The safety and efficacy of leflunomide in combination with infliximab in rheumatoid arthritis.

OBJECTIVE: To report the safety and efficacy of leflunomide (LEF) in combination with infliximab (INF) for the treatment of rheumatoid arthritis. METHODS: In an open, multicenter, retrospective study, data were collected on the safety and efficacy of LEF and INF. RESULTS: Eighty-eight patients received the combination of LEF and INF for an average of 6.6 months and a total exposure of 581 patient-months. The mean duration of LEF was 17 +/- 9 months (range 3-32 months; median 18.5 months) with an average of 4.8 INF infusions per patient. In all but 3 subjects, LEF was used initially and INF was added later. Infusion reactions occurred in 3 patients (0.7% of all infusions). A total of 34% of subjects experienced adverse events and in 6 (6.8% of the group) these were deemed serious. Ten infections occurred when patients were taking the combination; 9 patients recovered fully and 1 died of bacterial pneumonia. A lifetime smoker developed lung cancer and another patient was found to have colon cancer. CONCLUSIONS: The adverse events noted within the combination therapy group were in keeping with the known risks of each drug when used individually. Limited data were available on efficacy, but a general improvement in disease control was noted with the combination of drugs, which for most patients involved the addition of INF to previous use of LEF.

Tetralogy of Fallot: surgical management individualized to the patient.

BACKGROUND: Over the past four decades, the surgical trend has been toward early, complete repair of tetralogy of Fallot (TOF). Many centers currently promote all neonates for total correction irrespective of anatomy and symptoms, with some surgeons advocating hypothermic circulatory arrest for repair in small infants. We believe this approach increases morbidity. METHODS: Based on approximately 40 years' experience in 2,175 patients, we developed a management protocol focused on patient size, systemic arterial saturations, and anatomy. Symptomatic patients (hypercyanotic spells, ductal dependent pulmonary circulation) weighing less than 4 kg undergo palliative modified Blalock-Taussig shunt (BTS) followed by complete repair at 6 to 12 months. Asymptomatic patients, weighing less than 4 kg who have threatened pulmonary artery isolation, undergo BTS and repair at 6 to 12 months. All other patients undergo complete repair after 6 months. RESULTS: From July 1, 1995, to December 1, 1999, 144 patients underwent operation for TOF (129 patients) or TOF with atrioventricular septal defect (TOF/AVSD, 15 patients). Ninety-four patients underwent one stage complete repair (88 TOF, 6 TOF/AVSD). Thirty-nine patients underwent repair after initial BTS (32 TOF, 7 TOF/AVSD). Ten patients are awaiting repair after BTS. The mean age and weight at complete repair were 18 months and 9 kg. There were no operative deaths. There have been 3 late deaths with complete follow-up (mortality 3 of 144 [2.1%]). Four of 133 patients (3%) have required reoperation after total correction. CONCLUSIONS: This management strategy optimizes outcomes by individualizing the operation to the patient. Advantages include avoidance of circulatory arrest, low morbidity and mortality, and low incidence of reoperation after complete repair.

Concomitant subclavian and coronary artery disease.

BACKGROUND: Proximal subclavian artery occlusive disease in the presence of a patent internal mammary artery used as a conduit for a coronary artery bypass graft procedure may cause reversal of internal mammary artery flow (coronary-subclavian steal) and produce myocardial ischemia. METHODS: We reviewed outcome to determine whether subclavian artery revascularization can provide effective protection from and treatment for coronary-subclavian steal. Between 1985 and 1997, 20 patients had either concomitant subclavian and coronary artery disease diagnosed before operation (group 1, 5 patients) or symptomatic coronary-subclavian steal occurring after a previous coronary artery bypass graft procedure (group 2, 15 patients). Patients in group 1 received direct subclavian artery bypass and a simultaneous coronary artery bypass graft procedure in which the ipsilateral internal mammary artery was used for at least one of the bypass conduits. Patients in group 2 received either extrathoracic subclavian-carotid bypass (5 patients, 33.3%) or percutaneous transluminal angioplasty and stenting (10 patients, 66.7%) as treatment for symptomatic coronary-subclavian steal. RESULTS: All patients were symptom-free after intervention. One patient treated with percutaneous transluminal angioplasty and stenting died of progressive renal failure. Follow-up totaled 58.5 patient-years (mean, 3.1 years/patient). In group 1, primary patency was 100% (mean follow-up, 3.7 years). In group 2, one late recurrence was treated by operative revision, yielding a secondary patency rate of 100% (mean follow-up, 2.9 years). CONCLUSIONS: Subclavian artery revascularization can provide effective protection from and treatment for coronary-subclavian steal with acceptably low operative risk. Midterm follow-up demonstrates good patency.

