Biaxial Piezoelectric MEMS Mirrors with Low Absorption Coating for 1550 nm Long-Range LIDAR.

This paper presents the fabrication and characterization of a biaxial MEMS (MicroElectroMechanical System) scanner based on PZT (Lead Zirconate Titanate) which incorporates a low-absorption dielectric multilayer coating, i.e., a Bragg reflector. These 2 mm square MEMS mirrors, developed on 8-inch silicon wafers using VLSI (Very Large Scale Integration) technology are intended for long-range (>100 m) LIDAR (LIght Detection And Ranging) applications using a 2 W (average power) pulsed laser at 1550 nm. For this laser power, the use of a standard metal reflector leads to damaging overheating. To solve this problem, we have developed and optimised a physical sputtering (PVD) Bragg reflector deposition process compatible with our sol-gel piezoelectric motor. Experimental absorption measurements, performed at 1550 nm and show up to 24 times lower incident power absorption than the best metallic reflective coating (Au). Furthermore, we validated that the characteristics of the PZT, as well as the performance of the Bragg mirrors in terms of optical scanning angles, were identical to those of the Au reflector. These results open up the possibility of increasing the laser power beyond 2W for LIDAR applications or other applications requiring high optical power. Finally, a packaged 2D scanner was integrated into a LIDAR system and three-dimensional point cloud images were obtained, demonstrating the scanning stability and operability of these 2D MEMS mirrors.

First Comparison of Retroperitoneal Versus Transperitoneal Robot-Assisted Nephroureterectomy with Bladder Cuff: A Single Center Study.

INTRODUCTION: After recent presentation of the first complete robot-assisted retroperitoneal nephroureterectomy with bladder cuff (RRNU) for patients with upper tract urothelial cancer (UTUC), we aimed to compare this new surgical technique with robot-assisted transperitoneal nephroureterectomy (TRNU) representing the current standard of care. METHODS: Robot-assisted nephroureterectomies (NUs) were retrospectively analyzed and compared based on two groups: transperitoneal versus retroperitoneal approach. Baseline data were collected for patient demographics, tumor characteristics, intra- (EAUiaiC) and postoperative (Clavien-Dindo) complications, and perioperative variables. Tumor characteristics included grade of malignancy, clinical stage, and surgical margin status. Short-term follow-up data including 30-day readmission rates were collected. Statistical analyses were performed assuming a significant p-value of < 0.05. RESULTS: The analysis includes perioperative patient data after proven UTUC of 24 TRNU versus 12 RRNU (mean age: 70 versus 71 years; BMI: 25.9 versus 26.1 kg/m2; CCI score ≥ 4: 83% versus 75%; ASA score ≥ 3: 37% vs 33%). Intraoperative (16.4% vs 0%, p = 0.35) and postoperative (25% vs 12.5%, p = 0.64) complications demonstrated no significant discrepancy. Notably, RRNU demonstrated significantly shorter surgery time (p < 0.05) and length of stay (p < 0.05). There was no significant difference in histopathological tumor characteristics, whereas significantly more lymph nodes were removed through RRNU (11.0±3.3 vs. 6.4±5.1, p < 0.05). Finally, no statistical difference was shown in short-term follow-up. CONCLUSION: We report the first head-to-head comparison between RRNU and TRNU. RRNU proves to be a safe and feasible approach which appears to be non-inferior to TRNU. RRNU expands the spectrum of minimally invasive treatment options, particularly for patients with major previous abdominal surgery.

Assessment of a novel smartglass-based point-of-care fusion approach for mixed reality-assisted targeted prostate biopsy: A pilot proof-of-concept study.

