Eurotransplant donor‐risk‐index and recipient factors: influence on long‐term outcome after liver transplantation – A large single‐center experience

The organ shortage has led to increased use of marginal organs. The Eurotransplant Donor‐Risk‐Index (ET‐DRI) was established to estimate outcome after Liver Transplantation (LT). Currently, data on impact of ET‐DRI on long‐term outcome for different indications and recipient conditions are missing. Retrospective, single‐center analysis of long‐term graft survival (GS) of 1767 adult primary LTs according to indication, labMELDcategory (1: ≤18; 2: >18–25; 3: >25–35; 4: >35), and ET‐DRI. Mean ET‐DRI in our cohort was 1.63 (±0.43). One‐, 10, and 15‐yr GS was 83.5%, 63.3%, and 54.8%. Long‐term GS was significantly influenced by ET‐DRI. Accordingly, four ET‐DRI categories were defined and analyzed with respect to underlying disease. Significant impact of these categories was observed for: Alcohol, cholestatic/autoimmune diseases (CD/AIH), and HCV, but not for HCC, HBV, cryptogenic cirrhosis, and acute liver failure. labMELD categories showed no significant influence on graft, but on patient survival. Matching ET‐DRI categories with labMELD revealed significant differences in long‐term GS for labMELDcategories 1, 2, and 3, but not 4. In multivariate analysis, HCV combined with ET‐DRI > 2 and labMELDcategory 3 combined with ET‐DRI > 2 emerged as negative predictors. To achieve excellent long‐term graft survival, higher risk organs (ET‐DRI > 1.4) should be used restrictively for patients with CD/AIH or HCV. Organs with ET‐DRI > 2 should be avoided in patients with a labMELD of >25–35.     

Preoperative Nutrition and Postoperative Discomfort in an ERAS Setting: A Randomized Study in Gastric Bypass Surgery

Background

Many patients experience postoperative nausea and vomiting (PONV). Preoperative treatment with carbohydrate solutions seems to improve the course after different types of surgery. This study was undertaken to investigate the potential value of different models for preoperative hydration/nutrition, in addition to our ERAS (enhanced recovery after surgery) protocol.

Methods

Ninety non-diabetic women planned for elective laparoscopic gastric bypass and aged 18–65 years were included. All were on preoperative low-calorie diet (LCD). They were randomized into three arms, either a carbohydrate-rich drink, a protein-enriched drink, or tap water and instructed to drink 800 and 200 mL 16 and 2 h, respectively, prior to operation.Risk factors for PONV were recorded preoperatively. All patients were operated before lunch and received 1500–2000 mL of Ringer-Acetate solution during the 24–30-h postoperative hospital time. Four variables (nausea, pain, tiredness, and headache) were registered on 100-mm visual analog scales six times over 22 h. The need for additional medication was registered.

Results

Out of 90 patients, 73 complete datasets were obtained. Nausea peaked at 7 p.m. but with no statistically significant differences between groups for any of the variables. Pain peaked the first 2 h postoperatively, remained longer, and had not returned to baseline values at 6 a.m. the morning after surgery but with no difference between groups.

Conclusions

Inside our ERAS protocol, additional preoperative carbohydrate- or protein-enriched fluid treatment did not further reduce immediate patient discomfort in laparoscopic gastric bypass surgery.

     

Activation of the cortical pain network by soft tactile stimulation after injection of sumatriptan

The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including a dislike of being touched. With a double-blind cross-over design, we studied the effects of sumatriptan and saline on perception (visual analogue scale) and cortical processing (functional magnetic resonance imaging) of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n=6) was less pleasant (p<0.04) and evoked less activation of posterior insular cortex in the sumatriptan compared to the saline condition. Soft brushing activated pain processing regions (anterior insular, lateral orbitofrontal, and anterior cingulate cortices, and medial thalamus) only in the sumatriptan condition, whereas activation of somatosensory cortices was similar in both conditions. Soft brush stroking on the palm (n=6) was equally pleasant in both conditions. One possible mechanism for the activation of pain processing regions by brush stroking is sensitization of nociceptors by sumatriptan. Another possibility is inhibition of a recently discovered system of low-threshold unmyelinated tactile (CT) afferents that are present in hairy skin only, project to posterior insular cortex, and serve affective aspects of tactile sensation. An inhibition of impulse transmission in the CT system by sumatriptan could disinhibit nociceptive signalling and make light touch less pleasant. This latter alternative is consistent with the observed reduction in posterior insular cortex activation and the selective effects of stimulation on hairy compared to glabrous skin, which are not explained by the nociceptor sensitization account.     

Reproducibility and reliability of central corneal thickness determination in more and less profound corneal edema using ultrasound pachymetry,a Scheimpflug camera and anterior segment OCT

Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of this study is to determine the influence of different degrees of corneal edema on the reliability and...     

