The effectiveness of an extra-curricular lecture for STI prevention and sexual education.

While the incidence of infections with the human immunodeficiency virus largely remained unchanged in Germany, an increase of other sexually transmitted infections (STIs) was observed. The aim was to analyse the effectiveness of our sexual education lecture for students in improving the awareness, knowledge and prevention of STIs. We conducted a cross-sectional survey after students had attended our extra-curricular lecture at the Department of Dermatology of the Ludwig-Maximilians-University of Munich, Germany (LMU). We compared the data with a previously performed study in which the same survey was carried out before the lecture had started. A total of 5866 questionnaires were included in the analysis. After attending the lecture significantly more students were aware of STIs (syphilis: 36.8% (before) vs. 63.5% (after); chlamydia: 30.5% vs. 49.3%; gonorrhoea: 22.4% vs. 38.2%; human papillomaviruses (HPV): 17.7% vs. 30.2%), the transmission pathways of STIs (oral: 36.6% vs. 82.6%; vaginal: 81.8% vs. 97.3%; anal: 42.8% vs. 94.0%; penile: 68.7% vs. 92.1%), knew that the HPV vaccination is directed against a virus (36.8% vs. 56.9%) and were interested in receiving a vaccination (57.7% vs. 78.8%). This study demonstrates the positive educative effects of our lecture for awareness and improved knowledge of STIs. To satisfy the need for a comprehensive sexual education, a combination of school and health facility-based programmes should be implemented as one single lecture cannot convey the entire information about STIs.

Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab).

Background: The aim of this study was to evaluate patient preference and satisfaction for the subcutaneous (s.c.) versus intravenous (i.v.) formulation of rituximab given with chemotherapy in previously untreated patients with CD20+ diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients and methods: Patients received eight cycles of rituximab according to 2 schedules: Arm A received 1 cycle rituximab i.v. (375 mg/m2) and 3 cycles rituximab s.c. (1400 mg) then 4 cycles rituximab i.v.; Arm B received 4 cycles rituximab i.v. (375 mg/m2) then 4 cycles rituximab s.c. (1400 mg). Alongside rituximab, both arms received 6-8 cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (CVP), or bendamustine as per standard local practice). Preference for s.c. or i.v. administration was evaluated using the Patient Preference Questionnaire (PPQ) at cycles 6 and 8. Patient satisfaction and convenience were assessed using the Cancer Therapy Satisfaction Questionnaire (CTSQ), and Rituximab Administration Satisfaction Questionnaire (RASQ) at cycles 4 and 8. Results: At the primary data cut-off (19 January 2015), the intent-to-treat population comprised 743 patients. The majority had DLBCL (63%) and baseline characteristics were balanced between arms. At cycle 8, 81% of patients completing the PPQ preferred rituximab s.c. Preference was not impacted by treatment sequence or disease type. Patient satisfaction as measured by RASQ was higher for s.c. versus i.v. CTSQ scores were similar between arms. Adverse events were generally balanced between administration routes and no new safety signals were detected. Conclusion: Most previously untreated patients with CD20+ DLBCL or FL preferred s.c. to i.v. rituximab administration. Patient satisfaction with rituximab treatment was generally greater with s.c. administration. Registered clinical trial number: NCT01724021 (ClinicalTrials.gov).

RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features.

We evaluated the frequency, genetic architecture, clinico-pathologic features and prognostic impact of RUNX1 mutations in 2439 adult patients with newly-diagnosed acute myeloid leukemia (AML). RUNX1 mutations were found in 245 of 2439 (10%) patients; were almost mutually exclusive of AML with recurrent genetic abnormalities; and they co-occurred with a complex pattern of gene mutations, frequently involving mutations in epigenetic modifiers (ASXL1, IDH2, KMT2A, EZH2), components of the spliceosome complex (SRSF2, SF3B1) and STAG2, PHF6, BCOR. RUNX1 mutations were associated with older age (16-59 years: 8.5%; ⩾60 years: 15.1%), male gender, more immature morphology and secondary AML evolving from myelodysplastic syndrome. In univariable analyses, RUNX1 mutations were associated with inferior event-free (EFS, P<0.0001), relapse-free (RFS, P=0.0007) and overall survival (OS, P<0.0001) in all patients, remaining significant when age was considered. In multivariable analysis, RUNX1 mutations predicted for inferior EFS (P=0.01). The effect of co-mutation varied by partner gene, where patients with the secondary genotypes RUNX1mut/ASXL1mut (OS, P=0.004), RUNX1mut/SRSF2mut (OS, P=0.007) and RUNX1mut/PHF6mut (OS, P=0.03) did significantly worse, whereas patients with the genotype RUNX1mut/IDH2mut (OS, P=0.04) had a better outcome. In conclusion, RUNX1-mutated AML is associated with a complex mutation cluster and is correlated with distinct clinico-pathologic features and inferior prognosis.

