Chimeric Antigen Receptors (CAR) T-cell therapy is a ground-breaking discovery in immunotherapy, mainly known for its exceptional results in treating haematological malignancies. The latest research has revealed that the potential of CAR T-cell therapy extends far beyond its current capabilities and could represent a novel therapeutic approach for treating various cancers. This review aims to summarize the latest innovations in CAR T-cell therapy applied in cancer treatment, including multiple myeloma, osteosarcoma, glioblastoma, melanoma and various childhood malignancies. However, several challenges limit success of CAR T-cell therapy, including the antigen escape phenomenon, 'on-target off-tumour' toxicity, penetration into solid tumour tissue, alongside the cost-effectiveness concerns. The improvement of cancer immunotherapies currently available requires an increase in the effectiveness of CAR T-cells in managing refractory and solid cancers. This could be achieved by using CAR T-cells to target various antigens, enhancing their local delivery and tumour infiltration capabilities and utilizing CAR T-cells in combination with checkpoint blockade and immunotherapy, such as PD-1 blockade and CD19 CAR T-cell combined therapy. Although CAR T-cell treatment offers a lot of promise, its cost needs to be taken into account, especially in healthcare systems with limited funding. More importantly, frameworks for Health Technology Assessment (HTA) must adapt to incorporate ethical, sociological and psychological aspects. Reducing CAR T-cell toxicity is also essential, as it remains among biggest obstacles to their widespread application in clinical practice. Future research should therefore focus on enhancing our understanding of CAR T-cell therapy and expanding the application of immunotherapy in treatment.

ABSTRACT Introduction Interindividual variability in drug response remains a significant clinical challenge, leading to therapeutic failure and toxicity. Much of this variability is unexplained by classical host-centric pharmacokinetic (PK) models, highlighting a critical gap in understanding of drug disposition. This review addresses this gap by establishing the gut microbiome as an important determinant of drug fate. Areas covered This narrative review with scoping approach examines how microbial enzymes affect therapeutics through comprehensive analysis of mechanistic and clinical studies. Key examples discussed include irinotecan, digoxin, and sulfasalazine. We highlight specific situations where the influence of gut bacteria is particularly significant, such as with low-bioavailability drugs and in patients with an ileocolonic anastomosis, where gut bacteria directly impact drug absorption and metabolism. Additionally, we address the limitations of current PK models and explore the potential of new integrated approaches. Expert opinion We propose that the gut microbiome should be recognized as a ‘fifth pillar’ of PKs. This shift in perspective is crucial for advancing personalized medicine. In this new model, a ‘PK profile card’ integrating microbial, genomic, and clinical data will help guide dosing. We anticipate microbiome analysis to become a standard clinical tool to optimize drug efficacy and safety.

The exact cause of autism spectrum disorder (ASD) is yet unknown, although possible causes include early childhood, foetal development, gestation, delivery mode, genetics, and environmental variables. Approximately 1% of children worldwide have ASD, and this percentage is rising. The immunological, endocrine, gut microbiota and brain-gut axis quality influence the intensity of ASD symptoms. Deficits in the composition and diversity of gut microbiota are common in children with ASD, accounting for 9-90% of these illnesses, including elevated inflammatory cytokines, inflammation, leaky gut syndrome, and pathological microflora growth. Dysbiosis can be made worse by eating issues that are prevalent in ASD. B vitamins, such as cobalamin and folate, which are essential methyl donors for DNA epigenetic changes, are usually produced by a healthy gut microbiota. 50% of people with ASD have a vitamin B deficit. This work summarises research on the impact of gut microbiota on DNA methylation and B vitamin synthesis in ASD, as well as etiological variables connected to dysbiosis. Probiotics, postbiotics, and vitamin B therapies in kids with ASD should be investigated in future studies.

Background: All currently used therapeutic protocols and drugs for Clostridioides difficile infection (CDI) treatment do not have a satisfying success and usually cost a lot. Objectives: To compare the efficacy of vancomycin monotherapy vs modified dual therapy with vancomycin + nifuroxazide as a therapeutic protocol for a medium–severe form of CDI. In addition, the effects of a modified therapeutic protocol with standard monotherapy on the number of stools and stool consistency in a medium–severe CDI will be compared. Materials and Methods: A prospective, randomized, controlled clinical trial that included 60 patients divided into two groups was conducted. One group of patients was treated with vancomycin monotherapy. The other group was treated with the modified therapeutic protocol (vancomycin + nifuroxazide). Results: The modified therapy with vancomycin + nifuroxazide demonstrated enhanced pharmacological efficacy in the management of CDI compared to the standard vancomycin monotherapy. Patients treated with dual therapy reported a significantly lower number of stools in first, second and third control; first control (4.47 ± 2.20 compared to 5.70 ± 1.91 in vancomycin group (p = 0.024)), second control (2.37 ± 0.85 compared to 3.13 ± 0.90 in vancomycin group (p = 0.001)), and third control (1.53 ± 0.51 compared to 1.80 ± 0.61 in vancomycin group (p = 0.035)). Also, the first and third controls noted significant improvements in stool consistency, measured as a decrease in the number of completely watery stools (p = 0.011 and p < 0.001, respectively). Conclusions: Nifuroxazide and vancomycin have demonstrated accelerated improvement in patient status and hold promise as a novel dual therapeutic regimen for managing patients diagnosed with a medium–severe form of CDI.

