Case report: Fatal hepatic failure after aortic valve replacement and sevoflurane exposure

PURPOSE: To report a case of lethal hepatotoxicity possibly caused by sevoflurane. CLINICAL FEATURES: A 76-yr-old woman with a history of four previous minor surgical procedures developed acute liver failure after general anesthesia with sevoflurane, sufentanil and propofol for aortic valve replacement. After an uneventful procedure the patient was extubated 4.5 hr after surgery. On the second postoperative day, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased. On the third postoperative day liver failure occurred, ALT peaked at 10504 UxL(-1) and AST at 15516 UxL(-1), and coagulopathy with an international normalized ratio of 4.6 developed. Liver transplantation was considered but rejected as a therapeutic option. The patient died three days after the operation in multiple organ failure triggered by hepatic failure. Other possible causes for liver failure were excluded. CONCLUSIONS: Sevoflurane hepatitis as a cause for liver failure may be implicated in this patient undergoing valve surgery. Unlike other halogenated anesthetic drugs, sevoflurane is not metabolized to hepatotoxic trifluoroacetyl proteins. However, compound A may react with proteins and may be transformed into antigenic material. We suggest that all halogenated anesthetics may be implicated with acute liver injury.     

Chemotherapy in the post-MVAC era: the case for adjuvant chemotherapy

Radical cystectomy for muscle invasive and locally advanced bladder cancer is the standard treatment modality in most of the Western industrialised countries. Rates of perioperative mortality from radical cystectomy have decreased to less than 2% over the past two decades due to advances in surgical technique and perioperative care. However, at least 40% of patients with pT3 bladder cancer and 70% of patients with lymph node-positive disease develop tumour recurrence after radical treatment within the first 5 years when treated with radical cystectomy alone. After the efficacy of combination chemotherapy for metastatic urothelial cancer using methotrexate, vinblastine, adriamycin and cisplatin (MVAC) was first described in 1985, several cisplatin-based systemic regimens have been investigated as adjunctive treatment before or after therapy for locally advanced bladder cancer by radical surgery or radiation therapy. Three randomised studies have reported superior results of postoperative adjuvant systemic chemotherapy compared to radical cystectomy alone for locally advanced bladder cancer. All three studies demonstrated a significant survival benefit for bladder cancer patients receiving adjuvant combination therapy. Studies have been criticised for small patient numbers and statistical shortcomings. New effective antineoplastic agents, such as paclitaxel and gemcitabine, have evolved during the past decade as promising substances for the treatment of urothelial cancer. This article reviews adjuvant studies from the era of MVAC combination chemotherapy, as well as contemporary studies that discuss new antineoplastic agents for systemic adjuvant chemotherapy of locally advanced bladder cancer.     

Minimizing oxidative stress by gene delivery of superoxide dismutase accelerates regeneration after transplantation of reduced-size livers in the rat.

Transplantation of reduced-size livers may lead to a hypermetabolic state and increased production of oxygen radicals. Since oxygen radicals may cause liver injury and impair liver regeneration, we tested the hypothesis that overexpression of superoxide dismutase (SOD) in reduced-size livers (RSL) would accelerate regeneration and reduce injury in a rat model of transplantation of RSL. Donor rats were infected with adenoviruses either expressing SOD1 (Ad.SOD1) or beta-galactosidase (Ad.lacZ). Livers were harvested 72 hours later, reduced to 45% of weight, and transplanted. After transplantation, hepatic SOD activity, graft survival, histopathology, AST/ALT release, and bilirubin were examined. Regeneration was evaluated by BrdU-staining, graft weight, and expression of cyclin D1 and p21. In Ad.SOD1-treated livergrafts, SOD activity increased three-fold compared to controls. Survival was dramatically increased in recipients of Ad.SOD1-RSL (100% vs. 20% in Ad.lacZ-RSL), and peak levels of AST/ALT and bilirubin levels were reduced by 75% and 87.5%, respectively (P < 0.001). In histological sections, hepatocyte necrosis decreased from 24% after Ad.lacZ-treatment to 6% after Ad.SOD1-treatment (P <0.001). Regeneration was also accelerated after Ad.SOD1-treatment as demonstrated by an increase of BrdU-stained cells 24 hours after reperfusion and increased liver weight after 1 week. In conclusion, overexpression of SOD1 in RSL prevents primary non-function of reduced-size liver grafts and accelerates liver regeneration.     

