[Combination of RNase Binase and AKT1/2 Kinase Inhibitor Blocks Two Alternative Survival Pathways in Kasumi-1 Cells].

Treatment of malignant neoplasms often requires the use of combinations of chemotherapeutic agents. However, in order to select combinations that are effective against specific tumor cells, it is necessary to understand the mechanisms of action of the drugs that make up the combination. Bacillus pumilus ribonuclease (binase) is considered as an adjuvant antitumor agent, and the sensitivity of malignant cells to the apoptogenic effect of binase depends on the presence of certain oncogenes. In the acute myelogenous leukemia cell line Kasumi-1, binase blocks the proliferation pathway mediated by the mutant tyrosine kinase KIT, which, as shown in our work, activates an alternative proliferation pathway through AKT kinase. In Kasumi-1 cells, binase in combination with an Akt1/2 inhibitor induces apoptosis, and their toxic effects add up: the Akt1/2 inhibitor blocks the binase-induced pathway after suppression of the KIT-dependent pathway. Thus, a combination of binase and AKT kinase inhibitors can effectively block various pathways of tumor cell proliferation and be used for their elimination.

Efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (B-NHL): results of the randomized, open-label, non-inferiority AVOID neutropenia study.

BACKGROUND: Lipegfilgrastim has been shown to be non-inferior to pegfilgrastim for reduction of the duration of severe neutropenia (DSN) in breast cancer patients. This open-label, non-inferiority study assessed the efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (NHL) at high risk for chemotherapy-induced neutropenia. PATIENT AND METHODS: One hundred and one patients (median age, 75 years) were randomized to lipegfilgrastim or pegfilgrastim (6 mg/cycle) during six cycles of R-CHOP21. RESULTS: Lipegfilgrastim was non-inferior to pegfilgrastim for the primary efficacy endpoint, reduction of DSN in cycle 1. In the per-protocol population, mean (standard deviation) DSN was 0.8 (0.92) and 0.9 (1.11) days in the two groups, respectively; the adjusted mean difference between groups was - 0.3 days (95% confidence interval, - 0.70 to 0.19). Non-inferiority was also demonstrated in the intent-to-treat population. The incidence of severe neutropenia in cycle 1 was 51% (21/41) in the lipegfilgrastim group and 52% (23/44) in the pegfilgrastim group. Very severe neutropenia (ANC < 0.1 × 109/L) in cycle 1 was reported by 5 (12%) patients in the lipegfilgrastim group and 8 (18%) patients in the pegfilgrastim group. However, over all cycles, febrile neutropenia (strict definition) was reported by only 1 (2%) patient in each treatment group (during cycle 1 in the lipegfilgrastim group and cycle 6 in the pegfilgrastim group). The mean time to absolute neutrophil count recovery (defined as ≥ 2.0 × 109/L) was 8.3 and 9.4 days in the two groups, respectively. Serious adverse events occurred in 46% of patients in each group; none were considered treatment-related. Eight patients died during the study (2 in the lipegfilgrastim group, 5 in the pegfilgrastim group, and 1 who died before starting study treatment). No deaths occurred during the treatment period, and all were considered to be related to the underlying disease. CONCLUSIONS: This study shows lipegfilgrastim to be non-inferior to pegfilgrastim for the reduction of DSN in elderly patients with aggressive B cell NHL receiving myelosuppressive chemotherapy, with a comparable safety profile. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02044276; EudraCT number 2013-001284-23.

NMDA Receptor-Mediated Motor Cortex Plasticity After 20 Hz Transcranial Alternating Current Stimulation.

Transcranial alternating current stimulation (tACS) has been shown to modulate neural oscillations and excitability levels in the primary motor cortex (M1). These effects can last for more than an hour and an involvement of N-methyl-d-aspartate receptor (NMDAR) mediated synaptic plasticity has been suggested. However, to date the cortical mechanisms underlying tACS after-effects have not been explored. Here, we applied 20 Hz beta tACS to M1 while participants received either the NMDAR antagonist dextromethorphan or a placebo and the effects on cortical beta oscillations and excitability were explored. When a placebo medication was administered, beta tACS was found to increase cortical excitability and beta oscillations for at least 60 min, whereas when dextromethorphan was administered, these effects were completely abolished. These results provide the first direct evidence that tACS can induce NMDAR-mediated plasticity in the motor cortex, which contributes to our understanding of tACS-induced influences on human motor cortex physiology.

