A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation.

BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.

Use of platelet inhibitors for digital ulcers related to systemic sclerosis: EUSTAR study on derivation and validation of the DU-VASC model.

OBJECTIVE: To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. METHODS: We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. RESULTS: Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. CONCLUSION: The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Performance of two-dimensional shear wave elastography and transient elastography compared to liver biopsy for staging of liver fibrosis.

BACKGROUND: Staging of liver fibrosis traditionally relied on liver histology; however, transient elastography (TE) and more recently two-dimensional shear wave elastography (2D-SWE) evolved to noninvasive alternatives. Hence, we evaluated the diagnostic accuracy of 2D-SWE assessed by the Canon Aplio i800 ultrasound system using liver biopsy as reference and compared the performance to TE. METHODS: In total, 108 adult patients with chronic liver disease undergoing liver biopsy, 2D-SWE and TE were enrolled prospectively at the University Hospital Zurich. Diagnostic accuracies were evaluated using the area under the receiver operating characteristic (AUROC) analysis, and optimal cut-off values by Youden's index. RESULTS: Diagnostic accuracy of 2D-SWE was good for significant (≥F2; AUROC 85.2%, 95% confidence interval (95%CI):76.2-91.2%) as well as severe fibrosis (≥F3; AUROC 86.8%, 95%CI: 78.1-92.4%) and excellent for cirrhosis (AUROC 95.6%, 95%CI: 89.9-98.1%), compared to histology. TE performed equally well (significant fibrosis: 87.5%, 95%CI: 77.7-93.3%; severe fibrosis: 89.7%, 95%CI: 82.0-94.3%; cirrhosis: 96%, 95%CI: 90.4-98.4%), and accuracy was not statistically different to 2D-SWE. 2D-SWE optimal cut-off values were 6.5, 9.8 and 13.1 kPa for significant fibrosis, severe fibrosis and cirrhosis, respectively. CONCLUSIONS: Performance of 2D-SWE was good to excellent and well comparable with TE, supporting the application of this 2D-SWE system in the diagnostic workup of chronic liver disease.

Inter-Hospital Transfer of Patients With Ruptured Abdominal Aortic Aneurysm in Switzerland.

OBJECTIVE: To analyse the association between inter-hospital transfer and hospital mortality in patients with ruptured abdominal aortic aneurysms (rAAA) in Switzerland. METHODS: Secondary data analysis of case related hospital discharge data from the Swiss Federal Statistical Office for the years 2009 - 2018. All cases with rAAA as primary or secondary diagnosis were included. Cases with rAAA as a secondary diagnosis without surgical treatment and cases that had been transferred to another hospital without surgical treatment at the referring hospital were excluded. Logistic regression models for hospital mortality were constructed with age, sex, type of admission, van Walraven comorbidity score, type of treatment, insurance class, hospital level, and year of treatment as independent variables. RESULTS: A total of 1 798 cases with rAAA were treated either surgically (62.5%) or palliatively (37.5%) in Switzerland from 1 January 2009 to 31 December 2018. Of these cases, 72.9% were treated directly (surgically or palliatively) at the hospital of first presentation, whereas 27.1% of all cases with rAAA were transferred between hospitals. The overall crude hospital mortality was 50.3%; being 23.1% in the surgically treated cohort and 95.7% in the palliatively treated cohort. Inter-hospital transfer was associated with better survival compared with patients who were admitted directly (OR 0.52; 95% CI 0.36 - 0.75; p < .001). Treatment in major hospitals was associated with significantly higher mortality rate compared with university hospitals (OR 1.98; 1.41 - 2.79; p < .001). There was no evidence of an association between open repair and hospital mortality (OR 1.06; 0.77 - 1.48; p = .72) compared with endovascular repair. CONCLUSION: In a healthcare system such as Switzerland's with a highly specialised rescue chain, transfer of haemodynamically stable patients with rAAA is probably safe. In this setting, centralised medical care might outweigh the potential disadvantages of a short delay due to patient transfer. Further studies are needed to address potential confounding factors such as haemodynamic and anatomical features.

