Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil

OBJECTIVES:To investigate 3-year outcomes of surgical aortic valve replacement using the INSPIRIS RESILIA aortic valve bioprosthesis in patients with severe aortic stenosis. METHODS:IMPACT registry is a prospective, multicentre, international registry with a 5-year follow-up. After 3 years, haemodynamic performance, all-cause mortality, and valve-related mortality were determined. RESULTS:A total of 556 patients who underwent surgical aortic valve replacement with the INSPIRIS RESILIA aortic valve were enrolled between December 2019 and June 2021. The mean age was 63.4 ± 8.5 years, 29.0% were female, with a EuroSCORE II of 2.2 ± 2.5% and an STS score of 1.7 ± 2.2%. Hypertension (66.2%), coronary artery disease (34.7%), and diabetes (18.4%) were the most common comorbidities. A total of 49.3% of patients underwent full sternotomy, 58.3% isolated aortic valve replacement. The most commonly implanted valve sizes were 23 mm (35.4%) and 25 mm (30.9%). At 3 years, overall survival was 91.0%, freedom from valve-related mortality was 97.5%, from prosthetic endocarditis 96.0%, from stroke 91.5%, from valve-related dysfunction 98.0%, from reintervention 96.2%, from structural valve deterioration stage 2 96.8%, and from stage 3 99.4%. The mean transvalvular gradient was 11.9 mmHg at 3 years, with an indexed effective orifice area of 0.8 cm2/m2. Functional class improved from 41.2% class III or IV at baseline to 5.7% at 3 years. CONCLUSIONS:Three-year outcomes, including survival and haemodynamic and functional status after surgical aortic valve replacement using the INSPIRIS RESILIA bioprosthetic aortic valve, were reported in a real-world patient population with severe aortic stenosis. CLINICALTRIALS.GOV:NCT04053088.

Intensive Bemühungen und interdisziplinäre Zusammenarbeit haben die Mortalität mehrfach schwer verletzter Patienten deutlich gesenkt. Qualitativ hochwertige Leitlinienempfehlungen, die die prähospitale Phase, das Schockraummanagement und die erste operative Phase behandeln, werden regelmäßig aktualisiert. Der vorliegende Beitrag referiert den Teil einer neuen Leitlinie auf S3-Niveau, der die Behandlung polytraumatisierter und intensivmedizinisch betreuter Patienten nach der ersten operativen Phase fokussiert. Diese Patienten benötigen besondere Aufmerksamkeit u. a. hinsichtlich Monitoring, Schmerztherapie, Beatmungsstrategie, Ernährung etc. und müssen regelhaft noch der definitiven chirurgischen ihrer Verletzungen zugeführt werden. Der Beitrag fasst die aktuelle Literatur zusammen und gibt Empfehlungen hinsichtlich der frühen definitiven Versorgung polytraumatisierter Patienten, v. a. mit Blick auf ihren besten Zeitpunkt.

The treatment of polytraumatized patients is challenging. Intensive efforts and interdisciplinary teamwork have improved survival rates of severely injured patients over the last decades. High quality guideline recommendations focusing on the prehospital setting, emergency room management and also the initial surgical phase have been published and are frequently updated. The current manuscript is part of new guidelines on an S3 level that focuses on treatment of polytraumatized patients who were transferred to the intensive care unit after initial emergency treatment. These patients have special needs, especially with respect to monitoring, pain management, ventilation strategy, nutrition etc. and most often require definitive surgical stabilization of injuries to the thorax, abdomen, pelvis and extremities. This article summarizes the current literature and gives recommendations with respect to early definitive treatment of patients with multiple trauma and particularly with a view to the best possible timing of the definitive treatment.

In amyotrophic lateral sclerosis (ALS), heterogeneity of motor phenotypes is a fundamental hallmark of the disease. Distinct ALS phenotypes were associated with a different progression and survival. Despite its relevance for clinical practice and research, there is no broader consensus on the classification of ALS phenotypes. An expert consensus process for the classification of ALS motor phenotypes was performed from May 2023 to December 2024. A three-determinant anatomical classification was proposed which is based on the (1) region of onset (O), (2) the propagation of motor symptoms (P), and (3) the degree of upper (UMN) and/or lower motor neuron (LMN) dysfunction (M). Accordingly, this classification is referred to as the “OPM classification”. Onset phenotypes differentiate the site of first motor symptoms: O1) head onset; O2d) distal arm onset; O2p) proximal arm onset; O3r) trunk respiratory onset; O3a) trunk axial onset; O4d) distal leg onset; O4p) proximal leg onset. Propagation phenotypes differentiate the temporal propagation of motor symptoms from the site of onset to another, vertically distant body region: PE) earlier propagation (within 12 months of symptom onset); PL) later propagation (without propagation within 12 months of symptom onset), including the established phenotypes of “progressive bulbar paralysis” (O1, PL), “flail-arm syndrome” (O2p, PL), and “flail-leg syndrome” (O4d, PL); PN) propagation not yet classifiable as time since symptom onset is less than 12 months. Phenotypes of motor neuron dysfunction differentiate the degree of UMN and/or LMN dysfunction: M0) balanced UMN and LMN dysfunction; M1d) dominant UMN dysfunction; M1p) pure UMN dysfunction (“primary lateral sclerosis”, PLS); M2d) dominant LMN dysfunction; M2p) pure LMN dysfunction (“progressive muscle atrophy”, PMA); M3) dissociated motor neuron dysfunction with dominant LMN and UMN dysfunction of the arms and legs (“brachial amyotrophic spastic paraparesis”), respectively. This consensus process aimed to standardize the clinical description of ALS motor phenotypes in clinical practice and research – based on the onset region, propagation pattern, and motor neuron dysfunction. This “OPM classification” contributes to specifying the prognosis, to defining the inclusion or stratification criteria in clinical trials and to correlate phenotypes with the underlying disease mechanisms of ALS.

Background Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. Methods This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate- buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321. Findings From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 515 years (IQR 300-600). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 137 [95% CI -144 to 418]; placebo group mean 1920 [SD 1178] at baseline and 3091 [SD 1549] at day 168; NG101 group mean 1823 [SD 1514] at baseline and 3131 [1954] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group. Interpretation NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies.