Recent trends in early outcome of adult patients after heart transplantation: a single-institution review of 251 transplants using standard donor organs.

Older age, prior transplantation, pulmonary hypertension, and mechanical support are commonly seen in current potential cardiac transplant recipients. Transplants in 436 consecutive adult patients from 1994 to 1999 were reviewed. There were 251 using standard donors in 243 patients (age range 18-69 years). To emphasize recipient risk, 185 patients who received a nonstandard donor were excluded from analysis. The indications for transplant were ischemic heart disease (n = 123, 47%), dilated cardiomyopathy (n = 82, 32%), and others (n=56, 21%). One hundred and forty-nine (57%) recipients were listed as status I; 5 and 6% were supported with an intra-aortic balloon and an assist device, respectively. The 30-d survival and survival to discharge were 94.7 and 92.7%, respectively; 1-year survival was 89.1%. Causes of early death were graft failure (n = 6), infection (n = 4), stroke (n = 4), multiorgan failure (n = 3) and rejection (n = 2). Predictors were balloon pump use alone (OR= 11.4, p =0.002), pulmonary vascular resistance > 4 Wood units (OR = 5.7, p = 0.007), pretransplant creatinine > 2.0 mg/dL (OR = 6.9, p = 0.004) and female donor (OR = 8.3, p = 0.002). Recipient age and previous surgery did not affect short-term survival. Heart transplantation in the current era consistently offers excellent early and 1-year survival for well-selected recipients receiving standard donors. Early mortality tends to reflect graft failure while hospital mortality may be more indicative of recipient selection.     

Evaluation of the use of a biodegradable ureteral stent after retrograde endopyelotomy in a porcine model

PURPOSE: We evaluated the use of a poly-L-lactide-co-glycolide (PLGA) bioabsorbable ureteral stent after Acucise balloon incision (Applied Medical Resources, Rancho Santa Magarita, California) endopyelotomy in a porcine model. MATERIALS AND METHODS: After unilateral Acucise endopyelotomy in 9 female Yucatan minipigs a self-reinforced PLGA stent was placed in 5 (group 1) and a 7Fr double pigtail Percuflex stent (Boston Scientific, Natick, Massachusetts) was placed in 4 (group 2). Preoperatively, and 6 and 12 weeks postoperatively plain x-ray of the kidneys, ureters and bladder, cystography, side specific creatinine clearance and retrograde ureterography were done. The contralateral ureters served as untreated controls. The 7Fr stents were removed at 6 weeks. All animals were sacrificed at 12 weeks after bilateral flow studies. Histological specimens from 4 sites along the urinary tract were graded on a healing score of 0-normal, to 3-severe changes. RESULTS: Side specific creatinine clearance was similar to preoperative values at 6 and 12 weeks. At the 2 time points plain x-ray of the kidneys, ureters and bladder in group 1 showed retroperitoneal stent fragments in 3 of the 5 animals, which was confirmed at autopsy. Retrograde ureterography in group 1 showed mild hydronephrosis in all 5 ureters and saccular diverticula in 4, which was similar in 2 and 3 animals, respectively, in group 2. Cystography demonstrated grades 1 to 2 reflux in 2 animals at 6 weeks but none at 12 weeks in group 1 and no reflux at either time point in group 2. Flow rates and healing scores were statistically similar in the 2 groups but the latter trended toward less favorable healing of ureteral musculature with application of the absorbable stent. CONCLUSIONS: In this pilot study the use of self-reinforced PLGA biodegradable ureteral stents was feasible after Acucise endopyelotomy in a porcine model with radiographic and fluid flow results that were relatively similar to those of standard 7Fr stents but with less favorable biocompatibility.     

