Search Results (256)

Background: Consolidation therapy with durvalumab after definitive chemoradiotherapy (CRT) has become the standard care for patients with stage III non-small-cell lung cancer (NSCLC) following the PACIFIC trial. However, real-world data evaluating outcomes under routine clinical conditions remain limited, particularly in European cohorts. Methods: In this retrospective single-center study, we analyzed clinical data from 72 patients with stage III NSCLC treated with definitive CRT between 2017 and 2022. The patients were stratified by receipt of durvalumab consolidation. Univariable and multivariable Cox regression models were used to assess overall survival (OS) and progression-free survival (PFS). Stepwise variable selection based on the Akaike Information Criterion (AIC) was used to construct an optimized multivariable model. A sensitivity analysis with adjustment for treatment period (2017–2018 vs. 2019–2022) was conducted to account for the introduction of durvalumab into routine clinical practice. Results: Among 72 patients, 35 received durvalumab and 37 did not. The median OS was 2.08 years; the 3- and 5-year OS rates were 38.6% and 30.3%, respectively. Multivariable regression revealed significantly improved OS associated with Karnofsky performance status (KPS) > 80% (HR 0.29, p = 0.003), Charlson Comorbidity Index (CCI) ≤ 2 (HR 0.39, p = 0.009), and durvalumab treatment (HR 3.99, p = 0.008). PD-L1 expression ≥ 1% showed a trend toward improved OS (HR 3.72, p = 0.063). The median progression-free survival (PFS) for the total cohort was 1.17 years. The estimated 3- and 5-year PFS rates were 31.1% and 26.3%, respectively. Patients treated with durvalumab had a longer median PFS (20.5 months) compared to those without durvalumab (12.0 months). In the multivariable analysis, KPS > 80% (HR 0.29, p < 0.001), CCI ≤ 2 (HR 0.53, p = 0.048), and durvalumab treatment (HR 2.81, p = 0.023) were significantly associated with improved PFS. A sensitivity analysis adjusting for treatment period—reflecting the introduction of durvalumab into routine clinical practice from 2019—confirmed the robustness of these findings. Conclusions: Our findings support the clinical benefit of durvalumab consolidation following CRT in a real-world population, especially in patients with good performance status and low comorbidity burden. These results confirm and extend the PACIFIC trial findings into routine clinical practice, highlighting the prognostic value of functional status and comorbidity alongside PD-L1 expression. Full article

Biallelic pathogenic variants in DHCR7 result in decreased activity of 7-dehydrocholesterol (7-DHC) reductase, which converts 7-DHC to cholesterol, and causes Smith–Lemli–Opitz syndrome (SLOS). Elevated serum 7-DHC levels are indicative of SLOS as are intellectual disability (ID), growth retardation, microcephaly, craniofacial anomalies, and 2–3 toe syndactyly. Additional congenital malformations may be present in SLOS, and broad clinical variability has been recognized in SLOS. Rarely, biallelic pathogenic DHCR7 variants were reported with low-normal and normal intelligence quotient (IQ) and development. We report here a pair of siblings with mild global developmental delay, infrequent epileptic seizures, and elevated serum 7-DHC levels, associated with the homozygous DHCR7 variant c.988G>A (p.Val330Met). Remarkably, neither sibling displayed congenital anomalies nor dysmorphisms. Quattro-exome sequencing performed for global delay and mild ID in both siblings did not identify other ID causes. c.988G>A affects a highly conserved amino acid and displays a relatively high global population allele frequency of 0.04%, with absence of homozygotes from the population database gnomADv4.1.0. Our observation leads us to suggest that DHCR7 variant c.988G>A and other DHCR7 variants might be generally considered as underlying non-syndromic ID. Full article

