[Tobacco and tuberculosis: the nature of the links and the consequences of this association]. / Tabac et tuberculose : nature des liens et conséquences de cette association.

Tuberculosis and smoking are responsible for significant mortality worldwide. Smoking is spreading in emerging countries, and its prevalence is high in developed countries among socially disadvantaged populations; it could be the source of a resurgence of tuberculosis in future years. The aim of this review is to clarify the consequences of the association between smoking and tuberculosis, and the benefits of smoking cessation for smokers with tuberculosis.

[State of the art on the pathophysiology, diagnosis and treatment of non-alcoholic steatohepatitis (NASH)]. / État des lieux sur la physiopathologie, le diagnostic et les traitements de la stéato-hépatite non alcoolique (NASH).

NAFLD or non-alcoholic fatty liver disease is one of the complications of obesity and diabetes, the prevalence of which is increasing. The causes of the pathology and its development towards its severe form, NASH or non-alcoholic steatohepatitis, are multiple and still poorly understood. Many different pharmacological classes are being tested in clinical trials to treat NASH, but no pharmaceutical treatment is currently on the market. Moreover, the diagnosis of certainty is only possible by liver biopsy and histological analysis, an invasive procedure with high risk for the patient. It is therefore necessary to better understand the natural history of the disease in order to identify therapeutic targets, but also to identify markers for the diagnosis and monitoring of the disease using a blood sample, which will allow an improvement in patient management.

[The basophil: From control of immunity to control of leukemias]. / Le polynucléaire basophile : du contrôle de l'immunité à celui des leucémies.

The basophils, first described by Paul Ehlrich in 1879, are rare circulating cells, representing approximately 0.01 to 0.3% of the blood leukocytes. Until recently, these cells have been neglected because of their minority status among immune cells and because they show some similarities to mast cells residing in tissues. However, basophils and mast cells are now recognized as distinct cell lines and it appears that basophils have important and non-redundant functions, distinct from those of mast cells. On the one hand, basophils have beneficial contribution to protective immunity, in particular against parasitic infections. On the other hand, basophils are involved in the development of various benign and malignant pathologies, ranging from allergy to certain leukemias. Basophils interact with other immune cells or neoplastic cells through direct contacts or soluble mediators, such as cytokines and proteases, thus contributing to the regulation of the immune system but also to allergic responses, and probably to the process of neoplastic transformation. In this review, we will develop recent knowledge on the involvement of basophils in the modulation of innate and adaptive immunity. We will then describe the benign or malignant circumstances in which an elevation of circulating basophils can be observed. Finally, we will discuss the role played by these cells in the pathophysiology of certain leukemias, particularly during chronic myeloid leukemia.

[Anaphylaxis and pathophysiology]. / Physiopathologie de l'anaphylaxie.

Anaphylaxis is the most severe of the allergic hypersensitivity reactions. It is caused by the release of mediators from blood components such as mast cells and basophils into the bloodstream. Anaphylaxis is a common disease, its diagnosis is clinical and, given its pathophysiology, the treatment of choice is adrenaline.

COVID-19 pathophysiology and pharmacology: what do we know and how did Canadians respond? A review of Health Canada authorized clinical vaccine and drug trials.

Coronavirus disease 2019 (COVID-19) has resulted in the death of over 18 000 Canadians and has impacted the lives of all Canadians. Many Canadian research groups have expanded their research programs to include COVID-19. Over the past year, our knowledge of this novel disease has grown and has led to the initiation of a number of clinical vaccine and drug trials for the prevention and treatment of COVID-19. Here, we review SARS-CoV-2 (the coronavirus that causes COVID-19) and the natural history of COVID-19, including a timeline of disease progression after SARS-CoV-2 exposure. We also review the pathophysiological effects of COVID-19 on the organ systems that have been implicated in the disease, including the lungs, upper respiratory tract, immune system, central nervous system, cardiovascular system, gastrointestinal organs, the liver, and the kidneys. Then we review general therapeutics strategies that are being applied and investigated for the prevention or treatment of COVID-19, including vaccines, antivirals, immune system enhancers, pulmonary supportive agents, immunosuppressants and (or) anti-inflammatories, and cardiovascular system regulators. Finally, we provide an overview of all current Health Canada authorized clinical drug and vaccine trials for the prevention or treatment of COVID-19.

