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Suhr, Ole B.
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Publications (10 of 152) Show all publications
Wange, N., Anan, I., Ericzon, B.-G., Pennlert, J., Pilebro, B., Suhr, O. B. & Wixner, J. (2018). Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients. Transplantation, 102(2), e59-e66
Open this publication in new window or tab >>Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients
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2018 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 102, no 2, p. e59-e66Article in journal (Refereed) Published
Abstract [en]

Background. Central nervous system (CNS) complications are increasingly noted in liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis patients; this suggests that the increased survival allows for intracranial ATTRm formation from brain synthesized mutant TTR. However, atrial fibrillation (AF), a recognised risk factor for ischemic CNS complications, is also observed after LTx. The aim of the study was to investigate the occurrence of CNS complications and AF in LTx ATTRm amyloidosis patients. Methods. The medical records of all LTx ATTRm amyloidosis patients in the county of Vasterbotten, Sweden, were investigated for information on CNS complications, AF, anticoagulation (AC) therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological status. Results. Sixty-three patients that had survived for 3 years or longer after LTx were included in the analysis. Twenty-five patients had developed 1 or more CNS complications at a median of 21 years after onset of disease. AF was noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events (CVE) developed in 17 (median time to event 21 years). CVEs occurred significantly more often in patients with AF (P < 0.002). AC therapy significantly reduced CVEs, including bleeding in patients with AF (P = 0.04). Multivariate analysis identified AF as the only remaining regressor with a significant impact on CVE (hazard ratio, 3.8; 95% confidence interval 1.1-9.5; P = 0.029). Conclusions. AF is an important risk factor for CVE in LTx ATTRm amyloidosis patients, and AC therapy should be considered. However, the increased bleeding risk with AC therapy in patients with intracranial amyloidosis should be acknowledged.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-144941 (URN)10.1097/TP.0000000000001975 (DOI)000424093400004 ()29019809 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-06-09Bibliographically approved
Wixner, J., Suhr, O. B. & Anan, I. (2018). Management of gastrointestinal complications in hereditary transthyretin amyloidosis: a single-center experience over 40 years. Expert Review of Gastroenterology & Hepatology, 12(1), 73-81
Open this publication in new window or tab >>Management of gastrointestinal complications in hereditary transthyretin amyloidosis: a single-center experience over 40 years
2018 (English)In: Expert Review of Gastroenterology & Hepatology, ISSN 1747-4124, E-ISSN 1747-4132, Vol. 12, no 1, p. 73-81Article, review/survey (Refereed) Published
Abstract [en]

Introduction: Hereditary transthyretin amyloidosis (ATTRm amyloidosis) is a rare disease caused by the deposition and accumulation of insoluble non-native transthyretin fibrils in the body. The disease inevitably results in widespread organ disruption, and poor life expectancy. The GI tract is one organ system vulnerable to disruption and, although the clinical presentation of the disease varies, GI involvement affects most patients with ATTRm amyloidosis.

Areas covered: This article presents our experience with diagnosing and treating the GI symptoms of ATTRm amyloidosis patients at our center over the last 40 years, in the Swedish clustering area of the disease. Our aim is to help other physicians to better manage GI complications in patients with this rare but widespread condition.

Expert commentary: GI symptoms are debilitating complications for ATTRm amyloidosis patients to experience, yet with the appropriate questioning and diagnosis methods, symptomatic treatments of these symptoms can be implemented to provide relief. Further, patients with fewer GI complications and a good nutritional status are also better candidates for liver transplantation which, in selected cases, is the best disease-modifying treatment of ATTRm amyloidosis to date.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
amyloidosis, familial amyloid neuropathy, gastric emptying, gastrointestinal tract, liver, therapeutics, ansthyretin
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-146467 (URN)10.1080/17474124.2018.1397511 (DOI)000427553900008 ()29073801 (PubMedID)
Available from: 2018-04-10 Created: 2018-04-10 Last updated: 2018-06-09Bibliographically approved
Wiklund, U., Kadkhodaee, A., Andersson, K., Suhr, O. B. & Hörnsten, R. (2018). Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis. Amyloid: Journal of Protein Folding Disorders, 25(1), 54-61
Open this publication in new window or tab >>Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis
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2018 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 1, p. 54-61Article in journal (Refereed) Published
Abstract [en]

