Development of video tutorials to help parents manage children with acute illnesses using a modified Delphi method.

AIM: Children often fall sick, which causes concern among parents. Online health information can be confusing and difficult to understand. We aimed to produce simple, informative video tutorials on the symptoms ill children present. METHODS: We used a modified Delphi method to produce video tutorials on the symptoms of fever, vomiting and diarrhoea, abdominal pain, breathing difficulties, sore throat, red eyes, earache and rash. We identified the most common symptoms in acutely ill children. During the first consensus round, experts rated statements on out-of-hospital management from existing health information. Video tutorials were produced from statements rated to be included. The second consensus round involved video showings and editing. Two videos were evaluated in focus groups by parents. RESULTS: During the first round, experts rated a median of 79 (40-154) statements for each symptom. Panels consisted of a median of seven (6-11) experts, primarily. Panels reached a consensus on inclusion, neutrality or exclusion in 83% of statements. The second round led to adjustments to the videos and final approval by experts. Most parents evaluated the videos as 'informative, easy to understand and calming'. CONCLUSION: We produced video tutorials on the common symptoms ill children present using a modified Delphi method. Feedback from parents in focus groups was positive.

[Evaluation of Weaning Success in Long-Term Invasively Ventilated Patients at a Weaning Center]. / Ergebnisse der Re-Evaluation von Patienten aus der Intensivpflege in einem lokalen Weaning-Zentrum.

Despite the use of enormous personnel and other resources in German weaning centers, approximately 20 % of patients currently fail to get weaned from mechanical ventilation (MV) and need out-of-hospital ventilation.Between 03/2015 and 11/2019, we carried out a pilot project with 33 patients (48 % female, mean age 68 ±â€Š11 years at hospital admission) in order to re-evaluate their options of a possible weaning from MV. At this stage the patients had been invasively ventilated for 475 ±â€Š775 days. The mean stay in our weaning center was 26 ±â€Š19 days. 24/33 (73.53 %) patients were successfully weaned from MV. Of those, 11/24 (44 %) were discharged with non-invasive out-of-hospital ventilation. The completely weaned patients had a survival period of 3 or 12 months (92 % and 77 %), respectively. In those discharged with non-invasive ventilation, the survival period of 3 or months was 91 % and 81 %, respectively. In those discharged with invasive ventilation, this was 86 % and 71 %, respectively.The current results demonstrate that even those undergoing long-term out-of-hospital invasive ventilation can be successfully weaned from MV. Therefore, we suggest regular re-evaluations of weaning opportunities in invasively ventilated ambulatory patients.

[Treatment of extreme anemia with polymerized bovine hemoglobin : Case report and review of the literature]. / Therapie einer extremen Anämie mit vernetztem Rinderhämoglobin : Fallbericht mit Literaturüberblick.

This article reports the case of a 29-year-old female Jehovah's Witness with severe anemia after intrauterine fetal death in the 25th week of gestation, complicated by vaginal bleeding, acute renal failure and hemolysis. Due to her religious beliefs the patient categorically refused blood transfusions. Despite adhering to the recommendations for patient blood management, the hemoglobin (Hb) level gradually decreased to 1.9 g/dl on day 10, when she fainted and had to be sedated and invasively ventilated. Inhalative isoflurane was chosen for sedation because of its potential organ-protective effects and because it provides deep sedation with reduced oxygen requirements, while enabling rapid neurological examination during the sedation windows as well as regular and calm spontaneous breathing. Posthypoxic encephalopathy was demonstrated clinically and electroencephalographically by seizure activity during the sedation windows. Anticonvulsive treatment was started. At a hemoglobin of 1.8 g/dl, she received 2 units of polymerized bovine hemoglobin (Hemopure®, Hemoglogin Oxygen Therapeutics LLC, Souderton, PA, USA), repeated several times on subsequent days because of its short half-life. Considerable methemoglobinemia was noted. After subtracting methemoglobin, the hemoglobin rose by 0.4-0.8 g/dl after each 2 units, initially increasing the oxygen binding capacity of the blood by 33%. After a full neurological recovery and weaning from the ventilator but still on hemodialysis, the patient was transferred to another hospital after 38 days.If allogeneic blood transfusion is not an option, administration of polymerized bovine hemoglobin can temporarily increase the oxygen transport capacity as a last resort treatment. Reduction of oxygen requirements by deep inhaled sedation with isoflurane also seems beneficial and provides advantages.

