House dust mite immunotherapy: A real-world, prescription data-based analysis.

BACKGROUND: House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long-term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real-world evidence studies are available. METHODS: We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. RESULTS: Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: -34.0%, p < 0.0001; oSCIT: -25.7%, p < 0.0001; SLIT: -37.7%, p = 0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: -45.2%, p < 0.0001; oSCIT: -32.9%, p < 0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p = 0.0476; oSCIT OR: 0.815, p = 0.0339). CONCLUSION: Real-world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR.

Comparison of four methods to -determine cage width in tibial tuberosity advancement.

INTRODUCTION: The objective of this study was to test a method for determining the width of the tibial tuberosity advancement (TTA) cage without the need for extension of the stifle joint, while producing preoperative radiographs. TTA cage size was determined by applying 4 different methods using radiograph images in mediolateral direction of fully extended stifles of dogs (n=43), with and without naturally occurring cranial cruciate ligament disease: parallel shift (PS) method, common tangent (CT) method, «2,1¼ method (cage size = 2,1 × tibia plateau length - tibial tuberosity width), and margo cranialis (MC) method (cage size = length of MC/6*1,75). Two new methods, «2,1¼, and MC were compared to the existing CT and PS methods. All 4 methods resulted in reliable cage sizes. Intraclass correlation coefficients showed an excellent reliability of the CT and PS to the «2,1¼ method and a good reliability in regards to the MC method. In conclusion, TTA cage size of the tibia anatomy alone can be determined on radiographs without the need of full extension of the stifle joint. Based on the results, two different methods of cage size measurement are recommended in order to increase diagnostic accuracy and to prevent the insertion of suboptimal cages.

INTRODUCTION: L'objectif de cette étude était de tester une méthode pour déterminer la largeur de la cage d'avancement de la tubérosité tibiale (TTA) sans avoir besoin d'extension du grasset, tout en réalisant des radiographies préopératoires. La taille de la cage TTA a été déterminée en appliquant 4 méthodes différentes, utilisant des images radiographiques dans l'axe médiolatéral des grassets complètement étendus de chiens (n ​​= 43), avec et sans pathologie naturelle du ligament croisé antérieur: méthode du décalage parallèle (PS), méthode de la tangente commune (CT), méthode «2,1¼ (taille de la cage = 2,1 × longueur du plateau du tibia ­ largeur de la tubérosité tibiale) et méthode de la margo cranialis (MC) (taille de la cage = longueur de MC/6*1,75). Deux nouvelles méthodes, «2,1¼ et MC ont été comparées aux méthodes CT et PS existantes. Les 4 méthodes ont abouti à des tailles de cage fiables. Les coefficients de corrélation intra classe ont montré une excellente fiabilité du CT et du PS avec la méthode «2,1¼ et une bonne fiabilité vis-à-vis de la méthode MC. En conclusion, la taille de la cage TTA de l'anatomie du tibia seule peut être déterminée sur des radiographies sans qu'il soit nécessaire d'étendre complètement l'articulation du grasset. Sur la base des résultats, deux méthodes différentes de mesure de la taille des cages sont recommandées afin d'augmenter la précision du diagnostic et d'empêcher la mise en place de cages sous-optimales.

Pre-analytical stability of sorbitol dehydrogenase in equine heparinized plasma.

Sorbitol dehydrogenase (SDH) activity is one of the most sensitive and specific markers for hepatocellular injury in horses, but its reported lability makes it impractical for use in many clinical settings. To date, stability of SDH in equine samples has only been evaluated in a limited number of studies in serum samples of horses with activities within reference intervals. The objective of the study was to determine pre-analytical stability of equine SDH activity in heparinized plasma stored at different temperatures for up to 72 h. Twenty client-owned horses admitted to a veterinary teaching hospital for any reason were included in the study. Blood samples collected in lithium-heparin tubes were immediately centrifuged and SDH activity was analyzed within 1 h of collection (T0). Aliquots of plasma were stored at room temperature, 4 °C and -20 °C and SDH activity was re-analyzed after 4 h (T4), 24 h (T24) and 72 h (T72). A significant difference from values measured at T0 was found for samples stored at room temperature (P = 0.022) and -20 °C (P < 0.001), but not at 4 °C. The activity of SDH was within ±20% of that measured at T0 for all samples under all temperature conditions stored for 4 h, and for all samples stored at 4 °C for 24 h. Bland-Altman plots revealed narrow limits of agreement at T4 for all storage temperatures and at T24 for samples stored at 4 °C. The mean absolute percentage error and 95th percentile of the absolute percentage error were lower for samples stored at 4 °C than those stored at room temperature or -20 °C. The activity of SDH has adequate stability for 4 h regardless of storage temperature and 24 h if stored at 4 °C across a wide range of values. Knowledge of the pre-analytical stability of SDH may permit its broader use in assessing hepatic disorders in horses.

