Oncologic Conditions Research Articles

Economic evaluation of Polygenic Risk Scores in healthcare interventions: a systematic review

Abstract Background Polygenic Risk Scores (PRS) quantify genetic susceptibility to diseases, promising personalized healthcare. This review explores current evidence regarding the economic evaluation of strategies based on PRS or other polygenic risk stratification approaches, scrutinizing their methodologies. Methods The study protocol was registered in PROSPERO (CRD42023442780). A systematic search in PubMed, Scopus, and Web of Science identified full economic evaluations of intervention based on polygenic risk stratification strategies. The quality of the included articles was assessed using the Drummond checklist. This study was supported by the EC and MUR under PNRR - M4C2-I1.3 Project PE_00000019 ‘HEAL ITALIA”. Results Nineteen articles were included in the analysis, with oncological conditions being the most frequently investigated (13), followed by cardiovascular conditions (3). In nearly 80% of the studies, PRS was employed for screening interventions, with the general population being the primary target in 14 out of the 19 studies. All the economic analysis models investigated cost-utility in terms of QALYs, with Markov models and microsimulations being the most common structures. The majority of these models were based on simulated cohorts derived mostly from North American or European data, with 9 adopting a healthcare system perspective and 6 a societal perspective. Although delivery strategies for PRS testing were rarely addressed, PRS costs were included in nearly all studies. Indirect costs were examined in fewer than half of the studies. In 12 out of 19 studies, the conclusions claimed the cost utility of PRS involving strategies. Conclusions Despite the technique’s potential, evaluations of various strategies based on PRS approaches yield heterogeneous conclusions regarding cost-utility. Our study highlights the factors contributing to this heterogeneity and underscores the need for further exploration, ideally prioritizing real-world data. Key messages • PRS strategies evaluations vary in cost-utility conclusions, highlighting the need for further investigation. • Real-world data and practical implications should be prioritised in PRS research.

Multilayer Nanocarrier for the Codelivery of Interferons: A Promising Strategy for Biocompatible and Long-Acting Antiviral Treatment

Background: Interferons (IFNs) are cytokines involved in the immune response with a synergistic regulatory effect on the immune response. They are therapeutics for various viral and proliferative conditions, with proven safety and efficacy. Their clinical application is challenging due to the molecules’ size, degradation, and pharmacokinetics. We are working on new drug delivery systems that provide adequate therapeutic concentrations for these cytokines and prolong their half-life in the circulation, such as nanoformulations. Methods: Through nanoencapsulation using electrospray technology and biocompatible and biodegradable polymers, we are developing a controlled release system based on nanoparticles for viral infections of the respiratory tract. Results: We developed a controlled release system for viral respiratory tract infections. A prototype nanoparticle with a core was created, which hydrolyzed the polyvinylpyrrolidone (PVP) shell , releasing the active ingredients interferon-alpha (IFN-α) and interferon-gamma (IFN-γ). The chitosan (QS) core degraded slowly, with a controlled release of IFN-α. The primary and rapid effect of the interferon combination ensured an antiviral and immunoregulatory response from day one, induced by IFN-α and enhanced by IFN-γ. The multilayer design demonstrated an optimal toxicity profile. Conclusions: This formulation is an inhaled dry powder intended for the non-invasive intranasal route. The product does not require a cold chain and has the potential for self-administration in the face of emerging viral infections. This novel drug has applications in multiple infectious, oncological, and autoimmune conditions, and further development is proposed for its therapeutic potential. This prototype would ensure greater bioavailability, controlled release, fewer adverse effects, and robust biological action through the simultaneous action of both molecules.

Y Reverse: Modified technique in challenging airway management.

Self-expanding Y-metal stents (SEMS) are best suited lesions with involvement of the carina and proximal main bronchi; however, Y-stents can be difficult to place. These difficulties guided us to develop a modification of the classic technique that addresses some of the challenges during positioning. We present the Y reverse technique for Y stent insertion using a combination of rigid and flexible bronchoscopy. This retrospective study included 15 consecutive patients, suffering from tracheal-carina-lower main bronchi complex, hospitalized at the Thoracic Surgery Unit of the Vanvitelli University of Naples between October 2021 and October 2023. patients in which the length of the stenosis of the right bronchi was greater than that of the left bronchi, advanced oncological conditions, severe respiratory failure; exclusion criteria: Karnofsky scale with <40 points. All patients were admitted to the hospital and treated with Y-stent insertion using the modified technique Y reverse. The comparison between the group undergoing the Y reverse technique with the group undergoing the traditional positioning of the Y prosthesis has shown an improvement in respiratory function; prolongation of the mean survival time; improvement in SpO2 in spontaneous breathing; reduction mean time procedure. p < 0.05 was considered as statistically significant. Y Reverse is a safe and effective procedure that provides rapid symptom relief in individuals who have critical central airway obstruction near the distal portion of the trachea, carina, and main right and left bronchi.

