An 8-week injury prevention exercise program combined with change-of-direction technique training limits movement patterns associated with anterior cruciate ligament injury risk.

Knee ligament sprains are common during change-of-direction (COD) maneuvers in multidirectional team sports. This study aimed to compare the effects of an 8-week injury prevention exercise program containing COD-specific exercises and a similar program containing linear sprint exercises on injury- and performance-related variables during a 135° COD task. We hypothesized that the COD-specific training would lead to (H1) stronger reductions in biomechanical variables associated with anterior cruciate ligament (ACL) injury risk during COD, i.e. knee abduction moment and angle, hip internal rotation angle and lateral trunk lean, and (H2) more effective improvements in COD performance according to the COD completion time, executed angle, ground contact time, and approach speed. Twenty-two sports science students (40% female) completed biomechanical assessments of COD movement strategies before and after participating in two supervised 25-min training sessions per week over 8 weeks. We observed significant 'training x group' interaction effects in support of H1: the COD-specific training but not the linear sprint training led to reduced peak knee abduction moments (interaction, p = 0.027), initial knee abduction (interaction, p < 0.001), and initial lateral trunk lean angles (interaction, p < 0.001) compared to baseline. Although the COD-specific training resulted in sharper executed angles (interaction, p < 0.001), the sprint-specific training group showed reduced COD completion (interaction, p = 0.037) and ground contact times (interaction, p < 0.001). In conclusion, a combination of generic and COD-specific injury prevention training resulted in COD technique adaptations that can help to avoid ACL injury-prone COD movements but may negatively affect COD speed.

[MEK inhibitor-associated retinopathy under binimetinib treatment for cutaneous malignant melanoma]. / MEK-Inhibitor-assoziierte Retinopathie unter Binimetinib-Therapie bei kutanem malignem Melanom.

The treatment options for patients with metastatic melanoma (MM) have been dramatically expanded in recent years with the approval of new drugs. The MEK (mitogen-acitvated protein kinase kinase) and BRAF (serine/threonine-protein kinase B-Raf coding gene) inhibitor combination therapy is currently part of the standard of care for stage IIIC/IV of BRAF mutant melanoma. The MEK inhibitor-associated retinopathy (MEKAR) is observed in patients with MM who are treated (or have been treated) with such a combination therapy. This article reports the case of a 72-year-old male patient, who suffered from such a pathological condition under treatment with binimetinib in combination with nivolumab. This case study illustrates the importance of interdisciplinary collaboration in the treatment of MM patients.

[Helping people to help themselves : 10 years of successful graduate medical training in otorhinolaryngology in Rwanda (Africa)]. / Hilfe zur Selbsthilfe : 10 Jahre erfolgreiche Weiterbildung von Hals-Nasen-Ohren-Ärzten in Ruanda (Afrika).

After the horrifying genocide in Rwanda in 1994, medical care of the small country almost broke down completely. During the following years, different medical fields had to be redeveloped. However, until 2009, there was no training program for otorhinolaryngology offered in Rwanda. Together with the University of Rwanda, we established a Master of Medicine Program that started in 2010. With the support of German otorhinolaryngologists, 10 ENT specialists have completed their training to date and 15 colleagues are currently still undergoing education in the program.

[Intraoperative optical coherence tomography in explorative vitrectomy in patients with vitreous haemorrhage-a case series]. / Intraoperative optische Kohärenztomographie bei explorativer Vitrektomie an Patienten mit Glaskörperblutung ­ eine Fallserie.

BACKGROUND: High-resolution spectral domain optical coherence tomography (SD-OCT) is a gold standard technique for diagnosis, management and monitoring of patients with vitreoretinal diseases. Preoperative diagnostics for evaluation of intraocular and retinal status in patients with vitreous haemorrhage are limited, thus final therapeutic decisions can only be made during explorative vitrectomy. We evaluated the use of intraoperative SD-OCT (iSD-OCT) as a real-time additional diagnostic tool during explorative vitrectomy in patients with vitreous haemorrhage. METHODS: We report on 9 patients (11 eyes) with vitreous haemorrhage. Preoperative ultrasound was performed to evaluate intraocular status. Subsequently, an explorative 23G pars plana vitrectomy was performed under visualisation with the OPMI Lumera 700 surgical microscope (Carl Zeiss Meditec, Jena, Germany) equipped with a fully integrated iSD-OCT device (Rescan 700, Carl Zeiss Meditec, Jena, Germany) as a real-time diagnostic tool. RESULTS: In all patients, intraoperative iSD-OCT allowed real-time evaluation of the preretinal, intraretinal and subretinal structures in addition to the intraoperative en face image. The further surgical strategy, i. e. necessity for peeling of epiretinal membranes (ERM) or of the inner limiting membrane (ILM), application of intravitreal medication and selection of the appropriate tamponade, was based on and optimised according to the iSD-OCT images. CONCLUSION: Intraoperative iSD-OCT is highly useful as an additional intraoperative diagnostic tool in patients with vitreous haemorrhage. In addition to the en face microscope image, it facilitates intraoperative real-time diagnosis and aids therapeutic decision-making during surgery.

