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Simple Summary: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies but is often associated with significant adverse events. As these events affect up to 80% of patients, they constitute a crucial problem to overcome. This review focuses on the monitoring process of CAR-T cell therapy including the monitoring of the persistence, activity, and phenotyping of the cells. The implementation of tools like flow cytometry and polymerase chain reaction provides insights into cellular responses, enabling the optimization of CAR-T cell therapy for more precise and personalized treatment and addressing the challenge of tumor relapse. Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment for relapsed/refractory B-cell lymphomas. Despite its success, this therapy is accompanied by a significant frequency of adverse events, including cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), or cytopenias, reaching even up to 80% of patients following CAR-T cell therapy. CRS results from the uncontrolled overproduction of proinflammatory cytokines, which leads to symptoms such as fever, headache, hypoxia, or neurological complications. CAR-T cell detection is possible by the use of flow cytometry (FC) or quantitative polymerase chain reaction (qPCR) assays, the two primary techniques used for CAR-T evaluation in peripheral blood, bone marrow (BM), and cerebrospinal fluid (CSF). State-of-the-art imaging technologies play a crucial role in monitoring the distribution and persistence of CAR-T cells in clinical trials. Still, they can also be extended with the use of FC and digital PCR (dPCR). Monitoring the changes in cell populations during disease progression and treatment gives an important insight into how the response to CAR-T cell therapy develops on a cellular level. It can help improve the therapeutic design and optimize CAR-T cell therapy to make it more precise and personalized, which is crucial to overcoming the problem of tumor relapse. [ABSTRACT FROM AUTHOR]

Patients with unstable angina present clinical characteristics of atherosclerotic plaque vulnerability, contrary to chronic coronary syndrome patients. The process of athersclerotic plaque destabilization is also regulated by microRNA particles. In this study, the investigation on expression levels of microRNAs inhibiting the expression of proteins that protect from atherosclerotic plaque progression (miR-92a inhibiting KLF2, miR-10b inhibiting KLF4, miR-126 inhibiting MerTK, miR-98 inhibiting IL-10, miR-29b inhibiting TGFβ1) was undertaken. A number of 62 individuals were enrolled—unstable angina (UA, n = 14), chronic coronary syndrome (CCS, n = 38), and healthy volunteers (HV, n = 10). Plasma samples were taken, and microRNAs expression levels were assessed by qRT-PCR. As a result, the UA patients presented significantly increased miR-10b levels compared to CCS patients (0.097 vs. 0.058, p = 0.033). Moreover, in additional analysis when UA patients were grouped together with stable patients with significant plaque in left main or proximal left anterior descending ("UA and LM/proxLAD" group, n = 29 patients) and compared to CCS patients with atherosclerotic lesions in other regions of coronary circulation ("CCS other" group, n = 25 patients) the expression levels of both miR-10b (0.104 vs. 0.046; p = 0.0032) and miR-92a (92.64 vs. 54.74; p = 0.0129) were significantly elevated. In conclusion, the study revealed significantly increased expression levels of miR-10b and miR-92a, a regulator of endothelial protective KLF factors (KLF4 and KLF2, respectively) in patients with more vulnerable plaque phenotypes. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T-cell (CAR-T) therapy is a novel anticancer therapy using autologous or allogeneic T-cells. To date, six CAR-T therapies for specific B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphomas (NHL), and multiple myeloma (MM) have been approved by the Food and Drug Administration (FDA). Significant barriers to the effectiveness of CAR-T therapy include cytokine release syndrome (CRS), neurotoxicity in the case of Allogeneic Stem Cell Transplantation (Allo-SCT) graft-versus-host-disease (GVHD), antigen escape, modest antitumor activity, restricted trafficking, limited persistence, the immunosuppressive microenvironment, and senescence and exhaustion of CAR-Ts. Furthermore, cancer drug resistance remains a major problem in clinical practice. CAR-T therapy, in combination with checkpoint blockades and bispecific T-cell engagers (BiTEs) or other drugs, appears to be an appealing anticancer strategy. Many of these agents have shown impressive results, combining efficacy with tolerability. Biomarkers like extracellular vesicles (EVs), cell-free DNA (cfDNA), circulating tumor (ctDNA) and miRNAs may play an important role in toxicity, relapse assessment, and efficacy prediction, and can be implicated in clinical applications of CAR-T therapy and in establishing safe and efficacious personalized medicine. However, further research is required to fully comprehend the particular side effects of immunomodulation, to ascertain the best order and combination of this medication with conventional chemotherapy and targeted therapies, and to find reliable predictive biomarkers. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut–brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1β (IL-1β), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers. [ABSTRACT FROM AUTHOR]

