Infrared thermography in vascular disorders:screening and follow-up

Abstract Diabetes constitutes a growing healthcare burden and diabetes-related foot problems are the leading cause of hospitalization among diabetics. Atherosclerosis is also a common disease of the lower extremities and peripheral arterial disease (PAD) has become an indicator for generalized atherosclerosis. However, PAD is less well known than coronary and cerebral artery disease, and this impairs the diagnosis and treatment of the disease and the management of risk factors. The purpose of this study is to evaluate the use of infrared thermography (IRT) in clinical work in patients with circulatory disorders compared to conventional non-invasive methods. This thesis consists of four parts. The first and second parts examined the diagnostic potential of IRT in patients with diabetes and patients with PAD. The patient groups were compared to the healthy controls. In the third part, patients were followed before and after revascularization. The fourth part separately presents the results for those patients in which transcutaneous oxygen pressure measurements were performed. Side-to-side differences and local variations in temperature are the most significant factors for identifying pathology findings in both patients with diabetes or PAD. After successful revascularization, these side-to-side differences decrease and skin temperature differences were moderate during follow-up. Diabetes-related neuropathy raises the skin temperature. Surprisingly, even if toe pressure or oxygen pressure of the tissue decreases, skin temperature rises significantly. Also, an ulcer without inflammation raises the skin temperature. The infrared image provides information for broad regions of interest rather than merely the local temperature of a small area currently in use of screening diabetic feet. IRT is a useful tool in prevention, especially in high risk patients with diabetes, allowing even asymptomatic skin temperature-related symptoms such as inflammation to be detected earlier. Individual variations in skin temperature are broad, however, and IRT might not be sufficient as a single screening measurement in a clinical use among patients with vascular disorders, but it does have the potential for providing additional information.Tiivistelmä Diabetes ja siihen liittyvät jalkaongelmat ovat merkittävä kansanterveydellinen haitta ja aiheuttavat isoimman osan diabeetikoiden sairaalahoitoa vaativista käynneistä. Myös ateroskleroosi on yleistyvä kansantauti ja alaraajojen tukkivan valtimokovettumatauti yksi ateroskleroosin kolmesta tavallisimmasta ilmenemismuodosta. Alaraajojen valtimokovettumatauti tunnetaan kuitenkin huonommin kuin sepelvaltimo- ja aivovaltimotauti ja tämä heikentää taudin diagnostiikkaa ja hoitoa sekä riskitekijöiden hallintaa. Tutkimusten tarkoitus on selvittää lämpökameran käyttöä kliinisessä työssä verenkiertohäiriöpotilailla verrattuna perinteisiin ei-invasiivisiin menetelmiin. Tämä väitöskirja koostuu neljästä osatyöstä. Ensimmäisessä ja toisessa selvitettiin lämpökamerakuvantamisen diagnostisia mahdollisuuksia diabetespotilailla ja valtimokovettumatautia sairastavilla potilailla. Potilasryhmiä verrattiin terveisiin verrokkeihin. Kolmannessa osatyössä seurattiin potilaita ennen ja jälkeen verenkierron palauttamisen. Neljännessä osatyössä esitetään erikseen potilaat, joille tehtiin kudoksen happiosapainemittaukset. Lämpötilan puolierot ja paikalliset vaihtelut ovat merkittävimmät seikat poikkeavien löydösten identifioimiseksi verenkiertohäiriöpotilaan jalassa sekä diabeetikoilla että ateroskleroosipotilailla. Onnistuneen verenkierron palauttamisen jälkeen lämpötilaerot tasoittuvat ja puoliero pienenee seurannan aikana. Sokeritautiin liittyvä neuropatia nostaa ihon lämpötilaa. Ja yllättäen vaikka varvaspaine tai kudoksen happipitoisuus laskevat, nousee ihon lämpötila merkitsevästi. Myös haava ilman tulehdusta nostaa ihon lämpötilaa. Erityisesti diabeetikon jalassa esiintyvien lämpötilojen paikalliset erot lämpökamera havaitsee laajemmin kuin nykyisin käytössä oleva yksittäisten pistemäisten lämpötilojen käyttö, jolloin oireettomatkin ihon lämpötilaan vaikuttavat taudinkuvat kuten tulehdukset voidaan havaita aikaisemmin. Kuitenkin yksilöllinen ihon lämpötilan vaihtelu on suurta ja yksittäistä kuvausta voidaan käyttää muiden tutkimusmenetelmien tukena

Induction of CD73 prevents death after emergency open aortic surgery for a ruptured abdominal aortic aneurysm: a randomized, double-blind, placebo-controlled study

Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). This is a multi-center phase II double-blind, 2:1 randomized, parallel group comparison of the efficacy and safety of IV IFN beta-1a vs. placebo for the prevention of death after open surgery for an infra-renal RAAA. All study patients presented a confirmed infra-renal RAAA, survived the primary emergency surgery and were treated with IFN beta-1a (10 μg) or matching placebo for 6 days after surgery. Major exclusion criteria included fatal hemorrhagic shock, chronic renal replacement therapy, diagnosed liver cirrhosis, severe congestive heart failure, advanced malignant disease, primary attempt of endovascular aortic repair (EVAR), and per-operative suprarenal clamping over 30 min. Main outcome measure was all-cause mortality at day 30 (D30) from initial emergency aortic reconstruction. The study was pre-maturely stopped due to a reported drug-drug interaction and was left under-powered. Out of 40 randomized patients 38 were included in the outcome analyses (27 IFN beta-1a and 11 placebo). There was no statistically significant difference between treatment groups at baseline except more open-abdomen and intestinal ischemia was present in the IFN beta-1a arm. D30 all-cause mortality was 22.2% (6/27) in the IFN beta-1a arm and 18.2% (2/11) in the placebo arm (OR 1.30; 95% CI 0.21–8.19). The most common adverse event relating to the IFN beta-1a was pyrexia (20.7% in the IFN beta-1a arm vs. 9.1% in the placebo arm). Patients with high level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids and the presence of IFN beta-1a neutralizing antibodies associated with a poor CD73 response and survival. The initial aim of the trial, if postoperative INF beta-1a treatment results on better RAAA survival, could not be demonstrated. Nonetheless the anticipated target mechanism up-regulation of CD73 was associated with 100% survival. According to present results the INF beta-1a induced up-regulation of serum CD73 was blocked with both use of glucocorticoids and serum IFN beta-1a neutralizing antibodies. The study was pre-maturely stopped due to interim analysis after a study concerning the use if IV IFN beta-1a in ARDS suggested that the concomitant use of glucocorticoids and IFN beta-1a block the CD73 induction. Trial registration: ClinicalTrials.gov NCT03119701. Registered 19/04/2017 (retrospectively registered)