Ultraflexible Nanowire Array for Label- and Distortion-Free Cellular Force Tracking.

Living cells interact with their immediate environment by exerting mechanical forces, which regulate important cell functions. Elucidation of such force patterns yields deep insights into the physics of life. Here we present a top-down nanostructured, ultraflexible nanowire array biosensor capable of probing cell-induced forces. Its universal building block, an inverted conical semiconductor nanowire, greatly enhances both the functionality and the sensitivity of the device. In contrast to existing cellular force sensing architectures, microscopy is performed on the nanowire heads while cells deflecting the nanowires are confined within the array. This separation between the optical path and the cells under investigation excludes optical distortions caused by cell-induced refraction, which can give rise to feigned displacements on the 100 nm scale. The undistorted nanowire displacements are converted into cellular forces via the nanowire spring constant. The resulting distortion-free cellular force transducer realizes a high-resolution and label-free biosenor based on optical microscopy. Its performance is demonstrated in a proof-of-principle experiment with living Dictyostelium discoideum cells migrating through the nanowire array. Cell-induced forces are probed with a resolution of 50 piconewton, while the most flexible nanowires promise to enter the 100 femtonewton realm.

An approach to generate noncontact ACL-injury prone situations on a computer using kinematic data of non-injury situations and Monte Carlo simulation.

ACL-injuries are one of the most common knee injuries in noncontact sports. Kinematic data of injury prone situations provide important information to study the underlying ACL-injury mechanisms. However, these data are rare. In this work an approach is presented to generate injury prone situations for noncontact ACL-injuries on a computer. The injury prone situations are generated by a musculoskeletal simulation model using kinematic data of a non-injury situation and the method of Monte Carlo simulation. The approach is successfully applied to generate injury prone landings in downhill ski racing. The characteristics of the obtained injury prone landings are consistent with video recordings of injury cases.

Radiation exposure of adrenal vein sampling: a German Multicenter Study

Objective: Adrenal vein sampling (AVS) represents the current diagnostic standard for subtype differentiation in primary aldosteronism (PA). However, AVS has its drawbacks. It is invasive, expensive, requires an experienced interventional radiologist and comes with radiation exposure. However, exact radiation exposure of patients undergoing AVS has never been examined. Design and Methods: We retrospectively analyzed radiation exposure of 656 AVS performed between 1999 and 2017 at four university hospitals. The primary outcomes were dose area product (DAP) and fluoroscopy time (FT). Consecutively the effective dose (ED) was approximately calculated. Results: Median DAP was found to be 32.5 Gy*cm2 (0.3­3181) and FT 18 min (0.3­184). The calculated ED was 6.4 mSv (0.1­636). Remarkably, values between participating centers highly varied: Median DAP ranged from 16 to 147 Gy*cm2, FT from 16 to 27 min, and ED from 3.2 to 29 mSv. As main reason for this variation, differences regarding AVS protocols between centers could be identified, such as number of sampling locations, frames per second and the use of digital subtraction angiographies. Conclusions: This first systematic assessment of radiation exposure in AVS not only shows fairly high values for patients, but also states notable differences among the centers. Thus, we not only recommend taking into account the risk of radiation exposure, when referring patients to undergo AVS, but also to establish improved standard operating procedures to prevent unnecessary radiation exposure.

[Update on endocrine hypertension]. / Update endokrine Hypertonie.

Endocrine disorders are the most common causes of secondary hypertension. Early diagnosis and specific treatment are crucial for improvement of the prognosis. This article provides an overview on which clinical constellations point to an increased risk of secondary causes of hypertension. These include spontaneous hypokalemia, young age at onset of hypertension, adrenal incidentaloma and therapy refractive arterial hypertension. The basic diagnostics include determination of the aldosterone to renin ratio, measurement of free plasma metanephrines and a 1 mg dexamethasone suppression test. Borderline results require repeated control testing and/or confirmatory testing under standardized test conditions. In cases of repeatedly conspicuous results referral to a specialized clinic should be considered for further clarification and confirmation of the diagnosis. Imaging diagnostics may constitute an adjunct to laboratory testing after the diagnosis has been confirmed. Therapeutic algorithms vary depending on the underlying endocrine disease.