Failure Modes in Orthopedic Oncologic Reconstructive Surgery: A Review of Imaging Findings and Failure Rates.

Limb salvage surgeries utilizing endoprostheses and allografts are performed for a variety of oncologic conditions. These reconstructions can fail and require revision for many reasons, which are outlined and classified into mechanical failures (soft tissue failures, aseptic loosening, structural failure), non-mechanical failures (infection, tumor progression), and pediatric failures (physeal arrest, growth dysplasia). Distinct radiologic and clinical findings define specific failure subtypes but are sparsely illustrated in the radiology literature. Specifically, an understanding of the organizational structure of the failure modes can direct radiologists' search for post-reconstruction complications, enhance an appreciation of their prognostic significance, and facilitate research by standardizing the language and conceptual framework around outcomes. The purpose of this review is to highlight the key radiologic findings and imaging studies of each failure mode in orthopedic oncologic reconstructive surgery in the context of risk factors, failure rates, prognosis and survival statistics, and clinical decision-making regarding chemotherapy, radiation, and revision surgery.

Survival Dynamics of Invasive Fungal Diseases in Pediatric Hemato-Oncology Patients at a Tertiary Medical Facility in Mexico from July 2020 to July 2023

Abstract Background Invasive fungal diseases (IFD) have been increasing in prevalence over the past two decades, with filamentous fungi being the most common cause. However, candidiasis remains the predominant etiology of infection, especially in cases of neutropenic fever accompanied by neutropenic colitis. The prevalence of infections caused by Aspergillus species, Mucor species, Fusarium, and other species is higher among individuals with severe and extended neutropenia and those who have undergone hematopoietic progenitor cell transplantation. Methods A retrospective, descriptive, observational study was conducted to identify cases of patients diagnosed with invasive fungal diseases, categorizing them as possible, probable, or confirmed. In our comprehensive analysis of cases, we prioritize the examination of diseases induced by filamentous fungi, while considering the specific chemotherapy regimen administered and the particular oncological condition. Results The predominant etiology observed was invasive aspergillosis, followed by mucormycosis. A total of 18 cases suggestive of invasive Aspergillosis were identified, but clinical or histopathological investigations were not conducted due to limitations. The majority of cases were pulmonary, accounting for 92% of cases, while rhinosinusal involvement was identified in 8%. Factors such as clinical characteristics, imaging studies, serum galactomannan determination, and microbiological culture were considered. The patient survival rate was found to be 86.7%, with an average treatment duration of six weeks. A mortality rate of 3.7% was observed due to the underlying disease during the consolidation phase of invasive fungal diseases. Conclusion In our study, invasive aspergillosis emerged as the predominant invasive fungal disease in pediatric hemato-oncology patients. Despite challenges in conducting comprehensive investigations, our findings underscore the importance of timely diagnosis and management. The 86.7% survival rate reflects the efficacy of the treatment approach employed, while the observed mortality emphasizes the impact of underlying diseases on outcomes. This study contributes valuable insights to the understanding and improvement of survival dynamics in pediatric patients facing invasive fungal diseases.

Personalized Brachytherapy: Applications and Future Directions

Brachytherapy offers a highly conformal and adaptive approach to radiation therapy for various oncologic conditions. This review explores the rationale, applications, technological advances, and future directions of personalized brachytherapy. Integration of advanced imaging techniques, 3D-printed applicators, and artificial intelligence are rapidly enhancing brachytherapy delivery and efficiency, while genomic tests and molecular biomarkers are refining patient and dose selection. Emerging research on combining brachytherapy with immunotherapy offers unique synergistic potential, and technologies such as intensity-modulated and shielded brachytherapy applicators present novel opportunities to further optimize dose distributions. Despite these promising advances, the field faces challenges including a need to train more practitioners and develop new approaches to treating a broader range of malignancies. As personalized medicine evolves, brachytherapy’s ability to deliver highly targeted, individualized treatments positions it as a critical component in future cancer care.

