The importance of early cancer diagnosis and improved cancer therapy has been clear for years and has initiated worldwide research towards new possibilities in the care strategy of patients with cancer using technological innovations. One of the key research fields involves the separation and detection of circulating tumor cells (CTC) because of their suggested important role in early cancer diagnosis and prognosis, namely, providing easy access by a liquid biopsy from blood to identify metastatic cells before clinically detectable metastasis occurs and to study the molecular and genetic profile of these metastatic cells. Provided the opportunity to further progress the development of technology for treating cancer, several CTC technologies have been proposed in recent years by various research groups and companies. Despite their potential role in cancer healthcare, CTC methods are currently mainly used for research purposes, and only a few methods have been accepted for clinical application because of the difficulties caused by CTC heterogeneity, CTC separation from the blood, and a lack of thorough clinical validation. Therefore, the standardization and clinical application of various developed CTC technologies remain important subsequent necessary steps. Because of their suggested future clinical benefits, we focus on describing technologies using whole blood samples without any pretreatment and discuss their advantages, use, and significance. Technologies using whole blood samples utilize size-based, immunoaffinity-based, and density-based methods or combinations of these methods as well as positive and negative enrichment during separation. Although current CTC technologies have not been truly implemented yet, they possess high potential as future clinical diagnostic techniques for the individualized therapy of patients with cancer. Thus, a detailed discussion of the clinical suitability of these new advanced technologies could help prepare clinicians for the future and can be a foundation for technologies that would be used to eliminate CTCs in vivo.

The aim of this review is to evaluate the present status of the use of cell-free DNA and its fraction of circulating tumor DNA (ctDNA) because this year July 2022, an ESMO guideline was published regarding the application of ctDNA in patient care. This review is for clinical oncologists to explain the concept, the terms used, the pros and cons of ctDNA; thus, the technical aspects of the different platforms are not reviewed in detail, but we try to help in navigating the current knowledge in liquid biopsy. Since the validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, ctDNA may be used for this soon in routine clinical practice and in other different areas as well. The cfDNA fragments can be obtained by liquid biopsy and can be used for diagnosis, prognosis, and selecting among treatment options in cancer patients. A great proportion of cfDNA comes from normal cells of the body or from food uptake. Only a small part (<1%) of it is related to tumors, originating from primary tumors, metastatic sites, or circulating tumor cells (CTCs). Soon the data obtained from ctDNA may routinely be used for finding minimal residual disease, detecting relapse, and determining the sites of metastases. It might also be used for deciding appropriate therapy, and/or emerging resistance to the therapy and the data analysis of ctDNA may be combined with imaging or other markers. However, to achieve this goal, further clinical validations are inevitable. As a result, clinicians should be aware of the limitations of the assays. Of course, several open questions are still under research and because of it cfDNA and ctDNA testing are not part of routine care yet.

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis. In addition, 60–80% of patients express anti-citrullinated protein antibodies (ACPAs), which serve as a diagnostic marker for RA. The effector functions of these autoantibodies can be heavily affected by the N-glycosylation of their Fc region. Here we present a comparison of the Fc N-glycosylation of ACPA IgG to that of non-ACPA IgG from the same patients, and of healthy controls, in an IgG isoform-specific manner. We isolated ACPA and normal serum IgG, digested by trypsin, and separated the resulting peptide mixture by a reversed-phase nanoLC coupled to a Bruker Maxis II Q-TOF, and determined the relative abundance of glycoforms. The paired analysis of galactosylation and sialylation of the IgG subclasses of ACPA and non-ACPA IgG has shown a significant, moderate negative correlation with the inflammatory markers, the level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as with rheuma-factor (RF), but not with the disease activity score (DAS) or cyclic citrullinated peptide specific antibodies (anti-CCP). However, we detected a significant negative correlation between glycosylation and DAS in the non-ACPA IgG fractions. Furthermore, the isoform-specific analysis revealed additional insight into the changes of the glycosylation features of IgG in RA: changes in the frequencies of the bisecting GlcNAc unit between sample groups could be explained by only the IgG1 isoform; while invariance in fucosylation is the result of the superposition of two isoforms with opposite changes. These results highlight the importance of analyzing immunoglobulin glycosylation in an isoform-specific manner.

The proportion of elderly patients is getting increased in the developed countries as a consequence of which pharmacotherapy takes a more and more important place in the healthcare system. Important biological alterations are characteristic for the elderly subjects, which have effect on the pharmacokinetics and pharmacodynamics of the pharmaceuticals. Gradually decreased kidney function may demand the modification of the administration of the pharmaceuticals. Certain pharmaceuticals and drug-interactions are potentially dangerous for this population. Therefore several factors have to be taken into account in conjunction with the therapy of elderly patients including co-morbidities, cognitive function and the social state. At the same time, the risk–benefit ratio of the pharmaceuticals is the worst among elderly patients with pharmaceutical therapy including polypragmasy. Thus, it is inevitable for the development of geriatric pharmacotherapy that the physiologic alteration of elderly has to be taken into account not only in the daily practice but also during the development and formulation of a pharmaceutical. The present paper gives an overview of the most important factors influencing the pharmacotherapy of the elderly. Orv Hetil. 2019; 160(23): 896–907.