Intramed

Faculty of Medicine's internal website

Menu

Half Time Reviews - the Department of Translational Medicine

2022

 

Januari

 

Linnea Ekman

28 januari, klockan 9
Projekt: ”Peripheral neuropathy in diabetes – methods for detecting large and small nerve fiber neuropathy”
Lokal: Handkirurgens bibliotek, Jan Waldenströms gata 5, Sus Malmö
Huvudhandledare: Lars Dahlin
Bihandledare: Elisabet Englund, Eero Lindholm och Elisabeth Brogren
Opponenter: Andreas Arvidsson och Sven Karlsson

 

Abstract

Background
Peripheral neuropathy is a frequent long-term complication in diabetes mellitus, affecting up to 50 % of all people with type 2 diabetes mellitus. It affects both myelinated and non-myelinated nerve fibers, among which small non-myelinated nerve fibers are reported to be the first to be affected. Dysfunction of nerve fibers can be evaluated by a number of methods but novel screening methods are needed. 

Vibration perception thresholds (VPTs), i.e. the lowest vibrational intensity possible to perceive at a particular frequency, are known to be impaired at an early stage in different neuropathies. However, normative values for VPTs investigated through multi-frequency vibrometry is lacking. Another novel method for investigation of small nerve fiber dysfunction is the assessment of intraepidermal nerve fiber density (IENFD) in skin biopsies. Normative values for IENFD are only available from smaller populations and for more complex methodologies. 

Aim and methods
The aim of this thesis is to constitute normative values of VPTs and IENFD, as well as to investigate the potential affecting factors. Additionally, it aims to investigate the clinical implication of both methods in patients with type 1 and 2 diabetes in order to achieve a greater knowledge on the effect of diabetes on the peripheral nervous system. 

Preliminary results
In paper I, I present a reference material of VPT values investigated through multi-frequency vibrometry in 913 healthy adults. The results suggest that VPTs are mainly affected by age, but also skin temperature and height influence VPTs to some extent. In paper IV, I investigated the temporal trend of IENFD in healthy people and patients with type 2 diabetes. IENFD was reduced over time for both groups and although healthy subjects had significantly higher levels at baseline, IENFD was equally low for the two groups at follow-up. These results indicate an earlier decline in IENFD in patients with diabetes but also a significant effect of ageing, regardless of health status. 

Importance
Since treatment for peripheral neuropathy is lacking, it is of great clinical importance to detect early changes of neuropathy and enable proactive care. Examination of VPTs or IENFDs are potential future diagnostic tools to be used in a clinical practice. 

Published articles
Ekman L, Lindholm E, Brogren E, Dahlin LB. Normative values of the vibration perception thresholds at finger pulps and metatarsal heads in healthy adults. PLoS One. 2021;16(4):e0249461. 

Ekman L, Pourhamidi K, Englund E, Lagali N, Rolandsson O, Dahlin LB. Temporal trend of small nerve fibre degeneration in people with and without type 2 diabetes mellitus. Diabet Med. 2021;00:e14691. 


2021

 

Oktober 


Juni

 

Anni Gålne

8 juni, klockan 13
Projekt: "Quantification of 68Ga-DOTA-TATE/TOC uptake in neuroendocrine tumors on PET-CT images"
Via Zoom: https://lu-se.zoom.us/j/65933282994
Handledare: Elin Trägårdh
Granskare: Sigrid Leige Svegborn, docent LU, och Anders Sundin, professor, Uppsala universitet

 

Abstract

Background
Patients with neuroendocrine tumors (NETs) do oftenhave metastasized disease at diagnosis, but the tumors can be indolent andpatients can survive for long. Quantification of tumors measured on positronemitting tomography – computed tomography (PET-CT) is of value both during thediagnostic work-up, during follow-up and when evaluating treatments. The overallaim of this thesis is to increase the knowledge about the uptake of 68Ga-DOTA-TATE/TOCin NETs and to develop an automatic method for quantification of NETs withartificial intelligence (AI). 

Aims and Methods
The aim of the first study was to evaluate iflong-acting somatostatin analog (LA-SSA) treatment changes the uptake of 68Ga-DOTA-TATEin patients with NETs. The effect of LA-SSA on 68Ga-DOTA-TATE uptakein tumors and normal liver tissue was evaluated in a clinical trial - Gapetto -designed as a prospective observational study. The aim of the second study wasto evaluate if total tumor burden manually segmented on PET-CT images, correlatedto health related quality of life (HRQoL), in a cohort of patients with metastasized gastroenteropancreaticNETs. Analysis of data is ongoing. The aim of the third study is to develop amethod with AI to detect and quantify tumor burden. Manual segmentations oftumors will be used for training of AI-networks and thereafter evaluated. This studyis ongoing. The aim of the fourth study is to evaluate the method developed inthe third study, this study has not started.

Preliminary results
No significantchanges were seen in the uptake in tumor lesions, but significant lower uptakein normal liver tissue after treatment initiation with LA-SSA. No significantcorrelations were found between total tumor burden and HRQoL.

Significance
Treatment with LA-SSA does not change the uptake intumor lesions, but decreases the uptake in normal liver tissue. These findings areimportant when interpreting 68Ga-DOTA-TATE PET-CT images and forguidelines regarding discontinuation of treatment before PET-CT scan. HRQoLdoes not seem to be correlated with the magnitude of the tumor burden, which isof importance when treating a patient. An automatic method for quantificationof tumors can save time when interpreting images and potentially provide moreinformation from the images.

Published papers
Gålne A,Almquist H, Almquist M, et al. A Prospective Observational Study to Evaluatethe Effects of Long-Acting Somatostatin Analogs on 68Ga-DOTATATEUptake in Patients with Neuroendocrine Tumors. J Nucl Med.2019;60(12):1717-1723


Oskar Olsson

1 juni, klockan 13
Projekt: "Immune pathogenesis of active tuberculosis in HIV infection"
Lokal: Belfragesalen på plan 6, Infektionskliniken Sus Malmö, Ruth Lundskogs Gata 3
Via Zoom: https://lu-se.zoom.us/j/64555539466
Supervisors: Per Björman, Professor, Clincal Infection Medicine, Department of Translational Medicine, Lund University, and Marianne Jansson, Associate professor, Division of Medical Microbiology, Department of Laboratory Medicine, Lund University
External reviewers: Maria Lerm, Professor, Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, and Adam Linder, Associate professor, Infection Medicine, Department of Clinical Sciences, Lund University 

 

Abstract

Background and aims
Tuberculosis (TB) remains a major cause of death in people with HIV (PWH).Several circumstances are involved in this phenomenon, especially inefficient immuneresponses to TB infection and lack of effective screening methods for TBcase-finding in PWH. In this thesis, I aim to explore the role of smallnon-coding RNAs (sncRNA) in TB/HIV coinfection, and to investigate hostbiomarkers that may be used for TB screening in PWH.

Methods
These studies are mainly based on a cohort of 833 treatment naïve PWHrecruited and followed at Ethiopian health centres. Participants have beensystematically investigated for active TB, with collection of blood atinclusion and during follow-up. Persons with and without TB have been compared inrelation to concentrations of nine cytokines and acute-phase proteins in plasma,as well as kynurenine/tryptophan ratio. Moreover, longitudinal sncRNAexpression levels in blood have been compared in persons with TB with andwithout HIV coinfection.

Results
- Levelsof most plasma inflammation markers analysed were higher in TB-coinfected PWH. Thebest performance for discriminating TB coinfection was achieved with acombination of the CRP and suPAR markers.

- Kynurenine/tryptophanratio was significantly increased in PWH with TB. However, compared to previousstudies, the performance of this ratio for TB case-finding was limited. 

- MicroRNAexpression was strongly altered and linked to HIV status in persons with TB,whereas small nucleolar RNA expression was downregulated in TB, regardless ofHIV status, compared to healthy controls. After initiation of treatment for TBand HIV normalization of sncRNA expression patterns towards the control groupwas noted.

Significance
The dysregulated sncRNA expression observed in TB/HIV coinfection suggesta role for this regulatory mechanism in the immune pathogenesis of TB in HIVinfection. Selected sncRNAs might also have potential as biomarkers for TB inPWH. Inflammatory mediators and kynurenine/tryptophan ratio may also be usefulfor this purpose.

Published paper
Olsson O, Björkman P, Jansson M,Balcha TT, Mulleta D, Yeba H, Valfridsson C, Carlsson F, Skogmar S. 2019. Plasma profiles of inflammatorymarkers associated with active tuberculosis in antiretroviral therapy-naivehuman immunodeficiency virus-positive individuals. Open Forum Infect Dis 6.

