| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Bolkan, Håkon A, et al.
(författare)
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The Surgical Workforce and Surgical Provider Productivity in Sierra Leone: A Countrywide Inventory.
- 2016
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 40:6, s. 1344-1351
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Tidskriftsartikel (refereegranskat)abstract
- Limited data exist on surgical providers and their scope of practice in low-income countries (LICs). The aim of this study was to assess the distribution and productivity of all surgical providers in an LIC, and to evaluate correlations between the surgical workforce availability, productivity, rates, and volume of surgery at the district and hospital levels.
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| 8. |
- Edqvist, Per-Henrik D., et al.
(författare)
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Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma
- 2015
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 137:3, s. 529-537
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Tidskriftsartikel (refereegranskat)abstract
- Objective For endometrial carcinoma, prognostic stratification methods do not satisfactorily identify patients with adverse outcome. Currently, histology, tumor grade and stage are used to tailoring surgical treatment and to determine the need for adjuvant treatment. Low-risk patients are not considered to require adjuvant therapy or staging lymphadenectomy. For patients with intermediate or high risk, some guidelines recommend tailoring adjuvant treatment according to additional negative prognostic factors. Our objective was to evaluate the biomarker potential of the ASRGL1 protein in endometrial carcinoma. Methods Using The Human Protein Atlas (www.proteinatlas.org), the l-asparaginase (ASRGL1) protein was identified as an endometrial carcinoma biomarker candidate. ASRGL1 expression was immunohistochemically evaluated with an extensively validated antibody on two independent endometrial carcinoma cohorts (n = 229 and n = 286) arranged as tissue microarrays. Staining results were correlated with clinical features. Results Reduced expression of ASRGL1, defined as < 75% positively stained tumor cells, was significantly associated with poor prognosis and reduced disease-specific survival in endometrioid endometrial adenocarcinoma (EEA). In multivariate analysis the hazard ratios for disease-specific survival were 3.55 (95% CI = 1.10-11.43; p = 0.003) and 3.23 (95% CI = 1.53-6.81; p = 0.002) in the two cohorts, respectively. Of the 48 cases with Grade 3 Stage I tumor all disease-related deaths were associated with low ASRGL1 expression. Conclusions Loss of ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has a positive impact on survival. ASRGL1 immunohistochemistry has potential to become an additional tool for prognostication in cases where tailoring adjuvant treatment according to additional prognostic factors besides grade and stage is recommended.
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| 9. |
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| 10. |
- Løvvik, Tone S., et al.
(författare)
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Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2) : a randomised, double-blind, placebo-controlled trial
- 2019
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 7:4, s. 256-266
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy complications. Epi-analysis of two previous randomised controlled trials that compared metformin with placebo during pregnancy in women with PCOS showed a significant reduction in late miscarriages and preterm births in the metformin group. The aim of this third randomised trial (PregMet2) was to test the hypothesis that metformin prevents late miscarriage and preterm birth in women with PCOS.Methods: PregMet2 was a randomised, placebo-controlled, double-blind, multicentre trial done at 14 hospitals in Norway, Sweden, and Iceland. Singleton pregnant women with PCOS aged 18-45 years were eligible for inclusion. After receiving information about the study at their first antenatal visit or from the internet, women signed up individually to participate in the study. Participants were randomly assigned (1: 1) to receive metformin or placebo by computer-generated random numbers. Randomisation was in blocks of ten for each country and centre; the first block had a random size between one and ten to assure masking. Participants were assigned to receive oral metformin 500 mg twice daily or placebo during the first week of treatment, which increased to 1000 mg twice daily or placebo from week 2 until delivery. Placebo tablets and metformin tablets were identical and participants and study personnel were masked to treatment allocation. The primary outcome was the composite incidence of late miscarriage (between week 13 and week 22 and 6 days) and preterm birth (between week 23 and week 36 and 6 days), analysed in the intention-to-treat population. Secondary endpoints included the incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension, and admission of the neonate to the neonatal intensive care unit. We also did a post-hoc individual participant data analysis of pregnancy outcomes, pooling data from the two previous trials with the present study. The study was registered with ClinicalTrials. gov, number NCT01587378, and EudraCT, number 2011-002203-15.Findings: The study took place between Oct 19, 2012, and Sept 1, 2017. We randomly assigned 487 women to metformin (n=244) or placebo (n=243). In the intention-to-treat analysis, our composite primary outcome of late miscarriage and preterm birth occurred in 12 (5%) of 238 women in the metformin group and 23 (10%) of 240 women in the placebo group (odds ratio [OR] 0.50, 95% CI 0.22- 1.08; p = 0.08). We found no significant differences for our secondary endpoints, including incidence of gestational diabetes (60 [25%] of 238 women in the metformin group vs 57 [24%] of 240 women in the placebo group; OR 1.09, 95% CI 0.69-1.66; p=0.75). We noted no substantial between-group differences in serious adverse events in either mothers or offspring, and no serious adverse events were considered drug-related by principal investigators. In the post-hoc pooled analysis of individual participant data from the present trial and two previous trials, 18 (5%) of 397 women had late miscarriage or preterm delivery in the metformin group ]compared with 40 (10%) of 399 women in the placebo group (OR 0.43, 95% CI 0.23-0.79; p=0.004).Interpretation: In pregnant women with PCOS, metformin treatment from the late first trimester until delivery might reduce the risk of late miscarriage and preterm birth, but does not prevent gestational diabetes.
