Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan?

OBJECTIVE: Marfan syndrome is a systemic connective tissue disorder caused by mutations in the fibrillin-1 gene. It was originally believed that Marfan syndrome results exclusively from the production of abnormal fibrillin-1 that leads to structurally weaker connective tissue when incorporated into the extracellular matrix. This effect seemed to explain many of the clinical features of Marfan syndrome, including aortic root dilatation and acute aortic dissection, which represent the main causes of morbidity and mortality in Marfan syndrome. METHODS: Recent molecular studies, most based on genetically defined mouse models of Marfan syndrome, have challenged this paradigm. These studies established the critical contribution of fibrillin-1 haploinsufficiency and dysregulated transforming growth factor-beta signaling to disease progression. RESULTS: It seems that many manifestations of Marfan syndrome are less related to a primary structural deficiency of the tissues than to altered morphogenetic and homeostatic programs that are induced by altered transforming growth factor-beta signaling. Most important, transforming growth factor-beta antagonism, through transforming growth factor-beta neutralizing antibodies or losartan (an angiotensin II type 1 receptor antagonist), has been shown to prevent and possibly reverse aortic root dilatation, mitral valve prolapse, lung disease, and skeletal muscle dysfunction in a mouse model of Marfan syndrome. CONCLUSION: There are indicators that losartan, a drug widely used to treat arterial hypertension in humans, offers the first potential for primary prevention of clinical manifestations in Marfan syndrome.

Surgical suturing of articular cartilage induces osteoarthritis-like changes

INTRODUCTION: In clinical tissue-engineering-based approaches to articular cartilage repair, various types of flap are frequently used to retain an implanted construct within the defect, and they are usually affixed by suturing. We hypothesize that the suturing of articular cartilage is associated with a loss of chondrocytes from, and osteoarthritis-like changes within, the perisutural area. MATERIALS AND METHODS: We established a large, partial-thickness defect model in the femoral groove of adult goats. The defects were filled with bovine fibrinogen to support a devitalized flap of autologous synovial tissue, which was sutured to the surrounding articular cartilage with single, interrupted stitches. The perisutural and control regions were analyzed histologically, histochemically and histomorphometrically shortly after surgery and 3 weeks later. RESULTS: Compared to control regions, chondrocytes were lost from the perisutural area even during the first few hours of surgery. During the ensuing 3 weeks, the numerical density of cells in the perisutural area decreased significantly. The cell losses were associated with a loss of proteoglycans from the extracellular matrix. Shortly after surgery, fissures were observed within the walls of the suture channels. By the third week, their surface density had increased significantly and they were filled with avascular mesenchymal tissue. CONCLUSIONS: The suturing of articular cartilage induces severe local damage, which is progressive and reminiscent of that associated with the early stages of osteoarthritis. This damage could be most readily circumvented by adopting an alternative mode of flap affixation, such as gluing with a biological adhesive.

Surgical approach for synovial cyst of the atlantoaxial joint: a case report and review of the literature

STUDY DESIGN: Case report and review of the literature. OBJECTIVE: We describe the first case of a synovial cyst arising from pseudarthrosis of a previous dens fracture. The literature is reviewed and etiological, diagnostic, and therapeutic options of atlantoaxial cysts are discussed. SUMMARY OF BACKGROUND DATA: Symptomatic synovial cysts of the atlantoaxial joint are rare. To the authors' knowledge only 24 cases have been reported.A 60-year-old patient presented with bilateral hand numbness, quadrihyperreflexia, and gait deterioration. Magnetic resonance imaging of the cervical spine disclosed a cystic mass located at the transverse ligament of dens axis causing bulbomedullary compression. METHODS: Surgery was performed via transoral image guided approach. The ventral atlas arch, dens, transverse ligament, tectorial membrane, and the compressing cyst were removed, followed by a C0-C3 fusion. RESULTS: Two months postsurgery the patient recovered completely from the cervical myelopathy with transient remnant dysparesthesia of the finger tips. CONCLUSION: Magnetic resonance imaging findings are not specific enough to establish a preoperative diagnosis. Radical resection via image-guided transoral route followed by posterior fusion allows complete resection of the cystic lesion and results in excellent long-term decompression.

