Do PET-positive supradiaphragmatic lymph nodes predict overall survival or the success of primary surgery in patients with advanced ovarian cancer?

OBJECTIVES: Compared to conventional computed tomography (CT), fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) detects higher rates of lymph node and distant metastases in patients with ovarian cancer. However, FDG-PET/CT is not routinely performed during preoperative work-up. Therefore, we investigated the prognostic value of preoperative FDG-PET/CT in advanced epithelial ovarian cancer (EOC) and its predictive value for surgical resection in patients with no residual disease. The potential significance of PET-positive supradiaphragmatic lymph nodes (SDLNs) for these parameters was evaluated. METHODS: All patients with FIGO IIA-IVB EOC diagnosed between March 2014 and January 2021 at our certified gynaecological cancer centre, who underwent FDG PET/CT before primary surgery were retrospectively included. RESULTS: Fifty-three consecutive patients were included in the study. Eighteen (34 %) patients had PET-positive SDLNs. We could not demonstrate a significant correlation between PET-positive SDLNs and median overall survival (OS; SDLN-positive: 58.76 months, SDLN-negative: 60.76 months; p = 0.137) or intra- or perioperative outcomes. CONCLUSIONS: FDG PET/CT has a higher detection rate for SDLNs in patients with ovarian cancer than CT has, as described in the literature. Moreover, PET-positive SDLNs failed to predict intraoperative outcomes or overall survival.

Comparing CT-Like Images Based on Ultra-Short Echo Time and Gradient Echo T1-Weighted MRI Sequences for the Assessment of Vertebral Disorders Using Histology and True CT as the Reference Standard.

BACKGROUND: Several magnetic resonance (MR) techniques have been suggested for radiation-free imaging of osseous structures. PURPOSE: To compare the diagnostic value of ultra-short echo time and gradient echo T1-weighted MRI for the assessment of vertebral pathologies using histology and computed tomography (CT) as the reference standard. STUDY TYPE: Prospective. SUBJECTS: Fifty-nine lumbar vertebral bodies harvested from 20 human cadavers (donor age 73 ± 13 years; 9 male). FIELD STRENGTH/SEQUENCE: Ultra-short echo time sequence optimized for both bone (UTEb) and cartilage (UTEc) imaging and 3D T1-weighted gradient-echo sequence (T1GRE) at 3 T; susceptibility-weighted imaging (SWI) gradient echo sequence at 1.5 T. CT was performed on a dual-layer dual-energy CT scanner using a routine clinical protocol. ASSESSMENT: Histopathology and conventional CT were acquired as standard of reference. Semi-quantitative and quantitative morphological features of degenerative changes of the spines were evaluated by four radiologists independently on CT and MR images independently and blinded to all other information. Features assessed were osteophytes, endplate sclerosis, visualization of cartilaginous endplate, facet joint degeneration, presence of Schmorl's nodes, and vertebral dimensions. Vertebral disorders were assessed by a pathologist on histology. STATISTICAL TESTS: Agreement between T1GRE, SWI, UTEc, and UTEb sequences and CT imaging and histology as standard of reference were assessed using Fleiss' κ and intra-class correlation coefficients, respectively. RESULTS: For the morphological assessment of osteophytes and endplate sclerosis, the overall agreement between SWI, T1GRE, UTEb, and UTEc with the reference standard (histology combined with CT) was moderate to almost perfect for all readers (osteophytes: SWI, κ range: 0.68-0.76; T1GRE: 0.92-1.00; UTEb: 0.92-1.00; UTEc: 0.77-0.85; sclerosis: SWI, κ range: 0.60-0.70; T1GRE: 0.77-0.82; UTEb: 0.81-0.92; UTEc: 0.61-0.71). For the visualization of the cartilaginous endplate, UTEc showed the overall best agreement with the reference standard (histology) for all readers (κ range: 0.85-0.93). DATA CONCLUSIONS: Morphological assessment of vertebral pathologies was feasible and accurate using the MR-based bone imaging sequences compared to CT and histopathology. T1GRE showed the overall best performance for osseous changes and UTEc for the visualization of the cartilaginous endplate. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Mesonephric-like adenocarcinoma of the female genital tract: possible role of KRAS-targeted treatment-detailed molecular analysis of a case series and review of the literature for targetable somatic KRAS-mutations.