Podophyllotoxin (PPT) is an active pharmaceutical ingredient (API) with established antitumor potential. However, due to its systemic toxicity, its use is restricted to topical treatment of anogenital warts. Less toxic PPT derivatives (e.g., etoposide and teniposide) are used intravenously as anticancer agents. PPT has been exploited as a scaffold of new potential therapeutic agents; however, fewer studies have been conducted on the parent molecule than on its derivatives. We have undertaken a study of ultrastructural changes induced by PPT on HaCaT keratinocytes. We have also tracked the intracellular localization of PPT using its fluorescent derivative (PPT-FL). Moreover, we performed molecular docking of both PPT and PPT-FL to compare their affinity to various binding sites of tubulin. Using the Presto blue viability assay, we established working concentrations of PPT in HaCaT cells. Subsequently, we have used selected concentrations to determine PPT effects at the ultrastructural level. Dynamics of PPT distribution by confocal microscopy was performed using PPT-FL. Molecular docking calculations were conducted using Glide. PPT induces a time-dependent cytotoxic effect on HaCaT cells. Within 24 h, we observed the elongation of cytoplasmic processes, formation of cytoplasmic vacuoles, progressive ER stress, and shortening of the mitochondrial long axis. After 48 h, we noticed disintegration of the cell membrane, progressive vacuolization, apoptotic/necrotic vesicles, and a change in the cell nucleus's appearance. PPT-FL was detected within HaCaT cells after ~10 min of incubation and remained within cells in the following measurements. Molecular docking confirmed the formation of a stable complex between tubulin and both PPT and PPT-FL. However, it was formed at different binding sites. PPT is highly toxic to normal human keratinocytes, even at low concentrations. It promptly enters the cells, probably via endocytosis. At lower concentrations, PPT causes disruptions in both ER and mitochondria, while at higher concentrations, it leads to massive vacuolization with subsequent cell death. The novel derivative of PPT, PPT-FL, forms a stable complex with tubulin, and therefore, it is a useful tracker of intracellular PPT binding and trafficking. [ABSTRACT FROM AUTHOR]

Aim of study. The Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD) is a novel, disease-specific self-report questionnaire used to quantitatively assess features of gastrointestinal dysfunction symptoms in patients with Parkinson's Disease. The aim of this paper was to validate the Polish translation of the scale, to summarise its consistency with the English language version, and to assess its clinimetric properties. Clinical rationale for study. Gastrointestinal dysfunction is a common and often debilitating manifestation of Parkinson's Disease (PD). Gastrointestinal symptoms are also considered to be prodromal features of this disease. To date, there has been no scale in Polish that has precisely assessed gastrointestinal symptoms in patients with PD. Material and methods. The GIDS-PD was translated into Polish by two investigators (M.K. and J.N.). A back-translation was completed by two separate investigators (M.F. and A.A.) who were not involved in the original translation. Afterwards, 10 Polish PD patients underwent cognitive pre-testing. After the final translation was officially approved by the Movement Disorder Society, it was tested on 64 individuals with PD during field testing. For the purpose of testing scale reliability, 20 of the patients recruited for field testing underwent the GIDS-PD for a second time after 8-12 weeks. Results. The GIDS-PD demonstrated overall good consistency (Cronbach's alpha of 0.74, ICC of 0.74). Regarding the individual domains, the constipation subscore demonstrated good reliability, the bowel irritability subscore demonstrated moderate reliability, and the upper GI subscore demonstrated poor reliability. Upper GI symptoms seem to be less pronounced, and also more varied, in the Polish PD population than in its English language counterpart. Conclusions and clinical implications. This paper provides a validated Polish translation of the GIDS-PD questionnaire. We highly recommend using the GIDS-PD for research purposes, as well as everyday clinical practice in the Polish PD population. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease driven by lipid accumulation in the arteries, leading to narrowing and thrombosis that causes mortality. Emerging evidence has confirmed that atherosclerosis affects younger people and is involved in the majority of deaths worldwide. EVs are associated with critical steps in atherosclerosis, cholesterol metabolism, immune response, endothelial dysfunction, vascular inflammation, and remodeling. Endothelial cell-derived EVs can interact with platelets and monocytes, thereby influencing endothelial dysfunction, atherosclerotic plaque destabilization, and the formation of thrombus. EVs are potential diagnostic and prognostic biomarkers in atherosclerosis (AS) and cardiovascular disease (CVD). Importantly, EVs derived from stem/progenitor cells are essential mediators of cardiogenesis and cardioprotection and may be used in regenerative medicine and tissue engineering. [ABSTRACT FROM AUTHOR]

