Drone-Facilitated Real-Time Video-Guided Feedback Helps to Improve the Quality of Lay Bystander Basic Life Support. A Randomized Controlled Simulation Trial.

OBJECTIVES: Telephone instructions are commonly used to improve cardiopulmonary resuscitation (CPR) by lay bystanders. This usually implies an audio but no visual connection between the provider and the emergency medical telecommunicator. We aimed to investigate whether video-guided feedback via a camera drone enhances the quality of CPR. METHODS: We conducted a randomized controlled simulation trial. Lay rescuers performed 8 min of CPR on an objective feedback manikin. Participants were randomized to receive telephone instructions with (intervention group) or without (control group) a drone providing a visual connection with the telecommunicator after a 2-min run-in phase. Performed work (total compression depth minus total lean depth) was the primary outcome. Secondary outcomes were the proportion of effective chest compressions, average compression depth, subjective physical strain measured every 2 min, and dexterity in the nine-hole peg test after the scenario. Outcomes were compared using the t- and Mann Whitney-U tests. A two-sided p-value of <0.05 was considered significant. RESULTS: We included 27 individuals (14 (52%) female, mean age 41 ± 14 years). Performed work was greater in the intervention than in the control group (41.3 ± 7.0 vs. 33.9 ± 10.9 m; absolute difference 7.5, 95% CI 1.4 to 14.8; p = 0.046), with higher average compression depth (49 ± 7 vs. 40 ± 13 mm; p = 0.041), and higher proportions of adequate chest compressions (43 (IQR 14-60) vs. 3 (0-29) %; p = 0.041). We did not find any significant differences regarding the remaining secondary outcomes. CONCLUSION: Video-guided feedback via drones might be a helpful tool to enhance the quality of telephone-assisted CPR in lay bystanders.

Severe Hyperthermia in Mountaineering: Coincidence of Heat Stroke and Infection.

Heat illness is a condition that is sometimes seen in those undertaking physical activities. This case report focuses on a female hiker who developed heat stroke during a trek in the Dachstein region of Upper Austria. The patient's presentation was initially unclear and could only be confirmed by the use of a thermometer. This had a significant impact on the medical decision-making process during a complex rescue operation.

Sexual dysfunction in female and male people with multiple sclerosis: disability, depression and hormonal status matter.

BACKGROUND AND PURPOSE: Sexual dysfunction (SD) in people with multiple sclerosis (pwMS) is common and an often underestimated issue in the care of pwMS. The objective of the study was to evaluate risk factors for SD in pwMS, correlate its prevalence with patient-reported measures (quality of life and physical activity) and analyse its association with hormonal status. METHODS: Sexual dysfunction was determined in 152 pwMS using the Multiple Sclerosis Intimacy and Sexuality Questionnaire 19. A logistical regression model was used to identify independent risk factors for SD. RESULTS: The prevalence of SD in pwMS was 47%. Independent risk factors for the development of SD were ever-smoking (odds ratio [OR] 3.4, p = 0.023), disability as measured by the Expanded Disability Status Scale (OR 2.0, p < 0.001), depression (OR 4.3, p = 0.047) and bladder and bowel dysfunction (OR 8.8, p < 0.001); the use of disease-modifying treatment was associated with a lower risk for SD (OR 0.32, p = 0.043). SD was associated with worse quality of life (Multiple Sclerosis Impact Scale 29: physical score 6.3 vs. 40.0; psychological score 8.3 vs. 33.3; both p < 0.001) and lower physical activity (Baecke questionnaire, p < 0.001). Laboratory analysis revealed significantly higher luteinizing hormone and follicle-stimulating hormone levels and lower 17-beta oestradiol, androstenedione, dehydroepiandrosterone sulfate, oestrone and anti-Mullerian hormone levels in female pwMS with SD. In male pwMS and SD, there was a significant decrease in inhibin B levels. CONCLUSIONS: Our findings highlight the requirement of a holistic approach to SD in MS including physical, neurourological and psychosocial factors. Active screening for SD, especially in patients with disability, depression or bladder and bowel dysfunction, is recommended.

Serum sPD-L1 levels are elevated in patients with viral diseases, bacterial sepsis or in patients with impaired renal function compared to healthy blood donors.

