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Halvtidskontroller IKVM

2021

 

December

 

Örvar Arnarson

17 december, klockan 13
Projekt: "Postoperative complications after surgery for colon cancer and management of acute colon cancer"
Lokal: Biblioteket plan 3, på kirurgiska kliniken, Carl-Bertil Laurells gata 9, Skånes universitetssjukhus Malmö
Supervisor: Ingvar Syk
Co-supervisor: Salma Butt-Tunå

 

Abstract

Background
Postoperative complications after surgery for colorectal cancer are associated with increased mortality and may affect long-term oncological outcome. Today most high-volume hospitals have specialized colorectal units managing all elective cases of colorectal cancer and emergency surgery units dealing with a wide spectrum of emergency cases, including acute colon cancer. The concept of bridge to surgery (BtS) has been introduced to decrease morbidity in patients with acute malignant large-bowel obstruction, in which the patient undergoes decompression of the colon as a first stage, followed by a postponed definitive resection surgery. Operative and follow-up details are uploaded into the Swedish Colorectal Cancer Registry. Data validity is crucial and defined as the proportion of cases in a dataset matching the source data. 

Aims
Study 1: analyse whether postoperative complications inflicting inflammatory response are associated with increased recurrence rate, impaired overall and disease-free survival based on population data from SCRCR

Study 2: evaluate the impact of surgeon specialization on short- and long-term outcome in patients undergoing emergent colon cancer surgery

Study 3: compare BtS by either DS or SEMS with emergent resection in acute malignant large-bowel obstruction, with focus on short- and long-term survival in a population-based material.

Study 4: assess the validity of the SCRCR. 

Preliminary results
Study 1: Severe complications after surgery for colon cancer are associated with impaired overall and disease-free survival, but not increased rate of recurrence.

Study 2: long-term survival after emergent resection of colon cancer was not influenced by the specialization of the surgical unit and no difference in post-operative morbidity or mortality rate was noted

Study 3: Bridge-to-surgery management in acute malignant large-bowel obstruction was associated with lower perioperative and long-term mortality rates compared to emergent resection but not 3-year recurrence-free survival. 

Study 4: No results yet 

Importance
Measures to avoid or promptly address postoperative complications should be implemented. A surgeon specialized in acute surgery does not need to refrain from treating acute presented colon cancer. BtS management of malignant large-bowel obstruction should be preferred over emergent resection.

Publicerade delarbeten 
Arnarson, O., S. Butt-Tuna, and I. Syk, Postoperative complications following colonic resection for cancer are associated with impaired long-term survival. Colorectal Dis, 2019. 21(7): p. 805-815.


Hanna Markstad

10 December, klockan 9
Project: "Linking lipid markers and coronary computed tomography imaging to fight cardiovascular disease" 
Venue: CRC (Clinical Research Center), House 60, floor 12, room 15, conference rum 60-12-15, Jan Waldenströmgs gata 35, Malmö
Or on zoom: https://lu-se.zoom.us/j/66796657763
Head supervisor: Isabel Gonçalves
Co-supervisor: Gunnar Engström
Reviewers: Prof Henrik Engblom (Karolinska Institute, Stockholm) and Associate Prof Viktor Hamrefors (Clinical Sciences Malmö, Lund University

 

Abstract

Background
Cardiovasculardisease (CVD) stands for 32% of global deaths, strokes and heart attacks 89% ofthese. Biological and imaging markers to detect subjects at risk for CVD areurgently needed. 

Methods
Paper 1: CirculatingSoluble Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 (sLOX-1) weredetermined for 4703 participants in Malmö Diet Cancer cohort. Incidence ofischemic stroke was studied. For 202 patients undergoing carotidendarterectomy, sLOX-1 was analyzed in plasma and plaque, and related to atheroscleroticplaque inflammation. 

Paper 2: 434patients with chest pain who underwent coronary computed tomography angiography(CCTA) at Skåne University Hospital and 197 SCAPIS participants were included. Atherosclerosiswas assessed in all.

Coronaryartery bridging (CB), a coronary anomaly, prevalence and characteristics werecompared in these two cohorts with or without chest pain. 

Preliminary results
Paper 1:Higher sLOX-1 are related to future stroke (HR 1.75 for highest tertile ofsLOX-1 compared to the lowest (p<0.001)) remaining 1,44 (p 0,032) afteradjusting for CV risk factors, and more so in the presence of carotid plaque. Plaqueswith high sLOX-1 had more oxLDL, proinflammatory cytokines, and matrixmetalloproteinases.

Paper 2: CB is extremely common, being found in 95% of the 631 subjects inat least one segment. Of 4587 segments, 45% had CB. CB was more common in individualswithout chest pain in segment 6 and M1 compared to those with chest pain. Forthose with chest pain, CB was longer in LAD than in those without chest pain. CBwas deeper in segments IM17 and M1 for those without chest pain.

Importance
LOX-1 playsa role in atherosclerosis and might be a target for CV interventions. A bloodtest to predict risk for stroke might motivate patients to CV prevention andimprove their risk stratification and treatment.

Chest painis very common in CVD leading to increased assessment with CCTA, whereatherosclerosis and fat tissue can be depicted. CB is increasingly identifiedby CCTA, but its implications and relation with CVD are still unknown,warranting our studies regarding imaging markers in CVD. 

Published work 
MarkstadH, Edsfeldt A, Yao Mattison I, Bengtsson E, Singh P, Cavalera M, Asciutto G,Björkbacka H, Fredrikson GN, Dias N, Volkov P, Orho-Melander M, Nilsson J,Engström G, Gonçalves I. High Levels of Soluble Lectinlike Oxidized Low-DensityLipoprotein Receptor-1 Are Associated With Carotid Plaque Inflammation andIncreased Risk of Ischemic Stroke. J Am Heart Assoc. 2019 Feb 19;8(4):e009874.doi: 10.1161/JAHA.118.009874. PMID: 30744454; PMCID: PMC6405674.


Johan Korduner

7 december, klockan 13
Projekt: "The heterogeneity of obesity for risk of cardiometabolic disease - epidemiological and clinical aspects"
Lokal: 60-12-015 på Clinical Research Centre (CRC), Jan Waldenströms gata 35, Skånes universitetssjukhus Malmö (Sus Malmö)
Via Zoom: https://lu-se.zoom.us/j/66511073954
Huvudhandledare: Martin Magnusson (professor, överläkare på kardiologiska kliniken Sus Malmö)
Bihandledare: Peter Nilsson (professor, överläkare), Hannes Holm (PhD, ST-läkare på kardiologiska kliniken Sus Malmö) och Erasmus Bachus (PhD, specialistläkare i kardiologi/internmedicin)
Opponenter: Sofia Enhörning (Docent, ST-läkare på internmedicinska kliniken Sus Malmö) och Erik Uddman (PhD, överläkare på endokrinologiska kliniken Sus Malmö) 

 

Abstract

Background
Obesityhas become a growing global pandemic, contributing to the risk of cardiovasculardisease (CVD). However, obesity is a heterogeneous phenotypewith large variation in the individual risk of developing obesity-associated CVD.

Thus, researchershave tried to characterize the so-called Metabolically Healthy Obesity (MHO),defined by obese individuals with significantly lower risk for cardiovascular complications. These subjects will not escape long-term complications that are instead postponed, but mortality risk is not increased. 

Research question and method
The aim of the PhD project is to investigate the characteristics and prospective risk of MHO individuals as compared to Metabolically Unhealthy Obesity (MUO) and non-obese controls (NOC). Cross-sectional studies have been carried out in the Malmö Diet and Cancer Study (MDCS), where MHO individuals have been defined by using a novel approach of a history of non-hospitalization status up until mid-life. Prospective risk for total mortality and incident CVD, along with descriptive data and biomarker analysis (proteomics, lipidomics, metabolomics, anti-phosphoryl choline antibodies; n=433) has been analyzed and described in three different published articles. The fourth paper will investigate if levels of metabolic/catabolic biomarkers (n=92 biomarkers) vary between different BMI-groups of patients with heart failure, and their prognostic significance. 

Preliminary results
MHO individuals experienced a decreased risk of both total mortality and incident CVD, compared to MUO during a 20-year follow-up period. When comparing MHO to NOC, there were no significant differences in terms of mortality or CVD risk. Descriptive data suggests that potential protective factors result in a more favorable lipid and glucose profile, downregulation of potential harmful proteomic biomarkers and practicing a less sedentary lifestyle. Moreover, lower plasma level of antibodies against anti-phosphoryl choline(anti-PC) were associated with higher risk of being MUO. 

