bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of bacteriophage typing to distinguish Propionibacterium acne types I and II
Authors: Webster G F , Cummins C S
Published: June 2021

Strains of serotypes I and II of Propionibacterium were compared for phage sensitivity. The two serotypes could be distinguished by using a typing set consisting of 16 bacteriophages at concentrations that demonstrated selective lysis of serotype I or II bacterial strains. Seven phage types were found; three were composed exclusively of serotype I, and four were exclusively composed of serotype II organisms. Generally, serotype I strains were more sensitive to phage lysis than were serotype II strains. No correlation was found between phage type and site of isolation.
Laboratory and clinical investigation of recovery of Salmonella typhi from blood
Authors: Watson K C
Published: June 2021

An experimental study was undertaken of isolation of Salmonella typhi from artificially infected whole blood and blood clot prepared either with small numbers of freshly isolated strains or with the S. typhi Ty2 strain. Results showed that 8 ml of whole blood required a minimum of 50 ml of bile salt broth to dilute the bactericidal effect of the serum. However, the isolation rate for recovery in 210 cases of enteric fever was only 64% when 50 ml of medium was used, as compared to 92% recovery from blood clot from the same group incubated in streptokinase bile salt broth. This probably reflects a very low grade bacteremia in many of the patients. Further investigation showed that, ideally, between 150 and 200 ml of medium is required for satisfactory whole-blood culture. Both the experimental study of artificially infected clots and recovery rates from patients indicate that rapid clot dissolution with streptokinase is preferable to whole-blood culture; this experience has been amply confirmed by almost 5,000 cases over a 20-year period. A 15-ml volume of bile salt broth with 100 U of streptokinase is adequate for the clot from 8 ml of blood, and savings on media and incubator space have considerable cost benefits in developing countries.
Pigment production by Cryptococcus neoformans and other Cryptococcus species from aminophenols and diaminobenzenes
Authors: Chaskes S , Tyndall R L
Published: June 2021

Cryptococcus neoformans and other Cryptococcus species can produce pigment(s) from many aminophenol and diaminobenzene compounds. Pigment production from these compounds is similar to the conversion of diphenols to melanin by C. neoformans. Several pigmentation patterns (resulting in the identification or grouping of Cryptococcus species) have been observed by using diaminobenzene and aminophenol compounds as substrates. The most common pigmentation pattern observed was pigment production by both C. neoformans and C. terreus. In contrast to the diphenols, only two aminophenols (4-hydroxymetanilamide and 3-aminotyrosine) were found to be highly specific as substrates. They allowed only C. neoformans to produce pigment. When 4-aminosalicylic acid was the substrate, a unique pattern was observed because only C. terreus, C. diffluens, and C. albidus produced pigment. Finally, a pattern was observed in which C. neoformans produced large amounts of pigment from aminophenol and diaminobenzene compounds, whereas the other Cryptococcus species produced smaller amounts. A simplified scheme with three substrates resulted in the identification of C. terreus and C. neoformans as well as two groups of other Cryptococcus species, group I (C. albidus and C. diffluens) and group II (C. laurentii and C. luteolus).
Analysis of group B streptococcal types associated with disease in human infants and adults
Authors: Wilkinson H W
Published: June 2021

It is important to resolve existing differences of opinion regarding group B streptococcal type distribution in human disease because of the relevance of type prevalence to future programs of prevention. This report compares data obtained from typing 392 group B streptococci isolated from systemic infections in both infants and adults in the United States from 1972 through 1975. The data showed a substantial predominance of type III among strains isolated from cases of infant meningitis and from "late-onset" septicemia but did not confirm a prior report that type Ia causes most cases of "early-onset" infant septicemia. Type II was the predominant serotype among 11 cerebrospinal fluid isolates from adults. The fact that over one-fourth of the isolates were types other than Ia or III means that future epidemiological studies, including definition of immunological factors, must include all five group B types.
Aerobic bacterial flora of oral and nasal fluids of canines with reference to bacteria associated with bites
Authors: Bailie W E , Stowe E C , Schmitt A M
Published: June 2021

Oral and nasal fluids of 50 dogs were examined to determine the prevalence of aerobic bacteria frequently associated with animal bite wounds. The most frequently isolated microorganisms included: IIj, EF-4, Pasteurella multocida, Staphylococcus aureus, Staphylococcus epidermidis, group D streptococci, Corynebacterium sp., Enterobacteria, Neisseria sp., Moraxella sp., and Bacillus sp. Other species and genera were infrequently recovered and may represent transient flora. The high incidence of IIj, EF-4, P. multocida, and S. aureus, all known human pathogens, suggests that they should be considered as probably contaminants in bite wounds.
Impedimetric screening for bacteriuria
Authors: Cady P , Dufour S W , Lawless P , Nunke B , Kraeger S J
Published: June 2021