OBJECTIVES: Immune checkpoints play an important role in maintaining the balance of the immune system and in the development of autoimmune diseases. A central checkpoint molecule is the programmed cell death protein 1 (PD-1, CD279) which is typically located on the surface of T cells. Its primary ligand PD-L1 is expressed on antigen presenting cells and on cancer cells. Several variants of PD-L1 exist, among these soluble molecules (sPD-L1) present in serum at low concentrations. sPD-L1 was found elevated in cancer and several other diseases. sPD-L1 in infectious diseases has received relatively little attention so far and is therefore subject of this study. METHODS: sPD-L1 serum levels were determined in 170 patients with viral infections (influenza, varicella, measles, Dengue fever, SARS-CoV2) or bacterial sepsis by ELISA and compared to the levels obtained in 11 healthy controls. RESULTS: Patients with viral infections and bacterial sepsis generally show significantly higher sPD-L1 serum levels compared to healthy donors, except for varicella samples where results do not reach significance. sPD-L1 is increased in patients with impaired renal function compared to those with normal renal function, and sPD-L1 correlates significantly with serum creatinine. Among sepsis patients with normal renal function, sPD-L1 serum levels are significantly higher in Gram-negative sepsis compared to Gram-positive sepsis. In addition, in sepsis patients with impaired renal function, sPD-L1 correlates positively with ferritin and negatively with transferrin. CONCLUSIONS: sPD-L1 serum levels are significantly elevated in patients with sepsis, influenza, mesasles, Dengue fever or SARS-CoV2. Highest levels are detectable in patients with measles and Dengue fever. Also impaired renal function causes an increase in levels of sPD-L1. As a consequence, renal function has to be taken into account in the interpretation of sPD-L1 levels in patients.

Efficacy and Safety of Methoxyflurane for Treatment of Acute Traumatic Pain by EMTs during Alpine Rescue Operations: The "PainDrop" Trial.

Background: Treatment of acute traumatic pain is a core task for mountain rescue services. Intravenous access, however, is often difficult, and the vast majority of missions are carried out without a physician at the scene. The spectrum of analgesics available for use by non-physician personnel is limited. Inhaled analgesics, such as methoxyflurane, might prove useful, but currently no data exist on their application by non-physicians in the alpine setting.Methods: This prospective observational alpine field study was conducted over a period of 15 months. Patients suffering traumatic injuries with moderate to severe pain (pain score ≥ 5) after downhill bike accidents in the Tyrol mountains (1,362 m to 2,666 m above sea level) were enrolled. Teams of four mountain rescue service members, one of them a trained EMT, treated the patients with 3 ml of methoxyflurane by inhaler. We measured efficacy as reduction in pain from baseline to 15 minutes after treatment on a numerical rating scale. Safety was assessed by change in vital signs or occurrence of side-effects. Sample-size calculations were based on the efficacy outcome and yielded a need for 20 patients at a power of 0.8.Results: From June 29, 2020 to September 30, 2021, a total of 20 patients (two females; mean age 37 years) were included. The mean initial pain score was 7.2 (SD 1.0) points. After 15 minutes, pain was significantly reduced by a mean of 2.9 (SD 1.4) points. No major adverse events or relevant changes in vital signs were observed.Conclusion: The use of methoxyflurane by EMTs during alpine rescue operations in our study proved to be safe and efficient. We observed no reduction in the efficacy of the inhaler device at moderate altitude.

Usability and effectiveness of inhaled methoxyflurane for prehospital analgesia - a prospective, observational study.