Background: The heart rate (HR) response to paced deep breathing (DB) is a common test of cardiac autonomic function, where high heart rate variability (HRV) is considered to reflect normal autonomic function. We evaluated the DB test in patients with hereditary transthyretin amyloid (ATTRm) amyloidosis, where autonomic dysregulation and atrial arrhythmias are common.Methods: Paced DB was performed during one minute (six breaths/min) in 165 recordings in adult ATTRm amyloidosis patients with the TTR Val30Met mutation, 42 hypertrophic cardiomyopathy (HCM) patients and 211 healthy subjects. HRV was scored by traditional DB indices and by a novel regularity index, estimating the fraction of the HRV that was coherent with the breathing pattern.Results: Twenty per cent of ATTRm amyloidosis patients presented with age-adjusted HRV scores within normal limits but poor regularity due to subtle atrial arrhythmias and cardiac conduction disturbances. Forty-seven per cent of ATTRm amyloidosis patients presented with HRV scores below normal limits, whereas HCM patients presented with higher HRV than ATTRm amyloidosis patients.Conclusions: Reduced HRV is common in ATTRm amyloidosis patients during DB, however, autonomic function cannot be evaluated in patients presenting with the combination of normal scores and low regularity, since their HR responses often reflects dysrhythmias.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2018
Keywords
HRV, heart rate variability, amyloidosis hereditary, transthyretin, autonomic function
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-146594 (URN)10.1080/13506129.2018.1434140 (DOI)000428570300008 ()29394116 (PubMedID)
Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-06-09Bibliographically approved
Adams, D., Gonzalez-Duarte, A., O'Riordan, W. D., Yang, C.-C. -., Ueda, M., Kristen, A. V., . . . Suhr, O. B. (2018). Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. New England Journal of Medicine, 379(1), 11-21
Open this publication in new window or tab >>Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
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2018 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 379, no 1, p. 11-21Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.

METHODS: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters] x albumin level in grams per liter; lower values indicated worse nutritional status).

RESULTS: A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (+/- SD) mNIS+7 at baseline was 80.9 +/- 41.5 in the patisiran group and 74.6 +/- 37.0 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.0 +/- 1.7 versus 28.0 +/- 2.6 (difference, -34.0 points; P<0.001) at 18 months. The mean (+/- SD) baseline Norfolk QOL-DN score was 59.6 +/- 28.2 in the patisiran group and 55.5 +/- 24.3 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.7 +/- 1.8 versus 14.4 +/- 2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08 +/- 0.02 m per second with patisiran versus -0.24 +/- 0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7 +/- 9.6 versus -119.4 +/- 14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups.

CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis.

Place, publisher, year, edition, pages
Massachusetts Medical Society, 2018
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-150728 (URN)10.1056/NEJMoa1716153 (DOI)000437254200005 ()29972753 (PubMedID)2-s2.0-85049655756 (Scopus ID)
Available from: 2018-08-28 Created: 2018-08-28 Last updated: 2018-08-28Bibliographically approved
Pilebro, B., Arvidsson, S., Lindqvist, P., Sundström, T., Westermark, P., Antoni, G., . . . Sörensen, J. (2018). Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR). Journal of Nuclear Cardiology, 25(1), 240-248
Open this publication in new window or tab >>Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR)
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2018 (English)In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 25, no 1, p. 240-248Article in journal (Refereed) Published
Abstract [en]

Background: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing 11C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer’s disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis.

Methods: Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers.

Results: PIB-RI was increased in all patients (P < 0.001), but was significantly higher in type B than in type A (0.129 ± 0.041 vs 0.040 ± 0.006 min−1, P = 0.009). Cardiac DPD uptake was elevated in group A and absent in group B.

Conclusion: PIB-PET, in contrast to DPD scintigraphy, has the potential to specifically identify cardiac amyloid depositions irrespective of amyloid fibril composition. The heart appears to be a target organ for amyloid deposition in ATTR amyloidosis.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Cardiomyopathy, amyloidosis, Pittsburgh compound B
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-127300 (URN)10.1007/s12350-016-0638-5 (DOI)000423585200038 ()27645889 (PubMedID)2-s2.0-84988421982 (Scopus ID)
Available from: 2016-11-07 Created: 2016-11-07 Last updated: 2018-06-09Bibliographically approved
Henein, M. Y., Suhr, O. B., Arvidsson, S., Pilebro, B., Westermark, P., Hörnsten, R. & Lindqvist, P. (2018). Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis. Amyloid: Journal of Protein Folding Disorders, 25(1), 46-53
Open this publication in new window or tab >>Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis
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2018 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 1, p. 46-53Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement.

