A facile method for high-throughput screening of drug-eluting coatings in droplet microarrays based on ultrasonic spray deposition.

Coating modification such as drug-eluting coating is one of the most important approaches for the functionalization of biomedical devices. However, the throughputs are limited in conventional coating methods and the concept of miniaturization is rarely fulfilled. A droplet microarray (DMA), as a unique high-throughput platform, can avoid cross-contamination and reduce the consumption of materials which is inherently suitable for coating research yet is difficult to apply with coating materials via traditional methods. Here, we bring up a facile method based on ultrasonic spray deposition to integrate coating materials into a DMA. Several common polymer materials were selected to fabricate a DMA, and the obtained DMA showed the ability to anchor water droplets and form specific patterns. Coating arrays with a typical sandwich structure were also prepared for the high-throughput screening of drug-eluting coatings to demonstrate the potential of the platform in coating research. This developed method is efficient and compatible and enriches the choices of materials that can be applied in DMAs.

Rapid build-up of high-throughput screening microarrays with biochemistry gradients via light-induced thiol-ene "click" chemistry.

Microarrays have become extremely powerful experimental tools for high-throughput screening of cell behaviors in multivariate microenvironments. Herein, a microarray-based high-throughput platform with biochemistry gradients was developed using poly(limonene carbonate) (PLimC) as a substrate through thiol-ene click chemistry. ATR-IR, XPS, Raman spectrum, and water contact angle results demonstrated that the sulfhydryl molecules, including PEG (polyethylene glycol) and RGD (arginine-glycine-aspartic acid) peptide, could be grafted onto PLimC substrates, while the grafting density could be well controlled by regulating the intensity of UV irradiation. Then, microarrays with a gradient of RGD grafting density were fabricated by using UV irradiation patterned by a photomask and a gradient light filter. Adhesion experiments of smooth muscle cells and 3T3-L1 mouse embryonic fibroblast cells proved that the cell behaviors were highly determined by the RGD density. This platform puts forward a facile, high-throughput method to study the effect of biochemical signal density on cell behaviors.

Aortic aneurysm and aortic graft infection related to Mycobacterium bovis after intravesical Bacille Calmette-Guérin therapy-a case series.

BACKGROUND: So called "mycotic" aortic aneurysms account for only 0.7 to 1.3% of all aortic aneurysms and are commonly caused by Staphylococcus aureus and Salmonella species. Bacillus Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is part of the therapy of non-muscle-invasive bladder cancer (NMIBC). CASE PRESENTATION: We report a case series of three patients with a mycobacterial graft infection related to BCG after surgical treatment of a presumed mycotic aortic aneurysm as an extremely rare complication after NMIBC treatment. All three patients developed aortic aneurysm after BCG instillation and subsequent mycobacterial graft infection. CONCLUSION: Diagnosis requires a high degree of suspicion because of its nonspecific symptoms and imaging. The pathogen is not detected by standard microbiological testing. Treatment includes triple antimycobacterial therapy and radical surgical interventions. Graft preservation may be considered if no anastomosis is involved.

Environmental exposure enhances the internalization of microplastic particles into cells.

Microplastic particles ubiquitously found in the environment are ingested by a huge variety of organisms. Subsequently, microplastic particles can translocate from the gastrointestinal tract into the tissues likely by cellular internalization. The reason for cellular internalization is unknown, since this has only been shown for specifically surface-functionalized particles. We show that environmentally exposed microplastic particles were internalized significantly more often than pristine microplastic particles into macrophages. We identified biomolecules forming an eco-corona on the surface of microplastic particles, suggesting that environmental exposure promotes the cellular internalization of microplastics. Our findings further indicate that cellular internalization is a key route by which microplastic particles translocate into tissues, where they may cause toxicological effects that have implications for the environment and human health.

Evaluation of urinary selenium as a biomarker of human occupational exposure to elemental and inorganic selenium.