Purpose: While several biopsy techniques and platforms for magnetic resonance imaging (MRI)-guided targeted biopsy of the prostate have been established, none of them has proven definite superiority. Augmented and virtual reality (mixed reality) smartglasses have emerged as an innovative technology to support image-guidance and optimize accuracy during medical interventions. We aimed to investigate the benefits of smartglasses for MRI-guided mixed reality-assisted cognitive targeted biopsy of the prostate. Methods: For prospectively collected patients with suspect prostate PIRADS lesions, multiparametric MRI was uploaded to a smartglass (Microsoft® Hololens I), and smartglass-assisted targeted biopsy (SMART TB) of the prostate was executed by generation of a cognitive fusion technology at the point-of-care. Detection rates of prostate cancer (PCA) were compared between SMART TB and 12-core systematic biopsy. Assessment of SMART-TB was executed by the two performing surgeons based on 10 domains on a 10-point scale ranging from bad (1) to excellent (10). Results: SMART TB and systematic biopsy of the prostate were performed for 10 patients with a total of 17 suspect PIRADS lesions (PIRADS 3, n = 6; PIRADS 4, n = 6; PIRADS 5, n = 5). PCA detection rate per core was significant (p < 0.05) higher for SMART TB (47%) than for systematic biopsy (19%). Likelihood for PCA according to each core of a PIRADS lesion (17%, PIRADS 3; 58%, PIRADS 4; 67%, PIRADS 5) demonstrated convenient accuracy. Feasibility scores for SMART TB were high for practicality (10), multitasking (10), execution speed (9), comfort (8), improvement of surgery (8) and image quality (8), medium for physical stress (6) and device handling (6) and low for device weight (5) and battery autonomy (4). Conclusion: SMART TB has the potential to increase accuracy for PCA detection and might enhance cognitive MRI-guided targeted prostate biopsy in the future.

[Virtual and augmented reality in urology]. / Virtual und Augmented Reality in der Urologie.

Although continuous technological developments have optimized and evolved medical care throughout time, these technologies were mostly still comprehensible for users. Driven by immense financial efforts, modern innovative products and technical solutions are transforming medicine today and will do so even more in the future: virtual and augmented reality. This review critically summarizes the current literature and future uses of virtual and augmented reality in the field of urology.

Therapeutic drug monitoring-guided high dose meropenem therapy of a multidrug resistant Acinetobacter baumannii - A case report.

BACKGROUND: Infections with multidrug resistant Acinetobacter baumannii in immunocompromised patients are life-threatening. Therapeutic options are rare in this context, but patients are dependent on an effective antibiotic therapy. Thus, new antibiotic strategies are deemed necessary. CASE PRESENTATION: This case report recounts the therapeutic drug monitoring-guided meropenem therapy of a 32 years old patient admitted with acute exacerbation of cystic fibrosis. Veno-venous extracorporeal membrane oxygenation was initiated on the first day of admission to the intensive care unit. The patient showed insufficient serum trough levels of meropenem despite the maximum approved dose (2g every 8h) was administered which was due to augmented renal clearance. Through continuous infusion of the same cumulative dose, target levels were reached. On day 17 of admission, the patient underwent successful double-lung-transplant surgery and extracorporeal membrane oxygenation was ended. Unfortunately, the donor's lung was colonized with a multidrug resistant Acinetobacter baumannii that was positive for OXA-23 carbapenemase. Hence a combination therapy of intravenous sulbactam, tigecycline, meropenem and inhalative colistin was established, with a known minimal inhibitory concentration for meropenem of 32 mg/l. Under continuous infusion of 8 g meropenem/day, serum levels exceeded 32 mg/l over 12 days. The patient was transferred from the intensive care unit to a general ward without any signs of infection. CONCLUSIONS: Therapeutic drug monitoring-guided meropenem may be a sound new therapeutic option in eradicating multidrug resistant Acinetobacter and offer a novel therapeutic option in the field of personalized medicine.

Mucin-Poor Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Presented with Multiple Metastases Two Years after Nephrectomy: An Atypical Behaviour of a Rare, Indolent Tumour.

BACKGROUND: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of renal cell carcinoma, whose clinical behaviour and metastatic potential have not been fully elucidated to date. There are only a few metastatic cases in the literature, which all either featured sarcomatoid differentiation or were synchronously metastasised at diagnosis. CASE PRESENTATION: We report a case of a 49-year-old male with end-stage kidney disease on dialysis, presenting with multiple osseous metastases of a mucin-poor variant of MTSCC of the kidney, without sarcomatoid differentiation, two years after bilateral nephrectomy for papillary renal cell carcinoma (RCC) at a curable stage. After retrospectively reexamining the initial nephrectomy specimens, the tumour of the right kidney was also diagnosed as a mucin-poor variant of MTSCC, while the tumour of the left kidney was confirmed as a papillary RCC. CONCLUSIONS: It is proposed that MTSCC can be associated with end-stage renal disease and that particularly the mucin-poor variant is easily confused with papillary renal cell carcinoma, as happened in this case. Although it is considered as a relatively indolent malign entity, it can metastasise even years after successful primary surgical treatment. This implies, besides accurate diagnosis, that MTSCC patients should be monitored closely in the follow-up period.

