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  1. Article ; Online: Response.

    Saleem, Naveed / Snow, Timothy Arthur Chandos / Arulkumaran, Nishkantha

    Chest

    2023  Volume 163, Issue 1, Page(s) e48

    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 1032552-9
    ISSN 1931-3543 ; 0012-3692
    ISSN (online) 1931-3543
    ISSN 0012-3692
    DOI 10.1016/j.chest.2022.09.039
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  2. Article: Immunophenotyping patients with sepsis and underlying haematological malignancy reveals defects in monocyte and lymphocyte function.

    Snow, Timothy Arthur Chandos / Serisier, Aimee / Brealey, David / Singer, Mervyn / Arulkumaran, Nishkantha

    Intensive care medicine experimental

    2024  Volume 12, Issue 1, Page(s) 3

    Language English
    Publishing date 2024-01-11
    Publishing country Germany
    Document type Letter
    ZDB-ID 2740385-3
    ISSN 2197-425X
    ISSN 2197-425X
    DOI 10.1186/s40635-023-00578-4
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  3. Article ; Online: High-flow nasal oxygen versus conventional oxygen therapy and noninvasive ventilation in COVID-19 respiratory failure: a systematic review and network meta-analysis of randomised controlled trials.

    Pisciotta, Walter / Passannante, Alberto / Arina, Pietro / Alotaibi, Khalid / Ambler, Gareth / Arulkumaran, Nishkantha

    British journal of anaesthesia

    2024  Volume 132, Issue 5, Page(s) 936–944

    Abstract: Background: Noninvasive methods of respiratory support, including noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), and high-flow nasal oxygen (HFNO), are potential strategies to prevent progression to requirement for invasive ... ...

    Abstract Background: Noninvasive methods of respiratory support, including noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), and high-flow nasal oxygen (HFNO), are potential strategies to prevent progression to requirement for invasive mechanical ventilation in acute hypoxaemic respiratory failure. The COVID-19 pandemic provided an opportunity to understand the utility of noninvasive respiratory support among a homogeneous cohort of patients with contemporary management of acute respiratory distress syndrome. We performed a network meta-analysis of studies evaluating the efficacy of NIV (including CPAP) and HFNO, compared with conventional oxygen therapy (COT), in patients with COVID-19.
    Methods: PubMed, Embase, and the Cochrane library were searched in May 2023. Standard random-effects meta-analysis was used first to estimate all direct pairwise associations and the results from all studies were combined using frequentist network meta-analysis. Primary outcome was treatment failure, defined as discontinuation of HFNO, NIV, or COT despite progressive disease. Secondary outcome was mortality.
    Results: We included data from eight RCTs with 2302 patients, (756 [33%] assigned to COT, 371 [16%] to NIV, and 1175 [51%] to HFNO). The odds of treatment failure were similar for NIV (P=0.33) and HFNO (P=0.25), and both were similar to that for COT (reference category). The odds of mortality were similar for all three treatments (odds ratio for NIV vs COT: 1.06 [0.46-2.44] and HFNO vs COT: 0.97 [0.57-1.65]).
    Conclusions: Noninvasive ventilation, high-flow nasal oxygen, and conventional oxygen therapy are comparable with regards to treatment failure and mortality in COVID-19-associated acute respiratory failure.
    Prospero registration: CRD42023426495.
    MeSH term(s) Humans ; Oxygen/therapeutic use ; Noninvasive Ventilation/methods ; COVID-19/therapy ; COVID-19/etiology ; Pandemics ; Network Meta-Analysis ; Respiratory Insufficiency/therapy ; Respiratory Insufficiency/etiology ; Oxygen Inhalation Therapy/methods ; Respiratory Distress Syndrome/therapy ; Randomized Controlled Trials as Topic
    Chemical Substances Oxygen (S88TT14065)
    Language English
    Publishing date 2024-02-02
    Publishing country England
    Document type Meta-Analysis ; Systematic Review ; Journal Article ; Review
    ZDB-ID 80074-0
    ISSN 1471-6771 ; 0007-0912
    ISSN (online) 1471-6771
    ISSN 0007-0912
    DOI 10.1016/j.bja.2023.12.022
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  4. Article ; Online: Creating complex protocells and prototissues using simple DNA building blocks.

    Arulkumaran, Nishkantha / Singer, Mervyn / Howorka, Stefan / Burns, Jonathan R

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 1314

    Abstract: Building synthetic protocells and prototissues hinges on the formation of biomimetic skeletal frameworks. Recreating the complexity of cytoskeletal and exoskeletal fibers, with their widely varying dimensions, cellular locations and functions, represents ...

