Prediction of time to prosthesis implantation as a function of joint anatomy in patients with developmental dysplasia of the hip

BACKGROUND: Developmental dysplasia of the hip (DDH) can lead to pain and premature secondary osteoarthritis at an early stage. Joint-preserving osteotomy is an established solution to this problem. In contrast, a conservative approach would result in pain persistence, ultimately raising the patients question for a possible date of expected prosthesis implantation. The aim of the study was to identify the relationship between the dysplastic hip anatomy and the time of prosthesis implantation in order to enable prognostic predictions in younger patients with symptomatic DDH. MATERIALS AND METHODS: Data from 129 hips who received THA due to secondary DDH osteoarthritis were evaluated. The preoperative hip anatomy was evaluated for AI and LCE angle. Multiple linear regression analyses were then used to correlate the influence of these parameters with the patient's age at the time of surgery. In addition, a graphical relationship was derived by the method of power least squares curve fitting with second-degree polynomials. RESULTS: The mean age for THA was 54.3 ± 11 years. The time of surgery correlated significantly with LCE (0.37) and AI (- 0.3) (p < 0.001). The mean age of patients with LCE angle ≤ 10° was 41.9 ± 14.0 years, for LCE 11-20° 52.7 ± 9.5 years, and for LCE 21-30° 57.0 ± 10.3 years. The following formula could then be determined for the calculation of the potential patient age at the time of THA as a function of LCE angle: age pTHA = 40.2 + 0.8 × LCE angle - 0.01 × (LCE angle)2. CONCLUSION: A significant correlation between the extent of dysplasia and the time of prosthesis implantation was identified. In particular, the LCE and the AI correlated strongly with the time of implantation. The more dysplastic the angles were, the sooner the THA was necessary. Using the calculations presented in this study, the probable age of prosthesis implantation can be prognosticated and included in a counseling session about treatment options for DD

The Preoperative Microbial Detection is No Prerequisite for the Indication of Septic Revision in Cases of Suspected Periprosthetic Joint Infection

Aim of this study. Periprosthetic joint infections (PJIs) require a special antimicrobial regimen, fundamentally different from an aseptic treatment, making a correct preoperative diagnosis essential. However, a successful preoperative microbe detection is not always possible. We wanted to find out (1) if a preoperative microbe detection is a prerequisite before starting a septic revision in suspected PJIs or if the preoperative diagnosis can solely be based on (para) clinical signs (persistent CRP >1 mg/dl, early X-ray loosening signs in the first 5 years, leucocytes joint aspiration >1700/mu l, conspicuous history, and clinical signs like redness, pain, hyperthermia, swelling, and loss of function); (2) if patients with and without preoperative microbe detection have a different outcome; and (3) if the microbial growth is the most important criterion of a multifactorial PJI definition. Methods. We included all first-line two-stage hip (49) and knee (47) revisions, performed in our department from 06/2013 on, with an available 2-year follow-up. A PJI was defined as one of the following four criteria: fistula or purulence, Krenn Morawietz type 2 or 3, joint aspirate >2000/mu l leukocytes or >70% granulocytes, and microbial growth. This multifactorial PJI definition was based on the European Bone and Joint Infection Society (EBJIS). The standardized diagnostic algorithm is described in detail. Results. (1) 24 hip and 16 knee cases were treated without preoperative microbe detection solely on the basis of a (para) clinical diagnosis (see above). In the hip 91.6% (22 of 24 cases) showed an intraoperative microbe detection. In the knee, in 68.7% (11 of 16 cases) a microbe was detected intraoperatively and in 93.7% (15 of 16) at least one secure PJI criterion could be confirmed intraoperatively. (2) No statistical significant (p.517) difference between patients with (n = 56, reinfection rate 8.9%) and without (n = 40, 15%) preoperative microbe detection was found in a 2-year follow-up. (3) Microbial growth remains the overall (pre- and intraoperatively) most important criterion (hip 95.9%; knee 89.3%), followed by Krenn Morawietz for the intraoperative diagnosis (hip 67.3%, knee 48.9%), and joint aspiration for the knee and fistula for the hip, respectively, as preoperative criteria. Conclusion. High rates of intraoperatively fulfilled EBJIS PJI criteria show that a preoperative microbe detection is not necessary before intervening in suspected PJIs. The indication for a septic revision can solely be based on (para) clinical signs. The new established diagnostic algorithm based on a multifactorial PJI definition showed high precision in finding PJIs

Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX biomarker panel

No biomarker panel is established for prediction of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), a major complication of allogeneic stem cell transplantation (alloSCT). We compared the potential of the Endothelial Activation and Stress Index (EASIX), based on lactate dehydrogenase, creatinine, and thrombocytes, with that of the SOS/VOD CIBMTR clinical risk score to predict SOS/VOD in two independent cohorts. In a third cohort, we studied the impact of endothelium-active prophylaxis with pravastatin and ursodeoxycholic acid (UDA) on SOS/VOD risk. The cumulative incidence of SOS/VOD within 28 days after alloSCT in the training cohort (Berlin, 2013-2015, n=446) and in the validation cohort (Heidelberg, 2002-2009, n=380) was 9.6% and 8.4%, respectively. In both cohorts, EASIX assessed at the day of alloSCT (EASIX-d0) was significantly associated with SOS/VOD incidence (p<0.0001), overall survival (OS) and non-relapse mortality (NRM). In contrast, the CIBMTR score showed no statistically significant association with SOS/VOD incidence, and did not predict OS and NRM. In patients receiving pravastatin/UDA, the cumulative incidence of SOS/VOD was significantly lower at 1.7% (p<0.0001, Heidelberg, 2010-2015, n=359) than in the two cohorts not receiving pravastatin/UDA. The protective effect was most pronounced in patients with high EASIX-d0. The cumulative SOS/VOD incidence in the highest EASIX-d0 quartiles were 18.1% and 16.8% in both cohorts without endothelial prophylaxis as compared to 2.2% in patients with pravastatin/UDA prophylaxis (p<0.0001). EASIX-d0 is the first validated biomarker for defining a subpopulation of alloSCT recipients at high risk for SOS/VOD. Statin/UDA endothelial prophylaxis could constitute a prophylactic measure for patients at increased SOS/VOD risk

Challenges and pitfalls of experimental bariatric procedures in rats

Introduction: The impact of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on obesity and obesity-related diseases is unquestionable. Up to now, the technical descriptions of these techniques in animals/rats have not been very comprehensive. Methods: For SG and RYGB, operating time, learning curve, and intraoperative mortality in relation to weight of the rat and type of anesthesia were recorded. Furthermore, a review of the literature on experimental approaches towards SG and RYGB in rats was carried out, merging in a detailed technical description for both procedures. Results: The data presented here revealed that the mean operating time for SG (69.4 +/- 22.2 min (SD)) was shorter than for RYGB (123.0 +/- 20.7 min). There is a learning curve for both procedures, resulting in a reduced operating time of up to 60% in SG and 35% in RYGB (p < 0.05; t-test). However, with increased weight, operating time increases to about 80 min for SG and about 120 min for RYGB. Obese rats have an increased intraoperative mortality rate of up to 50%. After gaseous anesthesia the mortality can be even higher. The literature search revealed 40 papers dealing with SG and RYGB in rats. 18 articles (45%) contained neither photographs nor illustrations; 14 articles (35%) did not mention the applied type of anesthesia. The mortality rate was described in 15 papers (37.5%). Conclusion: Experimental obesity surgery in rats is challenging. Because of the high mortality in obese rats operated under gaseous anesthesia, exercises to establish the techniques should be performed in small rats using intraperitoneal anesthesia. Copyright (C) 2012 S. Karger GmbH, Freibur

Detailed mapping of the complex fiber structure and white matter pathways of the chimpanzee brain

Long-standing questions about human brain evolution may only be resolved through comparisons with close living evolutionary relatives, such as chimpanzees. This applies in particular to structural white matter (WM) connectivity, which continuously expanded throughout evolution. However, due to legal restrictions on chimpanzee research, neuroscience research currently relies largely on data with limited detail or on comparisons with evolutionarily distant monkeys. Here, we present a detailed magnetic resonance imaging resource to study structural WM connectivity in the chimpanzee. This open-access resource contains (1) WM reconstructions of a postmortem chimpanzee brain, using the highest-quality diffusion magnetic resonance imaging data yet acquired from great apes; (2) an optimized and validated method for high-quality fiber orientation reconstructions; and (3) major fiber tract segmentations for cross-species morphological comparisons. This dataset enabled us to identify phylogenetically relevant details of the chimpanzee connectome, and we anticipate that it will substantially contribute to understanding human brain evolution

