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Background:Activation of the type I interferon (IFN) pathway has been implicated in the initiation of systemic lupus erythematosus(SLE) and most SLE patients show increased expression of IFN-regulated genes in peripheral blood mononuclear cells or whole blood. However, the IFN signature in lupus kidney is not well examined especially at single cell resolution.Objectives:To clarify the significance of the IFN signature in lupus kidney at single cell resolutionMethods:18 lupus kidney (LN) and 34 transplanted kidney (KTx) samples were included in the study. Residual frozen kidney biopsies were collected after clinical diagnosis. The tissue from one donor was split into two. One portion was used for total RNA-Seq (tRNA-Seq) by SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Takara/Clontech). The rest was used for single nucleus RNA-Seq (snRNA-Seq) using Chromium Single Cell 3’ Reagent Kits v3 (10x Genomics) (7 LN and 17 KTx). For the tRNA-Seq, the sequence reads were aligned to Ensembl genome annotation (Ens93) by STAR and the aligned reads were counted by htseq. IFN score of tRNA-Seq was calculated using the reported method [1] per each module (M1.2, M3.4 and M5.12). For the snRNA-Seq, the sequenced reads were processed on the standard pipeline of CellRanger (10x Genomics) and the data was visualized using Seurat. IFN score of snRNA-Seq was computed by the method reported by Arazi A,et al[2].Clinical outcomes of LN were examined on the medical records retrospectively and the clinical remission in 56 weeks for LN was defined as a urinary protein/creatinine ratio less than 0.5 g/gCr.Results:11 LN had clinical remission and 7 LN showed non remitted disease within 56 weeks after the biopsy. There were no statistical significance co-variants such as age, gender and WHO class in pathology. IFN score of M1.2, M3.4 and M5.12 were significantly increased in LN with remission within 56 weeks (median 0.773 vs 0.659, 0.595 vs 0.243 and 0.415 vs 0.100: p-value 0.03, 0.01 and 0.02 [Wilcox rank-test]) in tRNA-Seq. In the snRNA-Seq, the lupus kidney with low IFN score showed restricted IFN signature in the endothelial cells mainly, which can be detected even in the controls, but those with high IFN score indicated broadly spread IFN signature among all of the cell types.Conclusion:LN with high IFN score in kidney tissue is correlated with remission within 56 weeks. LN with low IFN score showed IFN signature restricted to endothelial cells but those with a higher IFN score revealed broadly affected cell types with IFN signature. These results suggest that the IFN signature of LN may start from endothelial cells and then spread to the whole kidney.References:[1]Chiche L, Jourde-Chiche N, Whalen E,et al.Modular Transcriptional Repertoire Analyses of Adults With Systemic Lupus Erythematosus Reveal Distinct Type I and Type II Interferon Signatures.Arthritis & Rheumatology2014;66:1583–95.doi:10.1002/art.38628[2]Arazi A, Rao DA, Berthier CC,et al.The immune cell landscape in kidneys of patients with lupus nephritis.Nat Immunol2019;20:902–14.doi:10.1038/s41590-019-0398-xDisclosure of Interests: :Masatoshi Kanda: None declared, Takahiro Tsuji: None declared, Masaya Mukai: None declared, Hiroki Takahashi: None declared, Tatsuya Atsumi Grant/research support from: Eli Lily Japan K.K., Alexion Pharmaceuticals, Inc., Bristol-Myers Squibb Co., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Consultant of: Gilead Sciences, Inc., Eli Lilly Japan K.K., UCB Japan Co. Ltd., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Speakers bureau: Eli Lilly Japan K.K., UCB Japan Co. Ltd., Bristol-Myers Squibb Co., AbbVie Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Norbert Hübner: None declared

