Urinary cell mRNA profiles and differential diagnosis of acute kidney graft dysfunction.

Noninvasive tests to differentiate the basis for acute dysfunction of the kidney allograft are preferable to invasive allograft biopsies. We measured absolute levels of 26 prespecified mRNAs in urine samples collected from kidney graft recipients at the time of for-cause biopsy for acute allograft dysfunction and investigated whether differential diagnosis of acute graft dysfunction is feasible using urinary cell mRNA profiles. We profiled 52 urine samples from 52 patients with biopsy specimens indicating acute rejection (26 acute T cell-mediated rejection and 26 acute antibody-mediated rejection) and 32 urine samples from 32 patients with acute tubular injury without acute rejection. A stepwise quadratic discriminant analysis of mRNA measures identified a linear combination of mRNAs for CD3ε, CD105, TLR4, CD14, complement factor B, and vimentin that distinguishes acute rejection from acute tubular injury; 10-fold cross-validation of the six-gene signature yielded an estimate of the area under the curve of 0.92 (95% confidence interval, 0.86 to 0.98). In a decision analysis, the six-gene signature yielded the highest net benefit across a range of reasonable threshold probabilities for biopsy. Next, among patients diagnosed with acute rejection, a similar statistical approach identified a linear combination of mRNAs for CD3ε, CD105, CD14, CD46, and 18S rRNA that distinguishes T cell-mediated rejection from antibody-mediated rejection, with a cross-validated estimate of the area under the curve of 0.81 (95% confidence interval, 0.68 to 0.93). Incorporation of these urinary cell mRNA signatures in clinical decisions may reduce the number of biopsies in patients with acute dysfunction of the kidney allograft.

Segment 4 architecture and proposed parenchyma-wise technique for Ex vivo graft procurement and implantation.

A parenchyma-wise technique for the ex vivo procurement of segment 4 (S4) grafts, based on the detailed architecture of the segment, is proposed. Eighteen normal, fresh livers from adult cadavers were injected differentially with colored latex; dissection casts were prepared; and the intricate architecture of S4 was studied. The portal vein elements of the sheath forming most of the inferior part of S4 (S4b) and the superficial major fraction of its superior part (S4a) arose constantly from the medial aspect of the umbilical part of the left portal vein branch. The arterial elements arose constantly from a branch, whose diameter ranged from 2.00 to 3.35 mm (mean = 2.61 ± 0.54 mm) and whose length ranged from 15.15 to 45.65 mm (mean = 27.98 ± 12.13 mm). The biliary elements coalesced as a single duct at the corner, which was formed from the umbilical and transverse parts of the left portal vein branch; the duct's diameter ranged from 2.90 to 6.85 mm (mean = 3.90 ± 1.34 mm). Theoretically, this parenchymal mass-S4b and the superficial fraction of S4a-could be procured for implantation in an infant, and the rest of the liver could be split for an adult and a child. The portal vein branches of the graft would be procured with a patch from the medial aspect of the donor's umbilical portion of the left portal vein branch. This umbilical portion would be reconstructed with a patch from the donor's round ligament. The recipient's portal vein would be reconstructed through the fashioning of a conduit anastomosed with the graft's venous patch.

Organ transplantation in Egypt.

Concern has increasingly been expressed about the growing number of reports of medical personnel participating in the transplantation of human organs or tissues taken from the bodies of executed prisoners, handicapped patients, or poor persons who have agreed to part with their organs for commercial purposes. Such behavior has been universally considered as ethically and morally reprehensible, yet in some parts of the world the practice continues to flourish. The concept of justice demands that every person have an equal right to life, and to protect this right, society has an obligation to ensure that every person has equal access to medical care. Regrettably, the Egyptian system does not legally recognize brain death and continues to allow the buying and selling of organs. For more than 30 years in Egypt, the ability to pay has determined who receives an organ and economic need has determined who will be the donor. As transplant professionals, it is important that we advocate on behalf of all patients, potential recipients, and donors and for those who are left out and not likely to receive a donor organ in an economically based system. Current issues associated with this debate are reviewed and recommendations about how to address them in Egypt are discussed.

