| 1. |
- Lindgren, Marie, 1971, et al.
(författare)
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Survival and risk of vascular complications in myelofibrosis—A population-based study from the Swedish MPN group
- 2022
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 109:4, s. 336-342
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To gain knowledge of underlying risk factors for vascular complications and their impact on life expectancy in myelofibrosis. Methods: From a cohort of 392 myelofibrosis patients registered in the Swedish MPN registry 58 patients with vascular complications during follow-up were identified. Patients with vascular complications were compared with both 1:1 matched controls and the entire myelofibrosis cohort to explore potential risk factors for vascular complications and their impact on survival. Results: Incidence of vascular complications was 2.8 events per 100 patient-years and the majority of complications were thrombotic. Patients with complications were significantly older and had lower hemoglobin when compared to the entire cohort. In the case–control analysis, no significant risk factor differences were observed. The major cause of death was vascular complications and median survival was significantly impaired in patients with vascular complications (48 months) compared to controls (92 months). Inferior survival in patients with vascular complications was found to be dependent on IPSS risk category in a Cox regression model. Conclusion: Vascular complications have a considerable impact on survival in MF. At diagnosis, risk assessment by IPSS does not only predict survival but is also associated with the risk of vascular complications.
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| 2. |
- Hagstrom, H., et al.
(författare)
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Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers
- 2021
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Ingår i: Liver International. - : Wiley. - 1478-3223 .- 1478-3231. ; 41:3, s. 545-553
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. Methods We identified 3645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population. We ascertained incident outcomes until the end of 2017 by linkage to national registers. Studied outcomes were HH, cirrhosis, hepatocellular carcinoma (HCC), breast cancer (in women), colorectal cancer, type 1 and 2 diabetes, hypothyroidism, Parkinson's disease and mortality. Cox proportional hazards regression was used to estimate hazard ratios for these outcomes. Results Median age at diagnosis was 52 years, 44% were females. During a mean follow-up of 7.9 years, we found an increased risk for HCC, HH, cirrhosis, type 2 diabetes, osteoarthritis and death. Excess mortality was only seen in men. No increased risk was seen for colorectal or breast cancer. Liver-related outcomes were rare, with a cumulative incidence of HFE mutation carriers in a university hospital setting had an increased risk for mortality in men, along with increased risks of cirrhosis, HCC, diabetes type 2, and osteoarthritis. In general, the absolute risk for adverse outcomes was low and no increased risk for colon or breast cancer was observed.
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| 3. |
- Carrwik, Christian, 1977-, et al.
(författare)
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Survival after surgery for spinal metastatic disease: a nationwide multiregistry cohort study.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate survival after surgery and indications for surgery due to spinal metastatic disease.A retrospective longitudinal multiregistry nationwide cohort study.19 public hospitals in Sweden with spine surgery service, where 6 university hospitals account for over 90% of the cases.1820 patients 18 years or older undergoing surgery due to spinal metastatic disease 2006-2018 and registered in Swespine, the Swedish national spine surgery registry.Decompressive and/or stabilising spine surgery due to spinal metastatic disease.Survival (median and mean) after surgery.Indications for surgery, types of surgery and causes of death.The median estimated survival after surgery was 6.2 months (95% CI: 5.6 to 6.8) and the mean estimated survival time was 12.2 months (95% CI: 11.4 to 13.1). Neurologic deficit was the most common indication for surgery and posterior stabilisation was performed in 70.5% of the cases. A neoplasm was stated as the main cause of death for 97% of the patients.Both median and mean survival times were well above the generally accepted thresholds for surgical treatment for spinal metastases, suggesting that patient selection for surgical treatment on a national level is adequate. Further research on quality of life after surgery and prognostication is needed.
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| 4. |
- Axman, Erik, et al.