Paraneoplastic systemic lupus erythematosus associated with dysgerminoma: a case report and literature review.

Rheumatic paraneoplastic syndromes are rare and generally occur no longer than two years before diagnosis of the associated malignancy. Therefore, it can be an essential clue to occult malignancy. A healthy 18-year-old female with no underlying diseases was referred to the rheumatology clinic due to morning stiffness in her hands and a new rash on her fingers. Her labs showed a positive ANA, anti-double strand DNA antibody, anti-RNP, and anti-ribosomal P. Nine months after the diagnosis with SLE, the patient presented with elevated levels of lactate dehydrogenase. A total-body computed tomography scan revealed a solid mass in the pelvis. The pathological findings corresponded to a dysgerminoma tumor. Following surgical tumor removal and chemotherapy, the patient went into remission with both SLE and her oncology conditions, with no relapse of her lupus symptoms in a one-year follow-up. This case underscores the importance of considering malignancy in unexplained lupus symptoms, a crucial point for all physicians to be aware of. We identified 13 cases of paraneoplastic SLE in a literature review. In most cases, SLE is resolved after the tumor has been treated.

Superscan Pattern on Bone Scintigraphy: A Comprehensive Review

Background/Objectives: The superscan pattern is a characteristic finding on bone scintigraphy, associated with a variety of metabolic bone diseases, malignancies, and other conditions. This pattern is characterized by a diffuse and intense uptake of radiotracer throughout the entire skeleton. Despite being a relatively rare finding, the superscan pattern can have significant clinical implications. Methods: This comprehensive review summarizes the available literature on the superscan pattern, focusing on its pathophysiology, clinical significance, and differential diagnoses. Relevant studies and case reports were analyzed to outline the diagnostic challenges associated with the interpretation of bone scintigraphy featuring the superscan pattern. Results: The literature highlights the clinical significance of the superscan pattern in various metabolic and oncologic conditions. Misinterpretation of this pattern can lead to diagnostic challenges, especially in distinguishing it from other pathologic conditions. Differential diagnosis remains crucial in the accurate interpretation and subsequent management of patients with this finding. Conclusions: This review provides a comprehensive overview of the superscan pattern on bone scintigraphy, aiming to assist clinicians in recognizing and managing this rare yet clinically important finding.

Synthesis of novel organophosphonate Schiff bases: A potential agents for post-cancer treatment and diabetics management

Schiff bases (SBs) and organophosphonates (OPs) are recognized for their extensive pharmaceutical applications; however, examples of compounds containing both functionalities are rarely reported. This study focuses on synthesizing novel phosphonate Schiff bases (PSBs) by condensing 3-amino benzoic acid with various aldehydes, followed by phosphorylation using triethylphosphite. This synthetic strategy and oxalyl chloride modification of the carboxyl group enabled incorporation of the phosphonate moiety without the need for NH₂ blocking agents, under mild, catalyst-free conditions. Twelve PSBs were synthesized and characterized using ¹H, ¹³C NMR, and HRMS. The compounds exhibited good to excellent yields. Biological evaluations showed significant cytotoxicity and α-glucosidase inhibitory activity. Specifically, compounds P1, P6, P8, and P9 demonstrated potent inhibition with IC₅₀ values of 9.40 ± 0.27, 6.88 ± 0.15, 5.20 ± 0.13, and 10.52 ± 0.26 µM, respectively. These results suggest that PSBs could be promising candidates for treating oncological and diabetic conditions. Advance in vivo studies and clinical trials are required to further establish their pharmacotherapeutic potential.

The future of diagnosis: artificial intelligence and advancing technologies in radiology

The transformative impact of AI on radiology extends across a broad spectrum from emergency cases to chronic diseases and oncological conditions. The documented successes underscore the critical role of ongoing research in this field, emphasizing its paramount importance in enhancing diagnostic accuracy, saving lives, and providing improved services to healthcare professionals

Male Fertility as a Proxy for Health.

Male fertility is affected by a wide range of medical conditions that directly and indirectly affect spermatogenesis. As such, it can be useful as both an indicator of current health and a predictive factor for future health outcomes. Herein, we discuss the current literature regarding the association between male fertility and systemic health conditions and exposures. We review the connection between male fertility and genetics, medications, diet, and environmental pollutants, as well as its effects on future oncologic, cardiovascular, and autoimmune conditions. Understanding this interplay will allow more health care providers to engage in health counseling that will not only improve men's reproductive outcomes but also their overall health.

