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- Medizin (147) (remove)
Einleitung: Am 16.12.06 wurde im Eurotransplant-Gebiet der MELD-Score (MELD) als Allokationsbasis zur Lebertransplantation (OLT) eingeführt. Ziel ist eine Reduktion der Sterblichkeit auf der Warteliste. Material und Methoden: 100 Patienten wurden in die prospektive Analyse der MELD-Allokation vom 16.12.06 bis 15.09.07 einbezogen. Ergebnisse: Aktuell warten 68 Pat., 28 Pat. wurden transplantiert, 4 Pat. sind auf der Warteliste (WL) verstorben (4%). Der mittlere MELD auf der WL beträgt 17,2 +/- 5,2 (7-28). Bei 12 Pat. liegt eine Standard-exception (SE) (n=10 HCC, n=2 metabolische Erkrankung) mit einem Match-MELD von 25,6 +/-2,06 vor (24-28). Die Todesursachen der vier auf der WL verstorbenen Pat. waren eine akute Varizenblutung (MELD 9), zwei kardiale Versagen (MELD 13, 18) und eine MRSA-Sepsis (MELD 29, NT-Status). Die 28 transplantierten Pat. hatte zum Zeitpunkt der Transplantation einen mittleren MELD von 27,66 +/- 5,1 Punkten (21 bis 40). 20 Pat. wurden aufgrund des Labor-MELD (28,4 +/- 5,3, 24-40) transplantiert, wobei 7 Pat. einen MELD über 30 aufwiesen. Die Wartezeit lag bei 11,55 +/- 5,3 Tagen. 8 Pat. erhielten bei SE bei HCC (MELD 24 +/- 0, 24) ein Organ nach einer Wartezeit von 320 +/- 9,7 Tagen. Aktuell leben 23 der 28 transplantierten Pat. Bei zwei verstorbenen Pat. war die Todesursache ein kardiales Versagen, bei zwei Patienten eine primäre Non-Funktion sowie ein septisches Multiorganversagen. Schlussfolgerung: Während der ersten Monate der MELD Allokation lag die Letalität auf der WL in unserem Zentrum bei 4%. Patienten mit einem mittleren MELD über 27 erhielten Organangebote und konnten nach kurzer Wartezeit transplantiert werden.
Aim: To compare clinical success and complications of uncovered self-expanding metal stents (SEMS) vs covered SEMS (cSEMS) in obstruction of the small bowel.
Methods: Technical success, complications and outcome of endoscopic SEMS or cSEMS placement in tumor related obstruction of the duodenum or jejunum were retrospectively assessed. The primary end points were rates of stent migration and overgrowth. Secondary end points were the effect of concomitant biliary drainage on migration rate and overall survival. The data was analyzed according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.
Results: Thirty-two SEMS were implanted in 20 patients. In all patients, endoscopic stent implantation was successful. Stent migration was observed in 9 of 16 cSEMS (56%) in comparison to 0/16 SEMS (0%) implantations (P = 0.002). Stent overgrowth did not significantly differ between the two stent types (SEMS: 3/16, 19%; cSEMS: 2/16, 13%). One cSEMS dislodged and had to be recovered from the jejunum by way of laparotomy. Time until migration between SEMS and cSEMS in patients with and without concomitant biliary stents did not significantly differ (HR = 1.530, 95%CI 0.731-6.306; P = 0.556). The mean follow-up was 57 ± 71 d (range: 1-275 d).
Conclusion: SEMS and cSEMS placement is safe in small bowel tumor obstruction. However, cSEMS is accompanied with a high rate of migration in comparison to uncovered SEMS.
Background/aims: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels.
Methods: We performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence.
Results: 19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5.
Conclusion: A rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.
Erratum for: Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells.Journal of biological chemistry, 2002 Nov 15;277(46):43623-30. doi: 10.1074/jbc.M203926200. Epub 2002 Sep 5.
MutLα is essential for human DNA mismatch repair (MMR). It harbors a latent endonuclease, is responsible for recruitment of process associated proteins and is relevant for strand discrimination. Recently, we demonstrated that the MMR function of MutLα is regulated by phosphorylation of MLH1 at serine (S) 477. In the current study, we focused on S87 located in the ATPase domain of MLH1 and on S446, S456 and S477 located in its linker region. We analysed the phosphorylation-dependent impact of these amino acids on DNA binding, MMR ability and thermal stability of MutLα. We were able to demonstrate that phosphorylation at S87 of MLH1 inhibits DNA binding of MutLα. In addition, we detected that its MMR function seems to be regulated predominantly via phosphorylation of serines in the linker domain, which are also partially involved in the regulation of DNA binding. Furthermore, we found that the thermal stability of MutLα decreased in relation to its phosphorylation status implying that complete phosphorylation might lead to instability and degradation of MLH1. In summary, we showed here, for the first time, a phosphorylation-dependent regulation of DNA binding of MutLα and hypothesized that this might significantly impact its functional regulation during MMR in vivo.
Recent genome-wide association studies (GWAS) have identified genetic variations near the IL28B gene which are strongly associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. Protective IL28B variations are strongly associated with on-treatment viral kinetics and approximately 2-fold increased sustained virologic response (SVR) rates in HCV genotype 1 and 4 patients. In HCV genotype 1 patients, IL28B variations were shown to be the strongest pre-treatment predictor of virologic response. In the treatment of HCV genotype 2 and 3 infected patients, IL28B variations play only a minor role. Preliminary data indicate that IL28B variations are also associated with treatment outcome of regimens, including directly acting antiviral (DAA) agents, though their impact seems to be attenuated compared to standard treatment. Here, we review these important findings and discuss possible implications for clinical decision making in the treatment of HCV infection.
Ribavirin in combination with peginterferon alfa shows strong clinical efficacy against chronic hepatitis C, and is now established as the standard of care. However, the precise role of ribavirin is still being defined, suggesting that optimal ribavirin dose should be maintained over the whole treatment period. Ribavirin dosage varies by bodyweight for genotype 1 disease (1000 mg/day in patients ⩽75 kg and 1200 mg/day in patients >75 kg), whereas 800 mg/day is sufficient to ensure optimal response in all genotype 2/3 patients. Similarly, genotype 1 patients benefit from 48 weeks of therapy, while 24 weeks is sufficient for genotype 2/3 disease.
Recent data suggest treatment success is dependent on cumulative ribavirin exposure, as patients who receive <60% of the planned dose have lower response rates, regardless of whether reductions are from temporary interruptions or premature cessation of therapy. All patients should be monitored for hemolytic anemia, as early diagnosis allows management through small dose reductions and stepwise return to the target dose, maximizing cumulative exposure. Despite these recent advances in our knowledge, many questions remain, such as whether the role of ribavirin will change or even be eliminated as new therapies are developed.
Forewarned is forearmed
(2009)