Remission of a B cell CLL-associated membranoproliferative glomerulonephritis Type I with rituximab and bendamustine.

In a 56-year-old white male patient, a membranoproliferative glomerulonephritis Type I was diagnosed after a 12-month history of low grade B cell lymphoma (Binet A). HIV, Hepatitis B and C serology were negative. Due to an impairment of renal function despite chemotherapy with COP, an immunochemotherapy consisting of rituximab (6 cycles) and bendamustine (4 cycles) was given. This therapeutic approach caused a complete remission of the nephrotic syndrome. Renal function and arterial hypertension improved markedly. In addition, urinary sediment became normal and proteinuria disappeared completely.

Operative intervention for carotid restenosis is safe and effective.

Carotid stenting has been proposed as an alternative to reoperative carotid endarterectomy (rCEA) for recurrent carotid stenosis. The purpose of this study is to prove the safety, effectiveness and durability of reoperation in long term follow up of 18 years in a community hospital setting. From March 1988 to April 2005 80 patients, 46 men and 34 women (mean age: 64.1 years) underwent a total of 83 operations. Symptomatic recurrent stenosis (>70%) was the indication in 32, asymptomatic high-grade stenosis (>80%) in 49, intimal flap in one and fibromuscular dysplasia (F.M.D), in one. The initial operation was carotid endarterectomy with primary closure in 60 and prosthetic patch in 23. The mean recurrences were at 23.3 months in 33 with myointimal hyperplasia, 105.4 months in 29 with recurrent atherosclerosis, 61.4 months in 19 with both hyperplasia and atherosclerosis, 2 months in one with intimal flap and 8 months in one with F.M.D bands. Reoperation utilized primary closure (3), vein patch (14), prosthetic patch (55), Gore-Tex interposition grafts (7), vein interposition grafts (3) and intraoperative dilation (1). No perioperative strokes or deaths occurred. One patient died from cardiac complications following combined rCEA and coronary artery bypass grafting. Operative morbidity consisted of reversible nerve injury (5), irreversible recurrent laryngeal nerve injury (1) and hematoma requiring evacuation (3). During follow up (3-153 months; mean: 50.9) carotid occlusion resulted in mild ipsilateral stroke in one patient, and one non-hemispheric stroke. There were 26 late deaths due to all causes, one due to CVA. Eight patients required reoperation (mean 53.4 months). Seven of these were hypertensive. Kaplan-Meier analysis of long-term follow up shows relatively high stroke free rates; at 153 months (12.75 years) the hemispheric stroke free rate was 98.67% and the all-stroke free rate was 95.85%. The survival estimate following redo surgery was 69.97% at 5 years and 40.23% at 10 years. We found that individuals on statin therapy (p-value=0.0042), and those on combination of statin and aspirin (p-value=0.0320), had significantly increased interval between primary and secondary operation. Increased age was correlated to a decreased time to redo surgery (p-value=<0.0001). We conclude that reoperation for recurrent carotid stenosis using standard vascular techniques is safe, effective, durable and cost effective. It should continue to be the mainstay of treatment when secondary intervention is required. Statins have a salutary effect on durability of the procedure and should be used when indicated.

Results of a national consensus workshop: therapeutic algorithm in patients with follicular lymphoma--role of radioimmunotherapy.

Radioimmunotherapy (RIT) was approved for the treatment of relapsed or refractory CD20-positive follicular lymphoma (FL), subsequent to rituximab containing primary therapy. However, an increasing number of clinical studies have suggested that RIT may be more efficacious in an earlier phase of the disease. Therefore, a consensus meeting was held in May 2005 to define the optimal setting of RIT in the therapeutic algorithm of patients with advanced stage of FL. RIT is an established therapeutic option in relapsed FL. According to the reviewed data, RIT should be preferably used as consolidation after initial tumor debulking. First-line RIT may be applied in patients not appropriate for chemotherapy induction. Current study concepts evaluate the role of RIT consolidation in combination with antibody maintenance to achieve a potentially curative approach even in patients with advanced stage disease.

Reduced-dose cladribine (2-CdA) plus mitoxantrone is effective in the treatment of mantle-cell and low-grade non-Hodgkin's lymphoma.

