Clinical implications of fracture-associated vascular damage in extremity and pelvic trauma.

BACKGROUND: Vascular damage in polytrauma patients is associated with high mortality and morbidity. Therefore, specific clinical implications of vascular damage with fractures in major trauma patients are reassessed. METHODS: This comprehensive nine-year retrospective single center cohort study analyzed demography, laboratory, treatment and outcome data from 3689 patients, 64 patients with fracture-associated vascular injuries were identified and were compared to a control group. RESULTS: Vascular damage occurred in 7% of patients with upper and lower limb and pelvic fractures admitted to the trauma room. Overall survival was 80% in pelvic fracture and 97% in extremity fracture patients and comparable to non-vascular trauma patients. Additional arterial damage required substantial fluid administration and was visible as significantly anemia and disturbed coagulation tests upon admission. Open procedures were done in over 80% of peripheral extremity vascular damage. Endovascular procedures were predominant (87%) in pelvic injury. CONCLUSION: Vascular damage is associated with high mortality rates especially in combination with pelvic fractures. Initial anemia, disturbed coagulation tests and the need for extensive pre-clinical fluid substitution were observed in the cohort with vascular damage. Therefore, fast diagnosis and early interventional and surgical procedures are necessary to optimize patient-specific outcome.

The incidence of incisional hernia after aortic aneurysm is not higher than after benign colorectal interventions: A retrospective control-matched cohort study.

BACKGROUND: Abdominal aortic aneurysms (AAA) have most probably an inflammatory origin, whereby the elastica is the layer actually involved. In the past, collagen weackness was supposed to be the shared cause of both, AAA and incisional hernias. Since the development of new techniques of closure of the abdominal wall over the last decade, collagen deficency seems to play only a secondary etiologic role. OBJECTIVES: The aim of the study was to investigate whether the incidence of incisional hernia following laparotomy due to AAA differs from that of colorectal interventions. MATERIAL AND METHODS: This was a retrospective control matched cohort study. After screening of 403 patients with colorectal interventions and 96 patients with AAA, 27 and 72 patients, respectively were included. The match criteria for inclusion of patients with colorectal interventions were: age, benign underlying disease and median xiphopubic laparotomy. The primary endpoint was the incidence of an incisional hernia. The secondary endpoints were the risk profile, length of stay in the intensive care unit and postoperative complications. Data analysis was carried in the consecutive collective from 2006 to 2008. RESULTS: In the group with AAA the mean follow-up was 34.5±18.1 months and in the group with colorectal interventions 35.7±21.4 months. The incidence of incisional hernias showed no significant differences between the two groups. In the AAA group 10 patients (13.8%) developed an incisional hernia in contrast to 7 patients in the colorectal intervention group (25.9%). CONCLUSIONS: In our collective patients with AAA did not show an increased incidence of incisional hernia in comparison to patients with colorectal interventions with comparable size of the laparotomy access and age. The quality of closure of the abdominal wall seems to be an important factor for the prevention of incisional hernia.

Perioperative quality assessment of varicose vein surgery : Commission for quality assessment of the German Society for Vascular Surgery.

PURPOSE: An estimated 350,000 varicose vein (VV) surgical procedures are performed in Germany each year, with annual treatment costs amounting to about 800 million Euro. To evaluate the outcome quality of this treatment, we examined the intraoperative and postoperative complication rates on record in the VV surgery quality assessment (QA) registry of the German Society for Vascular Surgery (GSVS). METHODS: Data on 89,647 patients (27,463 men, 62,184 women; average age 52.8 years, range 15-96 years) collected in the GSVS varicose surgery QA registry between 2001 and 2009 were analyzed. In these patients, 95,214 surgical procedures were performed on 105,296 limbs. Complication rates were correlated with the type of VV surgical procedure, with whether surgery was performed on an inpatient or outpatient basis, and with the CEAP classification (C stage) and American Society of Anaesthesiologists' (ASA) stage at the time of surgery. Statistical analyses were performed using a chi-square test, a Cochrane-Armitage test, and an odds ratio calculation. RESULTS: Intraoperative and postoperative complication was low (0.18 and 0.43 %, respectively), being the lowest for radiofrequency ablation (0.25 %) but not differing significantly from those for endovenous laser therapy and high ligation and stripping. General complications occurred in 0.67 % of outpatients and in 0.25 % of inpatients, a highly significant statistical difference (p < 0.0001, chi-square test). With regard to C stage, the higher the stage, the higher the local complication rate. A clear correlation was also found between preoperative ASA stage and postoperative complication rates: for ASA stages I and II, the complication rates were 0.2 and 0.5 %, respectively, increasing for ASA stage III to 1.2 % and for ASA IV to 2.2 %. The differences between the ASA classes were highly statistically significant (p < 0.0001, Cochrane-Armitage test) CONCLUSIONS: Outcome quality as reflected in the intraoperative and postoperative complication rates was very good for all patients undergoing inpatient or outpatient VV surgery. Data from the GSVS QA registry shows that VV surgery is performed with very good perioperative results in specialized centers in Germany.

