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Anna-Lena Klauser,1 Marc Hirschfeld,1– 3 Andrea Ritter,1,2 Gerta Rücker,1,4 Markus Jäger,1,2 Julia Gundarova,1 Daniela Weiss,1,2 Ingolf Juhasz-Böss,1,2 Kai Berner,1,2 Thalia Erbes,1,2 Jasmin Asberger1,2 1Faculty of Medicine, University of Freiburg, Freiburg, Germany; 2Department of Obstetrics and Gynecology, Medical Center – University of Freiburg, Freiburg, Germany; 3Institute of Veterinary Medicine, University of Göttingen, Göttingen, Germany; 4Institute of Medical Biometry and Statistics, Medical Center – University of Freiburg, Freiburg, GermanyCorrespondence: Jasmin AsbergerDepartment of Obstetrics and Gynecology, Faculty of Medicine and Medical Center – University of Freiburg, Hugstetterstr. 55, Freiburg, 79106, GermanyTel +49 761 270 30020Fax +49 761 270 30370Email jasmin.asberger@uniklinik-freiburg.dePurpose: In 2020, breast cancer still represents the most common type of cancer in women worldwide. Depending on the specific molecular subtype, clinical breast cancer management comprises surgery, radiotherapy, chemotherapy and targeted therapy. Furthermore, there are some therapeutic approaches from the field of complementary and alternative medicine. Current research focuses on the elucidation of new therapeutic targets for treatment development. Odorant substances affect apoptosis, proliferation and cell cycle in healthy and cancerous cells. Exact signalling pathways involved are not entirely clear. The present study aims to analyse their therapeutic potential in breast cancer.Methods: This study focuses on the effect of commonly used odorant substances (citral, citrathal R, cyclovertal, para-cymol, hexylacetat, herbavert, dihydromyrcerol and limonen) on the breast cancer cell lines MDA-MB-231, T47-D and BT474. Methodologically, this study applied cell culturing, MTT assay for detection of IC50 of the odorant substance, RNA purification followed by qRT-PCR, protein isolation and Western Blot, as well as immunocytochemistry. Further, this study investigates the role of transient receptor potential channel V1 (TRPV1), involved in the mechanisms of action for some odorant substances. Therefore, capsazepine, a TRPV1 antagonist, was used.Results: The odorant substances citral, citrathal R and cyclovertal have significant pro-apoptotic (p < 0.001), anti-proliferative (p < 0.001) and cell cycle-arresting effects measurable in RNA expression as well as in protein levels and immunocytochemical staining. The combination of citral and capsazepine no longer showed significant pro-apoptotic, antiproliferative, and cell cycle inhibitory effects compared to the compounds alone. This indicates that TRPV1 is necessary for the signal transduction of citral.Conclusion: This present study reveals three odorant substances with effects on cell viability, indicating their potential use in breast cancer therapy.Keywords: citral, citrathal R, cyclovertal, odorant substances, olfactory receptor and breast cancer

Summary: Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti‐emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta‐analyses to compare, and rank in terms of efficacy and safety, single anti‐emetic drugs and their combinations, including 5‐hydroxytryptamine3, dopamine‐2 and neurokinin‐1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo‐controlled and head‐to‐head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta‐Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class‐specific side‐effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin‐1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18–0.38); ramosetron, 0.44 (0.32–0.59); granisetron, 0.45 (0.38–0.54); dexamethasone, 0.51 (0.44–0.57); and ondansetron, 0.55 (0.51–0.60). It was moderate for fosaprepitant, 0.06 (0.02–0.21) and droperidol, 0.61 (0.54–0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side‐effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation. [ABSTRACT FROM AUTHOR]

Ravindra Gopaul,1 Robert A Waller,1 Ricci Kalayanamitra,2 Garrett Rucker,3 Andrew Foy4 1Department of Emergency Medicine, Penn State Hershey Medical Center, Hershey, PA, USA; 2Department of Emergency Medicine, Staten Island University Hospital, New York, NY, USA; 3Penn State Milton S. Hershey College of Medicine, Hershey, PA, USA; 4Department of Internal Medicine, Division of Cardiology, Penn State Hershey Medical Center, Hershey, PA, USACorrespondence: Ravindra Gopaul, Email rgopaul@pennstatehealth.psu.eduObjective: The HEART Score is a clinically validated risk stratification tool for patients with chest pain. Using five parameters (History, Electrocardiogram, Age, Risk factors, and Troponin), this instrument categorizes patients as low, moderate, or high risk for major adverse cardiac events within six weeks after evaluation. Of these parameters, History is the most subjective, as providers independently assign their level of clinical suspicion. Overestimation of history, and ultimately the HEART Score, can result in increased resource utilization, expense, and patient risk. We sought to evaluate bias in provider assessment of history when determining the HEART Score.Methods: Emergency medicine (EM) and Cardiology providers received surveys with one of two versions of clinical vignettes randomized at the question level and were asked to estimate the history component of the HEART Score. Vignettes differed by age, risk factors, sex, and socioeconomic status (SES), but both versions should have received the same score for history. Statistical analysis was then used to assess differences in history assessment between vignettes.Results: Of the 884 responses analyzed, most providers overestimated the historical portion of the HEART Score when assessing risk factors, patient distress, age, and lower SES. Many underestimated history with knowledge of a previous negative stress test. When controlling for specialty, the universal theme was overestimation by EM providers and underestimation by cardiologists. Despite the presence of hypertension, gender differences, and the appearance of mild distress, cardiologists were more likely to correctly estimate history compared to EM providers. SES consideration generally led to an underestimation of history by cardiologists. These findings were all statistically significant.Conclusion: Our study demonstrates that both EM and cardiology providers overestimate history when considering prognosticators that are frequently viewed as concerning. Further education on proper usage of the HEART Score is needed for more appropriate scoring of history and improved resource allocation for hospital systems.Keywords: HEART score, physician, provider, history