Baveno VII was introduced to help identify patients with compensated advanced chronic liver disease (ACLD) who should undergo screening gastroscopy to detect varices needing treatment (VNT), with a positive predictive value exceeding 90%. We performed a study at our centre to evaluate the impact of implementing this strategy, which has the potential to lower both healthcare costs and the risks associated with invasive procedures. We carried out a retrospective, single-centre analysis between 2021 and 2024, reviewing screening gastroscopies for oesophageal varices. Data reviewed included gastroscopy findings, transient elastography (TE) results performed within the preceding six months, and platelet count. The underlying cause of liver disease was also recorded. The primary aim was to evaluate the real-world application of the Baveno VII recommendations and estimate their impact on screening endoscopy utilisation and associated healthcare costs. We reviewed a total of 592 gastroscopies performed for variceal screening. Fifty-four patients were eligible for analysis after exclusion criteria were applied. Twenty-one of 54 patients (38.8%) did not meet the criteria for variceal surveillance. Notably, five out of these 21 patients (23.8%) were found to have VNT. Among the 33 patients who did meet the screening criteria, the positive predictive value for detecting VNT was 48.5% in our cohort. Applying the Baveno VII criteria would have excluded 16 patients who ultimately did not have VNT, potentiating cost savings of 29,120 Australian dollars (AUD). Application of the Baveno VII criteria in our cohort could have reduced unnecessary screening gastroscopies, resulting in cost savings and reduced procedural risk to patients. Although a small number of patients outside the screening criteria were found to have varices needing treatment, these findings should be interpreted in the context of the study's retrospective design, single-centre setting, and limited sample size. Nevertheless, this study provides a real-world example of the potential for Baveno VII-guided screening to reduce healthcare utilisation, costs, and patient exposure to invasive procedures.
Critically ill patients requiring treatment in the intensive care unit (ICU) suffer from muscle weakness that persists for years. As compared with healthy subjects, skeletal muscle of patients biopsied five years post-ICU revealed an abnormal transcriptome partially associated with poor muscle strength. We now hypothesized that skeletal muscle of long-term ICU survivors is "epigenetically aged", as determined by a muscle-specific epigenetic clock, and that such accelerated epigenetic aging contributes to their long-term muscle weakness. Muscle DNA-methylation data from former ICU patients at 5-year follow-up (N = 118) and healthy controls (N = 160), aged 18-89 years, were analyzed by the MEATv2 epigenetic clock. First, epigenetic age (DNAmAge), epigenetic minus chronological age (AADiff) and epigenetic age acceleration (AAResid) were compared between 97 former patients and 97 controls, propensity score-matched for age and sex. Next, the impact of any muscle-specific epigenetic aging of ICU survivors was investigated, via multivariable models, as a potential contributor to the altered transcriptome and reduced muscle strength. Former ICU patients showed a significantly higher muscle DNAmAge, AADiff, and AAResid than matched controls. In adjusted models, higher muscle DNAmAge, AADiff, or AAResid did not substantially contribute to differentially expressed muscle RNAs in former patients as compared with controls and was not associated with the poor long-term muscle strength. In conclusion, five years after ICU discharge, former patients showed accelerated epigenetic aging in skeletal muscle. However, the muscle-specific epigenetic clock did not capture molecular changes that are associated with long-term muscle weakness, which highlights the need for other muscle-specific biological predictors of age-related physical impairment. Trail Registration: ClinicalTrials.gov: NCT00512122.
Background Early inflammatory and fibrotic responses play important roles in tissue remodeling during wound healing. We developed a novel high-density collagen xerogel thread (CXT) and evaluated its effects on early urethral tissue responses in a rat urethral injury model. Methods A rat urethral incision model was used to compare CXT with conventional absorbable Vicryl® sutures (Ethicon, Inc., Somerville, NJ, USA). Histological evaluation was performed using hematoxylin-eosin staining and immunohistochemical analyses for alpha-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and leukocyte common antigen (LCA) on postoperative day 7. Results Compared with Vicryl sutures, CXT was associated with reduced urethral mucosal thickening, lower numbers of CTGF-positive cells and LCA-positive cells, and less prominent stromal α-SMA expression during early wound healing. Conclusions CXT was associated with altered inflammatory and fibrotic tissue responses during early urethral wound healing in rats.
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Astragalus membranaceus is a Traditional Chinese Medicine (TCM) often used to modulate intestinal flora. This study aims to analyze the effects of Astragalus membranaceus on intestinal flora and chemotherapy-related complications in patients undergoing chemotherapy for colon cancer through clinical research and to explore the possible mechanism. The study included 86 patients with colon cancer who were assigned to the Chemotherapy (Che) and Astragalus (Ast) groups. The Che group was treated with bevacizumab combined with oxaliplatin and capecitabine and the Ast group was treated with Astragalus granules on the basis of the Che group. The intestinal flora and the incidence of chemotherapy-related complications were compared between the two groups. Astragalus granules can reduce a variety of complications during chemotherapy in patients with colon cancer. At the same time, this study detected the feces of patients before and after chemotherapy and found that Astragalus can effectively increase the content of intestinal Bifidobacterium and Lactobacillus and reduce the content of Enterococcus and Escherichia coli in patients. In addition, by detecting the serum of patients in this study, it was found that Astragalus granules can increase the level of serum CD4+ T cells and reduce the level of CD8+ T cells in patients. At the same time, Astragalus granules can also relieve the inflammatory state of patients during chemotherapy. TCM formula based on astragalus can effectively regulate the intestinal flora of patients, reduce the complications of chemotherapy and relieve the inflammatory state of the body during the chemotherapy of patients with colon cancer. Astragalus membranaceus has significant advantages in effectively improving the imbalance of intestinal flora caused by chemotherapy, improving the immune function of patients and reducing the incidence of chemotherapy-related complications.
Directed self-assembly (DSA) of block copolymer (BCP) thin films is a promising strategy for fabricating nanoscale patterns. However, defects and limited controllability during processing remain significant barriers to practical implementation. In this study, we introduce solvent immersion annealing (SIA) as a facile and effective approach to improving alignment quality and suppressing defect formation in shear-aligned polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) thin films. By immersing shear-aligned films in solvent mixtures, SIA provides enhanced control over polymer swelling and chain mobility, enabling rapid annihilation of defects and long-range ordering within minutes. Systematic analysis of immersion time, solvent composition, and swelling behavior reveals that the optimal SIA process is achieved by preserving a delicate balance between chain rearrangement and film stability during solvent immersion. Compared to solvent vapor annealing (SVA), SIA offers superior swelling controllability and reduced sensitivity to external factors such as ambient humidity. Furthermore, large-area SEM and GISAXS analyses confirm that SIA enables scalable fabrication of well-aligned nanopatterns across extended surfaces. Taken together, this work highlights SIA as a robust and efficient strategy for achieving BCP nanopatterns with substantially reduced defect density, therefore offering potential for future lithography applications.
Acute microglia-mediated neuroinflammation and oxidative stress play important roles in the pathogenesis of gas explosion (GE)-induced traumatic brain injury (TBI). Curcumin has documented neuroinflammatory protective properties; however, its effects on gas explosion (GE)-induced TBI and the underlying mechanism remain unclear. In this study, we established a male rat model of acute TBI and an in vitro model of acute microglial impact injury using shockwave physiotherapy. The effects of curcumin on the extent of the brain injury, as well as the levels of inflammatory cytokines, oxidative stress indicators, microglia polarization, and toll-like receptor 4 (TLR4) protein expression in model rats and microglial cells were evaluated using histological staining, western blotting, qPCR, immunohistochemistry, immunofluorescence, and biochemical assays. The results showed that curcumin reduced the pathological changes induced by GE and significantly inhibited the expression of neuron-specific enolase (NSE) (P < 0.05), a marker of microglial activation. Curcumin treatment also promoted M2 polarization of microglia (P < 0.05) and reduced the protein expression levels of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB (P < 0.05), and the pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and NLRP3 (P < 0.05). Moreover, curcumin treatment significantly reduced the levels of oxidative stress factors in rat tissues (P < 0.05). In summary, our findings indicated that curcumin alleviated acute neuroinflammation and oxidative stress induced by GE in vivo and in vitro by inhibiting TLR4-mediated M2 polarization of microglia, thus providing a new treatment target for the neuroinflammation associated with TBI caused by explosives.