Manuscripts
Expression of miRNA is dysregulated by HIVwhile tuberculosis drives snoRNA alterations in coinfected individuals. OlssonO, Tesfaye Tegegn F, Søkilde R, Abebe M, Aseffa A, Skogmar S,  Balcha T.T, Rovira C, Björkman P, Jansson M

Ratio of kynurenine to tryptophan as a screening marker for tuberculosisin antiretroviral therapy naïve people living with HIV. OlssonO, Skogmar S, Balcha T.T., Jansson M, Björkman P


Maj

 

Mattias Rydberg

28 maj, klockan 9
Projekt: “The diabetic hand – epidemiology and pathophysiology of diabetic hand problems based on data from local and national registries in Sweden”
Lokal: Handkirurgens konferensrum plan 3, Jan Waldenströms gata 5, Skånes universitetssjukhus
Via Zoom: Uppdateras snart!
Huvudhandledare: Lars Dahlin
Bihandledare: Malin Zimmerman, Anders Gottsäter och Peter M Nilsson
Granskare/opponenter: Maria Cöster och Isabel Drake

 

Abstract

Background
”The diabetic hand” includes diseases in the peripheral nerves and connective tissues in the upper extremity, ultimately resulting in diagnoses such as Carpal tunnel syndrome (CTS), ulnar nerve entrapment at the elbow (UNE), trigger finger (TF), Dupuytren’s disease (DD), and possibly also osteoarthritis (OA) of the first carpometacarpal (CMC-1) joint. However, both the incidence and the prevalence of these diagnoses are still unknown in the population with diabetes mellitus (DM). Furthermore, the pathophysiology most probably differs between type 1 diabetes (T1D), where hyperglycaemia is the main underlying factor, and type 2 diabetes (T2D), where hyperlipidaemia is a major contributor to the underlying pathophysiology. This might affect the appearance of hand complications included in the diabetic hand. 

Aim
The aim of this thesis is to increase our understanding of the diabetic hand – if and why the prevalence of hand disorders is more frequent in the population with DM and how to best treat these patients. 

Method
By linking local, regional and national patient registers, the dissertation will result in the following projects with the following aims:

-  To calculate the prevalence and incidence of five common hand surgical diagnoses in the population with T1D and T2D in Region Skåne (I).

-  To identify metabolic risk factors associated with compression neuropathies in the upper extremity (II).

-  To identify the role of a high BMI for the development of OA of the CMC-1 joint. (III).

-  To identify metabolic risk factors for the development of DD (IV).

-  To explore surgical outcome after TF surgery among patients with T1D and T2D using patient reported outcome measurements (V).

-  To explore if strict blood sugar control effectively lowers the risk of TF among patients with T1D and T2D (VI) 

Preliminary results
CTS, UNE, TF, DD and OA of the CMC-1 joint are more prevalent among individuals with T1D and T2D. Furthermore, a high body mass index is associated with increased risk of the development of OA of the CMC-1 joint. Finally, DM is a major risk factor for both CTS and UNE. 

Significance
Through increased knowledge on how DM affects both the risk of development and the surgical outcome of the aforementioned diagnoses, the author hopes to shed lights on the diabetic hand, ultimately leading to better care of these patients.

Publications
Accepted

High body mass index is associated with increased risk for osteoarthritis of the first carpometacarpal joint during more than 30 years of follow-up. Rydberg M, Dahlin LB, Gottsäter A, et al. RMD Open. 2020;6:e001368. doi: 10.1136/rmdopen-2020-001368 

Diabetes mellitus as a risk factor for compression neuropathy: a longitudinal cohort study from southern Sweden. Rydberg M, Zimmerman M, Gottsäter A et al. BMJ Open Diabetes Research and Care. 2020;8:e001298. doi: 10.1136/bmjdrc-2020-001298 

Submitted
Metabolic factors and the risk of Dupuytren’s Disease – data from 30,000 individuals followed for over 20 years. Rydberg M, Dahlin LB, Gottsäter A, et al. Submitted to Scientific reports dec 2020. 

The Diabetic Hand – prevalence and incidence of diabetic hand problems using data from 1.3 million inhabitants in southern Sweden. Rydberg M, Zimmerman M, Dahlin LB et al. Submitted to American Journal of Hand Surgery April 2021. 

Congress abstract
Oral presentation

Diabetes mellitus as a risk factor for compression neuropathy: a longitudinal cohort study from southern Sweden. Rydberg M, Zimmerman M, Gottsäter A, PM Nilsson, O Melander, L Dahlin; Federation of European Societies for Surgery of the Hand yearly congress September 2020 

Increasing Body Mass Index and the risk for Carpal Tunnel Syndrome – a large cohort study from Sweden. Rydberg M, Zimmerman M, Gottsäter A, PM Nilsson, O Melander, L Dahlin; Federation of European Societies for Surgery of the Hand yearly congress September 2020


Alexandros Arvanitakis

26 maj, klockan 8.30
Plats: Koagulationsmottagningens konferensrum, Jan Waldenströms gata 14, plan 3
Handledare: Jan Astermark (professor)
Granskare: Rolf Ljung (professor) och Eva Norström (dr)

 

Abstract

Background
Prophylacticfactor VIII replacement therapy in Hemophilia A hasdrastically reduced the incidence of bleedings. However, bleedings still occur potentiallyresulting in arthropathy. Difference in FVIII pharmacokinetics and discrepancyin the assays (chromogenic and one-stage) used to measure FVIII levels caninfluence treatment results. Population-based pharmacokinetic (PK) can thushelp optimize treatment and reduce costs by individualizing the regimen to eachindividual patient, with the help of tools such as MyPKFiT and WAPPS-HEMO. Thechoice of FVIII product, degree of arthropathy, patient compliance anddifferent management practices of hemophilia centers can also influenceoutcomes. 

Methods
In study I, the PK estimations by MyPKFiT and WAPPS-Hemo were comparedand evaluated in the context of the patients´ clinical phenotype. In study II,treatment outcomes such as bleeding episodes, arthropathy, adherence totreatment and FVIII consumption were evaluated in patients treated at twoScandinavian Hemophilia centers prior and after the switch to treatment withthe recombinant FVIII product octocog alfa. 

Results
Study I showed that MyPKFiT and WAPPS-HEMO yielded similar t½ despitesignificant assay discrepancy. However, there were significant differences inthe time to reach 1%, 3% and 5%. Accordingly, the doses estimated by WAPPS-Hemowere between 28% and 100% of those proposed by MyPKFiT. Study II showed thatthe study cohort had excellent adherence to treatment  and very low bleeding rates (medianannualized bleeding rate (ABR) and annualized joint bleed rate (AJBR) were both0) prior and after the switch to octocog alfa, despite a relatively high degreeof arthropathy. There was non-significant slightly lower mean ABR (0.7 vs 0.4)and AJBR (0.7 vs 0.3) after the switch. The mean annual factor consumption of octocogalfa was 3,862 IU/kg/year at the Malmö center and 2,337 IU/kg/year) at the Oslocentre (p=0.006), with slightly lower mean bleeding rate of 0.33 vs. 0.42. 

Significance
Population-based PK tools WAPPS-Hemo and MyPKFiTovercome assay discrepancy but WAPPS-HEMO produced lower dosing estimationsthan MyPKFiT which may impact treatment optimization. However, individualized prophylaxisregimens and excellent adherence to treatment can still achieve excellenthemostatic activity despite lower FVIII consumption. 

Papers

I. Arvanitakis A, Berntorp E, AstermarkJ. A comparison of MyPKFiT and WAPPS-Hemo as dosing tools for optimizingprophylaxis in patients with severe haemophilia A treated with Octocog alfa.Haemophilia. 2021 Mar 10. doi: 10.1111/hae.14295.

II. Arvanitakis A, Berntorp E, AndreHolme P, Astermark J Beneficial treatment outcome, high adherence rate andvarying dosing in Scandinavian patients with hemophilia A on individualizedprophylaxis (manuscript) 


Victor Dahlblom

25 maj, klockan 9
Projekt: "Can breast cancer screening be improved with artificial intelligence?"
Via Zoom: https://lu-se.zoom.us/j/64447623496
Handledare: Sophia Zackrisson
Bihandledare: Magnus Dustler och Anders Tingberg
Granskare: Sonja Aits, lektor Lunds universitet och Lars Edenbrandt, professor Göteborgs universitet

 

Abstract

Background
Screening for breast cancer with digital mammography (DM) is implemented in order to detect breast cancer earlier and reduce breast cancer mortality. Still, many breast cancer cases are diagnosed between screening occasions. Digital breast tomosynthesis (DBT) has been shown to be able to detect more cancer in screening, but requires longer reading time. Artificial intelligence might open new possibilities in screening, either by making reading faster or by increasing sensitivity. 

