Activated coagulation during open and endovascular abdominal aortic aneurysm repair

OBJECTIVE: The study was conducted to determine activation of coagulation in patients undergoing open and endovascular infrarenal abdominal aortic aneurysm repair (EVAR). METHODS: In a prospective, comparative study, 30 consecutive patients undergoing open repair (n = 15) or EVAR (n = 15) were investigated. Blood samples to determine fibrinopeptide A, fibrin monomer, thrombin-antithrombin complex, and D-dimer were taken up to 5 days postoperatively. Routine hematologic and hematochemical parameters as well as clinical data were collected. RESULTS: Both groups showed comparable demographic variables. Operating time was longer in open repair (249 +/- 77 minutes vs 186 +/- 69 minutes, P < .05). Perioperatively elevated markers of coagulation were measured in both groups. Fibrinopeptide A levels did not differ significantly between the groups (P = .55). The levels of fibrin monomer and thrombin-antithrombin complex were significantly higher in patients undergoing EVAR (P < .0001), reflecting increased thrombin activity and thrombin formation compared with open surgery. The D-dimer level did not differ significantly between the groups. These results were also valid after correction for hemodilution. CONCLUSION: These data suggest increased procoagulant activity in EVAR compared with open surgery. A procoagulant state may favor possible morbidity derived from micro- and macrovascular thrombosis, such as in myocardial infarction, multiple organ dysfunction, venous thrombosis and thromboembolism, or disseminated intravascular coagulation.

Tenofovir-containing nucleoside/nucleotide-only antiretroviral maintenance therapy: decision making and virological outcome

OBJECTIVE: To assess the virological outcome of patients with undetectable human immunodeficiency (HI) viremia switched to tenofovir (TDF)-containing nucleosideonly (NUKE-only) treatments and to investigate the factors influencing the physicians' decision for application of a nonestablished therapy. METHOD: Patients' characteristics and history were taken from the cohort database. To study the decision-making process, questionnaires were sent to all treating physicians. RESULTS: 49 patients were changed to TDF-containing NUKE-only treatment and 46 had a follow-up measurement of HI viremia. Virological failure occurred in 16 (35%) patients. Virological failure was associated with previous mono or dual therapy and with a regimen including didanosine or abacavir. No failure occurred in 15 patients without these predisposing factors. The main reasons for change to TDF-containing NUKE-only treatment were side effects and presumed favorable toxicity profile. The rationale behind this decision was mainly analogy to the zidovudine/lamivudine/abacavir maintenance therapy. CONCLUSION: TDF-containing NUKE-only treatment is associated with high early failure rates in patients with previous nucleoside reverse transcriptase inhibitor mono or dual therapy and in drug combinations containing didanosine or abacavir but not in patients without these predisposing factors. In HIV medicine, treatment strategies that are not evidence-based are followed by a minority of experienced physicians and are driven by patients' needs, mainly to minimize treatment side effects.

Transcatheter repair of iatrogenic left ventricular free-wall perforation

Left ventricular free-wall perforation can complicate catheter-based diagnostic or interventional procedures and may require immediate needle pericardiocentesis followed by surgical repair in about 20% of the cases. We describe the transcatheter closure of a left ventricular free-wall perforation as an option in the event of maintained access to the perforation site after defect creation.

Repair of superficial osteochondral defects with an autologous scaffold-free cartilage construct in a caprine model: implantation method and short-term results

