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  1. Article: Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis.

    O'Byrne, Aoife M / de Jong, Tineke A / van Baarsen, Lisa G M

    Frontiers in medicine

    2022  Volume 8, Page(s) 820232

    Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein ... ...

    Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.
    Language English
    Publishing date 2022-01-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2021.820232
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis.

    Kim, Lisa H Y / Saleh, Carol / Whalen-Browne, Anna / O'Byrne, Paul M / Chu, Derek K

    JAMA

    2021  Volume 325, Issue 24, Page(s) 2466–2479

    Abstract: Importance: The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.: Objective: To systematically synthesize the ... ...

    Abstract Importance: The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.
    Objective: To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma.
    Data sources: MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction.
    Study selection: Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma.
    Data extraction and synthesis: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence.
    Main outcomes and measures: Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events.
    Results: Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence).
    Conclusions and relevance: Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.
    MeSH term(s) Administration, Inhalation ; Adrenal Cortex Hormones/administration & dosage ; Adrenergic beta-2 Receptor Agonists/administration & dosage ; Adult ; Anti-Asthmatic Agents/administration & dosage ; Anti-Asthmatic Agents/adverse effects ; Asthma/drug therapy ; Asthma/mortality ; Asthma/physiopathology ; Child ; Drug Therapy, Combination/adverse effects ; Forced Expiratory Volume ; Humans ; Muscarinic Antagonists/administration & dosage ; Nebulizers and Vaporizers ; Quality of Life ; Severity of Illness Index ; Symptom Flare Up ; Xerostomia/chemically induced
    Chemical Substances Adrenal Cortex Hormones ; Adrenergic beta-2 Receptor Agonists ; Anti-Asthmatic Agents ; Muscarinic Antagonists
    Language English
    Publishing date 2021-06-16
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Meta-Analysis ; Systematic Review
    ZDB-ID 2958-0
    ISSN 1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
    ISSN (online) 1538-3598
    ISSN 0254-9077 ; 0002-9955 ; 0098-7484
    DOI 10.1001/jama.2021.7872
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis

    Aoife M. O'Byrne / Tineke A. de Jong / Lisa G. M. van Baarsen

    Frontiers in Medicine, Vol

    2022  Volume 8

    Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein ... ...

    Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.
    Keywords rheumatoid arthritis ; lymph node ; synovium ; tolerance ; fibroblasts ; T cells ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction.

    O'Byrne, Lisa / Webster, Katie E / MacKeith, Samuel / Philpott, Carl / Hopkins, Claire / Burton, Martin J

    The Cochrane database of systematic reviews

    2022  Volume 9, Page(s) CD013876

    Abstract: Background: Olfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little guidance on how best to treat this condition. A variety of interventions ... ...

    Abstract Background: Olfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little guidance on how best to treat this condition. A variety of interventions have been suggested to promote recovery, including medication and olfactory training. However, it is uncertain whether any intervention is of benefit. This is an update of the 2021 review with one additional study added.  OBJECTIVES: 1) To evaluate the benefits and harms of any intervention versus no treatment for people with persisting olfactory dysfunction due to COVID-19 infection.  2) To keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021.   SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance that had persisted for at least four weeks. We included any intervention compared to no treatment or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome.
    Main results: We included two studies with 30 participants. The studies evaluated the following interventions: systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant and palmitoylethanolamide plus luteolin.  Systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant compared to no intervention We included a single RCT with 18 participants who had anosmia for at least 30 days following COVID-19 infection. Participants received a 15-day course of oral corticosteroids combined with nasal irrigation (consisting of an intranasal corticosteroid/mucolytic/decongestant solution) or no intervention. Psychophysical testing was used to assess olfactory function at 40 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results. Palmitoylethanolamide plus luteolin compared to no intervention We included a single RCT with 12 participants who had anosmia or hyposmia for at least 90 days following COVID-19 infection. Participants received a 30-day course of palmitoylethanolamide and luteolin or no intervention. Psychophysical testing was used to assess olfactory function at 30 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results.
    Authors' conclusions: There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.
    MeSH term(s) Adrenal Cortex Hormones ; Anosmia ; COVID-19/complications ; Expectorants ; Humans ; Luteolin ; Nasal Decongestants ; Randomized Controlled Trials as Topic ; Smell
    Chemical Substances Adrenal Cortex Hormones ; Expectorants ; Nasal Decongestants ; Luteolin (KUX1ZNC9J2)
    Language English
    Publishing date 2022-09-05
    Publishing country England
    Document type Journal Article ; Review ; Systematic Review ; Research Support, Non-U.S. Gov't
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD013876.pub3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.