Computational analysis of Nitinol stent-graft for endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA): Crimping, sealing and fluid-structure interaction (FSI).

OBJECTIVES: We evaluate the crimping strain, sealing stress and contact forces on a Nitinol stent deployed in the aorta during endovascular aortic (or aneurysm) repair (EVAR) procedures. Nitinol shape memory effect (SME) is used. We also study the fluid-structure interaction (FSI) of the blood flow on the stented aorta. METHODS: We employ Solidworks to generate a closed-cell honeycomb stent structure used to treat abdominal aortic aneurysm (AAA). We use the commercial Abaqus/Simulia finite element (FEM) simulation package to study the displacements and stresses experienced by the stent during the crimping phase and deployment into the aortic segment. The Nitinol stent is covered with Dacron, a popular graft material. We implement our own user-material (UMAT) subroutines to model the shape memory effect (SME) of Nitinol. The effect of the stent geometry is analyzed. We use the FSI analysis in Abaqus/Simulia to understand the effect of hemodynamic loading on the stent. RESULTS: Results indicate that the crimping strain increases as the stent strut spacing increases. This is also the case for the radius of curvature. Maximum strains developed on the stent during crimping are in the order of 10%. Stresses exerted by the stent needed to completely seal the aorta are found to be below the yield stress values of Nitinol (700 MPa). Wall shear stresses (WSS) on the stented aorta are close to WSS obtained on the aorta alone. CONCLUSION: Using Nitinol's thermo-reactivity property as opposed to its superelasticity causes the stent-graft to deploy more gently.

Fluid-structure interaction (FSI) analysis of stent-graft for aortic endovascular aneurysm repair (EVAR): Material and structural considerations.

The effect of hemodynamic load on various stent-graft designs used for endovascular aneurysm repair (EVAR) in cardiovascular treatments is studied using a numerical fluid-structure interaction (FSI) analysis that couples computational fluid dynamics (CFD) and finite element analysis (FEA). Radial displacements, mechanical stresses, wall shear stress and wall compliance quantities are evaluated for four stent materials and one graft material. The strut thickness is varied from 0.3 mm to 1 mm. The materials are assumed linearly elastic and isotropic while blood is assumed as a Newtonian and incompressible medium with a pulsatile and turbulent flow profile. Time dependent pressure conditions are assumed at the inlet and outlet. Results are benchmarked against a study taken from the literature and indicate that the stent material and the strut thickness greatly influence the mechanical behavior of the structure. This computational study will serve as an additional tool to vascular surgeons when assessing the choice of material and design for stent-graft recipients.

Compatible ABO mismatch and liver transplantation: a single center's experience.

OBJECTIVES: The current shortage of suitable donor organs and clinical urgency can lead to implanting grafts from ABO-mismatched donors. One-year graft survival rates for patients in this scenario have been reported as ranging between 25% and 75% less than those for ABO-identical or ABOcompatible grafts. We review and compare our experiences with transplanting ABO-identical and ABO-compatible mismatched livers. MATERIALS AND METHODS: Considering orthotopic liver transplantation (OLTx), 520 were performed at our institution between November 1992 and May 2003, 55 of which were ABO-compatible mismatched transplants. We retrospectively reviewed the data and compared patient and graft survival rates. RESULTS: Overall 1-month and 1-, 5-, and 10-year patient survival rates among identical (group 1) and mismatched (group 2) groups were 97% and 91%, 90%, and 88.5%, and 79%, and 74%, 66%, and 65%, respectively. No significant difference existed between the 2 groups (P>.05). Similarly, 1-month, and 1-, 5-, and 10-year graft survival rates among groups 1 and 2 were 96% and 87%, 89% and 83%, 78% and 71% and 66% and 59%, respectively; these were not significant either (P>.05). All of the patients in the mismatched group had a high status according to the United Network for Organ Sharing (UNOS). Only 1 person received an incompatible mismatched graft (B to A), which subsequently developed primary nonfunction. CONCLUSIONS: ABO-compatible mismatch OLTx is unavoidable given the current state of organ shortage. Our results suggest that this type of OLTx can be performed with minimal risk among patients who require urgent transplantation and have high rankings according to the UNOS and the model for end-stage liver disease (MELD) system.

