Neonatal surgical reconstruction and peri-operative care for hypoplastic left heart syndrome: current strategies.

The management of newborns with hypoplastic left heart syndrome has changed significantly over the past three decades, with an associated dramatic improvement in outcomes. The aim of this paper is to discuss current peri-operative and palliative surgical strategies. Owing to the fact that comparative outcomes for these strategies have been addressed in a limited number of prospective trials and extractions from multi-centred databases, the primary focus of this review is descriptive.

A traveling team concept to expedite the transfer and management of unstable patients in cardiopulmonary shock.

Emergent mechanical support with transfer of patients in acute cardiopulmonary shock to specialty centers for definitive management is often required at non-transplant centers. An alternative approach to the traditional "hub and spoke" model is presented. A team of health care specialists from our hospital is deployed to the community hospital for stabilization, possible implantation, and transfer of patients to our tertiary care facility. Patient assessment can be made with intervention, allowing stabilization and safe transfer by our team to our institution. This method provides tertiary level care at the referring hospital and may improve survival for a sub-set of patients in the community hospital setting.

BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways.

We present a novel cell-signaling paradigm in which bone morphogenetic protein 2 (BMP-2) consecutively and interdependently activates the wingless (Wnt)-ß-catenin (ßC) and Wnt-planar cell polarity (PCP) signaling pathways to facilitate vascular smooth muscle motility while simultaneously suppressing growth. We show that BMP-2, in a phospho-Akt-dependent manner, induces ßC transcriptional activity to produce fibronectin, which then activates integrin-linked kinase 1 (ILK-1) via α4-integrins. ILK-1 then induces the Wnt-PCP pathway by binding a proline-rich motif in disheveled (Dvl) and consequently activating RhoA-Rac1-mediated motility. Transfection of a Dvl mutant that binds ßC without activating RhoA-Rac1 not only prevents BMP-2-mediated vascular smooth muscle cell motility but promotes proliferation in association with persistent ßC activity. Interfering with the Dvl-dependent Wnt-PCP activation in a murine stented aortic graft injury model promotes extensive neointima formation, as shown by optical coherence tomography and histopathology. We speculate that, in response to injury, factors that subvert BMP-2-mediated tandem activation of Wnt-ßC and Wnt-PCP pathways contribute to obliterative vascular disease in both the systemic and pulmonary circulations.

Closure of a penetrating ulcer of the descending aorta using an Amplatzer occluder.

Symptomatic patients with penetrating atherosclerotic ulcers of the descending thoracic aorta have traditionally been treated by using an open surgical repair. The emergence of thoracic aortic stent-graft technologies has introduced a less invasive treatment option, which often involves covering excess portions of a normal aorta with stent-graft material. We describe the mid-term follow-up of a patient with a symptomatic penetrating atherosclerotic ulcer of the descending thoracic aorta treated with an Amplatzer septal occluder device (AGA Medical Corp, Plymouth, MN), which is typically used for structural heart disease.

Cavo-atrial tumor resection under total circulatory arrest without a sternotomy.

Surgical management of intracardiac tumors arising in the inferior vena cava often requires total circulatory arrest for safe and adequate resection. Total circulatory arrest has traditionally been accomplished by accessing the great vessels through a sternotomy. Combination of a sternotomy and a large abdominal incision results in excellent exposure but also creates the potential for significant morbidity. We report here the resection of cavoatrial tumors by achieving total circulatory arrest through femoral arterial and venous cannulation without requiring a sternotomy. This minimal-access total circulatory approach has the potential to greatly diminish morbidity when managing tumors of the inferior vena cava.

Laparoscopic cholecystectomy in a patient with a biventricular cardiac assist device.

