Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes

Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity.Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity

Biomechanischer Vergleich operativ rekonstruierter Achillessehnenrupturen unter Verwendung unterschiedlicher distaler Verankerungen im ex vivo Schweinemodell

Die Therapie der akuten Achillessehnenruptur gliedert sich in konservative und operative Verfahren. Unter den operativen gibt es offen-chirurgische und minimal-invasiv perkutane Techniken. Weiter können die Nähte in belastbare und adaptierende Nähte unterteilt werden. Kann ein Knochenanker für die offen-chirurgische Versorgung der Achillessehnenruptur der Krackow-Naht vorgezogen werden? Die Krackow-Naht gilt als Benchmark für die biomechanischen Studien zur Achillessehnennaht. An 48 rechten hinteren Schweinefüßen wurde mit der Materialprüfmaschine Zwicki-Line 2,5kN und der optischen Messeinheit PONTOS 5M eine biomechanische ex vivo Studie durchgeführt. Eine Gruppe umfasste dabei 16 Präparate. Die Gruppe M0 wurde mit der Krackow-Naht versorgt. Die Gruppe M1 erhielt einen Mitek-Anker. Die Gruppe M2 erhielt eine transossäre Bohrung in der Sagittalebene des Calcaneus, durch welche die Fäden geführt wurden. Als relevanter Unterschied wurden 50 N (ca. 5kg) als Testkriterium festgelegt. Der mechanische Teil der Studie bestand in der Präparation der Schweinesehnen, der Anpassung der Prüfmaschinen an die biologischen Strukturen und der Naht selbst. Der mitgelieferte Faden im Mitek-Anker, OrthocordTM , wurde in allen Versuchen verwendet. Sowohl Fallzahlplanung, Definition der Prüfkriterien als auch Auswertung wurden vom Institut für Klinische Epidemiologie und angewandte Biometrie in Tübingen unterstützt. Bezüglich der Maximalkraft Fmax[N] kam es zu keinem relevanten oder signifikanten Unterschied zwischen den drei Gruppen. Aufgrund der Streuung kann keine Ebenbürtigkeit festgestellt werden. Die Mittelwerte der drei Gruppen liegen im Bereich von 600 bis 629 N nah beieinander. Die Streuung der Messewerte überspannt einen Bereich von 550 bis 670 N. Die Ergebnisse konnten die Hypothese der Forschungsfrage nicht ausreichend bedienen, da die Gruppen einander zu ähnlich waren. Im Einzelvergleich mit denselben Techniken anderer Autoren gliedern sich die Ergebnisse dieser Arbeit sehr gut ein. Somit bleibt aufgrund der Datenlage dem Operateur nur die Krackow-Naht zu empfehlen, da sie verglichen mit dem Mitek-Anker und der transossären Technik das geringste OP-Trauma verursacht

Needle penetration test - qualifying examination of 3D printable silicones for vascular models in surgical practice

Background!#!During cardiogenic shock blood circulation is minimal in the human body and does not suffice to survive. The extracorporeal life support system (ECLS) acts as a miniature heart-lung-machine that can be temporarily implanted over major vessels e.g. at the groin of the patient to bridge cardiogenic shock. To perform this procedure in an emergency, a proper training model is desirable. Therefore, a 3-dimensional-printable (3D) material must be found that mimics large vessel needle penetration properties. A suitable test bench for material comparison is desirable.!##!Methods!#!A test setup was built, which simulated the clinically relevant wall tension in specimens. The principle was derived from an existing standardized needle penetration test. After design, the setup was fabricated by means of 3D printing and mounted onto an universal testing machine. For testing the setup, a 3D printable polymer with low Shore A hardness and porcine aorta were used. The evaluation was made by comparing the curves of the penetration force to the standardized test considering the expected differences.!##!Results!#!3D printing proved to be suitable for manufacturing the test setup, which finally was able to mimic wall tension as if under blood pressure and penetration angle. The force displacement diagrams showed the expected curves and allowed a conclusion to the mechanical properties of the materials. Although the materials forces deviated between the porcine aorta and the Agilus30 polymer, the graphs showed similar but still characteristic curves.!##!Conclusions!#!The test bench provided the expected results and was able to show the differences between the two materials. To improve the setup, limitations has been discussed and changes can be implemented without complications

The elastic capacity of a tendon-repair construct influences the force necessary to induce gapping.