Zinc Oxide Patches Are a Highly Effective Treatment for Chronic Prurigo: A Randomized Split-Body Study.

BACKGROUND: Chronic prurigo (CPG) presents with pruriginous lesions and reduced quality of life (QoL). Established treatment options are often unsatisfying. Little is known about the efficacy of topical occlusive treatments. Patients often report rapid relief of symptoms when using topical occlusive zinc oxide patches (ZOP). We, therefore, aimed to assess the efficacy of ZOP. METHODS: In this randomized controlled split-body crossover study, 22 participants were analyzed, receiving three treatments sequentially: ZOP, topical betamethasone 17-valerate (topical glucocorticosteroids [TGCs]), and both ZOP and TGC combined (ZOP + TGC). Each intervention was applied to either the right or left side of the body for seven consecutive days. Outcomes were a count of active excoriated pruriginous lesions (APLs), itch, recurrence of APL, QoL, and treatment comfort. They were assessed through photographs and questionnaires: modified Prurigo Activity and Severity Score, modified Itchy Quality of Life Questionnaire, and Therapy Comfort Score. RESULTS: We observed a significant reduction of 46% in APL count for ZOP (95% CI from 30% to 58%, p value: <0.0001). Similar reduction was seen for ZOP + TGC, and a lower reduction was seen for TGC alone (48% [95% CI from 33% to 60%, p value: <0.0001] vs. 26% [95% CI from 4% to 43%, p value: 0.02]). APL counts on the non-treated side remained stable. Significant reduction in itch was observed after all treatments, with the largest improvement for ZOP + TGC, followed by TGC and, lastly, ZOP alone (-2.3 units [95% CI from -3.5 to -1.1, p value: 0.00015] vs. -1.5 units [95% CI from -2.8 to -0.3, p value: 0.01 vs. -1.4 units [95% CI from -2.6 to -0.2, p value: 0.02]). QoL increased significantly after ZOP + TGC as well as after TGC (-8.3 units [95% CI from -13.6 to -3.1, p value: 0.0018] vs. -5.7 units [95% CI from -10.9 to -0.5, p value: 0.03]). A good subjective response concerning treatment comfort was observed. CONCLUSION: ZOP are effective in reducing APL after 1 week of treatment. Adding TGC to ZOP did not add considerable benefit in reducing APL. All three treatments reduced itch and improved QoL, with the largest improvement shown by ZOP combined with TGC. Patients tolerated ZOP well and reported no adverse events. We therefore suggest ZOP combined with TGC as an effective, fast-acting, low-cost treatment for reducing APL and itch in patients with CPG.

Neurovascular disease in Switzerland: 10-year trends show non-traditional risk factors on the rise and higher exposure in women.

BACKGROUND AND PURPOSE: Effective risk factor modification is the prerequisite to prevent neurovascular disease such as stroke or vascular dementia. Non-traditional vascular risk factors (nt-vrfs) including stress significantly add to the risk of neurovascular disease arising from traditional vascular risk factors (t-vrfs). In order to discover sex-specific changes that may underlie previously reported inclines in the prevalence of neurovascular and cardiovascular disease in women, 10-year trends in the prevalence of vrfs in Switzerland were assessed. METHODS: Anonymized data from 22,134 participants (51% women) of the governmental Swiss Health Survey, performed every 5 years (2007, 2012 and 2017), were obtained. Epidemiological parameters, t-vrfs and nt-vrfs were analyzed in a cross-sectional study design. RESULTS: Over the observation period, the number of women having full-time jobs increased considerably (2007 38%, 2012 39%, 2017 44%). This was accompanied by a substantial rise in the prevalence of nt-vrfs in women and men including stress at work (2007, not available; 2012 women/men 58%/60%; 2017 women/men 66%/65%), low locus of control (women/men: 2007 21%/19%, 2012 22%/19%, 2017 25%/22%) and sleep disorders (women/men: 2007 30%/22%, 2012 28%/20%, 2017 32%/26%). Amongst t-vrfs, only the prevalence of obesity and hypercholesterolemia increased over time in both sexes, whilst other t-vrfs remained stable (hypertension [27%], diabetes [5%]) or decreased (smoking [9.4 cigarettes/day]). CONCLUSIONS: A rise in women's economic participation alongside a higher affection with nt-vrfs in the female Swiss population emphasizes the need to improve vascular risk stratification and implement effective preventive measures for neurovascular and cardiovascular disease.

