An update on cardiac enzymes

Determination of plasma total and MB CK concentration provides accuracy superior to any other currently available method for the diagnosis of acute MI. Nevertheless, elevation of MB CK is occasionally detected in the absence of acute MI for several reasons, some of them assay-dependent; consequently, the clinician should suspect a noncardiac source of MB CK or a spurious result if assay determinations are discordant with the clinical setting. In addition to providing precise diagnosis of acute MI, quantitative MB CK assays can also be used to obtain an accurate estimate of infarct size. In recent years, accuracy in the diagnosis of acute MI has assumed even greater importance, since the choice and timing of a variety of diagnostic and therapeutic options following coronary care unit admission hinge on whether infarction has occurred. Furthermore, the advent of thrombolytic therapy of acute MI has emphasized the need for more sensitive biochemical markers of necrosis in the first hours; the newly discovered subforms of MM and MB CK show promise as a means of proving an early diagnosis of acute MI and also as a means of assessing reperfusion noninvasively.     

心脏淀粉样变性的诊断进展

淀粉样变性是由于淀粉样蛋白沉积在细胞外基质,造成沉积部位组织和器官损伤的一组疾病,出现心脏受累时即为心脏淀粉样变性,该病病情重、进展快、治疗困难、病死率高,但临床少见且识别率低。本文着重叙述其诊断手段和相关进展,并对诊断流程进行了归纳,以协助临床了解并正确诊断该病,使患者获得及时治疗并从中获益。     

Neuromuscular blockade in cardiac surgery: an update for clinicians

There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary) sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.     

An update on bisphosphonates

Over the past 15 years, bisphosphonates have been demonstrated as effective therapy for the treatment of osteoporosis based on their ability to suppress bone turnover resulting in increased bone mineral content and increased bone strength. The mechanism of action at the cellular level has been identified, and the more potent nitrogen-containing bisphosphonates clearly have reduced the risk of vertebral and nonvertebral fractures in patients with osteoporosis. Future use of these therapies is evolving to less frequent administration, and the interaction with anabolic therapies is presently being defined. Data to date support long-term safety with bisphosphonates in small numbers of patients treated for 5 to 10 years, and continued vigilant follow-up of the post-marketing experience will be necessary to determine if sustained bone turnover suppression is associated with rare musculoskeletal adverse events. Further development of bisphosphonates as adjunctive therapy to reduce bone metastases is in progress, and trials evaluating bisphosphonates as a structure modifying agent in osteoarthritis are nearing completion.     

An update on bronchiectasis

Bronchiectasis is associated with heterogeneous predisposing conditions that cause abnormal dilatation and persistent inflammation in the bronchial tree and lung parenchyma. The disease remains a common cause of significant morbidity and mortality, especially when associated with hereditary disorders such as cystic fibrosis, ciliary dyskinesia, and immunodeficiency states. Recent investigations have focused on the inflammatory mediators involved in the pathogenesis of bronchiectasis. High-resolution computed tomography is now the diagnostic modality of choice and may also contribute to clinical management. Computed tomography and high-resolution computed tomography have identified bronchiectasis in individuals with HIV and alpha-1-antitrypsin deficiency. Early identification of predisposing disorders and aggressive management of symptoms has already been demonstrated by prolonged survival and decreased morbidity in cystic fibrosis patients, and similar management may benefit other populations with bronchiectasis. New treatments such as recombinant human DNase have been shown to improve pulmonary function and quality of life in cystic fibrosis patients and may prove useful in other chronic inflammatory lung disease.     

An update on gout

Gout is the most common cause of inflammatory arthritis in men aged more than 50, affecting approximately 1–2% of adult men in the Western world. The incidence and prevalence of gout is on the rise. Increasing longevity, dietary trends, obesity, metabolic syndrome, hypertension, increased use of low-dose aspirin, major organ transplantation and increased survival from coronary artery disease and end-stage renal disease have been implicated as the possible contributory factors. By far, the commonest cause of hyperuricaemia (that accounts for 90% of patients with gout) is decreased renal clearance. Patients with gout should avoid excess of alcohol (beer and spirits, particularly), red-meat and sea-food. Vegetarian food and dairy products reduce the risk of gouty arthritis. For the treatment of acute gout, options include non-steroidal antirheumatic drugs (NSAIDs), steroids (systemic or intra-articular) and colchicine. High dose of colchicine often results in diarrhoea and should be best avoided. Most patients respond within 18 hours to a dose of 0.5 mg twice daily. Colchicine is contraindicated if creatinine clearance is lower than 30 ml/min. Optimal treatment of chronic gout requires long-term reduction of serum urate to the lower half of the normal uric acid reference range. Prevention of attacks requires modification of lifestyle factors such as weight loss, moderation in the consumption of alcohol and meat and withdrawal of drugs known to cause elevated uric acid levels. Drugs used for chronic gout can be divided in three categories: (a) Uricostatic (xanthine oxidase inhibitor), e.g. allopurinol, oxipurinol, febuxostat, (b) Uricosuric, e.g. benzbromarone, sulfinpyrazone, probenecid, losartan, fenofibrate and (c) Uricolytic, e.g. uricozyme, rasburicase. Febuxostat is a new oral xanthine oxidase inhibitor, which has been shown to be more powerful in lowering uric acid levels compared to allopurinol. The drug is mainly metabolised by the liver and can be used in renal and hepatic insufficiency with no dose adjustment. Benzbromarone is an excellent uricosuric agent. Pegylated uricase is currently under development.     