    Abstract Building synthetic protocells and prototissues hinges on the formation of biomimetic skeletal frameworks. Recreating the complexity of cytoskeletal and exoskeletal fibers, with their widely varying dimensions, cellular locations and functions, represents a major material hurdle and intellectual challenge which is compounded by the additional demand of using simple building blocks to ease fabrication and control. Here we harness simplicity to create complexity by assembling structural frameworks from subunits that can support membrane-based protocells and prototissues. We show that five oligonucleotides can anneal into nanotubes or fibers whose tunable thicknesses and lengths spans four orders of magnitude. We demonstrate that the assemblies' location inside protocells is controllable to enhance their mechanical, functional and osmolar stability. Furthermore, the macrostructures can coat the outside of protocells to mimic exoskeletons and support the formation of millimeter-scale prototissues. Our strategy could be exploited in the bottom-up design of synthetic cells and tissues, to the generation of smart material devices in medicine.
    MeSH term(s) Artificial Cells/chemistry ; DNA/chemistry ; Nanotubes
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2023-03-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-36875-5
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  5. Article ; Online: Effect of dexamethasone dose on outcomes in acute COVID-19 disease: A systematic review and meta-analysis.

    Snow, Timothy Arthur Chandos / Arulkumaran, Nishkantha / Singer, Mervyn / Choi, Sang-Ho

    The Journal of infection

    2023  Volume 87, Issue 6, Page(s) 490–497

    Abstract: Introduction: The impact of different doses of dexamethasone on outcomes from acute COVID-19 pneumonia is unknown.: Methods: We performed a systematic review and meta-analysis of randomised control trials comparing different doses of dexamethasone in ...

    Abstract Introduction: The impact of different doses of dexamethasone on outcomes from acute COVID-19 pneumonia is unknown.
    Methods: We performed a systematic review and meta-analysis of randomised control trials comparing different doses of dexamethasone in adult patients with COVID-19. High dose dexamethasone treatment was defined as 12-24 mg daily, whereas low-dose treatment was 6-8 mg daily. Primary outcome was 28-day mortality.
    Results: Eight trials including 3469 patients were identified, with 1775 patients receiving high dose dexamethasone. There was no difference in mortality between patients receiving high dose or low-dose dexamethasone (22.0% vs. 20.2%; odds ratio 1.20 [95% confidence interval 0.86-1.67]; p = 0.29; I
    Conclusions: The mortality of patients with acute COVID-19 receiving high-dose dexamethasone is similar to patients receiving low-dose dexamethasone, although high-dose dexamethasone is associated with an increased risk of hyperglycaemia.
    MeSH term(s) Adult ; Humans ; COVID-19 ; Dexamethasone/adverse effects ; COVID-19 Drug Treatment ; Hyperglycemia/drug therapy
    Chemical Substances Dexamethasone (7S5I7G3JQL)
    Language English
    Publishing date 2023-09-25
    Publishing country England
    Document type Meta-Analysis ; Systematic Review ; Journal Article
    ZDB-ID 424417-5
    ISSN 1532-2742 ; 0163-4453
    ISSN (online) 1532-2742
    ISSN 0163-4453
    DOI 10.1016/j.jinf.2023.09.008
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  6. Article ; Online: Clarithromycin as an immunomodulator in sepsis: still a (IN)CLASS act.

    Snow, Timothy Arthur Chandos / Cesar, Antonio / Singer, Mervyn / Arulkumaran, Nishkantha

    Critical care (London, England)

    2022  Volume 26, Issue 1, Page(s) 238

    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Clarithromycin/pharmacology ; Clarithromycin/therapeutic use ; Humans ; Immunologic Factors/pharmacology ; Immunologic Factors/therapeutic use ; Multiple Organ Failure/drug therapy ; Sepsis/drug therapy
    Chemical Substances Anti-Bacterial Agents ; Immunologic Factors ; Clarithromycin (H1250JIK0A)
    Language English
    Publishing date 2022-08-05
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2041406-7
    ISSN 1466-609X ; 1364-8535
    ISSN (online) 1466-609X
    ISSN 1364-8535
    DOI 10.1186/s13054-022-04104-y
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  7. Article ; Online: "L'histoire se répète", one size does not fit all. Author's reply.

    Snow, Timothy Arthur Chandos / Saleem, Naveed / Singer, Mervyn / Arulkumaran, Nishkantha

    Intensive care medicine

    2021  Volume 47, Issue 10, Page(s) 1171–1172

    Language English
    Publishing date 2021-08-06
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 80387-x
    ISSN 1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
    ISSN (online) 1432-1238
    ISSN 0340-0964 ; 0342-4642 ; 0935-1701
    DOI 10.1007/s00134-021-06497-w
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    Zs.A 1089: Show issues Location:
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  8. Article ; Online: Biological sex is associated with heterogeneous responses to IL-6 receptor inhibitor treatment in COVID-19-A retrospective cohort study.

    Stein, Dan F / Foley, Conor / Byott, Matt / Nastouli, Eleni / Ambler, Gareth / Arulkumaran, Nishkantha

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 13504

    Abstract: COVID-19 is associated with higher inflammatory markers, illness severity and mortality in males compared to females. Differences in immune responses to COVID-19 may underpin sex- specific outcome differences. We hypothesised that anti-IL-6 receptor ... ...

