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Context—Tacrolimus is an immunosuppressant that undergoes therapeutic drug monitoring. The laboratory at our institution changed its immunoassay techniques from the fluorescence polarization immunoassay to the cloned enzyme donation immunoassay.Objective—To evaluate the relationship between the 2 assays and to determine the impact of the change on clinical decision making.Design—A retrospective study of patients admitted to the hospital during the assay transition period. Tacrolimus values for the 2 assays were collected for 4 weeks and compared.Setting—An academic health center.Patients—Liver transplant patients hospitalized from February 18, 2008, to March 18, 2008.Main Outcome Measure—The primary outcome was the agreement between the results of the 2 immunoassays. Secondary outcome was agreement of clinical decision making with established patient-specific therapeutic ranges or with a 30% difference in absolute values between the assays.Results—Seventy-nine pairs of tacrolimus concentrations were colle...

In at-risk populations, shared routes of transmission lead to high rates of concordance between infection with human immunodeficiency virus (HIV) type 1 and hepatitis C virus (HCV). In the era of highly active antiretroviral therapy (HAART), end-stage liver disease (ESLD) has emerged as a leading cause of mortality in coinfected patients. HAART-related toxicities have been implicated, especially when given to patients with viral hepatitis. Rates of response to treatment for HCV infection in coinfected patients continue to lag behind those in monoinfected patients, even with the advent of pegylated interferons. Liver transplantation has been approached with caution in this population because of concern about the sequelae of immunosuppression and HAART-related hepatotoxicity, and results have been conflicting. Clinical and serological markers of ESLD in coinfected patients, management of cirrhosis, and the appropriateness of transplantation are discussed.

Since the introduction of the laparoscopic cholecystectomy, there has been explosive growth in the field of minimally invasive surgery. Commonly accepted laparoscopic procedures have now come to include bariatric and anti reflux procedures, distal pancreatectomy, splenectomy, hernia repair, and colon resection. The adoption of laparoscopy to the field of liver surgery; however, has been slower to take off. Initial concerns included inadequate exposure and ability to attain hemostasis, fear of gas embolism, and doubts over the oncologic adequacy of the less invasive procedure. The earliest reports of laparoscopic liver surgery were limited to wedge resections for staging or isolated metastases(Lefor, AT & Flowers, JL 1994). Laparoscopic liver resection finally started to gain serious widespread attention after publication of Cherqui’s initial thirty patient experience(Cherqui, D et al 2000). Since that time, the field has seen explosive growth, with over 2,804 cases now described in the world literature(Nguyen, KT et al 2009). Despite its widespread acceptance, laparoscopic liver resection remains a daunting technical challenge suited to a relatively small number of centers that have taken the time and effort to develop concurrent expertise in both open hepatic surgery and laparoscopy. Once these hurdles are overcome; however, laparoscopic liver resection is a safe and highly effective procedure offering numerous patient benefits. In this chapter, we will describe the indications for laparoscopic liver resection, and outline the steps that should be taken by fledgling groups wishing to embark upon creating a laparoscopic liver resection program.

Hepatitis C virus (HCV) is becoming the most common indication for liver retransplantation (ReLTx). This study was a retrospective review of the medical records of liver transplant patients at our institution to determine factors that would identify the best candidates for ReLTx resulting from allograft failure because of HCV recurrence. The patients were divided into 2 groups on the basis of indication for initial liver transplant. Group 1 included ReLTx patients whose initial indication for LTx was HCV. Group 2 included patients who received ReLTx who did not have a history of HCV. We defined chronic allograft dysfunction (AD) as patients with persistent jaundice (> 30 days) beginning 6 months after primary liver transplant in the absence of other reasons. HCV was the primary indication for initial orthotopic liver transplantation (OLT) in 491/1114 patients (44%) from July 1996 to February 2004. The number of patients with AD undergoing ReLTx in Groups 1 and 2 was 22 and 12, respectively. The overall patient and allograft survival at 1 year was 50% and 75% in Groups 1 and 2, respectively (P = .04). The rates of primary nonfunction and technical problems after ReLTx were not different between the groups. However, the incidence of recurrent AD was higher in Group 1 at 32% versus 17% in Group 2 (P = .04). Important factors that predicted a successful ReLTx included physical condition at the time of ReLTx (P = .002) and Child-Turcotte-Pugh score (P = .008). In conclusion, HCV is associated with an increased incidence of chronic graft destruction with a negative effect on long-term results after ReLTx. The optimum candidate for ReLTx is a patient who can maintain normal physical activity. As the allograft shortage continues, the optimal use of cadaveric livers continues to be of primary importance. The use of deceased donor livers in patients with allograft failure caused by HCV remains a highly controversial issue. (Liver Transpl 2004;10:1497–1503.)