PURPOSE: Mesonephric-like adenocarcinomas (MLA) of the female genital tract represent a rare and relatively recently described neoplasm exhibiting characteristic morphologic and immunohistochemical findings commonly associated with a KRAS-mutation. Most cases display an aggressive clinical behavior, but knowledge about treatment approaches is limited, especially for targeting KRAS. METHODS: We report a series of eight cases with a detailed molecular analysis for KRAS. These cases as well as the data of previously published cases with detailed information regarding KRAS-mutational events were reviewed for a potential targeted approach and its prognostic impact. RESULTS: Both the uterine and ovarian MLA harbor a somatic KRAS-mutation in about 85% of the reported cases, affecting the hotspot codons 12 and 13. 15.7% of the endometrial and 15.6% of ovarian MLA are wild type for KRAS. A p.G12A-alteration was seen in 5.6% (5/89) of the endometrial and in 6.2% (2/32) of the ovarian tumors, for p.G12C in 7.9% and 6.2%, for p.G12D in 32.6% and 34.5% and for p.G12V in 36% and 37.5%, respectively. Very limited data are available regarding the prognostic impact of different mutational sites within the KRAS-gene without significant prognostic impact. CONCLUSION: Because of a specific p.G12C-KRAS somatic mutation, only the minority of MLA (7.9% with uterine and 6.2% with ovarian primary) are potentially targetable by sotarasib in that rare but aggressive subtype of adenocarcinoma of the female genital tract. Until now, the different location of a somatic KRAS-mutation is of no prognostic impact.

Leukocytes carrying Clonal Hematopoiesis of Indeterminate Potential (CHIP) Mutations invade Human Atherosclerotic Plaques.

Background: Leukocyte progenitors derived from clonal hematopoiesis of undetermined potential (CHIP) are associated with increased cardiovascular events. However, the prevalence and functional relevance of CHIP in coronary artery disease (CAD) are unclear, and cells affected by CHIP have not been detected in human atherosclerotic plaques. Methods: CHIP mutations in blood and tissues were identified by targeted deep-DNA-sequencing (DNAseq: coverage >3,000) and whole-genome-sequencing (WGS: coverage >35). CHIP-mutated leukocytes were visualized in human atherosclerotic plaques by mutaFISH™. Functional relevance of CHIP mutations was studied by RNAseq. Results: DNAseq of whole blood from 540 deceased CAD patients of the Munich cardIovaScular StudIes biObaNk (MISSION) identified 253 (46.9%) CHIP mutation carriers (mean age 78.3 years). DNAseq on myocardium, atherosclerotic coronary and carotid arteries detected identical CHIP mutations in 18 out of 25 mutation carriers in tissue DNA. MutaFISH™ visualized individual macrophages carrying DNMT3A CHIP mutations in human atherosclerotic plaques. Studying monocyte-derived macrophages from Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET; n=941) by WGS revealed CHIP mutations in 14.2% (mean age 67.1 years). RNAseq of these macrophages revealed that expression patterns in CHIP mutation carriers differed substantially from those of non-carriers. Moreover, patterns were different depending on the underlying mutations, e.g. those carrying TET2 mutations predominantly displayed upregulated inflammatory signaling whereas ASXL1 mutations showed stronger effects on metabolic pathways. Conclusions: Deep-DNA-sequencing reveals a high prevalence of CHIP mutations in whole blood of CAD patients. CHIP-affected leukocytes invade plaques in human coronary arteries. RNAseq data obtained from macrophages of CHIP-affected patients suggest that pro-atherosclerotic signaling differs depending on the underlying mutations. Further studies are necessary to understand whether specific pathways affected by CHIP mutations may be targeted for personalized treatment.

Dark-field X-ray imaging for the assessment of osteoporosis in human lumbar spine specimens.

