Factors associated with acute kidney injury in the Helsinki Burn Centre in 2006-2015.

BACKGROUND: Acute kidney injury (AKI) is a common complication in severe burns and can lead to significantly poorer outcomes. Although the prognosis has improved in recent decades, the mortality of AKI remains considerable. We investigated the factors that increase the risk of AKI and death after severe burn injury. METHODS: Intensive care patients with ≥20% burned total body surface area (TBSA%) between January 2006 and December 2015 treated in Helsinki Burn Centre were enrolled retrospectively. Patients who arrived > 36 h after burn injury or died < 48 h from arrival were excluded. A total of 187 patients were included in the final analysis. Serum creatinine ≥120 µmol/l (1.4 mg/dl) was the criterion for AKI. RESULTS: Fifty-one patients (27.3%) developed AKI during hospital stay and 21 (11.2%) required renal replacement therapy (RRT); 37 patients (19.8%) died during hospital stay. Mortality was significantly higher in the AKI group (52.9%) than in the AKI-negative group (7.4%). The Abbreviated Burn Severity Index (ABSI), Baux, and the modified Baux score were nearly equivalent in predicting mortality during ICU stay (AUC: 0.83-0.84). The risk of death and AKI were minimal with Baux scores < 80. LD50 was 112 for Baux score in all patients. In flame burns, the risk of death increased rapidly after Baux score > 80. Multivariate logistic regression model detected age, TBSA%, sepsis, and rhabdomyolysis as independent risk factors for AKI. Age (per 10 yrs. OR 1.99), TBSA% (per 10% OR 1.64), and AKI predicted mortality during hospital stay; AKI had an odds ratio of (OR) of 5.97 (95% confidence interval [CI] 2.2-16.2). CONCLUSIONS: Age, TBSA%, and AKI were the strongest independent factors in predicting outcome in severe burns. Even a major burn (> 50% TBSA) has a relatively good prognosis without simultaneous AKI. Prognosis is poorer even in minor burns for patients with AKI.

Nanofibrillar cellulose wound dressing in skin graft donor site treatment.

BACKGROUND: Although new therapeutic approaches for burn treatment have made progress, there is still need for better methods to enhance wound healing and recovery especially in severely burned patients. Nanofibrillar cellulose (NFC) has gained attention due to its renewable nature, good biocompatibility and excellent physical properties that are of importance for a range of applications in pharmaceutical and biomedical fields. In the present study, we investigated the potential of a wood based NFC wound dressing in a clinical trial on burn patients. Previously, we have investigated NFC as a topical functionalized wound dressing that contributes to improve wound healing in mice. METHODS: Wood based NFC wound dressing was tested in split-thickness skin graft donor site treatment for nine burn patients in clinical trials at Helsinki Burn Centre. NFC dressing was applied to split thickness skin graft donor sites. The dressing gradually dehydrated and attached to donor site during the first days. During the clinical trials, physical and mechanical properties of NFC wound dressing were optimized by changing its composition. From patient 5 forward, NFC dressing was compared to commercial lactocapromer dressing, Suprathel® (PMI Polymedics, Germany). RESULTS: Epithelialization of the NFC dressing-covered donor site was faster in comparison to Suprathel®. Healthy epithelialized skin was revealed under the detached NFC dressing. NFC dressing self-detached after 11-21days for patients 1-9, while Suprathel® self-detached after 16-28days for patients 5-9. In comparison studies with patients 5-9, NFC dressing self-detached on average 4days earlier compared with Suprathel®. Lower NFC content in the material was evaluated to influence the enhanced pliability of the dressing and attachment to the wound bed. No allergic reaction or inflammatory response to NFC was observed. NFC dressing did not cause more pain for patients than the traditional methods to treat the skin graft donor sites. CONCLUSION: Based on the preliminary clinical data, NFC dressing seems to be promising for skin graft donor site treatment since it is biocompatible, attaches easily to wound bed, and remains in place until donor site has renewed. It also detaches from the epithelialized skin by itself.

The Use of Blood Products in Adult Patients with Burns.