Ants are key drivers of biodiversity in both tropical and temperate forests, though the underlying mechanisms of this remain debated. In tropical lowland rainforests, ants dominate the canopy as opportunistic predators, shaping arthropod abundance and community structure. By contrast, few arboreal ant species exist in temperate forests due to climatic constraints, and predation pressure is generally low. This changes when ground-nesting Formica species enter the canopy to forage. Using insecticidal knockdown, we collected arthropod communities from trees with high and low ant abundance in both tropical and temperate forests and in different seasons. We found consistently higher arthropod abundances on trees with strong ant dominance, including preferred prey taxa such as Diptera, Psocoptera, and Lepidoptera. In temperate forests, high arthropod densities may be driven by aphid-produced honeydew, whereas in tropical rainforests, the absence of large hemipteran aggregations suggests that other mechanisms are involved. Consequently, this mechanism fails to explain high arthropod abundance in tropical primary forests. In contrast, secondary tropical forests host structurally and compositionally altered ant communities, resulting in reduced predation pressure and a marked increase in the abundance of individual species, including potential pest species. These findings suggest that biodiversity maintenance in the canopy depends on intact, diverse ant communities. Recolonization from nearby primary forests is essential for recovery, yet even after five decades, secondary forests remain ecologically distinct, rendering full restoration to primary forest conditions unlikely within a management-relevant timeframe. Full article

Background: The project ‘Multicenter Renal Pharmacist Group—Implementation of Pharmaceutical Care for Patients with Renal Impairment at four Non-University Hospitals in Germany’ started in the beginning of 2020 with the goal to establish high-quality pharmaceutical care to improve patient safety for hospitalized patients with renal impairment at German non-university hospitals. Pharmaceutical service quality should be optimized by intense and effective intraprofessional collaboration within the network. Methods: Over a period of two years (2020–2022), we implemented renal pharmacists (RPs) for patients with renal impairment (RI) at four non-university hospitals in Germany (Starnberg Hospital, Rudolf Virchow Hospital Glauchau, Catholic Hospital in the Märkisch District (KKiMK), and Hospital Sindelfingen-Boeblingen). The RPs conducted medication analyses identifying renal-drug-related problems (rDRPs) two to five days a week. The rDRPs, including recommendations to solve them, were forwarded to the attending physicians via written consultations or personally during ward rounds. The RPs were mentored by a renal pharmacist expert from LMU Munich and formed a multicentered team with close collaboration. Data about the RP service were collected and were retrospectively evaluated. Results: During the two-year project period, a total of 3924 patients from various disciplines were visited across all four locations. In total, 1425 patients (36.3%; with a range from 22.7 to 56.4% between hospitals) received one or more interventions by RPs concerning 2454 rDRPs (a median of one to three rDRPs per patient). In cooperation with the physicians, 77.6 to 88.2% of the rDRPs were solved. The most common causes were ‘dosage too high’ and ‘contraindication’. Conclusion: The implementation of pharmaceutical care for patients with renal impairment at four non-university hospitals in Germany increased appropriate prescribing by physicians. The multicenter team proved to be an excellent support for the newly established services. Full article

Introduction: This study investigated the effectiveness of e-learning compared to traditional teaching methods in ultrasound education, centring on a focus cardiac ultrasound (FoCUS) course for third-year undergraduate medical students. With the rise of digital teaching methods, it is essential to evaluate their impact on the development of theoretical and practical skills in ultrasound training. Methods: A prospective, randomised, controlled trial was conducted involving two groups of students participating in a one-day FoCUS course delivered in a flipped classroom format. The study group used e-learning resources, while the control group used hard-copy lecture notes. Assessments were conducted at three stages: before the course, during the preparation phase, and after the course. Evaluations included self-assessment surveys, theory tests, and practical exams using direct observation of procedural skills (DOPS) tests. The study group had 15% less practice time compared to the control group. Results: A total of 109 complete datasets (study group, n = 52; control group, n = 57) were analysed. Both groups showed an equivalent initial level of and a continuous and significant (p < 0.01) increase in subjective and objective skills over the evaluated time frame. The study group achieved significantly (p = 0.03) higher results in DOPS (T2) than the control group. No significant differences were found in the total scores of the theory tests (T2 + T3) or DOPS (T3). Both groups rated their teaching materials, motivation, and the course concept in similarly high scale ranges. Conclusions: The findings suggest that e-learning is as effective as traditional methods in developing ultrasound skills and may serve as a viable alternative, even with reduced face-to-face interaction. These results indicate that accreditation processes could be applied similarly to those for traditional formats without requiring in-person training as a prerequisite for quality Full article

Background/Objectives: The aim of this study was to demonstrate the importance of ⁶⁸Gallium (⁶⁸Ga)–prostate specific membrane antigen (PSMA)–positron emissions tomography (PET)/computed tomography (CT)(PET/CT) in prostate cancer patients for therapy management with individual analyses regarding the Gleason score, prostate specific antigen (PSA) value, and the risk groups defined by D’Amico. Methods: We retrospectively analyzed 562 ⁶⁸Ga-PSMA-11-PET/CT examinations performed from January 2015 to March 2023 at University Hospital Marburg. We assessed treatment changes post ⁶⁸Ga-PSMA-11-PET/CT and categorized the cases based on PSA values, Gleason scores, and D’Amico risk groups. Results: In 415/562 (73.8%) of ⁶⁸Ga-PSMA-11-PET/CT examinations, a modification in the therapy concept was recorded. Patients categorized as high risk or patients with Gleason scores of 7 through 10 or with PSA levels above 0.5 ng/mL (particularly within the ranges of 1.01–2 ng/mL, 3.01–5 ng/mL, and values exceeding 10 ng/mL) demonstrated a statistically significant association with treatment change. While no evidence of the disease was found most frequently in 38% of cases in the “Therapy continued without explicit reference” group, in the group with the adapted therapy, there was a considerable higher proportion of local tumors (19.2%) compared to the other groups (4.4% and 1.4%). Conclusions: Our results show the high impact of ⁶⁸Ga-PSMA-PET/CT for patients with prostate cancer regarding therapy management planning, which is even more important for some patient groups. Full article

The use of inertial actuators to control the radiated sound pressure of a steel ship model at a lake measurement facility is examined. Therefore, methods of active vibration control as well as active control of target sound fields are applied using a fixed configuration of twelve accelerometers, eight control actuators, and five hydrophones. A narrowband feedforward active control system is used to manipulate the sound pressure at hydrophone positions, focusing not only on reducing but also on adding spectral lines in the radiated signature. The performance is assessed using measured data by additional accelerometers inside the ship model as well as by hydrophones surrounding the measurement facility. It is found that less control effort is necessary for the generation of additional tones compared to the control of a present disturbance at hydrophones. In the frequency range considered (below 500 Hz), the actively induced change in the mean structural velocity is not necessarily proportional to the change in the radiated sound pressure. In contrast to the vibration velocity, no unwanted amplification of the sound pressure is found for the frequencies observed. Full article

Background/Objectives: Acute obstructions of the upper respiratory tract are emergencies that may require a cricothyrotomy as ultima ratio. For this, precise identification of the conic ligament is essential. Point-of-care ultrasound (POCUS) offers a reliable tool for anatomical localization in challenging cases and could be used by a range of emergency medicine workers. This prospective, controlled observational study assesses the development of competencies of paramedics (PMs) in point-of-care ultrasound (POCUS) assisted identification of the conic ligament after structured training, and compares their competence level to emergency physicians (EPs). Methods: PMs and a control group of EPs received an identical structured training program as part of an ultrasound course. It included a 10-min theoretical introduction, a 10-min video, and a 45-min practical session with ultrasound devices. Questionnaires and a practical test assessed both group’s previous experiences, satisfaction with training, and the development of subjective and objective competencies before (T₁) and after (T₂) the training. Results: A total of 120 participants (N = 92 PMs and N = 28 EPs) participated. A minority had previously performed a cricothyrotomy even in training settings (PMs 17%; EPs 11%), and none had identified the conic ligament using POCUS. The study group’s subjective and objective competencies increased significantly (p < 0.001). At T2, the study group demonstrated comparable subjective (p = 0.22) and objective (p = 0.81) competencies to those of the control group. The study group needed significantly (p < 0.01) less time to perform the DOPS. While both groups were satisfied with the study material (PMs 2.2 ± 1.2 vs. Eps 1.6 ± 1.0; p = 0.02) and the training (PMs 1.8 ± 1.0 vs. EPs 1.4 ± 0.7, p = 0.03), the study group rated both significantly better. Conclusions: After structured training, paramedics successfully identified the conic ligament using POCUS comparably to emergency physicians. Integrating POCUS into paramedic training may improve prehospital airway management and enhance patient safety. Further studies should investigate long-term skill retention and real-life application. Full article

