Cerebral perfusion changes in acute subdural hematoma.

INTRODUCTION: Acute subdural hematoma (aSDH) is one of the main causes of high mortality and morbidity in traumatic brain injury. Prognosis is poor due to the rapid volume shift and mass effect. Cerebral perfusion is likely affected in this condition. This study quantifies perfusion changes in aSDH using early ER polytrauma CT with perfusion imaging (CTP). METHODS: Data of 54 patients with traumatic aSDH were retrospectively collected. Glasgow Coma scale (GCS), perfusion parameters, therapeutic decisions and imaging data including hematoma thickness, midline shift, and hematoma localization were analyzed. The cortical perfusion parameters of each hemisphere, the area anterior to the hematoma (AAH), area below the hematoma (ABH), area posterior to the hematoma (PAH), and corresponding mirrored contralateral regions were determined. RESULTS: We found a significant difference in Tmax in affected and unaffected whole-hemisphere data (mean 4.0 s vs. 3.3 s, p < 0.05) and a significantly different mean for Tmax in ABH and for the corresponding mirrored area (mABH) (mean 3.8 s vs. 3.1 s, p < 0.05). No significant perfusion changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were found. CONCLUSION: There was a significant elevation of time to maximum (Tmax) values in the underlying cortical area of aSDH. Possible pathophysiological explanations, the influence on immediate surgical decision-making and further therapeutic consequences have to be evaluated.

Single nucleotide polymorphisms in long noncoding RNA, ANRIL, are not associated with severe periodontitis but with adverse cardiovascular events among patients with cardiovascular disease.

BACKGROUND AND OBJECTIVE: Biological plausibility of an association between severe periodontitis and cardiovascular disease (CVD) has been proven. Genetic characteristics play an important role in both complex inflammatory diseases. Polymorphisms (single nucleotide polymorphisms [SNPs]) in the long noncoding RNA, antisense noncoding RNA in the INK4 locus (ANRIL), were shown to play a leading role in both diseases. The primary objectives of the study were to assess, among cardiovascular (CV angiographically proven ≥50% stenosis of a main coronary artery) patients, the impact of ANRIL SNPs rs133049 and rs3217992 on the severity of periodontitis and the previous history of coronary events, as well as on the occurrence of further adverse CV events. MATERIAL AND METHODS: The prevalence of severe periodontitis was analyzed in 1002 CV patients. ANRIL SNPs rs133049 and rs3217992 were genotyped. The prognostic value of both ANRIL SNPs for combined CV endpoint (stroke/transient ischemic attack [TIA], myocardial infarction, death from a CV-related event, death from stroke) was evaluated after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for established CV risk factors applying Cox regression. RESULTS: ANRIL SNPs rs133049 and rs3217992 were not associated with severe periodontitis or history of CVD in CV patients. In the Kaplan-Meier survival curve including the log rank-test (P = .036) and Cox regression (hazard ratio = 1.684, P = .009) the AA genotype of rs3217992 was shown to be an independent predictor for adverse CV events after 3 years of follow-up. CONCLUSION: SNPs in ANRIL are not risk modulators for severe periodontitis and history of CVD in CV patients. The AA genotype of ANRIL SNPs rs3217992 possesses prognostic power for further CV events within 3 years of follow-up.

Use of floss/interdental brushes is associated with lower risk for new cardiovascular events among patients with coronary heart disease.

