Verisuonikirurgian haaste : alaraajan iskeeminen haava

There is a widespread reporting habit of combining the outcomes for patients with rest pain (Fontaine III) and tissue loss (Fontaine IV) under the single category of critical leg ischaemia (CLI). This study focused on patients with ischaemic tissue loss treated with infrainguinal bypass surgery (IBS). All patients included in the study were treated at Helsinki University Central Hospital in 2000-2007. First, ulcer healing time after IBS and factors influencing healing time were prospectively assessed in 2 studies including 148 and 110 patients, respectively. Second,the results of redo IBS were retrospectively evaluated in 593 patients undergoing primary IBS for CLI with tissue loss . Third,long-term outcome were retrospectively analysed in 636 patients who underwent IBS for CLI with tissue loss . Fourth, the outcome of IBS was retrospectively compared with endovascular treatment (PTA) of the infrapopliteal arteries in 1023 CLI patients. Fifth, the influence multidrug resistant Pseudomans aeruginosa (MDR Pa) bacteria contamination in CLI patients treated with IBS was retropectively assessed. Sixty-four patients with positive MDR Pa -culture were matched with 64 MDR Pa - negative controls. Complete ulcer healing rate, including the ischemic ulcers and incisional wounds, was 40% at 6 months after IBS and 75% at one year. Diabetes was a risk factor for prolonged complete ulcer healing time. Ischaemic tissue lesions located in mid-and hindfoot healed poorly. At one year after IBS 50% of the patients were alive with salvaged leg and completely healed ulcers. The absence of gap between tertiary graft patency and leg salvage rates indicates the importance of a patent infrainguinal graft to save a leg with ischaemic tissue loss. Long-term survival for patients with ischaemic tissue loss was poor, 38% at 5 years. Only 30% of the patients were alive without amputation at 5 years. Several of the patient comorbidities increased independently the mortality risk; coronary artery disease, renal insufficiency, chronic obstructive lung disease and high age. When both PTA and bypass is feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized. MDR Pa in a patient with CLI should be considered as a serious event with increased risk of early major amputation or death. Conclusion: Despite a successful infrainguinal bypass healing of the ischaemic ulcers and incisional wounds ulcer healing is a slow process especially in diabetics. Bypass surgery and PTA improve the outcome of the ischaemic leg but the mortality rate of the patients is high due to their severe comorbidities.Kriittisessä alaraajaiskemiassa verenkierto on siinä määrin huonontunut että kudoksen elinkelpoisuus on uhattuna. Krooninen kriittinen iskemia ilmenee usein ensin leposärkynä (luokitus Fontaine III), myöhemmin haavaumana (Fontaine IV). Alaraajan valtimo-ohitusleikkaus on tärkein hoitomenetelmä raajan pelastamiseksi laaja-alaisessa tukkivassa valtimokovettumataudissa. Leposärky- ja haavapotilaat ovat perinteisesti tutkimuksissa käsitelty yhtenä ryhmänä. Tämän tutkimuksen tarkoituksena oli selvittää alaraajan valtimo-ohitusleikkauksen tuloksia potilailla joilla oli kriittisestä alaraaja-iskemiasta johtuva haava (Fontaine IV). Tutkimuksen aineistona oli 1265 potilasta joille tehtiin iskeemisen alaraajahaavan (1038 potilasta) tai leposärkyn takia (227) Helsingin Yliopstollisessta Keskussairaalassa vuosina 2000-2007 alaraajavaltimon ohitusleikkaus (1003) tai -pallolaajennus (262). Tutkimuksessa todettiin että ohitusleikkauksen jälkeen 60 %:lla potilaista leikkaushaavojen ja iskeemisten haavojen paranemiseen kului yli puoli vuotta. Vuoden kohdalla 25%:lla oli vielä haava auki. Diabetes hidasti haavojen paranemista. Myös iskeemisten haavojen sijainti jalassa vaikutti paranemisaikaan, kantapään alueen haavat paranivat huonosti. Tutkimus osoitti että toimiva alaraaja ohite on tärkeä raajan säilyttämiseksi mikäli potilaalla on iskeeminen haava. Ohitteen tukkeutuminen johti 52%:lla vuoden sisällä amputaatioon ellei uusitaleikkausta tehty. Uusintaleikatuilla potilailla vastaava luku oli 14%. Pitkäaikaistulokset osoittivat että ohitusleikkauksella pystytään valtaosa, 5 vuoden kohdalla 76%, alaraajoista säilyttämään. Sen sijaan potilaiden kuolleisuus oli suuri. Viiden vuoden kohdalla 38% oli elossa ja 30% elossa ilman amputaatiota. Suurentunutta kuolleisuutta ennustivat korkea ikä, sepelvaltimotauti, munuaisten vajaatoiminta ja keuhkoahtaumatauti. Lisäksi todettiin että mikrobilääkkeille vastaustuskykyinen Pseudomonas aeruginosa- tartunta lisäsi riskiä menettää alaraaja tai kuolla. Mikäli suonensisäinen pallolajennus on mahdollinen polven alapuolisiin valtimoihin sillä voidaan saavuttaa samanlaiset tulokset kuin ohitusleikkauksella mutta pallolaajennushoito johtaa useamiin uusintatoimenpiteisiin ohitusleikkaukseen verrattuna. Yhteenveto: Tutkimus osoittaa että iskeemisten haavojen paraneminen on hidas tapahtuma, etenkin diabeetikoilla. Onnistunut alaraajan ohitusleikkaus tai pallolaajennus parantaa alaraaajan ennustetta, mutta potilaiden pitkä-aikaisennuste on heikko perussairauksista johtuen

