Amyloidosis: A changing clinical perspective

Primary amyloidosis is a plasma cell dyscrasia characterised by excess production of abnormal immunoglobulin light chains with their subsequent accumulation in kidneys, heart, liver as well as gastrointestinal tract and bone marrow [1–2]. These tissue deposits take the form of a fibrillar protein which damages the involved organ in proportion to the extent of the infiltration and roughly parallels the duration of the disease. Most cases have evidence of the underlying lymphoplasmacytoid neoplasm recognisable in two ways. Firstly, the monoc1one appears in the serum [2]. Secondly is a morphologically and immunohistochemically distinctive cellular infiltrate in the bone marrow [3] that has a specific microscopic and ultrastructural pattern [4–5]. Interestingly occasional patients, who survive long enough, may progress to multiple myeloma [6] but the correlation is variable [7].     

Exercise induced asthma: A clinical perspective

Exercise is a very common precipitant of asthma. Inflammation and edema are felt to be important components of the asthmatic response. Heat and water loss from the airway mucosa are most likely important in its pathogenesis, although the exact etiology remains unknown. A good history combined with proper diagnostic testing can usually determine the diagnosis, and prevention is the key to effective management. Although modified training techniques are often helpful, medications are usually needed for both prevention and treatment. While antiinflammatory agents are gaining therapeutic importance, inhaled beta-agonists remain the treatment of choice. With appropriate diagnosis and management, exercise-induced asthma should not limit participation nor performance in athletics for the great majority of the population. Offprint requests to: K. Gleeson     

Management of alcoholic hepatitis: A clinical perspective

Alcohol-associated liver disease is the primary cause of liver-related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol-associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short-term mortality. During the COVID-19 pandemic, rates of alcohol-associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol-associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short-term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology-based therapeutic approaches include anti-inflammatory agents, modifications of the gut-liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient-centred treatment approaches to improve prognosis.     

Autoantibodies in chronic hepatitis C: A clinical perspective

Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus(HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of glutenrelated seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon(IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmunedisease may be present or may be precipitated by IFNbased HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations.     

A clinical cardiology perspective of thrombophilias

Thrombophilias, an inherited and/or acquired predisposition to vascular thrombosis beyond hemostatic needs are common in cardiovascular medicine and include systemic disorders such as coronary atherosclerosis, atrial fibrillation, exogenous obesity, metabolic syndrome, collagen vascular disease, human immunodeficiency virus, blood replacement therapy and several commonly used medications. A contemporary approach to patients with suspected thrombophilias, in addition to a very selective investigation for gain-of-function and loss-of-function gene mutations affecting thromboresistance, must consider prevalent diseases and management decisions encountered regularly by cardiologists in clinical practice. An appropriate recognition of common disease states as thrombophilias will also stimulate platforms for much needed scientific investigation.     

Ximelagatran: a clinical perspective

Ximelagatran is a novel oral anticoagulant belonging to a class of drugs known as direct thrombin inhibitors. Numerous recent large-scale, randomised controlled clinical trials have given the drug a large clinical platform. These include data on the thromboprophylaxis of venous thromboembolism following major orthopaedic surgery and knee arthroscopy, as well as in the treatment of deep vein thrombosis and prevention of stroke with nonvalvular atrial fibrillation. One phase II study has also shown the efficacy and safety of ximelagatran in secondary prevention post-myocardial infarction. Unfortunately, approximately 6% of patients develop usually self-limiting derangement of liver dysfunction, and frequent monitoring of liver function is likely to be recommended for the first 6 months of treatment. Unlike the vitamin K antagonists, ximelagatran has a wide therapeutic interval with few food, alcohol or drug interactions, and it does not require anticoagulant monitoring. The aim of this overview is to review the clinical trials pertaining to this new drug, which is the first new oral anticoagulant for over 60 years, and one that is likely to influence our management of thrombosis-related disorders.     

Gastrointestinal motility problems in critical care: A clinical perspective

Advances in surgery, anesthesia and intensive care have led to a dramatic increase in the number of patients who spend time in our intensive care units (ICU). Gastrointestinal (GI) motility disorders are common complications in the intensive care setting and are predictors of increased mortality and length of the stay in the ICU. Several risk factors for developing GI motility problems in the ICU setting have been identified and include sepsis, being on mechanical ventilation and the use of vasopressors, opioids or anticholinergic medications. Our focus is on the most common clinical manifestations of GI motor dysfunction in the ICU patient: gastroesophageal reflux, gastroparesis, ileus and acute pseudo‐obstruction of the colon.     

A review of venous thromboembolism in COVID-19: A clinical perspective

Coronavirus disease-19 (COVID-19) started in Wuhan, China in December 2019 and spread to all around the world in a short period of time. Hospitalized patients with COVID-19 mostly could suffer from an abnormal coagulation activation risk with increased venous thrombosis events and a poor clinical course. The reported incidence rates of thrombotic complications in hospitalized COVID-19 patients vary between 2.6 and 85% (both in non-critically ill and critically ill patients). The risk of venous thromboembolism is not known in non-hospitalized patients with COVID-19. There are numerous studies and guidelines for administration of thromboprophylaxis for COVID-19 cases. All hospitalized COVID-19 patients should take pharmacological thromboprophylaxis if there is no contraindication. However, there is no consensus on this issue. In this review, we discussed all these approaches in a critical perspective.     

