Pathophysiological Reasoning Research Articles

Impact of Cortisol-Cosecretion on Adrenal Venous Sampling Results in Primary Aldosteronism: Study of 225 Cases

Background/Objectives: Mild autonomous cortisol secretion (MACS) can coexist with primary aldosteronism (PA). The purpose of our study was to evaluate whether (MACS) influences parameters analyzed during adrenal venous sampling (AVS) in patients with PA. Methods: Patients with PA from the SPAIN-ALDO Registry and the German Conn’s Registry with available 1 mg-dexamethasone suppression test (DST) and AVS were included. MACS was defined as a post-DST cortisol > 1.8 µg/dL in the absence of specific signs and symptoms of Cushing’s syndrome. Results: Two-hundred and twenty-five patients were included, 98 (43.6%) of whom had concomitant MACS. The mean age was 54 ± 10 years and 37.3% were women. AVS was performed by simultaneous catheterization of both adrenal veins and analysis of basal samples in 157 patients (69.8%), with both basal and post-ACTH samples in 15 patients (6.7%), and during continuous ACTH infusion in 53 patients (23.6%). AVS was considered technically unsuccessful in 40 cases (17.8%), suggesting unilateral secretion in 106 (47.1%) and bilateral secretion in 79 (35.1%). We did not find significant differences in the percentage of unilateral and bilateral results, cortisol, corrected aldosterone, or selectivity indices in the dominant and non-dominant veins, nor in the lateralization index or the contralateral suppression index between patients with and without MACS. They also had similar rates of surgical treatment and biochemical and clinical response. Conclusions: Although pathophysiological reasoning suggests that MACS could hinder AVS identification of unilateral forms of PA, our data suggest that such interference, if it exists, is of moderate clinical relevance.

Reflections on internal medicine in Poland on the occasion of the 100th anniversary of <i>Polish Archives of Internal Medicine</i>

Dynamic development of medicine in the 20th and 21st centuries has only been possible due to its split into narrow specialties. The increasingly complicated and costly technologies used in clinical practice can only be mastered by small groups of highly‑ qualified specialists; however, diagnosis and treatment are not about matching a patient with the latest and most sophisticated technologies but about finding an optimal patient‑ oriented solution, as it is the human being as a whole that needs help. To achieve this goal, a close collaboration of different specialists is required, but the key role rests with a physician with good general internal medicine skills and the right motivation to act. Management of patients presenting to internal medicine departments requires not only the skill of appropriate pathophysiological reasoning based on extensive knowledge and acquired experience, but many times also the civil courage of the physician. The task is further complicated by chronic underfunding of these wards. The aim of the present review is to reflect on the current state and prospects of Polish internal medicine as well as to attempt a definition of an internist and their role in the integration of different medical specialties. It also stresses the importance of a master in the teaching and practice of medicine and presents profiles of 4 eminent Polish internists.

The conceptualization of acute bronchitis in general practice – a fuzzy problem with consequences? A qualitative study in primary care

BackgroundAcute bronchitis is one of the most frequent diagnoses in primary care. Scientifically, it is conceptualized as a viral infection. Still, general practitioners (GPs) often prescribe antibiotics for acute bronchitis. The explanation for this discrepancy may lie in a different conceptualization of acute bronchitis. Therefore, we wanted to know, how GPs conceptualize acute bronchitis, and how they differentiate it from common cold and pneumonia. Furthermore, we tried to find out the GPs’ reasons for prescribing antibiotics in those cases.MethodsTo answer our study questions, we conducted a qualitative study with GPs in Bavaria, Germany, by using semi-structured guided interviews. The analysis of the data was conducted using the documentary method according to Ralf Bohnsack. The transcripts were subdivided into categories. Analyzing each part by reflective interpretation, first manually, secondly with the help of RQDA, we extracted the most representative citations and main messages from the interviews.ResultsThe term acute bronchitis seems to be applied when there is neither certainty of the diagnosis common cold, nor of pneumonia. It seems it bridges the gap of uncertainty between supposedly harmless clinical pictures (common cold/viral), to the more serious ones (pneumonia/bacterial). The conceptual transitions between common cold and acute bronchitis on the one side, and acute bronchitis and pneumonia on the other are fluid. The diagnosis acute bronchitis cannot solve the problem of uncertainty but seems to be a label to overcome it by offering a way to include different factors such as severity of symptoms, presumed signs of bacterial secondary infection, comorbidities, and presumed expectations of patients. It seems to solve the pathophysiologic riddle of bacterial or viral and of decision making in prescribing antibiotics.ConclusionAcute bronchitis as an "intermediate category" proved difficult to define for the GPs. Applying this diagnosis leaves GPs in abeyance of prescribing an antibiotic or not. As a consequence of this uncertainty in pathophysiologic reasoning (viral or bacterial) other clinical and social factors tip the balance towards antibiotic prescribing. Teaching physicians to better think in probabilities of outcomes instead of pathophysiologic reasoning and to deal with uncertainty might help reducing antibiotic overprescribing.

