Communication gaps associated with donor-derived infections.

The detection and management of potential donor-derived infections is challenging, in part due to the complexity of communications between diverse labs, organ procurement organizations (OPOs), and recipient transplant centers. We sought to determine if communication delays or errors occur in the reporting and management of donor-derived infections and if these are associated with preventable adverse events in recipients. All reported potential donor-derived transmission events reviewed by the Organ Procurement and Transplantation Network Ad Hoc Disease Transmission Advisory Committee from January 2008 to June 2010 were evaluated for communication gaps between the donor center, OPO and transplant centers. The impact on recipient outcomes was then determined. Fifty-six infection events (IEs; involving 168 recipients) were evaluated. Eighteen IEs (48 recipients) were associated with communication gaps, of which 12 resulted in adverse effects in 69% of recipients (20/29), including six deaths. When IEs and test results were reported without delay, appropriate interventions were taken, subsequently minimizing or averting recipient infection (23 IEs, 72 recipients). Communication gaps in reported IEs are frequent, occur at multiple levels in the communication process, and contribute to adverse outcomes among affected transplant recipients. Conversely, effective communication minimized or averted infection in transplant recipients.

De novo sirolimus and reduced-dose tacrolimus versus standard-dose tacrolimus after liver transplantation: the 2000-2003 phase II prospective randomized trial.

We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared to standard-dose tacrolimus, after liver transplantation is safe, tolerated and efficacious. In an international multicenter, open-label, active-controlled randomized trial (2000-2003), adult primary liver transplant recipients (n=222) were randomly assigned immediately after transplantation to conventional-dose tacrolimus (trough: 7-15 ng/mL) or sirolimus (loading dose: 15 mg, initial dose: 5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough: 3-7 ng/mL). The study was terminated after 21 months due to imbalance in adverse events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%, p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of acute cellular rejection were similar between the two groups. Early use of sirolimus using a loading dose followed by maintenance doses and reduced-dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss, death and sepsis when compared to the use of conventional-dose tacrolimus alone.

Donor-transmitted malignancies in organ transplantation: assessment of clinical risk.

The continuing organ shortage requires evaluation of all potential donors, including those with malignant disease. In the United States, no organized approach to assessment of risk of donor tumor transmission exists, and organs from such donors are often discarded. The ad hoc Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) formed an ad hoc Malignancy Subcommittee to advise on this subject. The Subcommittee reviewed the largely anecdotal literature and held discussions to generate a framework to approach risk evaluation in this circumstance. Six levels of risk developed by consensus. Suggested approach to donor utilization is given for each category, recognizing the primacy of individual clinical judgment and often emergent clinical circumstances. Categories are populated with specific tumors based on available data, including active or historical cancer. Benign tumors are considered in relation to risk of malignant transformation. Specific attention is paid to potential use of kidneys harboring small solitary renal cell carcinomas, and to patients with central nervous system tumors. This resource document is tailored to clinical practice in the United States and should aid clinical decision making in the difficult circumstance of an organ donor with potential or proven neoplasia.

Derivation of the uncontrolled donation after circulatory determination of death protocol for New York city.

Evidence from Europe suggests establishing out-of-hospital, uncontrolled donation after circulatory determination of death (UDCDD) protocols has potential to substantially increase organ availability. The study objective was to derive an out-of-hospital UDCDD protocol that would be acceptable to New York City (NYC) residents. Participatory action research and the SEED-SCALE process for social change guided protocol development in NYC from July 2007 to September 2010. A coalition of government officials, subject experts and communities necessary to achieve support was formed. Authorized NY State and NYC government officials and their legal representatives collaboratively investigated how the program could be implemented under current law and regulations. Community stakeholders (secular and religious organizations) were engaged in town hall style meetings. Ethnographic data (meeting minutes, field notes, quantitative surveys) were collected and posted in a collaborative internet environment. Data were analyzed using an iterative coding scheme to discern themes, theoretical constructs and a summary narrative to guide protocol development. A clinically appropriate, ethically sound UDCDD protocol for out-of-hospital settings has been derived. This program is likely to be accepted by NYC residents since the protocol was derived through partnership with government officials, subject experts and community participants.