PURPOSE: Selenium (Se) is an essential trace element, which however, exhibits a narrow safe range of intake. Selenium also occurs at several workplaces, which results in an inhalative selenium exposure of the employees. Thus, an efficient exposure assessment strategy is demanded. The most established parameter, selenium in plasma, mostly consists of protein-bound selenium. This study aimed to investigate urinary total selenium (Se-U) as an additional biomarker of recent human occupational exposure to elemental and inorganic selenium. METHODS: Pre- and post-shift urine samples from employees with exposure to selenium-containing dust were analyzed to total selenium and compared with Se levels in urine samples from controls without occupational exposure to selenium as well as correlated with the recent ambient Se exposure by personal air monitoring. RESULTS: Se-U in post-shift samples was considerably increased compared to the levels in pre-shift samples as well as to the controls. However, Se-U in pre-shift urine was elevated compared to the Se-U in controls too. Se-U in post-shift urine and even better the shift increment in Se-U correlated with the air exposure of the present shift. A rough estimation by Se-U shift increment and external exposure accounted for an inhalative resorption rate of about 1%. CONCLUSION: Our data indicate that Se-U can display the exposure. Pre-shift Se-U levels may be based on previous exposure and indicate a slow urinary elimination kinetics. The results hint for a rather low resorption rate of selenium and inorganic selenium compounds via the lung.

Urine neutrophil gelatinase-associated lipocalin predicts outcome and renal failure in open and endovascular thoracic abdominal aortic aneurysm surgery.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been evaluated as a biomarker for AKI detection and adverse outcome in open and endovascular thoracoabdominal aortic aneurysm surgery. This observational, retrospective study included 52 patients. UNGAL was measured peri-operatively (48 h) and correlated with AKI requiring dialysis, tracheotomy and adverse outcome. Mean patients' age was 64.5 years. A total of 26.9% (n = 14) developed AKI, and 21.1% (n = 11) required dialysis, tracheotomy rate was 19.2% (n = 10) and in-hospital mortality rate was 7.6% (n = 4). uNGAL levels were related to AKI requiring dialysis at ICU (p = 0.0002), need for tracheotomy at baseline and admission on ICU (p = 0.0222, p = 0.0028, respectively), as well as adverse discharge modality (p = 0.0051, p = 0.0048, respectively). Diagnostic quality was good for uNGAL levels at admission to ICU regarding AKI requiring dialysis (sensitivity: 81.8% [48.2-97.7]; specificity: 87.8% [73.8-95.9]; area under the curve (AUC): 0.874 [0.752-0.949]). The diagnostic quality of uNGAL was favorable for the prediction of tracheotomy (sensitivity: 70.0% [34.8-93.3]; specificity: 83.3% [68.6-93.0]; AUC: 0.807 [0.674-0.903]) and adverse discharge (sensitivity: 77.8% [40.0-97.2]; specificity: 83.7% [69.3-93.2]; AUC: 0.817 [0.685-0.910]). uNGAL may be valuable as an post-operative predictor of AKI and adverse outcome after open and endovascular TAAA repair.

The combined effect of formulation and pH on properties of polyethylene oxide composite fiber containing egg albumen protein.

The aim of this work was to elucidate the influence of egg white albumen (EA) protein loaded on the electrospinning of PEO solutions under different concentrations and pHs conditions. Properties of the electrospun fiber mats, such as morphology, thermal properties, and wettability were analyzed. In addition, rheological behavior of the polymer solutions was measured to explain the electrospinnability for fiber formation. The rheological results showed that the addition of EA protein affects the molecular entanglement required to electrospin PEO, being able to incorporate up to 75wt% EA protein. The diameter of most of the PEO/EA fibers was in the range of 200-400nm. When comparing the effect of concentration and pH of the electrospinning solution, the morphology of the fibers was found to be mainly affected by the second one. FTIR analysis of the blend fibers confirmed the presence of the protein and revealed that the secondary structure changed with pH. From a thermodynamic point of view, the EA protein and PEO showed a high degree of mutual incompatibility. The presence of EA protein influenced PEO polymer thermal behavior, lowering its melting point and decreasing the quantity of PEO crystallites. All the PEO/EA electrospun fiber mats showed rapid water absorption, which increased as PEO concentration became higher, and similarly, when lowering protein concentration.