BACKGROUND: Pain relief in the prehospital setting is often insufficient, as the administration of potent intravenous analgesic drugs is mostly reserved to physicians. In Australia, inhaled methoxyflurane has been in routine use by paramedics for decades, but experience in Central European countries is lacking. Thus, we aimed to assess whether user friendliness and effectiveness of inhaled methoxyflurane as sole analgesic match the specific capabilities of local ground and air-based EMS systems in Austria. METHODS: Observational study in adult trauma patients (e.g. dislocations, fracture or low back pain following minor trauma) with moderate to severe pain (numeric rating scale [NRS] ≥4). Included patients received a Penthrop® inhaler containing 3 mL of methoxyflurane (maximum use 30 min). When pain relief was considered insufficient (NRS reduction < 3 after 10 min), intravenous analgesics were administered by an emergency physician. The primary endpoint was effectiveness of methoxyflurane as sole analgesic for transport of patients. Secondary endpoints were user friendliness (EMS personell), time to pain relief, vital parameters, side effects, and satisfaction of patients. RESULTS: Median numeric pain rating was 8.0 (7.0-8.0) in 109 patients. Sufficient analgesia (reduction of NRS ≥3) was achieved by inhaled methoxyflurane alone in 67 patients (61%). The analgesic effect was progressively better with increasing age. Side effects were frequent (n = 58, 53%) but mild. User satisfaction was scored as very good when pain relief was sufficient, but fair in patients without benefit. Technical problems were observed in 16 cases (14.7%), mainly related to filling of the inhaler. In every fifth use, the fruity smell of methoxyflurane was experienced as unpleasant. No negative effects on vital signs were observed. CONCLUSION: In prehospital use, inhaled methoxyflurane as sole analgesic is effective for transport of trauma patients (62%) with moderate to severe pain. Older patients benefit especially from inhaled methoxyflurane. Side effects are mild and vital parameters unaffected. Thus, inhaled methoxyflurane could be a valuable device for non-physician EMS personnel rescue services also in the central Europe region.

[Volatile anesthetics for prehospital analgesia by paramedics-An overview]. / Volatile Anästhetika zur präklinischen Analgesie durch Rettungssanitäter ­ Eine Übersicht.

Treatment of acute pain is a central task in emergency medicine. Yet, prehospital pain relief is often insufficient or delayed since the administration of potent intravenous analgesic drugs (such as opioids) is mostly limited to physicians due to legal restrictions or training deficiencies in Germany and Austria. Frequently, prehospitally operating emergency physicians have to be demanded later for anguished patients limiting disposability of physicians for patients who are in a potentially life-threatening condition. Thus, inhaled analgesics could represent an interesting alternative.A mixture of 50% nitrous oxide and 50% oxygen (N2O, Livopan®) has been available in Germany and Austria for several years; however, prehospital use of Livopan has been merely realized and only one trial has been published. In addition, methoxyflurane (Penthrop®), a volatile anesthetic from the group of the dialkyl esters (2-dichloro-1:1-difluoroethyl-methyl-ester) was approved for the treatment of moderate to severe pain following trauma in adults in many European countries in recent years and was brought onto the market in Austria in 2018. Several in-hospital trials demonstrated high effectiveness in this setting.This article discusses the effects and prehospital areas of application of both substances in the light of the existing literature. We provide a narrative overview of the current study situation and report on a recently performed prehospital application study of methoxyflurane (Penthrop®) from Austria.The need for pressurized gas cylinders for the use of N2O represents a certain limitation in prehospital use. Furthermore, in certain injuries such as of the inner ear or a pneumothorax N2O should not be used and the risk of diffusion hypoxemia has to be addressed. Users should be particularly careful and limit the use in alcohol addicts and vegans. The advances of N2O are that it is odorless, has a fast onset of action, the usability in patients over 1 month old and has stabilizing effects on the circulation. Plenty of literature regarding prehospital as well as in-hospital use of nitrous oxide in emergency, obstetric and pediatric settings show its effectiveness as a single drug as well as in combination with other analgesics, such as paracetamol or various opioids. Its long tradition in Anglo-American countries is also based on its safety and low rate of side effects.Methoxyflurane is easier to store and handle and may be slightly more effective in severe pain after trauma; however, its approval is restricted to adults, where it works significantly better with increasing age, based on the declining minimal alveolar concentration (MAC) of all inhaled anesthetics with increasing age. Furthermore, decades of use of inhaled methoxyflurane in Australia have shown the drug is effective, safe and low in side effects and has a broad spectrum of applications. The use of methoxyflurane is limited in patients with severe hepatic or renal insufficiency and the characteristic odor has been described as unpleasant by some patients. In Europe, three large in-hospital trials showed strong pain relief in trauma patients, even comparable to opioids.Overall, based on the current evidence, the use of nitrous oxide and even more of methoxyflurane may be recommended also for prehospital use by skilled paramedics.

Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial.

