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The Lancet. Microbe May 2024Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of...
Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.
BACKGROUND
Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes.
METHODS
In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery.
FINDINGS
The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors.
INTERPRETATION
Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment.
FUNDING
US National Institutes of Health.
PubMed: 38815595
DOI: 10.1016/S2666-5247(24)00015-6 -
PLoS Biology May 2024Glioblastoma, the most aggressive and prevalent form of primary brain tumor, is characterized by rapid growth, diffuse infiltration, and resistance to therapies.... (Review)
Review
Glioblastoma, the most aggressive and prevalent form of primary brain tumor, is characterized by rapid growth, diffuse infiltration, and resistance to therapies. Intrinsic heterogeneity and cellular plasticity contribute to its rapid progression under therapy; therefore, there is a need to fully understand these tumors at a single-cell level. Over the past decade, single-cell transcriptomics has enabled the molecular characterization of individual cells within glioblastomas, providing previously unattainable insights into the genetic and molecular features that drive tumorigenesis, disease progression, and therapy resistance. However, despite advances in single-cell technologies, challenges such as high costs, complex data analysis and interpretation, and difficulties in translating findings into clinical practice persist. As single-cell technologies are developed further, more insights into the cellular and molecular heterogeneity of glioblastomas are expected, which will help guide the development of personalized and effective therapies, thereby improving prognosis and quality of life for patients.
Topics: Humans; Glioblastoma; Single-Cell Analysis; Brain Neoplasms; Transcriptome; Animals
PubMed: 38814900
DOI: 10.1371/journal.pbio.3002640 -
Scientific Reports May 2024Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy...
Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both p < 0.001), with changes most evident after 30 weeks gestation. A significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, p = 0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.
Topics: Humans; Female; Pregnancy; Heart Defects, Congenital; Adult; Placenta; Placentation; Magnetic Resonance Imaging; Case-Control Studies
PubMed: 38811636
DOI: 10.1038/s41598-024-63087-8 -
Pediatric Quality & Safety 2024Screening for early detection of microalbuminuria signaling kidney disease should begin as early as the time of diagnosis of youth-onset type 2 diabetes. This quality...
BACKGROUND
Screening for early detection of microalbuminuria signaling kidney disease should begin as early as the time of diagnosis of youth-onset type 2 diabetes. This quality improvement initiative aimed to standardize urine nephropathy screening in pediatric patients with type 2 diabetes at a tertiary academic medical center and increase a baseline screening rate of 56%-75% over 6 months (September 2022-February 2023) and sustain that increase for 6 months (March through August 2023).
METHODS
A multi-disciplinary team used quality improvement methods and iterative Plan-Do-Study-Act cycles. Targeted interventions included previsit planning workflow, education, and a new-onset triage protocol. The team collected data at baseline and prospectively by reviewing electronic medical records. The primary outcome measure was pediatric type 2 diabetes clinic visits in diabetes clinic with urine nephropathy screening before or on the visit date.
RESULTS
A total of 121 youth were scheduled for T2D clinic visits between September 2021 and August 2023. The mean age was 14.5 years, and 60% were women, 40% were non-Hispanic Black, 28% were Hispanic/Latino, and 15% reported Spanish as their preferred language. Following the interventions of this project, urine nephropathy screening increased from 56% to 75%, and this change was sustained for 6 months.
CONCLUSIONS
Interventions focused on efficient recognition of the population needing screening, coordinated internal processes around screening, a shared understanding between all stakeholders, and practical support in the healthcare system increased urine nephropathy screening with sustained improvement.
PubMed: 38807582
DOI: 10.1097/pq9.0000000000000734 -
Infectious Disease Reports May 2024Necrotizing fasciitis (NF) is a critical disease with high morbidity and mortality rates that poses significant challenges in diagnosis and treatment. Prognostic factors...
INTRODUCTION
Necrotizing fasciitis (NF) is a critical disease with high morbidity and mortality rates that poses significant challenges in diagnosis and treatment. Prognostic factors for the clinical course of NF remain unclear and are currently under research. This study aims to identify such factors in a large cohort of patients which represents a major comprehensive investigation of prognostic factors for NF.
METHODS
Retrospective analysis was conducted on necrotizing fasciitis cases from 2003 to 2023 at two German hospitals. Data included demographics, comorbidities, laboratory findings, infection site, causative microorganisms and outcomes. Statistical analysis involved -tests, chi-square tests, and ROC analysis.
RESULTS
A total of 209 patients were included, with a mortality rate of 18%. Patients were categorized into survivors ( = 171) and non-survivors (n = 38). Non-survivors were significantly older (68.9 ± 13.9 years vs. 55.9 ± 14.3 years; < 0.01) and exhibited a higher prevalence of peripheral vascular diseases, cancer, and heart, liver, or renal insufficiency. Laboratory findings and scoring results also varied significantly between the two groups. The ROC curve analysis identified age as a predictor of mortality, with an optimal cut-off value of 68.5 years (sensitivity: 60.5%, specificity: 81.9%). Higher age was associated with increased mortality risk.
CONCLUSIONS
The patient's age stands out as the primary predictive element for mortality in necrotizing fasciitis. Additionally, we advocate for employing the Laboratory and Anamnestic Risk Indicator for Necrotizing Fasciitis (LARINF-score), which holds substantial prognostic significance and is straightforward to calculate. Considering our findings, crafting a clinical algorithm or scoring mechanism to forecast mortality in NF would be a promising target for future research.
PubMed: 38804445
DOI: 10.3390/idr16030035 -
Heliyon May 2024Natural language processing (NLP) can generate diagnoses codes from imaging reports. Meanwhile, the International Classification of Diseases (ICD-10) codes are the...