[Above and beyond BMI : Alternative methods of measuring body fat and muscle mass in critically ill patients and their clinical significance]. / Jenseits des BMI : Alternative Methoden zur Erfassung von Körperfett und Muskelmasse in der Intensivmedizin und deren klinischer Stellenwert.

Obesity leads to better survival in critically ill patients. Although there are several studies confirming this thesis, the "obesity paradox" is still surprising from the clinician's perspective. One explanation for the "obesity paradox" is the fact that the body mass index (BMI), which is used in almost all clinical evaluations to determine weight categories, is not an appropriate measure of fat and skeletal muscle mass and its distribution in critically ill patients. In addition, height and weight are frequently estimated rather than measured. Central obesity has been identified in many disorders as an independent risk factor for an unfavourable outcome. The first clues are to be found in intensive care. Along with obesity, an individual's entire muscle mass is a variable that has an influence on outcome. Central obesity can be measured relatively easily with an abdominal calliper, but the calculation of muscle mass is more complex. A valid and detailed measurement of this can be obtained using computed tomography (CT) images, acquired during routine care. For future clinical observation or interventional studies, single cross-sectional CT is a more sophisticated tool for measuring patients' anthropometry than a measuring tape and callipers. Patients with sarcopenic obesity, for example, who may be at a particular risk, can only be identified using imaging procedures such as single cross-sectional CT. Thus, BMI should take a back seat as an anthropometric tool, both in the clinic and in research.

Role of personality and expectations for itch and scratching induced by audiovisual itch stimuli.

Itch is an unpleasant, bodily sensation, which--similar to pain--evokes behavioral reactions. As a response to itch, people start scratching. There are different ways to provoke itch and subsequent scratching in experimental settings. A non-invasive method to induce itch and scratching is the presentation of itch-related (audio-) visual stimulus material, like slide-supported lectures on skin diseases or crawling insects. Also, watching videos showing other people scratching provokes itch and the desire to scratch. In this review, we focus on psychological factors, which were shown to be associated with itch and scratching provoked by (audio-) visual itch stimuli. First, we summarize the findings on the relationship between personality characteristics and (audio-) visually induced itch. Agreeableness and self-consciousness were shown to be associated with induced itch and scratching in patients with chronic skin diseases, while neuroticism was linked to induced itch in healthy subjects. Second, we present results of a recent study, in which we altered the expectations towards audio-visually induced itch and scratching by changing the information given on upcoming itch stimuli. It was shown that subjects being informed about itch stimuli in a neutral way displayed a shorter scratch duration in itch inducing situations than subjects having catastrophizing expectations. Also, the increase in scratch duration and in the number of scratch movements induced by audiovisual itch stimuli was higher when the patients were not informed about itch induction. Thus, in itch patients neither catastrophizing nor trivializing symptoms seems to be helpful.

Quantification of propionaldehyde in breath of patients after lung transplantation.

Oxygen-derived free radicals (ROS) have been identified to contribute significantly to ischemia-reperfusion (I/R) injury by initiating chain reactions with polyunsaturated membrane lipids (lipid peroxidation, LPO) resulting in the generation of several aldehydes and ketones. Due to their volatile nature these LPO products can be measured noninvasively in breath. We hypothesized that one of these markers, namely propionaldehyde, will be increased in lung and heart-lung transplant patients where severe oxidative stress due to I/R injury with early graft dysfunction represents one of the major postoperative complications resulting in prolonged ventilation and increased in-hospital morbidity and mortality. Expiratory air measurements for acetone, isoprene, and propionaldehyde were performed in seven patients after lung (n = 5) or heart-lung (n = 2) transplantation, ventilated patients (n = 12), and healthy volunteers (n = 17) using online ion-molecule reaction mass spectrometry. Increased concentrations of acetone (transplanted: 3812 [2347-12498]; ventilated: 1255 [276-1959]; healthy: 631 [520-784] ppbv; P < .001) and propionaldehyde (transplanted: 270 [70-424]; ventilated: 82 [41.8-142]; healthy: 1.7 [0.1-11.8] ppbv; P < .001) were found in expiratory air of transplanted and ventilated patients. Propionaldehyde resulting from spontaneous fragmentation of peroxides due to free radical-induced LPO after I/R injury in patients after lung or heart-lung transplantation can be quantified in expired breath.

