| 1. |
- Bergqvist, Michael, et al.
(författare)
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Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010-2016 in Sweden : A nationwide observational study
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:9, s. 2510-2517
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of our study was to investigate time trends in treatment pattern and prognostic factors for overall survival (OS) in epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) treated nonsmall cell lung cancer (NSCLC) patients. Utilizing Swedish nationwide registers, we identified all Stage IIIB-IV NSCLC patients treated with EGFR TKIs and followed them from diagnosis (2010-2015) until death or end of observation (2016). Multivariable Cox regression analyses were performed to test associations of patient-, tumor-related factors with OS. Of 9,992 Stage IIIB-IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less >= 1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non-TKI treated patients. After TKI initiation, 7% (n = 100) of the patients switched, 4% (n = 62) rechallenged a TKI treatment, 65% (n = 919) discontinued and 24% (n = 338) had died. A more recent diagnosis demonstrated shorter time to EGFR TKI initiation, prolonged treatment length and longer median OS (15.3 months 2010-2011; 14.4 months 2012-2013; 18.6 months 2014-2015). Prognostic factors for longer OS when treated with EGFR TKIs were younger age, adenocarcinoma, less advanced clinical stage and less comorbid disease. In conclusion, during the observation period, survival improved for EGFR TKI treated NSCLC patients, as did the accessibility for targeted therapies for these patients.
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| 2. |
- Bergqvist, Rita, et al.
(författare)
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HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden : A registry-based cohort study
- 2021
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between statin treatment and Coronavirus Disease 2019 (COVID-19) mortality has been discussed due to the pleiotropic effects of statins on coagulation and immune mechanisms. However, available observational studies are hampered by study design flaws, resulting in substantial heterogeneity and ambiguities. Here, we aim to determine the relationship between statin treatment and COVID-19 mortality.Methods and findings: This cohort study included all Stockholm residents aged 45 or older (N = 963,876), followed up from 1 March 2020 until 11 November 2020. The exposure was statin treatment initiated before the COVID-19-pandemic, defined as recorded statin dispensation in the Swedish Prescribed Drug Register between 1 March 2019 and 29 February 2020. COVID-19-specific mortality was ascertained from the Swedish Cause of Death Registry. Hazard ratios (HRs) were calculated using multivariable Cox regression models. We further performed a target trial emulation restricted to initiators of statins.In the cohort (51.6% female), 169,642 individuals (17.6%) were statin users. Statin users were older (71.0 versus 58.0 years), more likely to be male (53.3% versus 46.7%), more often diagnosed with comorbidities (for example, ischemic heart disease 23.3% versus 1.6%), more frequently on anticoagulant and antihypertensive treatments, less likely to have a university-level education (34.5% versus 45.4%), and more likely to have a low disposable income (20.6% versus 25.2%), but less likely to reside in crowded housing (6.1% versus 10.3%).A total of 2,545 individuals died from COVID-19 during follow-up, including 765 (0.5%) of the statin users and 1,780 (0.2%) of the nonusers. Statin treatment was associated with a lowered COVID-19 mortality (adjusted HR, 0.88; 95% CI, 0.79 to 0.97, P = 0.01), and this association did not vary appreciably across age groups, sexes, or COVID-19 risk groups. The confounder adjusted HR for statin treatment initiators was 0.78 (95% CI, 0.59 to 1.05, P = 0.10) in the emulated target trial. Limitations of this study include the observational design, reliance on dispensation data, and the inability to study specific drug regimens.Conclusions: Statin treatment had a modest negative association with COVID-19 mortality. While this finding needs confirmation from randomized clinical trials, it supports the continued use of statin treatment for medical prevention according to current recommendations also during the COVID-19 pandemic.
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| 3. |
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| 4. |
- Huang, Hua, 1986-, et al.
(författare)
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ELTD1-deletion reduces vascular abnormality and improves T-cell recruitment after PD-1 blockade in glioma.