A rapid, automated instrumental procedure for distinguishing urine cultures containing greater than 10(5) organism per ml is described. The method is based upon the measurement of changes in impedance that take place as microorganisms alter the chemical composition of the medium. The time required to detect impedance change is inversely related to the initial concentration of microorganisms in the sample. By defining an impedance-positive culture as one that gives detectable impedance change within 2.6 h, 95.8% of 1,133 urine cultures tested were correctly classified as containing more than or fewer than 10(5) organisms per ml. Selection of a longer detection time decreases false negative results at the cost of increased false positive results. Impedance screening is compared with screening data reported in the literature using adenosine-5'-triphosphate detection, microcalorimetry, electrochemical measurements, and optical microscopy.
Use of the Minitek system for biotyping Haemophilus species
Authors: Back A E , Oberhofer T R
Published: June 2021

The Minitek system was used for characterization and identification of Haemophilus. The system was simple to use and provided rapid and clear-cut test results.
Piliation and colonial morphology among laboratory strains of meningococci
Authors: DeVoe I W , Gilchrist J E
Published: June 2021

Colonial morphology and piliation were studied on twelve strains from various serogroups of Neisseria meningitidis. Six different colony types (M1 to M6) were identified. Most strains elaborated only an M1 colonial type, which is similar to gonococcus T4. Several combinations of piliation and colonial morphology were observed: (i) colonial variation in which neither parent nor variant were piliated; (ii) colonial variation involving piliated and nonpiliated cells; (iii) dissociation of piliated from nonpiliated cells with no colonial change; and (iv) colonial variation in which both variants were piliated but with distinctly different pili. Results of this study demonstrate that correlations between piliation and colony morphology within N. meningitidis are exceptions rather than the rule.
Plaque Formation by Strains of Spotted Fever Rickettsiae in Monolayer Cultures of Various Cell Types
Authors: Johnson James W. , Pedersen Carl E.
Published: June 2021

Some strains of spotted fever rickettsiae could be distinguished by their ability or inability to form plaques in monolayer cultures of various mammalian and avian cell types.
Comparison of a Radiometric Procedure with Conventional Methods for Identification of
Neisseria
Authors: Strauss Robert R. , Holderbach John , Friedman Herman
Published: June 2021

A radiometric procedure was compared with the conventional cystine tryptic agar (CTA) sugar fermentation method for identification of
Neisseria
species. Four different ATCC cultures of
Neisseria
were identified by both procedures with identical results. The only difference noted was that the radiometric procedure required 3 h for completion, whereas the conventional CTA sugar method required overnight incubation. The radiometric procedure was also compared with the fluorescent antibody (FA) and CTA methods for identification of
Neisseria gonorrhoeae
. The organisms examined were gram-negative, oxidase-positive diplococci isolated from 49 clinical specimens sent to the laboratory for bacteriological analysis. Results obtained by both CTA and FA procedures were comparable. However, the radioisotope method appeared to be superior to the other two methods in that only one isolate identified as positive by both the CTA and FA methods was not identified radiometrically, whereas four isolates positive by the radiometric method were not identified by the other two procedures. Thus, a total of seven more positive identifications were made radiometrically than by either of the two other methods. All positive identifications were confirmed by a reference laboratory. These results indicate that the radiometric procedure is more rapid and reliable as compared with both the CTA and direct FA methods and, thus, may serve as a valuable addition to the methodology available for diagnostic microbiology.
New medium for selection and presumptive identification of the Bacteroides fragilis group
Authors: Livingston S J , Kominos S D , Yee R B
Published: June 2021

A medium, Bacteroides fragilis bile-esculin (BBE) agar, was designed for the selection and, presumptive identification of the B. fragilis group. BBE agar contains bile, esculin, ferric ammonium citrate, hemin, and gentamicin in a Trypticase soy agar base. Growth in the presence of 20% bile and esculin hydrolysis, detected by blackening of the medium, provide presumptive evidence for the identification of the B. fragilis group. In addition to stimulating the growth of many strains of the B. fragilis group, hemin provides the option of testing isolates for catalase production. Gentamicin and bile prevent the growth of most organisms other than the esculin-positive bacteroides that can tolerate bile. Of 160 clinical isolates of the B. fragilis group tested on BBE agar, 159 grew well on the medium and 157 blackened it. Other anaerobes, Enterobacteriaceae, and enterococci either failed to grow on BBE agar or did not produce the characteristic morphology and blackening associated with isolates of the B. fragilis group. In a clinical laboratory trial, 687 specimens from patients were inoculated onto BBE agar plates. The B. fragilis group was recovered from 81 (11.8%) of these specimens in 24 to 48 h. Use of BBE agar in the clinical laboratory enables earlier recovery and identification of this important pathogen.
Evaluation of the API 20E system for identification of nonfermentative Gram-negative bacteria
Authors: Shayegani M , Maupin P S , McGlynn D M
Published: June 2021

