The Effect of Histidine-tryptophan-ketoglutarate Solution and University of Wisconsin Solution: An Analysis of the Eurotransplant Registry.

BACKGROUND: Both University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are currently used in the Eurotransplant region for preservation of liver allografts. Previous studies on their effect have led to a lot of discussion. This study aims to compare the effect of HTK and UW on graft survival. METHODS: First liver transplantations in recipients 18 years or older from January 1, 2007, until December 31, 2016, were included. Graft survival was compared for livers preserved with HTK and UW at 30 days, 1, 3, and 5 years. Multivariable analysis of risk factors was performed and outcome was adjusted for important confounders. RESULTS: Of all 10 628 first liver transplantations, 8176 (77%) and 2452 (23%) were performed with livers preserved with HTK and UW, respectively. Kaplan-Meier curves showed significant differences in graft survival between HTK and UW at 30 days (89% vs 93%, P=<0.001), 1 year (75% vs 82%, P=<0.001), 3 years (67% vs 72%, P<0.001), and at 5 years (60% vs 67%, P<0.001). No significant differences in outcome were observed in separate analyses of Germany or non-German countries. In multivariable analysis, UW was associated with a decreased risk of graft loss at 30 days (HR 0.772, P=0.002) and at 1 year (0.847 (0.757-0.947). When adjusted for risk factors, no differences in long term outcome could be detected. CONCLUSIONS: Because the use of preservation fluids is clustered geographically, differences in outcome by preservation fluids are strongly affected by regional differences in donor and recipient characteristics. When adjusted for risk factors, no differences in graft survival exist between transplantations performed with livers preserved with either HTK or UW.

Efficacy of Jian'ganle () versus Hugan Pian (), glucuronolactone and reduced glutathione in prevention of antituberculosis drug-induced liver injury.

Evidence-based medicine is advocated by WHO and adopted by developed countries for many years. In China, however, the selection of essential medicine and various medical insurance reimbursement schemes medicine is usually based on experts' experience of prescription practice which is under heavy critics resulting from the lack of related comparative efficacy and evidence-based research. The efficacy of Jian'ganle in prevention of drug-induced liver injury (DILI) caused by antituberculotics was evaluated in this study by comparison with Hugan Pian, glucuronolactone and reduced glutathione. Evidence was provided for relevant sectors such as Ministry for Human Resources and Social Security of the People's Republic of China and National Health and Family Planning Commission of the People's Republic of China to select and renew the Essential Medicine List (EML), the new rural cooperative medical scheme in China (NRCMS) list or the reimbursement list of industrial injury insurance. A total of 189 patients with initial pulmonary tuberculosis were divided into four groups who took antituberculotics combined with Jian'ganle, Hugan Pian, glucuronolactone and reduced glutathione respectively. Their liver function profile including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), total protein (TP), albumin (A) and globulin (G) were detected at admission as baseline and after treatment. The Jian'ganle group was compared with the three others by chi-square tests. In an aspect of maintaining bilirubin indexes normal, Jian'ganle was more efficacious than glucuronolactone. And Jian'ganle had a little more efficacy than reduced glutathione to maintain protein indexes normal as well. And the therapeutic regimen of antituberculotics combined with Jian'ganle was the best in treating tuberculosis and preventing DILI at the same time. The study showed that among the four hepatinicas which demonstrated similar prevention of DILI caused by antituberculotics, Jian'ganle has more advantages over the three others to some extent, which provides a reliable basis for health sectors to select and renew the EML, NRCMS List or the reimbursement list of industrial injury insurance.

[Assessment of the protective effect of calcium-magnesium infusion and glutathione on oxaliplatin-induced neurotoxicity].

OBJECTIVE: To assess the efficacy of calcium-magnesium (Ca/Mg) infusion and glutathione (GSH) for preventing the neurotoxicity induced by oxaliplatin. METHODS: This is a randomized, double blind, placebo controlled clinical trail. The patients receiving FOLFOX4 chemotherapy for their solid tumor were randomized to receive Ca/Mg, GSH or normal saline with chemotherapy simultaneously. The incidence and severity of oxaliplatin-induced neurotoxicity were observed. The ECOG performance status was recorded and compared among the 3 groups. RESULTS: Ninety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study, including 29 patients in the Ca/Mg group, 33 in the GSH group and 31 in the chemotherapy alone group. The incidences of acute neurotoxicity were 82.8%, 90.9% and 93.5%, respectively. At the third cycle, the incidences of grade 1-2 chronic neurotoxicity were 37.9%, 48.5% and 42.0%, respectively. No grade 3 neuropathy was observed. After 6 cycles, the incidence of grade 1-2 neuropathy was increased to 68.2%, 88.9% and 85.2%, respectively. A lower percentage was observed in Ca/Mg arm without a statistically significant difference, and grade 3 neuropathy occurred in 5 patients. After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms. Changes of patient's ECOG score after chemotherapy were similar. CONCLUSION: This study didn't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity.

Treatment of MDS: something old, something new, something borrowed...

As opposed to the treatment landscape for myelodysplastic syndromes (MDS) two decades ago, potential therapies now abound for the treatment of lower-risk and higher-risk populations. In lower-risk patients, decision tools can be used to determine the likelihood of response to erythropoiesis stimulating agents (ESAs), which have demonstrated survival advantages in retrospective studies in patients with MDS, and whether these patients should be treated initially with ESAs or non-growth factor ("active") therapies. Lenalidomide has shown good activity in transfusion-dependent patients with the del(5q) cytogenetic abnormality and modest activity in other lower-risk patients. In higher-risk patients, the DNA methyltransferase inhibitors produce complete and partial responses in 20% to 30% of patients, and for the first time, the MDS drug azacitidine has demonstrated a survival advantage when compared with conventional therapies. Newer therapies stimulate platelet production and target novel pathways, while a panoply of combination studies are underway or recently completed and that likely represent the next frontier in MDS therapy.

