considerations for CRSwNP care

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise. The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included.Peer reviewe

CD4 Down-Modulation by Human Immunodeficiency Virus Type 1 Nef Correlates with the Efficiency of Viral Replication and with CD4(+) T-Cell Depletion in Human Lymphoid Tissue Ex Vivo

The human immunodeficiency virus type 1 (HIV-1) Nef protein is an important virulence factor. Nef has several functions, including down-modulation of CD4 and class I major histocompatibility complex cell surface expression, enhancement of virion infectivity, and stimulation of viral replication in peripheral blood mononuclear cells. Nef also increases HIV-1 replication in human lymphoid tissue (HLT) ex vivo. We analyzed recombinant and primary nef alleles with highly divergent activity in different in vitro assays to clarify which of these Nef activities are functionally linked. Our results demonstrate that Nef activity in CD4 down-regulation correlates significantly with the efficiency of HIV-1 replication and with the severity of CD4(+) T-cell depletion in HLT. In conclusion, HIV-1 Nef variants with increased activity in CD4 down-modulation would cause severe depletion of CD4(+) T cells in lymphoid tissues and accelerate AIDS progression

Enantioselective Nickel-Catalyzed Mizoroki–Heck Cyclizations To Generate Quaternary Stereocenters

The development of enantioselective carbon–carbon bond couplings catalyzed by nonprecious metals is highly desirable in terms of cost efficiency and sustainability. The first nickel-catalyzed enantioselective Mizoroki–Heck coupling is reported. This transformation is accomplished via mild reaction conditions, leveraging on QuinoxP* as a chiral ligand to afford oxindoles containing quaternary stereocenters. Good reactivity and selectivity are observed in the presence of various functional groups. Computational studies suggest that the oxidative addition assembles an atropisomeric intermediate responsible for the facial selectivity of the insertion step

Enantioselective Nickel-Catalyzed Mizoroki–Heck Cyclizations To Generate Quaternary Stereocenters

The development of enantioselective carbon–carbon bond couplings catalyzed by nonprecious metals is highly desirable in terms of cost efficiency and sustainability. The first nickel-catalyzed enantioselective Mizoroki–Heck coupling is reported. This transformation is accomplished via mild reaction conditions, leveraging on QuinoxP* as a chiral ligand to afford oxindoles containing quaternary stereocenters. Good reactivity and selectivity are observed in the presence of various functional groups. Computational studies suggest that the oxidative addition assembles an atropisomeric intermediate responsible for the facial selectivity of the insertion step