The API 20E system for Enterobacteriaceae, recently broadened to include identification of nonfermentative gram-negative bacteria, was evaluated and compared with the conventional method for complete identification of 221 nonfermenters, which were well distributed into 48 species or biotypes and included organisms not listed in the API 20E data base. The results of 16 tests common to both systems were in close agreement. The API 20E system correctly identified 71 (43%) of the 165 organisms included in the API 20E data base. However, almost 90% of Acinetobacter calcoaceticus, three species of Pseudomonas, and Bordetella bronchiseptica were correctly identified to species.
Endocarditis associated with cardiac catheterization due to a Gram-positive coccus designated Micrococcus mucilaginosus incertae sedis
Authors: Rubin S J , Lyons R W , Murcia A J
Published: June 2021

A gram-positive coccus, presently named Micrococcus mucilaginosus incertae sedis, was isolated from 14 blood cultures from a patient with endocarditis. The first positive blood culture was drawn 5 days after the patient underwent cardiac catheterization.
Burden of out-of-pocket payments among patients with cardiovascular disease in public and private hospitals in Ibadan, South West, Nigeria: a cross-sectional study
Authors: Adeniji Folashayo
Published: June 2021

Objective

Given that the mechanism for financial protection is underdeveloped in Nigeria, out-of-pocket (OOP) payment for treating cardiovascular disease could impose substantial financial burden on individuals and their families. This study estimated the burden of OOP expenditures incurred by a cohort of patients with cardiovascular disease (CVD) in Ibadan, Nigeria.

Design and settings

This study used a descriptive cross-sectional study design. A standardised survey questionnaire originally developed by Initiative for Cardiovascular Health Research in Developing Countries was used to electronically collect data from all the 744 patients with CVD who accessed healthcare between 4 November 2019 and 31 January 2020 in the cardiology departments of private and public hospitals in Ibadan, Nigeria. Baseline characteristics of respondents were presented using percentages and proportions. The OOP payments were reported as means±SDs. Costs/OOP payments were in Nigerian Naira (NGN). The average US dollar to NGN at the time of data collection was ₦362.12 per $1. All quantitative data were analysed using STATA V.15.

Outcome measures

The burden of outpatient, inpatient and rehabilitative care OOP payments.

Results

Majority of the patients with CVD were within the age range of 45–74 years and 68.55% of them were women. The diagnostic conditions reported among patients with CVD were hypertensive heart failure (84.01%), dilated cardiomyopathy (4.44%), ischaemic heart disease (3.9%) and anaemic heart failure (2.15%). Across all the hospital facilities, the annual direct and indirect outpatient costs were ₦421 595.7±₦855 962.0 ($1164.2±$2363.8) and ₦19 146.5±₦53 610.1 ($52.87±$148.05). Similarly, the average direct and indirect OOP payments per hospitalisation across all facilities were ₦182 302.4±₦249 090.4 ($503.43±$687.87) and ₦14 700.8±₦ 69 297.1 ($40.60±$191.37), respectively. The average rehabilitative cost after discharge from index hospitalisation was ₦30 012.0 ($82.88).

Conclusion

The burden of OOP payment among patients with CVD is enormous. There is a need to increase efforts to achieve universal health coverage in Nigeria.
Exploring the frequency, duration and experience of seclusion for women in a forensic mental health setting: a mixed-methods study protocol
Authors: Hansen Alison Claire , Hazelton Michael , Rosina Robyn , Inder Kerry J
Published: June 2021

Introduction

Seclusion use is high in forensic mental health settings and is associated with avoidable physical and psychological harm. The use of seclusion causes significant distress and trauma for those secluded and women in these settings are particularly vulnerable. This study protocol aims to identify factors associated with the use of seclusion and the experience of seclusion for women in forensic mental health settings.

Methods and analysis

This study will use a prospective mixed-methods design. Quantitative data on the frequency and duration of seclusion and potential explanatory demographic and clinical variables will be collected prospectively from consecutive medical records of women admitted to a forensic mental health service over a 2-year period. Data will be analysed using descriptive statistics and logistic regression techniques. Qualitative data will be collected from individual face-to-face semistructured interviews with women who have experienced seclusion about the reason for seclusion, whether they agreed with the reason for seclusion, their experience of the seclusion event and the seclusion environment and support provided while in seclusion using qualitative description methods. Data will be analysed using thematic analysis.

Ethics and dissemination

Ethical approval has been granted by the University of Newcastle Human Research Ethics Committee (H-2019–0122) and organisational support granted from the participating forensic mental health service. Participation will be voluntary and written informed consent is required. Results will be disseminated via the first author’s doctoral thesis, in peer-reviewed journals and at conferences. Results will inform recommendations for policy, and evidence for timely and specific interventions to support the reduction of seclusion for women in forensic mental health settings.
Longitudinal cohorts for harnessing the electronic health record for disease prediction in a US population
Authors: Manemann Sheila M , St Sauver Jennifer L , Liu Hongfang , Larson Nicholas B , Moon Sungrim , Takahashi Paul Y , Olson Janet E , Rocca Walter A , Miller Virginia M , Therneau Terry M , Ngufor Che G , Roger Veronique L , Zhao Yiqing , Decker Paul A , Killian Jill M , Bielinski Suzette J
Published: June 2021

Purpose

The depth and breadth of clinical data within electronic health record (EHR) systems paired with innovative machine learning methods can be leveraged to identify novel risk factors for complex diseases. However, analysing the EHR is challenging due to complexity and quality of the data. Therefore, we developed large electronic population-based cohorts with comprehensive harmonised and processed EHR data.