OBJECTIVES: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR).

METHODS: Forty-six patients with confirmed ATTR amyloidosis on abdominal biopsy were studied. Assessment with 2D echocardiography and 2D strain showed 31 patients had increased LV wall thickness (LVWT) (septal thickness >12 mm), and 15 had normal LVWT. In addition to conventional measurements, LV and LA global longitudinal strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done to assess fibril type. ATTR patients with increased LVWT were compared with 23 patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR amyloidosis patients also underwent 24 hour Holter monitoring to determine the presence of atrial arrhythmia.

RESULTS: Atrial deformation during atrial systole was reduced in ATTR amyloidosis patients with increased LVWT independent of LA size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had ECG evidence of significant atrial arrhythmic events. LA strain rate, during atrial systole, was the only independent predictor of atrial arrhythmia (β = 3.28, p = .012).

CONCLUSION: In ATTR cardiomyopathy with increased LVWT, LA myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA myocardial SR during atrial systole, irrespective of cavity volume, E/e' and LV deformation, is also a strong predictor for atrial arrhythmic events.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Arrhythmia, Holter ECG, deformation echocardiography, left atrial function
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-145431 (URN)10.1080/13506129.2018.1430027 (DOI)000428570300007 ()29369708 (PubMedID)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-08-07Bibliographically approved
Westermark, P., Nowak, G., Suhr, O. B. & Ericzon, B.-G. (2017). Domino liver transplantation: full-length transthyretin in donor and recipient patients with ATTR Val30Met amyloidosis. Paper presented at 15th International Symposium on Amyloidosis, JUL 03-07, 2016, Uppsala, SWEDEN. Amyloid: Journal of Protein Folding Disorders, 24, 128-129
Open this publication in new window or tab >>Domino liver transplantation: full-length transthyretin in donor and recipient patients with ATTR Val30Met amyloidosis
2017 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, p. 128-129Article in journal, Meeting abstract (Refereed) Published
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-135292 (URN)10.1080/13506129.2017.1294058 (DOI)000399943700070 ()28434334 (PubMedID)
Conference
15th International Symposium on Amyloidosis, JUL 03-07, 2016, Uppsala, SWEDEN
Available from: 2017-05-24 Created: 2017-05-24 Last updated: 2018-06-09Bibliographically approved
Polydefkis, M., Ebenezer, G., Adams, D., Coelho, T., Conceicao, I., Waddington Cruz, M., . . . Suhr, O. (2017). EFFECT OF PATISIRAN ON NERVE FIBER DENSITY AND AMYLOID CONTENT IN SKIN: RESULTS FROM PHASE 2 OPEN LABEL EXTENSION (OLE) STUDY IN HATTR AMYLOIDOSIS. Paper presented at Peripheral-Nerve-Society Meeting, JUL 08-12, 2017, Sitges, SPAIN. Journal of the peripheral nervous system, 22(3), 360-360
Open this publication in new window or tab >>EFFECT OF PATISIRAN ON NERVE FIBER DENSITY AND AMYLOID CONTENT IN SKIN: RESULTS FROM PHASE 2 OPEN LABEL EXTENSION (OLE) STUDY IN HATTR AMYLOIDOSIS
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2017 (English)In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 22, no 3, p. 360-360Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-140054 (URN)000409243500336 ()
Conference
Peripheral-Nerve-Society Meeting, JUL 08-12, 2017, Sitges, SPAIN
Available from: 2018-01-04 Created: 2018-01-04 Last updated: 2018-06-09Bibliographically approved
Kristen, A. V., Maurer, M. S., Rapezzi, C., Mundayat, R., Suhr, O. B. & Damy, T. (2017). Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS). PLoS ONE, 12(4), Article ID e0173086.
Open this publication in new window or tab >>Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0173086Article in journal (Refereed) Published
Abstract [en]

Aim: Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking.