Treatment of osteoporosis after liver transplantation with ibandronate

Osteoporosis is a major side‐effect after liver transplantation (LTX). Therefore, the objective of the study was to evaluate the efficacy of ibandronate to reduce fractures after LTX. Seventy‐four patients after LTX were included in the study and measurements of bone mineral density (BMD) of lumbar spine and proximal femur using dual energy X‐ray absorptiometry (DEXA) were performed prior to and 3, 6, 12 and 24 months after surgery. The study group (IBA) consisted of 34 patients who received calcium (1 g/day), vitamin D3 (800–1000 IE/day) and ibandronate 2 mg every 3 months intravenously for 1 year. The control group consisted of 40 patients (CON) who received calcium and vitamin D3 at the same dosages. Prevalence of new fractures was predefined as primary endpoint. Changes of BMD and biochemical markers of bone metabolism were also investigated. In all patients, we found a reduction of BMD in the first few months after LTX. In the lumbar spine and the proximal femur the maximum reduction occurred 3 and 6 months post‐LTX. One and 2 years after transplantation, the group receiving ibandronate demonstrated a better recovery from loss of BMD and a significantly lower prevalence of fractures (IBA 2 vs. CON 10 P < 0.04, χ²). Ibandronate with calcium and vitamin D3 reduces the BMD‐loss after LTX and decreases the rate of bone fractures significantly.     

A single nucleotide polymorphism of macrophage migration inhibitory factor is related to inflammatory response in coronary bypass surgery using cardiopulmonary bypass.

OBJECTIVE: Cardiac surgery causes induction and release of inflammatory mediators that may be regulated by genetic background. Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator that is known to be up-regulated in patients undergoing cardiac operations. Here we analyzed genotype distribution and allele frequency of the MIF-173*G/C single nucleotide polymorphism (SNP) and MIF plasma levels in patients undergoing surgical revascularization with (on-pump, n=45) and without (off-pump, n=34) cardiopulmonary bypass (CPB). METHODS: Genotyping was performed using a real-time PCR-based system with a hybridization probe system specific for the MIF-173*G/C SNP. In on-pump patients, blood samples were drawn before start of CPB, after termination of CPB and 12h postoperatively. In off-pump patients, blood samples were collected before stabilizer placement, after removal of the stabilizer and 12h postoperatively. MIF levels were measured using ELISA technique. RESULTS: Genotype distribution and allele frequencies were comparable between on-pump and off-pump patients. When comparing patients according to MIF genotype, a significant increase of MIF plasma levels after completed coronary bypass grafting using CPB was found in patients heterozygous for the MIF-173*G/C SNP (p<0.05). Moreover, on-pump patients showed significantly decreased MIF plasma levels after 12h postoperatively (p<0.05). In off-pump patients, MIF plasma levels were not significantly different over the time-course and were independent of the genotype. CONCLUSIONS: Patients carrying the C-allele showed significantly increased levels of the proinflammatory cytokine MIF compared to G/G homozygous when revascularization was carried out using CPB. The G/C genotype may be associated with a severe inflammatory reaction and therefore preoperative screening could be beneficial for patients undergoing cardiac surgery using CPB.     

The influence of enamel matrix derivative on the angiogenic activity of primary endothelial cells

Kasaj A, Meister J, Lehmann K, Stratul SI, Schlee M, Stein JM, Willershausen B, Schmidt M. The influence of enamel matrix derivative on the angiogenic activity of primary endothelial cells. J Periodont Res 2012; 47: 479–487. © 2011 John Wiley & Sons A/S Background and Objective: Angiogenesis plays a crucial role in early wound healing and tissue regeneration. Although enamel matrix derivative (EMD) has demonstrated the potential to stimulate periodontal regeneration, the biological effects of EMD on angiogenesis and underlying mechanisms have not been fully elucidated. The aim of the present study was to examine the angiogenic effects of EMD in vitro. Material and Methods: Human umbilical vein endothelial cells (HUVECs) were used to assess the effect of EMD on proliferation, survival, adhesion and migration. The effect of EMD on HUVEC angiogenesis was assessed by a three‐dimensional sprouting assay. In order to understand the signalling mechanism of altered cell proliferation of HUVECs caused by EMD, the phosphorylation status of ERK1/2 and of the serine/threonine protein kinase Akt was analysed by western blot using phospho‐specific antibodies. Results: The proliferation of HUVECs was stimulated by 50 μg/mL EMD, whereas higher concentrations (≥ 100 μg/mL) resulted in an increased apoptotic rate. The mitogenic response to EMD was associated with the activation of ERK1/2. Enamel matrix derivative did not affect cell adhesion, but all concentrations of EMD tested (0.1–250 μg/mL) promoted migration of HUVECs. Furthermore, EMD induced capillary‐like sprout formation from HUVEC spheroids in a dose‐dependent manner. Conclusion: Our data indicate that EMD acts as a proangiogenic factor in vitro and, as such, might contribute to periodontal tissue regeneration by stimulation of vessel formation during wound healing.     

