Wiener Klinische Wochenschrift最新文献

Extracorporeal membrane oxygenation (ECMO) initiation at a non-ECMO-capable facility by specialized mobile teams aims for a stabilization prior to center admission, internationally referred to as ECMO retrieval. It is a recommended strategy to avoid primary interhospital transfer of compromised patients with a high risk of life-threatening incidents and potentially death. Deploying the unique skill set of ECMO installation and transportation to an unfamiliar environment, however, adds a further degree of complexity to the demanding fields of both transporting the critically ill and ECMO management itself. Although recommendations for the initiation of ECMO retrieval programs exist, centers globally tailor their course of action to local individual needs and so do we.The purpose of this work is to portray the decision-tree-based protocol of the intensive care unit 13i2 (Department of Medicine I, Medical University of Vienna) with its operational standards for optimal patient selection and transport organization.

Background: Next-generation sequencing (NGS) has recently entered routine acute myeloid leukemia (AML) diagnostics. It is paramount for AML risk stratification and identification of molecular therapeutic targets. Most NGS feasibility and results data are derived from controlled clinical intervention trials (CCIT). We aimed to validate these data in a real-world setting.

Patients, materials and methods: This study retrospectively analyzed 447 AML patients treated at an Austrian tertiary cancer care center. A total of 284 out of the 447 cases were treated between 2013-2023 when NGS was locally available for the clinical routine.

Results: The NGS was successfully performed from bone marrow biopsies and aspirates, with processing times decreasing from 22 days in 2013/2014 to 10 days in 2022. Molecular therapeutic target(s) were identified by NGS in 107/284 (38%) cases and enabled risk stratification in 10 cases where conventional karyotyping failed. Concerning molecular landscape, TET2 (27%), FLT3 (25%), DNMT3A (23%), and NPM1 (23%) were most frequently mutated. Comparing older and younger patients (cut-off 70 years) showed enrichment in older people for mutations affecting DNA methylation (72% vs. 45%; P < 0.001) and the spliceosome (28% vs. 11%; P = 0.006) and more cellular signaling mutations in younger patients (61% vs. 46%; P = 0.022). Treatment outcomes corroborated a significant survival benefit in the recent NGS era and patients treated with novel/molecularly targeted drugs. Ultimately, biospecimens of these patients are stored within a leukemia biobank, generating a valuable tool for translational science.

Conclusion: Our study validates data from CCIT and supports their relevance for treatment decisions in a real-world setting. Moreover, they demonstrate the feasibility and benefits of NGS within a routine clinical setting.

Background: Besides surgery, chemotherapy including high-dose methotrexate is a mainstay of osteosarcoma treatment. Methotrexate is known to accumulate in tissues and cavities, so-called third spaces (e.g., periprosthetic seromas) leading to local toxicity and delayed elimination (third space effect). We compared the concentrations of methotrexate in serum and periprosthetic seromas to evaluate a potential toxic risk based on a third space effect.

Methods: In 45 osteosarcoma patients who were treated with endoprosthesis and high-dose methotrexate (HDMTX) between 1991 and 2011 we retrospectively analyzed methotrexate concentrations in periprosthetic seromas and serum. Differences were assessed by means of the Wilcoxon test.

Results: A total of 112 periprosthetic seroma punctures were performed in 18 out of 45 patients. At 24 h the periprosthetic seroma concentrations were in median 14.86-fold (range 1.49-42.97-fold, p = 0.001), at 48 h in median 8.50-fold (range 1.36-52.56, p < 0.001) and at 72 h in median 2.66-fold (range 0.66-5.82, p = 0.015) of the corresponding serum concentrations. At 24 h highly toxic concentrations (≥ 20 μmol/l) were observed in 30% of all analyzed seromas (median 109.83 μmol/l, range 4.91-170.71 μmol/l). A significantly higher serum concentration (range 0.16-0.75 μmol/l, median 0.36 µmol/l) was found in patients with prior puncture than patients without puncture at 45 h after HDMTX.

Conclusion: Methotrexate concentrations of periprosthetic seromas are significantly higher than corresponding serum concentrations possibly contributing to a third space effect. To avoid severe adverse effects punctures of these effusions should be considered.

Amyloid-beta (Aβ) antibody treatment has emerged as a promising approach for the treatment of Alzheimer's disease (AD), targeting the accumulation of Aβ plaques, which are a hallmark of the disease. This review provides an update on recent clinical trial data, highlighting the efficacy and safety of various antibodies targeting Aβ. Recent trials have demonstrated that certain Aβ antibodies can reduce amyloid plaques and slow cognitive decline in patients with early AD. Key findings from trials of drugs are discussed, including their mechanisms of action, dosing regimens, and observed side effects. The potential for Aβ antibody therapy to be integrated into routine clinical practice is also explored. While Aβ antibody therapy represents a significant advancement in AD treatment, ongoing research is needed to optimize their use and understand their long-term impact. This review underscores the importance of personalized medicine in AD and the need for continued innovation in therapeutic strategies.

Impaired immune response to COVID-19 (coronavirus disease 2019) vaccination has been reported in patients with inborn errors of immunity (IEI). Repetitive vaccinations are recommended for this vulnerable group. Due to the high diversity within IEI patients, additional safety and immunogenicity data are needed to better understand these aspects especially in less common immunodeficiency syndromes. In this prospective open-label clinical trial, we assessed the humoral immune response and the T‑cell response in patients with IEI or severe MBL (mannose-binding lectin) deficiency (IEI/MBLdef) after three vaccinations. A total of 16 patients and 16 matched healthy controls (HC) with suboptimal humoral response defined by anti-SARS-CoV‑2 RBD (severe acute respiratory syndrome coronavirus type 2 receptor binding domain) antibodies below 1500 BAU/ml (binding antibody units per ml) after the second COVID-19 vaccination were enrolled in this study and qualified for a third mRNA vaccine dose. After 4 weeks following vaccination, 100% of HC and 75% of IEI/MBLdef patients exhibited anti-SARS-CoV‑2 RBD antibodies > 1500 BAU/ml, although the difference was not statistically significant (75% vs. 100%; p = 0.109). Although post-vaccination IEI/MBLdef patients demonstrated significantly increased anti-SARS-CoV‑2 RBD antibodies and neutralizing antibodies compared to baseline, these responses were significantly lower in IEI/MBLdef patients compared to HCs. Notably, the third vaccination augmented the cellular immune response to both wild-type and omicron peptide stimulation. No serious adverse events were reported within the 4‑week follow-up period and, importantly, vaccination had little to no effect on the long-term disease activity and fatigue. This trial strongly supports the recommendation of repeated COVID-19 vaccinations for patients suffering from immunodeficiencies, especially when they exhibit an initially limited response to the vaccine.

From 2011-2020 the number of reported cases of Lyme disease in the USA was lower in each even-numbered year compared with the preceding odd-numbered year. This observation suggests that fewer nymphal stage Ixodes scapularis ticks infected with Borrelia burgdorferi were present during even-numbered years in locations where people spend time.