Reconstructing GRACE-type time-variable gravity from the Swarm satellites.

The Gravity Recovery and Climate Experiment (GRACE) mission has enabled mass changes and transports in the hydrosphere, cryosphere and oceans to be quantified with unprecedented resolution. However, while this legacy is currently being continued with the GRACE Follow-On (GRACE-FO) mission there is a gap of 11 months between the end of GRACE and the start of GRACE-FO which must be addressed. Here we bridge the gap by combining time-variable, low-resolution gravity models derived from European Space Agency's Swarm satellites with the dominating spatial modes of mass variability obtained from GRACE. We show that the noise inherent in unconstrained Swarm gravity solutions is greatly reduced, that basin averages can have root mean square errors reduced to the order of [Formula: see text] of equivalent water height, and that useful information can be retrieved for basins as small as [Formula: see text]. It is found that Swarm data contains sufficient information to inform the leading three global mass modes found in GRACE at the least. By comparing monthly reconstructed maps to GRACE data from December 2013 to June 2017, we suggest the uncertainty of these maps to be [Formula: see text] of equivalent water height.

[Improved patient safety through a clinical decision support system in laboratory medicine]. / Verbesserte Patientensicherheit durch "clinical decision support systems" in der Labormedizin.

BACKGROUND: Laboratory diagnostics are essential for diagnosis, initiation of therapy, and monitoring of patients. Laboratory results that are overlooked or incorrectly interpreted lead to adverse events and endanger patient safety. Clinical decision support systems (CDSSs) may facilitate appropriate interpretation of results and subsequent medical response. OBJECTIVES: The research project on digital laboratory medicine (AMPEL) aims at developing a CDSS based on laboratory diagnostics, which supports practitioners in ensuring the necessary medical consequences. MATERIALS AND METHODS: A literature review of CDSSs describes the current state of research. The research project AMPEL is presented with its objectives, challenges, and first results. Furthermore, the development of a framework and reporting system is illustrated through the clinical example of severe hypokalemia. RESULTS AND CONCLUSION: Through interdisciplinary development and constant optimization, a specific CDSS with high acceptance among clinicians was developed. Initial results in the case of severe hypokalemia show a positive effect on patient care. Thereby, more complex frameworks such as sepsis diagnostics or acute coronary syndrome are implemented. The limited availability of standardized and digital clinical data is challenging. In addition to the application of classic decision trees in CDSS, the use of machine learning offers a promising perspective for future developments.

Recurrent ischaemic cerebrovascular events as presenting manifestations of myeloproliferative neoplasms.

