Entries from September 2008
The hepatorenal syndrome.
Med Clin North Am. 2008 Jul;92(4):813-37, viii-ix
Authors: Munoz SJ
The onset of renal failure in a patient with cirrhosis or acute liver failure is alarming because it raises the possibility of the hepatorenal syndrome (HRS). Periodic surveillance of renal function is helpful in patients with severe liver disease to detect HRS early and to help correct reversible contributing factors. Once established, HRS responds relatively poorly to medical management, although recent advances have brought hope for an improved prognosis. In this article the diagnosis, pathophysiology, and management of HRS are discussed in detail, with an emphasis on recent diagnostic and therapeutic advances.
PMID: 18570944 [PubMed - indexed for MEDLINE]
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Tags: Med Clin North Am
Effect of darbepoetin alfa administered once monthly on maintaining hemoglobin levels in older patients with chronic kidney disease.
Am J Geriatr Pharmacother. 2008 Jun;6(2):49-60
Authors: Silver MR, Agarwal A, Krause M, Lei L, Stehman-Breen C
BACKGROUND: The anemia of chronic kidney disease (CKD) is associated with increased hospitalizations, increased cardiovascular morbidity and mortality, and diminished quality of life in the elderly. Darbepoetin alfa is an erythropoiesis-stimulating agent that has been shown to be effective in treating anemia in patients with CKD (but not on dialysis) when administered using extended-dosing regimens. OBJECTIVE: The purpose of this post hoc analysis was to examine the efficacy and safety profile of once-monthly (QM) darbepoetin alfa in study patients stratified according to age (ie, <65, 65-74, and > or =75 years). METHODS: Patients with CKD but not on dialysis, receiving darbepoetin alfa every other week (Q2W), and with stable hemoglobin (Hb) levels between 11 and 13 g/dL, inclusive, were enrolled in this 33-week, multicenter, open-label, single-arm study. The study was carried out at 36 US centers and consisted of a 24-week QM darbepoetin alfa dose-titration period followed by an 8-week evaluation period. Hb levels were measured Q2W. Study results were stratified according to patient age (<65, 65-74, and > or =75 years). RESULTS: A total of 152 patients (79 women, 73 men) were enrolled; 55 patients (36%) were <65 years of age, 46 (30%) were 65 to 74 years of age, and 51 (34%) were > or =75 years of age. In patients who received > or =1 dose of darbepoetin alfa, Hb levels > or =11 g/dL were maintained in 76%, 80%, and 71% of patients aged <65, 65 to 74, and > or =75 years, respectively. For patients who completed the study, the proportions who maintained Hb levels > or =11 g/dL were 83%, 88%, and 85%, respectively, for the 3 age groups. The safety profile of QM darbepoetin alfa in this study was consistent with that expected in patients with CKD not receiving dialysis. CONCLUSIONS: Darbepoetin alfa administered QM maintained Hb levels > or =11 g/dL in patients with CKD (not on dialysis) aged <65, 65 to 74, and > or =75 years. This treatment regimen may help optimize anemia management for older community-dwelling and long-term care patients.
PMID: 18675764 [PubMed - indexed for MEDLINE]
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Tags: Am J Geriatr Pharmacother
Thrombocytopenia associated with chronic liver disease.
J Hepatol. 2008 Jun;48(6):1000-7
Authors: Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R
Thrombocytopenia (platelet count <150,000/microL) is a common complication in patients with chronic liver disease (CLD) that has been observed in up to 76% of patients. Moderate thrombocytopenia (platelet count, 50,000/microL-75,000/microL) occurs in approximately 13% of patients with cirrhosis. Multiple factors can contribute to the development of thrombocytopenia, including splenic platelet sequestration, bone marrow suppression by chronic hepatitis C infection, and antiviral treatment with interferon-based therapy. Reductions in the level or activity of the hematopoietic growth factor thrombopoietin (TPO) may also play a role. Thrombocytopenia can impact routine care of patients with CLD, potentially postponing or interfering with diagnostic and therapeutic procedures including liver biopsy, antiviral therapy, and medically indicated or elective surgery. Therapeutic options to safely and effectively raise platelet levels could have a significant effect on care of these patients. Several promising novel agents that stimulate TPO and increase platelet levels, such as the oral platelet growth factor eltrombopag, are currently in development for the prevention and/or treatment of thrombocytopenia. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease.
