1.
Indian J Pharmacol. 2020 Jan-Feb;52(1):56-65. doi: 10.4103/ijp.IJP_115_20. Epub 2020 Mar 11.
Drug targets for corona virus: A systematic review.
Prajapat M1, Sarma P1, Shekhar N1, Avti P2, Sinha S3, Kaur H1, Kumar S1, Bhattacharyya A4, Kumar H1, Bansal S1, Medhi B1.
Abstract
The 2019-novel coronavirus (nCoV) is a major source of disaster in the 21th century. However, the lack of specific drugs to prevent/treat an attack is a major need at this current point of time. In this regard, we conducted a systematic review to identify major druggable targets in coronavirus (CoV). We searched PubMed and RCSB database with keywords HCoV, NCoV, corona virus, SERS-CoV, MERS-CoV, 2019-nCoV, crystal structure, X-ray crystallography structure, NMR structure, target, and drug target till Feb 3, 2020. The search identified seven major targets (spike protein, envelop protein, membrane protein, protease, nucleocapsid protein, hemagglutinin esterase, and helicase) for which drug design can be considered. There are other 16 nonstructural proteins (NSPs), which can also be considered from the drug design perspective. The major structural proteins and NSPs may serve an important role from drug design perspectives. However, the occurrence of frequent recombination events is a major deterrent factor toward the development of CoV-specific vaccines/drugs.
Copyright: © 2020 Indian Journal of Pharmacology.
KEYWORDS:
Coronavirus; Middle East respiratory syndrome; drug targets; severe acute respiratory syndrome
2.
BMJ. 2020 Mar 22;368:m1163. doi: 10.1136/bmj.m1163.
Covid-19 mass testing facilities could end the epidemic rapidly.
Peto J1.
3.
Lancet Psychiatry. 2020 Apr;7(4):e22. doi: 10.1016/S2215-0366(20)30089-4.
Mental health care for international Chinese students affected by the COVID-19 outbreak.
4.
Lancet Psychiatry. 2020 Apr;7(4):e21. doi: 10.1016/S2215-0366(20)30090-0.
Patients with mental health disorders in the COVID-19 epidemic.
5.
Lancet Glob Health. 2020 Apr;8(4):e452-e453. doi: 10.1016/S2214-109X(20)30085-1.
Deciphering the power of isolation in controlling COVID-19 outbreaks.
Comment on
- Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts. [Lancet Glob Health. 2020]
6.
Eur Respir J. 2020 Mar 20;55(3). pii: 2000352. doi: 10.1183/13993003.00352-2020. Print 2020 Mar.
More awareness is needed for severe acute respiratory syndrome coronavirus 2019 transmission through exhaled air during non-invasive respiratory support: experience from China.
7.
BMJ. 2020 Mar 20;368:m1117. doi: 10.1136/bmj.m1117.
Challenges for NHS hospitals during covid-19 epidemic.
8.
mBio. 2020 Mar 20;11(2). pii: e00398-20. doi: 10.1128/mBio.00398-20.
Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection.
Abstract
Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection.
Copyright © 2020 Fedson et al.
KEYWORDS:
COVID-19; endothelial dysfunction; generic drugs; host response treatment
9.
BMJ. 2020 Mar 20;368:m1141. doi: 10.1136/bmj.m1141.
Covid-19: control measures must be equitable and inclusive.
10.
Swiss Med Wkly. 2020 Mar 19;150:w20225. doi: 10.4414/smw.2020.20225. eCollection 2020 Mar 9.
COVID-19 epidemic in Switzerland: on the importance of testing, contact tracing and isolation.
Salathé M1, Althaus CL2, Neher R3, Stringhini S, Hodcroft E, Fellay J4, Zwahlen M2, Senti G5, Battegay M6, Wilder-Smith A7, Eckerle I8, Egger M2, Low N2.
Abstract
Switzerland is among the countries with the highest number of coronavirus disease-2019 (COVID-19) cases per capita in the world. There are likely many people with undetected SARS-CoV-2 infection because testing efforts are currently not detecting all infected people, including some with clinical disease compatible with COVID-19. Testing on its own will not stop the spread of SARS-CoV-2. Testing is part of a strategy. The World Health Organization recommends a combination of measures: rapid diagnosis and immediate isolation of cases, rigorous tracking and precautionary self-isolation of close contacts. In this article, we explain why the testing strategy in Switzerland should be strengthened urgently, as a core component of a combination approach to control COVID-19.
11.
PLoS One. 2020 Mar 19;15(3):e0230548. doi: 10.1371/journal.pone.0230548. eCollection 2020.
Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China.
Abstract
Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. 27 patients included 12 men and 15 women, with median age of 60 years (IQR 47-69). 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63-73) vs 55 (IQR 35-60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7-13) vs 12 (IQR 11-43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality. 2019-nCoV was more likely to infect elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.
- PMID:
- 32191764
- PMCID:
- PMC7082074
- DOI:
- 10.1371/journal.pone.0230548
- [Indexed for MEDLINE]
12.
N Engl J Med. 2020 Mar 19;382(12):e30. doi: 10.1056/NEJMe2005759.
Audio Interview: New Research on Possible Treatments for Covid-19.
13.
N Engl J Med. 2020 Mar 19;382(12):1150-1159. doi: 10.1056/NEJMcpc1909621.
Case 9-2020: A 64-Year-Old Man with Shortness of Breath, Cough, and Hypoxemia.
14.
Lancet Child Adolesc Health. 2020 Apr;4(4):e8. doi: 10.1016/S2352-4642(20)30073-0. Epub 2020 Mar 6.
Managing neonates with respiratory failure due to SARS-CoV-2.
Comment in
- Managing neonates with respiratory failure due to SARS-CoV-2 - Authors' reply. [Lancet Child Adolesc Health. 2020]
Comment on
- A contingency plan for the management of the 2019 novel coronavirus outbreak in neonatal intensive care units. [Lancet Child Adolesc Health. 2020]
15.
Lancet Child Adolesc Health. 2020 Apr;4(4):e9. doi: 10.1016/S2352-4642(20)30072-9. Epub 2020 Mar 6.
Managing neonates with respiratory failure due to SARS-CoV-2 - Authors' reply.
Comment on
- A contingency plan for the management of the 2019 novel coronavirus outbreak in neonatal intensive care units. [Lancet Child Adolesc Health. 2020]
- Managing neonates with respiratory failure due to SARS-CoV-2. [Lancet Child Adolesc Health. 2020]
16.
Exerc Immunol Rev. 2020;26:56-78.
Key viral immune genes and pathways identify elite athletes with URS.
Colbey C1, Drew MK2,3,4, Cox AJ1, Vider J1, Pyne DB2,3, Vlahonich N3,5, Hughes D3, Waddington G2,3, Appaneal R2,3, Burke LM3,6, Lundy B3,6, Toomey M7, Watts D8, Lovell G2,3, Praet S2, Halson SL9, Welvaert M2,3, Zhang P1, Cripps AW10, West NP1.
Abstract
PURPOSE:
Habitual intense exercise may increase the incidence of upper respiratory symptoms (URS) in elite athletes. This study investigated whether immune gene expression could identify gene markers that discriminate athletes with a higher prevalence of URS.
METHODS:
This cross-sectional analysis of elite Australian athletes from various sports investigated whether athletes retrospectively reporting URS for two days or more in a month (n=38), had an altered immune gene expression profile compared with asymptomatic athletes (n=33). Peripheral blood samples were collected during Olympic selection events with corresponding URS data collected for the one-month period before sampling. Digital immune gene expression analysis was undertaken using the NanoString PanCancer Immune Profiling panel.
RESULTS:
Fifty immune genes were differentially expressed between the groups (p<0.05) and approximately 78% of these genes were more highly expressed in athletes reporting URS. Many of these genes were interferon-stimulated genes or genes involved in the Jak/Stat signalling pathway. Only interferon alpha inducible protein 27 (IFI27), an interferon stimulated gene involved in viral response, remained significantly higher in athletes reporting URS (log2 fold-difference=2.49, odds ratio 1.02 per unit increase; p<0.01) post-adjustment and discriminated athletes reporting URS from asymptomatic athletes with 78% accuracy.
CONCLUSIONS:
Expression of IFI27 could differentiate athletes reporting URS from asymptomatic athletes, a gene that is upregulated in the immune response to viral infection. Upregulation of viral signalling pathways provides novel information on the potential aetiology of URS in elite Olympic athletes.
Copyright © 2020 International Society of Exercise and Immunology. All rights reserved.
KEYWORDS:
NanoString; digital immune gene expression; elite athletes; respiratory illness
17.
Lancet Psychiatry. 2020 Apr;7(4):e19. doi: 10.1016/S2215-0366(20)30079-1. Epub 2020 Feb 19.
Mental health services for older adults in China during the COVID-19 outbreak.
18.
Lancet Psychiatry. 2020 Apr;7(4):e20. doi: 10.1016/S2215-0366(20)30076-6. Epub 2020 Feb 19.
The neglected health of international migrant workers in the COVID-19 epidemic.
19.
Lancet Psychiatry. 2020 Apr;7(4):e17-e18. doi: 10.1016/S2215-0366(20)30077-8. Epub 2020 Feb 19.
Online mental health services in China during the COVID-19 outbreak.
20.
Lancet Psychiatry. 2020 Apr;7(4):e15-e16. doi: 10.1016/S2215-0366(20)30078-X. Epub 2020 Feb 19.
Mental health care for medical staff in China during the COVID-19 outbreak.
21.
Int J Antimicrob Agents. 2020 Mar;55(3):105924. doi: 10.1016/j.ijantimicag.2020.105924. Epub 2020 Feb 17.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges.
Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24-3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.
Copyright © 2020 Elsevier Ltd. All rights reserved.
KEYWORDS:
2019-nCoV; COVID-19; China; Epidemic; Remdesivir; SARS-CoV-2
22.