Materials and methods
Projects 1-4 are based on data collected in the Malmö Breast Tomosynthesis Screening Trial (MBTST), where almost 15000 women were examined with both DM and DBT at one screening occasion. In project 1 it is studied if an AI system can exclude normal cases from screen reading. Project 2 investigates the ability of the AI system to detect more cancers on DM, otherwise only detected with DBT, and if the AI system correctly localises cancers. In project 3 the AI system is used to analyse DBT examinations and a number of different ways of using AI to reduce the total reading time is evaluated. Project 4 will focus on if AI can detect more cancers in DBT. Project 5 involves building a database of DM examinations in order to test AI in a larger material. 

Preliminary results
Project 1 showed that AI can identify a proportion of examinations as free of cancer, thereby potentially reducing the reading burden as well as the number of false positives. In project 2 the AI system could detect almost half of the DBT-only screening-detected cancers in the MBTST based on DM data. Project 3 concluded that AI can exclude the half of cases with lowest risk of breast cancer from reading and still almost all cancers would be detected, while the number of false positives is reduced. Project 4 and 5 are still ongoing and no preliminary results are yet available. 

Significance
We have shown that AI can potentially improve breast cancer screening, either by detecting more cancers on DM (2), or by reducing reading time on DM and DBT (1 and 3), which can open possibilities to introduce new methods, e.g. DBT, in screening. 

Published papers
Kristina Lång, Magnus Dustler, Victor Dahlblom, Anna Åkesson, Ingvar Andersson, Sophia Zackrisson. Identifying normal mammograms in a large screening population using artificial intelligence. Eur Radiol. 2021 Mar;31(3):1687-1692. Epub 2020 Sep 2. 

Manuscripts
Victor Dahlblom, Ingvar Andersson, Kristina Lång, Anders Tingberg, Sophia Zackrisson and Magnus Dustler. Could digital mammography aided by artificial intelligence match the performance of digital breast tomosynthesis in breast cancer screening? Under review.

Victor Dahlblom, Magnus Dustler, Anders Tingberg, Ingvar Andersson and Sophia Zackrisson. Stand-alone artificial intelligence in breast cancer screening with digital breast tomosynthesis - Potential implementations in a screen-reading workflow.


Li Sturesdotter

4 maj, klockan 9
Projekt: "Tumor features in breast imaging - correlation to diagnosis and prognosis"
Via Zoom: https://lu-se.zoom.us/j/69096354059
Handledare: Hanna Sartor
Bihandledare Sophia Zackrisson, MD PhD och Anna-Maria Larsson, MD PhD
Granskare: Salma Butt, MD PhD och Sara Alkner, MD PhD

 

Abstract

Background
Breast imaging is fundamental in early detection, diagnosis, and follow-up in breast cancer. Mammography is the most used method, however ultrasound, digital breast tomosynthesis and magnetic resonance imaging (MRI) are also employed in clinical diagnostics. Apart from diagnostic information, radiological images harbor features that can aid in treatment choices and prognostication, although their full potential is not used in clinical practice. The aim of this thesis is to further investigate how imaging features relate to clinicopathological factors and survival in breast cancer, using both an epidemiological and an explorative approach.

Materials and methods
Project 1 – 3 uses data from the Malmö Diet and Cancer Study. Project 1 and 2 includes women diagnosed with invasive breast cancer 1991 – 2014 (n = 1116). Project 1 focuses on how mammographic tumor appearance is related to clinicopathological factors. Project 2 investigates whether tumor appearance and mammographic breast density impacts breast cancer specific survival. The detection mode, screening or clinically detected cancer, is considered in analyses. Project 3 includes a subset of spiculated tumors. Here, we develop a clinical mammography tool that can potentially pinpoint tumors with a favorable outcome. Project 4 is an explorative study using high field breast MRI, with the aim to better understand the tumor composition in relation to the surrounding breast tissue.

Preliminary results
Project 1 established that spiculated breast tumors tend to have favorable characteristics, such as positivity for estrogen receptor, progesterone receptor, lower Ki67 expression and lower histological grade. They are also more often of the Luminal A-like subtype, which carries a good prognosis. In project 2 no significant impact on breast cancer specific survival was seen for different tumors appearances, nor for breast density level. Projects 3 and 4 are ongoing, currently in data-collection phase.

Significance
We have investigated relations between imaging parameters and clinicopathological factors

(1) and patient outcomes (2), which we hope can extend the use of the radiological image in clinical practice. With novel analyses on an imaging tool and MRI we hope to further deepen imaging knowledge. This thesis aims to highlight and advance the central part of imaging in multidisciplinary breast cancer care, using different approaches. 

Published papers
Sturesdotter L, Sandsveden M, Johnson K, Larsson AM, Zackrisson S, Sartor H. Mammographic tumour appearance is related to clinicopathological factors and surrogate molecular breast cancer subtype. Scientific reports. 2020;10(1):20814. 

Manuscript
Sturesdotter L, Larsson AM, Zackrisson S, Sartor H.
Investigating the prognostic value of mammographic breast density and mammographic tumor appearance in women with invasive breast cancer: The Malmö Diet and Cancer Study 


Januari

 

Mimmi Bjöersdorff

15 januari klockan 9
Projekt: "PET-CT in prostate cancer: Study of protocol optimization, diagnostic performance and biokinetics"
Via Zoom: https://lu-se.zoom.us/j/69338845782
Huvudhandledare: Elin Trägårdh
Granskare: Katarina Gleisner Sjögreen, Fredrik Liedberg

 

Abstract

Positron emission tomography – computed tomography (PET-CT) is a hybrid imaging modality that combines a nuclear medicine technique (PET) with the ability to show the spatial distribution of metabolic or biochemical activity in the body fused with a CT to obtain anatomic images. Recently, a novel generation of PET-CT scanners, with digital Silicon photomultiplier (SiPM)-based technology was introduced. This digital PET-CT system is hoped to increase the diagnostic accuracy due to its high resolution.

The overall aim of the project is to evaluate the different aspects of PET-CT imaging in patients with prostate cancer: image reconstruction and optimization of digital PET-CT protocols for 18F-Choline , diagnostic accuracy for 18F-Choline using histopathology as reference method and biokinetics of a novel radiopharmaceutical: 18F-PSMA.

My research project is divided into four partial studies. The first study was an optimization study of a novel reconstruction algorithm of the new PET-CT system. In paper 2 the accuracy of detecting lymph node metastases using 18F-choline PET-CT was evaluated with lymph node dissection as reference method in a clinical context and the in paper 3 we wanted to examine whether the conventional PET-CT system are performing at the same level as the digital PET-CT system.  The aim of paper 4 is to understand the distribution of 18F-PSMA-1007 in the body at patients with prostate cancer and to calculate the absorbed dose for different organs and to the whole patient.

Paper 1 show that based on contrast to noise-ratio, CNR, and signal to noise-ratio, SNR, to use beta factor 400-550 with 1.5min/bed position or beta factor 300-550 with 2 min/bed position at 4MBq/kg 18F-Choline. Paper 2 states the poor performance of 18F-Choline PET-CT to predict lymph node metastases in prostate cancer. In paper 3 the conventional and digital PET-CT systems had similar overall diagnostic performance in detecting lymph node metastases but marked difference in sensitivity and specificity. For paper 4, data collection is in progress.

