Grietje Beck

Background: In acute respiratory distress syndrome (ARDS), global airway pressures do not distinguish lung from chest wall mechanics, limiting bedside identification of regional overdistension. Anterior chest wall loading (ACWL) has been proposed to transiently increase nondependent pleural pressure and unmask regional overdistension, but its dose-dependent effects remain uncertain. The authors hypothesized that low loads reduce transpulmonary driving pressure (ΔP) whereas higher loads promote derecruitment and hemodynamic compromise. Methods: In this prospective, exploratory study, 30 patients with moderate-to-severe ARDS (Pao ₂ /F i o ₂ ratio of 150 mmHg or less) underwent ACWL. In a dose–response cohort (phase 1, n = 20), ACWL at 5%, 10%, 15%, and 20% of body weight was applied in random order; 5% body weight was then assessed in a separate cohort (phase 2, n = 10) using electrical impedance tomography. The primary endpoint was transpulmonary ΔP; secondary endpoints included partitioned respiratory mechanics, end-expiratory lung volume, gas exchange, and hemodynamics. Results: ACWL dose-dependently increased esophageal pressures, reducing transpulmonary pressures and end-expiratory lung volume, with nonlinear, baseline-dependent compliance responses. At 5% body weight, ACWL reduced transpulmonary ΔP (median [interquartile range], 6 [4, 7] vs. 7 [5, 8] cm H ₂ O; P = 0.015) and lung stress (13.0 [10.2, 15.1] vs. 14.4 [11.8, 17.1] cm H ₂ O; P = 0.001) compared with baseline, with increased nondependent lung compliance. End-expiratory lung volume was lower (1,559 [1,107, 2,051] vs. 1,784 [1,325, 2,332] ml; P < 0.001), with a predominantly dependent decline in regional end-expiratory lung impedance, consistent with derecruitment. At 5% body weight, gas exchange worsened, and cardiac output and oxygen delivery declined. Conclusions: In moderate-to-severe ARDS, ACWL induced dose-dependent changes in pleural pressure and respiratory mechanics. By increasing nondependent pleural pressure, it relieved nondependent overdistension and lowered transpulmonary ΔP, but simultaneously caused dependent derecruitment and, by increasing central venous pressure, hemodynamic compromise. These findings support ACWL as a physiologic probe of lung–chest wall interactions rather than a therapeutic intervention.

BACKGROUND: Exercise intolerance, promoted by skeletal muscle- and mitochondrial dysfunction, has been identified as a therapeutic target in heart failure with preserved ejection fraction (HFpEF). In the context of mitochondrial dysfunction, altered cardiolipin integrity has been reported in the myocardium of HFpEF, suggesting Elamipretide, a cardiolipin stabilizing agent, as potential therapeutic approach. The present study investigated cardiolipin dysregulation in the skeletal muscle of HFpEF rats and analyzed the effect of Elamipretide treatment. METHODS: Female zucker fatty spontaneously hypertensive heart failure F1 hybrid lean (n=10, control) and obese rats (n=24, HFpEF) were included. At 20 weeks of age, HFpEF rats were randomized into 2 groups receiving NaCl (n=12) or Elamipretide (n=12) for 12 weeks. Skeletal muscle tissue was collected for whole-muscle force, single-fiber mechanics, mitochondrial respiration, histology and molecular analyses. RESULTS: HFpEF rats exhibited reduced cardiolipin levels (−6.8%, P =0.007) and maturation (shown via tafazzin expression), contractile dysfunction, titin hyperphosphorylation, fiber atrophy and increased oxidative stress markers. Elamipretide improved whole muscle (soleus: +8.2%, P =0.041, extensor digitorum longus: +10.9%, P =0.016) and single-fiber (soleus: +173.2%, P P =ns) contractile function and titin phosphorylation (soleus: −35.4%, P P P =0.001, extensor digitorum longus: +54.8%, P <0.001). Improved mitochondrial function, presumably through cardiolipin-mediated improvements in oxidative phosphorylation, could be associated with muscle force and cardiolipin integrity. CONCLUSIONS: Our data highlight cardiolipin stabilization as a key modulator of mitochondrial and contractile function in HFpEF, identifying Elamipretide as a promising therapeutic approach for skeletal muscle dysfunction.