Background: Dark-field imaging is a novel imaging modality that allows for the assessment of material interfaces by exploiting the wave character of x-ray. While it has been extensively studied in chest imaging, only little is known about the modality for imaging other tissues. Therefore, the purpose of this study was to evaluate whether a clinical X-ray dark-field scanner prototype allows for the assessment of osteoporosis. Materials and methods: In this prospective study we examined human cadaveric lumbar spine specimens (vertebral segments L2 to L4). We used a clinical prototype for dark-field radiography that yields both attenuation and dark-field images. All specimens were scanned in lateral orientation in vertical and horizontal position. All specimens were additionally imaged with CT as reference. Bone mineral density (BMD) values were derived from asynchronously calibrated quantitative CT measurements. Correlations between attenuation signal, dark-field signal and BMD were assessed using Spearman's rank correlation coefficients. The capability of the dark-field signal for the detection of osteoporosis/osteopenia was evaluated with receiver operating characteristics (ROC) curve analysis. Results: A total of 58 vertebrae from 20 human cadaveric spine specimens (mean age, 73 years ±13 [standard deviation]; 11 women) were studied. The dark-field signal was positively correlated with the BMD, both in vertical (r = 0.56, p < .001) and horizontal position (r = 0.43, p < .001). Also, the dark-field signal ratio was positively correlated with BMD (r = 0.30, p = .02). No correlation was found between the signal ratio of attenuation signal and BMD (r = 0.14, p = .29). For the differentiation between specimens with and without osteoporosis/osteopenia, the area under the ROC curve (AUC) was 0.80 for the dark-field signal in vertical position. Conclusion: Dark-field imaging allows for the differentiation between spine specimens with and without osteoporosis/osteopenia and may therefore be a potential biomarker for bone stability.

The Impact of Gender and Age in Obese Patients on Sternal Instability and Deep-Sternal-Wound-Healing Disorders after Median Sternotomy.

OBJECTIVE: The aim of this study was to investigate the relationship between age and sex in regard to the development of deep sternal wound infections and sternal instability following median sternotomy. METHODS: A propensity-score-matching analysis was conducted on 4505 patients who underwent cardiac surgery between 2009 and 2021, all of whom had a BMI of ≥30 kg/m2. A total of 1297 matched pairs were determined in the sex group, and 1449 matched pairs we determined in the age group. The distributions of sex, age, diabetes mellitus, delirium, unstable sterna, wire refixation, wire removal, superficial vacuum-assisted wound closure, deep vacuum-assisted wound closure, clamp time, bypass time, logistic EuroSCORE, and BMI were determined. RESULTS: The 30-day in-hospital mortality was found to be similar in the older and younger groups (8.149% vs. 8.35%, p = 0.947), and diabetes mellitus was also equally distributed in both groups. However, postoperative delirium occurred significantly more often in the older group (29.81% vs. 17.46%, p < 0.001), and there was a significantly higher incidence in men compared with women (16.96% vs. 26.91%, p < 0.001). There were no differences found in the incidence of sternum instability, fractured sternum, superficial vacuum-assisted wound closure, and deep vacuum-assisted wound closure between the age and sex groups. CONCLUSIONS: In conclusion, this study found that sternal instability and deep-wound-healing problems occur with equal frequency in older and younger patients and in men and women following median sternotomy. However, the likelihood of postoperative delirium is significantly higher in older patients and in men. These findings suggest that a higher level of monitoring and care may be required for these high-risk patient groups to reduce the incidence of postoperative delirium and improve outcomes following median sternotomy.

The influence of the menstrual cycle and hormonal contraceptives on cardiorespiratory fitness in physically active women: A systematic review and meta-analysis.