PMID: 18433919 [PubMed - indexed for MEDLINE]
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Tags: J Hepatol
Anemia treatment in chronic kidney disease: shifting uncertainty.
Heart Fail Rev. 2008 Dec;13(4):425-30
Authors: Pfeffer MA
Epidemiologic observations showing associations between higher levels of some biologic markers such as blood pressure and serum cholesterol with heightened risk of death and non-fatal cardiovascular events have provided important data to develop hypotheses regarding pharmacologic therapies to modify these markers to improve prognosis. Randomized controlled trials have shown that strategies to reduce blood pressure with a variety of antihypertensive agents and LDL cholesterol with statins do, indeed, result in important improvements in clinical outcomes. However, there are several instances where a hypothesis based on strong observational data has been rejected based on surprising counterintuitive evidence generated from randomized controlled clinical trials. Use of inotropic therapies for patients with reduced left ventricular ejection fraction heart failure, administration of class I antiarrhythmic agents to suppress ventricular arrhythmias in high-risk patients, and use of hormone replacement therapy for postmenopausal women have each shown that therapies presumed to be of benefit may actually be producing unfavorable clinical results. Use of erythropoietic stimulating agents (ESA) in chronic kidney disease patients with anemia is similarly based on strong observational data indicating that the degree of anemia is independently associated with higher risk for cardiovascular morbidity and mortality. In non-dialysis patients with mild to moderate anemia, current clinical outcome studies have only addressed arbitrary hemoglobin targets for ESA therapy and have shown that targeting the higher hemoglobin levels was not associated with the benefit and may even result in harm. This review will outline the importance of having a placebo-controlled trial in this patient population to better assess the risk benefit profile of this therapy.
PMID: 18401704 [PubMed - indexed for MEDLINE]
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Tags: Heart Fail Rev
Gastrointestinal stromal tumor.
Surg Oncol. 2008 Aug;17(2):129-38
Authors: Gupta P, Tewari M, Shukla HS
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These form a distinct category of tumors characterized by oncogenic mutations of the KIT receptor tyrosine kinase in a majority of patients. KIT is used not only for diagnosis but also for targeted therapy of GISTs. Imatinib, a tyrosine kinase inhibitor, is widely used in the treatment of advanced and metastatic GISTs and has been recently employed in the neo adjuvant and adjuvant set-up with encouraging results. Certain specific mutations in an exon (such as in exon 9) of the KIT gene result in GISTs that are relatively unresponsive to the Imatinib treatment. New therapeutic agents like Sunitinib have now been approved for the treatment of Imatinib-resistant GIST. This review summarizes the salient features of GIST along with a detailed review of targeted multi-disciplinary approach to the treatment of these special tumors.
PMID: 18234489 [PubMed - indexed for MEDLINE]
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Tags: Surg Oncol
Avascular necrosis of the femoral head in HIV infected patients.
Braz J Infect Dis. 2007 Feb;11(1):31-4
Authors: Matos MA, Alencar RW, Matos SS
Avascular necrosis (AVN) of the femoral head is an emerging complication in HIV infected patients. It has been suggested that the increased incidence of AVN in this population may be caused by an increased prevalence of predisposing factors for osteonecrosis, including protease inhibitors, hyperlipidemia, corticosteroid use, alcohol and intravenous drug abuse. The aim of this study was to assess the risk factors for avascular necrosis developing in the femoral head of HIV infected individuals. This study consisted of meta-analysis of the secondary data extracted from current literature. The selected articles allowed two study groups to be drawn up for comparison. Group 1 comprised 324 individuals infected by the HIV virus, who did not present femoral head AVN. Group 2 comprised 32 HIV positive patients, who presented femoral head AVN. The parameters used for analysis were as follows: age, gender, sexual preference, use of intravenous drugs, time of diagnosis, CD4+ cell count, use of antiretroviral agents and duration, serum cholesterol and serum triglycerides. The present study found a statistically significant association between hypertriglyceridemia, hypercholesterolemia, sexual preference and intravenous drug abuse. The authors concluded that femoral head osteonecrosis is associated with hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) and intravenous drug abuse. This study supports the hypothesis that protease inhibitors play a role in the development of osteonecrosis through a tendency to cause hyperlipidemia.
