According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected ...by tuberculosis, the emergence of Mycobacterium tuberculosis drug‐resistance is complicating tuberculosis control in many high‐burden countries. During the past 5 years, the global number of patients identified with multidrug‐resistant tuberculosis (MDR‐TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR‐TB. The management of MDR‐TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug‐resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor‐made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR‐TB. The challenge now is to bring these adances to those patients that need them most.
Content List ‐ Read more articles from the symposium: “The 10th International Conference on the Pathogenesis of Mycobacterial Infections”.
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.
To report a multicenter real-life experience of a ...group of patients with psoriasis undergoing treatment with guselkumab and a history of cancer.
We conducted a multicenter retrospective Spanish study enrolling patients with moderate-to-severe plaque psoriasis and neoplasia being treated with guselkumab for their psoriasis.
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.
Guselkumab not only demonstrates high efficacy in treating psoriasis but also exhibits a favorable safety profile in patients with neoplasms.
The purpose of this prospective registry case-series study was to determine the biological, mechanical, and aesthetic improvements made to the additively manufactured sub-periosteal jaw implant ...(AMSJI) after timed installation. A total of nine patients received maxillary AMSJIs in three sessions over a 2-year period. Architectural changes, topological optimization, and amendments to biofunctionalization were performed after each phase through the use of computer-aided design, finite element analysis, and growing clinical experience. Biological improvements included sandblasting (large grit alumina) and acid-etching; increased hydrophilicity by plasma surface activation; deletion of the crestal connecting struts; relocation of the anterior post in front of the anterior part of the basal loop; protection of the Schneiderian membrane from fixation screw penetration; high polishing of the posts; major platform switch with equigingival connections; the use of removable posts that require local anaesthesia and do not inflict major biological damage; scaffolding for secondary stability; and the provision of an incision guide. Mechanical improvements included the creation of a generic design based on finite element analysis and the resulting topological optimization, a shortening of the wings, and a reduction in the number of fixation screws. Aesthetic improvements included relocation of the anterior post, as described above, and pink anodization of the posts.
Today's Biochemical Engineer may contribute to advances in a wide range of technical areas. The recent Biochemical and Molecular Engineering XXI conference focused on “The Next Generation of ...Biochemical and Molecular Engineering: The role of emerging technologies in tomorrow's products and processes”. On the basis of topical discussions at this conference, this perspective synthesizes one vision on where investment in research areas is needed for biotechnology to continue contributing to some of the world's grand challenges.
This perspective discusses the present and future of biochemical engineering as a discipline. Several sub‐fields are highlighted.
Dasatinib is an oral second-generation tyrosine kinase inhibitor known to be used widely in Philadelphia chromosome-positive (Ph
) chronic myeloid leukemia (CML) and Ph
acute lymphoblastic leukemia ...(ALL). Notably, although a high pharmacokinetic variability in patients and an increased risk of pleural effusion are attendant, fixed dosing remains standard practice. Retrospective studies have suggested that dasatinib exposure may be associated with treatment response (efficacy/safety). Therapeutic drug monitoring (TDM) is gradually becoming a practical tool to achieve the goal of individualized medicine for patients receiving targeted drugs. With the help of TDM, these patients who maintain response while have minimum adverse events may achieve long-term survival. This review summaries current knowledge of the clinical pharmacokinetics variation, exposure-response relationships and analytical method for individualized dosing of dasatinib, in particular with respect to therapeutic drug monitoring. In addition, it highlights the emerging insights into several controversial issues in TDM of dasatinib, with the aim of presenting up-to-date evidence for clinical decision-making and insights for future studies.
Advances in radiogenomics in precision radiotherapy YE Fei, YU Ying
Ji chu yi xue yu lin chuang = Jichu yixue yu linchuang = Basic medical sciences and clinics,
05/2020, Letnik:
40, Številka:
5
Journal Article
Recenzirano
Odprti dostop
In the background of precision medicine, radiogenomics is a new strategy that combines radiomics and genomics for multi-omics research. It has unique advantages in predicting changes of genome ...expression and structure and establishing the physics model of radiobiology. Especially in terms of precision radiotherapy, a model of radiation genomics that encompasses the two dimensions of images-gene can provide multi-omics information and accurately guide clinical therapy, which increases the rate of patient survival and reduces the radiotherapy band coming complications.
Background: As drug-metabolizing enzyme activities are affected by a variety of factors, such as drug-drug interactions, a method to evaluate drug-metabolizing enzyme activities in real time is ...needed. In this study, we developed a novel SPECT imaging probe for evaluation of hepatic CYP2D activity. Methods: Iodine-123- and 125-labeled 4-iodobenzylmequitazine ( 123/125 I-BMQ) was synthesized with high labeling and purity. CYP isozymes involved in the metabolism of 125 I-BMQ in mouse liver microsomes were evaluated, and the utility of 123/125 I-was assessed from biological distribution and SPECT imaging evaluation in normal and CYP2D-inhibited mice. Results: In vitro metabolite analysis using mouse liver microsomes showed that 125 I-BMQ is specifically metabolized by CYP2D. Biological distribution and SPECT imaging of 123/125 I-BMQ in normal mice showed that injection 123/125 I-BMQ accumulated early in the liver and was excreted into the gallbladder and intestines. In CYP2D-inhibited mice, accumulation in the liver was increased, but accumulation in the gallbladder and intestines, the excretory organ, was delayed. Since only metabolites of 125 I-BMQ are detected in bile, visualization and measuring of the accumulation of metabolites over time in the intestine, where bile is excreted, could predict the amount of metabolites produced in the body and evaluate CYP2D activity, which would be useful in determining the dosage of various drugs metabolized by CYP2D. Conclusion: 123/125 I-BMQ is useful as a SPECT imaging probe for comprehensive and direct assessment of hepatic CYP2D activity in a minimally invasive and simple approach.
Purpose
Health-related quality of life (HRQL) instruments are essential in value-driven health care, but patients often have more specific, personal priorities when seeking surgical care. The ...Scoliosis Research Society-22R (SRS-22R), an HRQL instrument for spinal deformity, provides summary scores spanning several health domains, but these may be difficult for patients to utilize in planning their specific care goals. Our objective was to create preoperative predictive models for responses to individual SRS-22R questions at 1 and 2 years after adult spinal deformity (ASD) surgery to facilitate precision surgical care.
Methods
Two prospective observational cohorts were queried for ASD patients with SRS-22R data at baseline and 1 and 2 years after surgery. In total, 150 covariates were used in training machine learning models, including demographics, surgical data and perioperative complications. Validation was accomplished via an 80%/20% data split for training and testing, respectively. Goodness of fit was measured using area under receiver operating characteristic (AUROC) curves.
Results
In total, 561 patients met inclusion criteria. The AUROC ranged from 56.5 to 86.9%, reflecting successful fits for most questions. SRS-22R questions regarding pain, disability and social and labor function were the most accurately predicted. Models were less sensitive to questions regarding general satisfaction, depression/anxiety and appearance.
Conclusions
To the best of our knowledge, this is the first study to explicitly model the prediction of individual answers to the SRS-22R questionnaire at 1 and 2 years after deformity surgery. The ability to predict individual question responses may prove useful in preoperative counseling in the age of individualized medicine.
Graphic abstract
These slides can be retrieved under Electronic Supplementary Material.
Patients with deep brain stimulation devices highly benefit from postoperative MRI exams, however MRI is not readily accessible to these patients due to safety risks associated with RF heating of the ...implants. Recently we introduced a patient-adjustable reconfigurable coil technology that substantially reduced local SAR at tips of single isolated DBS leads during MRI at 1.5 T in 9 realistic patient models. This contribution extends our work to higher fields by demonstrating the feasibility of scaling the technology to 3T and assessing its performance in patients with bilateral leads as well as fully implanted systems. We developed patient-derived models of bilateral DBS leads and fully implanted DBS systems from postoperative CT images of 13 patients and performed finite element simulations to calculate SAR amplification at electrode contacts during MRI with a reconfigurable rotating coil at 3T. Compared to a conventional quadrature body coil, the reconfigurable coil system reduced the SAR on average by 83% for unilateral leads and by 59% for bilateral leads. A simple surgical modification in trajectory of implanted leads was demonstrated to increase the SAR reduction efficiency of the rotating coil to >90% in a patient with a fully implanted bilateral DBS system. Thermal analysis of temperature-rise around electrode contacts during typical brain exams showed a 15-fold heating reduction using the rotating coil, generating <1°C temperature rise during ∼4-min imaging with high-SAR sequences where a conventional CP coil generated >10°C temperature rise in the tissue for the same flip angle.
•Reconfigurable MRI technology for low-SAR imaging of deep brain stimulation implants.•Patient-adjustable MRI coils.•RF safety of bilateral isolated DBS leads and fully-implanted systems.•DBS surgical lead management for MRI safety.
The implementation of tailor-made dosage forms is currently one of the biggest challenges in the health sector. Over the last years, different approaches have been introduced to provide an individual ...and precise dispensing of the appropriate dose of an active pharmaceutical ingredient (API). A more recent approach, which has been intensively researched in the last years, is 3D-printing of medicines.
The aim of this work was to develop printing formulations free of organic solvents for a pressure-assisted microsyringe printing method (PAM), which should also be printable over several days of storage. Furthermore, the printed dosage forms should provide a sustained release of the incorporated API. A mixture of polyvinyl acetate/polyvinylpyrrolidone copolymer (PVAc-PVP), hydroxypropyl methylcellulose (HPMC) and highly dispersed silicon dioxide (SiO2) was found to be a feasible polymer matrix to achieve a sustained drug release. Levetiracetam (LEV) was used as model drug.
The printed formulations were analyzed regarding mass variation, friability and thickness. Furthermore, the dissolution behavior of freshly printed tablets and tablets printed from stored printing formulations were investigated. The dissolution profiles indicate that the dissolution of LEV could be modified by varying the amount of HPMC and by changing the infill design of tablets. Tablet-like geometries with an infill design of 0.35 mm and 5% HPMC released 50% of the incorporated drug after 4 h, while for tablets with a higher HPMC amount the release was decreased (10% HPMC: 5.5 h; 15% HPMC: 8 h). All printed tablets exhibit a friability < 0.5%, indicating that PAM printing is suitable for the manufacturing of tablets with a high structural integrity. Furthermore, this study demonstrates the ability of producing tablets with a uniform content and mass using PAM printing.
Display omitted
PDF
