Ureterorenoscopic Stone Removal without Antibiotic Prophylaxis.

INTRODUCTION: The aim of this study was to assess the feasibility of sparing routine antibiotic prophylaxis in patients without preoperative urinary tract infection undergoing ureterorenoscopy (URS) for stone removal. METHODS: A retrospective, monocentric study was conducted to evaluate the outcome of a modified perioperative antibiotic management strategy according to the principles of antibiotic stewardship. Patients with preoperative unremarkable urine culture received no antibiotic prophylaxis for URS stone removal (NoPAP). The NoPAP group was compared to a historic URS cohort, when antibiotic prophylaxis (PAP) was standard of care. Analysis focused on postoperative complications. RESULTS: Postoperative fever occurred in 1% of the NoPAP and 2% of the PAP patients (p = 0.589). Clavien 1-3 complications did not differ between groups with 9% in the NoPAP and 6.2% in the PAP (p = 0.159). No Clavien 4-5 complications were seen. We identified a residual stone (p = 0.033) and an ASA score 3-4 (p = 0.004) as significant risk factors for postoperative fever. By sparing routine antibiotic prophylaxis, the overall antibiotic usage was reduced from 100% (PAP) to 8.3% (NoPAP). CONCLUSION: Sparing a routine antibiotic prophylaxis during URS for stone removal seems feasible in patients with unremarkable preoperative urine culture for most of the patients. A prospective validation is warranted.

pH-dependent structural transitions in cationic ionizable lipid mesophases are critical for lipid nanoparticle function.

Lipid nanoparticles (LNPs) are advanced core-shell particles for messenger RNA (mRNA) based therapies that are made of polyethylene glycol (PEG) lipid, distearoylphosphatidylcholine (DSPC), cationic ionizable lipid (CIL), cholesterol (chol), and mRNA. Yet the mechanism of pH-dependent response that is believed to cause endosomal release of LNPs is not well understood. Here, we show that eGFP (enhanced green fluorescent protein) protein expression in the mouse liver mediated by the ionizable lipids DLin-MC3-DMA (MC3), DLin-KC2-DMA (KC2), and DLinDMA (DD) ranks MC3 ≥ KC2 > DD despite similar delivery of mRNA per cell in all cell fractions isolated. We hypothesize that the three CIL-LNPs react differently to pH changes and hence study the structure of CIL/chol bulk phases in water. Using synchrotron X-ray scattering a sequence of ordered CIL/chol mesophases with lowering pH values are observed. These phases show isotropic inverse micellar, cubic Fd3m inverse micellar, inverse hexagonal [Formula: see text] and bicontinuous cubic Pn3m symmetry. If polyadenylic acid, as mRNA surrogate, is added to CIL/chol, excess lipid coexists with a condensed nucleic acid lipid [Formula: see text] phase. The next-neighbor distance in the excess phase shows a discontinuity at the Fd3m inverse micellar to inverse hexagonal [Formula: see text] transition occurring at pH 6 with distinctly larger spacing and hydration for DD vs. MC3 and KC2. In mRNA LNPs, DD showed larger internal spacing, as well as retarded onset and reduced level of DD-LNP-mediated eGFP expression in vitro compared to MC3 and KC2. Our data suggest that the pH-driven Fd3m-[Formula: see text] transition in bulk phases is a hallmark of CIL-specific differences in mRNA LNP efficacy.

Combining molecular dynamics simulations and x-ray scattering techniques for the accurate treatment of protonation degree and packing of ionizable lipids in monolayers.

The pH-dependent change in protonation of ionizable lipids is crucial for the success of lipid-based nanoparticles as mRNA delivery systems. Despite their widespread application in vaccines, the structural changes upon acidification are not well understood. Molecular dynamics simulations support structure prediction but require an a priori knowledge of the lipid packing and protonation degree. The presetting of the protonation degree is a challenging task in the case of ionizable lipids since it depends on pH and on the local lipid environment and often lacks experimental validation. Here, we introduce a methodology of combining all-atom molecular dynamics simulations with experimental total-reflection x-ray fluorescence and scattering measurements for the ionizable lipid Dlin-MC3-DMA (MC3) in POPC monolayers. This joint approach allows us to simultaneously determine the lipid packing and the protonation degree of MC3. The consistent parameterization is expected to be useful for further predictive modeling of the action of MC3-based lipid nanoparticles.