Pedophiles and stalkers as transplant candidates: one program's experience.

Transplant assessment of pedophiles and stalkers presents a challenge for clinicians and requires the ability to separate the science from the hysteria. Although rarely seen in organ transplant clinics, the presence of psychosexual disorders can result in both criminal charges and harsh societal reactions. Clinicians must be able to assess and make informed recommendations about the suitability of the candidate and any potential risks for staff, other patients, and society at large. Six patients (5 pedophiles and 1 stalker) were assessed at our major regional multiorgan transplant program; each patient presented with unique and challenging assessment, treatment, and selection issues for the transplant team. The objectives of this article are to raise awareness of the issues associated with pedophiles and stalkers, and to provide the basis for better-informed discussions based on one program's struggles with its candidate selection and follow-up.

Peri and postoperative pulmonary complications among cirrhotic individuals.

Surgical intervention among cirrhotic individuals carries a high risk for peri-and postoperative complications. We review the literature regarding the frequency and consequences of pulmonary complications in cases of cirrhosis. The experience with hepato-pulmonary syndrome and porto-pulmonary hypertension in liver transplant recipients is also presented.

Unusual presentation of hepatic vascular tumors as fulminant hepatic failure.

Epithelioid hemangioendothelioma and angiosarcoma of the liver are rare neoplasms of vascular origin. They can present with nonspecific symptoms such as malaise and weight loss, as well as with liver-related symptoms such as abdominal pain, tender hepatomegaly and jaundice. Portal hypertension and rarely liver failure can occur. We hereby report two cases of fulminant hepatic failure that were eventually diagnosed with epithelioid hemangioendothelioma and angiosarcoma of the liver.

Experience with liver dialysis in acetaminophen induced fulminant hepatic failure: a preliminary report.

BACKGROUND/AIMS: Our aim was to assess the efficacy of the liver dialysis unit (LDU) in the treatment of patients with acetaminophen-induced fulminant hepatic failure. METHODS: Seventeen patients with acetaminophen-induced fulminant hepatic failure between January 1996 and December 2001 were retrospectively studied. A liver dialysis unit became available in our Unit in July 2000, and as of December 2001, four of these 17 patients had undergone treatment with liver dialysis. RESULTS: Mean age was 29 years (range: 14-47) and 76% were women. Four of 17 patients underwent a total of 12 (range: 1-4) LDU sessions. Ammonia level tended to be lower following the LDU and all four patients recovered without a need for orthotopic liver transplantation (OLT). Prior to July 2000, eight of 13 patients survived with supportive therapy, three expired and two underwent OLT. No major bleeding episodes were observed during the LDU course. A significant difference was found between the three cases who died and the cases that survived with respect to the grade of encephalopathy (p<0.001). There was significant difference in the admission serum creatinine among survivors (p<0.05). CONCLUSION: In conclusion, the Liver Dialysis Unit treatment appeared to benefit patients with acetaminophen-induced fulminant hepatic failure by reverse of the encephalopathy and spontaneous recovery of the damaged liver in selected patients.

Portal, superior mesenteric and splenic vein thrombosis secondary to hyperhomocysteinemia with pernicious anemia: a case report.