Clinical Consequences of Hypertriglyceridemia-Associated Proteinuria in Miniature Schnauzers.

BACKGROUND: Primary hypertriglyceridemia is a common condition in older Miniature Schnauzers that recently has been associated with proteinuria and underlying glomerular pathology, particularly glomerular lipid thromboemboli. Consequences of glomerular disease can include hypertension, thromboembolic disease, and cardiac disease. The incidence of these sequelae in Miniature Schnauzers with hypertriglyceridemia-associated proteinuria (HTGP) is unknown. OBJECTIVE: To investigate prevalence of hypertension, decreased antithrombin III activity, and cardiac disease in Miniature Schnauzers with and without HTGP. ANIMALS: Thirty-two Miniature Schnauzers ≥7 years old. METHODS: Prospective case-control study. Data collected from dogs included a CBC, biochemistry panel, urinalysis, urine protein-to-creatinine ratio, urine cortisol-to-creatinine ratio, serum total thyroxine concentration, fasting serum triglyceride concentration, indirect blood pressure, antithrombin III activity, and serum cardiac troponin I concentration. Results from dogs with HTGP (serum triglyceride concentration ≥ 100 mg/dL and urine protein-to-creatinine ratio >0.5) were statistically compared to normotriglyceridemic, nonproteinuric dogs. RESULTS: Eighteen of the 32 dogs (56%) had primary hypertriglyceridemia. Of those dogs, 8 of 18 had proteinuria. None of the HTGP dogs were azotemic or hypoalbuminemic. Serum albumin concentration, alkaline phosphatase activity, and cholesterol concentration were significantly increased in dogs with HGTP compared to those without HGTP. No increased risk of hypertension, decreased antithrombin III activity, or cardiac disease was noted. Limited data from 8 dogs with HTGP showed no development of hypoalbuminemia or azotemia over a median follow-up period of 18 months. CONCLUSIONS AND CLINICAL IMPORTANCE: Geriatric Miniature Schnauzers with HGTP may have a good prognosis overall, and are not typically azotemic or hypoalbuminemic.

Re-treatment with radium-223: first experience from an international, open-label, phase I/II study in patients with castration-resistant prostate cancer and bone metastases.

BACKGROUND: Six radium-223 injections at 4-week intervals is indicated for patients with castration-resistant prostate cancer and symptomatic bone metastases. However, patients usually develop disease progression after initial treatment. This prospective phase I/II study assessed re-treatment safety and efficacy of up to six additional radium-223 injections. PATIENTS AND METHODS: Patients had castration-resistant prostate cancer and bone metastases and six initial radium-223 injections with no on-treatment bone progression; all had subsequent radiologic or clinical progression. Concomitant agents were allowed at investigator discretion, excluding chemotherapy and initiation of new abiraterone or enzalutamide. The primary endpoint was safety; additional exploratory endpoints included time to radiographic bone progression, time to total alkaline phosphatase and prostate-specific antigen progression, radiographic progression-free survival, overall survival, time to first symptomatic skeletal event (SSE), SSE-free survival, and time to pain progression. RESULTS: Among 44 patients, 29 (66%) received all six re-treatment injections. Median time from end of initial radium-223 treatment was 6 months. Forty-one (93%) reported ≥1 treatment-emergent adverse event. No grade 4-5 hematologic treatment-emergent adverse events occurred. Only one (2%) patient had radiographic bone progression; eight (18%) had radiographic soft tissue tumor progression (three lymph node and five visceral metastases). Median times to total alkaline phosphatase and prostate-specific antigen progression were not reached and 2.2 months, respectively. Median radiographic progression-free survival was 9.9 months (12.8-month maximum follow-up). Five (11%) patients died and eight (18%) experienced first SSEs. Median overall survival, time to first SSE, and SSE-free survival were not reached. Five (14%) of 36 evaluable patients (baseline worst pain score ≤7) had pain progression. After 2 years of follow-up, 28 (64%) patients died, and the median overall survival was 24.4 months. CONCLUSIONS: Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials.

Bystander capability to activate speaker function for continuous dispatcher assisted CPR in case of suspected cardiac arrest.