BACKGROUND: After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking. METHODS: In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis. We conducted a detailed questionnaire, clinical examination, laboratory testing, lung function analysis, echocardiography and thoracic low-dose computed tomography (CT). RESULTS: Data from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnoea being most frequent (36%). Accordingly, patients still displayed an impaired lung function, with a reduced diffusing capacity in 21% of the cohort being the most prominent finding. Cardiac impairment, including a reduced left ventricular function or signs of pulmonary hypertension, was only present in a minority of subjects. CT scans unveiled persisting lung pathologies in 63% of patients, mainly consisting of bilateral ground-glass opacities and/or reticulation in the lower lung lobes, without radiological signs of pulmonary fibrosis. Sequential follow-up evaluations at 60 and 100 days after COVID-19 onset demonstrated a vast improvement of symptoms and CT abnormalities over time. CONCLUSION: A relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with radiological pulmonary abnormalities >100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.

Evaluation of four commercial, fully automated SARS-CoV-2 antibody tests suggests a revision of the Siemens SARS-CoV-2 IgG assay.

OBJECTIVES: Serological tests detect antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the ongoing coronavirus disease-19 (COVID-19) pandemic. Independent external clinical validation of performance characteristics is of paramount importance. METHODS: Four fully automated assays, Roche Elecsys Anti-SARS-CoV-2, Abbott SARS-CoV-2 IgG, Siemens SARS-CoV-2 total (COV2T) and SARS-CoV-2 IgG (COV2G) were evaluated using 350 pre-pandemic samples and 700 samples from 245 COVID-19 patients (158 hospitalized, 87 outpatients). RESULTS: All tests showed very high diagnostic specificity. Sensitivities in samples collected at least 14 days after disease onset were slightly lower than manufacturers' claims for Roche (93.0%), Abbott (90.8%), and Siemens COV2T (90.3%), and distinctly lower for Siemens COV2G (78.8%). Concordantly negative results were enriched for immunocompromised patients. ROC curve analyses suggest a lowering of the cut-off index for the Siemens COV2G assay. Finally, the combination of two anti-SARS-CoV-2 antibody assays is feasible when considering borderline reactive results. CONCLUSIONS: Thorough on-site evaluation of commercially available serologic tests for detection of antibodies against SARS-CoV-2 remains imperative for laboratories. The potentially impaired sensitivity of the Siemens COV2G necessitates a switch to the company's newly filed SARS-CoV-2 IgG assay for follow-up studies. A combination of tests could be considered in clinical practice.

Clinical validation of the Siemens quantitative SARS-CoV-2 spike IgG assay (sCOVG) reveals improved sensitivity and a good correlation with virus neutralization titers.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections cause coronavirus disease 2019 (COVID-19) and induce a specific antibody response. Serological assays detecting IgG against the receptor binding domain (RBD) of the spike (S) protein are useful to monitor the immune response after infection or vaccination. The objective of our study was to evaluate the clinical performance of the Siemens SARS-CoV-2 IgG (sCOVG) assay. METHODS: Sensitivity and specificity of the Siemens sCOVG test were evaluated on 178 patients with SARS-CoV-2-infection and 160 pre-pandemic samples in comparison with its predecessor test COV2G. Furthermore, correlation with virus neutralization titers was investigated on 134 samples of convalescent COVID-19 patients. RESULTS: Specificity of the sCOVG test was 99.4% and sensitivity was 90.5% (COV2G assay 78.7%; p<0.0001). S1-RBD antibody levels showed a good correlation with virus neutralization titers (r=0.843; p<0.0001) and an overall qualitative agreement of 98.5%. Finally, median S1-RBD IgG levels increase with age and were significantly higher in hospitalized COVID-19 patients (median levels general ward: 25.7 U/mL; intensive care: 59.5 U/mL) than in outpatients (3.8 U/mL; p<0.0001). CONCLUSIONS: Performance characteristics of the sCOVG assay have been improved compared to the predecessor test COV2G. Quantitative SARS-CoV-2 S1-RBD IgG levels could be used as a surrogate for virus neutralization capacity. Further harmonization of antibody quantification might assist to monitor the humoral immune response after COVID-19 disease or vaccination.

Low acceptance of osteoanabolic therapy with parathyroid hormone in patients with fragility fracture of the pelvis in routine clinical practice: a retrospective observational cohort study.

INTRODUCTION: A recent randomized controlled trial has reported full patient compliance and no adverse events from therapy with parathyroid hormone (PTH) for osteoporosis and accelerated healing of fragility fractures of the pelvis. The purpose of the presented study was to evaluate if similar results can be achieved with comprehensive PTH therapy in routine clinical practice. We hypothesised that patients' burden of PTH therapy is underestimated in the literature. PATIENTS AND METHODS: Osteoanabolic PTH therapy was recommended to 79 patients suffering from an acute fragility fracture of the pelvis (FFP). Case finding, initiation of therapy and follow-up were performed by a fracture liaison service team. Primary outcome was PTH initiation rate. Secondary outcomes were implementation rate of alternative antiresorptive pharmaceutical therapy for osteoporosis and participation rate in a bone metabolic workup. Adverse events and effects potentially related to the therapy with bone-active drugs were documented as exploratory outcomes. RESULTS: Osteoanabolic PTH therapy as suggested was accepted by 32%, whereas antiresorptive therapy was implemented in another 14% of the patients. DEXA scans were available in 38% of the patients (+ 27% when compared to baseline). A bone-specific laboratory analysis was done in 18 patients, uncovering 7 pathological findings. Two patients terminated PTH therapy early because of side effects. CONCLUSION: The experiences with PTH therapy in FFP patients with respect to, implementation rate, frequency of side effects and of pathological findings in laboratory controls as reported from a previous RCT could not be reproduced in routine clinical practice.

Aortic annulus to left coronary distance as a predictor for persistent left bundle branch block after TAVI.

OBJECTIVES: To identify potential predictors for ventricular conduction delay and to evaluate the impact of interventricular dyssynchrony on mortality after implantation of a balloon-expandable aortic valve (BEV). METHODS AND RESULTS: Clinical, computertomographical (CT), and electrocardiographical (ECG) data from 225 transcatheter aortic valve implantation (TAVI) patients were analyzed. Procedures were performed between May 2010 and September 2013 via transfemoral access using a BEV. Incidence of new-onset left bundle branch block (NOP-LBBB) at discharge was 23.1% (n = 52). Predictive factors for NOP-LBBB were first degree atrioventricular (AV) block (odds ratio (OR): 3.91, 95% confidence interval (CI): 1.58 to 9.64), area cover index (OR: 1.83, 95% CI: 1.26 to 2.67), annulus calcification > first degree (OR: 3.01, 95% CI: 1.36 to 6.66), and annulus to left coronary distance (OR: 0.65, 95% CI: 0.44 to 0.96). At 1-year follow-up, no significant difference was observed concerning all-cause mortality (15.6% among non NOP-LBBB and 9.6% among NOP-LBBB patients, P = 0.278) and cardiovascular mortality (4.6% among non NOP-LBBB and 5.8% among NOP-LBBB patients, P = 0.737). CONCLUSION: In addition to previous predictors, annulus to left coronary distance and area cover index have been identified as new predictors for NOP-LBBB. NOP-LBBB showed no relevant impact on mortality after one year. Further investigation including larger populations and longer follow-up is required to confirm these findings and develop an algorithm for identification of patients at risk for NOP-LBBB associated adverse events. © 2016 Wiley Periodicals, Inc.

Comparative in vitro and in vivo pharmacological investigation of platinum(IV) complexes as novel anticancer drug candidates for oral application.

Platinum(IV) complexes are promising candidates as prodrugs for oral application in anticancer chemotherapy. However, only a few Pt(IV) compounds entered (pre)clinical trials, e.g. satraplatin, while most of the others were only tested in vitro. Aim of the study was investigation of the in vivo pharmacological behavior as well as the anticancer activity of two novel platinum(IV) complexes vs. satraplatin. The drugs were selected due to significantly different in vitro cytotoxicity while sharing some physicochemical properties (e.g. lipophilicity). Initial experiments indicated that the highly in vitro cytotoxic compound 1 ((OC-6-33)-dichloridobis((4-ethoxy)-4-oxobutanoato)-bis(ethylamine)platinum(IV)) was also characterized by high drug absorption and tissue platinum levels after oral application. Interestingly, analysis of serum samples using SEC-ICP-MS revealed that the administered drugs have completely been metabolized and/or bound to proteins in serum within 2 h after treatment. With regard to the activity in vivo, the outcomes were rather unexpected: although potent anticancer effect of 1 was observed in cell culture, the effects in vivo were rather minor. Nevertheless, 1 was superior to 2 ((OC-6-33)-diammine(cyclobutane-1,1-dicarboxylato)-bis((4-cyclopentylamino)-4-oxobutanoato)platinum(IV)) after i.p. administration, which was, at least to some extent, in accordance to the cell culture experiments. After oral gavage, both compounds exhibited comparable activity. This is remarkable considering the distinctly lower activity of 2 in cell culture as well as the low platinum levels detected both in serum and tissues after oral application. Consequently, our data indicate that the prediction of in vivo anticancer activity by cell culture experiments is not trivial, especially for orally applied drugs.