Res Social Adm Pharm. 2020 Apr;16(4):583-586. doi: 10.1016/j.sapharm.2020.02.003. Epub 2020 Feb 12.
Community pharmacist in public health emergencies: Quick to action against the coronavirus 2019-nCoV outbreak.
Ung COL1.
Abstract
The 2019-nCoV infection that is caused by a novel strain of coronavirus was first detected in China in the end of December 2019 and declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Community pharmacists in one of the first areas that had confirmed cases of the viral infection, Macau, joined the collaborative force in supporting the local health emergency preparedness and response arrangements. This paper aimed to improve the understanding of community pharmacists' role in case of 2019-CoV outbreak based on the practical experiences in consultation with the recommendations made by the International Pharmaceutical Federation on the Coronavirus 2019-nCoV outbreak.
Copyright © 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
2019-nCoV; Community pharmacy; Macau; Outbreak; Pharmacist
23.
N Engl J Med. 2020 Mar 19;382(12):1177-1179. doi: 10.1056/NEJMc2001737. Epub 2020 Feb 19.
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients.
24.
BMC Infect Dis. 2020 Jan 28;20(1):79. doi: 10.1186/s12879-019-4750-4.
Use of a rapid recombinase-aided amplification assay for Mycoplasma pneumoniae detection.
Abstract
BACKGROUND:
Mycoplasma pneumoniae is one of the most common causative pathogens of community-acquired pneumonia (CAP), accounting for as many as 30-50% of CAP during peak years. An early and rapid diagnostic method is key for guiding clinicians in their choice of antibiotics.
METHODS:
The recombinase-aided amplification (RAA) assay is a recently developed, rapid detection method that has been used for the detection of several pathogens. The assays were performed in a one-step single tube reaction at 39° Celsius within 15-30 min. In this study, we established an RAA assay for M. pneumoniae using clinical specimens for validation and commercial real-time PCR as the reference method.
RESULTS:
The analytical sensitivity of the RAA assay was 2.23 copies per reaction, and no cross-reactions with any of the other 15 related respiratory bacterial pathogens were observed. Compared with the commercial real-time PCR assay used when testing 311 respiratory specimens, the RAA assay obtained 100% sensitivity and 100% specificity with a kappa value of 1.
CONCLUSIONS:
These results demonstrate that the proposed RAA assay will be of benefit as a faster, sensitive, and specific alternative tool for the detection of M. pneumoniae.
KEYWORDS:
Detection; Molecular diagnostic technique; Mycoplasma pneumoniae; Recombinase; Recombinase-aided amplification
- PMID:
- 31992210
- PMCID:
- PMC6988361
- DOI:
- 10.1186/s12879-019-4750-4
- [Indexed for MEDLINE]
25.
BMC Infect Dis. 2020 Jan 28;20(1):80. doi: 10.1186/s12879-020-4792-7.
Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016.
Godoy P1,2,3, Torner N4,5,6, Soldevila N5,6, Rius C5,7, Jane M4,5, Martínez A4,5,6, Caylà JA5,7, Domínguez A5,6; Working Group on the Surveillance of Severe Influenza Hospitalized Cases in Catalonia.
Abstract
BACKGROUND:
In addition to outbreaks of nosocomial influenza, sporadic nosocomial influenza infections also occur but are generally not reported in the literature. This study aimed to determine the epidemiologic characteristics of cases of nosocomial influenza compared with the remaining severe cases of severe influenza in acute hospitals in Catalonia (Spain) which were identified by surveillance.
METHODS:
An observational case-case epidemiological study was carried out in patients aged ≥18 years from Catalan 12 hospitals between 2010 and 2016. For each laboratory-confirmed influenza case (nosocomial or not) we collected demographic, virological and clinical characteristics. We defined patients with nosocomial influenza as those admitted to a hospital for a reason other than acute respiratory infection in whom ILI symptoms developed ≥48 h after admission and influenza virus infection was confirmed using RT-PCR. Mixed-effects regression was used to estimate the crude and adjusted OR.
RESULTS:
One thousand seven hundred twenty-two hospitalized patients with severe laboratory-confirmed influenza virus infection were included: 96 (5.6%) were classified as nosocomial influenza and more frequently had > 14 days of hospital stay (42.7% vs. 27.7%, P < .001) and higher mortality (18.8% vs. 12.6%, P < .02). The variables associated with nosocomial influenza cases in acute-care hospital settings were chronic renal disease (aOR 2.44 95% CI 1.44-4.15) and immunodeficiency (aOR 1.79 95% CI 1.04-3.06).
CONCLUSIONS:
Nosocomial infections are a recurring problem associated with high rates of chronic diseases and death. These findings underline the need for adherence to infection control guidelines.
KEYWORDS:
Healthcare-associated infection; Hospitalized patients; Influenza; Nosocomial infection
- PMID:
- 31992207
- PMCID:
- PMC6988218
- DOI:
- 10.1186/s12879-020-4792-7
- [Indexed for MEDLINE]
26.
Asian Cardiovasc Thorac Ann. 2020 Jan;28(1):29-32. doi: 10.1177/0218492319896515. Epub 2019 Dec 15.
Deep cervical and paratracheal drainage for descending necrotizing mediastinitis.
Sakai T1, Matsutani N2, Ito K3, Mochiki M3, Mineda J3, Shirai S1, Kanaoka R1, Yamauchi Y1, Saito Y1, Sakao Y1, Kawamura M1.
KEYWORDS:
Drainage; infection; mediastinal diseases; mediastinitis; thoracic surgical procedures
27.
Int J Antimicrob Agents. 2020 Mar;55(3):105862. doi: 10.1016/j.ijantimicag.2019.105862. Epub 2019 Dec 16.
Diversity of amino acid substitutions in PmrCAB associated with colistin resistance in clinical isolates of Acinetobacter baumannii.
Gerson S1, Lucaßen K1, Wille J2, Nodari CS3, Stefanik D1, Nowak J1, Wille T1, Betts JW4, Roca I5, Vila J5, Cisneros JM6, Seifert H2, Higgins PG7.
Abstract
This study aimed to investigate the mechanisms of colistin resistance in 64 Acinetobacter baumannii isolates obtained from patients with ventilator-associated pneumonia hospitalised in Greece, Italy and Spain. In total, 31 A. baumannii isolates were colistin-resistant. Several novel amino acid substitutions in PmrCAB were found in 27 colistin-resistant A. baumannii. Most substitutions were detected in PmrB, indicating the importance of the histidine kinase for colistin resistance. In two colistin-resistant isolates, 93 amino acid changes were observed in PmrCAB compared with A. baumannii ACICU, and homologous recombination across different clonal lineages was suggested. Analysis of gene expression revealed increased pmrC expression in isolates harbouring pmrCAB mutations. Complementation of A. baumannii ATCC 19606 and ATCC 17978 with a pmrAB variant revealed increased pmrC expression but unchanged colistin MICs, indicating additional unknown factors associated with colistin resistance. Moreover, a combination of PmrB and PmrC alterations was associated with very high colistin MICs, suggesting accumulation of mutations as the mechanism for high-level resistance. The pmrC homologue eptA was detected in 29 colistin-susceptible and 26 colistin-resistant isolates. ISAba1 was found upstream of eptA in eight colistin-susceptible and one colistin-resistant isolate and eptA was disrupted by ISAba125 in two colistin-resistant isolates. Whilst in most isolates an association of eptA with colistin resistance was excluded, in one isolate an amino acid substitution in EptA (R127L) combined with a point mutation in ISAba1 upstream of eptA contributed to elevated colistin MICs. This study helps to gain an insight into the diversity and complexity of colistin resistance in A. baumannii.
Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
KEYWORDS:
Colistin; ISAba1; Mutation; Whole-genome sequencing; pmrCAB operon
28.
PLoS One. 2019 Dec 3;14(12):e0225793. doi: 10.1371/journal.pone.0225793. eCollection 2019.
Circulation of influenza virus from 2009 to 2018 in Cameroon: 10 years of surveillance data.
Njouom R1, Monamele CG1, Munshili Njifon HL1, Kenmoe S1, Ripa Njankouo M1; Network of influenza surveillance in Cameroon.
Abstract
Since the recent emergence of several subtypes of influenza viruses with pandemic potentials, there has been growing interest on the control of this infection worldwide. This study aimed to describe the 10 years of influenza activity in Cameroon between January 2009 and December 2018. Respiratory samples were collected from sentinel sites responsible for influenza surveillance in Cameroon and analyzed for the presence of influenza. Globally, 9 of the 10 administrative regions of the country were represented with at least 1 year of data. A total of 11816 respiratory samples were collected and influenza virus detection rate was 24.0%. The most represented age group was the 0-1 years representing more than 40% of the collected samples and possessing the lowest proportion of influenza cases (16.2%). Meanwhile higher proportions of influenza positive cases was found in the 2-4, 5-14 and 15-49 years age group at ≥29%. Among outpatients, the frequency of influenza virus was 24.8% while in hospitalized patients, 18.7% of samples were positive for influenza virus. We noted year-round circulation of influenza virus in Cameroon with 2 peaks in activity: a major peak in the months of September to December and a minor peak in the months of March to July. Antigenic characterization of influenza isolates showed 37.5% (6/16) vaccine match between the predominant Cameroon strains and the Northern hemisphere vaccine strains with majority of vaccine match observed in influenza B/Victoria subtype (4/6; 66.7%). Data collected from this surveillance system is essential to add to global information on the spread of influenza.
- PMID:
- 31794579
- PMCID:
- PMC6890244
- DOI:
- 10.1371/journal.pone.0225793
- [Indexed for MEDLINE]
29.
Am J Nurs. 2019 Dec;119(12):20-21. doi: 10.1097/01.NAJ.0000615764.71666.f0.
New Antibiotic for Community-Acquired Bacterial Pneumonia.
30.
Virol J. 2019 Oct 29;16(1):124. doi: 10.1186/s12985-019-1231-8.
Identifying novel biomarkers of the pediatric influenza infection by weighted co-expression network analysis.