Comparison of electrodiagnosis, neurosonography and MR neurography in localization of ulnar neuropathy at the elbow.

INTRODUCTION: In patients with ulnar neuropathy at the elbow (UNE) the precise determination of the site of lesion is important for subsequent differential diagnostic considerations and therapeutic management. Due to a paucity of comparable data, to better define the role of different diagnostic tests, we performed the first prospective study comparing the diagnostic accuracy of short segment nerve stimulation, nerve ultrasonography, MR neurography (MRN), and diffusion tensor imaging (DTI) in patients with UNE. METHODS: UNE was clinically diagnosed in 17 patients with 18 affected elbows. For all 18 affected elbows in patients and 20 elbows in 10 healthy volunteers, measurements of all different diagnostic tests were performed at six anatomical positions across the elbow with measuring points from distal (D4) to proximal (P6) in relation to the medial epicondyle (P0). Additional qualitative assessment regarding structural changes of surrounding nerve anatomy was conducted. RESULTS: The difference between affected arms of patients and healthy control arms were most frequently the largest at measure intervals D2 to P0 and P0 to P2 for electrophysiological testing, or measure points P0 and P2 for all other devices, respectively. At both levels P0 and at P2, T2 contrast-to-noise ratio (CNR) of MRN and mean diffusivity (MD) of DTI-based MRN showed best accuracies. DISCUSSION: This study revealed differences in diagnostic performance of tests concerning a specific location of UNE, with better results for T2 contrast to noise ratio (CNR) in MRN and mean diffusivity of DTI-based MRN. Additional testing with MRN and nerve ultrasonography is recommended to uncover anatomical changes.

Circle of Willis variants and their association with outcome in patients with middle cerebral artery-M1-occlusion stroke.

BACKGROUND: An incomplete circle of Willis (CoW) has been associated with a higher risk of stroke and might affect collateral flow in large vessel occlusion (LVO) stroke. We aimed to investigate the distribution of CoW variants in a LVO stroke and transient ischemic attack (TIA) cohort and analyze their impact on 3-month functional outcome. METHODS: CoW anatomy was assessed with time-of-flight magnetic resonance angiography (TOF-MRA) in 193 stroke patients with acute middle cerebral artery (MCA)-M1-occlusion receiving endovascular treatment (EVT) and 73 TIA patients without LVO. The main CoW variants were categorized into four vascular models of presumed collateral flow via the CoW. RESULTS: 82.4% (n = 159) of stroke and 72.6% (n = 53) of TIA patients had an incomplete CoW. Most variants affected the posterior circulation (stroke: 77.2%, n = 149; TIA: 58.9%, n = 43; p = 0.004). Initial stroke severity defined by the National Institutes of Health Stroke Scale (NIHSS) on admission was similar for patients with and without CoW variants. CoW integrity did not differ between groups with favorable (modified Rankin Scale [mRS]): 0-2) and unfavorable (mRS: 3-6) 3-month outcome. However, we found trends towards a higher mortality in patients with any type of CoW variant (p = 0.08) and a higher frequency of incomplete CoW among patients dying within 3 months after stroke onset (p = 0.119). In a logistic regression analysis adjusted for the potential confounders age, sex and atrial fibrillation, neither the vascular models nor anterior or posterior variants were independently associated with outcome. CONCLUSION: Our data provide no evidence for an association of CoW variants with clinical outcome in LVO stroke patients receiving EVT.

Comparison of the resonance sonorheometry based Quantra® system with rotational thromboelastometry ROTEM® sigma in cardiac surgery - a prospective observational study.