(författare)
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Assessing the Validity and Cover Rate of the National Swedish Hernia Register
- 2021
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Ingår i: CLINICAL EPIDEMIOLOGY. - : Dove Press. - 1179-1349. ; 13, s. 1129-1134
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To assess the validity and cover rate of the Swedish hernia register. Material and Methods: Since the start of the Swedish Hernia register an annual review of randomly selected hospitals has been carried out, and since 2013 in a more standardized form to allow a systematic data collection and evaluation. 10% of all clinics were randomly selected each year in a specific region of Sweden, ensuring a systematic validation of all regions from north to south. Data from 2013 to 2018 were analyzed regarding data quality and from 2014 to 2018 regarding cover rate. All operations registered at the validated clinics were compared with the Swedish Hernia Register to assess cover rate. Fifty operations were randomly selected at each clinic and data in the Swedish Hernia register were compared with the medical records to evaluate data quality. Results: Fifty-five clinics was evaluated and a total of 73,764 variables were compared with the medical records. Cover rate between 2014 and 2018 was 97%. The proportion of correct variables was 98% between 2013 and 2018. Most frequent errors were ASA score, date at which the patient was put on the waiting list and postoperative complications. Conclusion: This unique validation of a national hernia register shows a high cover rate and good quality of data. Efforts to maintain and improve national registers are of great importance. Research with data from the Swedish hernia register should be evaluated on the basis of the results presented in this study.
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| 5. |
- Carstam, Louise, et al.
(författare)
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WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas.
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and Methods: A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.Results: There was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01-1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00-1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00-1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01-1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).Conclusion: Our findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.
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| 6. |
- Gómez Vecchio, Tomás, et al.
(författare)
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Classification of Adverse Events Following Surgery in Patients With Diffuse Lower-Grade Gliomas
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, the Therapy-Disability-Neurology (TDN) was introduced as a multidimensional reporting system to detect adverse events in neurosurgery. The aim of this study was to compare the novel TDN score with the Landriel–Ibanez classification (LIC) grade in a large cohort of patients with diffuse lower-grade glioma (dLGG). Since the TDN score lacks validation against patient-reported outcomes, we described health-related quality of life (HRQoL) change in relation to TDN scores in a subset of patients.Methods: We screened adult patients with a surgically treated dLGG World Health Organization (WHO) grade 2 and 3 between 2010 and 2020. Up until 2017, it consists of a retrospective cohort (n = 158). From 2017 and onwards, HRQoL was registered using EuroQoL-5-dimension, three levels of response (EQ-5D 3L) questionnaire at baseline and 3 months follow-up, in a prospectively recruited cohort (n = 102). Both the LIC grade and TDN score were used to classify adverse events.Results: In total, 231 patients were included. In 110/231 (47.6%) of the surgical procedures, a postoperative complication was registered. When comparing the TDN score to LIC grades, only a minor shift towards complications of higher order could be observed. EQ-5D 3L was reported for 45 patients. Patients with complications related to surgery had pre- to postoperative changes in EQ-5D 3L index values (n = 27; mean 0.03, 95% CI −0.06 to 0.11) that were comparable to patients without complications (n = 18; mean −0.06, 95% CI −0.21 to 0.08). In contrast, patients with new-onset neurological deficit had a deterioration in HRQoL at follow-up, with a mean change in the EQ-5D 3L index value of 0.11 (n = 13, 95% CI 0.0 to 0.22) compared to −0.06 (n = 32, 95% CI −0.15 to 0.03) for all other patients.Conclusions: In patients with dLGG, TDN scores compared to the standard LIC tend to capture more adverse events of higher order. There was no clear relation between TDN severity and HRQoL. However, new-onset neurological deficit caused impairment in HRQoL. For the TDN score to better align with patient-reported outcomes, more emphasis on neurological deficit and function should be considered.
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| 7. |
- Alevronta, Eleftheria, et al.
