The effect of prophylactic penicillin treatment on the course of arthritis episodes in patients with Behçet's disease. A randomized clinical trial

Objective. Because exposure to streptococcal antigens might be a major disease activity—provoking factor in Behçet's disease, this study was undertaken to evaluate the effectiveness of benzathine penicillin in the prophylaxis of recurrent arthritis episodes during the course of this disease. Methods. A prospective, randomized study design was used to allocate patients to receive colchicine alone or colchicine plus benzathine penicillin for 24 months. Results. The duration, severity, and pattern of arthritis episodes were found to be similar in the 2 treatment groups, but the number of arthritis episodes was significantly reduced, and the duration of episode-free time significantly prolonged, in the penicillin group compared with the colchicine-alone group. Conclusion. Penicillin treatment was demonstrated to offer adjunctive benefits in the prevention of arthritis episodes which are not obtainable with colchicine monotherapy. This finding could provide additional evidence for antigen triggering in the pathogenesis of Behçet's disease.     

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t)ide analogs after liver transplantation.     

Microsatellite instability is not a common feature in medullary breast cancer

Microsatellite instability (MSI) is a form of genomic instability associated with defective DNA mismatch repair in tumors. MSI is found in 85-90% of hereditary nonpolyposis colorectal cancer cases; however, its occurrence in breast carcinogenesis still remains to be clarified. In addition, data are limited on the incidence of MSI in the medullary subtype. The purpose of this study was to investigate the occurrence of MSI in medullary breast cancer (MBC). The study included a total of 16 patients with MBC, nine with typical and seven with atypical histology. The incidence of MSI in five microsatellite loci (D2S123, D3S1611, D17S807, D17S796 and Xq11-12) was determined by comparing paired normal and tumor tissue DNA after PCR amplification from paraffin-embedded tissues. All 16 tumors showed stability at five loci. Although the number of microsatellite markers and DNA samples may limit the value of our results, we conclude that the MSI phenotype is uncommon in human MBC.     

Effects of a beta-blocker on ventricular late potentials in patients with acute anterior myocardial infarction receiving successful thrombolytic therapy

Late potentials (LP) detected on the signal-averaged electrocardiogram (SAECG) predict arrhythmic events after acute myocardial infarction (AMI). It is also well established that successful thrombolytic therapy reduces the incidence of LP. Our aim was to evaluate the effects of a beta-blocker on LP in patients receiving thrombolytic therapy. We studied 40 patients presenting with anteroseptal AMI (< 6 hours). All patients received thrombolytic therapy and were evaluated with coronary angiography at predischarge. Eighteen patients received metoprolol (5 mg IV on admission followed by 50 mg BID). SAECG recordings were obtained serially using an ART system (40-250 Hz filter, noise < 0.5 mV) prior to thrombolytic therapy, after 48 hours and after 10 days. LP was defined as posi-tive if the SAECG met at least 2 of the Gomes criteria. Changes observed in SAECG recordings after thrombolytic therapy were correlated with angiographic and clinical data with regard to the usage of BB. The frequencies of LP before and after thrombolytic therapy were compared with the McNemar test. There were no significant differences between the clinical characteristics, risk factors, and angiographic findings (including infarct related artery patency and LV functions) of the groups. Baseline SAECG findings were also similar between the groups. The incidence of LP significantly decreased after TT in the BB group, however, this change was not observed in patients who did not receive BB (P = 0.012, McNemar test). Beta-blockers reduce the incidence of LPs following thrombolytic therapy in patients with anterior AMI. This might be explained by the possible beneficial effect of BB on the arrhythmogenic substrate.     

Long‐term entecavir or tenofovir disoproxil fumarate therapy in treatment‐naïve chronic hepatitis B patients in the real‐world setting