Prevention, monitoring and treatment of cardiovascular adverse events in myeloma patients receiving carfilzomib A consensus paper by the European Myeloma Network and the Italian Society of Arterial Hypertension.

BACKGROUND: The novel proteasome inhibitor carfilzomib alone or in combination with other agents is already one of the standard therapies for relapsed and/or refractory multiple myeloma (MM) patients and produces impressive response rates in newly diagnosed MM as well. However, carfilzomib-related cardiovascular adverse events (CVAEs) - including hypertension (all grades: 12.2%; grade ≥3: 4.3%), heart failure (all grades: 4.1%; grade ≥3: 2.5%) and ischemic heart disease (all grades: 1.8%; grade ≥3: 0.8%) - may lead to treatment suspensions. At present, there are neither prospective studies nor expert consensus on the prevention, monitoring and treatment of CVAEs in myeloma patients treated with carfilzomib. METHODS: An expert panel of the European Myeloma Network in collaboration with the Italian Society of Arterial Hypertension and with the endorsement of the European Hematology Association aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk-benefit ratio of diagnostic and therapeutic tools, thereby achieving myeloma response with novel combination approaches whilst preventing CVAEs. RESULTS: Patients scheduled to receive carfilzomib need a careful cardiovascular evaluation before treatment and an accurate follow-up during treatment. CONCLUSIONS: A detailed clinical assessment before starting carfilzomib treatment is essential to identify patients at risk for CVAEs, and accurate monitoring of blood pressure and of early signs and symptoms suggestive of cardiac dysfunction remains pivotal to safely administer carfilzomib without treatment interruptions or dose reductions.

[Resuscitative endovascular balloon occlusion of the aorta : Bridge to surgery]. / "Resuscitative endovascular balloon occlusion of the aorta" : Überbrückende Maßnahme bis zur operativen Versorgung.

BACKGROUND: Severe hemorrhage remains the leading cause of death among trauma patients. Resuscitative balloon occlusion of the aorta (REBOA) is an endovascular alternative to the established emergency room thoracotomy with cross-clamping of the aorta in patients with severe abdominal or pelvic bleeding. OBJECTIVE: The article reports on initial experiences with REBOA. METHODS: Based on the literature and own experiences the pathophysiology, indications, contraindications, technical details and first results with REBOA are presented. RESULTS: The REBOA procedure is indicated in patients with treatment-refractive hemorrhagic shock with severe abdominal or pelvic bleeding. Via a transfemoral approach a balloon catheter is placed in the aorta and inflated. Depending on the indication the aortic occlusion is located in a supradiaphragmatic (zone 1) or infrarenal (zone 3) position. Experimental results proved a significant increase in central perfusion pressure after performance of REBOA. Furthermore, first clinical data indicate an improved patient survival rate after trauma. Improvements of the devices and minimizing the access trauma using small 7 Fr sheaths decreased the perioperative complication rate. CONCLUSION: The REBOA procedure is a promising endovascular technique for temporary stabilization of the circulation in patients with hemorrhagic shock. Further clinical studies and registries have yet to prove its superiority over emergency room thoracotomy.

[Vascular surgical training concept for military surgeons in Germany]. / Gefäßchirurgisches Ausbildungskonzept für Militärchirurgen in Deutschland.

BACKGROUND: Due to the increasing threat of terrorist attacks and assassinations even in Europe, the interest in management of severe vascular injuries, which, with an increased incidence of 10% are to be expected with such penetrating wounds, is also growing; however, with increasing subspecialization in surgery there is a threat that the know-how in vascular surgery will become lost among non-vascular surgical specialists. Therefore, the Germany military established an educational program, the so-called DUOplus concept, to ensure that future military surgeons acquire and retain the experience and skills to fulfill the demanding role of a deployed surgeon. OBJECTIVE: The DUOplus concept of the German Medical Forces is introduced with a special focus on vascular surgery training. RESULTS: All trainee German military surgeons attain a second specialization alongside general surgery. This residency includes several courses in various surgical specialties as well as a 12-month rotation in a vascular surgery department. The core elements of vascular trauma training are two practical courses on life-like models. In these courses, which were developed especially for the needs of non-vascular surgeons in hands-on training, open surgical techniques and damage control measures including resuscitative endovascular balloon occlusion of the aorta (REBOA) are taught on suitable models and intensively practiced. CONCLUSION: All surgeons potentially confronted with traumatic and iatrogenic vascular injuries should have some basic competence in the management of vascular trauma. Especially the courses in vascular surgery for non-vascular surgeons offer such a skill set for every surgeon. Next to the German military surgeons, the courses are attended more and more by civilian and military surgeons from different surgical specialties and nationalities.

