| 96301. |
- Berglund, Sofia, et al.
(författare)
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Diagnostic accuracy and safety of short-term teledermoscopic monitoring of atypical melanocytic lesions
- 2020
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 34:6, s. 1233-1239
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short-term dermoscopic monitoring (STDM) of atypical melanocytic lesions (AML) after 3.0–4.5months can be used to detect featureless melanomas without performing countless unnecessary excisions of nevi. Recently, short-term teledermoscopic monitoring (STTM) was incorporated into the STDM clinical routine at Sahlgrenska University Hospital in Gothenburg, Sweden. Follow-up images for STTM were taken by an assistant nurse with subsequent teledermoscopic assessment by a dermatologist. Objectives: The purpose of this study was to evaluate the diagnostic accuracy and safety of STTM. Methods: In this retrospective observational study, data from electronic health records of patients with teledermoscopically monitored AMLs were explored. The number of changed and excised AMLs and their histopathological diagnoses were recorded. The excised AMLs were categorized into three subgroups according to when they changed and were excised: (i) following STTM, (ii) after planned long-term follow-up or (iii) after unplanned long-term follow-up. Results: A total of 686 patients with 883 AMLs were monitored with STTM. Sixty-two AMLs (7.0%) were excised following STTM, 14 (1.6%) after planned long-term follow-up and 10 (1,1%) after unplanned long-term follow-up. Twenty-one melanomas were detected using STTM, three after planned long-term follow-up and three after unplanned long-term follow-up. All melanomas were insitu (n=20) or thin and non-ulcerated (n=7; median Breslow thickness 0.4mm, range 0.3–0.8mm). The sensitivity for the diagnosis of melanoma by means of STTM with the option of additional planned follow-up was 88.9%, and the specificity was 93.9%. The number of AMLs needed to monitor in order to detect one melanoma with the STTM routine was 32.7, and the number needed to excise was 3.2. Conclusions: STTM of AMLs was safe and allowed for high diagnostic accuracy. All detected melanomas were insitu or thin and non-ulcerated. Furthermore, a considerable number of unnecessary excisions were spared. © 2019 European Academy of Dermatology and Venereology
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| 96302. |
- Berglund, Sofia, et al.
(författare)
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Incomplete Excisions of Melanocytic Lesions: Rates and Risk Factors.
- 2021
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057. ; 101:3
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Tidskriftsartikel (refereegranskat)abstract
- Incomplete excisions of melanocytic lesions occur despite the intention of complete removal. The aim of this study was to determine the incomplete excision rates for benign and malignant melanocytic lesions and the associated risk factors. Demographic, clinical, and histo-pathological data possibly associated with incomplete excision were collected from 2,782 consecutive excisions between 2014 and 2015. Of these, 269 melanocytic lesions (9.7%) were incompletely excised. Multivariate analysis revealed the following risk factors for significantly higher incomplete excision rates: lesions located in the head and neck area (odds ratio (OR) 3.95, 95% confidence interval (95% CI) 2.35-6.65), surgery performed by general practitioners (OR 3.01, 95% CI 2.16-4.19), the use of a punch excision technique (OR 2.83, 95% CI 1.96-4.08), and excision of non-dysplastic naevi (OR 1.58, 95% CI 1.11-2.23). In conclusion, more caution should be taken when excising melanocytic lesions in the head and neck area, general practitioners require more surgical training, and punch excisions of melanocytic lesions should be avoided.
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| 96303. |
- Berglund, Staffan K., et al.
(författare)
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The impacts of maternal iron deficiency and being overweight during pregnancy on neurodevelopment of the offspring
- 2017
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 118:7, s. 533-540
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Tidskriftsartikel (refereegranskat)abstract
- Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI >= 25 kg/m(2)) may negatively affect offspring brain development. However, the two risk factors correlate and their independent effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113.3 (SD 9.9) v. 117.1 (SD 9.2), P=0.039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114.0 (SD 9.7) v. 121.5 (SD 10.9), P = 0.039) and lower receptive, expressive and composite (99.5 (SD 8.6) v. 107.6 (SD 8.3), P= 0.004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12.3 (SD 2.0) v. 13.0 (SD 2.1), P = 0.037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women.
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| 96304. |
- Berglund, U. W., et al.
(författare)
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Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
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| 96305. |
- Berglund, Åke, et al.
(författare)
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First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies
- 2015
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Ingår i: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 33:6, s. 1232-1241
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Melflufen (melphalan flufenamide, previously designated J1) is an optimized and targeted derivative of melphalan, hydrolyzed by aminopeptidases overexpressed in tumor cells resulting in selective release and trapping of melphalan, and enhanced activity in preclinical models. Methods This was a prospective, single-armed, open-label, first-in-human, dose-finding phase I/IIa study in 45 adult patients with advanced and progressive solid tumors without standard treatment options. Most common tumor types were ovarian carcinoma (n = 20) and non-small-cell lung cancer (NSCLC, n = 11). Results In the dose-escalating phase I part of the study, seven patients were treated with increasing fixed doses of melflufen (25-130 mg) Q3W. In the subsequent phase IIa part, 38 patients received in total 115 cycles of therapy at doses of 30-75 mg. No dose-limiting toxicities (DLTs) were observed at 25 and 50 mg; at higher doses DLTs were reversible neutropenias and thrombocytopenias, particularly evident in heavily pretreated patients, and the recommended phase II dose (RPTD) was set to 50 mg. Response Evaluation Criteria In Solid Tumors (RECIST) evaluation after 3 cycles of therapy (27 patients) showed partial response in one (ovarian cancer), and stable disease in 18 patients. One NSCLC patient received nine cycles of melflufen and progressed after 7 months of therapy. Conclusions In conclusion, melflufen can safely be given to cancer patients, and the toxicity profile was as expected for alkylating agents; RPTD is 50 mg Q3W. Reversible and manageable bone marrow suppression was identified as a DLT. Clinical activity is suggested in ovarian cancer, but modest activity in treatment of refractory NSCLC.