Participants

All individuals 30 years of age or older who resided in Olmsted County, Minnesota on 1 January 2006 were identified for the discovery cohort. Algorithms to define a variety of patient characteristics were developed and validated, thus building a comprehensive risk profile for each patient. Patients are followed for incident diseases and ageing-related outcomes. Using the same methods, an independent validation cohort was assembled by identifying all individuals 30 years of age or older who resided in the largely rural 26-county area of southern Minnesota and western Wisconsin on 1 January 2013.

Findings to date

For the discovery cohort, 76 255 individuals (median age 49; 53% women) were identified from which a total of 9 644 221 laboratory results; 9 513 840 diagnosis codes; 10 924 291 procedure codes; 1 277 231 outpatient drug prescriptions; 966 136 heart rate measurements and 1 159 836 blood pressure (BP) measurements were retrieved during the baseline time period. The most prevalent conditions in this cohort were hyperlipidaemia, hypertension and arthritis. For the validation cohort, 333 460 individuals (median age 54; 52% women) were identified and to date, a total of 19 926 750 diagnosis codes, 10 527 444 heart rate measurements and 7 356 344 BP measurements were retrieved during baseline.

Future plans

Using advanced machine learning approaches, these electronic cohorts will be used to identify novel sex-specific risk factors for complex diseases. These approaches will allow us to address several challenges with the use of EHR.
Effects of a modified muscle sparing posterior technique in hip hemiarthroplasty for displaced intracapsular fractures on postoperative function compared to a standard lateral approach (HemiSPAIRE): protocol for a randomised controlled trial
Authors: Price Anna , Ball Susan , Rhodes Shelley , Wickins Robert , Gordon Elizabeth , Aylward Alex , Cockcroft Emma , Morgan-Trimmer Sarah , Powell Roy , Timperley John , Charity John
Published: June 2021

Introduction

Currently National Institute for Health and Care Excellence clinical guidelines in the UK suggest that surgeons performing partial hip replacements (hemiarthroplasty) should consider using the lateral approach. Alternatively, a newer, modified posterior approach using a muscle sparing technique named ‘Save Piriformis and Internus, Repairing Externus’ (SPAIRE) can be used leaving the major muscles intact. This randomised controlled trial (RCT) aims to compare the SPAIRE approach to the standard lateral approach, to determine if it allows patients to mobilise better and experience improved function after surgery.

Methods and analysis

HemiSPAIRE is a two-arm, assessor-blinded, definitive pragmatic RCT with nested pilot and qualitative studies. Two hundred and twenty-eight participants with displaced intracapsular fractures requiring hip hemiarthroplasty will be individually randomised 1:1 to either the SPAIRE, or control (standard lateral approach) surgical procedure. Outcomes will be assessed at postoperative day 3 (POD3) and 120 (POD120). The primary outcome measure will be level of function and mobility using the Oxford Hip Score at POD120. Secondary outcomes include: De Morton Mobility Index (DEMMI), Cumulated Ambulatory Score and Numeric Pain Rating Scale (NPRS) at POD3; DEMMI, NPRS and EQ-5D-5L at POD120, complications, acute and total length of hospital stay, and mortality. Primary analysis will be on an intention-to-treat basis. Participant experiences of the impact of surgery and recovery period will be examined via up to 20 semi-structured telephone interviews.

Ethics and dissemination

The protocol has been approved by Yorkshire and the Humber—Bradford Leeds Research Ethics Committee. Recruitment commenced in November 2019. Findings will be disseminated via research articles in peer-reviewed journals, presentations at conferences, public involvement events, patient groups and media releases. A summary of the trial findings will be shared with participants at the end of the study.

Trial registration number

NCT04095611.
Role of systems science in preventing and controlling emerging infectious diseases: protocol for a scoping review
Authors: Mansouri Mariam Abdulmonem , Kee Frank , Garcia Leandro , Bradley Declan T
Published: June 2021

Introduction

In recent history, many new infectious diseases have affected humans for the first time or have appeared in previously unaffected areas of the world; these diseases are known as emerging infectious diseases (EIDs). Examples of EIDs include COVID-19, Middle East respiratory syndrome and Ebola virus disease. EIDs are known for their complexity. Multiple factors play a role in their spread, including increases in human population, conflicts, urbanisation, air travel, global trade and inequalities in wealth distribution and access to healthcare. In order to gain a better understanding of such complexity, we aim to explore the role of systems science, which allows us to view EIDs in the context of complex adaptive systems rather than simple causes and effects. The objectives of this scoping review are to explore and map the theoretical concepts and key characteristics of studies that use systems methods in controlling EIDs, to identify the gaps in knowledge and disseminate the results.