Published papers

  1.  Bjoersdorff, M. et al. Impact of penalizing factor in a block-sequential regularized expectation maximization reconstruction algorithm for 18F-flurocholine PET-CT regarding image quality and interpretation. EJNMMI Physics. 6:5 (2019)

2020

 

December

 

Fregenet Tesafye

15 december, klockan 9
Project: "Dynamics of immune control of latent tuberculosis infection in relation to pregnancy"
Zoom: https://lu-se.zoom.us/j/62751690053
Supervisor: Per Björkman, Lund University, Malmö
Co-Supervisors: Marianne Jansson, Erik Sturegård and Taye Tolera Balcha
Opponents: Susanna Brighenti and Oonagh Shannon 

 

Abstract

Women infected with Mycobacterium tuberculosis (Mtb) have increased incidence of active tuberculosis (TB) in connection to pregnancy, with a particularly high risk in HIV co-infected individuals. The reason may be linked to the physiological immune modulation during pregnancy, which could disrupt the immune control of Mtb replication, and may consequently trigger reactivation of latent TB infection (LTBI). While the mechanisms involved cannot be explored at the pulmonary site of latent infection in humans, these phenomena may be reflected by patterns of immune mediators secreted during pregnancy and post-partum. Furthermore, this immune alternation could affect the performance of immune-based assays for LTBI diagnosis. The overall aim of this thesis is to investigate how pregnancy affects the immune control of LTBI.

This project is based on a prospective cohort of 2093 women recruited 2015-2018 during pregnancy, with follow-up post-partum in public health clinics in Adama, Ethiopia. Blood samples are collected at inclusion and at defined time points during pregnancy and post-partum for LTBI testing. This is performed by interferon-γ (IFN-γ) quantification after incubation with Mtb antigens using the QuantiFERON-TB Gold Plus assay (a new version of QFT; including two preparations [TB1 and TB2] of Mtb-specific antigens).

In study I, a cross-sectional analysis was performed to evaluate the performance of QFT-Plus assay from 829 pregnant women (49 HIV-positive) included during pregnancy. Two hundred seventy seven (33%) of these were QFT-positive using the recommended cut-off level 0.35 IU/ml, with high agreement between TB1 and TB2 antigens. QFT IFN-γ borderline results (defined as 0.20-0.70 IU/ml) were noted for a high proportion (29%) of HIV-positive women (compared to 7.6% among HIV-negative women), who also had significantly lower median IFN-g release compared to HIV-negative participants (TB1: 0.47 vs. 2.16 IU/ml; p<0.01, TB2: 0.49 vs. 2.24 IU/ ml; p<0.001).

In study II, we explored alternative cytokine markers in supernatants of whole blood stimulated with Mtb antigens, separately or in combinations to evaluate the LTBI status of pregnant women with QFT IFN-γ results in the borderline range. For this, we selected 96 pregnant women from the cohort based on QFT IFN-γ results, divided into three categories (QFT-low: <0.20 IU/ml, QFT- borderline: 0.20–0.70 IU/ml, QFT-high: >0.70 IU/ml), including 12 HIV-positive women in each group. Samples from HIV-negative women with QFT<0.20 IU/ml obtained >9 months after delivery were included as controls. We measured the concentration of eight markers (IL-1ra, IL-6, IL-8, IP-10, MCP-1, MCP-2, osteopontin and resistin) using Luminex assay. Classification analysis was performed using two different machine-learning algorithms to categorize participants with regard to their likelihood of having LTBI. The concentrations of MCP-2, IP-10 and IL-1ra in Mtb-antigen stimulated supernatants could distinguish women with IFN-γ borderline results. A combination of these three markers classified 42% of women with borderline results as having high likelihood of LTBI.  

In study III, we performed QFT testing on samples from women followed longitudinally during pregnancy (1st/2nd and 3rd trimesters) and post-partum to study the impact of pregnancy on the Mtb-triggered IFN-γ secretion. For this analysis, we chose a lower cut-off (IFN-γ≥0.20 IU/ml) to define QFT positive results, in order to account for reduced IFN-γ secretion during pregnancy. In total, 404 women (10% HIV-positive) sampled on two and/or three occasions had persistently positive QFT results. We observed that median IFN-γ secretion was elevated during the 3rd trimester compared to 1st/2nd trimester (TB1: 2.8 vs 1.6 IU/ml, p=0.01; TB2: 3.2 vs 2.7 IU/ml, p=0.05) and post-partum (TB1: 2.9 vs 2.2 IU/ml, p=0.009; TB2: 3.0 vs 2.16 IU/ml, p=0.04). Instead, mitogen-stimulated IFN-γ levels were lower at the 3rd trimester compared with the 1st/2nd trimester (8.0 vs 9.1, p=0.02).

In study IV, we hypothesise that analysis of additional immune mediators triggered by Mtb-antigen stimulation could provide more detailed information on how pregnancy affects the immune control of LTBI. For this study, additional immunological markers related to pregnancy and TB infection were screened in a pilot study. Four markers (IL-2, granzyme B, TGF-β1and MCP-3) from this pilot and three markers (IP-10, MCP-2, IL-1ra) from study II have been selected for the longitudinal analysis. Currently, we are performing the quantification of these immune mediators in QFT samples obtained longitudinally from women at different stages of pregnancy and post-partum. We estimate to complete the laboratory analysis at the end of this year.

Overall, these studies, based on Mtb antigen-stimulated whole blood from women living in a TB-endemic setting, suggest that analyzing alternative immune mediators, instead of repeated IFN-γ testing, is potentially a promising approach to assess LTBI status of pregnant women. The three biomarkers (IP-10, MCP-2 and IL-1ra) analysed in study II could distinguish women with IFN-γ borderline results, with similar performance in women with and without HIV infection. In the longitudinal analysis, elevated Mtb-specific IFN-γ secretion during later stages of pregnancy (despite reduced mitogen-triggered response) suggests increased immune cell exposure to Mtb antigens at later stages of pregnancy. We anticipate that analysis of a range of other immune mediators will provide further knowledge on how pregnancy affects immune control of LTBI.  

Publications
Tesfaye F , Sturegård E, Walles J, Winqvist N , Balcha TT, Karlson S, Mulleta D , Isberg PE, Jansson M , Björkman P. Alternative biomarkers for classification of latent tuberculosis infection  status in pregnant women with borderline Quantiferon plus results. Tuberculosis 2020; 124 https://doi.org/10.1016/j.tube.2020.101984 

Walles JK, Tesfaye F, Jansson M, Balcha TT, Winqvist N, Kefeni M, Garoma S, Belachew F, Sturegård E, Björkman P. Performance of QuantiFERON-TB gold plus for detection of latent tuberculosis infection in pregnant women living in a tuberculosis- and HIV-endemic setting. PloS One 2018;13 https://doi.org/10.1371/journal.pone.0193589

Manuscript
Longitudinal Mycobacterium tuberculosis specific interferon-γ responses in Ethiopian women during pregnancy and post-partum. Fregenet Tesfaye, John Walles, Erik Sturegård, Niclas Winqvist, Taye Tolera Balcha, Mestawet Kefeni, Marianne Jansson  and Per Björkman.


Kristina Kihlberg

9 december, klockan 9
Projekt: "A characterization of Hemophilia B – diagnostics and correlation between genotype, phenotype and clinical outcome"
Lokal: koagulationsmottagningens konferensrum, Jan Waldenströms gata 14, plan 3, Skånes Universitetssjukhus Malmö
Handledare: Jan Astermark, professor
Reviewers: Bodil Ohlsson, professor, och Björn Rosengren, professor

 

Abstract

Introduction
Hemophilia B (HB), caused by the deficiency of coagulation factor IX (FIX), is an inherited X-linked bleeding disorder. Because of the rarity of the disease much of our knowledge and treatment recommendations for HB have been extrapolated from studies based on patients with the more common hemophilia A (HA). HA and HB have historically been seen as identical disorders but there are important differences between the diseases. The diagnosis and severity of hemophilia is based on the factor activity. Assay discrepancy in factor VIII activity between the one-stage and the chromogenic assays has been described in non-severe haemophilia A. Whether assay discrepancy may also occur in patients with hemophilia B is previously not known. The aim of this project was to bring a better understanding to hemophilia B, its phenotype, diagnostics and treatment, based on studies focusing on hemophilia B patients. 

Methods
In study I, plasma samples from patients with HB were collected and analyzed with both the one-stage and the chromogenic assays. Study II, a cross-sectional, retrospective study in the Nordic countries, gathered information on patients with severe HB to evaluate the treatment outcome and to compare this to a control group of patients with HA. Study III, an international, prospective, observational study included patients with all severities of HB to evaluate the phenotype within and between families. 

Preliminary results
Results from study I implies that assay discrepancy does occur for FIX activity and that this might be due to the underlying genotype. Study II showed a relatively high prevalence of FIX inhibitors of 14%. Lower Hemophilia Joint Health Scores among patients with HB compared to HA suggest that patients with severe HB suffer from a milder arthropathy than patients with severe HA. Study III has finished enrolment of 240 patients from 24 centres in Asia, Europe and North America and the dataset has been finalized. 