INTRODUCTION: Burn anemia represents a common complication following a burn injury. Burn anemia etiology carries distinct features occurring at each stage of the post-injury and treatment periods resulting from different causes. We aimed to analyze the use of blood components in Finnish burn victims and to identify patient- and injury-related factors influencing their use. METHODS: To study the use of blood products in burn patients, we used data collected from the Optimal Use of Blood registry, developed through co-operation between 10 major hospital districts and the Finnish Red Cross Blood Service. Burn patients ⩾18 years treated at the Helsinki University Hospital between 2005 and 2011 with an in-hospital stay ⩾1 day who received at least one transfusion during their hospital stay were included in this study. RESULTS: Among all 558 burn patients, 192 (34%) received blood products during their hospital stay. The transfused cohort comprised 192 burn patients. The study cohort received a total of 6087 units of blood components, 2422 units of leukoreduced red blood cells, 1728 units of leukoreduced platelets, and 420 units of single-donor fresh frozen plasma or, after 2007, 1517 units of Octaplas(®) frozen plasma. All three types of blood components were administered to 29% of patients, whereas 45% received only red blood cells and 6% received only Octaplas. Transfused patients were significantly older (p < 0.001), experienced fire-/flame-related accidents and burns to multiple locations (p < 0.001), and their in-hospital mortality exceeded that for non-transfused burn patients fivefold (p < 0.05). DISCUSSION: We show that Finnish adult burn patients received ample transfusions. The number of blood components transfused varied according to the anatomical location of the injury and patient survival. Whether the additional mortality is related directly to transfusions or is merely a manifestation of the more severe burn injury remains unknown.

Outcome after injections of crushed tablets in intravenous drug abusers in the Helsinki University Central Hospital.

OBJECTIVE: To retrospectively analyse injection drug users (IDUs) with complications after intra- or extra-vasal administration of dissolved tablets. DESIGN: A retrospective study. METHODS: The hospital discharge registers were used to identify the patients admitted in different clinics in Helsinki University Central Hospital during 2000-2005. The patient demographics and social background were clarified. The type of the crushed drugs, the injection route and the timing of administration were registered. Medical interventions, examinations and surgical procedures were recorded. RESULTS: Between January 2000 and December 2005, 24 patients had been treated on 30 occasions for manifestations caused by injecting crushed tablets. The main types of manifestations were acute limb ischaemia (16 patients) and infection (eight patients), and eight cases led to distal or proximal amputations. Men (19 of 24) were affected more frequently than were women (5 of 24). Their ages ranged between 20 and 39 years (mean: 26 years). All the patients had a previous history of intravenous drug abuse, and they lived in Greater Helsinki region. The incidence of seropositivity for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) was 33% (n=8), 88% (n=21) and 4% (n=1), respectively. The time between injection and presentation to the Emergency Department varied between 3h and 10 days (mean: 62 h). Buprenorphine was the most commonly used drug in 10 of the 24 patients, and benzodiazepine derivatives were also used in 11 of the 24 patients. CONCLUSIONS: Intra- or extra-vasal administration of dissolved tablets leads to serious consequences, including limb amputations. Vascular and soft-tissue imaging may be helpful in the diagnosis. Prompt drainage of any abscess and fasciotomies for compartment syndrome treatment are essential. Controversy exists over the best medical therapy.

Merkel cell carcinoma in a young pregnant woman.

SUMMARY: We present a 27-year-old pregnant woman with Merkel cell carcinoma on the forehead. In early pregnancy, the lesion was excised as an epidermal cyst. It was only after recurrence that a diagnosis of Merkel cell carcinoma was made. Sentinel-node biopsy, excision with 2 cm margins and reconstruction with free microvascular radial forearm flap was carried out, and the patient received postoperative radiotherapy. No evidence of recurrence or disease progression was found 24 months after surgery.

Intranasal administration of chlamydial outer protein N (CopN) induces protection against pulmonary Chlamydia pneumoniae infection in a mouse model.