[Histopathological features due to the SARS-CoV-2]. / Les lésions histologiques associées à l'infection par le SARS-CoV-2.

The infection due to the SARS-CoV-2 leads lesions mainly observed at the respiratory tract level, but not exclusively. The analyses of these lesions benefited from different autopsy studies. Thus, these lesions were observed in different organs, tissues and cells. These observations allowed us to rapidly improve the knowledge of the pathophysiological mechanisms associated with this emergent infectious disease. The virus can be detected in formalin fixed paraffin embedded tissues using immunohistochemistry, in situ hybridization, molecular biology and/or electron microscopy approaches. However, many uncertainties are still present concerning the direct role of the SARS-CoV-2 on the different lesions observed in different organs, outside the lung, such as the heart, the brain, the liver, the gastrointestinal tract, the kidney and the skin. In this context, it is pivotal to keep going to increase the different tissue and cellular studies in the COVID-19 positive patients aiming to better understanding the consequences of this new infectious disease, notably considering different epidemiological and co-morbidities associated factors. This could participate to the development of new therapeutic strategies too. The purpose of this review is to describe the main histological and cellular lesions associated with the infection due to the SARS-CoV-2.

[Synkinesis in facial palsy: What do we know about the physiopathology?] / Syncinésies dans la paralysie faciale : que savons-nous de la physiopathologie ?

INTRODUCTION: Synkinesis is a disabling sequelae of facial palsy, which worsens facial asymmetry and diminishes the patients' quality of life. Their physiopathology is partially known, but cannot explain all the synkinesis. MATERIAL AND METHODS: We report a literature review of the state of the art concerning the knowledge on synkinesis physiopathology, as well as their management. RESULTS: It is accepted that the physiopathological mechanism of synkinesis is mixed. The phenomena of cerebral plasticity, aberrant nerve regrowth, hyperexcitability of the facial nerve nucleus and ephaptic nerve transmission, have been observed. We propose a new physiopathological hypothesis: synkinesis could be the consequence of latent circuits activation, preexisting in the healthy subject. We could propose three potential latent circuits: physiological synergistic contractions, adjacent motor units recruitment, and reactivation of remote latent circuits for function compensation. The treatment options are multiple, dominated by chemodenervation, whose effectiveness is undeniable. Rehabilitation has also proven its effectiveness, particularly with feedback techniques. Finally, surgery helps with these options. However, the indications of the different treatments remain to be codified. CONCLUSION: The validation of our physiopathological hypothesis would allow a better understanding and a better screening of synkinesis, in order to propose a more adapted treatment.

[Idiosyncratic drug-induced agranulocytosis: 7 year-analysis in a French university hospital]. / Agranulocytoses médicamenteuses idiosyncrasiques : analyse de 7 ans dans un hôpital universitaire français.

