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Excess weight and obesity relate to multiple comorbidities, lost quality of life and mortality and cause major burden to healthcare and society. Most obesity seems to trace to changes in lifestyle and the food environment in the last few decades. The comorbidities related to obesity are increasingly viewed as a result of low-grade inflammation characterizing the state of excess adiposity. On microscopic level, this associates with the infiltration of immune cells, particularly macrophages, into adipose tissue. Bariatric surgery and weight loss repeal these alterations. In this thesis, two behaviorally distinct macrophage pools are identified in subcutaneous adipose tissue of subjects with obesity. Of these, only the macrophages associated with pyroptotic adipocyte deaths decreased after laparoscopic Roux-en-Y gastric bypass for obesity. These macrophages were also highly imbued by known pro-inflammatory proteins, NLRP3 inflammasome and Caspase-1. The surgery associated with a shift of adipocyte size towards smaller populations. In addition, a novel method was developed for fat cell size and count analysis using free open-source software., Tiivistelmä Ylipainoon ja lihavuuteen liittyy lukuisia liitännäissairauksia, alentunut elämänlaatu ja lisääntynyt kuolleisuus sekä kasvanut terveyspalvelujen kulutus. Viime vuosikymmenten lihavuusepidemia selittynee ensisijaisesti länsimaalaistuneella elämäntavalla ja ruokaympäristön muutoksilla. Viime aikoina on herätty ylimääräisen rasvakudoksen aiheuttamaan matala-asteisen tulehduksen ja liitännäissairauksien yhteyksiin. Rasvakudoksessa tulehdus ilmenee erityisesti paikallisena syöjäsolujen eli makrofagien kertymisenä. Lihavuuskirurgia ja painonpudotus vähentävät sekä rasvakudoksen että elimistön yleistä tulehdustilaa. Tässä väitöskirjassa tunnistettiin kaksi eri tavoin mahalaukun ohitusleikkaukseen reagoivaa makrofagiryhmää. Osoitamme, että ainoastaan rasvasolujen tulehdukselliseen hajoamiseen ja kuolemaan liittyvät makrofagit vähentyvät leikkauksen jälkeen muun makrofagimäärän pysyessä muuttumattomana. Erityisesti rasvasolujen hajoamiseen liittyvien makrofagien osoitettiin myös ilmentävän runsaasti tulehduksellisia NLRP3- ja Caspase-1-proteiineja. Leikkauksen jälkeen rasvasolujen keskimääräinen koko pieneni. Kolmantena osatyönä esitetään uusi, ilmaista avoimen lähdekoodin ohjelmistoa käyttävä menetelmä rasvasolujen koon ja määrän mittaamiseen.

Background: Preoperative esophageal stenting is proposed to have a negative effect on outcomes. The aim was to compare a 5-year survival in patients undergoing esophagectomy for esophageal cancer with and without preoperative esophageal stent in a population-based nationwide cohort from Finland. The secondary outcome was 90-day mortality. Methods: This study included curatively intended esophagectomies for esophageal cancer in Finland between 1999 and 2016, with follow-up until December 31, 2019. Cox proportional hazards models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of overall 5-year and 90-day mortality. Model 1 was adjusted for age, sex, year of the surgery, comorbidities, histology, pathological stage, and neoadjuvant therapy. Model 2 included also albumin level and BMI. Result: Of 1064 patients, a total of 134 patients underwent preoperative stenting and 930 did not. In both adjusted models 1 and 2, higher 5-year mortality was seen in patients with preoperative stent with HRs of 1.29 (95% CI 1.00–1.65) and 1.25 (95% CI 0.97–1.62), respectively, compared to no stenting. The adjusted HR of 90-day mortality was 2.49 (95% CI 1.27–4.87) in model 1 and 2.49 (95% CI 1.25–4.99) in model 2. When including only neoadjuvant-treated patients, those with preoperative stent had a 5-year survival of 39.2% compared to 46.4% without stent (adjusted HR 1.34, 95% CI 1.00–1.80), and a 90-day mortality rate of 8.5% and 2.5% (adjusted HR 3.99, 95% CI 1.51–10.50). Discussion: This nationwide study reports worse 5-year and 90-day outcomes in patients with preoperative esophageal stent. Since residual confounding remains possible, observed difference could be only an association rather than the cause.