Implications
The heterogeneity of obesity is indisputable. Our studies show, in line with previous research, that MHO individuals might possess a lower CVD risk and mortality compared to MUO, and similar risk in comparison with NOC. By mapping MHO, we have gained a deeper understanding of risk determinants for obesity as well as biological mechanisms, life style and social factors. Ultimately this might provide insight into improving treatment strategies and individualized care. 

Publications at halftime
Korduner J, Bachus E, Jujic A, Magnusson M, Nilsson PM. Metabolically healthy obesity (MHO)in the Malmö diet cancer study - Epidemiology and prospective risks. ObesityResearch and Clinical Practice. 2019;13(6):548-554. (Paper I) 

Nilsson PM, KordunerJ, Magnusson M. Metabolically Healthy Obesity(MHO)-New Research Directions for Personalised Medicine in Cardiovascular Prevention (Review). Current Hypertension Reports. 2020 feb 17;22(2):1-5. 18. 

Korduner J, Nilsson PM, Melander O, Gerl MJ, Engström G, BachusE, Magnusson M, Ottosson F. Proteomic and metabolomic characterization of Metabolically Healthy Obesity – A descriptive study from a Swedish cohort. Journal of Obesity. 2021;2021:6616983. (Paper II)

Jujić A, Korduner J, Holm H, Engström G, Bachus E, Bhattacharya P, Nilsson PM, Frostegård J, Magnusson M. Antibodies against phosphorylcholine in hospitalized versus non-hospitalized obese subjects. Scientific Reports. 2021;11(1):20246. (Paper III)


Adugna Negussie Gudeta     

1 december, klockan 9
Projekt: "Traditional Ethiopian Food (TEF) and early life exposures on the risk of celiac disease autoimmunity in HLA-genotyped children from the Oromia region in Central Ethiopia: TEF study"
Lokal: Clinical Research Center (CRC), Jan Waldenströms gata 35, Malmö (rum 60-12-015)
Via Zoom: https://lu-se.zoom.us/j/61271877995
Huvudhandledare: Daniel Agardh (adjungerad professor, överläkare)
Bihandledare: Carin Andrén Aronsson (PhD, dietist)
Opponenter: Klas Sjöberg (adjungerad professor, överläkare) och Ola Andersson (docent, överläkare)

 

Abstract

Background
The global prevalence of celiac disease varies dependent on distribution of HLA risk genotypes, consumption of gluten-containing foods and exposures to triggering environmental factors in the general population. The prevalence of celiac disease remains unknown in most countries worldwide due to lack of mass screening. 

Research question and method

  1. What is the prevalence of celiac disease autoimmunity (CDA) in Ethiopian children compared with adults?
  2. What is the prevalence of HLA-risk genotypes for celiac disease in the Ethiopian population?
  3. Are traditional infant feeding practices affected by sociodemographic factors in Ethiopian children?
  4. Do latent maternal tuberculosis and Helicobacter pylori infections associate with CDA? 

TEF study screens for CDA and prospectively collects dietary and infectious data in a birth cohort of children to 4 years of age selected from the general population in the city of Adama in Ethiopia. 

Preliminary results
In Study 1, a cross-sectional study of 1942 Ethiopian women at the median age of 25 (range 15-45) years found a 0.05% prevalence of CDA indicating that celiac disease is rare in the Ethiopian adult population. 

In Study 2, 1193 Ethiopian children were genotyped for HLA-genotyped and compared with 2000 Swedish children. There was no difference between Ethiopian and Swedish children with moderate to very high-risk HLA genotypes (27.4% vs 29.0%) (p=0.3504). 

In Study 3, data on infant feeding practices and sociodemographic factors were prospectively collected from 1054 mother-child pairs. Vegetables, cereals, and fruits were most often the earliest types of foods introduced. Timely introduction of complementary foods was 85%, which is according to the WHO recommendations.

In ongoing studies, the incidence of CDA will be estimated in the full TEF cohort. Preliminary results show that 1% of children have signs of celiac disease autoimmunity. Studies on complementary foods and early infectious exposures on the risk of CDA are pending.

Implications
The genetic propensity for celiac disease in Ethiopia is equally as high as in Caucasians. CDA in Ethiopia children is higher than previously described, indicating that incidence of celiac disease is increasing. Changes in early life exposures could be contributing factors associated with this increase in CDA. 

Publications at half time review
Paper I: Adugna Negussie Gudeta, Charlotte Brundin, Daba Muleta Feyissa, Taye Tolera Balcha, and Daniel Agardh, “Prevalence of Celiac Disease Autoimmunity in Ethiopian Pregnant Women: A Cross Sectional Study from the Oromia region.” International Journal of Celiac Disease, vol. 7, no. 3 (2019): 74-77. doi: 10.12691/ijcd-7-3-1 

Paper II: Gudeta AN, Ramelius A, Balcha TT, Girma A, Ilonen J, Agardh D. Distribution of HLA-DQ risk genotypes for celiac disease in Ethiopian children. HLA. 2020;96: 681–687. https://doi.org/10.1111/tan.14119 

Paper III: Gudeta AN, Aronsson CA, Balcha TT and Agardh D (2021). Complementary Feeding Habits in Children Under the Age of 2 Years Living in the City of Adama in the Oromia Region in Central Ethiopia: Traditional Ethiopian Food Study. Front. Nutr. 8:672462.

doi: 10.3389/fnut.2021.672462. 


Yanni Li

1 december, klockan 9
Projekt: "Liquid biopsy-based biomarkers for early detection and diagnosis of cancer"
Via Zoom: https://lu-se.zoom.us/j/6104692163
Main supervisor: Ashfaque Memon
Co-supervisors: Kristina Sundquist
Reviewers: Christer Larsson och Kazi Uddin

 

Abstract

Background
Cancer ranks as a leading cause of death worldwide, accounting for almost 19.3 million new cases and 10.0 million deaths in 2020. Earlier clinical detection may improve survival as well as offer opportunities for less invasive treatment options. Cancer cells shed information into circulation during tumorigenesis and that provides us a great opportunity to detect cancer in the blood long before it may be detected by prevalent clinical diagnostic methods. However, detection is difficult due to few circulating copies of nuclear genomes in the blood at an early stage of cancer. Mitochondrial genomes may therefore provide an excellent opportunity for earlier detection because, unlike the nuclear genome, it has multiple copies circulating in the blood. The overall aim of my PhD project is to explore whether mitochondrial genomes analyzed in the blood can be used as novel method for the earlier detection of different cancers.

Research Aims and Methods:

  1. To investigate if mitochondrial dysfunction (mtDNA copy number)/telomere length is associated with cancers – paper 1, quantitative real-time PCR, droplet digital PCR (ddPCR)
  2. To investigate somatic mitochondrial mutations as potential biomarkers for the early diagnosis of breast cancer – whole mitochondrial genome sequencing and bioinformatics analysis, ddPCR 
  3. To investigate the role of mitochondrial-related genes as drivers or passengers in multiple cancer types – differential expression analysis, co-expression analysis, Mendelian randomization analysis
  4. To investigate the molecular alterations and mitochondrial dynamics in the initiation of breast cancer – cell reprogramming and organoid differentiation, RNA-sequencing, seahorse metabolic assays.

Preliminary results

  • Study 1: We found that mtDNA-CN and telomere length was significantly associated with prevalent and incident cancer and cancer mortality. However, these associations were cancer-type specific and need further investigation (published).
  • Study 2: We have identified multiple novel mutations in the mitochondrial genome and some mtDNA mutations were significantly associated with mitochondrial dysfunction.
  • Study 3: We have now extracted RNAseq data for 18 types of cancer from the online database (TCGA and GTEx). All sequencing data were processed and differentially expressed mitochondrial-related genes were shortlisted for different cancers.
  • Study 4: Two benign cell lines and one breast cancer cell line were successfully reprogrammed and confirmed as iPSCs.

Significance
We will investigate whether mitochondrial genomes from DNA, RNA, and protein levels as biomarkers for earlier detection of cancer. If successful, this project will lay the foundation for early molecular diagnosis of cancers using innovative, non-invasive methods. It may thus become an aid in existing screening programs for the earlier diagnosis of cancers. It will also pave the way for further depicting mitochondria biological functions in cancers.

Publications
Li Y, Sundquist K, Wang X, Zhang N, Hedelius A, Sundquist J, Memon AA. ‘Association of Mitochondrial DNA Copy Number and Telomere Length with Prevalent and Incident Cancer and Cancer Mortality in Women: A Prospective Swedish Population-Based Study.’ Cancers 2021, 13(15), 3842; https://doi.org/10.3390/cancers13153842


November

 

 

Beatrice Yang

30 november, klockan 9
Projekt: "Impact of epigenetic mechanisms in human pancreatic islets on the pathogenesis of type 2 diabetes"
Lokal: 60:13:14, CRC, Jan Waldenströms gata 35, Sus Malmö
Huvudhandledare: Charlotte Ling
Bihandledare: Marloes Dekker-Nitert och Karl Bacos
Granskare: Anna Wendt och Rashmi Prasad

 

Abstract

Background
Type 2 diabetes (T2D) is a multifactorial disease,characterized by hyperglycemia due to impaired insulin secretion and insulinresistance in target tissues. It develops due to genetic and environmentalfactors. 