P232 EXERTIONAL BREATHLESSNESS IN HYPERTROPHIC CARDIOMYOPATHY: OBSTRUCTION–INDEPENDENT SYMPTOMS IN A “PARADOXICAL” RESPONSE TO EXERCISE

Abstract A 66–y.o. man with hypertrophic cardiomyopathy presented with residual exertional dyspnea NYHA III a few years after surgical myectomy, mitral valve repair and ICD implantation. Echocardiography showed residual mild septal hypertrophy and mitral regurgitation (MR), and a variable obstruction of left ventricular outflow tract (LVOT), witnessed by a pressure gradient ranging from 15 to 50–70 mmHg (Figure 1). Exercise echocardiography did not suggest exercise–induced LVOT obstruction (LVOTO) or functional MR. We thus performed a thorough invasive hemodynamic evaluation at rest and during exercise. LVOTO was present at rest, with a maximum pressure gradient of 90–100 mmHg and typical “spike–and–dome” configuration of the aortic pulse contour (Figure 2), with LV end–diastolic pressure (LVEDP) at the upper limit of normal (15 mmHg) and normal pulmonary hemodynamics. During exercise, we observed a paradoxical reduction of the LVOTO (30–40 mmHg at peak, Figure 2). Pulmonary hypertension developed during exercise, due to LV diastolic dysfunction, witnessed by a marked increase in pulmonary artery wedge pressure and LVEDP (up to 25 mmHg and 30 mmHg at peak, respectively). Cardiac output (CO) reserve was at the lower limits of normal, mainly due to chronotropic incompetence, responsible for a mildly reduced exercise capacity (peak oxygen consumption was 20 mL/Kg/min, 75% of predicted). Thus, cardiac catheterization confirmed the presence of a relevant LVOTO at rest, that was not directly related to exertional symptoms. These latter were mainly attributable to LV diastolic dysfunction and reduced CO reserve. These findings helped us driving treatment decision in a tailored way: beta–blockers were not uptitrated, because of their negative inotropic effect, and high–risk septal reduction therapies were excluded, since exertional symptoms were unrelated to LVOTO. However, an attempt to reduce LVOTO was done by DDD sequential pacing through the ICD. Pacing could induce mechanical dyssynchrony and reduce LVOTO by increasing the end–systolic LVOT diameter. The simultaneous echocardiographic monitoring highlighted an acute reduction of LVOT gradient from 50–70 mmHg to 20–30 mmHg (Figure 3). This case suggests that, in well–selected cases, patients’ management based on pathophysiological reasoning may help to define the etiopathogenetic mechanism underlying symptoms, and to drive treatment decision in a patient–centered way.

Perioperative management of the brain-dead organ donor : Anesthesia between ethics and evidence