Cladribine (2-chlorodeoxyadenosine) (2-CdA) has been shown to be effective in mantle-cell (MCL) and low-grade lymphomas (lgNHL). The aim of this multicentre study was to evaluate the rate and duration of remissions and to examine the toxicity of the combination of reduced-dose 2-CdA and mitoxantrone (CdM) in MCL and lgNHL as first-line therapy or for patients in their relapse. A total of 285 courses, median of five courses per patient, were administered to 62 evaluable patients (42 previously untreated, 20 relapsed) with 5 mg/m(2) 2-CdA per day given as an intermittent 2-h infusion over 3 consecutive days combined with 8 mg/m(2) mitoxantrone on days 1 and 2 for the untreated patients or 12 mg/m(2) mitoxantrone on day 1 for patients in their first relapse for a maximum of six cycles every four weeks. 32 follicular, 18 MCL, 9 lymphoplasmacytoid, 2 marginal zone and 1 unclassified low-grade B-cell lymphoma were involved in the study. 56 of the 62 patients responded to CdM resulting in an overall response rate of 90% (95% confidence interval (CI), 80-96%) with a complete remission (CR) rate of 44% (95% CI, 31-57%) and a median duration of remission of 25 months (range 6-42+). The overall survival rate at 48 months was 80%. For 42 previously untreated patients, the overall response rate was 88% (95% CI, 74-96%) with a CR rate of 38% (95% CI, 24-54%), whereas the response rate for the group of 20 previously treated patients was similar with a 95% overall response (95% CI, 75-100%) and a CR rate of 55% (95% CI, 32-77%). In MCL, CdM showed a high activity, achieving a response rate of 100% (95% CI, 81-100%) with a CR rate of 44% and a median duration of remission of 24 months (range 6-35+). Myelosuppression was the major toxicity with 23% grade 3 granulocytopenia and 50% grade 4. Thrombocytopenia was less commonly observed, with only 8% grades 3 and 4. These results demonstrate that the combination of reduced-dose 2-CdA and mitoxantrone is a highly active regimen in the treatment of low-grade lymphomas, and in particular of MCL.

Treatment of aggressive, or progressing indolent peripheral T- and NK-cell neoplasias by combination of fludarabine, cyclophosphamide and doxorubicine.

BACKGROUND: Regarding standardization of treatment, classification, and pathophysiology of peripheral T- and NK-cell neoplasias the current knowledge is markedly behind that of B-cell lymphomas, which are approximately 10 times more frequent. In May 2000, the study group 'Peripheral T- and NK-cell Neoplasias' was founded in Frankfurt/M. This group decided on a clinical protocol and a scientific program for research on the pathophysiology of these entities. Rationales for the therapeutic regimen are the efficacy of cyclophosphamide and doxorubicine as shown in protocols for treatment of high grade lymphoma, the synergism of cyclophosphamide and fludarabine, and reports demonstrating the efficacy of fludarabine in T-cell neoplasias. PATIENTS AND METHODS: Patients will be treated with a combination of fludarabine (30 mg/m(2) days 1-3), cyclophosphamide (1000 mg/m(2) day 1) doxorubicine (25 mg/m(2) day 2+3) (FCD). For patients > or =65 years a dose-reduced FCD regimen will be administered. In patients included in the treatment study and additionally in patients with indolent disease not requiring therapy, scientific projects on the biology of peripheral T- and NK-cell neoplasias will be performed. CONCLUSIONS: Expected conclusions of the projected study are the establishment of treatment and diagnostic standards, and improvement of classification of these entities by clinical, morphologic and biologic parameters.

Clinical evaluation of a positive pressure device to prevent central venous catheter occlusion: results of a pilot study.

One of the complications related to central venous catheters is occlusion secondary to thrombus formation within or surrounding the catheter lumen. Historically, methods to prevent these occlusions have included vigorous flushing, coordinated flushing-clamping techniques, and antithrombotic prophylaxis using low-dose warfarin or low molecular weight heparin. Positive displacement devices recently have become available that prevent retrograde blood flow and consequently reduce the risk of thrombus formation in the catheter lumen. Maintaining catheter patency results in fewer treatment delays and diagnostic procedures, decreased use of thrombolytics, lower costs, and increased patient satisfaction. A trial of a positive displacement device was conducted on an inpatient oncology unit to determine its effectiveness in preventing catheter occlusions. The easy-to-use device effectively reduced the number of occlusions and resulted in significant cost savings when compared to thrombolytic therapy.

