Plastic Surgery

In the lab. Photo: Carina Warme

Plastic Surgery includes the following research areas:

  1. The Bone and Connective Tissue Activation Programme
  2. Cleft and Craniofacial Research Programme
  3. The Uppsala Burn Research Programme
  4. Reconstructive Microsurgery

The programs are primarily patient-based and success is heavily related to an adequate number of patients and consequently the size of the scientifically active staff.

Uppsala University Hospital and Uppsala University has been appointed national centers for craniofacial surgery and for severely burned individuals. This has guaranteed a solid basis for research to thrive.

Network structure

In order to optimize collaborative work the national network SwedBurn has been initiated with an initiative from our research group (http://www.swedburn.se). The purpose is to stimulate burn related projects requiring intellectual and functional resources from different departments and universities.
 

The Bone and Connective Tissue Activation Programme

Principal investigators: Daniel Nowinski and Bengt Gerdin

This programme is composed of two main projects: A) research around conditions where an activation or dysregulation of connective tissue cells and the connective tissue matrix are central pathophysiologic components; B) development of new degradable scaffolds for bone regeneration and research on the fundamental mechanisms behind premature fusion of the calvarial sutures in craniosynostosis. The projects includes the development, use and exploitation of sophisticated culture models.

  1. The project on connective tissue activation deals with two main problem areas: a) excessive connective tissue deposition in hypertropic cars/keloids; and b) formation of an aberrant connective tissue matrix in the stromal compartment of tumors.
    • Studies have focused on interaction between epidermal cells (keratinocytes) and dermal fibroblasts. Paracrine factors from keratinocytes generally down-regulate fibrotic response. The project aims to further elucidate different mechanisms in the paracrine intercellular communication between the epithelial layer of the skin, the keratinocytes, and fibroblasts that regulate various events during the activation of the supportive loose connective tissue during tissue repair and wound healing. Keratinocyte-fibroblast interactions are investigated in organotypic cocultures. Cells from keloids and hypertrophic scars are compared to those from normal skin. 
    • Studies of interactions between malignant keratinocytes, predominantly from oral squamous cell carcinomas, and fibroblasts. Malignant keratinocyte differ in their effects on fibroblasts when compared to normal keratinocytes. The group has demonstrated that malignant keratinocytes are deficient in their capacity to downregulate profibrotic mechanisms in fibroblast. Future studies will focus on the effects of radiation on cancer cell mediated regulation of stromal cells.
  2. The project on bone regeneration is conducted in close collaboration with the group around Jöns Hilborn, Chemistry, Polymer chemistry, Ångström laboratory. The aim is to develop degradable scaffolds that can be used for reconstruction of calvarial defects in the pediatric population. The project on mechanisms behind craniosynostosis will exploit the above described collagen-matrix based culture models for the investigation of molecular mechanisms behind premature fusion of calvarial sutures. A biobank with primary cells and tissue from patients operated for craniosynostosis is currently being established.

Members of the programme during 2016

Daniel Nowinski, MD, PhD, Associate Professor
Bengt Gerdin, Professor
Malin Hakelius, MD
Elizabeth Kiwanuka, MD
Daniel Saiepour, MD, PhD
Kristofer Rubin, Professor, IMBIM
Mikael Ivarsson, PhD, Örebro University
Mohamad Nassir, MD
Eva Lindell-Jonsson, MD
Åsa Forsberg, Research Engineer

Cleft and Craniofacial Programme

Principal investigator: Daniel Nowinski

This research programme gathers clinical research projects around two principal problem areas: craniosynostosis and orofacial clefts. Projects around craniosynostosis rest on the platform generated by the national care assignment for craniofacial surgery and are conducted in close collaboration with neurosurgery, psychiatry, clinical genetics and anesthesiology.

The group is partner in an Indian-Swedish research consortium, with researches around associated professor Anders Rydberg at the Department of Engineering Sciences, Ångström laboratory, for the development of a bone mineral density analysis system (BDAS). The system will be used to investigate the dynamics of bone formation after craniosynostosis surgery.

The part of the programme on orofacial clefts is currently mainly dealing with investigations of long-term outcomes, and predictors for outcomes, after secondary bone grafting to the cleft alveolus and after primary reconstruction of the cleft lip. Dissertation on secondary alveolar bone grafting is planned for May 20th, 2016.

Members of the programme during 2016

Alberto Delgado, MD, PhD
Daniel Nowinski, MD, PhD, Associate Professor
Malin Hakelius, MD
Daniel Saiepour, MD, PhD
Fatima Jabbari, DDS
Åsa Forsberg, Research Engineer

The Uppsala Burn Research Program

Principal investigator: Fredrik Huss

A burn injury is a good model for understanding the response to a severe trauma, viewed from a short as well as a long perspective. The disastrous experience of being afflicted with an extensive burn injury affects all main integrating systems in the body (i.e. nervous, endocrine and immune). The acute phase is characterized by a relatively intense and rapidly developing physiologic inflammatory response, not only in the immediate vicinity of injured tissue, but also in a generalized syndrome of systemic inflammation, which in general is proportional to the magnitude of injury. In the most severe cases it can lead to circulatory shock, organ dysfunction, and death.

