Publications by authors named "Clark D Russell"

Background: While inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation.

Methods: We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19.

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Background: Staphylococcus aureus bacteremia (SAB) is a clinically heterogeneous disease. The ability to identify subgroups of patients with shared traits (subphenotypes) is an unmet need to allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically relevant subphenotypes can be reproducibly identified among patients with SAB.

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  • The study tested whether metastatic infection from Staphylococcus aureus bacteremia (SAB) leads to different outcomes compared to death from the same infection.
  • It analyzed data from 464 adults with SAB, finding that mortality was associated with older age and multiple health issues, while metastatic infections were tied to community-acquired cases and persistent symptoms.
  • The findings suggest a need to differentiate between these clinical endpoints in future research to tailor interventions effectively.
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Objective: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies.

Design/patients: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study).

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We characterized the epidemiology, host-pathogen characteristics, and outcomes of severe adult pulmonary Streptococcus pyogenes infections that coincided with a high community caseload in central Scotland, UK. The pulmonary infections had high illness and death rates and were associated with socioeconomic deprivation, influenza A co-infection, and the M1 lineage of S. pyogenes.

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Pressure-ulcer related pelvic osteomyelitis is managed with little high-quality evidence. We undertook an international survey of orthopedic surgical management, covering diagnostic parameters, multidisciplinary input, and surgical approaches (indications, timing, wound closure, and adjunctive therapies). This identified areas of consensus and disagreement, representing a starting point for future discussion and research.

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  • Researchers analyzed genetic data from 24,202 critically ill COVID-19 cases, showing that host genetics can help identify effective immunomodulatory therapies.
  • They conducted a meta-analysis that revealed 49 significant genetic associations, including 16 new ones not previously reported.
  • Key findings include potential drug targets related to inflammation, immune response, and viral entry, which could lead to new treatment strategies for severe COVID-19 cases.
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The influence of comorbidities on COVID-19 outcomes has been recognized since the earliest days of the pandemic. But establishing causality and determining underlying mechanisms and clinical implications has been challenging-owing to the multitude of confounding factors and patient variability. Several distinct pathological mechanisms, not active in every patient, determine health outcomes in the three different phases of COVID-19-from the initial viral replication phase to inflammatory lung injury and post-acute sequelae.

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Background: An increase in infections with nontuberculous mycobacteria (NTM) has been noted globally, and their incidence has overtaken that of complex (MTBc) in many countries. Using data from a national reference laboratory, we aimed to determine if this trend could be observed in Scotland.

Methods: We undertook a retrospective review of all NTM isolates received by the Scottish Mycobacteria Reference Laboratory (SMRL) over 9 years from 2011 to 2019 inclusive.

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Background: Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic.

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  • Diagnosis of internal external ventricular drain (EVD)-related infections (iERI) is challenging, often starting treatment based on clinical suspicion due to limited guidance on managing confirmed vs. suspected cases.
  • A study in the UK analyzed data from 21 neurosurgical units, revealing that 9.3% of EVD insertions were suspected to have infections, primarily caused by Staphylococci, but no significant differences were found in clinical signs between confirmed and suspected infections.
  • Findings suggest that suspected iERI might indicate sterile inflammation rather than true infections, highlighting the need for better diagnostic tools and biomarkers for effective treatment.
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  • This study focuses on methods for combining gene lists from various biomedical research to enhance the reliability of findings in biological processes or diseases.
  • Researchers evaluated different ranking aggregation methods using both simulated datasets and real genomic data to determine their performance under various conditions, such as data quality and the presence of unranked lists.
  • The findings are summarized in a flowchart and an automated implementation tool is provided for selecting the best aggregation method based on data characteristics, accessible through a GitHub repository.
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  • SARS-CoV-2 has led to over 550 million infections and around 6.4 million deaths by July 2022, causing significant global health challenges.
  • The virus continues to evolve, reducing the effectiveness of current vaccines and treatments, particularly against the Omicron BA.4 and BA.5 variants.
  • To combat these ongoing issues, it is crucial to deepen our understanding of how the virus causes disease and to develop more specific treatment options.
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The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide.

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We systematically evaluated randomized-controlled trials (RCTs) for Staphylococcus aureus bacteremia (SAB). There was intertrial heterogeneity in cohort characteristics, including bacteremia source, complicated SAB, and comorbidities. Reporting of cohort characteristics was itself variable, including bacteremia source and illness severity.

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Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.

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COVID-19 is clinically characterised by fever, cough, and dyspnoea. Symptoms affecting other organ systems have been reported. However, it is the clinical associations of different patterns of symptoms which influence diagnostic and therapeutic decision-making.

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Background: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.

Methods: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen.

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  • Critical COVID-19 is linked to immune system damage in the lungs, showing that genetics play a key role in severe cases requiring hospitalization.
  • The GenOMICC study analyzes the genomes of 7,491 critically ill patients against 48,400 controls, uncovering 23 genetic variants that increase the risk for severe COVID-19, including new associations related to immune response and blood type.
  • The findings suggest that both viral replication and heightened lung inflammation contribute to critically ill cases, highlighting potential genetic targets for new treatments.
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