Panayiotis D. Ziakas

Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis.

OBJECTIVE: To estimate the effect of combined heparin and aspirin compared with aspirin monotherapy in pregnant women with antiphospholipid syndrome and recurrent pregnancy loss. DATA SOURCES: We searched the PubMed database up to December 2009 for English-language studies using the key words “aspirin AND (heparin OR low molecular weight heparin), (antiphospholipid OR anticardiolipin OR aPL) AND pregnancy.” METHODS OF STUDY SELECTION: Two hundred ninety- two studies were initially screened. Randomized controlled trials comparing the effect of heparin (unfractionated heparin or low molecular weight heparin) plus aspirin compared with aspirin alone on the live-birth rate in women with a history of at least two miscarriages and antiphospholipid antibodies were eligible. TABULATION, INTEGRATION, AND RESULTS: The pooled effect of unfractionated heparin and low molecular weight heparin was evaluable in three and two randomized controlled studies, respectively, with regard to live births, which was the major outcome. Overall, treatment effects were in favor of heparin against first-trimester losses (odd ratio [OR] 0.39, 95% confidence interval [CI] 0.24–0.65, number needed to treat 6). More specifically, unfractionated heparin displayed a significant effect (OR 0.26, 95% CI 0.14–0.48, number needed to treat 4), while the pooled effect of low molecular weight heparin was insignificant (OR 0.70, 95% CI 0.34–1.45). Combination therapy of either unfractionated heparin or low molecular weight heparin with aspirin failed to display any significant effect in the prevention of late-pregnancy losses. No significant differences were observed between treatment and control groups for any other outcomes. CONCLUSION: The combination of unfractionated heparin and aspirin confers a significant benefit in live births. However, the efficacy of low molecular weight heparin plus aspirin remains unproven, highlighting the urgent need for large controlled trials.

Prognosis and outcome of non-Hodgkin lymphoma in primary Sjögren syndrome.

AbstractSjögren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32–6.76) and 1.08 (95% CI, 0.79–1.45), respectively. A “watch and wait” policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach.

Anaemia in systemic lupus erythematosus: from pathophysiology to clinical assessment

Haematological abnormalities are common in systemic lupus erythematosus. Anaemia is found in about 50% of patients, with anaemia of chronic disease being the most common form. Impaired erythropoietin response and presence of antibodies against erythropoietin may contribute to the pathogenesis of this type of anaemia. Patients with autoimmune haemolytic anaemia usually belong to a distinct category, which is associated with anticardiolipin antibodies, thrombosis, thrombocytopenia, and renal disease, often in the context of secondary antiphospholipid syndrome. Autoantibodies, T lymphocytes, and deregulation of the cytokine network can affect bone marrow erythropoiesis, leading to anaemia.

Thrombosis in paroxysmal nocturnal hemoglobinuria: sites, risks, outcome. An overview

MEDLINE Database (1953 to 2006) has been extensively reviewed using the terms PNH, Thrombosis and Paroxysmal Nocturnal Hemoglobinuria, Thrombosis as search criteria; 294 citations were retrieved. Eligible articles were reviews, cohort studies, and case reports providing individual patient data on the site of thrombosis and outcome (death or survival) related to the thrombotic event. Ninety-three articles (nine cohort studies and 84 case reports and reviews of published cases) provided data on 363 PNH cases with thrombosis and outcome in 339 cases. When the same case was reported twice, in a review article and as a case report, only one of the citing articles was included as a data source. When either the site of thrombosis or the outcome was not evident, this case was excluded. Our study population finally consisted of 339 cases of PNH with thrombosis. Treatment options were available in 162 cases and were classified as conventional (n 1⁄4 118) (for those receiving unfractionated heparin, low molecular weight heparin, or warfarin) and interventional modalities (n 1⁄4 44), either to restore blood flow (thrombolysis, anatomic shunts, angioplasty) or reverse coagulation defect (bone marrow transplantation). Odds ratios with their corresponding 95% confidence intervals (CIs) were measured to quantify relative risk of death (RR) in univariate and multivariate logistic regression models. A score chart was developed to facilitate the practical application of the multivariate regression model. The regression coefficients of the significant covariates were rounded off to the proximal 0.5. The value of each predictor (site of thrombosis) has a corresponding score in the chart. The scores are added, resulting in a sum score, which corresponds to a probability according to a logistic transformation. For the significant sites of thrombosis associated with mortality, the population attributable mortality (PAM) was also calculated and depicted. PAM is defined as the proportion of deaths occurring in the total study population (PNH patients with thrombosis) that can be explained by the risk factor (site of thrombosis). Assigned score corresponds to an individual’s probability to die when a thrombosis at this specific site occurs. Instead, PAM refers to the proportion of deaths in the whole study population that is attributed to the particular exposure (specific site of thrombosis). Significance was set to 0.05. The STATA V8 (Stata Corporation, College Station, TX, USA) package was used for statistical analysis.

