Background: The treatment of psoriasis in patients with a personal history of cancer is a matter of debate and limited evidence is available to guide clinicians. Objectives: To report a multicenter ...real-life experience of a group of patients with psoriasis undergoing treatment with guselkumab and a history of cancer. Methods: We conducted a multicenter retrospective Spanish study enrolling patients with moderate-to-severe plaque psoriasis and neoplasia being treated with guselkumab for their psoriasis. Results: Twenty patients with moderate-to-severe psoriasis and at least 12 weeks of ongoing treatment were included. For the analysis, a 52 week follow-up period was evaluated in terms of efficacy and safety. Most of the malignancies in these patients were solid tumors. The percentage of patients achieving psoriasis area and severity index ≤3 at week 12 and week 52 was 80% and 87.5%, respectively, whereas 68.8% of patients achieved psoriasis area and severity index ≤1. A 52-week survival rate of 100% in the study population was observed (n = 20), including those patients with concomitant active cancers (n = 14). No adverse effects or dropouts related to guselkumab safety profile were detected. Limitations: Modest sample size and the retrospective nature of the study. Conclusion: Guselkumab not only demonstrates high effectiveness in treating psoriasis but also exhibits a favorable safety profile in patients with neoplasms.
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Interest in orodispersible films (ODF) is growing day-by-day, since this dosage form overcomes some therapeutic obstacles, such as impaired swallowing, and offers several benefits, ...such as the possibility to adapt the dosing requirements for a subset of patients. As a consequence, technologies to produce ODF have risen attention for possible applications in the development of patient-centric formulations. This review critically discusses current trends in the technology platforms proposed to manufacture ODF, including the innovation and opportunities to produce very small batches in a pharmacy setting. Although the main Pharmacopoeias recommend testing customized dosage forms for quality assurance, pharmaceutical assays are a matter of debate due to the complexity and high cost of conventional methods. Alternatively, non-disruptive online analytic methods can be proposed to assay ODF properties, above all to assure the uniformity of drug content.
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Trauma- and disease-related skeletal defects and illnesses are plaguing millions of people especially in an ageing globe. Recently, the convergence of additive manufacturing (AM) and ...bone tissue engineering (BTE) has opened up an era of “Personalized Bone Healthcare”, wherein “design”, “printing”, and “engineering” inputs are judiciously orchestrated to yield custom 3D architected (bio)scaffolds, per relevant AM paradigms, to address biological/pathological complexities of host tissues. In this review, a systematic overview of fundamental theories, recent advances, and future trends in this domain is provided. It starts with a general introduction to BTE and AM, followed by emergent topics, including: (i) the design and choices of biomaterials or bioinks for AM paradigms including acellular 3D printing, 3D bioprinting, 4D (bio)printing, and hierarchical printing; (ii) the utilization of computational tools, design–property relationships, and emerging metamaterial strategies to afford predictive, bionic or smart scaffold geometries; and (iii) the engineering of AM systems, processes, and printed parts, by hardware modification, technology fusion, or material functionalization. The ultimate goal is to produce (bio)scaffolds with customized/biomimetic form (geometry, hierarchy, heterogeneity, cellular microenvironments, etc.) and function. Subsequently, the state‐of‐the‐art orthopedic applications are summarized, covering interweaved frontiers of therapy and repair/regeneration. The convergence of AM and BTE as well as clinical translation are also discussed. Finally, current challenges and foreseeable opportunities are outlined to foster future growth. This panoramic review could provide helpful guidance for the design, development, and adoption of AM-based biomaterials for next-generation bone healthcare.
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The establishment of 3D-printing as manufacturing process for oral solid dosage forms enables new options for the individualized medicine.
The aim of this work was to develop a novel ...drug-printing model using pressure-assisted microsyringe (PAM) technology, which allows the precise dispensing of drug substances.
Printed tablets with different numbers of layers, mimicking different doses for pediatric subgroups, were analyzed regarding mass variation, friability, thickness and disintegration time. Furthermore, the uniformity of dosage units and the dissolution behavior were investigated.
Friability was <0.3% in all cases, which demonstrates the ability of PAM printing to manufacture robust solid dosage. Disintegration results showed the dependency of the disintegration on the number of layers and therefore on the compact mass of polymer. However, all tablets disintegrated within 3 min and fulfilled the requirements of immediate release tablets of the USP and orodispersible tablets according to the Ph. Eur. Results of uniformity dosage units confirmed the successful manufacturing of the intended individualized doses. Drug dissolution appeared to be dependent on the number of layers. An increase of layers resulted in a decrease of the drug release rate. Further, the drug release could be correlated to the surface area/volume (SA/V) ratio.
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Fast and accurate manufacturing of individually tailored solid dosage forms is one of the main challenges for personalized medicine. The use of 3D printers has recently been studied ...to determine their suitability for personalized drug manufacturing.