The electrochemical nitrogen reduction reaction (eNRR) for electrochemical ammonia (NH₃) synthesis is considered a promising alternative to the energy-intensive and highly CO₂-emitting Haber-Bosch process. In numerous experiments, the Nafion membrane has been used as an electrolyte or separator. However, Nafion adsorbs and desorbs NH₃, leading to erroneous measurements and making reproducibility extremely difficult. This study systematically investigates the interaction between NH₃ and Nafion, underscoring the strength of the interaction between ammonium-ions (NH₄⁺) and protons (H⁺). We found that minute quantities of synthesized NH₃ are prone to persist within the membrane, albeit without affecting the ion conductivity and resistivity of Nafion. Consequently, the removal of NH₃ from the membrane can occur under conditions where synthesis is not viable. The objective of this work is to heighten awareness regarding the interaction between NH₃ and Nafion and contribute to the attainment of reliable and reproducible outcomes in eNRRs. Full article

A comprehensive X-ray topography analysis of two selected aluminum nitride (AlN) bulk crystals is presented. We compare surface inspection X-ray topography in back-reflection geometry with high-energy transmission topography in the Lang and Laue configuration using the monochromatic K_α1 excitation wavelength of copper, silver, and tungsten, respectively. A detailed comparison of the results allows the assessment of both the high- and low-energy X-ray topography methods with respect to performance and structural information, giving essential feedback for crystal growth. This is demonstrated for two selected AlN freestanding faceted crystals up to 8 mm in thickness grown in all directions using the physical vapor transport (PVT) method. Structural defects of all facets of the crystals are determined using the X-ray topography in back-reflection geometry. The mean threading dislocation densities are 480 ± 30 cm⁻² for both crystals of either the Al- or N-face. Clustering of dislocations could be observed. The m-facets show the presence of basal plane dislocations and their accumulation as clusters. The integral transmission topographs of the $10\overline{1}0$ (m-plane) reflection family show that basal plane dislocations of the screw type in ${\displaystyle \frac{1}{3}}⟨\overline{1}2\overline{1}0⟩$ directions decorate threading dislocation clusters. Three-dimensional section transmission topography reveals that the basal plane dislocation clusters mainly originate at the seed boundary and propagate in the ${\displaystyle \frac{1}{3}}⟨\overline{1}2\overline{1}0⟩$ direction along the growth front. In newly laterally grown material, the Borrmann effect has been observed for the first time in PVT-grown bulk AlN, indicating very high structural perfection of the crystalline material in this region. This agrees with a low mean FWHM of 10.6 arcsec of the $10\overline{1}0$ reflection determined through focused high-energy Laue transmission mappings. The latter method also opens the analysis of the $∆2\theta$-shift correlated to the residual stress distribution inside the bulk crystal, which is dominated by dislocation clusters. Contrary to Lang transmission topography, the de-focused high-energy Laue transmission penetrates the 8 mm-thick crystal enabling a defect analysis in the bulk. Full article

Background/Objectives: The vast amount of research and data on periprosthetic joint infection (PJI) is focussed on infections in hip and knee replacements. This article aims to highlight the special features of PJI in shoulders. Methods: This narrative review is based on the recent and most relevant literature regarding PJI in general, and in shoulders in particular. Results: While the majority of findings for PJI in hips and knees can be transferred to infected shoulder arthroplasties, shoulder PJI represents a unique entity with a different microbial profile and its own diagnostic challenges. Conclusions: As profound evidence for shoulder PJI is lacking, diagnostic and therapeutic algorithms should be transferred from those for PJI in hips and knees. Further research is necessary to determine optimal management of shoulder PJI. Full article

The Active Radar Interferometer (AcRaIn) represents a novel approach in secondary radar technology, aimed at environments with high reflective clutter, such as pipes and tunnels. This study introduces a compact design minimizing peripheral components and leveraging commercial semiconductor technologies operating in the 24 GHz ISM band. A heterodyne principle was adopted to enhance unambiguity and phase coherence without requiring synchronization or separate communication channels. Experimental validation involved free-space and pipe measurements, demonstrating functionality over distances up to 150 m. The radar system effectively reduced interference and achieved high precision in both straight and bent pipe scenarios, with deviations below 1.25% compared to manual measurements. By processing signals at intermediate frequencies, advantages such as improved efficiency, isolation, and system flexibility were achieved. Notably, the integration of amplitude modulation suppressed passive clutter, enabling clearer signal differentiation. Key challenges identified include optimizing signal processing and addressing logarithmic signal attenuation for better precision. These findings underscore AcRaIn’s potential for pipeline monitoring and similar applications. Full article