- 2021
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 24:3, s. 398-411
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tumor vessels in glioma are molecularly and functionally abnormal, contributing to treatment resistance. Proteins differentially expressed in glioma vessels can change vessel phenotype and be targeted for therapy. ELTD1 (Adgrl4) is an orphan member of the adhesion G-protein-coupled receptor family upregulated in glioma vessels, and has been suggested as a potential therapeutic target. However, the role of ELTD1 in regulating vessel function in glioblastoma is poorly understood.METHODS: ELTD1 expression in human gliomas and its association with patient survival was determined using tissue microarrays and public databases. The role of ELTD1 in regulating tumor vessel phenotype was analyzed using orthotopic glioma models and ELTD1 -/- mice. Endothelial cells isolated from murine gliomas were transcriptionally profiled to determine differentially expressed genes and pathways. The consequence of ELTD1-deletion on glioma immunity was determined by treating tumor bearing mice with PD-1-blocking antibodies.RESULTS: ELTD1 levels were upregulated in human glioma vessels, increased with tumor malignancy, and were associated with poor patient survival. Progression of orthotopic gliomas was not affected by ELTD1-deletion, however, tumor vascular function was improved in ELTD1 -/- mice. Bioinformatic analysis of differentially expressed genes indicated increased inflammatory response and decreased proliferation in tumor endothelium in ELTD1 -/- mice. Consistent with an enhanced inflammatory response, ELTD1-deletion improved T-cell infiltration in GL261-bearing mice after PD-1 checkpoint blockade.CONCLUSION: Our data demonstrate that ELTD1 participates in inducing vascular dysfunction in glioma, and suggests that targeting of ELTD1 may normalize the vessels and improve the response to immunotherapy.
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| 5. |
- Huckriede, Joram, et al.
(författare)
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Evolution of NETosis markers and DAMPs have prognostic value in critically ill COVID-19 patients
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 19 (COVID-19) presents with disease severities of varying degree. In its most severe form, infection may lead to respiratory failure and multi-organ dysfunction. Here we study the levels and evolution of the damage associated molecular patterns (DAMPS) cell free DNA (cfDNA), extracellular histone H3 (H3) and neutrophil elastase (NE), and the immune modulators GAS6 and AXL in relation to clinical parameters, ICU scoring systems and mortality in patients (n = 100) with severe COVID-19. cfDNA, H3, NE, GAS6 and AXL were increased in COVID-19 patients compared to controls. These measures associated with occurrence of clinical events and intensive care unit acquired weakness (ICUAW). cfDNA and GAS6 decreased in time in patients surviving to 30 days post ICU admission. A decrease of 27.2 ng/mL cfDNA during ICU stay associated with patient survival, whereas levels of GAS6 decreasing more than 4.0 ng/mL associated with survival. The presence of H3 in plasma was a common feature of COVID-19 patients, detected in 38% of the patients at ICU admission. NETosis markers cfDNA, H3 and NE correlated well with parameters of tissue damage and neutrophil counts. Furthermore, cfDNA correlated with lowest p/f ratio and a lowering in cfDNA was observed in patients with ventilator-free days.
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| 6. |
- Järhult, Josef D., 1975-, et al.
(författare)
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The impact of viremia on organ failure, biomarkers and mortality in a Swedish cohort of critically ill COVID-19 patients
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The spread of virus via the blood stream has been suggested to contribute to extra-pulmonary organ failure in Coronavirus disease 2019 (COVID-19). We assessed SARS-CoV-2 RNAemia (RNAemia) and the association between RNAemia and inflammation, organ failure and mortality in critically ill COVID-19 patients. We included all patients with PCR verified COVID-19 and consent admitted to ICU. SARS-CoV-2 RNA copies above 1000/ml measured by PCR in plasma was defined as RNAemia and used as surrogate for viremia. In this cohort of 92 patients 59 (64%) were invasively ventilated. RNAemia was found in 31 patients (34%). Hypertension and corticosteroid treatment was more common in patients with RNAemia. Extra-pulmonary organ failure biomarkers and the extent of organ failure were similar in patients with and without RNAemia, but the former group had more renal replacement therapy and higher mortality (26 vs 16%; 35 vs 16%, respectively, p=0.04). RNAemia was not an independent predictor of death at 30 days after adjustment for age. SARS-CoV2 RNA copies in plasma is a common finding in ICU patients with COVID-19. Although viremia was not associated with extra pulmonary organ failure it was more common in patients who did not survive to 30 days after ICU admission.Trial registration: ClinicalTrials NCT04316884.