Ambulatory electrocardiography. A clinical perspective.

Advances in modern technology have made it possible to record and analyze the electrocardiographic data of ambulatory persons for as many as 24 h or more. This capability and an increasing awareness of cardiac dysrhythmias and myocardial ischemia as a cause of morbidity and mortality have led to the more widespread use of ambulatory electrocardiography in the examination of patients for various clinical conditions. From a clinical viewpoint, we review and summarize the present state-of-the-art of ambulatory electrocardiography and discuss when such studies are indicated, frequently warranted, or may be useful.     

Amyloidosis: a changing clinical perspective

Primary amyloidosis is a plasma cell dyscrasia characterised by excess production of abnormal immunoglobulin light chains with their subsequent accumulation in kidneys, heart, liver as well as gastrointestinal tract and bone marrow 1-21, 2. These tissue deposits take the form of a fibrillar protein which damages the involved organ in proportion to the extent of the infiltration and roughly parallels the duration of the disease. Most cases have evidence of the underlying lymphoplasmacytoid neoplasm recognisable in two ways. Firstly, the monoclone appears in the serum [2]. Secondly is a morphologically and immunohistochemically distinctive cellular infiltrate in the bone marrow [3] that has a specific microscopic and ultrastructural pattern 4-54, 5. Interestingly occasional patients, who survive long enough, may progress to multiple myeloma [6] but the correlation is variable [7].     

Rheumatoid cachexia: a clinical perspective

Rheumatoid cachexia is under-recognized in clinical practice. The loss of lean body tissue, which characterizes cachexia, is often compensated for by gain in body fat-so called 'cachectic obesity'-so that 85% or more RA patients have a normal BMI. Severe cachexia with loss of weight leads to increased morbidity and premature mortality but loss of muscle bulk with a normal BMI also associates with poor clinical outcomes. Increasing BMI, even into the obese range, is associated with less joint damage and reduced mortality. Measurement of body composition using DXA and other techniques is feasible but the results must be interpreted with care. Newer techniques such as whole-body MRI will help define with more confidence the mass and distribution of fat and muscle and help elucidate the relationships between body composition and outcomes. Cachexia shows little response to diet alone but progressive resistance training and anti-TNF therapies show promise in tackling this potentially disabling extra-articular feature of RA.     

New insights into central nervous system lupus: A clinical perspective

Patients with systemic lupus erythematosus (SLE) experience a wide array of neurologic (N) and psychiatric (P) events, some of which are directly attributable to lupus. Regardless of attribution, NP events have a significant impact on individual patient’s health-related quality of life. Primary immunopathogenic mechanisms of NP-SLE include vasculopathy, autoantibody production, and intrathecal inflammatory mediators. The recently described anti-NR2 glutamate receptor antibodies have been implicated in animal models of neuronal injury, but their role in the pathogenesis of human NP-SLE is unclear. The diagnosis of NP-SLE remains largely one of exclusion, although the detection of select autoantibodies, CSF analysis, and appropriate use of neuroimaging and neuropsychometric testing may provide support in the evaluation of individual patients. Therapeutic options include symptomatic therapies, immunosuppression, and anticoagulation.     

Factors determining heterogeneity in coronary collateral development: A clinical perspective

The mechanisms responsible for collateral development have attracted considerable attention in cellular and molecular research because these vessels have the capacity to protect against myocardial infarction and reduce exercise-induced ischemia. This has led to a number of phase I trials employing angiogenic peptides, genes and cell transplantation. However, there are significant differences in the degree of collateral development among patients even with similar patterns of coronary disease. Understanding the factors responsible for this heterogeneity has important implications for the efficacy of future therapeutic strategies. Therefore, this review will examine these factors from the clinical perspective integrating the clinical evidence with recent molecular and cellular studies. The role of specific pharmacological agents and novel investigational strategies will be discussed.     

A clinical perspective of parathyroid hormone related hypercalcaemia

Reviews in Endocrine and Metabolic Disorders - There are many causes of hypercalcaemia including hyperparathyroidism, drugs, granulomatous disorders and malignancy. Parathyroid hormone (PTH)...     

Silent myocardial ischemia. A clinical perspective.

Silent myocardial ischemia has been shown to occur far more frequently than anginal episodes in patients with coronary artery disease. Both an increase in myocardial oxygen demand and abnormalities of coronary vasomotor tone appear to play a significant role in the genesis of silent ischemia. Recent data show that in excess of 40% of patients with stable angina have frequent episodes of silent ischemia. The presence of silent ischemia predicts an increased risk of coronary events and cardiac death. Based on these data, it has been proposed that anti-ischemic therapy should be directed toward control of total ischemic burden. Although several recent studies have demonstrated efficacy of various antianginal drugs in reducing the number and duration of silent ischemic episodes, none has demonstrated beneficial effect on the associated adverse prognosis.