Recent studies further suggest that epigeneticfactors, such as DNA methylation, may contribute to T2D development [1,2].Thus, the aim of this thesis is to investigate if T2D is associated withaltered DNA methylation in human pancreatic islets. By analyzing DNAmethylation levels of specific candidate genes, as well as genome-wide DNAmethylation in islets, we want to determine if epigenetic dysregulation ofislets contributes to islet dysfunction in subjects with T2D. 

With the candidate gene approach, we showed that DNAmethylation of INS (encoding insulin) and PDX-1 (encoding a keytranscription factor for beta-cell function [3]) was increased in islets fromdonors with T2D. Furthermore, we found that the mRNA expression, insulincontent and glucose-stimulated insulin secretion (GSIS) were decreased in thesame diabetic islets [4,5]. 

Mitochondrial oxidative phosphorylation (OXPHOS) isknown to play a critical role in GSIS [6]. We therefore investigated whetherOXPHOS genes have altered expression and DNA methylation levels in islets fromT2D donors. Indeed, we found downregulation of some OXPHOS genes in islets fromdiabetic donors. We also demonstrated that islet expression of multiple OXPHOSgenes correlated positively with GSIS, suggesting that decreased isletexpression of OXPHOS genes may contribute to impaired GSIS in T2D. However, wefound no DNA methylation changes in selected OXPHOS candidate genes (NDUFA5,COX11 and ARP6V1H) in islets from diabetic compared withnon-diabetic donors [7]. 

Finally, ageing is a known non-genetic risk factorassociated with T2D, and the upcoming study is moving beyond the candidategene(s) approach and is aimed to replicate and expand on associations betweenage and genome-wide epigenetic changes in human islets, further connecting thefindings with GSIS and diabetes [8]. 

Overall, we have identified epigeneticmodifications with potential functional effects in pancreatic islets frompatients with T2D, suggesting a role for epigenetic factors in T2D. However,further research is needed to enhance our knowledge about the molecularmechanisms linking environmental factors and the disease.

References

1. Ling,C. and L. Groop (2009). "Epigenetics: a molecular link betweenenvironmental factors and type 2 diabetes." Diabetes 58(12): 2718-2725.

2. Ling,C. and T. Ronn (2019). "Epigenetics in Human Obesity and Type 2Diabetes." Cell Metab 29(5):1028-1044.

3. Melloul,D., S. Marshak and E. Cerasi (2002). "Regulation of pdx-1 geneexpression." Diabetes 51Suppl 3: S320-325.

4. Yang,B. T., T. A. Dayeh, C. L. Kirkpatrick, J. Taneera, R. Kumar, L. Groop, C. B.Wollheim, M. D. Nitert and C. Ling (2011). "Insulin promoter DNAmethylation correlates negatively with insulin gene expression and positivelywith HbA(1c) levels in human pancreatic islets." Diabetologia 54(2): 360-367.

5.  Yang, B. T., T. A.Dayeh, P. A. Volkov, C. L. Kirkpatrick, S. Malmgren, X. Jing, E. Renstrom, C.B. Wollheim, M. D. Nitert and C. Ling (2012). "Increased DNA methylationand decreased expression of PDX-1 in pancreatic islets from patients with type2 diabetes." Mol Endocrinol 26(7): 1203-1212.

6. Wiederkehr,A. and C. B. Wollheim (2006). "Minireview: Implication of Mitochondria inInsulin Secretion and Action." Endocrinology 147(6): 2643-2649.

7. Olsson,A. H., B. T. Yang, E. Hall, J. Taneera, A. Salehi, M. D. Nitert and C. Ling(2011). "Decreased expression of genes involved in oxidativephosphorylation in human pancreatic islets from patients with type 2diabetes." Eur J Endocrinol 165(4):589-595.

8. Bacos,K., L. Gillberg, P. Volkov, A. H. Olsson, T. Hansen, O. Pedersen, A. P.Gjesing, H. Eiberg, T. Tuomi, P. Almgren, L. Groop, L. Eliasson, A. Vaag, T.Dayeh and C. Ling (2016). "Blood-based biomarkers of age-associatedepigenetic changes in human islets associate with insulin secretion anddiabetes." Nat Commun 7:11089.


Angelos Karelis

26 november klockan 9
Projekt: "Advanced endovascular treatment for complex aorto-iliac aneurysms including ruptured aneurysms"
Lokal: Konferensrummet, Ruth Lundskogs gata 10, Skånes universitetsjukhus Malmö
Delta via Zoom: https://lu-se.zoom.us/j/65894989349
Handledare: Nuno Dias, docent, överläkare i kärlkirurgi, kärlcentrum Sus Malmö
Bihandledare: Björn Sonesson, docent, överläkare i kärlkirurgi, kärlcentrum, Sus Malmö
Opponenter:
1. Carl Wahlgren, adjungerad professor, institutionen molekylär medicin och kirurgi, Karolinska institutet
2. Håkan Roos, medicine doctor, avdelningen för molekylär och klinisk medicin vid institutionen för medicin, Sahlgrenska akademin, Göteborgs universitet

 

Abstract

Background
Endovascular aneurysm repair (EVAR) of complex aortic aneurysms, particularly on the acute setting of rupture, are a challenging situation with high mortality rates. However, new methods and endovascular techniques show promising mid-term results, but accurate patient selection is crucial.

The aim of the project is to evaluate new methods and techniques, minimizing the morbidity and mortality through improved selection of patients with more complex anatomy.

Methods
All patients who underwent emergency EVAR and iliac branch device (IBD) plus more complex aortic stentgrafts at the Vascular Center of Malmö since 2004 were examined retrospectively. Pre-, intra- and postoperative images and clinical data were reviewed. Even a multicenter validation of findings with a greater proportion of patients has been initiated.

Aims of project

I  – Multicenter outcomes of redo Fenestrated/Branched endovascular aneurysm repair to rescue failed Fenestrated endografts.

II  – Assess the feasibility of acute branched endovascular repair of ruptured aortoiliac aneurysms.

III - Multicenter outcomes of internal iliac artery revascularization versus intentional occlusion for endovascular repair of ruptured aortoiliac aneurysms.

IV  - Study the influence of the anatomy of ruptured abdominal aortic aneurysm on the prediction of failure due to aortic neck dilatation after endovascular repair.

Preliminary results
Study I: F/BEVAR-in-FEVAR is a technically challenging but feasible solution to rescue failed FEVAR. The outcomes are promising in many aortic centres but need to be confirmed by further studies with longer follow up. (1)

Study II: The use of iliac branched devices (IBD) in the acute setting is feasible to exclude ruptured aorto-iliac aneurysms while maintaining pelvic circulation. The secondary intervention rate is considerable, however the midterm assisted primary patency rates are promising. Further studies are needed to guide patient selection. (2)

Study III: The use of IBD in ruptured aorto-iliac aneurysms has promising midterm assisted primary patency in many experienced aortic centers. Further studies are needed to guide patient selection and to evaluate longer term outcomes. (manuscript)

Significance
Improving the selection of patients with complex anatomy and ruptures for advanced endovascular treatments with the aim of higher long-term survival while avoiding common postoperative complications. 

Published Projects

  1. Karelis A, Haulon S, Sonesson B, Adam D, Kölbel T, Oderich G, Cieri E, Mesnard T, Verhoeven E, Dias N; contributors. Multicentre Outcomes of Redo Fenestrated/Branched Endovascular Aneurysm Repair to Rescue Failed Fenestrated Endografts. Eur J Vasc Endovasc Surg. 2021 Aug 12:S1078- 5884(21)00548-7. doi: 10.1016/j.ejvs.2021.06.038. Epub ahead of print. PMID: 34393056. 
  1. Karelis A, Dijkstra ML, Singh B, Vaccarino R, Sonesson B, Dias NV. The Use of Iliac Branched Devices in the Acute Endovascular Repair of Ruptured Aortoiliac Aneurysms. Ann Vasc Surg. 2020 Aug;67:171-177. doi: 10.1016/j.avsg.2020.02.019. Epub 2020 Mar 20. PMID: 32205247.

