Thrombophilias: when should we test and how does it help?

Venous thromboembolism can be a life-threatening event, occurring in ~1 in 1000 adults annually. An underlying cause for thrombosis can now be identified in up to 80% of cases, including both inherited and acquired causes of thrombophilia. In fact, it is often a combination of these risk factors that leads to the development of thrombosis. Knowing what these risk factors are for an individual patient can help with decisions regarding duration of anticoagulation, and how best to prevent a recurrent event. This article reviews both the inherited and the acquired causes of thrombophilia, focusing on the clinical scenarios in which these disorders should be suspected and on how to appropriately test for them when clinically indicated. By the conclusion of this article, the clinician should be equipped with an algorithm of how to approach a patient with a thromboembolic event, from decisions regarding which thrombophilia tests to order to how the results of these tests affect patient management.     

Which patient requires neuroendocrine assessment following traumatic brain injury,when and how?

Traumatic brain injury (TBI) is an important public health problem, particularly among young adults in industrialized countries. Hypopituitarism is a common occurrence among survivors of TBI and may contribute to the associated morbidity seen in the acute and chronic phases following injury. The available data suggest that survivors of moderate to severe TBI should undergo screening for hypopituitarism particularly in the first year after injury. This requires a close liaison between endocrinologists, neurosurgeons, neuropsychologists, intensive care and rehabilitation physicians. Patients who suffer milder forms of TBI should also be considered for endocrine evaluation if they exhibit any clinical features of pituitary hormone deficiencies.     

Chemotherapy-associated cardiotoxicity: how often does it really occur and how can it be prevented?

Cardiotoxicity remains the limiting factor for many forms of cancer therapy and is the focus of growing research and clinical emphasis. This article outlines the current clinical evidence for left ventricular dysfunction and heart failure for the two most important classes of cardiotoxic chemotherapeutic agents, examines the potential pitfalls that have led to underestimated rates of left ventricular dysfunction from these agents, and reviews strategies for screening for and providing prophylaxis against chemotherapy-associated left ventricular dysfunction.     

Reperfusion injury: does it exist?

It is well established that reperfusion of the heart is the optimal method of salvaging previously ischemic myocardium. However, the idea of reperfusion injury, i.e. injury caused by the process of reperfusion per se, still remains a controversial issue. In this review, we present mounting evidence supporting the concept that reperfusion injury exists, based on work conducted with adenosine and opioid receptor ligands, and the discovery of two new concepts regarding reperfusion injury: 'postconditioning' (POC) and the reperfusion injury salvage kinase (RISK) signaling pathway.     

Clopidogrel: How good is it and how does it work?

Until recently, long-term antiplatelet therapy for the treatment and prevention of the complications of atherothrombotic disease was limited to aspirin. Although an incredibly costeffective therapy, in placebo-controlled clinical trials approximately 75% of patients at risk continue to experience thrombotic events despite chronic aspirin therapy. The availability of the thienopyridines, in particular clopidogrel, represents an important addition to the physician’s armamentarium. A number of clinical trials have confirmed the efficacy of the combination of clopidogrel and aspirin therapy compared with aspirin alone, with multiple other important largescale clinical trials currently ongoing. The exact mechanism of this benefit is still being elucidated but is clearly related to the inhibition of the many consequences of platelet activation—vascular inflammation, endothelial dysfunction, and localized angiogenesis/mitogenesis—and not just aggregation.     

Targeting prandial hyperglycemia: How important is it and how best to do this?

The contribution of postprandial glucose (PPG) excursions to the overall hyperglycemia of patients with type 2 diabetes depends on the degree of diabetic control. PPG is a major contributor in patients with hemoglobin A_1c (HbA_1c) levels below 7.3%, whereas the contribution of fasting plasma glucose (FPG) is preponderant in poorly controlled patients. In addition, the loss of postprandial glycemic control precedes stepwise degradation of fasting with worsening diabetes. As a consequence, monitoring after meals is particularly important in patients with HbA_1c levels ranging from 6.5% to 8%. In such patients, targeting PPG below 140 mg/dL should be one of the main objectives to achieve HbA_1c less than 6.5%. The new hypoglycemic agents, such as the glucagon-like peptide-1 analogues and the dipeptidyl peptidase-4 inhibitors which have a gluco-dependent insulinotropic effect, should normally reinforce our therapeutic armamentarium for achieving the glycemic targets that should include the three components of the glucose triad: HbA_1c, FPG, and PPG.     

