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Background/Objective: The introduction of Ketoconazole (KZ, Nizoral&#xae;) in 1977 by Janssen Pharmaceutica marked a significant milestone in medical mycology as the first broad-spectrum oral antifungal agent. However, KZ is a highly lipophilic compound, presenting significant challenges in the development of efficient topical formulations. Moreover, oral KZ has undergone labeling revisions and market withdrawal due to serious hepatic side effects. This study aimed to design, optimize, and evaluate KZ-loaded nanoemulsions (NEs; KZ-NEs) as a delivery platform that could improve skin bioavailability and antifungal activity. Methods: Optimized KZ-NEs were converted to a mucoadhesive formulation (KZ-NEC) by the addition of Carbopol&#xae; 940 NF to enhance the adherence of the formulations to the skin surface. NEs were evaluated concerning physical appearance, globule size, polydispersity index, zeta potential, pH, viscosity, and drug content. Optimized KZ-NE and lead KZ-NEC formulations were further evaluated for in vitro release, ex vivo skin permeation and deposition, skin irritation, and in vivo studies. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KZ over 24 h. The ex vivo permeability coefficients of KZ from the optimized KZ-NE and lead KZ-NEC formulations were approximately four- and three-fold greater than that achieved with the marketed cream formulation, respectively. In addition, the Cmax of the lead KZ-NEC formulation (14.4 &#xb1; 1.1 &#x3bc;g/mL) was significantly higher (p < 0.05) compared with the marketed cream formulation (10.5 &#xb1; 0.5 &#x3bc;g/mL). Moreover, in vitro antifungal susceptibility testing showed that KZ demonstrated improved antifungal efficacy when incorporated into the KZ-NE and KZ-NEC formulations. Neither of the NE-based formulations caused any alterations in skin color or morphology during the 24 h visual observation period. Both NE-based formulations were stable for 90 days (the last time-point tested) at three different storage conditions. Conclusions: NE-based formulation could serve as an effective topical delivery platform for KZ and could improve therapeutic outcomes for patients with topical fungal infections.

Based on the structure of NTM-006, a selective adenosine A3 receptor (A3AR) agonist developed by Janssen Pharmaceutica NV, a series of novel analgesics was designed and synthesized. Their analgesic activity was evaluated using the acetic acid-induced writhing model in mice. Among the 46 target compounds, 15 of them exhibited significant inhibition of writhing responses at 100&#xa0;mg/kg (inhibition rate&#xa0;&#x2265;&#xa0;32.89%), with analgesic efficacy comparable to that of the positive controls (NTM-006 and acetaminophen), indicating their potential for further development as analgesic agents. Dose-response studies revealed that compounds 37 and 40 inhibited writhing in a dose-dependent manner within the range of 30-300&#xa0;mg/kg. Molecular docking further elucidated their potential binding modes with A3AR, and molecular dynamics (MD) simulations revealed that compound 37 exhibited superior binding affinity and stability toward A3AR compared to the lead compound NTM-006. The studies of preliminary structure-activity relationships and potential mechanisms of action provided insights for the design and development of novel analgesics targeting A3AR.