INTRODUCTION: Idiosyncratic drug-induced agranulocytosis is a rare but potentially serious haematological disorder. The pathophysiological mechanisms are complex and poorly understood. We aimed at investigating agranulocytosis drug related causes from the myelograms with "myeloid maturation arrest" performed in our university hospital over the last seven years. METHODS: A retrospective analysis of myelograms collected for agranulocytosis was performed from 1st January 2010 to 31th December 2016. We used the method of Bégaud et al. for drug causality assessment. RESULTS: Among the 104 myelograms analysed, 41 agranulocytosis were drug-induced, whose 28 were idiosyncratic. Among these 28 cases, 26 different drugs were involved. Agranulocytosis was a known adverse reaction in the summary of the product characteristics for 24 drugs, mainly associated with undetermined frequency (n=7). Mean onset latency was 38.1 days after starting the drug (calculated for n=23 cases) and granulocyte growth factors were used in 50% of cases without shortening the mean delay of blood count recovery. Bone marrow presented hypereosinophilia in 29% of cases. Pharmacovigilance reporting rate was 48%. CONCLUSION: A "maturation arrest" in the myelogram is not pathognomonic for idiosyncratic drug-induced agranulocytosis. This rare event require multidisciplinary care involving haematologists, biologists and pharmacovigilance experts. Agranulocytosis reporting rate was high compared with usual adverse drug reaction reporting rate (5 to 10%), probably related to the potential severity of this event.

[Pathophysiology of overactive bladder]. / Physiopathologie du syndrome clinique d'hyperactivité vésicale.

INTRODUCTION: The pathophysiology knowledge of the overactive bladder syndrome has evolved considerably over the past 20 years. The objective of this work was, from a review of the literature, to synthesize current knowledge on the pathophysiology of the overactive bladder syndrome. METHOD: A systematic review based on Pubmed, Embase, Google Scholar, was conducted in February 2020 using the keywords "overactive bladder" and "pathophysiology". RESULTS: Four pathophysiological mechanisms involved in the overactive bladder syndrome development can be described. They include the detrusor muscle dysfunction, an urothelial or sub-urothelial origin, a neurological origin and a change in the urinary microbiome. At the same time, it should be noted that all of the pathophysiological mechanisms described above are favored by different clinical conditions such as aging, ischemia, metabolic syndrome, menopause and the dysfunction of other abdominopelvic systems. CONCLUSION: The pathophysiology of the overactive bladder syndrome is complex and includes several mechanisms most often associated.

[Focus on cystic fibrosis]. / La mucoviscidose, mise au point.

Cystic fibrosis is a genetic disease whose most common symptoms are of respiratory nature. Mortality has been drastically reduced through better treatment of the various symptoms. Life expectancy at birth is currently over 50 years.

[Physical activity in patients with schizophrenia: From neurobiology to clinical benefits]. / L'activité physique chez les patients atteints de schizophrénie : de la neurobiologie aux bénéfices cliniques.

Schizophrenia is a severe chronic mental disorder that mainly manifests by positive symptoms, negative symptoms, disorganized behavior and thought and cognitive impairments. Taken together, these symptoms have substantial impact on quality of life, well-being and functional outcome. Patients with schizophrenia have dramatically higher levels of cardiovascular and metabolic morbidity than the general population due to poor physical fitness and to sedentary lifestyle. They have a reduced life expectancy, and an excess mortality being two or three times more than that in the general population. Moreover, despite major therapeutic advances in the overall management of these patients, some symptomatic dimensions, and more specifically the negative and cognitive ones, remain to be resistant to the usual pharmacological approaches. Moreover, antipsychotics can also reinforce the global cardiovascular risk due to side effects and low neurometabolic tolerance. The benefits of physical activity on health are now well described in the general population and in many medical diseases. More recently, physical activity has also found its place as an adjuvant therapy in severe mental illnesses, particularly in schizophrenia. In the literature physical activity programs, in addition to pharmacological treatments, appear to be feasible in patients and improve both physical and mental health as well as functional outcome. Clinical benefits of physical activity would be underpinned by biological and cerebral mechanisms, which remain unclear. In this review, we propose to present a state of the art and to present an update of the interests of physical activity in the management of patients with schizophrenia. We emphasize the clinical benefits of physical activity regarding the different symptomatic dimensions and its impact specifically on cognitive deficits. Finally, we describe the various underlying pathophysiological mechanisms in particular in the neurobiological, cerebral and physiological fields. We then discuss the barriers, facilitators and motivating factors towards physical activity to enhance health promotion initiatives, to optimize resource allocation when delivering physical activity programs in clinical practice, and to maximize physical activity participation. Physical activity appears to be an original and novel adjunctive therapeutic approach in the management of patients with schizophrenia and would both reduce schizophrenic symptoms and act like pro-cognitive therapy, improve quality of life and long-term functioning in daily life and reduce cardiovascular comorbidities. However, efforts are still needed to increase the motivating factors and adherence towards physical activity participation for people with schizophrenia.