Donor-derived disease transmission events in the United States: data reviewed by the OPTN/UNOS Disease Transmission Advisory Committee.

Donor-derived disease transmission is increasingly recognized as a source of morbidity and mortality among transplant recipients. Policy 4.7 of the Organ Procurement and Transplantation Network (OPTN) currently requires reporting of donor-derived events. All potential donor-derived transmission events (PDDTE) reported to OPTN/UNOS were reviewed by the Disease Transmission Advisory Committee (DTAC). Summary data from January 1, 2005-December 31, 2007, were prepared for presentation. Reports of PDDTE have increased from 7 in 2005, the first full year data were collected, to 60 in 2006 and to 97 in 2007. More detailed information is available for 2007; a classification system for determining likelihood of donor-derived transmission was utilized. In 2007, there were four proven and one possible donor-derived malignancy transmissions and four proven, two probable and six possible donor-derived infectious diseases transmissions. There were nine reported recipient deaths attributable to proven donor transmissions events arising from eight donors during 2007. Although recognized transmission events resulted in significant morbidity and mortality, transmission was reported in only 0.96% of deceased donor donations overall. Improved reporting, through enhanced recognition and communication, will be critical to better estimate the transmission risk of infection and malignancy through organ transplantation.

Transmission of anaplastic large cell lymphoma via organ donation after cardiac death.

Recently, donation after cardiac death (DCD) has been encouraged in order to expand the donor pool. We present a case of anaplastic T-cell lymphoma transmitted to four recipients of solid organ transplants from a DCD donor suspected of having bacterial meningitis. On brain biopsy, the donor was found to have anaplastic central nervous system T-cell lymphoma, and the recipient of the donor's pancreas, liver and kidneys were found to have involvement of T-cell lymphoma. The transplanted kidneys and pancreas were excised from the respective recipients, and the kidney and pancreas recipients responded well to chemotherapy. The liver recipient underwent three cycles of chemotherapy, but later died due to complications of severe tumor burden. We recommend transplanting organs from donors with suspected bacterial meningitis only after identification of the infectious organism. In cases of lymphoma transmission, excision of the graft may be the only chance at long-term survival.

Immunohistochemical detection of hepatitis C antigen by monoclonal antibody TORDJI-22 compared with PCR viral detection.

We sought to determine the sensitivity and specificity of immunohistochemistry using the TORDJI-22 MoAb (BioGenex, San Ramon, Calif), which is specific for the C-100 protein of the hepatitis C virus, compared with reverse transcriptase-polymerase chain reaction (RT-PCR) of tissue for viral RNA. RT-PCR had been performed on 52 fixed tissue specimens. Immunohistochemistry was performed using prediluted antibody with the alkaline phosphatase/fast red (BioGenex) technique. Predigestion with Protease XXIV (BioGenex) and other procedures followed the manufacturer's protocols. Positive immunohistochemistry was narrowly defined as tightly clumped, perinuclear red granules in hepatocytes. Of the specimens, 28 were positive by RT-PCR. With RT-PCR as the standard of comparison, immunohistochemistry yielded a sensitivity of 70% and specificity of 84%. Positive cells, when present, were usually very rare. With stringent criteria, immunohistochemistry with the TORDJI-22 monoclonal antibody is a very specific, fairly sensitive diagnostic test for hepatitis C virus in fixed liver tissues.

Pharmacokinetics of ceftriaxone in liver-transplant recipients.

