Treatment of sleep apnoea early after myocardial infarction with adaptive servo-ventilation - a proof-of-concept randomised controlled trial.

INTRODUCTION: Sleep-disordered breathing has been associated with less myocardial salvage and smaller infarct size reduction after acute myocardial infarction (AMI). The Treatment of sleep apnoea Early After Myocardial infarction with Adaptive Servo-Ventilation (TEAM-ASV I) trial investigated the effects of adding adaptive servo-ventilation (ASV) for sleep-disordered breathing (SDB) to standard therapy on myocardial salvage index (MSI) and change in infarct size within 12 weeks after AMI. METHODS: In this multicentre, randomised, open-label trial, patients with AMI and successful percutaneous coronary intervention within 24 h after symptom onset plus SDB (apnoea-hypopnoea index ≥15/h) were randomised to standard medical therapy alone (control) or plus ASV (starting 3.6±1.4 days post-AMI). The primary outcome was MSI at 12 weeks post-AMI. Cardiac magnetic resonance (CMR) imaging was performed at ≤5 days and 12 weeks after AMI. RESULTS: Seventy-six individuals were enrolled from February 2014 to August 2020; 39 had complete CMR data for analysis of the primary endpoint. MSI was significantly higher in the ASV versus control group (difference 14.6% of left ventricular mass [LVM]; 95% confidence interval 0.14-29.1; p=0.048). At 12 weeks, absolute [interquartile range] (6.6 [4.8-8.5] versus 2.8 [0.9-4.8] %LVM; p=0.003) and relative (44 [30-57] versus 21 [6-35] % of baseline; p=0.013) reductions in infarct size were greater in the ASV versus control group. No serious treatment-related adverse events occurred. CONCLUSIONS: Early treatment of SDB with ASV improved the MSI and decreased the infarct size at 12 weeks after AMI. Larger randomised trials are required to confirm these findings.

Irinotecan and temozolomide in combination with dasatinib and rapamycin versus irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma (RIST-rNB-2011): a multicentre, open-label, randomised, controlled, phase 2 trial.

BACKGROUND: Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the combination of irinotecan-temozolomide and dasatinib-rapamycin (RIST) in patients with relapsed or refractory neuroblastoma. METHODS: The multicentre, open-label, randomised, controlled, phase 2, RIST-rNB-2011 trial recruited from 40 paediatric oncology centres in Germany and Austria. Patients aged 1-25 years with high-risk relapsed (defined as recurrence of all stage IV and MYCN amplification stages, after response to treatment) or refractory (progressive disease during primary treatment) neuroblastoma, with Lansky and Karnofsky performance status at least 50%, were assigned (1:1) to RIST (RIST group) or irinotecan-temozolomide (control group) by block randomisation, stratified by MYCN status. We compared RIST (oral rapamycin [loading 3 mg/m2 on day 1, maintenance 1 mg/m2 on days 2-4] and oral dasatinib [2 mg/kg per day] for 4 days with 3 days off, followed by intravenous irinotecan [50 mg/m2 per day] and oral temozolomide [150 mg/m2 per day] for 5 days with 2 days off; one course each of rapamycin-dasatinib and irinotecan-temozolomide for four cycles over 8 weeks, then two courses of rapamycin-dasatinib followed by one course of irinotecan-temozolomide for 12 weeks) with irinotecan-temozolomide alone (with identical dosing as experimental group). The primary endpoint of progression-free survival was analysed in all eligible patients who received at least one course of therapy. The safety population consisted of all patients who received at least one course of therapy and had at least one post-baseline safety assessment. This trial is registered at ClinicalTrials.gov, NCT01467986, and is closed to accrual. FINDINGS: Between Aug 26, 2013, and Sept 21, 2020, 129 patients were randomly assigned to the RIST group (n=63) or control group (n=66). Median age was 5·4 years (IQR 3·7-8·1). 124 patients (78 [63%] male and 46 [37%] female) were included in the efficacy analysis. At a median follow-up of 72 months (IQR 31-88), the median progression-free survival was 11 months (95% CI 7-17) in the RIST group and 5 months (2-8) in the control group (hazard ratio 0·62, one-sided 90% CI 0·81; p=0·019). Median progression-free survival in patients with amplified MYCN (n=48) was 6 months (95% CI 4-24) in the RIST group versus 2 months (2-5) in the control group (HR 0·45 [95% CI 0·24-0·84], p=0·012); median progression-free survival in patients without amplified MYCN (n=76) was 14 months (95% CI 9-7) in the RIST group versus 8 months (4-15) in the control group (HR 0·84 [95% CI 0·51-1·38], p=0·49). The most common grade 3 or worse adverse events were neutropenia (54 [81%] of 67 patients given RIST vs 49 [82%] of 60 patients given control), thrombocytopenia (45 [67%] vs 41 [68%]), and anaemia (39 [58%] vs 38 [63%]). Nine serious treatment-related adverse events were reported (five patients given control and four patients given RIST). There were no treatment-related deaths in the control group and one in the RIST group (multiorgan failure). INTERPRETATION: RIST-rNB-2011 demonstrated that targeting of MYCN-amplified relapsed or refractory neuroblastoma with a pathway-directed metronomic combination of a multkinase inhibitor and an mTOR inhibitor can improve progression-free survival and overall survival. This exclusive efficacy in MYCN-amplified, relapsed neuroblastoma warrants further investigation in the first-line setting. FUNDING: Deutsche Krebshilfe.

