Evaluation of a lumbal spondylodesis by APC-modified titanium implants

Prothesenlockerungen, insbesondere aseptische, sind ein bislang ungelöstes Problem in der modernen Endoprothetik. Die bisherige medizinisch- wissenschaftliche Forschung auf diesem Gebiet konnte eine verbesserte Osteointegration durch diverse unterschiedliche Oberflächenmodifikationen zeigen. Leider offenbaren alle bisherigen Modifikationsverfahren verschiedene Nachteile. Besonders die schwache Oberflächenstärke der Beschichtungen schränkt deren Verwendung massiv ein. Anodic-plasma-chemical (APC) Behandlung ermöglicht die Herstellung von Implantaten, bei denen Kalziumphosphat direkt in eine metallische Oberfläche inkorporiert ist. Durch diese Behandlung erhält man eine wesentlich bessere Oberflächenstärke als mit bisher verwendeten Modifikationsmethoden. Zusätzlich führt die bioaktive Metalloberfläche zu einer verbesserten Osteointegration. Da die gute Zytokompatibilität bereits durch in-vitro Versuche bestätigt worden ist wurde diese Studie mit der Zielsetzung durchgeführt, die Zytokompatibilität (wenig Osteolysen und wenig aseptische Entzündungsreaktion) in belasteter Umgebung in einem in-vivo Modell bei lumbaler Spondylodese nachzuweisen. Als Vergleichsmaterialien wurden ein herkömmliches Titanoxid- und ein mit dem Plasma-sprayed-Verfahren behandeltes Titanmaterial verwendet. Die Spondylodeseimplantate wurden in die Lendenwirbelsäulen von weiblichen Merino-Mix Schafen mit einer postoperativen Standzeit von sechs beziehungsweise zwölf Wochen implantiert (zwei Auswertungszeitpunkte). Osteoklasten als Marker für Osteolysen und Neovaskularisation als Marker für Entzündungsreaktionen wurden nach immunhistologischer Färbung quantitativ ausgewertet. Es wurden keine signifikanten Unterschiede zwischen den getesteten Oberflächen-modifikationen gefunden. Dieses Ergebnis führt zu der Schlussfolgerung, dass die APC behandelten Implantate eine mindestens ebenso gute Biokompatibilität haben, wie die verwendeten Vergleichsmaterialien. Der aktuellen Studienlage nach ermöglicht das APC-Verfahren eine bisher nicht gekannte bioaktive und dennoch starke Oberfläche in Verbindung mit einer in-vivo nachgewiesenen guten Biokompatibilität, bei vergleichsweise einfacher, schneller und kostengünstiger Herstellung. Aus diesen Gründen scheint das APC- Oberflächenmodifikationsverfahren großes Potenzial für die zukünftige Herstellung von metallischen Implantatmaterialien zu haben.Implant failure is an unsolved problem by now. By modifying the implant surface a better oteointegration could be achieved, but still there are some limitations. Especially weak surface strength limits the usage. Anodic-plasma- chemical treatment allows incorporation of calcium-phosphate directly into the metallic surface which leads to enhanced surface strength. Because cytocompatibility has been shown already in-vitro we studied it in a loaded environment in an in-vivo sheep-spine-model. We compared APC to implants made of titaniumodixe an an implant modified by plasma-sprayed treatment. After 6 respectively 12 weeks post-operationem I examined osteolytic an inflammatory immunhistologically. I found no significant differences between the tested surfaces. This leads to the conclusion that APC-treated implants have the same cytocompatibility as the compared materials. But APC-treatment enables to produce a biocompatible surface of titanium-implants by a cheap and fast production of the surface. Conclusively APC-treatment seems to have a great potential for future metallic implants

Noninvasive Neurally Adjusted Ventilator Assist Ventilation in the Postoperative Period Produces Better Patient-Ventilator Synchrony but Not Comfort