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease affecting peripheral and axial joints, entheses, skin, and nails, requiring coordinated multidisciplinary management. Since the 2018 edition of ESPOGU&#xcd;A, significant advances-including the availability of IL-17A/F, IL-23, and JAK inhibitors, as well as emerging evidence regarding axial PsA-have prompted the need for an updated guideline. The 2024 ESPOGU&#xcd;A provides evidence-based recommendations for the diagnosis and management of PsA, integrating multidisciplinary collaboration, active nursing participation, lifestyle counseling, and specific considerations for axial disease. A panel comprising rheumatologists, dermatologists, gastroenterologists, ophthalmologists, nurses, methodologists, and patient representatives formulated clinical questions using the Population, Intervention, Comparator, and Outcomes (PICO) framework. Systematic literature reviews were performed, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to critically assess the quality of evidence and guide the formulation of recommendations. The guideline emphasizes early intervention and the appropriate use of conventional synthetic DMARDs, biologic therapies, and JAK inhibitors across different disease domains, including the management of extra-musculoskeletal manifestations. Lifestyle measures, such as smoking cessation and weight management, are highlighted due to their demonstrated impact on disease activity and long-term outcomes. The essential role of specialized rheumatology nurses in patient education, treatment adherence, and counseling on modifiable risk factors is also underscored. ESPOGU&#xcd;A 2024 provides a comprehensive, multidisciplinary, and patient-centered framework for PsA management, including axial involvement, and identifies persistent gaps in early diagnosis, biomarker development, and long-term outcomes, thereby outlining priorities for future research. Diagnosing and Treating Psoriatic Arthritis: Highlights from the 2024 Spanish Clinical Guidelines Psoriatic arthritis (PsA) is a long-term inflammatory disease that can affect the joints, spine, skin, nails, and enthesis. Symptoms and disease severity vary widely, so many people with PsA need care from several healthcare professionals working together. Since the last Spanish clinical guideline was published in 2018, major advances have been made in PsA treatment. New targeted medicines are now available, and there is better understanding of PsA that affects the spine (axial PsA). These changes led to an update of the guideline. The 2024 ESPOGU&#xcd;A guideline provides clear, evidence-based recommendations for diagnosing and managing PsA. It emphasizes multidisciplinary care, including the important role of nurses, and highlights the value of healthy lifestyle habits such as stopping smoking and maintaining a healthy weight. The guideline also includes specific advice for people with spinal involvement. A multidisciplinary group of doctors, nurses, researchers, and patient representatives developed the guideline using internationally accepted methods. They reviewed the best available scientific evidence and assessed its quality before making recommendations. The updated recommendations focus on early diagnosis and timely treatment to reduce symptoms and prevent long-term damage. They cover the use of conventional treatments, biological therapies, and newer targeted drugs, depending on individual disease features. Conditions affecting organs beyond the joints are also addressed. Specialized rheumatology nurses are recognized as key members of the care team, supporting patient education, treatment adherence, and lifestyle counselling. Overall, ESPOGU&#xcd;A 2024 offers a comprehensive, patient-centred approach to psoriatic arthritis care and identifies priorities for future research, including earlier diagnosis and better long-term outcomes.

Neurolymphomatosis frequently impairs physical function, rendering patients unable to tolerate chimeric antigen receptor T-cell therapy (CAR-T). An alternative treatment strategy which can cross the blood-nerve barrier is warranted. A 64-year-old woman had a history of MYD88L265P mutated diffuse large B-cell lymphoma (DLBCL) successfully treated with Pola-R-CHP plus high-dose methotrexate one year prior. However, she developed progressive muscle weakness in her limbs, with a three-month history. Upon admission, she was bedridden, unable to resist gravity, and experienced bladder and rectal disturbances. Imaging studies revealed neurolymphomatosis involving the bilateral trigeminal nerves, cervical/brachial plexus, brachial nerves, lumbosacral plexus, and femoral nerves. Ibrutinib 560 mg/day combined with rituximab led to complete remission, and she regained the ability to walk within three months. Unfortunately, neurolymphomatosis relapsed after six months of ibrutinib treatment. Epcoritamab led to another complete remission, with a progression-free survival of six months. The adverse events were manageable, including Grade 1 cytokine release syndrome. This report is the first to demonstrate the effectiveness of epcoritamab in treating neurolymphomatosis. Bispecific antibodies may serve as a valuable bridging therapy for CAR-T, helping to restore their physical function. Bruton's tyrosine kinase inhibitors could also be an option for MYD88L265P mutated disease.

