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.

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.

[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.

TDCS effects on pointing task learning in young and old adults.

Skill increase in motor performance can be defined as explicitly measuring task success but also via more implicit measures of movement kinematics. Even though these measures are often related, there is evidence that they represent distinct concepts of learning. In the present study, the effect of multiple tDCS-sessions on both explicit and implicit measures of learning are investigated in a pointing task in 30 young adults (YA) between 27.07 ± 3.8 years and 30 old adults (OA) between 67.97 years ± 5.3 years. We hypothesized, that OA would show slower explicit skill learning indicated by higher movement times/lower accuracy and slower implicit learning indicated by higher spatial variability but profit more from anodal tDCS compared with YA. We found age-related differences in movement time but not in accuracy or spatial variability. TDCS did not skill learning facilitate learning neither in explicit nor implicit parameters. However, contrary to our hypotheses, we found tDCS-associated higher accuracy only in YA but not in spatial variability. Taken together, our data shows limited overlapping of tDCS effects in explicit and implicit skill parameters. Furthermore, it supports the assumption that tDCS is capable of producing a performance-enhancing brain state at least for explicit skill acquisition.

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.

Prognostic factors for survival after allogeneic transplantation in acute lymphoblastic leukemia.

Allogeneic stem cell transplantation (allo-SCT) offers a curative option in adult patients with acute lymphoblastic leukemia (ALL). Prognostic factors for survival after allo-SCT have not been sufficiently defined: pheno-/genotype, patients´ age, conditioning regimens and remission at allo-SCT are under discussion. We analyzed the outcome of 180 consecutive adult ALL-patients undergoing allo-SCT at our center between 1995 and 2018 to identify specific prognostic factors. In our cohort 19% were older than 55 years, 28% had Philadelphia-positive B-ALL, 24% T-ALL. 54% were transplanted in first complete remission (CR1), 13% in CR2 after salvage therapy, 31% reached no remission (8% within first-line, 23% within salvage therapy). In 66% conditioning contained total body irradiation (TBI). With a median follow-up of 10 years, we observed an overall survival of 33% at 10 years, and a progression free survival of 31%. The cumulative incidence of relapse was 41% at 10 years, the cumulative incidence of non-relapse mortality 28%. Acute graft-versus-host disease (GvHD) II°-IV° occurred in 31%, moderate/severe chronic GvHD in 27%. Survival was better in patients reaching CR before allo-SCT and in those receiving TBI. No difference between patients younger/older than 55 years and between different phenotypes was observed. Survival after allo-SCT improved considerably over the last decades.

Psychological burden, stressors and resources of social workers working with women and children who suffered extreme violence by the 'Islamic state': A mixed method study.

OBJECTIVE: This explorative study aimed to determine the extent of psychological burden in social workers working with traumatized refugees. In addition, distressing and helpful factors determining the psychosocial burden were to be identified and described. METHODS: Cross-sectional, mixed method design using quantitative and qualitative methods. The quantitative part included the Perceived Stress Questionnaire (PSQ) and items to assess specific factors of the working-context. The qualitative part is based on 5 focus groupdiscussions and 16 individual interviews. Evaluation was carried out using qualitative content analysis (QCA) including cross-analysis along the subscales of the PSQ to organise the qualitative material. RESULTS: N = 54 social workers completed the questionnaire. High scores were found for all subscales of the PSQ. The distressing factor rated the highest was need of interpreters to communicate (M = 5.1, SD = 1.71), the helpful factor rated the highest was communication skills (M = 6.35, SD = 0.73). In the QCA, aspects of distressing and helpful factors were identified and further detailed. CONCLUSION: According to the here presented study results, the psychological burdens of social workers working with refugees seem to be high. The impact of distressing factors such as working with interpreters and exposure to trauma content or PTSD symptoms might be reduced by offering specific education and supervision. The individual extent of psychological burden should be considered and (re-)evaluated on a regular basis as secondary prevention. Helpful factors like self-care, teamwork, networking and cooperation are evident and should be supported by implementing professional and psychological support.