Background: Moderate to severe postoperative pain is common among patients following thoracotomy and serves as a risk factor for developing chronic post-thoracotomy pain (CPTP). This randomized controlled trial evaluated the effects of pre-emptively administered ketamine compared to placebo and standard care on both acute postoperative pain and CPTP. Methods: Two hundred patients were enrolled in this prospective, randomized trial. The presence and severity of pain were assessed before surgery, first 6 hours after surgery, on postoperative days (PODs) 1–8, 30, and 90. For documentation of neuropathic pain, the Leeds Assessment Score for Neuropathic Symptoms and Signs (LANSS) was used pre- and postoperatively. The incidence and severity of CPTP was assessed by a telephone survey, the self-assessment LANSS (S-LANSS) 30 and 90 days after surgery. Results: There was significant difference in numeric rating scale (NRS) pain scores when coughing in the first 6 hours after surgery, with less pain in the ketamine group. No difference was seen in NRS pain scores at rest and coughing between the ketamine and placebo group on PODs 1–8. There was no difference in the opioid consumption between the two groups. Thirty-four (18.7%) of the patients had a S-LANSS score ≥12 30 days following surgery, 12 (12.8%) in the ketamine group vs. 22 (25%) in the placebo group (P=0.001). Thirty-three (18.2%) of all patients had a S-LANSS score ≥12 90 days following surgery 8 (8.5%) in the ketamine group vs. 25 (28.4%) in the placebo group (PConclusions: In summary, pre-emptive ketamine does not reduce opioid consumption and NRS scores after thoracotomy but more importantly it lowers significantly the incidence of chronic postoperative pain, especially neuropathic pain. Trial Registration: The study was registered at ClinicalTrials.gov (NCT 03105765).

Zusammenfassung Die Integration von künstlicher Intelligenz (KI) in die Intensivmedizin zeigt in neuesten Studien besonders in den Bereichen der prädiktiven Analytik, der Früherkennung von Komplikationen und der Entwicklung von Entscheidungsunterstützungssystemen beachtliche Fortschritte. Die Hauptherausforderungen bestehen weiterhin in der Verfügbarkeit und Qualität der Daten, der Reduzierung von Verzerrungen und der Notwendigkeit erklärbarer Ergebnisse von Algorithmen und Modellen. Methoden zur Erklärung dieser Systeme sind essenziell, um Vertrauen, Verständnis und ethische Überlegungen bei Gesundheitsfachkräften und Patienten zu stärken. Eine fundierte Ausbildung des medizinischen Personals in KI-Prinzipien, Terminologie, ethischen Überlegungen und in der praktischen Anwendung ist für den erfolgreichen Einsatz von KI entscheidend. Die sorgfältige Bewertung der Auswirkungen von KI auf Patientenautonomie und Datenschutz ist unabdingbar für deren verantwortungsvolle Nutzung in der Intensivmedizin. Hierbei ist die Balance zwischen ethischen und praktischen Erwägungen zu wahren, um eine patientenzentrierte Versorgung bei gleichzeitiger Einhaltung von Datenschutzbestimmungen zu gewährleisten. Eine synergistische Zusammenarbeit zwischen Klinikern, KI-Ingenieuren und Regulierungsbehörden ist entscheidend, um das volle Potenzial der KI in der Intensivmedizin zu realisieren und ihre positive Wirkung auf die Patientenversorgung zu maximieren. Zukünftige Forschungs- und Entwicklungsanstrengungen sollten sich auf die Verbesserung von KI-Modellen für Echtzeitvorhersagen, die Steigerung der Genauigkeit und des Nutzens KI-basierter Closed-loop-Systeme sowie die Überwindung ethischer, technischer und regulatorischer Herausforderungen, insbesondere bei generativen KI-Systemen, fokussieren.

Background: The purpose of this report is to describe the seminal case of a near-term human fetus with a life-threatening left diaphragmatic hernia that underwent fetoscopic tracheal occlusion (FETO) combined with fetoscopic partial removal of herniated bowel from the fetal chest by fetoscopic laparoschisis (FETO-LAP). Case summary: A life-threatening left diaphragmatic hernia (liver-up; o/e LHR of ≤25%; MRI lung volume ≤ 20%) was observed in a human fetus at 34 weeks of gestation. After counselling the mother about the high risks of postnatal demise if left untreated, the expected limitations of fetoscopic tracheal occlusion (FETO), and the previously untested option of combining FETO with fetoscopic laparoschisis, i.e., partial removal of the herniated bowel from the fetal chest (FETO-LAP), she consented to the latter novel treatment approach. FETO-LAP was performed at 36 + 5 weeks of gestation under general maternofetal anesthesia. Mother and fetus tolerated the procedure well. The neonate was delivered and the balloon removed on placental support at 37 + 2 weeks of gestation. On ECMO, a rapid increase in tidal volume was seen over the next eight days. Unfortunately, after this period, blood clots obstructed the ECMO circuit and the neonate passed away. Discussion: This seminal case shows that in a fetus with severe left diaphragmatic hernia, partial removal of the herniated organs from the fetal chest is not only possible by minimally invasive fetoscopic techniques but also well tolerated. As the effect of FETO alone is limited in saving severely affected fetuses, combining FETO with fetoscopic laparoschisis (FETO-LAP) offers a new therapeutic route with multiple, potentially life-saving implications.