How persons with systemic mastocytosis describe the time between symptom onset and receiving diagnosis

Aim: The aim of the study was to explore how persons with systemic mastocytosis (SM) described the time between the onset of symptoms and signs and getting the diagnosis. Background: SM is a rare disease caused by the accumulation of clonal mast cells with abnormal function. The symptoms and signs of the disease are varied, often diffuse and affect individuals differently. Due to this complexity, a multi-disciplinary diagnostic approach is required, in which general practitioners play an important part in identifying and referring patients relevant for such investigations. Methods: Sixteen persons with SM were interviewed about their experiences of the time before the diagnosis was received. Systematic text condensation was used in the analysis process. Findings: The time between symptom and signs onset and diagnosis was perceived as difficult. SM often had a complex and unpredictable effect on a person’s daily life, long before diagnosis. In the analysis, three themes were found. Having symptoms and signs with an unknown cause included the participants’ descriptions of numerous symptoms and signs, often years before diagnosis. These could be severe and result in worries for both participants and their next-of-kin. Dealing with the symptoms and signs encompassed the different ways in which the participants coped with the symptoms and signs, and sought relief. Being a patient without a diagnosis underlined the lack of information and knowledge within healthcare, often resulting in a delayed or incorrect diagnosis. The study highlighted the importance of a person-centred approach and the need to increase knowledge of the disease within primary care, to shorten this stressful and vulnerable time

AroCell TK 210 ELISA for determination of TK1 protein: age-related reference ranges and comparison with other TK1 assays

Thymidine kinase 1 (TK1) is an enzyme involved in DNA precursor synthesis that has been used as a biomarker for prognosis and monitoring of different malignancies. In this study, we compared two immunoassays for measuring TK1 protein concentrations: the TK 210 ELISA (AroCell AB) and TK1 ELISA from Abcam. Overall, the TK 210 ELISA showed higher sensitivity than the Abcam TK1 ELISA for differentiating hematological malignancies (sensitivity of 0.77 vs 0.45) as well as for distinguishing sera of patients with solid tumors from those of apparently healthy individuals (0.61 vs 0.20). There was no significant difference in the TK1 protein levels determined with the TK 210 ELISA between different age groups from apparently healthy individuals. These results strongly indicate that the AroCell TK 210 ELISA is accurate and sensitive enough to be a valuable tool in cancer management.METHOD SUMMARYThymidine kinase 1 (TK1) is an enzyme that leaks from S phase cells as a result of high cell turnover. Commercially available TK activity assays have certain limitations; to overcome these, we developed a dual monoclonal antibody-based ELISA, the AroCell TK 210 ELISA, which is commercially available. The ELISA includes a preincubation procedure with a special buffer that reduces high molecular weight complexes of serum TK1 and exposes the TK1 epitope to facilitate antibody binding. This provides a robust and convenient assay for the determination of TK1 protein concentrations in sera from patients with different malignancies

AroCell TK 210 ELISA for determination of TK1 protein : age-related reference ranges and comparison with other TK1 assays

Thymidine kinase 1 (TK1) is an enzyme involved in DNA precursor synthesis that has been used as a biomarker for prognosis and monitoring of different malignancies. In this study, we compared two immunoassays for measuring TK1 protein concentrations: the TK 210 ELISA (AroCell AB) and TK1 ELISA from Abcam. Overall, the TK 210 ELISA showed higher sensitivity than the Abcam TK1 ELISA for differentiating hematological malignancies (sensitivity of 0.77 vs 0.45) as well as for distinguishing sera of patients with solid tumors from those of apparently healthy individuals (0.61 vs 0.20). There was no significant difference in the TK1 protein levels determined with the TK 210 ELISA between different age groups from apparently healthy individuals. These results strongly indicate that the AroCell TK 210 ELISA is accurate and sensitive enough to be a valuable tool in cancer management. METHOD SUMMARY Thymidine kinase 1 (TK1) is an enzyme that leaks from S phase cells as a result of high cell turnover. Commercially available TK activity assays have certain limitations; to overcome these, we developed a dual monoclonal antibody-based ELISA, the AroCell TK 210 ELISA, which is commercially available. The ELISA includes a preincubation procedure with a special buffer that reduces high molecular weight complexes of serum TK1 and exposes the TK1 epitope to facilitate antibody binding. This provides a robust and convenient assay for the determination of TK1 protein concentrations in sera from patients with different malignancies

