Thirty Years of Neuroscientific Investigation of Placebo and Nocebo: The Interesting, the Good, and the Bad

Over the past 30 years there has been a surge of research on the placebo effect using a neuroscientific approach. The interesting aspects of this effort are related to the identification of several biological mechanisms of both the placebo and nocebo effects, the latter of which is defined as a negative placebo effect. Some important translational implications have emerged both in the setting of clinical trials and in routine medical practice. One of the principal contributions of neuroscience has been to draw the attention of the scientific and medical communities to the important role of psychobiological factors in therapeutic outcomes, be they drug related or not. Indeed, many biological mechanisms triggered by placebos and nocebos resemble those modulated by drugs, suggesting a possible interaction between psychological factors and drug action. Unfortunately, this new knowledge regarding placebos has the potential of being dangerously exploited by pseudoscience. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Shaping the Future of Smart Dentistry: From Artificial Intelligence (AI) to Intelligence Augmentation (IA)

Digitization is the emerging process in the current transformation of industry. Understanding the role and socio-economic consequences of digitalization is crucial for the way technology is being deployed in each sector. One of the affected sectors is dentistry. This study highlights the current advances and challenges in integrating and merging artificial intelligence (AI), intelligence augmentation (IA), and machine learning (ML) in dentistry. We conduct a comparative analysis to give an overview of which technology is being currently deployed and what role IA and AI will play in dentistry, as AI plays an assistive role in advancing human capabilities. We find that challenges range from AI finding its way into routine medical practice to qualitative challenges of retrieving adequate data input. Other challenges lie in the yet unanswered questions of liability in how to reduce deployment costs of new technology. Given these challenges, we provide an outlook of how future technology can be deployed in daily-life dentistry and how robots and humans will interact, given the current technology developments. The aim of this paper is to discuss the future of dentistry and whether it is AI or IA conquering the modern dentistry era.

Why do we need "Real-World Data & Evidence", the new scientific electronic journal?

The modern request of the global healthcare system is the collection and analysis of the information obtained during the analysis of data collected in research of routine medical practice, namely real-world data (RWD), and the evidence based on it, real-world evidence (RWE).

Transmural Response and Transmural Healing Defined by Intestinal Ultrasound - New Potential Therapeutic Targets?

Background and Aims Intestinal ultrasound (IUS) is a useful modality to monitor patients with inflammatory bowel diseases (IBD). Little is known about the use of IUS and appropriate definitions for transmural response (TR) and healing (TH). We aimed to establish the use of IUS in monitoring TH as a potential target in routine medical practice. Methods Based on the prospective, non-interventional, multicentre studies TRUST and TRUST&UC, we conducted a post-hoc analysis of 351 IBD patients with increased bowel wall thickness (BWT). We analysed the rates of patients achieving TR and TH, comparing three definitions of TH. In 137 Crohn’s disease (CD) patients, the predictive value of TR and TH was investigated for the clinical and sonographic outcome at week 52. Results Within 12 weeks of treatment intensification, 65.6% (n = 118) of CD patients and 76.6% (n = 131) of ulcerative colitis (UC) patients showed a TR. Depending on the definition, 23.9%–37.2% (n=58/67/43) of CD patients and 45.0%–61.4% (n=90/105/77) of UC patients had TH at week 12. CD patients with TH were more likely to reach clinical remission at week 12 (OR 3.33 [1.09–10.2]; p = 0.044) and a favourable sonographic outcome (OR 5.59 [1.97–15.8]; p = 0.001) at week 52 compared with patients without TH. Conclusions IUS response and TH in a relevant proportion of patients suggests that IUS is a useful method to assess transmural inflammatory activity in daily clinical practice. TR and TH are predictive for the sonographic outcome at week 52.

Hyperferritinemia—A Clinical Overview

Ferritin is one of the most frequently requested laboratory tests in primary and secondary care, and levels often deviate from reference ranges. Serving as an indirect marker for total body iron stores, low ferritin is highly specific for iron deficiency. Hyperferritinemia is, however, a non-specific finding, which is frequently overlooked in general practice. In routine medical practice, only 10% of cases are related to an iron overload, whilst the rest is seen as a result of acute phase reactions and reactive increases in ferritin due to underlying conditions. Differentiation of the presence or absence of an associated iron overload upon hyperferritinemia is essential, although often proves to be complex. In this review, we have performed a review of a selection of the literature based on the authors’ own experiences and assessments in accordance with international recommendations and guidelines. We address the biology, etiology, and epidemiology of hyperferritinemia. Finally, an algorithm for the diagnostic workup and management of hyperferritinemia is proposed, and general principles regarding the treatment of iron overload are discussed.