Cardiorespiratory Markers Relate to Change-of-Direction Performance During Incremental Endurance Tests and Friendly Matches in Professional Male Handball Players.

PURPOSE: To compare the standard Yo-Yo intermittent recovery (IR) test and an agility Yo-Yo IR test with a higher number of change-of-direction movements to cardiorespiratory match performance. METHODS: The study included 11 professional male handball players (age 24.5 [4.6] y) of a German second-league team. The performance parameters of the players of the seasons 2016-17 to 2018-19 were analyzed. The Yo-Yo IR test was compared to a Yo-Yo IR test with multiple multidirectional changes of direction in response to visual stimuli, which was conducted on a SpeedCourt (Yo-Yo SC IR). Peak oxygen uptake (VO2peak) and maximum heart rate (HRmax) were measured. Between-methods differences of individual athletes were quantified with Bland-Altman plots. RESULTS: HRmax was not statistically different during the Yo-Yo SC IR test compared to the Yo-Yo IR test (181 [10] vs 188 [8] beats·min-1; P = .16). Agreement between the 2 tests was moderate for HRmax and good for heart rates >180 beats·min-1. Mean average VO2peak was 51.7 (3.9) and 50.9 (2.8) mL·min-1·kg-1 for the Yo-Yo SC IR test and the Yo-Yo IR test (P = .693), respectively. CONCLUSIONS: A Yo-Yo test with multidirectional changes of direction in response to visual stimuli yielded good agreement with the frequently used linear running tests and can be used to assess players' VO2peak. The HRmax achieved during this test should be used with caution.

NaV1.8 as Proarrhythmic Target in a Ventricular Cardiac Stem Cell Model.

The sodium channel NaV1.8, encoded by the SCN10A gene, has recently emerged as a potential regulator of cardiac electrophysiology. We have previously shown that NaV1.8 contributes to arrhythmogenesis by inducing a persistent Na+ current (late Na+ current, INaL) in human atrial and ventricular cardiomyocytes (CM). We now aim to further investigate the contribution of NaV1.8 to human ventricular arrhythmogenesis at the CM-specific level using pharmacological inhibition as well as a genetic knockout (KO) of SCN10A in induced pluripotent stem cell CM (iPSC-CM). In functional voltage-clamp experiments, we demonstrate that INaL was significantly reduced in ventricular SCN10A-KO iPSC-CM and in control CM after a specific pharmacological inhibition of NaV1.8. In contrast, we did not find any effects on ventricular APD90. The frequency of spontaneous sarcoplasmic reticulum Ca2+ sparks and waves were reduced in SCN10A-KO iPSC-CM and control cells following the pharmacological inhibition of NaV1.8. We further analyzed potential triggers of arrhythmias and found reduced delayed afterdepolarizations (DAD) in SCN10A-KO iPSC-CM and after the specific inhibition of NaV1.8 in control cells. In conclusion, we show that NaV1.8-induced INaL primarily impacts arrhythmogenesis at a subcellular level, with minimal effects on systolic cellular Ca2+ release. The inhibition or knockout of NaV1.8 diminishes proarrhythmic triggers in ventricular CM. In conjunction with our previously published results, this work confirms NaV1.8 as a proarrhythmic target that may be useful in an anti-arrhythmic therapeutic strategy.

Nocturnal hypoxemic burden and micro- and macrovascular disease in patients with type 2 diabetes.