Evaluation and management of abdominal pathology in patients with ventricular assist devices is likely to become increasingly important as the utilization of these devices expands. Ventricular assist devices represent a class of intracorporeal or paracorporeal mechanical devices that augment cardiac output in patients with congestive heart failure. Patients with ventricular assist devices supporting both right and left ventricles (biventricular assist devices) are uniquely challenging to the general surgeon because these devices restrict direct access to the abdominal cavity and because of the perioperative implications of biventricular heart failure. We describe herein the first reported successful laparoscopic cholecystectomy in a patient with a paracorporeal biventricular assist device. Cholecystectomy was performed in this patient for acute cholecystitis that occurred while the patient was awaiting heart transplantation. Our results add weight to the small body of evidence that laparoscopy is well tolerated in ventricular assist devices patients. The unique aspects of the biventricular assist device patient make laparoscopic abdominal intervention particularly suitable in this patient population.

Intramyocardial injection of allogenic bone marrow-derived mesenchymal stem cells without immunosuppression preserves cardiac function in a porcine model of myocardial infarction.

BACKGROUND: We investigated the efficacy of directly injected allogenic bone marrow-derived mesenchymal stem cells in improving left ventricular function in a porcine model of myocardial infarction. METHODS: Left ventricular infarction was created in 16 adult Yorkshire pigs by coil embolization and thrombotic occlusion distal to the second diagonal artery. One month after myocardial infarction was induced, the animals were randomized to either direct injection of allogenic mesenchymal stem cells or sham treatment (culture medium). Allogenic bromodeoxyuridine-labeled mesenchymal stem cells (2 +/- 0.1 x 10(8)) were directly injected into the infarct and peri-infarct areas during an open chest procedure. No immunosuppressive therapy was used. The left ventricular function was measured using serial biplane left ventricular angiography at baseline, 30, 60, and 90 days before sacrifice. Mesenchymal stem cells were localized using bromodeoxyuridine, and differentiation of mesenchymal stem cells was assessed by confocal microscopic colocalization of bromodeoxyuridine with immunofluorescent antibodies specific for cardiomyocytes (troponin I and MF-20) and endothelial cells (von Willebrand factor). RESULTS: Mesenchymal stem cells labeled with bromodeoxyuridine engrafted the peri-infarct zone and colocalized with both cardiomyocyte-specific and endothelial cell-specific immunofluorescence. No intramyocardial bromodeoxyuridine was observed in sham-treated animals. At the time of the mesenchymal stem cell injection 30 days after myocardial infarction, the left ventricular ejection fraction (LVEF) was 58% +/- 3% in mesenchymal stem cell-treated pigs and 56% +/- 2% in sham-treated pigs (P = NS). LVEF deteriorated progressively thereafter in untreated pigs (8.5% and 10.5% decline at 60 days and 90 days after myocardial infarction, respectively), but was preserved in mesenchymal stem cell-treated pigs (2.1% increase and -2.0% decline at 60 and 90 days post-MI respectively) (P < .05). CONCLUSIONS: Direct intramyocardial injection of mesenchymal stem cells results in successful intramyocardial engraftment and differentiation into cardiomyocytes and endothelial cells and preserves left ventricular function after myocardial infarction in pigs.

Preservation of bowel and urinary continence in the management of locally recurrent rectal cancer.

BACKGROUND: The management of locally recurrent rectal cancer should achieve local tumor control and potentially improving disease-free and overall survival. Radical pelvic resection has traditionally been associated with permanent fecal and urinary diversion. However, as advanced techniques have evolved to allow restoration of intestinal and urinary continence, we reviewed the use of these techniques in patients with recurrent rectal cancer. METHODS: Patients with recurrent rectal cancer who underwent a resection at Norris Comprehensive Cancer Center between 1993 and 1999 were retrospectively reviewed. Data collected included demographic data, surgical and oncological history, patterns of recurrence, treatment modalities, and outcome. Follow-up data was obtained from the last clinic visit and/or tumor registry. RESULTS: Sixty-seven patients with locally recurrent rectal cancer (male/female 45/22, age 32-81 years) were included in the analysis. Continence was re-established in 22 (33%) patients, urinary continence was restored in 12 patients, and intestinal continuity in 14 patients (both in 4 patients). A temporary diverting ostomy was necessary in 5 out of 14 (36%) patients. Mortality was zero and morbidity was low and included two urinary leaks and one fecal leak all of which could be managed non-operatively. At a median follow-up of 16 months (range 5-55), 11 (50%) patients were still alive, 7 (31%) without evidence of disease. Comparison of the groups of patients either with or without continence preservation showed no statistically significant difference in disease-free survival and overall survival rates. High quality of life was achieved with restoration of continuity, no patient with restored continuity expressed a desire for a diversion. CONCLUSION: If an oncologically adequate resection of the recurrent rectal cancer can be performed without impairment of the pelvic floor integrity, continence preservation is feasible and results in good functional and oncological outcome.