BACKGROUND: Measures of the sonorheometry based Quantra® viscoelastic hemostatic analyzer (HemoSonics, LCC, Charlottesville, VA, USA) were compared with corresponding results of the ROTEM® sigma device (Instrumentation Laboratory, Bedford, MA, USA). METHODS: In thirty-eight patients scheduled for elective cardiac surgery between December 2018 and October 2019, blood samples were taken after induction of anesthesia (sample 1) and after heparin neutralization (sample 2) and measured on Quantra (QPlus® Cartridge) and ROTEM sigma (ROTEM® sigma complete + hep Cartridge). Clot times and clot stiffness values were recorded. Clot stiffness values of ROTEM amplitudes (A in mm) were converted to shear modulus (G) in hectoPascal (hPa): G (hPa) = (5 x A)/(100-A). Additionally, time-to-results was recorded. Spearman rank test correlation and Bland Altman analysis were performed. RESULTS: Clot stiffness parameters of the Quantra correlated strongly with corresponding measurements of the ROTEM with r = 0.93 and 0.94 for EXTEM A10 vs CS and r = 0.94 and 0.96 for FIBTEM A10 vs FCS for sample 1 and 2, respectively. Quantra clot time correlated strongly with ROTEM INTEM CT with r = 0.71 for sample 1 and r = 0.75 for sample 2. However, Bland Altman analysis showed no agreement in all compared assays of both methods. The median time to delivery of first and complete results was significantly shorter for Quantra (412 and 658 s) compared to ROTEM sigma (839 and 1290 s). CONCLUSIONS: The Quantra showed a strong correlation with the ROTEM sigma for determining clot times and clot stiffness and the parameters assess similar aspects of clot development. However, these parameters are not directly interchangeable and implicate that separate cut-off values need to be established for users of the Quantra device. Word count: 278. TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov (ID: NCT04210830 ) at December 20th 2019.

Surgical Outcomes of Orbital Fracture Reconstruction Using Patient-Specific Implants.

PURPOSE: Patient-specific implants (PSIs) are known to yield reliable outcomes in orbital wall fracture reconstruction (high precision, smoother operating techniques, and shorter surgical duration). This study analyzed the surgical error and clinical and esthetic outcomes of orbital reconstructions with PSIs. METHODS: This ambispective cohort study enrolled patients who underwent orbital reconstruction using PSIs between October 2016 and January 2018. The study end points were surgical error, indication and duration of surgery, long-term sequelae, revision surgeries, and surgical complications. Surgical error was analyzed by superimposing the postoperative implant position onto the preoperative virtual plan. Both qualitative (heat map) and quantitative (distance) measurements were obtained. RESULTS: Three patients were enrolled prospectively, and 23 were enrolled retrospectively. Indications for surgery were defect size (25 patients), diplopia (10 patients), impaired eye motility (4 patients), and significant enophthalmos (6 patients). At the last patient visit, there were 5 cases of diplopia, 1 case of exophthalmos, and 6 cases of slight enophthalmos of incremental degree. In terms of surgical error, a mean distance of 0.6 mm (95% confidence interval, 0.49 to 0.76), with a mean maximal distance of 3.4 mm (95% confidence interval, 2.79 to 4.02), was noted. No revision surgery was necessary. Lid malposition complications were not observed. However, 1 case each of symblepharon and scleral show were observed. No time-saving component was observed. CONCLUSIONS: PSI use in orbital reconstruction guarantees a preplanned 3-dimensional anatomical shape with a mean surgical error of just 0.6 mm. Our clinical results were similar to those of other protocols; however, warranting a complex 3-dimensional anatomical shape also in large orbital fractures with a low mean surgical error is feasible by using PSIs.

Quantitative 3D Analysis of Levator Ani Muscle Subdivisions in Nulliparous Women: MRI Feasibility Study.