Induction of apoptosis using 2',2' difluorodeoxycytidine (gemcitabine) in combination with antimetabolites or anthracyclines on malignant lymphatic and myeloid cells. Antagonism or synergism depends on incubation schedule and origin of neoplastic cells.

Induction of apoptosis in vitro using gemcitabine (dFdC) in combination with cladribine (2-CdA) and other cytotoxic drugs on malignant mononuclear cells (MNCs) of patients with acute myeloid leukemia (AML, n=20) and chronic lymphocytic leukemia (CLL, n =20) in myeloid (HL60, HEL) and lymphatic cell lines (HUT78, JURKAT) was investigated using different incubation conditions (simultaneous and consecutive). Furthermore, the influence of dFdC on the level of intracellular metabolites of 2-CdA was studied using high-performance liquid chromatography (HPLC). Apoptosis was evaluated using flow cytometry with 7-aminoactinomycin D. In MNCs of patients with CLL, dFdC + 2-CdA showed an antagonistic effect when applied simultaneously. This antagonism was reduced by consecutive application. The combination of dFdC with doxorubicin was synergistic, independent of incubation schedule. In blasts from newly diagnosed patients with de novo AML, all drug combinations (dFdC+2-CdA, doxorubicin, or cytosine arabinoside) were antagonistic by simultaneous incubation. Reduced antagonism or even synergism was shown (P<0.001) by consecutive incubation. The simultaneous combination of dFdC with 2-CdA in all tested cell lines resulted in a competitive inhibition on the rate of apoptosis. By changing the incubation period to a consecutive schedule, the antagonism was diminished or synergism of apoptosis was measured (P< 0.001). Using similar incubation conditions, these experiments were supported by HPLC measurement of intracellular metabolites of 2-CdA influenced by dFdC application. In conclusion, we demonstrated that the efficacy of dFdC in vitro in combination with other cytotoxic drugs depends on the incubation condition and on the origin of neoplastic cells (lymphatic vs myeloid). The data suggest that simultaneous combination therapy with purine and pyrimidine analogues may not improve the clinical efficacy of one or the other drug administered alone.

Induction of apoptosis by 2-chloro-2'deoxyadenosine (2-CdA) alone and in combination with other cytotoxic drugs: synergistic effects on normal and neoplastic lymphocytes by addition of doxorubicin and mitoxantrone.

2-CdA is active as a single agent in the treatment of low-grade lymphomas. We analyzed the induction of apoptosis by 2-CdA alone (n=5) and in combination with other drugs in peripheral lymphocytes from 25 patients with leukemic low-grade lymphomas and from 25 healthy volunteers. 2-CdA was tested in 4 escalating concentrations (0.05 microg/ml to 0.4 microg/ml). Linear regressions showed a dose dependent apoptosis rate of 0.29 x microg 2-CdA/ml + 0.11 (r2=0.88, p=0.006) in normal cells and 0.41 x microg 2-CdA/ml + 0.15 (r2=0.88, p=0.005) in leukemic cells. Intracellular metabolization of 2-CdA into 2-CdA-5'mono-, -di- and the active metabolite -triphosphate was analyzed by HPLC and paralleled the dose dependent increase of apoptosis. The combination of 2-CdA with doxorubicin or mitoxantrone had a synergistic effect on the induction of apoptosis (p<0.001) in both normal and neoplastic lymphocytes, whereas 2-CdA plus etoposide or cytosine arabinoside were only additive. Due to the flat slope of the dose response of 2-CdA concentration on apoptosis we assume that higher in vivo dosages of 2-CdA in the treatment of low-grade lymphomas may not result in a higher clinical efficacy. The synergistic lymphocytotoxic effect of 2-CdA combined with doxorubicin or mitoxantrone may be relevant for new treatment approaches.

Intermittent 2-hour-infusion of cladribine as first-line therapy or in first relapse of progressive advanced low-grade and mantle cell lymphomas.