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| 11. |
- Munkvold, Bodil Karoline Ravn, et al.
(författare)
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Variations in the management of diffuse low-grade gliomas : A Scandinavian multicenter study
- 2021
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Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 8:6, s. 706-717
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Tidskriftsartikel (refereegranskat)abstract
- Background. Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected "high-risk" patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems.Methods. Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored.Results. A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy.Conclusions. Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.
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| 12. |
- Rydén, Isabelle, et al.
(författare)
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Return to work following diagnosis of low-grade glioma: A nationwide matched cohort study.
- 2020
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 95:7
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Tidskriftsartikel (refereegranskat)abstract
- Return-to-work (RTW) following diagnosis of infiltrative low-grade gliomas (LGG) is unknown.Swedish patients with histopathological verified WHO grade II diffuse glioma diagnosed between 2005-2015 were included. Data were acquired from several Swedish registries. A total of 381 patients aged 18-60 were eligible. A matched control population (n=1900) was acquired. Individual data on sick leave, compensations, comorbidity and treatments assigned were assessed. Predictors were explored using multivariable logistic regression.One year before surgery/index date, 88 % of cases were working compared to 91 % of controls. The proportion of controls working remained constant, while patients had a rapid increase in sick leave approximately six months prior to surgery. After one and two years respectively, 52 % and 63 % of the patients were working. Predictors for no-RTW after one year were previous sick leave (OR 0.92, 95 % CI 0.88-0.96, p <0.001), older age (OR 0.96, 95 % CI 0.94-0.99, p=0.005) and lower functional level (OR 0.64 95% CI, 0.45-0.91 p=0.01). Patients receiving adjuvant treatment were less likely to RTW within the first year. At two years, biopsy (as opposed to resection), female sex and comorbidity were also unfavorable, while age and adjuvant treatment were no longer significant.Approximately half of the patients RTW within the first year. Lower functional status, previous sick leave, older age and adjuvant treatment were risk factors for no-RTW at one year after surgery. Female sex, comorbidity and biopsy only were also unfavorable for RTW at two years.
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| 13. |
- Thurin, Erik, et al.
(författare)
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Impact of meningioma surgery on use of antiepileptic, antidepressant, and sedative drugs : A Swedish nationwide matched cohort study
- 2021
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 10:9, s. 2967-2977
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Tidskriftsartikel (refereegranskat)abstract
- Background: Meningioma is the most common primary intracranial tumor and surgery is the main treatment modality. As death from lack of tumor control is rare, other outcome measures like anxiety, depression and post-operative epilepsy are becoming increasingly relevant. In this nationwide registry-based study we aimed to describe the use of antiepileptic drugs (AED), antidepressants and sedatives before and after surgical treatment of an intracranial meningioma compared to a control population, and to provide predictors for continued use of each drug-group two years after surgery.Methods: All adult patients with histopathologically verified intracranial meningiomas were identified in the Swedish Brain Tumor Registry and their data were linked to relevant national registries after assigning five matched controls to each patient. We analyzed the prescription patterns of antiepileptic drugs (AED), antidepressants and sedative drugs in the two years before and the two years following surgery.Results: For the 2070 patients and 10312 controls identified the use of AED, antidepressants and sedatives was comparable two years before surgery. AED use at time of surgery was higher for patients than for controls (22.2% vs. 1.9%, p < 0.01), as was antidepressant use (12.9% vs. 9.4%, p < 0.01). Both AED and antidepressant use remained elevated after surgery, with patients having a higher AED use (19.7% vs. 2.3%, p < 0.01) and antidepressant use (14.8% vs. 10.6%, p < 0.01) at 2 years post-surgery. Use of sedatives peaked for patients at the time of surgery (14.4% vs. 6.1%, p < 0.01) and remained elevated at two years after surgery with 9.9% versus 6.6% (p < 0.01). For all the studied drugs, previous drug use was the strongest predictor for use 2 years after surgery.Conclusion: This nationwide study shows that increased use of AED, antidepressants and sedatives in patients with meningioma started perioperatively, and remained elevated two years following surgery.