INTRODUCTION: Acute portomesenteric vein thrombosis is an uncommon but serious condition with potential sequelae, such as small-bowel gangrene and end-stage hepatic failure. It is known to be caused by various pro-thrombotic states, including hyperhomocysteinemia. We describe what is, to the best of our knowledge, the first reported case of concomitant thrombosis of portal, superior mesenteric and splenic veins due to hyperhomocysteinemia secondary to pernicious anemia and no other risk factors. CASE PRESENTATION: A 60-year-old Indian man presented with epigastric pain, diarrhea and vomiting. An abdominal imaging scan showed that he had concomitant pernicious anemia and concomitant portal, superior mesenteric and splenic vein thrombosis. A work-up for the patient's hypercoagulable state revealed hyperhomocysteinemia, an undetectable vitamin B12 level and pernicious anemia with no other thrombophilic state. He developed infarction with perforation of the small bowel and subsequent septic shock with multi-organ dysfunction syndrome, and he ultimately died due to progressive hepatic failure. CONCLUSION: This report demonstrates that pernicious anemia, on its own, can lead to hyperhomocysteinemia significant enough to lead to lethal multiple splanchnic vein thrombosis. Our case also underscores the need to (1) consider portomesenteric thrombosis in the differential diagnosis of epigastric abdominal pain, (2) perform a complete thrombotic work-up to elucidate metabolic abnormalities that could be contributing to a pro-thrombotic state and (3) initiate aggressive measures, including early consideration of multi-visceral transplantation, in order to avoid decompensation and a significant adverse outcome.

Knowledge and attitudes of health care professionals toward organ donation and transplantation.

To identify and assess the level of knowledge and attitudes of health care professionals (HCP) in Qatar toward organ donation and transplantation, this cross-sectional study was carried out from October 2007 to February 2008 in the Accident and Emergency Departments and Intensive Care Units of the hospitals of the Hamad Medical Corporation (HMC). A representative sample of 585 HCP working in the hospitals of the HMC was approached and 418 staff gave consent to participate in the study (71.5%). 36.8% were physicians, 48.6% nurses and 14.6% Emergency Medical Service (EMS) technicians. Of the surveyed HCP, 40.7% were males and 59.3% were females. Majority of the staff were in the age group of 30-39 years (58.6%). More than half of the physicians (59.7%) and technicians (57.4%) assumed that organs can be bought and sold in the State of Qatar. Most of the physicians (76.6%) and nurses (75.9%) knew that brain-dead persons are eligible for organ donation, whereas only 57.4% of the EMS technicians thought so. Majority of the HCP supported organ donation; physicians (89.0%), nurses (82.3%) and technicians (70.5%). The attitude of the physicians (24.0%) and nurses (20.2%) to donate a kidney to a family member was very poor compared with the attitude of the technicians (44.3%). Although the HCP support organ donation (83%), more than half of the physicians (51.3%), nurses (61.6%) and technicians (54.1%) wanted to be buried with all their organs intact. The findings, although they give cause for hope, suggest that there is much work yet to be done before organ donation and transplantation can become fully accepted by the medical community in Qatar.

Multiplex cytokine profiling of initial therapeutic response in patients with chronic hepatitis C virus infection.

Currently available prognostic tools are inadequate to discern the molecular basis of the heterogenic response in hepatitis C virus (HCV)-infected patients treated with the current standard of therapy. The expression and biological function of immune mediators have been shown to be critical in all phases of the immune response to HCV infection and likely therefore influence host response. Herein, a biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effects of host response in 10 HCV patients. Serum levels of 17 cytokines were compared before and after 1 month of treatment and against controls. Overall serum cytokine levels were significantly higher in patients (P < 0.05) than controls. Additionally, viral titers decreased in all patients after 1 month of therapy, as did overall serum cytokine levels in the cohort (P < 0.05). To assess relationships between changes in cytokine levels and changes in viral titer, the cohort was divided into three statistically distinct subgroups based on changes in viral titers. Specific sets of cytokines decreased in each group: decreases in CCL4, interleukin (IL)-2, CXCL8, and IL-1beta correlated with the greatest drops in viral titer, decreases in IL-5, granulocyte colony stimulating factor (G-CSF), and CCL4 correlated with moderate drops in viral titer, and only CCL2 correlated with the lowest drops in viral titer. Interestingly, decreases in CCL4 levels correlated with decreases in viral titers in all patients. CCL4 controls leukocyte influx and thus propagates inflammation. In conclusion, these data raise the possibility that characteristic changes in host response modulate the therapeutic response, demonstrating the prognostic power of serum cytokine profiling in chronic HCV.