An update on cardio-oncology

Over the past decades, there have been great advancements in the survival outcome of patients with cancer. As a consequence, treatment regimens are being extended to patient populations that would not have qualified in the past based on comorbidities and age. Furthermore, the anti-cancer regimens, which have been and are being used, can cause considerable morbidity and even mortality. In fact, new drugs such as tyrosine kinase inhibitors have yielded unanticipated side effects in frequency and severity. The cardiovascular disease spectrum is an important element in all of these. In order to optimize the outcome of cancer patients with cardiovascular diseases existing prior to cancer treatment or developing as a consequence of it, a new discipline called “cardio-oncology” has evolved over the past few years. Herein, we review the latest developments in this field including cardiotoxicities, vascular toxicities, and arrhythmias. This field is taking on more shape as cardiologists, oncologists, and hematologists are forming alliances, programs, and clinics, supported by the development of expert consensus statements on best management approaches and care of the cancer patient with cardiovascular diseases.     

An update on hypercoagulable disorders

Venous thrombosis is a cause of considerable morbidity and is often responsible for chronic venous disorders that frequently lead to visits to dermatologists and others involved in wound healing. Over the past several years, many new causes of thrombophilia have been identified and have dramatically altered the approach to patients presenting with thrombosis. Newly described abnormalities associated with thrombophilia include the syndrome of activated protein C resistance, the prothrombin 20210A mutation, hyperhomocysteinemia, and elevated levels of coagulation factors VIII and XI. Clinicians can now frequently determine causes of thromboses that have previously been deemed idiopathic.     

An update on glucocorticoid-induced osteoporosis

PURPOSE OF REVIEW: Glucocorticoids are widely used, often long term, and a major side effect is osteoporosis and increased risk of fracture. This review considers how common is the problem, the patients who are most at risk, our current understanding of mechanisms, and how to prevent and effectively treat glucocorticoid-induced osteoporosis. The actions currently being undertaken in clinical practice are reviewed. RECENT FINDINGS: Glucocorticoid-induced osteoporosis is an increasing problem that occurs not only in those on high-dose therapy. Advances in our knowledge of the cellular and cytokine mechanisms of bone turnover and glucocorticoid mechanisms of action are leading to a better understanding of how glucocorticoids affect bone cells and novel ways of prevention. Although there are effective treatments to prevent and control glucocorticoid-induced osteoporosis as well as guidelines for their use, they are still not being applied in routine clinical practice. SUMMARY: Glucocorticoid-induced osteoporosis is a significant problem. Although our understanding of effective prevention and treatment strategies is improving, there needs to be better implementation of these strategies.     

An update on diastolic dysfunction

Diastolic dysfunction refers to abnormal diastolic filling properties of the left ventricle regardless of whether systolic function is normal or the patient has symptoms. Diastolic heart failure (HF), or more accurately, HF with preserved systolic function, is a distinct clinical entity characterized by the presence of the triad of impaired diastolic function, normal systolic function (left ventricular ejection fraction > 50%), and symptoms of HF. Patients with HF with preserved systolic function are frequently symptomatic from both acute and chronic elevations in left ventricular end-diastolic pressure and/or left atrial pressure.     

An update on drug-induced arthritis

A large and heterogeneous group of drugs can cause drug-induced arthritis. No single pathogenetic mechanism or drug class unifies these diverse culprits. Recognizing that joint symptoms may, in fact, be drug-related not only saves time and unnecessary investigations but can also prevent needless suffering and morbidity due to late recognition of a drug-induced arthritic condition. The extent of drug-induced arthritis is variable and ranges from minor short-lived and reversible arthralgia to a prolonged and occasionally destructive arthritis. The onset of arthritis due to various medications in relation to the timing of drug initiation is also variable and may range from a few days to several months.     

An update on cirrhotic cardiomyopathy

Introduction: Cirrhosis with portal hypertension and related complications are associated with a high mortality. Excess of circulating vasodilators and cardiodepressive substances lead to a hyperdynamic circulation with changed myocardial structure and function. The entity cirrhotic cardiomyopathy seems to be involved in different aspects of hepatic decompensation, which focuses on new targets of treatment.

