Vesa Koivukangas

Cost-utility of bariatric surgery for morbid obesity in Finland.

The aim of this study was to evaluate the cost–utility of bariatric surgery (gastric bypass, sleeve gastrectomy and gastric banding) compared with ordinary treatment in the Finnish healthcare system.

Organ system dysfunction following open cholecystectomy for acute acalculous cholecystitis in critically ill patients

Background:  Acute acalculous cholecystitis (AAC) refers to cholecystitis without gallstones and is a serious complication of critical illness. We describe the time course of organ system dysfunction associated with cholecystectomy in critically ill patients with AAC.

Tight junction proteins in gallbladder epithelium: different expression in acute acalculous and calculous cholecystitis.

There is a paucity of information of tight junction (TJ) proteins in gallbladder epithelium, and disturbances in the structure of these proteins may play a role in the pathogenesis of acute acalculous cholecystitis (AAC) and acute calculous cholecystitis (ACC). Using immunohistochemistry, we investigated the expression of TJ proteins claudin-1, −2, −3, and −4, occludin, zonula occludens (ZO-1), and E-cadherin in 9 normal gallbladders, 30 gallbladders with AAC, and 21 gallbladders with ACC. The number of positive epithelial and endothelial cells and the intensity of the immunoreaction were determined. Membrane-bound and cytoplasmic immunoreactivities were separately assessed. We found that TJ proteins were uniformly expressed in normal gallbladder epithelium, with the exception of claudin-2, which was present in less than half of the cells. In AAC, expression of cytoplasmic occludin and claudin-1 were decreased, as compared with normal gallbladder. In ACC, expression of claudin-2 was increased, and expression of claudin-1, −3, and −4, occludin, and ZO-1 were decreased, as compared with normal gallbladder or AAC. We conclude that there are significant differences in expression of TJ proteins in AAC and ACC, supporting the idea that AAC represents a manifestation of systemic inflammatory disease, whereas ACC is a local inflammatory and often infectious disease.

Markers of collagen synthesis and degradation are increased in serum in severe sepsis: a longitudinal study of 44 patients.

IntroductionSepsis-related multiple organ dysfunction is a common cause of death in the intensive care unit. The effect of sepsis on markers of tissue repair is only partly understood. The aim of this study was to measure markers of collagen synthesis and degradation during sepsis and investigate the association with disease severity and outcome.MethodsForty-four patients with severe sepsis participated in the study and 15 volunteers acted as controls. Blood samples were collected for 10 days after the first sepsis-induced organ dysfunction and after three and six months. Procollagen type I and III aminoterminal propeptides (PINP and PIIINP) and cross-linked telopeptides of type I collagen (ICTP) were measured.ResultsThe PIIINP concentration was elevated in the septic patients (8.8 ug/L, 25th to 75th percentile = 6.8 to 26.0) when compared with controls (3.0 ug/L, 25th to 75th percentile = 2.7 to 3.3; P < 0.001) on day one. Maximum serum PIIINP concentrations during sepsis were higher in non-survivors compared with survivors (26.1 ug/L, 25th to 75th percentile = 18.7 to 84.3; vs. 15.1 ug/L, 25th to 75th percentile = 9.6 to 25.5; P = 0.033) and in multiple organ failure (MOF) compared with multiple organ dysfunction syndrome (MODS) (24.2 ug/L, 25th to 75th percentile = 13.4 to 48.2; vs. 8.9 ug/L, 25th to 75th percentile = 7.4 to 19.4; P = 0.002). Although the PINP values of the septic patients remained within the laboratory reference values, patients with MOF had higher values than patients with MODS (79.8, 25th to 75th percentile = 44.1 to 150.0; vs.40.4, 25th to 75th percentile = 23.6 to 99.3; P = 0.007). Day one ICTP levels were elevated in septic patients compared with the controls (19.4 ug/L, 25th to 75th percentile = 12.0 to 29.8; vs. 4.1 ug/L, 25th to 75th percentile = 3.4 to 5.0; P < 0.001).ConclusionsMarkers of collagen metabolism are increased in patients with severe sepsis and can be investigated further as markers of disease severity and outcome.