Significance
To be able to better understand the HB disease and to improve the care for our patients, studies focusing on the HB population are of importance. This is of even more significance today with new possibilities of individualized treatment. 

Papers

I.  Kihlberg K, Strandberg K, Rosén S, Ljung R, Astermark J. Discrepancies between the one- stage clotting assay and the chromogenic assay in haemophilia B. Haemophilia. 2017;23(4).


Fabian Uddén

1 december, klockan 14.30
Projekt: "Streptococcus pneumoniae – studies on the antipneumococcal immune response and epidemiology in Skåne and Angola"
Lokal: patologens föreläsningssal, Jan Waldenströms gata 59, Skånes universitetssjukhus Malmö
Handledare: Kristian Riesbeck, professor
Bihandledare: Jonas Ahl
Reviewers: Ander P Håkanson, professor, och Magnus Rasmussen, institutionen för kliniska vetenskaper i Lund

 

Abstract

Background
Streptococcus pneumoniae, the pneumococcus, is a colonizer of the human nasopharynx and a common aetiology of respiratory tract and systemic infections causing significant morbidity and mortality worldwide. Based upon the specific antibody response elicited by pneumococcal capsular polysaccharides, pneumococcal conjugate vaccines (PCVs) including 10-13 of the 100 known serotypes are used in infant immunization programmes. For vaccine evaluation purposes and due to the risk of emerging virulent or antibiotic resistant nonvaccine serotypes, surveillance of pneumococcal epidemiology is important. Furthermore, it is unknown to what extent an episode of pneumococcal infection results in functional adaptive immunity.

Methods
To characterize the spectrum of S. pneumoniae circulating related to PCV use in Skåne and Angola, pneumococci were isolated from clinical respiratory tract cultures and a nasopharyngeal carriage study was performed, respectively. Additionally, the spectrum of bacteria related to chronic suppurative otitis media in Angola was studied. Pneumococcal isolates were serotyped using a polymerase chain reaction scheme and antibiotic susceptibility patterns were determined. In parallel, the humoral immune response of patients with pneumococcal pneumonia and/or bacteraemia with different serotypes was assessed with an opsonophagocytic assay.

Results
The introduction of PCV in Skåne resulted in a decreased proportion of PCV-included serotypes, from 45% in 2007-2008 to 17% in 2016-2018, although the vaccine-serotypes 3 and 19A were still prevalent in the nonvaccinated age group. In Angola, colonization with PCV-included serotypes was prevalent (14%) among PCV-unvaccinated children 4 years after the introduction of PCV, and these serotypes were associated with penicillin non-susceptibility (p=0.003). A nonfunctional opsonic antibody response was commonly observed (43%) after pneumococcal pneumonia and/or bacteraemia and was associated with low-invasive serotypes (p=0.015) and bacteraemia (p=0.019).

Significance
Continued occurrence of PCV-serotypes among certain age groups in Skåne may indicate limitations of PCV herd effects regarding certain serotypes. A first description on pneumococcal epidemiology in Angola is reported, providing baseline data for future studies. Studies of the immune response induced by exposure to S. pneumoniae are scarce but may improve our understanding of the human immune system and possibly have implications for future vaccine strategies. 

Publications

  1. Littorin N, Ahl J, Uddén F, Resman F, Riesbeck K. Reduction of Streptococcus pneumoniae in upper respiratory tract cultures and a decreased incidence of related acute otitis media following introduction of childhood pneumococcal conjugate vaccines in a Swedish county. BMC Infect Dis. 2016;16(1):407. doi: 10.1186/s12879-016-1750-5.
  2. Uddén F, Filipe M, Reimer Å, Paul M, Matuschek E, Thegerström J, Hammerschmidt S, Pelkonen T, Riesbeck K. Aerobic bacteria associated with chronic suppurative otitis media in Angola. Infect Dis Poverty. 2018;7(1):42. doi: 10.1186/s40249-018-0422-7.
  3. Littorin N, Uddén F, Ahl J, Resman F, Slotved HC, Athlin S, Riesbeck K. Serotypes With Low Invasive Potential Are Associated With an Impaired Antibody Response in Invasive Pneumococcal Disease. Front Microbiol. 2018;9:2746. doi: 10.3389/fmicb.2018.02746.
  4. Uddén F, Filipe M, Slotved HC, Yamba-Yamba L, Fuursted K, Kuatoko PP, Larsson M, Bjurgert J, Månsson V, Pelkonen T, Reimer Å, Riesbeck K. (In press). Pneumococcal carriage among children aged 4 – 12 years in Angola 4 years after the introduction of a pneumococcal conjugate vaccine. Vaccine.

November

 

Dawit Assefa

Tuesday 17 November, 13:15
Projekt: "The HIV–1 epidemic in Ethiopia – transmission patterns, antiretroviral drug resistance and treatment outcomes" 
Lokal: Segerfalksalen, BMC, Sölvegatan 19, Lund
Handledare: Patrik Medstrand, professor, Lunds universitet
Bihandledare: Per Björkman, Taye Tolera Balch och Joakim Esbjörnsson, Lunds universitet
Granskare: Ujjwal Neogi, docent, Karolinska institutet, och Mattias Höglund, professor, Lunds universitet

 

Abstract

Background
Human immunodeficiencyvirus type 1 (HIV-1) is characterised by extensive genetic heterogeneity thathas implications for diagnosis, vaccine development, and clinical management ofHIV infection. Previous studies have shown that subtype C is dominant inEthiopia although a detailed survey of subtypes and CRFs has not been performedrecently. A nation-wide monitoring of the HIV epidemic, through geneticcharacterization of HIV drug resistance prevalence and the dynamics of themolecular epidemiology will be instrumental for designing new public healthpolicies, which will be important in prevention and treatment interventions. 

The expansion ofantiretroviral therapy (ART) has markedly reduced HIV-related morbidity,mortality, and transmission. However, the emergence and transmission of HIVdrug resistance (HIVDR) constitutes a threat to the outcome of treatmentprograms and is an imminent obstacle for the planned elimination of HIV as apublic health threat. In Ethiopia, there is limited information on theprevalence of HIVDR (acquired and transmitted). Thus, there is a need todetermine the magnitude of the problem of HIVDR among general population andhigh-risk group (female sex workers). 

Objective

1. To determine the prevalence ofHIVDR before ART initiation and during ART in patients receiving care both inhealth centres and hospital

2. To characterize the subtypedistribution and the spread of HIV-1 in Ethiopia by virological geneticanalyses, including studies of the epidemic in and between different regions ofEthiopia, along major highways in Ethiopia, and among groups with differentrisk profiles 

Study questions

1. What are the major HIV-1subtype (sub-subtype) circulating in Ethiopia? When and how the HIV-1 epidemicspread in Ethiopia?

2. What is the prevalence of HIVDRamong recently infected, chronically infected and patient on ART? What is theimplication on this on treatment program?

3. Are female sex workers at highrisk for the emergency of and transmission of HIVDR to the general population?

4. Are female sex workers drivingthe HIV epidemic in Ethiopia? 

Significance
Our molecularepidemiology result will provide information on dynamics of the HIV1 epidemicin Ethiopia that are crucial for effective treatment strategies, as well as forthe planning of medical interventions and for the design of effectiveprevention programs targeting both the general population and most at riskpopulations. The HIV drug resistance information from the different study groupwill be very important for the strengthening the national ART program forEthiopia and other countries with similar situation.


October

 

Oskar Thofte

Monday 19 October, 14:30
Projekt: “The emerging pathogen Haemophilus Influenzae - host/pathogen interactions"
Lokal: patologens föreläsningssal, Jan Waldenströms gata 59, Skånes universitetssjukhus Malmö
Handledare: prof. Kristian Riesbeck
Bihandledare: prof. Karin Leandersson och med. dr. Farshid Jalalvand
Examinatorer: prof. Ann Hermansson och med. dr. Erik Senneby

 

Abstract

Background
Non-typeable Haemophilus influenzae (NTHi) is a pathogen that commonly colonizes the na-sopharynx of preschool children, causing opportunistic infections including acute otitis me-dia (AOM). Patients suffering from chronic obstructive pulmonary disease (COPD) are per-sistently colonized with NTHi and occasionally suffer from exacerbations by the bacterium leading to increased morbidity. Elongation-factor thermo unstable (EF-Tu), a protein critical for bacterial protein synthesis, has been found to “moonlight” on the bacterial surface where it is involved in the interaction with the host. 

