Tandem high-dose chemotherapy and autologous stem cell transplantation in refractory/relapsed Hodgkin's lymphoma: a monocenter prospective study

We designed a prospective study to evaluate the feasibility and efficacy of tandem high-dose chemotherapy (HDCT) in the treatment of refractory or relapsed Hodgkin's lymphoma (HL). Thirty-two patients were treated with salvage chemotherapy (IGEV, ifosfamide, gemcitabine, and vinorelbine) and chemo-sensitive patients received a first HDCT course with melphalan 200 mg/m(2) (MEL200) and a second BEAM course. The median time interval between the two HDCT courses was 66 days. The median number of reinfused CD34(+) cells was 4.7 x 10(6)/kg after MEL200 and 5.8 x 10(6)/kg after BEAM. The hematological reconstitution after both HDCT courses did not differ. No grade III or IV renal, hepatic, lung, cardiac, and neurological toxicity was observed. Severe (grade III and IV) oral mucositis was the most prominent complication affecting 60 and 50% of patients after MEL200 and BEAM, respectively. Fever of unknown origin occurred in 65 and 70% of patients after MEL200 and BEAM, respectively. One patient died from septic shock during the aplasia period following BEAM. In an intention-to-treat analysis, the overall response rate increased after each stage of protocol, ranging from 47% to 65% and 75% after IGEV, MEL200, and BEAM, respectively. Tandem HDCT is feasible and effective in patients with relapsed or refractory HL.     

Physiological aspects of soccer refereeing performance and training

The role of the referee is far from minimal in the economy of soccer, as very often, particularly in professional soccer, a wrong judgment may have profound implications on the outcome of the game. In this regard, a better knowledge of soccer refereeing can obviously benefit the game. Recent studies have shown that during a competitive match, an elite soccer referee may cover 9-13 km attaining approximately 85-90% and approximately 70-80% of maximal heart rate and maximal oxygen uptake (VO2max), respectively. Of the total distance covered about 4-18% is covered at high intensity. Blood lactate concentration has been reported to be in the range of 4-5 mmol/L; however, during competitive matches, blood lactate concentrations as high as 14 mmol/L have been observed. This figure is similar to that extensively reported for soccer players, specifically paralleling that observed in midfield players. However, compared with players, referees are 15-20 years older, often have a non-professional status and cannot be substituted during the game. Furthermore, this important physical stress superimposes onto a high perceptual-cognitive workload throughout the entire game. In relation to fitness status, referees possess VO2max values somewhat lower than the players they officiate, with mean values in the range of 44-50 mL/kg/min. However, the methods used by the Federation Internationale de Football Association and the Union of European Football Associations to test referee fitness need to be changed as the current fitness tests do not relate to match performance. More task-specific tests such as the Yo-Yo Intermittent Recovery Test (YYIRT) have been devised and validated for use with referees. Given that aerobic performance is positively correlated with match performance, it is important that referees are trained to improve their ability to cover large distances during a match and also to repeat high-intensity efforts. A number of studies have shown large improvements in YYIRT performance following both short-term (12 weeks) and long-term (16 months) high-intensity interval training. Future research needs to focus on a number of important areas including the decision-making ability of referees when officiating under different conditions, such as high thermal strain, and the impact of age on both physical and mental performance.     

Effect of tecarfarin,a novel vitamin K epoxide reductase inhibitor,on coagulation in beagle dogs

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.     

Neutropenic enterocolitis: is there a right timing for surgery? Assessment of a clinical case

Neutropenic enterocolitis is a severe and potentially life-threatening complication that may affect patients undergoing chemotherapy for acute leukemia or lymphoma. These patients may develop systemic sepsis through bacterial or fungal translocation across the intestinal wall. In many cases neutropenic enterocolitis is confined to the cecum, but the entire colon is sometimes involved. Most patients are treated conservatively because an improvement occurs when the absolute neutrophil count rises. However, a surgical approach consisting of resection of the colon may sometimes be necessary, even in patients with complete aplasia and a high risk of complications. The right time to perform surgery is hard to define. Intestinal wall thickness, evaluated by ultrasound, is an important prognostic factor which could act as a guide to surgical indication. We analyze a case of neutropenic enterocolitis which occurred in a patient with acute myeloid leukemia during chemotherapy and we suggest that, as well as intestinal wall thickness, hemodynamic worsening should be considered an indication for surgery.     

Anterior-superior internal impingement of the shoulder: an evidence-based review

Purpose  

Internal impingement syndrome is a painful shoulder condition related to the impingement of the soft tissue, including the rotator cuff, joint capsule and the long head of the biceps tendon and glenoid labrum. Two types of internal impingement syndrome can be differentiated: posterior-superior impingement and anterior-superior impingement (ASI). The aetiology of ASI in particular is not clear. The purpose of this paper is to discuss the different aetiological theories relating to ASI, try to clarify the clinical, radiological and arthroscopic findings and, finally, suggesting treatment for this complex shoulder syndrome.     

Italian version of ASES questionnaire for shoulder assessment: cross-cultural adaptation and validation

The patient-oriented measures, represented by self-administered questionnaire, have become an important aspect of clinical outcome assessment. To be used with different language groups and in different countries, questionnaires must be translated and adapted to new cultural characteristics and then validated by a widely accepted process to evaluate reliability and validity, fundamental characteristic for each measure. The aim of the study is to perform the cross-cultural adaptation and to assess the Italian version instrument reliability and validity. The study design is a cross-cultural adaptation and cross-sectional study of a sample of patients affected by shoulder disorder with a subsample followed prospectively for retest reliability. The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form was culturally adapted for Italian-speaking people, following the simplified Guillemin criteria. Reliability and validity were assessed in a cross-sectional study of 50 consecutive patients affected by shoulder disorder. A sub-sample of 20 patients was followed prospectively for retest reliability. The results were compared with other validated patient-oriented measures. The ASES scales showed a high correlation with other patient-oriented measures, as hypothesized, and it also showed good values with regard to reproducibility, consistency and validity, to the original versions published in English. These findings suggest that the evaluation capacities of the Italian version of ASES are equivalent to those of English language version.     

Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.