Background: The prognostic value of preoperative hemoglobin in patients undergoing esophagectomy is unknown. The aim of this study was to examine whether preoperative hemoglobin is associated with prognosis in patients undergoing esophagectomy for cancer. Materials and methods: This was a population-based nationwide retrospective cohort study in Finland, using Finnish National Esophago-Gastric Cancer Cohort (FINEGO). Esophagectomy patients with available preoperative hemoglobin measurement were included. Multivariable cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for calendar period of surgery, age at surgery, sex, comorbidity (Charlson Comorbidity Index), tumor histology, tumor stage, neoadjuvant therapy, type of surgery (minimally invasive or open) and annual hospital volume. Results: Of the 1313 patients, 932 (71.0%) were men and 799 (60.9%) had esophageal adenocarcinoma. Overall all-cause mortality was significantly higher in the lowest hemoglobin count tertile (HR 1.26 (1.07–1.47)) compared to the highest tertile, but this association was attenuated after adjustment for confounding. No differences were found between the preoperative hemoglobin groups in the adjusted analyses of 90-day all-cause, 5-year all-cause, and 5-year cancer-specific mortality. Conclusions: In this population-based nationwide study, preoperative hemoglobin count had no independent prognostic significance in esophageal cancer.

Cancer is a deadly disease worldwide. In light of the requisite of convincing therapeutic methods for cancer, immune checkpoint inhibition methods such as anti-PD-1/PD-L1 therapy appear promising. Human microbiota have been exhibited to regulate susceptibility to cancer as well as the response to anti-PD-1/PD-L1 therapy. However, the probable contribution of bacterial extracellular vesicles (bEVs) in cancer pathophysiology and treatment has not been investigated much. bEVs illustrate the ability to cross physiological barriers, assemble around the tumor cells, and likely modify the tumor microenvironment (EVs). This systematic review emphasizes the correlation between cancer-associated extracellular vesicles, particularly bEVs and the efficacy of anti-PD-1/PD-L1 therapy. The clinical and pharmacological prospective of bEVs in revamping the contemporary treatments for cancer has been further discussed.

Objective: This case–control study aimed to analyze the dynamics of macrophage infiltration in subcutaneous adipose tissue following bariatric surgery or conservative treatment of obesity and to clarify whether these features predict the weight loss outcome after the surgery. Methods: Subcutaneous tissue samples taken before and 12 months after laparoscopic Roux-en-Y gastric bypass surgery (n = 39) or conservative (n = 43) treatment for obesity were analyzed. Fat cell size was determined, and with CD68 immunohistochemistry, crown-like structures (CLS) were counted and single macrophages were quantitated. Results: A major decline in CLS density from 4.1 (SD 3.5) to 1.1 (SD 0.8) per 1000 fat cells (p < 0.000) was found, regardless of the degree of weight loss after the surgery. Surgery had no effect on the fraction of infiltrating single-cell macrophages in subcutaneous adipose tissue. The abundance of these macrophage populations before the intervention did not predict the degree of postsurgery weight loss or suboptimal response to the surgery. Conclusions: The effect of gastric bypass on adipose tissue inflammatory status associates closely with CLS density even in subjects with suboptimal weight loss. The study suggests that factors related to bypass surgery other than weight loss modify the inflammatory response in adipose tissue.

Obesity is associated with low-grade inflammation and increased systemic oxidative stress. Roux-en-Y gastric bypass (RYGB) surgery is known to ameliorate the obesity-induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non-diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA-LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first-line defense against microbes, and their production is markedly altered with RYGB surgery.

Changes in adipose tissue morphology, depicted by cell morphology alterations such as enlargement of fat cells, always accompany over-weight and obesity. The variables related to cell size have been shown to associate with low-grade inflammation of adipose tissue and common obesity-related comorbidities including metabolic syndrome and type 2 diabetes. Quantifying fat cell morphology from images of histological specimens can be tedious. Here, we present a straightforward method for the task using the free open-source software QuPath with its inbuilt tools only. Measurements of human adipose tissue samples with the described protocol showed an excellent correlation with those obtained with ImageJ software with Adipocyte Tools plugin combined with manual correction of misdetections. Intraclass correlation between the two methods was at good to excellent level. The method described here can be applied to considerably large tissue areas, even whole-slide analysis.

