Endotoxin Activity in Patients With Extracorporeal Membrane Oxygenation Life Support: An Observational Pilot Study

Background: Extracorporeal membrane oxygenation (ECMO) life support has become an integral part of intensive care. The endotoxin activity assay (EAA) is a useful test to measure endotoxemia severity in whole blood. To date, no information is available regarding the EAA levels and their effect on clinical outcomes in critically ill patients with ECMO support.Methods: This prospective observational pilot study enrolled adult critically ill patients with ECMO support from August 2019 to December 2020. The EAA levels were measured within 24 h (T1), and at 25–48 (T2), 49–72 (T3), and 73–96 h (T4) after ECMO initiation. This study primarily aimed to investigate the incidence of high EAA levels (≥0.6) at each time point. Subsequent exploratory analyses were conducted to compare the EAA levels of venoarterial ECMO (VA-ECMO) patients between 30-day survivors and non-survivors. Post-hoc analysis was performed to compare the clinical outcomes of VA-ECMO patients with elevated EAA levels at T3 (vs. T1) and those without elevated EAA levels.Results: A total of 39 VA-ECMO patients and 15 venovenous ECMO (VV-ECMO) patients were enrolled. At T1, the incidence of high EAA level (≥0.6) was 42% in VV-ECMO patients and 9% in VA-ECMO patients (P = 0.02). At T2, the incidence of high EAA level was 40% in VV-ECMO patients and 5% in VA-ECMO patients (P = 0.005). In VA-ECMO patients, EAA levels at T3 were significantly higher in 30-day non-survivors than in survivors (median [interquartile range]: 0.49 [0.37–0.93] vs. 0.31 [0.19–0.51], median difference 0.16 [95% confidence interval [CI], 0.02–0.31]; P = 0.024). Moreover, VA-ECMO patients with elevated EAA levels at T3 (vs. T1) had lower 30-day survival than patients without elevated EAA levels (39 vs. 83%, P = 0.026) and fewer ECMO free days by day 30 (median: 3 vs. 23 days, median difference 12 days [95% CI, 0–22]; P = 0.028).Conclusions: A certain proportion of patients experienced high EAA levels (≥0.6) after VV-ECMO or VA-ECMO initiation. VA-ECMO patients with an elevated EAA level at 49–72 h were associated with poor clinical outcomes.

Auswirkungen auf den vorderen Augenabschnitt beim Andocken eines Femtosekundenlasers an das Patienteninterface

Purpose. To compare the intraoperative OCT (optical coherence tomographer) of the femtosecond laser LenSx (Alcon Pharma GmbH, Freiburg) with a Scheimpflug-tomographer and an anterior segment OCT and thus to investigate a possible influence on the anterior segment of the eye when docking the patient’s interface. Material and Methods. A prospective cross-sectional study was conducted with 57 subjects who underwent a planned femtosecond laser-assisted cataract surgery or refractive lens exchange. The eye to be operated on was measured prior to the operation in mydriasis with the Visante OCT (Carl Zeiss Meditec AG, Jena) and the Pentacam AXL (Oculus Optikgeräte GmbH, Wetzlar). During the surgery, images of the anterior segment of the eye were taken by the integrated intraoperative OCT of the laser, which were evaluated afterwards and compared to the values of the other devices. The parameters examined were the internal anterior chamber depth (ACD), nasal and temporal chamber angles, central corneal thickness (CCT) and central lens thickness (LT). Results. The comparison of the intraoperative OCT and the two other devices showed clinically relevant differences in all parameters. The intraoperative OCT showed a 9.19 ± 27.55 μm larger CCT, 0.96 mm (median difference) larger LT, 0.05 mm smaller ACD than the Pentacam AXL and a 21.36 ± 25.50 μm larger CCT, 0.10 mm (median difference) smaller ACD than the Visante OCT. Conclusion. The comparison of the intraoperative OCT with the Visante OCT and the Pentacam AXL shows clinically relevant differences. Changes in the anterior segment of the eye may be due to errors in measurement or docking of the patient’s interface. Keywords. femtosecond laser, OCT, anterior segment of the eye, cataract surgery, refractive lens exchange

Three K2 Campaigns Yield Rotation Periods for 1013 Stars in Praesepe

We use three campaigns of K2 observations to complete the census of rotation in low-mass members of the benchmark, ≈670 Myr old open cluster Praesepe. We measure new rotation periods (P rot) for 220 ≲1.3 M ⊙ Praesepe members and recovery periods for 97% (793/812) of the stars with a P rot in the literature. Of the 19 stars for which we do not recover a P rot, 17 were not observed by K2. As K2’s three Praesepe campaigns took place over the course of 3 yr, we test the stability of our measured P rot for stars observed in more than one campaign. We measure P rot consistent to within 10% for >95% of the 331 likely single stars with ≥2 high-quality observations; the median difference in P rot is 0.3%, with a standard deviation of 2%. Nearly all of the exceptions are stars with discrepant P rot measurements in Campaign 18, K2’s last, which was significantly shorter than the earlier two (≈50 days rather than ≈75 days). This suggests that, despite the evident morphological evolution we observe in the light curves of 38% of the stars, P rot measurements for low-mass stars in Praesepe are stable on timescales of several years. A P rot can therefore be taken to be representative even if measured only once.