Multidisciplinary management of pediatric soft-tissue sarcoma.

The management of pediatric soft-tissue sarcomas has improved drastically through the use of multimodal therapy. These tumors include rhabdomyosarcomas and nonrhabdomyosarcomas. Both are staged using physical, radiographic, and histologic evaluation, and both have intricate staging and grouping systems that correlate closely with prognosis. However, approaches to therapy for the two tumor types remain somewhat different. Rhabdomyosarcomas are treated primarily with chemotherapy. Surgical intervention is limited to initial biopsy, wide local excision when clear margins are feasible, and resection of residual disease. Radiation therapy is reserved for patients with persistent or recurrent disease and may be delivered by external beam or brachytherapy. Nonrhabdomyosarcomas are best treated primarily by surgical resection, although radiation and chemotherapy are now being used with some success. Another major difference concerns evaluation of lymphatics. Nonrhabdomyosarcomas in children frequently behave similarly to adult sarcomas, and less commonly involve regional lymph nodes, whereas pediatric patients with rhabdomyosarcomas often have nodal involvement necessitating surgical evaluation of regional lymph nodes as part of the staging protocol. Multimodal therapy has led to improved survival as well as better functional and cosmetic results. With further clinical trials and improved techniques such as brachytherapy and lymphatic mapping with sentinel node biopsy, we expect to continue to optimize therapy for pediatric patients with soft-tissue sarcomas.

Con: beating-heart surgery for coronary revascularization: is it the most important development since the introduction of the heart-lung machine?

Contrary to what the media tend to suggest, beating-heart coronary artery bypass grafting (BHCABG) is not a new technique. It has been performed since the advent of coronary revascularization but, until recently, was largely abandoned in favor of cardiopulmonary bypass (CPB) and cardioplegic techniques. However, with the introduction of minimally invasive coronary surgery and mechanical methods for target-artery stabilization, interest in BHCABG has been renewed. In carefully selected cases, this approach has the advantages of simplicity, avoidance of the inflammatory response caused by CPB, and a decreased need for blood transfusion. Nevertheless, BHCABG may be technically difficult in some patients, and it involves a steep learning curve. Potential risks include incomplete revascularization, ischemia during temporary target-artery occlusion, and suboptimal anastomoses. Because of the need for special equipment, BHCABG can be expensive and time consuming. It may benefit older or sicker patients who are poor candidates for CPB, especially those with left anterior descending or right coronary artery lesions, but it should be used with discretion and not be considered for all coronary patients.

Single-clamp technique for aneurysms of the descending thoracic aorta: report of 132 consecutive cases.

OBJECTIVE: To determine the efficacy of a single-clamp technique in preventing spinal cord ischemia during repair of aneurysms of the descending thoracic aorta. PATIENTS AND METHODS: From January 1989 to May 1999, 132 consecutive patients (91 men and 41 women, aged 31-86 years), with aneurysms of the descending thoracic aorta underwent repair using a single-clamp technique and temporary partial distal exsanguination. The diseased aortic segment was replaced with a Dacron graft. Blood was re-infused from an auto-transfusion device, and the segmental vessels were over-sewn but not implanted into the graft. RESULTS: The average aortic cross-clamp time was 26.4 min (range, 11-67 min) for the overall group and 37.4 min for patients who had spinal cord complications. An average of 2066 ml of blood was auto-transfused (range, 450-6100 ml). During the first 30 postoperative days, 17 patients (12.9 %) died. Eleven patients (8.3%) had spinal cord dysfunction, six patients (4.5%) had lower-extremity paraparesis, and five patients (3.8%) had paraplegia. Nine patients (6.8%) had renal failure necessitating hemodialysis. Other complications included bleeding in 15 cases (11.4%), respiratory failure in 12 cases (9.1%), wound-related sequelae in five cases (3.8%), distal embolism in five cases (3.8%), and bowel ischemia in two cases (1.5%). CONCLUSION: The single-clamp technique yielded an acceptable complication rate, and the mortality was comparable to that seen after the use of more complex methods. For satisfactory results, the cross-clamp time should not exceed 30 min.

Apicoaortic conduit for left ventricular outflow tract obstruction: revisited.