Association between the Ile164 ß2 Adrenergic Receptor Polymorphism and Fatigue in Patients with Rheumatoid Arthritis.

INTRODUCTION: In the present work, the frequency of inherited polymorphisms of the beta 2 adrenergic receptor (ß2AR) gene and their association with fatigue in patients with rheumatoid arthritis (RA) was examined. METHODS: An allele-specific polymerase chain reaction was used to determine the common variants of the ß2AR at position 16, 27, and 164 in 92 German RA outpatients. Health Assessment Questionnaire (HAQ-DI), Beck Depression Inventory (BDI), Perceived Stress Questionnaire (PSQ-30), Multidimensional Fatigue Inventory (MFI-20) were utilized. RESULTS: 34.7% of German RA patients were diagnosed with associated fatigue. Fatigued patients were more likely to carry the Ile allele at position 164 (OR 7.33, 95% CI 1.09-59.8, p = 0.049). Comparing these risk factors' contribution to different fatigue dimensions revealed that Ile164 carriers only had significantly higher MFI-20 mean values for general fatigue (p = 0.014) while the clinical difference among other MFI subscales was the largest for mental fatigue (carrier: 8.23, SD: 4.22, noncarrier: 5.67, SD: 1.56, p = 0.089, Cohen's d = 0.629). Disease activity, perceived stress, and depression were also associated with fatigue with higher mean values for DAS28CRP (p = 0.038), PSQ (p < 0.001), and BDI-II (p < 0.001) in fatigued patients. Physical fatigue was correlated with disease activity (p = 0.009) and depression (p = 0.001) while mental fatigue showed associations with depression (p = 0.001) and perceived stress (p = 0.028). CONCLUSION: The discovery study indicates that the Ile164 polymorphism might in contrast to other ß2AR polymorphisms affect fatigue levels in RA patients. This association was observed especially with mental fatigue. Further replication studies are warranted to determine further role of ß2AR polymorphisms in RA patients.

3D-printed SAXS chamber for controlled in situ dialysis and optical characterization.

3D printing changes the scope of how samples can be mounted for small-angle X-ray scattering (SAXS). In this paper a 3D-printed X-ray chamber, which allows for in situ exchange of buffer and in situ optical transmission spectroscopy, is presented. The chamber is made of cyclic olefin copolymers (COC), including COC X-ray windows providing ultra-low SAXS background. The design integrates a membrane insert for in situ dialysis of the 100 µl sample volume against a reservoir, which enables measurements of the same sample under multiple conditions using an in-house X-ray setup equipped with a 17.4 keV molybdenum source. The design's capabilities are demonstrated by measuring reversible structural changes in lipid and polymer systems as a function of salt concentration and pH. In the same chambers optical light transmission spectroscopy was carried out measuring the optical turbidity of the mesophases and local pH values using pH-responsive dyes. Microfluidic exchange and optical spectroscopy combined with in situ X-ray scattering enables vast applications for the study of responsive materials.

Development of a Novel Adapter to Enable Less-Invasive Left Ventricular Assist Device Implantation via the Left Ventricular Apex.