BACKGROUND: Micro- and macrovascular diseases are common in patients with type 2 diabetes mellitus (T2D) and may be partly caused by nocturnal hypoxemia. The study aimed to characterize the composition of nocturnal hypoxemic burden and to assess its association with micro- and macrovascular disease in patients with T2D. METHODS: This cross-sectional analysis includes overnight oximetry from 1247 patients with T2D enrolled in the DIACORE (DIAbetes COhoRtE) study. Night-time spent below a peripheral oxygen saturation of 90% (T90) as well as T90 associated with non-specific drifts in oxygen saturation (T90non - specific), T90 associated with acute oxygen desaturation (T90desaturation) and desaturation depths were assessed. Binary logistic regression analyses adjusted for known risk factors (age, sex, smoking status, waist-hip ratio, duration of T2D, HbA1c, pulse pressure, low-density lipoprotein, use of statins, and use of renin-angiotensin-aldosterone system inhibitors) were used to assess the associations of such parameters of hypoxemic burden with chronic kidney disease (CKD) as a manifestation of microvascular disease and a composite of cardiovascular diseases (CVD) reflecting macrovascular disease. RESULTS: Patients with long T90 were significantly more often affected by CKD and CVD than patients with a lower hypoxemic burden (CKD 38% vs. 28%, p < 0.001; CVD 30% vs. 21%, p < 0.001). Continuous T90desaturation and desaturation depth were associated with CKD (adjusted OR 1.01 per unit, 95% CI [1.00; 1.01], p = 0.008 and OR 1.30, 95% CI [1.06; 1.61], p = 0.013, respectively) independently of other known risk factors for CKD. For CVD there was a thresholdeffect, and only severly and very severly increased T90non-specific was associated with CVD ([Q3;Q4] versus [Q1;Q2], adjusted OR 1.51, 95% CI [1.12; 2.05], p = 0.008) independently of other known risk factors for CVD. CONCLUSION: While hypoxemic burden due to oxygen desaturations and the magnitude of desaturation depth were significantly associated with CKD, only severe hypoxemic burden due to non-specific drifts was associated with CVD. Specific types of hypoxemic burden may be related to micro- and macrovascular disease.

Sleep-Disordered Breathing, Advanced Age, and Diabetes Mellitus Are Associated with De Novo Atrial Fibrillation after Cardiac Surgery.

Background: Postoperative de novo atrial fibrillation (POAF) is one of the most frequently encountered complications following cardiac surgery. Despite the identification of several risk factors, the link between sleep-disordered breathing (SDB) and POAF has barely been examined. The objective of this prospective observational study was to determine whether severe SDB is associated with POAF in patients after elective coronary artery bypass grafting (CABG) surgery. Study design and methods: The incidence and preoperative predictors of in-hospital POAF were assessed in 272 patients undergoing CABG surgery at the University Medical Center Regensburg (Germany). In-hospital POAF was detected by continuous telemetry-ECG monitoring and 12-lead resting ECGs within the first seven postoperative days. POAF that occurred after hospital discharge within 60 days post CABG surgery was classified as post-hospital POAF and was ascertained by standardized phone interviews together with the patients' medical files, including routinely performed Holter-ECG monitoring at 60 days post CABG surgery. The night before surgery, portable SDB monitoring was used to assess the presence and type of severe SDB, defined by an apnea-hypopnea index ≥ 30/h. Results: The incidence of in-hospital POAF was significantly higher in patients with severe SDB compared to those without severe SDB (30% vs. 15%, p = 0.009). Patients with severe SDB suffered significantly more often from POAF at 60 days post CABG surgery compared to patients without severe SDB (14% vs. 5%, p = 0.042). Multivariable logistic regression analysis showed that severe SDB (odds ratio, OR [95% confidence interval, CI]: 2.23 [1.08; 4.61], p = 0.030), age ≥ 65 years (2.17 [1.04; 4.53], p = 0.038), and diabetes mellitus (2.27 [1.15; 4.48], p = 0.018) were significantly associated with in-hospital POAF. After additional adjustment for heart failure, the association between sleep apnea and postoperative atrial fibrillation was attenuated (1.99 [0.92; 4.31], p = 0.081). Conclusions: Amongst established risk factors, severe SDB was significantly associated with in-hospital POAF in patients undergoing CABG surgery. Whether SDB contributes to POAF independently of heart failure and whether risk for POAF may be alleviated by proper treatment of SDB merits further investigation.

Intravenous Opioid Medication with Piritramide Reduces the Risk of Pneumothorax During CT-Guided Percutaneous Core Biopsy of the Lung.

