Granular bone substitute systems are widely used to treat complex and irregular defects due to their adaptability and prefabricated nature, which eliminates in situ setting-related instability. However, their limited mechanical stability makes their performance highly dependent on intraoperative handling and increases the risk of impaired tissue ingrowth.In this study, granular brushite- and monetite-based calcium phosphate cements (CPCs) were developed and systematically investigated to improve mechanical performance and cytocompatibility through a dual-setting approach. Silicate-based precursors, specifically tetraethyl orthosilicate (TEOS) and 1,8-bis(triethoxysilyl)octane (BTESO), were incorporated into the CPC formulation prior to granulation to establish a reinforcing secondary network within the cement matrix. Structural and mechanical properties were assessed, including compression-induced changes, which were analysed using micro-computed tomography (μCT). The biocompatibility of the CPCs was further investigated using WST assays, cell counting, DNA quantification, and scanning electron microscope with energy-dispersive X-ray spectroscopy (SEM-EDX).The incorporation of TEOS significantly increased mechanical stability and cytocompatibility compared to conventional formulations. TEOS-modified granules exhibited less than one-third of the compression-induced deformation observed for the control, which showed a height reduction of more than 5 mm. μCT analysis further revealed a shift in the intergranular pore-size peak from approximately 350 to 250 μm after compression in the control, whereas no apparent shift was observed for TEOS-modified granules. Granule size itself affected intergranular pore geometry, with larger granules showing higher metabolic activity. TEOS-modified granules showed the most favourable overall biological response, whereas the addition of BTESO provided no further mechanical or biological benefit. Furthermore, a cryosectioning approach enabled fluorescence imaging of osteoblast-like cells on CPCs with high autofluorescence, allowing visualisation of cell morphology on the material surface.Overall, the dual-setting approach, particularly using TEOS, improved resistance to compression while preserving intergranular pore architecture and maintaining favourable cytocompatibility, thereby addressing a key limitation of granular CPC-based bone substitute systems. In parallel, cryosectioning enables reliable fluorescence-based visualisation of cells on highly autofluorescent materials, offering a practical approach for the biological assessment of such systems.
Background Attention-deficit/hyperactivity disorder (ADHD) has been linked to obesity and type 2 diabetes, suggesting heightened cardiovascular risk. Whether adults with ADHD also show increased rates of metabolic syndrome (MetS), a cluster of central obesity, dyslipidemia, impaired glucose regulation, and hypertension, remains unclear. Methods We examined a young to middle-aged adult cohort of 83 patients and 82 healthy controls (HC). The primary objective was to test whether MetS (Joint Interim Statement criteria) was more prevalent in ADHD than in HC. To explore potential pathways linking ADHD with cardiovascular risk, we additionally assessed anthropometric indices, 24-h blood pressure (BP), heart rate (HR), and inflammatory markers (interleukin-6, C-reactive protein). Finally, we fitted a serial mediation model examining whether hyperactivity/impulsivity (HI), eating behavior, and body mass index (BMI) mediated the association between ADHD and BP. Results A higher proportion of ADHD patients fulfilled MetS criteria (OR 2.29). Adults with ADHD showed higher waist circumference, BMI, and overweight/obesity rates but did not differ in glucose and blood lipid levels. Non-stimulant medication and psychiatric comorbidity were more common among patients with MetS. Inflammatory markers were unrelated to ADHD. However, ADHD patients demonstrated slightly higher mean 24-h HR and nighttime systolic BP. The association between ADHD and nighttime systolic BP was mediated by obesity as a MetS constituent, and by HI and disordered eating as behavioral risk factors. Conclusion Young to middle-aged adults with ADHD displayed increased MetS prevalence and subtle elevations in nighttime BP and HR, suggesting an early cardiovascular risk trajectory. Behavioral factors, particularly overeating and weight gain, and psychiatric comorbidity appear to contribute to this risk. These findings support early cardiovascular screening and weight-management interventions in adults with ADHD.
Abstract Background As improvements in anti-cancer treatments have extended survival, patients with advanced cancer and their family caregivers face existential tension between engaging in life and coping with uncertainty about illness trajectory and the course of treatment. For a subgroup, this tension is associated with overwhelming fear and existential distress. Such adjustment difficulties may increase the risk of mental disorders, poor quality of life, and suicidality, and impair prognostic awareness and patient-clinician communication. Despite growing interest in open conversations about end-of-life issues, systematic evidence on effective psychotherapies to best support psychological adaptation in patients with high levels of existential distress is still scarce. We aim to evaluate the effectiveness of a short-term psychodynamic therapy (ORPHYS) to mitigate existential distress compared to usual psycho-oncological treatment (TAU). Methods We conduct a two-arm parallel randomized controlled trial with an active control group. ORPHYS is a manualized individual face-to-face psychotherapy focusing on emotional and relational conflicts specific to cancer patients’ illness situation. Treatment lasts between 5 and 11 months with 15 to 31 weekly sessions (50 min). TAU includes at least one individual session provided by physicians or psychologists with experience in psycho-oncological care. Patients will be assessed pre-intervention and 3, 6, 9, and 12 months after baseline. Target sample size is 160 randomized participants. We recruit patients with stage III/IV solid tumors or advanced hematological cancer and clinically significant existential distress from psycho-oncology clinics and referring oncologists at Hamburg, Düsseldorf, and Würzburg Comprehensive Cancer Centers, Germany. The primary outcome is demoralization (Demoralization Scale-II). Secondary outcomes include diagnoses of affective, anxiety and stress-related disorders, death anxiety, dignity-related distress, and quality of life. Outcome assessments are conducted via self-report questionnaires and diagnostic interviews. Linear mixed models examine outcome differences between trial arms. A confirmatory test of the group contrast at 6-month follow-up after baseline is conducted. Discussion Due to an aging population and prolonged survival, there is a growing demand to help patients deal with existential challenges undergoing palliative cancer care. The study will contribute to knowledge about how clinicians can best help patients with advanced cancer who substantially struggle with uncertainty at the end of life. Trial registration German Clinical Trials Registry, DRKS00038173. Registered October 20th, 2025, https://drks.de/search/en/trial/DRKS00038173 . ClinicalTrials.gov, NCT07312760. Registered December 30, 2025, https://clinicaltrials.gov/study/NCT07312760 .
Since the benefit of nirmatrelvir-ritonavir (N-R) may have changed in contemporary patients, we assessed the effectiveness of N-R for preventing hospitalization and death among outpatients with COVID-19 in the Omicron era. This was a meta-analysis of cohort studies comparing rates of hospitalization and/or mortality in outpatients treated with N-R compared with untreated patients. Analysis was limited to studies conducted since December 2021 that performed an adjusted multivariate analysis. Quality was assessed using the Newcastle-Ottawa Scale. Summary estimates of adjusted relative risks (aRR) with 95
BACKGROUND:We aimed to conduct an individual patient data meta-analysis on blood neurofilament light chain (NfL) in ischemic stroke (IS) to enhance its clinical applicability. METHODS:We performed a systematic literature search of studies on blood NfL measured in adult patients within 30 days after IS onset and derived age- and BMI-adjusted Z-scores based on a previously published reference population of healthy controls. We collected clinical, radiological and biochemical parameters of IS patients and tested associations of NfL at defined timepoints after IS onset (D1: < 24 h; D2: 24-48 h; D3: 48-72 h; D4-5: 72-120 h; D6-7: 120-168 h; D8-30: > 168 h) with baseline characteristics and 3-month follow-up outcomes (modified Rankin Scale, mRS; survival). RESULTS:We included 4081 blood NfL values from 2872 participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts. In patients with IS, NfL Z-score progressively increased from D1 [median: 2.0 (IQR: 0.9-2.9)] to D6-7 [median: 3.5 (IQR: 3.0-3.8)], with discriminative ability being high for IS vs. controls (AUC: 0.79-0.97) and fair for IS vs. TIA (AUC: 0.64-0.80). Higher NfL Z-score at D1 was associated with greater risk of symptomatic intracranial hemorrhage (aOR = 1.33, p = 0.014) and, from D2 onwards, with larger infarct lesion volume (highest Spearman's rho: 0.795 at D6-7). NfL independently predicted a mRS > 2 (aOR = 1.31, p < 0.001) and mortality (aOR = 1.67, p < 0.001) at 3 months. CONCLUSIONS:Blood NfL level was progressively elevated after IS, could discriminate IS from healthy controls with high accuracy and had prognostic value for intra-hospital complications and 3-month clinical outcomes in IS.