Methods

We will follow the Joanna Briggs Institute guidance for this scoping review, comprising the following stages: formulating the research question and subquestions, scanning the literature for available data, selecting relevant publications, charting the data by two independent reviewers, aggregating the findings, reporting, summarising and disseminating the results. We will review peer-reviewed articles, preprints and grey literature available in all languages.

Discussion

We intend that this scoping review will contribute to a better understanding of the use of systems methods to inform policymakers about how to prevent and control EIDs.

Ethics and dissemination

Research ethics approval is not required for a scoping review because it is based on reviewing and collecting data from publicly available sources. To disseminate the findings, results will be shared through academic publications, seminars and conferences.
Bidirectional association between migraine and rheumatoid arthritis: two longitudinal follow-up studies with a national sample cohort
Authors: Kim Yoo Hwan , Lee Jung Woo , Kim Yerim , Bae Jong Seok , Kim Yeo Jin , Min Chanyang , Choi Hyo Geun
Published: June 2021

Objective

To investigate the bidirectional association between migraine and rheumatoid arthritis (RA).

Design

Two longitudinal follow-up studies.

Setting

Data collected from a national cohort between 2002 and 2013 by the Korean National Health Insurance Service-Health Screening Cohort.

Participants

In cohort 1, matching resulted in the inclusion of 31 589 migraine patients and 126 356 control I participants. In cohort 2, matching resulted in the inclusion of 9287 RA patients and 37 148 control II participants.

Primary and secondary outcome measures

The HRs for RA in patients with migraine (cohort 1) and migraine in patients with RA (cohort 2) were analysed using stratified Cox proportional hazard models after adjusting for autoimmune disease, Charlson Comorbidity Index scores without rheumatoid diseases, obesity (body mass index), smoking and history of alcohol intake. Subgroup analyses stratified by age, sex, income and region of residence were also performed.

Results

The incidence of RA in the migraine group (2.0% (640/31 589)) was higher than that in the control I group (1.4% (1709/126 356), p<0.001). The adjusted HR for RA in the migraine without aura group was 1.48 (95% CIs=1.34 to 1.63, p<0.001).

The incidence of migraine in the RA group (6.4% (590/9287)) was higher than that in the control II group (4.6% (1721/37 148), p<0.001). The adjusted HR for migraine without aura in the RA group was 1.35 (95% CI=1.23 to 1.49, p<0.001).

Conclusion

Migraine increases the risk of RA, and RA is also associated with an increased risk of migraine.
Which ethical values underpin England’s National Health Service reset of paediatric and maternity services following COVID-19: a rapid review
Authors: Chiumento Anna , Baines Paul , Redhead Caroline , Fovargue Sara , Draper Heather , Frith Lucy
Published: June 2021

Objective

To identify ethical values guiding decision making in resetting non-COVID-19 paediatric surgery and maternity services in the National Health Service (NHS).

Design

A rapid review of academic and grey literature sources from 29 April to 31 December 2020, covering non-urgent, non-COVID-19 healthcare. Sources were thematically synthesised against an adapted version of the UK Government’s Pandemic Flu Ethical Framework to identify underpinning ethical principles. The strength of normative engagement and the quality of the sources were also assessed.

Setting

NHS maternity and paediatric surgery services in England.

Results

Searches conducted 8 September–12 October 2020, and updated in March 2021, identified 48 sources meeting the inclusion criteria. Themes that arose include: staff safety; collaborative working – including mutual dependencies across the healthcare system; reciprocity; and inclusivity in service recovery, for example, by addressing inequalities in service access. Embedded in the theme of staff and patient safety is embracing new ways of working, such as the rapid roll out of telemedicine. On assessment, many sources did not explicitly consider how ethical principles might be applied or balanced against one another. Weaknesses in the policy sources included a lack of public and user involvement and the absence of monitoring and evaluation criteria.

Conclusions

Our findings suggest that relationality is a prominent ethical principle informing resetting NHS non-COVID-19 paediatric surgery and maternity services. Sources explicitly highlight the ethical importance of seeking to minimise disruption to caring and dependent relationships, while simultaneously attending to public safety. Engagement with ethical principles was ethics-lite, with sources mentioning principles in passing rather than explicitly applying them. This leaves decision makers and healthcare professionals without an operationalisable ethical framework to apply to difficult reset decisions and risks inconsistencies in decision making. We recommend further research to confirm or refine the usefulness of the reset phase ethical framework developed through our analysis.
Seroprevalence study of SARS-CoV-2 antibodies in healthcare workers following the first wave of the COVID-19 pandemic in a tertiary-level hospital in the south of Ireland
Authors: Faller Eamonn , Wyse Adrianne , Barry Rachel , Conlon Kevin , Everard Cormac , Finnegan Paula , Foran Claire , Herlihy Emer , Kerr Gerry , Lapthorne Susan , McGreal-Bellone Aimee , Morrissey Edmond , O’Sullivan Deirdre , O’Sullivan Grainne , Eustace Joseph A , Spillane Declan , Dempsey Catherine , Benson John , Prentice Mike , Gallagher John , MacSharry John , Fanning Liam J , O’Riordan Stephen , Horgan Mary , Sadlier Corinna
Published: June 2021