Einige Patienten weisen ein erhohtes Risiko auf, in der fruhpostoperativen Phase nach aortokoronarer Bypassoperation ein Pumpversagen zu erleiden. Es besteht das klinische Interesse, das allgemeine systemische Stoffwechselmonitoring auf den direkten zellularen Stoffwechsel des Herzens zu erweitern. Mit dem Verfahren der Mikrodialyse besteht die Moglichkeit, in allen Geweben Stoffwechselveranderungen semikontinuierlich auf zellularer Ebene zu erfassen. Mikrodialysekatheter wurden in ein dyskinetische Segment des linken Ventrikels und in ein normokontraktares Areal der rechten Kammer platziert. Es wurden myokardiale Glucose-, Pyruvat-, Glycerol- und Latatkonzentrationen bestimmt und hieraus anschliesend der Laktat-Glucose-Quotient (GLQ) sowie der Laktat-Pyruvat-Quotient (LP) ermittelt. Die Glycerolkonzentration erreichten wahren der Aorten klemmzeit signifikant in den dyskinetischen Segmenten deutlich hohere Werte (Glycerol: 146±67 μmol/l vs. 72±36 μmol/l). Der GLQ erzielte im Bereich der normokontraktilen Gebiete der Klemmzeit deutlich bessere Werte (1,46±0,75 μmol/l vs. 0,61±0,25). Fruhpostoperativ zeigten beide Ventrikel eine schnelle Erholung aller Parameter. Bei drei Patienten kam es fruhpostoperativ aufgrund einer Bypassdysfunktion zu einem Wiederanstieg des LP-Quotienten (15±7 vs. 108±67) sowie zu einem erneutem Abfall des GLQ. Diese Art der Stoffwechseluberwachung kann sehr gut geeignet sein, die bisherigen Methoden des Monitorings zu erganzen und hinsichtlich der Diagnostik und Therapiesteuerung kritisch kranker Patienten wertvolle zusatzliche Informationen zu liefern. Es lassen sich fruhzeitig Veranderungen aufdecken, obwohl das hamodynamische Monitoring oder der systemische Stoffwechsel noch unauffallig sein kann.

Background: Post-operative ischemia after coronary artery bypass grafting (CABG) is well described but effective intervention requires immediate diagnosis. One possible way of increasing efficacy of peri-operative myocardial monitoring is using the microdialysis technique. Methods: In 30 patients undergoing routine CABG, a microdialysis catheter was inserted in the left heart in an area of abnormal ventricular contraction. A second catheter was placed in normal tissue of the right ventricle. Microdialysis measurements were performed at time intervals before, during and 24 h after cardiopulmonary bypass (CPB) and retrospectively compared with standard clinical monitoring and clinical course. Results: During CPB, both ventricles showed signs of poor tissue oxygenation. Glycerol was significantly higher in the left myocardium (146 ± 67 vs. 72 ± 36 μmol/l) and the glucose/lactate ratio (GLR), as a marker of nutritional disorder of the right ventricle (41 ± 15% vs. 67 ± 17%, P < 0.05), had significantly better values at this time point. Myocardial lactate concentrations were significantly higher in the dyskinetic segments (2.82 ± 0.81 vs. 1.5 ± 0.81 μM). During this period, no abnormal clinical standard monitoring results were observed. Post-operative significantly increased lactate/pyruvate ratios of three patients were clinically associated with peri-operative myocardial infarction (108 ± 67 vs. 38 ± 9, P < 0.05). The lactate/pyruvate ratio started rising before any other standard monitoring tools showed abnormal values. Conclusions: Peri-operative microdialytic measurements of parameters related to ischemia can be safely performed in a clinical setting, resulting in faster and more reliable detection of ongoing or new ischemia.