Optical polymers with tunable refractive index for nanoimprint technologies.

In order to realize a versatile high throughput production of micro-optical elements, UV-curable polymer composites containing titanium dioxide nanoparticles were prepared and characterized. The composites are based on an industrial prototype epoxy polymer. Titanium dioxide nanoparticles smaller than 10 nm were synthesized by the nonaqueous sol method and in situ sterically stabilized by three different organic surfactants. The composites exhibit high transparency. Distinct alteration of optical transmission properties for visible light and near IR wavelength range could be avoided by adaption of the stabilizing organic surfactant. Most importantly, the refractive index (RI) of the composites that depends on the fraction of incorporated inorganic nanoparticles could be directly tuned. E.g. the RI at a wavelength of 635 nm of a composite containing 23 wt% titanium dioxide nanoparticles is increased to 1.626, with respect to a value of 1.542 for the pure polymer. Furthermore, it could be demonstrated that the prepared inorganic-organic nanocomposites are well suited for the direct fabrication of low-cost micro-optical elements by nanoimprint lithography. A low response of the optical composite properties to temperature treatment up to 220 °C with a shrinkage of only about 4% ensures its application for integrated micro-optical elements in industrial production.

EHR Big Data Deep Phenotyping. Contribution of the IMIA Genomic Medicine Working Group.

OBJECTIVES: Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support the definition of deep phenotypes in medical records. METHODS: As the vast stores of genomic information increase with next generation sequencing, the importance of deep phenotyping increases. The growth of genomic data and adoption of Electronic Health Records (EHR) in medicine provides a unique opportunity to integrate phenotype and genotype data into medical records. The method by which collections of clinical findings and other health related data are leveraged to form meaningful phenotypes is an active area of research. Longitudinal data stored in EHRs provide a wealth of information that can be used to construct phenotypes of patients. We focus on a practical problem around data integration for deep phenotype identification within EHR data. The use of big data approaches are described that enable scalable markup of EHR events that can be used for semantic and temporal similarity analysis to support the identification of phenotype and genotype relationships. CONCLUSIONS: Stead and colleagues' 2005 concept of using light standards to increase the productivity of software systems by riding on the wave of hardware/processing power is described as a harbinger for designing future healthcare systems. The big data solution, using flexible markup, provides a route to improved utilization of processing power for organizing patient records in genotype and phenotype research.

Evaluation of resistless Ga⁺ beam lithography for UV NIL stamp fabrication.

This paper presents an alternative rapid prototyping approach for the fabrication of stamps for UV nanoimprint lithography. In this process, areas implanted with gallium serve as an etch mask for the dry etching of quartz. The implantation is performed using a focused ion beam system. To avoid charging of the quartz substrate the use of thin layers of chromium or carbon on the quartz substrate has been evaluated. The resulting quartz structures exhibit very smooth surfaces after dry etching, if the implantation dose is high enough to form a stable etch mask. Furthermore, anisotropic etching could be realized by optimization of a quartz etching process involving C4F8 and O2 after the use of resistless Ga(+) beam lithography. Finally, imprints into a UV curing resist are performed successfully with the manufactured stamps, proving that the presence of Ga rich areas on the stamp is not detrimental to the curing of the resist or the functionality of the anti-sticking layer.

Influence of hepatitis C virus infection and high virus serum load on biliary complications in liver transplantation.

