Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome

With a mortality rate of 46% before the onset of COVID-19, acute respiratory distress syndrome (ARDS) affected 200,000 people in the US, causing 75,000 deaths. Mortality rates in COVID-19 ARDS patients are currently at 39%. Extrapulmonary support for ARDS aims to supplement mechanical ventilation by providing life-sustaining oxygen to the patient. A new rapid-onset, human-sized pig ARDS model in a porcine intensive care unit (ICU) was developed. The pigs were nebulized intratracheally with a high dose (4 mg/kg) of the endotoxin lipopolysaccharide (LPS) over a 2 h duration to induce rapid-onset moderate-to- severe ARDS. They were then catheterized to monitor vitals and to evaluate the therapeutic effect of oxygenated microbubble (OMB) therapy delivered by intrathoracic (IT) or intraperitoneal (IP) administration. Post-LPS administration, the PaO2 value dropped below 70 mmHg, the PaO2/FiO2 ratio dropped below 200 mmHg, and the heart rate increased, indicating rapidly developing (within 4 h) moderate-to- severe ARDS with tachycardia. The SpO2 and PaO2 of these LPS-injured pigs did not show significant improvement after OMB administration, as they did in our previous studies of the therapy on small animal models of ARDS injury. Furthermore, pigs receiving OMB or saline infusions had slightly lower survival than their ARDS counterparts. The OMB administration did not induce a statistically significant or clinically relevant therapeutic effect in this model; instead, both saline and OMB infusion appeared to lower survival rates slightly. This result is significant because it contradicts positive results from our previous small animal studies and places a limit on the efficacy of such treatments for larger animals under more severe respiratory distress. While OMB did not prove efficacious in this rapid-onset ARDS pig model, it may retain potential as a novel therapy for the usual presentation of ARDS in humans, which develops and progresses over days to weeks

Einfluss der Verarbeitungstechnologie und Werkstoffzusammensetzung auf die Struktur-Eigenschafts-Beziehungen von thermoplastischen Nanoverbundwerkstoffen

Die Einarbeitung von nanoskaligen Füllstoffen zur Steigerung von polymeren Eigenschaftsprofilen ist sehr viel versprechend und stößt daher heutzutage sowohl in der Forschung als auch in der Industrie auf großes Interesse. Bedingt durch ausgeprägte Oberflächen und hohe Anziehungskräfte, liegen Nanopartikel allerdings nicht singulär sondern als Partikelanhäufungen, so genannten Agglomeraten oder Aggregaten, vor. Zur Erzielung der gewünschten Materialverbesserungen gilt es, diese aufzuspalten und homogen in der polymeren Matrix zu verteilen. Bei thermoplastischen Kunststoffen ist die gleichläufige Doppelschneckenextrusion eines der gängigsten Verfahren zur Einarbeitung von Additiven und Füllstoffen. Aus diesem Grund war es Ziel dieser Arbeit, mittels dieses Verfahrens verbesserte Verbundwerkstoffe mit Polyamid 66- und Polyetheretherketon-Matrix, durch Einarbeitung von nanoskaligem Titandioxid (15 und 300 nm), zu generieren. In einem ersten Schritt wurden die verfahrenstechnischen Parameter, wie Drehzahl und Durchsatz, sowie die Prozessführung und damit deren Einfluss auf die Materialeigenschaften beleuchtet. Der spezifische Energieeintrag ist ausschlaggebend zur Deagglomeration der Nanopartikel. Dieser zeigte leichte Abhängigkeiten von der Drehzahl und dem Durchsatz und verursachte bei der Einarbeitung der Partikel keine wesentlichen Unterschiede in der Aufspaltung der Partikel sowie gar keine in den resultierenden mechanischen Eigenschaften. Die Prozessführung wurde unterteilt in Mehrfach- und Einfachextrusion. Die Herstellung eines hochgefüllten Masterbatches, dessen mehrfaches Extrudieren und anschließendes Verdünnen, führte zu einer sehr guten Deagglomeration und stark verbesserten Materialeigenschaften. Mittels Simulation des Extrusionsprozesses konnte festgestellt werden, dass das Vorhandensein von ungeschmolzenem Granulat in der Verfahrenszone zu einer Schmelze/Nanopartikel/ Feststoffreibung führt, die die Ursache für eine sehr gute Aufspaltung der Partikel zu sein scheint. Durch Modifikation des Extrusionsprozesses erreichte die Einfachextrusion annähernd den Grad an Deagglomeration bei Mehrfachextrusion, wobei die Materialien bei letzterem Verfahren die besten Eigenschaftsprofile aufwiesen. In einem zweiten Schritt wurde ein Vergleich der Einflüsse von unterschiedlichen Partikelgrößen und –gehalten auf die polymeren Matrizes vollzogen. Die 15 nm Partikel zeigten signifikant bessere mechanische Ergebnisse auf als die 300 nm Partikel, und die Wirkungsweise des 15 nm Partikels auf Polyetheretherketon war stärker als auf Polyamid 66. Es konnten Steigerungen in Steifigkeit, Festigkeit und Zähigkeit erzielt werden. Rasterelektronenmikroskopische Aufnahmen bestätigten diese Ergebnisse. Eine Berechnung der Plan-Selbstkosten von einem Kilogramm PEEK-Nanoverbundwerkstoff im Vergleich zu einem Kilogramm unverstärktem PEEK verdeutlichte, dass ein Material kreiert wurde, welches deutlich verbesserte Eigenschaften bei gleichem Preis aufweist. Zusammenfassend konnte in dieser Arbeit ein tieferes Verständnis des Extrusionsvorganges zur Herstellung von kostengünstigen und verbesserten Thermoplasten durch das Einbringen von Nanopartikeln gewonnen werden