OBJECTIVE: To compare four different implantation modalities for the repair of superficial osteochondral defects in a caprine model using autologous, scaffold-free, engineered cartilage constructs, and to describe the short-term outcome of successfully implanted constructs. METHODS: Scaffold-free, autologous cartilage constructs were implanted within superficial osteochondral defects created in the stifle joints of nine adult goats. The implants were distributed between four 6-mm-diameter superficial osteochondral defects created in the trochlea femoris and secured in the defect using a covering periosteal flap (PF) alone or in combination with adhesives (platelet-rich plasma (PRP) or fibrin), or using PRP alone. Eight weeks after implantation surgery, the animals were killed. The defect sites were excised and subjected to macroscopic and histopathologic analyses. RESULTS: At 8 weeks, implants that had been held in place exclusively with a PF were well integrated both laterally and basally. The repair tissue manifested an architecture similar to that of hyaline articular cartilage. However, most of the implants that had been glued in place in the absence of a PF were lost during the initial 4-week phase of restricted joint movement. The use of human fibrin glue (FG) led to massive cell infiltration of the subchondral bone. CONCLUSIONS: The implantation of autologous, scaffold-free, engineered cartilage constructs might best be performed beneath a PF without the use of tissue adhesives. Successfully implanted constructs showed hyaline-like characteristics in adult goats within 2 months. Long-term animal studies and pilot clinical trials are now needed to evaluate the efficacy of this treatment strategy.

[Spontaneous and post-therapeutic cartilage repair: evaluation criteria.]

Articular cartilage has poor reparative capacities, and once damaged cartilage lesions remain chronic and can lead to osteoarthritis. Over the last decade, several innovative therapies have been introduced to promote the regeneration of articular cartilage while sustaining sufficient mechanical stress and permitting a pain free motion. An important measure of outcome is the morphological characterization of the repair tissue in order to allow for cross-study evaluation. The International Cartilage Repair Society has developed a analogue visual scale to quantify repair tissue, which is described in this paper.

The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study

BACKGROUND: IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. OBJECTIVE: To examine the relationship of a genetic, haplotype-tagging promotor variant -137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. METHODS: Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. RESULTS: The G-allele of the IL-18 promotor variant (-137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 -137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66-1.94). The interaction between IL-18 -137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. CONCLUSION: Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.

Laparoscopic ventral hernia repair is safe and cost effective

BACKGROUND: Ventral hernia repair is increasingly performed by laparoscopic means since the introduction of dual-layer meshes. This study aimed to compare the early complications and cost effectiveness of open hernia repair with those associated with laparoscopic repair. METHODS: Open ventral hernia repair was performed for 92 consecutive patients using a Vypro mesh, followed by laparoscopic repair for 49 consecutive patients using a Parietene composite mesh. RESULTS: The rate of surgical-site infections was significantly higher with open ventral hernia repair (13 vs 1; p = 0.03). The median length of hospital stay was significantly shorter with laparoscopic surgery (7 vs 6 days; p = 0.02). For laparoscopic repair, the direct operative costs were higher (2,314 vs 2,853 euros; p = 0.03), and the overall hospital costs were lower (9,787 vs 7,654 euros; p = 0.02). CONCLUSIONS: Laparoscopic ventral hernia repair leads to fewer surgical-site infections and a shorter hospital stay than open repair. Despite increased operative costs, overall hospital costs are lowered by laparoscopic ventral hernia repair.

The feasibility, efficacy and functional outcome of local anaesthetic repair of anterior and posterior vaginal wall prolapse

INTRODUCTION: Urogenital prolapse is a very common condition in women with a prevalence of 30%. If conservative therapy fails or is not desired by the patient, prolapse repair is usually performed under general or regional anaesthetic. The aim of the study was to evaluate feasibility, efficacy and functional outcome after fascial prolapse repairs under local anaesthetic (LA). PATIENTS AND METHODS: Between November 1999 and December 2000, 130 consecutive patients presenting with anterior or posterior prolapse or both were invited to have their procedure performed under LA. All patients with a symptomatic minimum stage II prolapse were included. Prior to surgery all women completed a standardized questionnaire examining the specific and non-specific symptoms of prolapse and their situation was classified using the ICS Pelvic Organ Prolapse (POP-Q) system. Follow up was 30 months. Objective success was defined as a stage 1 or less and no symptoms of bulge, subjective success was defined as lack of specific or non-specific symptoms of prolapse. RESULTS: There were 128 patients who agreed to have their operations performed under LA: 68 in the anterior group, 52 in the posterior group and 8 with a combined anterior and posterior repair. Objective cure rate was 88% for posterior repair, 87% for anterior repair and 63% for combined repair. Success rates were no different in primary from recurrent cases. There were no intraoperative complications and operating time was 21 min (anterior repair) or 23 min (posterior repair). There was no de novo postoperative urinary or stool incontinence and all patients but two would have the operation performed again under the same circumstances. The two remaining refused due to embarrassment but for no other reason. CONCLUSION: Local anaesthetic prolapse repair is feasible and effective in middle term results. It is well accepted by the patients who benefit from less side effects and short hospital stay.