Fatal paraneoplastic embolisms in both circulations in a patient with poorly differentiated neuroendocrine tumour.

Arterial embolism with lower limb ischemia is a rare manifestation of paraneoplastic hypercoagulability in cancer patients. We report a unique case of fatal thromboembolism involving both circulations associated with a poorly differentiated neuroendocrine tumor of the lung with rapid progress despite high doses of unfractioned heparin and review the current literature on anticoagulative regimen in tumour patients.

In vivo detection of Staphylococcus aureus in biofilm on vascular prostheses using non-invasive biophotonic imaging.

OBJECTIVES: Biophotonic imaging was compared to standard enumeration method both for counting Staphylococcus aureus in biofilm and bacterial susceptibility tests of different graft materials. DESIGN: Prospective, randomized, controlled animal study. MATERIAL AND METHODS: Five types of vascular grafts were placed subcutaneously in 35 mice and challenged with bioluminescent S. aureus. The mice were divided into equal groups as follows: group A (polyester), group B (polytetrafluoroethylene), group C and D (two types of silver acetate-coated polyester) and group E (bovine pericardium). Controls were given only the bacteria. The bioluminescence signal of S. aureus, able to predict number of viable bacteria in biofilm without any manipulation, was measured at different time points. Five days postinfection, regular cultures of adherent bacteria on grafts were obtained. Comparative analyses between bioluminescence activity and culture enumeration were performed. RESULTS: The number of viable bacteria on silver-coated prostheses was the slightest, indicating superior bacterial resistance. The density of bacteria on polytetrafluoroethylene and polyester was comparable, with a non-significant advantage for polytetrafluoroethylene. Moreover, bioluminescence detected the number of viable S. aureus in biofilm more exactly compared to enumeration of bacteria. CONCLUSION: Bioluminescence imaging can be considered a useful tool to characterize susceptibility of any graft material to bacterial biofilm prior to implantation.

Surgical management of prosthetic vascular graft infection: comparative retrospective analysis of 30 consecutive cases.

BACKGROUND: Graft infection after vascular prosthetic reconstruction for the treatment of peripheral arterial occlusive disease (PAOD) is a rare but severe complication with poor outcome. The options for surgical treatment are not uniformly accepted and remain controversial. PATIENTS AND METHODS: We retrospectively analyzed the histories of 30 patients treated for prosthetic graft infection (Szilagyi grade III) in our hospital between 1994 and 1999 to determine which forms of treatment were best suited for which types of patient. In the majority of cases the initial treatment was lower-extremity bypass surgery. The most frequent location of infection was the groin (73%). Staphylococci (13% of which were methicillin resistant) were the most common type of bacteria. The overall incidence of prosthetic infection was 2.3%. RESULTS: After confirmation of the infection by computed tomography (CT) or white blood cell scintigraphy, one of the following 5 forms of surgical treatment was performed: 1. Removal of the infected prosthesis and its simultaneous replacement by an autologous vein bypass. 2. Bypass removal and secondary replacement by an autologous vein. 3. Extra-anatomical replacement. 4. Graft removal and primary amputation. 5. Local therapy with debridement and secondary wound healing. In some patients primary amputation after graft infection was necessary to prevent further deterioration with fulminant sepsis. The overall mortality was 17%, the amputation rate was 60%. CONCLUSIONS: The best results were achieved by early complete removal of the alloplastic material and one-step replacement by either an autologous vein or extra-anatomic bypass. This resulted in a limb salvage rate of 54% and 40% and mortality rates of 9% and 0%, respectively.