    Abstract COVID-19 is associated with higher inflammatory markers, illness severity and mortality in males compared to females. Differences in immune responses to COVID-19 may underpin sex- specific outcome differences. We hypothesised that anti-IL-6 receptor monoclonal antibodies are associated with heterogenous treatment effects between male and female patients. We conducted a retrospective cohort study assessing the interaction between biological sex and anti-IL-6 receptor antibody treatment with respect to hospital mortality or progression of respiratory failure. We used a Cox proportional hazards regression model to adjust for age, ethnicity, steroid use, baseline C-reactive protein, and COVID-19 variant. We included 1274 patients, of which 58% were male and 15% received anti-IL-6 receptor antibodies. There was a significant interaction between sex and anti-IL-6 receptor antibody use on progression to respiratory failure or death (p = 0.05). For patients who did not receive anti-IL-6 receptor antibodies, the risk of death was slightly higher in males (HR = 1.13 (0.72-1.79)), whereas in patients who did receive anti-IL-6 receptor antibodies, the risk was lower in males (HR = 0.65 (0.32-1.33)). There was a heterogenous treatment effect with anti-IL-6 receptor antibodies between males and females; with anti-IL-6 receptor antibody use having a greater benefit in preventing progression to respiratory failure or death in males (p = 0.05).
    MeSH term(s) Humans ; Female ; Male ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Antibodies, Monoclonal/therapeutic use ; Receptors, Interleukin-6
    Chemical Substances Antibodies, Monoclonal ; Receptors, Interleukin-6
    Language English
    Publishing date 2023-08-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-40744-y
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  9. Article ; Online: Respiratory fluoroquinolone monotherapy vs. β-lactam plus macrolide combination therapy for hospitalized adults with community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials.

    Choi, Sang-Ho / Cesar, Antoni / Snow, Timothy Arthur Chandos / Saleem, Naveed / Arulkumaran, Nishkantha / Singer, Mervyn

    International journal of antimicrobial agents

    2023  Volume 62, Issue 3, Page(s) 106905

    Abstract: Introduction: Guidelines recommend respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy as first-line options for hospitalized adults with mild-to-moderate community-acquired pneumonia (CAP). Efficacy of these regimens ... ...

    Abstract Introduction: Guidelines recommend respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy as first-line options for hospitalized adults with mild-to-moderate community-acquired pneumonia (CAP). Efficacy of these regimens has not been adequately evaluated.
    Methods: A systematic review of randomized controlled trials (RCTs) comparing respiratory fluoroquinolone monotherapy and β-lactam plus macrolide combination therapy in hospitalised adults with CAP was performed. A meta-analysis was performed using a random effects model. The primary outcome was clinical cure rate. Quality of evidence (QoE) was evaluated using GRADE methodology.
    Results: A total of 4140 participants in 18 RCTs were included. Levofloxacin (11 trials) or moxifloxacin (6 trials) were the predominant respiratory fluoroquinolones evaluated, and the β-lactam plus macrolide group used ceftriaxone plus a macrolide (10 trials), cefuroxime plus azithromycin (5 trials), and amoxicillin/clavulanate plus a macrolide (2 trials). Patients receiving respiratory fluoroquinolone monotherapy had a significantly higher clinical cure rate (86.5% vs. 81.5%; odds ratio [OR] 1.47; 95% confidence interval [95% CI: 1.17-1.83]; P = 0.0008; I
    Conclusion: Respiratory fluoroquinolone monotherapy demonstrated an advantage in clinical cure and microbiological eradication; however, it did not impact mortality.
    MeSH term(s) Adult ; Humans ; beta-Lactams/therapeutic use ; Fluoroquinolones/therapeutic use ; Macrolides/therapeutic use ; Pneumonia, Bacterial/drug therapy ; Drug Therapy, Combination ; Randomized Controlled Trials as Topic ; Anti-Bacterial Agents/therapeutic use ; Community-Acquired Infections/drug therapy
    Chemical Substances beta-Lactams ; Fluoroquinolones ; Macrolides ; Anti-Bacterial Agents
    Language English
    Publishing date 2023-06-28
    Publishing country Netherlands
    Document type Meta-Analysis ; Systematic Review ; Journal Article ; Review
    ZDB-ID 1093977-5
    ISSN 1872-7913 ; 0924-8579
    ISSN (online) 1872-7913
    ISSN 0924-8579
    DOI 10.1016/j.ijantimicag.2023.106905
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    Zs.A 3368: Show issues Location:
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  10. Article ; Online: The utility of CRP with the use of dexamethasone and Tocilizumab in critically ill patients with COVID-19.

    Zacharias, Harry / Mungara, Ritwik / Wilson, Andrew Peter / Singer, Mervyn / Arulkumaran, Nishkantha

    Journal of critical care

    2022  Volume 70, Page(s) 154053

    MeSH term(s) Antibodies, Monoclonal, Humanized ; Critical Illness ; Dexamethasone/therapeutic use ; Humans ; COVID-19 Drug Treatment
    Chemical Substances Antibodies, Monoclonal, Humanized ; Dexamethasone (7S5I7G3JQL) ; tocilizumab (I031V2H011)
    Language English
    Publishing date 2022-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632818-0
    ISSN 1557-8615 ; 0883-9441
    ISSN (online) 1557-8615
    ISSN 0883-9441
    DOI 10.1016/j.jcrc.2022.154053
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