Abstract
BACKGROUND:
Despite the high yearly prevalence of Influenza, the pathogenesis mechanism and involved genes have not been fully known. Finding the patterns and mapping the complex interactions between different genes help us to find the possible biomarkers and treatment targets.
METHODS:
Herein, weighted gene co-expression network analysis (WGCNA) was employed to construct a co-expression network among genes identified by microarray analysis of the pediatric influenza-infected samples.
RESULTS:
Three of the 38 modules were found as the most related modules to influenza infection. At a functional level, we found that the genes in these modules regulate the immune responses, protein targeting, and defense to virus. Moreover, the analysis of differentially expressed genes disclosed 719 DEGs between the normal and infected subjects. The comprehensive investigation of genes in the module involved in immune system and viral defense (yellow module) revealed that SP110, HERC5, SAMD9L, RTP4, C19orf66, HELZ2, EPSTI1, and PHF11 which were also identified as DEGs (except C19orf66) have the potential to be as the biomarkers and also drug targeting for the treatment of pediatric influenza.
CONCLUSIONS:
The WGCN analysis revealed co-expressed genes which were involved in the innate immune system and defense to virus. The differentially expressed genes in the identified modules can be considered for designing drug targets. Moreover, modules can help to find pathogenesis routes in the future.
KEYWORDS:
Biomarker; Co-expression network; Influenza; Pathogenesis
- PMID:
- 31665046
- PMCID:
- PMC6819563
- DOI:
- 10.1186/s12985-019-1231-8
- [Indexed for MEDLINE]
31.
Biomed Res Int. 2019 Sep 29;2019:1035730. doi: 10.1155/2019/1035730. eCollection 2019.
Extracorporeal Life Support: The Next Step in Moderate to Severe ARDS-A Review and Meta-Analysis of the Literature.
Abstract
Despite the use of lung protective ventilation (LPV) strategies, a severe form of acute respiratory distress syndrome (ARDS) is unfortunately associated with high mortality rates, which sometimes exceed 60%. Recently, major technical improvements have been applied in extracorporeal life support (ECLS) systems, but as these techniques are costly and associated with very serious adverse events, high-quality evidence is needed before these techniques can become the "cornerstone" in the management of moderate to severe ARDS. Unfortunately, evaluation of previous randomized controlled and observational trials revealed major methodological issues. In this review, we focused on the most important clinical trials aiming at a final conclusion about the effectiveness of ECLS in moderate to severe ARDS patients. Totally, 20 published clinical studies were included in this review. Most studies have important limitations with regard to quality and design. In the 20 included studies (2,956 patients), 1,185 patients received ECLS. Of them, 976 patients received extracorporeal membrane oxygenation (ECMO) and 209 patients received extracorporeal carbon dioxide removal (ECCO2R). According to our results, ECLS use was not associated with a benefit in mortality rate in patients with ARDS. However, when restricted to higher quality studies, ECMO was associated with a significant benefit in mortality rate. Furthermore, in patients with H1N1, a potential benefit of ECLS in mortality rate was apparent. Until more high-quality data are derived, ECLS should be an option as a salvage therapy in severe hypoxemic ARDS patients.
Copyright © 2019 Diamanto Aretha et al.
32.
BMC Pulm Med. 2019 Oct 12;19(1):176. doi: 10.1186/s12890-019-0952-1.
Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis.
Numata T1, Nakayama K2,3, Utsumi H2, Kobayashi K2, Yanagisawa H2, Hashimoto M2, Minagawa S2, Ishikawa T2, Hara H2, Araya J2, Kuwano K2.
Abstract
BACKGROUND:
Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice.
OBJECTIVE:
To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma.
METHODS:
From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations.
RESULTS:
The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [- 71.3 ± 37.0% vs - 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [- 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5-336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14).
CONCLUSION:
Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.
KEYWORDS:
Asthma; Eosinophilic chronic rhinosinusitis; Mepolizumab; Predictive factor; Staphylococcus enterotoxin
- PMID:
- 31606052
- PMCID:
- PMC6790020
- DOI:
- 10.1186/s12890-019-0952-1
- [Indexed for MEDLINE]
33.
ACS Appl Mater Interfaces. 2019 Oct 30;11(43):39648-39661. doi: 10.1021/acsami.9b15118. Epub 2019 Oct 21.
Bioinspired Heteromultivalent Ligand-Decorated Nanotherapeutic for Enhanced Photothermal and Photodynamic Therapy of Antibiotic-Resistant Bacterial Pneumonia.
Abstract
Pseudomonas aeruginosa can cause a multitude of inflammations in humans. Due to its ability to form biofilm, the bacteria show durable resistance to drugs. Herein, we developed a heteromultivalent ligand-decorated nanotherapeutic inspired by living system for inhibition of antibiotic-resistant bacterial pneumonia. The nanotherapeutic with a heteromultivalent glycomimetic shell can specifically recognize P. aeruginosa to inhibit its biofilm formation and protect native cells from bacterial infection; the rate of biofilm inhibition was up to 85%. The nanotherapeutic with a bioresponsive hydrophobic core can protonate and control drug release in the microenvironment of bacterial infections. By utilizing these properties, the nanotherapeutics can effectively penetrate the internal structure of biofilms to release the drug, dispersing the biofilm by over 80% under laser irradiation. In vivo bioinspired nanotherapeutics have the potential to efficiently inhibit antibiotic-resistant P. aeruginosa-induced pneumonia. Collectively, we expect biomimicking systems to be the next generation of prevention and treatment as integrated antibacterial agents against P. aeruginosa.
KEYWORDS:
Pseudomonas aeruginosa antibiotic resistance; bioinspired; heteromultivalency; photodynamic therapy; pneumonia
34.
Ann Thorac Surg. 2019 Dec;108(6):e405-e407. doi: 10.1016/j.athoracsur.2019.06.104. Epub 2019 Aug 27.
Surgical Management of Iatrogenic Left Ventricle Perforation by Chest Tube Insertion.
Abstract
Chest tube thoracostomy is a standard procedure in every intensive care unit. Although it is regarded as a safe procedure in experienced hands, rare complications do occur. This report describes iatrogenic perforation of the left ventricle after placement of an intercostal catheter and the successful surgical management of this injury. Various operative situations that may arise in relation to iatrogenic perforation of the left ventricle are also discussed, as well as steps to manage this potentially life-threatening complication.
Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
35.
Clin Lung Cancer. 2019 Nov;20(6):442-450.e4. doi: 10.1016/j.cllc.2019.07.006. Epub 2019 Aug 1.
Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors.
Fukihara J1, Sakamoto K2, Koyama J3, Ito T4, Iwano S5, Morise M1, Ogawa M6, Kondoh Y7, Kimura T7, Hashimoto N1, Hasegawa Y1.
Abstract
INTRODUCTION:
Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those without, few data are available on the prognosis of those treated with PD-1 inhibitors who developed immune-related pneumonitis (IRP). Additionally, the robust risk factors of IRP have not been well elucidated.
PATIENTS AND METHODS:
A retrospective review of patients with recurrent or advanced NSCLC who took a PD-1 inhibitor (nivolumab or pembrolizumab monotherapy) between January 2016 and March 2018 was undertaken. Radiologic findings such as unilateral infiltration were also defined as IRP as long as they were deemed relevant to PD-1 inhibitors.
RESULTS:
Twenty-seven (16%) of 170 patients developed IRP. Although 22 (81%) of 27 patients with IRP recovered with drug cessation with or without corticosteroid therapy, 8-week landmark analysis showed the overall survival after administration of the PD-1 inhibitor was significantly shorter in patients with IRP than in those without (8.7 vs. 23.0 months, P = .015). Patients with IRP tended to not receive next-line treatment and choose best supportive care after cessation of PD-1 inhibitor therapy. In the multivariate analysis, pembrolizumab (vs. nivolumab) and low serum albumin were independent risk factors for IRP.
CONCLUSION:
Development of IRP was correlated with poor prognosis in patients with NSCLC. Further study is necessary for establishing the best prediction and management strategies for IRP.
Copyright © 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
Drug-induced lung disease; Immune checkpoint inhibitor; Immune-related adverse event; PD-1 inhibitor
36.
Epidemiol Infect. 2019 Jan;147:e212. doi: 10.1017/S0950268819000979.
Healthcare utilisation and cost expenditures for pneumonia in individuals with diabetes mellitus in the USA.
Abstract
Pneumonia is one of the leading causes of hospitalisations among adults in the USA. Individuals with diabetes mellitus (DM) have been associated with increased risk for pneumonia and complications including death. The objectives of this study were to (1) compare the prevalence and healthcare utilisation patterns for pneumonia in individuals with and without DM, and (2) identify risk factors for pneumonia in those with DM. We performed a retrospective, cross-sectional analysis of the US adult population using Medical Expenditure Panel Surveys (MEPS) data from 2014. Overall, the data represented 24 million individuals with DM and 218 million without DM in the USA. The population-based rate for a pneumonia event was 34 per 1000 persons for individuals with DM and 19 per 1000 persons without DM. Compared to the non-DM group, individuals with DM were treated 1.8x, 2.6x and 1.4x more in the ED, hospital and outpatient, respectively. Furthermore, the average cost per pneumonia event was significantly higher among individuals with DM compared to non-DM in the inpatient setting ($11 931 vs. $7751; P < 0.001). Among individuals with DM, female sex, DM complications, smokers and administration of pneumococcal vaccines were significant factors associated with a pneumonia event.
KEYWORDS:
Diabetes; epidemiology; pneumonia
- PMID:
- 31364575
- PMCID:
- PMC6624864
- DOI:
- 10.1017/S0950268819000979
- [Indexed for MEDLINE]
37.
Epidemiol Infect. 2019 Jan;147:e201. doi: 10.1017/S0950268819000876.
Influenza vaccine effectiveness against hospitalisation due to laboratory-confirmed influenza in children in England in the 2015-2016 influenza season - a test-negative case-control study.
