Should hyperhomocysteinemia be treated in patients with atherosclerotic disease?

Numerous retrospective and prospective observational studies support an association between elevated homocysteine and increased risk for myocardial infarction, stroke, and peripheral vascular disease. Although folic acid therapy substantially reduces homocysteine levels, recent large, randomized controlled trials failed to translate folic acid-induced homocysteine reduction into clinical benefit for the secondary prevention of cardiovascular events. These studies are compelling and have generated some newfound skepticism regarding a clinical role for folic acid therapy. Because these intervention trials have been limited to patients with mild hyperhomocysteinemia, the results of the trials imply that folic acid therapy may be best suited for individuals with more robustly elevated homocysteine levels. Furthermore, the potential benefit of folic acid therapy for primary prevention in individuals at low-or intermediate-risk for atherothrombotic disease has not been studied to date. Thus, at this time, folic acid therapy for borderline or mild hyperhomocysteinemia is not recommended. However, the role of folic acid therapy in patients with intermediate or severe hyperhomocysteinemia, or for primary prevention of cardiovascular diseases, remains unresolved.     

Should cisapride be avoided in patients with diabetic gastroparesis?

The gastrointestinal motility stimulants, cisapride and erythromycin, have been used in the management of diabetic gastroparesis. However, drug interactions may result in prolongation of the electrocardiographic QT interval with the risk of ventricular arrhythmias. These drugs should, therefore, not be used in combination. We report two cases that illustrate inappropriate use of these agents. Moreover, patients with recurrent severe hypoglycemia or renal impairment may be at increased risk from cisapride-related cardiotoxicity. Thus, even as monotherapy, cisapride may pose dangers for high-risk diabetic patients.     

Should Pneumocystis jiroveci prophylaxis be recommended with Rituximab treatment in ANCA-associated vasculitis?

Reports in haematology, transplantation medicine and rheumatology indicate that Rituximab, a B cell depleting therapy, increases the risk for Pneumocystis jiroveci pneumopathy. Patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis have an increased incidence of P. jiroveci pneumopathy compared to other autoimmune diseases and Rituximab is often used to induce and maintain remission. Herein, we present a case of a patient with granulomatosis with polyangiitis treated with Rituximab for relapse that developed P. jiroveci pneumopathy 3 months after and we review the relevant literature to assess P. jiroveci pneumopathy incidence and risks factors under Rituximab. We also discuss whether P. jiroveci screening before Rituximab and P. jiroveci pneumopathy prophylaxis under Rituximab are indicated. P. jiroveci colonisation is found in 25 % of patients with autoimmune diseases. However, the association between colonisation and P. jiroveci pneumopathy development is not very strong. P. jiroveci pneumopathy incidence in ANCA-associated vasculitis patients treated with Rituximab is found to be 1.2 %. Therefore, evidence and practice do not support the use of P. jiroveci pneumopathy chemoprophylaxis in all ANCA-associated vasculitis patients receiving Rituximab. CD4 cell count cut-off does not work well in patients treated with Rituximab as it does not reflect T cell impairment following B cell depletion. To help stratify the risk of both colonisation and P. jiroveci pneumopathy development, assessment of the patient’s net state of immunodeficiency before administering Rituximab—including age, renal or lung involvement, previous infections due to T cell dysfunction, blood tests (lymphocytopenia, low CD4 cell count) and concomitant therapy—is warranted.     

Should carcinoembryonic antigen be used in the management of patients with colorectal cancer?