Strict self-isolation did not protect Swedish cancer patients on active treatment from the risk of becoming seropositive for SARS-CoV-2

Background: Swedish recommendations to reduce the risk of COVID-19 relied on each citizen’s own sense of responsibility rather than mandatory lockdowns. We studied how COVID-19-related self-isolation and anxiety correlated to SARS-CoV-2 seropositivity and PCR-positivity in patients with active cancer treatment. Methods: In a longitudinal cohort study at Uppsala University Hospital patients and cancer personnel were included between April 1st 2020 to August 1st 2020. Serological testing for SARS-CoV-2 was done every 8–12-weeks until 30 March 2021. Patients completed a survey at inclusion regarding self-reported COVID-19-related anxiety and self-isolation. Results: A total of 622 patients [n = 475 with solid malignancies (SM), n = 147 with haematological malignancies (HM)], and 358 healthcare personnel were included. The seropositivity rate was lower for patients than for personnel; 10.5% for SM patients, 6.8% for HM patients, and 16.2% for personnel (p = 0.005). Strict adherence to self-isolation guidelines was reported by 54% of patients but was not associated with a lower risk of becoming seropositive [OR = 1.4 (0.8–2.5), p = 0.2]. High anxiety was expressed by 32% of patients, more often by SM patients than HM patients (34% vs 25% [OR = 1.6 (1.1–2.5, p = 0.03)]). Female gender [OR = 3.5 (2.4–5.2), p  0.001] and being born outside of Europe [OR = 2.9 (1.4–6.4), p = 0.007] were both associated with high anxiety. Patients reporting high anxiety became seropositive to a similar degree as those with low anxiety [OR = 0.7 (0.3–1.2), p = 0.2]. HM patients with PCR-positive COVID-19 were more likely than SM patients to require oxygen therapy, including non-invasive ventilation/intubation (69% vs. 26%, p = 0.005). Conclusion: For Swedish patients on active cancer treatment, high self-assessed COVID-19-related anxiety or strict adherence to self-isolation guidelines were not associated with a lower risk of COVID-19. Patients with HM were less likely to develop serological antibody response after COVID-19 and were more likely to require advanced hospital care, but expressed less COVID-19-related anxiety than patients with SM.</p

Delineating functional and molecular impact of ex vivo sample handling in precision medicine

Consistent handling of samples is crucial for achieving reproducible molecular and functional testing results in translational research. Here, we used 229 acute myeloid leukemia (AML) patient samples to assess the impact of sample handling on high-throughput functional drug testing, mass spectrometry-based proteomics, and flow cytometry. Our data revealed novel and previously described changes in cell phenotype and drug response dependent on sample biobanking. Specifically, myeloid cells with a CD117 (c-KIT) positive phenotype decreased after biobanking, potentially distorting cell population representations and affecting drugs targeting these cells. Additionally, highly granular AML cell numbers decreased after freezing. Secondly, protein expression levels, as well as sensitivity to drugs targeting cell proliferation, metabolism, tyrosine kinases (e.g., JAK, KIT, FLT3), and BH3 mimetics were notably affected by biobanking. Moreover, drug response profiles of paired fresh and frozen samples showed that freezing samples can lead to systematic errors in drug sensitivity scores. While a high correlation between fresh and frozen for the entire drug library was observed, freezing cells had a considerable impact at an individual level, which could influence outcomes in translational studies. Our study highlights conditions where standardization is needed to improve reproducibility, and where validation of data generated from biobanked cohorts may be particularly important.Peer reviewe