Antibiotic-resistant bacteria are currently an important public health concern posing a serious threat due to their resistance to the current arsenal of antibiotics. Uropathogens Escherichia coli (UPEC), Proteus mirabilis, Klebsiella pneumoniae and Enterococcus faecalis, antibiotic-resistant gram-negative bacteria, cause serious cases of prolonged UTIs, increasing healthcare costs and potentially even leading to the death of an affected patient. This review discusses current knowledge about the increasing resistance to currently recommended antibiotics for UTI therapy, as well as novel therapeutic options. Traditional antibiotics are still a part of the therapy guidelines for UTIs, although they are often not effective and have serious side effects. Hence, novel drugs are being developed, such as combinations of β-lactam antibiotics with cephalosporins and carbapenems. Siderophoric cephalosporins, such as cefiderocol, have shown potential in the treatment of individuals with significant gram-negative bacterial infections, as well as aminoglycosides, fluoroquinolones and tetracyclines that are also undergoing clinical trials. The use of cranberry and probiotics is another potential curative and preventive method that has shown antimicrobial and anti-inflammatory effects. However, further studies are needed to assess the efficacy and safety of probiotics containing cranberry extract for UTI prevention and treatment. An emerging novel approach for UTI treatment is the use of immuno-prophylactic vaccines, as well as different nanotechnology solutions such as nanoparticles (Nanoparticles). Nanoparticles have the potential to be used as delivery systems for drugs to specific targets. Furthermore, nanotechnology could enable the development of nano antibiotics with improved features by the application of different Nanoparticles in their structure, such as gold and copper Nanoparticles. However, further high-quality research is required for the synthesis and testing of these novel molecules, such as safety evaluation and pharmacovigilance.

This study explores the anatomical relationship between iliac blood vessels and the lower lumbar spine during supine and prone patient positions. The average height of participants was 174.02 cm ± 9.01, while the average weight was 80.38 kg ± 13.48. Body mass index (BMI) analyses showed differences (p = 0.002), with 34.7% classified as normal weight, 53.1% as overweight, and 12.2% as moderately obese. The study examined the distances between iliac arteries and veins in relation to intervertebral anterior and posterior disc contours. Patient positioning significantly affected these measurements at both L4/L5 and L5/S1 levels. The findings highlight the critical influence of body position on anatomical relationships in the context of lower lumbar spine surgery. The study underscores the importance of preoperative awareness of vascular anatomy to prevent iatrogenic lesions during spine surgery, contributing valuable insights for optimizing surgical approaches and minimizing complications in spine surgery, particularly microdiscectomy.

Aim To investigate the correlation of body mass index (BMI) with severity of intervertebral disc degeneration. Methods The study enrolled patients who had undergone surgical intervention for a herniated disc at the Department of Neurosurgery of the Cantonal Hospital Zenica. Patients underwent thorough preoperative evaluation, including medical history, neurological and physical assessments, and radiological analysis. The surgical intervention consisted of a posterior lumbar discectomy, and the excised disc material was preserved and subjected to histopathological analysis based on Histopathologic Degeneration Score (HDS). Patients were divided in two groups according to Body Mass Index (BMI): study group with BMI≥25 and control group with BMI<25. Results Among 69 patients with herniated IVD, 26 (37.7%) were with BMI≥25 (study group), and 43 (62.3%) were with BMI<25 (controls). The study group displayed substantial increase in height, 1.80±0.06 m compared to controls, 1.74±0.06 m (p=0.001). Weight and BMI were significantly higher in the study group of patients (weight: 91.60±10.22 vs. 67.37±9.20 kg, BMI: 28±2 vs. 22±2; p<0.001). Differences were confirmed in HDS values in the study group comparing to the control group (p<0.001). The study group exhibited significant differences in chondrocyte proliferation, tears and clefts, granular changes, and mucous degeneration (p<0.05), and positive correlations were found between BMI and these alterations found in the herniated discs (p<0.05). Therefore, HDS showed positive correlations with BMI (R=0.599; p<0.001) and weight (R=0.696; p<0.001). Conclusion The study's findings confirmed that BMI has a significant impact on intervertebral disc degeneration, emphasizing the importance of weight management in preventing disc degeneration.