PURPOSE Most biomechanical investigations of tendon repairs were based on output measures from hydraulic loading machines, therefore, accounting for construct failure rather than true gapping within the rupture zone. It was hypothesized that the elastic capacity of a tendon-repair construct influences the force necessary to induce gapping. METHODS A tendon-repair model was created in 48 porcine lower hind limbs, which were allocated to three fixation techniques: (1) Krackow, (2) transosseous and (3) anchor fixation. Loading was performed based on a standardized phased load-to-failure protocol using a servohydraulic mechanical testing system MTS (Zwick Roell, Ulm, Germany). Rupture-zone dehiscence was measured with an external motion capture device. Factors influencing dehiscence formation was determined using a linear regression model and adjustment performed as necessary. A 3-mm gap was considered clinically relevant. Analysis of variance (ANOVA) was used for comparison between groups. RESULTS The elastic capacity of a tendon-repair construct influences the force necessary to induce gapping of 3 mm (F3mm) [β = 0.6, confidence interval (CI) 0.4-1.0, p < 0.001]. Furthermore, the three methods of fixation did not differ significantly in terms of maximum force to failure (n.s) or F3mm (n.s). CONCLUSION The main finding of this study demonstrated that the higher the elastic capacity of a tendon-repair construct, the higher the force necessary to induce clinically relevant gapping. LEVEL OF EVIDENCE Controlled biomechanical study

Mitral Valve Surgery via Upper Ministernotomy: Single-Centre Experience in More than 400 Patients

Background: Minimally invasive mitral valve (MV) surgery has emerged as an alternative to conventional sternotomy aiming to decrease surgical trauma. The aim of the study was to describe our experience with minimally invasive MV surgery through partial upper sternotomy (PUS) regarding short- and long-term outcomes. Methods: From January 2004 through March 2014, 419 patients with a median age of 58.9 years (interquartile range 18.7; 31.7% females) underwent isolated primary MV surgery using PUS. Myxomatous degenerative MV disease was the predominant pathology (77%). The patients’ mean EuroSCORE II risk profile was 3.9 ± 3.6%. Results: Mitral valve repair was performed in 384 patients (91.6%) and replacement in 35 patients (8.4%). Thirty-day mortality was 3.1%. In total, 29 (6.9%) deaths occurred during the follow-up. The overall estimated survival at 1, 5, and 10 years was 93.1 ± 1.3%, 87.1 ± 1.9%, and 81.1 ± 3.4%. Reoperation was necessary in 14 (3.3%) patients. The overall freedom from MV reoperation at 1, 5, and 10 years was 98.2 ± 0.7%, 96.1 ± 1.2%, and 86.7 ± 6.7% and the overall freedom from recurrent MV regurgitation &gt; grade 2 in repaired valves at 1, 5, and 10 years was 98.8 ± 0.6%, 98.8 ± 0.6%, and 94.6 ± 3.3%. Conclusions: Minimally invasive MV surgery via PUS can be performed with particularly good early and late results. Thus, the PUS approach with the use of standard surgical instruments and cannulation techniques can be a valuable option for the MV surgery either in patients contraindicated or not suitable to minithoracotomy

Mitral Valve Surgery via Upper Ministernotomy: Single-Centre Experience in More than 400 Patients

Background: Minimally invasive mitral valve (MV) surgery has emerged as an alternative to conventional sternotomy aiming to decrease surgical trauma. The aim of the study was to describe our experience with minimally invasive MV surgery through partial upper sternotomy (PUS) regarding short- and long-term outcomes. Methods: From January 2004 through March 2014, 419 patients with a median age of 58.9 years (interquartile range 18.7; 31.7% females) underwent isolated primary MV surgery using PUS. Myxomatous degenerative MV disease was the predominant pathology (77%). The patients’ mean EuroSCORE II risk profile was 3.9 ± 3.6%. Results: Mitral valve repair was performed in 384 patients (91.6%) and replacement in 35 patients (8.4%). Thirty-day mortality was 3.1%. In total, 29 (6.9%) deaths occurred during the follow-up. The overall estimated survival at 1, 5, and 10 years was 93.1 ± 1.3%, 87.1 ± 1.9%, and 81.1 ± 3.4%. Reoperation was necessary in 14 (3.3%) patients. The overall freedom from MV reoperation at 1, 5, and 10 years was 98.2 ± 0.7%, 96.1 ± 1.2%, and 86.7 ± 6.7% and the overall freedom from recurrent MV regurgitation > grade 2 in repaired valves at 1, 5, and 10 years was 98.8 ± 0.6%, 98.8 ± 0.6%, and 94.6 ± 3.3%. Conclusions: Minimally invasive MV surgery via PUS can be performed with particularly good early and late results. Thus, the PUS approach with the use of standard surgical instruments and cannulation techniques can be a valuable option for the MV surgery either in patients contraindicated or not suitable to minithoracotomy