T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) is an inhibitory receptor linked to decreased antitumor activity of immune cells. S095018 is a human anti-TIM-3 IgG2 antibody that blocks the binding of phosphatidyl serine to TIM-3. Sym021 is a humanized IgG1 antibody that inhibits the binding of programmed cell death protein-1 (PD-1) to its ligands programmed death-ligand 1 (PD-L1) and PD-L2. S095018 in combination with Sym021 was tested in patients with advanced/metastatic biliary tract cancers (BTC) whose disease progressed under treatment with at least 1 line of systemic therapy and who had not received prior treatment with PD-(L)1 inhibitors (NCT04641871). Patients received 3&#x2009;mg/kg of Sym021 and 10&#x2009;mg/kg of S095018 once every 2 weeks. Primary endpoints included overall response rate and incidence/severity of adverse events. Key secondary endpoints included pharmacokinetics, immunogenicity assessment, progression-free survival (PFS) and overall survival (OS). 35 patients with stage IV BTC received S095018 in combination with Sym021. A partial response was achieved in 2 patients (5.7%) and stable disease in 11 patients (31.4%) for a disease control rate of 37%; 4 patients were not evaluable for response. Median PFS and OS were 1.9 months (90% CI 1.8 to 3.7)&#x2009;and 13.4 months (90%&#x2009;CI 8.2 to 27.1), respectively. The most common treatment-emergent adverse events of any grade included fatigue, pruritus, infusion-related reaction, and increases in amylase (8.6% each). Exploratory biomarker analyses in paired tumor biopsies showed an increase in intratumoral CD8 T-cell density and an upregulation of gene signatures related to interferon-&#x3b3; signaling, antigen presentation, and T-cell activation with treatment without, however, clear association with efficacy endpoints. Dual PD-1/TIM-3 inhibition was tolerable but exhibited modest antitumor activity in patients with advanced/metastatic recurrent BTC who had not received prior anti-PD-(L)1 treatment.

Early identification and treatment of psoriatic arthritis (PsA) among patients with psoriasis is important to prevent joint damage. Insights in arthritis onset and the associated clinical factors among pediatric and young adult patients with psoriasis is scarce. To describe pediatric patients with psoriasis who subsequently developed psoriatic arthritis at pediatric age or in young adulthood (JPsA/PsA). We focused on clinical features and timing of onset, and compared clinical features to characteristics of a large cohort of pediatric psoriasis patients. Data on patients with pediatric onset of psoriasis were obtained from the prospective, daily practice, ChildCAPTURE registry. Descriptive statistics were used. ILAR and CASPAR criteria were used for classification of JPsA and PsA, respectively. The time to JPsA/PsA diagnosis following psoriasis onset was analyzed using Kaplan-Meier survival analysis. Among 717 pediatric and young adult patients with psoriasis, 15 (2.1%) developed arthritis, of which 8 patients before the age of 18&#xa0;years (1.1%, JPsA) and 7 patients in young adulthood (1.0%, PsA), with an estimated incidence of 2.8% within 10&#xa0;years after psoriasis diagnosis. The median interval between psoriasis onset and JPsA/PsA development was 4.8&#xa0;years. Male sex, obesity, and nail involvement were common clinical features of patients developing JPsA/PsA, and these were observed more frequently compared to the total pediatric psoriasis cohort. The incidence of JPsA/PsA among patients with pediatric onset of psoriasis is low. If the clinical features male sex, obesity and nail involvement are present, extra awareness for the development of JPsA/PsA is warranted.

