Background: Drug resistance is a common problem in cancer chemotherapy. Results: Transcriptomic and metabolomic data show that resistant leukemia cells exhibit reduced glutamine dependence, enhanced glucose dependence, and altered fatty acid metabolism.
Conclusion:The metabolism of resistant leukemia cells is fundamentally rewired. Significance: Understanding the metabolic cost of resistance can lead to novel therapeutic strategies.
Background
Understanding the false negative rates of SARS-CoV-2 RT-PCR testing is pivotal for the management of the COVID-19 pandemic and it has implications for patient management. Our aim was to determine the real-life clinical sensitivity of SARS-CoV-2 RT-PCR.
Methods
This population-based retrospective study was conducted in March–April 2020 in the Helsinki Capital Region, Finland. Adults who were clinically suspected of SARS-CoV-2 infection and underwent SARS-CoV-2 RT-PCR testing, with sufficient data in their medical records for grading of clinical suspicion were eligible. In addition to examining the first RT-PCR test of repeat-tested individuals, we also used high clinical suspicion for COVID-19 as the reference standard for calculating the sensitivity of SARS-CoV-2 RT-PCR.
Results
All 1,194 inpatients (mean [SD] age, 63.2 [18.3] years; 45.2% women) admitted to COVID-19 cohort wards during the study period were included. The outpatient cohort of 1,814 individuals (mean [SD] age, 45.4 [17.2] years; 69.1% women) was sampled from epidemiological line lists by systematic quasi-random sampling. The sensitivity (95% CI) for laboratory confirmed cases (repeat-tested patients) was 85.7% (81.5–89.1%) inpatients; 95.5% (92.2–97.5%) outpatients, 89.9% (88.2–92.1%) all. When also patients that were graded as high suspicion but never tested positive were included in the denominator, the sensitivity (95% CI) was: 67.5% (62.9–71.9%) inpatients; 34.9% (31.4–38.5%) outpatients; 47.3% (44.4–50.3%) all.
Conclusions
The clinical sensitivity of SARS-CoV-2 RT-PCR testing was only moderate at best. The relatively high false negative rates of SARS-CoV-2 RT-PCR testing need to be accounted for in clinical decision making, epidemiological interpretations, and when using RT-PCR as a reference for other tests.
Figure 1 Multimodal MRI findings during the course of an episode of hemiplegic migraine. (A) Day 1, 6 hours post-onset. Dense hemiparesis, aphasia, and severe headache associated with normal diffusion weighted imaging (DWI), magnetic resonance angiography (MRA), and gross hyperperfusion of the left hemisphere on factor analysis of dynamic studies (FADS). (B) Day 4. Weakness improving, dysphasic, persistent headache. Hyperperfusion of inferior frontal lobe on FADS. (C) Three months. Asymptomatic. Full resolution of perfusion changes. (DWI not repeated at three months).
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