Quality-improvement project to reduce actual fasting times for fluids and solids before induction of anaesthesia

Background Despite well-defined recommendations, prolonged fasting times for clear fluids and solids are still common before elective surgery in adults. Extended fasting times may lead to discomfort, thirst, hunger and physiological dysfunctions. Previous studies have shown that prolonged fasting times are frequently caused by patients being misinformed as well as inadequate implementation of the current guidelines by medical staff. This study aimed to explore how long elective surgery patients fast in a German secondary care hospital before and after the introduction of an educational note for patients and re-training for the medical staff. Methods A total of 1002 patients were enrolled in this prospective, non-randomised interventional study. According to the power calculation, in the first part of the study actual fasting times for clear fluids and solids were documented in 502 consecutive patients, verbally instructed as usual regarding the recommended fasting times for clear fluids (2 h) and solids (6 h). Subsequently, we implemented additionally to the verbal instruction a written educational note for the patients, including the recommended fasting times. Furthermore, the medical staff was re-trained regarding the fasting times using emails, newsletters and employee meetings. Thereafter, another 500 patients were included in the study. We hypothesised, that after these quality improvement procedures, actual fasting times for clear fluids and solids would be more accurate on time. Results Actual fasting times for clear fluids were in the median 11.3 (interquartile range 6.8–14.3; range 1.5–25.5) h pre-intervention, and were significantly reduced to 5.0 (3.0–7.2; 1.5–19.8) h after the intervention (median difference (95%CI) − 5.5 (− 6.0 to − 5.0) h). The actual fasting times for solids also decreased significantly, but only from 14.5 (12.1–17.2; 5.4–48.0) h to 14.0 (12.0–16.3; 5.4–32.0) h after the interventions (median difference (95%CI) − 0.52 (− 1.0 to − 0.07) h). Conclusions The study showed considerably extended actual fasting times in elective adult surgical patients, which were significantly reduced by simple educational/training interventions. However, the actual fasting times still remained considerably longer than defined in recommended guidelines, meaning further process optimisations like obligatory fluid intake in the early morning are necessary to improve patient comfort and safety in future. Trial registration German registry of clinical studies (DRKS-ID: DRKS 00020530, retrospectively registered).

Multi-modality imaging in hypertrophic cardiomyopathy: intermodal discrepancies in key prognostic parameters

Background/Introduction Multi-modality imaging is crucial for confirming diagnosis and assessing prognosis in patients with hypertrophic cardiomyopathy (HCM). However, inter-modality discrepancies in key parameters are commonly reported. Purpose To assess real-world inter-modal reporting discrepancies between transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging in the measurement of four key parameters in HCM patients. Methods Consecutive HCM patients with TTE and CMR performed within 6 months of each other at a tertiary centre were retrospectively assessed for reported maximum wall thickness (MWT), left atrial diameter (LAd), left ventricular ejection fraction (LVEF) and presence of left ventricular apical aneurysm (LVAA). The CMR report was considered gold standard. Data are reported as mean ± standard deviation (SD) or median and interquartile range (IQR) as appropriate. Results 353 consecutive HCM patients (72% male, median age 60.9 years, IQR 49.8–71.6 years) with TTE and CMR within 6 months (median difference 1.7 months, IQR 1.1–3.4 months) were assessed between 4th January 2018 and 9th April 2019. Of 284 patients with paired MWT data, median difference was 0.0 mm (IQR −1.0 to 3.0 mm, p=0.02), likely representing a difference in distributions of MWT. TTE both over and underestimated MWT (in 36% and 46% cases respectively). Of the 94 patients with paired LAd data, mean difference was 0.4±5.7 mm (95% CI −0.8010 to 1.546, p=0.5). N=320 patients with paired LVEF data (after excluding patients with atrial fibrillation (n=20)). Median difference in LVEF was 12% (IQR 5–19% p<0.0001). TTE underestimated LVEF in 88% of cases. CMR and TTE both identified 14 (5%) patients as having LVEF <50%. There were however 8 cases of disagreement in classification of LVEF <50%, due to over (n=4) or underestimation (n=4) by TTE. LVAA was accurately identified by TTE in only 9/30 (30%) of those patients with demonstrable LVAA by CMR (p=0.0008). TTE evidence of a discreet apical chamber (paradoxical jet on spectral or colour Doppler) was present in 16/21 (76%) cases where TTE failed to overtly identify LVAA. However, apical or mid-cavity obliteration was reported in 15/21 (71%) cases where TTE failed to identify LVAA. Conclusion(s) Echocardiography and CMR measurements are often used interchangeably in clinical practice but inter-modality discrepancies can affect diagnosis and sudden cardiac death (SCD) risk assessment. This is particularly important for binary risk factors such as LVEF<50% or LVAA which are considered major SCD risk factors in the latest American Heart Association guidelines. 25 (7%) patients in our cohort had major risk factors identified by CMR that were not identified on TTE. CMR is an important, recommended tool where TTE imaging is suboptimal, but attention to more subtle elements of abnormal intracavity blood flow may be able to increase LVAA detection during TTE. FUNDunding Acknowledgement Type of funding sources: None.