BACKGROUND AND PURPOSE: Myeloproliferative neoplasms (MPNs) - polycythemia vera, essential thrombocythemia and primary myelofibrosis - are associated with increased risk for ischaemic cerebrovascular events (ICVEs). Due to their low prevalence, MPNs often remain undiagnosed as the cause of ICVEs. METHODS: Case records at the University of Tübingen between 2014 and 2017 were screened to identify patients with MPN-related ICVEs. Clinical features, brain imaging, laboratory findings, applied treatments and neurological outcomes were assessed. RESULTS: In all, 3318 patients with ICVEs were identified, and amongst them 17 patients with MPN-related ICVEs were included in a retrospective study. In 58% of these patients, ICVEs were the first manifestation of the underlying MPN; 24% presented with transient ischaemic attack and 76% with ischaemic stroke. Potentially concurrent ICVE etiologies were noted in 70% of the patients. The majority (94%) of patients were positive for the JAK2 V617F mutation, whilst in 29% recurrent ICVEs (range two to three) were noted prior to MPN diagnosis. Early MPN diagnosis and management was the only significant prognostic factor for ICVE recurrence (P < 0.001). DISCUSSION: Evidence is provided that, although rare, MPNs represent an underdiagnosed cause of recurrent ICVEs. High clinical awareness is warranted to identify an underlying MPN in patients presenting with sustained, abnormal blood count findings. Clinical algorithms for prompt MPN diagnosis and initiation of MPN treatment (e.g. cytoreductive therapy, phlebotomy) are required. As MPN management comprises a significant protective factor against ICVE recurrence, induction of MPN treatment should be regarded as an integral component of secondary stroke prevention in MPN-associated ICVEs.

[Follicular penetration of nanocarriers is an important penetration pathway for topically applied drugs]. / Bedeutung des follikulären Penetrationswegs für den Wirkstofftransport mittels Nanocarriern.

BACKGROUND: The hair follicle represents a significant penetration route for topically applied substances. ISSUE: The percutaneous absorption of substances can be significantly increased and accelerated by the involvement of hair follicles. In addition, nanoparticles have the characteristic to penetrate deeply and effectively into the hair follicles. MATERIALS AND METHODS: An optimization of drug delivery for topically applied substances is possible if the nanoparticles act solely as a carrier to transport active ingredients into the hair follicle. Once the nanocarrier has penetrated into the hair follicle, the active substance must be released there. This can be triggered by various mechanisms. RESULTS: The released drug can thus pass into the living tissue surrounding the hair follicle independently. With the help of this innovative strategy, the bioavailability of topically applied substances can be significantly improved. CONCLUSION: The transport of active ingredients into the hair follicles with the help of particles and the release of active substances there is a very effective new method for transporting active substances through the skin barrier.

Gestational chronodisruption leads to persistent changes in the rat fetal and adult adrenal clock and function.

KEY POINTS: Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Here we explored the developmental impact of gestational chronodisruption (chronic photoperiod shift, CPS) on adult and fetal adrenal biorhythms and function. We found that gestational chronodisruption altered fetal and adult adrenal function, at the molecular, morphological and physiological levels. The differences between control and CPS offspring suggest desynchronization of the adrenal circadian clock and steroidogenic pathway, leading to abnormal stress responses and metabolic adaptation, potentially increasing the risk of developing chronic diseases. ABSTRACT: Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Indeed, an abnormal photoperiod during gestation alters fetal development, inducing long-term effects on the offspring. Accordingly, we carried out a longitudinal study in rats, exploring the impact of gestational chronodisruption on the adrenal biorhythms and function of the offspring. Adult rats (90 days old) gestated under chronic photoperiod shift (CPS) decrease the time spent in the open arm zone of an elevated plus maze to 62% and increase the rearing time to 170%. CPS adults maintained individual daily changes in corticosterone, but their acrophases were distributed from 12.00 h to 06.00 h. CPS offspring maintained clock gene expression and oscillation, nevertheless no daily rhythm was observed in genes involved in the regulation and synthesis of steroids. Consistent with adult adrenal gland being programmed during fetal life, blunted daily rhythms of corticosterone, core clock gene machinery, and steroidogenic genes were observed in CPS fetal adrenal glands. Comparisons of the global transcriptome of CPS versus control fetal adrenal gland revealed that 1078 genes were differentially expressed (641 down-regulated and 437 up-regulated). In silico analysis revealed significant changes in Lipid Metabolism, Small Molecule Biochemistry, Cellular Development and the Inflammatory Response pathway (z score: 48-20). Altogether, the present results demonstrate that gestational chronodisruption changed fetal and adult adrenal function. This could translate to long-term abnormal stress responses and metabolic adaptation, increasing the risk of developing chronic diseases.

TDM-controlled ring resonator arrays for fast, fixed-wavelength optical biosensing.