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| 96306. |
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| 96307. |
- Berglund, Åke, 1961-
(författare)
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Optimisation of Chemotherapy Treatment in Advanced Colorectal Cancer
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer is one of the most common malignant diseases in Sweden – more than 5000 new cases are diagnosed each year. The overall five-year survival is about 60% and in cases of recurrence the prognosis is poor.In a phase III study in advanced colorectal cancer the response rate was doubled when 5-FU was given as a bolus injection versus as a short infusion. The toxicity was similar and time to progression was longer in the injection group. However, overall survival was not significantly different. Dose-effect relationships of 5-FU were studied in another phase III study recruiting 312 patients. A decrease from 500 mg/m2 to 400 mg/m2 worsened the treatment results. A low incidence of severe toxicity was seen in both groups. An increase to 600 mg/m2 worsened the toxicity without any improvement of the results.A cytotoxic drug sensitivity test in different tumour types, mainly gastrointestinal cancer, poorly predicted treatment outcome in a phase II study.The conventional Nordic Flv regimen was split in a phase I/II trial. An escalation of dose was possible and the response rate was 20%.Thymidylate synthase (TS) and the gene expression of p53 were investigated by immunohistochemical technique in the primary tumours of 132 patients. None of the markers predicted the later palliative chemotherapy result. However, TS significantly predicted time to recurrence.Serum markers were analysed before and during FLv treatment to early predict outcomes among 87 patients. TPS is promising, both as a predictive marker before start of treatment and after a short period of treatment. In the same setting, CEA had lower predictive value. S-VEGF and S-bFGF did not yield any prognostic information of later outcome. In all studies B-haemoglobin values, performance status and subjective response were strong markers, both for prediction of objective response and for survival.
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| 96308. |
- Berglundh, Sofia, et al.
(författare)
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Maternal caffeine intake during pregnancy and child neurodevelopment up to eight years of age-Results from the Norwegian Mother, Father and Child Cohort Study.
- 2021
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Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 60:2, s. 791-805
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Tidskriftsartikel (refereegranskat)abstract
- Current knowledge of the effect of prenatal caffeine exposure on the child's neurodevelopment is contradictory. The current study aimed to study whether caffeine intake during pregnancy was associated with impaired child neurodevelopment up to 8years of age.A total of 64,189 full term pregnancies from the Norwegian Mother, Father and Child Cohort Study were included. A validated food-frequency questionnaire administered at gestational week 22 was used to obtain information on maternal caffeine intake from different sources. To assess child neurodevelopment (behaviour, temperament, motor development, language difficulties) validated scales were used to identify difficulties within each domain at 6, 18, 36months as well as 5 and 8years of age. Adjusted logistic regression models and mixed linear models were used to evaluate neurodevelopmental problems associated with maternal caffeine intake.Prenatal caffeine exposure was not associated with a persistently increased risk for behaviour, temperament, motor or language problems in children born at full-term. Results were consistent throughout all follow-ups and for different sources of caffeine intake. There was a minor trend towards an association between consumption of caffeinated soft drinks and high activity level, but this association was not driven by caffeine.Low to moderate caffeine consumption during pregnancy was not associated with any persistent adverse effects concerning the child's neurodevelopment up to 8years of age. However, a few previous studies indicate an association between high caffeine consumption and negative neurodevelopment outcomes.
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| 96309. |
- Bergman, Annika, et al.
(författare)
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A high frequency of germline BRCA1/2 mutations in western Sweden detected with complementary screening techniques
- 2005
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Ingår i: Familial Cancer. - : Springer. - 1389-9600 .- 1573-7292. ; 4:2, s. 89-96
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Tidskriftsartikel (refereegranskat)abstract
- Dominant inheritance is presumed in 6-10% of breast and ovarian cancers. Mutations in BRCA1 and BRCA2 genes are the most commonly identified causative genes in such families. The frequency of mutation carriers with breast/ovarian cancer depends on the population studied, and display considerable variation that coincides with ethnic and geographical diversity. Mutation analyses were performed in 143 families registered at the Cancer Genetic Counseling Clinic of western Sweden. In a thorough mutation screening procedure, the entire BRCA1 and BRCA2 genes were analyzed using a combination of complementary mutation detection techniques. Mutations in either BRCA1 or BRCA2 were detected in 36% (52 out of 143) of all screened families. All families were clinically evaluated regarding age at diagnosis, type of cancer and number of cancer cases in the family. Among high-risk families, the mutation detection rate was 39% (46 out of 117). The detection rate observed among families with cases of ovarian cancer (42 out of 62, 68%), was substantially higher than in families with only breast cancer (10 out of 81, 12%). Age at ovarian cancer did not seem to have an effect on the detection rate. The analyses revealed 11 frameshift mutations, 4 nonsense mutations and 2 large deletions. Notably, the BRCA1 c.3171ins5 mutation accounted for 34 of 52 (65%) identified mutations. Seven mutations are novel: BRCA1c.409_410del; c.1912T>G; c.2228_2229del; c.3029delA; c.3433delA, a large deletion covering exons 1-3 of BRCA1and one BRCA2 mutation; BRCA2c.6287_6290del. We have shown that the founder mutation BRCA1 c.3171ins5 has a great influence on western Swedish breast/ovarian cancer families along with a high number of mutations unique for the region. In order to achieve a high mutation detection rate we suggest a combination of several detection techniques.
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| 96310. |
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