Aim of this multicenter-study was to evaluate rate and duration of remissions and to examine toxicity of cladribine in low-grade lymphomas as first-line therapy or in first relapse using intermittent 2-hour-infusion of cladribine. A total of 294 courses, median of 5 courses per patient, were administered to 66 evaluable patients (53 previously untreated, 13 relapsed) with 5 mg/m2 cladribine given as intermittent 2-hour-infusion over 5 consecutive days for a maximum of 6 cycles every four weeks. Entities: 26 follicle center, 20 lymphoplasmacytoid, 12 mantle cell, 6 T-cell, 2 marginal zone lymphomas. Fifty of 66 patients responded to cladribine corresponding to an overall response rate of 76% (95% confidence interval (95% CI): 64%-85%) with 38% CR (95% CI: 26%-51%) and a median time of remission duration of 23 months (range 6-45+). The overall survival rate at 48 months was 72%. For 49 previously untreated patients with B-cell lymphomas the overall response rate was 86% (95% CI: 73%-94%) with a high CR rate of 43% (95% CI: 29%-58%). Response rate for the group of 23 previously untreated patients with follicle center lymphomas was high with 96% overall response (95% CI: 78%-100%) and 57% CR rate (95% CI: 34%-77%). Cladribine also showed activity in patients with mantle cell lymphomas achieving a response rate of 58% (95% CI: 28%-85%). Myelosuppression was the major toxicity with 17% neutropenia grade 3 and 4. Thrombocytopenia was rare with only 2% grade 3 and 4. A prolonged CD4-lymphocytopenia was observed in all patients. Life threatening complications were not observed. These results confirm the major single-agent activity of cladribine in a large cohort of patients with untreated low-grade lymphomas using the intermittent 2-hour-infusion dosage-regimen. To improve treatment results furthermore, cladribine should be combined with other agents active in low-grade lymphomas.

Fludarabine and epirubicin in the treatment of chronic lymphocytic leukaemia: a German multicenter phase II study.

PURPOSE: Fludarabine has been reported to be the most effective single-agent in previously treated chronic lymphocytic leukaemia (CLL). Based on the in vitro synergism of fludarabine with anthracyclines and on results showing a higher efficacy of CHOP against COP we attempted to improve treatment results with a combination of fludarabine and an anthracycline. PATIENTS AND METHODS: The aim of the multicenter study was to evaluate the rate and duration of remissions and investigate the toxic and immunosuppressive effects of fludarabine and epirubicin in the treatment of CLL in Binet stages B and C as first-line therapy or in first relapse. Thirty-eight patients were treated with fludarabine 25 mg/m2 on days 1-5 and epirubicin 25 mg/m2 on days 4 and 5. RESULTS: The overall response rate (OR) was 82% (95% confidence interval (95% CI): 66%-92%) with a CR rate of 32% (95% CI: 18%-49%). For the 25 previously untreated patients the OR was 92% (95% CI: 74%-99%) including 40% CRs (95% CI: 21%-61%). Granulocytopenia grade 3 occurred in 23% of all evaluable cycles, and grade 4 in 17%. The median remission duration was 19 months (range 6-37 months). CONCLUSION: The results show that the combination of fludarabine and epirubicin is tolerable and highly effective in the treatment of CLL. With the addition of epirubicin to fludarabine, it appears possible to achieve a higher response rate and a more rapid response, especially of nodal manifestations. This regimen can be administered in an outpatient facility except for the first cycle because of the risk of a tumour lysis. The possible benefit of the combination presented here in the treatment of CLL in comparison to single-agent fludarabine treatment is presently under study in a prospective randomized multicenter study.

Treatment of mantle-cell lymphomas with intermittent two-hour infusion of cladribine as first-line therapy or in first relapse.

PURPOSE: Cladribine (2-chlorodeoxyadenosine, 2-CdA) has been reported to be effective in the treatment of low-grade lymphomas. The objective of this multicenter study was to evaluate the activity of cladribine in mantle-cell lymphomas as first-line therapy or in first relapse using an intermittent two-hour infusion of cladribine. PATIENTS AND METHODS: A total of 47 courses, or an average of four courses per patient, were administered to 12 patients (seven untreated, five relapsed) with 5 mg/m2 cladribine given as an intermittent two-hour infusion over five consecutive days for a maximum of six cycles every four weeks. RESULTS: Cladribine showed activity in patients with mantle-cell lymphomas, achieving a response rate of 58% (95% confidence interval (95% CI): 28%-85%). Myelosuppression was the major toxicity with 17% of grade 3 and 4 neutropenia. Thrombocytopenia was rare with only 2% of grade 3 and 4. CONCLUSION: These results demonstrate single-agent activity of cladribine in mantle-cell lymphomas using the intermittent two-hour infusion dosage regimen. To further improve treatment results, cladribine should be combined with other agents active in mantle-cell lymphomas.

Successful reconstruction of a complex traumatic carinal disruption.

Complex traumatic tracheobronchial disruption often results in mortality or prolonged morbidity. This case report highlights a successful strategy for diagnosis and management of an unusually extensive carinal disruption in a patient with multiple trauma.