The optimal antithrombotic therapy for patients with chronic coronary syndrome (CCS) who also require long-term oral anticoagulation (OAC) remains uncertain. The aim of this study was to evaluate the safety and efficacy of OAC monotherapy compared with OAC plus single antiplatelet therapy (SAPT) in CCS patients with an indication for long-term anticoagulation. Randomized trials comparing OAC monotherapy with OAC plus SAPT in patients with CCS and indication for long-term OAC from the PubMed, Cochrane Central, Web of Science, and Scopus databases up to November 10, 2025 were included in this systematic review and meta-analysis. HRs and 95% CIs were estimated through a random-effects meta-analytical framework. The primary efficacy endpoint was trial-defined major adverse cardiovascular events, and the primary safety endpoint was any bleeding. Six trials comprising 5,924 patients were included. The median follow-up duration was 2.3 years (Q1-Q3: 1.3-2.9 years), the median CHA2DS2-VASc score was 4.2 (Q1-Q3: 4.0-4.6), and the median time from revascularization to randomization 3.8 years (Q1-Q3: 3.2-4.4 years). Compared with OAC plus SAPT, OAC monotherapy showed similar rates of major adverse cardiovascular events (6.8% vs 8.2%; HR: 0.85; 95% CI: 0.64-1.09; I2 =23%) and reduced risk of bleeding (8.9% vs 16.1%; HR: 0.49; 95% CI: 0.44-0.55; I2 =8%). OAC monotherapy also reduced cardiovascular death (HR: 0.69; 95% CI: 0.48-0.97; I2 =0%), net adverse clinical events (HR: 0.60; 95% CI: 0.47-0.78; I2 =66%), and major bleeding (HR: 0.46; 95% CI: 0.32-0.66; I2 =47%) compared with OAC plus SAPT. There were no significant differences in myocardial infarction, stroke, or all-cause mortality. In patients with CCS requiring long-term OAC, OAC monotherapy was associated with reduced bleeding, cardiovascular death, and net adverse clinical events compared with OAC plus SAPT. (Anticoagulation Alone vs Anticoagulation Plus Antiplatelet Therapy in Atrial Fibrillation With Stable Coronary Disease: A Meta-Analysis of Randomized Trials; CRD420251174643).

Immunocompromised patients are at high risk of pneumonia, with associated poor outcomes. Rapid microbiologic diagnosis is crucial, yet diagnostic yields vary widely. We evaluated the variability in diagnostic yield of usual care testing and plasma microbial cell-free DNA (mcfDNA) sequencing in the prospective observational Pneumonia in the Immunocompromised-Use of the Karius Test for the Detection of Undiagnosed Pathogens (PICKUP) study, specifically focusing on timing of testing relative to the onset of pneumonia. In this exploratory analysis, patient characteristics, variability in diagnostic yield, and the timing of bronchoscopy and mcfDNA sequencing from date of first abnormal imaging associated with suspected pneumonia were evaluated across enrolling sites. A total of 222 patients from 10 enrolling sites were analyzed. Usual care diagnostic yield varied across sites (range, 7.7%-57.7%). Patient characteristics did not differ between sites, and median time from abnormal imaging to bronchoscopy was not different across sites (3 days [IQR, 3]). Diagnostic yield of bronchoscopy was significantly higher when performed &#x2264;3 days (early) from abnormal imaging (38.5% [52/135]) versus >3 days (delayed) (21.8% [19/87]) (difference, 16.7% [95% CI, 2.5%-28.3%]; P = .009). Adding mcfDNA sequencing to usual care testing increased overall diagnostic yield by 7.9% for patients undergoing early bronchoscopy, and by 16.3% for delayed bronchoscopy. Early bronchoscopy enhances diagnostic yield in immunocompromised patients with suspected pneumonia. Irrespective of timing, plasma mcfDNA sequencing increases overall diagnostic yield in this clinical scenario. These findings underscore the importance of prompt diagnostic strategies in this patient population.

Patients with gastric cancer and isolated positive peritoneal cytology have stage IV disease. The clinical significance of cytologic conversion is poorly understood. Our objectives are to (1) describe the clinicopathologic characteristics of patients with gastric cancer and isolated positive peritoneal cytology and their association with survival, (2) evaluate patients who underwent second cytologic evaluation for assessment of cytologic conversion, and (3) describe recurrence patterns in patients with cytologic conversion who underwent resection. Patients with gastric adenocarcinoma and isolated positive peritoneal cytology were identified from a prospectively maintained institutional database from 1996 to 2020 for this cohort study. Patients were characterized by selection for second cytologic evaluation following chemotherapy, cytologic conversion, and selection for surgical resection. Factors associated with overall survival (OS) were evaluated by time-dependent multivariable Cox regression models. Overall, 174 patients were identified, 62 (35.6%) were selected for second cytologic evaluation, 43 (69.4%) were cytologic converters, and 32 (74.4, 18.4% overall) underwent resection. Selection for second cytologic evaluation was associated with improved OS (hazard ratio [HR] 0.56, 95% CI 0.37-0.86), and among those patients, cytologic conversion was associated with improved OS (HR 0.17, 95% CI 0.08-0.35). Ten patients (31.3%) had no evidence of recurrence following resection during the study period. The peritoneum was the most common site of recurrence (n = 17, 53.1%). Among patients with gastric cancer and isolated positive peritoneal cytology, second cytologic evaluation can provide prognostic information and inform treatment decisions. Cytologic conversion was documented in 25% of patients, with rare instances of long-term disease control.