The contribution of carcinoembryonic antigen carcinoembryionic antigen for the effective management of colorectal cancer patients remains a controversial issue. The aim of this study is to attempt to get some valid answers to its function in the diagnosis, prognosis, and overall management of colorectal cancer patients. METHODS: A retrospective review of colorectal cancer patientsmanaged and prospectively registered by the authors between 1985 and 1998 was performed. Serum carcinoembryionic antigen levels were determined preoperatively in 209 patients with primary colorectal cancer and postoperatively in 196 patients who had undergone curative resection of their tumors, according to a fixed schedule. A maximum value of 5 ng/ml was accepted as being normal. With the exception of endoscopy, all other diagnostic techniques were only used after an abnormal carcinoembryionic antigen result (a raised value found twice consecutively). RESULTS: carcinoembryionic antigen preoperative values were raised only in 40 percent of patients and were related to disease stage, with the highest values found in patients with Stage IV disease. However, an elevated preoperative carcinoembryionic antigen value had a very marked prognostic importance, with a statistically significant difference in survival curves (Kaplan-Meier); the same was valid for curatively resected patients (Stages I, II, and III) and for Stages II and III patients considered separately. Multivariate analysis using the Cox proportional hazards technique confirmed these results, showing preoperative carcinoembryionic antigen to have an independent prognostic value, with a relative risk of recurrence of 3.74 for patients with raised preoperative carcinoembryonic antigen levels. In postoperative follow-up, carcinoembryionic antigen elevation was found to be a very accurate marker of recurrence (sensitivity, 77 percent; specificity, 98 percent), mainly in liver metastasis (sensitivity, 100 percent), and the best marker of asymptomatic recurrence (63 percent of cases). However, carcinoembryionic antigen's impact on overall survival was negligible because of the poor results of surgical treatment of recurrences. CONCLUSIONS: Preoperative carcinoembryionic antigen is a very important prognostic indicator and should be considered in future trials. Postoperative carcinoembryionic antigen elevation is a very sensitive marker of recurrence and even of asymptomatic recurrence, but its impact on overall survival does not seem to be relevant. Nevertheless, carcinoembryionic antigen should continue to be used in colorectal cancer patients until better methods of diagnosis and treatment of recurrence are developed.Presented at the meeting of the American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Should albumin be used in all patients with spontaneous bacterial peritonitis?

Patients with cirrhosis who develop spontaneous bacterial peritonitis (SBP) have been reported to experience a high incidence of renal impairment and mortality. Renal dysfunction is possibly related to altered systemic hemodynamics that leads to decreased effective arterial blood volume. Albumin, a plasma volume expander, has been investigated to determine whether it plays a role in patients with SBP. The current literature suggests that albumin can reduce renal impairment and mortality in high-risk SBP patients, defined as patients with a serum bilirubin level of greater than 68.4 μmol/L, a blood urea nitrogen level of greater than 10.7 mmol/L or a serum creatinine level greater than 88.4 μmol/L. The rationale for albumin and other volume expanders in SBP is discussed, accompanied by a review of the current literature.     

Should all patients with metabolic syndrome be treated with statins?

The metabolic syndrome is a constellation of cardiovascular risk factors that include atherogenic dyslipidemia, elevated blood pressure, abdominal/truncal obesity, and glucose intolerance. Current National Cholesterol Education Program (NCEP) recommendations for specific treatment of the metabolic syndrome are centered on therapeutic lifestyle changes. A recent publication from the NCEP Adult Treatment Panel III suggests pharmacologic intervention for parameters of metabolic syndrome, including dyslipidemia, hypertension, and hyperglycemia, to prevent cardiovascular disease, based on risk category. This review looks at the clinical trial evidence to support the use of statins in metabolic syndrome.     

Should vitamin D status be assessed in patients with congestive heart failure?

For decades the vitamin D biological system has been considered almost exclusively as the master integrator of calcium-phosphate homeostasis and bone metabolism. More recently, the discovery that many human tissues and cells, which do not directly participate in mineral ion homeostasis, express the vitamin D receptor (VDR) and are able to convert the circulating pro-hormone 25-hydroxyvitamin D in its active form, 1,25-dihydroxyvitamin D, has provided new insights into the biological function of this peculiar endocrine system. Several reports have highlighted a variety of human diseases possibly related to vitamin D insufficiency or deficiency (respectively defined as 25-hydroxyvitamin D serum levels lower than 30 or lower than 20 ng/ml). In particular, experimental and observational studies, including those published in this journal issue, support the concept that vitamin D deficiency is involved in the pathogenesis of congestive heart failure, a disabling condition affecting over 15 million of patients worldwide. Considering that circulating levels of 25-hydroxyvitamin D represent the accepted clinical indicator of individual vitamin D status, the measurement of this pro-hormone can be regarded as an appropriate and cost-effective screening tool in patients with chronic heart failure.     

Should brain natriuretic peptides be measured in patients with aortic valve disease?

This editorial refers to ‘Relation of N-terminal pro B-typenatriuretic peptide to progression of aortic valve disease’by Weber et al., on page 1023 Close to 3% of the population over the age of 65 suffers fromsignificant aortic valve disease, a figure likely to rise inour aging population. The current guidelines reflect the ampleevidence supporting surgical intervention in symptomatic patients.¹However, optimal treatment of asymptomatic patients with severedisease remains undetermined. The risk of surgical interventionoutweighs the risk of sudden cardiac death in asymptomatic patientswith severe aortic