Physiopathologie de la dermatite atopique: Pathophysiology of atopic dermatits.

Atopic dermatitis is a multifactorial disease due to a combination of genetic and environmental factors. The pathophysiological mechanisms involved in AD are multiple: innate functional abnormality in the skin barrier partly linked to mutations of the filaggrin, a major structural protein of the skin; and genes involved in innate and adaptive immunity; Finally, the model of the hygiene theory has been clarified in recent years: environmental factors alter the diversity of skin and digestive microbiomes, and this diversity seems to play a major role in the development of atopy.

[What's new in dermatological research?] / Quoi de neuf en recherche dermatologique ?

This manuscript provides a selection of dermatological research manuscripts published from September 2016 to August 2017. It is not an exhaustive review but rather a selection of manuscripts susceptible to modify the dermatological practice or affording new pathophysiologic mechanisms and new therapeutic approaches. The following areas of interest are concerned: recognition of dermatological images by artificial intelligence, new concepts in atopic dermatitis, wound repair and hair growth cycle. New data concerning melanomagenesis, epidermolysis bullosa simplex and drug eruption are also highlighted.

[Perstimulus asystole during electroconvulsive therapy: Clinical case and critical literature review]. / Asystolie perstimulus résultant d'une hypertonie parasympathique au cours des électroconvulsivothérapies : cas clinique, brève revue de la littérature et discussion.

INTRODUCTION: Electroconvulsive therapy (ECT) is most frequently indicated for episodes of melancholic depression, but is also useful in the treatment of maniac syndrome and some schizophrenia subtypes. ECT is part of the treatment of movement disorders, neuroleptic malignant syndrome and even in the treatment of severe conversions. Although the therapeutic results are excellent when used appropriately, the mortality rate is estimated between 2 and 4 for 100,000 shocks. Despite this mortality rate, the benefit-risk ratio remains very positive and serious complications are extremely rare. ECT results in a biphasic cardiological effect: firstly a perstimulus parasympathetic hypertonia contemporary to the seizure's tonic phase, then a phase of contemporary sympathetic hypertonia during the epileptic clonic movement. We will focus on the perstimulus asystole as it is by far the most frequent. Very few cases and even less studies have been referenced in the literature; here, we present a clinical case followed by a discussion. CLINICAL CASE: The patient is in his fifties and has been treated for many years for a unipolar mood disorder with recurrent melancholic depressive episodes. With each new depressive episode, the clinical evolution is rapidly positive after a few sessions of ECT. Maintenance ECT was not retained due to the supra-annual periodicity of the melancholic depressive episodes and rapid recovery after electric treatment. Then, this patient developed another depressive decline in mood comparable to the previous one, despite adapted blood lithium levels associated with a new generation antidepressant treatment. According to his history, a hospitalisation was programmed to carry out a new course of ECT. Considering the short duration of the first seizures, the intensity of the stimulus was progressively increased. At 180 joules, the patient presented an immediate per-stimulus asystole of 20seconds which ceased spontaneously. The specialized cardiologic consultation following the rhythmic episode was reassuring: the patient's cardiac condition remained stable. However, after discussion with the patient and his family, we decided to stop the ECT. Was this a reasonable decision? DISCUSSION: According to the literature, the patient's medical history, sex, psychiatric diagnosis, the shock parameters (level of energy applied, duration of the stimulus, number of shocks) and clinical results, are not predictive factors in the occurrence of an asystole. Concerning the ECT protocol, the vagus nerve seems less stimulated during bifrontal stimulations in opposition to unilateral stimulations. Perasystolic patients are younger and have less prior history of cardiovascular disease or ECG abnormalities. Although the patients receiving ECT are often taking several medications (antipsychotics, benzodiazepines, antidepressants, anticholinergic correctors, calcium channel blockers, loop diuretics, converting enzyme inhibitors), these drugs are not considered as facilitating asystoles. No increase in the frequency of asystole had been observed when taking an average dose psychotropic treatment allowing the continuation of an antidepressant treatment at the recommended dose. Differently, lithium is regularly stopped during the shock phase as it could - even a few days after being stopped - potentiate the effects of succinylcholine and increase the vagal tone. Succinylcholine seems to promote asystole, whilst caffeine, methohexital and trimethaphan do not. The hypersympathetic phase can be controlled by a betablocker (propranolol, esmolol, labetalol) that does not increase the prior risk of asystole. Anticholinergic premedication using atropine does not appear to be systematic and could even potentially induce tachy-dysarrhythmia. However, in the case of perstimulus asystole, most authors recommend continuing the shocks with doses of atropine around 0.4 to 1mg. PHYSIOPATHOLOGY: Vagal stimulation is preferentially central and directly linked to the electric excitation of the lateral dorsal motor nucleus of the vagus nerve. Younger patients with no cardiac history are more at risk. This could be explained by the fact that juvenile tissue conducts electricity more rapidly than senescent (the difference being probably due to the fibrosis and adipose tissue which reduce its conductive capacity). Finally, it is appropriate to question the direct therapeutic aspect of vagal stimulation which constitutes an experimental treatment of resistant depression. CONCLUSIONS: The occurrence of perstimulus asystole is not considered as a serious complication of ECT and therefore as a contra-indication to any future sessions. On the contrary, most authors are campaigning for the continuation of shocks with the possibility of adding prophylactic intravenous atropine. Cardiac arrest reminds us that ECT requires a special attention to its cardiovascular effect, which emphasizes the role of interdisciplinarity between anaesthesiologists and psychiatrists.