Background: Differences in serum creatinine (SCr) between the Jaffe and enzymatic methods affect the detection and staging of chronic kidney disease in kidney transplant recipients (KTRs). However, there are very limited data on the extent to which the detection of acute kidney injury (AKI) is affected, what impact immunosuppression can have and whether a KTR-specific estimated glomerular filtration rate (eGFR) formula is beneficial. Methods: A total of 12,081 parallel Jaffe/enzymatic SCr (eSCr) measurements of adult outpatient KTRs (61% male, median age 53 years) in the same serum sample at the University Hospital Essen (Germany) between January 2020 and October 2023 were evaluated. AKI and CKD were defined according to current KDIGO guidelines. The GFR was estimated using CKD-EPI and KTR-specific formulas. Results: In about 1% of all measurements and 5% of the KTR patients, the SCr difference between the two methods was ≥ 0.3 mg/dl. A total of 81% of these patients were male; the median age was 52 years. High levels of immunosuppression, including when Belatacept was used, did not seem to have a clinically relevant impact on the difference between Jaffe and eSCr. The KTR-specific eGFR formula generally showed a greater agreement between Jaffe and eSCr than the CKD-EPI eGFR formula, but they showed differences in the classification of CKD stages, especially in less severe stages. Conclusions: Clinically relevant SCr differences between Jaffe and SCr are rare and depend on the type of immunosuppression. A KTR-specific eGFR formula could be beneficial in some cases, but there are limitations in less severe CKD stages. Full article

Endothelial dysfunction mediated by elevated levels of autoantibodies against vasoactive peptides occurring after COVID-19 infection is proposed as a possible pathomechanism for orthostatic intolerance in long COVID patients. This case-control study comprised 100 long COVID patients from our prospective POSTCOV registry and three control groups, each consisting of 20 individuals (Asymptomatic post-COVID group; Healthy group = pan-negative for antispike protein of SARS-CoV-2; Vaccinated healthy group = no history of COVID-19 and vaccinated). Autoantibodies towards muscarinic acetylcholine receptor M3, endothelin type A receptor (ETAR), beta-2 adrenergic receptor (Beta-2 AR), angiotensin II receptor 1 and angiotensin 1-7 (Ang1-7) concentrations were measured by enzyme-linked immunosorbent assay in long COVID patients and controls. Orthostatic intolerance was defined as inappropriate sinus tachycardia, postural tachycardia, orthostatic hypotonia and other dysautonomia symptoms, such as dizziness or blurred vision (n = 38 long COVID patients). Autoantibody concentrations were compared with routine laboratory parameters and quality of life questionnaires (EQ-5D). The concentration of ETAR autoantibodies were significantly higher in long COVID, Asymptomatic and Vaccinated groups compared to the antispike protein pan-negative Healthy group. A trend towards higher plasma levels of Beta-2 AR and Ang1-7 was measured in long COVID patients, not related to presence of orthostatic intolerance. ETAR autoantibody concentration showed significant positive correlation with the EQ-5D item “Problems in performing usual activities”. Full article

Objectives: The gold standard for electrocochleography (ECochG) is using dedicated recording devices for auditory evoked potentials. However, these have a very limited time window for recording. The aim of this study is to evaluate EEG amplifiers for ECochG, in particular for recording cochlear microphonics (CMs) without time restriction. Methods: Three high-resolution EEG amplifiers and different types of electrodes were analyzed and compared with a clinical system for recording auditory evoked potentials. For this, CMs were recorded after stimulation with various stimuli in a dummy and in human subjects. In the latter, recordings were made from the tympanic membrane and, during otosurgical procedures, from the promontory. Our evaluation focused on comparing signal amplifiers and electrode types, considering the signal-to-noise ratio, recording characteristics, and measurement reliability. Results: Using a dummy model, we observed significant differences among devices, electrode types, and stimulus frequencies. These findings were subsequently confirmed in human participant measurements. Nevertheless, EEG amplifiers proved to be feasible for ECochG recordings and offered a recording fidelity comparable to proprietary clinical methods. Importantly, with EEG amplifiers, we were able to record cochlear potentials in response to speech stimuli, revealing a strong correlation (r = 0.78) between recorded signals and the input stimulus. Conclusions: Our findings indicate that high resolution EEG amplifiers are suitable for recording cochlear potentials, in particular, CMs. This allows for evaluating cochlear signals in response to extended stimuli, in particular, speech stimuli. Full article