Management of Vascular Complications following Femoral Artery Catheterization with and without Percutaneous Arterial Closure Devices

Percutaneous arterial closure devices allow earlier mobilization and discharge of patients after arterial catheterization than with manual compression for puncture site hemostasis. We reviewed our recent experience managing the complications of femoral artery catheterization with and without these devices on the vascular surgery service at a tertiary hospital. Thirty-one patients presenting over an 18-month period with complications after femoral artery catheterization with manual compression (n = 21) or percutaneous arterial closure devices (n = 10) were retrospectively reviewed.     

Long-term followup after laparoscopic radical nephrectomy

PURPOSE: Laparoscopic radical nephrectomy has been shown to be less morbid than traditional open radical nephrectomy. The long-term oncological effectiveness of laparoscopic radical nephrectomy remains to be established. MATERIALS AND METHODS: At 3 centers patients undergoing laparoscopic radical nephrectomy before November 1, 1996 with pathologically confirmed renal cell carcinoma were identified. A representative group of patients undergoing open radical nephrectomy for clinical T1, T2 lesions was also identified. Staging, operative details and postoperative course were reviewed. Followup consisted of review of clinical, laboratory and radiological records. Kaplan-Meier analysis was performed. RESULTS: The study included 64 patients treated with laparoscopic and 69 treated with open radical nephrectomy with respective average ages of 60.6 and 61.3 years at surgery. On preoperative imaging open lesions were larger (6.2 cm., range 2.5 to 15) than laparoscopic radical nephrectomy lesions (4.3 cm., range 2 to 10, p <0.001). Pathology reports revealed no difference in specimen weight (425 and 495 gm., p = 0.146) or average Fuhrman grade (1.88 and 1.78, p = 0.476) between laparoscopic and open radical nephrectomy, respectively. Median followup was 54 months (range 0 to 94) for laparoscopic and 69 months (range 8 to 114) for open radical nephrectomy. Kaplan-Meier analysis with log rank comparison revealed 5-year recurrence-free survival of 92% and 91% for laparoscopic and open radical nephrectomy, respectively (p = 0.583). At 5 years cancer specific survival was 98% and 92% (p = 0.124), and nonspecific survival was 81% and 89% (p = 0.260) for laparoscopic and open radical nephrectomy, respectively. CONCLUSIONS: Laparoscopic radical nephrectomy confers long-term oncological effectiveness equivalent to traditional open radical nephrectomy.     

The Aachen MiniHLM--a miniaturized heart-lung machine for neonates with an integrated rotary blood pump

The operation of congenital heart defects in neonates often requires the use of heart-lung machines (HLMs) to provide perfusion and oxygenation. This is prevalently followed by serious complications inter alia caused by hemodilution and extrinsic blood contact surfaces. Thus, one goal of developing a HLM for neonates is the reduction of priming volume and contact surface. The currently available systems offer reasonable priming volumes for oxygenators, reservoirs, etc. However, the necessary tubing system contains the highest volumes within the whole system. This is due to the use of roller pumps; hence, the resulting placement of the complete HLM is between 1 and 2 m away from the operating table due to connective tubing between the components. Therefore, we pursued a novel approach for a miniaturized HLM (MiniHLM) by integrating all major system components in one single device. In particular, the MiniHLM is a HLM with the rotary blood pump centrically integrated into the oxygenator and a heat exchanger integrated into the cardiotomy reservoir which is directly connected to the pump inlet. Thus, tubing is only necessary between the patient and MiniHLM. A total priming volume of 102 mL (including arterial filter and a/v line) could be achieved. To validate the overall concept and the specific design we conducted several in vitro and in vivo test series. All tests confirm the novel concept of the MiniHLM. Its low priming volume and blood contact surface may significantly reduce known complications related to cardiopulmonary bypass in neonates (e.g., inflammatory reaction and capillary leak syndrome).     