Fibrodysplasia ossificans progressiva. A case report and focus on the BMP signaling pathway.

Fibrodysplasia ossificans progressiva is a very rare heritable disease characterized by a progressive heterotopic endochondal ossification, occurring in the first decade of life, and leading thereafter to a severe ankylosis of the spine, limbs and jaw, with a progressive and severe functional disability. To date the cause of the disease remains unknown and no medical treatment has been proved efficient. It has recently been shown that a recurrent mutation in activation domain of the activin-receptor IA (ACVR1), a BMP receptor, could lead to an abnormal signalling pathway of BMP-4 and contribute to the occurrence of the devastating lesions characteristic of the disease.

Cellular and molecular mechanisms in the pathophysiology of systemic sclerosis.

Fibrosis is characterized by disproportionate accumulation of collagens and other extracellular matrix substances, resulting in organ dysfunction and failure. In systemic sclerosis, cellular and molecular mechanisms involved in the pathophysiology of fibrosis are highly complex and yet barely understood. Anatomopathological findings showed the coexistence of patchy inflammatory cell infiltration, microvascular injuries, and fibrotic foci. One of the most commonly accepted hypotheses considers endothelial activation as the triggering phenomenon inducing inflammatory and autoimmunity activation. The resulting cytokines and autoantibodies production accelerates the proliferating rate of normal fibroblasts and their transformation into myofibroblasts, leading to diffuse fibrosis. This review aims to focus on cellular and molecular mechanisms implicated in the fibrogenesis of systemic sclerosis.

News and controversies regarding essential tremor.

