Evaluation of therapy support through a standardized nursing consultation for patients undergoing oral tumor therapy in gynecological oncology within the prospective CAMPA initiative

Purpose The increase of oral tumor therapies (OTT) poses new challenges in patient care. Within CAMPA (Care improvement for advanced or metastatic breast and ovarian cancer patients treated with PARP-inhibitors), additional nursing support for patients treated with PARP-inhibitors was developed. Methods Additional nursing support (1 year) was evaluated in breast and gynecooncological cancer patients at an academic and a non-academic outreach center. From 02/22 to 02/24, quality of life, contacts, adherence, documentation of drug intake, hospitalization, and adverse events were evaluated, using CANKADO-ePRO and validated questionnaires reviewed by the Ethics Committee of Medical Faculty, LMU Munich. Satisfaction with care was recorded from 03/23 to 02/24. Supporting materials and interprofessional checklists were explored. Results The collective (n = 50) included 41 patients with ovarian, 4 with fallopian tube and 5 with breast cancer. Adherence measured by continuous documentation of medication intake was high among patients (78.0%). Quality of life improved from 68.6% to 81.4%, strongly correlating with decreasing numbers of side effects (p = 0.003) (Spearman |ρ| = 0.93). Satisfaction with care was very high (4.97 out of 5 points). 94.6% agreed that nursing consultation was essential for therapy safety compared to the doctor's consultation alone (p < 0.05). The reduction in time and care effort was significant (p < 0.05), having its maximum within the first three months. Conclusion Standardized nursing consultation was highly appreciated with an important contribution to adherence and improvement in quality of life. Delegation of therapy management to nurses reduces time effort and increases their responsibility, improving interprofessional care at academic and non-academic institutions. Trial registration Clinical Trials Registry, LMU university hospital, Germany, Healthcare research project, number: 21–0848

Pragmatic algorithm for visual assessment of 4-Repeat tauopathies in [18F]PI-2620 PET Scans

Aim : Standardized evaluation of [18F]PI-2620 tau-PET scans in 4R-tauopathies represents an unmet need in clinical practice. This study aims to investigate the effectiveness of visual evaluation of [18F]PI-2620 images for diagnosing 4R-tauopathies and to develop a straight-forward reading algorithm to improve objectivity and data reproducibility. Methods : A total of 83 individuals with [18F]PI-2620 PET scans were included. Participants were classified as probable 4R-tauopathies (n = 29), Alzheimer's disease (AD) (n = 20), α-synucleinopathies (n = 15), and healthy controls (n = 19) based on clinical criteria. Visual assessment of tau-PET scans (choice: 4R-tauopathy, AD-tauopathy, no-tauopathy) was conducted using either 20–40-minute or 40–60-minute intervals, with raw (common) and cerebellar grey matter scaled standardized reading settings (intensity-scaled). Two readers evaluated scans independently and blinded, with a third reader providing consensus in case of discrepant primary evaluation. A regional analysis was performed using the cortex, basal ganglia, midbrain, and dentate nucleus. Sensitivity, specificity, and interrater agreement were calculated for all settings and compared against the visual reads of parametric images (0–60-minutes, distribution volume ratios, DVR). Results : Patients with 4R-tauopathies in contrast to non-4R-tauopathies were detected at higher sensitivity in the 20–40-minute frame (common: 79%, scaled: 76%) compared to the 40–60-minute frame (common: 55%, scaled: 62%), albeit with reduced specificity in the common setting (20–40-min: 78%, 40–60-min: 95%), which was ameliorated in the intensity-scaled setting (20–40-min: 91%, 40–60-min: 96%). Combined assessment of multiple brain regions did not significantly improve diagnostic sensitivity, compared to assessing the basal ganglia alone (76% each). Evaluation of intensity-scaled parametric images resulted in higher sensitivity compared to intensity-scaled static scans (86% vs. 76%) at similar specificity (89% vs. 91%). Conclusion : Visual reading of [18F]PI-2620 tau-PET scans demonstrated reliable detection of 4R-tauopathies, particularly when standardized processing methods and early imaging windows were employed. Parametric images should be preferred for visual assessment of 4R-tauopathies

Human Footprint and Forest Disturbance Reduce Space Use of Brown Bears (Ursus arctos) Across Europe