Insight in dementia: when does it occur? Evidence for a nonlinear relationship between insight and cognitive status

Lack of insight or impaired awareness of deficits in patients with dementia is a relatively neglected area of study. The aim of this study was to evaluate insight in a group of demented patients with two assessment scales and to assess their relationship with the cognitive level of disease severity. Sixty-nine consecutive patients affected by Alzheimer's disease (n = 37) and vascular dementia (n = 32) with a wide range of cognitive impairment (MMSE = 17.0 +/- 6.4) were recruited. Insight was evaluated with the Guidelines for the Rating of Awareness Deficits (GRAD)--specifically targeted to memory deficits--and the Clinical Insight Rating scale (CIR), evaluating a broader spectrum of insight (reason for the visit, cognitive deficits, functional deficits, and perception of the progression of the disease). In the whole sample, GRAD and CIR were significantly associated with MMSE (Spearman's coefficient = .51, p < .001; and r = -.55, p < .001) and with Clinical Dementia Rating scale (-.57, p < .001; and r = .57, p < .001) respectively. The shape of the relationship of MMSE with CIR and GRAD scales was assessed with spline smoothers suggesting that the relationship follows a trilinear pattern and is similar for both scales. Insight was uniformly high for MMSE scores > or = 24, showed a linear decrease between MMSE scores of 23 and 13, and was uniformly low for MMSE scores < or = 12. The trilinear model of the association between insight and cognitive status reflects more closely the observable decline of insight and can provide estimates of when the decline of insight begins and ends.     

Anal sensitivity test: What does it measure and do we need it?

PURPOSE: This study was undertaken to determine the anal sensitivity in controls and in different patient groups and to establish factors that determine anal sensitivity. METHODS: Anorectal function tests were performed in 387 patients with different anorectal diseases. Anal sensitivity was measured in 36 controls. Anal sensitivity was measured by means of mucosal electrosensitivity (MES) using a catheter with two electrodes placed in the anal canal. A constant current (square wave stimuli 100 μsec, pulses per second) was increased stepwise from 1 to 20 mAmp until the threshold sensation was reached. Other tests used were anal manometry (maximum basal pressure, maximum squeeze pressure, rectal compliance (maximum rectal volume and pressure), endosonography (submucosal thickness), defects and thickness of internal and external sphincter), electromyography (maximum contraction pattern, Grade 1 (solitary contractions) to Grade 4 (interference pattern)), and pudendal nerve terminal motor latency. Multiple regression analysis was performed. It was postulated that age, local conditions (anal scars, anal fissures, hemorrhoids, mucosal prolapse, proctitis, sphincter thickness and defects, and submucosal thickness), and neurologic factors could influence anal sensitivity. RESULTS: Controls had an MES of 3.4±1.7. MES was significantly increased compared with controls in patients with fecal incontinence, soiling, hemorrhoids, mucosal prolapse, constipation, anal scars, anal surgery, and sphincter defects; patients with fecal incontinence had the highest MES (6.7±4.3;P <0.0001). Patients with anal fissures and proctitis showed no differences compared with controls. MES correlated significantly with age (R =0.29), maximum basal pressure (R =?0.29), maximum squeeze pressure (R =?0.32), submucosal thickness (R =0.19), maximum contraction pattern (R =?0.39), single-fiber electromyography (R =0.39), and maximum rectal volume and pressure (0.14). Multiple regression analysis showed that age, internal sphincter defects, and submucosal thickness significantly influenced anal sensitivity, but explained only 10 percent of the variance. CONCLUSION: Anal sensitivity is diminished in all patients with anorectal diseases except for anal fissures and proctitis. There are correlations with other anorectal function tests. Anal sensitivity is determined for 10 percent by age, internal sphincter defects, and thickness of the submucosa. Anal sensitivity measurement, therefore, has limited clinical value and should be used in conjunction with other tests in a research setting.