The first prototype of an adapter to enable left ventricular assist device (LVAD) implantation solely via the left ventricular (LV) apex and without requiring cardiopulmonary bypass (CPB) was tested in healthy and acutely failing pig hearts. The adapter consists of a fixation, blood guiding, and connecting module fitting to a HeartMate 3 (HM3; Abbott, Chicago, IL) pump. Implantation was performed via a left thoracotomy in five pigs (96 ± 18 kg). Invasive blood pressure was measured before (CTRL), 30 minutes after HM3 initiation (HM3_CTRL), during acute heart failure (HF) induced by rapid pacing (CTRL_HF), and 5 minutes after initiating HM3 support (HM3_HF). To further estimate the LVAD performance, blood pressure amplitudes were calculated in the healthy heart without (CTRL) and with HM3 support (HM3_CTRL) as: systolic-diastolic blood pressure. Our adapter implantation and connection to the HM3 pump succeeded in all animals. Compared to the normal beating healthy heart, blood pressure amplitudes were significantly smaller during HM3 support (CTRL: 41 ± 5 mm Hg vs. HM3_CTRL: 20 ± 4 mm Hg; p < 0.05). Under HF conditions, mean blood pressure returned to normal values after pump initiation (CTRL_HF: 29 ± 6 mm Hg, HM3_HF: 83 ± 24 mm Hg). The adapter prototype allowed safe, straightforward, and less-invasive LVAD implantation solely via the LV apex without using CPB and support of the LV during acute HF in the pig heart.

Geriatric Patients and Symptomatic Urinary Tract Infections: Analysis of Bacterial Range and Resistance Rates at a 3rd Level of Care Hospital in Germany.

BACKGROUND: Increasing life expectancy and demographic change result in a rising number of geriatric patients, but knowledge about geriatric treatment options and adapted diagnostic pathways is low. Simultaneously, urinary tract infections (UTIs) are common in older people and often difficult to treat. METHODS: Patients with a UTI at a urological outpatient department between January 01, 2016, and December 31, 2017, were retrospectively identified in the data system. One thousand one hundred fifteen patients with "N30" and "N39" diagnosis were included in this study, 965 of which were under the age of 75 (group 1) and 150 of which 75 years or older (group 2). RESULTS: Of 150 patients in group 2, 41.6% had nitrite-positive urine (vs. 20.9% in group 1, p < 0.05 in χ2 testing). Patients in group 2 often had indwelling devices (30.3 vs. 6.0%, p < 0.05) and presented a sterile urine culture in only 20.7% (vs. 40.1% in group 1). Regarding calculated antibiotic therapy, there were significant differences concerning prescription of ciprofloxacin (34.9 vs. 25%, p < 0.05) and fosfomycin (12.7 vs. 40.7%, p < 0.05). CONCLUSION: UTI in geriatric patients should be treated differently than in younger patients because antibiotic resistance is high. The group with indwelling devices is complex. Individual strategies for geriatric patients should be considered.

The power of shared positivity: organizational psychological capital and firm performance during exogenous crises.

This study examines the influence of organizational psychological capital on the performance of small and medium-sized companies (SMEs) during crises. We argue that SMEs use their intangible resources to cope with difficult situations such as the COVID-19 pandemic. Therefore, we investigate how organizational psychological capital impacts performance and creative innovation through such intangible resources, namely, organizational citizenship behavior, solidarity, and cooperation. Methodologically, we combine structural equation modelling and regression analysis on a dataset of 379 SMEs. Our results support the notion that organizational psychological capital positively influences creative innovation of SMEs and thus performance during crises. Our research contributes to the organizational behavior literature by showing that psychological resources of SMEs can strengthen performance in times of crisis and help to prepare for future ones.