Microglia, the resident immune cells of the brain, are increasingly recognized as key contributors to Alzheimer&#x2019;s disease (AD) pathology. Multiple studies have identified microRNA-132 (miR-132) as one of the most significantly downregulated microRNAs in AD. Apart from well-established pleiotropic regulatory functions in neurons, previous evidence also suggested a role for miR-132 in regulating (neuro)inflammation. Yet, the precise mechanisms by which miR-132 impacts microglia remain unknown. In this study, we investigated the role of miR-132 in modulating microglial gene expression and function using gain- and loss-of-function approaches in human-induced pluripotent stem cell (iPSC)-derived microglia (iMGs) from both healthy controls and sporadic AD (sAD) patients. Our findings indicate that while miR-132 may not be indispensable for some baseline microglial functions, increasing its expression in sAD iMGs can reverse disease-associated gene expression changes and attenuate inflammatory responses. To further explore its therapeutic potential, we overexpressed miR-132 in hippocampal neurons of an AD mouse model, employing a clinically relevant adeno-associated viral (AAV) delivery method. miR-132 overexpression was well-tolerated and induced non-cell autonomous effects in microglia. This study sheds light into the regulatory role of miR-132 in microglia under both physiological and AD conditions, and emphasizes the importance of optimizing safe dosage parameters for future clinical applications.

Chronic hand eczema is a multifactorial, inflammatory skin disease associated with itch, pain, and a substantial physical and psychosocial burden. Delgocitinib cream (2%, 20 mg/g), a topical, non-steroidal, pan-Janus kinase inhibitor, is approved for the treatment of moderate to severe chronic hand eczema in adults. We aimed to assess the efficacy and safety of delgocitinib cream in adolescents with moderate to severe chronic hand eczema. DELTA TEEN was a double-blind, vehicle-controlled, multicentre, phase 3 randomised controlled trial conducted at 29 trial sites in Australia, Belgium, Canada, France, Poland, Spain, and the UK. Adolescents (aged 12-17 years) with moderate to severe chronic hand eczema were randomly assigned 3:1 via an interactive response technology system to twice-daily application of delgocitinib cream or cream vehicle for 16 weeks. The primary endpoint was the Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as an IGA-CHE score of 0 or 1 (clear or almost clear) with a 2 step or greater improvement from baseline. Efficacy of delgocitinib cream versus cream vehicle was assessed in all randomly assigned patients exposed to trial treatment, and safety was assessed in all patients exposed to trial treatment. This trial is registered with clinicaltrials.gov, NCT05355818, and is complete. DELTA TEEN was conducted between July 14, 2022, and Dec 17, 2024. Patients (N=98, of whom 58 [59%] were female and 40 [41%] were male, and 89 (91%) patients were White) were randomly assigned to delgocitinib cream (n=74) or cream vehicle (n=24). Superiority of delgocitinib cream to cream vehicle was shown for the primary endpoint (IGA-CHE treatment success at week 16). 47 (64%) of 74 of patients treated with delgocitinib versus seven (29%) of 24 patients treated with the cream vehicle had IGA-CHE treatment success at week 16 (difference 37&#xb7;9%; 95% credibility interval 13&#xb7;5-58&#xb7;2). Adverse events were reported by 37 (50%) patients treated with delgocitinib and eight (33%) patients treated with the cream vehicle. All adverse events with delgocitinib cream were mild or moderate in severity. No serious adverse events were reported in either group. Delgocitinib cream showed superior efficacy compared with cream vehicle and was well tolerated over 16 weeks. The results support delgocitinib cream as a treatment option for adolescents with moderate to severe chronic hand eczema. LEO Pharma.