    Webster, Katie E / O'Byrne, Lisa / MacKeith, Samuel / Philpott, Carl / Hopkins, Claire / Burton, Martin J

    The Cochrane database of systematic reviews

    2022  Volume 9, Page(s) CD013877

    Abstract: Background: Loss of olfactory function is well recognised as a symptom of COVID-19 infection, and the pandemic has resulted in a large number of individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves ... ...

    Abstract Background: Loss of olfactory function is well recognised as a symptom of COVID-19 infection, and the pandemic has resulted in a large number of individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority the symptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance. This is an update of the 2021 review with four studies added.
    Objectives: 1) To evaluate the benefits and harms of any intervention versus no treatment for people with acute olfactory dysfunction due to COVID-19 infection.  2) To keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021.
    Selection criteria: We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance, which had been present for less than four weeks. We included any intervention compared to no treatment or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were the presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome.  MAIN RESULTS: We included five studies with 691 participants. The studies evaluated the following interventions: intranasal corticosteroid sprays, intranasal corticosteroid drops, intranasal hypertonic saline and zinc sulphate.  Intranasal corticosteroid spray compared to no intervention/placebo We included three studies with 288 participants who had olfactory dysfunction for less than four weeks following COVID-19. Presence of normal olfactory function The evidence is very uncertain about the effect of intranasal corticosteroid spray on both self-rated recovery of olfactory function and recovery of olfactory function using psychophysical tests at up to four weeks follow-up (self-rated: risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; psychophysical testing: RR 2.3, 95% CI 1.16 to 4.63; 1 study; 77 participants; very low-certainty evidence).  Change in sense of smell The evidence is also very uncertain about the effect of intranasal corticosteroid spray on self-rated change in the sense of smell (at less than 4 weeks: mean difference (MD) 0.5 points lower, 95% CI 1.38 lower to 0.38 higher; 1 study; 77 participants; at > 4 weeks to 3 months: MD 2.4 points higher, 95% CI 1.32 higher to 3.48 higher; 1 study; 100 participants; very low-certainty evidence, rated on a scale of 1 to 10, higher scores mean better olfactory function). Intranasal corticosteroids may make little or no difference to the change in sense of smell when assessed with psychophysical testing (MD 0.2 points, 95% CI 2.06 points lower to 2.06 points higher; 1 study; 77 participants; low-certainty evidence, 0- to 24-point scale, higher scores mean better olfactory function).  Serious adverse effects The authors of one study reported no adverse effects, but their intention to collect these data was not pre-specified so we are uncertain if these were systematically sought and identified. The remaining two studies did not report on adverse effects.  Intranasal corticosteroid drops compared to no intervention/placebo We included one study with 248 participants who had olfactory dysfunction for ≤ 15 days following COVID-19. Presence of normal olfactory function Intranasal corticosteroid drops may make little or no difference to self-rated recovery at > 4 weeks to 3 months (RR 1.00, 95% CI 0.89 to 1.11; 1 study; 248 participants; low-certainty evidence). No other outcomes were assessed by this study.  Data on the use of hypertonic saline nasal irrigation and the use of zinc sulphate to prevent persistent olfactory dysfunction are included in the full text of the review.
    Authors' conclusions: There is very limited evidence available on the efficacy and harms of treatments for preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.
    MeSH term(s) Adrenal Cortex Hormones/therapeutic use ; COVID-19/complications ; Chronic Disease ; Humans ; Olfaction Disorders/etiology ; Olfaction Disorders/prevention & control ; Randomized Controlled Trials as Topic ; Rhinitis/drug therapy ; Smell ; Zinc Sulfate
    Chemical Substances Adrenal Cortex Hormones ; Zinc Sulfate (7733-02-0)
    Language English
    Publishing date 2022-09-05
    Publishing country England
    Document type Journal Article ; Review ; Systematic Review ; Research Support, Non-U.S. Gov't
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD013877.pub3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Neurocognitive function and health-related quality of life in adolescents and young adults with CHD with pulmonary valve dysfunction.