A randomized trial on chlorhexidine dressings for the prevention of catheter-related bloodstream infections in neutropenic patients.

BACKGROUND: Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing catheter securement dressings may prevent CRBSI. PATIENTS AND METHODS: A multicenter randomized, controlled trial was conducted at 10 German hematology departments. We compared chlorhexidine-containing dressings with non-chlorhexidine control dressings in neutropenic patients. The primary end point was the incidence of definite CRBSI within the first 14 days (dCRBSI14) of CVC placement. Secondary end points included combined incidence of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), incidence of unscheduled dressing changes and adverse events. RESULTS: From February 2012 to September 2014, 613 assessable patients were included in the study. The incidence of dCRBSI14 was 2.6% (8/307) in the chlorhexidine and 3.9% (12/306) in the control group (P = 0.375). Both dpCRBSI14 and dpCRBSI were significantly less frequent in the study group with dpCRBSI14 in 6.5% (20/307) of the chlorhexidine group when compared with 11% (34/306) in the control group (P = 0.047), and dpCRBSI in 10.4% (32/307) versus 17% (52/306), respectively (P = 0.019). The frequency of dressing intolerance with cutaneous and soft tissue abnormalities at the contact area was similar in both groups (12.4% and 11.8%; P = 0.901). CONCLUSIONS: Although the trial failed its primary end point, the application of chlorhexidine containing catheter securement dressings reduces the incidence of definite or probable CRBSI in neutropenic patients. CLINICAL TRIALS NUMBER: NCT01544686 (Clinicaltrials.gov).

High Rates of Thromboembolic Events in Patients with Germ Cell Cancer Undergoing Cisplatin-Based Polychemotherapy.

BACKGROUND: We examined whether or not extended prophylaxis with low molecular weight heparin (LMWH) would significantly reduce thromboembolic event (TEE) rates in germ cell cancer patients undergoing cisplatin-based chemotherapy. PATIENTS AND METHODS: LMWH prophylaxis was given from the first day of chemotherapy until 21 days after completing the last chemotherapy cycle to 45 out of 93 (48.4%) patients (extended), and to 48 out of 93 (51.6%) patients during their hospitalization only (limited) between January 2008 and December 2013. Patients were analyzed retrospectively for TEEs such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) or peripheral arterial thrombosis. RESULTS: A total of 22/93 (23.7%) patients experienced 30 TEE during chemotherapy: 12 out of 30 (40%) deep vein thrombosis, 4 out of 30 (13.3%) MI, 10 out of 30 (33.3%) PE and 4 out of 30 peripheral arterial thrombosis (13.3%). TEE rates in both groups did not differ significantly (extended: 26.7 vs. limited: 20.8%). CONCLUSIONS: The introduction of extended LMWH prophylaxis did not significantly reduce TEE rates in our patient cohort.

[Acute therapeutic measures for limb salvage Part 1 : Haemorrhage control, emergency revascularization, compartment syndrome]. / Akute Maßnahmen beim "limb salvage"-Prozedere Teil 1 : Blutungskontrolle, Notfallrevaskularisation, Kompartmentsyndromtherapie.

The primary care of Gustilo-Anderson type IIIC extremity injuries with relevant vessel lacerations is decisive for the success of a limb salvage procedure. This article shall present substantial emergency procedures for the salvage of the nutritive perfusion of a mangled extremity, based on the current literature. After provisory control of a peripheral haemorrhage (e. g. by manual pressure or tourniquet), an immediate decision must be made about the kind of emergency revascularization to be implemented as the limb salvage procedure. Here, the temporary intravascular shunt will be the fastest technique that can ensure a sufficient tissue perfusion in the case of vessel lacerations. Regarding the treatment of a fracture versus perfusion recovery, a shortening of ischemia time should have priority over fracture stabilization.If an acute compartment syndrome is suspected, a documented monitoring has to be performed in the limb salvage situation for 24 hours with clinical controls every 4 hours. Disproportional pain that does not respond to analgesics, and passive muscle stretching pain can be seen as cardinal symptoms. The positive predictive value of clinical findings is <15 %. During the observation period with an impending but not manifest compartment syndrome, an elevation of the extremity above heart level or its cooling are contraindicated. An intracompartmental pressure measurement is the most important instrument-based supplemental diagnostic method. The open fasciotomy of the affected compartments is the only causal therapy and should be performed as fast as possible. A decision against fasciotomy in cases of non-explicit clinical signs should not be made without a documented intracompartmental pressure measurement.