Influence of Oral Contraceptives on Lipid Profile and Trajectories in Healthy Adolescents-Data From the EVA-Tyrol Study.

PURPOSE: Oral contraception is one of the most popular contraceptive methods both in adults and adolescents. However, the effects of oral contraception on lipids in adolescents are not well studied. METHODS: Lipid profiles were measured and contraceptive use was assessed in 14- to 19-year-old female participants of the prospective population-based Early Vascular Ageing-Tyrol Study between 2015 and 2018, twice on average 22 months apart. RESULTS: For this analysis, data from 828 young women with a median age of 17.0 years were available. Of them, 317 (38%) used oral contraceptives (OCs). OC users had a slightly higher systolic and diastolic blood pressure and larger changes over time and were more likely to use cigarettes than nonusers. Total cholesterol (179.6 vs. 162.4 mg/dL), low-density lipoprotein-cholesterol (106.4 vs. 94.6 mg/dL), and triglycerides (104.0 vs. 67.0 mg/dL) were significantly higher in OC users after multivariable adjustment in linear regression models. No difference in high-density lipoprotein-cholesterol between the two groups was found. In 558 females, follow-up data were available. Those who initiated OC use had on average 15.4 mg/dL higher low-density lipoprotein-cholesterol and 36.2 mg/dL higher triglyceride level changes between baseline and follow-up than never users. Duration of OC use did not show a significant association with lipid levels and changes. DISCUSSION: We showed an independent association between OC use and blood lipids as well as lipid trajectories over time in a large cohort of healthy adolescents. These changes are especially relevant to consider in adolescents with other risk factors for dyslipidemia or other cardiovascular risk factors.

Laboratory parameters related to disease severity and physical performance after reconvalescence of acute COVID-19 infection.

Research into the molecular basis of disease trajectory and Long-COVID is important to get insights toward underlying pathophysiological processes. The objective of this study was to investigate inflammation-mediated changes of metabolism in patients with acute COVID-19 infection and throughout a one-year follow up period. The study enrolled 34 patients with moderate to severe COVID-19 infection admitted to the University Clinic of Innsbruck in early 2020. The dynamics of multiple laboratory parameters (including inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), neopterin] as well as amino acids [tryptophan (Trp), phenylalanine (Phe) and tyrosine (Tyr)], and parameters of iron and vitamin B metabolism) was related to disease severity and patients' physical performance. Also, symptom load during acute illness and at approximately 60 days (FU1), and one year after symptom onset (FU2) were monitored and related with changes of the investigated laboratory parameters: During acute infection many investigated laboratory parameters were elevated (e.g., inflammatory markers, ferritin, kynurenine, phenylalanine) and enhanced tryptophan catabolism and phenylalanine accumulation were found. At FU2 nearly all laboratory markers had declined back to reference ranges. However, kynurenine/tryptophan ratio (Kyn/Trp) and the phenylalanine/tyrosine ratio (Phe/Tyr) were still exceeding the 95th percentile of healthy controls in about two thirds of our cohort at FU2. Lower tryptophan concentrations were associated with B vitamin availability (during acute infection and at FU1), patients with lower vitamin B12 levels at FU1 had a prolonged and more severe impairment of their physical functioning ability. Patients who had fully recovered (ECOG 0) presented with higher concentrations of iron parameters (ferritin, hepcidin, transferrin) and amino acids (phenylalanine, tyrosine) at FU2 compared to patients with restricted ability to work. Persistent symptoms at FU2 were tendentially associated with IFN-γ related parameters. Women were affected by long-term symptoms more frequently. Conclusively, inflammation-mediated biochemical changes appear to be related to symptoms of patients with acute and Long Covid.

Exercise-Induced Fluid Retention, Cardiac Volume Overload, and Peripheral Edema in Ultra-Distance Cyclists.