The widespread use of miniaturized chemical sensors to monitor clinically important analytes such as PO2, PCO2, pH, electrolytes, glucose and lactate in a continuous, real-time manner has been seriously hindered by the erratic analytical results often obtained when such devices are implanted in vivo. One major factor that has influenced the analytical performance of indwelling sensors is the biological response they elicit when in contact with blood or tissue (e.g. thrombus formation on the device surface, inflammatory response, encapsulation, etc.). Nitric oxide (NO) has been shown to be a potent inhibitor of platelet adhesion and activation as well as a promoter of wound healing in tissue. Herein, we review recent work aimed at the development of hydrophobic NO-releasing polymers that can be employed to coat catheter-type amperometric oxygen sensors without interfering with the analytical performance of these devices. Such modified sensors are shown to exhibit greatly enhanced hemocompatibility and improved analytical performance when implanted within porcine carotid and femoral arteries for up to 16 h. Further, results from preliminary studies also demonstrate that prototype fluorescent oxygen sensors, catheter-style potentiometric carbon dioxide sensors and subcutaneous needle-type enzyme-based amperometric glucose sensors can also be fabricated with new NO-release outer coatings without compromising the analytical response characteristics of these devices. The NO-release strategy may provide a solution to the lingering biocompatibility problems encountered when miniature chemical sensors are implanted in vivo.

Introduction. The importance of HLA matching for renal transplantation outcomes has been appreciated for several decades. It has been hypothesized that as pharmacologic immunosuppression becomes stronger and more specific, the impact of HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated to both decrease acute rejection and improve three-year graft survival. It is possible that with new immunosuppressive regimens containing MMF the relative effect of HLA matching may be altered. To determine the relative impact of HLA matching in patients on MMF we undertook an analysis of the United States Renal Transplant Data Registry (USRDS). Methods. All primary, solitary renal transplants registered at the USRDS between January 1995 and June 1997, on initial immunosuppression that included either MMF or AZA were followed until June 1998. Primary study end points were graft and patient survival. Kaplan-Meier analysis was performed to compare AZA vs. MMF treated patients by HLA mismatch. Cox proportional hazard models were used to investigate the interaction between HLA mismatch and AZA versus MMF therapy on the study endpoints. All multivariate analyses were corrected for 13 potential confounding pretransplant variables including intention to treat immunosuppression. Results. A total of 19,675 patients were analyzed (8,459 on MMF and 11,216 on AZA). Overall three year graft survival was higher in the MMF group when compared to the AZA group (87% vs. 84% respectively P

The ligand-receptor binding requirements for achieving full B cell activation through the membrane immunoglobulin (mIg) signaling pathway are relatively demanding, and mIg-antigen engagements which fall below these critical thresholds cause, at most, only the partial activation of B cells. In an effort to resolve new means of enhancing the efficacy of mIgM-mediated signal transduction, as well as to further understand the process by which mIgM-mediated signals are initiated, we have explored the mechanism for a previously reported synergy between certain mixtures of murine anti-IgM mAbs in eliciting human B cell DNA synthesis. We here report that striking synergy occurs when any of several relatively high affinity mAbs specific for diverse domains of mIgM are combined in culture with the relatively low affinity C mu 4-specific ligand, mAb IG6. Although B cell activation was dependent upon the bivalency, and hence mIgM cross-linking potential, of the high affinity ligand, low affinity mAb IG6 could enhance the activation process when present as a monovalent Fab' fragment. This did not appear due to F(ab')2 contamination or Fab' aggregation, since IG6 Fab' preparations were notably compromised in several other functions requiring ligand bivalency. Pulsing studies revealed that the C mu 4-specific ligand exhibits its functional effects only when stimulatory mIgM receptor cross-links are being formed by bivalent ligands, and that IG6 Fab' enhancement is most notable during the later interval of the prolonged mIgM signaling process that leads to S phase entry. A unique region of the membrane-proximal IgM domain may be important for Fab'-mediated enhancement, since Fab' fragments that bind with higher affinities to distinct sites on C mu 4 were not as effective at mediating this phenomenon. Several possibilities for the adjuvant effects of this C mu 4-specific Fab' on B cell responses triggered by mIgM crosslinking ligands are discussed, including the possibility that IG6 Fab' influences the potential for mIgM dimer formation or interactions of mIgM with other signal-transducing molecules.

