CD301 and LSECtin glycan-binding receptors of innate immune cells serve as prognostic markers and potential predictors of immune response in breast cancer subtypes.

Glycosylation is a prominent posttranslational modification, and alterations in glycosylation are a hallmark of cancer. Glycan-binding receptors, primarily expressed on immune cells, play a central role in glycan recognition and immune response. Here, we used the recombinant C-type glycan-binding receptors CD301, Langerin, SRCL, LSECtin, and DC-SIGNR to recognize their ligands on tissue microarrays (TMA) of a large cohort (n = 1859) of invasive breast cancer of different histopathological types to systematically determine the relevance of altered glycosylation in breast cancer. Staining frequencies of cancer cells were quantified in an unbiased manner by a computer-based algorithm. CD301 showed the highest overall staining frequency (40%), followed by LSECtin (16%), Langerin (4%) and DC-SIGNR (0.5%). By Kaplan-Meier analyses, we identified LSECtin and CD301 as prognostic markers in different breast cancer subtypes. Positivity for LSECtin was associated with inferior disease-free survival in all cases, particularly in estrogen receptor positive (ER+) breast cancer of higher histological grade. In triple negative breast cancer, positivity for CD301 correlated with a worse prognosis. Based on public RNA single-cell sequencing data of human breast cancer infiltrating immune cells, we found CLEC10A (CD301) and CLEC4G (LSECtin) exclusively expressed in distinct subpopulations, particularly in dendritic cells and macrophages, indicating that specific changes in glycosylation may play a significant role in breast cancer immune response and progression.

Implementation of a software-based decision support tool for guideline-appropriate preoperative evaluation: a prospective agreement study.

BACKGROUND: Guideline adherence in the medical field leaves room for improvement. Digitalised decision support helps improve compliance. However, the complex nature of the guidelines makes implementation in clinical practice difficult. METHODS: This single-centre prospective study included 204 adult ASA physical status 3-4 patients undergoing elective noncardiac surgery at a German university hospital. Agreement of clearance for surgery between a guideline expert and a digital guideline support tool was investigated. The decision made by the on-duty anaesthetists (standard approach) was assessed for agreement with the expert in a cross-over design. The main outcome was the level of agreement between digital guideline support and the expert. RESULTS: The digital guideline support approach cleared 18.1% of the patients for surgery, the standard approach cleared 74.0%, and the expert approach cleared 47.5%. Agreement of the expert decision with digital guideline support (66.7%) and the standard approach (67.6%) was fair (Cohen's kappa 0.37 [interquartile range 0.26-0.48] vs 0.31 [0.21-0.42], P=0.6). Taking the expert decision as a benchmark, correct clearance using digital guideline support was 50.5%, and correct clearance using the standard approach was 44.6%. Digital guideline support incorrectly asked for additional examinations in 31.4% of the patients, whereas the standard approach did not consider conditions that would have justified additional examinations before surgery in 29.4%. CONCLUSIONS: Strict guideline adherence for clearance for surgery through digitalised decision support inadequately considered patients, clinical context. Vague formulations, weak recommendations, and low-quality evidence complicate guideline translation into explicit rules. CLINICAL TRIAL REGISTRATION: NCT04058769.

Susceptibility of AutoML mortality prediction algorithms to model drift caused by the COVID pandemic.

BACKGROUND: Concept drift and covariate shift lead to a degradation of machine learning (ML) models. The objective of our study was to characterize sudden data drift as caused by the COVID pandemic. Furthermore, we investigated the suitability of certain methods in model training to prevent model degradation caused by data drift. METHODS: We trained different ML models with the H2O AutoML method on a dataset comprising 102,666 cases of surgical patients collected in the years 2014-2019 to predict postoperative mortality using preoperatively available data. Models applied were Generalized Linear Model with regularization, Default Random Forest, Gradient Boosting Machine, eXtreme Gradient Boosting, Deep Learning and Stacked Ensembles comprising all base models. Further, we modified the original models by applying three different methods when training on the original pre-pandemic dataset: (Rahmani K, et al, Int J Med Inform 173:104930, 2023) we weighted older data weaker, (Morger A, et al, Sci Rep 12:7244, 2022) used only the most recent data for model training and (Dilmegani C, 2023) performed a z-transformation of the numerical input parameters. Afterwards, we tested model performance on a pre-pandemic and an in-pandemic data set not used in the training process, and analysed common features. RESULTS: The models produced showed excellent areas under receiver-operating characteristic and acceptable precision-recall curves when tested on a dataset from January-March 2020, but significant degradation when tested on a dataset collected in the first wave of the COVID pandemic from April-May 2020. When comparing the probability distributions of the input parameters, significant differences between pre-pandemic and in-pandemic data were found. The endpoint of our models, in-hospital mortality after surgery, did not differ significantly between pre- and in-pandemic data and was about 1% in each case. However, the models varied considerably in the composition of their input parameters. None of our applied modifications prevented a loss of performance, although very different models emerged from it, using a large variety of parameters. CONCLUSIONS: Our results show that none of our tested easy-to-implement measures in model training can prevent deterioration in the case of sudden external events. Therefore, we conclude that, in the presence of concept drift and covariate shift, close monitoring and critical review of model predictions are necessary.

Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer's disease.

Background: The prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer's disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer's disease animal models have been developed. The Tg2576 model of Alzheimer's disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer's disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice. Methods: After governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models. Results: During general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits. Conclusion: Isoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare.

Anaesthesiologists' guideline adherence in pre-operative evaluation: a retrospective observational study.

BACKGROUND: Surveys suggest a low level of implementation of clinical guidelines, although they are intended to improve the quality of treatment and patient safety. Which guideline recommendations are not followed and why has yet to be analysed. In this study, we investigate the proportion of European and national guidelines followed in the area of pre-operative anaesthetic evaluation prior to non-cardiac surgery. METHODS: We conducted this monocentric retrospective observational study at a German university hospital with the help of software that logically links guidelines in such a way that individualised recommendations can be derived from a patient's data. We included routine logs of 2003 patients who visited our pre-anaesthesia outpatient clinic between June 2018 and June 2020 and compared the actual conducted pre-operative examinations with the recommendations issued by the software. We descriptively analysed the data for examinations not performed that would have been recommended by the guidelines and examinations that were performed even though they were not covered by a guideline recommendation. The guidelines examined in this study are the 2018 ESAIC guidelines for pre-operative evaluation of adults undergoing elective non-cardiac surgery, the 2014 ESC/ESA guidelines on non-cardiac surgery and the German recommendations on pre-operative evaluation on non-cardiothoracic surgery from the year 2017. RESULTS: Performed ECG (78.1%) and cardiac stress imaging tests (86.1%) indicated the highest guideline adherence. Greater adherence rates were associated with a higher ASA score (ASA I: 23.7%, ASA II: 41.1%, ASA III: 51.8%, ASA IV: 65.8%, P < 0.001), lower BMI and age > 65 years. Adherence rates in high-risk surgery (60.5%) were greater than in intermediate (46.5%) or low-risk (44.6%) surgery (P < 0.001). 67.2% of technical and laboratory tests performed preoperatively were not covered by a guideline recommendation. CONCLUSIONS: Guideline adherence in pre-operative evaluation leaves room for improvement. Many performed pre-operative examinations, especially laboratory tests, are not recommended by the guidelines and may cause unnecessary costs. The reasons for guidelines not being followed may be the complexity of guidelines and organisational issues. A software-based decision support tool may be helpful. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT04843202.

Noninvasive Electromagnetic Phrenic Nerve Stimulation in Critically Ill Patients: A Feasibility Study.

BACKGROUND: Electromagnetic stimulation of the phrenic nerve induces diaphragm contractions, but no coils for clinical use have been available. We recently demonstrated the feasibility of ventilation using bilateral transcutaneous noninvasive electromagnetic phrenic nerve stimulation (NEPNS) before surgery in lung-healthy patients with healthy weight in a dose-dependent manner. RESEARCH QUESTION: Is NEPNS feasible in critically ill patients in an ICU setting? STUDY DESIGN AND METHODS: This feasibility nonrandomized controlled study aimed to enroll patients within 36 h of intubation who were expected to remain ventilated for ≥ 72 h. The intervention group received 15-min bilateral transcutaneous NEPNS bid, whereas the control group received standard care. If sufficient, NEPNS was used without pressure support to ventilate the patient; pressure support was added if necessary to ventilate the patient adequately. The primary outcome was feasibility, measured as time to find the optimal stimulation position. Further end points were sessions performed according to the protocol or allowing a next-day catch-up session and tidal volume achieved with stimulation reaching only 3 to 6 mL/kg ideal body weight (IBW). A secondary end point was expiratory diaphragm thickness measured with ultrasound from days 1 to 10 (or extubation). RESULTS: The revised European Union regulation mandated reapproval of medical devices, prematurely halting the study. Eleven patients (five in the intervention group, six in the control group) were enrolled. The median time to find an adequate stimulation position was 23 s (interquartile range, 12-62 s). The intervention bid was executed in 87% of patients, and 92% of patients including a next-day catch-up session. Ventilation with 3 to 6 mL/kg IBW was achieved in 732 of 1,701 stimulations (43.0%) with stimulation only and in 2,511 of 4,036 stimulations (62.2%) with additional pressure support. A decrease in diaphragm thickness was prevented by bilateral NEPNS (P = .034) until day 10. INTERPRETATION: Bilateral transcutaneous NEPNS was feasible in the ICU setting with the potential benefit of preventing diaphragm atrophy during mechanical ventilation. NEPNS ventilation effectiveness needs further assessment. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05238753; URL: www. CLINICALTRIALS: gov.