The disposition of ceftriaxone was studied after a single 2 g intravenous dose in seven patients 3 to 5 days after liver transplantation. Ceftriaxone concentrations in plasma, urine, and bile were measured by HPLC, and plasma protein binding was determined by equilibrium dialysis. Plasma protein binding was nonlinear, and the unbound fraction varied between 0.05 and 0.56. Both capacity and affinity were markedly different from reported values for normal subjects. The pharmacokinetic parameters obtained were: total body clearance (TBC), 11.2 +/- 7.8 mL/hr/kg total and 44.8 +/- 29.1 mL/hr/kg unbound; volume of distribution (V(area)), 224 +/- 76 mL/kg total and 767 +/- 432 mL/kg unbound; steady-state volume of distribution (Vss), 212 +/- 68 mL/kg total and 651 +/- 368 mL/kg unbound; terminal disposition half-life (t1/2), 21.6 +/- 14.3 hour total and 16.3 +/- 11.1 hour unbound. TBC for both total and free drug was considerably lower than literature values for normal subjects. V(area) for total drug was greater than normal, whereas the corresponding value for free drug was smaller than normal. The plasma ceftriaxone concentrations at 12 and 24 hours were above the reported minimum inhibitory concentration (MIC). The fraction of the administered dose excreted in urine over 24 hours was 38 +/- 29% and did not differ markedly from that reported for normal subjects. Less than 2% of the administered dose was excreted in 24-hour bile; however, biliary concentrations were always above MIC. Ceftriaxone can be administered once or twice daily at a dose of 2 g/day for prophylaxis in liver transplant recipients.

Oral contraceptive history as a risk indicator in patients with pituitary tumors with hyperprolactinemia: a case comparison study of twenty patients.

This report presents a retrospective case comparison study of 20 hyperprolactinemic patients with pituitary adenomas treated at the Mount Sinai Hospital (1976-1079). An association between oral contraceptive (OC) use and 20 subjects with pituitary tumors was substantiated using discordant paired analysis. The comparison group consisted of appendectomy patients admitted during the same time period and matched for sex and age. The estimated relative risk was 4.0 (P less than 0.025). This study suggests that there is a significant association between OC use and pituitary tumors associated with hyperprolactinemia.

PIP: A retrospective case-comparison study of 20 hyperprolactinemic patients with pituitary adenomas is presented. Cases were from the period 1976-1979. Using discordant paired analysis, an association between oral contraceptive use and 20 subjects with pituitary tumors was substantiated. For comparison, a group of appendectomy patients admitted during the same time period and matched for sex and age was studied. An estimated relative risk of 4 (P .025) was found based on this comparison, and it is concluded that a significant association between use of oral contraceptives and pituitary tumors associated with hyperprolactinemia is suggested.

Nutritional support after liver transplantation: a randomized prospective study.

Nutritional support in patients with advanced cirrhosis is difficult due to protein, fluid and salt restrictions. Successful liver transplantation should improve nutrient tolerance. We randomly assigned 28 hypoalbuminemic cirrhotic patients to receive, immediately after liver transplantation, one of three regimens: group 1, no nutritional support (n = 10); group 2, total parenteral nutrition (TPN) (35 kcal/kg/day) with standard amino acids (1.5 g/kg/day) (n = 8); or group 3, isocaloric isonitrogenous TPN with added branched-chain amino acids (n = 10). Therapy was continued for 7 days posttransplant. Jaundice resolution was unaffected by nutritional support. Nitrogen balance favored both TPN groups. Branched-chain amino acid (BCAA) aromatic amino acid ratios were highest in group 3. Coma scores and serum ammonia levels were similar in all groups. Both TPN groups achieved respirator independence earlier; this difference was not statistically significant. Group 1 patients stayed longest in ICU; the difference was statistically significant. TPN with either standard or BCAA- enriched amino acids is tolerated well immediately after successful liver transplant. Positive nitrogen balance is achieved; large protein loads do not worsen encephalopathy. Nutritional support may improve respiratory muscle function, allowing earlier weaning from ventilatory support. A shortened length of ICU stay justifies the expense of TPN.