[Bilateral surgical lung volume reduction in severe emphysema]

OBJECTIVE: To report preliminary results with a new surgical method of treating terminal emphysema by bilateral reduction of lung volume. PATIENTS AND METHODS: In a prospective study, the results obtained with the first 20 consecutive patients (mean FEV1: 590 +/- 180 ml) who underwent operative reduction of lung volume were recorded. 19 of the 20 patients had required continuous oxygen supply. RESULTS: The patients were extubated 8.5 +/- 6 h postoperatively; thoracic drainage was removed after 9 +/- 6 days. The degree of dyspnoea was decreased in all patients (3.5 +/- 0.5 vs 0.5 +/- 0.1). Significant reduction of overinflation occurred soon after the operation (residual volume 273 +/- 125 to 201 +/- 107% of normal; total capacity from 142 +/- 18 to 109 +/- 22% of normal), as well as reduction in the degree of obstruction (FEV1 from 18 +/- 6 to 24 +/- 7% of normal; for each, P < 0.05). One patient died 3 weeks post-operatively of Candida infection. CONCLUSION: The method looks promising for the treatment of selected patients and may thus provide an alternative to lung transplantation.

Bronchial circulation after experimental lung transplantation: the effect of direct revascularization of a bronchial artery

Direct revascularization of a bronchial artery has been proposed as a measure to alleviate the problem of bronchial ischemia after lung transplantation. To assess the effect of restoration of arterial blood flow to the transplanted bronchus, bronchial mucosal blood flow was measured in a model of modified unilateral lung transplantation in pigs. Laser Doppler velocimetry (LDV) and radioisotope studies using radio-labeled erythrocytes (RI) were used to measure blood flow at the donor main carina (DC) and upper lobe carina (DUC) after 3 h of reperfusion. The recipient carina was used as a reference point; values obtained by LDV and RI were expressed as percentage of blood flow at the recipient carina. Two groups of animals were studied. In group 1 (n = 6) standard unilateral transplantation was performed; in group 2 (n = 6) a left bronchial artery was reimplanted into the descending thoracic aorta of the recipient. No differences were observed between the two groups with respect to preoperative or postoperative gas exchange or hemodynamics. In group 1, bronchial blood flow at the DC was 37.6 +/- 2.2% (LDV) and 44.1 +/- 14.8% (RI) of reference blood flow. At the DUC, blood flow was 54.9 +/- 7.7% (LDV) and 61.6 +/- 25.7% (RI) of normal flow. In group 2, blood flow was increased at the DC as measured by LDV (55.3 +/- 17.1%; p less than 0.05) and by RI (60.8 +/- 25.3%; p less than 0.2). A similar increase was found at the DUC (LDV: 81.8 +/- 19.3%; p less than 0.05; RI: 88.6 +/- 31.0%; p less than 0.2). It is concluded that there is a significant gradient of blood flow from intra- to extrapulmonary airways after lung transplantation. Reimplantation of a bronchial artery results in significant improvement of graft bronchial blood flow. Restoration of bronchial perfusion to normal levels, however, cannot be achieved, suggesting a possible defect in the microcirculation of the donor airways.

A new surgical approach for exclusion of renal artery aneurysms avoiding organ ischemia

INTRODUCTION: Surgical treatment of renal artery aneurysms is inevitably associated with temporary renal artery occlusion and risk of ischemic injury. We present a technique for renal artery grafting and aneurysm exclusion without interrupting renal blood flow. REPORT: A symptomatic renal artery aneurysm was bypassed with a venous graft between the abdominal aorta and the very distal renal artery utilizing a distal anastomotic device without interruption of renal blood flow. The aneurysm was then excluded by means of hemostatic clips. CONCLUSION: The presented surgical technique offers the major advantage of avoiding organ ischemia and accelerating the surgical procedure.

Surgical approach in massive intraoperative atherosclerotic embolism

We describe a case of massive embolization of atherosclerotic material during aortic cannulation and the surgical approach chosen to treat it, that is, retrograde cerebral perfusion and subtotal arch replacement in deep hypothermic circulatory arrest.