Hepatic artery thrombosis remains one of the most serious complications after orthotopic liver transplantation. Sepsis, biliary leakage and strictures, and retransplantation are often the result of this devastating complication. Because retransplantation or reoperation is sometimes not possible or advisable, other means of reestablishing hepatic artery continuity are desirable. We describe a liver transplant recipient who developed a dissection of an iliac artery conduit after retransplantation that was treated with fibrinolytic therapy followed by successful placement of an endovascular stent.

As more expanded-criteria organ donors are used to bridge the widening gap between organ supply and demand, non-heart-beating (NHB) donors will become increasingly important. The purpose of this study was to analyze renal transplant outcomes using this source of cadaveric (CAD) organs and compare the results with heart-beating organ sources.Data from 98,698 adult CAD renal transplant recipients and 34,531 living donor renal transplant recipients registered in the U. S. Renal Data System database between January 1993 and June 2000 were analyzed. Kaplan-Meier survival curves were used to compare graft and patient survival rates between NHB, CAD, and living donor transplant recipients. Cox proportional hazards models were used to identify risk factors for NHB donor recipients, while adjusting for potential confounding variables.Recipients of NHB donor organs experienced nearly twice the incidence of delayed graft function (DGF) compared with heart-beating donors (42.4% vs. 23.3%, respectively). NHB donor transplants experienced comparable allograft survival when compared with CAD transplants at 6 years (73.2% vs. 72.5%, respectively; P=NS); patient survival was greater at 6 years for NHB compared with CAD renal transplant recipients (80.9% vs. 77.8%, respectively; P=NS). Significant factors for allograft loss for NHB donor organ recipients included the following: organ used for repeat transplants; DGF; donor age older than 35 years; and head trauma as a cause of initial injury (relative risk 2.74, 1.90, 1.78, and 1.41, respectively).Although exhibiting elevated DGF rates, allograft and patient survival rates of transplants from NHB donor sources are equivalent to those from conventional CAD sources. Donor age, recipient transplant number, female recipient, mechanism of injury, and DGF were the most pertinent variables leading to poor outcomes.

Previous studies have shown more women than men among living donors (LD) and more men among recipients of those kidneys. In this study, we compared the evolving demographics of LD transplants.We retrospectively analyzed all LD transplants performed in our center between 1964 and 2000.Among 1182 LD cases, 1035 (88%) were biologically related (LRD) and 147 (12%) were unrelated (LURD). LURD donors and recipients were significantly older than LRD donors and recipients, respectively (P=0.0001). More LURD allograft recipients were male (71%) compared with LRD recipients (57%) (P=0.0013). The proportion of female donors was 55% in both groups. Spousal donations were predominantly wife-to-husband (69%). Compared with the LRD group, there was a greater proportion of female-to-male LURD transplants (46 vs. 30%) and a smaller proportion of female-to-female LURD transplants (10 vs. 25%) (P=0.0001). When spousal pairs were excluded from the analysis, there was a higher proportion of male-to-male (48 vs. 27%) donations and a lower proportion of male-to-female (18 vs. 9%) and female-to-female (25 vs. 17%) transplants in the LURD group (P=0.001).Gender disparities in LD transplantation are primarily due to a higher proportion of wife-to-husband donations and a lower incidence of male-to-female grafts among nonspousal LURD transplants. Strategies should be devised to ensure access for women to renal transplantation and to encourage and facilitate donation by men.

Effect of waiting time on renal transplant outcome.BackgroundNumerous factors are known to impact on patient survival after renal transplantation. Recent studies have confirmed a survival advantage for renal transplant patients over those waiting on dialysis. We aimed to investigate the hypothesis that longer waiting times are more deleterious than shorter waiting times, that is, to detect a “dose effect” for waiting time.MethodsWe analyzed 73,103 primary adult renal transplants registered at the United States Renal Data System Registry from 1988 to 1997 for the primary endpoints of death with functioning graft and death-censored graft failure by Cox proportional hazard models. All models were corrected for donor and recipient demographics and other factors known to affect outcome after kidney transplantation.ResultsA longer waiting time on dialysis is a significant risk factor for death-censored graft survival and patient death with functioning graft after renal transplantation (P < 0.001 each). Relative to preemptive transplants, waiting times of 6 to 12 months, 12 to 24 months, 24 to 36, 36 to 48, and over 48 months confer a 21, 28, 41, 53, and 72% increase in mortality risk after transplantation, respectively. Relative to preemptive transplants, waiting times of 0 to 6 months, 6 to 12 months, 12 to 24 months, and over 24 months confer a 17, 37, 55, and 68% increase in risk for death-censored graft loss after transplantation, respectively.ConclusionsLonger waiting times on dialysis negatively impact on post-transplant graft and patient survival. These data strongly support the hypothesis that patients who reach end-stage renal disease should receive a renal transplant as early as possible in order to enhance their chances of long-term survival.