HintergrundDie Anzahl postmortal gespendeter Organe ist in Deutschland weit geringer als der Bedarf. Dies unterstreicht die Wichtigkeit einer optimalen Versorgung während des gesamten Prozesses der Organspende.FragestellungEs existieren internationale Leitlinien und nationale Empfehlungen zu intensivmedizinischen organprotektiven Maßnahmen beim Organspender. Für das anästhesiologische Management fehlen evidenzbasierte Empfehlungen. Ziel dieser Übersichtsarbeit ist es, anhand der vorhandenen Evidenz die pathophysiologischen Veränderungen des irreversiblen Hirnfunktionsausfalls zu rekapitulieren und sich kritisch mit den empfohlenen Behandlungsstrategien und therapeutischen Zielgrößen auseinanderzusetzen. Auch auf ethische Aspekte der Betreuung des postmortalen Organspenders wird eingegangen.MethodeDiese Übersichtsarbeit basiert auf einer selektiven Literaturrecherche in PubMed (Suchwörter: „brain dead donor“, „organ procurement“, „organ protective therapy“, „donor preconditioning“, „perioperative donor management“, „ethical considerations of brain dead donor“). Internationale Leitlinien und nationale Empfehlungen wurden besonders berücksichtigt.ErgebnisseInsgesamt ist die Evidenz für optimale intensivmedizinische und perioperative organprotektive Maßnahmen beim postmortalen Organspender sehr gering. Nationale und internationale Empfehlungen zu Zielwerten und medikamentösen Behandlungsstrategien unterscheiden sich teilweise erheblich: kontrollierte randomisierte Studien fehlen. Der Stellenwert einer Narkose zur Explantation bleibt sowohl unter pathophysiologischen Gesichtspunkten als auch aus ethischer Sicht ungeklärt.SchlussfolgerungenDie Kenntnisse über die pathophysiologischen Prozesse im Rahmen des irreversiblen Hirnfunktionsausfalls und die organprotektiven Maßnahmen sind ebenso Grundvoraussetzung wie die ethische Auseinandersetzung mit dem Thema postmortale Organspende. Nur dann kann das Behandlungsteam in dieser herausfordernden Situation sowohl dem Organempfänger als auch dem Organspender und seinen Angehörigen gerecht werden.

Epilepsy and cannabis: facing reality.

EDITOR–Pediatric drug-resistant epilepsy (DRE) can have a devastating impact on the quality of life and daily functioning of the child and family. It also affects their health and development, and creates an ongoing heavy load for health services. Despite new antiseizure medication (ASM), occasional precision therapy, advances in epilepsy surgery and neuromodulation, and the use of various ketogenic diets, the population of patients with DRE has not decreased significantly.1, 2 Cannabidiol (CBD)-enriched cannabis may be of benefit to some of these children.3 CBD-enriched cannabis for (pediatric) epilepsy has notably been championed by both parents and the pharmaceutical industry. Indications for the FDA and EMA approved pure CBD (Epidiolex) are still limited to Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, partly based on pathophysiological reasoning but also because the approval process is faster and easier for such rare disorders. As neurologists, we are exposed to increasing (mostly low-level) literature on artisanal CBD's efficacy and safety, and we are increasingly asked by families to consider it as a therapy. Owing to various reasons (mainly economic and political), artisanal CBD has mostly escaped the systematic sound research process necessary to document the safety and efficacy of ASM before it comes to market. This has occurred in a context where various cannabis products are being marketed in many countries for medical and non-medical purposes, most of them produced using uncontrolled methods resulting in unreliable composition.4 Kirkpatrick and O'Callaghan provide important clues for clinicians and researchers to address the issue ethically and realistically, with insights stemming from a British perspective. In Israel, we worked together with the Ministry of Health on strict regulations of growing cannabis by approved growers/producers; controlling the oil extraction following a Good Manufacturing Practice-like process; selecting the correct compositions and requiring precise product content to be accurately measured and declared; moving the distribution of the products from the growers/producers to regular pharmacies; and defining guidelines on who is eligible to be treated:currently in Israel, this includes seizures which are refractory to at least four appropriate ASMs, which is more strict than the usual drug-resistant epilepsy definition. Meanwhile, we keep educating treating neurologists on the use of CBD in epilepsy, limiting the eligible dosages of CBD and tetrahydrocannabinol (THC) allowed, and disseminating knowledge on adverse effects and possible drug interactions. We also try to ensure consistency in the oil used by the patient (as there may be differences in the other compounds) and the follow-up of treated patients. At the same time, we should all try to continue promoting research in animal models and design placebo-controlled treatment trials with different compounds and formulations in various populations, and in addition accumulate as much data as possible on long-term effects.

Bioreactance-Based Noninvasive Fluid Responsiveness and Cardiac Output Monitoring: A Pilot Study in Patients with Aneurysmal Subarachnoid Hemorrhage and Literature Review.