A novel control concept for serial ring resonator arrays based on a time-division multiplex (TDM) approach is presented. It allows fast sampling rates in terms of biological kinetics. The novelty consists of using both thermal tuning of the effective refractive index and thermo-optical multiplexing for the silicon-on-insulator (SOI) ring resonator arrays, without the need for a tunable laser source. Using a fixed wavelength, fast read-out rates of 100 Hz are demonstrated for each ring.

Whole-heart 4D flow cardiac magnetic resonance in healthy dogs.

INTRODUCTION: In cardiac magnetic resonance imaging (CMR), accurate flow measurements rely on perpendicular plane-alignment with flow direction. For 2D phase contrast (PC) cardiac magnetic resonance measurements, planes have to be defined during the examination of the heart, which is time consuming and error-prone. Collection of flow information of the entire volume of the heart by a 4D flow CMR postpones plane alignment to post-processing. Sampling of such a large amount of data requires acceleration of data acquisition with techniques such as SENSitivity Encoding (k-t SENSE) or Broad-use Linear Acquisition Speed-up Technique (k-t BLAST). Objectives of the study were to compare 4D flow CMR, accelerated with two different acceleration methods with the established 2D PC CMR based on assessment of stroke volume at all four cardiac valves. The values of stroke volume acquired with the 4D flow CMR SENSE did not differ significantly when compared to the 2D PC CMR SENSE at the left side of the heart (aortic and mitral valve). Significant differences between the techniques were seen at the pulmonic and tricuspid valves. Acceleration with k-t BLAST revealed significantly lower values of stroke volume at all cardiac valves, except at the mitral valve.

INTRODUCTION: Lors d'examens cardiaques par résonnance magnétique (CMR), le plan pour des mesures de flux précises doit être défini perpendiculairement à la direction de flux sanguin. Dans la CMR en contraste de phases 2D (PC), le choix de ce plan se fait durant l'examen, ce qui prend du temps et peut être sujet à des problèmes. Avec la mesure de toutes les données relatives au flux sanguin dans l'ensemble du coeur au moyen d'un 4D flow CMR, on déplace le moment de ce choix dans la phase de traitement des données. La collecte d'une quantité aussi élevée de données nécessite une accélération de la technique de mesures comme par exemple SENSitivity Encoding (k-t SENSE) ou Broad-use Linear Acquisition Speed-up Technique (k-t BLAST). Le but de cette étude était de comparer la CMR 4D, accélérée avec deux méthodes différentes avec la CMR 2D bien établie, ceci sur la base de la détermination du volume d'éjection systolique au niveau des quatre valvules cardiaques. Les valeurs du volume d'éjection pour le coeur gauche (valvules aortiques et mitrales) obtenues par 4D flow CMR k-t SENSE n'étaient pas significativement différentes de celles obtenues par 2D PC CMR k-t SENSE. Par contre, des différences significatives entre les deux techniques étaient constatées au niveau des valvules pulmonaires et tricuspid. L'accélération par k-t-BLAST donnait de façon générale des valeurs du volume d'élection plus basses au niveau de toutes les valvules, à l'exception de la valvule mitrale.

Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: A retrospective, real-world database analysis.

BACKGROUND: Allergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT. OBJECTIVES: To assess the real-world, long-term efficacy of grass pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression. METHODS: In a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression analysis was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups. RESULTS: After applying all selection criteria, 2851 SLIT and 71 275 control patients were selected for the study. After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pretreatment period) in SLIT tablet group than in the non-AIT group (P<.001). Asthma onset was less frequent in SLIT tablet group than in non-AIT group (odds ratio: 0.696, P=.002), and time to asthma was significantly longer (hazard ratio: 0.523; P=.003). After SLIT cessation, asthma medication use fell by an additional 16.7 percentage points (relative to the pretreatment period) in the SLIT tablet group vs the non-AIT group (P=.004). CONCLUSIONS: Real-world treatment of AR patients with grass pollen SLIT tablets was associated with slower AR progression, less frequent asthma onset, and slower asthma progression.

Puberty arises with testicular alterations and defective AMH expression in rams prenatally exposed to testosterone.