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| 14. |
- Werlenius, Katja, et al.
(författare)
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Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma: A Randomized Clinical Trial.
- 2023
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Disulfiram has demonstrated broad antitumoral effect in several preclinical studies. One of the proposed indications is for the treatment of glioblastoma.To evaluate the efficacy and safety of disulfiram and copper as add-on to alkylating chemotherapy in patients with recurrent glioblastoma.This was a multicenter, open-label, randomized phase II/III clinical trial with parallel group design. Patients were recruited at 7 study sites in Sweden and 2 sites in Norway between January 2017 and November 2020. Eligible patients were 18 years or older, had a first recurrence of glioblastoma, and indication for treatment with alkylating chemotherapy. Patients were followed up until death or a maximum of 24 months. The date of final follow-up was January 15, 2021. Data analysis was performed from February to September 2022.Patients were randomized 1:1 to receive either standard-of-care (SOC) alkylating chemotherapy alone, or SOC with the addition of disulfiram (400 mg daily) and copper (2.5 mg daily).The primary end point was survival at 6 months. Secondary end points included overall survival, progression-free survival, adverse events, and patient-reported quality of life.Among the 88 patients randomized to either SOC (n=45) or SOC plus disulfiram and copper (n=43), 63 (72%) were male; the mean (SD) age was 55.4 (11.5) years. There was no significant difference between the study groups (SOC vs SOC plus disulfiram and copper) in 6 months survival (62% [26 of 42] vs 44% [19 of 43]; P=.10). Median overall survival was 8.2 months (95% CI, 5.4-10.2 months) with SOC and 5.5 months (95% CI, 3.9-9.3 months) with SOC plus disulfiram and copper, and median progression-free survival was 2.6 months (95% CI, 2.4-4.6 months) vs 2.3 months (95% CI, 1.7-2.6 months), respectively. More patients in the SOC plus disulfiram and copper group had adverse events grade 3 or higher (34% [14 of 41] vs 11% [5 of 44]; P=.02) and serious adverse events (41% [17 of 41] vs 16% [7 of 44]; P=.02), and 10 patients (24%) discontinued disulfiram treatment because of adverse effects.This randomized clinical trial found that among patients with recurrent glioblastoma, the addition of disulfiram and copper to chemotherapy, compared with chemotherapy alone, resulted in significantly increased toxic effects, but no significant difference in survival. These findings suggest that disulfiram and copper is without benefit in patients with recurrent glioblastoma.ClinicalTrials.gov Identifier: NCT02678975; EUDRACT Identifier: 2016-000167-16.
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| 15. |
- Baranov, Anton, et al.
(författare)
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Assessment of Cesarean hysterotomy scar before pregnancy and at 11–14 weeks of gestation : a prospective cohort study
- 2017
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692. ; 50:1, s. 105-109
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the appearance and measurement of Cesarean hysterotomy scar before pregnancy and at 11–14 weeks in a subsequent pregnancy. Methods: This was a prospective cohort study of women aged 18–35 years who had one previous Cesarean delivery (CD) at ≥ 37 weeks. Women were examined with saline contrast sonohysterography 6–9 months after CD. A scar defect was defined as large if scar thickness was ≤ 2.5 mm. Women were followed up and those who became pregnant were examined by transvaginal ultrasound at 11–14 weeks. Scar thickness was measured and scars were classified subjectively as a scar with or without a large defect. A receiver–operating characteristics curve was constructed to determine the best cut-off value for scar thickness to define a large scar defect at the 11–14-week scan. Results: A total of 111 women with a previous CD were scanned in the non-pregnant state and at 11–14 weeks in a subsequent pregnancy. The best cut-off value for scar thickness to define a large scar defect at 11–14 weeks was 2.85 mm, which had 90% sensitivity (18/20), 97% specificity (88/91) and 95% accuracy (106/111). In the non-pregnant state, large scar defects were found in 18 (16%) women and all were confirmed at the 11–14-week scan. In addition, a large defect was found in three women at 11–14 weeks that was not identified in the non-pregnant state. Conclusion: The appearance of the Cesarean hysterotomy scar was similar in the non-pregnant state and at 11–14 weeks in a subsequent pregnancy.