    Zampi, Jeffrey D / Heinrich, Kimberley P / Bergersen, Lisa / Goldstein, Bryan H / Batlivala, Sarosh P / Fuller, Stephanie / Glatz, Andrew C / O'Byrne, Michael L / Marino, Bradley / Afton, Katherine / Lowery, Ray / Yu, Sunkyung / Goldberg, Caren S

    Cardiology in the young

    2023  , Page(s) 1–8

    Abstract: Background: Neurocognitive impairment and quality of life are two important long-term challenges for patients with complex CHD. The impact of re-interventions during adolescence and young adulthood on neurocognition and quality of life is not well ... ...

    Abstract Background: Neurocognitive impairment and quality of life are two important long-term challenges for patients with complex CHD. The impact of re-interventions during adolescence and young adulthood on neurocognition and quality of life is not well understood.
    Methods: In this prospective longitudinal multi-institutional study, patients 13-30 years old with severe CHD referred for surgical or transcatheter pulmonary valve replacement were enrolled. Clinical characteristics were collected, and executive function and quality of life were assessed prior to the planned pulmonary re-intervention. These results were compared to normative data and were compared between treatment strategies.
    Results: Among 68 patients enrolled from 2016 to 2020, a nearly equal proportion were referred for surgical and transcatheter pulmonary valve replacement (53% versus 47%). Tetralogy of Fallot was the most common diagnosis (59%) and pulmonary re-intervention indications included stenosis (25%), insufficiency (40%), and mixed disease (35%). There were no substantial differences between patients referred for surgical and transcatheter therapy. Executive functioning deficits were evident in 19-31% of patients and quality of life was universally lower compared to normative sample data. However, measures of executive function and quality of life did not differ between the surgical and transcatheter patients.
    Conclusion: In this patient group, impairments in neurocognitive function and quality of life are common and can be significant. Given similar baseline characteristics, comparing changes in neurocognitive outcomes and quality of life
    Language English
    Publishing date 2023-11-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 1078466-4
    ISSN 1467-1107 ; 1047-9511
    ISSN (online) 1467-1107
    ISSN 1047-9511
    DOI 10.1017/S1047951123003979
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The Need for Surgery After Vascular or Cardiac Trauma, or Technical Adverse Events in the Congenital Cardiac Catheterization Laboratory.

    Holzer, Ralf / Batlivala, Sarosh P / Boe, Brian / Goldstein, Bryan / Gudausky, Todd / Hasan, Babar / O'Byrne, Michael / Quinn, Brian / Sathanadam, Shyam / Shahanavaz, Shabana / Trucco, Sara M / Zampi, Jeffrey D / Bergersen, Lisa

    Pediatric cardiology

    2023  Volume 44, Issue 4, Page(s) 795–805

    Abstract: Data on the frequency and outcome of surgical interventions as a result of adverse events (AE) encountered in the pediatric and congenital cardiac catheterization laboratory are limited. This study analyzes the outcomes of specific types of AE that are ... ...