BACKGROUND: Biliary complications (BCs) and recurrent hepatitis C virus (HCV) infection are among the major causes of morbidity and graft loss following liver transplantation. The influence of HCV on BCs has not been definitely clarified. PATIENTS AND METHODS: We performed a retrospective cohort study to analyze risk factors and outcome of post orthotopic liver transplantation (OLT) BCs in 352 liver transplant recipients over 12 years in Munich, Germany (n = 84 with HCV; living donor and re-OLT were excluded). BCs diagnosed with imaging techniques and abnormal liver enzyme pattern, requiring an intervention, were considered. RESULTS: In a multivariate analysis, HCV serostatus and a high pre-and post-surgery HCV RNA serum load were independent risk factors for anastomotic strictures. HCV positivity and BCs alone did not alter graft loss. HCV-positive patients with BCs, however, had a significantly worse graft outcome (P = 0.02). Non-anastomotic strictures, bile leaks, and the number of interventions needed to treat bile leaks led to worse graft outcome in all patients. CONCLUSION: HCV positivity and a high HCV RNA serum load were risk factors for anastomotic strictures. BCs and HCV had an additive effect on graft loss.

Sorafenib and pegylated interferon-α2b in advanced metastatic melanoma: a multicenter phase II DeCOG trial.

BACKGROUND: The combination of sorafenib, a multikinase inhibitor, and pegylated interferon-α2b (Peg-IFN-α2b) could potentially lead to an improved antitumoral response. Previously, combinations of interferon and sorafenib have been used in renal cell cancer. PATIENTS AND METHODS: Patients with stage IV metastatic melanoma and no previous systemic therapies apart from adjuvant immunotherapy received Peg-IFN-α2b 3 µg/kg once per week, and sorafenib 400-mg b.i.d. for a minimum of 8 weeks. The primary study end point was disease control rate (DCR). RESULTS: Between February 2008 and February 2009, 55 patients were enrolled with a median age of 64 years (20-85). At 8 weeks, 2 patients (3.6%) had a partial response (PR) and 14 patients a stable disease (25.5%), for a DCR of 29.1% in the intention-to-treat (ITT) population. The median progression-free survival in the ITT population was 2.47 months (95% confidence interval 1.22-3.72 months). The toxicity of sorafenib and Peg-IFN-α2b combination was characterized by mainly hematological side-effects, including one treatment-related bleeding complication with a fatal outcome. Other grade 3/4 toxic effects were fatigue and flu-like symptoms. CONCLUSION: The combination of sorafenib and Peg-IFN-α2b showed modest clinical activity and some serious side-effects including fatal bleeding complications.

Usefulness of exhaled nitric oxide to guide risk stratification for bronchiolitis obliterans syndrome after lung transplantation.

The aim of this study was to assess fractional exhaled nitric oxide (FeNO) for the early diagnosis of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). 611 FeNO measurements in 166 consecutive patients were classified depending on BOS stage at the time of assessment and course during minimum follow-up of 3 months: (1) stable non-BOS, (2) unstable non-BOS, (3) stable BOS and (4) unstable BOS. Unstable course was defined as new onset of BOS≥1 or progression of BOS. FeNO before unstable course was significantly increased in comparison to their stable counterparts (non-BOS: 28.9 ± 1.2 ppb, n = 40 vs. 16.4 ± 0.8 ppb, n = 131 and BOS: 32.5 ± 1.3 ppb, n = 35 vs. 15.3 ± 0.8 ppb, n = 26; p = 0.01 each). Average time from FeNO reading to onset of deterioration was 117 ± 9 days in non-BOS and 136 ± 9 days in BOS patients. The positive and negative predictive value of FeNO >20 ppb for BOS was 69.0% and 96.9%, respectively. Serial measurements demonstrated significantly lower mean individual variation in stable recipients as compared to stable patients switching to unstable course (3.2 ± 0.3 ppb vs. 12.7 ± 1.4 ppb, p = 0.02). In particular, the excellent negative predictive value of persistently low FeNO readings for future BOS make FeNO assessments a useful tool for continuous risk stratification after LTX.

[Pandemic influenza A/H1N1 2009 : Challenge for intensive care medicine]. / Neue Influenza-A/H1N1-2009-Virus-Pandemie : Herausforderung für die Intensivmedizin.