Objective: To systematically review and summarize the existing evidence related to the influence of the menstrual cycle (MC) and hormonal contraceptive (HC) use on V˙O2max in physically active women. Methods: This systematic review and meta-analysis conforms to the PRISMA statement guidelines. Four (sub-)meta-analyses were performed. Two focused on longitudinal studies examining the same women several times to compare the V˙O2max during the different menstrual phases or oral contraceptive (OC) use and withdrawal. Two meta-analyses examined if there is a difference in V˙O2max between OC users and normally menstruating women by analyzing cross-sectional studies assigning physically active women to one of these two groups as well as intervention-based studies (cross-over studies, randomized controlled trials considering only the data of the intervention group) comparing women intra-individually with and without OCs. Results: Nine of the included studies (107 women) evaluated the influence of the MC, five studies (69 women) the impact of OCs on V˙O2max, and six studies investigated both topics (88 women). A mean difference of V˙O2max -0.03 ml/kg/min (95%CI -1.06 to 1.01) between the early follicular and luteal menstrual phase was observed. Between the active and inactive phases of OCs, a mean difference of -0.11 ml/kg/min (95%CI -2.32 to 2.10) was found. The inter-individual comparison of naturally menstruating women and OC users showed a mean difference in V˙O2max of 0.23 ml/kg/min (95% CI -2.33 to 2.79) in favor of OC use. The intra-individual comparison of the same women showed a mean decrease in V˙O2max of -0.84 ml/kg/min (95% CI -2.38 to 0.70) after a new start with OCs. Conclusions: Our meta-analyses showed no effects of the MC or the OCs on V˙O2max. More high-quality studies are needed determining the MC phases more precisely, including OCs with the current standard formulations and comparing the influence of different progestins.

Complement and platelets: prothrombotic cell activation requires membrane attack complex-induced release of danger signals.

Complement activation in the diseases paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) results in cytolysis and fatal thrombotic events, which are largely refractory to anticoagulation and/or antiplatelet therapy. Anticomplement therapy, however, efficiently prevents thrombotic events in PNH and aHUS, but the underlying mechanisms remain unresolved. We show that complement-mediated hemolysis in whole blood induces platelet activation similarly to activation by adenosine 5'-diphosphate (ADP). Blockage of C3 or C5 abolished platelet activation. We found that human platelets failed to respond functionally to the anaphylatoxins C3a and C5a. Instead, complement activation did lead to prothrombotic cell activation in the whole blood when membrane attack complex (MAC)-mediated cytolysis occurred. Consequently, we demonstrate that ADP receptor antagonists efficiently inhibited platelet activation, although full complement activation, which causes hemolysis, occurred. By using an established model of mismatched erythrocyte transfusions in rats, we crossvalidated these findings in vivo using the complement inhibitor OmCI and cobra venom factor. Consumptive complement activation in this animal model only led to a thrombotic phenotype when MAC-mediated cytolysis occurred. In conclusion, complement activation only induces substantial prothrombotic cell activation if terminal pathway activation culminates in MAC-mediated release of intracellular ADP. These results explain why anticomplement therapy efficiently prevents thromboembolisms without interfering negatively with hemostasis.

Multimodal analysis of granulocytes, monocytes, and platelets in patients with cystic fibrosis before and after Elexacaftor-Tezacaftor-Ivacaftor treatment.

Cystic fibrosis (CF) is a monogenetic disease caused by an impairment of the cystic fibrosis transmembrane conductance regulator (CFTR). CF affects multiple organs and is associated with acute and chronic inflammation. In 2020, Elexacaftor-Tezacaftor-Ivacaftor (ETI) was approved to enhance and restore the remaining CFTR functionality. This study investigates cellular innate immunity, with a focus on neutrophil activation and phenotype, comparing healthy volunteers with patients with CF before (T1, n = 13) and after six months (T2, n = 11) of ETI treatment. ETI treatment reduced sweat chloride (T1: 95 mmol/l (83|108) vs. T2: 32 mmol/l (25|62), p < 0.01, median, first|third quartile) and significantly improved pulmonal function (FEV1 T1: 2.66 l (1.92|3.04) vs. T2: 3.69 l (3.00|4.03), p < 0.01). Moreover, there was a significant decrease in the biomarker human epididymis protein 4 (T1: 6.2 ng/ml (4.6|6.3) vs. T2: 3.0 ng/ml (2.2|3.7), p < 0.01) and a small but significant decrease in matrix metallopeptidase 9 (T1: 45.5 ng/ml (32.5|140.1) vs. T2: 28.2 ng/ml (18.2|33.6), p < 0.05). Neutrophil phenotype (CD10, CD11b, CD62L, and CD66b) and function (radical oxygen species generation, chemotactic and phagocytic activity) remained largely unaffected by ETI treatment. Likewise, monocyte phenotype and markers of platelet activation were similar at T1 and T2. In summary, the present study confirmed a positive impact on patients with CF after ETI treatment. However, neither beneficial nor harmful effects of ETI treatment on cellular innate immunity could be detected, possibly due to the study population consisting of patients with well-controlled CF.