We report the synthesis and characterization of a series of isomeric indacenodithiophenes (iso-IDTs) bearing various ethynyl substituents at the apical carbons. Absorption spectroscopy, cyclic voltammetry, and density functional theory (DFT) calculations were performed to investigate the electronic properties of these compounds. Notably, analogues with reduced steric protection (i.e., trimethylsilyl, adamantyl) were also successfully isolated and investigated. Computed nucleus-independent chemical shifts and ring current plot analyses reveal that iso-IDTs display reduced antiaromatic character compared to indenofluorene (IF) and the previously reported syn- and anti-fused IDT isomers, suggesting that the π-bond arrangement within the indacenodithiophene π-system can be leveraged for tuning their optoelectronic properties.
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is one of the important procedure-related complications of ERCP. Periprocedural intravenous hydration with lactated Ringer's solution has been considered a simple and feasible measure for reducing this complication. The present trial was designed to assess whether aggressive hydration with lactated Ringer's solution was more effective than standard hydration in preventing post-ERCP pancreatitis (PEP). This randomized controlled trial was performed at two tertiary care hospitals. A total of 126 patients undergoing first-time ERCP were included and randomly distributed into two equal treatment groups. Patients in group A were managed with standard hydration, whereas patients in group B received aggressive hydration using lactated Ringer's solution. The main outcome measure was the development of PEP. Other recorded outcomes were post-ERCP hyperamylasemia, isolated hyperamylasemia, serial pain scores on the visual analog scale, serum amylase levels, duration of hospital stay, and fluid-related adverse effects. All 126 randomized patients completed the 24-hour assessment. PEP developed in 14 patients in the standard hydration arm and four patients in the aggressive hydration arm (22.2% versus 6.3%; p = 0.020; RR = 0.29, 95% CI = 0.10-0.82). Total post-ERCP hyperamylasemia was less frequent after aggressive hydration than standard hydration (14.3% versus 41.3%; p = 0.001). Isolated hyperamylasemia was recorded in 7.9% and 19.0% of patients, respectively (p = 0.116). Pain scores remained lower with aggressive hydration at 4, 12, and 24 hours (all p < 0.001). Hospital stay was also reduced (1.8 versus 3.0 days; p < 0.001). Aggressive hydration with lactated Ringer's solution significantly reduced PEP, post-procedure hyperamylasemia, pain scores, and hospital stay compared with standard hydration. The regimen was well tolerated in selected patients without fluid-overload risk.
Acute decompensated heart failure (ADHF) remains a leading cause of hospitalization worldwide. The prognostic value of spot urinary sodium concentration in determining clinical outcomes for patients with ADHF treated with diuretics remains uncertain. This systematic review with meta-analysis was registered in the International Prospective Register of Systematic Reviews (CRD42024626912). MEDLINE, Cochrane, and Embase were searched from inception to May 2026 for studies comparing high and low urine sodium, measured after the first void or within six hours of diuretic use, in adult patients admitted for ADHF. The primary outcomes of interest were mortality, length of hospitalization/stay (LOS), inotrope use, and worsening renal function. Odds ratios (ORs) with 95% confidence intervals (CI) were pooled with a random-effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. A total of eight studies comprising 1,359 patients were included in the meta-analysis, of which 923 (67.9%) were categorized in the high urinary sodium group and 464 (32.1%) in the low urinary sodium group. In patients with ADHF, high urine sodium was associated with lower mortality (OR, 0.28; 95% CI, 0.12-0.68), reduced inotrope use (OR, 0.40; 95% CI, 0.25-0.62), lower worsening renal function (OR, 0.53; 95% CI, 0.32-0.86), and shorter LOS (mean difference, -4.35; 95% CI, -7.88 to -0.81) compared with low urine sodium. In patients with ADHF treated with diuretics, high urine sodium is associated with improved outcomes, including reduced mortality, inotrope use, worsening renal function, and shorter LOS, compared with patients with low urine sodium.
