•Long COVID symptoms after Wild-type infection can persist over 18 months.•Primary or secondary Omicron infection did not increase long COVID risk.•COVID-19 vaccination before Omicron infection was ...not associated with long COVID.•A potential protective effect of physical/social activities should be further studied.
The long-term sequelae of coronavirus disease 2019 (COVID-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with COVID-19 ...and associated risk factors.
This is a prospective cohort study of children (≤18 years old) admitted to hospital with confirmed COVID-19. Children admitted between 2 April 2020 and 26 August 2020 were included. Telephone interviews used the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 Health and Wellbeing Follow-up Survey for Children. Persistent symptoms (>5 months) were further categorised by system(s) involved.
518 out of 853 (61%) eligible children were available for the follow-up assessment and included in the study. Median (interquartile range (IQR)) age was 10.4 (3-15.2) years and 270 (52.1%) were girls. Median (IQR) follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms, among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age "6-11 years" (OR 2.74, 95% CI 1.37-5.75) and "12-18 years" (OR 2.68, 95% CI 1.41-5.4), and a history of allergic diseases (OR 1.67, 95% CI 1.04-2.67).
A quarter of children experienced persistent symptoms months after hospitalisation with acute COVID-19 infection, with almost one in 10 experiencing multisystem involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.
Prior molecular profiling of hepatocellular carcinoma (HCC) has identified actionable findings that may have a role in guiding therapeutic decision-making and clinical trial enrollment. We ...implemented prospective next-generation sequencing (NGS) in the clinic to determine whether such analyses provide predictive and/or prognostic information for HCC patients treated with contemporary systemic therapies.
Matched tumor/normal DNA from patients with HCC (
= 127) were analyzed using a hybridization capture-based NGS assay designed to target 341 or more cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles.
WNT/β-catenin pathway (45%) and
(33%) alterations were frequent and represented mutually exclusive molecular subsets. In sorafenib-treated patients (
= 81), oncogenic PI3K-mTOR pathway alterations were associated with lower disease control rates (DCR, 8.3% vs. 40.2%), shorter median progression-free survival (PFS; 1.9 vs. 5.3 months), and shorter median overall survival (OS; 10.4 vs. 17.9 months). For patients treated with immune checkpoint inhibitors (
= 31), activating alteration WNT/β-catenin signaling were associated with lower DCR (0% vs. 53%), shorter median PFS (2.0 vs. 7.4 months), and shorter median OS (9.1 vs. 15.2 months). Twenty-four percent of patients harbored potentially actionable alterations including
(8.5%) inactivating/truncating mutations,
(6.3%) and
(1.5%) amplifications, and
missense mutations (<1%). Six percent of patients treated with systemic therapy were matched to targeted therapeutics.
Linking NGS to routine clinical care has the potential to identify those patients with HCC likely to benefit from standard systemic therapies and can be used in an investigational context to match patients to genome-directed targeted therapies.
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Targeted next-generation sequencing of DNA has become more widely used in the management of patients with lung adenocarcinoma; however, no clear mitogenic driver alteration is found in some cases. We ...evaluated the incremental benefit of targeted RNA sequencing (RNAseq) in the identification of gene fusions and
exon 14 (
ex14) alterations in DNA sequencing (DNAseq) driver-negative lung cancers.
Lung cancers driver negative by MSK-IMPACT underwent further analysis using a custom RNAseq panel (MSK-Fusion). Tumor mutation burden (TMB) was assessed as a potential prioritization criterion for targeted RNAseq.
As part of prospective clinical genomic testing, we profiled 2,522 lung adenocarcinomas using MSK-IMPACT, which identified 195 (7.7%) fusions and 119 (4.7%)
ex14 alterations. Among 275 driver-negative cases with available tissue, 254 (92%) had sufficient material for RNAseq. A previously undetected alteration was identified in 14% (36/254) of cases, 33 of which were actionable (27 in-frame fusions, 6
ex14). Of these 33 patients, 10 then received matched targeted therapy, which achieved clinical benefit in 8 (80%). In the 32% (81/254) of DNAseq driver-negative cases with low TMB 0-5 mutations/Megabase (mut/Mb), 25 (31%) were positive for previously undetected gene fusions on RNAseq, whereas, in 151 cases with TMB >5 mut/Mb, only 7% were positive for fusions (
< 0.0001).
Targeted RNAseq assays should be used in all cases that appear driver negative by DNAseq assays to ensure comprehensive detection of actionable gene rearrangements. Furthermore, we observed a significant enrichment for fusions in DNAseq driver-negative samples with low TMB, supporting the prioritization of such cases for additional RNAseq.