The skin is the largest organ of the body. Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The protective function of the skin is compromised in sepsis, and septic patients are prone to problems in tissue repair, which causes increased morbidity. However, there are only a few human studies exploring wound healing in sepsis. In this study we observed skin wound healing and the molecular mechanisms behind it in 44 septic patients and 14 healthy controls. From sepsis and healthy sera, metabolites were analyzed with proton nuclear magnetic spectroscopy, and cytokines using multiplex assay. The effect of sepsis and healthy sera was tested in vitro on keratinocyte proliferation, migration and viability. Suction blister wounds were induced on 15 patients and 10 controls and biopsied for immunohistochemical analyses. Serum levels of glucose, glycine, 3-hydroxybutyrate, creatinine and glycoprotein acetyls were significantly higher in sepsis patients compared to healthy controls, whereas levels of histidine and citrate were significantly lower in sepsis. Keratinocyte viability, proliferation and migration were reduced in sepsis in vitro. Sepsis sera supplemented with epithelial growth factor (EGF) or tumor necrosis factor alpha (TNF-α) improved and EGF receptor inhibition reduced keratinocyte migration in healthy and septic wounds. Extracellular vesicles added to healthy or sepsis serum media inhibited keratinocyte migration. Higher serum concentrations of TNF-α and vascular endothelial growth factor (VEGF) and lower levels of EGF were detected in sepsis sera compared to healthy sera. In skin immunohistochemistry samples, the levels of EGF, VEGF and transforming growth factor beta as well as syndecan-1 were increased in septic patients compared to healthy controls. Extracellular matrix (ECM) components tenascin-C and laminin-332 had lower expression in septic skin compared to healthy skin. The results of t, Tiivistelmä Elimistön väärin mitoitettu vaste tulehdukseen vaurioittaa sen omia kudoksia sepsiksessä. Iho on ihmisen suurin elin ja suoja ulkoisia haittatekijöitä vastaan. Kudosparanemisesta sepsiksessä on vain vähän tietoa. Tutkimuksen tarkoituksena on selvittää ihohaavan paranemista ja taustalla vaikuttavia molekyylitason mekanismeja sepsiksessä. Tutkimusta varten otettiin verinäytteet 44 sepsispotilaalta ja 14 terveeltä verrokilta. Lisäksi 15 potilaalle ja 10 terveelle verrokille tehtiin imurakkulahaavat iholle, ja yksi paraneva haava poistettiin kudosnäytteeksi. Aineenvaihduntatuotteiden määrää veressä tutkittiin ydinmagneettisella resonanssispektroskopialla. Haavan paranemista sepsiksessä tutkittiin mittaamalla keratinosyyttien elinkykyisyyttä, lisääntymistä ja liikkumista soluviljelymenetelmin. Lisäksi mitattiin veren kasvutekijäpitoisuuksia. Imurakkulahaavanäytteille tehtiin immunohistokemialliset tutkimukset. Veren glukoosin, glysiinin, 3-hydroksibutyraatin, kreatiniinin ja glykoproteiiniasetyylien pitoisuudet olivat sepsispotilailla korkeammat ja sitraatin ja histidiinin pitoisuudet matalammat terveisiin verrattuna. Keratinosyyttien elinvoimaisuus, liikkuminen ja lisääntyminen keinotekoisessa haavassa olivat alentuneet sepsiksessä terveisiin verrokkeihin verrattuna. Solunulkoiset vesikkelit estivät ja epiteliaalisen kasvutekijän (EGF) tai tuumorinekroositekijä alfan (TNF-α) lisäys haavoille paransi keratinosyyttien liikkumista. Veren TNF-α:n ja verisuonikasvutekijän (VEGF) pitoisuudet olivat sepsiksessä korkeammat, kun taas EGF:n pitoisuus oli matalampi. Paranevan ihohaavan solunulkoisen väliaineen komponenttien tenaskiini-C:n sekä laminiini-332:n määrä oli sepsiksessä vähäisempi ja solun pintareseptori syndekaani-1:n, transformoivan kasvutekijä beetan (TGF-β), VEGF:n ja EGF:n määrä puolestaan korkeampi. Tässä tutkimuksessa saadut tulokset tukevat aiempia kliinisiä havaintoja heikentyneestä haavan paranemisesta sepsiksessä sekä antavat lisäti