Clinical and socio-demographic profile of children receiving pediatric palliative care in a tertiary hospital of a metropolitan city in India.

Pediatric palliative care is a holistic care of children suffering from life-threatening or life-limiting illnesses and encompasses care of a child's body, mind, and spirit and involves giving support to the family. According to the Global Atlas of Palliative Care, 6% of the global need for palliative care is in children. In order to provide palliative care, one needs to identify and diagnose the conditions requiring palliative care. There has always been a confusion in identifying pediatric conditions requiring palliative care. There is a lot of inconsistency in the diagnosis of such conditions particularly in pre-verbal patients. This study attempts to generate more data about the common palliative care conditions and complaints with which the children present to tertiary care hospitals. To study the socio-demographic details, clinical profile, CCC (complex chronic conditions) designation, and the ACT/ RCPCH (Association for Children with Life-threatening or Terminal Conditions and the Royal College of Pediatrics and Child Health) classification of children suffering from chronic conditions requiring palliative care. The study was conducted as a single-center retrospective observational study of pediatric patients enrolled for palliative care at a tertiary care hospital in a metropolitan city in India from 01.06.2021 to 31.06.2022. The total sample size was 400. The socio-demographic data and the clinical profile were recorded from the case records of all the 400 patients. Classification of the conditions was done as per the CCC as well as the ACT/ RCPCH classification system. The mean age in our study was 5.15years and there was a slighter male (59.5%) preponderance. They presented in OPDs with acute symptoms such as fatigue and fever, and they had other symptoms like tightness of the body, constipation, seizures, and difficulty in swallowing. Majority of the children (55%) were suffering from neurologic and neuromuscular conditions as per CCC followed by hematologic and immunologic conditions (10%). Category 4 (irreversible but non-progressive conditions causing severe disability, leading to susceptibility to health) was reported as the most common category according to the ACT/RCPCH. Conclusion: Children suffering from chronic disease conditions requiring palliative care usually suffer from multiple symptoms which affect their daily life. As most of the patients belong to category 4 according to ACT/RCPCH which is an irreversible but non-progressive life-limiting condition, the course of the disease is prolonged, therefore requiring comprehensive care and services for a long time. It is necessary to establish more pediatric palliative care units to address the needs of such children. What is known: • Pediatric palliative care is a specialized area within palliative care, which focusses on the needs of children with life-limiting illnesses. • Data on pediatric palliative care has largely been limited to oncological conditions. There is a paucity of literature documenting the needs among children suffering from non-cancerous chronic conditions. What is new: • This study provides vital information with respect to palliative care burden among children mainly suffering from non-oncological conditions. • It also provides clinical and socio-demographic profile of the children suffering from chronic life-limiting conditions requiring palliative care in a tertiary hospital setting in a LMIC (low- or middle-income country).

Falls among Pediatric Patients Receiving Home Care.

Children with medical complexity (CMC) often require home healthcare services to manage chronic health conditions. Evaluation of home safety is recommended when children transition from hospital to home care, though despite best efforts, safety events, such as falls, still occur. Understanding the prevalence and causal factors of falls in CMC is critical for the development of fall prevention interventions and protocols. This study aims to describe demographics and reasons for falls reported in CMC receiving home healthcare services. A retrospective analysis was performed using data from an incident reporting database from January 2019 to March 2023. Participants included CMC who received home healthcare services from a single institution and had at least one documented fall. A total of 43 falls were experienced by 31 unique participants. The participants were predominantly male (58.1%), White (71.0%), and non-Hispanic/Latino (96.8%), with a median age of 10 years at the time of the fall. Primary diagnoses of CMC with falls included neurological disorders (41.9%), congenital chromosomal abnormalities (25.8%), and oncological conditions (16.1%). The most common reasons for falls were loss of balance (32.6%), unknown factors (19.6%), and trip/slips (17.4%). Half of falls were deemed to be potentially preventable. This study provides valuable insight into falls among CMC receiving home healthcare services and emphasizes the multifactorial nature of fall risks in this population. Understanding demographic characteristics, diagnoses, and causal factors of falls is critical in the development of proactive fall prevention strategies. Responding proactively to mitigate fall risks is an important step in enhancing the safety and quality of life for CMC. Future collaborative research efforts are warranted to validate findings and evaluate potentially successful fall prevention interventions.