BACKGROUND: The levator ani muscle (LAM) is crucial for pelvic floor stability, yet its quantitative MRI assessment is only a recent focus. Our study aims to standardize the quantitative analysis of the LAM morphology within the 3D Pelvic Inclination Correction System (3D-PICS). METHODS: We analyzed 35 static MR datasets from nulliparous women examining the pubovisceral (PVM), iliococcygeal (ICM), coccygeal (COC), and puborectal muscle (PRM). The PVM consists of three origin-insertion pairs, namely the puboanal (PAM), puboperineal (PPM) and pubovaginal muscle (PVaM). The analysis included a quantitative examination of the morphology of LAM, focusing on the median location (x/y/z) (x: anterior-posterior, y: superior-inferior, z: left-right) of the origin and insertion points (a), angles (b) and lengths (c) of LAM. Inter-rater reliability was calculated. RESULTS: Interindividual variations in 3D coordinates among muscle subdivisions were shown. In all, 93% of all origin and insertion points were found within an SD of <8 mm. Angles to the xz-plane range between -15.4° (right PRM) and 40.7° (left PAM). The PRM is the largest pelvic muscle in static MRI. The ICC indicated moderate-to-good agreement between raters. CONCLUSIONS: The accurate morphometry of the LAM and its subdivisions, along with reliable inter-rater agreement, was demonstrated, enhancing the understanding of normal pelvic anatomy in young nulliparous women.

Optical recognition of the eggs of four Aedine mosquito species (Aedes albopictus, Aedes geniculatus, Aedes japonicus, and Aedes koreicus).

The continuous expansion of exotic Aedine mosquito species potential vectors of pathogens into new areas is a public health concern. In continental Europe, the surveillance of these mosquitoes is hindered by the simultaneous presence of three main invasive species (i.e., Aedes albopictus, Ae. japonicus, and Ae. koreicus). Standard low-cost surveillance methods (i.e., the deployment of oviposition traps and count of eggs under stereoscopic microscope) fail to distinguish the eggs of the different species. Identification of eggs by molecular methods is costly and time consuming and prevents measuring the density of invasive species and detecting early new invaders. Here we tested whether certain species could be identified by the patterns on the exochorionic membrane of their eggs. In a first step, we examined Aedine eggs of the three mentioned invasive and one indigenous (i.e., Ae. geniculatus) species with a high-resolution stereomicroscope and we identified each egg by MALDI-TOF mass spectrometry. In a second step, we submitted images of the eggs to 60 entomology experts and non-experts and tested their ability to distinguish among the species after an initial short training. The results obtained were consistent. Participants did not encounter difficulties in determining Ae. albopictus and Ae. geniculatus, while they had more difficulties in distinguishing Ae. japonicus from Ae. koreicus. In general, the quality of the exochorion seemed to play a more important role than the expertise level of the rater. The feasibility to differentiate Ae. albopictus from the other two invasive species is a significant achievement, as this is currently the most problematic species at the level of public health in Europe. Due to the presence of multiple invasive species that might prevent the correct quantification of mosquito population densities using standard surveillance methods and due to Ae. aegypti threat, it is recommended to optically determine also other species.

Sex hormones and cortisol during experimental trauma memory consolidation: Prospective association with intrusive memories.

Background Trauma- and stress-related disorders, such as post-traumatic stress disorder (PTSD), are more common in females than in males. Sex hormones affect learning and emotional memory formation and may be associated with the development of PTSD. Most previous studies have indexed these hormones in isolation. Objectives: To investigate associations of sex hormones and cortisol during memory consolidation on the development of intrusive memories. Methods: We employed an experimental trauma film paradigm in 61 healthy women and indexed salivary testosterone, progesterone, estradiol, and cortisol on day one and day two post experimental trauma exposure and their effects on intrusion frequency, distress, and vividness. Intrusive trauma memories were indexed by means of a diary in which participants documented intrusion frequency, distress, and vividness. Results and conclusion: Participants reported an average of 5.3 intrusions over the course of seven days (SD = 4.6, range 0-26). Progesterone, and estradiol indexed on day one predicted intrusion frequency, with higher progesterone and lower estradiol predicting more intrusive memories (p-values AUC progesterone 0.01 and estradiol 0.02). There was no evidence for associations between hormone concentration indices on day two and intrusion outcomes. Further research on the roles of gonadal and adrenal hormones in trauma memory formation is needed to advance our efforts to understand their influence on PTSD development.

