Ifeanyi Kingsley Uche

Despite major advances in systemic therapy, surgery still plays a valuable role in the management of metastatic melanoma. This review summarizes the historical evolution of surgical management, outlines the traditional clinical risk factors, and examines biochemical, molecular, and mutational factors that impact melanoma tumor biology. Emerging tools such as predictive biomarker assays, gene expression profiling, and circulating tumor DNA are discussed in the context of patient selection. Finally, we consider contemporary indications for surgery, the management of oligoprogression, sequence of treatment, and optimal timing of resection while highlighting how operative intervention integrates with modern melanoma care.

Mycobacterium abscessus complex (MABC) comprises a group of rapidly growing, nontuberculous mycobacteria (NTM) capable of causing a wide spectrum of infections. MABC is classified into three subspecies namely abscessus, bolletii, and massiliense, each with distinct antibiotic resistance patterns. Over the past decade, cases of NTM inoculation during tattooing have increased, with Mycobacterium abscessus being the most commonly implicated NTM pathogen. Herein we describe the case of a 37-year-old woman who presented with erythematous papules over a tattoo on her right upper chest 15 days after getting a tattoo. Importantly, our report highlights the challenges in diagnosing Mycobacterium abscessus infections due to its multidrug resistance and discusses the available treatment options. Furthermore, our case also highlights the need for stricter regulation and enforcement of sterile practices during the production and use of tattoo inks, as well as the sterilization of tattooing equipment, to help reduce the risk of infection.

Tuberculosis (TB) remains a major global health concern. While it primarily affects the lungs, TB can also present in extrapulmonary forms, with cervical tuberculous lymphadenitis (CTL) or scrofula being the most common. Herein, we report a case of a 19-year-old female with a six-month history of progressively enlarging left-sided neck swelling. The patient was diagnosed with CTL. Diagnosing extrapulmonary TB can be challenging. In cases like ours, excisional biopsy or fine-needle aspiration (FNA) cytology with acid-fast bacilli (AFB) smear, culture, or polymerase chain reaction (PCR) analysis is critical for diagnosis. Our case highlights the importance of maintaining a high index of suspicion to differentiate mycobacterial infection from other causes of lymphadenopathy, particularly in immunocompetent adolescent patients.

The recent success of cancer immunotherapies, such as immune checkpoint inhibitor (ICIs), monoclonal antibodies (mAbs), cancer vaccines, and adoptive cellular therapies (ACTs), has revolutionized traditional cancer treatment. However, these immunotherapeutic modalities have variable efficacies, and many of them exhibit adverse effects. Oncolytic viral Immunotherapy (OViT), whereby viruses are used to directly or indirectly induce anti-cancer immune responses, is emerging as a novel immunotherapy for treating patients with different types of cancer. The herpes simplex virus type-1 (HSV-1) possesses many characteristics that inform its use as an effective OViT agents and remains a leading candidate. Its recent clinical success resulted in the Food and Drug Administration (FDA) approval of Talimogene laherparevec (T-VEC or Imlygic) in 2015 for the treatment of advanced melanoma. In this review, we discuss recent advances in the development of oncolytic HSV-1-based OViTs, their anti-tumor mechanism of action, and efficacy data from recent clinical trials. We envision this knowledge may be used to inform the rational design and application of future oHSV in cancer treatment.

Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases. We recently developed CancerOmicsNet, an artificial intelligence model employing graph-based algorithms to predict the cancer cell response to treatment with kinase inhibitors. The performance of this approach has been evaluated in large-scale benchmarking calculations, followed by the experimental validation of selected predictions against several cancer types. To shed light on the decision-making process of CancerOmicsNet and to better understand the role of each kinase in the model, we employed a customized saliency map with adjustable channel weights. The saliency map, functioning as an explainable AI tool, allows for the analysis of input contributions to the output of a trained deep-learning model and facilitates the identification of essential kinases involved in tumor progression. The comprehensive survey of biomedical literature for essential kinases selected by CancerOmicsNet demonstrated that it could help pinpoint potential druggable targets for further investigation in diverse cancer types.

The development of cancer causes disruption of anti-tumor immunity required for surveillance and elimination of tumor cells. Immunotherapeutic strategies aim for the restoration or establishment of these anti-tumor immune responses. Cancer immunotherapies include immune checkpoint inhibitors (ICIs), adoptive cellular therapy (ACT), cancer vaccines, and oncolytic virotherapy (OVT). The clinical success of some of these immunotherapeutic modalities, including herpes simplex virus type-1 derived OVT, resulted in Food and Drug Administration (FDA) approval for use in treatment of human cancers. However, a significant proportion of patients do not respond or benefit equally from these immunotherapies. The creation of an immunosuppressive tumor microenvironment (TME) represents an important barrier preventing success of many immunotherapeutic approaches. Mechanisms of immunosuppression in the TME are a major area of current research. In this review, we discuss how oncolytic HSV affects the tumor microenvironment to promote anti-tumor immune responses. Where possible we focus on oncolytic HSV strains for which clinical data is available, and discuss how these viruses alter the vasculature, extracellular matrix and immune responses in the tumor microenvironment.

Previous work has highlighted the complicated and distinctive dynamics that set signal evolution during a train of spin echoes, especially with nonuniform echo spacing applied to complex molecules like fats. The work presented here regards those signal patterns as codes that can be used as a contrast mechanism, capable of distinguishing mixtures of molecules with an imaging sequence, sidestepping many challenges of spectroscopy. For particular arrays of echo spacings, non-monotonic and distinctive signal evolution can be enhanced to improve contrast between target species. This work presents simulations that show how contrast between two molecules: (a) depends on the specific sequence of echo spacing, (b) is directly linked to the presence of J-coupling, and (c) can be relatively insensitive to variations in B0, T2 and B1. Imaging studies with oils demonstrate this phenomenon experimentally and also show that spin echo codes can be used for quantification. Finally, preliminary experiments apply the method to human liver in vivo, verifying that the presence of fat can lead to nonmonotonic codes like those seen in vitro. In summary, nonuniformly spaced echo trains introduce a new approach to molecular imaging of J-coupled species, such as lipids, which may have implications diagnosing metabolic diseases.

Human metapneumovirus (HMPV) is one of the leading causes of respiratory diseases in infants and children worldwide. Although this pathogen infects mainly young children, elderly and immunocompromised people can be also seriously affected. To date, there is no commercial vaccine available against it. Upon HMPV infection, the host innate arm of defense produces interferons (IFNs), which are critical for limiting HMPV replication. In this review, we offer an updated landscape of the HMPV mediated-IFN response in different models as well as some of the defense tactics employed by the virus to circumvent IFN response.