Increased collagen synthesis in psoriasis in vivo

Psoriasis is an inflammatory skin disease of unknown a etiology which also involves changes in dermal elements. Previous in vitro studies have shown an increased collagen synthesis rate in cultured fibroblasts. In this study collagen synthesis was studied in vivo in the uninvolved skin of psoriatic patients using a newly developed method in which collagen propeptides were measured in suction blister fluid. Both type I and type III collagen synthesis rates, as measured in terms of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP), were increased about two-fold in uninvolved psoriatic skin as compared with controls, the mean level of PICP being 870 and 457 Μg, respectively (P<0.001), and of PIIINP being 294 and 124 Μg, respectively (P<0.01). The increased collagen synthesis rate was also confirmed by in situ hybridization using specific probes. Collagen mRNAs were found to be particularly abundant in psoriatic patients, who also demonstrated a high collagen synthesis rate when assayed by measuring collagen propeptides. The increased rate of collagen synthesis in the uninvolved psoriatic skin seemed not to be related to the severity of the disease or to various treatments such as UVB, PUVA, retinoids or cytostatic drugs, but seemed more likely to be due to the psoriasis itself. Interestingly, skin thickness was not increased in the patients with psoriasis, even though collagen synthesis was markedly elevated, perhaps suggesting that in psoriasis the turnover rate of collagen is enhanced.

Matrix-metalloproteinase-2, -8 and -9 in serum and skin blister fluid in patients with severe sepsis.

IntroductionMatrix metalloproteinases (MMPs) have various roles in inflammatory states. They seem to be able to modulate endothelial barriers and regulate the activity of chemokines and cytokines. The timely development of the levels during severe sepsis and thereafter have not been investigated. In addition it was of interest to study alterations of MMP-levels in intact skin, as the skin is the largest barrier against external pathogens and MMPs have not been studied at organ level in human sepsis. The aim of this study was to investigate the timely development of serum and skin MMP-2, -8 and -9 levels in human severe sepsis and their association with disease severity and mortality.MethodsForty-four patients with severe sepsis and fifteen healthy controls were included in this prospective longitudinal study. The amounts of MMP-2, -8 and -9 were analyzed from serum at days 1, 4, 6, 8, and 10, and from skin suction blister fluid at days 1 and 5 from the beginning of severe sepsis. Additionally, samples from the survivors were obtained after three and six months.ResultsThe levels of MMP-2 and -8 were up-regulated in severe sepsis in comparison to healthy controls in skin blister fluid and serum. Compared to the controls MMP-9 levels were lower in sepsis from the fourth day on in serum and both the first and fifth day in skin blister fluid. Active forms of MMP-2 and -9 were present only in severe sepsis. The non-survivors had higher pro- and active MMP-2 levels than the survivors in skin blister fluid samples. Furthermore, MMP-2 levels were more pronounced in blister fluid and serum samples in patients with more severe organ failures. In the survivors at 3 and 6 month follow-up the MMP levels had returned to normal.ConclusionsMMP-2 and -8 are elevated in serum and blister fluid in severe sepsis, implying that they may play a significant role in the pathogenesis of severe sepsis and organ dysfunctions. Active forms of MMP-2 and 9 were only present in patients with severe sepsis, and higher MMP-2 levels in skin blister and serum were associated with more severe organ dysfunctions.

Ethical Issues of Obesity Surgery—a Health Technology Assessment

New surgical technologies may challenge societal values, and their adoption may lead to ethical challenges. Despite proven cost-effectiveness, obesity (bariatric) surgery and its public funding have been questioned on ethical arguments relating to, for example, the self-inflicted or non-disease nature of obesity. Our aim was to analyze the ethical issues relevant to bariatric surgery. A comprehensive health technology assessment was conducted on bariatric surgery for morbid obesity using the EUnetHTA method, including a fully integrated ethical analysis. The ethical arguments suggesting that obesity should not be surgically treated because it is self-inflicted were rejected. Medicalization of obesity may have both positive and negative effects that impact the various stakeholders differently, thus being difficult to balance. Informing bariatric surgery patients and actively supporting their autonomy is exceptionally important, as the benefits and harms of both obesity and bariatric surgery are complex, and the outcome depends on how well the patient understands and adheres to the life-long changes in eating habits required. Justice considerations are important in organizing surgical treatment of obesity, as the obese are discriminated against in many ways and obesity is more common in socioeconomically disadvantaged populations who might have problems of access to treatments. Obesity should be treated like other diseases in health care, and obesity surgery rationed like other cost-effective treatments. Positive actions to ensure patient autonomy and just access to surgical treatments may be warranted.

Epidermal wound healing in severe sepsis and septic shock in humans.