IKZF1 expression is a prognostic marker in newly diagnosed standard-risk multiple myeloma treated with lenalidomide and intensive chemotherapy: a study of the German Myeloma Study Group (DSMM).

Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial. We found that IKZF1 mRNA expression levels are significantly associated with progression-free survival (PFS). Patients in the lowest quartile (Q1) of IKZF1 expression had a superior PFS compared with patients in the remaining quartiles (Q2-Q4; 3-year PFS of 86 vs 51%, P=0.01). This translated into a significant better overall survival (100 vs 74%, P=0.03). Subgroup analysis revealed a significant impact of IKZF1, IKZF3 and BSG expression levels on PFS in cytogenetically defined standard-risk but not high-risk patients. Our data suggest a prognostic role of IKZF1, IKZF3 and BSG expression levels in lenalidomide-treated multiple myeloma.

Bio-based polycarbonate as synthetic toolbox.

Completely bio-based poly(limonene carbonate) is a thermoplastic polymer, which can be synthesized by copolymerization of limonene oxide (derived from limonene, which is found in orange peel) and CO2. Poly(limonene carbonate) has one double bond per repeating unit that can be exploited for further chemical modifications. These chemical modifications allow the tuning of the properties of the aliphatic polycarbonate in nearly any direction. Here we show synthetic routes to demonstrate that poly(limonene carbonate) is the perfect green platform polymer, from which many functional materials can be derived. The relevant examples presented in this study are the transformation from an engineering thermoplastic into a rubber, addition of permanent antibacterial activity, hydrophilization and even pH-dependent water solubility of the polycarbonate. Finally, we show a synthetic route to yield the completely saturated counterpart that exhibits improved heat processability due to lower reactivity.

[The Compression Syndrome of Lumbar Arteries - Case Report of a Rare Disease Pattern]. / Das Kompressionssyndrom der Lumbalarterien - Kasuistik eines seltenen Krankheitsbilds.

STUDY DESIGN: We present a monocentric analysis of the lumbar artery compression syndrome (LACS) in the form of a case report. OBJECTIVES: Literature information was collected about the symptoms, diagnosis and treatment of this rare disorder in the context of the existing data. METHODS: The current medical literature includes only one report about three cases of LACS, collected over 20 years in France and Germany. We compared these cases with the experience of the European Vascular Center Aachen-Maastricht. RESULTS: The symptoms of this rare disorder are dominated by reversible, motion-dependent paralysis of the legs. Compression of the right lumbar arteries by muscular fibres or connective tissue is a fundamental cause. CONCLUSION: Surgical treatment, which means decompression of the lumbar arteries via a thoracolaparotomy, is an appropriate therapy with few complications and good long-term results.

Treatment of symptomatic aberrant subclavian arteries.

OBJECTIVE: The aim of this study is to present experience with 10 patients with symptomatic aberrant subclavian artery (ASA) and aneurysm of ASA who underwent surgical treatment. METHODS: From 2008 to 2011 10 patients with symptomatic aberrant subclavian artery (mean age 60 years [range 24-90 years]) were studied. Symptoms were dysphagia (n = 7), dyspnea (n = 4), acute chest pain (n = 1), respiratory distress syndrome (n = 1), superior cava syndrome, and shock (n = 1). Six patients had aneurysm formation of the ASA (mean diameter of 7.1 cm [range 3.0-12.4 cm]; rupture [n = 1], dissection [n = 1]). All data were analyzed retrospectively. RESULTS: Treatment was performed as a hybrid procedure in eight patients. This included thoracic endoluminal graft exclusion with revascularization of the ASA, a pure endovascular procedure with two occluders in one patient, and an open procedure in one patient with ligation of the aberrant artery through a thoracotomy. Three patients died during the early postoperative period owing to pulmonary complications. All three suffered from a symptomatic aneurysm, and two were treated as an emergency procedure. Median follow-up was 20 months (range 12-49 months). CONCLUSION: A symptomatic ASA and its associated aneurysmal formation should be excluded after diagnosis. In most cases, a hybrid procedure consisting of thoracic endografting and revascularization of the ASA is feasible.