In the current work, formulations free of organic solvents were developed for a pressure-assisted microsyringe printing method (PAM). The water soluble polymer polyvinyl alcohol-polyethylene glycol graft copolymer (PVA-PEG) was used as matrix, while levetiracetam (LEV) was used as model drug. Furthermore, the influence of a second polymer, polyvinylpyrrolidone-vinyl acetate copolymer (PVP-PVAc) on the properties of the printed tablets was investigated. Tablets were printed using a 3D-Bioplotter. The printed formulations were analyzed regarding mass variation, friability and thickness. Furthermore, the disintegration behavior and dissolution profile were analyzed. Investigations of the dissolution profiles of printed tablets show that an immediate release of the API could be achieved. For tablets with PVA-PEG the drug is released completely within 10 min while the additional use of PVP-PVAc leads to a slightly delay with a complete release within 20 min. The same trend is observed regarding the disintegration time of printed tablets. Tablets with PVA-PEG disintegrated within 95 ± 10 s while tablets with additional PVP-PVAc disintegrated within 130 ± 20 s.
Friability of <0.5% indicate that the used PAM printing method provides tablets without loss of structural integrity during handling. Furthermore, it could be shown that the production of tablets with a good content uniformity using a 3D Bioplotter is suitable.
Antihistamines, especially H1 antihistamines, are widely used in the treatment of allergic diseases such as urticaria and allergic rhinitis, mainly for reversing elevated histamine and anti‐allergic ...effects. Antihistamines are generally safe, but some patients experience adverse reactions, such as cardiotoxicity, central inhibition and anticholinergic effects. There are also individual differences in antihistamine efficacy in clinical practice. The concept of individualized medicine has been deeply rooted in people's minds since it was put forward. Pharmacogenomics is the study of the role of inheritance in individual variations in drug response. In recent decades, pharmacogenomics has been developing rapidly, which provides new ideas for individualized medicine. Polymorphisms in the genes encoding metabolic enzymes, transporters and target receptors have been shown to affect the efficacy of antihistamines. In addition, recent evidence suggests that gene polymorphisms influence urticaria susceptibility and antihistamine therapy. Here, we summarize current reports in this area, aiming to contribute to future research in antihistamines and clinical guidance for antihistamines use in individualized medicine.
Parkinson’s: a syndrome rather than a disease? Titova, Nataliya; Padmakumar, C.; Lewis, Simon J. G. ...
Journal of Neural Transmission,
08/2017, Letnik:
124, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain ...neuronal networks lead to a syndrome that is commonly known as Parkinson’s disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson’s to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson’s is a multi-organ disorder. The Parkinson’s phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.
See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, ...perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions.
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•Gastroretentive floating tablets were developed using HME coupled FDM 3D printing.•HPC and PVP VA 64 in combination produced 3D printable filaments.•Extruded filaments possessed good ...mechanical strength suitable for 3D printing.•3D design of tablets has significant impact on drug release characteristics.•Buoyancy kinetics of 3D printed floating tablets.
Three-dimensional printing could serve as a platform to fabricate individualized medicines and complex-structured solid dosage forms. Herein, hot melt extrusion was coupled with 3D printing to develop a unique gastro retentive dosage form to personalize treatment of cinnarizine or other narrow absorption window drugs. The mechanical strength of the extruded strands was optimized for printing by combining two polymers, hydroxypropyl cellulose and vinylpyrrolidone vinyl acetate copolymer. The unit dose, floating force, and release profile were controlled by the printing parameters and object design. The tablets floated immediately within the FaSSGF, and floating force was relatively constant up to 12 h. Drug release followed zero-order kinetics and could be controlled from 6 h to ≥ 12 h. Input variables had a good correlation (R > 0.95) with unit dose, floating force, and dissolution profile (p < 0.05). Authors successfully proposed and tested a new paradigm of individualized medicine fabrication to meet individual patient needs.
A major barrier to effective treatment of glioblastoma (GBM) is the large intertumoral heterogeneity at the genetic and cellular level. In early phase clinical trials, patient heterogeneity in ...response to therapy is commonly observed; however, how tumor heterogeneity is reflected in individual drug sensitivities in the treatment-naïve glioblastoma stem cells (GSC) is unclear.
We cultured 12 patient-derived primary GBMs as tumorspheres and validated tumor stem cell properties by functional assays. Using automated high-throughput screening (HTS), we evaluated sensitivity to 461 anticancer drugs in a collection covering most FDA-approved anticancer drugs and investigational compounds with a broad range of molecular targets. Statistical analyses were performed using one-way ANOVA and Spearman correlation.
Although tumor stem cell properties were confirmed in GSC cultures, their in vitro and in vivo morphology and behavior displayed considerable tumor-to-tumor variability. Drug screening revealed significant differences in the sensitivity to anticancer drugs (p < 0.0001). The patient-specific vulnerabilities to anticancer drugs displayed a heterogeneous pattern. They represented a variety of mechanistic drug classes, including apoptotic modulators, conventional chemotherapies, and inhibitors of histone deacetylases, heat shock proteins, proteasomes and different kinases. However, the individual GSC cultures displayed high biological consistency in drug sensitivity patterns within a class of drugs. An independent laboratory confirmed individual drug responses.
This study demonstrates that patient-derived and treatment-naïve GSC cultures maintain patient-specific traits and display intertumoral heterogeneity in drug sensitivity to anticancer drugs. The heterogeneity in patient-specific drug responses highlights the difficulty in applying targeted treatment strategies at the population level to GBM patients. However, HTS can be applied to uncover patient-specific drug sensitivities for functional precision medicine.
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