Why are physicians not persuaded by scientific evidence? A grounded theory interview study.

BACKGROUND: The government-led "evidence-based guidelines for cataract treatment" labelled pirenoxine and glutathione eye drops, which have been regarded as the standard care for cataracts in Japan, as lacking evidence of effectiveness, causing great upset among ophthalmologists and professional ophthalmology societies. This study investigated the reasons why such "scientific evidence of treatment effectiveness" is not easily accepted by physicians, and thus, why they do not change their clinical practices to reflect such evidence. METHODS: We conducted a qualitative study based on grounded theory to explore physicians' awareness of "scientific evidence" and evidence-supported treatment in relation to pirenoxine and glutathione eye drops, and to identify current barriers to the implementation of evidence-based policies in clinical practice. Interviews were conducted with 35 ophthalmologists and 3 general practitioners on their prescribing behaviours, perceptions of eye drop effectiveness, attitudes toward the eye drop guideline recommendations, and their perceptions of "scientific evidence." RESULTS: Although few physicians believed that eye drops are remarkably effective, the majority of participants reported that they prescribed eye drops to patients who asked for them, and that such patients accounted for a considerable proportion of those with cataracts. Physicians seldom attempted to explain to patients the limitations of effectiveness or to encourage them to stop taking the eye drops. Physicians also acknowledged the benefits of prescribing such drugs, which ultimately outweighed any uncertainty of their effectiveness. These benefits included economic incentives and a desire to be appreciated by patients. Changes in clinical practice were considered to bring little benefit to physicians or patients. Government approval, rarity of side effects, and low cost of the drops also encouraged prescription. CONCLUSION: Physicians occasionally provide treatment without expecting remarkable therapeutic effectiveness, as exemplified by the use of eye drops. This finding highlights that scientific evidence alone cannot easily change physicians' clinical practices, unless evidence-based practices are accepted by the general public and supported by health policy.

Corneal endothelial cell protection with a dispersive viscoelastic material and an irrigating solution during phacoemulsification: low-cost versus expensive combination.

PURPOSE: To evaluate the protective effect on corneal endothelial cells of a low-cost and an expensive combination of a dispersive viscoelastic material and an irrigating solution during phacoemulsification. SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This prospective randomized examiner- and patient-masked study comprised 90 eyes of 45 consecutive patients with age-related cataract in both eyes. For each patient, the first eye was randomly assigned to receive hydroxypropyl methylcellulose 2% (Ocucoat) and Ringer's solution (low-cost combination) or sodium chondroitin sulfate 4%-sodium hyaluronate 3% (Viscoat) and an enriched balanced salt solution (BSS Plus) (expensive combination) during phacoemulsification. The contralateral eye received the other treatment. Endothelial cell function was evaluated by measuring corneal thickness (CT) using partial coherence interferometry, morphology assessment, and endothelial cell counts. RESULTS: The acute postoperative increase in CT was +9.8 microm in the low-cost group and +10.9 microm in the expensive group; the difference between groups was not significant. After 1 month, the CT still differed significantly from baseline in the low-cost group. Three months after surgery, the CT had returned to baseline values in both groups. There was no significant between-group difference in endothelial cell counts or morphology. CONCLUSIONS: During phacoemulsification in a nonselected patient population, there was no difference in acute postoperative corneal edema and endothelial cell morphology after 3 months between a Viscoat and BSS Plus combination and an Ocucoat and Ringer's solution combination. Eyes receiving the expensive combination had marginally faster recovery of corneal swelling by 3 months. However, the cost of Viscoat and 500 mL BSS Plus is 5 times that of Ocucoat and Ringer's solution.

In vitro amylase release of preserved pancreas: a simple test to assess the viability of pancreatic allograft during preservation in the pigs.

To determine an in vitro marker of viability during pancreatic preservation, 12 pigs underwent total pancreas harvesting, and graft were stored in Euro-Collins or Belzer perfusion solution for up to 24 hours. Amylase concentration of the storage solution was analyzed in regular periods and tissue samples were taken for acridine-orange histochemical evaluation of viability in the same time. In vitro pancreatic amylase release (IU/g pancreas tissue) was calculated from the volume of solution and the weight of graft. A significant increase of amylase release was found in the course of preservation in both media. Comparing amylase release in different solutions we found significant difference between Euro-Collins and Belzer media (4 hours: 6.45 IU/g vs. 2.2 IU/g, 8 hours: 11.5 vs. 3.58, 24 hours: 8.7 vs. 42.8, respectively). Comparison of amylase release with histochemical evaluation of viability showed strict correlation. We concluded that amylase release is a good marker for exocrine tissue destruction as well as viability of preserved pancreas. Our data confirms that Belzer solution is superior in pancreatic preservation. It is suggested that after adaptation into human model in vitro pancreatic amylase release could be a time- and cost-saving, useful method in predicting pancreatic transplant function prior graft implantation.

Organ preservation.

Our clinical transplantation results have been very satisfying, with about 90% graft survival after 1 year. Currently, preservation of the liver, pancreas, and kidney, although not ideal, appears to meet all our clinical needs. Improvements in heart and lung preservation are needed and will result in increasing the number of cadaveric organs available for patients with end-stage intrathoracic organ diseases. In the future, machine perfusion may become the standard method for organ preservation for most organs because of the excellent preservation results and long-term preservation achieved.