Haemoglobin F Texas II (α2γ26 Glu→Lys), the Second of the Haemoglobin F Texas Variants

S ummary A survey of 13 ,000 cord bloods in Great Britain yielded an electrophoretically abnormal variant of Haemoglobin F which resembled Haemoglobin F Texas. Haemoglobin F Texas might be either α₂γ₂^5G1u→Lys or α₂γ₂^6Glu→Lys. The first has been described and was named Haemoglobin F Texas I. The present variant has the same substitution in the sixth residue of the γ chain and is designated as Haenioglobin F Texas II.     

A comparison of higher order aberrations in eyes implanted with AcrySof IQ SN60WF and AcrySof SN60AT intraocular lenses

PURPOSE: To evaluate the efficacy of AcrySof SN60WF aspheric intraocular lens (IOL) in decreasing spherical aberration and total higher order aberrations (HOAs) after cataract surgery compared to the spherical SN60AT lens. METHODS: Wavefront analysis was conducted on 28 eyes of 28 patients that underwent un-complicated phacoemulsification with implantation of either SN60WF (15 eyes) or SN60AT lenses (13 eyes). Eyes with a history of uveitis, retinal diseases, and previous surgery were excluded. RESULTS: SN60WF eyes had less mean absolute spherical aberration than SN60AT eyes both at 4 mm (0.04+/-0.03 vs 0.11+/-0.03 RMS, p<0.0001) and 6 mm pupils (0.09+/-0.04 vs 0.43+/-0.12 RMS, p<0.0001). Mean total HOAs was lower in the SN60WF group at 6 mm pupils (0.44+/-0.14 vs 0.56+/-0.13 RMS, p=0.0274), while no difference was seen at 4 mm pupils (0.20+/-0.10 vs 0.25+/-0.08 RMS, p=0.160). There were no clinically significant differences between the SN60WF and SN60AT IOLs both at 4 and 6 mm pupils in terms of coma (0.16+/-0.07 vs 0.18+/-0.09 RMS, p=0.514 and 0.25+/-0.12 vs 0.23+/-0.12 RMS, p=0.664) and trefoil (0.14+/-0.09 vs 0.10+/-0.05 RMS, p=0.167 and 0.28+/-0.12 vs 0.23+/-0.07 RMS, p=0.199). There were no differences be-tween groups in mean age, axial length, postoperative spherical equivalent, IOL power, or corneal curvature. CONCLUSIONS: An aspheric posterior optic IOL design with thinner center effectively reduces the positive ocular spherical aberration observed in the pseudophakic and elderly eyes, especially at larger pupillary diameters (6 mm), with no notable increase in coma. However, reduction in total ocular HOAs was only significant at 6 mm pupils.     

Cigarette smoking as a triggering factor of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory skin disease involving the axillary, inguinal and anogenital regions and sometimes, in addition, the submammary or sacral areas. The etiology of this condition is unknown. OBJECTIVE: A matched-pair case-control study was performed to evaluate the influence of smoking habits on the manifestation of this disease. METHODS: Patients who had received surgical treatment for hidradenitis suppurativa in two dermatological centers completed a questionnaire dealing with family history, course of the disease and smoking habits. To form a randomized matched-pair control group, an equal number of patients admitted for various other skin diseases such as atopic dermatitis, varicose veins, skin tattoos, alopecia areata or melanoma was matched for sex and age and evaluated for smoking habits. Statistical analysis was performed by use of several chi2 tests in a cross-table setting. Moreover, a comparison to the expected smoking prevalence in Germany based on national statistics was performed. RESULTS: Out of 84 patients treated for hidradenitis suppurativa, 63 subjects (27 men, 36 women) completed the questionnaire. The rate of active cigarette smokers was 88.9% (56 patients), whereas 4 subjects (6.4%) had never smoked. 3 patients (4.8%) stated to be ex-smokers, but 2 of these had quit smoking only recently and after onset of the disease. The rate of smokers in the matched-pair control group was 46%. The significantly higher proportion of active smokers among patients with hidradenitis suppurativa can be expressed by an odds ratio of 9.4, the calculated 95% confidence interval was 3.7-23.7 (p < 0.001). The expected smoking prevalence in Germany was 26.7% according to national statistics. 73% of our patients had no family history of hidradenitis suppurativa whereas 27% reported at least one affected first-degree relative. CONCLUSION: From the exceedingly high rate of smokers among patients with this condition we conclude that cigarette smoking is a major triggering factor of hidradenitis suppurativa. Remarkably, the disease can be categorized as a smoking sequel that is neither of vascular nor neoplastic nature. Because familial occurrence was rather rarely reported, and because an environmental factor in the form of cigarette smoking appears to be of crucial importance to trigger the disease, we assume that the genetic basis of hidradenitis suppurativa is polygenic rather than mendelian. Smoking cessation should be encouraged particularly in patients with hidradenitis suppurativa although it is unknown whether this improves the course of the disease.