In the current era, complete revascularization improves survival after coronary artery bypass surgery.

BACKGROUND: Complete revascularization has been the standard for coronary bypass grafting. However, surgical intervention has evolved with increasing use of arterial conduits and off-pump techniques. METHODS: Patients undergoing non-redo bypass surgery from January 1998 through December 2000 were followed up with questionnaires and telephone contact. Incomplete revascularization was defined as absence of bypass grafts placed to a coronary territory supplied by a vessel with 50% or greater stenosis. RESULTS: One thousand thirty-four patients were followed for a mean of 3.3 +/- 1.6 years. Complete revascularization was found in 937 (90.6%) patients, and incomplete revascularization was found in 97 (9.4%) patients. Eight hundred twenty-seven (80.4%) patients underwent on-pump operations, and 207 (19.6%) underwent off-pump operations. Incomplete revascularization was more prevalent in off-pump versus on-pump operations (21.7% vs 6.3%, P < .001). Multivariable Cox regression analysis indicated that in-hospital cerebrovascular accidents (hazard ratio, 5.49; P < .001), chronic obstructive pulmonary disease (hazard ratio, 1.97; P = .019), and incomplete revascularization (hazard ratio, 1.85; P = .040) predicted an increased hazard (risk) of cardiac death. Left internal thoracic artery (hazard ratio, 0.38; P = .047), right internal thoracic artery (hazard ratio, 0.25; P = .019), and radial artery (hazard ratio, 0.36; P < .001) grafting reduced the risk of cardiac death. The 5-year unadjusted survival rate was 52.6% versus 82.4% in patients undergoing incomplete and complete revascularization ( P < .001), with cardiac survival rates of 74.5% versus 93.1%, respectively ( P < .001). However, this difference in cardiac survival was smaller in octogenarians with incomplete versus complete revascularizations (77.4% vs 87.6%, P = .101) and was essentially absent in off-pump versus on-pump operations if complete revascularization was achieved in both cases (93.6% vs 93.1%, P > .200). CONCLUSIONS: Complete revascularization and arterial grafting improve 5-year survival. Off-pump techniques do not affect survival. Complete revascularization should be performed whenever possible.

Prevalence and control of dyslipidemia among persons with diabetes in the United States.

OBJECTIVE: We assessed the prevalence, treatment, and control of dyslipidemia among United States (U.S.) adults with diabetes. METHODS: Among 498 adults (projected to 13.4 million) aged >or=18 years with diabetes representative of the U.S. population and surveyed within the cross-sectional National Health and Nutrition Examination Survey 1999-2000, control of lipids was classified according to American Diabetes Association criteria. The extent of low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) control was examined by gender and ethnicity, in comparison to those without diabetes, and according to lipid-lowering treatment. Analyses were weighted to the U.S. population. RESULTS: Less than one-third of men and only one-fifth of women with diabetes are in control for LDL-C, defined as <2.6 mmol/l (<100mg/dl); over 70% are not at goal. Over half of men and over two-thirds of women have low levels of HDL-C (or=1.7 mmol/l [150 mg/dl]). Low HDL-C was more common in Caucasians (70.1%) than in Hispanics (58.8%) or African-Americans (41.5%) (p<0.001). 28.2% of subjects with diabetes were on lipid-lowering treatment. Control of LDL-C did not differ by treatment status and only 3% of subjects were controlled to target levels for all lipids. CONCLUSION: Many persons with diabetes remain uncontrolled for dyslipidemia. Intensified efforts at screening and treatment according to current guidelines are warranted.