Rozita Torkpoor

19 november, klockan 13
Projekt: "Cognitive assessment in foreign born – with special reference to interpretation, communication and cognitive tests"
Lokal: Sal Pion, i ingången på minnesmottagningen i Malmö vidTriangeln, St Johannesgatan 6, Malmö
Handledare: Elisabet Londos

 

Abstract

Background
Cognitivetesting is fundamental in the investigation of cognitive disorders/dementia(Fields et al., 2011). Most conventional cognitive tests are influenced by language,culture and educational background, and may mislead the investigation offoreign born patients (Ardila, 2005; Nielsen et al., 2011). The prevalence ofolder foreign born increases and therefor the availability of proper methodsfor correct evaluations are increasingly important. (Franzen et al., 2020).  In Skane more than 20% of the inhabitants areborn outside Sweden. This doctoral thesis investigates some of these aspects.

Objective
To investigate the role of the interpretation, communication and constructionof cognitive tests in the dementia investigation of foreign borns.

Preliminaryresult
In aqualitative study of 19 filmed and recorded first visits at a Memory clinicwhere a doctor or nurse, the patient and an interpreter are present. Thedialogues were analysed with an ethnographic qualitative method and revealedimportant mistakes in the interpretation and the communication. Theinterpretation aspect is presented in an article accepted for publication andthe communication with focus on the role of the health personnel is analysedbut not yet submitted.

Anotherstudy was performed to validate newer cognitive tests shown to be lessinfluenced by culture and education, RUDAS (The Rowland Universal Dementia Assessment Scale) and MCE (Multicultural cognitive examination),in a Swedish context which is not done before. 127 individuals, Swedish andforeign-born were exposed to these tests beside the traditional investigationbattery in 4 memory clinics in Skane. The main findings confirm previousstudies showing that the traditional instrument, MMSE, is influenced byeducation and culture while the newer instruments are not. Interestingly thepattern of specific cognitive diagnoses seems differ whether the patient isSwedish or foreign born, while the cognitive results, depression scale andpractical ADL performance do not.

Importance
The results of this thesis will give tools to offer a more equal and safe dementia investigation and carefor foreign born persons in the Swedish society. 

Published articles
“I know hyena, do you know hyena? Challenges in interpreter-mediated dementia assessment, focusing on the role of the interpreter” is the first article, accepted for publication in Journal of Cross-Cultural Gerontology 2021.


Giovanni Cagnotto

18 november, klockan 9
Projekt: “Predictors of treatment outcomes in rheumatoid arthritis”
Plats: rehabrummet, plan 2, reumatologmottagningen, Jan Waldenströms gata 1B, Skånes universitetssjukhus Malmö
Huvudhandedare: Carl Turesson
Bihandledare: Lennart Jacobsson
Granskare: Andreas Jönsen (reumatologi, Lund), Olof Grip (gastroenterologi, Malmö)

 

Abstract

Background
Implementation of evidence-based treatment strategies and the development of new effective drugs have improved the prognosis of patients with rheumatoid arthritis (RA) in the last 20 years. Yet, a significant proportion of patients does not benefit from a chosen treatment and needs to test several different drugs in order to find the best fitting alternative, thus leading to waste of time and resources and increased risk of adverse events. This project aims to find possible predictors of treatment outcome in RA, which could inform the choice of a suitable drug for each single patient in a clinical setting.

Methods
The project includes 4 studies. In a cohort study of RA patients treated with abatacept and included in the Swedish rheumatology quality register (SRQ) between 2006 and 2017, predictors for survival on drug were analyzed by means of cox-regression analysis. A second study involved patients with early RA included in SRQ between 2012 and 2016 and in the Malmö early arthritis cohort between 1995-2005. The role of sex as a predictor of outcomes was investigated by logistic regression after stratification for autoantibodies profile in each cohort and in the pooled cohorts. A third prospective study will include consecutive RA patients considered to need treatment with a biologic drug by their rheumatologist at the outpatient clinic in Malmö. Patients will undergo ultrasonography of the joints that will be performed by a blinded investigator at treatment start. The predictive value of ultrasound for clinical outcome at 12 months will be investigated through logistic regression. The last study consists of a systematic literature review with metanalysis aiming to evaluate efficacy and harms of TNF inhibitors in the treatment of seronegative RA. It will be performed according to Cochrane methodology.

Preliminary results
Our first study showed that bionaïve patients and male patients were more likely to remain on abatacept with a major clinical response. The second one showed that male sex predicted a good treatment outcome in patients with seronegative RA.

Significance
A combination of clinical parameters could be an effective tool to predict treatment outcome in different subgroups of RA patients.


Megan Mulholland

17 november, klockan 13
Project: "Regulation of T cells in Atherosclerosis"
Location: Medelhavet, Wallenberglaboratoriet
Zoom link: https://lu-se.zoom.us/j/64418369312
Supervisor: Daniel Engelbertsen
Co-supervisor: Harry Björkbacka
Reviewers: Professor Karin Leandersson (Lund University) and Professor Daniel Ketelhuth (Syddansk Universitet)

Abstract

Background
Cardiovascular disease is the leading cause of mortality worldwide. Atherosclerosis, the formation of lipid-rich inflammatory plaques in arteries, is the main pathological process causing myocardial infarction and stroke. Though once viewed as a strict metabolic disorder, today atherosclerosis is regarded as a multifactorial chronic inflammatory disease. 

Research question and method
T cells have been shown to contribute to plaque inflammation, but the mechanism and the site of action remains unclear. To address the question of how plaque T cells affect plaque development we are using multiple complementary approaches:

1. To investigate the role of non-classical cytokine-mediated T cell activation in atherosclerotic plaques, we used a non-depleting IL-2Rβγ blocking antibody in atherosclerotic mice and analyzed the effects (published).

2. T cell receptor (TCR)- and cytokine-reporter mice (Nur77-GFP and IFN-γ-YFP) are being utilized to determine if, or to what degree, T-cell activation and cytokine production takes place in the plaque during disease course.

3. Administration of an IL-1 receptor accessory protein (IL-1RAP) antibody to atherosclerotic mice, with and without adjunct therapy (checkpoint blockade), to determine the role of IL-1 signaling in plaque pathogenesis. 

Preliminary results

1. The results of this study have been published and showed that while total plasma cholesterol was lowered with anti- IL-2Rβγ treatment, overall plaque burden and phenotype were unchanged.

2. Preliminary results indicate that levels of cytokine release observed are above levels of TCR-mediated T cell activation, suggesting that antigen-driven activation of T cells in the plaque is not key for mediating T cell-driven atherosclerosis. Our results suggest that PD-1 expression best identified aortic IFN-γ-producing T cells, thus we are conducting further studies to elucidate both the phenotypical and functional characteristics of aortic PD-1 expressing T cells.

3. Preliminary results and supplementary studies are ongoing. 

Significance
While atherosclerosis is partially treatable by lipid-lowering medication, risk of a cardiovascular event still remains for these patients. This residual risk needs to be addressed by next-generation immunomodulatory drugs, and targeting T-cell driven mechanisms may be key. 

Publications
Mulholland, et al. IL-2Rβγ signalling in lymphocytes promotes systemic inflammation and reduces plasma cholesterol in atherosclerotic mice. Atherosclerosis. 2021 Jun;326:1-10. doi: 10.1016/j.atherosclerosis.2021.04.010.


Ursula Aho Fält

12 november, klockan13
Projekt: "Anal fistulas – three-dimensional endoanal ultrasound and the anal fistula plug"
Lokal: kirurgiska klinikens bibliotek, Carl Bertil Laurells gata 9, mp B plan 3, Skånes universitetssjukhus Malmö
Huvudhandledare: Sara Regnér, docent, överläkare
Biträdande handledare: Louis Johnson, docent, överläkare, Marianne Starck MD, PhD
Granskare: Steen Buntzen, professor emeritus, Aarhus universitetssjukhus, Danmark och Pär Myrelid, biträdande professor i kirurgi, Linköpings universitet

 

Abstract

Background
Treating complex anal fistulas with sphincter-preserving techniques remains a therapeutic challenge. The anal fistula plug (AFP) was introduced in 2005 and reported success rates vary between 14-100%. Few studies include follow-up periods longer than the first post-operative year, and the AFP has not been adequately evaluated for treatment of fistulising Crohn’s disease.

Magnetic resonance imaging (MRI) is sometimes used to diagnose anal fistulas and for the follow-up after the AFP. A small number of studies examine the use of three-dimensional (3D) endoanal ultrasound (EAUS) in diagnostics and treatment of anal fistulas. Documented knowledge of intra/interobserver agreement and anatomical variation in morphology is limited when it comes to 3D EAUS. 