PMID: 17625723 [PubMed - indexed for MEDLINE]
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Tags: Braz J Infect Dis
Indeterminate colitis: a review of the concept–what’s in a name?
Inflamm Bowel Dis. 2008 Jun;14(6):850-7
Authors: Geboes K, Colombel JF, Greenstein A, Jewell DP, Sandborn WJ, Vatn MH, Warren B, Riddell RH,
The precise diagnosis of colitis cannot always be established with the available diagnostic tools. The subgroup of patients with an uncertain diagnosis has been classified as “indeterminate colitis” (IC). The definition of “indeterminate,” however, has changed over the years. Originally, IC was proposed by pathologists for colectomy specimens, usually from patients operated on for severe colitis, showing overlapping features of ulcerative colitis (UC) and Crohn’s disease (CD). Later, the same terminology was used for patients showing no clear clinical, endoscopic, histologic, and other features allowing a diagnosis of either UC or CD. Therefore, it is difficult to compare different studies. An International Organization of Inflammatory Bowel Diseases (IOIBD) working party confirmed 1) the ambiguous nature of the term, and 2) proposes an updated classification for the category of patients with an unclear diagnosis. According to this, the term IBD unclassified (IBDU) is confirmed, as suggested by the Montreal Working Party 2005 for patients with clinically chronic colitis, that clearly have IBD but when definitive features of CD or UC are absent. In resected specimens the term “colitis of uncertain type or etiology” (CUTE) is preferred. It is accepted that most of the time this may have a prefix, such as severe, chronic. The classification of IBD varies when based only on biopsies rather than on a colectomy specimen. The vast majority of these have severe colitis. For those that cannot bear to abandon the highly ambiguous term IC, if it is used at all, this is where it can be used parenthetically.
PMID: 18213696 [PubMed - indexed for MEDLINE]
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Tags: Inflamm Bowel Dis
Crohn’s disease: current treatment options.
Arch Dis Child. 2008 Sep;93(9):787-92
Authors: Akobeng AK
There is no known cure for Crohn’s disease (CD), but a better understanding of the evidence base of both established treatments (such as enteral nutrition, corticosteroids, 5-aminosalicylates and immunosuppressive agents) and emerging treatments (such as the anti-tumour necrosis factor-alpha (anti-TNF-alpha) agents, infliximab and adalimumab) provides opportunities to improve and maintain the quality of life for children with the disease. This article provides an overview of the evidence base of current medical treatments that are used to induce and maintain remission in CD. Exclusive enteral nutrition is recommended as the first line of treatment for the induction of remission in paediatric CD. Corticosteroids are also effective for inducing remission but may be associated with significant adverse events. Patients with chronically active CD may benefit from immunosuppressive agents such as azathioprine and methotrexate. Infliximab is effective for inducing remission in patients who continue to have significant active disease despite the use of conventional treatments. Adalimumab may be indicated for patients who develop a severe allergic reaction to infliximab or those who initially respond to infliximab but subsequently lose their response. Treatments that have been shown to be effective for the maintenance of remission include azathioprine, methotrexate, infliximab and adalimumab. Recent evidence also suggests that long-term enteral nutritional supplementation with patients taking about half of their daily calorie requirements as enteral nutrition may be an effective strategy for the maintenance of remission in CD. The available evidence does not support the use of corticosteroids or 5-aminosalicylates as maintenance therapy for CD.
PMID: 18456695 [PubMed - indexed for MEDLINE]
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Tags: Arch Dis Child
Clinical course of ulcerative colitis.