The aim of this study was to determine the long‐term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on the natural course of disease in chronic hepatitis B patients (CHB) with/without cirrhosis in clinical practice. A total of 355 treatment‐naïve CHB patients were enrolled into the study. The primary outcome measure was viral suppression as defined by serum HBV DNA level <20 IU/mL. A secondary outcome measure was to determine the development of Hepatocellular carcinoma (HCC). Virological and biochemical responses were similar between the two treatment groups over time. The presence of cirrhosis and hepatitis B e antigen (HBeAg) positivity did not appear to impact viral suppression. The cumulative probability of HBeAg loss was 41% at 4 years of therapy. Hepatitis B surface antigen (HBsAg) loss occurred in four patients. Model for End‐Stage Liver Disease score was significantly improved from baseline to week 48 and 96 under antiviral therapy (P = 0.013, P = 0.01). HCC was diagnosed in 17 patients (4.8%). The cumulative probability of the development of HCC was 3.3% at 1 year and 7.3% at 4 years of therapy. The development of HCC was independently associated with older age (P = 0.031) and the presence of cirrhosis (P = 0.004). Serum creatinine levels and creatinine clearance remained stable over time. ETV and TDF effectively maintained virological and biochemical responses in long‐term follow‐up of CHB patients with/without cirrhosis. HCC may still develop, although at a lower rate, and is more likely to develop in patients with cirrhosis, especially in older patients.     

Serum IL-18 levels in tuberculosis: comparison with pneumonia, lung cancer and healthy controls

OBJECTIVE: The aim of the present study was to document the serum IL-18 levels in patients with pulmonary tuberculosis (P-TB), extrapulmonary tuberculosis (EP-TB), pneumonia, lung cancer and in healthy controls, and to investigate whether it may assist in the differential diagnosis of P-TB. METHODOLOGY: A total of 116 patients were included in the study. The study population consisted of patients with P-TB, EP-TB, pneumonia and lung cancer and controls. P-TB patients were graded according to sputum positivity and extent of disease. Serum levels of IL-18 (ELISA) were compared between groups and with other clinical measures of disease. RESULTS: Compared with the controls, all groups of patients had increased serum levels of IL-18. The highest mean concentration of IL-18 was observed in P-TB. Serum levels of IL-18 in the patients with P-TB correlated well with the extent of disease. CONCLUSIONS: Although increased serum levels of IL-18 were not specific for TB, the increased levels may favour active TB in radiologically advanced disease where CXR findings are difficult to interpret, and sputum smears or cultures are not helpful.     

Evaluation of amphotericin B interpretive breakpoints for Candida bloodstream isolates by correlation with therapeutic outcome

One hundred seven Candida bloodstream isolates (51 C. albicans, 24 C. glabrata, 13 C. parapsilosis, 13 C. tropicalis, 2 C. dubliniensis, 2 C. krusei, and 2 C. lusitaniae strains) from patients treated with amphotericin B alone underwent in vitro susceptibility testing against amphotericin B using five different methods. Fifty-four isolates were from patients who failed treatment, defined as death 7 to 14 days after the incident candidemia episode, having persistent fever of >or=5 days' duration after the date of the incident candidemia, or the recurrence of fever after two consecutive afebrile days while on antifungal treatment. MICs were determined by using the Clinical Laboratory Standards Institute (formally National Committee for Clinical Laboratory Standards) broth microdilution procedure with two media and by using Etest. Minimum fungicidal concentrations (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640 medium generated a restricted range of MICs (0.125 to 1 microg/ml); the corresponding MFC values ranged from 0.5 to 4 microg/ml. Broth microdilution tests with antibiotic medium 3 produced a broader distribution of MIC and MFC results (0.015 to 0.25 microg/ml and 0.06 to 2 microg/ml, respectively). Etest produced the widest distribution of MICs (0.094 to 2 microg/ml). However, none of the test formats studied generated results that significantly correlated with therapeutic success or failure.     

European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma

Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high- versus standard-risk groups (2B). Novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients remains the standard of care (1A). Induction therapy should include a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone (1A), or with cyclophosphamide and dexamethasone (2B). Currently, allogeneic stem cell transplantation may be considered for young patients with high-risk disease and preferably in the context of a clinical trial (2B). Thalidomide (1B) or lenalidomide (1A) maintenance increases progression-free survival and possibly overall survival (2B). Bortezomib-based regimens are a valuable consolidation option, especially for patients who failed excellent response after autologous stem cell transplantation (2A). Bortezomib-melphalan-prednisone or melphalan-prednisone-thalidomide are the standards of care for transplant-ineligible patients (1A). Melphalan-prednisone-lenalidomide with lenalidomide maintenance increases progression-free survival, but overall survival data are needed. New data from the phase III study (MM-020/IFM 07-01) of lenalidomide-low-dose dexamethasone reached its primary end point of a statistically significant improvement in progression-free survival as compared to melphalan-prednisone-thalidomide and provides further evidence for the efficacy of lenalidomide-low-dose dexamethasone in transplant-ineligible patients (2B).