Background: Minimally invasive esophagectomy (MIE) is a complex procedure with learning associated morbidity. The aim was to evaluate the learning curve for MIE focusing on short-term outcomes in two settings: (I) experienced MIE surgeon in new hospital (Hospital 1); (II) surgeons experienced with open esophagectomy and minimally invasive surrogate surgery (Hospital 2). Methods: In Hospital 1 and Hospital 2, on intent-to-treat basis number of MIEs were 132 and 57, respectively. The primary outcomes were major complications and anastomosis leaks. Secondary outcomes were operative time, blood loss, lymph node yield, hospital stay and 1-year mortality. Length of learning curves were analyzed with risk-adjusted cumulative sum (RA-CUSUM) method. Results: In Hospital 1, major complication and anastomosis leak rates were 9.8% and 4.5%, 22.8% and 12.3% in Hospital 2, respectively. In Hospital 1, complication and leak rates remained stable. In Hospital 2, improvement occurred after 34 cases in major complications and 29 cases in leaks. Of secondary outcomes, improvements were seen in Hospital 1 in operative time after 61, blood loss after 86, lymph node yield after 52, hospital stay after 19 and 1-year mortality after 24 cases. In Hospital 2, improvement occurred in operative time after 30, blood loss after 15, lymph node yield after 45, hospital stay after 50 and 1-year mortality after 15 cases. Conclusions: According to this study, learning phase of the individual surgeon determines the outcomes of MIE, not the institutional learning phase.

Background: Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for obesity, which improves cardiovascular health and reduces the risk of premature mortality. However, some reports have suggested that RYGB may predispose patients to adverse health outcomes, such as inflammatory bowel disease (IBD) and colorectal cancer. Objectives: The present prospective study aimed to evaluate the impact of RYGB surgery on cardiovascular risk factors and gastrointestinal inflammation in individuals with and without type 2 diabetes (T2D). Setting: University hospital setting in Finland. Methods: Blood and fecal samples were collected at baseline and 6 months after surgery from 30 individuals, of which 16 had T2D and 14 were nondiabetics. There were also single study visits for 6 healthy reference patients. Changes in cardiovascular risk factors, serum cholesterol, and triglycerides were investigated before and after surgery. Fecal samples were analyzed for calprotectin, anti-Saccharomyces cerevisiae immunoglobulin A antibodies (ASCA), active lipopolysaccharide (LPS) concentration, short-chain fatty acids (SCFAs), intestinal alkaline phosphatase activity, and methylglyoxal-hydro-imidazolone (MG-H1) protein adducts formation. Results: After RYGB, weight decreased on average −21.6% (−27.2 ± 7.8 kg), excess weight loss averaged 51%, and there were improvements in cardiovascular risk factors. Fecal calprotectin levels (P < 0.001), active LPS concentration (P < 0.002), ASCA (P < 0.02), and MG-H1 (P < 0.02) values increased significantly, whereas fecal SCFAs, especially acetate (P < 0.002) and butyrate (P < 0.03) levels, were significantly lowered. Conclusion: The intestinal homeostasis is altered after RYGB, with several fecal markers suggesting increased inflammation; however, clinical significance of the detected changes is currently uncertain. As chronic inflammation may predispose patients to adverse health effects, our findings may have relev

Background: Esophagectomy is the mainstay of surgical treatment of esophageal cancer, but involves high operative risk. The aim of this study was to review the evolution surgical treatment of esophageal cancer in Northern Finland, with introduction of minimally invasive techniques. Methods: All elective esophagectomies performed in Oulu University Hospital between years 1987 and 2020 were included. Treatment strategies were compared to current guidelines including staging and use of neoadjuvant therapy, and benchmark values including postoperative morbidity, hospital stay, readmissions and 90-day mortality. Long-term survival was compared to previous national studies. Results: Between years 1987 and 2020 a total of 341 underwent an esophagectomy. Transhiatal resection was performed to 167 (49.3%), Ivor Lewis to 129 (38.1%) and McKeown to 42 (12.4%) patients. MIE was performed to 49 (14.5%) patients. During the past four years 83.7% of locally advanced diseases received neoadjuvant treatment. Since 1987, gradual improvements have occurred especially in incidence of pleural effusion requiring additional drainage procedure (highest in 2011–2013 and in last four years 14.0%), recurrent nerve injuries (highest in 2008–2010 29.4% and lowest in 2017–2020 1.8%) and in 1-year survival rate (1987–1998 68.4% vs. 2017–2020 82.1%). No major changes in comorbidity, complication rate, anastomosis leaks, hospital stay or postoperative mortality were seen. Conclusions: Esophageal cancer surgery has gone through major changes over three decades. Current guideline-based treatment has resulted with progressive improvement in mid- and long-term survival. However, despite modern protocol, no major improvement has occurred for example in major complications, anastomosis leak rates or hospital stay.