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| 16. |
- Baranov, A., et al.
(författare)
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Validation of prediction model for successful vaginal birth after Cesarean delivery based on sonographic assessment of hysterotomy scar
- 2018
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 51:2, s. 189-193
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To validate a prediction model for successful vaginal birth after Cesarean delivery (VBAC) based on sonographic assessment of the hysterotomy scar, in a Swedish population. Methods: Data were collected from a prospective cohort study. We recruited non-pregnant women aged 18–35 years who had undergone one previous low-transverse Cesarean delivery at ≥ 37 gestational weeks and had had no other uterine surgery. Participants who subsequently became pregnant underwent transvaginal ultrasound examination of the Cesarean hysterotomy scar at 11 + 0 to 13 + 6 and at 19 + 0 to 21 + 6 gestational weeks. Thickness of the myometrium at the thinnest part of the scar area was measured. After delivery, information on pregnancy outcome was retrieved from hospital records. Individual probabilities of successful VBAC were calculated using a previously published model. Predicted individual probabilities were divided into deciles. For each decile, observed VBAC rates were calculated. To assess the accuracy of the prediction model, receiver–operating characteristics curves were constructed and the areas under the curves (AUC) were calculated. Results: Complete sonographic data were available for 120 women. Eighty (67%) women underwent trial of labor after Cesarean delivery (TOLAC) with VBAC occurring in 70 (88%) cases. The scar was visible in all 80 women at the first-trimester scan and in 54 (68%) women at the second-trimester scan. AUC was 0.44 (95% CI, 0.28–0.60) among all women who underwent TOLAC and 0.51 (95% CI, 0.32–0.71) among those with the scar visible sonographically at both ultrasound examinations. Conclusion: The prediction model demonstrated poor accuracy for prediction of successful VBAC in our Swedish population.
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| 21. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 22. |
- Grontvedt, GR, et al.
(författare)
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Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden
- 2022
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:11, s. e2243232-
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Tidskriftsartikel (refereegranskat)abstract
- Identification of proteins and genetic factors that reduce Alzheimer disease (AD) pathology is of importance when searching for novel AD treatments. Heterozygosity of the KL-VS haplotype has been associated with reduced amyloid and tau burden. Whether this association is mediated by the Klotho protein remains unclear.ObjectivesTo assess concentrations of Klotho in cerebrospinal fluid (CSF) and plasma among cognitively healthy controls and patients with AD and to correlate these findings with KL-VS heterozygosity status and amyloid and tau burden.Design, Setting, and ParticipantsThis case-control study combined 2 independent case-control AD cohorts consisting of 243 referred patients with AD and volunteer controls recruited from January 1, 2009, to December 31, 2018. Klotho levels were measured in CSF and plasma and correlated with KL-VS heterozygosity status and levels of CSF amyloid-β 42 (Aβ42), total tau, and phosphorylated tau. Statistical analysis was performed from January 1, 2021, to March 1, 2022.Main Outcomes and MeasuresAssociations of Klotho levels in CSF and plasma with levels of CSF biomarkers were analyzed using linear regression. Association analyses were stratified separately by clinical groups, APOE4 status, and KL-VS heterozygosity. Pearson correlation was used to assess the correlation between CSF and plasma Klotho levels.ResultsA total of 243 participants were included: 117 controls (45 men [38.5%]; median age, 65 years [range, 41-84 years]), 102 patients with mild cognitive impairment due to AD (AD-MCI; 59 men [57.8%]; median age, 66 years [range, 46-80 years]), and 24 patients with dementia due to AD (AD-dementia; 12 men [50.0%]; median age, 64.5 years [range, 54-75 years]). Median CSF Klotho levels were higher in controls (1236.4 pg/mL [range, 20.4-1726.3 pg/mL]; β = 0.103; 95% CI, 0.023-0.183; P = .01) and patients with AD-MCI (1188.1 pg/mL [range, 756.3-1810.3 pg/mL]; β = 0.095; 95% CI, 0.018-0.172; P = .02) compared with patients with AD-dementia (1073.3 pg/mL [range, 698.2-1661.4 pg/mL]). Higher levels of CSF Klotho were associated with lower CSF Aβ42 burden (β = 0.519; 95% CI, 0.201-0.836; P &lt; .001) and tau burden (CSF total tau levels: β = −0.884; 95% CI, 0.223 to −0.395; P &lt; .001; CSF phosphorylated tau levels: β = −0.672; 95% CI, −1.022 to −0.321; P &lt; .001) independent of clinical, KL-VS heterozygosity, or APOE4 status. There was a weak correlation between Klotho CSF and plasma levels among the entire cohort (Pearson correlation r = 0.377; P &lt; .001).Conclusions and RelevanceThe findings of this case-control study suggest that Klotho protein levels were associated with clinical stages of AD, cognitive decline, and amyloid and tau burden and that these outcomes were more clearly mediated by the protein directly rather than the KL-VS heterozygosity variant. When selecting individuals at risk for clinical trials, the Klotho protein level and not only the genetic profile should be considered.