Plantar pressure changes in hindfoot relief devices of different designs.

BACKGROUND: It is frequently observed that overloading the foot can impair bone and soft tissue healing and can lead to harmful sequelae (i.e. ulcers, stress reactions) in context of pre-existing tissue disabilities. In terms of offloading, hindfoot relief devices are commonly applied as a non-operative treatment as well as after various surgical procedures for hindfoot disorders. Despite their common use, there is a paucity of data comparing different orthotic devices with respect to changes in plantar pressure distributions. The aim of this study was to investigate plantar loadings in hindfoot relief devices of different designs. METHODS: Twenty-five healthy participants (13 women, 12 men; (mean ± SD) age 37 ± 14 years; BMI 23 ± 4 kg/m2) were recruited. Plantar pressure distributions were collected using i.) a neutral shoe, ii.) a hindfoot relief shoe (HRS) and iii.) a hindfoot relief orthosis (HRO). Peak pressure values were measured via dynamic pedobarography during walking and were analysed from four different plantar regions: the hindfoot, midfoot, metatarsal I-V and forefoot. As a reference standard, the normal walk using neutral shoes served as the condition for full weight-bearing. RESULTS: Concerning the hindfoot, using the HRS as well as the HRO resulted in significant decreases in plantar pressures compared to baseline values that were obtained with the neutral shoe (- 52% for the HRS and - 52% for the HRO, p < 0.001). Significant increases in peak pressures were found in the midfoot region for both devices (HRS: 32%, p = 0.002; HRO: 47%, p < 0.001). For the metatarsal region, peak pressures were found to decrease significantly (HRS: - 52%, p < 0.001; HRO: -17%, p = 0.034). With respect to the forefoot, a significant reduction in peak pressures using the HRS (- 41%, p < 0.001) was detected, whereas the HRO did not lead to significant changes (- 4%, p = 0.691). CONCLUSIONS: Both the HRO and HRS significantly reduced plantar hindfoot pressure, corresponding to a relative decrease of nearly 50% of the baseline. Nevertheless, the adjacent midfoot zone displayed a significant increase in plantar pressure values for both devices. Supported by these findings, physicians should cautiously consider a substantial increase in midfoot loading, especially in patients affected by additional midfoot injuries or accompanying impairments of tissue healing. LEVEL OF EVIDENCE: IV, Case series.

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.

Critical mercury concentration in tropical soils: Impact on plants and soil biological attributes.

Mercury is a toxic element that becomes a problem when present at high concentrations in soils. Mercury toxicity in soils varies depending on chemical species, concentration, exposure routes, and organism vulnerability. There is little information regarding the toxicity of Hg in tropical soils, especially for establishing safe levels of this pollutant. The purpose of this study was to investigate Hg concentrations in two tropical soils and their effect on oats and common beans, as well as on soil biological attributes. The experiment was carried out in a greenhouse, following ISO 11.269-2 and OECD-208 guidelines. Oat and common bean were cultivated in a Typic Hapludox (TyHpx) and Rhodic Acrudox (RhAcx) contaminated with HgCl2 at the following concentrations: 0, 2.5, 5.0, 10.0, 20.0, 40.0, and 80.0 mg of Hg kg-1 of dry soil. The biological variables analyzed were seedling emergence, vegetative growth, chlorophyll content (SPAD index), gas exchange (photosynthetic rate, internal CO2 concentration, transpiration rate, and stomatal conductance), and Hg concentration and accumulation in shoot dry matter. Microbial biomass carbon, soil basal respiration, and metabolic quotient (qCO2) were also analyzed. Due to the sorptive characteristics of TyHpx, it had higher Hg concentrations than RhAcx. Mercury showed toxic effects on both oat and common bean species. However, common bean was affected only at concentrations higher than 20 mg kg-1. The microbial community showed high sensitivity to soil Hg concentrations, but external factors, such as the plant species cultivated, influenced the sensitivity of the community. The microbiota was most sensitive in pots with common bean, and this effect was more pronounced at low clay and low organic matter contents (TyHpx). In this study, the concentration of 0.36 mg kg-1 was critical for Hg in these soils, based on its deleterious effects on oat and common bean and on biological soil attributes.