The novel pandemic influenza A/H1N1v has also led to a rapid increase in the number of new cases in Germany. In the majority of patients the disease has taken a mild clinical course. However, in isolated cases severe complications requiring hospitalization or intensive care treatment have occurred. Most of the current recommendations refer to outpatients or mild diseases and are not always suitable and practicable for the management of a life-threatening influenza A/H1N1v infection in an intensive care setting. The aim of this review is to present a reliable diagnostic and therapeutic approach for critically ill patients, considering the current literature, case-based experiences from our own intensive care unit and including relevant recommendations of public health authorities. Initial measures regarding therapeutic, diagnostic and isolation precautions arise from past medical history, current anamnesis and characteristic symptoms and their progression. Patients suspected of having acquired an influenza A/H1N1v infection should be isolated. Early laboratory diagnosis of A/H1N1v infection ideally utilizes the reverse transcriptase polymerase chain reaction (RT-PCR) as the most sensitive diagnostic method. Emerging evidence suggests that incidence and severity of life-threatening influenza A/H1N1v infection increase with several risk factors (e.g. pregnancy, immunosuppression, obesity). Treatment decisions should not be delayed to await laboratory confirmation in these patients as early initiation of antiviral therapy is recommended. Elements of supportive care depend on the presentation of complications and secondary organ failure. If rapidly progressive lung dysfunction occurs, refractory to routine mechanical ventilation, early reporting to centers experienced in the use of extracorporeal membrane oxygenation (ECMO) should be established.

[Severe sepsis and disseminated intravascular coagulation. Supplementation with antithrombin]. / Schwere Sepsis und disseminierte intravasale Gerinnung. Substitution von Antithrombin.

Administration of high-dose antithrombin (AT) was investigated on a large collective of patients with severe sepsis in the KyberSept study. In the total study the administration of AT resulted in no significant reduction of the mortality rate in comparison to a placebo. However, in the protocol of this study subgroups were predefined, which when analyzed revealed that the group of patients who received AT but not simultaneously heparin did show a reduction of the mortality rate in comparison to the placebo group. The reduction of the absolute mortality rate of 15% reached statistical significance on day 90. Even patients classified as risk group grade II according to the Simplified Acute Physiology Score (SAPS), showed a significant reduction of the mortality rate of approximately 22% after 90 days without simultaneous administration of heparin. Such a positive result for administration of AT without simultaneous heparin treatment can also be found when severe sepsis complicated by disseminated intravascular coagulation (DIC) is present. Coagulation diagnostic assists the recognition of latent or fulminant DIC and also in surveillance of the course and development. The results of AT supplementation for severe sepsis and DIC are in agreement with earlier studies on smaller patient collectives and suggest that a randomized controlled clinical study should be carried out on a subcollective of severely ill patients.

Radioguided occult lesion localization (ROLL) for treatment and diagnosis of malignant and premalignant breast lesions combined with sentinel node biopsy: a prospective clinical trial with 100 patients.

UNLABELLED: Advanced breast cancer screening techniques and their availability increased the number of non-palpable breast lesions requiring surgery. Consequently reliable and efficient therapeutic management permitting accurate localization and removal of these occult lesions is essential. AIMS: In our study we evaluated radioguided occult lesion localization (ROLL) for effectiveness of localization, oncological safety and feasibility of concomitant sentinel node biopsy. METHODS: Hundred patients (120 lesions) underwent ROLL and tumour excision with or without sentinel node biopsy after confirmed histopathological findings via intra-tumoral injection of Tc99m-labelled macro-aggregate albumin for ROLL and Tc99m-labelled nanocolloids with periareolar-subdermal injection for simultaneous sentinel node biopsy. RESULTS: Our detection rate for ROLL was 98.3%, respectively, 98.6% for sentinel nodes in cases of concomitant sentinel node biopsy. We had a radical excision rate of 55 out of 69 cases of invasive ductal cancer and 17 out of 26 cases of DCIS to achieve 1mm, respectively, 10 mm tumour-free margins. CONCLUSIONS: Intra-tumoral tracer injection of for ROLL and periareolar-subdermal tracer injection for simultaneous sentinel node biopsy seem to be a sensitive technique. According to our results ROLL is a safe, precise and simple technique permitting definitive therapeutic removal of malignant or premalignant breast lesions. The high detection rate of the sentinel node in cases with concomitant sentinel node biopsy shows that the combination of both procedures is possible and safe. In our opinion ROLL is an excellent therapeutic option after histological confirmation of malignancy or premalignant disease.