Tuberculosis (TB) remains a major health threat, while the increasing occurrence of drug-resistant strains underscores the need for new antitubercular drugs. A promising strategy to combat TB is based on disrupting the mycobacterial redox homeostasis by inhibiting an NADPH-dependent oxidoreductase, mycothione reductase (Mtr). Using high-throughput screening, we recently identified potent and selective Mtr inhibitors. Here we report high-resolution X-ray structures of Mtr from Mycobacterium tuberculosis and Mycobacterium xenopi, including the M. tuberculosis enzyme complexed with a novel inhibitor, Respiri-1093. Our findings demonstrate that Respiri-1093 competes with the NADP(H) binding rather than mycothione binding. Analysis of the binding site explains the observed selectivity of the inhibitor towards the M. tuberculosis enzyme. These results provide a structural basis for rational drug design.

Climate change may increase the spread of allergenic plants such as ragweed. Ragweed pollen is assumed to be more allergenic than birch pollen. Determining pollen threshold concentrations triggering symptoms is challenging. Technical modifications to the Fraunhofer allergen challenge chamber (ACC) now allow investigation of very low pollen concentrations. Based on Total Nasal Symptom Score (TNSS) data from 15 subjects with birch pollen allergic rhinitis (AR), a birch pollen threshold between 50 and 100 pollen grains/m3 of air was previously derived. This study explored threshold concentrations of ragweed pollen. Two ragweed pollen AR patients were exposed to varying concentrations of ragweed pollen for 4 h. TNSS was recorded every 20 min, and nasal secretion and peak nasal inspiratory flow hourly. Area under the curve (AUC0-240) values were calculated. Ex vivo basophil activation tests with varying concentrations of ragweed pollen, Amb a 1, birch pollen, and Bet v 1 were performed for both ragweed pollen AR patients and 6 of the 15 birch pollen AR patients. Mean effective concentrations (EC50) for CD63 expression were calculated. Ragweed pollen exposure resulted in the following TNSS AUC0-240 values: 28/23 at 0, 18/17 at 50, 13/27 at 100, 40/40 at 200, 29/16 at 300, and 55/47 at 1,000 pollen grains/m3. For CD63 expression, the mean EC50 was 277 pollen/mL for ragweed pollen, 884 ng/mL for Amb a 1, 11 pollen/mL for birch pollen, and 0.13 ng/mL for Bet v 1. On average, the proportion of Amb a 1 in ragweed pollen was 0.17%, and the proportion of Bet v 1 in birch pollen 1.96%. The modified Fraunhofer ACC can investigate pollen threshold concentrations under defined conditions. The assumed differences in threshold concentrations of ragweed and birch pollen for triggering symptoms were not confirmed. To derive reliable threshold concentrations for ragweed pollen, larger studies have to be followed.