BACKGROUND AND OBJECTIVE: Periodontitis has been found to be associated with coronary heart disease (CHD) and stroke. However, only little is known about whether periodontitis and associated confounders are associated with new cardiovascular events among patients with CHD. MATERIAL AND METHODS: A total of 942 inpatients with CHD were examined regarding periodontitis, oral care habits, bacteria in the subgingival biofilm and the expression of interleukin-(IL)-6 c. (coding DNA)-174 genotypes (rs 1800793) to determine whether these confounders are associated with new cardiovascular events within a 1-year follow-up period. Adjusted hazard ratios (HR) with respect of age, gender, smoking, body mass index, use of aids for interdental hygiene, plaque index, occurrence of severe periodontitis and further internal diseases such as diabetes, hypertension, dyslipoproteinemia, number of missing teeth, serological parameters and IL-6 genotypes were generated with Cox regression. RESULTS: In all, 941 cardiovascular patients completed the 1-year follow up and 7.3% of the patients achieved the primary endpoint (myocardial infarction: 2.1%, stroke/transient ischemic attack: 1.8%, cardiovascular deaths: 3.4%). Patients who reported practicing interdental cleaning were younger, less likely to be male or to have severe periodontitis, had a reduced tobacco exposure, had fewer missing teeth, less indices for plaque and bleeding on probing and a significant decreased adjusted risk for new cardiovascular events (HR = 0.2, CI 0.06-0.6, p = 0.01) than those patients with CHD who did not report practicing interdental cleaning. We did not obtain significant increased HR for patients with severe periodontitis (HR = 1.2, CI 0.7-2.1, p = 0.53), carriers of the IL-6 genotypes GC or CC (HR = 1.4, CI 0.8-2.5, p = 0.24) and did not find a significant association between the number of detected various oral species and the incidence of the combined endpoint (HR = 0.9, CI 0.8-1.01, p = 0.07). CONCLUSIONS: These findings suggest that flossing and brushing of interdental spaces might reduce the risk for new cardiovascular events among patients with CHD. The hypothesis that interdental cleaning per se reduces the risk of new cardiovascular events should be examined in an interventional study.

Inter-hospital transfer of ECMO-assisted patients with a portable miniaturized ECMO device: 4 years of experience.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) in patients with severe pulmonary failure is able to keep patients alive until organ regeneration, until shunting out for further diagnostic and therapeutic options or until transportation to specialized centers. Nonetheless, extracorporeal techniques require a high degree of expertise, so that a confinement to specialized centers is meaningful. Following from this requirement, the need for inter-hospital transfer of patients with severely compromised pulmonary function is rising. METHODS: We report about our experience with a portable ECMO system during inter-hospital air or ground transfer of patients with cardiopulmonary failure. RESULTS: The portable ECMO system was used for transportation to the center and in-hospital treatment in 36 patients with an average age of 53 years suffering from respiratory failure. Accordingly, the ECMO system was implanted as a veno-venous extracorporeal system. Pre-ECMO ventilation time was 5.2 (2-9) days. Twelve patients were transported to our institution by ground and 24 patients by air ambulance over a median distance of 46 km. With the assistance of the ECMO device, prompt stabilization of cardiopulmonary function could be achieved in all patients without any technical complications. Post-ECMO ventilation was 9.8 days. Weaning from the ECMO system was successful in 61% of all patients after a median device working period of 12.7 days; median ICU stay was 34 days and a survival rate of 64% of patients was achieved. Technical (8%) and device-associated bleeding (11%)/thromboembolic (8%) complication rates showed very acceptable levels. CONCLUSION: Our experience demonstrates that miniaturized, portable ECMO therapy allows location-independent, out-of-center stabilization of pulmonary compromised patients with consecutive inter-hospital transfer and further in-house treatment, so that sophisticated ECMO therapy can be offered to every patient, even in hospitals with primary healthcare.

[Sexually transmitted infections as a cause for solid rectal pseudo tumors]. / Sexuell übertragbare Infektionen als Ursache von solide imponierenden Pseudotumoren des Rektums.

Two cases of symptomatic proctitis with rectal tumors suspicious for malignancy are presented. A florid regenerative proctitis was shown in the histological examination. In both cases a sexually transmitted infection (STI) was causing the symptoms. In rare cases STIs present as pseudo tumors mimicking malignancy in clinical examination and endoscopic/radiological analysis. A close collaboration between gastroenterologist and pathologist is necessary for a correct diagnosis and to prevent unnecessary surgical treatment.

First experiences with a combined usage of veno-arterial and veno-venous ECMO in therapy-refractory cardiogenic shock patients with cerebral hypoxemia.

The use of extracorporeal membrane oxygenation (ECMO) is becoming a popular tool in the treatment of cardiogenic shock. We present two case reports where classical veno-arterial peripherally cannulated ECMO therapy proved insufficient with profuse cerebral hypoxemia. After augmenting the setting into veno-veno-arterial ECMO, we achieved a remarkable improvement of all oxygenation parameters. The simultaneous use of veno-venous and veno-arterial ECMO might display as a novel strategy to counteract the coronary and cerebral hypoxemia in veno-arterial ECMO therapy in patients with therapy-refractory cardiogenic shock or in combined cardiopulmonary failure. In this manuscript, the veno-veno-arterial ECMO setup is described in full detail and different venous cannulas are discussed.