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its’ very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of numerous drugs with an increasingly significant role in clinical therapy especially of cancer patients. Here, we provide an overview of clinical epigenetics within the context of network analysis. We illustrate achievements to date and discuss how we can move from traditional medicine into the era of network medicine (NM), where pathway-informed molecular diagnostics will allow treatment selection following the paradigm of precision medicine.

Proprioception in Immersive Virtual Reality

Currently, in connection with the advent of virtual reality (VR) technologies, methods that recreate sensory sensations are rapidly developing. Under the conditions of VR, which is an immersive environment, a variety of multimodal sensory experiences can be obtained. It is urgent to create explicit immersive environments that allow maximizing the full potential of VR technology. Activation of the proprioceptive sensory system, coupled with the activation of the visual analyzer system, allows you to achieve sensations of interaction with VR objects, identical to the sensations of the real physical world. Today, the activation of proprioceptive sensations is achieved using various devices, including robotic ones, which are not available for use in routine medical practice. The immersive multisensory environment makes it possible to significantly personalize the rehabilitation process, ensuring its continuity and effectiveness at various stages of the pathological process and varying degrees of severity of physical disorders, while significantly reducing the burden on the healthcare system by automating the rehabilitation process and objectively assessing the effectiveness. Further development and increased availability of VR technologies and devices that allow achieving an increase in immersion due to sensory immersion will be in great demand as a technology that allows teaching patients motor skills.

‘Pleural Triage’ facilitates effective management of a pleural service in the COVID-19 era

The COVID-19 pandemic has created new challenges for management of pleural diseases. As resources and staff have been redirected to manage acutely unwell COVID-19 patients, routine medical practice and service provision for pleural diseases have been severely disrupted. We recognised the impact this had for patients with pleural diseases, who can be highly vulnerable to infection and often have conditions for which treatment cannot be safely delayed. The pleural service was reviewed in a tertiary centre, focusing on the changes that allowed maintenance of a service whilst maximising patient and staff safety, with the aim that these service transformations can be adopted elsewhere to improve care for pleural patients during and beyond COVID-19.

DIAGNOSIS AND TREATMENT OF PRIMARY MINOR IMMUNODEFICIENCIES IN PATIENTS WITH RECURRENT UROGENITAL INFECTIONS AND IMMUNE-DEPENDENT INFERTILITY

It has now been established that immunosuppressive status is observed in patients with recurrent urogenital infections caused by opportunistic and low virulent microflora. A pooled analysis of the known prevalence rates of the 30 currently known mild human immune dysfunctions suggests that at least 20% of the current population (in one in five people) is currently affected by at least one primary minor immunodeficiency. This contradicts the established but erroneous view of the rarity of primary immunodeficiencies in humans.Therefore, the diagnosis of primary minor immunodeficiencies should be an integral part of modern routine medical practice of specialists in various fields. This article presents the classification of minor primary human immunodeficiencies, considers the differences between major and minor immune dysfunctions, as well as the algorithm of clinical diagnosis of primary minor immunodeficiencies and modern approaches to treatment.Detection of genetically determined disease of the immune system can not only explain the atypical course of opportunistic or low virulent infections of the urogenital tract and reduced fertility, but can also open the way to the appointment of targeted immunotherapy to compensate for the causative immunodeficiency. This can take the effectiveness of the applied interventions to a qualitatively new level, solving even severe clinical problems.

The revised pancreatitis etiology-based classification system TIGAR-O, version 2: adaptation for the Russian clinical practice

The discoveries in molecular genetics and breakthrough visualization techniques in the last 20 years have changed our understanding of the pancreatitis causes and biomarkers, expanded our knowledge on the pathophysiology of the disease, and promoted the development of new additional conservative treatments. From the practical perspective, the physician's comprehension of the etiology is of particular importance. It is for this reason that the activities to elaborate an etiology-based classification of pancreatitis have been already started since long ago. The first internationally acknowledged system was TIGAR-O checklist, introduced in 2001. Being innovative at the time, it structured our understanding of the etiology of chronic pancreatitis. The revised version (version 2) was published in 2019 and is less known to the Russian medical community, although from the authors' point of view, it has been substantially extended and structured to be maximally convenient and useful for physicians in routine medical practice. The review presents key provisions of the TIGAR-O, version 2 and recommendations for its adaption to the Russian clinical setting.