Aims

  • Study 1: To evaluate the long-term success rate of the AFP treatment for complex anal fistulas.
  • Study 2: To explore the utilisation of 3D EAUS for the follow-up of the AFP treatment.
  • Study 3: To investigate the use of 3D EAUS for preoperative assessment of newly diagnosed anal fistulas.
  • Study 4: To explore the use of 3D EAUS for measurement of anal canal length. 

Methods

  • Study 1: Single-centre study of 95 consecutive patients treated with the AFP between 2006-2009.
  • Study 2: Retrospective analysis of 3D EAUS investigations collected during Study 1.
  • Studies 3 and 4: Prospective cohort of 94 patients with newly diagnosed anal fistulas. 

Preliminary results

Study 1: After a median period of 110 (range: 93-138) months, the overall healing rate after one to five AFP procedures was 38%. No statistically significant difference in success rate was found between the cryptoglandular fistula group and the Crohn’s fistula group (P = 0.37).

Study 2: Gas in fistula at 3 months and at 6-12 months, inflammation at 3 months, and visible fistula at 3 months and at 6-12 months, were statistically significant ultrasound findings for AFP failure. 

Importance
There is no statistically significant difference between success rates of the AFP for treatment of cryptoglandular or Crohn’s fistulas at a follow-up more than 5 years after surgery. Postoperative 3D EAUS at 3 months or later can be used predict AFP failure. 

Published manuscript
Aho Fält, U., Zawadzki, A., Starck, M., Bohe M., Johnson, LB. Long-term outcome of the Surgisis® (Biodesign®) anal fistula plug for complex cryptoglandular and Crohn’s fistulas. Colorectal Dis 2021; 23:178-85. DOI: 10.1111/codi.15429


Jens Wilkens

12 november, klockan 10
Projekt: "Primary care in transition: evaluation of effects on utilization and distribution of digital primary care in  Sweden"
Venue: 93-10-007, CLinical Research Centre, Jan Waldenströms gata 35, Malmö
Supervisor: Björn Ekman, Social Medicine and Global Health (SMGH), IKVM, LU
Co-supervisor: Hans Thulesius, IKVM, LU and Linnéus University
Reviewers: Lina Maria Ellegård, Department of Economics, LU and Mehdi Osooli, IKVM, LU

 

Abstract

Background
Expanding the scope and effectiveness of primary health care is high on the agenda in Sweden as well as globally. In parallel, new digital forms of remote primary health care services are developing fast. The effects of this development are largely unknown, still intensively discussed in media, among health professionals, and by policy makers. While the changing landscape of care seeking behaviour and service provision is likely to continue and also have large health system effects, the evidence base to support governance in this field is still weak. 

Research question and method
The PhD project’s overall aim is to evaluate health system performance effects from the emerging digital primary care provision in Sweden. The method is quantitative, using retrospective analysis on a purpose-built database with data from 2017 to 2018. Qualitative findings in related research are used for framing the project and contextualising study results. The project specifies research questions for both effects on clinical practice and utilization of services. After the first two publications (below), the study for the third publication estimates if there is a difference in prescribing and choice of antibiotics between visits to traditional in-office primary care and digital contacts. Regression analysis methods from the potential outcomes framework are applied to estimate the average treatment effects. The fourth publication evaluates if there are differences in service utilization across socio-economic groups and health care need, by applying concentration index analysis, estimate expected needs-adjusted utilisation, and decompose inequality effects into different factors. 

Preliminary results
Preliminary findings from this research project show that effects of the emerging digital primary care provision are significant, but do not unanimously go in a specific direction. 

Significance
The PhD projects will increase knowledge and evidence about effects of digital primary health care. The methods in publications three and four are applied for the first time to the specific research questions and thereby complement other research in the specific field. 

Publications

  1. Ekman B, Thulesius H, Wilkens J, Lindgren A, Cronberg O, Arvidsson E. Utilization of digital primary care in Sweden: Descriptive analysis of claims data on demographics, socioeconomics, and diagnoses. Int J Med Inform. 2019;127:134-40. 
  1. Wilkens J, Thulesius H, Arvidsson E, Lindgren A, Ekman B. Study protocol: effects, costs and distributional impact of digital primary care for infectious diseases—an observational, registry-based study in Sweden. BMJ Open. 2020;10(8):e038618.

Anna Sellgren Engskov

10 november, klockan 16.15
Projekt: "Nociceptive perception of pain – physiological aspects and impact of gender"
Lokal: kirurgiska klinikens bibliotek, plan 3 (kirurgibyggnaden, Carl Bertil Laurells gata 9, Sus Malmö
Halvtidskontrollen sker även digitalt, kontakta ansvariga om du vill delta!
Handledare: Jonas Åkesson
Oppontenter: Dag Lundberg, professor emeritus i anestesiologi och intensivvård, Lund, och Lars-Erik Dyrehag, medicine doktor och överläkare i anestesiologi och intensivvård, Halmstad

 

Abstract

Background
I: Few previous preclinical studies have reported selective induction and evaluation of C-fibre- mediated pain. Our main study hypothesis was that selective induction of delayed pain perception is possible with individually titrated carbon dioxide laser stimulation in humans.

II: Individual perception of pain is believed to depend on both physiological and psychosocial factors. Based on available data, our main study hypothesis was that subjects have lower pain sensitivity when evaluated by a female than by a male, and further on, that females have higher pain sensitivity than males. 

Aims and methods
I: The first study was designed to selectively induce delayed nociceptive pain responses. Forty- four (14 female) healthy volunteers were subjected to repeated dermal stimulation with individually titrated energy levels of carbon dioxide laser, assessed with visual analogue scale (VAS).

II: The second study in 40 adult volunteers (22 females) was designed to evaluate, with a randomized paired crossover design, potential impact of gender of study investigators and participants on electrical pain threshold (EPT) levels assessed with VAS.

Results
I: In the first study, 29 (11 female) out of 42 (12 female) subjects reported double (immediate and delayed) pain responses to each nociceptive stimulus. Single-pain responses were delayed and induced with lower energy levels than were double-pain responses. Significantly higher energy levels were used to induce mild pain in male subjects evaluated by a female than by a male study investigator.

II: In the second study, significantly higher EPT levels were determined by a female than by a male investigator at similar levels of reported pain intensity. The EPT levels determined did not differ between subject genders. 

Implications 
I.  Ability to selectively induce and evaluate delayed nociceptive pain, most likely reflecting C-fibre-mediated transmission, in study subjects might promote future research on perception and management of C-fibre-mediated pain in humans.

II.  Significantly higher EPT levels determined by female investigators in study subjects of both genders at the same level of reported pain intensity – indicating potential impact of investigator gender on individual perception of pain – might facilitate future interpretation and understanding of pain conditions in both preclinical and clinical settings. 

Publications 
I.  Sellgren Engskov A, Troilius Rubin A, Åkeson J. Single and double pain responses to individually titrated ultra-short laser stimulation in humans. BMC Anesthesiol 2019;19:1-5. 

II.  Sellgren Engskov A, Lejbman I, Åkeson J. Randomized cross-over evaluation of investigator gender on pain thresholds in healthy volunteers. Germ Med Sci 2021. In press.


Kenta Okuyama

November 4, 13:00
Project: "Neighborhood environments and cardiovascular-related outcomes in diverse populations"
Location: Video conference room at CRC in Malmö, Jan Waldenströms gata 35 (28-11-026) 
Participate on Zoom: https://lu-se.zoom.us/j/65351461444
Supervisor: Kristina Sundquist
Co-supervisor: Xinjun Li
Opponent: Martin Lindström (Professor at Social Medicine and Health Policy), and Emelie Stenman (Associate Professor at Family Medicine and Clinical Epidemiology)

 

Abstract

Background
Cardiovascular diseases (CVDs) are the leading cause of death, causing approximately 18 million premature deaths every year. Despite the knowledge and effort to modify individual behavioral and clinical risk factors, such as physical inactivity, unhealthy eating, and obesity, noticeable reduction in the burdens of CVDs have not been achieved at the population level. Identifying neighborhood environmental factors for CVD related outcomes could facilitate policy and environmental interventions to lessen the burdens of CVDs at the population level. 

Research question / Method
We aim to provide scientific evidence that can be incorporated into public health practices and policies for environmental-level interventions by identifying modifiable neighborhood environmental factors for CVD related outcomes. We will utilize nation- and region-wide population health and geographical databases in Sweden and Japan. Our target population are middle- and older aged adults who are affected by the CVDs the most. 

Preliminary result
First study investigated neighborhood modifiable environment and risk of obesity among Swedish adults. We found that neighborhood availability of fast food or physical activity facilities were not strong drivers of obesity among middle-aged Swedish adults based on 11-years longitudinal study. Second study investigated multiple neighborhood environmental factors and physical activity among rural Japanese older adults. We found that neighborhood hilliness and access to community center were associated with physical inactivity among rural older adults. Third study investigated neighborhood hilliness and risk of depressive symptoms among rural Japanese older adults. We found potential association between hilliness and increased risk of depressive symptoms among rural older adults. 