Evaluation of the heat sensitivity of Trichophyton rubrum and Trichophyton interdigitale.

BACKGROUND: Onychomycosis affects up to 50% of patients in the older population. OBJECTIVES: This study aimed to explore heat sensitivity of Trichophyton rubrum and Trichophyton interdigitale as pathogens of onychomycosis. MATERIALS & METHODS: The fungi were heated in sterile saline solution up to 100°C for five or 10 minutes with or without additional previous treatment with 1% ciclopirox solution or chitinase and 1,3 -galactidase or for 45 minutes at 40°C or 60°C with washing powder. Subsequently, the fungi were cultured and regrowth was assessed after one week. RESULTS: After heating T. rubrum for five minutes at 60°C, growth was completely inhibited. After heating T. interdigitale for five minutes at 60°C, all of the samples regrew, and at 95°C, none of the samples regrew. No difference between five and 10-minute heating was observed. Previous incubation with 1% ciclopirox solution for 24 hours inhibited the growth of T. rubrum completely. T. interdigitale was still able to regrow to 100% after five minutes at 40°C, to 33% after 60°C, and to 22% after 80°C. Incubation for 45 minutes with washing powder solution at 40°C or 60°C did not lead to significant growth reduction of T. rubrum or interdigitale. Two hours incubation with -1,3-glucanase and chitinase prior to five minutes of heating to 60°C and 80°C reduced the heat resistance of T. interdigitale; growth was inhibited in 56% and 100% of the samples, respectively. CONCLUSION: The heat resistance of T. rubrum and interdigitale should be considered using non-medical thermal treatment.

How Can We Best Measure Frailty in Cardiosurgical Patients?

BACKGROUND: Frailty is gaining importance in cardiothoracic surgery and is a risk factor for adverse outcomes and mortality. Various frailty scores have since been developed, but there is no consensus which to use for cardiac surgery. METHODS: In an all-comer prospective study of patients presenting for cardiac surgery, we assessed frailty and analyzed complication rates in hospital and 1-year mortality, as well as laboratory markers before and after surgery. RESULTS: 246 included patients were analyzed. A total of 16 patients (6.5%) were frail, and 130 patients (52.85%) were pre-frail, summarized in the frail group (FRAIL) and compared to the non-frail patients (NON-FRAIL). The mean age was 66.5 ± 9.05 years, 21.14% female. The in-hospital mortality rate was 4.88% and the 1-year mortality rate was 6.1%. FRAIL patients stayed longer in hospital (FRAIL 15.53 ± 8.5 days vs. NON-FRAIL 13.71 ± 8.94 days, p = 0.004) and in intensive/intermediate care units (ITS/IMC) (FRAIL 5.4 ± 4.33 days vs. NON-FRAIL 4.86 ± 4.78 days, p = 0.014). The 6 min walk (6 MW) (317.92 ± 94.17 m vs. 387.08 ± 93.43 m, p = 0.006), mini mental status (MMS) (25.72 ± 4.36 vs. 27.71 ± 1.9, p = 0.048) and clinical frail scale (3.65 ± 1.32 vs. 2.82 ± 0.86, p = 0.005) scores differed between patients who died within the first year after surgery compared to those who survived this period. In-hospital stay correlated with timed up-and-go (TUG) (TAU: 0.094, p = 0.037), Barthel index (TAU-0.114, p = 0.032), hand grip strength (TAU-0.173, p < 0.001), and EuroSCORE II (TAU 0.119, p = 0.008). ICU/IMC stay duration correlated with TUG (TAU 0.186, p < 0.001), 6 MW (TAU-0.149, p = 0.002), and hand grip strength (TAU-0.22, p < 0.001). FRAIL patients had post-operatively altered levels of plasma-redox-biomarkers and fat-soluble micronutrients. CONCLUSIONS: frailty parameters with the highest predictive value as well as ease of use could be added to the EuroSCORE.