BACKGROUND: We have used a variety of techniques to correct left ventricular outflow tract obstructions, including, in the past, placement of an apicoaortic valved conduit to bypass the outflow tract. Because the operation was technically difficult, it had fallen into disuse. Recently, we used a simplified transthoracic approach to implant apicoaortic conduits in 7 patients with complex lesions of the left ventricular outflow tract. METHODS: The thoracic cavity was entered through the fifth intercostal space in all 7 patients. The distal end of the valve-containing conduit was attached to the aorta with continuous 3-0 or 4-0 polypropylene sutures after incising the pleura over the distal descending aorta. The pericardium was opened to expose the left ventricular apex, which was cored so that the proximal end of the conduit could be inserted into the left ventricular cavity. RESULTS: Five of the patients recovered completely. The 2 patients who died had severe heart disease and multiple comorbidities. CONCLUSIONS: The transthoracic approach gives direct access to the descending aorta and avoids a redo sternotomy. The technique, which is simple to perform, does not compromise major coronary arteries, the conduction system, or other valves; and may be useful in patients who are not good candidates for other, more conventional procedures.

Infected postcarotid endarterectomy pseudoaneurysms: retrospective review of a series.

The development of infected pseudoaneurysms (PAs) following carotid endarterectomy (CEA) is extremely rare. We retrospectively reviewed the data from 13 such aneurysms (in 12 patients) repaired over a period of 35 years at the Texas Heart Institute (THI) and included an overview of published cases to analyze the epidemiology, mode of presentation, methods of repair, and outcome. The diagnosis of PA should be considered when a patient develops a persistent hematoma, recurrent bleeding from the wound, or late wound infection. Sepsis is occasionally a presenting symptom. Surgical therapy for infected PAs can be challenging; excision of the aneurysm followed by autologous grafting constitutes the favored approach. Traditionally, Dacron patch repair has been associated with a high incidence of reinfection. Carotid artery ligation is required in a large percentage of cases (22.7%) and is associated with a prohibitive rate of death/major stroke (50%) compared with a low (12%) risk following arterial reconstruction. Prevention and early diagnosis of infected PAs are essential to limit complications and mortality.

Extracranial carotid artery aneurysms: Texas Heart Institute experience.

BACKGROUND AND PURPOSE: Aneurysms of the extracranial carotid artery (ECA) are rare. Large single-institution series are seldom reported and usually are not aneurysm type-specific. Thus, information about immediate and long-term results of surgical therapy is sparse. This review was conducted to elucidate etiology, presentation, and treatment for ECA aneurysms. METHODS: We retrospectively reviewed the case records of the Texas Heart Institute/St Luke's Episcopal Hospital, Houston, and found 67 cases of ECA aneurysms treated surgically (the largest series to date) between 1960 and 1995: 38 pseudoaneurysms after previous carotid surgery and 29 atherosclerotic or traumatic aneurysms. All aneurysms were surgically explored, and all were repaired except two: a traumatic distal internal carotid artery aneurysm and an infected pseudoaneurysm in which the carotid artery was ligated. RESULTS: Four deaths (three fatal strokes and one myocardial infarction) and two nonfatal strokes were directly attributed to a repaired ECA aneurysm (overall mortality/major stroke incidence, 9%); there was one minor stroke (incidence, 1.5%). The incidence of cranial nerve injury was 6% (four cases). During long-term follow-up (1.5 months-30 years; mean, 5.9 years), 19 patients died, mainly of cardiac causes (11 myocardial infarctions). CONCLUSION: The potential risks of cerebral ischemia and rupture as well as the satisfactory long-term results achieved with surgery strongly argue in favor of surgical treatment of ECA aneurysms.

Sinus of Valsalva aneurysm or fistula: management and outcome.

BACKGROUND: Few large or long-term series exist regarding the management of patients with sinus of Valsalva aneurysms or fistulas (SVAFs). METHODS: Between 1956 and 1997, 129 patients presented with a ruptured (64 cases; 49.6%) or nonruptured (65 cases; 50.4%) SVAF. The patients included 88 men and 41 women, with a mean age of 39.1 years. Associated findings included a history of endocarditis (42 cases; 32.6%), a bicuspid aortic valve (21 cases; 16.3%), a ventricular septal defect (15 cases; 11.6%), and Marfan's syndrome (12 cases; 9.3%). Operative procedures included simple plication (61 cases; 47.3%), patch repair (52 cases; 40.3%), aortic root replacement (16 cases; 12.4%), and aortic valve replacement/repair (75 cases; 58.1%). RESULTS: There were five in-hospital deaths (3.9%): four due to preexisting sepsis and endocarditis and one that followed dehiscence of the repair in a patient with Marfan's syndrome. Two patients (1.6%) had strokes during the early postoperative period. The survivors were followed up for 661.1 patient-years (5.3 years/patient). The following late complications occurred: prosthetic valve malfunction (5 cases; 3.9%), prosthetic valve endocarditis (3 cases; 2.3%), SVAF recurrence (2 cases; 1.6%), thrombosis (1 case; 0.8%), and anticoagulation-related bleeding (1 case; 0.8%). CONCLUSIONS: Resection and repair of SVAF entails an acceptably low operative risk and yields long-term freedom from symptoms. Early, aggressive treatment is recommended to prevent endocarditis or lesional enlargement, which causes worse symptoms and necessitates more extensive repair.