Objective

This study investigated seroprevalence of SARS-CoV-2-specific IgG antibodies, using the Abbott antinucleocapsid IgG chemiluminescent microparticle immunoassay (CMIA) assay, in five prespecified healthcare worker (HCW) subgroups following the first wave of the COVID-19 pandemic.

Setting

An 800-bed tertiary-level teaching hospital in the south of Ireland.

Participants

Serum was collected for anti-SARS-CoV-2 nucleocapsid IgG using the Abbott ARCHITECT SARS-CoV-2 IgG CMIA qualitative assay, as per the manufacturer’s specifications.

The groups were as follows: (1) HCWs who had real-time PCR (RT-PCR) confirmed COVID-19 infection (>1-month postpositive RT-PCR); (2) HCWs identified as close contacts of persons with COVID-19 infection and who subsequently developed symptoms (virus not detected by RT-PCR on oropharyngeal/nasopharyngeal swab); (3) HCWs identified as close contacts of COVID-19 cases and who remained asymptomatic (not screened by RT-PCR); (4) HCWs not included in the aforementioned groups working in areas determined as high-risk clinical areas; and (5) HCWs not included in the aforementioned groups working in areas determined as low-risk clinical areas.

Results

Six of 404 (1.49%) HCWs not previously diagnosed with SARS-CoV-2 infection (groups 2–5) were seropositive for SARS-CoV-2 at the time of recruitment into the study.

Out of the 99 participants in group 1, 72 had detectable IgG to SARS-CoV-2 on laboratory testing (73%). Antibody positivity correlated with shorter length of time between RT-PCR positivity and antibody testing.

Quantification cycle value on RT-PCR was not found to be correlated with antibody positivity.

Conclusions

Seroprevalence of SARS-CoV-2 antibodies in HCWs who had not previously tested RT-PCR positive for COVID-19 was low compared with similar studies.
Clinical spectrum of paediatric and adult eosinophilic oesophagitis in the North East of England from 2016 to 2019
Authors: Shillitoe Ben , Lee Ji Ching , Hussien Mohammed , Beintaris Iosif , Stothard Mark , Johnston Matthew , Dallal Helen Jane , Michaelis Louise J , Attwood Stephen , Dhar Anjan
Published: June 2021

Background and study aims

Eosinophilic oesophagitis (EoE) is a common disease with a significant impact on physical health and quality of life (QoL). Outcomes and management vary widely, with no agreed UK national guideline. This paper aims to describe an up-to-date description of demographics, clinical spectrum and outcomes for paediatric and adult patients with EoE from the North East of England between 2016 and 2019.

Patients and methods

Patients from two large University Hospitals and the specialist paediatric hospital for the North East of England with histologically or clinically confirmed EoE were included in this analysis. Data were collected retrospectively via electronic patient records. Remission was defined as either the resolution of symptoms or improvement on histology.

Results

Data were collected on 74 paediatric and 59 adult patients. Dysphagia was the most common presenting symptom in both groups, accounting for 51%–84% of all presentations. Proton pump inhibitors and dietary manipulation were the most common therapies associated with remission in children (95% of those achieving remission), whereas the use of swallowed topical steroids was more prevalent in the treatment of adults (55% achieving remission).

Conclusions

EoE is a complex disease and poses significant challenges. Outcomes vary widely and need to be tailored to individual patient groups. Dietary manipulation plays a major role in treatment for EoE, but this is likely to be challenging for patients, especially children. Future work should continue to assess the outcomes in EoE, including on QoL and potential novel targeted therapies.
Understanding the role of the gut in undernutrition: what can technology tell us?
Authors: Thompson Alex J , Bourke Claire D , Robertson Ruairi C , Shivakumar Nirupama , Edwards Christine A , Preston Tom , Holmes Elaine , Kelly Paul , Frost Gary , Morrison Douglas J
Published: June 2021

Gut function remains largely underinvestigated in undernutrition, despite its critical role in essential nutrient digestion, absorption and assimilation. In areas of high enteropathogen burden, alterations in gut barrier function and subsequent inflammatory effects are observable but remain poorly characterised. Environmental enteropathy (EE)—a condition that affects both gut morphology and function and is characterised by blunted villi, inflammation and increased permeability—is thought to play a role in impaired linear growth (stunting) and severe acute malnutrition. However, the lack of tools to quantitatively characterise gut functional capacity has hampered both our understanding of gut pathogenesis in undernutrition and evaluation of gut-targeted therapies to accelerate nutritional recovery. Here we survey the technology landscape for potential solutions to improve assessment of gut function, focussing on devices that could be deployed at point-of-care in low-income and middle-income countries (LMICs). We assess the potential for technological innovation to assess gut morphology, function, barrier integrity and immune response in undernutrition, and highlight the approaches that are currently most suitable for deployment and development. This article focuses on EE and undernutrition in LMICs, but many of these technologies may also become useful in monitoring of other gut pathologies.
Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease
Authors: Urban Stephan , Neumann-Haefelin Christoph , Lampertico Pietro
Published: June 2021

Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5–10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.
Three-antibody classifier for muscle invasive urothelial carcinoma and its correlation with p53 expression
Authors: Olkhov-Mitsel Ekaterina , Hodgson Anjelica , Liu Stanley K , Vesprini Danny , Xu Bin , Downes Michelle R
Published: June 2021

Aims

To assess the utility of a three-antibody immunohistochemistry panel to classify muscle invasive bladder cancers (MIBCs) in correlation with morphological features and p53 status.

Methods

A retrospective review of 243 chemotherapy naïve MIBC cystectomy specimens was performed to assess morphological features. A tissue microarray was sequentially stained with CK5/6, GATA-3 and p16. Subgroups were assigned as basal-like (CK5/6+, GATA3−) and luminal (CK5/6−, GATA3+), with the latter subdivided into genomically unstable (GU, p16+) and urothelial like (Uro, p16−) subgroups. p53 staining was assessed as abnormal/wild type. Cases from the The Cancer Genome Atlas (TCGA) portal were assessed as external validation.

Results

We identified 78.8% luminal, 21.2% basal cases within our cohort and 63.4% luminal, 36.6% basal in the TCGA dataset. Divergent differentiation (p<0.001) was significantly associated with basal-subtype cases in both cohorts. Within the luminal subgroup (n=186), 81 cases were classified as GU and 105 as Uro. Abnormal p53 staining was noted in 48.0% of basal, 80.2% GU and 38.1% Uro cases. Further, basal-subtype tumours significantly correlated with disease-specific death compared with Uro cases in multivariate survival analysis.

Conclusions

This retrospective study demonstrates the potential utility of a three-antibody immunohistochemistry panel to differentiate luminal and basal MIBC.
Heterogeneity in tertiary lymphoid structure B-cells correlates with patient survival in metastatic melanoma
Authors: Lynch Kevin T , Young Samuel J , Meneveau Max O , Wages Nolan A , Engelhard Victor H , Slingluff Jr Craig L , Mauldin Ileana S
Published: June 2021

Background

Tertiary lymphoid structures (TLSs) are immune aggregates in peripheral tissues that may support adaptive immune responses. Their presence has been associated with clinical response to checkpoint blockade therapy (CBT), but it is unknown whether TLS have prognostic significance independent of CBT in melanoma. We hypothesized that TLS in melanoma metastases would be associated with increased intratumoral lymphocyte infiltration, but that the intra-TLS immunological milieu would be distinct from the intratumoral immunological milieu. We also hypothesized that the presence of TLS would be associated with improved survival, and that TLS maturation or intra-TLS lymphocyte activity would also correlate with survival.

Methods

Cutaneous melanoma metastases (CMM) from 64 patients were evaluated by multiplex immunofluorescence for the presence and maturation status of TLS. Intra-TLS lymphocyte density, proliferation and B-cell Ig somatic hypermutation (AID+) were analyzed, as were markers of T-cell exhaustion and Th1/Tc1 differentiation. Associations between TLS maturation and intra-TLS immunologic activity were assessed, as well as associations with intratumoral immune cell infiltration. Independent associations with overall survival (OS) were assessed using log-rank tests and Cox proportional hazards models.

Results

TLS were identified in 30 (47%) of 64 CMM (TLS+) and were associated with increased intratumoral lymphocyte infiltration. However, proliferation of intra-TLS lymphocytes did not correlate with intratumoral lymphocyte proliferation. Most were early TLS; however, subsets of primary or secondary follicle-like TLS were also present. TLS+ lesions were associated with lower risk of tumor recurrence after metastasectomy and with improved OS in multivariate analyses (HR 0.51, p=0.04). OS was longer for TLS with low fractions of CD21+ B-cells (HR 0.29, p=0.02) and shorter for those with low AID+ fraction of B-cells (HR 2.74, p=0.03).

Conclusions

The presence of TLS in CMMs is associated with improved OS in patients treated with surgery before CBT, but TLS vary widely in maturation state, in proportions of proliferating T and B cells, and in markers of B cell function, including AID and CD21. Importantly, these features have additional prognostic significance, which suggest that some TLS may have regulatory function, while others functioning to support antigen-driven immune responses, depending on the cellular composition and activation status.
Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases
Authors: Grunseich Christopher , Sarkar Nathan , Lu Joyce , Owen Mallory , Schindler Alice , Calabresi Peter A , Sumner Charlotte J , Roda Ricardo H , Chaudhry Vinay , Lloyd Thomas E , Crawford Thomas O , Subramony S H , Oh Shin J , Richardson Perry , Tanji Kurenai , Kwan Justin Y , Fischbeck Kenneth H , Mankodi Ami
Published: June 2021

Background

We used a multimodal approach including detailed phenotyping, whole exome sequencing (WES) and candidate gene filters to diagnose rare neurological diseases in individuals referred by tertiary neurology centres.