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Multicenter, prospective, cohort study.
To estimate the Minimal Clinically Important Difference (MCID) for the physical (PCS) and mental (MCS) component summaries of Short Form SF-12 (SF-12), in ...patients with low back pain (LBP).
Quality of life is one of the core domains recommended to be assessed in patients with LBP. SF-12 is the most widely used instrument for this purpose, but its MCID was unknown.
A total of 458 patients with subacute and chronic LBP were consecutively recruited across 21 practices. LBP, referred pain, disability, PCS, and MCS were assessed upon recruitment and 12 months later. Self-reported health status change between baseline and 12 month-assessment, was used as the external criterion. The MCID for SF-12 was estimated following four anchor-based methods; minimal detectable change (MDC); average change (AC); change difference (CD); and receiver operating characteristic curve (ROC), for which the area under the curve (AUC) was calculated. The effect on MCID values of pain duration and baseline scores was assessed.
Values for PCS were: MDC: 0.56, AC: 2.71, CD: 3.29, and ROC: 1.14. Values for MCS were: MDC: 3.77, AC: 3.54, CD: 1.13, and ROC: 4.23. AUC values were <0.7; MCID values were smaller among chronic patients and those with better baseline quality of life.
Different methods for MCID calculation lead to different results. In patients with subacute and chronic LBP, improvements >3.77 in MCS and >3.29 in PCS, can be considered clinically relevant. MCID is smaller in patients with longer pain duration and better baseline quality of life.
2.
Visualization of biological targets such as crucial cells and biomolecules in living subjects is critical for the studies of important biological processes. Though
H magnetic resonance imaging (MRI) ...has demonstrated its power in offering detailed anatomical and pathological information, its capacity for in vivo tracking of biological targets is limited by the high biological background of
H.
F distinguishes itself from its competitors as an exceptional complement to
H in MRI through its high sensitivity, low biological background, and broad chemical shift range. The specificity and sensitivity of
F MRI can be further boosted with activatable nanoprobes. The advantages of
F MRI with activatable nanoprobes enable in vivo detection and imaging at the cellular or even molecular level in deep tissues, rendering this technique appealing as a potential solution for visualization of biological targets in living subjects. Here, recent progress over the past decades on activatable
F MRI nanoprobes made from three major
F-containing compounds, as well as present challenges and potential opportunities, are summarized to provide a panoramic prospective for the people who are interested in this emerging and exciting field.
Abstract Background Burnout and work engagement have been viewed as opposite, yet distinct states of employee well-being. We investigated whether work-related indicators of well-being (i.e. burnout ...and work engagement) spill-over and generalize to context-free well-being (i.e. depressive symptoms and life satisfaction). More specifically, we examined the causal direction: does burnout/work engagement lead to depressive symptoms/life satisfaction, or the other way around? Methods Three surveys were conducted. In 2003, 71% of all Finnish dentists were surveyed ( n = 3255), and the response rate of the 3-year follow-up was 84% ( n = 2555). The second follow-up was conducted four years later with a response rate of 86% ( n = 1964). Structural equation modeling was used to investigate the cross-lagged associations between the study variables across time. Results Burnout predicted depressive symptoms and life dissatisfaction from T1 to T2 and from T2 to T3. Conversely, work engagement had a negative effect on depressive symptoms and a positive effect on life satisfaction, both from T1 to T2 and from T2 to T3, even after adjusting for the impact of burnout at every occasion. Limitations The study was conducted among one occupational group, which limits its generalizability. Conclusions Work-related well-being predicts general wellbeing in the long-term. For example, burnout predicts depressive symptoms and not vice versa. In addition, burnout and work engagement are not direct opposites. Instead, both have unique, incremental impacts on life satisfaction and depressive symptoms.
Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the ...performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity.
The 6689 participants 2482 cancer (>50 cancer types), 4207 non-cancer were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization.
Performance was consistent in training and validation sets. In validation, specificity was 99.3% 95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR). Stage I–III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for ∼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%.
cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.
•Targeted methylation analysis of cfDNA simultaneously detected and localized >50 cancer types, including high-mortality cancers that lack screening paradigms.•Cancers were detected across all stages (stage I–III sensitivity: 43.9%; stage I–IV sensitivity: 54.9%) at a specificity of >99% and a single false positive rate of <1%.•This targeted methylation approach localized the tissue of origin with >90% accuracy, which will be critical for directing follow-up care.•This supports the continued investigation of this test with the goal of population-scale early multi-cancer detection.
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