A nutritional screening threshold for optimal outcomes after Hartmann\u27s reversal

PURPOSE: Determining is nutritionally replete enough for Hartmann\u27s reversal (HR) can be controversial and multifactorial. While there are many preoperative nutritional screening tools, the impact of malnourishment on HR has not been evaluated. The study aims to clarify how often patients undergoing HR are high risk for malnourishment at the time of surgery and how this impacts postoperative outcomes. METHODS: From 2012-2019, all elective HRs were identified in ACS-NSQIP. Patients were categorized in a malnourished group if they met one of the following criteria: (1) BMI \u3c 18.5 kg/m, (2) albumin \u3c 3.5 g/dL, or (3) \u3e 10% body weight loss in the last 6 months. Bivariate associations of preoperative demographics and postoperative outcomes were analyzed. Multivariable logistic regression was performed to identify independent predictors for 30-day mortality and organ space wound infection. RESULTS: 8878 procedures were evaluated (well-nourished = 7116 and malnourished = 1762). The malnourished group had higher mortality (p \u3c 0.001), shorter operating time (p \u3c .001), longer length of stay (p = 0.016), and higher rates of infection (p = 0.011), reintubation (p = 0.002), bleeding (p \u3c 0.001), sepsis (p = 0.001), and reoperation (p = 0.018). In multivariate regression models, malnourishment was an independent predictor for mortality (OR = 2.72, p \u3c 0.001) and wound infection (OR = 1.19, p = 0.028). CONCLUSION: A large percentage of patients undergoing HR were classified as being high-risk for malnutrition. Malnourishment was associated with some worse postoperative compilations including death and wound infection. Surgeons should routinely use preoperative screening for malnutrition to identify and attempt to optimize nutritional status prior to undergoing Hartmann\u27s Reversal

Use of the T-1470 LiteTouch™ Laser in the En Bloc Resection of an Upper Tract Urothelial Cancer

Background. Endoscopic laser-ablative therapy of upper tract urothelial carcinoma offers kidney-sparing treatment for well-selected low-risk tumors. The traditional technique consists of tumor biopsy with flexible forceps or nitinol basket for pathologic assessment of stage and grade, followed by laser ablation of the tumor. In this case, we present the use of the new T-1470 LiteTouch™ laser for intraoperative tumor en bloc resection, affording both tissue acquisition and tumor ablation. Case Presentation. An 81-year-old female with a past medical history significant for stage 4 chronic kidney disease, peripheral artery disease, coronary artery disease, type 2 diabetes mellitus, and gout was diagnosed with a 2 cm left upper tract high-grade papillary urothelial carcinoma confirmed by cytology with cell block preparation. Using a novel approach, the tumor was resected, en bloc, using the T-1470 LiteTouch™ laser which allowed for sufficient tissue resection for pathologic examination and strong hemostasis. This new technique is the first recorded example of tumor en bloc resection using the T-1470 LiteTouch™ laser of an upper tract urothelial carcinoma. Conclusion. The use of the T-1470 LiteTouch™ laser offers promise for its use as a novel laser for the endoscopic treatment of upper tract urothelial carcinoma. It shows potential for advantages over current techniques through its ability to achieve en bloc resection and superior hemostasis

Current laser therapy options for endoscopic treatment of upper tract urothelial carcinoma

Abstract. Endoscopic management via retrograde ureteroscopic laser ablation of upper tract urothelial carcinoma (UTUC) has become the preferred treatment modality for low-risk tumors. The most popular ablative lasers over the past 15–20 years have been the holmium:yttrium-aluminum-garnet (Ho:YAG) and neodymium (Nd:YAG) lasers, but recently the thulium (Th:YAG) laser has emerged as a potential alternative. This review compares the mechanism of action, physiological properties and effects, and oncologic outcomes of Ho:YAG/Nd:YAG lasers versus the Th:YAG laser for UTUC treatment. Potential advantages of the Th:YAG laser over existing technologies are outlined, followed by a discussion of emerging laser technologies in UTUC management

Daam2-PIP5K Is a Regulatory Pathway for Wnt Signaling and Therapeutic Target for Remyelination in the CNS

Wnt signaling plays an essential role in developmental and regenerative myelination of the CNS; however, contributions of proximal regulators of the Wnt receptor complex to these processes remain undefined. To identify components of the Wnt pathway that regulate these processes, we applied a multifaceted discovery platform and found that Daam2-PIP5K comprise a novel pathway regulating Wnt signaling and myelination. Using dorsal patterning of the chick spinal cord we found that Daam2 promotes Wnt signaling and receptor complex formation through PIP5K-PIP2. Analysis of Daam2 function in oligodendrocytes (OLs) revealed that it suppresses OL differentiation during development, after white matter injury (WMI), and is expressed in human white matter lesions. These findings suggest a pharmacological strategy to inhibit Daam2-PIP5K function, application of which stimulates remyelination after WMI. Put together, our studies integrate information from multiple systems to identify a novel regulatory pathway for Wnt signaling and potential therapeutic target for WMI

Rhodamine B pentyl ester and its methyl, ethyl, propyl, and butyl homologues

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