Clinical outcome at ten years after laparoscopic fundoplication: Nissen versus Toupet

Laparoscopic surgery has become the elective approach for the surgical treatment of gastroesophageal reflux disease in the last decade. Outcome data beyond 10 years are available for open fundoplication, with good-to-excellent results, but few studies report long-term follow-up after laparoscopic fundoplication. We performed a retrospective study of all the patients that underwent laparoscopic Nissen and Toupet fundoplications as antireflux surgery between 1995 and 1998 in our institution. To evaluate the long-term results, a face-to-face interview was performed in 2009. One hundred and six patients were included in the study. Surgical techniques performed were Nissen fundoplication (NF) in 56 patients and Toupet (TF) in 50. Complication rate was 4 per cent in both groups (nonsignificant [NS]). Two patients (4%) of NF required reoperation because of dysphagia. After 10 years, 10 per cent of the patients remain symptomatic in both groups. Fifteen per cent of NF take daily inhibitors of the proton pump versus 14 per cent of TF (NS). Twenty per cent of NF refer dysphagia, all of them without evidence of stenosis at endoscopy or contrasted studies. The satisfaction rate of the patients was 96 per cent in NF and 98 per cent in TF. Laparoscopic Toupet fundoplication seems to be as safe and long-term effective as Nissen, but with a lower incidence of postoperative dysphagia. In our experience Toupet fundoplication should be the elective approach for the surgical treatment of gastroesophageal reflux disease.     

Different effects of raloxifene and estrogen on interleukin-1beta and interleukin-1 receptor antagonist production using in vitro and ex vivo studies

The increase in lumbar spine BMD in response to Raloxifene (RLX), a selective estrogen receptor modulator, is smaller in magnitude compared to the response to treatment with estradiol (E2). The reasons for this observation are unclear. Estrogen has a potent effect on the production of proinflammatory cytokines which support osteoclastogenic and bone resorption. Therefore the different response to RLX may relate, at least in part, to a difference in the ability of RLX to modulate the production of proinflammatory cytokines which are abundant in the red marrow of the vertebrae. The aim of this study was to determine the effect of RLX and E2 both in vitro and ex vivo on the production of the pro-resorptive cytokine interleukin-1beta (IL-1beta) and its antagonist, interleukin-1 receptor antagonist (IL-1ra). We obtained samples of peripheral blood from (a) 10 untreated postmenopausal women with osteopenia (ages 53 to 72 years, mean 61 years), (b) 15 postmenopausal women (ages 52 to 72 years, mean 63 years) at baseline and after 6 months of RLX therapy (60 mg/day) and (c) 10 postmenopausal women (ages 60 to 75 years, mean 64 years) at baseline and 6 months after a single E2 implant (25 mg). Cultures of whole blood from the untreated women were incubated with RLX or 17beta-E2 at 1 pM, 100 pM, 10 nM and 1 microM concentrations. LPS-stimulated whole blood cultures from the raloxifene- and estradiol-treated women were prepared at baseline and at 6 months. IL-1beta and IL-1ra were measured by ELISA in the conditioned media. In vitro there was a significant dose-dependent decrease in IL-1beta and IL-1ra in response to 17beta-E2 (both P<0.0001) which was not apparent in response to RLX (both P>0.05). In ex vivo cultures from women receiving 6 months treatment with E2 implants, there was a significant decrease in IL-1beta (-36+/-8%, P=0.01) but no significant change in IL-1ra (+29+/-20%, P=0.3). There was no significant change in either IL-1beta or IL-1ra after 6 months RLX therapy (+20+/-14% and +12+/-10%, both P>0.05). We conclude that treatment with RLX, unlike estradiol does not modulate the production of the proinflammatory cytokines IL-1beta and IL-1ra using in vitro or ex vivo whole blood culture methods. This may account, at least in part for the reduced efficacy of RLX therapy compared to estrogen which has been observed in vivo on bone mineral density, bone turnover and reduction in fracture risk.     