Dig Liver Dis. 2008 Jul;40 Suppl 2:S247-52
Authors: Cottone M, Scimeca D, Mocciaro F, Civitavecchia G, Perricone G, Orlando A
AIM: To provide a review of studies on prognosis in ulcerative colitis by reviewing the relevant population-based cohort studies. On the basis of incidence and population studies, ulcerative colitis has a favourable clinical course, with good quality of life, a chronic course characterized by at least one relapse, and a surgery rate of 30% after 10 years from diagnosis. Patients affected by severe ulcerative colitis have a higher risk of colectomy, and some clinical variables may predict the disease's clinical course. Most patients respond to steroids and only a low percentage become dependent, or non-responders to steroids. Patients who have a long-lasting ulcerative colitis (>10 years) or are affected by an extensive disease have an increased risk of developing colorectal cancer, while those treated with immunosuppressants for long period of time may have an increased risk of developing lymphomas. Data on mortality in ulcerative colitis patients are not homogeneous, but if a real risk exists it is in patients with extensive or severe disease. The evidence that patients with severe ulcerative colitis are often non-smokers may explain why in one study the mortality rate was lower.
PMID: 18598996 [PubMed - indexed for MEDLINE]
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Tags: Dig Liver Dis
Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial.
Lancet. 2008 Sep 24;
Authors: Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B,
BACKGROUND: New treatments for type 2 diabetes mellitus are needed to retain insulin-glucose coupling and lower the risk of weight gain and hypoglycaemia. We aimed to investigate the safety and efficacy of liraglutide as monotherapy for this disorder. METHODS: In a double-blind, double-dummy, active-control, parallel-group study, 746 patients with early type 2 diabetes were randomly assigned to once daily liraglutide (1.2 mg [n=251] or 1.8 mg [n=247]) or glimepiride 8 mg (n=248) for 52 weeks. The primary outcome was change in proportion of glycosylated haemoglobin (HbA(1c)). Analysis was done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NTC00294723. FINDINGS: At 52 weeks, HbA(1c) decreased by 0.51% (SD 1.20%) with glimepiride, compared with 0.84% (1.23%) with liraglutide 1.2 mg (difference -0.33%; 95% CI -0.53 to -0.13, p=0.0014) and 1.14% (1.24%) with liraglutide 1.8 mg (-0.62; -0.83 to -0.42, p<0.0001). Five patients in the liraglutide 1.2 mg, and one in 1.8 mg groups discontinued treatment because of vomiting, whereas none in the glimepiride group did so. INTERPRETATION: Liraglutide is safe and effective as initial pharmacological therapy for type 2 diabetes mellitus and leads to greater reductions in HbA(1c), weight, hypoglycaemia, and blood pressure than does glimepiride. FUNDING: Novo Nordisk A/S.
PMID: 18819705 [PubMed - as supplied by publisher]
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Tags: Lancet
Approaches to the treatment of anaemia in patients with chronic heart failure.
Heart Fail Rev. 2008 Dec;13(4):431-8
Authors: Murphy CL, McMurray JJ
An association between anaemia, poor functional status and, compared to non-anaemic patients, worse clinical status and a higher risk of hospitalisation and death has been consistently reported in chronic heart failure (CHF), although cause an effect has not been proven. While it is attractive to think that correction of a co-morbidity that exacerbates already diminished delivery of oxygen to the tissues in heart failure is likely to beneficial, the possible haemodynamic effects of increasing haemoglobin, for example vasoconstriction, might not be. Consequently, the balance of benefit and risk of anaemia correction in CHF is uncertain, may vary according to the severity of anaemia (and other factors) and needs to be properly evaluated. To date, most studies of anaemia correction in CHF have used erythropoiesis stimulating agents (ESAs). The trials with erythropoietin have been of small size, uncontrolled or unblended/single blind, raising concerns again about interpretation of subjective outcomes. In addition, the analyses of these trials have been suboptimal. Two double-blind, placebo-controlled, darbepoetin studies have been published in full. Neither showed an improvement in functional capacity or consistent effect on patient reported symptoms/quality of life. Darbepoetin is, however, currently being tested in a large-scale, phase III morbidity and mortality trial, the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF) which should contribute important information of the safety and efficacy of ESAs in this syndrome. Other approaches, notably parenteral iron supplementation, are also being evaluated and other agents for anaemia correction are under development.