Management of volume status, arterial blood pressure, and cardiac output are core elements in approaching the patients with aneurysmal subarachnoid hemorrhage (SAH). For the prevention and treatment of delayed cerebral ischemia (DCI), euvolemia is advocated and caution is made towards the avoidance of hypervolemia. Induced hypertension and cardiac output augmentation are the mainstays of medical management during active DCI, whereas the older triple-H paradigm has fallen out of favor due to lack of demonstrable physiological or clinical benefits and serious concern for adverse effects such as pulmonary edema and multiorgan system dysfunction. Furthermore, insight into clinical hemodynamics of patients with SAH becomes salient when one considers the frequently associated cardiac and pulmonary manifestations of the disease such as SAH-associated cardiomyopathy and neurogenic pulmonary edema. In terms of fluid and volume targets, less attention has been paid to dynamic markers of fluid responsiveness despite the well-established, in the general critical care literature, superiority of these as compared to traditionally used static markers such as central venous pressure (CVP). Based on this literature and sound pathophysiologic reasoning, reliance on static markers (such as CVP) is unjustified when one attempts to assess strategies augmenting stroke volume (SV), arterial blood pressure, and oxygen delivery. There are several options for continuous bedside cardiorespiratory monitoring and optimization of SAH patients. We, here, review a noninvasive monitoring technique based on thoracic bioreactance and focusing on continuous cardiac output and fluid responsiveness markers.

Selective Apheresis of C-Reactive Protein for Treatment of Indications with Elevated CRP Concentrations

Almost every kind of inflammation in the human body is accompanied by rising C-reactive protein (CRP) concentrations. This can include bacterial and viral infection, chronic inflammation and so-called sterile inflammation triggered by (internal) acute tissue injury. CRP is part of the ancient humoral immune response and secreted into the circulation by the liver upon respective stimuli. Its main immunological functions are the opsonization of biological particles (bacteria and dead or dying cells) for their clearance by macrophages and the activation of the classical complement pathway. This not only helps to eliminate pathogens and dead cells, which is very useful in any case, but unfortunately also to remove only slightly damaged or inactive human cells that may potentially regenerate with more CRP-free time. CRP action severely aggravates the extent of tissue damage during the acute phase response after an acute injury and therefore negatively affects clinical outcome. CRP is therefore a promising therapeutic target to rescue energy-deprived tissue either caused by ischemic injury (e.g., myocardial infarction and stroke) or by an overcompensating immune reaction occurring in acute inflammation (e.g., pancreatitis) or systemic inflammatory response syndrome (SIRS; e.g., after transplantation or surgery). Selective CRP apheresis can remove circulating CRP safely and efficiently. We explain the pathophysiological reasoning behind therapeutic CRP apheresis and summarize the broad span of indications in which its application could be beneficial with a focus on ischemic stroke as well as the results of this therapeutic approach after myocardial infarction.

Hemodialysis treatment in patients with severe electrolyte disorders: Management of hyperkalemia and hyponatremia.

Significant deviations of serum potassium and sodium levels are frequently observed in hospitalized patients and are both associated with increased all‐cause and cardiovascular mortality. The presence of acute or chronic renal failure facilitates the pathogenesis and complicates the clinical management. In the absence of reliable outcome data in the context of dialysis prescription, requirement of renal replacement therapy in patients with severe electrolyte disturbances constitutes a therapeutic challenge. Recommendations for intradialytic management are based on pathophysiologic reasoning and clinical observations only, and as such, heterogeneous and limited to expert opinion level. This article reviews current strategies for the management of severe hyperkalemia and hyponatremia in hemodialysis patients.

Evidence-based medicine, shared decision making and the hidden curriculum: aqualitative content analysis.

IntroductionMedical education should portray evidence-based medicine (EBM) and shared decision making (SDM) as central to patient care. However, misconceptions regarding EBM and SDM are common in clinical practice, and these biases might unintentionally be transmitted to medical trainees through a hidden curriculum. The current study explores how assumptions of EBM and SDM can be hidden in formal curriculum material such as PowerPoint slides.MethodsWe conducted a qualitative content analysis using a purposive sample of 18 PowerPoints on the management of upper respiratory tract infections. We identified concepts pertaining to decision making using theory-driven codes taken from the fields of EBM and SDM. We then re-analyzed the coded text using a constructivist latent thematic approach to develop a rich description of conceptualizations of decision making in relation to EBM and SDM frameworks.ResultsPowerPoint slides can relay a hidden curriculum, which can normalize: pathophysiological reasoning, unexplained variations in clinical care, the use of EBM mimics, defensive medicine, an unrealistic portrayal of benefits, and paternalism.DiscussionAddressing the hidden curriculum in formal curricular material should be explored as a novel strategy to foster a positive attitude towards EBM and SDM and to improve patient outcomes by encouraging the use of these skills.Electronic supplementary materialThe online version of this article (10.1007/s40037-020-00578-0) contains supplementary material, which is available to authorized users.

