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1.
  • Pottel, Hans, et al. (författare)
  • Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex
  • 2023
  • Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 388:4, s. 333-343
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUNDThe accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C–based EKFC equation would increase the accuracy of estimated GFR is unknown.METHODSWe used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.RESULTSOn the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83+0.005×(age–50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.CONCLUSIONSThe EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations.
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2.
  • Pottel, Hans, et al. (författare)
  • Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex
  • 2023
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 388:4, s. 333-343
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C–based EKFC equation would increase the accuracy of estimated GFR is unknown.MethodsWe used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.ResultsOn the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83+0.005×(age–50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.ConclusionsThe EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.)
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3.
  • Silins, Isabella, 1983-, et al. (författare)
  • First-in-human evaluation of [18F]CETO : a novel tracer for adrenocortical tumours
  • 2023
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Nature. - 1619-7070 .- 1619-7089. ; 50:2, s. 398-409
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose[11C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [11C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[18F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[18F]fluoroethyletomidate positron emission computed tomography ([18F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers.MethodsFifteen patients underwent [18F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [15O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [18F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis.ResultsUptake of [18F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [18F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K1. Both K1 and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K1, SUV65–70, and SUV120 were 25, 22, and 17%.ConclusionsHigh adrenal uptake combined with a low unspecific liver uptake suggests that 18F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate Ki.Trial registrationClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083
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4.
  • Calissendorff, Jan, et al. (författare)
  • Adrenal cysts : an emerging condition.
  • 2023
  • Ingår i: Nature Reviews Endocrinology. - : Springer Nature. - 1759-5029 .- 1759-5037. ; 19, s. 398-406
  • Tidskriftsartikel (refereegranskat)abstract
    • Adrenal cysts are rare lesions representing approximately 1-2% of adrenal incidentalomas. The majority of these rare lesions are benign. Rarely, phaeochromocytomas and adrenal malignant masses can present as cystic lesions and can occasionally be difficult to distinguish from benign cysts. Histologically, adrenal cysts are subdivided into pseudocysts, endothelial cysts, epithelial cysts and parasitic cysts. The radiological appearance of an adrenal cyst is generally similar to that of cysts in the kidney. They are thus well demarcated, usually rounded, with a thin wall and homogenous internal structure, low attenuating (<20 Hounsfield Units) on CT, low signalling on T1-weighted MRI sequences and high signalling on T2-weighted MRI sequences, and anechoic or hypoechoic on ultrasonography. Benign adrenal cysts have a slight female predominance and are usually diagnosed between the ages of 40 and 60. Most adrenal cysts are asymptomatic and are detected incidentally, although very large adrenal cysts can lead to mass effect symptoms, with surgery required to alleviate the symptoms. Thus, conservative management is usually recommended for asymptomatic cysts. However, when uncertainty exists regarding the benign nature of the cyst, additional work-up or follow-up is needed. The management of an adrenal cyst should preferably be discussed at an adrenal multidisciplinary team meeting.
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5.
  • Dam, Gitte, et al. (författare)
  • Nordic 2023 guidelines for the diagnosis and treatment of lung neuroendocrine neoplasms.
  • 2023
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 62:5, s. 431-437
  • Tidskriftsartikel (refereegranskat)abstract
    • Lung neuroendocrine neoplasms (NEN) are a heterogeneous population of neoplasms with different pathology, clinical behavior, and prognosis compared to the more common lung cancers. The diagnostic work-up and treatment of patients with lung- NEN has undergone major recent advances and new methods are currently being introduced into the clinic. These Nordic guidelines summarize and update the Nordic Neuroendocrine Tumor Group's current view on how to diagnose and treat lung NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients. This review reflects our view of the current state of the art of diagnosis and treatment of patients with lung-NEN. Small cell lung carcinoma (SCLC) is not included in these guidelines.
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6.
  • Dogra, Prerna, et al. (författare)
  • Rare benign adrenal lesions
  • 2023
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press. - 0804-4643 .- 1479-683X. ; 188:4, s. 407-420
  • Tidskriftsartikel (refereegranskat)abstract
    • While most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.
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7.
  • Edfeldt, Katarina, 1979-, et al. (författare)
  • Improved health‐related quality of life during peptide receptor radionuclide therapy in patients with neuroendocrine tumours
  • 2023
  • Ingår i: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 35:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroendocrine tumours (NETs) can arise in different locations in the body, and may give rise to hormonal symptoms, which amongst other factors may affect patients' health-related quality of life (HRQoL). Up to four cycles of peptide receptor radionuclide therapy (PRRT) have been shown effective for symptom alleviation and prolonging progression-free survival. The aim of this study was to assess the patient's perspective regarding changes in their HRQoL during PRRT. HRQoL was assessed using the questionnaires for cancer in general, EORTC QLQ-C30, and the gastrointestinal NET-specifically EORTC QLQ-GINET21. Patients with NET (n = 204) rated their HRQoL before PRRT cycles one and four. The medical records of patients were reviewed and their HRQoL was compared to a matched reference population (n = 4910). HRQoL was found to improve during PRRT in aspects of global quality of life; role, social, and emotional functioning, and multiple symptom relief. Potential risk groups for worse HRQoL during PRRT were patients with overweight (BMI >25) who completed four cycles of PRRT and older patients (>65 years old). In conclusion, we found that PRRT improves HRQoL in patients with NETs. The results of this study may be used to improve person-centred care.