ATUALIZAÇÕES EM BIOMARCADORES PARA DIAGNÓSTICO PRECOCE DE DOENÇAS ÓSSEAS

Introduction: Biomarkers play a crucial role in the early identification of diseases and the assessment of treatment response. This study aims to explore the efficacy of different biomarkers in predicting and monitoring chronic diseases, with a focus on cardiovascular and oncological conditions. Methodology: A systematic review of studies published between 2010 and 2023 was conducted, analyzing the validity and applicability of specific biomarkers such as troponin, BNP (B-type natriuretic peptide), and CA-125. Randomized controlled trials, cohort studies, and meta-analyses were included. The quality of the studies was assessed using the Jadad scale and the Newcastle-Ottawa method. Results: The analyzed biomarkers showed high sensitivity and specificity for early diagnosis and monitoring of diseases. Troponin was particularly effective in detecting myocardial infarction, while BNP performed well in assessing heart failure. CA-125 was useful for monitoring ovarian cancer progression but had limitations in early detection. Discussion: The analysis indicates that biomarkers can provide valuable information for managing chronic diseases, improving diagnosis and treatment follow-up. However, the accuracy of biomarkers may be affected by variables such as comorbidities and individual patient characteristics. Further studies are needed to validate and refine the use of these biomarkers in different clinical contexts. Conclusion: Biomarkers are promising tools for the detection and monitoring of chronic diseases, with the potential to transform clinical practice. The implementation of biomarkers should be accompanied by further studies to ensure their efficacy and accuracy in various clinical scenarios.

A rare case report of paratesticular leiomyosarcoma

A leiomyosarcoma (LMS) is a malignant mesenchymal tumor of soft tissue that rarely presents in the scrotal region. This case report describes a primary paratesticular LMS originating in the dartos layer of the scrotum in a symptomatic 37-year-old male with a history of hypertension, generalized seizure disorder post-excision of meningioma, and an extensive family history of cancer. Primary paratesticular LMSs in the superficial dartos layer are exceedingly rare. Given the rarity of this particular type of LMS, this case report includes a discussion on its prevalence and incidence. The rarity of this tumor also warrants a review of the literature and related cases to inform the treatment plan and enhance understanding of these oncologic conditions.

Enhancing the Clinical Utility of Radiomics: Addressing the Challenges of Repeatability and Reproducibility in CT and MRI.

Radiomics, which integrates the comprehensive characterization of imaging phenotypes with machine learning algorithms, is increasingly recognized for its potential in the diagnosis and prognosis of oncological conditions. However, the repeatability and reproducibility of radiomic features are critical challenges that hinder their widespread clinical adoption. This review aims to address the paucity of discussion regarding the factors that influence the reproducibility and repeatability of radiomic features and their subsequent impact on the application of radiomic models. We provide a synthesis of the literature on the repeatability and reproducibility of CT/MR-based radiomic features, examining sources of variation, the number of reproducible features, and the availability of individual feature repeatability indices. We differentiate sources of variation into random effects, which are challenging to control but can be quantified through simulation methods such as perturbation, and biases, which arise from scanner variability and inter-reader differences and can significantly affect the generalizability of radiomic model performance in diverse settings. Four suggestions for repeatability and reproducibility studies are suggested: (1) detailed reporting of variation sources, (2) transparent disclosure of calculation parameters, (3) careful selection of suitable reliability indices, and (4) comprehensive reporting of reliability metrics. This review underscores the importance of random effects in feature selection and harmonizing biases between development and clinical application settings to facilitate the successful translation of radiomic models from research to clinical practice.

Non-Operating Room Anesthesia (NORA) for Ultrasound-Guided Liver Radiofrequency Ablation.