Laser-structured spike surface shows great bone integrative properties despite infection in vivo.

Implant associated infections can result in devastating consequences for patients. One major cause is the formation of bacterial biofilms, which result in increased resistance against antimicrobial therapeutics. A reduction of implant associated infections can be achieved by functionalization of implant surfaces. The generation of three dimensional surface structures by femtosecond laser ablation is one method to fabricate bacterial repellent large scaled surfaces without altering the material chemical composition. The challenge is to reduce bacterial growth while improving cellular ongrowth. For this purpose, spike structures were created as small as possible by used fabrication method on cubic Ti90/Al6/V4-rods and their effectiveness against bacterial colonization was compared to unstructured Ti90/Al6/V4-rods. Rods were implanted in the rat tibia and infected intraoperatively with 103 CFU of Staphylococcus aureus. Besides clinical behaviour and lameness, the vital bacterial biomass, morphological appearance and the volume of eukaryotic cells were determined on the implant surface after 21 days. Bone alterations were examined by radiological and histological techniques. Unexpectedly, the laser-structured implants did not show a lower bacterial load on the implant surface and less severe infection related bone and tissue alterations compared to the group without structuring. Simultaneously, a better bony integration and a higher cellular colonization with eukaryotic cells was detected on the laser-structured implants. These findings don't support the previous in vitro results. Nevertheless, the strong integration into the bone is a powerful argument for further surface modifications focussing on the improvement of the antibacterial effect. Additionally, our results underline the need for in vivo testing of new materials prior to clinical use.

MILOS and EMILOS repair of primary umbilical and epigastric hernias.

BACKGROUND: The currently mainly used techniques of primary ventral hernia repair have specific disadvantages and risks. METHODS: To minimize complications of the existing open and laparoscopic techniques of ventral hernia repair, the endoscopic-assisted or endoscopic Mini- or Less-Open Sublay (E/MILOS) concept was developed. This paper reports on our experience with the E/MILOS concept for the management of primary umbilical and epigastric hernias. All E/MILOS operations were prospectively documented in the German hernia registry "Herniamed". For 1 year follow-up, all patients and their general practitioners received a questionnaire. RESULTS: Five hundred and twenty primary umbilical and 554 epigastric E/MILOS operations with complete 1-year follow-up were included. Concomitant RD were treated in 18.3% and 14.1% of the umbilical and epigastric hernia cohort, respectively. Total perioperative complication rates and reoperation rates were 1.2% and 0.9% for both umbilical and epigastric hernias, respectively. Infection rates were 0.0% and 0.2% after umbilical and epigastric hernia operations, respectively. Recurrence rates 1 year after E/MILOS umbilical and epigastric hernia were 0.0% and 0.5%, respectively. One year rates of chronic pain at rest, chronic pain during physical activities, and chronic pain requiring treatment after umbilical and epigastric hernia repair were 1.5% and 2.7%, 2.1% and 4.2%, and 0.6% and 1.8%; respectively. CONCLUSION: The E/MILOS concept allows the endoscopically assisted (MILOS) or endoscopic (EMILOS) transhernial minimal invasive sublay mesh repair of primary umbilical and epigastric hernias with or without rectus diastasis with low complication, recurrence, and chronic pain rates.

[German Translation and Linguistic Validation of the Multidimensional Dyspnea Profile (MDP)]. / Deutsche Übersetzung und sprachliche Validierung des multidimensionalen Dyspnoe-Profils (MDP).

BACKGROUND: Dyspnea is characterized as a subjective perception of breathing discomfort. This includes distinct sensory qualities with distinct intensities. The detection and quantization of these quality distinctions can be quite difficult. As yet, there is no instrument in German covering the multidimensionality of dyspnea. Banzett et al. developed the Multidimensional Dyspnea Profile (MDP) in 2015 to meet and to understand the multidimensional nature of dyspnea, disease span and at varying times or situations. METHODS: This paper presents the German translation of the MDP. The MAPI Research Trust has developed the German version in accordance with the recognized guidelines for intercultural adaption of patient reported outcomes. That included a linguistic validation in patients with this condition. RESULTS: The Multidimensional Dyspnea Profile measures the intensity of dyspneic breathing discomforts. It tests five sensory qualities that describe the patient's dyspnea in its respective intensity. Additionally, it includes five potential reactions. The MDP is designed to refer to a specific event in time. CONCLUSION: The authors made the instrument freely available for academic use in English language. In addition, the German version is finally available and can be used in both everyday clinical practice and laboratory research.