Wir berichten von einem 26jahrigen Dachdecker, der durch einen Sturz aus ca. 5 m Hohe ein stumpfes Thoraxtrauma mit Ruptur des linken Herzvorhofs erlitt. Erst nach zweistundiger Reanimationsdauer konnte bei dem be-reits am Unfallort drucklosen und komatosen Patienten (Glasgow Coma Scale 3 Punkte) ein marginaler Blutdruck erzielt werden. Unter dem Verdacht auf eine gedeckte Ruptur der Aorta ascendens wurde der bei Asystolie erneut reanimationspflichtige Patient in die nachstgelegene Kardiochirurgie verlegt und unter fortgesetzter Reanimation sofort an die Herz-Lungen-Maschine angeschlossen. Bei optimaler Exposition konnten die intrathorakalen Organe inspiziert, und die Vorhofruptur versorgt werden. Das Herz konnte effektiv entlastet, und durch Perfusion in tiefer Hypothermie eine Reduktion des Sauerstoffbedarfs aller Organe insbesondere des Gehirns erreicht werden. In Restitutio ad integrum wurde der Patient 18 Tage nach dem Unfall entlassen. Unsere Fallbeschreibung zeigt, das ein Uberleben mit Restitutio ad integrum nach stumpfem Thoraxtrauma und Verletzung des Herzens bei reanimationspflichtigen Patienten mit aussichtslos scheinender Prognose moglich ist. Wir empfehlen, kardiopulmonale Reanimationsmasnahmen erst nach Anschlus eines Patienten an die Herz-Lungen-Maschine zu beenden, sollte auch so keine Stabilisierung der Hamodynamik moglich sein.

Bei 2788 Patienten, die im Zeitraum von 11/95 bis 4/97 an unserer Klinik am Herzen operiert wurden, sind 45 (1,6%) einer perkutanen Dilatations-Tracheotomie unterzogen worden. Die Indikationsstellung erfolgte ab dem zweiten postop. Tag, wenn eine Extubation in den nachsten Tagen nicht absehbar war. Die Tracheotomie erfolgte im Mittel am 6. postop. Tag, die Intubationsdauer lag im Mittel bei 13 Tagen. Wir sahen bei 5 Patienten insgesamt 6 Komplikationen (13,3%). Bei keiner der 45 durchgefuhrten Tracheotomien trat im weiteren Verlauf eine Mediastinitis oder eine Wundheilungsstorung im Bereich der Sternotomie auf. Es gab keinen Todesfall aufgrund der Tracheotomie. Klinisch evidente Auffalligkeiten im respiratorischen Bereich nach Extubation wurden nicht beobachtet. Die perkutane Dilatations-Tracheotomie ist fruhoperativ nach herzchirurgischen Eingriffen eine schnelle, effiziente und risikoarme Methode. Die Methode ist unserer Ansicht nach der konventionellen chirurgischen Methode deutlich uberlegen.

During November 95 to April 97, 45 percutaneous dilatational tracheostomies were performed in a nonselected patient series of 2788 open cardiac surgery cases. Tracheostomy was performed as early as the 2nd postoperative day (median: 6th day), when extubation was not foreseen within the next few days. Duration of intubation was 13 days (mean). We observed 6 complications in 5 patients (13.3%), namely bleeding, misplacement of the tube, subcutaneous emphysema, and superficial infection of the tracheostoma. Mediastinitis and wound infection of the sternal wound did not occur in any single case. There was no death due to tracheostomy. Clinically evident tracheal stenosis and inadequate granulation of the stoma were not observed after extubation. In our opinion, percutaneous dilatational tracheostomy is justifiable, shows good results, and entails minimal risk if done early after cardiac surgery, and it is also superior to standard surgical tracheostomy. Increased incidence of mediastinitis was not seen.

Octaplex is a new prothrombin complex concentrate that is indicated for treatment or perioperative prophylaxis of bleeding in patients with deficiency of the prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists or by liver failure, when rapid correction of bleeding is required. The study was conducted to demonstrate both prevention of bleeding and achievement of haemostasis in acute bleeding and to obtain further information about the safety of administration of Octaplex.

Bei 15 Patienten mit akuten Leukamien wurden gleichzeitig zytogenetische Untersuchungen und quantitative zytochemische DNS-Bestimmungen durchgefuhrt.

With modern turbines operating at a high level of efficiency, sophisticated design techniques are needed for further improvements. With the aid of computers 3-D aspect like end wall contouring and airfoil stacking can be integrated into the design process. The possibilities presented by the latter to control reaction, loading and secondary flow effects are analyzed and compared with experimental results. The implications for the resulting airfoil geometry are shown and limitations are discussed.Copyright © 1985 by ASME