Multidrug-resistant neuroblastoma cells are responsive to arsenic trioxide at both normoxia and hypoxia

Despite intensive treatment, the outcome of high-risk neuroblastoma patients is poor with acquired multidrug resistance as an important cause. Previously, our group has shown that arsenic trioxide (As(2)O(3)) kills multidrug-resistant neuroblastoma cells in vitro and in vivo at clinically tolerable doses. Regions of tissue hypoxia often arise in aggressive solid tumors, and hypoxic tumors exhibit augmented invasiveness and metastatic ability in several malignancies. Furthermore, hypoxia may impair the treatment efficiency; therefore, we have studied the cytotoxic effect of As(2)O(3) on neuroblastoma cells grown under normoxic as well as hypoxic (1% oxygen) conditions. At both normoxia and hypoxia, 2 and 4 mumol/L As(2)O(3) induced evident cell death in the drug-sensitive SH-SY5Y and IMR-32 cells as well as in the multidrug-resistant SK-N-BE(2)c (with a mutated p53) and SK-N-FI cells after 72 hours of exposure. In contrast, the conventional chemotherapeutic drug etoposide showed lowered efficiency in hypoxic IMR-32 cells. In accordance with our previously published results, although not to the same extent as in their normoxic counterparts, Bax is proteolytically cleaved also in neuroblastoma cells exposed to As(2)O(3) at hypoxia. This suggests that similar molecular mechanisms are involved in As(2)O(3)-induced neuroblastoma cell death during hypoxia compared with normoxia. Together, our results support As(2)O(3) as a potential candidate drug as a complement to conventional treatments for high-risk neuroblastoma patients and perhaps also for patients with other multidrug-resistant solid tumors.     

Evaluation of urinary myoglobin assay test for myocardial infarction.

Serial determinations of urinary myoglobulin, beta2-microglobulin and albumin, and of serum myoglobin, were performed in twenty-eight consecutive patients admitted to a coronary care unit. Patients with myocardial infarction (MI patients) all had higher serum levels of myoglobin then those with other diagnoses (OBS patients). Myoglobinuria occurred in 80% of MI patients and in half of the OBS patients. The appearance of myoglobin in urine was mainly accounted for by an impaired renal reabsorption of low molecular weight proteins. Measurement of urinary myoglobulin, in contrast to serum myoglobulin, is of little value for the diagnosis of myocardial infarction.     

Junger Patient mit ungewöhnlicher Raumforderung am Unterlid

Die Ophthalmologie - Eine Raumforderung der Lider im jungen Erwachsenenalter ist oft ein Zeichen einer Entzündung, eines Traumas oder einer benignen Neoplasie. Ziel dieser Kasuistik ist es,...     

Use of a linearization approximation facilitating stochastic model building

The objective of this work was to facilitate the development of nonlinear mixed effects models by establishing a diagnostic method for evaluation of stochastic model components. The random effects investigated were between subject, between occasion and residual variability. The method was based on a first-order conditional estimates linear approximation and evaluated on three real datasets with previously developed population pharmacokinetic models. The results were assessed based on the agreement in difference in objective function value between a basic model and extended models for the standard nonlinear and linearized approach respectively. The linearization was found to accurately identify significant extensions of the model’s stochastic components with notably decreased runtimes as compared to the standard nonlinear analysis. The observed gain in runtimes varied between four to more than 50-fold and the largest gains were seen for models with originally long runtimes. This method may be especially useful as a screening tool to detect correlations between random effects since it substantially quickens the estimation of large variance–covariance blocks. To expedite the application of this diagnostic tool, the linearization procedure has been automated and implemented in the software package PsN.     

Preoperative MRI of the Breast (POMB) Influences Primary Treatment in Breast Cancer: A Prospective,Randomized, Multicenter Study

Background

Breast magnetic resonance imaging (MRI) has shown high sensitivity in determining tumor extent, multifocality, and occult contralateral breast cancer. Low specificity, unnecessary mastectomies, and costs are arguments against MRI. The purpose of this study was to determine whether preoperative breast MRI would affect primary surgical management, reduce reexcision/reoperation procedures, and influence the choice of neoadjuvant treatment in patients with newly diagnosed breast cancer.

Methods

This prospective, randomized, multicenter study included 440 breast cancer patients younger than aged 56 years from three, Swedish, large-volume breast units. Patients were randomly allocated on a 1:1 basis to either preoperative staging with breast MRI (n = 220) or no breast MRI (n = 220) (control group). Treatment planning of all patients was discussed at multidisciplinary team conferences.

Results

In patients randomized to the MRI group, who had an observed higher percentage of planned breast-conserving surgery (BCS) compared with the control group, a change from suggested breast conservation to mastectomy occurred in 23 of 153 (15 %) patients. Breast MRI provided additional information in 83 of 220 (38 %) patients, which caused a change in treatment plan in 40 (18 %). The breast reoperation rate was significantly lower in the MRI group: 11 of 220 (5 %) versus 33 of 220 (15 %) in the control group (p < 0.001). The number of mastectomies, axillary reoperations, and the number of patients receiving neoadjuvant chemotherapy after definitive treatment did not differ significantly between the groups.

Conclusions

Preoperative staging with breast MRI in women younger than age 56 years altered the treatment plan in 18 % of the patients. Although a higher MRI-related conversion rate from breast conservation to mastectomy was found, the final numbers of mastectomies did not differ between the two groups. The breast reoperation rate in the MRI group was significantly reduced.