Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. METHODS: The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. DISCUSSION: Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

Predictive value of shock index variants on 30-day mortality of trauma patients in helicopter emergency medical services: a nationwide observational retrospective multicenter study.

The original shock index (SI) has been further developed to increase its prognostic value. We aimed to evaluate the predictive value of different SI variants on 30-day mortality among severely injured trauma patients in pre-hospital critical care settings. Adult trauma patients in the national Helicopter Emergency Medical Services (HEMS) registry were evaluated based on the primary outcome of 30-day mortality. SI, SIA (SI multiplied by age), SI/G (SI divided by Glasgow Coma Scale (GCS)), SIA/G (SI multiplied by age and divided by GCS), and SS (SI divided by oxygen saturation) were calculated based on the first vital signs measured at the time of HEMS contact. The area under the receiver operating curve (AUROC) was calculated for each SI variant. In total 4108 patients were included in the study. The overall 30-day mortality was 13.5%. The SIA/G and SI/G had the highest predictive ability (AUROC 0.884 [95% CI 0.869-0.899] and 0.8000 [95% CI 0.7780-0.8239], respectively). The SIA/G yielded good predictive performance between 30-day survivors and non-survivors in the pre-hospital critical care setting.

The effect of time of measurement on the discriminant ability for mortality in trauma of a pre-hospital shock index multiplied by age and divided by the Glasgow Coma Score: a registry study.

BACKGROUND: The shock index (SI) and its derivatives have been shown to predict mortality in severely injured patients, both in pre-hospital and in-hospital settings. However, the impact of the time of measurement on the discriminative ability of the pre-hospital SI is unknown. The aim of this study was to evaluate whether the time of measurement influences the discriminative ability of the SI multiplied by age (SIA) and divided by the Glasgow Coma Score (SIA/G). METHODS: Registry data were obtained from the national helicopter emergency medical services (HEMS) on trauma patients aged ≥ 18 years. The SI values were calculated based on the first measured vitals of the trauma patients by the HEMS unit. The discriminative ability of the SIA/G, with 30-day mortality as the endpoint, was evaluated according to different delay times (0 - 19, 20 - 39 and ≥ 40 min) from the initial incident. Sub-group analyses were performed for trauma patients without a traumatic brain injury (TBI), patients with an isolated TBI and patients with polytrauma, including a TBI. RESULTS: In total, 3,497 patients were included in the study. The SIA/G was higher in non-survivors (median 7.8 [interquartile range 4.7-12.3] vs. 2.4 [1.7-3.6], P < 0.001). The overall area under the receiver operator characteristic curve (AUROC) for the SIA/G was 0.87 (95% CI: 0.85-0.89). The AUROC for the SIA/G was similar in the short (0.88, 95% CI: 0.85-0.91), intermediate (0.86, 95% CI: 0.84-0.89) and long (0.86, 95% CI: 0.82-0.89) measurement delay groups. The findings were similar in the three trauma sub-groups. CONCLUSIONS: The discriminative ability of the SIA/G in predicting 30-day mortality was not significantly affected by the measurement time of the index in the pre-hospital setting. The SIA/G is a simple and reliable tool for assessing the risk of mortality among severely injured patients in the pre-hospital setting.

Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients.

BACKGROUND: We report the findings from 4437 individuals (3219 patients and 1218 relatives) who have been analyzed by whole genome sequencing (WGS) at the Genomic Medicine Center Karolinska-Rare Diseases (GMCK-RD) since mid-2015. GMCK-RD represents a long-term collaborative initiative between Karolinska University Hospital and Science for Life Laboratory to establish advanced, genomics-based diagnostics in the Stockholm healthcare setting. METHODS: Our analysis covers detection and interpretation of SNVs, INDELs, uniparental disomy, CNVs, balanced structural variants, and short tandem repeat expansions. Visualization of results for clinical interpretation is carried out in Scout-a custom-developed decision support system. Results from both singleton (84%) and trio/family (16%) analyses are reported. Variant interpretation is done by 15 expert teams at the hospital involving staff from three clinics. For patients with complex phenotypes, data is shared between the teams. RESULTS: Overall, 40% of the patients received a molecular diagnosis ranging from 19 to 54% for specific disease groups. There was heterogeneity regarding causative genes (n = 754) with some of the most common ones being COL2A1 (n = 12; skeletal dysplasia), SCN1A (n = 8; epilepsy), and TNFRSF13B (n = 4; inborn errors of immunity). Some causative variants were recurrent, including previously known founder mutations, some novel mutations, and recurrent de novo mutations. Overall, GMCK-RD has resulted in a large number of patients receiving specific molecular diagnoses. Furthermore, negative cases have been included in research studies that have resulted in the discovery of 17 published, novel disease-causing genes. To facilitate the discovery of new disease genes, GMCK-RD has joined international data sharing initiatives, including ClinVar, UDNI, Beacon, and MatchMaker Exchange. CONCLUSIONS: Clinical WGS at GMCK-RD has provided molecular diagnoses to over 1200 individuals with a broad range of rare diseases. Consolidation and spread of this clinical-academic partnership will enable large-scale national collaboration.

[Surgical treatment of shoulder instability]. / Olkanivelen epävakauden leikkaushoito TYKS:n kokemusten valossa.

Most commonly, shoulder instability results from a traumatic dislocation of the shoulder joint, usually happening to men under the age of 30. The first uncomplicated dislocation is treated conservatively. Instability refers to symptomatic instability of the shoulder joint, i.e. recurrent dislocations or fear of dislocation. Clinical examination and X-ray are usually sufficient for diagnosis. While mechanical instability of the shoulder joint is an indication for surgery, the operative technique should be selected in a patient-specific manner.