LigaSure Impact™ versus conventional dissection technique in pylorus-preserving pancreatoduodenectomy in clinical suspicion of cancerous tumours on the head of the pancreas: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The pp-Whipple procedure requires extensive preparation. The conventional preparation technique is done with scissors for dissection and ligatures, and with clips and sutures for hemostasis. This procedure is very time-consuming and requires numerous changes of instruments. The LigaSure™ device allows dissection and hemostasis for preparation with one instrument. Up to now there has been no comparison of the two techniques with regard to operating time and the patients' outcome. It is still unclear which technique has the optimal benefit/risk ratio for the patient.</p> <p>Methods/Design</p> <p>A single-center, randomized, single-blinded, controlled superiority trial to compare two different techniques for dissection in a pp-Whipple procedure. 102 patients will be included and randomized pre-operatively. All patients aged 18 years or older scheduled for primary elective pp-Whipple procedure who signed the informed consent will be included. The primary endpoint is the operating time of the randomized technique. Control Intervention: Conventional dissection technique; experimental intervention: LigaSureTM dissection technique. Duration of study: Approximately 15 months; follow up time: 3 years. The trial is registered at German ClinicalTrials Register (DRKS00000166).</p

Laparoscopic mesh-augmented hiatoplasty without fundoplication as a method to treat large hiatal hernias

PURPOSE: Laparoscopic hiatal hernia repair with additional fundoplication is a commonly recommended standard surgical treatment for symptomatic large hiatal hernias with paraesophageal involvement (PEH). However, due to the risk of persistent side effects, this method remains controversial. Laparoscopic mesh-augmented hiatoplasty without fundoplication (LMAH), which combines hiatal repair and mesh reinforcement, might therefore be an alternative. METHODS: In this retrospective study of 55 (25 male, 30 female) consecutive PEH patients, the perioperative course and symptomatic outcomes were analyzed after a mean follow-up of 72 months. RESULTS: The mean DeMeester symptom score decreased from 5.1 to 1.8 (P < 0.001) and the gas bloating value decreased from 1.2 to 0.5 (P = 0.001). The dysphagia value was 0.7 before surgery and 0.6 (P = 0.379) after surgery. The majority of the patients were able to belch and vomit (96 and 92 %, respectively). Acid-suppressive therapy on a regular basis was discontinued in 68 % of patients. In 4 % of patients, reoperation was necessary due to recurrent or persistent reflux. A mesh-related stenosis that required endoscopic dilatation occurred in 2 % of patients. CONCLUSIONS: LMAH is feasible, safe and provides an anti-reflux effect, even without fundoplication. As operation-related side effects seem to be rare, LMAH is a potential treatment option for large hiatal hernias with paraesophageal involvement

A comprehensive description of a model-based, continous development process for AUTOSAR systems with integrated quality assurance