The fabrication of maxillary prostheses in patients with flap-reconstructed maxillary defects continues to present both clinical and technical challenges. Conventional impression techniques can be hazardous and often require multiple adjustments. This report presents a simplified digital approach using 3D scan data of an existing, well-adjusted prosthesis. The previously relined and adjusted prosthesis was scanned with an intraoral scanner, and the 3D surface data were used to print an occlusal record base. After recording the jaw relation, the teeth were arranged, and a functional impression was made at the try-in stage. Finally, the definitive prosthesis was fabricated using heat-cured acrylic resin. The printed record base provided accurate adaptation and minimized the clinical risks associated with conventional impression making. Incorporating the functional impression during the try-in stage further improved the fit and reduced the need for postdelivery adjustments. This technique offers a practical and simplified method for maxillary prosthesis fabrication. Reusing the morphology of a clinically adapted prosthesis eliminates complex digital processing and reduces clinical burden, making it especially useful in settings with limited access to advanced technical support.
Lymphoma can seriously affect the quality of life of patients. Both homoharringtonine (HHT) and tanshinone IIA (Tan IIA) have shown robust anti-proliferation and apoptosis-inducing effects in lymphoma cells. However, it is unclear whether they can be used in combination to treat acute myeloid leukemia and lymphoma. Cell Counting Kit-8 (CCK-8) was employed to measure cell viability, the 5-Ethynyl-20-deoxyuridine assay (EdU) was used to quantify cell proliferation, and the transwell migration assay was used to assess cell migration in U937 and Raji cells. Additionally, transmission electron microscopy and nanoparticle tracking analysis assays were used to observe and identify exosomal structure, respectively. Combined HHT and Tan IIA treatment synergistically inhibited the viability and proliferation of U937 and Raji cells, induced apoptosis, and reduced vascular endothelial growth factor (VEGF) levels in these cells. Additionally, VEGFA and VEGFC levels were significantly reduced in exosomes derived from Raji cells that had been treated with HHT and Tan IIA (ExoHHT + Tan IIA). Moreover, absorption of ExoHHT + Tan IIA significantly inhibited the viability, proliferation, and migration of human umbilical vein endothelial cells by downregulating the expression of serine/threonine kinase 1 (Akt), matrix metalloproteinase-2 (MMP2) and MMP9. ExoHHT + Tan IIA suppressed the tumor microenvironment. HHT and Tan IIA combined therapy synergistically suppressed lymphoma progression by downregulating the Akt/MMP signaling pathway, suggesting their use in treating lymphomas. Clinical trial number: Not applicable.
RNA interference (RNAi) provides a powerful tool for functional gene identification and pest management, and nanocarriers have recently enabled noninvasive transdermal RNAi delivery. However, the mechanism of nanocarrier-mediated double-stranded RNA (dsRNA) translocation across the insect cuticle remains unknown. We used a star cationic polymer (SPc) as a model to visualize this process and elucidate its interactions with aphid cuticle components. SPc self-assembled with dsRNA to form stable nanocomplexes via electrostatic and hydrophobic interactions. This assembly altered the wax layer morphology and increased chitin interfibrillar spacing, creating a permissive interface for dsRNA translocation. SPc also increased the contact area, reduced the contact angle, and significantly improved penetration through artificial wax/cuticle. Furthermore, SPc interacted with major cuticle components through various intermolecular forces, causing wax dissolution and reduced interfacial resistance at the chitin layer. These findings demonstrate that nanocarrier-mediated wax dissolution and chitin-layer barrier reduction facilitate dsRNA translocation across the insect cuticle, providing a theoretical foundation for transdermal delivery systems.