What predicts outcome after recanalization of chronic venous obstruction: hemodynamic factors, stent geometry, patient selection, anticoagulation or other factors?

In this review we evaluated the effect of different suggested factors associate with the outcome after recanalization of chronic venous obstruction (CVO). HEMODYNAMIC FACTORS: Based upon literature no clear suggestions can be made to identify the risk of stent occlusion in association with the hemodynamic effects. However it is evident that ensuring optimal in- and outflow of the stented tract is key in maintaining the patency. PATIENT SELECTION: Noninvasive imaging modalities are used to divide patients in three subgroups based on the place and extension of post-thrombotic changes. Moreover it should be noted that AV fistula in selected patients can reduce the risk of thrombosis or re-occlusion. GEOMETRY: Excessive oversizing of the stent and stent compression from outside are considered to be associated with stent occlusion. Additionally, overlapping rigid stents, unnatural angel between stents and in-stent kinking are other geometrical factors related to worse outcome after venous recanalization. ANTICOAGULATION: Adequate peri-and postoperative anticoagulation has a crutial role in stent patency. There is no data regarding the duration of anticoagulation therapy and recommendations vary between 6 weeks to 6 months. RESULT: impaired inflow or outflow, presence of a hypercoagulability, total number of treated segments and use of stents designed for implantation in arterial system are associated with decreased stent patency.

Anatomic changes of target vessels after fenestrated and branched aortic aneurysm repair.

AIM: Objective of this study was to evaluate the anatomic changes of the stented target vessels after endovascular repair of complex aortic aneurysms. METHODS: Between July 2011 and December 2013, 53 aortic aneurysms were treated in our department with fenestrated and branched stent-graft devices. Forty-two of these patients were pre- and postoperatively scanned with a high resolution computer tomography (CT) (Cook Zenith® fenestrated or branched, Australia Pty. Ltd., Brisbane, Australia: N.=19; AnacondaTM fenestrated, Vascutek, Glasgow, Scotland, UK: N.=23). The other 11 out of the 53 patients did not receive a CT scan, because of a pre-existing renal failure. In the CT scans we retrospectively evaluated the anatomic vessel deviation at the origin of the target vessel and the vessel shift distal to the stent. For the first measurement the CT scans were loaded into OsiriX MD®, and the pre- and postoperative angles of the target vessels were measured and subtracted. For matching, the CT-scans were normalized at vertebral body lumbar 2. The second measured angle was the maximal measured angle distal to the target vessel stent-graft. RESULTS: Altogether, 113 target vessels were stented (celiac trunk [CT] 15, superior mesenteric arteries [SMA] 26, renal arteries [RA] 72), with 97 balloon-expandable PTFE stents: 90 Atrium V12 (Maquet Getinge group, Hudson, NH, USA), 7 BeGrafts (Bentley InnoMed, Hechingen, Germany) and 16 self-expandable fluency PTFE stents (Bard, Karlsruhe, Germany). The mean anatomic deviation at the target vessel origin was 28±17.3 and the mean vessel shift distal to the stent was 36.3±18.8. There were no significant differences between the main device and the target vessel stent types. CONCLUSION: Fenestrated and branched stent-graft solutions for aortic aneurysm repair induce changes of the target vessel anatomy. We did not observe significant differences between the several devices.

Late rupture after EVAR: a new trend?