PURPOSE: CT-guided percutaneous core biopsy of the lung is usually performed under local anesthesia, but can also be conducted under additional systemic opioid medication. The purpose of this retrospective study was to assess the effect of intravenous piritramide application on the pneumothorax rate and to identify risk factors for post-biopsy pneumothorax. MATERIALS AND METHODS: One hundred and seventy-one core biopsies of the lung were included in this retrospective single center study. The incidence of pneumothorax and chest tube placement was evaluated. Patient-, procedure- and target-related variables were analyzed by univariate and multivariable logistic regression analysis. RESULTS: The overall incidence of pneumothorax was 39.2% (67/171). The pneumothorax rate was 31.5% (29/92) in patients who received intravenous piritramide and 48.1% (38/79) in patients who did not receive piritramide. In multivariable logistic regression analysis periinterventional piritramide application proved to be the only independent factor to reduce the risk of pneumothorax (odds ratio 0.46, 95%-confidence interval 0.24, 0.88; p = 0.018). Two or more pleura passages (odds ratio 3.38, 95%-confidence interval: 1.15, 9.87; p = 0.026) and prone position of the patient (odds ratio 2.27, 95%-confidence interval: 1.04, 4.94; p = 0.039) were independent risk factors for a higher pneumothorax rate. CONCLUSION: Procedural opioid medication with piritramide proved to be a previously undisclosed factor decreasing the risk of pneumothorax associated with CT-guided percutaneous core biopsy of the lung. LEVEL OF EVIDENCE 4: small study cohort.

Temporal association of ventricular arrhythmias and respiratory events in heart failure patients with central sleep apnoea.

In contrast to obstructive sleep apnoea, the peak of sympathetic tone in central sleep apnoea occurs during the hyperventilation phase. To explore the temporal association of premature ventricular complex (PVC) burden in the context of the apnoea/hypopnoea-hyperpnoea cycle, the duration of apnoea/hypopnoea was defined as 100 %. We assessed the PVC burden throughout the apnoea/hypopnoea-hyperpnoea cycle during the periods of ±150 % in 50 % increments before and after the apnoea/hypopnoea phase. In this subanalysis of 54 SERVE-HF patients, PVC burden was 32 % higher in the late hyperventilation period (50-100 % after apnoea/hypopnoea) compared to the apnoea/hypopnoea phase.

The translocator protein 18kDa ligand etifoxine in the treatment of depressive disorders-a double-blind, randomized, placebo-controlled proof-of-concept study.

BACKGROUND: Recent developments suggest that neurosteroids may achieve rapid antidepressant effects. As such, neurosteroidogenesis mediated by the translocator protein 18 kDa (TSPO) might constitute a promising option for the treatment of depression. Therefore, the current clinical trial aims to get the first evidence of whether TPSO ligands promote rapid antidepressant effects. Furthermore, we study which mechanisms of action, e.g., modulation of distinct neuronal networks, neurosteroidogenesis, endocrinological mechanisms, TSPO expression or microbiome composition, contribute to their putative antidepressant effects. METHODS: This is a randomized, placebo-controlled, double-blind single-center trial of 2-week treatment with the TSPO ligand etifoxine versus placebo in depressive patients. Main eligibility criteria: male or female individuals aged 18 to 65 years with unipolar/bipolar depressive disorder with no other psychiatric main diagnosis or acute neurological/somatic disorder or drug/alcohol dependence during their lifetime. The primary endpoint is the time point at which 50% of the maximal effect has occurred (ET50) estimated by the scores of the Hamilton Depression Scale (HAMD-21). A total of 20 patients per group are needed to detect changes of therapeutic efficacy about 5% and changes of ET50 about 10% with a power of 70%. Assuming a drop-out rate of 10-20%, 50 patients will be randomized in total. The study will be conducted at the Department of Psychiatry and Psychotherapy of the University of Regensburg. DISCUSSION: This study will provide a first proof-of-concept on the potential of the TSPO ligand etifoxine in the treatment of depressive disorders. TRIAL REGISTRATION: Clinical Trials Register (EudraCT number: 2021-006773-38 , registration date: 14 September 2022) and German Register of Clinical Studies (DRKS number: DRKS00031099 , registration date: 23 January 2023).

The effects of Phoniatric PREhabilitation in Head and Neck Cancer patients on Aspiration and Preservation of Swallowing (PREHAPS): study protocol of a monocentric prospective randomized interventional outcome-blinded trial.