Sustainability in healthcare by reducing low-value imaging - A narrative review.

OBJECTIVES: This narrative review aims to present the concept of value in imaging and explore why we conduct low-value procedures, how to reduce this wasteful use, and what we could gain from reducing low-value imaging. KEY FINDINGS: Imaging of low value to the patient contributes to thousands of metric tons of CO2 emissions, costing several billion US dollars annually. With a 20% reduction in low-value imaging, we would reduce the waste of resources related to 7.2 million procedures and, at the same time, reduce the risk of incidentalomas, overdiagnosis, and overtreatment and reduce wait times for patients in need of imaging services of high value. Multi-component initiatives targeting barriers in all levels of society and healthcare are needed to reduce low-value imaging. Radiographers are key actors in medical imaging and can make substantial contributions to this effort by, together with the radiologists, referrers, and managers, ensuring that all imaging procedures conducted are sustainable along four dimensions of sustainability: value, cost, risk, and environment. CONCLUSION: Efforts to secure sustainable imaging considering the four crucial dimensions (value, cost, radiation, and environment) should be made at all levels of society and healthcare, from governmental management to the individual healthcare worker. Radiographers are vital in obtaining sustainability to ensure only sustainable imaging procedures are conducted. IMPLICATIONS FOR PRACTICE: When assessing the appropriateness of imaging procedures, we need to consider the environment, safety, effectiveness, and efficiency. To obtain this, we need a collective and coordinated effort locally, nationally, and internationally to deliver sustainable imaging services.

Studies on the mechanisms of action of MR33317.

MR33317 was synthesized as an acetylcholinesterase-inhibitor and an agonist at brain 5-HT4-receptors. MR33317 might be used to treat Morbus Alzheimer. This therapeutic action of MR33317 might be based on MR33317´s dual synergistic activity. We tested the hypothesis that MR33317 also stimulates 5-HT4-receptors in the heart. MR33317 (starting at 10 nM) increased force of contraction and beating rate in isolated atrial preparations from mice with cardiac confined overexpression of the human 5-HT4-serotonin receptor (5-HT4-TG) but was inactive in wild type mouse hearts (WT). Only in the presence of the phosphodiesterase III-inhibitor cilostamide, MR33317 raised force of contraction under isometric conditions in isolated paced (1 Hz) human right atrial preparations (HAP). This increase in force of contraction in human atrium by MR33317 was attenuated by 10 µM tropisetron or GR125487. These data suggest that MR33317 is an agonist at human 5-HT4-serotonin receptors in the human atrium. Clinically, one would predict that MR33317 may lead to atrial fibrillation.

Contractile effects of stimulation of D1-dopamine receptors in the isolated human atrium.

Dopamine receptors have been claimed not to directly increase contractility in the human heart. Therefore, we performed contraction experiments in isolated electrically driven human atrial preparations (HAP). For comparison, we performed contraction experiments with left atrial preparations of transgenic mice which harbor a cardiac overexpression of human D1-dopamine receptors (D1-TG). In D1-TG, first we noted that dopamine (10 nM-10 µM cumulatively applied) in the presence of propranolol exerted a concentration- and time-dependent positive inotropic effect in D1-TG. In a similar fashion, dopamine increased force of contraction in the presence of 0.4 µM propranolol in HAP and these effects were amplified by pre-treatment with inhibitor of phosphodiesterase III (1 µM) cilostamide. Moreover, contractile effects of dopamine in the presence of propranolol 0.4 µM in HAP were antagonized by odapipam, haloperidol, or raclopride. Ten micromolars of fenoldopam in the presence of cilostamide increased force of contraction in HAP and this effect was antagonized by SCH 23390. We conclude that stimulation of human D1-dopamine receptors can increase force of contraction in the HAP.

Thromboelastometric detection of clotting Factor XIII deficiency in cardiac surgery patients.