Research question
The overall aim of my PhD project is to study the host-pathogen interaction of NTHi, with focus on EF-Tu and outer membrane protein P5. 

Results
In paper 1 we show that EF-Tu from NTHi is surface exposed and recognized by antibodies mediating host innate immunity against NTHi. We could also observe a prominent cross-reaction with other unencapsulated respiratory tract bacteria.1 

In paper 2 we found that antibodies against NTHi EF-Tu were present in children al-ready at 18 months of age, and that the IgG antibody titers increased with age. Children harboring NTHi in the nasopharynx displayed significantly higher IgG concentrations and children suffering from AOM had significantly higher anti-EF-Tu IgG levels when NTHi was the causative agent. Finally, we demonstrated that immunization of BALB/c and otitis-prone Junbo (C3H/HeH) mice with recombinant EF-Tu promoted lower infection rates in the nasopharynx and middle ear, respectively.2 

Published papers

  1. Thofte, O. et al. EF-Tu From Non-typeable Haemophilus influenzae Is an Immunogen-ic Surface-Exposed Protein Targeted by Bactericidal Antibodies. Front Immunol 9, 2910 (2018).
  2. Thofte, O. et al. Anti‐EF‐Tu IgG titers increase with age and may contribute to protec-tion against the respiratory pathogen Haemophilus influenzae. European Journal of Im-munology 49, 490-499 (2019).

September

 

Wednesday 9 September, 13:00
Magdalena Kuras, ”Targeting Malignant Melanoma Patient Survival by Proteogenomic Molecular Expression in Tumors"
Lokal: BMC i Lund i I-huset, rum I1308, Sölvegatan 19, 223 62 Lund
Huvudhandledare: Johan Malm 
Bihandledare: György Marko-Varga och Melinda Rezeli 
Examinatorer: Carol Nilsson, senior lecturer at Translational Cancer Pharmacology, Ann Brinkmalm, Ph.D, Docent at Neuroscience and Physiologi, Göteborgs universitet, och Martin Johansson, professor i patologi vid Göteborgs universitet och universitetslektor vid Lunds universitet, klinisk patologi, Malmö

 

August

 

Friday 21 August, 09:00
Martin Senneby, "Quantification of myocardial perfusion scintigraphy images"
Lokal: Klinisk fysiologi, Carl Bertil Laurells gata 9, Skånes universitetssjukhus Malmö
Handledare: Elin Trägårdh
Bihandledare: Per Wollmer, Lars Edenbrandt
Examinatorer: Isabel Goncalves och Gustav Brolin

 

June

 

Friday 12 June, 09:00
Antanas Bukartas, "Mobile measurement data analysis in radiological emergency situations using Bayesian statistical methods"
Venue: Sören Mattson library, Carl-Bertil Laurells gata 9, plan 4, Skåne University Hospital, Malmö
Via Zoom: https://lu-se.zoom.us/j/69917417037 (Meeting ID: 699 1741 7037) 
Supervisor: Christopher Rääf
Co-supervisor: Jonas Wallin and Robert Finck

 

Friday 5 June, 13:00
Johan Abrahamsson, "Advanced urothelial cancer – aspects on treatment and survival"
Zoom-meeting: https://lu-se.zoom.us/j/62247350740
Handledare: Fredrik Liedberg
Bihandledare: Lisa Rydén och Gottfrid Sjödahl

 

Wednesday 10 June, 9:00
Felicia-Elena Marginean, "Prostate Cancer Tissue Biomarkers”
Venue: Via Zoom, https://lu-se.zoom.us/j/67796671977
Supervisor: Professor Anders Bjartell, Urological Cancers, Lund University
Co-supervisors: Associate Professor Rebecka Hellsten, Urological Cancers, Lund UniversityAssistant researcher Agnieszka Krzyzanowska, Urological Cancers, Lund University
Opponents: Professor Martin Johansson, Sahlgrenska Cancer Center, University of Gothenburg, and Assistant researcher, Dr Med Sci Jens Ceder, Systemic Radiation Therapy, Lund University 

 

Monday 1 June, 13:00
Marcus Fager Ferrari, "Genetic Screening and Validation of Genetic Variants of Unknown Significance in Patients Suspected of Inherited Bleeding Disorders"
Huvudhandledare: Eva Zetterberg, docent
Bihandledare: Eva Leinoe, MD, PhD,  Maria Rossing, docent och Eva Norström, MD, PhD
Granskare: Ulf Tedgård MD, PhD, barnkliniken Sus, och Ole Halfdan Larsen, docent, genetisk klinik, Universitetssjukhuset i Århus, Danmark

 

May

 

 

Monday 18 May, 13:00
John Walles, "Clinical implications of tuberculosis infection in pregnancy"
Lokal: Belfragesalen, infektionskliniken Malmö, plan 6, Ruth Lundskogs gata 3, Skånes universitetssjukhus Malmö
Huvudhandledare: Per Björkman, professor vid klinisk infektionsmedicin, Lunds universitet, Malmö
Biträdande handledare: Niclas Winqvist, PhD, epidemiolog smittskydd Skåne, Stefan Hansson, professor obstetrik och gynekologi, Lunds universitet, Lund
Huvudopponent: Åse Bengård Andersen, professor vid infektionsmedicinsk klinik, Center for Hjerte-,Kar-,Lunge- og Infektionssygdomme. Rigshospitalet, Danmark
Biträdande opponent: Malin Inghammar, docent, avdelningen för infektionsmedicin, Lunds universitet, Lund

 

Thursday 7 May, 9:00
Olof Elvstam, "Low-Level Viremia in People Living with HIV Receiving Antiretroviral Therapy"
Lokal: Petrénsalen, plan 6, Ruth Lundskogs gata 3, Skånes universitetssjukhus Malmö
Huvudhandledare: Per Björkman, professor vid klinisk infektionsmedicin, Lunds universitet, Malmö
Bihandledare: Patrik Medstrand, professor vid klinisk virologi, Lunds universitet, Malmö, Magnus Gisslén, professor vid avdelningen för infektionssjukdomar, Sahlgrenska universitetssjuhkuset/Göteborgs universitet och Gaetano Marrone, forskare vid global folkhälsa, Karolinska institutet, Stockholm
Granskare: Lars Omland, forskare vid infektionsmedicinsk klinik, Rigshospitalet, Köpenhamn, och Fredrik Resman, docent vid klinisk infektionsmedicin, Lunds universitet, Malmö

 

April

 

Friday 24 April, 13:00
Emma Byström, "Vaccine hesitancy and attitudes towards vaccinations within the Swedish National Immunization Program"
Venue: Folkhälsomyndigheten, Nobels väg 18, Solna
More ways to join your meeting: https://meet.starleaf.com/4073739056
Supervisor: Adam Roth
Co-supervisors: Ann Lindstrand and Kristian Riesbeck
Opponents: Prof. Johan Giesecke, Karolinska Institute, and Dr. Lina Magnusson, Lund
The lecture will be in English and the discussion in Swedish. 

 

Friday 24 April, 9:00
John Ly, "Artificial Intelligence in PET-CT: From image enhancement to imaging biomarkers"
Huvudhandledare: Elin Trådgårdh
Bihandledare: Per Wollmer och Lars Edenbrandt 
Examinatorer: Mats Jerkeman, professor onkologi, och Sophia Zackrisson, professor radiologi

 

Friday 17 April, 09:00
Fríða Björk Gunnarsdóttir, "Unconventional antigen presenting cells (APCs) in tumor specific immune responses"
Via LU Zoom: Meeting ID 507-750-246 (https://lu-se.zoom.us/j/507750246)
Supervisor: Professor Karin Leandersson
Opponents: Professor Anita Sjölander and Associate Professor Kristina Aaltonen

 

Thursday 16 April, 13:15
George Makau Nduva, "Disentangling transmission dynamics and the molecular epidemiology of HIV-1 in Kenya"
Via LU Zoom: Meeting ID: 856-440-699 (https://lu-se.zoom.us/j/856440699)
Supervisor: Joakim Esbjörnsson
Granskare: Mattias Höglund, professor vid Lunds universitet och Johan Nordgren, docent vid Linköpings universitet

 

March

 

 

Tuesday 24 March, 13:15
Jamirah Nazziwa, "Genetic characterization and evolutionary dynamics of HIV-1 within and between hosts"
Venue: Segerfalkssalen, Biomedicinskt centrum (BMC), Sölvegatan 19, Lund
Supervisor: Joakim Esbjörnsson
Co-supervisors: Johan Malmström, Amin S Hassan, Phillipe Lemey and Sarah Rowland-Jones
Opponents: Lennart Svensson and Claus Christiansen