Percutaneous ultrasound-guided radiofrequency ablation (RFA) is a well-studied treatment option for locally non-advanced hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLMs). Sedation is of crucial interest as it enables safe and pain-free procedures. Whether the type of sedation has an impact on procedural outcome is still not well investigated. We retrospectively collected data on patients undergoing liver RFA for various oncological conditions. Procedures were conducted in a non-operating room anesthesia (NORA) setting. Procedural-related complications and short-term oncological outcomes were analyzed. Thirty-five patients (mean age 71.5 y, 80% male) were treated for HCC (26), CRLM (6) and gastric cancer metastases (3). Mean lesion size was 21 mm (SD ± 10.1 mm), and the most common tumor localization was the right hepatic lobe. RFA was performed in a step-up sedation approach, with subcutaneous lidocaine injection prior to needle placement and subsequent deep sedation during ablation. No anesthesia-related early or late complications occurred. One patient presented with pleural effusion due to a large ablation zone and was treated conservatively. Local tumor-free survival after 1 and 6 months was 100% in all cases where a curative RFA approach was intended. NORA for liver RFA comes with high patient acceptance and tolerance, and optimal postoperative outcomes and oncologic results.

Peripheral nervous system immune-related adverse events due to checkpoint inhibition.

Immune checkpoint inhibitors have revolutionized cancer therapy and are increasingly used to treat a wide range of oncological conditions, with dramatic benefits for many patients. Unfortunately, the resulting increase in T cell effector function often results in immune-related adverse events (irAEs), which can involve any organ system, including the central nervous system (CNS) and peripheral nervous system (PNS). Neurological irAEs involve the PNS in two-thirds of affected patients. Muscle involvement (immune-related myopathy) is the most common PNS irAE and can be associated with neuromuscular junction involvement. Immune-related peripheral neuropathy most commonly takes the form of polyradiculoneuropathy or cranial neuropathies. Immune-related myopathy (with or without neuromuscular junction involvement) often occurs along with immune-related myocarditis, and this overlap syndrome is associated with substantially increased mortality. This Review focuses on PNS adverse events associated with immune checkpoint inhibition. Underlying pathophysiological mechanisms are discussed, including antigen homology between self and tumour, epitope spreading and activation of pre-existing autoreactive T cells. An overview of current approaches to clinical management is provided, including cytokine-directed therapies that aim to decouple anticancer immunity from autoimmunity and emerging treatments for patients with severe (life-threatening) presentations.

Relating caregiver experiences to personalized "push" content in mobile applications among caregivers of pediatric patients with oncology conditions.

With the evolution of data algorithms and personalized push systems in mobile applications, patients who have searched for disease-related information may repeatedly receive similar content on app homepages or through notifications. This study aims to assess the influence of health-related content delivered through mobile applications on the anxiety and depression levels of caregivers of pediatric oncology patients. A survey consisting of 16 questions was conducted among 91 caregivers of pediatric oncology patients at the Children's Hospital affiliated with Chongqing Medical University. The questionnaire was designed by oncologists and the Hospital Anxiety and Depression Scale was used to assess the caregivers' psychological states. The study found that 31.5% of caregivers exhibited borderline anxiety symptoms, while 20.2% displayed borderline depression symptoms. Caregivers who noticed changes in homepage recommendations reported higher levels of anxiety (p=.004) and depression (p=.034). Additionally, 50.6% occasionally felt anxious or uneasy due to personalized notifications and 19.1% frequently felt this way. Moreover, 53.9% of the caregivers reported a negative impact on their emotions or daily life. Personalized push notifications related to disease information in mobile applications can impose a significant psychological burden on patients and their caregivers. Mobile application developers and healthcare providers must strengthen their support in the digital health domain to enhance the emotional well-being of cancer patients and their caregivers.

Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.

The Central Nervous System (CNS) is vulnerable to a range of diseases, including neurodegenerative and oncological conditions, which present significant treatment challenges. The blood-brain barrier (BBB) restricts molecule penetration, complicating the achievement of therapeutic concentrations in the CNS following systemic administration. Gene therapy using recombinant adeno-associated virus (rAAV) vectors emerges as a promising strategy for treating CNS diseases, demonstrated by the registration of six gene therapy products in the past six years and 87 ongoing clinical trials. This review explores the implementation of rAAV vectors in CNS disease treatment, emphasizing AAV biology and vector engineering. Various administration methods-such as intravenous, intrathecal, and intraparenchymal routes-and experimental approaches like intranasal and intramuscular administration are evaluated, discussing their advantages and limitations in different CNS contexts. Additionally, the review underscores the importance of optimizing therapeutic efficacy through the pharmacokinetics (PK) and pharmacodynamics (PD) of rAAV vectors. A comprehensive analysis of clinical trials reveals successes and challenges, including barriers to commercialization. This review provides insights into therapeutic strategies using rAAV vectors in neurological diseases and identifies areas requiring further research, particularly in optimizing rAAV PK/PD.