AIM: Endovascular aortic repair (EVAR) is an adequate therapy for abdominal aortic aneurysms (AAA). Late aortic ruptures caused by endoleaks after EVAR still remain a critical issue. The aim of this study was to assess the causes of ruptured aortic aneurysms after EVAR in a single center study. METHODS: All patients, who were treated in our University hospital with a ruptured juxtra- or infrarenal AAA between January 2011 and October 2013, were included in this retrospective analysis. RESULTS: Thirty patients with ruptured infra- or juxtrarenal aneurysms were treated in this time frame. Six out of these 30 patients had previous EVAR repair. The median maximal aneurysm diameter of these post-EVAR patients was 82 (75-95) mm. The median time between primary EVAR and rupture was 42.5 (14-99) months. Three patients with type Ia endoleaks were treated by stent removal and conventional aortic reconstruction. In two patients with type II endoleak the bleeding was controlled by occluding the back bleeding lumbar arteries. One type III endoleak was sealed by an additional stent-graft implantation into the right iliac artery. CONCLUSION: We observed a considerable number of patients with a ruptured AAA after EVAR. Surprisingly, we observed two ruptured aneurysms due to type II endoleaks.

A new shunting concept to prevent lower limb ischemia/reperfusion injury in prolonged fenestrated stent-graft procedures.

AIM: Complex endovascular procedures to treat thoracoabdominal aortic aneurysms (TAAA) can be time consuming and therefore comprise the risk of lower limb ischemia with subsequent reperfusion injury and compartment syndrome. Aim of this study was to evaluate a new protective method to prevent these postoperative problems. METHODS: In order to maintain blood perfusion to both legs during prolonged endovascular aortic procedures we developed a shunting technique with two additional 7 French (Fr) sheaths in both superficial femoral arteries. We evaluated the perfusion technique in 5 patients with fenestrated endovascular aortic aneurysms repair (FEVAR). First, we measured the flow in the 7 Fr sheaths; second, we clinically controlled the lower limb for developing compartment syndrome. Third we measured creatinine kinase (CK) as marker for postoperative muscular damage. RESULTS: In 5 male patients (median age 77, range 59-80 years) undergoing endovascular TAAA repair, the perfusion technique was feasible. The median flow per catheter was 102 mL/min (range 61-156.5 mL/min) and monophasic with a mean arterial blood pressure of 71 mmHg (range 56-82 mmHg). No patient developed a compartment syndrome. The CK levels were only lightly elevated. CONCLUSION: This simple perfusion technique allows adequate lower limb perfusion during prolonged complex endovascular aortic procedures.

[Clinical functional assessment of various surgical hand arthrodesis techniques]. / Klinisch-funktionelle Nachuntersuchung verschiedener handchirurgischer Versteifungsmethoden.

BACKGROUND: Total and partial arthrodesis of the wrist are currently sophisticated treatment options for many advanced pathological changes of the wrist. This retrospective study analyzed the subjective and objective outcome of different wrist arthrodesis techniques, e.g. total wrist arthrodesis, scaphotrapeziotrapezoid (STT) bone fusion and midcarpal arthrodesis. MATERIALS AND METHODS: Subjective physical and mental quality of life of 98 patients (total wrist arthrodesis n = 43, STT fusion n = 30 and midcarpal arthrodesis n = 25) was measured using the DASH questionnaire. The range of motion and grip strength were analyzed in 48 patients (total wrist arthrodesis n = 21, STT fusion n = 17 and midcarpal arthrodesis n = 10). RESULTS: Patients with partial wrist arthrodesis achieved a significantly better DASH score than patients with total wrist arthrodesis. Grip strength did not show any statistically significant differences between the two groups. Patients with STT fusion showed the best range of motion of the wrist. CONCLUSION: Partial arthrodesis seems to be superior to total wrist arthrodesis. Patients profit from a higher physical and mental quality of life.

Intentional left subclavian artery coverage without revascularization during TEVAR.

At present, endovascular therapy is a well-established treatment for different types of thoracic aortic pathologies. There is growing evidence, that thoracic endovascular aortic repair (TEVAR) has advantages over open repair with regard to perioperative morbidity and mortality in the treatment of thoracic aortic aneurysms. However, in up to 50% of TEVAR procedures the proximal end of the stent-graft will (partly) cover the origin of the left subclavian artery (LSA) in order to achieve a save sealing zone. Intracranial stroke and paraplegia are feared complications and might be associated with LSA exclusion from the circulation. Unfortunately, no reliable technique is available to assess the individual risk of stroke and paraplegia in case of LSA coverage, so that the indication for LSA revascularization continues to be matter of assuming and guessing. The quality of available evidence on necessity or superfluity to revascularize the LSA is very low and studies report, to some extent, controversial outcome after intentional LSA coverage. In the light of the devastating consequences for patients in case of neurological complications due to LSA coverage the question of prophylactic LSA revascularization remains a significant problem which is elucidated and discussed in this manuscript.