BACKGROUND: The European Resuscitation Council Guidelines 2015 recommend bystanders to activate their mobile phone speaker function, if possible, in case of suspected cardiac arrest. This is to facilitate continuous dialogue with the dispatcher including (if required) cardiopulmonary resuscitation instructions. The aim of this study was to measure the bystander capability to activate speaker function in case of suspected cardiac arrest. METHOD: In 87days, a systematic prospective registration of bystander capability to activate the speaker function, when cardiac arrest was suspected, was performed. For those asked, "can you activate your mobile phone's speaker function", audio recordings were examined and categorized into groups according to the bystanders capability to activate speaker function on their own initiative, without instructions, or with instructions from the emergency medical dispatcher. Time delay was measured, in seconds, for the bystanders without pre-activated speaker function. RESULTS: 42.0% (58) was able to activate the speaker function without instructions, 2.9% (4) with instructions, 18.1% (25) on own initiative and 37.0% (51) were unable to activate the speaker function. The median time to activate speaker function was 19s and 8s, with and without instructions, respectively. CONCLUSION: Dispatcher assisted cardiopulmonary resuscitation with activated speaker function, in cases of suspected cardiac arrest, allows for continuous dialogue between the emergency medical dispatcher and the bystander. In this study, we found a 63.0% success rate of activating the speaker function in such situations.

An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223.

Background: Baseline clinical variables are prognostic for overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). Their prognostic and predictive value with agents targeting bone metastases, such as radium-223, is not established. Patients and methods: The radium-223 ALSYMPCA trial enrolled patients with CRPC and symptomatic bone metastases. Prognostic potential of baseline variables was assessed using Cox models. Percentage changes in biomarker levels from baseline were evaluated during the trial period; changes from baseline to week 12 were evaluated for association with OS and surrogacy. Results: Eastern Cooperative Oncology Group performance status, total alkaline phosphatase (tALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) at baseline were associated with OS (P ≤ 0.0003) in the intent-to-treat population (radium-223, N = 614; placebo, N = 307). tALP declined from baseline within 4 weeks after beginning radium-223, by week 12 declining in 87% of radium-223 and 23% of placebo patients (P < 0.001). LDH declined in 51% and 34% (P = 0.003), whereas PSA declined in 27% and 14% (P = 0.160). Mean tALP change from baseline was 32.2% decrease with radium-223 and 37.2% increase with placebo. Radium-223 patients with tALP decline from baseline to week 12 (confirmed ≥3 weeks from week 12) had 55% lower risk of death (hazard ratio = 0.45; 95% CI 0.34-0.61) versus those with no confirmed tALP decline. Proportional treatment effect (PTE) values for tALP, LDH, and PSA changes from baseline at week 12 as OS surrogate markers were 0.34 (95% CI: 0-0.746), 0.07 (95% CI: 0-0.211), and 0 (95% CI: 0-0.082), respectively. Conclusions: Significant tALP declines (versus placebo) occurred as early as 4 weeks after beginning radium-223 therapy. tALP or LDH declines at 12 weeks correlated with longer OS, but did not meet statistical surrogacy requirements. Dynamic changes in tALP and LDH during radium-223 treatments may be useful to monitor, but do not serve as surrogates for survival.

Challenges in tissue engineering - towards cell control inside artificial scaffolds.

Control of living cells is vital for the survival of organisms. Each cell inside an organism is exposed to diverse external mechano-chemical cues, all coordinated in a spatio-temporal pattern triggering individual cell functions. This complex interplay between external chemical cues and mechanical 3D environments is translated into intracellular signaling loops. Here, we describe how external mechano-chemical cues control cell functions, especially cell migration, and influence intracellular information transport. In particular, this work focuses on the quantitative analysis of (1) intracellular vesicle transport to understand intracellular state changes in response to external cues, (2) cellular sensing of external chemotactic cues, and (3) the cells' ability to migrate in 3D structured environments, artificially fabricated to mimic the 3D environment of tissue in the human body.

[The influence of current social, medical, and political trends on the future of otorhinolaryngology]. / Auswirkungen aktueller Trends in Gesellschaft, Medizin und Politik auf die Zukunft der HNO-Heilkunde.

BACKGROUND: All medical specialties are changing permanently, including otorhinolaryngology. Analyzing trends in social changes, medical progress, and political decisions will allow the effects of these on ENT medicine to be at least partially anticipated. TRENDS: Demographic changes and medical progress lead to an increasing demand for medical treatments. In addition, increasing numbers of female physicians are observed, as are many changes in the lifestyles of young physicians. Medical treatment will develop toward more individualized therapies in the future. ENT surgery will become a more ambulatory medical specialty. Driven by political decisions, digital medicine will become more important. Particular services once provided by physicians will be delegated to non-physician professionals. DISCUSSION: The lack of physicians and the progress in medicine require better networking between in- and outpatient services in the future. The potential of such collaborations is currently not completely realized. However, these developments will also increase the cost of health care. CONCLUSION: These trends will develop otorhinolaryngology into a conservative and surgical ambulatory care driven medical specialty. Embedded in decentralized networks and cooperations, and supported by IT technologies and specialized non-physician professionals, ENT physicians will work in hospitals as well as in practices on a permanent basis. Nevertheless, the question of funding these changes has yet to be clarified.