Chlamydia pneumoniae is an intracellular pathogen that grows inside a vacuole, referred to as an inclusion. C. pneumoniae possess a type III secretion system (TTSS), which allows them to secrete effector molecules into the inclusion membrane and to the host cell cytosol. Proteins such as chlamydial outer protein N (CopN) that associate with the inclusion membrane are potential targets for the host's MHC-dependent antigen presentation, thereby representing ideal antigen candidates for T cell-based vaccination. The results of this study showed that intranasal immunization of BALB/c mice with heat-aggregated CopN protein and an Escherichia coli heat-labile toxin (LT) induced a strong immune response, detected as antigen-specific antibody production, lymphocyte proliferation and IFN-gamma production. Furthermore, the immunization induced statistically significant protection against intranasal C. pneumoniae challenge, the level of which correlated with the magnitude of CopN-specific lymphocyte proliferation. Both heat-aggregation of the antigen and the presence of LT adjuvant were required for maximal protective effect.

Clearance of Chlamydia pneumoniae infection in H-2 class I human leucocyte antigen-A2.1 monochain transgenic mice.

CD8+ T cells have been suggested to play an important role in protective immunity against pulmonary Chlamydia pneumoniae infection in mice. Moreover, several classical major histocompatibility complex class I - restricted cytotoxic CD8+ T lymphocytes (CTL) specific for C. pneumoniae- derived peptides have been identified. Here, we studied the outcome of C. pneumoniae infection in human leucocyte antigen (HLA)-A2.1 transgenic mice (HHD mice) that are only able to express a classical human class I molecule (HLA-A2.1). C. pneumoniae infection was self-restricted in HHD mice which were able to develop specific immune responses and a protective immunity against a subsequent rechallenge in a manner comparable to wildtype mice. Furthermore, accumulation of functional and C. pneumoniae-specific T cells to the site of infection was detected after challenge. Antigen processing and HLA-A2.1-dependent presentation was studied by immunizing the HHD mice with chlamydial outer protein N (CopN). Isolation of a peptide-specific CTL line from the CopN-immunized mice suggests that the HLA-A2.1 molecule can support the development of CTL response against a chlamydial protein in mice. These findings suggest that the transgenic mouse model can be used for further characterization of the HLA-A2.1-restricted CD8+ T-cell response during C. pneumoniae infection and for identification of CD8 epitopes from chlamydial antigens.

Surgery in the air--evacuating Finnish tsunami victims from Thailand.

In connection with the Asian tsunami disaster on December 26, 2004, a specially equipped Finnair B-757 airplane capable of evacuating badly injured patients was remodeled into an ambulance airplane. The vehicle could take up to 22 severely injured or ill patients and intensive care and limited surgical procedures could be provided to the patients. The plane was manned with a civilian medical team of 37 physicians and nurses. The plane left for Thailand to evacuate the most severely injured Finnish citizens within 10 hours of the evacuation decision. A total of 14 patients including 4 critically ill (two on ventilator) were transferred to Helsinki within 32 hours of takeoff. The medical team included a general, an orthopedic and a plastic surgeon. Soft tissue wounds, some of them severely infected, were the most common injuries, followed by extremity fractures and head injuries. The surgical procedures that were performed mid-air included wound surgery, to remove necrotic tissue, and external fixation and fasciotomy for a lower extremity fracture. The facilities under these circumstances would allow performing life-saving procedures to maintain airway and breathing, and surgical procedures of the soft tissues, extremity and pelvic fractures. Cavitary surgery would require additional equipment and resources.

Maintaining a glycerolized skin bank--a practical approach.

The Helsinki Burn Unit admits around 120-140 patients a year and, of these, 20-30 need intensive care. Before 1995, fresh, non-tested cadaver skin was used to cover widely meshed autografts in large burns. In 1995, we founded a skin bank to avoid the problems encountered in the use of fresh cadaver skin: contamination by viruses or bacteria, shortage of available skin, the occasionally poor quality of the cadaver skin, and the inconvenience of harvesting skin in the mortuary. Crucial to the work of the Skin Bank has been cooperation with the Transplantation Unit of our hospital. This reduces paperwork and guarantees the quality of the donors. It also enables us to harvest skin only from tested multiorgan donors in an operating theater setting. Also important is a well organized team to ensure the procurement of a sufficient amount of good-quality allografts. This requirement raises the otherwise low costs of a glycerolized skin bank.

Evaluation of blood flow in free microvascular flaps.