Total circulatory arrest for the replacement of the descending and thoracoabdominal aorta.

HYPOTHESIS: Hypothermic total circulatory arrest (TCA) in the resection and replacement of the thoracoabdominal and descending thoracic aorta is safe, will significantly decrease the incidence of postoperative renal failure, and should be preferentially performed over left heart bypass (LHB). DESIGN: Retrospective review case series. SETTING: Large, private, urban teaching hospital. PATIENTS: All adult patients with aortic disease that involved the distal aortic arch, the descending thoracic aorta, or the thoracoabdominal aorta who underwent resection and graft replacement of the diseased segment via LHB or TCA at our institution from 1989 to 2001 are included in this study. A total of 59 patients were evaluated: 10 had descending thoracic aneurysms, 20 had thoracoabdominal aneurysms, 22 had chronic type B dissections, 4 had acute type B dissections, and 3 had adult coarctations. INTERVENTIONS: In 1989 to 1994, LHB was primarily used; in 1994 to 2001, TCA was primarily used. MAIN OUTCOME MEASURES: Renal failure, 30-day operative mortality, paraplegia, and any other morbidities. RESULTS: A significant decrease occurred in the incidence of postoperative renal failure from 15% (3/20) in patients who underwent LHB to 0% (0/39) in patients who underwent TCA (P = .04). Furthermore, a significant decrease occurred in the 30-day operative mortality, which decreased from 20% (4/20) in patients who underwent LHB to 5% (2/39) in patients who underwent TCA (P = .04). Postoperative paraplegia decreased from 5% (1/20) in patients who underwent LHB to 2.6% (1/39) in patients who underwent TCA (P > .99). CONCLUSIONS: Our use of TCA in the resection and replacement of the diseased thoracoabdominal and descending thoracic aorta has produced excellent results. Our patients have experienced no postoperative renal failure and a low 30-day operative mortality. The use of TCA in this patient population is a viable option for surgeons comfortable with the technique.

Biventricular support in patients with profound cardiogenic shock: a single center experience.

Options for managing heart failure patients with cardiogenic shock refractory to inotropic and intra-aortic balloon pump (IABP) therapy are limited. Ventricular assist devices (VADs) can bridge these patients to heart transplantation. However, controversy exists over whether extracorporeal membrane oxygenation (ECMO) before VAD placement is beneficial. We report our use of biventricular assist devices (BiVADs) as a direct bridge to transplant. Since July 1999, 19 Thoratec BiVADs were implanted for heart failure unresponsive to medical therapy. Patient ages ranged from 20 to 67 years. Causes of heart failure included idiopathic 32%, ischemic 26%, postcardiotomy 21%, and other 21%. All patients were in cardiogenic shock, and three were receiving cardiopulmonary resuscitation (CPR) before implant. Preimplant conditions included IABP 89%, mechanical ventilation 68%, three or more inotropes 84%, hyperbilirubinemia 59%, acute renal failure 63%, and hemodialysis 16%. Fifty-nine percent of patients bridged successfully to transplantation, with 90% posttransplant survival. Duration of BiVAD support ranged from 0 to 91 days, with two patients currently on support awaiting transplantation. Complications included bleeding requiring reoperation 26%, stroke 11%, infection (any positive culture) 68%, and cannula site infection 5%. The Thoratec BiVAD can successfully be used as a direct bridge to transplantation in heart failure patients with cardiogenic shock.

Use of high-dose-rate brachytherapy in the management of locally recurrent rectal cancer.

