Factors predisposing to thrombosis after major joint arthroplasty.

BACKGROUND: Total joint arthroplasty is one of the most common options for end stage osteoarthritis of major joints. However, we must take into account that thrombosis after hip/knee arthroplasty may be related to mutations in genes encoding for blood coagulation factors and immune reactions to anticoagulants [heparin-induced thrombocytopenia (HIT)/thrombosis]. Identifying and characterizing genetic risk should help to develop diagnostic strategies or modify anticoagulant options in the search for etiological mechanisms that cause thrombophilia following major orthopedic surgery. AIM: To evaluate the impact of patients' coagulation profiles and to study specific pharmacologic factors in the development of post-arthroplasty thrombosis. METHODS: In 212 (51 male and 161 female) patients that underwent primary total hip arthroplasty (100) or total knee arthroplasty (112) due to osteoarthritis during a period of 1 year, platelet counts and anti-platelet factor 4 (PF4)/heparin antibodies were evaluated pre/postoperatively, and antithrombin III, methylenetetrahydrofolate reductase, factor V and prothrombin gene mutations were evaluated preoperatively. In a minimum follow-up of 3 years, 196 patients receiving either low-molecular-weight heparins (173) or fondaparinux (23) were monitored for the development of thrombocytopenia, anti-PF4/heparin antibodies, HIT, and thrombosis. RESULTS: Of 196 patients, 32 developed thrombocytopenia (nonsignificant correlation between anticoagulant type and thrombocytopenia, P = 0134.) and 18 developed anti-PF4/heparin antibodies (12/173 for low-molecular-weight heparins and 6/23 for fondaparinux; significant correlation between anticoagulant type and appearance of antibodies, P = 0.005). Odds of antibody emergence: 8.2% greater in patients receiving fondaparinux than low-molecular-weight heparins. Gene mutations in factor II or V (two heterozygotes for both factor V and II) were identified in 15 of 196 patients. Abnormal low protein C and/or S levels were found in 3 of 196 (1.5%) patients, while all patients had normal levels of von Willebrand factor, lupus anticoagulant, and antithrombin III. Four patients developed HIT (insignificant correlation between thrombocytopenia and antibodies) and five developed thrombosis (two had positive antibodies and two were heterozygotes for both factor II & V mutations). Thrombosis was not significantly correlated to platelet counts or HIT. The correlation of thrombosis to antibodies, factor II, factor V was P = 0.076, P = 0.043, P = 0.013, respectively. CONCLUSION: Screening of coagulation profile, instead of platelet monitoring, is probably the safest way to minimize the risk of post-arthroplasty thrombosis. In addition, fondaparinux can lead to the formation of anti-PF4/heparin antibodies or HIT.

Pleural effusions induced by human herpesviruses in the immunocompetent host.

METHODS: A computer-based search of the English literature for articles relative to Human Herpesviruses (HHVs) infection and pleural effusions (PEs) in the immunocompetent host was performed in PubMed and Scopus. The reference lists of the retrieved articles were also reviewed for relevant articles. RESULTS: A total of 20 articles satisfied the selection criteria and were included in the study. In the majority of the articles, PEs were reported as clinical complications of systemic HHV-induced infection. The frequency of HHVs within the reported cases was five for HHV-1/2, one for HHV-3, six for HHV-4, six for HHV-5 and one for HHV-6. One case involved HHV-4 and HHV-5 co-infection. No case of HHV-7 or HHV-8 related PE in the immunocompetent host was retrieved. CONCLUSIONS: Pleural effusions in the immunocompetent host occur in severe viral infections and can be due to comorbidities (or septic complications) or due to the direct HHV pathogenicity although research relative to the susceptibility of pleural mesothelial cells to HHV infection is lacking. HHV pathogenicity needs to be studied further as it could explain undiagnosed PEs.

Correction to: Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

The original version of this article contained a mistake. The name of Eirini Katroditou should have been Eirini Katodritou. The original article has been corrected.

Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

Identification and functional analysis of the BIM interactome; new clues on its possible involvement in Epstein-Barr Virus-associated diseases.

Epigenetic deregulation is a common feature in the pathogenesis of Epstein-Barr Virus (EBV)-related lymphomas and carcinomas. Previous studies have demonstrated a strong association between EBV latency in B-cells and epigenetic silencing of the tumor suppressor gene BIM. This study aimed to the construction and functional analysis of the BIM interactome in order to identify novel host genes that may be targeted by EBV. Fifty-nine unique interactors were found to compose the BIM gene network. Ontological analysis at the pathway level highlighted infectious diseases along with neuropathologies. These results underline the possible interplay between the BIM interactome and EBV-associated disorders.

"Real-world" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group.

Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the "real world" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (≥PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2(nd)-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease.

Relationship between the paraoxonase 1 (PON1) M55L and Q192R polymorphisms and lymphohaematopoietic cancers in a Greek agricultural population.

The aim of this study was to investigate the association between Paraoxonase 1 (PON1) gene polymorphisms (M55L and Q192R) and lymphohaematopoietic cancers (LHC) in an agricultural region of Greece. A hospital-based case-control study was conducted. A structured questionnaire including information on demographics, residence, occupation, agricultural practices, pesticide exposure, family history, smoking, alcohol consumption and medical history, was used. Genotyping of 316 cases of LHC and 351 healthy controls by using standard laboratory methods was performed. To control for confounders, Binary and Multinomial Logistic Regression analyses were used. Possession of QQ genotype or presence of the Q allele were associated with increased risk of developing LHC (OR 1.94, 95% CI 1.42-2.66 and OR 1.72, 95% CI 1.33-2.23 respectively). The QQ genotype in the recessive model was independently associated with LHC (OR 1.92, 95% CI 1.40-2.65), leukaemia (OR 1.99, 95% CI 1.13-3.49), lymphoma (OR 2.17, 95% CI 1.21-3.90) and plasmacell disease (OR 1.92, 95% CI 1.40-2.65) even after controlling for age, sex, pesticide exposure, smoking and family history (cancers, LHC and immunological disorders) as confounders. Possession of QQ genotype was found to have a stronger association with LHC in the high and medium pesticide exposed groups(OR 2.15, 95% CI 1.35-3.40, P-value 0.001 and OR 2.25, 95% CI 1.21-4.19, P-value 0.010 respectively), compared with the Low/No exposed group where the association was not statistically significant (OR 1.51, 95% CI 0.76-3.00, P-value 0.224). We found no association between M55L polymorphism and LHC. PON1 polymorphisms may influence the risk for LHC in our agricultural area. The results encourage further investigation on the PON1 polymorphisms and their importance on the individual's susceptibility especially when exposure to pesticides occurs.