    Abstract Data on the frequency and outcome of surgical interventions as a result of adverse events (AE) encountered in the pediatric and congenital cardiac catheterization laboratory are limited. This study analyzes the outcomes of specific types of AE that are most likely to require immediate surgical intervention. Data from the C3PO registry were analyzed to identify specific types of significant vascular/cardiac trauma or technical adverse events (stent/device/coil embolization/migration). The relationship between these AE and an "adverse outcome" (defined as either surgery, ECMO, or death) were analyzed. Between 01/2014 and 12/2017, 25,731 cases were entered into the C3PO registry. Vascular or cardiac trauma were observed in 92 cases (0.36% cases in C3PO), and technical adverse events were observed in 176 cases (0.68% cases in C3PO). The two highest procedure type risk categories (PREDIC3T) accounted for 61% of the cases in the cardiac/vascular trauma cohort, and 34% in the technical AE cohort. For vascular/cardiac trauma, 24 (26%) had an adverse outcome, with ECMO in 8 (9%), surgery in 19 (20%), and death in 9 (10%). For technical AE 25 (14%) had an adverse outcome, with ECMO in 3 (2%), surgery in 23 (13%), and death in 3 (2%). Survival after cardiac surgery secondary to an AE was 68% for cardiac/vascular trauma, and 96% for technical adverse events. RF perforation of the pulmonary valve was the procedure most likely to result in cardiac/vascular trauma (10%), with 57% of those having an adverse outcome. Atrial septal interventions accounted for 29% of all adverse outcomes in the cardiac/vascular trauma cohort. Non-elective or emergent cases were associated with a significantly higher incidence of an adverse outcome for both, cardiac/vascular trauma (OR 7.1) and technical adverse events (OR 2.7). Surgery within the last 30 days was associated with a significantly higher incidence of an adverse outcome for cardiac/vascular trauma only (OR 4.2). Significant cardiac/vascular trauma or stent/device/coil embolization/migration are rare, but high consequence AE. With appropriate surgical and ECMO backup, a high survival can be achieved. The potential need for and impact of immediate surgical backup seems to be higher for cardiac/vascular trauma (in particular after specific case types), than for device/coil migration/embolization, and as such case specific backup arrangements are required.
    MeSH term(s) Child ; Humans ; Heart Defects, Congenital ; Cardiac Catheterization/adverse effects ; Cardiac Surgical Procedures/adverse effects ; Pulmonary Valve ; Thoracic Surgery ; Treatment Outcome ; Risk Factors
    Language English
    Publishing date 2023-02-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 800857-7
    ISSN 1432-1971 ; 0172-0643
    ISSN (online) 1432-1971
    ISSN 0172-0643
    DOI 10.1007/s00246-023-03126-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Minimizing Sample Failure Rates for Challenging Clinical Tumor Samples.

    Fink, J Lynn / Jaradi, Binny / Stone, Nathan / Anderson, Lisa / Leo, Paul J / Marshall, Mhairi / Ellis, Jonathan / Waring, Paul M / O'Byrne, Kenneth

    The Journal of molecular diagnostics : JMD

    2023  Volume 25, Issue 5, Page(s) 263–273

    Abstract: Identification of somatic variants in cancer by high-throughput sequencing has become common clinical practice, largely because many of these variants may be predictive biomarkers for targeted therapies. However, there can be high sample quality control ( ...

    Abstract Identification of somatic variants in cancer by high-throughput sequencing has become common clinical practice, largely because many of these variants may be predictive biomarkers for targeted therapies. However, there can be high sample quality control (QC) failure rates for some tests that prevent the return of results. Stem-loop inhibition mediated amplification (SLIMamp) is a patented technology that has been incorporated into commercially available cancer next-generation sequencing testing kits. The claimed advantage is that these kits can interrogate challenging formalin-fixed, paraffin-embedded tissue samples with low tumor purity, poor-quality DNA, and/or low-input DNA, resulting in a high sample QC pass rate. The study aimed to substantiate that claim using Pillar Biosciences oncoReveal Solid Tumor Panel. Forty-eight samples that had failed one or more preanalytical QC sample parameters for whole-exome sequencing from the Australian Translational Genomics Centre's ISO15189-accredited diagnostic genomics laboratory were acquired. XING Genomic Services performed an exploratory data analysis to characterize the samples and then tested the samples in their ISO15189-accredited laboratory. Clinical reports could be generated for 37 (77%) samples, of which 29 (60%) contained clinically actionable or significant variants that would not otherwise have been identified. Eleven samples were deemed unreportable, and the sequencing data were likely dominated by artifacts. A novel postsequencing QC metric was developed that can discriminate between clinically reportable and unreportable samples.
    MeSH term(s) Humans ; Tissue Fixation ; Formaldehyde ; Australia ; Neoplasms/diagnosis ; Neoplasms/genetics ; DNA ; High-Throughput Nucleotide Sequencing/methods ; Biomarkers, Tumor/genetics ; Mutation ; Paraffin Embedding
    Chemical Substances Formaldehyde (1HG84L3525) ; DNA (9007-49-2) ; Biomarkers, Tumor
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2000060-1
    ISSN 1943-7811 ; 1525-1578
    ISSN (online) 1943-7811
    ISSN 1525-1578
    DOI 10.1016/j.jmoldx.2023.01.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Effect of Biologic Therapies on Airway Hyperresponsiveness and Allergic Response: A Systematic Literature Review.