The natural alpha angle of the femoral head-neck junction: a cross-sectional CT study in 1312 femurs.

Aims: Asphericity of the femoral head-neck junction is common in cam-type femoroacetabular impingement (FAI) and usually quantified using the alpha angle on radiographs or MRI. The aim of this study was to determine the natural alpha angle in a large cohort of patients by continuous circumferential analysis with CT. Methods: CT scans of 1312 femurs of 656 patients were analyzed in this cross-sectional study. There were 362 men and 294 women. Their mean age was 61.2 years (18 to 93). All scans had been performed for reasons other than hip disease. Digital circumferential analysis allowed continuous determination of the alpha angle around the entire head-neck junction. All statistical tests were conducted two-sided; a p-value < 0.05 was considered statistically significant. Results: The mean maximum alpha angle for the cohort was 59.0° (sd 9.4). The maximum was located anterosuperiorly at 01:36 on the clock face, with two additional maxima of asphericity at the posterior and inferior head-neck junction. The mean alpha angle was significantly larger in men (59.4°, sd 8.0) compared with women (53.5°, sd 7.4°; p = 0.0005), and in Caucasians (60.7°, sd 9.0°) compared with Africans (56.3°, sd 8.0; p = 0.007) and Asians (50.8°, sd 7.2; p = 0.0005). The alpha angle showed a weak positive correlation with age (p < 0.05). If measured at commonly used planes of the radially reconstructed CT or MRI, the alpha angle was largely underestimated; measurement at the 01:30 and 02:00 positions showed a mean underestimation of 4° and 6°, respectively. Conclusion: This study provides important data on the normal alpha angle dependent on age, gender, and ethnic origin. The normal alpha angle in men is > 55°, and this should be borne in mind when making a diagnosis of cam-type morphology. Cite this article: Bone Joint J 2018;100-B:570-8.

Increased innervation of forebrain targets by midbrain dopaminergic neurons in the absence of FGF-2.

Fibroblast growth factors (FGFs) regulate development and maintenance, and reduce vulnerability of neurons. FGF-2 is essential for survival of midbrain dopaminergic (DA) neurons and is responsible for their dysplasia and disease-related degeneration. We previously reported that FGF-2 is involved in adequate forebrain (FB) target innervation by these neurons in an organotypic co-culture model. It remains unclear, how this ex-vivo phenotype relates to the in vivo situation, and which FGF-related signaling pathway is involved in this process. Here, we demonstrate that lack of FGF-2 results in an increased volume of the striatal target area in mice. We further add evidence that the low molecular weight (LMW) FGF-2 isoform is responsible for this phenotype, as this isoform is predominantly expressed in the embryonic ventral midbrain (VM) as well as in postnatal striatum (STR) and known to act via canonical transmembrane FGF receptor (FGFR) activation. Additionally, we confirm that the phenotype with an enlarged FB-target area by DA neurons can be mimicked in an ex-vivo explant model by inhibiting the canonical FGFR signaling, which resulted in decreased extracellular signal-regulated kinase (ERK) activation, while AKT activation remained unchanged.

Selective gas adsorption in microporous metal-organic frameworks incorporating urotropine basic sites: an experimental and theoretical study.

The sorption of CO, CO2 and C2H2 by two urotropine-containing porous metal-organic framework materials [Zn4(dmf)(ur)2(ndc)4] (H2ndc = 2,6-naphthalenedicarboxylic acid; ur = urotropine; dmf = dimethylformamide) and [Zn11(H2O)2(ur)4(bpdc)11] (H4bpdc = 4,4'-biphenyldicarboxylic acid) incorporating free N-donors has been investigated. These materials show pronounced affinity for CO2 and C2H2, and these observations are supported by interaction energy and ab initio DFT calculations.

On the interaction of water-soluble binders and nano silicon particles: alternative binder towards increased cycling stability at elevated temperatures.