Increased Severe Adverse Outcomes and Decreased Emergency Room Visits for Pyelonephritis: First Report of Collateral Damage during COVID-19 Pandemic in Urology.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic is disrupting urology health-care worldwide. Reduced emergency room visits resulting in adverse outcomes have most recently been reported in pediatrics and cardiology. We aimed to compare patients with emergency room visits for pyelonephritis in 2019 (pre-COVID-19 era) and within the first wave of pandemic in 2020 (COVID-19 era) with regard to the number of visits and severe adverse disease outcomes. METHODS: We performed a retrospective multicentre study comparing characteristics and outcomes of patients with pyelonephritis, excluding patients with hydronephrosis due to stone disease, in 10 urology departments in Germany during a 1-month time frame in March and April in each 2019 and 2020. RESULTS: The number of emergency room visits for pyelonephritis in the COVID-19 era was lower (44 patients, 37.0%) than in the pre-COVID-19 era (76 patients, 63.0%), reduction rate: 42.1% (p = 0.003). Severe adverse disease outcome was more frequent in the COVID-19 era (9/44 patients, 20.5%) than in the pre-COVID-19 era (5/76 patients, 6.6%, p = 0.046). In detail, 7 versus 3 patients needed monitoring (15.9 vs. 3.9%), 2 versus no patients needed intensive-care treatment (4.5 vs. 0%), 2 versus no patients needed drain placement (4.5 vs. 0%), 2 versus no patients had a nephrectomy (4.5 vs. 0%), and 2 versus 1 patient died (4.5 vs. 1.3%). CONCLUSION: This report of collateral damage during CO-VID-19 showed that emergency room visits were decreased, and severe adverse disease outcomes were increased for patients with pyelonephritis in the COVID-19 era. Health authorities should set up information campaign programs actively encouraging patients to utilize emergency room services in case of severe symptoms specifically during the actual second wave of pandemic.

Impact of E-Cadherin and ß-Catenin as Prognostic Factor in Renal Cell Carcinoma with Tumor Thrombus of the Vena Cava.

PURPOSE: Renal cell carcinoma (RCC) forming tumor thrombus (TT) of vena cava (VC) is characterized by poor prognosis. Nevertheless, the outcome of patients after radical surgery varies. To date only limited data concerning prognostic biomarkers in this RCC subgroup are available. METHODS: Out of 159 patients with pT3b/c RCC, 95 patients without synchronous distant metastases at time of diagnosis were included in the study cohort. After immunohistochemical (IHC) evaluation of E-cadherin and ß-Catenin expression, association with clinical, histopathological and survival was assessed by univariate analysis, multivariate analysis, and Kaplan-Meier-analysis. Cancer-specific survival (CSS) rates and overall survival (OS) rates were estimated using Kaplan-Meier analysis and compared using Log rank test. RESULTS: We found a significant correlation between E-cadherin overexpression and initial lymph node metastasis (ρ = 0.300, p = 0.003), positive surgical margins (ρ = 0.210, p = 0.043), and the development of distant metastases (ρ = 0.258, p = 0.012). Furthermore, we observed a significant correlation of ß-Catenin overexpression with higher tumor stage pT3c (ρ = 0.230, p = 0.028) and initial lymph node metastases (ρ = 0.236, p = 0.025). Survival analysis revealed a statistically significant association of both E-cadherin and ß-Catenin overexpression with worse CSS (p < 0.001 and p = 0.007, respectively) and OS (p < 0.001 and p = 0.041, respectively). Multivariate analysis revealed initial lymph node metastasis as the only predictive factor for worse OS (HR 4.54, 95% CI 2.30-8.93; p < 0.001). E-Cadherin and ß-Catenin expression failed to be significant in multivariable analysis for OS and CSS. CONCLUSIONS: In a large series of RCC with TT of VC high IHC expression of E-cadherin and ß-Catenin was associated with initial lymph node metastasis and with both worse OS and worse CSS. This might help to identify patients at risk for recurrence who might benefit from adjuvant therapy or stricter follow-up.

Influence of Gender and Age on the Willingness to Reduce Nicotine Consumption-Results of a Survey in Urological Cancer Patients (KRAUT Study).

PURPOSE: Our objective was to investigate whether patients with urologic tumors were aware of smoking as a risk factor for the development and progression of several urologic cancers and the extent of the medical education they had received. Another aim was to investigate whether gender or age influenced patients' willingness to change their smoking habits. MATERIALS AND METHODS: Patients with histologically malignant urologic tumors were enrolled in our questionnaire-based study from September 2013 to December 2014 in 2 urology departments. Patients were asked about their smoking habits and their general understanding of the relationship between smoking and the onset of cancer (urologic cancer and lung cancer). Also, the extent of information they had acquired from a physician was assessed. The descriptive and oncologic data of the patients were recorded. RESULTS: Of 258 enrolled patients, 186 (72.1%) had never had an informational discussion with a doctor about smoking and their urologic tumor disease. Of the 160 active and former smokers, only 45 (28.1%) were planning to stop or reduce smoking because of their tumor disease. The willingness to change smoking habits was greater for women, with a statistically significant difference (odds ratio, 5.59; P = .002). Younger patients aged <58 years were also more willing to reduce or stop smoking. CONCLUSION: In our study, most patients with urologic cancer were unaware of smoking as the most probable cause of tumor development. The patients had not received proper counseling from doctors on smoking and the risk it poses for tumor progression. Efforts to balance compliance among the genders and age groups through risk-adapted counseling should be undertaken.