Three-quarters of the planet's land surface has been altered by humans, with consequences for animal ecology, movements and related ecosystem functioning. Species often occupy wide geographical ranges with contrasting human disturbance and environmental conditions, yet, limited data availability across species' ranges has constrained our understanding of how human pressure and resource availability jointly shape intraspecific variation of animal space use. Leveraging a unique dataset of 758 annual GPS movement trajectories from 375 brown bears (Ursus arctos) across the species' range in Europe, we investigated the effects of human pressure (i.e., human footprint index), resource availability and predictability, forest cover and disturbance, and area-based conservation measures on brown bear space use. We quantified space use at different spatiotemporal scales during the growing season (May–September): home range size; representing general space requirements, 10-day long-distance displacement distances, and routine 1-day displacement distances. We found large intraspecific variation in brown bear space use across all scales, which was profoundly affected by human footprint index, vegetation productivity, and recent forest disturbances creating opportunity for resource pulses. Bears occupied smaller home ranges and moved less in more anthropized landscapes and in areas with higher resource availability and predictability. Forest disturbances reduced space use while contiguous forest cover promoted longer daily movements. The amount of strictly protected and roadless areas within bear home ranges was too small to affect space use. Anthropized landscapes may hinder the expansion of small and isolated populations, such as the Apennine and Pyrenean, and obstruct population connectivity, for example between the Dinaric Pindos population and the Alpine or Carpathian population. Our findings call for actions to maintain bear movements across landscapes with high human footprint, for example by maintaining forest integrity, to support viable bear populations and their ecosystem functions

Line‐field confocal optical coherence tomography in lichen planopilaris and frontal fibrosing alopecia: A pilot study

Background and Objectives: Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are common causes of cicatricial alopecia. While several studies have demonstrated the usefulness of non-invasive imaging methods such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) for the diagnosis of scarring alopecia, this study aimed to identify characteristic features of cicatricial alopecia in LPP/FFA using line-field confocal OCT (LC-OCT). Patients and Methods: Fifty-one patients (26 LPP, 24 FFA, 1 LPP and FFA) were prospectively analyzed with LC-OCT at three defined locations on the scalp: (1) scarring area = lesion, (2) scar-hair boundary = transition zone and (3) healthy area for the presence of the following pre-defined criteria: no hair follicles left, destructed hair follicles, dermal sclerosis, no rimming of the dermal papillae, epidermal and dermal inflammatory infiltrate, infundibular hyperkeratosis, dilated blood vessels, hypervascularization, melanophages, epidermal pigment incontinence. Results: Comparison of the transition zone with healthy control sites revealed the four main LC-OCT features in LPP/FFA: dermal sclerosis (100%), dermal inflammatory infiltrate (90.2%), infundibular hyperkeratosis (60.8%) and hypervascularization (76.5%). Conclusions: LC-OCT detects specific criteria of pathological changes in LPP/FFA around hair follicles in the epidermis and dermis and therefore can be used for further studies investigating scarring alopecia

Dependence of mitochondrial calcium signalling and dynamics on the disaggregase, CLPB

Cells utilize protein disaggregases to avoid abnormal protein aggregation that causes many diseases. Among these, caseinolytic peptidase B protein homolog (CLPB) is localized in the mitochondrial intermembrane space and linked to human disease. Upon CLPB loss, MICU1 and MICU2, regulators of the mitochondrial calcium uniporter complex (mtCU), and OPA1, a main mediator of mitochondrial fusion, become insoluble but the functional outcome remains unclear. In this work we demonstrate that CLPB is required to maintain mitochondrial calcium signalling and fusion dynamics. CLPB loss results in altered mtCU composition, interfering with mitochondrial calcium uptake independently of cytosolic calcium and mitochondrial membrane potential. Additionally, OPA1 decreases, and aggregation occurs, accompanied by mitochondrial fragmentation. Disease-associated mutations in the CLPB gene present in skin fibroblasts from patients also display mitochondrial calcium and structural changes. Thus, mtCU and fusion activity are dependent on CLPB, and their impairments might contribute to the disease caused by CLPB variants

Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits

The legalization of cannabis for medical and recreational purposes has progressed internationally. Cannabis and cannabinoids are advocated for a plethora of medical indications. An increasing number of medical and nonmedical users regularly consume large doses of delta-9-Tetrahydrocannabinol (THC), the main active component of cannabis. Aim: to summarize the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Chronic patterns of cannabis use have been associated with multiple adverse outcomes that are of particular concern among adolescents and young adults, such as, disrupted learning, impaired cognitive performance, reduced educational attainment and an increased risk of CUD, psychosis/schizophrenia, mood and anxiety disorders and suicidal behaviors. There is debate about the extent to which cannabis use is a cause of these adverse outcomes. Physical health risks (e.g., respiratory and cardiovascular, prematurity and restricted fetal growth, hyperemesis syndrome among others) have also been linked with repeated consumption of cannabis with a high THC content. Findings on medical cannabis use: Herbal cannabis, medicines from extracted or synthetized cannabinoids—often used as adjuvants to standard medicines—may produce small to modest benefits. This is primarily the case in treating chronic pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and refractory epilepsy (in the case of cannabidiol, CBD). The evidence is inconclusive on their value in treating mental disorders and other medical conditions. Safety: Cannabis-based medicine is generally well tolerated. There is a risk of mild to moderate adverse effects and CUD