The Feasibility of Angiosome-Targeted Endovascular Treatment in Patients with Critical Limb Ischaemia and Foot Ulcer

Peer reviewe

Long-term Results of Inframalleolar Bypass for Critical Limb Ischaemia

Peer reviewe

Competing Risk Analysis of the Impact of Pedal Arch Status and Angiosome-Targeted Revascularization in Chronic Limb-Threatening Ischemia

Introduction In the context of chronic limb threatening ischemia (CLTI), the prognostic impact of angiosome-targeted revascularization and of the status of the pedal arch are debated. Materials and method This series includes 580 patients who underwent endovascular (n=407) and surgical revascularization (n=173) of the infrapopliteal arteries for CLTI associated with foot ulcer or gangrene. The risk of major amputation after infrapopliteal revascularization was assessed by a competing risk approach. A subanalysis was made separately for patients who underwent endovascular or open surgical revascualrization. Results At 2 years, survival was 65.1% and leg salvage was 76.1%. Multivariable competing risk analysis showed that C-reactive protein≥ 10 mg/dL, diabetes, rheumatoid arthritis, increased number of affected angiosomes and the incomplete or total absence of pedal arch compared to complete pedal arch were independent predictors of major amputation after infrapopliteal revascularization. Multivariable analysis showed increasing risk estimates of major amputation in patients with incomplete (SHR 2.131, 95%CI 1.282-3.543) and no visualized pedal arch (SHR 3.022, 95%CI 1.553-5.883) compared to complete pedal arch. Pedal arch was important even if angiosome-targeted revascularization was achieved: Angiosome-directed revascularization in presence of complete pedal arch had a lower risk of major amputation (adjusted SHR 0.463, 95%CI 0.240-0.894) compared to angiosome-directed revascularization without complete pedal arch. In the subanalysis, among patients who underwent endovascular revascularization, complete pedal arch (SHR 0.509, 95%CI 0.286-0.905) and angiosome-targeted revascularization (SHR 0.613, 95%CI 0.394-0.956) were associated with a lower risk of major amputation. Conclusions Competing risk analysis showed that a patent pedal arch had significant impact on leg salvage and that the subset of patients undergoing endovascular procedure may most benefit of an angiosome-targeted revascularization.Peer reviewe

In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages

Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF)1,2,3, its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos4. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis5,6, a high number of embryos containing abnormal cells can pass this strong selection barrier7,8. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages

Doubly Uniparental Inheritance of Mitochondria As a Model System for Studying Germ Line Formation