Environmental change is accelerating across West Africa, placing increasing pressure on communities whose livelihoods depend on smallholder and subsistence farming. In Senegal's Casamance region, shifting rainfall patterns, rising temperatures, soil salinization, and deforestation are undermining food production and altering culturally significant landscapes, including sacred forests. While ecological changes are well documented, fewer studies examine how local communities interpret these transformations and how these perceptions relate to food security. This study used a community-based participatory research design to examine how farmers in Basse-Casamance perceive environmental change, how these perceived changes affect food security and livelihoods, and what locally identified strategies emerge in response. Mixed methods were employed, including focus group discussions, in-depth interviews, and semi-structured surveys with 234 agricultural households across 13 communities. Qualitative analysis identified six major themes: the destruction of forests; decreasing and irregular rainfall; declining river and marine health; loss and degradation of farmland; the abandonment of land due to conflict; and locally proposed solutions such as reforestation, strengthened environmental governance, and support for sustainable farming practices. Quantitative results showed high levels of food insecurity, with 86% of participating households reporting some level of food access challenges. All participants reported that, based on their experience, the environment in the Casamance is changing, and 100% of participants reported that the changes in the environment are contributing to food insecurity. Community observations closely align with regional climate and ecological data, demonstrating that experiential and place-based knowledge provide an essential complement to scientific assessments. Findings highlight the interconnected ecological, social, and spiritual dimensions of environmental change. Participants emphasized that meaningful responses require upstream, system-level interventions, including policy reform, stronger governmental engagement, and support for agroecological and community-governed food systems. Such strategies are essential for strengthening resilience in the face of accelerating climate and environmental pressures. Environmental change in the Casamance is multifaceted, deeply felt, and closely tied to food security, cultural identity, and land stewardship. Community identified solutions included elevating community knowledge, protecting culturally significant landscapes, and prioritizing policy-level action that supports sustainable, women-led, and locally grounded food systems.

Tildrakizumab, an anti-IL-23p19 antibody, is registered for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Its effectiveness in specific patient subgroups-e.g. those with high body weight, high disease burden, involvement of high-impact areas or older patients-is often underrepresented in randomised clinical trials and better captured in real-world settings. To address this gap, the present meta-analysis was undertaken to synthesise data from four observational studies conducted in Germany (TILOT, TiGER, TIL-SENIOR, TIL-TWO), each focusing on distinct psoriasis populations. This meta-analysis of four prospective multicentre non-interventional studies evaluated the effectiveness and safety of tildrakizumab in different patient populations with moderate-to-severe plaque psoriasis. Outcome parameters assessed at baseline, week 16 and 28 included absolute Psoriasis Area Severity Index (PASI) values, proportion of patients with PASI&#x2009;<&#x2009;1,&#x2009;<&#x2009;3,&#x2009;<&#x2009;5, PASI 75, PASI&#xa0;90 and PASI 100, body surface area (BSA), Physician's Global Assessment (PGA) 0/1 and Dermatology Life Quality Index (DLQI) 0/1. The meta-analysis was conducted using a random effects model. The meta-analysis included 1504 patients. The course of the absolute PASI and BSA and the proportion of patients achieving PASI&#x2009;<&#x2009;3, PASI 75, 90, 100, PGA 0/1 and DLQI 0/1 at week 28 was comparable across all four studies. Overall, mean PASI scores decreased from 16.5 (95% confidence intervals (CI) 15.8-17.3) at baseline to 2.8 (95% CI 2.5-3.0) at week 28. The proportion of patients with PGA 0/1 and DLQI 0/1 increased from 1.8% and 3.7% at baseline to 63.5% and 51.2% at week 28, respectively. No new safety signals were identified. Tildrakizumab showed consistent effectiveness across different study populations. Substantial effectiveness was achieved over 28&#xa0;weeks. Safety results were comparable across populations, without outliers in older patients or patients with higher disease burden. Graphical abstract available for this article. Psoriasis is a common chronic systemic inflammatory disease. It has a substantial impact on patients&#x2019; quality of life. Biological compounds such as tildrakizumab have become important treatment options in moderate-to-severe psoriasis. Once a medication is approved, it is important to understand how well a drug works in different types of patients, for example, in the older population, in people with higher body weight, people with psoriasis in sensitive areas such as the scalp and those suffering from particularly severe disease. To explore this, four observational studies were conducted including these patient groups. In the present analysis, we explored whether the effect of tildrakizumab was comparable between the different studies. In total, the four studies included 1504 patients. The results showed that tildrakizumab improved disease severity, reduced the size of affected skin areas and enhanced quality of life across all groups. These improvements were seen over a period of 28&#xa0;weeks, and safety results were in line with previous studies. Overall, the findings suggest that tildrakizumab can be beneficial for a wide range of patients with psoriasis, regardless of age, body weight or psoriasis severity.