[Endovascular therapy in combination with conventional vascular surgery for the treatment of peripheral arterial obliterative disease]. / Endovaskuläre Kombinationstherapie von Beckenarterienstenosen - Management intra- und postoperativer Komplikationen -

INTRODUCTION: In a prospective trial we analysed the results and the management of complications following a combined endovascular and vascular surgical therapy of peripheral occlusive arterial disease (POAD). PATIENTS AND METHODS: From November 1998 until January 2001 a total number of 61 patients with 64 extremities were included in this study. By preoperative angiography 19 patients had stenoses at three levels, 42 patients suffered from stenoses at two levels. The iliac axis was recanalized by intraluminal angioplasty (ITA) plus stent placement under general anesthesia. Simultaneously an infrainguinal bypass reconstruction and a local thrombendarterectomy (TEA) rsp. were performed. Intra- and postoperative complications and the patency rates as assessed by colour doppler ultrasound and angiography were analysed. RESULTS: The rate of conversion from endovascular to conventional surgery was 12.5 %. In 56 cases the endovascular therapy of the iliac axis was successful. In 28 patients a distal bypass was implanted, in 25 patients a local TEA was performed. Intraoperatively 6 dissections (10.7 %) were noted, dislocation of stents were seen in 4 patients (7.1 %), perforations occurred in 2 patients (3.6 %). Both perforations and 5/6 dissections were detected intraoperatively and were treated by endovascular means without complications. The early postoperative patency rate was 98.2 %, the secondary patency rate was 100 % and the cumulative patency rate after two years was 98.2 %. DISCUSSION: ITA and stent placement in the iliac axis can be established quickly and safely by the vascular surgeon. Intraoperative complications can be managed by endovascular means in most cases. Stent dislocation is avoidable in most cases. The complication rate after such combined endovascular therapy and conventional vascular surgery is determined by the surgical but not the endovascular part. Excellent early results and low complication rates lead to the conclusion that endovascular therapy in combination with conventional vascular surgery seems to be a reasonable supplement to the therapeutic options for the treatment of POAD.

A short course of high-dose cyclophosphamide induces long-term survival of intestinal allografts in mice.

Several transplant programs have recently added cyclophosphamide (CyP) to their immune suppression protocols in an attempt to reduce intestinal graft rejection rates. The present study was undertaken to confirm the benefits of this drug in a murine small bowel transplant model. A short course of monotherapy with CyP 20 mg/kg per dose resulted in a mean survival time (MST) of 17.5 +/- 3.6 days, compared with a MST of 7.5 +/- 0.7 days in the untreated controls (P < 0.01). Cyclosporin A (CsA) 30 mg/kg per day produced comparable survival rates when used as monotherapy (MST: 14.2 +/- 1.3 days) or in combination with CyP 20 mg/kg per dose (MST: 21.3 +/- 5.1 days). Treatment with high dose CyP (40 mg/kg per dose) completely prevented graft loss in 8 of 10 animals (MST: 72.5 +/- 5.3 days, P < 0.01). However, adding CsA abrogated the induction of long-term survival achieved by CyP alone (MST: 23 +/- 0.4 days). These data have important implications for the use of CyP in clinical transplantation.

Allograft tolerance induced by cyclophosphamide without prior inoculation of donor cells--immune suppression and redirection.

OBJECTIVES: To determine the possibility and cellular mechanism of inducing allograft tolerance by multiple injection of a lower dose of cyclophosphamide without prior infusion of donor cells. METHODS AND RESULTS: Heterotopic heart grafts were performed in MHC mismatched strain combinations (C57/B6 vs. BALB/c). Cyclophosphamide (40 mg/kg) was given intravenously on days 0, 2, 4 and 7 without prior infusion of donor cells. Long-term (> 100 days) allograft survival with normal histology was achieved. The long-term survivors accepted the donor skin grafts, but rejected the third-party skin grafts. Cyclophosphamide treatment initially led to profound lymphocytopenia, inhibition of spontaneous blastogenesis and low levels of lymphocyte proliferation response to both donor and third-party antigens. Ultimately, donor-specific tolerance occurred demonstrated by normal levels of peripheral lymphocytes, spontaneous blastogenesis and lymphocyte proliferation response to third-party antigens, and low levels of lymphocyte proliferation response to donor antigen. A switch of cytokines from IFNgamma dominant to IL-4 dominant, a low level of IgM and a high level of IgG1 were found in tolerant mice. CONCLUSIONS: Allograft tolerance can be induced by a short course of cyclophosphamide without prior donor cell inoculation. Tolerance induced is characterized initially by non-specific immunosuppression, which progresses to donor-specific hyporesponsiveness associated with the development of a Th2 dominant cytokine response.

Complement inhibition with an anti-C5 monoclonal antibody prevents hyperacute rejection in a xenograft heart transplantation model.