Areas covered: This review deals with contemporary aspects of cirrhotic cardiomyopathy, and the literature search was undertaken by PubMed with ‘cirrhotic’ and ‘cardiomyopathies’ as MeSH Terms. Cirrhotic cardiomyopathy is defined as the presence of systolic and diastolic dysfunction and electrophysiological abnormalities. The diagnosis is based on contemporary Doppler/Echocardiography measurements or quantitative magnetic resonance imaging. Cirrhotic cardiomyopathy is independent of the etiology of the liver disease but related to severity and survival.

Expert commentary: The outcome of invasive procedures and liver transplantation is influenced by the presence of cardiac dysfunction. Therefore, a cautious cardiac evaluation should be included in the patient evaluation prior to liver transplantation. Liver transplantation ameliorates most of the abnormalities seen in cirrhotic cardiomyopathy, but no specific treatment can yet be recommended.     

An update on glucocorticoid-induced osteoporosis

In general, bone loss from glucocorticoid treatment occurs rapidly within the first 6 months of therapy. Glucocorticoids alter bone metabolism by multiple pathways; however, the bone loss is greatest in areas rich in trabecular bone. Preventive measures should be initiated early. It is the author's opinion that all subjects initiating treatment with prednisone at 7.5 mg or greater require calcium supplementation (diet plus supplement) at a dose of 1500 mg and vitamin D at a dose of 400 to 800 IU/d. If the patient is going to remain on this dose of glucocorticoid for more than 4 weeks, an antiresorptive agent should be started (e.g., estrogen, bisphosphonate, raloxifene). If a patient has established osteoporosis and is either initiating glucocorticoid therapy or is chronically treated with prednisone at 5 mg d or greater in addition to calcium and vitamin D supplementation, a potent antiresorptive agent (bisphosphonate) should be started. A bone mineral density measurement of either the lumbar spine or the hip may be helpful is assessing an individual's risk of osteoporosis, may improve compliance with treatment, and can be used to monitor the efficacy of the prescribed therapy. There is no reason to withhold treatment for glucocorticoid-induced bone loss until a bone mass measurement is taken, however. In motivated patients, a weight-bearing and resistance exercise program should be prescribed to help retain muscle strength and prevent depression. If hypercalciuria develops with glucocorticoid use, either thiazide diuretics or sodium restriction may be helpful. In patients who continue to lose bone or experience fracture's despite antiresorptive therapy while on glucocorticoids, bone-building anabolic agents (e.g., hPTH 1-34 or PTH 1-84) may be available someday soon.     

An update on primary hyperoxaluria

The autosomal recessive inherited primary hyperoxalurias types I, II and III are caused by defects in glyoxylate metabolism that lead to the endogenous overproduction of oxalate. Type III primary hyperoxaluria was first described in 2010 and further types are likely to exist. In all forms, urinary excretion of oxalate is strongly elevated (>1 mmol/1.73 m(2) body surface area per day; normal <0.5 mmol/1.73 m(2) body surface area per day), which results in recurrent urolithiasis and/or progressive nephrocalcinosis. All entities can induce kidney damage, which is followed by reduced oxalate elimination and consequent systemic deposition of calcium oxalate crystals. Systemic oxalosis should be prevented, but diagnosis is all too often missed or delayed until end-stage renal disease (ESRD) occurs; this outcome occurs in >30% of patients with primary hyperoxaluria type I. The fact that such a large proportion of patients have such poor outcomes is particularly unfortunate as ESRD can be delayed or even prevented by early intervention. Treatment options for primary hyperoxaluria include alkaline citrate, orthophosphate, or magnesium. In addition, pyridoxine treatment can be used to normalize or reduce oxalate excretion in about 30% of patients with primary hyperoxaluria type I. Time on dialysis should be short to avoid overt systemic oxalosis. Transplantation methods depend on the type of primary hyperoxaluria and on the particular patient, but combined liver and kidney transplantation is the method of choice in patients with primary hyperoxaluria type I and isolated kidney transplantation is the preferred method in those with primary hyperoxaluria type II. To the best of our knowledge, progression to ESRD has not yet been reported in any patient with primary hyperoxaluria type III.     

An update on vaginal microbicides

In response to an increasing prevalence of sexually transmitted diseases, especially AIDS, efforts to prevent further infections have been heightened. One of those approaches has been the development of topical microbicidal agents or microbicides. These are compounds designed to protect the body’s mucosal surfaces from infection by sexually transmitted disease-causing pathogens. Numerous candidates are currently in preclinical stages; however, only a handful have been tested for safety, and even fewer are ready for clinical efficacy trials. In this update, we describe some of the specific features of microbicide research and development, including preclinical screening algorithms, candidate’s ideal properties, examples of compounds presently in the pipeline, and future prospects.     

An update on iron physiology

Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron （1-2 mg/d） is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis （20-30 mg/d）. Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency （ID） and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores （functional ID）, and anemia of chronic disease （ACD）, which can evolve to ACD plus true ID （ACD ＋ ID）. In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia.