CRISPR-Cas9 system: a novel and promising era of genotherapy for beta-hemoglobinopathies, hematological malignancy, and hemophilia.

Gene therapy represents a significant potential to revolutionize the field of hematology with applications in correcting genetic mutations, generating cell lines and animal models, and improving the feasibility and efficacy of cancer immunotherapy. Compared to different genetic engineering tools, clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (Cas9) emerged as an effective and versatile genetic editor with the ability to precisely modify the genome. The applications of genetic engineering in various hematological disorders have shown encouraging results. Monogenic hematological disorders can conceivably be corrected with single gene modification. Through the use of CRISPR-CAS9, restoration of functional red blood cells and hemostasis factors were successfully attained in sickle cell anemia, beta-thalassemia, and hemophilia disorders. Our understanding of hemato-oncology has been advanced via CRIPSR-CAS9 technology. CRISPR-CAS9 aided to build a platform of mutated genes responsible for cell survival and proliferation in leukemia. Therapeutic application of CRISPR-CAS9 when combined with chimeric antigen receptor (CAR) T cell therapy in multiple myeloma and acute lymphoblastic leukemia was feasible with attenuation of CAR T cell therapy pitfalls. Our review outlines the latest literature on the utilization of CRISPR-Cas9 in the treatment of beta-hemoglobinopathies and hemophilia disorders. We present the strategies that were employed and the findings of preclinical and clinical trials. Also, the review will discuss gene engineering in the field of hemato-oncology as a proper tool to facilitate and overcome the drawbacks of chimeric antigen receptor T cell therapy (CAR-T).

Overview of Paraneoplastic Autoantibody-Mediated Cognitive Impairment and Behavioral Changes: A Narrative Review.

Cognitive dysfunction and behavioral change can be some of the manifestations of cancer, occurring as a part of paraneoplastic neurological syndrome, most commonly in small cell lung cancer. Paraneoplastic limbic encephalitis is the leading cause of cognitive disturbance and abnormal behavior in paraneoplastic syndromes, which is usually autoantibody-mediated. Autoantibodies are the main contributors to the development of cognitive dysfunction and behavioral change in cancer patients, with studies suggesting a higher liability for antibody-positive cancer patients to be affected. Anti-NMDAR and anti-AMPAR are antibodies targeted against surface antigens, manifesting predominantly as memory disturbance, abnormal behavior, psychiatric symptoms, and seizures. Other surface antigen-targeted antibodies include anti-GABA, anti-CASPR2, and anti-LGI1, which were shown to have cognitive function impairment and abnormal behavior as some of the main presentations, predominantly affecting memory. Cognitive deterioration and changes in behavior were also relatively common with some of the intracellular antigen-targeted antibodies, including anti-Hu, anti-SOX1, anti-PCA2, and anti-Zic2. Affected behavior and cognition, however, were reported less commonly in other paraneoplastic antibodies against intracellular antigens (anti-Yo, anti-GAD, anti-Ma2, anti-Ri, anti-CV2, and anti-KLHL11). Our article will provide a comprehensive review of the clinical manifestations of cognitive impairment and behavioral changes among cancer patients who develop paraneoplastic syndrome. Additionally, this review will discuss the role of specific paraneoplastic autoantibodies and the clinical spectrum linked to each separately.

Clinical Patterns and Factors Contributing to Ophthalmic and Otologic Events Associated With Immune Checkpoint Inhibitors: A Narrative Review.

Immune checkpoint inhibitors, which are a type of cancer immunotherapy, have been associated with the development of adverse events related to an overactive immune system caused by the effect of this type of therapy. It affects a wide range of organs, including the ear and eye. Ophthalmic toxicity related to immune checkpoint inhibitors usually occurs bilaterally. Corneal toxicity (mainly dry eye disease) and uveitis are the most commonly reported patterns of toxicity. Other patterns of involvement include optic neuritis, serous retinal detachment, keratitis, ophthalmoplegia, and ocular myasthenia, but are not limited to them. Potential factors contributing to the development of toxicity are age, previous history of ocular immune disease, type, doses, and duration of treatment, and race. Ototoxicity is also reported in the literature, usually manifesting as bilateral, symmetrical/asymmetrical hearing loss. Ear toxicity presenting as ear fullness, tinnitus, and vertigo has also been mentioned in the literature. Hearing loss is often associated with word/speech recognition. An audiogram usually shows a pattern of sensorineural hearing loss. Otitis media has also been reported to be a potential cause of ear toxicity. Immune checkpoint inhibitor toxicity was present more commonly when used along with other anti-neoplastic agents. Ear toxicity, which presumably results from damage to the melanocytes in the ear, often presents with other melanocytotic manifestations, like uveitis and vitiligo. According to the literature, some agents (ipilimumab, nivolumab, atezolizumab, and pembrolizumab) were more commonly associated with toxic effects on the eye and ear and more when combined with each other.