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| 24. |
- Hafström, Maria, 1962, et al.
(författare)
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Boys and girls differ in symptoms and neurodevelopmental outcome after perinatal metabolic acidosis, a population-based study
- 2019
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253. ; 108:8, s. 1427-1433
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Tidskriftsartikel (refereegranskat)abstract
- Aim To evaluate sex differences in infants born at term with metabolic acidosis with regard to perinatal health and symptomatology, and developmental outcome. Methods From a population-based cohort of infants born at term (n = 14 687), 78 were prospectively identified as having metabolic acidosis at birth. Two matched controls per case were selected. Sex differences in perinatal characteristics and in neurodevelopmental outcome at 6.5 years of age were analysed. Subgroup analysis was made based on need of neonatal care and planned follow-up. Results Acidotic boys who appeared healthy, that is with no need of specialised neonatal care respectively only followed at ordinary health care service, have worse perinatal symptoms and less favourable neurodevelopmental outcome compared to girls. The male disadvantage concerning neurodevelopmental outcome was also indicated in children without acidosis. Outcome at 6.5 years was associated with Apgar at 10 minutes (p = 0.03), need of neonatal care (p = 0.04) and sex (p = 0.02) but not acidosis per se (p = 0.54). Conclusion Sex affected immediate symptomatology in term acidotic infants and neurodevelopmental outcome at the age of 6.5 years. The findings were seen in those who appeared healthy in the neonatal period. The results suggest that sex should be considered in assessment of acidotic children.
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| 25. |
- Hara, Sozaburo, et al.
(författare)
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Effect of Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial.
- 2022
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Ingår i: JAMA. - 1538-3598. ; 328:15, s. 1506-1514
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Tidskriftsartikel (refereegranskat)abstract
- The use of spinal cord stimulation for chronic pain after lumbar spine surgery is increasing, yet rigorous evidence of its efficacy is lacking.To investigate the efficacy of spinal cord burst stimulation, which involves the placement of an implantable pulse generator connected to electrodes with leads that travel into the epidural space posterior to the spinal cord dorsal columns, in patients with chronic radiculopathy after surgery for degenerative lumbar spine disorders.This placebo-controlled, crossover, randomized clinical trial in 50 patients was conducted at St Olavs University Hospital in Norway, with study enrollment from September 5, 2018, through April 28, 2021. The date of final follow-up was May 20, 2022.Patients underwent two 3-month periods with spinal cord burst stimulation and two 3-month periods with placebo stimulation in a randomized order. Burst stimulation consisted of closely spaced, high-frequency electrical stimuli delivered to the spinal cord. The stimulus consisted of a 40-Hz burst mode of constant-current stimuli with 4 spikes per burst and an amplitude corresponding to 50% to 70% of the paresthesia perception threshold.The primary outcome was difference in change from baseline in the self-reported Oswestry Disability Index (ODI; range, 0 points [no disability] to 100 points [maximum disability]; the minimal clinically important difference was 10 points) score between periods with burst stimulation and placebo stimulation. The secondary outcomes were leg and back pain, quality of life, physical activity levels, and adverse events.Among 50 patients who were randomized (mean age, 52.2 [SD, 9.9] years; 27 [54%] were women), 47 (94%) had at least 1 follow-up ODI score and 42 (84%) completed all stimulation randomization periods and ODI measurements. The mean ODI score at baseline was 44.7 points and the mean changes in ODI score were -10.6 points for the burst stimulation periods and -9.3 points for the placebo stimulation periods, resulting in a mean between-group difference of -1.3 points (95% CI, -3.9 to 1.3 points; P = .32). None of the prespecified secondary outcomes showed a significant difference. Nine patients (18%) experienced adverse events, including 4 (8%) who required surgical revision of the implanted system.Among patients with chronic radicular pain after lumbar spine surgery, spinal cord burst stimulation, compared with placebo stimulation, after placement of a spinal cord stimulator resulted in no significant difference in the change from baseline in self-reported back pain-related disability.ClinicalTrials.gov Identifier: NCT03546738.
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