This study explored the development of an amorphous solid dispersion (ASD) of ibuprofen (IBU) with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) using single screw hot-melt extrusion (HME), for obtaining solid-oral dosage forms (SODFs) with the aid of fused deposition modelling (FDM) 3D printing and conventional tabletting by direct compression, providing a head-to-head platform comparison. Pre-formulation studies identified a suitable IBU to HPMC-AS ratio for obtaining stable ASDs and allowed for the selection of HME conditions. HME was used to produce ASD filaments which were subsequently processed into solid dosage forms through 3D printing by FDM or conventional tableting by direct compression. Filaments containing HPMC-AS, IBU and additives: plasticisers (triethyl citrate (TEC) and polyethylene glycol (PEG)), superdisintegrants (Kollidon&#xae; CL), pore formers (sorbitol), or combinations of them were successfully extruded at 120-140&#xa0;&#xb0;C. Physicochemical characterisation confirmed IBU content and amorphisation. 3DP SODFs initially showed a slow, controlled dissolution compared to conventionally manufactured tablets; however, modifying the 3DP design to minimize print overlap and print thickness to 0.25&#xa0;mm while maximizing exposed surface area, as well as adjusting the formulation, significantly improved 3D printing performance and allowed for tuning of drug release. from 5% at 60&#xa0;min to 85% at 60&#xa0;min. Reduced print thickness (from 0.8 to 0.25&#xa0;mm) and limited print infill overlap, by using a "parallel" infill pattern rather than the commonly used "grid" infill had a greater influence on drug release than composition, for the 3DP samples, while the conventionally manufactured tablets showcased a consistent, rapid drug release. Overall, single screw HME effectively produced stable IBU:HPMCAS filaments suitable for FDM 3DP, that allowed for a tuneable drug release, offering a versatile alternative to conventional tabletting.

Sarcopenia has been reported that as a prognostic factor in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs), mainly based on retrospective, imaging-based analyses. However, its prognostic value has not been prospectively evaluated. In this prospective study we investigated the clinical impact of sarcopenia and explored circulating proteins associated with muscle loss and ICI outcomes. Patients with advanced NSCLC who received ICIs as first-line therapy were enrolled. Before treatment initiation, muscle mass was assessed using bioelectrical impedance analysis, together with grip strength, walking speed, and physical activity. Pretreatment plasma samples were subjected to comprehensive protein profiling. Between October 2019 and August 2022, 41 patients were enrolled. Bothe overall survival and progression-free survival were significantly shorter in patients with sarcopenia. Notably, patients with pre-sarcopenia, defined as reduced muscle mass without impairment of muscle strength or physical performance, also exhibited poor clinical outcomes. Protein analysis identified penraxin-3 as being significantly associated with muscle loss and overall survival. These findings demonstrate, for the first time in a prospective setting, that even pre-sarcopenia is associated with poor prognosis in NSCLC patients treated with ICIs, and suggest that pentraxin-3 may serve as a biomarker linking sarcopenia to unfavorable outcomes.

Advanced non-small cell lung cancer (NSCLC) has undergone a profound transformation over the past two decades through the integration of molecular diagnostics, targeted therapies, and immunotherapy into clinical practice. Despite these advances, access to modern diagnostics and treatments remains highly uneven across regions and health-care systems, leading to persistent global disparities in diagnostic accuracy, therapeutic options, and patient outcomes. This review explores diagnostic and therapeutic disparities in advanced NSCLC across high-, middle-, and low-income settings, a disease context that is increasingly dependent on timely access to molecularly guided treatment decisions. We describe regional and income-related differences in the availability and implementation of molecular diagnostics and novel systemic therapies, and discuss structural and systemic factors influencing access to innovation, including health-care infrastructure, regulatory environments, and resource constraints. By synthesizing evidence from international guidelines, real-world studies, and global oncology literature, this narrative review highlights how unequal adoption of advances in NSCLC care continues to contribute to outcome differences worldwide and identifies key challenges relevant to future efforts aimed at reducing inequities.