AIM(S): In this article, we aimed to investigate plasma Factor XIII levels after extracorporeal circulation in cardiac surgery by thromboelastometric detection, as extracorporeal circulation causes various coagulation disorders due to the exposure of blood to artificial surfaces, inflammatory induction and mechanical destruction of platelets and coagulation factors, which may particularly affect factors with long half-lives, such as Factor XIII. BACKGROUND: Since transfusion algorithms are often empirical and laboratory analysis of Factor XIII plasma levels may not be available 24 h a day, bed-side testing using rotational thromboelastometry (ROTEM) could offer a splendid option to define the cause of excessive peri-operative bleeding disorders in general and Factor XIII levels in particular in a timely manner and thus facilitating exact substitution therapy. METHODS: In this trial, we investigated 25 cardiac surgery patients with extracorporeal bypass times over 100 min. Standard laboratory and ROTEM analyses were performed post-operatively at the time of intensive care unit admission and 6 h later. We implemented EXTEM with additional Factor XIII (teenTEM) as additional test by adding 0·625 IU Factor XIII to standard EXTEM reagents. RESULTS: In this observational study, we could not demonstrate a correlation between Factor XIII and MCFEXTEM , CFTEXTEM or MLEXTEM . Neither Factor XIII plasma levels nor MCFEXTEM could predict blood loss. In accordance with previous findings, we were able to demonstrate increased maximum clot firmness (MCF), decreased clot formation time and decreased maximum lysis by adding Factor XIII in vitro (teenTEM vs EXTEM) indicating an improvement in the coagulation process. As shown before, we also found a strong correlation between MCF and platelet and fibrinogen plasma levels. CONCLUSION: In summary, 'teenTEM' test does not seem to detect Factor XIII deficient patients in cardiac surgery. Furthermore, post-operative blood loss could not be predicted neither by ROTEM nor by laboratory analysis of Factor XIII. In vitro administration of Factor XIII appears to improve laboratory measures of haemostasis.

Immediate effects of individualized heparin and protamine management on hemostatic activation and platelet function in adult patients undergoing cardiac surgery with tranexamic acid antifibrinolytic therapy.

OBJECTIVE: This randomized prospective study was initiated to clarify whether individualized heparin and protamine dosing has immediate effects on hemostatic activation and platelet function in adult cardiac surgery. METHODS: Sixty adults undergoing elective coronary artery bypass grafting (CABG) were assigned to receive individualized heparin and protamine (HMS group, n= 29) or a standard dose (ACT group, n=24). Measures of thrombin generation and Multiplate (Verum Diagnostica, Munich, Germany) platelet function tests were performed before and after cardiopulmonary bypass (CPB). RESULTS: HMS patients received higher heparin (p = 0.006) and lower protamine (p<0.001) doses. Post-CPB, HMS managed patients showed significantly lower thrombin generation (thrombin-antithrombin (TAT) p<0.02) than the ACT group. Moreover, HMS managed patients had a better preservation of platelet function (COL p = 0.013; ADP p = 0.04; TRAP p = 0.04). CONCLUSION: An individualized and stable heparin concentration and appropriate dosing of protamine can reduce thrombin generation and preserve platelet function, even in short-time CPB.

Identification of the familial cylindromatosis tumour-suppressor gene.

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

Image rejects in digital skeletal radiography in two public hospitals in Norway.

INTRODUCTION: The proportion of diagnostic images not applied for diagnostic purposes is an indicator of image quality, safety, and efficiency in radiography. Despite increased awareness, image reject is still a substantial problem and needs continued observation and targeted measures. Accordingly, the objective of this study is to estimate the extent, variation, and characteristics of image rejects, in order to improve the quality, safety, and efficiency in radiography. METHODS: All skeletal images at two digital X-ray rooms at two public hospitals in Norway were reviewed for four weeks in 2020. The number of exposed images, type of examination, and number of deleted images were registered. For each deleted image the deduced reasons for deleting the image were recorded. RESULTS: 2183 and 1467 X-ray images were taken at Hospital 1 and 2 respectively. The corresponding reject rates were 14.2% and 9.1%. The reject rate varied greatly from day to day (from 0% to 22%), and the examinations with the highest reject rate were X-ray of extremities (knee, elbow, ankle, wrist) (12-25%) and of the spine (14-19%). The two clearly dominating reasons for image rejects were positioning and centering errors. CONCLUSION: The reject rate is high and reduces quality, safety, and efficiency of imaging services. The reasons for image rejects are typical professionally reducible errors indicating great potential for improvement. IMPLICATIONS FOR PRACTICE: Monitoring and assessing image rejects are of great importance to management, training, education, patient safety, and for quality improvement of imaging services.

Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria.

Cantharidin, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), is known to increase the force of contraction and shorten the time to relaxation in human ventricular preparations. We hypothesized that cantharidin has similar positive inotropic effects in human right atrial appendage (RAA) preparations. RAA were obtained during bypass surgery performed on human patients. These trabeculae were mounted in organ baths and electrically stimulated at 1 Hz. For comparison, we studied isolated electrically stimulated left atrial (LA) preparations and isolated spontaneously beating right atrial (RA) preparations from wild-type mice. Cumulatively applied (starting at 10 to 30 µM), cantharidin exerted a positive concentration-dependent inotropic effect that plateaued at 300 µM in the RAA, LA, and RA preparations. This positive inotropic effect was accompanied by a shortening of the time to relaxation in human atrial preparations (HAPs). Notably, cantharidin did not alter the beating rate in the RA preparations. Furthermore, cantharidin (100 µM) increased the phosphorylation state of phospholamban and the inhibitory subunit of troponin I in RAA preparations, which may account for the faster relaxation observed. The generated data indicate that PP1 and/or PP2A play a functional role in human atrial contractility.

On the normativity of evidence - Lessons from philosophy of science and the "VALIDATE" project.

"Evidence" is a key term in medicine and health services research, including Health Technology Assessment (HTA). Randomized clinical trials (RCTs) have undoubtedly dominated the scene of generating evidence for a long period of time, becoming the hallmark of evidence-based medicine (EBM). However, due to a number of misunderstandings, the lay audience and some researchers have sometimes placed too much trust in RCTs compared to other methods of investigation. One of the principal misunderstandings is to consider RCTs findings as isolated and self-apparent pieces of information. In other words, what has been essentially lacking was the awareness of the value-context of the evidence and, in particular, the value- and theory-ladenness (normativity) of scientific knowledge. This paper aims to emphasize the normativity that exists in the production of scientific knowledge, and in particular in the conduct of RCTs as well as in the performance of HTA. The work is based on some lessons learned from Philosophy of Science and the European project "VALIDATE" (VALues In Doing Assessments of healthcare TEchnologies"). VALIDATE was a three-year EU Erasmus+ strategic partnerships project (2018-2021), in which training in the field of HTA was further optimized by using insights from political science and ethics (in accordance with the recent definition of HTA). Our analysis may reveal useful insights for addressing some challenges that HTA is going to face in the future.

[Protein glycation as a pathological mechanism in diabetes]. / Proteinglykierung als pathophysiologischer Mechanismus bei Diabetes.

The incidence of diabetes has increased in the recent years. Diabetes is characterized by increased sugar concentrations in the blood. Due to this dysregulation, more carbohydrate-induced modification of proteins - so-called advanced glycation end products (AGEs) - are formed endogenously by non-enzymatic reactions. These are discussed to be at least in part responsible for diabetes-associated diseases. The accumulation of AGEs in the tissue can be used as a biomarker for patient outcome. In contrast, the effects of the uptake of AGEs from nutrition are still unclear.

RAGE influences obesity in mice. Effects of the presence of RAGE on weight gain, AGE accumulation, and insulin levels in mice on a high fat diet.

BACKGROUND: The metabolic syndrome is defined by the presence of obesity, insulin resistance, dyslipidemia, and hypertension. Advanced glycation end products (AGEs) are stable end products of the Maillard reaction, whereby AGE accumulation is considered not only a biomarker of aging but is also associated with several degenerative diseases. AGEs are recognized by several receptor molecules of which the receptor of AGEs (RAGE) is currently the most intensively studied receptor. Activation of RAGE causes an unfavorable proinflammatory state and deletion of RAGE in diabetic animals has been reported to protect against atherosclerosis. AGEs and a high fat diet are associated with cardiovascular diseases, whereas is still not clear whether a direct link between high fat nutrition and AGEs exists in vivo. MATERIALS AND METHODS: C57BL/6 and C57BL/6 RAGE -/- mice were fed a high fat diet to induce obesity. Weight, insulin, lipid levels, AGE modifications, and cardiac gene expression were analyzed. RESULTS: The absence of RAGE resulted in accelerated weight gain, increased plasma cholesterol, and higher insulin levels in obese mice. The hearts of normal and obese RAGE -/- mice contained lower levels of the AGE arginine-pyrimidine and 3DG-imidazolone than RAGE + / + animals. RAGE -/- mice also exhibited lower expression of the genes encoding the antioxidative enzymes MnSOD, Cu/ZnSOD, and ceruloplasmin in cardiac tissue, whereas the AGE receptors AGER-1, -2, and -3 were equally expressed in both genotypes. Obese mice of both strains expressed increased amounts of AGER-2. Only obese RAGE + / + mice exhibited a reduced mRNA accumulation of Cu/Zn SOD. CONCLUSION: These data suggest that RAGE is involved in the development of obesity and insulin resistance.