BACKGROUND: Dysphagia, with its negative impact on life expectancy and quality of life, is a major side effect of head and neck squamous cell carcinoma (HNSCC). In a typical Head and Neck Cancer Center, more than half of patients are affected. Improving treatment, and ideally prevention respectively prehabilitation, therefore seems more than desirable. METHODS: The study is planned as a monocentric, prospective, outcome-blinded, randomized interventional study comparing an advanced phoniatric-logopedic prehabilitation with a control (standard of care). Seventy patients (30 control group, 30 intervention group, 10 drop-out rate of 15%) with an initial diagnosis of invasive HNSCC and curative treatment intention will be included over a period of 17 months. In addition to the previous standard, both groups will undergo both detailed subjective assessment of swallowing function and quality of life by means of various questionnaires and objective analyses by bioelectrical impedance measurements and phoniatric endoscopic swallowing examinations. In the intervention group, risk-related nutritional counseling (face-to-face) and phoniatric-logopedic prehabilitation are provided: detailed counseling with video demonstration and exercises to strengthen and improve the range of motion of the oral, pharyngeal, and laryngeal muscles (guided by exercise diary). Controls are performed at 6 weeks, 3 and 6 months, and 9 or 12 months after the end of therapy during the regular tumor follow-up. Primary study endpoints are swallowing function and emotional distress at 6 weeks of control visit. DISCUSSION: Prehabilitation measures have already proven successful in other patient groups, e.g., transplant patients. In the field of head and neck oncology, interest in such concepts has increased significantly in recent years. However, usually, only subgroups, e.g., patients with swallowing problems after radiochemotherapy alone, are in focus. Our study aims to investigate the general benefit of prehabilitation with regard to swallowing function, which is so important for protection of aspiration and quality of life. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029676 . International Clinical Trials Registry Platform DRKS00029676 . Registered on 19 July 2022.

Clinical Characterization of Arrhythmia-Induced Cardiomyopathy in Patients With Tachyarrhythmia and Idiopathic Heart Failure.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AIC) is a known entity, but prospective evidence for its characterization is limited. OBJECTIVES: This study aimed to: 1) determine the relative frequency of the pure form of AIC in the clinically relevant cohort of patients with newly diagnosed, otherwise unexplained left ventricular systolic dysfunction (LVSD) and tachyarrhythmia; 2) assess the time to recovery from LVSD; and 3) identify parameters for an early diagnosis of AIC. METHODS: Patients were prospectively included, underwent effective rhythm restoration, and were followed-up at 2, 4, and 6 months to evaluate clinical characteristics, biomarkers, and cardiac imaging including cardiac magnetic resonance imaging. Patients with recurred arrhythmia were excluded from analysis. RESULTS: 41 of 50 patients were diagnosed with AIC 6 months after rhythm restoration. Left ventricular (LV) ejection fraction increased 2 months after rhythm restoration from 35.4% ± 8.2% to 52.7% ± 8.0% in AIC patients vs 37.0% ± 9.5% to 43.3% ± 7.0% in non-AIC patients. From month 2 to 6, LV ejection fraction continued to increase in AIC patients (57.2% ± 6.1%; P < 0.001) but remained stable in non-AIC patients (44.0% ± 7.8%; P = 0.628). Multivariable logistic regression analysis revealed that lower LV end-diastolic diameter at baseline could be used for early diagnosis of AIC, whereas biomarkers and other morphological or functional parameters, including late LV gadolinium enhancement, did not show suitability for early diagnosis. CONCLUSIONS: We observed a high prevalence of AIC in patients with otherwise unexplained LVSD and concomitant tachyarrhythmia, suggesting that this condition may be underdiagnosed in clinical practice. Most patients recovered fast, within months, from LVSD. A low initial LV end-diastolic diameter may constitute an early marker for diagnosis of AIC.

Deep learning-based differentiation of peripheral high-flow and low-flow vascular malformations in T2-weighted short tau inversion recovery MRI.

BACKGROUND: Differentiation of high-flow from low-flow vascular malformations (VMs) is crucial for therapeutic management of this orphan disease. OBJECTIVE: A convolutional neural network (CNN) was evaluated for differentiation of peripheral vascular malformations (VMs) on T2-weighted short tau inversion recovery (STIR) MRI. METHODS: 527 MRIs (386 low-flow and 141 high-flow VMs) were randomly divided into training, validation and test set for this single-center study. 1) Results of the CNN's diagnostic performance were compared with that of two expert and four junior radiologists. 2) The influence of CNN's prediction on the radiologists' performance and diagnostic certainty was evaluated. 3) Junior radiologists' performance after self-training was compared with that of the CNN. RESULTS: Compared with the expert radiologists the CNN achieved similar accuracy (92% vs. 97%, p = 0.11), sensitivity (80% vs. 93%, p = 0.16) and specificity (97% vs. 100%, p = 0.50). In comparison to the junior radiologists, the CNN had a higher specificity and accuracy (97% vs. 80%, p < 0.001; 92% vs. 77%, p < 0.001). CNN assistance had no significant influence on their diagnostic performance and certainty. After self-training, the junior radiologists' specificity and accuracy improved and were comparable to that of the CNN. CONCLUSIONS: Diagnostic performance of the CNN for differentiating high-flow from low-flow VM was comparable to that of expert radiologists. CNN did not significantly improve the simulated daily practice of junior radiologists, self-training was more effective.

