Citations

Paraplegia is a major complication associated with repair of thoracoabdominal aortic aneurysms (TAAA). A number of therapies have been tried over the years, none of which has been successful. Recently, regional lumbar epidural cooling has been tried in an attempt to prolong the safe ischemic time during aortic cross- clamping. In approximately 90 patients in whom the authors have tried this technique, there was no de crease in the incidence of paraplegia in patients with type II TAAAs. This is perhaps not unanticipated be cause the paraplegia is related to a number of factors including the duration of the aortic cross-clamping, the adequacy of collateral circulation, embolization during the procedure, and perhaps thrombosis in situ. Given the multimodal cause of paraplegia, perhaps it is naive to think that a single therapy would be of benefit. Additional studies are necessary to explore the mecha nisms and to prove efficacy or lack of benefit of any techniques designed to decrease the incidence of paraplegia in patients undergoing TAAA repair.

The postoperative care of a patient who receives an intra-abdominal organ transplant is in some ways simi lar to that of any major intra-abdominal procedure. However, certain features unique to organ transplanta tion, such as the variable functional status of the newly transplanted graft, complications that are specific to the organ transplanted, and the side effects from immuno suppressive drugs, suggest that transplantation inten sive care is a distinct subspecialty in critical care medicine. Today, the majority of patients receiving an intra-abdominal transplant will have a relatively uncom plicated postoperative course. However, preoperative disposition, intraoperative misadventure, or immediate postoperative difficulty will require the availability of an intensivist experienced in transplantation. The future of intra-abdominal transplantation will be highly depen dent on progress in immunotherapy. Newer, more spe cific immunomodulators with fewer nonimmune toxici ties should result in improved organ receptance, less graft dysfunction, and improved patient survival.

AbstractThe survival of patients with Waldenstrom macroglobulinemia (WM) varies enormously. The development of prognostic models in WM has been fraught by limited follow-up in current studies. Here, we update the outcome of a prospective WM trial with a median follow-up of 10 years for live patients. Of the 59 previously untreated patients who initially were observed, only 12 patients (21%) required therapy at a median follow-up of 100 months. Multivariate analysis among the 183 patients requiring therapy reaffirmed age 70 years or greater, previous nonprotocol therapy, and β-2 microglobulin (B2M) of 3 mg/dL or greater as prognostic factors. Importantly, increased serum lactate dehydrogenase (LDH) was identified as an additional independent variable, which improved risk assessment beyond the recent WM international prognostic scoring system (ISSWM). By using age, previous therapy, B2M, and LDH, we identified 3 risk groups with 8-year survival estimates of 55%, 33%, and 5% (P < .001). These data provide novel insights into factors predicting long-term outcome in WM. This trial has been registered with www.cancer.gov under ID 4852904.

OBJECTIVE—The purpose of this study was to determine the mechanism by which dipeptidyl peptidase-4 inhibitors lower postprandial glucose concentrations. RESEARCH DESIGN AND METHODS—We measured insulin secretion and action as well as glucose effectiveness in 14 subjects with type 2 diabetes who received vildagliptin (50 mg b.i.d.) or placebo for 10 days in random order separated by a 3-week washout. On day 9 of each period, subjects ate a mixed meal. Insulin sensitivity (SI), glucose effectiveness, and β-cell responsivity indexes were estimated using the oral glucose and C-peptide minimal models. At 300 min 0.02 unit/kg insulin was administered intravenously. RESULTS—Vildagliptin reduced postprandial glucose concentrations (905 ± 94 vs. 1,008 ± 104 mmol/6 h, P = 0.02). Vildagliptin did not alter net SI (7.71 ± 1.28 vs. 6.41 ± 0.84 10−4 dl · kg−1 · min−1 · μU−1 · ml−1, P = 0.13) or glucose effectiveness (0.019 ± 0.002 vs. 0.018 ± 0.002 dl · kg−1 · min−1, P = 0.65). However, the net β-cell responsivity index was increased (35.7 ± 5.2 vs. 28.9 ± 5.2 10−9 min−1, P = 0.03) as was total disposition index (381 ± 48 vs. 261 ± 35 10−14 dl · kg−1 · min−2 · pmol−1 · l−1, P = 0.006). Vildagliptin lowered postprandial glucagon concentrations (27.0 ± 1.1 vs. 29.7 ± 1.5 μg · l−1 · 6 h−1, P = 0.03), especially after administration of exogenous insulin (81.5 ± 6.4 vs. 99.3 ± 5.6 ng/l, P = 0.02). CONCLUSIONS—Vildagliptin lowers postprandial glucose concentrations by stimulating insulin secretion and suppressing glucagon secretion but not by altered insulin action or glucose effectiveness. A novel observation is that vildagliptin alters α-cell responsiveness to insulin administration, but the significance of this action is as yet unclear.

In the past decade there has been an increasing awareness of distinct, potentially lethal heritable cardiomyopathic and channelopathic syndromes as they pertain to sudden cardiac death in infants and children. This review highlights current clinical and molecular findings of two highly relevant structural cardiac abnormalities evident at autopsy, namely hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, as well as the cardiac channelopathies of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome, which may account for one third of autopsy-negative sudden unexplained deaths (SUDs) during childhood and adolescence. We also explore the role of postmortem genetic analysis (molecular autopsy) in cases of SUD, provide a critical analysis of the current spectrum and prevalence of channelopathies as the pathogenic basis for sudden infant death syndrome (SIDS), and provide a brief synopsis on genetic testing for such potentially lethal cardiac disorders.