Comparison of analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair

OBJECTIVE: To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. STUDY DESIGN: Blind, randomized clinical study. ANIMALS: Dogs with femoral (n=18) or pelvic (27) fractures. METHODS: Dogs were grouped by restricted randomization into 4 groups: group 1 = carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2 = carprofen immediately after extubation, no epidural anesthesia; group 3 = carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4 = mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. RESULTS: Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. CONCLUSIONS: Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. CLINICAL RELEVANCE: Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.

Cyclic nucleotide specific phosphodiesterases of Leishmania major

Background Leishmania represent a complex of important human pathogens that belong to the systematic order of the kinetoplastida. They are transmitted between their human and mammalian hosts by different bloodsucking sandfly vectors. In their hosts, the Leishmania undergo several differentiation steps, and their coordination and optimization crucially depend on numerous interactions between the parasites and the physiological environment presented by the fly and human hosts. Little is still known about the signalling networks involved in these functions. In an attempt to better understand the role of cyclic nucleotide signalling in Leishmania differentiation and host-parasite interaction, we here present an initial study on the cyclic nucleotide-specific phosphodiesterases of Leishmania major. Results This paper presents the identification of three class I cyclic-nucleotide-specific phosphodiesterases (PDEs) from L. major, PDEs whose catalytic domains exhibit considerable sequence conservation with, among other, all eleven human PDE families. In contrast to other protozoa such as Dictyostelium, or fungi such as Saccharomyces cerevisiae, Candida ssp or Neurospora, no genes for class II PDEs were found in the Leishmania genomes. LmjPDEA contains a class I catalytic domain at the C-terminus of the polypeptide, with no other discernible functional domains elsewhere. LmjPDEB1 and LmjPDEB2 are coded for by closely related, tandemly linked genes on chromosome 15. Both PDEs contain two GAF domains in their N-terminal region, and their almost identical catalytic domains are located at the C-terminus of the polypeptide. LmjPDEA, LmjPDEB1 and LmjPDEB2 were further characterized by functional complementation in a PDE-deficient S. cerevisiae strain. All three enzymes conferred complementation, demonstrating that all three can hydrolyze cAMP. Recombinant LmjPDEB1 and LmjPDEB2 were shown to be cAMP-specific, with Km values in the low micromolar range. Several PDE inhibitors were found to be active against these PDEs in vitro, and to inhibit cell proliferation. Conclusion The genome of L. major contains only PDE genes that are predicted to code for class I PDEs, and none for class II PDEs. This is more similar to what is found in higher eukaryotes than it is to the situation in Dictyostelium or the fungi that concomitantly express class I and class II PDEs. Functional complementation demonstrated that LmjPDEA, LmjPDEB1 and LmjPDEB2 are capable of hydrolyzing cAMP. In vitro studies with recombinant LmjPDEB1 and LmjPDEB2 confirmed this, and they demonstrated that both are completely cAMP-specific. Both enzymes are inhibited by several commercially available PDE inhibitors. The observation that these inhibitors also interfere with cell growth in culture indicates that inhibition of the PDEs is fatal for the cell, suggesting an important role of cAMP signalling for the maintenance of cellular integrity and proliferation.

