High-dose therapy with auto-SCT is feasible in high-risk cardiac amyloidosis.

Cardiac involvement in light-chain amyloidosis (AL) predicts poor prognosis and is associated with higher TRM and morbidity during high-dose therapy and auto-SCT (HDT-ASCT). We studied the outcomes of 30 patients with cardiac amyloidosis undergoing HDT-ASCT at our center between January 1998 and March 2012. The median age of the patients was 53 years (range, 36-74) with a median follow-up of 35 months (range, 0.4-97 months). Twenty-seven patients (90%) had more than one organ involved besides the heart with 37% with cardiac stage ⩾3. Melphalan-based conditioning regimen (140-200 mg/m(2)) was used for HDT-ASCT. One-year TRM is 10%. Three-year OS and EFS from HDT-ASCT was 83% and 56.8%, respectively. Cumulative incidence of relapse at 3 years was 38.5%. Negative factors affecting survival included age >60 years, lack of novel induction therapy and BM plasmacytosis >10%. We conclude that HDT-ASCT is well tolerated in patients with high-risk cardiac amyloidosis and can lead to improved overall outcomes.

Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective analysis with 14-year follow-up.

Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age <60 years, induction therapy with novel agents, kidney only involvement and Auto-SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.

Crystallization and preliminary X-ray diffraction analysis of L-threonine dehydrogenase (TDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis.

The enzyme L-threonine dehydrogenase catalyses the NAD(+)-dependent conversion of L-threonine to 2-amino-3-ketobutyrate, which is the first reaction of a two-step biochemical pathway involved in the metabolism of threonine to glycine. Here, the crystallization and preliminary crystallographic analysis of L-threonine dehydrogenase (Tk-TDH) from the hyperthermophilic organism Thermococcus kodakaraensis KOD1 is reported. This threonine dehydrogenase consists of 350 amino acids, with a molecular weight of 38 kDa, and was prepared using an Escherichia coli expression system. The purified native protein was crystallized using the hanging-drop vapour-diffusion method and crystals grew in the tetragonal space group P4(3)2(1)2, with unit-cell parameters a = b = 124.5, c = 271.1 A. Diffraction data were collected to 2.6 A resolution and preliminary analysis indicates that there are four molecules in the asymmetric unit of the crystal.

What percentage of surgically clipped intracranial aneurysms have residual necks?

OBJECTIVE: To determine the angiographically proven rate and persistence of occlusion of intracranial aneurysms after surgical clipping as reported in the literature. This should establish a basis for comparing surgery with new endovascular methods of treatment. METHODS: We reviewed the literature published during the period from 1979 through 1999, dividing the articles into two groups. The first group of articles reported patients undergoing surgical treatment with immediate postoperative angiography. The second group of articles documented symptomatic recurrence or regrowth of aneurysms that were surgically treated previously. The data from these articles are presented for analysis. RESULTS: During the period 1979 to 1999, six series of patients undergoing surgical treatment of aneurysms with immediate postoperative angiography were reported. These reported series comprised a total of 1,397 patients, of whom 1,370 underwent postoperative angiography demonstrating 1,569 clipped aneurysms. Residual filling was found in 82 aneurysms (5.2%) on postoperative angiography. Of the 1,370 patients, only 124 patients with 169 aneurysms were reported to have had any long-term angiographic follow-up. The second group consisted of 226 patients representing six reported groups of patients, who either presented up to 24 years after aneurysm clipping with recurrent symptoms of hemorrhage or mass effect, or had important findings on intraoperative and postoperative angiograms. CONCLUSION: The lack of information regarding both the frequency of residual filling or regrowth and long-term angiographic follow-up of patients with surgically treated aneurysms makes meaningful comparison between surgical treatments and new treatment methods for intracranial aneurysms difficult or impossible. Detailed analysis with high-quality angiography should be performed to determine the success of surgical treatment.

Role of magnetic resonance imaging and diagnostic and interventional angiography in vascular and neoplastic diseases of the skull base associated with vestibulocochlear symptoms.

There are many vascular and neoplastic diseases as well as normal variants that produce the vestibulocochlear symptoms of pulsatile tinnitus, hearing loss, dizziness, and ataxia. Magnetic resonance imaging may be diagnostic, and magnetic resonance angiography/magnetic resonance venography have added to the ability of magnetic resonance to image vascular abnormalities. The extent of neoplasms is accurately assessed and complication of vascular lesions are clearly seen. However, detailed vascular anatomy requires high-quality selective angiography. This enables optimal treatment planning. Endovascular therapeutic intervention has a major role to play in conjunction with surgery of skull base lesions and may be curative in certain conditions, avoiding major surgical procedures. The interventionalist, however, must have an excellent knowledge of the external carotid circulation and all of its potential communications with the internal circulation to avoid serious embolic complications.

Techniques of coiling cerebral aneurysms.

BACKGROUND: More than 200 aneurysms have been coiled at the UIC Medical Center within the last 5 years. We describe in detail the technical factors that increase the chance of complete occlusion of a cerebral aneurysm with coils. Aneurysms selected for coiling have good geometry or are in a location that is difficult to reach surgically. Patients with medical conditions that preclude surgical treatment may also undergo coiling. METHODS: Patients with aneurysms, either ruptured or unruptured, are treated under general anesthesia, fully anticoagulated and deeply paralyzed. Coiling is done under simultaneous biplane roadmapping. After the first coil has created a mesh, the aneurysm is densely packed with soft coils of decreasing diameter, until no more coils can be deployed into the aneurysm. RESULTS: The morbidity and mortality rates associated with the coiling procedure have continuously decreased over the last 5 years. The morphological outcomes have improved, due to extensive use of the remodeling technique and to advancements in materials, such as refinements in the coils themselves or the availability of over-the-wire balloon catheters in different sizes and hydrophilic wires with complex tip configurations. Twenty-one percent of the aneurysms were considered to be incompletely occluded immediately after coiling. Of this group, one-third of the aneurysms were found to be completely occluded on follow-up angiograms by 6 months; these have remained occluded. One-third were more than 95% occluded after the coiling procedure; in these patients, the dome was completely occluded, but there was a small neck remnant, which has remained stable in all patients on control angiograms obtained at 6 months and 1, 2, and 4 years; none have rebled. These patients are followed medically. The remaining one-third of the aneurysms in this subgroup were less than 95% occluded, although the dome was completely thrombosed. None of them have rebled, but the neck remnant in most has regrown over a period ranging from 6 months to 2 years. These patients have undergone a second treatment-either surgical clipping, permanent occlusion of the parent vessel, or repeat coiling using the remodeling technique. The overall rebleeding rate of incompletely occluded aneurysms is extremely low (less than 1%). CONCLUSION: The low morbidity and mortality rates and the good morphological outcome obtained in most cases make coiling a reasonable alternative to surgical clipping in properly selected cases.

Carotid-Cavernous Fistula Associated with Ehlers-Danlos Syndrome Type IV. A Case Report and Review of Literature.

SUMMARY: A case of traumatic, direct, carotid cavernous fistula (CCF) associated with Ehlers - Danlos syndrome (EDS) Type IV is reported along with a review of the literature. Excluding the present case, three similar cases associated with EDSTypeJV have already been reported by Gerard M. Debrun et Al(l). Despite the risks associated with endovascular manipulation, the fistula was successfully closed by intravascular embolisation but the patient expired a few days later because of underlying disease-associated vascular and visceral complications.