The male gonadal tissue can be a sensitive target to the reprogramming effects of testosterone (T) during prenatal development. We have demonstrated that male lambs born to dams receiving T during pregnancy-a model system to the polycystic ovary syndrome (PCOS)-show a decreased number of germ cells early in life, and when adult, a reduced amount of sperm and ejaculate volume. These findings are a key to put attention to the male offspring of women bearing PCOS, as they are exposed to increased levels of androgen during pregnancy which can reprogram their reproductive outcome. A possible origin of these defects can be a disruption in the expression of the anti-Müllerian hormone (AMH), due to its critical role in gonadal function at many postnatal stages. Therefore, we addressed the impact of prenatal T excess on the expression of AMH and factors related to its expression like AP2, SOX9, FSHR, and AR in the testicular tissue through real-time PCR during the peripubertal age. We also analyzed the testicular morphology and quantified the number of Sertoli cells and germ cells to evaluate any further defect in the testicle. Experiments were performed in rams at 24 wk of age, hence, prior puberty. The experimental animals (T-males) consisted of rams born to mothers receiving 30 mg testosterone twice a wk from Day 30 to 90 of pregnancy and then increased to 40 mg until Day 120 of pregnancy. The control males (C-males) were born to mothers receiving the vehicle of the hormone. We found a significant increase in the expression of the mRNA of AMH and SOX9, but not of the AP2, FHSR nor AR, in the T-males. Moreover, T-males showed a dramatic decrease in the number of germ cells, together with a decrease in the weight of their testicles. The findings of the present study show that before puberty, T-males are manifesting clear signs of disruption in the gonadal functions probably due to an alteration in the expression pattern of the AMH gene. The precise way by which T reprograms the expression of AMH gene remains to be established.

Femtosecond laser cutting of human corneas for the subbasal nerve plexus evaluation.

Assessment of various morphological parameters of the corneal subbasal nerve plexus is a valuable method of documenting the structural and presumably functional integrity of the corneal innervation in health and disease. The aim of this work is to establish a rapid, reliable and reproducible method for visualization of the human corneal SBP using femtosecond laser cut corneal tissue sections. Trephined healthy corneal buttons were fixed and processed using TissueSurgeon-a femtosecond laser based microtome, to obtain thick tissue sections of the corneal epithelium and anterior stroma cut parallel to the ocular surface within approximately 15 min. A near infrared femtosecond laser was focused on to the cornea approximately 70-90 µm from the anterior surface to induce material separation using TissueSurgeon. The obtained corneal sections were stained following standard immunohistochemical procedures with anti-neuronal ß-III tubulin antibody for visualization of the corneal nerves. Sections that contained the epithelium and approximately 20-30 µm of anterior stroma yielded excellent visualisation of the SBP with minimal optical interference from underlying stromal nerves. In conclusion, the results of this study have demonstrated that femtosecond laser cutting of the human cornea offers greater speed, ease and reliability than standard tissue preparation methods for obtaining high quality thick sections of the anterior cornea cut parallel to the ocular surface.

Meningitis and Bacteremia Due to Neisseria cinerea following a Percutaneous Rhizotomy of the Trigeminal Ganglion.

Neisseria cinerea is a human commensal. The first known case of meningitis and bacteremia due to Neisseria cinerea following percutaneous glycerol instillation of the trigeminal ganglion is reported. Conventional phenotypic methods and complete 16S RNA gene sequencing accurately identified the pathogen. Difficulties in differentiation from pathogenic neisseriae are discussed.

Triggered release of model drug from AuNP-doped BSA nanocarriers in hair follicles using IRA radiation.