Abstract
England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case-control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2-16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015-2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3-54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3-63.6) and 28.8% (95% CI -31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015-2016 and continues to support the rollout of the LAIV childhood programme.
KEYWORDS:
Children's vaccines; influenza; influenza (seasonal); vaccination (immunisation); vaccine effectiveness
- PMID:
- 31364557
- PMCID:
- PMC6624859
- DOI:
- 10.1017/S0950268819000876
- [Indexed for MEDLINE]
38.
Epidemiol Infect. 2019 Jan;147:e213. doi: 10.1017/S095026881900102X.
Prior exposure to immunogenic peptides found in human influenza A viruses may influence the age distribution of cases with avian influenza H5N1 and H7N9 virus infections.
Abstract
The epidemiology of H5N1 and H7N9 avian viruses of humans infected in China differs despite both viruses being avian reassortants that have inherited six internal genes from a common ancestor, H9N2. The median age of infected populations is substantially younger for H5N1 virus (26 years) compared with H7N9 virus (63 years). Population susceptibility to infection with seasonal influenza is understood to be influenced by cross-reactive CD8+ T cells directed towards immunogenic peptides derived from internal viral proteins which may provide some level of protection against further influenza infection. Prior exposure to seasonal influenza peptides may influence the age-related infection patterns observed for H5N1 and H7N9 viruses. A comparison of relatedness of immunogenic peptides between historical human strains and the two avian emerged viruses was undertaken for a possible explanation in the differences in age incidence observed. There appeared to be some relationship between past exposure to related peptides and the lower number of H5N1 virus cases in older populations, however the relationship between prior exposure and older populations among H7N9 virus patients was less clear.
KEYWORDS:
Avian flu; H5N1; H7N9; immunogenic peptides; influenza A
- PMID:
- 31364549
- PMCID:
- PMC6624876
- DOI:
- 10.1017/S095026881900102X
- [Indexed for MEDLINE]
39.
Epidemiol Infect. 2019 Jan;147:e192. doi: 10.1017/S0950268819000839.
The epidemiology of paediatric Mycoplasma pneumoniae pneumonia in North China: 2006 to 2016.
Abstract
Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2-3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2-3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.
KEYWORDS:
Epidemiology; Mycoplasma; paediatrics; pneumonia
- PMID:
- 31364532
- PMCID:
- PMC6518602
- DOI:
- 10.1017/S0950268819000839
- [Indexed for MEDLINE]
40.
Epidemiol Infect. 2019 Jan;147:e199. doi: 10.1017/S0950268819000840.
Seroprevalence of Bordetella pertussis toxin antibodies in children and adolescents in Tunis, Tunisia.
Abstract
Pertussis remains a public health concern in most countries. This cross-sectional study aims to investigate the distribution of pertussis toxin antibodies (anti-PT IgG) in Tunisian children and adolescents aged 3-18 years, to define optimal age for booster vaccination. Anti-PT IgG concentrations of enrolled participants were measured using commercial enzyme-linked immunosorbent assay. Concentrations were classified as: indicative of current/recent infection if ⩾100 IU/ml, indicative of recent exposure to Bordetella pertussis within the last year if 40-100 IU/ml and less likely revealing a recent exposure to B. pertussis if <40 IU/ml. Between March and June 2018, a total of 304 participants (mean age: 9.3 years) were included in this study. Overall, 12.8% (95% confidence interval (CI) 9.1%-16.6%) were seropositive (IgG levels ⩾40 IU/ml). Among them, 14.7% (95% CI 2.3%-23.3%) had levels indicative of a current/recent infection. The multivariate Poisson regression analysis suggested associations between female gender, as well as age group 13-18 years and 3-5 years and higher anti-PT IgG concentrations. Our results are consistent with the notion that vaccine-induced immunity decline, as well as circulation of pertussis among school children and adolescents enables them to be reservoirs of infection and disease transmission to vulnerable infants. Booster dose of acellular pertussis vaccine for school entrants is therefore recommended.
KEYWORDS:
Adolescents; Tunisia; children; pertussis; seroprevalence
- PMID:
- 31364527
- PMCID:
- PMC6536764
- DOI:
- 10.1017/S0950268819000840
- [Indexed for MEDLINE]
41.
PLoS One. 2019 Jul 24;14(7):e0220251. doi: 10.1371/journal.pone.0220251. eCollection 2019.
Empiric treatment of pulmonary TB in the Xpert era: Correspondence of sputum culture, Xpert MTB/RIF, and clinical diagnoses.
Kendall EA1,2, Kamoga C2, Kitonsa PJ2, Nalutaaya A2, Salvatore PP3, Robsky K2,3, Nakasolya O2, Mukiibi J2, Isooba D2, Cattamanchi A2,4, Kato-Maeda M4, Katamba A2,5, Dowdy DW2,3.
Abstract
BACKGROUND:
Clinical tuberculosis diagnosis and empiric treatment have traditionally been common among patients with negative bacteriologic test results. Increasing availability of rapid molecular diagnostic tests, including Xpert MTB/RIF and the new Xpert Ultra cartridge, may alter the role of empiric treatment.
METHODS:
We prospectively enrolled outpatients age > = 15 who were evaluated for pulmonary tuberculosis at three health facilities in Kampala, Uganda. Using sputum mycobacterial culture, interviews, and clinical record abstraction, we estimated the accuracy of clinical diagnosis relative to Xpert and sputum culture and assessed the contribution of clinical diagnosis to case detection.
RESULTS:
Over a period of 9 months, 99 patients were diagnosed with pulmonary tuberculosis and subsequently completed sputum culture; they were matched to 196 patients receiving negative tuberculosis evaluations in the same facilities. Xpert was included in the evaluation of 291 (99%) patients. Compared to culture, Xpert had a sensitivity of 92% (95% confidence interval 83-97%) and specificity of 95% (92-98%). Twenty patients with negative Xpert were clinically diagnosed with tuberculosis and subsequently had their culture status determined; two (10%) were culture-positive. Considering all treated patients regardless of Xpert and culture data completeness, and considering treatment initiations before a positive Xpert (N = 4) to be empiric, 26/101 (26%) tuberculosis treatment courses were started empirically. Compared to sputum smear- or Xpert-positive patients with positive cultures, empirically-treated, Xpert-negative patients with negative cultures had higher prevalence of HIV (67% versus 37%), shorter duration of cough (median 4 versus 8 weeks), and lower inflammatory markers (median CRP 7 versus 101 mg/L).
CONCLUSION:
Judged against sputum culture in a routine care setting of high HIV prevalence, the accuracy of Xpert was high. Clinical judgment identified a small number of additional culture-positive cases, but with poor specificity. Although clinicians should continue to prescribe tuberculosis treatment for Xpert-negative patients whose clinical presentations strongly suggest pulmonary tuberculosis, they should also carefully consider alternative diagnoses.
- PMID:
- 31339935
- PMCID:
- PMC6655770
- DOI:
- 10.1371/journal.pone.0220251
- [Indexed for MEDLINE]
42.
Ann Thorac Cardiovasc Surg. 2019 Dec 20;25(6):318-325. doi: 10.5761/atcs.oa.19-00128. Epub 2019 Jul 18.
A Double-Blind Randomized Controlled Trial to Determine the Preventive Effect of Hangekobokuto on Aspiration Pneumonia in Patients Undergoing Cardiovascular Surgery.
Abstract
PURPOSE:
This study aimed to assess whether hangekobokuto (HKT) can prevent aspiration pneumonia in patients undergoing cardiovascular surgery.
METHODS:
We performed a single-center, double-blinded, randomized, placebo-controlled study of HKT in patients undergoing cardiovascular surgery. JPS HKT extract granule (JPS-16) was used as HKT. The primary endpoint was defined as the prevention of postoperative aspiration pneumonia. The secondary endpoints included complete recovery from swallowing and coughing disorders.
RESULTS:
Between August 2014 and August 2015, a total of 34 patients were registered in this study. The rate of subjects with postoperative aspiration pneumonia was significantly lower in the HKT group than in the placebo group (p = 0.017). In high-risk patients for aspiration pneumonia, the rate was significantly lower in the HKT group than in the placebo group (p = 0.015). The rate of subjects with swallowing disorders tended to be lower in the HKT group than in the placebo group (p = 0.091), and in high-risk patients, the rate was significantly lower in the HKT group than in the placebo group (p = 0.038).
CONCLUSIONS:
HKT can prevent aspiration pneumonia in patients undergoing cardiovascular surgery. In high-risk patients for aspiration pneumonia, HKT can prevent aspiration pneumonia and improve swallowing disorders.
KEYWORDS:
Kampo medicine; aspiration pneumonia; dysphagia; hangekobokuto
- PMID:
- 31316037
- PMCID:
- PMC6923725
- DOI:
- 10.5761/atcs.oa.19-00128
- [Indexed for MEDLINE]
43.
J Hosp Infect. 2019 Oct;103(2):231-232. doi: 10.1016/j.jhin.2019.07.008. Epub 2019 Jul 13.
Cost analysis for electron time-flow taps and point of use filters: a comparison of two methods for Legionnaires' disease prevention in hospital water networks.
Totaro M1, De Vita E1, Mariotti T1, Bisordi C1, Giorgi S1, Gallo A2, Costa AL1, Casini B1, Valentini P1, Privitera G1, Baggiani A3.
44.
Methods Mol Biol. 2019;2010:197-209. doi: 10.1007/978-1-4939-9541-7_14.
Human Neutrophil Isolation and Degranulation Responses to Yersinia pestis Infection.