Endothelin-1 and acute myocardial infarction: a no-reflow mediator after successful percutaneous myocardial revascularization

AIMS: No-reflow after a primary percutaneous coronary intervention (PCI) is associated with a high incidence of left ventricular (LV) failure and a poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide and an important modulator of neutrophil function. Elevated systemic ET-1 levels have recently been reported to predict a poor prognosis in patients with acute myocardial infarction (AMI) treated by primary PCI. We aimed to investigate the relationship between systemic ET-1 plasma levels and no-reflow in a group of AMI patients treated by primary PCI. METHODS AND RESULTS: A group of 51 patients (age 59+/-9.9 years, 44 males) with a first AMI, undergoing successful primary or rescue PCI, were included in the study. Angiographic no-reflow was defined as coronary TIMI flow grade < or =2 or TIMI flow 3 with a final myocardial blush grade < or =2. Blood samples were obtained from all patients on admission for ET-1 levels measurement. No reflow was observed in 31 patients (61%). Variables associated with no-reflow at univariate analysis included culprit lesion of the left anterior coronary descending artery (LAD) (67 vs. 29%, P=0.006) and ET-1 plasma levels (3.95+/-0.7 vs. 3.3+/-0.8 pg/mL, P=0.004). At multivariable logistic regression analysis, ET-1 was the only significant predictor of no-reflow (P=0.03) together with LAD as the culprit vessel (P=0.04). CONCLUSION: ET-1 plasma levels predict angiographic no-reflow after successful primary or rescue PCI. These findings suggest that ET-1 antagonists might be beneficial in the management of no-reflow.

Impact of vessel size on angiographic and clinical outcomes of revascularization with biolimus-eluting stent with biodegradable polymer and sirolimus-eluting stent with durable polymer the LEADERS trial substudy

OBJECTIVES: We assessed the impact of vessel size on outcomes of stenting with biolimus-eluting degradable polymer stent (BES) and sirolimus-eluting permanent polymer stent (SES) within a randomized multicenter trial (LEADERS). BACKGROUND: Stenting of small vessels might be associated with higher rates of adverse events. METHODS: "All-comer" patients (n = 1,707) were randomized to BES and SES. Post-hoc-stratified analysis of angiographic and clinical outcomes at 9 months and 1 year, respectively, was performed for vessels with reference diameter 2.75 mm. RESULTS: Of 1,707 patients, 429 patients in the BES group with 576 lesions and 434 patients in the SES group with 557 lesions had only small vessels treated (50.6% of the patient cohort). In patients with small vessels there was no significant difference in overall major adverse cardiac events (MACE) rate (12.1% vs. 11.8%; p = 0.89) or target lesion revascularization (TLR) rate (9.6% vs. 7.4%; p = 0.26) between BES and SES. The MACE and TLR rates in the small-vessel patient population were higher than in the large-vessel population. The TLR rate was 9.6% versus 2.6%, and MACE rate was 12.1% versus 7.1% for small versus large vessels in the BES arm (TLR: hazard ratio [HR] = 3.724, p = 0.0013; MACE: HR = 1.720, p = 0.0412). In the SES arm, TLR was 7.4% versus 5.1%, and MACE was 11.8% versus 10.3% in small versus large vessels (TLR: HR = 1.435, p = 0.2594; MACE: HR = 1.149, p = 0.5546). CONCLUSIONS: Prevalence of small vessel disease is high in an "all-comer" population with higher TLR and MACE rates. The BES and SES seem equivalent in treatment outcomes of small vessels in this "all-comer" patient population.

Percutaneous coronary revascularization in patients with formerly "refractory angina pectoris in end-stage coronary artery disease" - not "end-stage" after all

BACKGROUND: Patients with refractory angina pectoris in end-stage coronary artery disease represent a severe condition with a higher reduction of life-expectancy and quality of life as compared to patients with stable coronary artery disease. It was the purpose of this study to invasively re-evaluate highly symptomatic patients with formerly diagnosed refractory angina pectoris in end-stage coronary artery disease for feasible options of myocardial revascularization. METHODS: Thirty-four patients formerly characterized as having end stage coronary artery disease with refractory angina pectoris were retrospectively followed for coronary interventions. RESULTS: Of those 34 patients 21 (61.8%) were eventually revascularized with percutaneous interventional revascularization (PCI). Due to complex coronary morphology (angulation, chronic total occlusion) PCI demanded an above-average amount of time (66 +/- 42 minutes, range 25-206 minutes) and materials (contrast media 247 +/- 209 ml, range 50-750 ml; PCI guiding wires 2.0 +/- 1.4, range 1-6 wires). Of PCI patients 7 (33.3%) showed a new lesion as a sign of progression of atherosclerosis. Clinical success rate with a reduction to angina class II or lower was 71.4% at 30 days. Surgery was performed in a total of8 (23.5%) patients with a clinical success rate of 62.5%. Based on an intention-to-treat 2 patients of originally 8 (25%) demonstrated clinical success. Mortality during follow-up (1-18 months) was 4.8% in patients who underwent PCI, 25% in patients treated surgically and 25% in those only treated medically. CONCLUSION: The majority of patients with end-stage coronary artery disease can be treated effectively with conventional invasive treatment modalities. Therefore even though it is challenging and demanding PCI should be considered as a first choice before experimental interventions are considered.