Internal iliac artery embolization before endovascular repair of aortoiliac aneurysms with a nitinol vascular occlusion plug

PURPOSE: To evaluate the acute and midterm effectiveness of a novel vascular occlusion device for embolization of the internal iliac artery (IIA) before endovascular repair of aortoiliac aneurysms. MATERIALS AND METHODS: Between March 2005 and April 2006, nine men (mean age, 75 years +/- 5; range, 66-83 y) with aortoiliac aneurysms underwent bifurcated endovascular stent-graft procedures. All these patients were referred specifically for embolization. Pre- and perioperatively, eight patients underwent unilateral embolization and one underwent bilateral embolization of the IIA to prevent type II endoleak. Via a contralateral femoral approach with a 6-F or 8-F sheath, the embolization procedure was performed with an Amplatzer Vascular Plug, a self-expandable cylindrical device consisting of a nitinol-based wire mesh. Technical success, clinical outcome, and complications were evaluated. Follow-up at 3, 6, and 12 months was performed with clinical and radiologic examinations. RESULTS: IIA embolization was technically successful in all cases and no procedure-related complications occurred. Imaging at discharge and at 3-, 6-, or 12-month follow-up was accomplished in all nine patients. Control computed tomography and magnetic resonance angiography did not reveal retrograde perfusion of the aneurysmal sac, ie, type II endoleak. Three of nine patients (33.3%) reported symptoms of buttock claudication that did not resolve completely. Clinical symptoms such as bowel ischemia or sexual dysfunction were not observed. CONCLUSIONS: The midterm results of this study suggest that preoperative IIA embolization with a nitinol vascular occlusion plug during endovascular treatment of aortoiliac aneurysms is safe and effective.

Anemia is associated with abdominal aortic aneurysm (AAA) size and decreased long-term survival after endovascular AAA repair

OBJECTIVE: Anemia is a common comorbid condition in various inflammatory states and an established predictor of mortality in patients with chronic heart failure, ischemic heart disease, and end-stage renal disease. The present study of patients with abdominal aortic aneurysm (AAA) undergoing endovascular repair (EVAR) assessed the relationships between baseline hemoglobin concentration and AAA size, as well as anemia and long-term survival. METHODS: Between March 1994 and November 2006, 711 patients (65 women, mean age 75.8 +/- 7.8 years) underwent elective EVAR. Anemia was defined as a hemoglobin level <13 g/dL in men and <12 g/dL in women. Post-EVAR mean follow-up was 48.3 +/- 32.0 months. Association of hemoglobin level with AAA size was assessed with multiple linear regression. Mortality was determined with use of the internet-based Social Security Death Index and the electronic hospital record. Kaplan-Meier survival curves of anemic and nonanemic patient groups were compared by the log-rank method. Multivariable logistic regression models were used to determine the influence of anemia on vital status after EVAR. RESULTS: A total of 218/711 (30.7%) of AAA patients undergoing EVAR had anemia at baseline. After adjustment for various risk factors, hemoglobin level was inversely related to maximum AAA diameter (beta: - .144, 95%-CI: -1.482 - .322, P = .002). Post-EVAR survival was 65.5% at 5 years and 44.4% at 10 years. In long-term follow-up, survival was significantly lower in patients with anemia as compared to patients without anemia (P < .0001 by log-rank). Baseline hemoglobin levels were independently related to long-term mortality in multivariable Cox regression analysis adjusted for various risk factors (adjusted HR: 0.866, 95% CI: .783 to .958, P = .005). Within this model, statin use (adjusted HR: .517, 95% CI: .308 to .868, P = .013) was independently related to long-term survival, whereas baseline AAA diameter (adjusted HR: 1.022, 95% CI: 1.009 to 1.036, P = .001) was an independently associated with increased mortality. CONCLUSIONS: Baseline hemoglobin concentration is independently associated with AAA size and reduced long-term survival following EVAR. Thus, the presence or absence of anemia offers a potential refinement of existing risk stratification instruments.