MTT Heterogeneity in Perfusion CT Imaging as a Predictor of Outcome after Aneurysmal SAH.

BACKGROUND AND PURPOSE: Impairment of tissue oxygenation caused by inhomogeneous microscopic blood flow distribution, the so-called capillary transit time heterogeneity, is thought to contribute to delayed cerebral ischemia after aneurysmal SAH but has so far not been systematically evaluated in patients. We hypothesized that heterogeneity of the MTT, derived from CTP parameters, would give insight into the clinical course of patients with aneurysmal SAH and may identify patients at risk of poor outcome. MATERIALS AND METHODS: We retrospectively analyzed the heterogeneity of the MTT using the coefficient of variation in CTP scans from 132 patients. A multivariable logistic regression model was used to model the dichotomized mRS outcome. Linear regression was used to eliminate variables with high linear dependence. T tests were used to compare the means of 2 groups. Furthermore, the time of the maximum coefficient of variation for MTT after bleeding was evaluated for correlation with the mRS after 6 months. RESULTS: On average, each patient underwent 5.3 CTP scans during his or her stay. Patients with high coefficient of variation for MTT presented more often with higher modified Fisher (P = .011) and World Federation of Neurosurgical Societies grades (P = .014). A high coefficient of variation for MTT at days 3-21 after aneurysmal SAH correlated significantly with a worse mRS score after 6 months (P = .016). We found no correlation between the time of the maximum coefficient of variation for MTT after bleeding and the patients' outcomes after 6 months (P = .203). CONCLUSIONS: Heterogeneity of MTT in CTP after aneurysmal SAH correlates with the patients' outcomes. Because the findings are in line with the pathophysiologic concept of the capillary transit time heterogeneity, future studies should seek to verify the coefficient of variation for MTT as a potential imaging biomarker for outcome.

Role of Cardiac A2A Receptors Under Normal and Pathophysiological Conditions.

This review presents an overview of cardiac A2A-adenosine receptors The localization of A2A-AR in the various cell types that encompass the heart and the role they play in force regulation in various mammalian species are depicted. The putative signal transduction systems of A2A-AR in cells in the living heart, as well as the known interactions of A2A-AR with membrane-bound receptors, will be addressed. The possible role that the receptors play in some relevant cardiac pathologies, such as persistent or transient ischemia, hypoxia, sepsis, hypertension, cardiac hypertrophy, and arrhythmias, will be reviewed. Moreover, the cardiac utility of A2A-AR as therapeutic targets for agonistic and antagonistic drugs will be discussed. Gaps in our knowledge about the cardiac function of A2A-AR and future research needs will be identified and formulated.

Fallacies in the arguments for new technology: the case of proton therapy.

In a seminal article in the Journal of Medical Ethics, Søren Holm and Tuja Takala analysed two protechnology arguments in bioethics: the hopeful principle and the automatic escalator. They showed how these arguments relate to problematic arguments such as the precautionary principle and the empirical slippery slope argument, and argued that they should be used with great caution. The present article investigates the recent debate on proton beam therapy, where the hopeful principle and the automatic escalator are identified. However, the debate reveals a series of other arguments that deserve similar caution. An analysis of these arguments indicates that the roots of their fallacies are to be found in the ignorance of the uncertainties about risks and benefits and an overly optimistic attitude towards technology and progress. The point is not to argue against proton therapy, but rather to point out that flawed arguments for new technologies, such as proton therapy, can actually hamper their implementation instead of promoting it. Patients deserve the best technology available, not only on the basis of the best available evidence, but also on the basis of the best arguments.