Methods

WES was performed on 66 individuals with neurogenetic diseases using candidate gene filters and stringent algorithms for assessing sequence variants. Pathogenic or likely pathogenic missense variants were interpreted using in silico prediction tools, family segregation analysis, previous publications of disease association and relevant biological assays.

Results

Molecular diagnosis was achieved in 39% (n=26) including 59% of childhood-onset cases and 27% of late-onset cases. Overall, 37% (10/27) of myopathy, 41% (9/22) of neuropathy, 22% (2/9) of MND and 63% (5/8) of complex phenotypes were given genetic diagnosis. Twenty-seven disease-associated variants were identified including ten novel variants inFBXO38, LAMA2, MFN2, MYH7, PNPLA6, SH3TC2andSPTLC1. Single-nucleotide variants (n=10) affected conserved residues within functional domains and previously identified mutation hot-spots. Established pathogenic variants (n=16) presented with atypical features, such as optic neuropathy in adult polyglucosan body disease, facial dysmorphism and skeletal anomalies in cerebrotendinous xanthomatosis, steroid-responsive weakness in congenital myasthenia syndrome 10. Potentially treatable rare diseases were diagnosed, improving the quality of life in some patients.

Conclusions

Integrating deep phenotyping, gene filter algorithms and biological assays increased diagnostic yield of exome sequencing, identified novel pathogenic variants and extended phenotypes of difficult to diagnose rare neurogenetic disorders in an outpatient clinic setting.
TNF-α inhibitors used as steroid-sparing maintenance monotherapy in parenchymal CNS sarcoidosis
Authors: Hilezian Frédéric , Maarouf Adil , Boutiere Clemence , Rico Audrey , Demortiere Sarah , Kerschen Philippe , Sene Thomas , Bensa-Koscher Caroline , Giannesini Claire , Capron Jean , Mekinian Arsene , Camdessanché Jean-Philippe , Androdias Géraldine , Marignier Romain , Collongues Nicolas , Casez Olivier , Coclitu Catalina , Vaillant Mathieu , Mathey Guillaume , Ciron Jonathan , Pelletier Jean , Audoin Bertrand
Published: June 2021

Objective

To assess the efficacy of tumour necrosis factor-α (TNF-α) inhibitors used as steroid-sparing monotherapy in central nervous system (CNS) parenchymal sarcoidosis.

Methods

The French Multiple Sclerosis and Neuroinflammation Centers retrospectively identified patients with definite or probable CNS sarcoidosis treated with TNF-α inhibitors as steroid-sparing monotherapy. Only patients with CNS parenchymal involvement demonstrated by MRI and imaging follow-up were included. The primary outcome was the minimum dose of steroids reached that was not associated with clinical or imaging worsening during a minimum of 3 months after dosing change.

Results

Of the identified 38 patients with CNS sarcoidosis treated with TNF-α inhibitors, 23 fulfilled all criteria (13 females). Treatments were infliximab (n=22) or adalimumab (n=1) for a median (IQR) of 24 (17–40) months. At treatment initiation, the mean (SD) age was 41.5 (10.5) years and median (IQR) disease duration 22 (14–49.5) months. Overall, 60% of patients received other immunosuppressive agents before a TNF-α inhibitor. The mean (SD) minimum dose of steroids was 31.5 (33) mg before TNF-α inhibitor initiation and 6.5 (5.5) mg after (p=0.001). In all, 65% of patients achieved steroids dosing <6 mg/day; 61% showed clinical improvement, 30% stability and 9% disease worsening. Imaging revealed improvement in 74% of patients and stability in 26%.

Conclusion

TNF-α inhibitors can greatly reduce steroids dosing in patients with CNS parenchymal sarcoidosis, even refractory.

Classification of evidence

This study provides Class IV evidence that TNF-α inhibitor used as steroid-sparing monotherapy is effective for patients with CNS parenchymal sarcoidosis.
Intravenous immunoglobulin treatment for mild Guillain-Barré syndrome: an international observational study
Authors: Verboon Christine , Harbo Thomas , Cornblath David R , Hughes Richard A C , van Doorn Pieter A , Lunn Michael P , Gorson Kenneth C , Barroso Fabio , Kuwabara Satoshi , Galassi Giuliana , Lehmann Helmar C , Kusunoki Susumu , Reisin Ricardo C , Binda Davide , Cavaletti Guido , Jacobs Bart C
Published: June 2021

Objective

To compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only.

Methods

We selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis.

Results

Of 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms.

Conclusion

In patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.