Methods and results: Patients (n = 1617) with any of the following cardiac biomarkers, BNP (n = 1079), NT-proBNP (n = 550), troponin T (n = 274), and troponin I (n = 108), available at baseline in the Transthyretin Amyloidosis Outcomes Survey (THAOS) were analyzed for differences between genotypes and phenotypes and their association with survival. Median level of BNP was 68.0 pg/mL (IQR 30.5–194.9), NT-proBNP 337.9 pg/mL (IQR 73.0–2584.0), troponin T 0.03 μg/L (IQR 0.01–0.05), and troponin I 0.08 μg/L (IQR 0.04–0.13). NT-proBNP and BNP were higher in wild-type than mutant-type ATTR, troponin T and I did not differ, respectively. Non-Val30Met patients had higher BNP, NT-proBNP and troponin T levels than Val30Met patients, but not troponin I. Late-onset Val30Met was associated with higher levels of troponin I and troponin T compared with early-onset. 115 patients died during a median follow-up of 1.2 years. Mortality increased with increasing quartiles (BNP/NT-proBNP Q1 = 1.7%, Q2 = 5.2%, Q3 = 21.7%, Q4 = 71.3%; troponin T/I Q1 = 6.5%, Q2 = 14.5%, Q3 = 33.9%, Q4 = 45.2%). Three-year overall-survival estimates for BNP/NT-proBNP and troponin T/I quartiles differed significantly (p<0.001). Stepwise risk stratification was achieved by combining NT-proBNP/BNP and troponin T/I. From Cox proportional hazards model, age, modified body mass index, mutation (Val30Met vs. Non-Val30Met) and BNP/NT-proBNP (Q1–Q3 pooled vs. Q4) were identified as independent predictors of survival in patients with mutant-type ATTR.

Conclusions: In this ATTR patient cohort, cardiac biomarkers were abnormal in a substantial percentage of patients irrespective of genotype. Along with age, mBMI, and mutation (Val30Met vs. Non-Val30Met), cardiac biomarkers were associated with surrogates of disease severity with BNP/NT-proBNP identified as an independent predictor of survival in ATTR.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-135285 (URN)10.1371/journal.pone.0173086 (DOI)000399371900005 ()28384285 (PubMedID)
Available from: 2017-05-24 Created: 2017-05-24 Last updated: 2018-06-09Bibliographically approved
Suhr, O. B., Lundgren, E. & Westermark, P. (2017). One mutation, two distinct disease variants: unravelling the impact of transthyretin amyloid fibril composition. Journal of Internal Medicine, 281(4), 337-347
Open this publication in new window or tab >>One mutation, two distinct disease variants: unravelling the impact of transthyretin amyloid fibril composition
2017 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 4, p. 337-347Article, review/survey (Refereed) Published
Abstract [en]

Although hereditary transthyretin (h-ATTR) amyloidosis is a monogenetic disease, a large variation in its phenotype has been observed. The common hypothesis of amyloid fibril formation involves dissociation of the transthyretin (TTR) tetramer into monomers that after misfolding reassemble into amyloid fibrils. This notion is partly challenged by the finding of two distinct types of amyloid fibrils. One of these, type A, consists of C-terminal ATTR fragments and full-length TTR, whereas the other, type B, consists only of full-length TTR. All organs of an individual patient contain ATTR deposits of either type A or type B fibrils, and the composition in each individual remains unchanged over time. The finding of two distinct types of ATTR fibrils suggests that there are at least two different pathways in operation for ATTR fibril formation. For the most common European mutation, TTR Val30Met, ATTR fibril composition is related to the outcome of liver transplantation, which is the first successful treatment for the disease, and the penetrance of the trait. In addition, the presence of C-terminal ATTR fragments has an impact on the affinity for various tracers used for noninvasive imaging of amyloid depositions such as 99 m-technetium-diphosphono-propanodicarboxylic acid scintigraphy and positron emission tomography utilizing Pittsburgh component B, and even for the gold standard diagnostic procedure, tissue biopsy stained by Congo red and examined under polarized light. The importance of amyloid fibril composition needs to be taken into consideration when designing clinical trials of treatment modalities, and also in the evaluation of diagnostic methods such as imaging techniques.

Keywords
amyloid cardiac hypertrophy, amyloid neuropathy, familial amyloidosis, pathology, therapeutics
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Clinical Laboratory Medicine
Identifiers
urn:nbn:se:umu:diva-131030 (URN)10.1111/joim.12585 (DOI)000397490100002 ()28093848 (PubMedID)
Available from: 2017-02-02 Created: 2017-02-02 Last updated: 2018-06-09Bibliographically approved
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