Competing Interests: Funding Support and Author Disclosures This study was supported by the National Institute of Cardiology in Warsaw, Poland (Grant 4.44/VI/21). Dr Sondergaard is the Chief Medical Officer and Divisional Vice President for Medical Affairs at Abbott Structural Heart. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Percutaneous coronary interventions (PCI) are the cornerstone of treatment in patients with coronary artery disease, generating substantial costs for the healthcare system. Considerable improvements in PCI technique, stent technology, and antiplatelet therapy led to a complication rate of <5%, a success rate of >95%, and lack of routine cardiothoracic surgical support. Thereby, the concept of same-day discharge following PCI has been proposed due to comparable efficacy, safety, and socioeconomic benefits of inpatient PCI. Although single-vessel disease was the primary indication for outpatient (OP) PCI, more complex scenarios such as multivessel disease, left main disease, and chronic total occlusions were also shown to be feasible and safe in the OP setting. Currently, available data show that OP PCI leads to cost optimization, increased capacity of PCI centers, decrease in the nosocomial infections rate, and increased patient satisfaction, along with good clinical outcomes. Although OP PCI seems promising in a subset of well-prepared and compliant patients without severe comorbidities, there are some challenges to overcome before its routine implementation. To prevent unnecessary hospitalization and unsafe same-day discharges, interventional cardiology teams should be trained to perform reliable risk-benefit assessments. Standardized forms should be created to obtain informed consent and instruct OP PCI patients and their relatives about postprocedural management. Here, we summarize the available data on OP and inpatient PCI outcomes, discuss the opportunities and challenges of OP PCI, and propose a periprocedural patient management checklist to facilitate the implementation of OP PCI in interventional cardiology centers.

Aim of Study: The Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD) is a novel, disease-specific self-report questionnaire used to quantitatively assess features of gastrointestinal dysfunction symptoms in patients with Parkinson's Disease. The aim of this paper was to validate the Polish translation of the scale, to summarise its consistency with the English language version, and to assess its clinimetric properties., Clinical Rationale for Study: Gastrointestinal dysfunction is a common and often debilitating manifestation of Parkinson's Disease (PD). Gastrointestinal symptoms are also considered to be prodromal features of this disease. To date, there has been no scale in Polish that has precisely assessed gastrointestinal symptoms in patients with PD., Material and Methods: The GIDS-PD was translated into Polish by two investigators (M.K. and J.N.). A back-translation was completed by two separate investigators (M.F. and A.A.) who were not involved in the original translation. Afterwards, 10 Polish PD patients underwent cognitive pre-testing. After the final translation was officially approved by the Movement Disorder Society, it was tested on 64 individuals with PD during field testing. For the purpose of testing scale reliability, 20 of the patients recruited for field testing underwent the GIDS-PD for a second time after 8-12 weeks., Results: The GIDS-PD demonstrated overall good consistency (Cronbach's alpha of 0.74, ICC of 0.74). Regarding the individual domains, the constipation subscore demonstrated good reliability, the bowel irritability subscore demonstrated moderate reliability, and the upper GI subscore demonstrated poor reliability. Upper GI symptoms seem to be less pronounced, and also more varied, in the Polish PD population than in its English language counterpart., Conclusions and Clinical Implications: This paper provides a validated Polish translation of the GIDS-PD questionnaire. We highly recommend using the GIDS-PD for research purposes, as well as everyday clinical practice in the Polish PD population.