Recent advances in the field of dermatotherapy have resulted in research efforts focusing on the use of particle-based drug delivery systems for the stimuli-responsive release of drugs in the skin and skin appendages, i.e. hair follicles and sebaceous glands. However, effective and innocuous trigger mechanisms which result in the release of the drugs from the nanocarriers upon reaching the target structures are still lacking. For the first time, the present study demonstrated the photo-activated release of the model drug fluorescein isothiocyanate (FITC) from topically applied gold nanoparticle-doped bovine serum albumin (AuNPs-doped BSA) particles (approx. 545nm) using water-filtered infrared A (IRA) radiation in the hair follicles of an ex vivo porcine skin model. The IRA radiation-induced plasmonic heating of the AuNPs results in the partial decomposition or opening of the albumin particles and release the model drug, while control particles without AuNPs show insignificant release. The results demonstrate the feasibility of using IRA radiation to induce release of encapsulated drugs from plasmonic nanocarriers for the targeting of follicular structures. However, the risk of radiation-induced skin damage subsequent to repeated applications of high infrared dosages may be significant. Future studies should aim at determining the suitability of lower infrared A dosages, such as for medical treatment regimens which may necessitate repeated exposure to therapeutics. STATEMENT OF SIGNIFICANCE: Follicular targeting using nanocarriers is of increasing importance in the prophylaxis and treatment of dermatological or other diseases. For the first time, the present study demonstrated the photo-activated release of the model drug fluorescein isothiocyanate (FITC) from topically applied gold nanoparticle-doped bovine serum albumin (AuNPs-doped BSA) particles using water-filtered infrared A (IRA) radiation in the hair follicles of an ex vivo porcine skin model. The results demonstrate the feasibility of using wIRA radiation to induce release of encapsulated drugs for the targeting of follicular structures, and provide a new vision on the development of optically addressable delivery systems for controlled release of drugs in the skin and skin appendages, i.e. hair follicles and sebaceous glands.

Can Routine Imaging After Neoadjuvant Chemotherapy in Breast Cancer Predict Pathologic Complete Response?

BACKGROUND: This study evaluated breast imaging procedures for predicting pathologic complete response (pCR = ypT0) after neoadjuvant chemotherapy (NACT) for breast cancer to challenge surgery as a diagnostic procedure after NACT. METHODS: This retrospective, exploratory, monocenter study included 150 invasive breast cancers treated by NACT. The patients received magnetic resonance imaging (MRI), mammography (MGR), and ultrasound (US). The results were classified in three response subgroups according to response evaluation criteria in solid tumors. To incorporate specific features of MRI and MGR, an additional category [clinical near complete response (near-cCR)] was defined. Residual cancer in imaging and pathology was defined as a positive result. Negative predictive values (NPVs), false-negative rates (FNRs), and false-positive rates (FPRs) of all imaging procedures were analyzed for the whole cohort and for triple-negative (TN), HER2-positive (HER2+), and HER2-negative/hormone-receptor-positive (HER2-/HR+) cancers, respectively. RESULTS: In 46 cases (31%), pCR (ypT0) was achieved. Clinical complete response (cCR) and near-cCR showed nearly the same NPVs and FNRs. The NPV was highest with 61% for near-cCR in MRI and lowest with 44% for near-cCR in MGR for the whole cohort. The FNRs ranged from 4 to 25% according to different imaging methods. The MRI performance seemed to be superior, especially in TN cancers (NPV 94%; FNR 5%). The lowest FPR was 10 % in MRI, and the highest FPR was 44% in US. CONCLUSION: Neither MRI nor MGR or US can diagnose a pCR (ypT0) with sufficient accuracy to replace pathologic diagnosis of the surgical excision specimen.

Clinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: A pilot study.

OBJECTIVE: In the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects. METHOD: The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment. RESULTS: Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated. CONCLUSION: The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.

[The Value of Ultrasonography Compared with Magnetic Resonance Imaging in the Diagnosis of Deltoid Ligament Injuries--Is there a Difference?]. / Vergleich der Sonografie und der Magnetresonanztomografie zur Diagnostik von Rupturen des Lig. deltoideum--gibt es einen Unterschied?