Partial Portal Vein Ligation Plus Thioacetamide: A Method to Obtain a New Model of Cirrhosis and Chronic Portal Hypertension in the Rat

To obtain a new model of chronic portal hypertension in the rat, two classical methods to produce portal hypertension, partial portal vein ligation and the oral administration of thioacetamide (TAA), have been combined. Male Wistar rats were divided into four groups: 1 (control; n?=?10), 2 [triple partial portal vein ligation (TPVL); n?=?9], 3 (TAA; n?=?11), and 4 (TPVL plus TAA; n?=?9). After 3 months, portal pressure, types of portosystemic collateral circulation, laboratory hepatic function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase) and liver histology were studied. The animals belonging to group 2 (TPVL) developed extrahepatic portosystemic collateral circulation, associated with mesenteric venous vasculopathy without hepatic destructurization or portal hypertension. Animals from group 3 (TAA) developed cirrhosis and portal hypertension but not extrahepatic portosystemic collateral circulation, or mesenteric venous vasculopathy. Finally, the animals from group 4 (TPVL?+?TAA) developed cirrhosis, portal hypertension, portosystemic collateral circulation, and mesenteric venous vasculopathy. The association of TPVL and TAA can be used to obtain a model of chronic portal hypertension in the rat that includes all the alterations that patients with hepatic cirrhosis usually have. This could, therefore, prove to be a useful tool to study the pathophysiological mechanisms involved in these alterations.     

Insights into the molecular pathogenesis of progression in multiple sclerosis: potential implications for future therapies

Despite recent advances in the diagnosis and treatment of multiple sclerosis, we still lack a consensus regarding the causes, pathogenesis, and mechanisms of disease progression. Current evidence indicates that multiple sclerosis is an inflammatory neurodegenerative disorder in which both adaptive and innate immunity play important roles in initiation and maintenance of the disease. Recent evidence supports the notion of molecular pathologic abnormalities beyond the plaques and dysfunction of neurons in normal appearing areas, in addition to the multifocal demyelination and axonal loss, as important features that may underlie early reversible changes in the disease. Chronic failure of remyelination, axonal regeneration, and neuronal dysfunction may contribute to disease progression. This article discusses the emerging molecular evidence for the progression of multiple sclerosis with particular focus on alterations in the local central nervous system microenvironment of neural and glial cells. The molecular pathways leading to structural and functional neurodegeneration and those that prevent regeneration need to be identified in order to design new therapeutic strategies that can halt or even reverse disease progression.     

Improving graft survival for patients undergoing liver transplantation

Dickson RC, Pungpapong S, Keaveny AP, Taner BC, Ghabril M, Aranda‐Michel J, Satyanarayana R, Bonatti H, Kramer DJ, Nguyen JH. Improving graft survival for patients undergoing liver transplantation.
Clin Transplant 2011: 25: E345–E355. © 2011 John Wiley & Sons A/S. Abstract: Liver transplant (LT) outcomes are reported to be improving in non‐HCV recipients but not for those infected with HCV. Our aim was to evaluate graft survival and predictors of outcome in HCV and non‐HCV patients before and after 2003. Patients with primary LT between February 1, 1998, and December 31, 2005, were included. Patients were divided into Era 1 (1998–2002) and Era 2 (2003–2005) with follow‐up through May 31, 2009. Graft survival was compared for HCV, non‐HCV, and all patients. There was significant improvement in graft survival in Era 2 for HCV patients. Graft survival in Era 2 of HCV patients was equivalent to non‐HCV patients. The most significant improvement between eras was in outcomes of grafts from donors ≥60 yr with three‐yr graft survival 58.6 (51.3–65.9) vs. 75.4 (68.9–81.9), p = 0.002. The use of donors ≥60 did not change between eras: 31% vs. 34%; however, utilization in HCV recipients decreased from 36% to 3% (p < 0.001). In conclusion, graft survival of HCV patients has improved significantly since 2003 and was comparable to non‐HCV patients up to three yr. The change in management of donor organs into HCV and non‐HCV patients likely contributed to this outcome.