Introduction: Ultracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and investigate the potential occurrence of peripheral edema. Methods: A total of 4 clinical visits were performed before, during, and after a 6-day bicycle ride in 13 ultracyclists (5 female, 8 male) including serial laboratory analyses of blood and urine, bioelectrical impedance, and echocardiography. Throughout the ride, participants continuously tracked fluid intake, measured extremity circumferences daily, and self-tested urinary electrolytes using a point-of-care testing device. Portrait photos were judged by 20 physicians for occurrence of facial and eyelid edema. Results: Participants covered a mean distance of 1205 km and 19,417 vertical meters. From baseline to day 6, body weight remained stable (P = 0.479); however, body composition changed with increasing total body water (TBW) (+1.98 l ± 1.37, P = 0.003) and plasma volume (+18.86 % ± 10.7, P < 0.001). A significant increase in N-terminal pro brain natriuretic peptide (NT-proBNP) (+297.99 ng/l ± 190.42, P < 0.001) until day 6 indicates concomitant cardiac volume overload. Swelling of face and eyelids peaked on day 5 (both P ≤ 0.033). On recovery, changes partly resolved. Although urinary sodium concentration showed a nadir on day 4 (-32.18 mmol/l ± 23.88, P = 0.022), plasma osmolality (+5.69 mmosmol/kg ± 5.88, P = 0.004) and copeptin (+38.28 pg/ml ± 18.90, P < 0.001) increased steadily until day 6. Conclusion: Ultracycling over multiple days induces extracellular volume expansion, peripheral edema, and cardiac volume overload. Renal sodium and water retention is likely contributing to this condition.

Determinants of non-alcoholic fatty liver disease in young people: Maternal, neonatal, and adolescent factors.

AIM: To assess the impact of maternal, neonatal, and adolescent factors on the development of non-alcoholic fatty liver disease (NAFLD) in a cohort of 14- to 19-year-old adolescents. METHODS: This study is part of the Early Vascular Ageing in the YOUth study, a single-center cross-sectional study conducted in western Austria. Maternal and neonatal factors were extracted from the mother-child booklet, adolescent factors were evaluated by a face-to-face interview, physical examination, and fasting blood analyses. Liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan® (Echosense, Paris, France). The association of maternal, neonatal, and adolescent factors with CAP values was analyzed using linear regression models. RESULTS: In total, 595 adolescents (27.2% male) aged 17.0 ± 1.3 years were included. 4.9% (n = 29) showed manifest NAFLD with CAP values above the 90th percentile. Male sex (p < 0.001), adolescent triglyceride levels (p = 0.021), Homeostatic Model Assessment for Insulin Resistance index and BMI z-score (p < 0.001, each) showed a significant association with liver fat content in the multivariable analysis. Maternal pre-pregnancy BMI was associated with CAP values after adjustment for sex, age, and birth weight for gestational age (p < 0.001), but this association was predominantly mediated by adolescent BMI (indirect effect b = 1.18, 95% CI [0.69, 1.77]). CONCLUSION: Components of the metabolic syndrome were the most important predictors of adolescent liver fat content. Therefore, prevention of NAFLD should focus on lifestyle modification in childhood and adolescence.

Influence of extracellular pH on the cytotoxicity, cellular accumulation, and DNA interaction of novel pH-sensitive 2-aminoalcoholatoplatinum(II) complexes.

Extracellular acidity is a frequent pathophysiological condition of solid tumors offering possibilities for improving the tumor selectivity of molecular therapy. This might be accomplished by prodrugs with low systemic toxicity, attaining their full antitumor potency only under acidic conditions, such as bis(2-aminoalcoholato-κ(2)N,O)platinum(II) complexes that are activated by protonation of alcoholato oxygen, resulting in cleavage of platinum-oxygen bonds. In this work, we examined whether the pH dependency of such compounds is reflected in differential biological activity in vitro. In particular, the pH dependence of cytotoxicity, cellular accumulation, DNA platination, GMP binding, effects on DNA secondary structure, cell cycle alterations, and induction of apoptosis was investigated. Enhanced cytotoxicity of five of these complexes in non-small-cell lung cancer (A549) and colon carcinoma (HT-29) cells at pH 6.0 in comparison with pH 7.4 was confirmed: 50 % growth inhibition concentrations ranged from 42 to 214 µM in A549 cells and from 35 to 87 µM in HT-29 cells at pH 7.4 and decreased at pH 6.0 to 11-50 and 7.3-25 µM, respectively. The effects induced by all five pH-sensitive compounds involve increased 5'-GMP binding, cellular accumulation, and DNA platination as well as stronger effects on DNA secondary structure at pH 6.0 than at pH 7.4. As exemplified by treatment of A549 cells with a 2-amino-4-methyl-1-pentanolato complex, induction of apoptosis is enhanced at pH 6.5. These results confirm the increased reactivity and in vitro activity of these compounds under slightly acidic conditions, encouraging further evaluation of ring-closed aminoalcoholatoplatinum(II) derivatives in solid tumors in vivo.