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| 7. |
- Källman, Mikael, et al.
(författare)
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Use of CAM among cancer patients : results of a regional survey in Sweden
- 2023
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Ingår i: BMC Complementary Medicine and Therapies. - : BioMed Central (BMC). - 2662-7671. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of complementary and alternative medicine (CAM) by patients is widespread. However, there is a lack of knowledge regarding the extent and details of patient CAM use in Sweden, especially in rural Sweden. The aim of this study was to estimate the extent and characteristics of CAM use among cancer patients in Region Gävleborg. Methods: A total of 631 questionnaires were distributed to which 376 responses were registered, yielding a response rate of 59.6%. Questionnaires were distributed to oncology patients at their first visit for curative treatment at the Department of Oncology, Gävle Hospital. Palliative patients were recruited at their first visit and during enrollment in palliative outpatient care in their own homes. The characteristics of the respondents were presented with standard descriptive statistics. A multivariable logistic model was fitted to calculate odds ratios (ORs) and identify potential predictors (Age, Gender, Education, Diagnosis) of CAM use post-cancer diagnosis. Results: 54% of all participants reported lifetime CAM use, 34% reported CAM use post-diagnosis. The most common CAM methods used after diagnosis are vitamins, health food preparations, herbal teas, prayer and dietary methods. The most common source of information reported is family and friends. Almost 70% of those who used CAM after their diagnosis stated that they did not discuss their use with healthcare professionals. Most patients reported that they would like some CAM modalities to be offered within conventional care regardless of their own CAM use. Conclusions: The use of CAM is common among patients with cancer in the region of Gävleborg, and previous studies show a similar use in Sweden in general. Based on the widespread use of CAM and patient interest in discussing CAM use with healthcare professionals, greater attention and focus should be placed on creating a basis for this dialogue. If we, as healthcare professionals, are to emphasise our commitment to providing patient-centred care, we must acknowledge that patients use CAM and are seeking a dialogue about CAM use in their care.
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| 8. |
- Lagedal, Rickard, et al.
(författare)
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Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March-September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5-34.4) and 4.2 (1.1-15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.
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| 9. |
- Lundin, Erik, 1970-, et al.
(författare)
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Radiotherapy as Elective Treatment of the Node-negative Neck in Oral Squamous Cell Cancer
- 2021
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 41:7, s. 3489-3498
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Previous studies of node-negative oral squamous cell carcinoma have shown a benefit of elective neck dissection compared to observation. Evidence for radiotherapy as single-modality elective treatment of the node-negative neck is so far lacking.PATIENTS AND METHODS: In a retrospective material of 420 early-stage oral cancers from 2000 to 2016, overall survival, disease-free survival, and regional relapse-free survival were calculated with the Kaplan-Meier method.RESULTS: At five years, overall survival was 59.7%, disease-specific survival was 77.2%, and regional relapse-free survival was 83.5%. Among those with adjuvant treatment of the neck after surgery of T1-T2 tumours during 2009-2016, regional relapse-free survival at five years was 85.7% for elective radiotherapy of the neck and 87.4% for elective neck dissection.CONCLUSION: Elective radiotherapy to the neck with a modern technique and adequate dose might be an alternative to neck dissection for patients with early-stage oral squamous cell cancer.
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| 10. |
- Nilsson, Jonas, et al.
(författare)
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Geographical Differences in Likelihood of Home Death Among Palliative Cancer Patients : A National Population-based Register Study
- 2020
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 40:7, s. 3897-3903
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Previous studies have shown discrepancies between patient's desired and actual death place. As planning of family support and involvement of palliative home care teams seem to improve the chance to meet patients preferences, geographical availability of specialized palliative home care could influence place of death.Patients and Methods: Data of patients diagnosed and deceased between January 2011 until December 2014 with lung, brain, colorectal, breast and prostate cancer was collected from Swedish national registers and multiple regression analyses were performed.Results: Patients with lung, brain, colorectal, and prostate cancer who resided in rural municipalities had a higher likelihood of dying at home than dying in hospital settings, compared to those who lived in urban areas.Conclusion: Patients in Sweden, with the exception of breast cancer patients, have a higher likelihood of home death than inpatient hospital death when residing in rural areas compared to when residing in urban areas.
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