Antecedentes: Los trastornos relacionados con el trauma y el estrés, como el trastorno de estrés postraumático (TEPT), son más comunes en mujeres que en hombres. Las hormonas sexuales afectan el aprendizaje y la formación de la memoria emocional y pueden estar asociadas con el desarrollo del TEPT. La mayoría de los estudios previos han indexado estas hormonas de forma aislada.Objetivos: Investigar las asociaciones de hormonas sexuales y cortisol durante la consolidación de la memoria en el desarrollo de recuerdos intrusivos.Métodos: Empleamos un paradigma de trauma experimental de película en 61 mujeres sanas e indexamos la testosterona salival, la progesterona, el estradiol y el cortisol en el día 1 y el día 2 después de la exposición al trauma experimental y sus efectos sobre la frecuencia de intrusión, la angustia y la vividez. Los recuerdos traumáticos intrusivos se indexaron por medio de un diario en el que los participantes documentaron la frecuencia, la angustia y la vividez de la intrusión.Resultados y conclusión: Los participantes informaron un promedio de 5,3 intrusiones en el transcurso de 7 días (SD = 4,6, rango 0-26). La progesterona y el estradiol indexados en el día 1 predijeron la frecuencia de intrusión, con progesterona más alta y estradiol más bajo prediciendo más recuerdos intrusivos (valores de p de AUC progesterona 0.01 y estradiol 0.02). No hubo evidencia de asociaciones entre los índices de concentración de hormonas en el día 2 y los resultados de la intrusión. Se necesita más investigación sobre los roles de las hormonas gonadales y suprarrenales en la formación de recuerdos traumáticos para avanzar en nuestros esfuerzos por comprender su influencia en el desarrollo del TEPT.

Hospital incidence and mortality of patients treated for abdominal aortic aneurysms in Switzerland - a secondary analysis of Swiss DRG statistics data.

AIM OF THE STUDY: To analyse hospital incidence and in-hospital mortality of patients treated for abdominal aortic aneurysms in Switzerland. METHODS: Secondary data analysis of case-related hospital discharge data of the Swiss Federal Statistical Office for the years 2009-2018. Patients who were hospitalised and surgically treated for nonruptured abdominal aortic aneurysms or hospitalised and treated for ruptured abdominal aortic aneurysms were included in the analysis. Standardised annual incidences rates were calculated using the European standard population 2013. In-hospital all-cause mortality rates were calculated as raw values and standardised for age, sex, and the van Walraven comorbidity score. RESULTS: A total of 10,728 cases were included in this study, of which 87.1% were male. Overall, 22.7% of the patients presented with a ruptured abdominal aortic aneurysm; 46% of these cases were surgically treated whereas 54% received conservative therapy. The age-standardised cumulative hospital incidences for treatment of nonruptured abdominal aortic aneurysms were 2.6 (95% confidence interval 2.5-2.8) and 19.7 (19.2-20.1) per 100,000 for women and men, respectively; for ruptured aneurysms it was 0.4 (0.3-2.4) per 100,000 in women, and 2.7 (2.6-2.9) in men. The annual incidence rates were stable in the decade observed. The adjusted mortality rates for treatment of nonruptured aneurysms decreased from 5.5% (2.6-11.2%) in 2009 to 1.4% (0.5-3.6%) in 2018 in women, and from 2.4% (1.3-4.5%) in 2009 to 0.6% (0.2-1.5%) in 2018 in men. The adjusted mortality rates for treatment of ruptured abdominal aortic aneurysms remained high without relevant improvements for either sex over time: for women 32.4% (24.1-42.1%), for men 19.7% (16.8-22.8%). CONCLUSIONS: The hospital incidence rates for nonruptured and ruptured abdominal aortic aneurysms remained unchanged in the decade observed. Compared with Germany, there was no evidence for a decrease in the annual incidence rates for ruptured abdominal aortic aneurysms in Switzerland. Mortality rates in the elective setting were low and decreased in the last decade but remained high in patients treated for ruptured aneurysms. Efforts to reduce the incidence of ruptured abdominal aortic aneurysms are needed to reduce aneurysm-related mortality in Switzerland.

Retrospective Investigation of Contralateral Hearing Thresholds of Patients With Sporadic Vestibular Schwannoma.