It is quite obvious that burn care is heavily multifactorial and multiprofessional, spanning from simple wound care to advanced tissue engineering/tissue culture, from intensive care to psycho-social support.

The Uppsala Burn Research Program is an umbrella for clinical research on burns and outcome after burns and is divided into modules containing the main parts of the treatment processes for burns:

  • Resilience and Vulnerability
  • Anaesthesiology and Intensive Care
  • Surgery / wound healing
  • Prevention
  • Rehabilitation
  • Family perspective
  • Patient satisfaction

A few of the ongoing projects are here described

Nosocomial infections caused by S. aureus in burn patients

Background: Staphyloccocus aureus is a bacterium that normally occurs in about 30% of the population and colonizes nose, mouth, armpit and groin, without necessarily causing infection.

Burn patients represents essentially a normal population but in which the burns themselves is a breeding ground for the establishment of infections and therefore a secondary influence on the immunological defense. Sepsis and serious wound infections due to S. aureus is very common in burn patients. According to other studies 50-60% of patients with major burns suffer infections caused by S. aureus.

Whether the infection is nosocomial or caused by the patient's own normal flora has never been investigated until now.

Artificial intelligence and computer assessment for diagnostics and clinical decision making: Applications for assessment of burns and skin lesions

The aim is to investigate the use of artificial intelligence (AI), machine learning (ML) and image processing in order to generate both a decision and also an opportunity to automate decision making.

The importance of nutrition after minor burns

Purpose: To study the importance of nutrition after minor burns (< 20% of the body area).

Hypothesis: Adequate nutritional status (adequate energy and protein intake as well as weight stability) after a minor burn leads to better results (faster wound healing, fewer infections).

Significance: The importance of nutrition after minor burns is relatively unexplored. By identifying energy and protein needs, we as clinicians can get guidance on how to better treat this patient group in the future. Since nutritional status and frequency of malnutrition after minor burns are poorly studied, results from this study can provide guidance on whether nutritional screening can be a future tool for identifying patients in need of continued nutritional care also after minor burns.

Resuscitation the first 24 hours. The use of a protocol to improve the adherence to a fluid treatment algorithm

An algorithm for fluid resuscitation has been developed and the adherence and outcome of the algorithm is studied.

Pain in ICU patients, subjective aspects and objective parameters

A study of objective parameters correlating to the patients’ description of pain-experiences to develop a protocol to use objective parameters in sedated patients for pain treatment.

Hydrogen peroxide, and other markers of severe sepsis and septic shock

The purpose of the study is to measure hydrogen peroxide, glutathione and other biomarkers in patients with severe sepsis and septic shock and significant burns. The concentrations of hydrogen peroxide and glutathione will be measured over time for several days to examine the variability of these markers and how these markers is influenced by usual treatment. Inflammatory mediators in the blood will also be analyzed. Correlation with SOFA and SAPS 3 scores, which are clinical markers of severity of the infection and 28 day mortality after onset of illness will be investigated. The septic patients’ biomarkers will be compared with the burn patients’ in order to investigate any differences between SIRS±sepsis and burns.

Epidemiology

Each year over 300 000 people die worldwide, and about 90% of burns occur in countries with low and middle incomes. The morbidity after large burns is often considerable and commonly associated with reduced quality of life. Older Scandinavian investigations have indicated that about 0.4% of the population seek medical care for burns each year. With the current population in Sweden this would extrapolate to about 38 000 burns treated each year. In several projects and from different aspects are we investigating the epidemiology of fire-related injuries and deaths in Sweden.

Intestinal flora in burn patients

A study of the intestinal flora, the presence of resistant intestinal bacteria, and the effect of faecestransplantation in patients with severe burns.

This study examines

  1. the intestinal microflora composition and the presence of resistant intestinal bacteria in patients who admitted to our burn center
  2. the intestinal flora and occurrence of resistant bacteria changes during hospitalization
  3. the relationship between the given antibiotic treatment and the intestinal flora as well as the risk of resistance development
  4. whether faecestransplantation performed after completion of treatment has a beneficial effect on the patient's intestinal flora and risk of carriage of resistant bacteria in the longer term.