Better early outcome with enhanced recovery total hip arthroplasty (ERAS-THA) versus conventional setup in randomized clinical trial (RCT).

INTRODUCTION: Numbers of total hip arthroplasty (THA) are steadily rising and patients expect faster mobility without pain postoperatively. The aim of enhanced recovery after Surgery (ERAS) programs in a multidisciplinary setup was to keep pace with the needs of quality and quantity of surgical THA-interventions and patients' expectations. METHODS: 194 patients undergoing THA procedures were investigated after single-blinded randomization to ERAS (98) or conventional setup group (96). Primary outcome variable was mobilization measured with the Timed Up and Go Test (TUG) in seconds. Secondary outcome variables were floor count and walking distance in meters as well as rest, mobilization and night pain on a numerous rating scale (NRS). All variables were recorded preoperatively and daily until the sixth postoperative day. To assess and compare clinical outcome and patient satisfaction, the PPP33-Score and PROMs were used. RESULTS: No complications such as thromboembolic complications, fractures or revisions were recorded within the first week postoperatively in either study group. Compared to the conventional group, the ERAS group showed significantly better TUG (p < 0.050) and walking distance results after surgery up to the sixth, and floor count up to the third postoperative day. On the first and second postoperative day, ERAS patients showed superior results (p < 0.001) in all independent activity subitems. Regarding the evaluation of pain (NRS), PPP33 and PROMS, no significant difference was shown (p > 0.050). CONCLUSION: This prospective single-blinded randomized controlled clinical trial was able to demonstrate excellent outcome with comparable pain after ERAS THA versus a conventional setup. Therefore, ERAS could be used in daily clinical practice.

Clinical Value and Operational Risks of MRI in ICU patients - A Retrospective Analysis Performed at a University Medical Center.

PURPOSE: Intensive care unit (ICU) patients have a high risk of developing complications when leaving the ICU for diagnostic procedures or therapeutic interventions. Our study examined the frequency of adverse events associated with magnetic resonance imaging (MRI) of intensive care patients and the extent of changes in therapy due to the MRI scan to weigh the risks associated with the scan against the potential benefits of an MR scan, using a change in therapy as an indicator of benefit. MATERIALS AND METHODS: 4434 ICU patients (January to December 2015) were identified by Hospital Information System (SAP-R/3 IS-H, Walldorf, Germany), ICU patient data management system Metavision (iMDsoft, Israel), and Radiology Information System (Nexus.medRIS, Version 8.42, Nexus, Germany). All intensive care and medical records (HIS) and MRI reports (RIS) were matched and further evaluated in a retrospective case-to-case analysis for biometric data, mechanical ventilation, ICU requirements, planned postoperative vs. emergency diagnostic requirements, complications and impact on further diagnosis or therapy. RESULTS: Out of 4434 ICU patients, 322 ICU patients (7.3 %) underwent a total of 385 MRI examinations. 167 patients needed a total of 215 emergency scans, while 155 patients underwent 170 planned postoperative MRI exams. 158 (94.6 %) out of 167 emergency scan patients were ventilated under continuous intravenous medication and monitoring. In the planned postoperative group, only 6 (3.9 %) out of 155 were ventilated, but a total of 38 (24.5 %) were under continuous medication. 111 patients were accompanied by nurses only during MRI. Only one severe adverse event (0.3 %) was noted and was attributed to study preparation (n = 385). In 8 MRI examinations (2.1 %), the examination was interrupted or cancelled due to the patients' condition. While all MRI examinations in the planned group were completed (n = 170, 100 %) (e. g., postoperative controls), only 207 out of 215 (96.3 %) could be performed for emergency diagnostic reasons. MRI influenced the clinical course with a change in diagnosis or therapy in 74 (19.2 %) of all 385 MRI examinations performed, and in the emergency diagnostic group it was 31.2 % (n = 67/215). CONCLUSION: Nearly 20 % of MRI examinations of ICU patients resulted in a change of therapy. With only one potentially life-threatening adverse event (0.3 %) during transport and the MRI examination, the risk seems to be outweighed by the diagnostic benefit. KEY POINTS: · The risk of adverse events associated with MRI scans in ICU patients is low.. · The rate of premature termination of ICU patients' MRI scans is low.. · Almost 20 % of ICU patients' MRI scans lead to a change of therapy..