4 Months of Rifampin Compared with 9 Months of Isoniazid for the Management of Latent Tuberculosis Infection: A Meta-analysis and Cost-Effectiveness Study That Focuses on Compliance and Liver Toxicity

BACKGROUND One-third of the worlds population is infected with tuberculosis, and 9 months of isoniazid monotherapy is the treatment of choice for latent tuberculosis infection. However, this approach has been associated with hepatotoxicity and poor compliance. A shorter (4-month) rifampin regimen has been evaluated in recent clinical trials. METHODS We performed a meta-analysis of the published studies to compare compliance, toxicity, and cost-effectiveness between the 2 strategies. Pooled effects were calculated as risk ratios (RRs) by means of random-effects and fixed-effects models. RESULTS Pooled data from 3586 patients suggested that 4-month rifampin therapy was associated with a significant reduction in the risk of noncompletion (RR for random-effects model, 0.53; 95% confidence interval [CI], 0.44-0.63). Noncompletion rates were lower among patients who received 4-month rifampin therapy (range, 8.6%-28.4%), compared with noncompletion rates among patients who received 9-month isoniazid therapy (range, 24.1%-47.4%). Also, rates of hepatotoxicity (defined as grade 3 or 4 liver failure leading to drug discontinuation) were lower for patients who received 4-month rifampin therapy (range, 0%-0.7%), compared with the corresponding rates for patients who received 9-month isoniazid therapy (range, 1.4%-5.2%), and rifampin was associated with significant reduction in the risk of hepatotoxicity (RR for fixed-effects model, 0.12; 95% CI, 0.05-0.30). Notably, with the data from our meta-analysis, we calculated that the 4-month rifampin strategy is also cost-effective and results in

Colonization With Toxinogenic C. difficile Upon Hospital Admission, and Risk of Infection: A Systematic Review and Meta-Analysis

213 savings per patient treated (

Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance

90/patient when doctor fees are not included). CONCLUSIONS The improved compliance, safety, and cost associated with the 4-month rifampin therapy suggest that the efficacy of this approach needs to be evaluated in detail. An extended posttreatment follow-up in future studies will clarify the unresolved issue of tuberculosis reactivation rates.

Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma

Objectives:It has been suggested that colonization with C. difficile protects from infection. Nevertheless, the association between carriage of toxinogenic strains and ensuing C. difficile infections (CDIs) has not been studied.Methods:We searched PubMed and EMBASE databases up to 20 June 2014, using the term “difficile”. Our primary outcomes of interest included the prevalence of isolation of toxinogenic C. difficile or its toxins from asymptomatic patients on hospital admission through stool or rectal swab testing and the risk of ensuing infection among colonized and noncolonized patients. Data on previous hospitalization, antibiotic, and proton pump inhibitor (PPI) use and prior CDIs among colonized and noncolonized patients were also extracted.Results:Nineteen out of 26,081 studies on 8,725 patients were included. The pooled prevalence of toxinogenic C. difficile colonization was 8.1% (95% confidence interval (CI) 5.7–11.1%), with an increasing trend over time (P=0.003), and 10.0% (95% CI 7.1–13.4%) among North American studies. Patients colonized upon hospital admission had a 5.9 times higher risk of subsequent CDIs compared with noncolonized patients (relative risk (RR) 5.86; 95% CI 4.21–8.16). The risk of CDI for colonized patients was 21.8% (95% CI 7.9–40.1%), which was significantly higher than that of noncolonized patients (3.4%; 95% CI 1.5–6.0%; P=0.03), with an attributable risk of 18.4%. History of hospitalization during the previous 3 months was associated with a higher risk of colonization (RR 1.63; 95% CI 1.13–2.34), as opposed to previous antibiotic (RR 1.07; 95% CI 0.75–1.53) and PPI use (RR 1.44; 95% CI 0.94–2.23), as well as history of CDI (RR 1.45; 95% CI 0.66–3.18) that had no impact.Conclusions:Over 8% of admitted patients are carriers of toxinogenic C. difficile with an almost 6 times higher risk of infection. These findings update current knowledge regarding the contribution of colonization in CDI epidemiology and stress the importance of preventive measures toward colonized patients.