 

Monday 16 March, 10:00
Lovisa Waldner, ”OSL dosimetry with NaCl pellets”
Venue: Möteslokal 4151 (preliminärt), Diagnostiskt centrum, Carl-Bertil Laurells gata 9, Skånes universitetssjukhus Malmö
Huvudhandledare: Christian Bernhardsson, universitetslektor i medicinsk strålningsfysik, Lunds universitet 
Bihandledare: Christopher L. Rääf, professor i medicinsk strålningsfysik, Lund universitet 
Granskare: Åsa Carlsson Tedgren, Linköpings universitet, och Ingela Hjelte, Landauer, Uppsala

 

Thursday 5 March,13:30
Carolina Axelsson, ”Extended Spectrum βeta Lactamase producing bacteria: an increasing source of causative infections”
Lokal:  Riesbeck lab, lokal ”Holken”, Jan Waldenströms gata 59, plan 3, Skånes universitetssjukhus i Malmö
Huvudhandledare: Ann-Sofi Rehnstam-Holm, professor i mikrobiologi, Högskolan Kristianstad
Biträdande handledare: Kristian Riesbeck, professor i klinisk mikrobiologi, Lunds universitet
Opponenter/granskare: Bodil Hernroth, professor i biomedicinsk laboratorievetenskap, och Celia Cabaleiro Lago, universitetslektor, Högskolan Kristianstad

 

January

 

Friday 17 January, 9:00
Goutham Vansarla, "The antibacterial and immunomodulatory activities of a human milk protein lipid complex,
HAMLET against Streptococcus pneumoniae"
Venue: Conference room 20:5:501, 5th floor, Wallenberg laboratory, Inga Marie Nilssons gata 53, Malmö
Supervisor: Anders P. Håkansson, Professor, Experimental infection medicine
Co-supervisor: Caroline Bergenfelz, PhD, Post doctoral Fellow, Experimental infection medicine
Reviewers: Karin Leandersson, Professor, Cancer Immunology and Serena Bettoni, PhD, Post doctoral Fellow, Protein chemistry

 

2019

 

December

 

Monday 9 December, 10:30
Syrina Fred Mehrabi, "The role of neutrophils in colon cancer and its microenvironment"
Lokal: sal 60-12-015, Clinical Research Center, Jan Waldenströms Gata 35
Huvudhandledare: Anita Sjölander
Sakkunniga: Camilla Rydberg-Millrud, PhD och Yvonne Lundberg Giwercman, professor vid molekylärgenetisk reproduktionsmedicin, Lunds universitet 

 

November

 

Tuesday 26 november, 10:00
Martin Nyberg, "Prostate cancer surgery – long-term outcomes after Radical Prostatectomy"
Venue:  ”Bokhörnan”, konferenscenter, Jan Waldenströms gata 5, Skånes universitetssjukhus Malmö
Supervisor: Anders Bjartell
Co-supervisor: Sigrid Carlsson
Opponents: Ulf Pettersson och Bengt Uvelius

 

Friday 22 November, 10:00
Emma Einarsson, "Multiparametric magnetic resonance imaging of tissue degeneration in knee osteoarthritis"
Venue: rum 4151, plan 4, medicinsk strålningsfysik, Carl-Bertil Laurells gata 9, Skånes universitetssjukhus Malmö
Supervisor: Jonas Svensson. Medical Physicist, Phd, Assoc. Prof.
Co-supervisors: Prof. Martin Englund, Doc. Patrik Önnerfjord, and Dr. Pernilla Peterson
Opponents: Johan Olsrud, sjukhusfysiker, docent, SUS/LU och Mikael Boesen, radiolog och professor vid Bispebjerg and Frederiksberg Hospital / Copenhagen University

 

Tuesday 5 November, 13:00
Ewelina Golec, "Novel intracellular functions of complement system"
Venue: Wallenberg laboratory, seminar room, floor 5th, Inga Marie Nilssons gata 53, Skånes universitetssjukhus Malmö
Supervisors: Prof. Anna Blom and Doc. Ben King 
Opponents: Prof. Lena Eliasson and Prof. Jens Lagerstedt 

 

October

 

Monday 28 October, 16:45
Amelie Stenqvist,"Sperm DNA breaks in relation to infertility treatment and the health of the offspring"
Lokal: Biblioteket, kvinnokliniken, Jan Waldenströms gata 47, Skånes universitetssjukhus Malmö
Handledare: Aleksander Giwercman
Bihandledare: Mona Bungum och Lars Rylander
Opponent: Stefan Arver och Povilas Sladkevicius

 

Thursday 24 October, 13:00
Oskar Ljungquist, "ESBL- the catharsis of antibiotic therapy"
Lokal: Rut Lundskogs gata 3, Malmö, plan 6 (lokal meddelas senare)
Huvudhandledare: Kristian Riesbeck
Bihandledare: Johan Tham och Fredrik Resman
Opponenter: Erik Sturegård och Pia Karlsson

 

 

May

Wednesday 29 May, 10:00
Sarah Lindgren Belal, ”Development of a Deep Learning-Based Imaging Biomarker for PET/CT in Patients with Prostate Cancer”
Lokal: Rum 4151, plan 4, bild- och funktion, Carl Bertil Laurells gata 9, Skånes universitetssjukhus Malmö
Handledare: Elin Trägårdh
Opponenter: Fredrik Liedberg och Peter Leander

 

April

Friday 26 April, 9:30
Yahia Al-Jebari, "Cancer, cancerbehandling och genetisk instabilitet i relation till avkommans hälsa"
Venue: Lokal 91-10-014, CRC, Jan Waldenströms gata 35, Skånes universitetssjukhus Malmö
Supervisor: Aleksander Giwercman, professor
Reviewers: Håkan Olsson, professor, Lunds universitet, Heather Boyd, PhD, Statens seruminstitut, Köpenhamn

 

Friday 5 April, 10:00
Kristin Johnson, "The Malmö Breast Tomosynthesis Screening Trial: Challenges and possibilities for a new screening era"
Venue:  Rum 2007, Diagnostiskt centrum, Skånes universitetssjukhus Malmö
Supervisor: Sophia Zackrisson
Co-supervisors: Kristina Lång och Aldana Rosso
Reviewers: Irma Fredriksson, med dr och överläkare Karolinska institutet, och Johan Wasselius, överläkare och docent vid Lunds universitet.

 

Friday 5 April, 9:00
Ilka Anker, "Entrapment of the ulnar nerve at the elbow – studies on risk factors, diagnostic methods, treatment, clinical outcome and predictive factors" 
Venue: Handkirurgens konferensrum, biblioteket, Jan Waldenströms gata 5, plan 3, SUS Malmö
Supervisor: Lars Dahlin

 

March

Friday 1 March, 09:00
Feiruz Alamiri , "Antibiotic resistance and pathogenesis of Streptococci with focus on Group A Streptococci"
Venue: MFC Conference room on floor 5 in Wallenberg, Inga Marie Nilssons gata 53, Sus Malmö. 
Supervisor: Anders P Håkansson, Professor in experimental infection medicine
Co-supervisor: Kristian Riesbeck, Professor in clinical microbiology
Reviewers: Mattias Collin, Associate Professor at division of infection medicine, Skånes universitetssjukhus Malmö and Pontus Nordenfelt

 

February

Thursday 14 February, 13:00
Petter Kollberg, "Invasive bladder cancer - aspects on diagnosis and treatment" 
Venue: MFC "Kandidaten", Jan Waldenströmsgata 5, plan 1, SUS Malmö
Supervisor: professor Fredrik Liedberg
Sakkunniga/Reviewers: docent Elin Trägårdh, nuklearmedicin, Malmö och professor Karin Jirström, onkologi och patologi, Kampradlab, Lund

 

2018

 

December

Tuesday 18 December, 13:00
Emilia Persson, “MRI only based radiotherapy of prostate cancer – technical and physical aspects”
Venue: Strålbehandlings konferensrum, plan 3, Klinikgatan 5, SUS Lund
Reviewers: Maria Ljungberg, Docent Sahlgrenska and Peter Larsson, Docent Linköpings university

 