OBJECTIVE: The aim of this study was to investigate the contralateral hearing of patients with sporadic vestibular schwannoma (VS). STUDY DESIGN: Retrospective cohort study. SETTING: Pure-tone audiograms of the contralateral ear from patients with a wait-and-scan strategy were compared to the ones who received therapy. Due to a possible bias caused by the therapy, hearing thresholds before and after radiotherapy or surgery were compared separately with the wait-and-scan group. METHODS: From 1979 to 2017, 508 patients with sporadic VS could be included in the study. Of these, 240 received regular controls in the sense of wait-and-scan, 72 underwent radiotherapy (63 audiograms before and 43 after radiotherapy), and 196 had a surgery (186 audiograms before and 146 after surgery). Age-normalized hearing thresholds of the contralateral ear from patients with a wait-and-scan strategy were compared to ones who received therapy. In addition, hearing thresholds were compared to norm values. RESULTS: There was no evidence for a difference in the contralateral hearing of patients with sporadic VS between the wait-and-scan and therapy groups. The mean difference of hearing thresholds in our sample to norm values was found to be larger for the high frequencies and more pronounced in male patients. CONCLUSION: There was no evidence for a difference in the contralateral hearing loss of patients with sporadic VS between the wait-and-scan and therapy groups. However, there was some indirect indication of poorer contralateral hearing in all patients with sporadic VS compared to normative values.

The incremental value of the contribution of a biostatistician to the reporting quality in health research-A retrospective, single center, observational cohort study.

BACKGROUND: The reporting quality in medical research has recently been critically discussed. While reporting guidelines intend to maximize the value from funded research, and initiatives such as the EQUATOR network have been introduced to advance high quality reporting, the uptake of the guidelines by researchers could be improved. The aim of this study was to assess the contribution of a biostatistician to the reporting and methodological quality of health research, and to identify methodological knowledge gaps. METHODS: In a retrospective, single center, observational cohort study, two groups of publications were compared. The group of exposed publications had an academic biostatistician on the author list, whereas the group of non-exposed publications did not include a biostatistician of the evaluated group. Rating of reporting quality was done in blinded fashion and in duplicate. The primary outcome was a sum score based on six dimensions, ranging between 0 (worst) and 11 (best). The study protocol was reviewed and approved as a registered report. RESULTS: There were 131 publications in the exposed group published between 2017 and 2018. Of these, 95 were either RCTs, observational, or prediction / prognostic studies. Corresponding matches in the group of non-exposed publications were identified in a reproducible manner. Comparison of reporting quality overall revealed a 1.60 (95%CI from 0.92 to 2.28, p <0.0001) units higher reporting quality for exposed publications. A subgroup analysis within study types showed higher reporting quality across all three study types. CONCLUSION: Our study is the first to report an association of a higher reporting quality and methodological strength in health research publications with a biostatistician on the author list. The higher reporting quality persisted through subgroups of study types and dimensions. Methodological knowledge gaps were identified for prediction / prognostic studies, and for reporting on statistical methods in general and missing values, specifically.

Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort.

OBJECTIVES: Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. METHODS: Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. RESULTS: Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. CONCLUSION: Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

[Care Management for Polytrauma Patients in a Level-1 Trauma Centre]. / Care Management für Polytrauma-Patientinnen und -Patienten in einem überregionalen Level-1- Traumazentrum.