Abstract
Neutrophils are the primary immune cell recruited to the site of bacterial infection, where they can rapidly deploy vesicles filled with various pro-inflammatory and anti-microbial proteins. This degranulation process, combined with oxidative and nitrosative mechanisms, is a major part of the initial host response to kill microorganisms. Neutrophils are one of the main cell types that interact with Yersinia pestis during infection, which is often lethal in the absence of prompt antibiotic treatment. Intradermal inoculation of Y. pestis results in bubonic plague, and inhalation of aerosolized droplets containing Y. pestis results in pneumonic plague. Although neutrophils are recruited to the site of inoculation during both bubonic and pneumonic plague, the neutrophils fail to clear Y. pestis, and, during pneumonic plague, contribute to the development of severe pneumonia. Subverting neutrophil responses is critical to the development of fulminant disease, yet the mechanisms by which Y. pestis impairs neutrophils are poorly understood. Cell culture models are important tools for studying Y. pestis interactions with immune cells. We describe a cell culture model for the infection of human neutrophils with Y. pestis. Neutrophils are isolated from human peripheral blood at high purity and subsequently infected with Y. pestis. We specifically focus on the application of this in vitro infection assay to the analysis of neutrophil degranulation responses.
KEYWORDS:
Cell culture; Degranulation; Flow cytometry; Granule exocytosis; Neutrophil; Neutrophil isolation; Plague; Yersinia pestis
45.
Methods Mol Biol. 2019;2010:141-150. doi: 10.1007/978-1-4939-9541-7_10.
Monitoring of Neutrophil Recruitment to Mice Lungs During Pneumonic Plague.
Abstract
Early sensing of bacterial infection and the immediate recruitment of neutrophils to the lung is a major and decisive stage of the innate immune response to pulmonary bacterial infections. This chapter details the preparation of lung tissue suspensions from mice infected intra-nasally (I.N.) with the plague bacterium Yersinia pestis to study in vivo neutrophil responses to the infection. The samples were used for the quantification of neutrophil levels and for the characterization of the pro-inflammatory response required for neutrophil recruitment to the lung. The specific requirements for performing the procedures under Biosafety Level 3 containment and the proper handling and sterilization of the samples are discussed.
KEYWORDS:
BSL-3; FACS analysis; Infection; Lung samples; Mouse model; Neutrophils isolation; Plague; Y. pestis
46.
Methods Mol Biol. 2019;2010:29-39. doi: 10.1007/978-1-4939-9541-7_3.
Standardized Method for Aerosol Challenge of Rodents with Yersinia pestis for Modeling Primary Pneumonic Plague.
Abstract
Primary pneumonic plague occurs when Yersinia pestis is inhaled into the lower respiratory tract where it invades the alveoli and grows. Rapid bacterial growth eventually elicits a neutrophilic inflammatory response that is ineffective and damaging, leading to accelerated progression of disease. In the laboratory, modeling of primary pneumonic plague can be accomplished by instillation of bacterial culture in the nares of anesthetized mice and rats. Although primary pneumonic plague can develop from this method, variability in dosing and side effects of anesthesia can complicate data interpretation. In contrast, aerosol challenge models allow for well-controlled studies of pneumonic plague with minimal experimental bias and unwanted side effects. For these reasons, antibiotic testing and the licensing of new treatments depend on efficacy data generated from aerosol delivery of Y. pestis in order to more accurately model transmission and the early stages of human pneumonic plague. In order to meet this need, we have extensively characterized pneumonic plague in mice and rats challenged by nose-only exposure to Yersinia pestis. With this approach, simultaneous challenge of large cohorts of animals, gently restrained and not anesthetized, assures safe, well-controlled, unbiased, and uniform infection. In this chapter, we present a standardized method for reproducible aerosol delivery of wild-type Y. pestis to rodents for experimental models of primary pneumonic plague.
KEYWORDS:
Aerosol; Animal model; Pneumonic plague; Yersinia pestis
47.
Methods Mol Biol. 2019;2010:17-28. doi: 10.1007/978-1-4939-9541-7_2.
Intranasal Inoculation of Mice with Yersinia pestis and Processing of Pulmonary Tissue for Analysis.
Abstract
Pneumonic plague is a rapidly progressing and highly lethal pneumonia caused by pulmonary infection with Yersinia pestis. Disease is marked by the rapid replication of bacteria in the lungs in the absence of symptoms, followed by the abrupt onset of a highly lethal inflammatory response. A murine intranasal infection model has been key to characterizing the progression of disease. Mice are a natural Y. pestis host, and murine disease closely mirrors what is seen during human infection. Intranasal inoculation of mice with fully virulent Y. pestis strains allows for the detailed analysis of key bacterial and host factors that define disease progression. In this chapter I describe a method for intranasal inoculation of mice with Y. pestis, as well as techniques for processing lung tissue for analysis. These include protocols for isolating whole lungs and lavage fluid for measure of bacterial burden, transcriptomics, cytokine/chemokine expression, and flow cytometry. These techniques can be used to evaluate disease parameters of interest during typical infection, infection with bacterial mutants, or infection in the presence of pharmacological agents aimed at targeting specific host or bacterial factors. Combining a highly relevant murine infection model with these techniques provides a powerful platform for fully evaluating the progression of pneumonic plague.
KEYWORDS:
Bronchoalveolar lavage; Intranasal infection; Plague; Pneumonia; Pneumonic plague; Pulmonary inflammation; Yersinia
48.
Int Forum Allergy Rhinol. 2019 Jun;9(6):571-572. doi: 10.1002/alr.22358.
Tumor surgery, the microbiome, and anaphylaxis.
49.
Clin Microbiol Infect. 2019 Dec;25(12):1553-1559. doi: 10.1016/j.cmi.2019.04.033. Epub 2019 May 13.
An automated smear microscopy system to diagnose tuberculosis in a high-burden setting.
Abstract
OBJECTIVES:
TB-EASM (Howsome, Shanghai, China), an automated system combining smear preparation, staining and microscopy in a single platform, was evaluated for tuberculosis (TB) diagnosis in a high disease-burden setting.
METHODS:
Sputum samples from individuals with pulmonary TB were processed in parallel using conventional manual smear microscopy (MS), TB-EASM, liquid culture and GeneXpert. Method sensitivity and specificity were compared with Mycobacterium tuberculosis detection by mycobacteria growth indicator tube (MGIT) and/or GeneXpert MTB/RIF.
RESULTS:
Of 524 samples, 496 met evaluation criteria for study inclusion. The proportion of M. tuberculosis detected by TB-EASM was 28.2% (150/496), significantly higher than for MS (111/496, 21.2%, p 0.01) and comparable to the rate for MGIT (163/496, 32.9%, p > 0.05). For 190 M. tuberculosis-positive cases identified using MGIT and/or GeneXpert MTB/RIF, the reference standard detection methods, TB-EASM detected 140 positive cases, for an overall sensitivity rate of 73.7% (140/190, 95% CI 67.4-79.9), which was significantly higher than for MS (105/190, 55.3%, 95% CI 48.2-62.3, p < 0.01). Specificities were 96.7% (296/306, 95% CI 94.7-98.7) for TB-EASM and 98.0% (300/306, 95% CI 96.5-99.6) for MS.
CONCLUSION:
TB-EASM outperformed conventional MS for M. tuberculosis detection in sputum specimens.
Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
KEYWORDS:
Automated; Diagnosis; Microscopy; TB-EASM; Tuberculosis
50.
Clin Pediatr (Phila). 2019 Jul;58(8):864-888. doi: 10.1177/0009922819847032. Epub 2019 May 12.
Echinococcus Granulosus in Childhood: A Retrospective Study of 187 Cases and Newer Data.
Abstract
Echinococcus granulosus, first reported by Goeze in 1782, is the causative parasite of cystic echinococcosis (hydatidosis) especially for countries that are endemic areas. Since the 1970s, the incidence of echinococcosis in Greece has been very high. Nevertheless, with the implementation of special prevention measures in the 1980s, a large reduction in the incidence of hydatidosis meant that it reached European levels. Therefore, we analyzed the demographics, multiple organ localizations of the parasite, diagnosis, and conservative and optimal surgical treatment over a total period of 39 years, especially for pulmonary and hepatic echinococcosis in children. The higher incidence of pulmonary echinococcosis compared with other localizations, male predominance, wide range of age, and various cystic sizes were some of the main demographics. Because cystic echinococcosis remains a main public health problem, we advocate a meticulous clinical investigation and treatment methodology to bridge the gap between knowledge and awareness of this important disease.
KEYWORDS:
childhood echinococcosis; childhood hydatidosis; children’s hydatidosis; echinococcal parasitosis
51.
Epidemiol Infect. 2019 Jan;147:e155. doi: 10.1017/S0950268818003680.
Estimating seasonal variation in Australian pertussis notifications from 1991 to 2016: evidence of spring to summer peaks.
Abstract
Unlike for many other respiratory infections, the seasonality of pertussis is not well understood. While evidence of seasonal fluctuations in pertussis incidence has been noted in some countries, there have been conflicting findings including in the context of Australia. We investigated this issue by analysing the seasonality of pertussis notifications in Australia using monthly data from January 1991 to December 2016. Data were made available for all states and territories in Australia except for the Australian Capital Territory and were stratified into age groups. Using a time-series decomposition approach, we formulated a generalised additive model where seasonality is expressed using cosinor terms to estimate the amplitude and peak timing of pertussis notifications in Australia. We also compared these characteristics across different jurisdictions and age groups. We found evidence that pertussis notifications exhibit seasonality, with peaks observed during the spring and summer months (November-January) in Australia and across different states and territories. During peak months, notifications are expected to increase by about 15% compared with the yearly average. Peak notifications for children <5 years occurred 1-2 months later than the general population, which provides support to the theory that older household members remain an important source of pertussis infection for younger children. In addition, our results provide a more comprehensive spatial picture of seasonality in Australia, a feature lacking in previous studies. Finally, our findings suggest that seasonal forcing may be useful to consider in future population transmission models of pertussis.
KEYWORDS:
Australia; notifications; pertussis; seasons; time-series; whooping cough
- PMID:
- 31063086
- PMCID:
- PMC6518527
- DOI:
- 10.1017/S0950268818003680
- [Indexed for MEDLINE]
52.
Clin Pediatr (Phila). 2019 Jul;58(8):927-930. doi: 10.1177/0009922819845159. Epub 2019 Apr 26.