Monday 17 December, 13:00
Emma Nilsson Condori, "Fertility after Bariatric Surgery"
Venue: Biblioteket, plan 3, Kvinnokliniken, Jan Waldenströms gata 47, 205 02 Malmö
Main supervisor: Britt Friberg, Assoc Professor
Co-supervisors: Aleksander Giwercman, Professor, Jan Hedenbro, Assoc Professor and Ann Thurin-Kjellberg, Assoc Professor
Reviewers: Pia Saldeen, Assoc Professor and Torsten Olbers, Professor

 

November

Wednesday 7 November, 13:00
Barbara Sahlin, "Testosterone related proteins and Disease"
Venue: D1513b Bengt Borgström BMC, Sölvegatan 19, Lund
Main supervisor: Johan Malm, Professor
Co-supervisors: Aleksander Giwercman, Professor and György Marko-Varga, Professor
Reviewers: Patrik Önnerfjord, Docent and Mikael Lantz, Attending Physician, Consultant

 

May

Monday 21 May, 12:00–14:00
John Thegerström "Aspects on antimicrobial resistance in the respiratory tract pathogen Haemophilus influenzae"
Venue: Riesbeck lab, Jan Waldenströms gata 59, 3rd floor, Malmö
Supervisor: Fredrik Resman Co-supervisor: Kristian Riesbeck
Reviewers: Anna Nilsson, Anders Bredberg

 

March

Tuesday 20 March, 08:30
Lena Trinh, "Fat composition and location: assessment by magnetic resonance imaging in muscle and adipose tissue”
Venue: Diagnostiskt Centrum, room 4151, Carl-Bertil Laurells gata 9, Skånes Universitetssjukhus, Malmö.
Experts: Dr. Karin Markenroth Bloch, Lund University Bioimaging Center, Associate Professor Peter Leander, Diagnostic Radiology, SUS Malmö

February

Thursday, 22 February, 13:00
Christian Gustafsson "MRI-based radiotherapy treatment planning for prostate cancer– Assessment of geometric distortion and detection of fiducial markers"
Venue: Föreläsningssalen, Strålbehandlingshuset, Level 3, Klinikgatan 5, Lund
Experts: Docent Anna Bäck, Sahlgrenska och Docent Johan Olsrud, Lund

Monday, 12 February, 09:00
Magnus Flondell (hand surgery), "Cerebral and clinical effects of carpal tunnel syndrome"
Venue: The rehab room at the hand surgery clinic, floor 4, Skåne University hospital, Jan Waldenströms gata 5, Malmö
Supervisor: Anders Björkman, Lund University

 

2017

October

Thursday, 26 October, 09:00
Karolina Bogefors "Androgen action and late effects of malignant diseases in young male cancer survivors"
Venue: Room 91 10 014, CRC, Jan Waldenströms gata 35, SUS, Malmö
Supervisor: Aleksander Giwercman, professor, Institutionen för translationell medicin, Lunds universitet
Experts: Maria Elfving, överläkare på Barn- och ungdomssjukhuset, SUS Lund, samt docent på enheten för barnendokrinologi, institutionen för Kliniska vetenskaper, Lunds universitet &
Signe Borgquist, överläkare på Kliniska Prövningsenheten, SUS, Lund samt docent vid avdelningen för onkologi och patologi, institutionen för Kliniska vetenskaper, Lunds universitet.

 

Friday 21 april, 13:00
Alexander Åkesson, ”Clinical evaluation and characterization of suspected atypical hemolytic uremic syndrome(aHUS)”
Venue: The Conference room, Koagulationscentrum, Jan Waldenströms gata 14, plan 3A, Skåne University Hospital, Malmö
Opponents: MD, Ph.D. Sophie Ohlsson, Doc Oonagh Shannon
Supervisor: Doc Eva Zetterberg
Assistant supervisor: MD, Ph.D. Jenny Klintman

 

2016

November

Friday 25 November 13:00.
Oliver Patschan, "Stage T1 Bladder Cancer – Aspects of Diagnosis and Treatment"
Venue: MFC "Lilla Aulan", Jan Waldenströmsgata 5, Skånes universitetssjukhus, Malmö.
Faculty opponent: Associate Professor Bas W.G. van Rhijn, M.D., Ph.D, Netherlands Cancer Institute, Amsterdam.
Chairman: Professor Per-Anders Abrahamsson, M.D., Ph.D. Department of Urology, SUS, Malmö
Supervisor: Fredrik Liedberg, Dept. of. Translational medicine, Division of Urological Research, Malmö.
Co-Supervisor: Mattias Höglund, Department of Clinical Sciences, Lund, Division of Oncology and Pathology.

 

Monday 21 november, 14:00
Marcus Ljungkvist ”Thrombin generation assay – calibrated automated thrombogram: a methodological and clinical study”
Venue: The conference room, Koagulationscentrum, Jan Waldenströms gata 14, level 3A, Malmö
Opponents: Doc Andreas Hillarp MD, PhD Vladimir Lazarevic
Supervisor: Doc Eva Zetterberg
Co-supervisor: Prof Erik Berntorp

 

September

Wednesday 21 September, 09:30
Marie-Louise Aurumskjöld (tidigare Olsson), "Iterativa bildrekonstruktioner inom CT-diagnostik med avseende på bildkvalitet och stråldos”
Venue: The Sören Mattsson library, level 4, Inga Marie Nilssons gata 49, SUS, Malmö 
Opponents: Reader Peter Leander, Professor Mats Nilsson
Main supervisor: Reader Anders Tingberg
Co-supervisor: Reader Marcus Söderberg, Ph.D. Kristina Ydström och Professor Sören Mattsson

 

August

Wednesday 24 August, 15:00
Janina Osman "CysLT1R signalling promotes tumorigenesis in mouse models of colon cancer"
Venue: Room 60-12-015, CRC, Jan Waldenströms gata 35, SUS, Malmö.
Opponents will be Professor Henrik Thorlacius and Assoc Professor Olof Grip
Main supervisor Professor Anita Sjölander and Co-supervisor Assoc Professor Karin Leandersson.

 

June

Thursday, June 23, 13:00 via Skype
Yousif Faruok Barzangy, Division of Urological Research
"The post-war recording on urological cancers, Department of Translational Medicine"
Venue: Video Conference rum 92-09-012, CRC, Jan Waldenströms gata 35, SUS, Malmö
Experts: Alber Salehi: Lund University, Dept. of Clinical Sciences, Diabets group. Agnieszka Krzyzanowska: Lund University, Dept. of Translational medicine, Urologic cancer unit.
Supervisor: Nishtman Dizeyi, Dept. of. Translational medicine, Division of Urological Research, Malmö.
Co-Supervisor: Per-Anders Abrahamsson, Dept. of. Translational medicine, Division of Urological Research, Malmö.
 
 

Tisdagen den 14 juni 2016 kl. 15:00
Natalia Mochalina, ”Antiarytmika och antikoagulantia vid förmaksflimmer”
Lokal: Inge Edler-salen, avd för kardiologi, EA-blocket, SUS, Lund
Opponenter: Doc Oscar Braun, Doc Karin Strandberg
Handledare: Prof Peter Svensson Biträdande handledare: Prof Pyotr Platonov PhD, Leg läk Mattias Wieloch

 

May

Tuesday 17 May, 13:00
Elena Holm "Von Willebrand disease – aspects on diagnosis, prophylaxis and outcome”
Venue: The conference room, Koagulationscentrum, Jan Waldenströms gata 14, level 3A, Skåne University Hospital, Malmö.
Experts: Professor Stefan Lethagen and reader Kerstin Westman
Supervisor: Professor Erik Berntorp, co-supervisor: Reader Eva Zetterberg

 

2015

 

November

Friday 27 November, 13:00
Oliver Patschan, Division of Urological Research 
"Stage T1 Bladder Cancer – Aspects on Diagnosis and Treatment"
Venue: MFC "Tidskriften", Jan Waldenströms gata 5, First floor, Skåne University Hospital, Malmö.
Experts: Associate Professor Amir Sherif, Department of Surgical and Perioperative Sciences, Urology, Umeå University.
Senior lecturer Martin Johansson, Dept. of. Translational medicine, Clinical pathology, Malmö.

 

October

Thursday 1 October,14:00
Aseem Anand, Division of Urological Cancers 
"Prostate cancer biomarkers – analytical and clinical qualification of bone scan index as quantitative imaging biomarker"
 Experts: Docent Annika Håkansson, Skåne University Hospital and senior teacher Lena M Jönsson, Medical radiation physics in Lund, Lund University
 Supervisor: Professor Anders Bjartell, Co-supervisor: Lars Edenbrandt

Site overview