[Physician Shortage: How to Prevent Generation Y From Staying Away - Results of a Nationwide Survey]. / Ärztemangel: Was tun, bevor Generation Y ausbleibt? Ergebnisse einer bundesweiten Befragung.

BACKGROUND: Medical students' attitudes and expectations about their future working life are changing. To hire the best talents from Generation Y, hospitals must pay attention to these factors to make working in patient care more attractive. However, little detailed knowledge about the professional and career expectations of today's medical students is available to date. METHOD: In a nationwide online survey, a total of 9079 medical students from all German medical faculties returned the questionnaire. Twenty-one questions related to future career choices and work satisfaction, followed by 21 questions dealing with reasons for not working in patient care. RESULTS: Factor analysis yielded five factors: work-life balance, career, professional needs, working atmosphere, and prestige. A correlation analysis between these factors and respondents' socio-demographic data revealed significant correlations with sex, specialty choice, and marital/parental status. A correlation analysis with "reasons for not working in patient care" revealed that work-life balance, career, professional needs, and working atmosphere had high priority for both sexes. DISCUSSION: It is crucial to collect data on the work satisfaction of Generation Y, whose members are motivated and willing to perform in today's highly demanding work environment. However, sex-dependent/independent expectations must be met to make the medical profession more attractive, to overcome the Germany-wide shortage of physicians, and to attract young doctors to the hospitals.

Aneurysmal bone cyst (ABC) : treatment options and proposal of a follow-up regime.

The aim of this study was to describe treatment -options and develop a follow-up regime for the -aneurysmal bone cyst, a neoplastic bone lesion with a noticeable recurrence rate. Reports of 28 patients and a mean follow-up of 42.2 months treated multidisciplinary were analysed. Data were complemented by a literature review including 790 patients. Patient age was from seven to 57 years, in line with the literature (1-69 years). Lesions most frequently affect long bones, spine and pelvis ; pain is the most common symptom. Treatment modalities vary, recurrences -occurred in 26.1% in our series, rates ranged from 0-60% in the literature, with the vast majority within 2 years. With regard to the findings we propose, irrespective of treatment, a follow-up regime including clinical survey and imaging, best with MRI, at 3 months, 6 months and at half-yearly intervals within the first two and yearly within the third to fifth year.

Trained clinical nurse specialists proficiently obtain bone marrow aspirates and trephine biopsies in a nearly painless procedure--a prospective evaluation study.

Patients often experience bone marrow examinations (BMEs) as frightening and painful. Varying operators and uncertainty about who will perform the BME worsen their anxiety. In our study, clinical nurse specialists (CNSs) were trained to perform BMEs to ensure continuity and to test the feasibility, patient satisfaction, and biopsy quality. This exploratory evaluation assessed 574 BMEs at our tertiary center between January 2012 and February 2013, 398 BMEs performed by CNS and 176 by physicians. Our aims were to determine whether BMEs by CNS yield results similar to those of physicians, analyzing (1) patient satisfaction with the BME (a) consent and (b) performance, (2) induced pain, and (3) quality of aspirates and length of trephine biopsies. When performed by CNS, 100 % of the patients were satisfied with the consent procedure and 99 % with the BME performance (physicians 99 and 91 %, respectively). The median pain score was low when both CNS and physicians performed the BME, with no or only mild pain in 92 and 76 % of patients, respectively. Bone marrow (BM) aspirates by CNS and physicians were assessed as technically evaluable in ~70 %; moreover, the median length of trephine biopsies was similar when performed by CNS or physicians with 12 and 13 mm, respectively. In conclusion, BMEs conducted by motivated CNS and within a structured training program are feasible and yield equal outcomes compared to physicians. The use of adequate pain management during BMEs by trained and experienced operators results in an extremely rare use of sedatives, low pain scores, and high patient satisfaction.

[Carotid aneurysm as a differential diagnosis of a cervical tumor]. / Karotisaneurysma als Differenzialdiagnose eines Halstumors.