A Rare Cause of Respiratory Distress in a Toddler.
53.
Clin Microbiol Infect. 2019 Dec;25(12):1539-1545. doi: 10.1016/j.cmi.2019.04.012. Epub 2019 Apr 18.
Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study.
To KKW1, Chan KH2, Ho J2, Pang PKP2, Ho DTY2, Chang ACH3, Seng CW3, Yip CCY4, Cheng VCC4, Hung IFN5, Yuen KY6.
Abstract
OBJECTIVES:
To determine the viral epidemiology and clinical characteristics of patients with and without clinically apparent respiratory tract infection.
METHODS:
This prospective cohort study was conducted during the 2018 winter influenza season. Adult patients with fever/respiratory symptoms (fever/RS group) were age- and sex-matched with patients without fever/RS (non-fever/RS group) in a 1:1 ratio. Respiratory viruses were tested using NxTAG™ Respiratory Pathogen Panel IVD, a commercially-available multiplex PCR panel.
RESULTS:
A total of 214 acutely hospitalized patients were included in the final analysis, consisting of 107 with fever/RS (fever/RS group), and 107 age- and sex-matched patients without fever/RS (non-fever/RS group). Respiratory viruses were detected in 34.1% (73/214) of patients, and co-infection occurred in 7.9% (17/214) of patients. The incidence of respiratory virus was higher in the fever/RS group than in the non-fever/RS group (44.9% (48/107) versus 23.4% (25/107), p 0.001). Influenza B virus, enterovirus/rhinovirus and coronaviruses were detected more frequently in the fever/RS group, whereas parainfluenza virus 4B and adenovirus were detected more frequently in the non-fever/RS group. Among the non-fever/RS group, chest discomfort was more common among patients tested positive for respiratory viruses than those without respiratory virus detected (44% (11/25) versus 22% (18/82), p 0.04).
CONCLUSIONS:
Respiratory viruses can be frequently detected among hospitalized patients without typical features of respiratory tract infection. These patients may be a source of nosocomial outbreaks.
Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
KEYWORDS:
Adenovirus; Cardiac complications; Influenza; Parainfluenza virus; Respiratory tract infection
54.
Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8493-8498. doi: 10.1073/pnas.1818522116. Epub 2019 Apr 10.
Regenerative therapy based on miRNA-302 mimics for enhancing host recovery from pneumonia caused by Streptococcus pneumoniae.
Abstract
Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide. A defining feature of pneumonia is lung injury, leading to protracted suffering and vulnerability long after bacterial clearance. Little is known about which cells are damaged during bacterial pneumonia and if the regenerative process can be harnessed to promote tissue repair and host recovery. Here, we show that infection of mice with Streptococcus pneumoniae (Sp) caused substantial damage to alveolar epithelial cells (AEC), followed by a slow process of regeneration. Concurrent with AEC regeneration, the expression of miRNA-302 is elevated in AEC. Treatment of Sp-infected mice with miRNA-302 mimics improved lung functions, host recovery, and survival. miRNA-302 mediated its therapeutic effects, not by inhibiting apoptosis and preventing damage, but by promoting proliferation of local epithelial progenitor cells to regenerate AEC. These results demonstrate the ability of microRNA-based therapy to promote AEC regeneration and enhance host recovery from bacterial pneumonia.
KEYWORDS:
alveolus; bacteria; miRNA; pneumonia; regeneration
- PMID:
- 30971494
- PMCID:
- PMC6486708
- DOI:
- 10.1073/pnas.1818522116
- [Indexed for MEDLINE]
55.
Cancer Lett. 2019 Jul 1;453:184-192. doi: 10.1016/j.canlet.2019.03.053. Epub 2019 Apr 3.
Epstein-Barr virus-positive pyothorax-associated lymphoma expresses CCL17 and CCL22 chemokines that attract CCR4-expressing regulatory T cells.
Higuchi T1, Matsuo K2, Hashida Y1, Kitahata K2, Ujihara T3, Taniguchi A4, Yoshie O5, Nakayama T2, Daibata M6.
Abstract
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas associated with chronic inflammation (DLBCL-CI) develop in patients with chronic inflammation but without any predisposing immunodeficiency. Given the expression of the EBV latent genes, DLBCL-CI should have mechanisms for evasion of host antitumor immunity. EBV-positive pyothorax-associated lymphoma (PAL) is a prototype of DLBCL-CI and may provide a valuable model for the study of immune evasion by DLBCL-CI. This study demonstrates that PAL cell lines express and secrete CCL17 and/or CCL22 chemokines, the ligands of C-C motif chemokine receptor 4 (CCR4), in contrast to EBV-negative DLBCL cell lines. Accordingly, culture supernatants of PAL cell lines efficiently attracted CCR4-positive regulatory T (Treg) cells in human peripheral blood mononuclear cells. PAL cells injected into mice also attracted CCR4-expressing Treg cells. Furthermore, this study confirmed that CCR4-expressing Treg cells were abundantly present in primary PAL tissues. Collectively, these findings provide new insight into the mechanisms of immune evasion by PAL, and further studies are warranted on whether such mechanisms eventually lead to the development of DLBCL-CI.
Copyright © 2019 Elsevier B.V. All rights reserved.
KEYWORDS:
Chemokine; Inflammation; Lymphoma; Treg; Virus
56.
Am J Epidemiol. 2019 Jul 1;188(7):1371-1382. doi: 10.1093/aje/kwz083.
Restriction of Pharmacoepidemiologic Cohorts to Initiators of Medications in Unrelated Preventive Drug Classes to Reduce Confounding by Frailty in Older Adults.
Abstract
Nonexperimental studies of the effectiveness of seasonal influenza vaccine in older adults have found 40%-60% reductions in all-cause mortality associated with vaccination, potentially due to confounding by frailty. We restricted our cohort to initiators of medications in preventive drug classes (statins, antiglaucoma drugs, and β blockers) as an approach to reducing confounding by frailty by excluding frail older adults who would not initiate use of these drugs. Using a random 20% sample of US Medicare beneficiaries, we framed our study as a series of nonrandomized "trials" comparing vaccinated beneficiaries with unvaccinated beneficiaries who had an outpatient health-care visit during the 5 influenza seasons occurring in 2010-2015. We pooled data across trials and used standardized-mortality-ratio-weighted Cox proportional hazards models to estimate the association between influenza vaccination and all-cause mortality before influenza season, expecting a null association. Weighted hazard ratios among preventive drug initiators were generally closer to the null than those in the nonrestricted cohort. Restriction of the study population to statin initiators with an uncensored approach resulted in a weighted hazard ratio of 1.00 (95% confidence interval: 0.84, 1.19), and several other hazard ratios were above 0.95. Restricting the cohort to initiators of medications in preventive drug classes can reduce confounding by frailty in this setting, but further work is required to determine the most appropriate criteria to use.
© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
KEYWORDS:
confounding factors (epidemiology); frail elderly; frailty; influenza vaccines
- PMID:
- 30927359
- PMCID:
- PMC6601528
- [Available on 2020-07-01]
- DOI:
- 10.1093/aje/kwz083
- [Indexed for MEDLINE]
57.
Clin Pediatr (Phila). 2019 Jul;58(8):912-914. doi: 10.1177/0009922819839242. Epub 2019 Mar 29.
Caregiver Assessment of Wheeze for Pediatric Pneumonia.
58.
Pediatr Transplant. 2019 May;23(3):e13375. doi: 10.1111/petr.13375. Epub 2019 Mar 5.
Infections among pediatric transplant candidates: An approach to decision-making.
L'Huillier AG1,2, Green M3, Danziger-Isakov L4, Chaudhuri A5, Höcker B6, Van der Linden D7, Goddard L8, Ardura MI9, Stephens D1, Verma A10, Evans HM11, McCulloch M8, Michaels MG3, Posfay-Barbe KM2, Allen UD1.
Abstract
INTRODUCTION:
The presence of infections in the immediate pretransplant period poses challenges in decision-making. Delaying transplantation because of these infections may be required, but is associated with a risk to the potential recipient. The aim of this project was to develop a structured framework based on expert opinion to guide decision-making regarding the safety of transplantation for candidates with infection immediately before transplant, and to show how this framework can be applied to clinical scenarios.
METHODS:
Categories were created as follows: Category A: no delay; Category B: brief delay (≤1 week); Category C: intermediate delay (>1 week); and Category D: more prolonged or indefinite delay. A survey containing 59 clinical scenarios was sent to members of the IPTA ID CARE committee. Answers were reviewed, and the level of agreement was characterized as follows: Level 1: ≥75% agreement; Level 2:51%-74% agreement; and Level 3: ≤50% agreement. 95% CIs were calculated for the mean overall agreement across 59 scenarios.
RESULTS:
Among the panel, the agreement level ranged from 33% to 92% with the mean overall agreement across the 59 scenarios being 61%. For 7/59 scenarios, the lower bound of 95% CI was greater than 50%, indicating a difference at the 5% level of significance between the observed proportion and the chance level of 0.5.
SUMMARY:
The document provides expert opinion regarding the need to delay transplantation in the setting of different infections. The most important points in the decision to proceed to SOT included the urgency of transplantation and the severity of infection.
© 2019 Wiley Periodicals, Inc.
KEYWORDS:
candidate; infection; pediatric; solid organ transplantation
59.
BMJ Open. 2019 Mar 1;9(2):e026624. doi: 10.1136/bmjopen-2018-026624.
Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts.
Phillips CJ1,2,3,4,5, Gilchrist M1,2, Cooke FJ3, Franklin BD2,6,7, Enoch DA3,4, Murphy ME3, Santos R8, Brannigan ET1, Holmes AH1,2.
Abstract
OBJECTIVE:
To investigate documentation of antimicrobial allergy and to determine prescribing adherence to local antibiotic guidelines for inpatients with and without reported penicillin allergy treated for infection in a National Health Service (NHS) context.