Effect of JAK2 V617F on thrombotic risk in patients with essential thrombocythemia: measuring the uncertain

Previous observations indicate that a lamividune-prophylaxis strategy results in a decrease of hepatitis B virus (HBV) reactivation rates. This report evaluates the benefits from this strategy among lymphoma patients. The findings of this study indicate that extended anti-HBV prophylaxis can improve survival rates by 2.4% in HBsAg-positive lymphoma patients receiving chemotherapy. Lamivudine prophylaxis is an effective strategy in HbSAg-positive patients receiving cancer chemotherapy. Recent data indicate that a lamividune-prophylaxis strategy results in a decrease of hepatitis B virus (HBV) reactivation rates, though its effect on HBV-mortality remains equivocal. This report evaluates the benefits from this strategy among lymphoma patients and develops a management approach for patients with prolonged immunosuppression. A Medline search was conducted to retrieve published trials on HBsAg-positive lymphoma patients receiving prophylactic lamivudine during chemotherapy. Basic inclusion criterion was to report HBV-reactivation rates with and without lamivudine prophylaxis. A meta-analysis of the risk of HBV-reactivation and HBV-related mortality was conducted, and the pooled effect was calculated as risk ratio (RR). We found that lamivudine prophylaxis is associated with a significant reduction in hepatitis B virus reactivation (RR 0.21, 95%CI 0.13–0.35) and a trend in reducing HBV-related mortality (RR 0.68, 95%CI 0.19–2.49). In order to study the long-term effects of anti-HBV prophylaxis when prolonged immunosuppression is needed, we used our findings to model a decision tree. Overall survival was the main outcome used in the analysis. Rituximab maintenance in B-cell lymphomas was used as a paradigm of prolonged immunosuppression. We found that extended anti-HBV prophylaxis can improve survival rates by 2.4% in HBsAg-positive patients. If 1,000 HBsAg-positive lymphoma patients receive prophylaxis, one will die from hepatitis B virus reactivation versus 25/1,000 if no prophylaxis is administered. This effect is probably mediated through a reduction of hepatitis B virus reactivation and HBV-related mortality. The ideal antiviral agent needs to be determined.

Cytokine Secretion in Long-standing Diabetes Mellitus Type 1 and 2: Associations with Low-grade Systemic Inflammation

Hepatocellular cancer ranks fifth among cancers and is related to chronic viral hepatitis, alcohol abuse, steatohepatitis and liver autoimmunity. Surgical resection and orthotopic liver transplantation have curative potential, but fewer than 20% of patients are suitable candidates. Interventional treatments are offered to the vast majority of patients. Radiofrequency (RFA) and microwave ablation (MWA) are among the therapeutic modalities, with similar indications which include the presence of up to three lesions, smaller than 3 cm in size, and the absence of extrahepatic disease. The therapeutic effect of both methods relies on thermal injury, but MWA uses an electromagnetic field as opposed to electrical current used in RFA. Unlike MWA, the effect of RFA is partially limited by the heat-sink effect and increased impedance of the ablated tissue. Compared with RFA, MWA attains a more predictable ablation zone, permits simultaneous treatment of multiple lesions, and achieves larger coagulation volumes in a shorter procedural time. Major complications of both methods are comparable and infrequent (approximately 2%-3%), and they include haemorrhage, infection/abscess, visceral organ injury, liver failure, and pneumothorax. RFA may incur the additional complication of skin burns. Nevertheless, there is no compelling evidence for differences in clinical outcomes, including local recurrence rates and survival.