Der AUTOSAR-Standard definiert neben einer durchgängig werkzeuggestützten und modellbasierten Methodik zur Entwicklung von Steuergeräte-Software eine technische Infrastruktur als standardisierte Steuergeräte-Basissoftware zur Implementierung dieser Systeme im Automobil. Die wesentlichen Herausforderungen in der Entwicklung automotiver Systeme ergeben sich dabei nicht nur aus der stetig steigenden Menge korrekt umzusetzender Funktionalität, sondern auch aus der wachsenden Anzahl zusätzlich zu erfüllender Qualitätsanforderungen, wie z.B. Sicherheit, Performanz oder Kosten. Die Integration von Ansätzen zur frühzeitigen, Entwicklungsphasen begleitenden Überprüfung von Korrektheits- und Qualitätskriterien kann dabei maßgeblich zur Beherrschbarkeit der Komplexität dieser Systeme beitragen. Es wird ein entsprechend durchgängig werkzeuggestützter und modellbasierter Entwicklungsprozess, basierend auf dem V-Modell sowie dessen Integration in die AUTOSAR-Methodik definiert. Neben der Überprüfung der funktionalen Korrektheit durch systematische Testverfahren sieht das erweiterte Prozessmodell die Bewertung beliebiger Qualitätskriterien für das zu entwickelnde System vor. Es wird beschrieben, wie insbesondere im AUTOSAR-Kontext der Entwurf der Systemarchitektur die hierfür entscheidende Design-Phase darstellt und als Grundlage für Qualitätsabschätzungen durch Architektur-Evaluation dienen kann. Die Vorgehensweise in den einzelnen Entwicklungsschritten wird detailliert anhand einer umfangreichen, vollständig AUTOSAR-konformen Fallstudie, bestehend aus einem vereinfachten PKW-Komfortsystem, demonstriert. Die durchgängige Toolkette umfasst alle Phasen von der Anforderungsspezifikation bis zur Implementierung auf einem prototypischen Hardware-Demonstrator bestehend aus vier über CAN vernetzten Steuergeräten und HIL-Schnittstellen für die Testdurchführung. Es wird auf ausgewählte Implementierungsdetails, notwendige Workarounds und Besonderheiten der prototypischen Umsetzung eingegangen.The AUTOSAR standard defines a seamless tool supported and model based methodology for ECU software design and engineering. Furthermore, the standard specifies a technical infrastructure by means of standardized basic software modules for ECU networks, serving as a uniform implementation platform for AUTOSAR systems. The major challenges in automotive systems development not only arise as a result of the contiuously growing amount of functionality to be realized correctly, but also from the increasing number of quality requirements to be taken into account, e.g. safety, performance, and costs. The integration of approaches for early checking of correctness and quality criteria accompanying the different development phases makes a significant contribution towards coping with the complexity of such systems. We describe such a model based development process and a corresponding tool chain based on the V-modell and its embedding into the AUTOSAR methodology. For the validation of functional correctness systematic testing approaches are applied, and for quality criteria according evaluation methods are used. We discuss that especially in the context of AUTOSAR, the phase of architectural system design is crucial for the quality properties of the system under development, and to what extent architecture evaluation can be used for quality estimation. The practices in the different development steps are illustrated in detail by means of a comprehensive, AUTOSAR compliant case study, i.e. a body comfort system. The tool chain proposed comprises all development stages, starting from the requirements specification, and concluding with the system implementation on a hardware demonstrator prototype. The demonstrator consists of ECUs coupled via CAN, as well as HIL interfaces for test case applications. We give detailled insights in selected impl. issues, workarounds required, and the configuration steps needed for the AUTOSAR operating system. A discussion of the pro's and con's regarding the potential of AUTOSAR concludes

Comparing the value of mono- vs coculture for high-throughput compound screening in hematological malignancies

Large-scale compound screens are a powerful model system for understanding variability of treatment response and discovering druggable tumor vulnerabilities of hematological malignancies. However, as mostly performed in a monoculture of tumor cells, these assays disregard modulatory effects of the in vivo microenvironment. It is an open question whether and to what extent coculture with bone marrow stromal cells could improve the biological relevance of drug testing assays over monoculture. Here, we established a high-throughput platform to measure ex vivo sensitivity of 108 primary blood cancer samples to 50 drugs in monoculture and coculture with bone marrow stromal cells. Stromal coculture conferred resistance to 52% of compounds in chronic lymphocytic leukemia (CLL) and 36% of compounds in acute myeloid leukemia (AML), including chemotherapeutics, B-cell receptor inhibitors, proteasome inhibitors, and Bromodomain and extraterminal domain inhibitors. Only the JAK inhibitors ruxolitinib and tofacitinib exhibited increased efficacy in AML and CLL stromal coculture. We further confirmed the importance of JAK-STAT signaling for stroma-mediated resistance by showing that stromal cells induce phosphorylation of STAT3 in CLL cells. We genetically characterized the 108 cancer samples and found that drug-gene associations strongly correlated between monoculture and coculture. However, effect sizes were lower in coculture, with more drug-gene associations detected in monoculture than in coculture. Our results justify a 2-step strategy for drug perturbation testing, with large-scale screening performed in monoculture, followed by focused evaluation of potential stroma-mediated resistances in coculture