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1.
Proc Natl Acad Sci U S A ; 120(3): e2216458120, 2023 01 17.
Article in English | MEDLINE | ID: covidwho-2243078

ABSTRACT

The lack of techniques for noninvasive imaging of inflammation has challenged precision medicine management of acute respiratory distress syndrome (ARDS). Here, we determined the potential of positron emission tomography (PET) of chemokine-like receptor-1 (CMKLR1) to monitor lung inflammation in a murine model of lipopolysaccharide-induced injury. Lung uptake of a CMKLR1-targeting radiotracer, [64Cu]NODAGA-CG34, was significantly increased in lipopolysaccharide-induced injury, correlated with the expression of multiple inflammatory markers, and reduced by dexamethasone treatment. Monocyte-derived macrophages, followed by interstitial macrophages and monocytes were the major CMKLR1-expressing leukocytes contributing to the increased tracer uptake throughout the first week of lipopolysaccharide-induced injury. The clinical relevance of CMKLR1 as a biomarker of lung inflammation in ARDS was confirmed using single-nuclei RNA-sequencing datasets which showed significant increases in CMKLR1 expression among transcriptionally distinct subsets of lung monocytes and macrophages in COVID-19 patients vs. controls. CMKLR1-targeted PET is a promising strategy to monitor the dynamics of lung inflammation and response to anti-inflammatory treatment in ARDS.


Subject(s)
Acute Lung Injury , COVID-19 , Respiratory Distress Syndrome , Humans , Mice , Animals , Lipopolysaccharides/toxicity , Acute Lung Injury/chemically induced , Acute Lung Injury/diagnostic imaging , Acute Lung Injury/metabolism , Lung/diagnostic imaging , Lung/metabolism , Chemokines/metabolism , Respiratory Distress Syndrome/diagnostic imaging , Molecular Imaging , Receptors, Chemokine
2.
European Journal of Surgical Oncology ; 48(5):e214, 2022.
Article in English | EMBASE | ID: covidwho-1859513

ABSTRACT

Introduction: Breast Incidentalomas occur as an unexpected abnormality demonstrated on imaging performed for unrelated symptoms. Pre-COVID19 pandemic management involved urgent referrals for initial breast team evaluation. Clinical encounters occurred prior to the Multi-Disciplinary Team meeting (MDT). COVID-19 restrictions necessitated streamlining and optimising service provision with clinically appropriate encounters. Our aim was to re-audit (SU-CA-21-22-068) findings and management of breast incidentalomas during the pandemic. Methods: Pre-pandemic analysis of practice (November 2019 - January 2020) led us to the intervention of all referrals straight to MDT without an unnecessary prior clinical encounter, with secondary planned investigations and clinical assessment thereafter. Completion of audit loop and analysis included referral information, MDT outcome, imaging, and clinical correspondence with descriptive analysis. Results: Post-intervention 61 patients were referred to the MDT over an 18-month period (February 2020 - October 2021). 90% of patients were referred following CT scans. Median age 71 (range 32-93), 38% of patients had no additional breast imaging and 74% of patients did not require a tissue biopsy. 15% (n=9) were diagnosed with new breast cancer, 36% were new benign, with 34% already known lesions. 16% of patients required no further intervention. Conclusion: 15% of incidentalomas were diagnosed as malignancies, compared to local 3-4% from one stop clinics. Prompt referral to MDT accelerates triple assessment and tissue diagnosis. Streamlining of patient care optimised appropriate clinical encounters for vulnerable patients. Early senior radiological assessment at the MDT of incidentalomas during COVID-19 provided confirmation of benign features and therefore no further intervention and reassurance for 16% of patients.

3.
Journal of Clinical Oncology ; 39(15 SUPPL), 2021.
Article in English | EMBASE | ID: covidwho-1339354

ABSTRACT

Background: The ASCO Registry was created to analyze the impact of COVID-19 (COVID) on treatment (Tx) and outcomes of patients (pts) with cancer. Methods: The Registry includes pts with 1) a confirmed COVID diagnosis (Dx) and 2) clinically evident cancer receiving Tx/supportive care or resected cancer on adjuvant Tx <12 mos since surgery. Practices report data on cancer Dx and Tx at COVID Dx, COVID symptoms, comorbidities, cancer/COVID Tx, and survival. Kaplan-Meier estimation provided 30- and 90- day mortality rate estimates for pts with COVID Dx before or since 6/1/20 within pt subgroups with 95% confidence intervals (CI). Data submission cutoff for all practices was 10/24/20, except one that was 11/16/20. Results: This analysis reports on 453 pts with COVID Dx 3/5/20 to 10/22/20 who were on anticancer drug Tx for regional (9%) or metastatic (53%) solid tumors or hematologic cancers (38%) at COVID Dx. 38 practices entered data: health system-owned 51% of pts, privately-owned 25%, academic 24%. 53% of pts have ≥30 days followup or died ≤30 days from COVID Dx. Median age is 64 years;53% of pts are female;28% of pts are asymptomatic at COVID Dx. Multiple myeloma was most frequent cancer (17%). Allcause mortality rates (30 and 90 days) increased with pts' age at COVID Dx [Table]. No mortality difference was seen based on sex, race, or comorbidities (hypertension, diabetes, pulmonary disease). Pts with COVID Dx before June 1 had worse survival than pts diagnosed on/after June 1. Pts with B-cell malignancies had higher mortality rates than pts with solid tumors. Conclusions: Severity of COVID illness and mortality were greater for patients with COVID Dx pre-June 1 than on/after June 1. Differences on/after June 1 may be attributed to improvements in COVID management, higher COVID testing rates, and more asymptomatic pts diagnosed. Variations in COVID-19 pt populations over time due to these changes should be considered when analyzing and interpreting pandemic data. Cancer pts with ed age and B-cell cancers are at greatest risk of death but mortality rates for all groups advanced age and B-cell cancers are at greatestrisk of death but mortality rates for all groups(except those admitted to ICU) improved after6/1/2020.

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