Thirteen new 4-acyl-5-amino-1H-imidazole alkaloids (1-13) were identified from cultures produced by the marine-derived Streptomyces sp. OUCMDZ-944 using feature-based molecular networking (FBMN)-guided isolation. Notably, compounds 1 and 2 were identified as phenyl-containing derivatives, specifically 5-amino-4-phenylpropionylimidazole (1) and 5-amino-4-phenylbutyrylimidazole (2). Ten isolates (4-13) are hydroxylated, with compound 13 being identified as a novel dimeric analogue. Furthermore, five methylated derivatives, 1a, 4a, 4b, 17a, and 17b, were synthesized. In an in vitro depression model, compounds 1, 4, 4a, 4b, 8, 16, and 17b were found to significantly reduce IL-1β levels, while compounds 1, 1a, 4b, and 10 notably reversed the corticosterone-induced decrease in brain-derived neurotrophic factor (BDNF) expression, suggesting a potential antidepressant-like activity. In the zebrafish anxiety model, compounds 1, 1a, 4b, 16, and 17b significantly enhanced spontaneous locomotor activity, reduced thigmotaxis behavior, and increased time spent in the inner zone under various lighting conditions, demonstrating clear anxiolytic-like effects. These five compounds were identified as promising lead candidates with dual anxiolytic and antidepressant potential.
Advanced glycation end products (AGEs) and their receptor receptor for AGEs (RAGE) promote tumor progression via activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Although 3-Hydroxyflavone exhibits anticancer properties, its role in oral squamous cell carcinoma (OSCC) and its interaction with the AGEs/RAGE/NF-κB axis remain unclear. This study investigated whether 3-Hydroxyflavone inhibits OSCC by modulating miR-142-5p within the AGEs/RAGE/NF-κB axis. The expression of p65 and miR-142-5p was analyzed in both OSCC tissues and Tca8113 cells. TargetScan prediction and dual-luciferase reporter assays confirmed that p65 is a direct target of miR-142-5p. The effects of 3-Hydroxyflavone on OSCC cells were evaluated using MTT and colony formation assays. Additionally, immunohistochemistry was performed to assess p65 expression in tumor tissues, and Kaplan-Meier analysis was used to evaluate patient survival. OSCC tissues showed increased p65 nuclear translocation and decreased miR-142-5p levels. The miR-142-5p directly inhibited p65. The 3-Hydroxyflavone treatment suppressed OSCC cell proliferation and colony formation by upregulating miR-142-5p and inhibiting the AGEs/RAGE/NF-κB pathway. High p65 expression correlated with poor survival, while 3-Hydroxyflavone treatment reduced p65 and improved survival. The 3-Hydroxyflavone inhibits OSCC proliferation and enhances survival by upregulating miR-142-5p, which suppresses AGEs/RAGE/NF-κB signaling, suggesting a novel therapeutic strategy.
Diabetic neuropathic pain (DNP) is a prevalent and debilitating complication of diabetes mellitus, characterized by persistent pain and neuroinflammation. Current treatments often provide inadequate relief, highlighting the need for novel therapeutic strategies targeting its underlying mechanisms. This study aimed to investigate the therapeutic potential of tetrandrine (Tet) in alleviating DNP and to elucidate its effects on two key pathological processes: neuronal autophagy and microglial polarization. To establish the DNP model, rats received an intraperitoneal injection of streptozotocin. Pain behavior was assessed weekly using mechanical withdrawal threshold and thermal withdrawal latency tests. Relevant markers were analyzed via reverse-transcription quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, or Western blot. To further investigate the underlying mechanisms, in-vitro experiments were conducted using high glucose-treated neuronal cells and lipopolysaccharide-stimulated BV2 microglia. Tet administration significantly alleviated pain hypersensitivity and neuroinflammation in DNP rats. Mechanistically, this effect might be achieved through a dual modulation of neuroimmune processes and intracellular clearance pathways. Tet shifted microglial polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 state. Concurrently, it enhanced autophagic activity, as evidenced by an increased LC3-II level and LC3-II/LC3-I ratio, restored expression of the mitophagy-related proteins PINK1 and parkin and reduced p62 accumulation. In-vitro findings corroborated these mechanisms: Tet balanced the expression of M1 and M2 markers in activated microglia and similarly upregulated key autophagy-related proteins (LC3-II, PINK1, parkin) in neurons under high-glucose stress. Tet alleviates DNP, potentially through the concurrent modulation of microglial phenotypic transition and neuronal autophagy. These findings identify Tet as a promising multi-target agent for DNP and elucidate its potential mechanisms of action.