BACKGROUND: The present study was undertaken to determine whether anti-complement 5 (C5) monoclonal antibodies (mAb) prevent hyperacute rejection (HAR) in a rat-to-presensitized mouse heart transplantation model and whether these mAb, combined with cyclosporine (CsA) and cyclophosphamide (CyP), can achieve long-term graft survival. METHODS: BALB/c mice were presensitized with 2x10(7) splenocytes from Lewis rats 14 days before grafting. Heart grafts from Lewis rats were heterotopically transplanted into BALB/c mice. Presensitized mice were treated with either anti-C5 mAb or a combination of anti-C5 mAb, CsA, and CyP. Controls included: presensitized mice with no treatment, presensitized mice treated with either CsA + CyP or IgG, and nonpresensitized mice with either no treatment or with CsA + CyP treatment. RESULTS: Although typical features of HAR were evident in the presensitized grafts, the mAb completely inhibited complement activation and successfully prevented HAR. Despite complement inactivation, the graft was rejected on postoperative day 6 with acute vascular rejection (AVR) also known as delayed xenograft rejection (DXR). Notably, this type of rejection cannot be effectively overcome by CsA and CyP. CONCLUSIONS: We conclude that (1) anti-C5 mAb prevents HAR, (2) AVR/DXR still occurs when HAR is prevented by complement inactivation, and (3) AVR/DXR cannot be overcome by conventional immunosuppression. These data suggest that anti-C5 mAb may be valuable for preventing HAR in future clinical xenotransplantation and that additional interventions may be required to address AVR/DXR.

Rat-to-mouse small bowel xenotransplantation: a novel model for studying acute vascular and hyperacute xenograft rejection and xenogenic cell migration.

The present study was undertaken to establish a rat-to-mouse vascularized small bowel xenotransplantation model to study acute vascular and hyperacute xenograft rejection, and xenogenic cell migration. Lewis rat small bowel grafts were transplanted heterotopically to group 1, Balb/c mice, and group 2, Balb/c mice pre-sensitized with a donor spleen cell injection. The grafts were examined by serial pathology and flow cytometry. In group 1, acute vascular rejection was present by the 5th post-operative day (POD). Immunohistology showed a strong endothelial deposition of IgG, IgM and C3, associated with a minimal lymphocytic infiltrate. There was a vigorous cell migration from the recipient to the graft, in which recipient origin cells comprised 80.1+/-6.9% of the graft mesenteric lymph node by POD 3. However, there was almost no cell migration from the graft to the recipient. The intestinal xenografts in the group 2 showed massive hemorrhage, fibrin deposition, vascular congestion and thrombosis 60 min after transplantation. IgG and C3 were present on the endothelium as early as 1 min after reperfusion. The vigorous humorally-mediated vascular damage and rapid elimination of donor cells seen with intestinal xenograft rejection are distinct from the usual picture of allograft rejection. Hyperacute rejection can be induced by recipient pre-sensitization with donor spleen cells. The potential advantages of studying xenotransplantation in this model include: (1) the wide range of immunologic reagents available for mice; (2) the opportunity to study the progression of vascular damage easily by performing serial biopsies in the same animal; and (3) the opportunity to study, in vivo, two-way cellular response by examining cell trafficking in the mesenteric lymph nodes.

Progress in experimental intestinal transplantation in small animal models.

The unique immune response after small bowel transplantation (SBT) has been the subject of extensive research using small animal models in rats and mice. These animals are inexpensive, for most societies ethically acceptable and the existence of inbred strains allows for reproducibility and defined immunobiological conditions. The basic immunological reactions, such as graft-versus-host-reactions (GVHR), host-versus-graft-reactions (HVGR), a combination of both reactions, chronic rejection and tolerance have been described. Almost all immunosuppressive agents of proven or potential clinical relevance have been tested for their efficacy in small bowel transplantation. All techniques which are applied to intestinal transplantation in humans including multiorgan transplantation, can also be performed in rats. Intestinal transplantation in mice is methodically restricted to heterotopic transplantation. The mouse however, offers several advantages compared to the rat model. A large number of congenic and knockout strains is available as well as many analytical tools. In the future, intriguing new insights into the unique immunological mechanisms of allograft rejection will be discovered using murine models.

Technical experiences with a microsurgical model of lymphatic reconstruction after intestinal transplantation in rats.

The surgical procedure of intestinal transplantation disrupts the graft's lymphatic drainage. Despite morphological regeneration, the functional impairment of the lymphatic system may contribute to many pathophysiological changes after transplant. We describe the technical details and results of a microsurgical model of lymphatic reconstruction (LR), which immediately reconstitutes lymphatic drainage of the intestinal graft in rats. A total of 42 orthotopic intestinal transplants with LR was performed. The patency of the LR was assessed between postoperative days 2 and 100 using either methylene-blue staining of the lymphatic vessels or mesenteric lymphoradiography. A total patency rate of 88% was achieved. Genetic background, occurrence of rejection, and immunosuppressive treatment with cyclosporine did not affect the patency rate. Technical aspects and potential applications of this model are discussed.