PMID: 18392791 [PubMed - indexed for MEDLINE]
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Tags: Heart Fail Rev
Effect of ximelagatran and warfarin on stroke subtypes in atrial fibrillation.
Can J Neurol Sci. 2008 May;35(2):160-5
Authors: Teitelbaum JS, von Kummer R, Gjesdal K, Kristinsson A, Gahn G, Albers GW,
BACKGROUND AND PURPOSE: The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke. METHODS: 7329 patients with AF and > or = 1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0–3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype. RESULTS: The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant. CONCLUSIONS: In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.
PMID: 18574928 [PubMed - indexed for MEDLINE]
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Tags: Can J Neurol Sci
Acute pancreatitis: etiology, clinical presentation, diagnosis, and therapy.
Med Clin North Am. 2008 Jul;92(4):889-923, ix-x
Authors: Cappell MS
Acute pancreatitis is a relatively common disease that affects about 300,000 patients per annum in America with a mortality of about 7%. About 75% of pancreatitis is caused by gallstones or alcohol. Other important causes include hypertriglyceridemia, medication toxicity, trauma from endoscopic retrograde cholangiopancreatography, hypercalcemia, abdominal trauma, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown after thorough investigation. This article discusses the causes, diagnosis, imaging findings, therapy, and complications of acute pancreatitis.
PMID: 18570947 [PubMed - indexed for MEDLINE]
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Tags: Med Clin North Am
Choledocholithiasis, ascending cholangitis, and gallstone pancreatitis.
Med Clin North Am. 2008 Jul;92(4):925-60, x
Authors: Attasaranya S, Fogel EL, Lehman GA
Gallstone disease is encountered commonly in clinical practice. The diagnosis of biliary stones has become less problematic with current, less-invasive imaging methods. The relatively invasive endoscopic techniques should be reserved for therapy and not used for diagnosis. Acute cholangitis and gallstone pancreatitis are two major complications that require prompt recognition and timely intervention to limit morbidity and prevent mortality or recurrence. Appropriate noninvasive diagnostic studies, adequate monitoring/supportive care, and proper patient selection for invasive therapeutic procedures are elements of good clinical practice.
PMID: 18570948 [PubMed - indexed for MEDLINE]
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Tags: Med Clin North Am
In-hospital stroke treated with intravenous tissue plasminogen activator.
Stroke. 2008 Sep;39(9):2614-6
Authors: Masjuan J, Simal P, Fuentes B, Egido JA, Díaz-Otero F, Gil-Núñez A, Novillo-López ME, Díez-Tejedor E, Alonso de Leciñana M
BACKGROUND AND PURPOSE: In-hospital strokes (IHSs) are potential candidates for thrombolysis. We analyzed the treatment procedures, safety, and efficacy of intravenous tissue plasminogen activator (IV-tPA) in IHSs compared with out-of-hospital strokes (OHSs). METHODS: This study was based on a multicenter prospective registry of patients treated with IV-tPA divided into IHSs and OHSs. We recorded intrahospital delays and stroke outcomes. RESULTS: Among 367 patients treated with IV-tPA, 30 were IHSs. Baseline characteristics were similar except for a greater proportion of diabetes (36.7% vs 17.5%, P=0.01), cardiac failure (16.7% vs 5.3%, P=0.014), and atrial fibrillation (33.3% vs 17.5%, P=0.034) in IHSs than OHSs. In-hospital delays were significantly longer in IHSs for door-to-computed tomography time (39.5+/-18.7 vs 22.6+/-19.7 minutes, P<0.0001) and computed tomography-to-treatment time (92.0+/-26.1 vs 65.4+/-25.8 minutes, P<0.0001). No differences were observed in safety or efficacy. CONCLUSIONS: In-hospital procedures for thrombolysis proceed more slowly in IHSs than in OHSs. Thrombolysis is safe and efficient in IHS.
PMID: 18635852 [PubMed - indexed for MEDLINE]
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Tags: Stroke
