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).

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.

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.

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.

Phorbol ester and cyclic AMP-mediated regulation of the melanoma-associated cell adhesion molecule MUC18/MCAM.

MUC18/MCAM is a melanoma-associated cell adhesion molecule that is also occasionally found on carcinomas and other tumor types. On melanomas, MUC18 expression increases with tumor progression and is found on more than 70% of metastatic lesions. To investigate the regulation of MUC18 expression, cell lines of diverse tissue origin were exposed to cytokines, regulators of intracellular cyclic AMP (cAMP), and to phorbol ester. MUC18 expression could not be induced in negative cell lines and could only be modulated by changes in cAMP levels or by exposure to phorbol ester in positive cells. An increase in intracellular cAMP led to an up-regulation in cell surface MUC18 that was maximal at 48 h. Increased MUC18 mRNA levels were observed as soon as 4 h and were 3-fold higher than in control cells by 48 h. Exposure of the cells to phorbol ester reduced MUC18 surface expression to background levels by 24 h. This downregulation was associated with decreased mRNA levels that were apparent at 8 h. By 24 h, steady-state levels of MUC18 mRNA had been reduced by 58%. Whereas similar changes in MUC18 surface expression were observed in MUC18-expressing glioma and carcinoma cell lines, melanoma cells were more resistant to the MUC18-modulating effects of cAMP analogues and phorbol ester. These observations suggest that the strong MUC18 expression observed in advanced melanomas may reflect disturbances in the normal regulation of this molecule.

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.

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.

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.

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.

Thrombolysis theraphy in patients with femoropopliteal synthetic graft occulsions.

BACKGROUND: The aim of this study was to evaluate the efficiency of thrombolysis in the presence of an occluded femoropopliteal synthetic graft. PATIENTS AND METHODS: Over a 3-year period, 46 occluded femoropopliteral grafts were treated with urokinase and reconstruction. The cases were divided into three groups: group 1 (n=25), complete thrombolysis followed by reconstruction or angioplasty or both; group 2 (n=5), complete thrombolysis alone; and group 3 (n=16), failure of thrombolysis requiring reconstruction or leading to amputation. Patients were completely observed after treatment for more than 1 year. RESULTS: There are no fatal complications among patients with thrombolytic therapy. In group 1, the 3-year patency rates were 12% and the 3-year limb salvage rates were 77%. In group 2, the 3-year patency rates and the limb salvage rates were 20% and 80%, respectively. The group 3 patency rates and the limb salvage were 8% and 40%, respectively. The best results were achieved in patients who had thrombolysis followed by reconstruction (group 1) and in those who had thrombolysis alone (group 2). limb salvage was poor in patients with failure of lytic therapy regardless of the reconstruction (P<0.01). CONCLUSION: The use of intra-arterial urokinase followed by secondary vascular reconstructive procedures was studied. The patient with synthetic graft occlusion still has a reasonably favorable prognosis for long-term limb salvage when thrombolysis is successful.

Relationship of runoff vessels to results following thrombolysis and revascularization for synthetic graft occlusions.

The objective of this study was to evaluate the relation between runoff vessels and the prognosis in patients who have had an occlusion of a previously placed peripheral arterial bypass graft. Over a 4-year period 77 occluded synthetic grafts were treated with urokinase and reconstruction after angiographic study. Follow-up ranged from 1 to 1627 days. The cases were divided into three groups according to the number of patent tibial vessels. Group I consisted of patients who had no vessel runoff. Group II consisted of patients who had single vessel runoff. Group III consisted of patients who had two or three runoff vessels. In Group I, the 1, 2, and 3-year patency rates were 35.8%, 8.9%, and 8.9%; and the limb salvage rates were 50.2%, 40.2%, and 40.2% for 1, 2, and 3 years, respectively. The Group II patency rates were 31.2%, 26.0%, and 13.0% and the limb salvage rates were 72.3%, 62.9%, and 62.9%. The Group III patency rates were 50.0%, 26.1%, and 20.9%; and the limb salvage rates were 93.1%, 79.1%, and 79.1%. There is no statistically significant difference in patency rates among any of the groups. The limb salvage rate was significantly increased in Group III, compared to I (P < 0.01) and Group II (P < 0.05), and in Group II, compared to Group I (P < 0.05). These results indicate that the higher rate of limb salvage in this study statistically correlated with the number of runoff vessels.

Evaluation of multiple vascular reconstructive procedures with synthetic graft occlusions.

The objective of this study was to evaluate the efficiency of multiple vascular reconstructive procedures in the presence of an occluded synthetic graft. Over a four year period seventy-seven occluded synthetic grafts were treated with urokinase and reconstruction. Follow-up ranged from 1 to 1627 days (4 years, 5 1/2 months). Kaplan-Meier and generalized Wilcoxon test were used to determine patency and limb salvage rates. The cases were divided into three groups according to the number of previous reconstructive events. Group I consisted of patients that had undergone one previous vascular reconstructive procedure. Group II consisted of patients that had undergone two previous vascular reconstructive procedures. Group III consisted of patients who had undergone three or more previous reconstructive procedures. In Group I, the one, two, and three year patency rates were 48.6%, 34.7%, and 26.0% and the limb salvage rates were 76.2%, 67.9%, and 67.9% for one, two, and three years respectively. The Group II patency rates were 41.9%, 24.4%, and 16.3% and the limb salvage rates were 73.7%, 66.3%, and 66.3%. The Group III patency rates were 31.8%, 5.5%, and 5.5% and the limb salvage rates were 76.6%, 54.8%, and 54.8%. The patency rate was significantly reduced when Group III was compared to Group I (p < 0.01). There was no statistically significant difference in limb salvage rates between any of the groups. These results indicate that the number of secondary vascular reconstructive procedures combined with thrombolysis had no correlation with the prognosis of limb salvage.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Thrombolysis of peripheral graft occlusion in patients with hypertension.

The objective of this study was to evaluate the effect of hypertension on the use of thrombolytic therapy in patients with occluded synthetic peripheral bypass grafts. Thrombolysis with urokinase was performed in 44 cases of occluded lower extremity bypass grafts. The cases were divided into two groups: Group I consisted of patients currently being treated for hypertension. Group II consisted of patients without a history of hypertension. A comparison of pre- or intra-lytic data revealed that there was no significant difference in each group. Complications occurred in 15 (32.6%) out of 46 cases. There was no significant increase in complication when the risk factors were compared. In Group I, the one, two, and three year patency rates were 42.7%, 23.0%, and 7.7% and the limb salvage rates were 93.3%, 73.9%, and 73.9% for one, two, and three years respectively. The Group II patency rates were 70.6%, 41.6%, and 41.6% and the limb salvage rates were 94.1%, 86.9%, and 86.9%. The patency rate was significantly reduced when Group I was compared to Group II (p < 0.05). There was no statistically significant difference in limb salvage rates between Groups I and II. In conclusion, hypertension is one of the important risk factors that reduce the patency rate after thrombolytic therapy in patients with peripheral arterial bypass graft.