Silicon based composites are among the most promising negative electrodes for lithium ion battery applications due to their high theoretical capacities. One major drawback of silicon based anodes are their large volume changes during lithiation and delithiation. Although many efforts have been made in view of new binder materials and improved electrolytes, the resulting battery cell suffers from severe capacity fading at ambient or elevated temperatures, respectively. The strong reactivity with the electrolyte is considered to be responsible for the reduced cycle life at elevated temperatures. In this work we introduce silicon composite anodes with a novel composition based on a gellan gum binder material that show an improved cycling performance at ambient temperature and at 60 °C. To elucidate the influence of the binder material, we investigated the structure of the silicon based composite anodes in order to understand the nature of the interaction of the gellan gum based binder polymers with the silicon particles in comparison with a common CMC binder. Also the influence of the choice of binder on the interactions at the interface between electrode surface and electrolyte were studied. A combination of powerful techniques including solid state NMR, TEM and EELS, XPS as well as FTIR were applied.

Switching intermolecular interactions by confinement in carbon nanotubes.

The encapsulation of trityl-functionalised C60 molecules inside carbon nanotubes drastically affects the intermolecular interactions for this species. Whilst the orientations of molecules in the crystal are often controlled by thermodynamics, the molecular orientations in nanotubes are a result of kinetic control imposed by the mechanism of entry into and encapsulation within the nanotube.

Establishing an optimal trajectory for calcaneotibial K-wire fixation in emergent treatment of unstable ankle fractures.

OBJECTIVE: In unstable ankle fractures the associated soft tissue damage can be a therapeutic challenge. The aim of this study was to optimize planning of minimally invasive stabilization of ankle fractures by calcaneotibial transfixation, which is a demanding technique due to the complex hind foot anatomy. METHODS: In a retrospective radiographic analysis the angles and dimensions of a safe drill tunnel for calcaneotibial K-wire insertion were defined on standard radiographs of the ankle joint. 165 lateral weight-bearing radiographs (77 right; 88 left) and 147 (80 right; 67 left) mortise views of 186 (90 right; 96 left) uninjured feet from 123 patients (74 women (114 feet); 49 men (72 feet)) were included in this study. The average patient age was 49 (range, 13-85) years. Inter- and intra-observer reliability was evaluated on 20 randomized radiographs that were analyzed in a default set, three times, by two different examiners on three different days. RESULTS: In the lateral view the drilling tunnel was orientated at 59.4° to the plantar plane with a maximum proximal variance of 7.1 image-mm. Distal variance cannot be tolerated since an ankle joint injury would ensue. In the mortise view the drill tunnel was directed with a mean angle of 18.4° to the distal tibial articular surface. At most a mean of 11° fibular- and 13.4° tibial- expansion can be tolerated. Intra- and inter-observer reliability was higher for the angles than for the drill corridors. CONCLUSION: The three-dimensional (3D) orientation for safe K-wire placement for calcaneotibial transfixation should adhere to the drill tunnels established in this study.

Percutaneous antegrade scaphoid screw placement: a feasibility and accuracy analysis of a novel electromagnetic navigation technique versus a standard fluoroscopic method.

BACKGROUND: Central screw positioning in the scaphoid provides biomechanical advantages. METHODS: A prospective randomized study of six fluoroscopically guided and six electromagnetically navigated screw (ENS) placements was performed on human cadavers. Accuracy of screw position was determined. Intraoperative fluoroscopy exposure times, readjustments of drilling directions, complete restarts and complications were documented. RESULTS: The ENS method provided a mean time benefit of 7.34 min compared with the standard method and the mean screw length ratio (SLR coronar: ENS 0.96 ± 0.04 mm, SFF: 0.92 ± 0.04 mm, P = 0.065; SLR sagittal: ENS 0.98 ± 0.02 mm, SFF: 0.91 ± 0.04 mm, P = 0.009) and the screw axis deviation angle (AD coronar: ENS 3.33 ± 2.34°, SFF: 10.33 ± 2.58°, P = 0.002; AD sagittal: ENS 2.83 ± 0.98°, SFF: 11.00 ± 6.16°, P = 0.002) were lower. Using the electromagnetic navigation procedure no drilling readjustments or restarts were required, no cortical breach occurred. CONCLUSIONS: Compared with the standard fluoroscopic technique, the ENS method used in this study showed higher accuracy, less complications, required less operation and radiation exposure time.