Evaluation of two fully automated ADAMTS13 activity assays in comparison to manual FRET assay.

INTRODUCTION: The objective of the present study was to evaluate and compare the validity and utility of two fully automated ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity assays for clinical diagnostic decision-making and to compare their performance. METHODS: Two automated ADAMTS13 activity assays (Werfen HemosIL® AcuStar ADAMTS13 Activity, Technoclone Technofluor ADAMTS13 Activity) were compared with a manual FRET assay (BioMedica ACTIFLUOR ADAMTS13 Activity). The following samples were used: 13 acute phase TTP (thrombotic thrombocytopenic purpura) samples from 11 different patients, one sample from a patient with congenital ADAMTS13 deficiency, 16 samples from control patients, three follow-up samples from TTP patients in long-term remission and one sample from a patient with stem cell transplantation related thrombotic microangiopathy (TMA). The WHO 1st International Standard for ADAMTS13 and several dilutions of normal plasma with ADAMTS13-depleted normal plasma were also tested. Statistical analysis included descriptive statistics, sensitivity and specificity, Passing & Bablok regression and Bland-Altman plot. RESULTS: The quantitative comparison between the HemosIL® (x) and Technofluor (y) methods showed a strong correlation (Pearson r = 0.98, n = 49). When considering an ADAMTS13 activity of <10% as a hallmark for the diagnosis of TTP, two fully automated assays were both able to identify all TTP- and non-TTP-samples correctly, resulting in sensitivities and specificities of 100%. CONCLUSION: Both fully automated ADAMTS13 activity assays showed a good diagnostic performance and quantitative correlation among themselves, discriminating reliably between TTP- and non-TTP-patients.

Influence of high altitude after a prior ascent on physical exhaustion during cardiopulmonary resuscitation: a randomised crossover alpine field experiment.

BACKGROUND: Performing cardiopulmonary resuscitation (CPR) inevitably causes significant physical, as well as psychological stress for rescuers. Physical activity at high altitude, a hypobaric and hypoxic environment, similarly adds to the level of stress and causes multiple physiological changes. Continuous measurement of pulse rate serves as an objective measure of fatigue during CPR. We therefore aimed to investigate rescuers' heart rates as a measure of physical strain during CPR in a high-altitude alpine environment to provide a better understanding of the physiological changes under these very special conditions. METHODS: Twenty experienced mountaineers performed basic life support (BLS) on a manikin for 16 min, both at baseline altitude and at high altitude (3454 m) following a quick and exhausting ascent over 1200 m. Sequence of scenarios was randomised for analysis. Heart rate was continuously measured and compared between baseline and high altitude by absolute differences and robust confidence intervals. RESULTS: During CPR at baseline, the average heart rate increased from 87 bpm (SD 16 bpm) to 104 bpm [increase 17 bpm (95% CI 8.24-24.76)], compared to an increase from 119 bpm (SD 12 bpm) to 124 bpm [increase 5 bpm (95% CI - 1.59 to 12.19)] at high altitude [difference between two groups 32 bpm (95% CI 25-39)]. Differences between periods of chest compressions and ventilations were very similar at baseline [19 bpm (95%CI 16.98-20.27)] and at high altitude [20 bpm 95% CI 18.56-21.44)], despite starting from a much higher level at high altitude. The average heart rates of rescuers at high altitude at any point were higher than those at baseline at any other point. CONCLUSION: Performing BLS CPR causes exhaustion both at base level and at a high altitude. A further increase during CPR might imply a physiological reserve for adapting to additional physical exertion at high altitude. Phases of ventilation are much needed recovery-periods, but heart rates remain very high. Subjective measures of exhaustion, such as the BORG-scale, might lead to rescuers' overestimation of their own performance.