Analysis of the Eurotransplant Kidney Allocation Algorithm: How Should We Balance Utility and Equity?

Background

Since 2014, expected graft and recipient survival are matched by the U.S. kidney allocation system to improve organ utility. This mechanism is based on the kidney donor profile index (KDPI) and the estimated posttransplant survival score (EPTS). Here we analyzed 1. the transferability of these scores into the Eurotransplant (ET) region and 2. the extent to which the ET kidney allocation algorithm promotes utility.

Association of plectin with Z-discs is a prerequisite for the formation of the intermyofibrillar desmin cytoskeleton

Plectin is a high-molecular mass protein (approximately 500 kd) that binds actin, intermediate filaments, and microtubules. Mutations of the plectin gene cause a generalized blistering skin disorder and muscular dystrophy. In adult muscle, plectin is colocalized with desmin at structures forming the intermyofibrillar scaffold and beneath the plasma membrane. To study the involvement of plectin in myofibrillogenesis, we analyzed the spatial and temporal expression patterns of plectin in cultured differentiating human skeletal muscle cells and its relationship to desmin intermediate filaments during this process. Northern and Western blot analyses demonstrated that at least two different plectin isoforms are expressed at all developmental stages from proliferating myoblasts to mature myotubes. Using immunocytochemistry, we show that the localization of plectin dramatically changes from a network-like distribution into a cross-striated distribution during maturation of myocytes. Double immunofluorescence experiments revealed that desmin and plectin are colocalized in premyofibrillar stages and in mature myotubes. Interestingly, plectin was often found to localize to the periphery of Z-discs during the actual alignment of neighboring myofibrils, and an obvious cross-striated plectin staining pattern was observed before desmin was localized in the Z-disc region. We conclude that the association of plectin with Z-discs is an early event in the lateral alignment of myofibrils that precedes the formation of the intermyofibrillar desmin cytoskeleton.     

CD4 deficiency in myelodysplastic syndrome with monosomy 7

Abstract We describe a patient with myelodysplastic syndrome with monosomy 7 presenting with a T-cell defect. He suffered from infections from the age of 10 years, when a CD4 deficiency and impaired lymphoproliferative responses in vitro were found. The only symptom of a myelodysplastic syndrome at that time was thrombocytopenia with giant platelets. Monosomy 7 was found in the bone marrow cells. At the age of 11 years he developed other characteristics of monosomy 7 including splenomegaly and anaemia. Some months later leukaemia was diagnosed.Conclusion In non-HIV CD4 deficiency myelodysplastic syndrome has to be considered.     

Anterior column fractures of the acetabulum.

We retrospectively reviewed 20 patients at three to 19 years after displaced anterior fracture-dislocations of the hip. Eighteen of them were treated by traction, after ensuring that the femoral head was adequately reduced beneath the undisrupted part of the weight-bearing dome. Two required operation. Although none of the 18 conservatively treated fractures was reduced anatomically, the results were good in ten patients and excellent in the seven in whom the fracture did not involve the weight-bearing dome. We conclude that anterior column fractures have a favourable prognosis after conservative treatment.     

An?sthesie und Schlaf-Apnoe-Syndrom

Ein Schlaf-Apnoe-Syndrom (SAS) erhöht das Risiko für perioperative Komplikationen bei anästhesierten und sedierten Patienten. Der Anteil an Patienten mittleren Alters mit signifikanten klinischen Symptomen wird bei Männern auf 4%, bei Frauen auf 2% geschätzt. Jedoch sind 80–95% der SAS-Erkrankten nicht diagnostiziert. Zur Identifikation und sicheren perioperativen Betreuung ist ein systematisches Vorgehen zwingend notwendig. Hierbei sollte es sich um ein interdisziplinäres Konzept handeln, das erhöhte Aufmerksamkeit bei dem pflegerischen/ärztlichen Personal, Evaluation der Intubationsverhältnisse, Abklärung kardiopulmonaler Vorerkrankungen, permanente Kontrolle der Atemwege, differenzierten und angepassten Einsatz von Anästhetika sowie konsequentes Monitoring beinhaltet. Der perioperative Einsatz und die Weiterführung einer Nasal-continuous-positive-airway-pressure- (CPAP-)Therapie sowie die postoperative Verlegung in eine entsprechende Überwachungseinheit sind unbedingt zu empfehlen. Insgesamt besteht noch ein erheblicher Bedarf an kontrollierten Studien zum perioperativen Management von SAS-Patienten.     