BACKGROUND. Noninvasive neurally adjusted ventilatory assist (NAVA) has been shown to improve patient-ventilator interaction in many settings. There is still scarce data with regard to postoperative patients indicated for noninvasive ventilation (NIV) which this study elates. The purpose of this trial was to evaluate postoperative patients for synchrony and comfort in noninvasive pressure support ventilation (NIV-PSV) vs. NIV-NAVA. METHODS. Twenty-two subjects received either NIV-NAVA or NIV-PSV in an object-blind, prospective, randomized, crossover fashion (observational trial). We evaluated blood gases and ventilator tracings throughout as well as comfort of ventilation at the end of each ventilation phase. Results. There was an effective reduction in ventilator delays () and negative pressure duration in NIV-NAVA as compared to NIV-PSV (). Although we used optimized settings in NIV-PSV, explaining the overall low incidence of asynchrony, NIV-NAVA led to reductions in the NeuroSync-index () and all types of asynchrony except for double triggering that was significantly more frequent in NIV-NAVA vs. NIV-PSV (); ineffective efforts were reduced to zero by use of NIV-NAVA. In our population of previously lung-healthy subjects, we did not find differences in blood gases and patient comfort between the two modes. CONCLUSION. In the postoperative setting, NIV-NAVA is well suitable for use and effective in reducing asynchronies as well as a surrogate for work of breathing. Although increased synchrony was not transferred into an increased comfort, there was an advantage with regard to patient-ventilator interaction. The trial was registered at the German clinical Trials Register (DRKS no.: DRKS00005408)

Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial

(1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood–brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possible functions of bile acids in the central nervous system, are not precisely understood. (2) Methods: We conducted a single-center observational trial. The concentrations of 15 individual bile acids were determined using an in-house LC-MS/MS method in 54 patients with various acute and severe disorders of the central nervous system. We analyzed CSF from ventricular drainage taken within 24 h after placement, and blood samples were drawn at the same time for the presence and quantifiability of 15 individual bile acids. (3) Results: At a median time of 19.75 h after a cerebral insult, the concentration of bile acids in the CSF was minute and almost negligible. The CSF concentrations of total bile acids (TBAs) were significantly lower compared to the serum concentrations (serum 0.37 µmol/L [0.24, 0.89] vs. 0.14 µmol/L [0.05, 0.43]; p = 0.033). The ratio of serum-to-CSF bile acid levels calculated from the respective total concentrations were 3.10 [0.94, 14.64] for total bile acids, 3.05 for taurocholic acid, 14.30 [1.11, 27.13] for glycocholic acid, 0.0 for chenodeoxycholic acid, 2.19 for taurochenodeoxycholic acid, 1.91 [0.68, 8.64] for glycochenodeoxycholic acid and 0.77 [0.0, 13.79] for deoxycholic acid; other bile acids were not detected in the CSF. The ratio of CSF-to-serum S100 concentration was 0.01 [0.0, 0.02]. Serum total and conjugated (but not unconjugated) bilirubin levels and serum TBA levels were significantly correlated (total bilirubin p = 0.031 [0.023, 0.579]; conjugated bilirubin p = 0.001 [0.193, 0.683]; unconjugated p = 0.387 [−0.181, 0.426]). No correlations were found between bile acid concentrations and age, delirium, intraventricular blood volume, or outcome measured on a modified Rankin scale. (4) Conclusions: The determination of individual bile acids is feasible using the current LC-MS/MS method. The results suggest an intact blood–brain barrier in the patients studied. However, bile acids were detected in the CSF, which could have been achieved by active transport across the blood–brain barrier

Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value

Background: Impaired liver function and cholestasis are frequent findings in critically ill patients and are associated with poor outcomes. We tested the hypothesis that hypoxic liver injury and hypoxic cholangiocyte injury are detectable very early in patients with ARDS, may depend on the severity of hypoxemia, and may be aggravated by the use of rescue therapies (high PEEP level and prone positioning) but could be attenuated by extracorporeal membrane oxygenation (ECMO). Methods: In 70 patients with ARDS, aspartate-aminotransferase (AST), alanin-aminotransferase (ALT) and gamma glutamyltransferase (GGT) were measured on the day of the diagnosis of ARDS and three more consecutive days (day 3, day 5, day 10), total bile acids were measured on day 0, 3, and 5. Results: AST levels increased on day 0 and remained constant until day 5, then dropped to normal on day 10 (day 0: 66.5 U/l; day 3: 60.5 U/l; day 5: 63.5 U/l, day 10: 32.1 U/l), ALT levels showed the exact opposite kinetic. GGT was already elevated on day 0 (91.5 U/l) and increased further throughout (day 3: 163.5 U/l, day 5: 213 U/l, day 10: 307 U/l), total bile acids levels increased significantly from day 0 to day 3 (p = 0.019) and day 0 to day 5 (p < 0.001), but not between day 3 and day 5 (p = 0.217). Total bile acids levels were significantly correlated to GGT on day 0 (p < 0.001), day 3 (p = 0.02), and in a trend on day 5 (p = 0.055). PEEP levels were significantly correlated with plasma levels of AST (day 3), ALT (day 5) and GGT (day 10). Biomarker levels were not associated with the use of ECMO, prone position, the cause of ARDS, and paO2. Conclusions: We found no evidence of hypoxic liver injury or hypoxic damage to cholangiocytes being caused by the severity of hypoxemia in ARDS patients during the very early phase of the disease. Additionally, mean PEEP level, prone positioning, and ECMO treatment did not have an impact in this regard. Nevertheless, GGT levels were elevated from day zero and rising, this increase was not related to paO2, prone position, ECMO treatment, or mean PEEP, but correlated to total bile acid levels