Gender-Related Outcomes after Surgical Resection and Level of Satisfaction in Patients with Left Atrial Tumors.

BACKGROUND: Cardiac tumors are rare, with a low incidence of between 0.0017 and 0.19%. The majority of cardiac tumors are benign and predominantly occur in females. The aim of our study was to examine how outcomes differ between men and women. METHODS: From 2015 to 2022, 80 patients diagnosed with suspected myxoma were operated on. In all patients, preoperative, perioperative, and postoperative data were recorded. Such patients were identified and included in a retrospective analysis focused on gender-related differences. RESULTS: Patients were predominantly female (n = 64; 80%). The mean age was 62.76 ± 13.42 years in female patients and 59.65 ± 15.84 years in male patients (p = 0.438). The body mass index (BMI) was comparable in both groups: between 27.36 ± 6.16 in male and 27.09 ± 5.75 (p = 0.945) in female patients. Logistic EuroSCORE (LogES) (female: 5.89 ± 4.6; male: 3.95 ± 3.06; p = 0.017) and EuroSCORE II (ES II) (female: 2.07 ± 2.1; male: 0.94 ± 0.45; p = 0.043), both scores to predict the mortality in cardiac surgery, were significantly higher in female patients. Two patients died early, within 30 days after surgery: one male and one female patient. Late mortality was defined as the 5-year survival rate, which was 94.8%, and 15-year survival rate, which was 85.3% in our cohort. Causes of death were not related to the primary tumor operation. The follow up showed that satisfaction with surgery and long-term outcome was high. CONCLUSION: Predominately female patients presented with left atrial tumors over a 17-year period. Relevant gender differences aside from that were not evident. Surgery could be performed with excellent early (within 30 days after surgery) and late results (follow up after discharge).

Impact of surface coating and systemic anticoagulants on hemostasis and inflammation in a human whole blood model.

BACKGROUND: Surface compatibility with blood is critical both for scientific investigations on hemostasis and clinical applications. Regarding in vitro and ex vivo investigations, minimal alteration in physiological hemostasis is of particular importance to draw reliable conclusions on the human coagulation system. At the same time, artificial coagulation activation must be avoided, which is relevant for the patient, for example to prevent stent graft occlusion. The aim was to evaluate the advantages and disadvantages of antithrombotic and antifouling surface coatings in the context of their suitability for ex vivo incubation and the study of coagulation properties. METHODS: We investigated the impact of different protocols for surface coating of synthetic material and different anticoagulants on hemostasis and platelet activation in ex vivo human whole blood. Blood samples from healthy donors were incubated in coated microtubes on a rotating wheel at 37°C. Two protocols for surface coating were analyzed for hemostatic parameters and metabolic status, a heparin-based coating (CHC, Corline Heparin Conjugate) without further anticoagulation and a passivating coating (MPC, 2-methacryloyloxethyl phosphorylcholine) with added anticoagulants (enoxaparin, ENOX; or fondaparinux, FPX). Employing the MPC-based coating, the anticoagulants enoxaparin and fondaparinux were compared regarding their differential effects on plasmatic coagulation by thrombelastometry and on platelet activation by flowcytometry and platelet function assays. RESULTS: Using the CHC coating, significant coagulation cascade activation was observed, whereas parameters remained mostly unchanged with MPC-based protocols. Extended incubation caused significantly elevated levels of the soluble membrane attack complex. Neither ENOX nor FPX caused a relevant impairment of platelet function or activation capacity and thrombelastometric parameters remained unchanged with both protocols. For translational purposes, we additionally modeled endotoxemia with the MPC-based protocols by incubating with lipopolysaccharide plus/minus thrombin. While coagulation parameters remained unchanged, elevated Interleukin 8 and Matrix Metalloproteinase 9 demonstrated preserved immune cell responsiveness. CONCLUSIONS: The MPC-based protocols demonstrated better hemocompatibility compared to CHC, and ENOX and FPX proved useful for additional anticoagulation. Furthermore, this simple-to-use whole blood model may be useful for experimental analyses of the early coagulatory and immunological response without decalcification.

[Dooring Bicycle Accidents with Severe Injury Patterns: 10-Year Study of a Level 1 Trauma Center]. / Dooring-Fahrradunfälle mit schweren Verletzungsmustern: 10-Jahres-Studie eines Level-1-Traumazentrums.

Dooring Bicycle Accidents with Severe Injury Patterns: 10-Year Study of a Level 1 Trauma Center Abstract. Studies in Switzerland, Germany and Austria have shown that, contrary to popular belief, dooring accidents are among the most common bicycle accidents. The resulting injuries are often serious and often lead to hospital admission. All dooring accidents of the Inselspital Emergency Department in Bern between 2012 and 2021 were identified and evaluated retrospectively. The data were generated from the database of the management system (Ecare) of the University Hospital Bern by means of a search query with the German keywords: "Autotüre", "Autotuere", "Dooring" and were anonymised. Most patients were female and on average 34 years old; most injuries occurred to the head and the extremities. Treatment was mostly done on an outpatient basis. The ISS (Injury Severity Score) was an average of 3.5. One of the patients needed emergency surgery. This is the first Swiss study to systematically record and evaluate dooring accidents. Since cycling is a trend, especially in urban areas, and consequently the number of cyclists is constantly increasing, it can be assumed that the number of dooring injuries will also increase and corresponding prevention measures will have to be taken. The current COVID-19 pandemic tends to aggravate the problem, as in the context of infection control the number of cyclists and, consequently, accidents is increasing, especially in urban areas, in the context of infection control. This said, it is crucial to gain more information about the time slots of the accidents and the casualties through appropriate studies in order to take adequate preventive and protective measures.

Combining Polar Organic Chemical Integrative Samplers (POCIS) with Toxicity Testing on Microalgae to Evaluate the Impact of Herbicide Mixtures in Surface Waters.

Pesticide risk assessment within the European Union Water Framework Directive is largely deficient in the assessment of the actual exposure and chemical mixture effects. Pesticide contamination, in particular herbicidal loading, has been shown to exert pressure on surface waters. Such pollution can have direct impact on autotrophic species, as well as indirect impacts on freshwater communities through primary production degradation. The present study proposes a screening method combining polar organic chemical integrative samplers (POCIS) with mode of action-specific toxicity testing on microalgae exposed to POCIS extracts as a standard approach to effectively address the problem of herbicide mixture effects detection. This methodology has been tested using Luxembourgish rivers as a case study and has proven to be a fast and reliable information source that is complementary to chemical analysis, allowing assessment of missing target analytes. Pesticide pressure in the 24 analyzed streams was mainly exerted by flufenacet, terbuthylazine, nicosulfuron, and foramsulfuron, with occasional impacts by the nonagricultural biocide diuron. Algae tests were more sensitive to endpoints affecting photosystem II and reproduction than to growth and could be best predicted with the concentration addition model. In addition, analysis revealed that herbicide mixture toxicity is correlated with macrophyte disappearance in the field, relating mainly to emissions from maize cultures. Combining passive sampler extracts with standard toxicity tests offers promising perspectives for ecological risk assessment. The full implementation of the proposed approach, however, requires adaptation of the legislation to scientific progress. Environ Toxicol Chem 2022;41:2667-2678. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

CALA: Cumulative Volume of Calcified Lesions of the Aorta in Cardiac Surgery.

One of the major key questions raised in this retrospective study was to identify any correlation of atherosclerotic plaque volume of the ascending aorta and aortic arch with adverse events such as postoperative stroke, critical illness polyneuropathy and myopathy, as well as delirium and all-cause in-hospital mortality. In a second phase of this study, we investigated the relationship between atherosclerotic plaque volume and adverse events regarding the construction of proximal anastomosis on coronary artery bypass grafting procedures using different clamping techniques such as construction of anastomosis on cross-clamping or cross-clamping plus consecutive partial clamping of the aorta. The key findings of our research were that the size of calcium lesions of the ascending aorta and aortic arch correlates with early mortality, critical illness polyneuropathy/myopathy, and delirium but not with stroke. On the other hand, there were no significant differences between isolated cross-clamping versus cross-clamping plus consecutive partial clamping of the aorta regarding the primary adverse events by means of mean plaque volume.

Tutorial: design and execution of CRISPR in vivo screens.