The incidence and prediction of automatically detected intraoperative cardiovascular events in noncardiac surgery

The objective of this study was to evaluate prognostic models for quality assurance purposes in predicting automatically detected intraoperative cardiovascular events (CVE) in 58458 patients undergoing noncardiac surgery. To this end, we assessed the performance of two established models for risk assessment in anesthesia, the Revised Cardiac Risk Index (RCRI) and the ASA physical status classification. We then developed two new models. CVEs were detected from the database of an electronic anesthesia record-keeping system. Logistic regression was used to build a complex and a simple predictive model. Performance of the prognostic models was assessed using analysis of discrimination and calibration. In 5249 patients (17.8%) of the evaluation (n = 29437) and 5031 patients (17.3%) of the validation cohorts (n = 29021), a minimum of one CVE was detected. CVEs were associated with significantly more frequent hospital mortality (2.1% versus 1.0%; P < 0.01). The new models demonstrated good discriminative power, with an area under the receiver operating characteristic curve (AUC) of 0.709 and 0.707 respectively. Discrimination of the ASA classification (AUC 0.647) and the RCRI (AUC 0.620) were less. Neither the two new models nor ASA classification nor the RCRI showed acceptable calibration. ASA classification and the RCRI alone both proved unsuitable for the prediction of intraoperative CVEs. IMPLICATIONS: The objective of this study was to evaluate prognostic models for quality assurance purposes to predict the occurrence of automatically detected intraoperative cardiovascular events in 58,458 patients undergoing noncardiac surgery. Two newly developed models showed good discrimination but, because of reduced calibration, their clinical use is limited. The ASA physical status classification and the Revised Cardiac Risk Index are unsuitable for the prediction of intraoperative cardiovascular events.     

The fractional excretion of soluble interleukin-2 receptor-alpha is an excellent predictor of the interleukin-2 receptor-alpha status after treatment with daclizumab

BACKGROUND: Daclizumab is a humanized monoclonal antibody against the alpha-chain of the interleukin (IL)-2 receptor (R). The authors previously have shown that the urinary excretion of soluble (s) IL-2Ralpha is dependent on the presence of daclizumab in serum. The authors investigated whether the IL-2Ralpha status, as assessed by flow cytometric analysis, is reflected by the concentration of sIL-2Ralpha in the urine and serum. METHODS: Two hundred seventy-two measurements were performed in 46 renal transplant recipients who were treated with daclizumab in combination with tacrolimus and mycophenolate mofetil. Soluble IL-2Ralpha was measured in urine and serum with Immulite IL-2R, a solid-phase enzyme-linked immunosorbent assay. Complete blockade of the IL-2Ralpha was defined as the presence of less than 5% IL-2Ralpha+ lymphocytes in the CD3+ population. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of serum and urine sIL-2Ralpha in predicting IL-2Ralpha blockade. RESULTS: The calculated fractional excretion of sIL-2Ralpha proved to be an excellent predictor of the blockade of IL-2Ralpha (ROC analysis area under the curve, 0.95+/-0.01). A calculated fractional excretion of sIL-2Ralpha lower than 0.5% had a specificity of 100% and a sensitivity of 75% for the assessment of blockade of IL-2Ralpha. CONCLUSIONS: Blockade of IL-2Ralpha after treatment with daclizumab can reliably be assessed by calculation of the fractional excretion of sIL-2Ralpha. This method is easier to use compared with flow cytometric analysis of IL-2Ralpha+ lymphocytes.