Lung transplantation following controlled hypothermic storage with a portable lung preservation device: first multicenter European experience

IntroductionCompared with traditional static ice storage, controlled hypothermic storage (CHS) at 4–10°C may attenuate cold-induced lung injury between procurement and implantation. In this study, we describe the first European lung transplant (LTx) experience with a portable CHS device.MethodsA prospective observational study was conducted of all consecutively performed LTx following CHS (11 November 2022 and 31 January 2024) at two European high-volume centers. The LUNGguard device was used for CHS. The preservation details, total ischemic time, and early postoperative outcomes are described. The data are presented as median (range: minimum–maximum) values.ResultsA total of 36 patients underwent LTx (i.e., 33 bilateral, 2 single LTx, and 1 lobar). The median age was 61 (15–68) years; 58% of the patients were male; 28% of the transplantations had high-urgency status; and 22% were indicated as donation after circulatory death. In 47% of the patients, extracorporeal membrane oxygenation (ECMO) was used for perioperative support. The indications for using the CHS device were overnight bridging (n = 26), remote procurement (n = 4), rescue allocation (n = 2), logistics (n = 2), feasibility (n = 1), and extended-criteria donor (n = 1). The CHS temperature was 6.5°C (3.7°C–9.3°C). The preservation times were 11 h 18 (2 h 42–17 h 9) and 13 h 40 (4 h 5–19 h 36) for the first and second implanted lungs, respectively, whereas the total ischemic times were 13 h 38 (4 h 51–19 h 44) and 15 h 41 (5 h 54–22 h 48), respectively. The primary graft dysfunction grade 3 (PGD3) incidence rates were 33.3% within 72 h and 2.8% at 72 h. Intensive care unit stay was 8 (4–62) days, and the hospital stay was 28 (13–87) days. At the last follow-up [139 (7–446) days], three patients were still hospitalized. One patient died on postoperative day 7 due to ECMO failure. In-hospital Clavien–Dindo complications of 3b were observed in six (17%) patients, and 4a in seven (19%).ConclusionCHS seems safe and feasible despite the high-risk recipient and donor profiles, as well as extended preservation times. PGD3 at 72 h was observed in 2.8% of the patients. This technology could postpone LTx to daytime working hours. Larger cohorts and longer-term outcomes are required to confirm these observations

Phase I Safety, Pharmacokinetics, and Inhibition of Src Activity Study of Saracatinib in Patients with Solid Tumors

PURPOSE: This dose-escalation study evaluated the safety, tolerability, and pharmacokinetics (PK) of the oral Src inhibitor saracatinib (AZD0530) in patients with advanced solid malignancies. Tumor biopsy samples were taken to investigate the effect of saracatinib on Src activity in tumors. EXPERIMENTAL DESIGN: Part A of the study followed a multiple-ascending dose design to establish the maximum tolerated dose (MTD) of saracatinib. Part B was a randomized, parallel-group, cohort-expansion phase to further assess tolerated doses. Safety, tolerability, and Src activity (immunohistochemistry and lysate-based methodologies) were assessed after 21 days of once-daily oral dosing. PK was assessed after single and multiple dosing. RESULTS: In part A, 30 patients received once-daily saracatinib at doses of 60 to 250 mg; the MTD was established as 175 mg. In part B, 51 patients were randomized to receive 50 mg (n = 16), 125 mg (n = 16), or 175 mg (n = 19) of saracatinib. The most common grade ≥3 events considered to be treatment related were anemia, diarrhea, and asthenia. Tumor Src activity was reduced following saracatinib treatment. The area under the concentration-time curve and C(max) of saracatinib increased with increasing dose. Saracatinib accumulated 4- to 5-fold on once-daily dosing to reach steady-state exposure after 10 to 17 days of dosing. The half-life was ∼40 hours. CONCLUSIONS: Saracatinib was well tolerated in patients with advanced solid malignancies. A reduction in tumor Src activity was observed. PK data show that saracatinib is suitable for once-daily oral dosing. Based on this study, the recommended dose for the phase II studies was chosen to be 175 mg/d

Successful double-lung transplantation from a donor previously infected with SARS-CoV-2

status: Published onlin

Antiinflammatorisch wirksame Phytotherapeutika und ihr mögliches Potential bei tumorkranken Menschen

Die Wirkstoffe pflanzlicher Arznei- und Heilmittel sind pleiotrope Vielstoffgemische mit Multi-Target Eigenschaften einschlieβlich antiinflammatorischer Wirkungen. Eine pleiotrope Entzündungshemmung könnte bei tumorkranken Menschen als Versuch der Verhinderung bzw. Verzögerung der Metastasierung eine bedeutsame Rolle spielen. Zahlreiche experimentelle Daten für europäische wie auch auβereuropäische Pflanzen und verschiedene phytotherapeutische Kombinationen weisen auf eine solche Möglichkeit hin. Trotz der bislang nur geringen Anzahl klinischer Untersuchungen könnten derartige phytotherapeutische Behandlungsversuche vertretbar erscheinen, wenn für solche Arznei- und Heilpflanzen aus Anwendungsbereichen bei nicht tumorkranken Menschen gesicherte Daten über Qualität und Sicherheit dokumentiert sind und eine Übertragung solcher Daten auf die Situation tumorkranker Menschen unter kritischer Abwägung möglich erscheint. Phytotherapeutika spielen zudem in der Supportivtherapie eine zunehmende Rolle, wobei zahlreiche dieser Phytotherapeutika neben ihrer symptomatischen supportiven Wirksamkeit auch antiinflammatorische Wirkungen zeigen. Die gezielte Auswahl von supportiv wirksamen Phytotherapeutika mit zusätzlichen antiinflammatorischen Effekten könnte für tumorkranke Menschen neben der Symptomlinderung simultan die Möglichkeit einer antiinflammatorischen antitumoralen Wirksamkeit bieten als eine Art personalisierter Phytotherapie. Zurzeit besteht diesbezüglich noch ein groβer Bedarf an therapeutisch orientierter klinischer Forschung. Copyright © 2011 S. Karger AG, Base