SETTING:
Data were collected at two English hospital NHS trusts over two time-periods: June 2016 and February 2017.
DESIGN:
Cohort study. Trust 1 data were sourced from prospective point prevalence surveys. Trust 2 data were extracted retrospectively from an electronic report.
PARTICIPANTS:
Inpatients treated for urinary tract infection (UTI), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and skin and soft tissue infection (SSTI). Data on allergy were collected, and antibiotic selection assessed for adherence to trust guidelines with differences between groups presented as adjusted ORs.
RESULTS:
A total of 1497 patients were included, with 2645 antibiotics orders. Patients were treated for CAP (n=495; 33.1%), UTI (407; 27.2%), HAP (330; 22%) and SSTI (265; 17.7%). There were 240 (16%) patients with penicillin allergy. Penicillin allergy was recorded as allergy (n=52; 21.7%), side effect (27; 11.3%) and no documentation (161; 67.1%). Overall, 2184 (82.6%) antibiotic orders were guideline-adherent. Adherence was greatest for those labelled penicillin allergy (453 of 517; 87.6%) versus no allergy (1731 of 2128; 81.3%) (OR 0.52 (95% CI 0.37 to 0.73) p<0.001). Guideline-adherence for CAP was higher if penicillin allergy (151 of 163; 92.6%) versus no allergy (582 of 810; 71.9%) (OR 0.20 (95% CI 0.10 to 0.37) p<0.001). There was no difference in adherence between those with and without penicillin allergy for UTI, HAP or SSTI treatment.
CONCLUSIONS:
A relatively high proportion of patients had a penicillin allergy and two thirds of these had no description of their allergy, which has important implications for patient safety. Patients with penicillin allergy treated for CAP, received more guideline adherent antibiotics than those without allergy. Future studies investigating the clinical impact of penicillin allergy should include data on adherence to antibiotic guidelines.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS:
drug allergy; guideline-adherence; penicillin; prescribing
- PMID:
- 30826801
- PMCID:
- PMC6398633
- DOI:
- 10.1136/bmjopen-2018-026624
- [Indexed for MEDLINE]
60.
BMJ Open. 2019 Feb 19;9(2):e026518. doi: 10.1136/bmjopen-2018-026518.
Selective citation in the literature on the hygiene hypothesis: a citation analysis on the association between infections and rhinitis.
Abstract
OBJECTIVE:
Our objective was to assess the occurrence and determinants of selective citation in scientific publications on Strachan's original hygiene hypothesis. His hypothesis states that lack of exposure to infections in early childhood increases the risk of rhinitis.
SETTING:
Web of Science Core Collection.
PARTICIPANTS:
We identified 110 publications in this network, consisting of 5551 potential citations.
PRIMARY AND SECONDARY OUTCOME MEASURES:
Whether a citation occurs or not, measured and analysed according to the preregistered protocol.
RESULTS:
We found evidence for citation bias in this field: publications supportive of the hypothesis were cited more often than non-supportive publications (OR adjusted for study design [adjOR] 2.2, 95% CI 1.6 to 3.1), and the same was the case for publications with mixed findings (adjOR 3.1, 95% CI 2.2 to 4.5). Other relevant determinants for citation were type of exposure, specificity, journal impact factor, authority and self-citation. Surprisingly, prospective cohort studies were cited less often than other empirical studies.
CONCLUSIONS:
There is clear evidence for selective citation in this research field, and particularly for citation bias.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS:
epidemiology; ethics (see medical ethics); immunology
- PMID:
- 30782945
- PMCID:
- PMC6377569
- DOI:
- 10.1136/bmjopen-2018-026518
- [Indexed for MEDLINE]
61.
Int Forum Allergy Rhinol. 2019 Jun;9(6):593-600. doi: 10.1002/alr.22309. Epub 2019 Feb 12.
Symptom importance, patient expectations, and satisfaction in chronic rhinosinusitis.
Abstract
BACKGROUND:
Sinonasal symptoms and poor quality of life (QOL) prompt chronic rhinosinusitis (CRS) patients to undergo sinus surgery (ESS). However, little is known regarding the symptoms most important to patients and how these impact expectations and postoperative satisfaction.
METHODS:
A prospective, multi-institutional cohort study of 100 CRS patients undergoing ESS completed a novel adaptation of the 22-item Sino-Nasal Outcome Test (SNOT-22) wherein they rated how important it was for specific symptoms to improve after surgery, along with preoperative expectations and postoperative satisfaction. The primary satisfaction measure was whether a patient would choose to undergo endoscopic sinus surgery (ESS) again. A multivariate, logistic regression model was built using demographics, objective measures, and the adapted SNOT-22 data. Spearman correlation analysis was also performed.
RESULTS:
Nasal obstruction was rated as "extremely" or "very" important by 93% of patients, followed by smell/taste, thick nasal discharge, need to blow nose, postnasal discharge, and sleep symptoms (range, 61-72%). Symptoms like sadness and embarrassment were not considered important by preoperative patients (≤28%). In multivariate logistic regression, postoperative satisfaction depended on preoperative expectations being met and ESS improving their most important symptoms (odds rato, 19.6-27.5; p < 0.005). Postoperative satisfaction was not correlated with achieving a minimal clinically important difference, but it was correlated with magnitude of change in SNOT-22 (r = 0.35; p < 0.05).
CONCLUSIONS:
Nasal, smell, and sleep-related symptoms were consdidered most important by this cohort. Meeting of preoperative expectations, improvement of the most important symptoms, and the magnitude of change in the SNOT-22 may drive postoperative satisfaction.
© 2019 ARS-AAOA, LLC.
KEYWORDS:
chronic sinusitis; expectations; patient-reported outcomes; satisfaction; sinus surgery
- PMID:
- 30748101
- PMCID:
- PMC6555643
- [Available on 2020-06-01]
- DOI:
- 10.1002/alr.22309
- [Indexed for MEDLINE]
62.
Int Forum Allergy Rhinol. 2019 Jun;9(6):665-673. doi: 10.1002/alr.22295. Epub 2019 Feb 12.
The impact of race and insurance status on baseline histopathology profile in patients with chronic rhinosinusitis.
Abstract
BACKGROUND:
Chronic rhinosinusitis (CRS) is an inflammatory disease process characterized by different phenotypes and histopathology profiles. Race and access to care have been implicated in CRS disease severity. Structural histopathology reporting may aid in delineating the inflammatory burden responsible for this effect.
METHODS:
A structured histopathology report of 14 variables was utilized to assess sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared by race (Black, White, Latino, and Asian) and insurance status (Medicare, Medicaid, and private insurance).
RESULTS:
A total of 201 CRS patients (124 White, 38 Black, 28 Latino, and 9 Asian) undergoing FESS were included. Black patients demonstrated increased SNOT-22 scores (50.74 ± 20.32 vs 41.47 ± 22.75, p < 0.022) and number of eosinophils per high-power field (>5/HPF) (60.5% vs 44.8%, p < 0.05). White patients demonstrated decreased eosinophil aggregates (22.6% vs 35.1%, p < 0.039) and eosinophils/HPF (<5/HPF) (42.7% vs 55.8%, p < 0.048). Medicaid patients showed increased SNOT-22 score (55.50 ± 24.46 vs 41.39 ± 21.74, p < 0.003), polypoid disease (61.5% vs 42.3%, p < 0.05), subepithelial edema (80.8% vs 53.1%, p < 0.006), hyperplastic/papillary changes (23.1% vs 8.0%, p < 0.028), fibrosis (61.5% vs 38.5%, p < 0.036), eosinophil aggregates (46.2% vs 24.6%, p < 0.022), and eosinophils/HPF (>5/HPF) (65.4% vs 45.1%, p < 0.043). When controlling for insurance status, Black race was no longer associated with increased SNOT-22 (p < 0.104) or eosinophils/HPF (>5/HPF) (p < 0.183).
CONCLUSION:
Black and Medicaid patients demonstrated more severe disease by histopathology and SNOT-22 scores. These findings were no longer significant among Black patients after adjusting for insurance status, suggesting that the prevailing factor influencing worse disease may be access to care.
© 2019 ARS-AAOA, LLC.
KEYWORDS:
chronic rhinosinusitis; insurance; race; sinus surgery; structured histopathology
63.
Int Forum Allergy Rhinol. 2019 Jun;9(6):582-592. doi: 10.1002/alr.22297. Epub 2019 Feb 5.
The difference in nasal bacterial microbiome diversity between chronic rhinosinusitis patients with polyps and a control population.
Abstract
BACKGROUND:
Little is known regarding the role of the microbiome of the paranasal sinuses and its contribution to sinus mucosal health and disease. Consequently, we examined the microbiome of chronic rhinosinusitis patients with polyps (CRSwNP) and a control population to provide new insights into the microbiota associated with the pathogenesis of CRSwNP.
METHODS:
Fifty-nine CRSwNP patients and 27 controls were enrolled in the study. The bacterial communities of the middle meatus were detected using 16S ribosomal RNA (rRNA)-targeted Illumina MiSeq sequencing after microbial DNA was extracted from swabs.
RESULTS:
Although there was no difference in diversity between the 2 groups, richness was lower in the CRSwNP group than in the control group (p = 0.03). At the phylum level, Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were predominant in both groups; however, the relative abundance was different, with the proportions of Actinobacteria (predominantly Corynebacterium) and Dolosigranulum being significantly higher in the control group than in the CRSwNP group.
CONCLUSION:
These results support the theory of microbial dysbiosis as the pathogenesis of CRSwNP. The reduction in the proportions of potentially protective bacteria may decrease the overall stability of the sinonasal bacterial community.
© 2019 ARS-AAOA, LLC.
KEYWORDS:
16S rRNA; 16S sequencing; bacteria; chronic rhinosinusitis; microbiome; nasal polyps
64.
Acta Biomed. 2019 Jan 14;90(2-S). doi: 10.23750/abm.v90i2-S.8103.
Ciliocytophthoria of nasal epithelial cells after viral infection: a sign of suffering cell.