This article presents the case of a patient with a submandibular cervical tumor initially suspected to be a large lymph node or glomus tumor. However, the diagnostic workup prior to taking a biopsy sample revealed an extracranial aneurysm of the internal carotid artery. In order to prevent a permanent neurologic deficit arising from thromboembolism, the aneurysm was excluded by resection and arterial continuity was restored. Extracranial aneurysms of the internal carotid artery are rare, but serious differential diagnoses of cervical nodes. It is of paramount importance that this differential diagnosis be considered before initiating invasive diagnostics of these tumors.

Incidence, risk factors, and implemented prophylaxis of varicella zoster virus infection, including complicated varicella zoster virus and herpes simplex virus infections, in lenalidomide-treated multiple myeloma patients.

In the era of high-dose chemotherapy and novel antimyeloma agents, the survival of multiple myeloma (MM) patients has substantially improved. Adverse effects, including infections, may however arise in the era of combination antimyeloma therapies. In general, MM patients have shown a risk of varicella zoster virus (VZV) infection of 1-4 %, increasing with bortezomib treatment or transplants, but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients, consecutively seen and treated in our department. Patients' data were analyzed via electronic medical record retrieval within our research data warehouse as described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV or other complicated VZV/HSV infections. These VZV patients showed defined risk factors as meticulously assessed, including suppressed lymphocyte subsets, substantial cell-mediated immune defects, and compromised humoral immune response. Due to our findings-and in line with an aciclovir prophylaxis in bortezomib and stem cell transplant protocols-we introduced a routine aciclovir prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events and to avoid discontinuation of lenalidomide treatment. Since then, we have observed no case of VZV/complicated HSV infection. Based on our data, we encourage other centers to also focus on these observations, assess viral infections, and-in those centers facilitating a research data warehouse-advocate an analogue data review as an appropriate multicenter approach.

[Multiple myeloma]. / Das multiple Myelom.

Multiple myeloma (MM) is a cancer originating from terminally differentiated B lymphocytes, the plasma cells and is classified as a B cell non-Hodgkin lymphoma. As clonal plasma cells secrete immunoglobulin molecules (lacking antigenic specificity), an "M component" can incidentally be detected. Besides intact immunoglobulin molecules, free light chains can be produced. Although there is no specific treatment for monoclonal gammopathy of undetermined significance (MGUS), which is the defined as the presence of clonal bone marrow plasma cells and low levels (serum and/or urine) of the M component, it should be followed up in affected individuals. The symptoms of MM are numerous and often nonspecific. Diagnosis includes the quantification of monoclonal proteins in serum and urine, blood count, electrolytes and renal function, imaging of the skeleton and bone marrow puncture. The cornerstone of therapy includes melphalan- or cyclophosphamide-based regimens incorporating one of the "novel drugs" (i.e. bortezomib, thalidomide, or lenalidomide).

Training in vascular trauma surgery for non-vascular surgeons: Vascular trauma surgery skills course.

Background: The experience of general and trauma surgeons in vascular trauma management has decreased with sub-specialization of surgery and working hours restrictions. We introduce a vascular trauma surgery skills course established to train German military surgeons prior to their deployment to conflict areas. Methods: The intention and implementation of the vascular trauma course for non-vascular surgeons is described in detail. Results: In hands-on courses, participants learn and train basic vascular surgical techniques on more realistic extremity, neck, and abdominal models with pulsatile vessels. A fundamental and an advanced course each provide military as well as civilian surgeons from different non-vascular specialties with a surgical skill set including direct vessel sutures, patch angioplasty, anastomosis, thrombectomy, and resuscitative endovascular balloon occlusion of the aorta (REBOA) in order to render them capable of managing major vascular injuries. Conclusion: The experiences of this vascular trauma surgical skills course, initially established for military surgeons, can also be of use to all civilian general, visceral, and trauma surgeons occasionally facing traumatic or iatrogenic vascular injuries. Thus, the introduced vascular trauma course is valuable for all surgeons working in trauma centers.

Effects of foam rolling on vastus intermedius and lateralis microvascular blood flow.