OBJECTIVE
Natural language processing (NLP) can generate diagnoses codes from imaging reports. Meanwhile, the International Classification of Diseases (ICD-10) codes are the United States' standard for billing/coding, which enable tracking disease burden and outcomes. This cross-sectional study aimed to test feasibility of an NLP algorithm's performance and comparison to radiologists' and physicians' manual coding.
METHODS
Three neuroradiologists and one non-radiologist physician reviewers manually coded a randomly-selected pool of 200 craniospinal CT and MRI reports from a pool of >10,000. The NLP algorithm () subdivided each report's Impression into "phrases", with multiple ICD-10 matches for each phrase. Only viewing the Impression, the physician reviewers selected the single best ICD-10 code for each phrase. Codes selected by the physicians and algorithm were compared for agreement.
RESULTS
The algorithm extracted the reports' Impressions into 645 phrases, each having ranked ICD-10 matches. Regarding the reviewers' selected codes, pairwise agreement was unreliable ( = ). Using unanimous reviewer agreement as "ground truth", the algorithm's sensitivity/specificity/F2 for top 5 codes was , and for the single best code was The engine tabulated "pertinent negatives" as negative codes for stated findings (e.g. "no intracranial hemorrhage"). The engine's matching was more specific for shorter than full-length ICD-10 codes ( = ).
CONCLUSIONS
Manual coding by physician reviewers has significant variability and is time-consuming, while the NLP algorithm's top 5 diagnosis codes are relatively accurate. This preliminary work demonstrates the feasibility and potential for generating codes with reliability and consistency. Future works may include correlating diagnosis codes with clinical encounter codes to evaluate imaging's impact on, and relevance to care.
PubMed: 38799748
DOI: 10.1016/j.heliyon.2024.e30106 -
Research Square May 2024Alzheimer's disease (AD) is a progressive form of dementia affecting almost 55 million people worldwide. It is characterized by the abnormal deposition of amyloid...
Alzheimer's disease (AD) is a progressive form of dementia affecting almost 55 million people worldwide. It is characterized by the abnormal deposition of amyloid plaques and neurofibrillary tangles within the brain, leading to a pathological cascade of neuron degeneration and death as well as memory loss and cognitive decline. Amyloid beta (Aβ) is an AD biomarker present in cerebrospinal fluid and blood serum and correlates with the presence of amyloid plaques and tau tangles in the brain. Measuring the levels of Aβ can help with early diagnosis of AD, which is key for studying novel AD drugs and delaying the symptoms of dementia. However, this goal is difficult to achieve due to the low levels of AD biomarkers in biofluids. Here we demonstrate for the first time the use of FLOWER (frequency locked optical whispering evanescent resonator) for quantifying the levels of post-mortem cerebrospinal fluid (CSF) Aβ42 in clinicopathologically classified control, mild cognitive impairment (MCI), and AD participants. FLOWER is capable of measuring CSF Aβ42 (area under curve, AUC = 0.92) with higher diagnostic performance than standard ELISA (AUC = 0.82) and was also able to distinguish between control and MCI samples. Our results demonstrate the capability of FLOWER for screening CSF samples for early diagnosis of Alzheimer's pathology.
PubMed: 38798660
DOI: 10.21203/rs.3.rs-4355995/v1 -
Journal of Movement Disorders May 2024
PubMed: 38797659
DOI: 10.14802/jmd.23230 -
European Journal of Obstetrics,... May 2024Maternal mortality data and review are important indicators of the effectiveness of maternity healthcare systems and an impetus for action. Recently, a rising incidence...
Maternal mortality data and review are important indicators of the effectiveness of maternity healthcare systems and an impetus for action. Recently, a rising incidence of maternal mortality in high income countries has been reported. Various publications have raised concern about data collection methods at country level, as this usually relies mainly on national vital statistics. It is therefore essential that the collected data are complete and accurate and conform to international definitions and disease classification. Accurate data and review can only be truly available when an Enhanced Obstetric Surveillance System is in place. EBCOG calls for action by national societies to work closely with their respective ministries of health to ensure that high quality surveillance systems are in place.
PubMed: 38797618
DOI: 10.1016/j.ejogrb.2024.05.022 -
Molecular Biology Reports May 2024Control of blackleg disease of canola caused by the fungus Leptosphaeria maculans relies on strategies such as the inhibition of growth with fungicides. However, other...
BACKGROUND
Control of blackleg disease of canola caused by the fungus Leptosphaeria maculans relies on strategies such as the inhibition of growth with fungicides. However, other chemicals are used during canola cultivation, including fertilizers and herbicides. There is widespread use of herbicides that target the acetolactate synthase (ALS) enzyme involved in branched chain amino acid synthesis and low levels of these amino acids within leaves of Brassica species. In L. maculans the ilv2 gene encodes ALS and thus ALS-inhibiting herbicides may inadvertently impact the fungus.
METHODS AND RESULTS
Here, the impact of a commercial herbicide targeting ALS and mutation of the homologous ilv2 gene in L. maculans was explored. Exposure to herbicide had limited impact on growth in vitro but reduced lesion sizes in plant disease experiments. Furthermore, the mutation of the ilv2 gene via CRISPR-Cas9 gene editing rendered the fungus non-pathogenic.
CONCLUSION
Herbicide applications can influence disease outcome, but likely to a minor extent.
Topics: Acetolactate Synthase; Plant Diseases; Herbicides; Amino Acids, Branched-Chain; Leptosphaeria; Mutation; Fungal Proteins; Gene Editing; Plant Leaves; CRISPR-Cas Systems; Brassica; Ascomycota
PubMed: 38796647
DOI: 10.1007/s11033-024-09620-4