Free flap surgery is routine today, yet little is known of its pathophysiology. In this study, the authors evaluated the hemodynamics in different types of free microvascular flaps, by measuring intraoperative transit-time flow. Eighty-six free transplants--21 free TRAM flaps for breast reconstruction, 18 radial forearm flaps for head and neck reconstructions, and 47 muscle flaps for head and neck, trunk and lower extremity reconstructions--were studied. Donor artery flow was highest in the radial artery (mean: 57.5 +/- 50 (SD) ml/min) but dropped (p < 0.001) to one tenth (6.1 +/- 2 ml/min) after anastomosis. The flow was lowest (4.9 +/- 3 ml/min) in the recipient artery of the TRAM flap but, after anastomosis, increased significantly (13.7 +/- 5 ml/min) to the level of the flow in the donor artery. The donor-artery flow in muscle flaps had a mean of 15.9 +/- 11 ml/min, and it significantly increased after anastomosing (23.9 +/- 12 ml/min). Weight-related intake of blood was highest in the radial forearm flap (18.5 +/- 6 ml/ min/100g) and lowest in the TRAM flap (2.5 +/- 1 ml/min/100g). The study showed that blood flow through a free microvascular flap does not depend on recipient artery flow. Even low-flow arteries can be used as recipients, because the flow increases according to free-flap requirements. The blood flow through a free microvascular flap depends on the specific tissue components of the flap.

Natural coral as bone-defect-filling material.

Natural coral (NC) has been studied experimentally and clinically as a bone substitute, but its resorption rate and possible replacement by bone still need to be defined in humans. In this study bicortical bone was harvested from the iliac crest of 10 patients. The defect was filled with a NC block, and changes were monitored by X-rays and quantitative CT scans for a mean of 2.1 years. A biopsy was taken at 1 year. The purpose of the study was to investigate the resorption rate and pattern of NC (Porites) implants and the replacement, if any, of the implant by new bone. The blocks underwent centripetal resorption, but all the blocks still could be detected by X-rays and CT scans at the end of the follow-up period. The density of the remaining block did not change. Seven of the 10 implants were smaller than 50% of their original size at the end of the study. Bone ingrowth could be observed only in two of seven biopsies. One implant had to be removed after 1.7 years due to infection. The study shows that resorption of natural coral proceeds centripetally and apparently more rapidly when accompanied by tissue ingrowth. None of the blocks resorbed completely, and the defect at the iliac crest had not been restored by the end of the study.

Acquired immunity to Chlamydia pneumoniae is dependent on gamma interferon in two mouse strains that initially differ in this respect after primary challenge.

The role of gamma interferon (IFN-gamma) in a Chlamydia pneumoniae mouse model was studied by in vivo neutralization in two inbred mouse strains. During primary C. pneumoniae infection, neutralization of IFN-gamma increased both the numbers of bacteria and the pneumonia score in the lungs of C57BL/6 mice but not BALB/c mice. During reinfection, the bacterial counts in the lungs were increased by IFN-gamma neutralization in both mouse strains. Thus, the effect of IFN-gamma neutralization was dependent on the genetic background in primary infection. However, IFN-gamma appeared to be equally important in both mouse strains during reinfection.

Immunity to Chlamydia pneumoniae induced by vaccination with DNA vectors expressing a cytoplasmic protein (Hsp60) or outer membrane proteins (MOMP and Omp2).

Immune responses induced by intramuscular DNA immunization with Chlamydia pneumoniae genes coding for the major outer membrane protein (MOMP), cysteine-rich outer membrane protein 2 (Omp2) or the heat shock protein 60 (Hsp60) were studied. BALB/c mice were vaccinated intramuscularly three times at 3-week intervals and challenged intranasally 2 weeks after the last injection. Immunization with pmomp or phsp60 showed 1.2-1.5 log reduction in the mean lung bacterial counts after the challenge. Specific antibodies were detected only in sera of the mice immunized with pomp2 and phsp60. Although immunization with pomp2 resulted in a strong serum antibody response against Omp2 protein, it failed to protect the mice. Immunization with any of the three vaccines did not reduce the severity of histologically assessed pneumonia, but resulted in significantly higher lymphoid reaction in the lung indicating immunological memory.

Compressive strength of calcium carbonate and hydroxyapatite implants after bone-marrow-induced osteogenesis.