    Spahn, Joseph D / Brightling, Christopher E / O'Byrne, Paul M / Simpson, Lisa J / Molfino, Nestor A / Ambrose, Christopher S / Martin, Neil / Hallstrand, Teal S

    Journal of asthma and allergy

    2023  Volume 16, Page(s) 755–774

    Abstract: Background: Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying ... ...

    Abstract Background: Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma.
    Methods: We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma.
    Results: Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified.
    Conclusion: Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.
    Language English
    Publishing date 2023-07-21
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2494877-9
    ISSN 1178-6965
    ISSN 1178-6965
    DOI 10.2147/JAA.S410592
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The Diagnostic Utility of Serum Metal Ion Markers for High-Grade Aseptic Lymphocyte-Dominated Vasculitis-Associated Lesions (ALVALs) in Revision Hip and Knee Arthroplasty: An International Multicenter Study.

    Sheridan, Gerard A / Neufeld, Michael E / Sidhu, Arsh / Kurmis, Andrew P / Kelly, Martin / O'Byrne, John M / Howard, Lisa C / Masri, Bassam A / Garbuz, Donald S

    The Journal of arthroplasty

    2023  Volume 39, Issue 1, Page(s) 206–210

    Abstract: Background: Aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) are typically described in the context of metal-on-metal (MoM) hip bearings. This study explores the diagnostic utility of preoperative serum cobalt and chromium ion levels ... ...

    Abstract Background: Aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) are typically described in the context of metal-on-metal (MoM) hip bearings. This study explores the diagnostic utility of preoperative serum cobalt and chromium ion levels in determining the histological grade of ALVAL in revision hip and knee arthroplasty.
    Methods: This was a multicenter retrospective review of 26 hips and 13 knees assessing the correlation between preoperative ion levels (mg/L (ppb)) and the histological grade of ALVAL from intraoperative specimens. The diagnostic ability of preoperative serum cobalt and chromium levels to determine high-grade ALVAL was assessed using a receiver operating characteristic (ROC) curve.
    Results: In the knee cohort, there was a higher serum cobalt level in high-grade ALVAL cases (10.2 mg/L (ppb) versus 3.1 mg/L (ppb)) (P = .0002). The Area Under the Curve (AUC) was 1.00 (95% confidence interval (CI) 1.00 to 1.00). There was a higher serum chromium level in high-grade ALVAL cases (12.25 mg/L (ppb) versus 7.77 mg/L (ppb)) (P = .0002). The AUC was 0.806 (95% CI 0.555 to 1.00). In the hip cohort, there was a higher serum cobalt level in high-grade ALVAL cases (333.5 mg/L (ppb) versus 119.9 mg/L (ppb)) (P = .0831). The AUC was 0.619 (95% CI 0.388 to 0.849). There was a higher serum chromium level in high-grade ALVAL cases (186.4 mg/L (ppb) versus 79.3 mg/L (ppb)) (P = .183). The AUC was 0.595 (95% CI 0.365 to 0.824).
    Conclusions: Histologically, high-grade ALVAL has significantly higher preoperative serum cobalt and chromium ion levels in revision TKA. Preoperative serum ion levels have excellent diagnostic utility in revision TKA. Cobalt levels in revision THA have a fair diagnostic ability and chromium levels had a poor diagnostic ability.
    MeSH term(s) Humans ; Arthroplasty, Replacement, Knee/adverse effects ; Arthroplasty, Replacement, Hip/adverse effects ; Hip Prosthesis/adverse effects ; Metals ; Cobalt ; Chromium ; Lymphocytes ; Biomarkers ; Vasculitis/diagnosis ; Vasculitis/pathology ; Prosthesis Design ; Metal-on-Metal Joint Prostheses/adverse effects ; Prosthesis Failure
    Chemical Substances Metals ; Cobalt (3G0H8C9362) ; Chromium (0R0008Q3JB) ; Biomarkers
    Language English
    Publishing date 2023-06-16
    Publishing country United States
    Document type Multicenter Study ; Journal Article
    ZDB-ID 632770-9
    ISSN 1532-8406 ; 0883-5403
    ISSN (online) 1532-8406
    ISSN 0883-5403
    DOI 10.1016/j.arth.2023.06.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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