Publications by authors named "Nishkantha Arulkumaran"

Antibiotics are the fundamental treatment for bacterial infections. However, they are associated with numerous side effects. Their adverse effects on the immune system are increasingly recognised, with several mechanisms identified.

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Article Synopsis
  • COVID-19 is linked to severe inflammation and blood clotting issues, leading to high mortality, prompting a study on the effects of plasma exchange (PEX) in critically ill patients.
  • A phase II randomized control trial was conducted with 22 patients, where 11 received PEX, resulting in reduced pro-thrombotic markers but no significant changes in inflammatory markers or overall respiratory failure.
  • Despite effectively lowering specific thrombotic markers, PEX did not improve respiratory function, reduce inflammatory responses, or decrease mortality rates within 28 days.
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Background: Post-operative infections are a common cause of morbidity following major surgery. Little is understood about how major surgery perturbs immune function leading to heightened risk of subsequent infection. Through analysis of paired blood samples obtained immediately before and 24 h following surgery, we evaluated changes in circulating immune cell phenotype and function across the first 24 h, to identify early immune changes associated with subsequent infection.

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Article Synopsis
  • - The study evaluates the effectiveness of noninvasive respiratory support methods (NIV, CPAP, and HFNO) compared to conventional oxygen therapy (COT) for patients with COVID-19 experiencing acute hypoxaemic respiratory failure.
  • - Researchers conducted a network meta-analysis using data from eight randomized controlled trials involving 2302 patients to assess treatment failure and mortality rates associated with these therapies.
  • - Findings indicate that NIV, HFNO, and COT show similar outcomes in terms of treatment failure and mortality, suggesting no significant advantage of one method over the others for managing COVID-19 related respiratory failure.
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Background: Lower fitness is a predictor of adverse outcomes after radical cystectomy. Lockdown measures during the COVID-19 pandemic affected daily physical activity. We hypothesised that lockdown during the pandemic was associated with a reduction in preoperative aerobic fitness and an increase in postoperative complications in patients undergoing radical cystectomy.

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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.

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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.

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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.

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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.

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Unlabelled: To ascertain the association between cholesterol and triglyceride levels on ICU admission and mortality in patients with sepsis.

Data Sources: Systematic review and meta-analysis of published studies on PubMed and Embase.

Study Selection: All observational studies reporting ICU admission cholesterol and triglyceride levels in critically ill patients with sepsis were included.

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Mitochondrial dysfunction and immune cell dysfunction are commonplace in sepsis and are associated with increased mortality risk. The short chain fatty acid, butyrate, is known to have anti-inflammatory effects and promote mitochondrial biogenesis. We therefore explored the immunometabolic effects of butyrate in an animal model of sepsis.

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Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality. Corticosteroids may be a beneficial adjunct in the treatment of bacterial pneumonia.

Research Question: Is there any benefit of corticosteroid therapy in the management of bacterial CAP among patients requiring hospitalization?

Study Design And Methods: PubMed, Cochrane Library, and Embase were searched to identify randomized controlled trials assessing the use of systemic corticosteroids compared with standard care in the management of CAP.

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Background: Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of doxycycline in adult patients with mild-to-moderate CAP.

Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of doxycycline versus comparator to assess the clinical efficacy.

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Introduction: Macrolide antibiotics have immunomodulatory properties which may be beneficial in viral infections. However, the precise effects of macrolides on T cell responses to COVID, differences between different macrolides, and synergistic effects with other antibiotics have not been explored.

Methods: We investigated the effect of antibiotics (amoxicillin, azithromycin, clarithromycin, and combined amoxicillin with clarithromycin) on lymphocyte intracellular cytokine levels and monocyte phagocytosis in healthy volunteer PBMCs stimulated ex vivo with SARS-CoV-2 S1+2 spike protein.

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Background: Bactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia.

Objectives: We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials (RCTs) of bactericidal versus bacteriostatic antibiotics to ascertain clinical superiority. Clinical cure rate was the primary outcome.

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Purpose: The integration of palliative care into intensive care units (ICUs) is advocated to mitigate physical and psychological burdens for patients and their families, and to improve end-of-life care. The most efficacious palliative care interventions, the optimal model of their delivery and the most appropriate outcome measures in ICU are not clear.

Methods: We conducted a systematic review of randomised clinical trials and observational studies to evaluate the number and types of palliative care interventions implemented within the ICU setting, to assess their impact on ICU practice and to evaluate differences in palliative care approaches across different countries.

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression.

Methods: We performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality.

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Objectives: Recent studies have demonstrated mortality benefits from corticosteroid use in COVID-19 patients requiring respiratory support. However, clinical practice may warrant the use of corticosteroids outside the context of a clinical trial. Such data are rarely, if ever, reported.

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