Prevalence and Risk Factors for Weaning Failure From Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Insufficiency.

OBJECTIVE: Analysis of the prevalence and risk factors for weaning failure from venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory insufficiency. DESIGN: Single-center retrospective observational study. SETTING: Sixteen beds medical ICU at the University Hospital Regensburg. PATIENTS: Two hundred twenty-seven patients with severe acute respiratory insufficiency requiring VV-ECMO support between October 2011 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients meeting our ECMO weaning criteria (Sp o2 ≥ 90% with F io2 ≤ 0.4 or Pa o2 /F io2 > 150 mm Hg, pH = 7.35-7.45, positive end-expiratory pressure ≤ 10 cm H 2 O, driving pressure < 15 cm H 2 O, respiratory rate < 30/min, tidal volume > 5 mL/kg, ECMO bloodflow ≈ 1. 5 L/min, sweep gas flow ≈ 1 L/min, heart rate < 120/min, systolic blood pressure 90-160 mm Hg, norepinephrine < 0.2 µg/[kg*min]) underwent an ECMO weaning trial (EWT) with pausing sweep gas flow. Arterial blood gas analysis, respiratory and ventilator parameters were recorded prior, during, and after EWTs. Baseline data, including demographics, vitals, respiratory, ventilator, and laboratory parameters were recorded at the time of cannulation. One hundred seventy-nine of 227 (79%) patients were successfully decannulated. Ten patients (4%) underwent prolonged weaning of at least three failed EWTs before successful decannulation. The respiratory rate (19/min vs 16/min, p = 0.002) and Pa co2 (44 mm Hg vs 40 mm Hg, p = 0.003) were higher before failed than successful EWTs. Both parameters were risk factors for ECMO weaning failure (Pa co2 : odds ratio [OR] 1.05; 95% CI, 1.001-1.10; p = 0.045; respiratory rate: OR 1.10; 95% CI, 1.04-1.15; p < 0.001) in multivariable analysis. The rapid shallow breathing index [42 (1/L*min), vs 35 (1/L*min), p = 0.052) was higher before failed than successful EWTs. The decline of Sa o2 and Pa o2 /F io2 during EWTs was higher in failed than successful trials. CONCLUSIONS: Seventy-nine percent of patients were successfully decannulated with only 4% needing prolonged ECMO weaning. Before EWT only parameters of impaired ventilation (insufficient decarboxylation, higher respiratory rate) but not of oxygenation were predictive for weaning failure, whereas during EWT-impaired oxygenation was associated with weaning failure.

Diagnosis of sarcopenia on thoracic computed tomography and its association with postoperative survival after anatomic lung cancer resection.

Computer tomography-derived skeletal muscle index normalized for height in conjunction with muscle density enables single modality-based sarcopenia assessment that accounts for all diagnostic criteria and cutoff recommendations as per the widely accepted European consensus. Yet, the standard approach to quantify skeletal musculature at the third lumbar vertebra is limited for certain patient groups, such as lung cancer patients who receive chest CT for tumor staging that does not encompass this lumbar level. As an alternative, this retrospective study assessed sarcopenia in lung cancer patients treated with curative intent at the tenth thoracic vertebral level using appropriate cutoffs. We showed that skeletal muscle index and radiation attenuation at level T10 correlate well with those at level L3 (Pearson's R = 0.82 and 0.66, p < 0.001). During a median follow-up period of 55.7 months, sarcopenia was independently associated with worse overall (hazard ratio (HR) = 2.11, 95%-confidence interval (95%-CI) = 1.38-3.23, p < 0.001) and cancer-specific survival (HR = 2.00, 95%-CI = 1.19-3.36, p = 0.009) of lung cancer patients following anatomic resection. This study highlights feasibility to diagnose sarcopenia solely by thoracic CT in accordance with the European consensus recommendations. The straightforward methodology offers easy translation into routine clinical care and potential to improve preoperative risk stratification of lung cancer patients scheduled for surgery.

Predictors of Nocturnal Hypoxemic Burden in Patients Undergoing Elective Coronary Artery Bypass Grafting Surgery.