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8.
  • Jahn, Ulrika, et al. (författare)
  • Impact of administered amount of peptide on tumor dosimetry at the first cycle of peptide receptor radionuclide therapy (PRRT) in relation to total tumor somatostatin receptor expression
  • 2023
  • Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 13:1, s. 45-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe accumulation of 177Lu-DOTATATE might be influenced by the amount of administered peptide in relation to the tumor somatostatin receptor expression. The effect of the administered peptide mass on the resulting absorbed dose in tumors and normal organs has not previously been assessed in relation to the patients’ tumor load.MethodPatients with small intestinal (n = 141) and pancreatic (n = 62) neuroendocrine tumors (NETs) who underwent PRRT were selected for retrospective evaluation. All patients had received 7.4 GBq 177Lu-DOTATATE, and the amount of administered peptide in the preparation varied from 93 to 456 µg. The absorbed dose in tumors and normal tissue at the first PRRT cycle was calculated, based on SPECT-measurements at day 1, 4, and 7 post-infusion. The total tumor somatostatin receptor expression (tTSSTRE) was calculated on SPECT after 24 h by multiplying the functional tumor volume, delineated by 42% cut-off VOIs of the highest activity, with the SUVmean for the respective tumor VOIs. Spearman’s rank correlation analyzed any relationship between the administered amount of peptide and the absorbed dose in tumors and normal organs, in relation to the patients’ tTSSTRE.ResultsThere was no correlation between the amount of peptide and any of the tested parameters in relation to tTSSTRE.ConclusionIn this retrospective analysis, no correlation between the amount of administered peptide in the 177Lu-DOTATATE preparation and the absorbed radiation doses in tumors and normal tissues was demonstrated in relation to the total tumor SSTR expression.
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9.
  • Jahn, Ulrika (författare)
  • Peptide Receptor Radionuclide Therapy in Neuroendocrine Neoplasms : Aspects of tumour characteristics, receptor recycling and peptide mass
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Neuroendocrine neoplasm (NEN) can arise in any part of the body, but most commonly in the lungs, bronchi, and the gastrointestinal tract including the pancreas. They combine neuroendocrine and tissue-of-origin-specific characteristics; explaining different symptoms depending on the organ of origin. NEN is divided into slow-growing neuroendocrine tumours (NETs) and the rarer aggressive neuroendocrine cancers (NECs). Some hormone producing NETs give rise to symptoms (functioning), generally detected earlier than the non-functioning NETs, which often are larger and metastatic at diagnosis. NETs commonly express an abundance of somatostatin receptors (SSTR). Synthetic copies of somatostatin (somatostatin analogues, SSA), supress hormonal symptoms such as diarrhoea and flush. The SSA-SSTR ligand-receptor complex interaction instantly internalises into the cells, separate, and the SSTR re-surface. Gallium-68 (68Ga)-labelled SSAs are used for PET/CT-camera visualisation of NETs, and SSA labelled with a therapeutic radionuclide, provide a means for internal radio-therapy, peptide receptor radionuclide therapy (PRRT).The aim of the thesis was to compare the tumour response to PRRT in small intestinal NET (SI-NET) and pancreatic NET (P-NET). Study I, II and IV are retrospective and include patients who underwent PRRT with 177Lu-DOTA-TATE at the Uppsala University Hospital. Study I, quantified and related the radiation dose in 25 SI-NETs to tumour shrinkage using two- and three-dimensional measurements, although no dose-response relationship was demonstrated. A relationship between tumour shrinkage and the total administered activity was however found. Study II compared the tumour response between SI-NETs from study I with P-NETs included in an earlier report, now re-evaluated by adding more tumour parameters, and with longer observation time. There radiation dose in P-NETs was the same as in SI-NETs. The radiation dose in P-NETs was highest at the first PRRT cycles, and then decreased significantly in consecutive cycles, which was not observed in SI-NETs.The prospective study III, mapped the recirculation time of SSTR in SI-NETs and normal organs. Twelve tumours were measured at repeated 68Ga-DOTA-SSA-PET examinations. Larger tumours (>4 cm) showed a faster SSTR turn-over rate than small tumours, demonstrating a turnover resembling that in the normal organs. These results open the possibility that pre-treatment could protect normal tissues during PRRT, and probably increase radioactivity tumour uptake and hence, the radiation dose.The retrospective study IV investigated the effects of various amounts of SSA delivered in the PRRT preparation, although the absorbed radiation dose to tumours and normal tissues, was unrelated to the amount of peptide and to the patient’s total tumour burden.  
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10.
  • Muth, Andreas, et al. (författare)
  • [Many adrenal incidentalomas are not adequately evaluated - updated guidelines to improve follow-up are presented].
  • 2023
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 120
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of cross-sectional imaging in Sweden has increased more than twofold in the last 20 years. Inadvertently discovered adrenal lesions, adrenal incidentalomas, are reported in about one per cent of abdominal investigations. The first Swedish guidelines for the management of adrenal incidentalomas were published in 1996 and have since then been regularly revised. Still, data indicate that less than half of patients receive adequate follow-up. Here we comment on the newly updated guidelines and briefly review the recommended clinical and radiological work-up.
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