Transforming personalized nutrition practice.

The strengths and limitations of current approaches to clinical nutrition practice and their underpinning research are explored in this article. It describes how a personalized nutrition practice approach supported by evidence-based pathophysiological reasoning could direct additional research, which could then transform practice and support food industry developments. Current use of the term "personalized nutrition" is reviewed and a definition is provided. Also explored are current approaches to personalized nutrition practice and evidence-based practice in clinical nutrition. Patient-centered practice, which involves individuals in their healthcare decisions, is currently being provided under the name "personalized." An evidence-based personalized practice approach should include the use of robust, standardized, and validated tools that gather a patient's signs and symptoms, health history, family history, genetics, environment, lifestyle, social life, diet, behavior and other factors that have an impact on physiological processes. It should also gather anthropometric measures as well as functional, diagnostic, and prognostic biomarkers for pathophysiological mechanisms. Such tools would pool n = 1 data into a case-by-case evidence base that uses computational network modelling to predict the efficacy of personalized nutrition interventions. Prediction of the efficacy of interventions should also be validated using, when possible, blinded, randomized, controlled, stratified intervention studies. This model would provide practitioners with data that support evidence-based pathophysiological reasoning. It would enable clinicians to prioritize interventions on the basis of the mechanisms of action of interventions and to ameliorate the mechanisms of pathophysiology, which are a priority for the individual. Interventions then may be applied using a patient-centered practice approach. This would transform evidence-based nutrition practice into a P4 medicine approach that is personalized, preventive, predictive, and participatory. Developing pathophysiological mechanistic understanding also provides new opportunities for stakeholders, including the food industry, researchers, healthcare practitioners, and consumers.

The Heart in COVID-19: Primary Target or Secondary Bystander?

SummaryIn the throes of the current coronavirus disease-2019 (COVID-19) pandemic, interest has burgeoned in the cardiovascular complications of this virulent viral infection. As troponin, a biomarker of cardiac injury, often rises in hospitalized patients, its interpretation and actionability require careful consideration. Fulminant myocarditis due to direct viral infection can certainly occur, but in patients with increased oxygen demands due to tachycardia and fever and reduced oxygen delivery due to hypotension and hypoxemia, COVID-19 disease can cause myocardial injury indirectly. Cytokines released during the acute infection can elicit activation of cells within pre-existing atherosclerotic lesions, augmenting thrombotic risk and risk of ischemic syndromes. Moreover, microvascular activation by cytokines can cause not only myocardial injury but can also harm other organ systems commonly involved in COVID-19 infections including the kidneys. Dealing with the immense challenge of COVID-19, confronted with severely ill patients in dire straits with virtually no rigorous evidence base to guide our therapy, we must call on our clinical skills and judgment. These touchstones can help guide us in selecting patients who might benefit from the advanced imaging and invasive procedures that present enormous logistical challenges in the current context. Lacking a robust evidence base, pathophysiologic reasoning can help guide our choices of therapy for individual clinical scenarios. We must exercise caution and extreme humility, as often plausible interventions fail when tested rigorously. But act today we must, and understanding the multiplicity of mechanisms of myocardial injury in COVID-19 infection will help us meet our mission unsupported by the comfort of strong data.

The continuous heart failure spectrum: moving beyond an ejection fraction classification.

Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as 'HFrEF' (HF with reduced LVEF), 'HFpEF' (HF with preserved LVEF), and more recently 'HFmrEF' (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone.

Management of the brain-dead donor in the ICU: general and specific therapy to improve transplantable organ quality.