The Clinical Advances of Oncolytic Viruses in Cancer Immunotherapy.

A promising future for oncology treatment has been brought about by the emergence of a novel approach utilizing oncolytic viruses in cancer immunotherapy. Oncolytic viruses are viruses that have been exploited genetically to assault malignant cells and activate a robust immune response. Several techniques have been developed to endow viruses with an oncolytic activity through genetic engineering. For instance, redirection capsid modification, stimulation of anti-neoplastic immune response, and genetically arming viruses with cytokines such as IL-12. Oncolytic viral clinical outcomes are sought after, particularly in more advanced cancers. The effectiveness and safety profile of the oncolytic virus in clinical studies with or without the combination of standard treatment (chemotherapy, radiotherapy, or primary excision) has been assessed using response evaluation criteria in solid tumors (RECIST). This review will comprehensively outline the most recent clinical applications and provide the results from various phases of clinical trials in a variety of cancers in the latest published literature.

Safety and Efficacy of Photodynamic Therapy in the Treatment of Circumscribed Choroidal Hemangioma: A Systematic Review.

Circumscribed choroidal hemangioma (CCH) is a sort of non-malignant hamartomatous tumor that occurs in the choroidal layer of the eye. It is a rare condition that affects people between their second and fourth decades of life, leading to significant deterioration of vision. One of the most catastrophic consequences of CCH is exudative retinal detachment (ERD), which has a severe impact on vision. This review aims to comprehensively assess the safety and efficacy of photodynamic therapy (PDT) using verteporfin as a therapeutic approach. Using the eligibility criteria, we analyzed the findings of 18 published articles from PubMed, Web of Science, Scopus, and Cochrane. The standard PDT protocol was used in all included studies, except two (one used half-dose, the other one used the double-dose) with an average of 1-2 sessions. PDT induced substantial tumor regression, with a mean thickness range from 0 to 2.3 mm. However, this contrasted with a previous study that reported a thickness of 3.46 mm as an indication of PDT failure. The mean tumor diameter varied from 4.8 mm to total tumor flattening. A suboptimal effect with a mean diameter ranging from 6mm to 8mm was found in two clinical studies. Significant improvement in vision was observed during the last follow-up, ranging from a normalization of Best Corrected Visual Acuity (BCVA) 20/20 to 20/80; counting finger vision persisted in two patients even after treatment. PDT successfully achieved complete subretinal fluid (SRF) resolution in 14 studies and resolved ERD in nine articles. Most studies did not report serious adverse events, but some reported macular atrophy, microcystic degeneration of the retina, transient visual disturbances, Retinal pigmented epithelium (RPE) metaplasia, and cystic degeneration of the retina. This systemic review demonstrated PDT's effectiveness and safety as a first-line management modality for CCH. Photodynamic therapy efficiently induced tumor regression, resulting in a notable reduction in both tumor diameter and thickness, with optimal efficacy to improve vision and resolution of the consequences of CCH, such as SRF and ERD.

Epidemiological Trends and Clinical Characteristics of Childhood Leukemia in Saudi Arabia: A Review.

Leukemia is the most prevalent type of cancer among children in Saudi Arabia. It has variable clinical presentations and accounts for a large scale of mortality and morbidity. Acute lymphoblastic leukemia (ALL) constituted the majority of pediatric leukemic cases with male gender predisposition. The most common first presentation that patients come with are manifestations of anemia, thrombocytopenia, and fever. Bone pain, fatigue, weight loss, organomegaly, and pale skin are among the commonest manifestations of pediatric leukemia. Childhood ALL and acute myeloid leukemia (AML) clinical manifestations seem to be very similar, even though there're some considerable differences in how common the clinical characteristics are. Chromosomal abnormalities are taken into consideration to determine survival and treatment. PubMed and Google Scholar were searched for the childhood leukemia population in Saudi Arabia. Our review article aims at providing comprehensible and updated statistical data on the different types of leukemia and their clinical presentations in Saudi Arabia.