Prediction of clinical outcomes using the pyrolysis, gas chromatography, and differential mobility spectrometry (Py-GC-DMS) system

AbstractBiological and molecular heterogeneity of human diseases especially cancers contributes to variations in treatment response, clinical outcome, and survival. The addition of new disease- and condition-specific biomarkers to existing clinical markers to track cancer heterogeneity provides possibilities for further assisting clinicians in predicting clinical outcomes and making choices of treatment options. Ionization patterns derived from biological specimens can be adapted for use with existing clinical markers for early detection, patient risk stratification, treatment decision making, and monitoring disease progression. In order to demonstrate the application of pyrolysis, gas chromatography, and differential mobility spectrometry (Py-GC-DMS) for human diseases to predict the outcome of diseases, we analyzed the ionized spectral signals generated by instrument ACB2000 (ACBirox universal detector 2000, ACBirox LLC, NJ, USA) from the serum samples of Mantle Cell Lymphoma (MCL) patients. Here, we have used mantle cell lymphoma as a disease model for a conceptual study only and based on the ionization patterns of the analyzed serum samples, we developed a multivariate algorithm comprised of variable selection and reduction steps followed by receiver operating characteristic curve (ROC) analysis to predict the probability of a good or poor clinical outcome as a means of estimating the likely success of a particular treatment option. Our preliminary study performed with small cohort provides a proof of concept demonstrating the ability of this system to predict the clinical outcome for human diseases with high accuracy suggesting the promising application of pyrolysis, gas chromatography, and differential mobility spectrometry (Py-GC-DMS) in the field of medicine

Heart Failure: Diagnosis, Management and Utilization

Despite the advancement in medicine, management of heart failure (HF), which usually presents as a disease syndrome, has been a challenge to healthcare providers. This is reflected by the relatively higher rate of readmissions along with increased mortality and morbidity associated with HF. In this review article, we first provide a general overview of types of HF pathogenesis and diagnostic features of HF including the crucial role of exercise in determining the severity of heart failure, the efficacy of therapeutic strategies and the morbidity/mortality of HF. We then discuss the quality control measures to prevent the growing readmission rates for HF. We also attempt to elucidate published and ongoing clinical trials for HF in an effort to evaluate the standard and novel therapeutic approaches, including stem cell and gene therapies, to reduce the morbidity and mortality. Finally, we discuss the appropriate utilization/documentation and medical coding based on the severity of the HF alone and with minor and major co-morbidities. We consider that this review provides an extensive overview of the HF in terms of disease pathophysiology, management and documentation for the general readers, as well as for the clinicians/physicians/hospitalists

Hematological entities with plasmacytic differentiation: a case report

Abstract Introduction Plasmacytoma, a localized tumor of monoclonal plasma cells without any clinical, radiological or physical evidence of plasma cell neoplasm (PCN), is a rare entity that accounts for 1% of PCN. Immunoglobulin M (IgM) extramedullary plasmacytoma of mediastinal region has never been reported and is a diagnostic challenge considering other differential diagnoses. Case presentation We present the case of a 51-year-old African-American female with progressively increasing cough, dyspnea, and dysphagia for 6 months with a computed tomography (CT) scan revealing a subcarinal mass. The histopathological analysis of the mass reveals a diagnosis of lymphoma with plasma cell differentiation, with a differential of lymphoplasmacytic lymphoma and plasma cell neoplasm. The lymphoma panel via next-generation sequencing (NGS) and a myeloma-targeted fluorescent in situ hybridization (FISH) panel confirmed the diagnosis of IgM extramedullary plasmacytoma, an entity of rare occurrence. Treatment with radiation led to complete regression of the plasmacytoma with normal blood work-up. Conclusions This report describes the challenges of diagnosing IgM extramedullary plasmactyoma. Our case report highlights the importance of cytogenetics and NGS in establishing a correct diagnosis that indeed has prognostic and therapeutic implications

Additional file 1 of Hematological entities with plasmacytic differentiation: a case report

Additional file 1: Table S1. The details of physical examination of the patient at the time of admission

The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds

Epidemiological studies link the herbicide paraquat to increased incidence of Parkinson's disease (PD). We previously reported that Drosophila exposed to paraquat recapitulate PD symptoms, including region-specific degeneration of dopaminergic neurons. Minocycline, a tetracycline derivative, exerts ameliorative effects in neurodegenerative disease models, including Drosophila. We investigated whether our environmental toxin-based PD model could contribute to an understanding of cellular and genetic mechanisms of minocycline action and whether we could assess potential interference with these drug effects in altered genetic backgrounds. Cofeeding of minocycline with paraquat prolonged survival, rescued mobility defects, blocked generation of reactive oxygen species, and extended dopaminergic neuron survival, as has been reported previously for a genetic model of PD in Drosophila. We then extended this study to identify potential interactions of minocycline with genes regulating dopamine homeostasis that might modify protection against paraquat and found that deficits in GTP cyclohydrolase adversely affect minocycline rescue. We further performed genetic studies to identify signaling pathways that are necessary for minocycline protection against paraquat toxicity and found that mutations in the Drosophila genes that encode c-Jun N-terminal kinase (JNK) and Akt/Protein kinase B block minocycline rescue