Updates in Molecular Pathology of Central Nervous System Gliomas in Adults.

Central nervous system (CNS) tumors are a heterogeneous group of neoplasms divided into two broad categories, glial and non-glial. Non-glial tumors are derived from such diverse structures as the pineal gland, meninges, germ cells, and hematopoietic cells, as well as metastases. Primary glial neoplasms, or those which originate from astrocytes, oligodendrocytes, or ependymal cells, include astrocytomas, oligodendrogliomas, ependymomas, and mixed gliomas. Each entity has a unique morphology and pattern of biologic behavior which portends a distinct prognosis and outcome. Individual outcomes show some variability based on tumor location and age of symptom onset; however, the underlying aggressiveness of the tumor often dictates the time course of the disease. With the advent and widespread use of fluorescent in-situ hybridization and polymerase chain reaction (PCR) techniques, molecular phenotyping of brain tumors has become mainstream and is now an integral part of patient care. The molecular genetics of CNS tumors is a rapidly growing field, and the volume of discoveries is growing at an ever increasing rate, compelling the need for updates in this exciting area of science.

Effects of magnetic field gradients on the aggregation dynamics of colloidal magnetic nanoparticles.

We have used low-field (1)H nuclear-magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) to investigate the aggregation dynamics of magnetic particles in ionic ferrofluids (IFFs) in the presence of magnetic field gradients. At the beginning of the experiments, the measured NMR spectra were broad and asymmetric, exhibiting two features attributed to different dynamical environments of water protons, depending on the local strength of the field gradients. Hence, the spatial redistribution of the magnetic particles in the ferrofluid caused by the presence of an external magnetic field in a time scale of minutes can be monitored in real time, following the changes in the features of the NMR spectra during a period of about an hour. As previously reported [Heinrich et al., Phys. Rev. Lett., 2011, 106, 208301], in the homogeneous magnetic field of a NMR spectrometer, the aggregation of the particles of the IFF proceeds in two stages. The first stage corresponds to the gradual aggregation of monomers prior to and during the formation of chain-like structures. The second stage proceeds after the chains have reached a critical average length, favoring lateral association of the strings into hexagonal zipped-chain superstructures or bundles. In this work, we focus on the influence of a strongly inhomogeneous magnetic field on the aforementioned aggregation dynamics. The main observation is that, as the sample is immersed in a certain magnetic field gradient and kept there for a time τinh, magnetophoresis rapidly converts the ferrofluid into an aggregation state which finds its correspondence to a state on the evolution curve of the pristine sample in a homogeneous field. From the degree of aggregation reached at the time τinh, the IFF sample just evolves thereafter in the homogeneous field of the NMR spectrometer in exactly the same way as the pristine sample. The final equilibrium state always consists of a colloidal suspension of zipped-chain bundles with the chain axes aligned along the magnetic field direction.

Relationship between jump landing kinematics and peak ACL force during a jump in downhill skiing: a simulation study.

Recent data highlight that competitive skiers face a high risk of injuries especially during off-balance jump landing maneuvers in downhill skiing. The purpose of the present study was to develop a musculo-skeletal modeling and simulation approach to investigate the cause-and-effect relationship between a perturbed landing position, i.e., joint angles and trunk orientation, and the peak force in the anterior cruciate ligament (ACL) during jump landing. A two-dimensional musculo-skeletal model was developed and a baseline simulation was obtained reproducing measurement data of a reference landing movement. Based on the baseline simulation, a series of perturbed landing simulations (n = 1000) was generated. Multiple linear regression was performed to determine a relationship between peak ACL force and the perturbed landing posture. Increased backward lean, hip flexion, knee extension, and ankle dorsiflexion as well as an asymmetric position were related to higher peak ACL forces during jump landing. The orientation of the trunk of the skier was identified as the most important predictor accounting for 60% of the variance of the peak ACL force in the simulations. Teaching of tactical decisions and the inclusion of exercise regimens in ACL injury prevention programs to improve trunk control during landing motions in downhill skiing was concluded.