Breast carcinoma is the most prevalent and lethal malignancy affecting females, and it always presents an essential healthcare problem. Doxorubicin (DOX) is a common chemotherapy utilized in treating breast carcinoma, but it also has dangerous side effects. Hence, searching for potent and safe anticancer compounds is urgent. An alkaloid, piperine, mostly found in pepper species, is a naturally occurring substance with anticancer properties. This work aims to assess the anticancer impact of piperine on breast carcinoma cells by potentially inhibiting the γ-secretase/Notch pathway, and to compare its impacts with those of DOX. The anti-proliferative effects of piperine and DOX were evaluated on various human breast carcinoma cell lines (MCF-7, T47D, and MDA-MB-231). Additionally, a flow cytometric analysis was carried out to identify the cell cycle arrest. Moreover, the protein expression levels of Notch-1, γ-secretase components, NICD, c-myc, p21, Bax, and Bcl-2 were assessed. The results demonstrated that among the tested cell lines, MDA-MB-231 cells exhibited the highest sensitivity to piperine treatment, with the lowest IC50 value (32.37 ± 2.5 µM). At the G2/M phase, piperine and DOX both stopped the cell cycle. Furthermore, piperine and DOX inhibited the Notch signaling by reducing Notch-1, γ-secretase components, and NICD expression. Piperine and DOX also reduced the levels of Notch target proteins, namely, p21 and c-myc. Lastly, both drugs induced apoptosis by elevating Bax and reducing Bcl-2 expression in malignant breast cells. The promise of piperine as a targeted therapy candidate for the treatment of breast cancer is substantially supported by this research.
Introduction Acne scarring represents a permanent structural sequela of acne vulgaris and is predominantly characterized by atrophic morphological patterns. Beyond cosmetic disfigurement, facial acne scars may contribute to significant psychosocial distress, including body image disturbance and quality-of-life impairment. Limited data are available correlating scar morphology with body image concerns and scar-specific quality-of-life impairment in the Indian population. Objectives The objectives of this study are to examine the morphological profile of facial acne scars, evaluate the body image concerns and quality of life among patients with acne scars, and determine the correlation of facial acne scarring with body image concerns and quality-of-life impairment. Materials and methods This cross-sectional observational study was conducted in the Department of Dermatology, Venereology and Leprosy, Adichunchanagiri Hospital and Research Centre, Karnataka, over a period of 18 months. It included 150 patients of either gender, aged 18-40 years, with facial acne scars. Morphological assessment was performed under standardized illumination. Scar severity was graded using the Goodman and Baron qualitative grading system and the Self-assessment of Clinical Acne-Related Scars (SCARS) questionnaire. The Body Image Concern Inventory (BICI) and Facial Acne Scar Quality of Life (FASQoL) questionnaires were used for fulfilling the respective objective. Statistical analysis was performed using Epi Info software. Correlations were assessed using Spearman's rank correlation coefficient. A p-value of < 0.05 was considered statistically significant. Results The majority of participants (63.3%; n=95) were aged 21-25 years, and 69.3% (n=104) were female. Icepick scars were the most common morphological type at 78.7% (n=118), followed by boxcar scars at 61.3% (n=92). Clinician-based grading revealed that 72.6% (n=109) of participants had moderate to severe acne scarring. Based on a SCARS assessment, 36.0% (n=54) had mild, 30.0% (n=45) had moderate, and 15.3% (n=23) had severe/very severe scarring. Mean BICI scores increased significantly across SCARS severity categories (p<0.001). The mean FASQoL score was 6.79 ± 7.11, with higher scores observed in severe scarring (p<0.001). Moderate