Successful Simultaneous Liver-Kidney Transplantation in the Presence of Multiple High-Titered Class I and II Antidonor HLA Antibodies.

The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents. The kidney transplant was delayed by 6 hours after the liver transplant to allow more time to the liver allograft to "absorb" donor-specific antibodies (DSA). Interestingly, the liver allograft did not prevent immediate antibody-mediated injury to the kidney allograft in this highly sensitized recipient. Anti-HLA single antigen bead analysis of liver and kidney allograft biopsy eluates revealed deposition of both class I and II DSA in both liver and kidney transplants during the first 2 weeks after transplant. Afterward, both liver and kidney allograft functions improved and remained normal after a year with progressive reduction in serum DSA values.

Pharmacogenomic assessment of Mexican and Peruvian populations.

BACKGROUND: Clinically relevant polymorphisms often demonstrate population-specific allele frequencies. Central and South America remain largely uncategorized in the context of pharmacogenomics. MATERIALS & METHODS: We assessed 15 polymorphisms from 12 genes (ABCB1 3435C>T, ABCG2 Q141K, CYP1B1*3, CYP2C19*2, CYP3A4*1B, CYP3A5*3C, ERCC1 N118N, ERCC2 K751Q, GSTP1 I105V, TPMT 238G>C, TPMT 460G>A, TPMT 719A>G, TYMS TSER, UGT1A1*28 and UGT1A1 -3156G>A) in 81 Peruvian and 95 Mexican individuals. RESULTS: Six polymorphism frequencies differed significantly between the two populations: ABCB1 3435C>T, CYP1B1*3, GSTP1 I105V, TPMT 460G>A, UGT1A1*28 and UGT1A1 -3156G>A. The pattern of observed allele frequencies for all polymorphisms could not be accurately estimated from any single previously studied population. CONCLUSION: This highlights the need to expand the scope of geographic data for use in pharmacogenomics studies.

Urine Discoloration Associated With Metronidazole: A Rare Occurrence.

Objective: To report a case of metronidazole-induced urine discoloration in a patient with Clostridium difficile sepsis. Case Summary: A 52-year old man was admitted with sepsis secondary to C difficile colitis, which developed after he had been recently treated with broad-spectrum antibiotics for community-acquired pneumonia. The C difficile infection was treated with metronidazole, and the patient subsequently developed cola-colored urine. When metronidazole was inadvertently stopped for 34 hours, the urine color returned to normal, but again darkened when the medication was restarted. The patient suffered no clinically adverse effects from the abnormal urine color. He completed the treatment course for colitis and was discharged to home. Discussion: Urine discoloration is a known side of metronidazole. However, it has been poorly reported in the literature, and many clinicians are unaware that it may happen. Here we report the case of a patient who developed dark urine while receiving treatment with metronidazole. Other potential causes of the urine discoloration were explored, including hemolysis, rhabdomyolysis, or adverse reactions to other medications, with no clear positive findings. An objective causality assessment (Naranjo probability scale) revealed that the urine discoloration was probably due to metronidazole. Conclusions: Metronidazole can cause urine discoloration without otherwise harming the patient. Clinicians should be aware of this potential side effect and provide reassurance to patients who develop abnormal urine that there are no clinically relevant adverse outcomes.

Examination of baseline risk factors for QTc interval prolongation in patients prescribed intravenous haloperidol.

BACKGROUND: Intravenous haloperidol can increase the risk for corrected QT interval (QTc) prolongation, torsades de pointes (TdP) and sudden death. There are a number of risk factors reported in the literature for QTc prolongation and TdP with intravenous haloperidol. OBJECTIVE: The purpose of this study was to determine the prevalence of baseline risk factors for QTc prolongation and TdP in hospitalized medical inpatients prescribed intravenous haloperidol. METHODS: This is a retrospective cohort study of medically ill hospitalized inpatients prescribed intravenous haloperidol between 30 June 2007 and 1 January 2010. Records were ascertained for the presence of baseline risk factors for QTc prolongation and TdP. RESULTS: A total of 175 subjects were identified as receiving intravenous haloperidol during the study period. Mean age was 62.9 ± 19.1 years, and 48.6% of subjects were female. At baseline, 85.7% of subjects had ≥1 risk factor for QTc prolongation and TdP, with the majority of these subjects (58.0%) having between two and five risk factors. Of the total study sample, 74.9% had a baseline ECG; mean QTc value was 457 msec (± 40.8 msec). Greater than 50% of subjects had a sex-specific QTc value higher than the increased risk threshold of 450 msec in males or 460 msec in females at baseline. Following intravenous haloperidol administration, 46.9% of subjects had a follow-up ECG obtained within 24 hours. At the time of intravenous haloperidol administration, 93.1% of subjects had a potassium value available and 62.9% had a magnesium value. Approximately 30% of subjects had either a potassium or magnesium value below the normal laboratory range. Of the 175 subjects, 43.4% were taking ≥1 concomitant QTc prolongation medication at the time of intravenous haloperidol administration. CONCLUSIONS: Consistent with previously published reports, patients in this study prescribed intravenous haloperidol had multiple risk factors, both modifiable and non-modifiable, at baseline for QTc prolongation and TdP. The modifiable risk factors may be important targets of interventions aimed at optimizing the safety of the use of intravenous haloperidol, while the non-modifiable risk factors may warrant closer scrutiny with consideration of alternative therapies and continuous monitoring.