Background: Open abdomen (OA) is a useful option for treatment strategy in many acute abdominal catastrophes. A number of temporary abdominal closure (TAC) methods are used with limited number of comparative studies. The present study was done to examine risk factors for failed delayed primary fascial closure (DPFC) and risk factors for mortality in patients treated with OA. Methods: This study was a multicenter retrospective analysis of the hospital records of all consecutive patients treated with OA during the years 2009 to 2016 at five tertiary referral hospitals and three secondary referral centers in Finland. Results: Six hundred seventy-six patients treated with OA were included in the study. Vacuum-assisted closure with continuous mesh-mediated fascial traction (VACM) was the most popular TAC method used (N = 398, 59%) followed by VAC (N = 128, 19%), Bogota bag (N = 128, 19%), and self-designed methods (N = 22, 3%). In multivariate analysis, enteroatmospheric fistula and the number of needed TAC changes increased the risk for failed DPFC (odds ratio [OR], 8.9; 95% confidence interval [CI], 6.2–12.8; p < 0.001 and OR, 1.1; 95% CI, 1.0–1.3; p < 0.001, respectively). Instead, VACM and ruptured abdominal aortic aneurysm as cause for OA both decreased the risk for failed DPFC (OR, 0.1; 95% CI, 0.0–0.3; p < 0.001 and OR, 0.2; 95% CI, 0.1–0.7; p = 0.012). The overall mortality rate was 30%. In multivariate analysis for mortality, multiorgan dysfunction (OR, 2.4; 95% CI, 1.6–3.6; p < 0.001), and increasing age (OR, 4.5; 95% CI, 2.0–9.7; p < 0.001) predicted increased mortality. Institutional large annual patient volume (OR, 0.4; 95% CI, 0.3–0.6; p < 0.001) and ileus and postoperative peritonitis in comparison to severe acute pancreatitis associated with decreased mortality (OR, 0.2; 95% CI, 0.1–0.4; p < 0.001; OR, 0.5; 95% CI, 0.3–0.8; p = 0.009). Kaplan-Meier analysis showed increased survival in patients treated with VACM in comparison

Background: Sepsis delays wound re-epithelialization. In this study we explored the effect of human sepsis sera as well as the effects of cytokines, growth factors and exosomes of sepsis sera treated normal fibroblasts (NF) on keratinocyte migration and proliferation in vitro. Methods: Serum samples were taken on days 1, 4, and 9 from 44 patients diagnosed with severe sepsis, and from 14 matching healthy controls. We evaluated the effects of sepsis serum with or without TNF-α, EGF, EGF receptor inhibitor or exosomes of sepsis sera treated NF on human keratinocyte (HaCaT) proliferation (BrdU assay), viability (MTT assay), and migration (horizontal wound healing model). Cytokine levels of sepsis and healthy sera were measured by multiplex assay. Comparisons between groups were carried out using SPSS statistics and P < 0.05 was considered significant. Results: Severe-sepsis sera collected on days 1, 4, and 9 reduced keratinocyte proliferation by 6% (P = 0.005), 20% (P = 0.001), and 18% (P = 0.002), respectively, compared to control sera. Cell viability in cultures exposed to sepsis sera from days 4 and 9 was reduced by 38% (P = 0.01) and 58% (P < 0.001), respectively. Open-surface wounds exposed to sepsis sera from days 1 and 4 were larger than those exposed to sera from healthy controls (60 vs. 31%, P = 0.034 and 66 vs. 31%, P = 0.023, respectively). Exosomes of sepsis or healthy sera treated NF inhibited keratinocyte migration. We detected higher serum levels of cytokines TNF-α (5.7 vs. 0.7 pg/ml, P < 0.001), IL-6 (24.8 vs. 3.8 pg/ml, P < 0.001), IL-10 (30.0 vs. 11.9 pg/ml, P = 0.040), and VEGF (177.9 vs. 48.1 pg/ml, P = 0.018) in sepsis sera. Levels of EGF were significantly lower in sepsis sera than in that of healthy controls (6.5 vs. 115.6 pg/ml, P < 0.001). Sepsis serum supplemented with EGF 5 ng/ml and TNF-α in all concentrations improved keratinocyte migration. Conclusions: Keratinocyte viability, proliferation and migration were reduce