INTRODUCTION: Locally recurrent rectal cancer is associated with poor quality of life and has justified aggressive surgical and adjuvant approaches to control the disease. This study was designed to evaluate the use of fractionated perioperative high-dose-rate brachytherapy in association with wide surgical excision (debulking). Our hypothesis is that this combined therapy can help control locally recurrent rectal cancer. METHODS: Patients with biopsy-proven locally recurrent rectal cancer that could not be completely removed surgically were considered candidates for this procedure. All patients had abdominal exploration, aggressive tumor debulking, and placement of afterloading brachytherapy catheters. Patients underwent simulation on postoperative Day 3 and received 1,200 to 2,500 (mean, 1,888) cGy of fractionated high-dose-rate brachytherapy between postoperative Days 3 and 5. All patients had involvement of the lateral pelvic sidewall and/or the sacrum. RESULTS: Twenty-seven patients (18 males) aged 32 to 79 years underwent therapy. Follow-up ranged from 18 to 93 (mean, 50) months and was available in 27 patients. Ten patients (37 percent) were alive at the time of this report. Nine patients are without evidence of disease. Five patients (18 percent) died of non-cancer-related causes without evidence of recurrent disease. Five complications potentially related to treatment (3 abscesses, 2 fistulas) occurred in five patients. CONCLUSION: High-dose radiation brachytherapy delivers high-dose, highly controlled, focused radiation to specific sites of disease, thereby minimizing injury to normal tissues. The results in this series suggest increased local control, better palliation, and increased salvage of patients.

5'-alkyl-benzothiadiazides: a new subgroup of AMPA receptor modulators with improved affinity.

AMPA receptors form a major subdivision of the glutamate receptor family that mediates excitatory synaptic transmission in the brain. Currents through AMPA receptors can be up- or down-regulated by compounds that allosterically modulate receptor kinetics through binding sites distinct from that for glutamate. One of those modulators is the benzothiadiazide IDRA-21 which has been reported to enhance synaptic transmission and be effective in behavioral tests, but typically requires threshold concentrations of at least 100 microM to be active in vitro. In this study, new benzothiadiazides were developed with IDRA-21 as lead compound and examined for their potency in modulating AMPA receptor kinetics. A significant increase in drug affinity was obtained by alkyl substitution at the 5'-position of IDRA-21; substitutions at other positions of the benzothiadiazide core generally did not yield a further gain in affinity and in some cases abolished drug binding. The 5'-ethyl derivative exhibited an EC(50) value in the order of 22 microM which represents about a 30-fold gain in affinity over that of IDRA-21. The EC(50) value is comparable to that of cyclothiazide, the most potent benzothiadiazide drug, but the effects on AMPA receptors differed substantially between these two compounds in that the 5'-ethyl derivative of IDRA-21 greatly increased the binding affinity for receptor agonists whereas cyclothiazide is known to reduce agonist binding. The structure--activity relationships reported here thus offer to provide new insights how receptor kinetics is linked to particular aspects of receptor--drug interactions.

Decompressive craniectomy in trauma patients with severe brain injury.

Decompressive craniectomy in the treatment of severe traumatic brain injury (TBI) is controversial. We conducted a retrospective review of prospectively collected data on all patients requiring surgery for TBI from 1995 through 2001 at Cedars-Sinai Medical Center. Patients were separated into two groups: Group A, craniectomy, and Group B, craniotomy. We had 120 patients; 24 (20%) had craniectomy and 96 (80%) had craniotomy. There were no significant differences in demographics or Injury Severity Scores. The craniectomy group had significantly more TBI as evidenced by more frequently collapsed basilar cisterns on CT scan (P = 0.0001). There was no significant difference in actuarial survival between the groups: 52.8 per cent in the craniectomy group and 79.2 per cent in the craniotomy group (P = 0.08). Calculated mortality for craniectomy was 37.5 per cent versus 18.8 per cent for craniotomy (P = NS). We found four preoperative findings to be significant predictors of mortality: 1) Glasgow Coma Scale score, 2) Injury Severity Score, 3) Simplified Acute Physiology Score, and 4) Acute Physiology and Chronic Health Evaluation II. The type of surgery was not found to be a significant predictor of death even when adjusted for severity of injury. Craniectomy may be helpful for patients with TBI associated with preoperative CT scan evidence of basilar cistern collapse. This is evidenced by similar survival rates between the two groups despite clinical evidence of greater TBI among craniectomy patients.