Extended retinacular soft-tissue flap for intra-articular hip surgery: surgical technique, indications, and results of application

Osteotomies of the proximal femur for hip joint conditions are normally done at the intertrochanteric or subtrochanteric level. Intra-articular osteotomies would be more direct and therefore allow a more powerful correction with no or very little undesired side correction. However, concerns about the risk of vascular damage and osteonecrosis of the femoral head have so far basically excluded this technique from practical use. Based on detailed knowledge of the vascular anatomy of the proximal femur, an approach to safely dislocate the femoral head has been described and successfully performed. Experience as well as further studies of femoral head perfusion allowed a substantial extension of this approach, with subperiosteal exposure of the circumference of the femoral neck with constant intraoperative control of the blood supply to the head. Using the extended retinacular soft-tissue flap, four surgical techniques (relative neck lengthening, subcapital realignment in slipped capital femoral epiphysis, true femoral neck osteotomy, and femoral head reduction osteotomy) evolved or became safer with respect to perfusion of the femoral head. The extended retinacular soft-tissue flap offers the technical and biologic possibility for a new class of intra articular procedures. Although meticulous execution of the surgical steps is important, the procedures have a high level of safety for femoral head perfusion.

Die operative Behandlung der Azetabulum-T-Fraktur über eine chirurgische Hüftluxation oder einen Stoppa-Zugang. [Operative treatment of T-type fractures of the acetabulum via surgical hip dislocation or Stoppa approach]

OBJECTIVE: Anatomic reduction and stable fixation by means of tissue- preserving surgical approaches. INDICATIONS Displaced acetabular fractures. Surgical hip dislocation approach with larger displacement of the posterior column in comparison to the anterior column, transtectal fractures, additional intraarticular fragments, marginal impaction. Stoppa approach with larger displacement of the anterior column in comparison to the posterior column. A combined approach might be necessary with difficult reduction. CONTRAINDICATIONS Fractures > 15 days (then ilioinguinal or extended iliofemoral approaches). Suprapubic catheters and abdominal problems (e.g., previous laparotomy due to visceral injuries) with Stoppa approach (then switch to classic ilioinguinal approach). SURGICAL TECHNIQUE: Surgical hip dislocation: lateral decubitus position. Straight lateral incision centered over the greater trochanter. Entering of the Gibson interval. Digastric trochanteric osteotomy with protection of the medial circumflex femoral artery. Opening of the interval between the piriformis and the gluteus minimus muscle. Z-shaped capsulotomy. Dislocation of the femoral head. Reduction and fixation of the posterior column with plate and screws. Fixation of the anterior column with a lag screw in direction of the superior pubic ramus. Stoppa approach: supine position. Incision according to Pfannenstiel. Longitudinal splitting of the anterior portion of the rectus sheet and the rectus abdominis muscle. Blunt dissection of the space of Retzius. Ligation of the corona mortis, if present. Blunt dissection of the quadrilateral plate and the anterior column. Reduction of the anterior column and fixation with a reconstruction plate. Fixation of the posterior column with lag screws. If necessary, the first window of the ilioinguinal approach can be used for reduction and fixation of the posterior column. POSTOPERATIVE MANAGEMENT: During hospital stay, intensive mobilization of the hip joint using a continuous passive motion machine with a maximum flexion of 90 degrees . No active abduction and passive adduction over the body's midline, if a surgical dislocation was performed. Maximum weight bearing 10-15 kg for 8 weeks. Then, first clinical and radiographic follow-up. Deep venous thrombosis prophylaxis for 8 weeks postoperatively. RESULTS: 17 patients with a mean follow-up of 3.2 years. Ten patients were operated via surgical hip dislocation, two patients with a Stoppa approach, and five using a combined or alternative approach. Anatomic reduction was achieved in ten of the twelve patients (83%) without primary total hip arthroplasty. Mean operation time 3.3 h for surgical hip dislocation and 4.2 h for the Stoppa approach. Complications comprised one delayed trochanteric union, one heterotopic ossification, and one loss of reduction. There were no cases of avascular necrosis. In two patients, a total hip arthroplasty was performed due to the development of secondary hip osteoarthritis.