positive correlations were observed between SCARS and BICI (rₛ=0.419, p<0.001), SCARS and FASQoL (rₛ=0.500, p<0.001), Goodman-Baron grade and FASQoL (rₛ=0.448, p<0.001), and Goodman-Baron grade and BICI (rₛ=0.367, p<0.001). Conclusion Body image concern is evident across domains of dissatisfaction with appearance, preoccupation with perceived flaws, and mirror-checking behaviors. Scar-specific quality-of-life impairment manifests as emotional distress, social self-consciousness, and reduced interpersonal confidence. Patient-perceived severity demonstrates a particularly strong relationship with psychosocial burden, underscoring the importance of integrating clinician-based grading with validated patient-reported outcome measures for comprehensive assessment and patient-centered management.
A comprehensive geriatric assessment (CGA) followed by geriatric assessment-guided interventions was demonstrated to reduce treatment-related toxicities CTCAE III°-V° in older adults with cancer undergoing systemic cancer treatments, but implementation remains insufficient. Thus, we aimed to evaluate the feasibility of implementing CGA into routine care and multidisciplinary tumor boards (MDTs) in Germany within a bicentric feasibility trial (DRKS00035569; 19.12.2024). Patients ≥ 65 years with positive geriatric screening (G8 < 15 points) and all patients ≥ 70 years received CGA as part of their routine care. Results were presented during MDT discussions to derive treatment recommendations. After CGA, patients were asked for trial participation which included data analysis and a telephone follow-up after 3 months. Clinicians participating in the MDT were asked about the added value of CGA presentation. Primary endpoint was the estimation of patient's willingness to participate with an accuracy of ± 7.5% to inform design for a later (cost) effectiveness trial. 75 patients received CGA (62.5% females). Of those, 72 (96%) agreed to participate (95% confidence interval, [0.8875; 0.9917]). With an accuracy of estimating the willingness to participate of < |7.5%|, the primary endpoint was reached. The median age was 76.7 years (range 69-92 years). A member of the geriatric team attended 2/3 of MDT meetings. Clinicians rated the integration of CGA results predominantly as useful. Integration of CGA into routine care of older cancer patients is feasible but will likely require adequate geriatric staffing per center. A larger implementation study, evaluating efficacy and cost-effectiveness in the German healthcare system, is necessary.
Fundus diseases are major causes of irreversible visual impairment. Retinal pharmacokinetic behavior may differ between diabetic retinopathy (DR) and age-related macular degeneration (AMD), but disease-specific dosing principles remain insufficiently defined. Disease-stratified retinal pharmacokinetic characteristics were evaluated, and a precision drug administration strategy for patients with fundus diseases was developed. Blood-retinal barrier (BRB) cell models, retinal organoids, retinal pigment epithelium (RPE) models, optical coherence tomography (OCT), serum biomarkers and clinical records were integrated. A retrospective, controlled clinical analysis was performed in patients with DR or AMD, in accordance with ethics approval No. 20240923. DR was characterized by greater barrier permeability and transporter-related retention, whereas AMD was characterized by lipid-associated RPE dysfunction and restricted trans-retinal penetration. The DR model predicted retinal peak concentration with R2 = 0.89, and the AMD model predicted drug half-life with 86% accuracy. Precision administration was associated with reduced injection frequency in DR and AMD and improved anatomical and visual outcomes. Disease-specific retinal pharmacokinetic differences support individualized dosing strategies for fundus diseases. The proposed platform provides a practical framework for precision anti-VEGF therapy and targeted retinal drug delivery.