Natural coral and structurally similar porous hydroxyapatite (HA) have been used as bone substitutes. They are not osteoinductive but bone formation can be induced by marrow cells, even in extraosseal sites. In our previous study we induced bone formation in porous coral and HA after having implanted the materials in intramuscular pockets in rat. New bone formed only in HA or coral implants soaked with marrow cells; fibrous tissue ingrowth alone was observed in the controls (without marrow). In the present study we examined the effect of tissue ingrowth on the mechanical properties of coral and HA implants obtained in a similar process to that used before. At 12 weeks the compressive strength of HA was higher in the marrow group than in the controls; it was also higher than that of the wet unimplanted material. The HA blocks did not show resorption. Coral resorbed quickly and lost its compressive strength, which was originally higher than in HA. At three weeks the marrow group was stronger than the control specimens. After six weeks only the marrow group, but not the controls, could be tested. Bone ingrowth seemed to maintain the strength of the coral implant even if it was dissolving. The mechanical strength of both materials was comparable to that of cancellous bone.

Return to employment after burn.

The increase in the survival rate of burned patients has stressed the need to study their rehabilitation. The purpose of our study was to characterize the factors influencing such patients' return to work. We conducted a mail survey among 316 patients aged 15-65 years, treated at Töölö Hospital Burns Unit between 11 November 1988 and 31 December 1994. Of 175 participants, 130 (74 per cent) were men and 45 (26 per cent) women. The mean TBSA was 14.0 per cent, mean FT 6.4 per cent and the mean time of hospital treatment (TOT) 17.5 days. Statistical significance was calculated by Mann-Whitney U test, Kruskall-Wallis one-way analysis of variance and Chi-square test as appropriate, with a probability level of 0.05. In the study, 54 per cent of patients whose burn area was 1-10 per cent, returned to work within 2 months. No difference was found between patients who had hand burns and those who had burn injuries in other parts of the body. Patients who did not return to work were significantly older (mean age 45 years) than those who did (mean ages varying from 33 to 36 years; P < 0.05). Total body surface area burned (TBSA), FT, TOT, age and employment status at the time of injury were the factors predicting the resumption of working ability after burn injury.

Microvascular free flaps in head and neck cancer surgery in Finland 1986-1995.

Microvascular free tissue transfer has in many cases replaced classic flap techniques and is now an established workhorse for head and neck reconstructions. In this retrospective study the over 300 patients, who had microvascular free flap reconstructions in head and neck cancer surgery in Finland during a 10-year period (1986-1995) were reviewed. The operations were performed in the University Hospitals by plastic surgeons, ENT specialists or maxillofacial surgeons. The cases consisted of defects resulting from resection of oral cavity tumors (63%), mid- or upper-face and skullbase tumors (20%) and hypopharyngo-esophageal tumors (17%). The series includes a wide range of flap types and analyses flap outcome and complications. A total of 313 cases was reconstructed by 317 flaps (forearm flaps 47%, latissimus dorsi flaps 19%, free jejunum or colon transfers 15%, free iliaca crest flaps 8% and other flaps 11%). Thrombosis of one of the vessels and haematoma were the most frequent causes of failure in microvascular free tissue transfer. A total flap necrosis occurred in 27 (8.5%) and a partial necrosis in 12 (4%) patients. The most reliable flap in terms of survival was the radial forearm flap. The ever-improving success of microvascular free tissue transfer has made it a useful procedure for head and neck reconstructions. There is also a growing need for microvascular team surgery in the field of head and neck cancer therapy.

Bone marrow induced osteogenesis in hydroxyapatite and calcium carbonate implants.

In this experimental study, blocks of natural coral (calcium carbonate) and its structurally similar derivate in the form of hydroxyapatite (calcium phosphate) were implanted in rat latissimus dorsi muscle with autogenous bone marrow to compare their bone-forming capability. A block without marrow placed in the opposite latissimus muscle served as a control. The animals were killed at 3, 6 and 12 weeks and, in the hydroxyapatite group, also at 24 weeks. The sections were analysed histologically and histomorphometrically. Bone was found only in implants containing bone marrow. Bone formation was significantly (p < 0.05) higher in coral than in hydroxyapatite implants at 3 weeks (10.8% versus 4.8%) and at 12 weeks (13.7% versus 6.3%, bone/total original block area). At 12 weeks all the coral implants had lost their original structure, and the cross-sectional area of the block had diminished to 40% of the original area.