The history of surgery of the thoracic aorta.

Until the late 19th century, treatment of thoracic aortic aneurysms relied on ligation of the parent vessel or introduction of foreign materials to promote coagulation or fibrosis. A major breakthrough occurred in 1888, when Rudolph Matas reported an internal repair technique known as endoaneurysmorrhaphy. In this approach, the clot was excised from the aneurysmal sac, and the orifices of the arteries that entered the sac were sutured from within, reestablishing continuous blood flow. At the beginning of the 20th century, Alexis Carrel and Charles Guthrie began to lay the foundation for modern vascular anastomotic techniques. Although isolated successes were reported, optimal treatment of thoracic aortic disease awaited the development of reliable synthetic grafts in the 1950s and 1960s. During the past 15 years, the treatment goal has reverted to endoaneurysmorrhaphy, involving the use of a suitable graft to restore aortic continuity.

Transmyocardial laser revascularization in the patient with unmanageable unstable angina.

BACKGROUND: Transmyocardial laser revascularization (TMR) provides relief for patients with chronic angina, nonamenable to direct coronary revascularization. Unmanageable, unstable angina (UUA) defines a subset of patients with refractory angina who are at high risk for myocardial infarction and death. Patients were classified in the UUA group when they had been admitted to the critical care unit with unstable angina for 7 days with three failed attempts at weaning them off intravenous antianginal medications. METHODS: Seventy-six treated patients were analyzed to determine if TMR is a viable option for patients with unmanageable unstable angina. These patients were compared with 91 routine protocol patients (protocol group [PG]) undergoing TMR for chronic angina not amenable to standard revascularization. The procedure was performed through a left thoracotomy without cardiopulmonary bypass. These patients were followed for 12 months after the TMR procedure. Both unmanageable and chronic angina patients had a high incidence of at least one prior surgical revascularization (87% and 91%, respectively). RESULTS: Perioperative mortality (< or = 30 days post-TMR) was higher in the UUAG versus PG (16% vs 3%, p = 0.005). Late mortality, up to 1 year of follow-up, was similar (13% vs 11%, UUAG vs PG; p = 0.83). A majority of the adverse events in the UUAG occurred within the first 3 months post-TMR, and patients surviving this interval did well, with reduced angina of at least two classes occurring in 69%, 82%, and 82% of patients at 3, 6, and 12 months, respectively. The percent improvement in angina class from baseline was statistically significant at 3, 6, and 12 months. A comparable improvement in angina was found in the protocol group of patients. CONCLUSIONS: TMR carried a significantly higher risk in unmanageable, unstable angina than in patients with chronic angina. In the later follow-up intervals, however, both groups demonstrated similar and persistent improvement in their angina up to 12 months after the procedure. TMR may be considered in the therapy of patients with unmanageable, unstable angina who otherwise have no recourse to effective therapy in the control of their disabling angina.

Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome.

BACKGROUND: There is controversy regarding the application of transfusion triggers in cardiac surgery. The goal of this study was to determine if lowering the hemoglobin threshold for red cell (RBC) transfusion to 8 g per dL after coronary artery bypass graft surgery would reduce blood use without adversely affecting patient outcome. STUDY DESIGN AND METHODS: Consecutive patients (n = 428) undergoing elective primary coronary artery bypass graft surgery were randomly assigned to two groups: study patients (n = 212) received RBC transfusions in the postoperative period if the Hb level was < 8 g per dL or if predetermined clinical conditions required RBC support, and control patients (n = 216) were treated according to individual physician's orders (hemoglobin levels < 9 g/dL as the institutional guideline). Multiple demographic, procedure-related, transfusion, laboratory, and outcome data were analyzed. Questionnaires were administered for patient self-assessment of fatigue and anemia. RESULTS: Preoperative and operative clinical characteristics, as well as the intraoperative transfusion rate, were similar for both groups. There was a significant difference between the postoperative RBC transfusion rates in study (0.9 +/- 1.5 RBC units) and control (1.4 +/- 1.8 RBC units) groups (p = 0.005). There was no difference in clinical outcome, including morbidity and mortality rates, in the two groups; group scores for self-assessment of fatigue and anemia were also similar. CONCLUSIONS: A lower Hb threshold of 8 g per dL does not adversely affect patient outcome. Moreover, RBC resources can be saved without increased risk to the patient.