Significance
The results are useful for public health practices and policy makers to consider which areas and populations they should intervene on, as well as what they should invest in to lessen the burdens of CVDs. The findings also provide directions for future studies and policies to take local geographic and socio-cultural features into account as the role of each neighborhood environmental factor may vary across different groups of population. 


Oktober

 

Shantanu Sharma

Monday October 25th, at 15–17
Project: "Early life programming of health, body function and disease in three Swedish population-based cohorts"
Venue: Conference room, BMC D-house, first floor, Lund
Via zoom: https://lu-se.zoom.us/j/67073968904
Main tutor: Peter M Nilsson, MD, PhD, Professor
Co-tutor: Louise Bennet, MD, PhD, Associated Professor, and Anders Christensson, MD, PhD, Adjunct Professor

 

Abstract

Background
Factors acting in early life are of importance to influence organ function and adult health as evidenced from both observational studies and animal experiments. This is of special relevance for the risk to develop cardiovascular disease (CVD) and type 2 diabetes. If babies are born small for gestational age this is a risk marker that may worsen if a rapid catch-up growth takes place during the first years of life due to overfeeding. 

Aims and Methods

1. To conduct a systematic review of papers describing the influence of early life factors on risk and prognosis of cancer (Paper 1).

2. To describe the association between early life factors and adult organ function (traits) in the Malmö cohorts (n= 6000) - Paper 2 and Paper 3 - and the LifeGene cohort (n= 21,000) - Paper 4. Further to investigate if these associations are modified by background factors such as age, gender, social characteristics, or medical comorbidities.

3. To study the prediction of early life factors for incident disease manifestations until later life, based on national registers. Events will be defined by hospitalisations, or specific drug use, as a marker of contacts within primary health care (prescriptions).

4. To study the prediction of cardiometabolic events in the historical Helsingborg Birth Cohort (HbgBC; n= 4000) after nearly 60 years of follow-up - Paper 5 – using national registers. 

Preliminary results
Deviations in birth weight is of importance for the prognosis of some cancers (1). Impaired fetal growth resulting in low birth weight, as well as catch-up growth patterns (lower than median birth weight, higher than median body weight at age 20 years), can influence adult central hemodynamics (blood pressure, augmentation index), risk markers for CVD (2). Low birth weight is a risk marker for adult deviations in skin autofluorescence Advanced Glycation End (AGE) products, a marker of hyperglycaemia), and ankle-brachial index (ABI), a marker of peripheral vascular changes linked to atherosclerosis (3). 

Importance
If a deeper understanding can be reached for how factors acting early in life may affect organ function and health in adult life, this may support preventive strategies to support pregnant women with risk factors (gestational diabetes, gestational hypertension, smoking, etc.) as well as optimal feeding (breast milk) to growth-retarded newborn with prematurity or low birth weight in order to avoid too rapid catch-up growth. 

Papers 

1. Sharma S, Kohli C, Johnson L, Bennet L, Brusselaers N, Nilsson PM. Birth size and cancer prognosis: a systematic review and meta-analysis. J Dev Orig Health Dis. 2020; 11(4):309-316.

doi: 10.1017/S2040174419000631. Epub 2019 Oct 24. PMID: 31647397. 

2. Sperling J, Sharma S, Nilsson PM. Birth Weight in Relation to Post-Natal Growth Patterns as Predictor of Arterial Stiffness and Central Hemodynamics in Young Adults from a Population-based Study. ARTERY Research 2021; 27 (3, September): 112 - 120. 

3. Sharma S, Jujic A, Bennet L, Christensson A, Nilsson PM. Associations between birth parameters and cardiometabolic traits in adulthood: The Malmö Offspring Study (in manuscript 2021). 

Additional papers
4. Sharma S, Skoog J, Timpka S, Ignell C. Pre-eclampsia and high blood pressure in early pregnancy as risk factor of severe maternal cardiovascular disease during 50 years of follow-up. Pregnancy Hypertension: An International Journal of Women´s Cardiovascular Health 2021 (accepted for publication). 

5. Laucyte A, Mallet A, Sharma S, Nilsson PM, Christensson A. Early life factors in relation to albuminuria and estimated glomerular filtration rate based on cystatin C and creatinine in adults from a Swedish population-based cohort study. J Nephrol 2021 (accepted for publication).


Juan Andres Vaz Leonidas

20 oktober, klockan 10
Projekt: Titel: The impact of socioeconomic status and comorbidity on liver cirrhosis and hepatocellular carcinoma in Sweden
Plats: CRC i Malmö
Huvudhandledare: Patrik Midlöv
Bihandledare: Ulf Strömberg, Berne Eriksson och David Buchebner
Granskare: Bodil Ohlsson och Isabel Drake

 

Abstract

Background
Liver cirrhosis is a major health concern that each year accounts for over one million deaths worldwide. It is also the main risk factor for primary liver cancer (especially hepatocellular carcinoma [HCC]), which in turn is the second cause of cancer-related death globally. Contemporary Swedish population-based studies on cirrhosis and/or HCC are scarce and none of them examine the role of socioeconomic status (SES) on prognosis and survival.

Research aims

  • Study 1: To describe the incidence, aetiology and related comorbidities of cirrhosis in the region of Halland between 2011 and 2018.
  • Study 2: To study the associations between SES and mortality risk in cohort from study 1.
  • Study 3: To study the associations between SES and incidence and prognosis among patients diagnosed with HCC in Sweden between 2012 and 2018.
  • Study 4: To study the associations between comorbidity/medications and prognosis and survival among patients diagnosed with HCC in Sweden between 2009 and 2018.

Methods

  • Study 1 and 2: retrospective cohort study based on data retrieved from 598 adult patients diagnosed with cirrhosis in the region of Halland.
  • Study 3 and 4: retrospective cohort study based on linked data from the Swedish registry for liver cancer (SweLiv), Statistics Sweden (SCB), and the National Board of Health and Welfare (Socialstyrelsen).

Results

  • Study 1: The incidence of cirrhosis in the region of Halland was considerable higher than expected. Metabolic comorbidities were common and non-alcoholic fatty liver disease (NAFLD) had become an important cause of cirrhosis.
  • Study 2: SES, measured by occupational skill level, was strongly associated with mortality risk. Patients with lowest SES had poorer mean survival (3.0 vs 6.4 years) and higher mortality risk (3.4 hazard ratio), compared to patients with highest SES.

Significance
The burden of cirrhosis in Sweden might be greater than previously reported. Cirrhosis might be underdiagnosed in the elderly, especially among those diagnosed with HCC at palliative stages. There a still large health care inequities among patients with cirrhosis, which further highlight the need of health promotion and disease prevention among the most vulnerable SES groups. 

Publications
Vaz J, Eriksson B, Strömberg U, Buchebner D, Midlöv P. Incidence, aetiology and related comorbidities of cirrhosis: a Swedish population-based cohort study. BMC Gastroenterol 2020; 20:84

Vaz J, Strömberg U, Eriksson B, Buchebner D, Midlöv P. Socioeconomic and marital status among liver cirrhosis patients and associations with mortality: a population-based cohort study in Sweden. BMC Public Health 2020; 20:1820


Naiqi Zhang

14 oktober, klockan 9
Projekt: "Drug repositioning in chemoprevention of colorectal cancer: a population-based study in Sweden"
Via Zoom: https://lu-se.zoom.us/j/7795410006
Huvudhandledare: Jianguang Ji (associate professor, MD, PhD)
Bihandledare: Kristina Sundquist (professor, MD, PhD)
Granskare: Laura Pazzagli och Yan Borné

 

Abstract

Background
Colorectal cancer (CRC) ranks the third most frequently occurring cancer and the second leading cause of cancer-related deaths worldwide. Although there have been great advances in cancer treatment, cancer remains an exceptionally complex disease to treat, and national healthcare services cannot support the current explosion in the cost of new oncology drugs. Insight of this situation, drug repurposing, the application of known drugs and compounds with a non-oncology primary purpose, might be an attractive strategy to offer a more effective option to patients as treatment or prevention at a low cost.

Research aims
Study 1: To investigate whether the use of melatonin was associated with a reduced CRC incidence in the elder Swedish population.

Study 2: To explore whether the use of aspirin and SSRIs - either as monotherapy or combined - can have a clinical benefit against CRC.

Study 3: To explore the association between exposure to SSRIs and the risk of CRC among people with family history of CRC.

Study 4: To conduct a Mendelian randomization study to seek repurposing opportunities for CRC.

Methods
Study 1 and 3: Nationwide cohort studies using a new-user study design.