Low bone mineral density in Thai children with systemic lupus erythematosus: prevalence and risk factors

Background Improvement of disease recognition and management has increased the survival of children with systemic lupus erythematosus (SLE), but has shifted the morbidity focus toward long-term complications, such as low bone mass and osteoporosis. Studies in adults with SLE show older age, chronic inflammation, and corticosteroid therapy are risk factors for low bone mineral density (BMD) and osteoporosis. Objectives To determine the prevalence of and identify risk factors associated with low BMD in Thai children with SLE. Methods We conducted a retrospective review of demographic data and clinical variables for a cohort of 60 Thai children with SLE who underwent 2 dual-energy X-ray absorptiometry (DXA) at their initial examination and later follow-up. We considered a BMD z score ≤ −2.0 to indicate low BMD. Binary logistic regression was used to assess risk factors potentially associated with low BMD. Results The prevalence of low BMD at the first visit was 40% and increased to 55% over follow-up. We found a significantly decreased hip BMD z score (median difference −0.25, 95% confidence interval [CI] −0.40 to −0.05; P = 0.016) and lumbar BMD z score (median difference −0.49, 95% CI −0.69 to −0.28; P < 0.001) over time. The cumulative steroid dose tended to be higher for patients with low BMD (adjusted odds ratio [OR] = 1.08, 95% CI 1.00 to 1.17; P = 0.050). Conclusion Low BMD has a 40% prevalence in Thai children newly diagnosed with SLE and progresses significantly over time. Higher cumulative corticosteroid dose tended to be associated with a low BMD, but we did not find a significant risk in this small sample.

Continuous positive airway pressure to reduce the risk of early peripheral oxygen desaturation after onset of apnoea in children: A double-blind randomised controlled trial

Continuous positive airway pressure (CPAP) during anaesthesia induction improves oxygen saturation (SpO2) outcomes in adults subjected to airway manipulation, and could similarly support oxygenation in children. We evaluated whether CPAP ventilation and passive CPAP oxygenation in children would defer a SpO2 decrease to 95% after apnoea onset compared to the regular technique in which no positive airway pressure is applied. In this double-blind, parallel, randomised controlled clinical trial, 68 children aged 2–6 years with ASA I–II who underwent surgery under general anaesthesia were divided into CPAP and control groups (n = 34 in each group). The intervention was CPAP ventilation and passive CPAP oxygenation using an anaesthesia workstation. The primary outcome was the elapsed time until SpO2 decreased to 95% during a follow-up period of 300 s from apnoea onset (T1). We also recorded the time required to regain baseline levels from an SpO2 of 95% aided by positive pressure ventilation (T2). The median T1 was 278 s (95% confidence interval [CI]: 188–368) in the CPAP group and 124 s (95% CI: 92–157) in the control group (median difference: 154 s; 95% CI: 58–249; p = 0.002). There were 17 (50%) and 32 (94.1%) primary events in the CPAP and control groups, respectively. The hazard ratio was 0.26 (95% CI: 0.14–0.48; p<0.001). The median for T2 was 21 s (95% CI: 13–29) and 29 s (95% CI: 22–36) in the CPAP and control groups, respectively (median difference: 8 s; 95% CI: -3 to 19; p = 0.142). SpO2 was significantly higher in the CPAP group than in the control group throughout the consecutive measures between 60 and 210 s (with p ranging from 0.047 to <0.001). Thus, in the age groups examined, CPAP ventilation and passive CPAP oxygenation deferred SpO2 decrease after apnoea onset compared to the regular technique with no positive airway pressure.

Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial

Objective To evaluate whether extended release metformin could be used to prolong gestation in women being expectantly managed for preterm pre-eclampsia. Design Randomised, double blind, placebo controlled trial. Setting Referral hospital in Cape Town, South Africa. Participants 180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks’ gestation undergoing expectant management: 90 were randomised to extended release metformin and 90 to placebo. Intervention 3 g of oral extended release metformin or placebo daily, in divided doses, until delivery. Main outcome measure The primary outcome was prolongation of gestation. Results Of 180 participants, one woman delivered before taking any trial drug. The median time from randomisation to delivery was 17.7 days (interquartile range 5.4-29.4 days; n=89) in the metformin arm and 10.1 (3.7-24.1; n=90) days in the placebo arm, a median difference of 7.6 days (geometric mean ratio 1.39, 95% confidence interval 0.99 to 1.95; P=0.057). Among those who continued to take the trial drug at any dose, the median prolongation of gestation in the metformin arm was 17.5 (interquartile range 5.4-28.7; n=76) days compared with 7.9 (3.0-22.2; n=74) days in the placebo arm, a median difference of 9.6 days (geometric mean ratio 1.67, 95% confidence interval 1.16 to 2.42). Among those who took the full dosage, the median prolongation of gestation in the metformin arm was 16.3 (interquartile range 4.8-28.8; n=40) days compared with 4.8 (2.5-15.4; n=61) days in the placebo arm, a median difference of 11.5 days (geometric mean ratio 1.85, 95% confidence interval 1.14 to 2.88). Composite maternal, fetal, and neonatal outcomes and circulating concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin did not differ. In the metformin arm, birth weight increased non-significantly and length of stay decreased in the neonatal nursery. No serious adverse events related to trial drugs were observed, although diarrhoea was more common in the metformin arm. Conclusions This trial suggests that extended release metformin can prolong gestation in women with preterm pre-eclampsia, although further trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible. Trial registration Pan African Clinical Trial Registry PACTR201608001752102 https://pactr.samrc.ac.za/ .

Testing the area–altitude balance ratio (AABR) and accumulation–area ratio (AAR) methods of calculating glacier equilibrium-line altitudes

In this study, we compare equilibrium-line altitudes (ELAs) calculated using the area–altitude balance ratio (AABR) and the accumulation–area ratio (AAR) methods, with measured ELAs derived from direct field observations. We utilise a GIS toolbox to calculate the ELA for 64 extant glaciers by applying the AABR and AAR methods to DEMs and polygons of their geometry. The calculated ELAs (c-ELAs) are then compared to measured zero-net balance ELAs (znb-ELAs) obtained from mass-balance time series held by the WGMS for the same glaciers. The correlation between znb-ELAs and AABR (1.56)/AAR (0.58) c-ELAs is very strong, with an r2 = 0.99. The smallest median difference between znb-ELAs and c-ELAs (i.e. 65.5 m) is obtained when a globally representative AABR of 1.56 is used. When applied to palaeoglacier-climate applications, this difference translates to ~0.42°C, well within the uncertainty of palaeotemperature proxies used to determine mean summer temperature at the ELA. The more widely used mean AABR of 1.75 is shown to be statistically invalid due to the skewness of the dataset. On this basis, when calculating glacier ELAs, we recommend the use of a global AABR value of 1.56.

Impact of dexmedetomidine supplemented analgesia on delirium in patients recovering from orthopedic surgery: A randomized controlled trial

Background Dexmedetomidine promotes normal sleep architecture; the drug also improves analgesia. We therefore tested the hypothesis that supplementing intravenous analgesia with dexmedetomidine reduces delirium in older patients recovering from orthopedic surgery. Methods In this double-blinded randomized controlled trial, we enrolled 712 older (aged 65–90 years) patients scheduled for major orthopedic surgery. Postoperative analgesia was provided by patient-controlled intravenous sufentanil, supplemented by randomly assigned dexmedetomidine (1.25 μg/mL) or placebo, for up to three days. The primary outcome was the incidence of delirium assessed twice daily with the Confusion Assessment Method. Among secondary outcomes, pain severity was assessed twice daily and sleep quality once daily, each with an 11-point scale where 0 = no pain/the best possible sleep and 10 = the worst pain/the worst possible sleep. Results The incidence of postoperative delirium was 7.3% (26 of 354) with placebo and 4.8% (17 of 356) with dexmedetomidine; relative risk 0.65, 95% CI 0.36 to 1.18; P = 0.151. Dexmedetomidine reduced pain both at rest (median difference -1 to 0 points, P ≤ 0.001) and with movement (-1 points, P < 0.001) throughout the first 5 postoperative days; it also improved subjective sleep quality during the first 3 postoperative days: day one median difference -1 point (95% CI -1 to 0), P = 0.007; day two 0 point (-1 to 0), P = 0.010; and day three 0 point (-1 to 0), P = 0.003. The incidence of adverse events was similar in each group. Conclusions Supplementing sufentanil intravenous analgesia with low-dose dexmedetomidine did not significantly reduce delirium, but improved analgesia and sleep quality without provoking adverse events. Trial registration www.chictr.org.cn: ChiCTR1800017182 (Date of registration: July 17, 2018); ClinicalTrials.gov:NCT03629262 (Date of registration: August 14, 2018).