Background: Nocturnal hypoxemia has been linked to increased cardiovascular morbidity and mortality. Several common diseases, such as sleep-disordered breathing (SDB), heart failure (HF), obesity, and pulmonary disease, coincide with an elevated nocturnal hypoxemic burden with and without repetitive desaturations. Research question: This study aimed to evaluate the association of relevant common diseases with distinctive metrics of nocturnal hypoxemic burden with and without repetitive desaturations in patients undergoing coronary artery bypass grafting surgery. Study design and methods: In this subanalysis of the prospective observational study, CONSIDER-AF (NCT02877745) portable SDB monitoring was performed on 429 patients with severe coronary artery disease the night before cardiac surgery. Pulse oximetry was used to determine nocturnal hypoxemic burden, as defined by total recording time spent with oxygen saturation levels < 90% (T90). T90 was further characterized as T90 due to intermittent hypoxemia (T90desaturation) and T90 due to nonspecific and noncyclic SpO2-drifts (T90non-specific). Results: Multivariable linear regression analysis identified SDB (apnea-hypopnea-index ≥ 15/h; B [95% CI]: 6.5 [0.4; 12.5], p = 0.036), obesity (8.2 [2.5; 13.9], p = 0.005), and mild-to-moderate chronic obstructive pulmonary disease (COPD, 16.7 [8.5; 25.0], p < 0.001) as significant predictors of an increased nocturnal hypoxemic burden. Diseases such as SDB, obesity and HF were significantly associated with elevated T90desaturation. In contrast, obesity and mild-to-moderate COPD were significant modulators of T90non-specific. Interpretation: SDB and leading causes for SDB, such as obesity and HF, are associated with an increased nocturnal hypoxemic burden with repetitive desaturations. Potential causes for hypoventilation syndromes, such as obesity and mild-to-moderate COPD, are linked to an increased hypoxemic burden without repetitive desaturations. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02877745.

Volume-Assisted Estimation of Remnant Liver Function Based on Gd-EOB-DTPA Enhanced MR Relaxometry: A Prospective Observational Trial.

In the context of liver surgery, predicting postoperative liver dysfunction is essential. This study explored the potential of preoperative liver function assessment by MRI for predicting postoperative liver dysfunction and compared these results with the established indocyanine green (ICG) clearance test. This prospective study included patients undergoing liver resection with preoperative MRI planning. Liver function was quantified using T1 relaxometry and correlated with established liver function scores. The analysis revealed an improved model for predicting postoperative liver dysfunction, exhibiting an accuracy (ACC) of 0.79, surpassing the 0.70 of the preoperative ICG test, alongside a higher area under the curve (0.75). Notably, the proposed model also successfully predicted all cases of liver failure and showed potential in predicting liver synthesis dysfunction (ACC 0.78). This model showed promise in patient survival rates with a Hazard ratio of 0.87, underscoring its potential as a valuable tool for preoperative evaluation. The findings imply that MRI-based assessment of liver function can provide significant benefits in the early identification and management of patients at risk for postoperative liver dysfunction.

Assessment of the quality of different commercial providers using artificial intelligence for automated cephalometric analysis compared to human orthodontic experts.

PURPOSE: The aim of this investigation was to evaluate the accuracy of various skeletal and dental cephalometric parameters as produced by different commercial providers that make use of artificial intelligence (AI)-assisted automated cephalometric analysis and to compare their quality to a gold standard established by orthodontic experts. METHODS: Twelve experienced orthodontic examiners pinpointed 15 radiographic landmarks on a total of 50 cephalometric X­rays. The landmarks were used to generate 9 parameters for orthodontic treatment planning. The "humans' gold standard" was defined by calculating the median value of all 12 human assessments for each parameter, which in turn served as reference values for comparisons with results given by four different commercial providers of automated cephalometric analyses (DentaliQ.ortho [CellmatiQ GmbH, Hamburg, Germany], WebCeph [AssembleCircle Corp, Seongnam-si, Korea], AudaxCeph [Audax d.o.o., Ljubljana, Slovenia], CephX [Orca Dental AI, Herzliya, Israel]). Repeated measures analysis of variances (ANOVAs) were calculated and Bland-Altman plots were generated for comparisons. RESULTS: The results of the repeated measures ANOVAs indicated significant differences between the commercial providers' predictions and the humans' gold standard for all nine investigated parameters. However, the pairwise comparisons also demonstrate that there were major differences among the four commercial providers. While there were no significant mean differences between the values of DentaliQ.ortho and the humans' gold standard, the predictions of AudaxCeph showed significant deviations in seven out of nine parameters. Also, the Bland-Altman plots demonstrate that a reduced precision of AI predictions must be expected especially for values attributed to the inclination of the incisors. CONCLUSION: Fully automated cephalometric analyses are promising in terms of timesaving and avoidance of individual human errors. At present, however, they should only be used under supervision of experienced clinicians.