INTRODUCTION: Foam Rolling (FR) as a technique of self-massage has become a widely used intervention in clinical and sports practice. It is assumed that FR leads to an increased intramuscular microvascular blood flow (MBF), and therefore is commonly recommended as a warm-up or regeneration method. However, no data validate the effects of FR on MBF. This study aimed to assess whether FR increases intramuscular MBF using contrast-enhanced ultrasound (CEUS). METHODS: Ten healthy athletes performed a standardized FR intervention applied to the lateral thigh (3 sets: 45 s FR, 20 s rest). Intramuscular perfusion was determined by CEUS under resting conditions (t0), immediately (t1), and 30 min (t2) after the intervention. Peak enhancement (PE), wash-in rate (WiR), and wash-in perfusion index (WiPI) were evaluated as quantitative perfusion parameters in vastus lateralis (VL) and intermedius (VI) muscle separately via regions of interest mapping. RESULTS: Immediately after the intervention (t1), perfusion parameters showed a non-significant decrease in VL (p = 0.3; PE: -32.1%, WiPI: -29.6%, WiR: -50.4%) and VI (p = 0.4; PE: -10.3%, WiPI: -6.4%, WiR: -35.6%). A non-significant decrease was found at t2 in VL (p = 0.2; PE: -34%, WiPI -33.9%, WiR -61.2%) and VI (p = 0.2; PE -17.6%, WiPI -13.8%, WiR -43.2%). CONCLUSIONS: The common assumption of intramuscular MBF improvement due to FR could not be confirmed for up to 30 min after the intervention. If an increase in intramuscular metabolism or MBF is intended, we recommend that alternative methods (i.e., traditional warm-up) should be preferred.

Critical limb ischaemia: initial treatment and predictors of amputation-free survival.

OBJECTIVES: To evaluate initial treatment and risk factors for amputation-free survival in patients with critical limb ischaemia (CLI). DESIGN: Prospective clinical cohort study at a single vascular surgical centre in Germany. METHODS: Data on 104 consecutive patients (115 ischaemic limbs) presenting with their first episode of CLI were collected prospectively over a 3-year period. Initial treatment was classified as conservative therapy, intervention, surgery, or major amputation. Patient co-morbidities were assessed by uni- and multivariate analysis to determine risk factors for limb salvage, survival and amputation-free survival. RESULTS: Indications for treatment were rest pain in 27 (23.5%) and tissue loss in 88 (76.5%) limbs. Revascularisation was attempted in 65% of all limbs: 45% by intervention and 55% by surgery. In 9% primary amputation was necessary and 22% received conservative therapy. Median follow-up was 28 months (1-42). The 3-year limb salvage, patient survival, and amputation-free survival rates were 73%, 41%, and 31%, respectively. Diabetes, cardiac disease and renal insufficiency were associated with poor survival. Combined cardiac and renal disease adversely affected amputation-free survival (HR, 3.68; 95% CI, 1.51-8.94; P < 0.001). CONCLUSIONS: At least two third of all patients presenting with CLI can be offered some type of direct revascularisation. In patients with major cardiac disease and renal insufficiency, a poor outcome in terms of amputation-free survival is to be anticipated.

Evidence level in the treatment of meningioma with focus on the comparison between surgery versus radiotherapy. A review.

In the majority of cases surgery of intracranial meningioma is the primary treatment option. If tumor regrowth occurs or a tumor remnant is left, radiotherapy or radiosurgery are performed. Purpose of this review is to clarify the question, if evidence based data exists regarding the treatment of meningiomas with special focus on the efficacy of stereotactic radiosurgery/ radiotherapy (SRS/ SRT) compared to surgery. A systematic literature search in the most relevant medical databases was done. Primary studies and systematic review with focus on epidemiologic problems and different therapeutic approaches for the treatment of meningioma were included. Standardized data extraction was performed. A total of 31 publications were included. Information and results in the data published with a surgical focus vary strongly regarding the localization of the meningiomas. No randomized clinical trials or prospective cohort studies could be identified. Comparison between surgical and radiotherapeutic success rates was not clearly possible due to different outcome scales (Simpson grading versus tumor volume reduction) used. Progression free survival was ranging from 77% to 97% (complete surgical resection) and 82% to 97% (surgical resection and additional radiotherapeutical treatment) in publications not differentiating between the location of the meningioma. Although no clear evidence exists that one treatment is better than the other, in symptomatic meningioma surgery is considered to be the primary treatment, if the surgical risk is acceptable. Stereotactic radiosurgery and radiotherapy are reserved to locations (optic sheet, cavernous sinus), where surgical risk is expected to be higher.