It is a generally accepted dogma that sepsis disturbs skin function and wound healing, but surprisingly there is only remote pathophysiological evidence available behind that presumption. As the skin is the largest defensive barrier, the skin dysfunction in severe sepsis deserves more attention. In this study, the suction blister model was used to create experimental wounds. The study population included 44 patients with severe sepsis and 15 controls. The blister fluid was collected to analyse cytokine profile of the skin. The transepidermal water loss and blood flow from the wound were measured. A 4mm biopsy was taken under local anaesthesia on the first and the eighth day of the study from the healthy looking skin. Then 15 healing suction blisters were excised. Serum samples were also collected on the first day of the study. The barrier restoration was diminished, and the inflammation in the wound was more intense in severe sepsis than in the controls. The expression of the basement membrane components Laminin-332 and type IV collagen decreased during the septic disease, but increased over the next 3 months without achieving the level oft he controls. The expression of tight junction proteins remained nearly intact in the healing wound in severe sepsis compared to the controls. The expression of occludin on the leading edge of the migrating keratinocytes was more restricted and late in severe sepsis compared to the controls. The levels of the tumour necrosis factor (TNF), interleukin-10 (IL-10) and IL-6 in skin blister fluid were higher in the sepsis compared to controls. The blister fluid and serum cytokine response in the sepsis differed since the levels of epidermal growth factor, vascular endothelial growth factor, TNF and basic fibroblastic growth factor (bFGF) in the blister fluid did not correlate with the levels of serum. The septic patients with multiple organ failure had higher levels of several cytokines than patients without organ failure. Sur, Tiivistelmä Sepsiksen ajatellaan heikentävän haavanparanemista, mutta tieteellistä näyttöä on niukasti. Iholla on keskeinen osa elimistön puolustuksessa ja tasapainon ylläpidossa, joten sen toiminnan häiriintyminen systeemisessä tulehduksessa ansaitsee suuremman huomion. Imurakkulahaavat tehtiin 44 septiselle potilaalle ja 15 kontrollille. Haavoista mitattiin veden haihtumista ja veren virtausta sekä otettiin imurakkulaneste näytteeksi sytokiinimäärityksiä varten. Tutkimuksen ensimmäisenä ja kahdeksantena päivänä otettiin 4mm biopsiat terveeltä iholta ja 15 potilaalta poistettiin näytteeksi paraneva imurakkulahaava. Seeruminäytteet otettiin tutkimuksen ensimmäisenä päivänä. Veden haihtuminen haavalta oli voimakkaampaa eli ihon barrierin palautuminen oli hidastunut septisillä potilailla verrattuna kontrolleihin. Haavassa havaittu tulehdus oli sepsiksessä voimakkaampi. Tyvikalvon komponenttien Laminiini-332:n ja tyypin IV kollageenin ilmentyminen oli vähäisempää sepsiksen aikana ja lisääntyi 3kk kohdalla, mutta ei kuitenkaan saavuttanut kontrollien tasoa. Tiivisliitosproteiinien ilmentyminen oli lähes muuttumatonta sepsiksessä kontrolleihin verrattuna. Okludiinin ilmentyminen sen sijaan paranevassa haavassa vaeltavien keratinosyyttien etureunassa oli rajoittuneempaa ja myöhäisempää sepsiksessä kuin kontrolleilla. Sytokiineistä tuumorinekroositekijä (TNF), interleukiini-10 (IL-10) ja IL-6 olivat koholla imurakkulanesteessä verrattuna kontrolleihin. Epidermaalinen kasvutekijä, verisuonten endoteelikasvutekijä, TNF ja perusfibroplastinen kasvutekijä (bFGF) pitoisuudet rakkulanesteessä erosivat seerumin pitoisuuksista eli ihon sytokiiniprofiili erosi systeemisestä sytokiiniprofiilista. Potilailla, joilla oli monielinvaurio, todettiin korkeampia sytokiinipitoisuuksia. Potilailla, jotka menehtyivät 30 vrk kuluessa, oli korkeammat pitoisuudet IL-10 ja bFGF rakkulanesteessä. Tämä tutkimus tarjoaa uutta tietoa ihosta ja haavanparanemisesta sepiksessä. Tulosten perusteella void