Thoracoabdominal aneurysms and changes in adjacent vertebral bodies.

AIM: The aim of this study was to assess if chronic intermittent pressure of a thoracoabdominal aortic aneurysm (TAAA) induces structural changes in vertebral bodies and if eroded vertebral bones can still be found after the extermination of syphilis. METHODS: A retrospective analysis of computed tomography (CT) scans of patients with TAAA was performed. In the anatomical regions were the TAAA was in close contact with the vertebral bodies, the vertebral body alteration was distinguished into 4 categories. Category 0: no changes; 1: discrete changes, minimal asymmetry; 2: obvious asymmetry of the vertebral body with sustained cortical layer; 3: severe destruction of the vertebral body with loss of the cortical layer. RESULTS: Eighty-six CT scans of patients (mean age 63; range 25-82 years) with TAAA pathology were examined (24 female, 62 male). The mean aneurysm diameter was 6.5 cm (4.3-14 cm). The results for scoring were: category 0: 33 patients; category 1: 46 patients; category 2: 5 patients and category 3: 2 patients. One of the category 3 patients suffered from acute spinal cord compression with complete paraplegia. In total, 62% of patients showed some degree of changes at vertebral bodies adjacent to the TAAA. CONCLUSION: Intermittent pressure by either dissecting or non-dissecting TAAAs may induce structural changes in the vertebral bodies of the spine. Severe destruction of the bone is a rare, but existing complication.

Bombardment induced ion transport--part III: experimental potassium ion conductivities in poly(para-xylylene).

The bombardment induced ion transport (BIIT) technique has been employed for studying the ionic conductivity of thin poly(p-xylylene) (PPX) films. The experiment is based on bombarding a PPX film with a c.w. potassium ion beam. The transport of ions through the film - which follows the laws of electrodiffusion - is detected as a neutralization current on the backside electrode on which the film has been deposited. This backside current scales quadratically with the acceleration potential of the ion beam and inversely cubically with the thickness of the film. This confirms theoretical predictions made in part I of this mini-series (Phys. Chem. Chem. Phys., 2011, 13, 20112-20122). This characteristic is markedly different from the Ohm-like current-voltage properties of a solid electrolyte, e.g. an ion conducting glass. The diffusion coefficient for K(+) in PPX is determined to be 8.528 × 10(-16) cm(2) s(-1) at 333 K. From the temperature dependence of the diffusion coefficient we conclude that a hopping mechanism with an activation energy of 2.74 eV ± 0.18 eV is operative.

[Aortic aneurysm 2012: open, hybrid or total endovascular repair?]. / Aortenaneurysma 2012 - offen, hybrid oder total endovaskulär?

During the past two decades, minimally invasive endovascular procedures have changed therapeutic strategies. Such techniques have now become the method of choice for practically all vascular and aortic pathologies. This development is especially apparent in the treatment of aortic aneurysms. The purpose of this report is to provide a critical review about the current standard of care of abdominal and thoracic aorta based on an electronic Medline literature search. For elective infrarenal aneurysms, endovascular aneurysm repair (EVAR) has become a widely accepted alternative to open repair in cases with appropriate morphology. Currently, fenestrated (FEVAR) or branched endografts offer promising short- and mid-term results in juxtarenal aneurysms, however, these techniques are complex, technically challenging, and expensive. The alternative chimney or sandwich graft technique are becoming more common because they are feasible using standard endografts. Thoracic endovascular aortic repair (TEVAR) is already the gold standard for some descending pathologies. Complex thoracoabdominal aneurysms still require open surgery in centres of excellence, whereby, total endovascular repair or hybrid procedures have proved to be feasible in such specialist centres for selected patients.