Background and Objectives: To investigate the role of augmented reality (AR) in skull base (SB) neurosurgery. Materials and Methods: Utilizing PRISMA methodology, PubMed and Scopus databases were explored to extract data related to AR integration in SB surgery. Results: The majority of 19 included studies (42.1%) were conducted in the United States, with a focus on the last five years (77.8%). Categorization included phantom skull models (31.2%, n = 6), human cadavers (15.8%, n = 3), or human patients (52.6%, n = 10). Microscopic surgery was the predominant modality in 10 studies (52.6%). Of the 19 studies, surgical modality was specified in 18, with microscopic surgery being predominant (52.6%). Most studies used only CT as the data source (n = 9; 47.4%), and optical tracking was the prevalent tracking modality (n = 9; 47.3%). The Target Registration Error (TRE) spanned from 0.55 to 10.62 mm. Conclusion: Despite variations in Target Registration Error (TRE) values, the studies highlighted successful outcomes and minimal complications. Challenges, such as device practicality and data security, were acknowledged, but the application of low-cost AR devices suggests broader feasibility.

This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing gene targets into distinct groups, this review explores their roles in cell cycle regulation, microenvironmental dynamics, interphase processes, and therapy resistance reduction. The complexity of CRISPR-Cas9 applications in GBM research is highlighted, providing unique insights into apoptosis, cell proliferation, and immune responses within the tumor microenvironment. The studies challenge conventional perspectives on specific genes, emphasizing the potential therapeutic implications of manipulating key molecular players in cell cycle dynamics. Exploring CRISPR/Cas9 gene therapy in GBMs yields significant insights into the regulation of cellular processes, spanning cell interphase, renewal, and migration. Researchers, by precisely targeting specific genes, uncover the molecular orchestration governing cell proliferation, growth, and differentiation during critical phases of the cell cycle. The findings underscore the potential of CRISPR/Cas9 technology in unraveling the complex dynamics of the GBM microenvironment, offering promising avenues for targeted therapies to curb GBM growth. This review also outlines studies addressing therapy resistance in GBM, employing CRISPR/Cas9 to target genes associated with chemotherapy resistance, showcasing its transformative potential in effective GBM treatments.

Drug-induced nephrotoxicity is still a significant obstacle in pharmacotherapy of various diseases and it accounts for around 25 % of serious side-effects reported after drug administration. Furthermore, some groups of drugs such as nonsteroidal anti-inflammatory drugs, antibiotics, antiviral drugs, antifungal drugs, immunosuppressants, and chemotherapeutic drugs have the "preference" for damaging the kidney and are often referred to as the kidney's "silent killer". Clinically, the onset of acute kidney injury associated with drug administration is registered in approximately 20 % of patients and many of them develop chronic kidney disease vulnerability. However, current knowledge about the mechanisms underlying this dangerous phenomenon is still insufficient with many unknowns. Hence, the valuable use of these drugs in clinical practice is significantly limited. The main aim of this study is to draw attention to commonly prescribed nephrotoxic drugs by clinicians or drugs bought over the counter. In addition, the complex relationship between immunological, vascular and inflammatory events that promote kidney damage is discussed. The practical use of this knowledge could be implemented in the engineering of novel biomarkers for early detection of drug-associated kidney damage such as Kidney Injury Molecule (KIM-1), lipocalin associated with neutrophil gelatinase (NGAL) and various microRNAs. In addition, the utilization of artificial intelligence (AI) for the development of computer algorithms that could detect kidney damage at an early stage should be further explored. Therefore, this comprehensive review provides a new outlook on drug nephrotoxicity that opens the door for further clinical research of novel potential drugs or natural products for the prevention of drug-induced nephrotoxicity and accessible education.

BACKGROUND Neuropathy is among the most often reported consequences of diabetes and the biggest cause of morbidity and mortality in people suffering from this life-long disease. Although different therapeutic methods are available for diabetic neuropathy, it is still the leading cause of limb amputations, and it significantly decreases patients' quality of life. AIM This study investigates potential novel therapeutic options that could ameliorate symptoms of DN. METHODOLOGY Research and review papers from the last 10 years were taken into consideration. RESULTS There are various traditional drugs and non-pharmacological methods used to treat this health condition. However, the research in the area of pathogenic-oriented drugs in the treatment of DN showed no recent breakthroughs, mostly due to the limited evidence about their effectiveness and safety obtained through clinical trials. Consequently, there is an urgent demand for the development of novel therapeutic options for diabetic neuropathy. CONCLUSION Some of the latest novel diagnostic methods for diagnosing diabetic neuropathy are discussed as well as the new therapeutic approaches, such as the fusion of neuronal cells with stem cells, targeting gene delivery and novel drugs.