Modulation of IL-33/ST2-TIR and TLR signalling pathway by fingolimod and analogues in immune cells.

For the immune modulatory drug fingolimod (FTY720), lymphocyte sequestration has been extensively studied and accepted as mode of action. Further, direct effects on immune cell signalling are incompletely understood. Herein, we used the parent drug and newly synthesized analogues to investigate their effects on dendritic cell (DC) calcium signalling and on Th1, Th2 and Th17 responses. DC calcium signalling was determined with a single cell-based confocal assay and IL-33/ST2-TIR Th2-like response with ST2-transduced EL4-6.1 thymoma cells. The Th1/Th17 responses were examined with a LPS/TLR-enhanced antigen presentation assay with OVA-TCRtg CD4 and CD8 spleen cells. Our results revealed a comparable influence of fingolimod and S1P on intracellular calcium level in DC, while an oxy-derivative of fingolimod exhibited an EC50 of 3.3 nm, being 14 times more potent than FTY720-P. The IL-33/ST2-TIR Th2-like response in ST2-EL4 cells was inhibited by fingolimod and analogues at varying degrees. Using the OVA-TCRtg LPS/TLR-enhanced spleen cell assay, we found that fingolimod inhibited both IL-17 and IFN-γ production. In contrast, fingolimod phosphate failed to decrease Th1 cytokines. Interestingly, the effects of the parent compound fingolimod were modulated by the PP2A inhibitor okadaic acid, thus suggesting PP2A as relevant intracellular target. These studies describe detailed immune-modulating properties of fingolimod, including interference with a prototypical Th2 response via IL-33/ST2-TIR. Moreover, differential effects of fingolimod versus its phosphorylated derivative on TLR-activated and antigen-dependent Th1 activation suggest PP2A as an additional target of fingolimod immune therapy. Together with the analogues tested, these data may guide the development of more specific fingolimod derivatives.

Percutaneous nerve evaluation based on electrode placement under control of autonomic innervation.

BACKGROUND: Foramen needle electrode placement for percutaneous nerve evaluation (PNE) is currently carried out while observing the somatic motor response. This study investigated electrode placement while observing the autonomic as well as the somatic response. METHODS: A consecutive series of ten patients (seven women) with a median age of 51.9 (range 30-75) years undergoing PNE for faecal incontinence (n = 6) and obstipation (n = 4) were investigated prospectively. Electrode placement was carried out under simultaneous electromyography (EMG) of the external anal sphincter (EAS) and internal anal sphincter (IAS) and cystomanometry. RESULTS: PNE under control of somatic and autonomic nerve responses was carried out in all patients. In three out of ten patients, initial needle electrode placement showed single evoked EMG signals from the EAS. Final electrode placement resulted in adequate somatic motor and autonomic responses in all patients. Comparison of the increases in IAS EMG amplitude on the right and left stimulation sites for sacral nerves S3 and S4 demonstrated significant differences [S3 right: median 15.3 (interquartile range (IQR) 10.4; 20.1) µV vs. S3 left: median 11.6 (IQR 8.6; 16.0) µV, p = 0.034 and S4 right: median 24.1 (IQR 20.1; 37.2) µV vs. S4 left: median 12.0 (IQR 10.7; 13.7) µV, p = 0.012]. Stimulation-induced bladder activation was achieved in all seven patients with concomitant urinary dysfunction. CONCLUSIONS: Control of not just the somatic motor response but also the autonomic nerve response during foramen needle electrode placement may objectify PNE.

[Telemonitoring of bike exercise training in patients with obstructive sleep apnoea]. / Telemonitoring von Fahrrad-Heimtraining bei Patienten mit obstruktiver Schlafapnoe.