PurposeTo provide a practical overview of the management of the potential organ donor in the intensive care unit.MethodsSeven areas of donor management were considered for this review: hemodynamic management; fluids and electrolytes; respiratory management; endocrine management; temperature management; anaemia and coagulation; infection management. For each subchapter, a narrative review was conducted.Results and conclusionsMost elements in the current recommendations and guidelines are based on pathophysiological reasoning, epidemiological observations, or extrapolations from general ICU management strategies, and not on evidence from randomized controlled trials. The cardiorespiratory management of brain-dead donors is very similar to the management of critically ill patients, and the same applies to the management of anaemia and coagulation. Central diabetes insipidus is of particular concern, and should be diagnosed based on clinical criteria. Depending on the degree of vasopressor dependency, it can be treated with intermittent desmopressin or continuous vasopressin, intravenously. Temperature management of the donor is an area of uncertainty, but it appears reasonable to strive for a core temperature of > 35 °C. The indications and controversies regarding endocrine therapies, in particular thyroid hormone replacement therapy, and corticosteroid therapy, are discussed. The potential donor should be assessed clinically for infections, and screening tests for specific infections are an essential part of donor management. Although the rate of infection transmission from donor to receptor is low, certain infections are still a formal contraindication to organ donation. However, new antiviral drugs and strategies now allow organ donation from certain infected donors to be done safely.

Hemodynamic target variables in the intensive care unit

Despite broad availability, extended hemodynamic monitoring is used in practice only in the minority of critical care patients. Pathophysiological reasoning suggests that systemic perfusion pressure (and thereby arterial as well as central venous pressure), cardiac stroke volume, and the systemic oxygen balance are key variables in maintaining adequate organ perfusion. In line with these assumptions, several studies support that agoal-directed optimization of these hemodynamic variables leads to areduction in morbidity and mortality. The appropriate monitoring modality should be selected following echocardiographic evaluation of biventricular function. Ideally, high-risk patients with limited right ventricular function should be monitored with apulmonary artery catheter. In patients with preserved right ventricular function, transpulmonary thermodilution with special consideration of extravascular lung water seems to be sufficient to guide hemodynamic therapy.

Circadian Rhythm and Alzheimer's Disease.

Alzheimer’s disease (AD) is a neurodegenerative disorder with a growing epidemiological importance characterized by significant disease burden. Sleep-related pathological symptomatology often accompanies AD. The etiology and pathogenesis of disrupted circadian rhythm and AD share common factors, which also opens the perspective of viewing them as a mutually dependent process. This article focuses on the bi-directional relationship between these processes, discussing the pathophysiological links and clinical aspects. Common mechanisms linking both processes include neuroinflammation, neurodegeneration, and circadian rhythm desynchronization. Timely recognition of sleep-specific symptoms as components of AD could lead to an earlier and correct diagnosis with an opportunity of offering treatments at an earlier stage. Likewise, proper sleep hygiene and related treatments ought to be one of the priorities in the management of the patient population affected by AD. This narrative review brings a comprehensive approach to clearly demonstrate the underlying complexities linking AD and circadian rhythm disruption. Most clinical data are based on interventions including melatonin, but larger-scale research is still scarce. Following a pathophysiological reasoning backed by evidence gained from AD models, novel anti-inflammatory treatments and those targeting metabolic alterations in AD might prove useful for normalizing a disrupted circadian rhythm. By restoring it, benefits would be conferred for immunological, metabolic, and behavioral function in an affected individual. On the other hand, a balanced circadian rhythm should provide greater resilience to AD pathogenesis.

Spinal cord bypass surgery in patients with the consequences of spinal cord injury

In the present study, author analyzes literature data that is devoted to spinal cord bypass surgery as a new method of restorative treatment of patients with the consequences of spinal cord injury. On the basis of experimental researches results author gave a pathophysiological reasoning of different methods of spinal cord bypass surgery. The article includes the results of experimental and clinical spinal cord bypass surgery researches and new prospects of this methods of surgical treatment developing.

Unpacking the process of interpretation in evidence-based decision making.