The causes of hypoxemia of COVID-19 ARDS: a combined MIGET and Dual-Energy CT study.

BACKGROUND Despite the fervent scientific effort, a state-of-the art assessment of the different causes of hypoxemia (shunt, ventilation-perfusion mismatch and diffusion limitation) in COVID-19 ARDS is currently lacking. In this study we aimed to understand what is the relative contribution of the different mechanisms of hypoxemia in this disease and what is their relationship with the distribution of tissue and blood within the lung. METHODS We prospectively enrolled 10 patients with COVID-19 ARDS, intubated for <7 days. We performed the Multiple Inert Gas Elimination Technique (MIGET) and a Dual-Energy Computed Tomography (DECT), which was quantitatively analyzed both for the tissue and blood volume. We also recorded variables related to the respiratory mechanics and invasive hemodynamics (PiCCO). RESULTS The population (51±15 years, PaO2/FiO2 172±86 mmHg) had a mortality of 50%. MIGET showed a shunt of 25±16% and a deadspace of 53±11%. The ventilation and perfusion were mismatched (LogSD, Q 0.86±0.33). Unexpectedly, we also found evidence of diffusion limitation/post-pulmonary shunting (Predicted PaO2= 1.6*measured PaO2 - 37.5 mmHg). In the well-aerated regions, the blood volume was in excess compared to the tissue, while the opposite happened in the atelectasis. Shunt was proportional to the blood volume of the atelectasis (R 2=0.70, p=0.003). VA/QT mismatch was correlated with the blood volume of the poorly-aerated tissue (R 2=0.54, p=0.016). The overperfusion coefficient was related to PaO2/FiO2 (R 2=0.66, p=0.002), excess tissue mass (R 2=0.84, p<0.001) and to EtCO2/PaCO2 (R 2=0.63, p=0.004). CONCLUSIONS These data support the hypothesis of a highly multifactorial genesis of hypoxemia. Evidence from autoptic studies (i.e., opening of Intrapulmonary Bronchopulmonary Anastomosis) may explain the unexpected post-pulmonary shunting. The hyperperfusion might be related to the disease severity

Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation

Objectives: Severe acute respiratory syndrome coronavirus 2 cell entry depends on angiotensin-converting enzyme 2 and transmembrane serine protease 2 and is blocked in cell culture by camostat mesylate, a clinically proven protease inhibitor. Whether camostat mesylate is able to lower disease burden in coronavirus disease 2019 sepsis is currently unknown. Design: Retrospective observational case series. Setting: Patient treated in ICU of University hospital Göttingen, Germany. Patients: Eleven critical ill coronavirus disease 2019 patients with organ failure were treated in ICU. Interventions: Compassionate use of camostat mesylate (six patients, camostat group) or hydroxychloroquine (five patients, hydroxychloroquine group). Measurements and Main Results: Clinical courses were assessed by Sepsis-related Organ Failure Assessment score at days 1, 3, and 8. Further, viral load, oxygenation, and inflammatory markers were determined. Sepsis-related Organ Failure Assessment score was comparable between camostat and hydroxychloroquine groups upon ICU admission. During observation, the Sepsis-related Organ Failure Assessment score decreased in the camostat group but remained elevated in the hydroxychloroquine group. The decline in disease severity in camostat mesylate treated patients was paralleled by a decline in inflammatory markers and improvement of oxygenation. Conclusions: The severity of coronavirus disease 2019 decreased upon camostat mesylate treatment within a period of 8 days and a similar effect was not observed in patients receiving hydroxychloroquine. Camostat mesylate thus warrants further evaluation within randomized clinical trials

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged >= 18 years on invasive mechanical ventilation for >= 4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n= 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean +/- SD) was 12.7 +/- 9.9 days and 14.1 +/- 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction