A microfluidic platform for chemoresistive testing of multicellular pleural cancer spheroids

This study reports on a microfluidic platform on which single multicellular spheroids from malignant pleural mesothelioma (MPM), an aggressive tumor with poor prognosis, can be loaded, trapped and tested for chemotherapeutic drug response. A new method to detect the spheroid viability cultured on the microfluidic chip as a function of the drug concentration is presented. This approach is based on the evaluation of the caspase activity in the supernatant sampled from the chip and tested using a microplate reader. This simple and time-saving method does only require a minimum amount of manipulations and was established for very low numbers of cells. This feature is particularly important in view of personalised medicine applications for which the number of cells obtained from the patients is low. MPM spheroids were continuously perfused for 48 hours with cisplatin, one of the standard chemotherapeutic drugs used to treat MPM. The 50% growth inhibitory concentration of cisplatin in perfused MPM spheroids was found to be twice as high as in spheroids cultured under static conditions. This chemoresistance increase might be due to the continuous support of nutrients and oxygen to the perfused spheroids.

Data-driven healthcare: from patterns to actions

The era of big data opens up new opportunities in personalised medicine, preventive care, chronic disease management and in telemonitoring and managing of patients with implanted devices. The rich data accumulating within online services and internet companies provide a microscope to study human behaviour at scale, and to ask completely new questions about the interplay between behavioural patterns and health. In this paper, we shed light on a particular aspect of data-driven healthcare: autonomous decision-making. We first look at three examples where we can expect data-driven decisions to be taken autonomously by technology, with no or limited human intervention. We then discuss some of the technical and practical challenges that can be expected, and sketch the research agenda to address them.

Biomarker-guided personalised emergency medicine for all - hope for another hype?

Polymorbid patients, diverse diagnostic and therapeutic options, more complex hospital structures, financial incentives, benchmarking, as well as perceptional and societal changes put pressure on medical doctors, specifically if medical errors surface. This is particularly true for the emergency department setting, where patients face delayed or erroneous initial diagnostic or therapeutic measures and costly hospital stays due to sub-optimal triage. A "biomarker" is any laboratory tool with the potential better to detect and characterise diseases, to simplify complex clinical algorithms and to improve clinical problem solving in routine care. They must be embedded in clinical algorithms to complement and not replace basic medical skills. Unselected ordering of laboratory tests and shortcomings in test performance and interpretation contribute to diagnostic errors. Test results may be ambiguous with false positive or false negative results and generate unnecessary harm and costs. Laboratory tests should only be ordered, if results have clinical consequences. In studies, we must move beyond the observational reporting and meta-analysing of diagnostic accuracies for biomarkers. Instead, specific cut-off ranges should be proposed and intervention studies conducted to prove outcome relevant impacts on patient care. The focus of this review is to exemplify the appropriate use of selected laboratory tests in the emergency setting for which randomised-controlled intervention studies have proven clinical benefit. Herein, we focus on initial patient triage and allocation of treatment opportunities in patients with cardiorespiratory diseases in the emergency department. The following five biomarkers will be discussed: proadrenomedullin for prognostic triage assessment and site-of-care decisions, cardiac troponin for acute myocardial infarction, natriuretic peptides for acute heart failure, D-dimers for venous thromboembolism, C-reactive protein as a marker of inflammation, and procalcitonin for antibiotic stewardship in infections of the respiratory tract and sepsis. For these markers we provide an overview on physiopathology, historical evolution of evidence, strengths and limitations for a rational implementation into clinical algorithms. We critically discuss results from key intervention trials that led to their use in clinical routine and potential future indications. The rational for the use of all these biomarkers, first, tackle diagnostic ambiguity and consecutive defensive medicine, second, delayed and sub-optimal therapeutic decisions, and third, prognostic uncertainty with misguided triage and site-of-care decisions all contributing to the waste of our limited health care resources. A multifaceted approach for a more targeted management of medical patients from emergency admission to discharge including biomarkers, will translate into better resource use, shorter length of hospital stay, reduced overall costs, improved patients satisfaction and outcomes in terms of mortality and re-hospitalisation. Hopefully, the concepts outlined in this review will help the reader to improve their diagnostic skills and become more parsimonious laboratory test requesters.

Prehospital ultrasound in emergency medicine: incidence, feasibility, indications and diagnoses

Sonography is an established diagnostic procedure in hospitals, but is not routinely used in prehospital emergency medicine. Several studies have addressed the use of ultrasound during helicopter flights and in emergency rooms, few in prehospital settings, but most focused on abdominal blunt trauma. Several case reports describe crucial decisions distinguished by ultrasound.

Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI))

Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures for specific clinical circumstances taking into account specific national health care structures. The 1(st) revision of the S-2k guideline of the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care (prevention, diagnosis, therapy and follow-up care) of critically ill patients with severe sepsis or septic shock. The guideline had been developed according to the "German Instrument for Methodological Guideline Appraisal" of the Association of the Scientific Medical Societies (AWMF). In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.

Differences in the quality of interpersonal care in complementary and conventional medicine

The study was part of a nationwide evaluation of complementary and alternative medicine (CAM) in Swiss primary care. The aim of the study was to compare patient-physician relationships and the respective patient-reported relief of symptoms between CAM and conventional primary care (COM).

Controversies in cardiovascular medicine: Chronic stable coronary artery disease: drugs vs. revascularization

Coronary artery disease remains the leading cause of mortality in most industrialized countries, although age-standardized mortality related to coronary artery disease (CAD) has decreased by more than 40% during the last two decades. Coronary atherosclerosis may cause angina pectoris, myocardial infarction, heart failure, arrhythmia, and sudden death. Medical management of atherosclerosis and its manifestation aims at retardation of progression of plaque formation, prevention of plaque rupture, and subsequent events and treatment of symptoms, when these occur as well as treatment of the sequelae of the disease. Revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is performed as treatment of flow-limiting coronary stenosis to reduce myocardial ischaemia. In high-risk patients with acute coronary syndromes (ACS), a routine invasive strategy with revascularization in most patients provides the best outcome with a significant reduction in death and myocardial infarction compared with an initial conservative strategy. Conversely, the benefit of revascularization among patients with chronic stable CAD has been called into question. This review will provide information that revascularization exerts favourable effects on symptoms, quality of life, exercise capacity, and survival, particularly in those with extensive CAD and documented moderate-to-severe ischaemia. Accordingly, CABG and PCI should be considered a valuable adjunct rather than an alternative to medical therapy.

One small scan for radiology, one giant leap for forensic medicine - Post-mortem imaging replaces forensic autopsy in a case of traumatic aortic laceration

The questions of cause and manner of death are the most pressing ones in any forensic investigation. Traditionally, autopsy is the means to provide answers to these questions and despite the increasing use of CT and MR in the post-mortem setting, imaging has usually been an adjunct to forensic autopsy. Here we describe a case where post-mortem CT and MR were performed instead of autopsy, at the request of the responsible public prosecutor. The forensic conclusions derived from imaging, including cause and manner of death were accepted by the legal authorities, thereby setting precedence for future cases. This case represents a landmark in forensic medicine and is another step toward the full realization of minimally invasive forensic autopsy.