Here we provide a detailed tutorial on CRISPR in vivo screening. Using the mouse as the model organism, we introduce a range of CRISPR tools and applications, delineate general considerations for 'transplantation-based' or 'direct in vivo' screening design, and provide details on technical execution, sequencing readouts, computational analyses and data interpretation. In vivo screens face unique pitfalls and limitations, such as delivery issues or library bottlenecking, which must be counteracted to avoid screening failure or flawed conclusions. A broad variety of in vivo phenotypes can be interrogated such as organ development, hematopoietic lineage decision and evolutionary licensing in oncogenesis. We describe experimental strategies to address various biological questions and provide an outlook on emerging CRISPR applications, such as genetic interaction screening. These technological advances create potent new opportunities to dissect the molecular underpinnings of complex organismal phenotypes.

Lung area estimation using functional tidal electrical impedance variation images and active contouring.

Objective.Electrical impedance tomography is a valuable tool for monitoring global and regional lung mechanics. To evaluate the recorded data, an accurate estimate of the lung area is crucial.Approach.We present two novel methods for estimating the lung area using functional tidal images or active contouring methods. A convolutional neural network was trained to determine, whether or not the heart region was visible within tidal images. In addition, the effects of lung area mirroring were investigated. The performance of the methods and the effects of mirroring were evaluated via a score based on the impedance magnitudes and their standard deviations in functional tidal images.Main results.Our analyses showed that the method based on functional tidal images provided the best estimate of the lung area. Mirroring of the lung area had an impact on the accuracy of area estimation for both methods. The achieved accuracy of the neural network's classification was 94%. For images without a visible heart area, the subtraction of a heart template proved to be a pragmatic approach with good results.Significance.In summary, we developed a routine for estimation of the lung area combined with estimation of the heart area in electrical impedance tomography images.

Optical Microscopy Systems for the Detection of Unlabeled Nanoparticles.

Label-free detection of nanoparticles is essential for a thorough evaluation of their cellular effects. In particular, nanoparticles intended for medical applications must be carefully analyzed in terms of their interactions with cells, tissues, and organs. Since the labeling causes a strong change in the physicochemical properties and thus also alters the interactions of the particles with the surrounding tissue, the use of fluorescently labeled particles is inadequate to characterize the effects of unlabeled particles. Further, labeling may affect cellular uptake and biocompatibility of nanoparticles. Thus, label-free techniques have been recently developed and implemented to ensure a reliable characterization of nanoparticles. This review provides an overview of frequently used label-free visualization techniques and highlights recent studies on the development and usage of microscopy systems based on reflectance, darkfield, differential interference contrast, optical coherence, photothermal, holographic, photoacoustic, total internal reflection, surface plasmon resonance, Rayleigh light scattering, hyperspectral and reflectance structured illumination imaging. Using these imaging modalities, there is a strong enhancement in the reliability of experiments concerning cellular uptake and biocompatibility of nanoparticles, which is crucial for preclinical evaluations and future medical applications.

Epigenetic drug screening defines a PRMT5 inhibitor-sensitive pancreatic cancer subtype.

Systemic therapies for pancreatic ductal adenocarcinoma (PDAC) remain unsatisfactory. Clinical prognosis is particularly poor for tumor subtypes with activating aberrations in the MYC pathway, creating an urgent need for novel therapeutic targets. To unbiasedly find MYC-associated epigenetic dependencies, we conducted a drug screen in pancreatic cancer cell lines. Here, we found that protein arginine N-methyltransferase 5 (PRMT5) inhibitors triggered an MYC-associated dependency. In human and murine PDACs, a robust connection of MYC and PRMT5 was detected. By the use of gain- and loss-of-function models, we confirmed the increased efficacy of PRMT5 inhibitors in MYC-deregulated PDACs. Although inhibition of PRMT5 was inducing DNA damage and arresting PDAC cells in the G2/M phase of the cell cycle, apoptotic cell death was executed predominantly in cells with high MYC expression. Experiments in primary patient-derived PDAC models demonstrated the existence of a highly PRMT5 inhibitor-sensitive subtype. Our work suggests developing PRMT5 inhibitor-based therapies for PDAC.