Essential tremor is the most common movement disorder in adults. It is characterized by a postural and kinetic tremor affecting the arms, but it can also affect other body parts. It evolves gradually and can be responsible for a functional impairment in activities of daily living. Its pathophysiology remains poorly understood and effective therapeutic options are limited. There are significant semiological variations between patients, and the term "essential tremor" seems to encompass a wide range of heterogeneous clinical phenotypes. The diagnostic criteria presented in 1998 are now challenged. Furthermore, there is a current debate concerning the etiology of this affection, as to whether essential tremor is a complex degenerative disorder or a functional reversible disorder of neuronal oscillation. In this review, we summarize some aspects of clinical, etiologic and therapeutic news, to better address the questioning on unravelling the clinical presentation and examine the current pathophysiological controversy in this disorder.

[Axillary web syndrome following axillary lymph node dissection for melanoma: 5 cases]. / Syndrome de la corde axillaire après chirurgie ganglionnaire dans un contexte de mélanome : 5 cas.

BACKGROUND: Axillary web syndrome is a rare disease similar to Mondor's disease and is usually seen after axillary surgery. Herein, we describe five new cases, all of which occurred in a setting of melanoma. PATIENTS AND METHODS: Five patients presented axillary web syndrome following sentinel node surgery, adenectomy or axillary curettage in a setting of melanoma. Therapy involving analgesics and physiotherapy to snap the cord-like structure helped accelerate resolution. DISCUSSION: Some debate continues to surround the physiopathology of axillary web syndrome in the literature, particularly regarding its relationship with Mondor's disease, which is considered to result from superficial venous thrombosis. The lymphatic and myofascial explanation for the syndrome appears to us to be more coherent and justifies the non-aggressive therapeutic approach we adopt for our patients, who receive assurances about the benign nature of their condition and the absence of sequelae. CONCLUSION: Axillary surgery in patients presenting melanoma appears to be a risk factor for axillary web syndrome. No relationship has as yet been demonstrated between this syndrome and the presence of axillary metastases.

Smoking and plastic surgery, part I. Pathophysiological aspects: update and proposed recommendations.

OBJECTIVES: Smoking patients undergoing a plastic surgery intervention are exposed to increased risk of perioperative and postoperative complications. It seemed useful to us to establish an update about the negative impact of smoking, especially on wound healing, and also about the indisputable benefits of quitting. We wish to propose a minimum time lapse of withdrawal in the preoperative and postoperative period in order to reduce the risks and maximize the results of the intervention. METHODS: A literature review of documents from 1972 to 2014 was carried out by searching five different databases (Medline, PubMed Central, Cochrane library, Pascal and Web of Science). RESULTS: Cigarette smoke has a diffuse and multifactorial impact in the body. Hypoxia, tissue ischemia and immune disorders induced by tobacco consumption cause alterations of the healing process. Some of these effects are reversible by quitting. Data from the literature recommend a preoperative smoking cessation period lasting between 3 and 8 weeks and up until 4 weeks postoperatively. Use of nicotine replacement therapies doubles the abstinence rate in the short term. When a patient is heavily dependent, the surgeon should be helped by a tobacco specialist. CONCLUSIONS: Total smoking cessation of 4 weeks preoperatively and lasting until primary healing of the operative site (2 weeks) appears to optimize surgical conditions without heightening anesthetic risk. Tobacco withdrawal assistance, both human and drug-based, is highly recommended.

[Psoriasis: physiopathology and immunogenetics]. / Le psoriasis: physiopathologie et immunogénétique.

Psoriasis is a multifactorial disease that involves genetic, immunological and environmental factors. During the last decade, several studies by genome scan on families or cases/controls helped to highlight more than ten loci "PSORS" located on different chromosomes and containing several candidate genes. Psoriasis appears as a genetic disease that follows the mixed model with the involvement of a major gene (PSORS1) and a set of minor genes with a variable penetrance depending on the locus. Genetic data have focused on the involvement of the immune system in the pathogenesis of psoriasis. It is now accepted that psoriasis is an immunological disease involving the response profiles TH1 and TH17. Much remains to be done to better elucidate the mechanisms involved in the genesis of psoriatic lesions to find new therapeutic targets.