Recording electric potentials from single adherent cells with 3D microelectrode arrays after local electroporation.

This short communication reports on the innovative method of the local micro-invasive needle electroporation (LOMINE) of single adherent cells. The investigation of cellular reactions in living cell cultures represents a fundamental method, e.g. for drug development and environmental monitoring. Existing classical methods for intracellular measurements using, e.g. patch clamp techniques are time-consuming and complex. Present patch-on-chip systems are limited to the investigation of single cells in suspension. Nevertheless, the most part of the cells of the human body is adherently growing. Therefore, we develop a new chip system for the growth of adherent cells with 64 micro-structured needle electrodes as well as 128 dielectrophoretic electrodes, located within a measuring area of 1 mm(2). With this analytical chip, the intracellular investigation of electro-chemical changes and processes in adherently growing cells will become possible in the near future. Here, we present first intracellular measurements with this chip system.

A three-day anatomy revision course taught by senior peers effectively prepares junior students for their national anatomy exam.

OBJECTIVES: this study examines whether peer-teaching, in the setting of a three-day revision course in anatomy, is effective in preparing medical students for their national anatomy exam. METHODS: the anatomy course was designed for candidates taking the first part of the German national medical exam. Increase of knowledge during the course was assessed by tests before and after the course (group A). To test equivalence, two control groups participated in the pre-test (group B) or in the course and in the post-test (group C). Participants anonymously rated 14 feedback items on a five-point Likert scale ranging from 1 (full agreement) to 5 (full disagreement). RESULTS: group A students' performance improved significantly during the course with a mean increase of 7.15 points (11.9% improvement; p<0.001). Equivalence testing showed that performance of group A students in the pre-/post-tests was equal to those of group B pre-tests and group C post-tests, respectively. Agreement on the 14 feedback items was highly significant (p<0.001 for all items), with a global median of 1. CONCLUSIONS: this study shows that a three-day anatomy revision course is effective and highly appreciated by medical students in their preparation for the national exam. Moreover, peer-teaching is reliable at this stage of the medical curriculum.

Modular glass chip system measuring the electric activity and adhesion of neuronal cells--application and drug testing with sodium valproic acid.

We developed a modular neurochip system by combining a small (16x16 mm2) glass neurochip (GNC) with a homemade head stage and commercial data acquisition hardware and software. The system is designed for the detection of the electric activity of cultivated nerve or muscle cells by a 52-microelectrode array (MEA). In parallel, cell adhesion can be registered from the electric impedance of an interdigitated electrode structure (IDES). The GNC was tested with various cell lines and primary cells. It is fully autoclavable and re-useable. Murine embryonic primary cells were used as a model system to correlate the electric activity and adhesion of neuronal networks in a drug test with sodium valproic acid. The test showed the advantage of the parallel IDES and MEA measurements, i.e. the parallel detection of cytotoxic and neurotoxic effects. Toxic exposure of the cells during neuronal network formation allows for the characterization of developmental neurotoxic effects even at drug concentrations below the EC50-value for acute neurotoxic effects. At high drug concentrations, the degree of cytotoxic damage can still be assessed from the IDES data in the event that no electric activity develops. The GNC provides optimal cell culture conditions for up to months in combination with full microscopic observability. The 4'' glass wafer technology allows for a high precision of the GNC structures and an economic production of our new system that can be applied in general and developmental toxicity tests as well as in the search for neuro-active compounds.