BACKGROUND: Doubly Uniparental Inheritance (DUI) of mitochondria occurs when both mothers and fathers are capable of transmitting mitochondria to their offspring, in contrast to the typical Strictly Maternal Inheritance (SMI). DUI was found in some bivalve molluscs, in which two mitochondrial genomes are inherited, one through eggs, the other through sperm. During male embryo development, spermatozoon mitochondria aggregate in proximity of the first cleavage furrow and end up in the primordial germ cells, while they are dispersed in female embryos. METHODOLOGY/PRINCIPAL FINDINGS: We used MitoTracker, microtubule staining and transmission electron microscopy to examine the mechanisms of this unusual distribution of sperm mitochondria in the DUI species Ruditapes philippinarum. Our results suggest that in male embryos the midbody deriving from the mitotic spindle of the first division concurs in positioning the aggregate of sperm mitochondria. Furthermore, an immunocytochemical analysis showed that the germ line determinant Vasa segregates close to the first cleavage furrow. CONCLUSIONS/SIGNIFICANCE: In DUI male embryos, spermatozoon mitochondria aggregate in a stable area on the animal-vegetal axis: in organisms with spiral segmentation this zone is not involved in cleavage, so the aggregation is maintained. Moreover, sperm mitochondria reach the same embryonic area in which also germ plasm is transferred. In 2-blastomere embryos, the segregation of sperm mitochondria in the same region with Vasa suggests their contribution in male germ line formation. In DUI male embryos, M-type mitochondria must be recognized by egg factors to be actively transferred in the germ line, where they become dominant replacing the Balbiani body mitochondria. The typical features of germ line assembly point to a common biological mechanism shared by DUI and SMI organisms. Although the molecular dynamics of the segregation of sperm mitochondria in DUI species are unknown, they could be a variation of the mechanism regulating the mitochondrial bottleneck in all metazoans

Local and global contaminants in Swedish waters : studies on PCBs, DDTs, 4,5,6-trichloroguaiacol and their transformation products in fish and sediments

This thesis is focused on studies on the environmental fate and methodological improvements for determination of the global contaminants, PCBs and DDTs, and locally discharged phenolics, e.g. 4,5,6-trichloroguaiacol (4,5,6-TCG), and their transformation products. 4,5,6-TCG is released from bleached pulp mills, and was chosen as a model substance, to study its fate and effects in aquatic environments. In a brackish water model ecosystem, 4,5,6-TCG was shown to be transformed via demethylation, dechlorination, and methylation reactions. Marine periphyton exposed to 4,5,6-TCG was shown to form demethylated, brominated and dimeric metabolites. Several of these metabolites were identified and quantified. Also more tightly bound chlorophenolics were recovered from the substrate, after harsh extraction procedures had been applied. Conjugates of chlorophenols in fish bile were determined as useful tracers for monitoring effluents from bleached pulp mills, even in areas far from the discharge point. To facilitate calculations of water concentrations, bile to water bioconcentration factors (bBCF-values) were determined for several phenolics, including also alkali-labile chlorocatechols. PCBs and DDTs, were assessed in Swedish lakes with background exposure of these global contaminants. A methodological study focus on the contamination risks of airborne PCBs, during freeze-drying and storage of dry sediment samples. Eutrophication has been proposed to cause lower levels of pollutants in biota in lakes due to biomass dilution but in this thesis examples of higher levels of PCBs in sediment traps, sediment and in perch, and also in higher fluxes of PCBs to the sediment, were observed. Phytoplankton are supposed to be responsible for most of the transport of the contaminants. The composition of DDTs in soil, sediment traps and in dated sediment cores was studied in some detail. PCBs, DDTs, HCB and HCHs were measured in sediments from 100 reference lakes included in the National Swedish Environmental Program. The lakes have a large variation in lake characteristics, representative for different areas in Sweden. A gradient was observed for sPCB with decreasing levels from the south west towards the north. The results suggests that longrange transport is the dominating mechanism for distribution of the contaminants analysed. In this study the levles of PCBs and DDTs were lower in eutrophic lakes than in oligotrophic lakes, in an area with similar atmospheric exposure.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Submitted. Paper 6: Manuscript.</p