(författare)
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Dose-response relationships of intestinal organs and excessive mucus discharge after gynaecological radiotherapy
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Background The study aims to determine possible dose-volume response relationships between the rectum, sigmoid colon and small intestine and the ‘excessive mucus discharge’ syndrome after pelvic radiotherapy for gynaecological cancer. Methods and materials From a larger cohort, 98 gynaecological cancer survivors were included in this study. These survivors, who were followed for 2 to 14 years, received external beam radiation therapy but not brachytherapy and not did not have stoma. Thirteen of the 98 developed excessive mucus discharge syndrome. Three self-assessed symptoms were weighted together to produce a score interpreted as ‘excessive mucus discharge’ syndrome based on the factor loadings from factor analysis. The dose-volume histograms (DVHs) for rectum, sigmoid colon, small intestine for each survivor were exported from the treatment planning systems. The dose-volume response relationships for excessive mucus discharge and each organ at risk were estimated by fitting the data to the Probit, RS, LKB and gEUD models. Results The small intestine was found to have steep dose-response curves, having estimated dose-response parameters: γ : 1.28, 1.23, 1.32, D : 61.6, 63.1, 60.2 for Probit, RS and LKB respectively. The sigmoid colon (AUC: 0.68) and the small intestine (AUC: 0.65) had the highest AUC values. For the small intestine, the DVHs for survivors with and without excessive mucus discharge were well separated for low to intermediate doses; this was not true for the sigmoid colon. Based on all results, we interpret the results for the small intestine to reflect a relevant link. Conclusion An association was found between the mean dose to the small intestine and the occurrence of ‘excessive mucus discharge’. When trying to reduce and even eliminate the incidence of ‘excessive mucus discharge’, it would be useful and important to separately delineate the small intestine and implement the dose-response estimations reported in the study.
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| 8. |
- Li, Xiangyu, et al.
(författare)
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Classification of clear cell renal cell carcinoma based on PKM alternative splicing
- 2020
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
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| 9. |
- Liedberg, Fredrik, et al.
(författare)
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Cumulative incidence of midline incisional hernia and its surgical treatment after radical cystectomy and urinary diversion for bladder cancer: A nation-wide population-based study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective To study the cumulative incidence and surgical treatment of midline incisional hernia (MIH) after cystectomy for bladder cancer. Methods In the nationwide Bladder Cancer Data Base Sweden (BladderBaSe), cystectomy was performed in 5646 individuals. Cumulative incidence MIH and surgery for MIH were investigated in relation to age, gender, comorbidity, previous laparotomy and/or inguinal hernia repair, operative technique, primary/secondary cystectomy, postoperative wound dehiscence, year of surgery, and period-specific mean annual hospital cystectomy volume (PSMAV). Results Three years after cystectomy the cumulative incidence of MIH and surgery for MIH was 8% and 4%, respectively. The cumulative incidence MIH was 12%, 9% and 7% in patients having urinary diversion with continent cutaneous pouch, orthotopic neobladder and ileal conduit. Patients with postoperative wound dehiscence had a higher three-year cumulative incidence MIH (20%) compared to 8% without. The corresponding cumulative incidence surgery for MIH three years after cystectomy was 9%, 6%, and 4% for continent cutaneous, neobladder, and conduit diversion, respectively, and 11% for individuals with postoperative wound dehiscence (vs 4% without). Using multivariable Cox regression, secondary cystectomy (HR 1.3 (1.0-1.7)), continent cutaneous diversion (HR 1.9 (1.1-2.4)), robot-assisted cystectomy (HR 1.8 (1-3.2)), wound dehiscence (HR 3.0 (2.0-4.7)), cystectomy in hospitals with PSMAV 10-25 (HR 1.4 (1.0-1.9)), as well as cystectomy during later years (HRs 2.5-3.1) were all independently associated with increased risk of MIH. Conclusions The cumulative incidence of MIH was 8% three years postoperatively, and increase over time. Avoiding postoperative wound dehiscence after midline closure is important to decrease the risk of MIH.
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| 10. |
- Arabpour, Mohammad, et al.
(författare)
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ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection
- 2022
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 15:4, s. 745-761
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Tidskriftsartikel (refereegranskat)abstract
- Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103(+) cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3-/- mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt(+) T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.
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