Study 2: A nested case-control study using nationwide Swedish registers.

Study 4: A two-sample Mendelian randomization study using data from ChEMBL, QTL databases and GWAS.

Results
Study 1: We found a significant negative association between melatonin use and risk of CRC (adjusted HR, 0.82; 95% CI, 0.72-0.92) among older adults.

Study 2: Both aspirin and SSRIs monotherapy were negatively associated with CRC risk, but the combined use of aspirin and SSRIs was associated with an even lower CRC risk (adjusted OR, 0.77, 95% CI, 0.67-0.89) than aspirin monotherapy (adjusted OR, 0.91, 95% CI, 0.87-0.97) or SSRIs monotherapy (adjusted OR, 0.93, 95% CI, 0.86-1.00).

Significance
We identified several potential chemopreventive agents against CRC. Our findings call for further studies to confirm the underlying mechanisms and the plausibility of clinical recommendation. 

Publications

  1. Zhang N, Sundquist J, Sundquist K, Ji J. Use of Melatonin Is Associated with Lower Risk of Colorectal Cancer in Older Adults. Clin Transl Gastroenterol. 2021 Aug 3;12(8):e00396.
  2. Zhang N, Sundquist J, Sundquist K, Zhang ZG, Ji J. Combined Use of Aspirin and Selective Serotonin Reuptake Inhibitors Is Associated with Lower Risk of Colorectal Cancer: A Nested Case-Control Study. Am J Gastroenterol. 2021 Jun 1;116(6):1313-1321.

Jessica Melin 

7 oktober, klockan 13
Projekt: "Psychosocial effects of participation in prospective studies of children with high risk for type 1 Diabetes"
Plats: Via Zoom
Supervisor: Helena Elding Larsson MD PhD
Co Supervisor: Carin Andrén Aronsson PhD
Co Supervisor: Markus Lundgren MD PhD

 

Abstract

Background
Type 1 diabetes (T1D) is one of the most common chronic diseases in children. Several studies, including DiPiS and TEDDY try to find out what trigger the autoimmune reaction by following at risk children during their childhood. The parent’s decision to screen their children, and then participate in a study is not always obvious.

Research aims and methods:

  1. Assess parental anxiety after 5 years participation in The Diabetes Prediction in Skåne study and factors associated with anxiety. Anxiety level was measured by STAI questionnaires. Published.
  2. Identify factors associated with parent study satisfaction with focus on staff consistency, in The Environmental Determinants of Diabetes in the Young. Parents satisfaction score was measured at 15 month and 4 years by questionnaires. Submitted.
  3. To describe the development of a short 6-item form of the State Anxiety Inventory for Children (SAI-C) after conducting an item analysis on the full 20-item version and there after examining the reliability and validity in the TEDDY study. Manuscript draft.
  4. To examine teenagers experience after participating in the DiPiS study in 15 years. By questionnaires. 

Results
Study 1. Anxiety was higher in mothers of children with autoantibodies and those perceiving their child had a higher risk for T1D. Frequency of worry, having a member with T1D and lower education was associated with parental anxiety.

Study 2. Factors associated with study satisfaction were similar for both mothers and fathers at both time points. Country of residence, education level, accurate risk perception of their child’s T1D risk, believed they can do something to prevent T1D and parental depression were all associated with study satisfaction after 15 month and 4 years. Staff consistency was associated with greater study satisfaction in Europe but not in the US parents. 

Significance
Knowledge of parental reactions and experience of participation in longitudinal screening studies can add to our understanding of the impact to the family. Previous studies have shown that satisfaction is associated with retention and compliance. To find modifiable variables associated with satisfaction can help future studies to keep the participant in the study and to increase compliance. 

Published manuscripts
Melin, J, Maziarz, M, Andrén Aronsson, C, Lundgren, M, Elding Larsson, H. Parental anxiety after 5 years of participation in a longitudinal study of children at high risk of type 1 diabetes. Pediatr Diabetes. 2020; 21: 878– 889. https://doi.org/10.1111/pedi.13024 

Manuscript in progress
Melin, J, Lynch, K, Lundgren, M, Aronsson, Carin A, Elding Larsson, H, Bennett Johnson, S. Is Staff Consistency Important to Parents’ Satisfaction in a Longitudinal Study of Children at Risk for Type 1 Diabetes: The TEDDY Study.


Thanisorn Sukalul 

6 oktober
Projekt: "Fragrance allergy"
Via Zoom: https://lu-se.zoom.us/j/66911333532 
Handledare: Cecilia Svedman
Bihandledare Magnus Bruze och Martin Mowitz

 

Abstract

Background
Contact allergy (CA) to fragrance iscommon. Improvement on diagnostics, knowledge on exposure routes and clinical relevance are needed.The approach to investigation and management in patients with suspected fragrance CA can gain by research in the field toprovide the best patient care. 

Research questions

· Epidemiology of fragrance CA

o  Dothe fragrance markers in thebaseline series need to be adjusted?

o Whatare the advantages and disadvantages of patch testing with the ingredients of fragrance mixes (FM)?

· The knowledge about oxidized (ox.) linalool and ox. limonene, emerging allergens, is limited.

o  Arethey suitable to be screening allergens?

o  Post-patch test management to establish clinicalrelevance is obligatory.

Methods
Retrospective analyses of patientsin 2013-2020. All patients were patch tested with the baseline series,the individual ingredients of FM I and II, ox. linalool and ox. limonene. 

Preliminary results
Patients with higher age weresignificantly related to fragrance allergy. Female sex was positively associated with FM I CA. The contactallergy frequency of lyral seemed to decrease, whereas oakmoss absolute remained unchanged after the ban of thesefragrances used in cosmetics came intoforce in 2017. Patch test with the additional ingredients of FMs could detectmore fragrance CA patients. Significantly increasing trends of CAto ox. linalool and ox. limonenewere also observed.

More than 95% of CA cases of CA toox. linalool and ox. limonene were identified on Day 3/4. Patients with CA to these 2 allergens werepredominantly female and significantly younger than those with CA to other fragrances. Strong reactions wereassociated with older age and multiple fragranceallergies. 

Significance

· The prevalence of CA to fragrance remainshigh.

· Theconcentrations of individual ingredients in FM I andFM II may need to beadjusted.

· Strongreactions to ox. terpenes were associated with older age and indicated multiple fragrance allergies.

· Futureresearch aiming at explaining the complexity between patch test reactions and exposure to the ox. terpenes is absolutelyneeded.


Einar Smith

5 oktober, klockan 13
 Projekt: Healthy dietary metabolites associate with lower risk for cardiovascular disease and diabetes
 Plats: CRC i Malmö
Via Zoom: https://lu-se.zoom.us/j/65576404429?pwd=NlhwdmZneVBwVnN2OS9DSmhyWUVvZz09
Huvudhandledare: professor Olle Melander
Bihandledare: biträdande forskare Filip Ottosson
Granskare: professor Stefan Acosta och docent Carl Brunius

 

Abstract

Background
Current evidence suggest that many cases of cardiovascular disease and diabetes are preventable by maintaining a healthy diet. Many different dietary habits are suggested to have potential benefits, but the mechanism by how dietary intake affects the metabolic health need further exploration. The measurement of dietary-related metabolites might add insight into the dietary effect on disease pathogenesis. Additionally, disease risk prediction based on dietary intake measurements could be refined by the addition of plasma metabolite data.

Research questions and method
We have measured plasma metabolites in three Malmö based cohorts, Malmö Diet and Cancer (MDC, n = 3833), Malmö Preventive Project (MPP, n = 1500) and Malmö Offspring Study (MOS, n = 3431). Associations between healthy dietary intake and plasma metabolites were tested in MDC. The associations with diet associated metabolites and risk for future cardiovascular disease and diabetes were investigated using cox regression. Additionally, we created a multivariate healthy dietary metabolite signature in MOS, and further used it as a proxy for dietary intake to assess the association between healthy dietary intake and disease risk in MDC and MPP.

Preliminary results
Among 6 healthy dietary associated metabolites ergothioneine, acetylornithine and proline betaine were associated with a lower risk for cardiovascular disease in MDC. The metabolic signature for healthy eating was associated with a lower risk for diabetes and cardiovascular disease in both MDC and MPP. The associations with diabetes remained significant after full adjustment in both cohorts.

Implications
The healthy dietary metabolite ergothioneine has been suggested to have several health benefits, and we are the first to show an association with lower risk for future disease. We further show that plasma metabolites are good markers for healthy eating and can be used to assess dietary effect on future disease risk even in cohorts without dietary data. Combined, our research provides new insight into potential mechanism by which dietary intake affects metabolic health and offers suggestion for plasma metabolic research in dietary research.