IntroductionThe effect of sepsis on epidermal wound healing has not been previously studied. It was hypothesised that epidermal wound healing is disturbed in severe sepsis.MethodsBlister wounds were induced in 35 patients with severe sepsis and in 15 healthy controls. The healing of the wounds was followed up by measuring transepidermal water loss and blood flow in the wound, reflecting the restoration of the epidermal barrier function and inflammation, respectively. The first set of suction blisters (early wound) was made within 48 hours of the first sepsis-induced organ failure and the second set (late wound) four days after the first wound. In addition, measurements were made on the intact skin.ResultsThe average age of the whole study population was 62 years (standard deviation [SD] 12). The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission was 25 (SD 8). The two most common causes of infections were peritonitis and pneumonia. Sixty-six percent of the patients developed multiple organ failure. The decrease in water evaporation from the wound during the first four days was lower in septic patients than in the control subjects (56 g/m2 per hour versus 124 g/m2 per hour, P = 0.004). On the fourth day, septic patients had significantly higher blood flow in the wound compared with the control subjects (septic patients 110 units versus control subjects 47 units, P = 0.001). No difference in transepidermal water loss from the intact skin was found between septic patients and controls. Septic patients had higher blood flow in the intact skin on the fourth and on the eighth day of study compared with the controls.ConclusionsThe restoration of the epidermal barrier function is delayed and wound blood flow is increased in patients with severe sepsis.

Laparoscopic versus open adhesiolysis for small bowel obstruction - a multicenter, prospective, randomized, controlled trial

BackgroundLaparoscopic adhesiolysis is emerging as an alternative for open surgery in adhesive small bowel obstruction. Retrospective studies suggest that laparoscopic approach shortens hospital stay and reduces complications in these patients. However, no prospective, randomized, controlled trials comparing laparoscopy to open surgery have been published.Methods/DesignThis is a multicenter, prospective, open label, randomized, controlled trial comparing laparoscopic adhesiolysis to open surgery in patients with computed-tomography diagnosed adhesive small bowel obstruction that is not resolving with conservative management. The primary study endpoint is the length of postoperative hospital stay in days.Sample size was estimated based on preliminary retrospective cohort, which suggested that 102 patients would provide 80% power to detect a difference of 2.5 days in the length of postoperative hospital stay with significance level of 0.05. Secondary endpoints include passage of stool, commencement of enteral nutrition, 30-day mortality, complications, postoperative pain, and the length of sick leave. Tertiary endpoints consist of the rate of ventral hernia and the recurrence of small bowel obstruction during long-term follow-up. Long-term follow-up by letter or telephone interview will take place at 1, 5, and 10 years.DiscussionTo the best of our knowledge, this trial is the first one aiming to provide level Ib evidence to assess the use of laparoscopy in the treatment of adhesive small bowel obstruction.Trial registrationClinicalTrials.gov identifier:NCT01867528. Date of registration May 26th 2013.

Diagnostic accuracy of computed tomography imaging of surgically treated acute acalculous cholecystitis in critically ill patients.

BACKGROUND Acute acalculous cholecystitis (AAC) is a potentially fatal condition mainly affecting critically ill patients. Current experience from computed tomography (CT) findings in AAC is contradictory. METHODS CT images of 127 mixed medical-surgical intensive care unit patients were retrospectively reviewed for the following findings: bile density, thickness and enhancement of the gallbladder (GB) wall, subserosal edema, greatest perpendicular diameters of the GB, width of extrahepatic bile ducts, gas within the GB, ascites, peritoneal fat edema, and diffuse tissue edema. Forty-three of these patients underwent open cholecystectomy, and 8 patients revealed a normal GB, 26 an edematous GB, and 9 a necrotic AAC. RESULTS Abnormal CT findings were present in 96% of all the intensive care unit patients. Higher bile density in the GB body and subserosal edema was associated with an edematous GB (specificity, 93.6%; sensitivity, 23.1%). The most specific findings predicting necrotic AAC were gas in the GB wall or lumen, lack of GB wall enhancement, and edema around the GB (specificity, 99.2%, 94.9%, and 92.4%, respectively; and sensitivity, 11.1%, 37.5%, and 22.2%, respectively). CONCLUSIONS The frequency of nonspecific abnormal findings in the GB of critically ill patients limits the diagnostic value of CT scanning in detecting AAC. However, in the case of totally normal GB findings in CT, the probability of necrotic AAC is low.