Members of the program during 2018

Morten Kildal, MD, PhD, Associate Professor, Department of Surgical Sciences, Plastic Surgery, and the Burn Center Department of Plastic- and Maxillofacial Surgery, Uppsala University Hospital
Fredrik Huss, MD, PhD, Associate Professor Department of Surgical Sciences, Plastic Surgery and the Burn Center, Department of Plastic- and Maxillofacial Surgery, Uppsala University Hospital
Caisa Öster, RN, PhD, Senior Lecturer, Department of Neuroscience, Psychiatry
Josefin Sveen, PhD, Department of Neuroscience, Psychiatry
Filip Fredén, MD, PhD, Dept of Surgical Sciences, Anesthesiology and Intensive Care and the Burn Center, Department of Plastic- and Maxillofacial Surgery, Uppsala University Hospital
Eva Tano, PhD, Microbiologist, Department of Medical Sciences, Section of Clinical Bacteriologyx
Aida Pleasan, MD, PhD Department of Surgical Sciences, Anesthesiology and Intensive Care
Miklós Lipcsey, MD, PhD Department of Surgical Sciences, Anesthesiology and Intensive Care
Mia Furebring, MD, PhD Department of Medical Sciences, Section of Infectious Diseases
Hanna Monteélin, MD, PhD-student Department of Medical Sciences, Section of Infectious Diseases
Ilaria Tocco-Tussardi, MD Burn Center, Department of Plastic- and Maxillofacial Surgery, Uppsala University Hospital
Marie Lindblad, RN, Research nurse Burn Center, Department of Plastic- and Maxillofacial Surgery, Uppsala University Hospital
Thomas Tängdén, MD, PhD Department of Medical Sciences, Section of Infectious Diseases
Anders Jonsson, Bsc, Div of Risk Management, Department of Environmental and Life Sciences, Karlstad University
Jian Fransén, MD, PhD-student. Dept of Surgery, Västerås Hospital and Department of Surgical Sciences, Plastic Surgery
Josefin Dimander, Nutritionist, PhD-student, the Burn Center Department of Plastic- and Maxillofacial Surgery, Uppsala University Hospital

Authorities supporting work / Financing

MSB (Myndigheten för samhällsskydd och beredskap)
Uppsala Universitetssjukhus (ALF)
Det svenska Läkaresällskapet (SLS)
Personskador till följd av bränder
  

Reconstructive Microsurgery Research Programme

Principal investigators: Andres Rodriguez and Maria Rydevik Mani

Within the area of reconstructive microsurgery several research projects are carried out.

Clinical Applied Anatomical Studies in Face transplantation and Facial Paralysis

This project is carried out in collaboration with the Department of Plastic Surgery of the University of Texas Southwestern Medical Center. Anatomical studies are performed to study the technical feasibility of the application of new techniques in the field of face transplantation and facial paralysis.

Virtual Planning in Microvascular Head and Neck Reconstruction

In collaboration with Maxillofacial Surgery and the Center of Image Analysis at Uppsala University a study is carried out to study the application of a new virtual planning system (UHASP) in microvascular reconstruction of the mandible using free vascularized fibula flap.

Clinical Studies in Facial Paralysis

In collaboration with the department of ENT and Electrophysiology, a study of the implications of different cranial nerves (V, XII, XI) in relation to the Facial Nerve (VII) is carried out by performing electrophysiological studies and Functional MRI to elucidate the cortical interconnections of this nerve and to analyze ways to increase the cortical plasticity after nerve transfers in facial paralysis.

Cancer Recurrence after Breast Reconstruction

Collaboration between department of general surgery (breast surgery) and department of oncology, Uppsala and Malmö, with the aim to evaluate potential risk of breast cancer recurrence after breast reconstruction. The project includes retrospective analysis of patients who was mastectomied in 1992-2009 and reconstructed between 2000 and 2009 as well as a prospective study arm.

Lymphoedema – risk of and treatment of lymphoedema

Evaluation of the risk of lymphoedema of the arm after microsurgery reconstruction of the breast and cephalic vein usage. Retrospective analysis of a cohort of already reconstructed patients as well as prospective study of patient operated 2014–2016. The project also includes evaluation of microsurgical treatment of lymphoedema by lymphnode transfer at the time of free flap reconstruction of the breast. The evaluation includes clinical measurements, displacement test, photographs and questionnaires.

Quality of Life, Patient satisfaction and Optimizing resources in Breast reconstruction

Collaboration with Breast Cancer Surgery, Patient Reported and Clinical Outcomes Research Group in Bristol, United Kingdom. Development of the Swedish version of the questionnaire EORTC BRR-24. International collaboration between more than 15 countries for a common instrument to use for breast reconstruction. This project further includes studies of patients already reconstructed and comparison of different methods as well as a prospective study. Parameters evaluated are QoL, patient satisfaction, resource management and socioeconomic impact.

Members of the group during 2016

Andres Rodriguez Lorenzo, MD, PhD, Associate Professor
Maria Rydevik Mani, MD, PhD
Morten Kildal, MD, PhD, Associate Professor
David Jensson, MD
Andreas Svee, MD
Magnus Kjelsberg, MD

Collaborators

Lars Jonsson, MD, PhD, Associate Professor, ENT, UU
Fredrik Wärnberg, MD, PhD, Associate Professor, UU
Gunilla Enblad, MD, PhD, Professor, Oncology, UU
Zoe Winters, MD, PhD, Univeristy of Bristol, UK
Yvonne Brandberg, Professor, Psychologist, (onco-psychology) Karolinska Institutet
Shai M. Rozen, MD, Associate Professor, UT Southwestern Medical Center, Dallas, USA
Jan Hirsch, DDS, PhD, Professor Emeritus, Maxillofacial Surgery, UU
Andreas Thor, DDS, PhD, Associate Professors, Maxillofacial Surgery, UU
Ingrid Carlbom, PhD, Professor, Institution for InformationTechnology, UU
Pontus Olsson, Doctorand, Institution for Information and Technology, UU
Fredrik Nysjö, Research Engineer, Intitution for Information and Technology, UU