Publications in half time
Smith E, Ottosson F, Hellstrand S, Ericson U, Orho-Melander M, Fernandez C, Melander O. Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. Heart. 2020;106:691-7.

Smith E et al. Healthy dietary metabolic signature predicts lower risk for type 2 diabetes. Submitted manuscript


September

 

Maria Glans

29 september, klockan 13
Projekt: "Readmission to hospital within 30 days of discharge – in older adults"
Lokal: 37:an på CRC, Jan Waldenströms gata 35, Skånes universitetssjukhus Malmö 
Via Zoom-: https://lu-se.zoom.us/j/64140398195
Huvudhandledare: Patrik Midlöv (professor)
Biträdande handledare: Annika Kragh Ekstam (PhD), Ulf Jakobsson, professor)och Åsa Bondesson (PhD)
Opponenter: Anne Wissendorf-Ekdahl (docent) och Bengt Zöller(professor)

 

Abstract

Background
Readmissions to hospital within 30 days of discharge pose a major risk to older adults. Many readmissions are preventable and attempts at decreasing the frequency are called for. 

Methods

  1. Retrospective study investigating risk factors of 30-day readmissions in older adults.
  2. Retrospective study investigating risk factors of medication related 30-day readmissions in older adults.
  3. Focus group study investigating obstacles and opportunities in the discharging process.
  4. Development and validation of a model predicting 30-day readmissions in older adults. 

Preliminary results

  1. Poor health, using 10 medications or more and living in the community with home care are risk factors of 30-day readmission. Readmissions occur more often after being discharged on a Friday or from a surgical unit.
  2. Approximately 40% of 30-day readmissions are possibly medication related. The odds are increased in comorbid, highly medicated patients living in their own home, alone and if medications are adjusted at initial discharge.
  3. There are various obstacles in the course of updating and transferring information on medications at discharge: Infrastructure (IT-Systems; Work organization and routines), Physician (Knowledge and education; Understanding and responsibility), and Patient/next of kin (Providing information; Understanding information). A central theme, We’re only human, encompass how physicians do their best despite difficult conditions. 

Meaning
The prediction model that will be developed has the potential to help identify patients at most risk of readmission. Combined with improved discharging routines and follow-up this may help decrease the frequency of 30-day readmissions in older adults. 

Publications and manuscripts
Glans M, Kragh Ekstam A, Jakobsson U, Bondesson Å, Midlöv P. Risk factors for hospital readmission in older adults within 30 days of discharge - a comparative retrospective study. BMC Geriatr. 2020;20(1):467. Published 2020 Nov 11.

Glans M, Kragh Ekstam A, Jakobsson U, Bondesson Å, Midlöv P. Medication-related hospital readmissions within 30 days of discharge-A retrospective study of risk factors in older adults. PLoS One. 2021;16(6):e0253024. Published 2021 Jun 10.

Glans M, Midlöv P, Kragh Ekstam A, Bondesson Å, Brorsson A. Obstacles and opportunities in information transfer regarding medications at discharge – a focus group study with Swedish hospital doctors. Submitted.


Francis Rezk

24 september, klockan 10
Projekt: "Prevention of surgical site infection after open vascular surgery in the lower limbs"
Via Zoom: https://lu-se.zoom.us/j/63614043869
Huvudhandledare: Stefan Acosta, professor
Bihandledare: Håkan Åstrand, MD PhD, länssjukhuset Ryhov, kirurgkliniken, Jönköping
Opponenter: Marcus Langenskiöld, associerad professor vid Göteborgs universitet, och Maria Henricson, associerad professor vid Högskolan í Borås, School of Health Science.

 

Abstract

Background
Surgical site infection (SSI) after open lower extremity revascularization is a common complication leading to increased morbidity and mortality. To reduce SSIs, a bundle of care approach seems to be essential. Current compliance with hygiene precaution guidelines among healthcare professionals (HCPs) is unclear. Incisional negative pressure wound therapy (iNPWT) on closed surgical incisions may prevent SSI.

Research question/Method
I.  Retrospective cohort study. Evaluate the shift of antibiotic prophylaxis from Cloxacillin/Cefotaxime to Trimethoprim/Sulfamethoxazole.

II.  Qualitative research study based on focus group interviews on how the HCPs perceive being observed and their adherence to standard precautions.

III.  Protocol of a randomized controlled trial (RCT) to evaluate the potential benefit of iNPWT over standard dressings on closed incisions after lower extremity revascularization.

Preliminary results
The change in antibiotic prophylaxis from Cloxacillin/Cefotaxime to Trimethoprim/Sulfamethoxazole was associated with an increased rate of inguinal SSI, 13.0% versus 27.8%, respectively, p=0.027.

The themes identified in the qualitative study were encompassing communication, behaviour, rules, and routines, and work environment, which influences the adherence of healthcare professionals to standard precautions to a considerable extent.

The power calculation showed a need to include 133 bypasses to be able to show a reduced SSI rate in the NPWT arm.

Significance
It is important that healthcare’s managers put into place sustainable hygiene care to reduce the rate of SSI. The iNPWT may, if proven effective, be introduced broadly. 

References

  1. Rezk F, Åstrand H, Acosta S: Antibiotic Prophylaxis With Trimethoprim/Sulfamethoxazole Instead of Cloxacillin/Cefotaxime Increases Inguinal Surgical Site Infection Rate After Lower Extremity Revascularization. The international journal of lower extremity wounds 2019, 18(2):135- 142
  2. Rezk F, Stenmarker M, Acosta S, Johansson K, Bengnér M, Åstrand H, Andersson A-C: Healthcare professionals’ experiences of being observed regarding hygiene routines: the Hawthorne effect in vascular surgery. BMC infectious diseases 2021, 21(1):1-10.
  3. Rezk F, Åstrand H, Acosta S: Incisional negative pressure wound therapy for the prevention of surgical site infection after open lower limb revascularization–Rationale and design of a multi- center randomized controlled trial. Contemporary clinical trials communications 2019, 16:100469. 

Alexandros Karagiannopoulos

16 September, klockan 13
 Project: “Understanding the pancreatic islet cell gene regulation by genome-wide data integration”
 Venue: CRC, room 60-12-15 (only for supervisors and reviewers)
 Via Zoom: https://lu-se.zoom.us/j/68902039014 (for public)
 Main supervisor: Lena Eliasson
 Co-supervisors: Rashmi Prasad, Jonathan Esguerra
 Reviewers:  Dan Holmberg, Dag Ahrén

 

Abstract

Background
Type 2 diabetes (T2D) is a chronic disease characterized by high blood glucose levels, due to insulin resistance and progressively failing beta cells.  The development of T2D is dependent on both lifestyle and genetic factors. High throughput genome-wide technologies have uncovered different levels of gene regulation in the pancreatic islet cells, which are affected under cellular stress or diseased conditions. Furthermore, post-transcriptional control by microRNAs have emerged as important regulatory mechanism in various cellular functions.

Research Aims and Methods
1) Decipher the molecular mechanisms behind glucocorticoid-induced diabetes.

Laboratory methods: Cell culturing, protein and transcript quantification, insulin secretion measurement, chromatin immunoprecipitation (ChIP) and gene overexpression.

Bioinformatics: RNA-seq analysis, functional annotation of gene sets, processing and integration of publicly available datasets: RNA-seq, ChIP-seq, islet-specific accessible chromatin regions and de novo sequencing motif discovery into a single pipeline.

2) Explore miRNA-mRNA networks that contribute to T2D pathogenesis.

Bioinformatics: Microarray miRNA analysis, miRNA-mRNA target detection, Weighted correlation network analysis (WGCNA) followed by functional annotation and phenotypic trait correlation, identification of miRNA expression quantitative trait loci (eQTL) and processing and integration of GWAS data

Results
1) Genes important for beta cell function have been found to be targeted by glucocorticoids in human beta cells. The distribution of the genomic sites that are affected by glucocorticoids has been predicted, revealing important genes as direct targets of glucocorticoids. ZBTB16, the most prominent target, seems to protect beta cells against the deleterious effects of glucocorticoids.

2) miRNAs with altered expression due to glycemic status were discovered. These miRNAs appear to regulate thousands of genes. Gene target clustering indicated groups of miRNAs that work synergistically and revealed several clusters of high-correlating genes. Two of these clusters appear to be islet-specific and include significant T2D-related genes. The miRNA expression was correlated with specific genomic variants (eQTLs) that overlap T2D-related SNPs, suggesting that miRNA might be involved in the T2D onset.

Significance
Due to the complicated pathophysiology of diabetes, high-throughput data utilization and integration methods introduced in this project offer a promising approach towards deciphering gene regulatory networks that are implicated in diabetes etiology.