Case studies in orthotopic liver transplantation for hepatitis B: a panel discussion.

Five cases that were referred to the Division of Transplantation at NYU School of Medicine for consideration for liver transplantation were discussed among a panel of hepatitis B and liver transplant experts. Opinions were obtained on the management at every stage of treatment of patients with the following initial information: Case one: young Asian woman in stage IV hepatic coma; intubated; prothrombin time (PT): 30 s; serum glutamic oxaloacetic transaminase (SGOT): 8,000 IU; total bilirubin: 25 mg/dL; hepatitis B surface antigen (HBsAg) positive. Case two: 70-yr-old woman, native of Greece; decompensated cirrhosis with encephalopathy; Child-Pugh Class C; HBsAg positive; hepatitis B surface antibody (HBsAb) negative; hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBeAb) negative; hepatitis B virus (HBV) DNA titer: 10,000. Case three: Muscular detective working full-time; cirrhosis; Child Pugh Class B; ascites controlled with spironolactone and furosemide; PT: 19s; HBsAg positive; HBsAb negative; HBV DNA titer: 50,000; low platelet count. Case four: 45-yr-old baker; cirrhosis and resectable 4-cm hepatoma; Child-Pugh Class B; PT: 16 s; Blood type O; United Network for Organ Sharing (UNOS) 2B; HBV DNA titer: 3,000. Case five: 40-yr-old Indian man; 300 pounds with massive ascites; Child Pugh Class C; PT: 17 s; HBsAg positive; HBV DNA titer: 22,000; transplanted with intra-operative hypotension; tacrolimus; graft functioning; HBIg 10,000 IU intra-operative and around the clock during the first post-operative week; required huge doses of hepatitis B immune globulin (HBIg) to maintain adequate HBsAb level; daily loss of 5 6 L of ascites fluid; post-operative day 8: anuric, blood urea nitrogen (BUN) 127, creatinine 3, mental status changes.

Transplantation in the hepatitis B patient and current therapies to prevent recurrence.

Hepatitis B is the sixth most common indication for liver transplantation in the United States, accounting for about 7% of all transplants among adults. Transplantation for hepatitis B is especially problematic because the virus is not eradicated and there is great potential for reinfection that can lead to graft failure or death. This risk is higher still in patients with active viral replication and chronic liver disease. Treatment with short-term hepatitis B immune globulin (HBIG) delays reinfection of the allograft, but only long-term treatment with HBIG has led to a decline in the reinfection rate. Combination therapy using HBIG with nucleoside analogues will likely become the standard of care to maintain stable serum titers of protective anti-HBs antibody and to prevent posttransplantation reinfection.

Incidence and treatment of recurrent hepatitis C after liver transplantation.

Recurrence of hepatitis C is a significant problem after liver transplantation. This prospective study was done to assess the rate of recurrence and discuss two possible treatment modalities that have been successful in avoiding retransplantation. Twenty-one patients underwent orthotopic liver transplantation for hepatitis C at a metropolitan medical center over a 34-month period. The mean follow-up interval was 13.4 +/- 2.2 months (range 5-28 months). The patients were routinely evaluated with clinic visits and liver function tests, specifically total bilirubin, serum glutamic-oxaloacetic transaminase, and gamma-glutamyl transpeptidase. If values were elevated, the patient was admitted to the hospital for liver biopsy. Ten of the 21 patients demonstrated recurrence on biopsy. Two of 10 patients required no therapy. Interferon A was initiated in the remaining eight. Three of the eight patients had no significant response to interferon and were given intravenous ribavirin under an experimental protocol. Two of these three showed significant improvement in liver function values. The third died of chronic rejection. The incidence of recurrent hepatitis C after liver transplantation is significant. Many centers have had to resort to retransplantation. Our results show that with early detection and aggressive treatment with interferon and ribavirin, hepatitis C can be controlled and retransplantation may be avoided.