Care Management for Polytrauma Patients in a Level-1 Trauma Centre Abstract. In our level-1 trauma institution, polytrauma patients with an Injury Severity Score of 16 or higher are facing waiting times for transfer to a rehabilitation facility, causing a negative financial outcome for our institution. The purpose of this study is to stimulate rapid transfer to a rehabilitation facility. In a single-centre case study, care management for (poly)trauma patients was started to ensure time-directed treatment for trauma patients related to Diagnosis-Related Groups (DRG). In the period of 2013-2018 there was an increase in trauma admissions up to 14 % (n = 16 157) with a mean length of hospital stay of 6.4 days, together with a reduction in the number of trauma bed capacity from 50 to 42. In relation to the DRGs, regular trauma patients who were not in need of a stationary rehabilitation facility stayed in line with the expected time of hospital stay. But (poly)trauma patients (n = 1831) with the need of a stationary stay in a rehabilitation centre were faced with waiting times before they could be transferred. The average excess waiting time in relation to DRG for polytrauma patients was 5.1 days. Trauma patients for a rehabilitation centre have a higher Case Mix Index (CMI) compared to those who do not require inpatient rehabilitation (4.22 versus 1.04, p <0.0001). With about 280 trauma patients annually waiting an extra 5.1 days for transfer to a rehabilitation facility, the financial burden for our department amounts to Swiss francs 885,360 without reimbursement. Since no extra bed capacities in rehabilitation facilities are available in our area, it may be advised to set up an early in-hospital trauma rehabilitation program in a level-1 trauma centre in order to reduce financial loss.

Serum lactate at 24 hours is associated with outcome in children requiring extracorporeal membrane oxygenation for pulmonary causes - a retrospective, observational study.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has become an essential life-saving tool. Being resource-intensive, judicious use and optimising the outcomes of this precious resource is important. This retrospective, explanatory, observational study aimed to quantify associations between factors and outcome after pulmonary ECMO in children. METHODS: This study included 39 consecutive ECMO runs in 38 children performed for pulmonary indications at our hospital from 2008 to 2018. Indications included acute respiratory distress syndrome, infection, drowning, meconium aspiration and pulmonary hypertension, among others. Depending on the need for haemodynamic support, 21 patients (53.8%) received veno-venous ECMO, while 18 (46.2%) received veno-arterial ECMO. We sought to compare the 11 non-survivors with the 27 survivors with respect to time-independent and time-dependent variables. Logistic regression models and Cox proportional hazards models were used. Threshold analysis was done using the “minimum p-value approach”. RESULTS: 27/39 (69%) ECMO runs could be weaned; 27/38 (71%) patients were discharged. 20/27 (74%) survivors had unremarkable neurological status, six (22%) had mild findings (convulsions, muscular hypotony, neuropathy) and one (4%) had a hemi-syndrome at discharge. Univariate analyses showed a hazard ratio (HR) of 0.48 for log(pH) (95% confidence interval [CI] 0.22 to 1.02, p = 0.055) and an HR of 4.48 for log(lactate) (95% CI 1.92 to 10.48, p = 0.0005). Multivariate models showed an HR of 0.99 for log(pH) (95% CI 0.43 to 2.26, p = 0.98) and an HR of 4.44 for log(lactate) (95% CI 1.65 to 11.95, p = 0.003). Threshold analysis showed lactate >4.1 to be associated with mortality, with an HR of 32.7 (95% CI 4.8 to 221.7, p = 0.0002). This threshold should, however, be interpreted very cautiously. Evidence of an association between serum lactate at 24 hours and mortality was found (difference between survivors and non-survivors: −2.78, 95% CI −5.36 to −0.20, p = 0.037). CONCLUSIONS: The results of ECMO for pulmonary indications are very good. Serum lactate may be an early prognostic indicator.

Is reporting quality in medical publications associated with biostatisticians as co-authors? A registered report protocol.

BACKGROUND: Quality in medical research has recently been criticized for being low, especially in observational research. Methodology is increasingly difficult, but collaboration between clinical researchers and biostatisticians may improve research and reporting quality. The aim of this study is to quantify the value of a biostatistician in the team of authors. METHODS: Single-center, retrospective observational study following the STROBE reporting guidelines. We will systematically review all medical publications with biostatisticians from our center as co-authors or authors and review corresponding papers without biostatisticians from our center during the same time range. We will compare aspects of reporting quality, overall and for the three study types observational, randomized trial, and prognostic separately. DISCUSSION: We anticipate that the results of the study will raise awareness of the importance of high methodological quality, as well as appropriate reporting quality in clinical research. CONCLUSION: Our study will have a direct impact on our center by making each of us more aware of the reporting guidelines for various research designs. This in turn will enhance reporting quality in future research with our involvement. Our study will also raise awareness of the important role that biostatisticians play in the design and analysis of health research projects.