Abstract
Ciliocytophthoria (CCP) defines a degenerative process of the ciliated cells consequent to viral infections, and it is characterized by typical morphological changes. We evaluated the distinct and characteristic phases of CCP, by means of the optical microscopy of the nasal mucosa (nasal cytology), in 20 patients (12 males and 8 females; aged between 18 and 40 years). Three phases of CCP by nasal cytology are detected. This outcome confirms that CCP represents a sign of suffering nasal epithelial cell.
- PMID:
- 30715030
- PMCID:
- PMC6502078
- DOI:
- 10.23750/abm.v90i2-S.8103
- [Indexed for MEDLINE]
65.
Int Forum Allergy Rhinol. 2019 Jun;9(6):601-606. doi: 10.1002/alr.22300. Epub 2019 Jan 31.
Does bilateral inferior turbinate reduction affect long-term quality-of-life outcomes in patients undergoing endoscopic sinus surgery?
Abstract
BACKGROUND:
The objective of this study was to evaluate the impact of bilateral inferior turbinate reduction (BITR) on patient-reported quality of life (QOL) following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS).
METHODS:
This was a prospective cohort study. Patients with CRS, who were recruited from 10 different otolaryngologic practices between 2011 and 2014, completed the 22-item Sino-Nasal Outcome Test (SNOT-22), Chronic Sinusitis Survey (CSS), and EuroQol 5 Dimension (EQ-5D) survey at baseline, and at 12, 24, 36, and 48 months after ESS. A total of 113 patients who underwent ESS with BITR were compared to 788 patients who underwent ESS without BITR.
RESULTS:
Significant demographic and comorbid differences between BITR and non-BITR cohorts included age (41 vs 49 years, p < 0.0001), presence of asthma (19% vs 36%, p < 0.0001), prior sinus surgery (22% vs 53%, p < 0.0001), and concurrent septoplasty (80% vs 53%, p < 0.0001), respectively. On univariate analysis, patients who underwent ESS with or without BITR were found to have statistically significant improvement in disease-specific (SNOT-22 and CSS) and general (EQ-5D) QOL scores at years 1 through 4 (p < 0.05). On multivariate regression, however, the performance of BITR was not associated with any improvements in these outcome measures.
CONCLUSION:
Patients undergoing ESS achieve similar long-term improvement in both disease-specific and general QOL regardless of the performance of concurrent BITR.
© 2019 ARS-AAOA, LLC.
KEYWORDS:
chronic rhinosinusitis; endoscopic sinus surgery; patient-reported outcome measure; quality of life
66.
Int Forum Allergy Rhinol. 2019 Jun;9(6):629-637. doi: 10.1002/alr.22290. Epub 2019 Jan 18.
Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis.
Cho DY1,2, Skinner D1, Mackey C1, Lampkin HB1, Elder JB1, Lim DJ1, Zhang S1, McCormick J1, Tearney GJ3, Rowe SM2,4,5,6, Woodworth BA1,2.
Abstract
BACKGROUND:
Enhancing chloride (Cl- ) secretion in sinus epithelia represents a novel therapeutic approach to chronic rhinosinusitis (CRS). Herbal dry extract BNO 1011 enhances mucociliary clearance (MCC) via upregulation of Cl- secretion in sinonasal cultures in vitro and murine epithelium in vivo. The objective of this study is to evaluate whether the BNO 1011 improves MCC and clinical parameters in a rabbit model of CRS.
METHODS:
After the development of CRS in 30 New Zealand white rabbits, animals were randomly assigned to receive oral placebo (n = 10), BNO 1011 (low dose [LD], 25 mg/kg/daily) (n = 10), or BNO1011 (high dose [HD], 125 mg/kg/daily) (n = 10) for 4 weeks. Outcomes included sinus opacification (Kerschner's rabbit sinus CT grade), maxillary epithelial Cl- secretion (sinus potential difference [PD] assay), airway surface liquid (ASL) depth using micro-optical coherence tomography (μOCT), and submucosal gland density (SMD) on histopathology. Outcome parameters were analyzed by 2 blinded investigators.
RESULTS:
BNO 1011 significantly cleared sinus opacification (HD = 1.21 ± 0.63, LD = 1.26 ± 0.37,) compared to placebo (4.02 ± 0.92) (p = 0.009). BNO 1011 resulted in markedly greater mean sinus PD polarization (HD = -12.23 ± 1.4 mV, LD = -12.0 ± 3.0 mV) when compared to rabbits treated with placebo (-4.1 ± 1.1 mV) (p = 0.03). ASL depth was significantly improved when treated with HD (4.08 ± 0.06 μm) and LD (4.05 ± 0.06 μm) compared to placebo (3.5 ± 0.05 μm) (post hoc analysis, p < 0.0001). Histologically, epithelial thickness (HD = 10.0 ± 0.7 μm; LD = 13.7 ± 0.9 μm; placebo = 21.1 ± 2.3 μm; p < 0.005), subepithelial thickness (HD = 63.1 ± 6.6 μm; LD = 103.2 ± 6.7 μm; placebo = 113.3 ± 6.0 μm; p < 0.001), and SMD (HD = 22.2 ± 2.9%; LD = 31.8 ± 1.1%; placebo = 43.8 ± 1.7%; p < 0.0001) were noticeably better with the HD.
CONCLUSION:
Herbal dry extract BNO 1011 improves radiographic, histologic, and MCC parameters in a rabbit model of CRS.
© 2019 ARS-AAOA, LLC.
KEYWORDS:
chronic rhinosinusitis; herbal dry extract; micro optical coherence tomography; mucociliary clearance; rabbit model of sinusitis; rabbit sinusitis; sinus potential difference
- PMID:
- 30657641
- PMCID:
- PMC6555666
- [Available on 2020-06-01]
- DOI:
- 10.1002/alr.22290
- [Indexed for MEDLINE]
67.
J Clin Microbiol. 2019 Feb 27;57(3). pii: e01281-18. doi: 10.1128/JCM.01281-18. Print 2019 Mar.
Clinical Impact of Rapid Point-of-Care PCR Influenza Testing in an Urgent Care Setting: a Single-Center Study.
Abstract
Seasonal influenza virus causes significant morbidity and mortality each year. Point-of-care (POC) testing using rapid influenza diagnostic tests (RIDTs), immunoassays that detect viral antigens, are often used for diagnosis by physician offices and urgent care centers. These tests are rapid but lack sensitivity, which is estimated to be 50 to 70%. Testing by PCR is highly sensitive and specific, but historically these assays have been performed in centralized clinical laboratories necessitating specimen transport and increasing the time to result. Recently, Clinical Laboratory Improvement Amendments (CLIA)-waived, POC PCR influenza assays have been developed with >95% sensitivity and specificity compared to centralized PCR assays. To determine the clinical impact of a POC PCR test for influenza, we compared antimicrobial prescribing patterns of one urgent care location using the Cobas LIAT Influenza A/B assay (LIAT assay; Roche Diagnostics, Indianapolis, IN) to other urgent care centers in our health system using traditional RIDT, with negative specimens being reflexed to PCR. Antiviral prescribing was lower in patients with a negative LIAT PCR result (2.3%) than in patients with a negative RIDT result (25.3%; P < 0.005). Antivirals were prescribed more often in patients that tested positive by LIAT PCR (82.4%) than in those testing positive by either RIDT or reflex PCR (69.9%; P < 0.05). Antibacterial prescriptions for patients testing negative by LIAT PCR were higher (44.5%) than for those testing negative by RIDT (37.7%), although the difference was not statistically significant. In conclusion, having results from a PCR POC test during the clinic visit improved antiviral prescribing practices compared to having rapid results from an RIDT.
Copyright © 2019 American Society for Microbiology.
KEYWORDS:
PCR; clinical impact; influenza; point-of-care testing; rapid diagnosis
68.
J Glob Antimicrob Resist. 2019 Mar;16:1-3. doi: 10.1016/j.jgar.2018.11.008. Epub 2018 Nov 13.
Draft genome sequence of an OXA-23, OXA-66, ADC-25 and TEM-1D co-producing Acinetobacter baumannii ST195 isolated from a patient with neonatal pneumonia in China.
Abstract
OBJECTIVES:
The rapid spread of multidrug-resistant (MDR) Acinetobacter baumannii poses a substantial threat for morbidity and mortality worldwide. In particular, carbapenem-resistant A. baumannii has caused a severe challenge to human health. Here we reported the draft genome sequence of A. baumannii S131434, an OXA-23, OXA-66, ADC-25 and TEM-1D co-producing strain recovered from a patient with neonatal pneumonia in China and belonging to the globally disseminated sequence type 195 (ST195) of clonal complex 92 (CC92).
METHODS:
Genomic DNA was sequenced using an Illumina HiSeq platform and the reads were de novo assembled into contigs using CLC Genomics Workbench. The assembled contigs were annotated and bioinformatics analysis was performed.
RESULTS:
The genome comprised a circular chromosome of 3898344bp. The presence of the blaOXA-23, blaOXA-66, blaADC-25 and blaTEM-1D genes was detected. In addition, genes conferring resistance to aminoglycosides, macrolides and tetracycline were also identified. Antimicrobial susceptibility testing revealed that the isolate was resistant to all of the tested antibiotics except for polymyxin B, piperacillin/sulbactam and trimethoprim/sulfamethoxazole.
CONCLUSION:
To our knowledge, this is the first report of a clinical A. baumannii ST195 (CC92) isolate producing OXA-23, OXA-66, ADC-25 and TEM-1D in southern China. This draft genome will facilitate further our understanding of the antimicrobial resistance and pathogenic mechanisms in this strain and provides valuable information regarding the colonisation and adaptation of MDR pathogens.
Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.
KEYWORDS:
Acinetobacter baumannii; Genome analysis; ST195; bla(OXA-23)
69.
Cytopathology. 2019 Mar;30(2):249-252. doi: 10.1111/cyt.12626. Epub 2018 Oct 3.
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