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.

[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.

Nonoperative treatment of muscle injuries - recommendations from the GOTS expert meeting.

BACKGROUND: Muscle injuries are some of the most common injuries in sports; they have a high recurrence rate and can result in the loss of ability to participate in training or competition. In clinical practice, a wide variety of treatment strategies are commonly applied. However, a limited amount of evidence-based data exists, and most therapeutic approaches are solely based on "best practice". Thus, there is a need for consensus to provide strategies and recommendations for the treatment of muscle injuries. METHODS: The 2016 GOTS Expert Meeting, initiated by the German-Austrian-Swiss Society for Orthopaedic Traumatologic Sports Medicine (GOTS), focused on the topic of muscle and tendon injuries and was held in Spreewald/Berlin, Germany. The committee was composed of twenty-two medical specialists. Nine of them were delegated to a subcommittee focusing on the nonoperative treatment of muscle injuries. The recommendations and statements that were developed were reviewed by the entire consensus committee and voted on by the members. RESULTS: The committee reached a consensus on the utility and effectiveness of the management of muscle injuries. MAIN RESULTS: the "PRICE" principle to target the first inflammatory response is one of the most relevant steps in the treatment of muscle injuries. Haematoma aspiration may be considered in the early stages after injury. There is presently no clear evidence that intramuscular injections are of use in the treatment of muscle injuries. The ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) should be regarded critically because there is currently no hard evidence to support their use, although they are appropriate in exceptional cases. CONCLUSIONS: The present work provides a structured overview of the various nonoperative treatment strategies of muscle injuries and evaluates their effectiveness with respect to the existing scientific evidence and clinical expertise in the context of basic science on the healing process of muscle injuries. The committee agreed that there is a compelling need for further studies, including high-quality randomized investigations to completely evaluate the effectiveness of the existing therapeutic approaches. The given recommendations may be updated and adjusted as further evidence will be generated.

Pharmacokinetics and Target Attainment of Ceftobiprole in Asian and Non-Asian Subjects.

Ceftobiprole is a broad-spectrum cephalosporin. The objective of this study was to test the hypothesis that the pharmacokinetics (PK) and exposure of ceftobiprole in Asian subjects are similar to those in non-Asian subjects. Three approaches were followed. The first compared the individual PK estimates between the 2 subgroups derived from a population PK model previously built. Next, it was determined whether "Asian subject" was a significant covariate. Finally, a pharmacodynamic analysis was performed by comparing measures of exposure and target attainment. No significant differences were found between PK parameter estimates for Asian and non-Asian subjects, with median values (range) for clearance of 4.82 L/h (2.12-10.47) and 4.97 L/h (0.493-20.6), respectively (P = .736). "Asian subject" was not a significant covariate in the population PK model. There were no significant differences between the measures of exposure. The geometric mean ratio for the fAUC was 1.022 (90%CI, 0.91-1.15), indicating bioequivalence. Taking a target of 60% coverage of the dose interval, more than 90% of the population in both subgroups was adequately exposed. This analysis demonstrated that there are no PK or pharmacodynamic differences between Asian and non-Asian subjects for a ceftobiprole dose of 500 mg every 8 hours as a 2-hour infusion.

[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.

Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel.

Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed. In this review, a panel of expert European hematologists updates the recommendations on the diagnosis and management of patients with solitary plasmacytoma.

Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network.

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drugs classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.Leukemia accepted article preview online, 18 December 2017. doi:10.1038/leu.2017.353.