Evidence-based medicine (EBM) has promoted the conscientious and systematic use of the best available scientific evidence in clinical decision making [1]. From an EBM point of view, only experimental evidence, especially results from randomized controlled trials and meta-analyses of trial results, count as strong evidence. Experiential evidence based upon expert opinion is classified as weak and placed at the bottom of the evidence hierarchy. EBM is often contrasted with traditional clinical medicine which considered pathophysiological reasoning and expert knowledge as the principal sources of clinical decision making. In a recently published article in Journal of Evaluation in Clinical Practice, Jeannette Hofmeijer describes EBM as a revision of medical epistemology and points to the neglected role of expert opinion and the lack of focus on the principles of reasoning underpinning EMB [2]. More specifically, she shows how EBM involves important processes of interpretation. Hofmeijer is mainly concerned with the role of interpretation in the production of scientific knowledge within the EBM tradition, and she illustrates how the quest for evidence relies upon interpretation both in formulating a hypothesis and in accepting the accumulated evidence as sufficient. We will argue a related but still different perspective demonstrating the principles of reasoning involved in the integration of experimental and experiential knowledge in clinical decisions and the role of interpretation in this respect. The goal of EBM is, according to Sackett et al., the integration of (1) clinical experience and expertise; (2) scientific evidence; and (3) patient values and preferences to provide high-quality services [1]. However, a weakness of EBM is the lack of guidance on how to combine the main knowledge components of the model. The EBM literature says little about how to create a fruitful interaction between research, clinical expertise and patient preferences. Although the principal aim of EBM is to promote more conscientious and systematic clinical decision making, an important element of the model remains black boxed: the principles of reasoning according to which the different knowledge sources are combined. This paper aims to make explicit the often implicit interpretational work involved when scientific evidence, clinical expertise and patient preferences are combined. We believe that better awareness about this process of interpretation can promote better and more trustworthy decision making. Lack of individualization is a recurrent criticism against EBM [3,4]. Randomized clinical trials measure average effects and do not necessarily match the local and complex situation of the individual patient [5]. The need for a situated, practice-based reasoning has been argued, and concepts such as clinical intuition [6], tacit knowledge [7], wisdom [8] and collectively defined ‘mind lines’ [9] have been introduced to challenge a unilateral focus on implementing research evidence. More recently, the literature on patient-centred medicine and shared decision making has emphasized the importance of involving patients in medical decisions and suggested useful methods and approaches [10,11]. In spite of these attempts, the principles of reasoning according to which the knowledge sources are combined and applied are still poorly understood. There are few, if any, models and concepts available which make explicit the interpretational operations involved when combining and applying the knowledge components. We intend to throw light on this process by drawing on a four-step model of knowing developed by the Canadian philosopher Bernard Lonergan [12].

High-density electroencephalography developmental neurophysiological trajectories.

Efforts to document early changes in the developing brain have resulted in the construction of increasingly accurate structural images based on magnetic resonance imaging (MRI) in newborn infants. Tractography diagrams obtained through diffusion tensor imaging have focused on white matter microstructure, with particular emphasis on neuronal connectivity at the level of fibre tract systems. Electroencephalography (EEG) provides a complementary approach with more direct access to brain electrical activity. Its temporal resolution is excellent, and its spatial resolution can be enhanced to physiologically relevant levels, through the combination of high-density recordings (e.g. by using 64 channels in newborn infants) and mathematical models (e.g. inverse modelling computation), to identify generators of different oscillation bands and synchrony patterns. The integration of functional and structural topography of the neonatal brain provides insights into typical brain organization, and the deviations seen in particular contexts, for example the effect of hypoxic-ischaemic insult in terms of damage, eventual reorganization, and functional changes. Endophenotypes can then be used for pathophysiological reasoning, management planning, and outcome measurements, and allow a longitudinal approach to individual developmental trajectories.

Phenotypic plasticity and the perception-action-cognition-environment paradigm in neurodevelopmental genetic disorders.

Careful study of the phenotype can have implications at several levels, namely clinical diagnosis, pathophysiological reasoning, management planning, and outcome measurement. Behavioural phenotypes involve cognition, communication, social skills, and motor control. They can be documented in a host of neurodevelopmental conditions and approached with the recently refined perception-action-cognition-environment (PACE) paradigm, which focuses on the neurodevelopmental processes that underlie learning and adaption to the environment through perception, action, and cognitive processing. Although this paradigm was originally developed in the context of cerebral palsy, it can be applied along developmental trajectories in several neurogenetic conditions, including Down syndrome, fragile X syndrome, Rett syndrome, Angelman syndrome, and Williams syndrome, to name but a few. It must be recognized, however, that relevant, valid tools for assessment and management strategies still need to be developed.