BACKGROUND: Ruptures of the deltoid ligament can lead to ankle instability which may cause arthrosis. Aim of this comparative clinical trial was to assess the value of ultrasonography (US) compared to magnetic resonance imaging (MRI) in the diagnosis of medial collateral (deltoid) ligament ruptures associated with Weber type B and C fractures. PATIENTS AND METHODS: All four components of the deltoid ligament of the ankles of 28 patients with Weber type B and 14 patients with Weber type C fractures were preoperatively evaluated by US and MRI for partial or complete ruptures. RESULTS: Deltoid ligament injuries were detected in 10 of 28 patients (35.7 %) with Weber type B and in 12 of 14 patients (85.7 %) with Weber type C fractures with MRI. US reliably identified all 17 patients with complete rupture of the deltoid ligament (sensitivity 100 %, specifity 92 %). However only half of the 6 patients who sustained a partial rupture were correctly identified (sensitivity 50 %, specifity 97.2 %). 26 of 30 ruptures (sensitivity 86.6 %, specifity 96.3 %) and 13 of 27 partial ruptures (sensitivity 48.1 %, specifity 97.8 %) of the four components of the deltoid ligament were correctly identified with US. CONCLUSION: US is a reliable procedure for detection of clinically relevant ruptures and uninjured components of the deltoid ligament after distal fibula fractures. However US is not suitable to reliably identify partial ruptures. The treatment decision for operation or conservative treatment of ankle fractures is based on the stability of the ankle. Patients with lateral malleolar fractures and intact medial malleolus but rupture of the deltoid ligament often show a spontaneous reduction of the talus in X-ray images and may therefore be falsely classified as stable (unrecognised medial instability). However, unstable malleolar fractures should be treated with open reduction and internal fixation in order to improve outcome. Hence US is able to influence therapeutic decisions by detecting medial ankle instability, which cannot be detected clinically or radiologically.

Persistence with opioid treatment in Germany in patients suffering from chronic non-malignant or cancer pain.

BACKGROUND: The aim of the present study was to assess factors influencing opioid persistence in a large patient cohort of 32,158 patients receiving opioid treatment for either chronic non-malignant or cancer pain. METHODS: Data from 32,158 patients with first-time prescription of an opioid in the timeframe from January 2009 until December 2013 treated in 115 orthopedic, 104 neurological and 1129 general practitioner practices were retrospectively analyzed (Disease Analyzer database Germany). A Cox proportional hazards regression model was used to estimate the relationship between non-persistence and the demographic and clinical variables described previously for a maximum follow-up period of 1 year. RESULTS: After 1 year of follow-up, 69% of patients treated with opioids had stopped medication intake (refill gap of 90 days). There was a significantly increased risk of treatment discontinuation for younger patients (<40 years HR: 1.45; 41-50 years HR: 1.37; 51-60 years HR: 1.23; 61-70 years HR: 1.22) as compared with patients aged >70. Cancer pain was associated with a significantly lower risk of therapy discontinuation (HR: 0.69), whereas persistence was considerably less probable for diagnoses such as various kinds of back pain (HR: 1.26), osteoarthritis (HR: 1.14) and spondylarthritis (HR: 1.09). Chronic comorbidities such as diabetes, hypertension, heart insufficiency, and dementia were associated with a decreased risk of treatment discontinuation. CONCLUSION: Our study showed that persistence with opioid treatment is associated with cancer pain, chronic comorbidities and depression, while younger age and chronic non-malignant pain (especially due to back pain) increase the possibility of opioid discontinuation. It will be the task of future studies to assess reasons for opioid discontinuation in more detail, which is an important step towards improving patient care and health outcomes.

Trapezius muscle activity increases during near work activity regardless of accommodation/vergence demand level.

AIM: To investigate if trapezius muscle activity increases over time during visually demanding near work. METHODS: The vision task consisted of sustained focusing on a contrast-varying black and white Gabor grating. Sixty-six participants with a median age of 38 (range 19-47) fixated the grating from a distance of 65 cm (1.5 D) during four counterbalanced 7-min periods: binocularly through -3.5 D lenses, and monocularly through -3.5 D, 0 D and +3.5 D. Accommodation, heart rate variability and trapezius muscle activity were recorded in parallel. RESULTS: General estimating equation analyses showed that trapezius muscle activity increased significantly over time in all four lens conditions. A concurrent effect of accommodation response on trapezius muscle activity was observed with the minus lenses irrespective of whether incongruence between accommodation and convergence was present or not. CONCLUSIONS: Trapezius muscle activity increased significantly over time during the near work task. The increase in muscle activity over time may be caused by an increased need of mental effort and visual attention to maintain performance during the visual tasks to counteract mental fatigue.