BACKGROUND: Patients with obstructive sleep apnoea (OSA) suffer from daytime sleepiness, cognitive disorders and are at increased risk of cardiovascular diseases. In addition to continuous positive airway pressure (CPAP), major lifestyle changes to increase physical activity contribute to risk reduction. The daily training duration should be at least 20 minutes to achieve a relevant effect. In addition to exercise training in groups, home training is useful. However, sufficiently intensive training is often not performed because of unavailable feedback (monitoring). It is not clear yet how many patients accept a bicycle home training and to what extent they meet the specified training time. METHOD: Of the 152 consecutive OSA patients surveyed, 74 (48.7 %) agreed to a 4-week home exercise bike training. After exclusion of 51 patients, 17 for logistical reasons, and 34 because of severe comorbidities, 23 patients remained (age 51.0 +/- 9.3 years, BMI 33.7 +/- 4.2, ESS score 10.4 +/- 6.7, AHI 33.8 +/- 24.0). The daily duration of training at the ventilatory threshold (VT1) was recorded and transmitted by a wireless module (Cinterion) via Internet to a doctor or instructor. RESULTS: The patients exercised during 27.3 +/- 2.9 days. 19 of the 23 patients (83 %) accomplished the training period of > 20 minutes per day. In 4 patients (17 %) the training time was well below this target level with 5.9 +/- 2.3 min. The average training time of all patients was 24.4 +/- 9.0 min. CONCLUSION: About 50 % of the OSA patients are interested in a regular physical exercise bike training with telemonitoring, and are performing it quite constantly. The described method of telemonitoring provides a simple and, compared to group training cost-effective way to reduce cardiovascular risk in OSA.

LC-MS/MS determination of FTY720 and FTY720-phosphate in murine intracellular compartments and human plasma.

A new analytical method for the quantitation of the orally active immunomodulatory drug FTY720 and its phosphate derivative in human plasma and murine subcellular compartments has been developed. The samples undergo a liquid-liquid extraction process before they are injected into a liquid chromatographic system coupled to a tandem mass spectrometer operating in positive ion mode. The quantitation is based on the analysis of two multiple reaction monitoring transitions per drug. The recovery of the analytical process is around 80% for all analytes. Intra- and interday precision and accuracy, as relative standard deviation and relative error, respectively, are lower than 12.5% in all cases. No important matrix effects were observed. The lower limits of quantitation for the analysed substances were 0.875 ng/mL and 2 ng/mL for FTY720 and FTY720-phosphate, respectively. Since no deuterated derivatives of the analytes were commercially available, the developed method was applied for quantifying the studied compounds using C17-sphingosine and C-17-sphingosine-1-phosphate as internal standards, in subcellular compartments of murine splenocytes. This method could be applied in the future for monitoring purposes in multiple sclerosis patients, since FTY720 has been approved by the American Food and Drug Administration and the European Medicines Agency for the pharmacological treatment of this disease.

[Whole-body MRI in preoperative diagnostics of breast cancer--a comparison with [corrected] staging methods according to the S 3 guidelines]. / Ganzkörper-MRT in der präoperativen Diagnostik des Mammakarzinoms--ein Vergleich mit den Stagingmethoden in der S 3-Leitlinie.

PURPOSE: The German Society of Senology (step-3 guidelines for the early recognition of breast cancer in Germany) recommends whole-body staging including chest X-ray, ultrasound of the liver and bone scintigraphy before systemic therapy in patients with breast cancer. The performance of these three examinations is time-consuming and involves radiation exposure. Whole-body MR imaging (WB-MRI) allows staging in a single examination without radiation exposure. The purpose of this study was to compare the diagnostic accuracy of WB-MRI with staging according to the guidelines. MATERIALS AND METHODS: During 04/07 and 06/09, the initial staging in 51 patients (56 ± 12 yrs) with breast cancer (24 patients with lymph node metastases) was performed according to the S 3-guidelines. Additionally, all patients underwent contrast-enhanced WB-MRI (1.5-Tesla-Magnetom Avanto, Siemens, Erlangen). The findings of the different modalities were compared after correlation of the lesions by follow-up. The detection of suspicious findings and the accuracy of prediction of malignancy of the detected lesions were evaluated. RESULTS: Overall, 14 metastases were detected in 4 of 51 patients after completion of the follow-up. By means of WB-MRI, all 14 metastases could be detected, while just 4 of these metastases were identified by the conventional methods. CONCLUSION: The detection of distant metastases has an important impact on patient management. In this study WB-MRI in breast cancer staging has shown promising results in regard to possible clinical implementation as a matter of routine staging.