Metastatic Ovarian Clear Cell Carcinoma in the Context of In Vitro Fertilization Pregnancy

Adnexal masses are routinely encountered in the clinical practice. However, adnexal masses during pregnancy are incidental findings and usually resolve spontaneously or can be managed conservatively during pregnancy due to their benign nature. Ovarian malignancy is a rare event to occur during pregnancy. Only a few cases of ovarian clear cell carcinoma (OCCC), a subtype of epithelial ovarian cancers, have been reported in pregnancy and all of which have undergone cystectomy or pregnancy termination prior to the last trimester of pregnancy. We present a unique case of OCCC in a pregnant 38-year old female of Asian ethnicity with endometriosis and an in vitro fertilization (IVF) pregnancy. The OCCC, initially suspected to be of benign nature, was removed via emergency cesarean section during delivery in the late preterm period. The Positron Emission Tomography scan performed a few weeks after delivery confirmed metastatic lesions. Our case study not only emphasizes the need for definitive treatment option for endometriosis but also a close surveillance of all masses diagnosed during pregnancy, in particular with a background of other risk factors such as endometriosis and Asian ethnicity. In addition, our study advocates the need for the guidelines for management of such rare cases

Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents

none10siDespite advances in the development of clinical agents for treating Mantle Cell Lymphoma (MCL), treatment of MCL remains a challenge due to complexity and frequent relapse associated with MCL. The incorporation of conventional and novel diagnostic approaches such as genomic sequencing have helped improve understanding of the pathogenesis of MCL, and have led to development of specific agents targeting signaling pathways that have recently been shown to be involved in MCL. In this review, we first provide a general overview of MCL and then discuss about the role of biomarkers in the pathogenesis, diagnosis, prognosis, and treatment for MCL. We attempt to discuss major biomarkers for MCL and highlight published and ongoing clinical trials in an effort to evaluate the dominant signaling pathways as drugable targets for treating MCL so as to determine the potential combination of drugs for both untreated and relapse/refractory cases. Our analysis indicates that incorporation of biomarkers is crucial for patient stratification and improve diagnosis and predictability of disease outcome thus help us in designing future precision therapies. The evidence indicates that a combination of conventional chemotherapeutic agents and novel drugs designed to target specific dysregulated signaling pathways can provide the effective therapeutic options for both untreated and relapse/refractory MCL.openArati A. Inamdar, Andre Goy, Nehad M. Ayoub, Christen Attia, Lucia Oton, Varun Taruvai, Mark Costales, Yu-Ting Lin, Andrew Pecora, K. Stephen SuhInamdar, Arati A.; Andre, Goy; Ayoub, Nehad M.; Christen, Attia; OTON GONZALEZ, Lucia; Varun, Taruvai; Mark, Costales; Yu-Ting, Lin; Andrew, Pecora; Stephen Suh, K

Biomarkers and novel therapeutic approaches for diffuse large B-cell lymphoma in the era of precision medicine

Despite the great efforts for better treatment options for diffuse large B-cell lymphoma (DLBCL) (most common form of non-Hodgkin lymphoma, NHL) to treat and prevent relapse, it continues to be a challenge. Here, we present an overview of DLBCL and address the diagnostic assays and molecular techniques used in its diagnosis, role of biomarkers in detection, treatment of early and advanced stage DLBCL, and novel drug regimens. We discuss the significant biomarkers that have emerged as essential tools for stratifying patients according to risk factors and for providing insights into the use of more targeted and individualized therapeutics. We discuss techniques such as gene expression studies, including next-generation sequencing, which have enabled a more understanding of the complex pathogenesis of DLBCL and have helped determine molecular targets for novel therapeutic agents. We examine current treatment approaches, outline the findings of completed clinical trials, and provide updates for ongoing clinical trials. We highlight clinical trials relevant to the significant fraction of DLBCL patients who present with complex cases marked by high relapse rates. Supported by an increased understanding of targetable pathways in DLBCL, clinical trials involving specialized combination therapies are bringing us within reach the promise of an effective cure to DLBCL using precision medicine. Optimization of therapy remains a crucial objective, with the end goal being a balance between high survival rates through targeted and personalized treatment while reducing adverse effects in DLBCL patients of all subsets

Discovery of a nitric oxide-dependent response and a functional analysis of genes regulating the response in a Drosophila model of Parkinson's disease

The processes of neuroinflammation and oxidative stress are thought to be among the primary mechanisms playing roles in the etiology and pathophysiology of Parkinson's disease (PD). Recently, it has been proposed that microglia, the innate immune cells of the mammalian brain, become hyperactivated and deregulated in response to neuronal dysfunction in PD and thereby, accelerate dopaminergic neuronal loss. The mechanisms for neuroinflammatory responses that exaggerate neurotoxicity are poorly understood. Moreover, the studies to date that investigate neuroinflammatory mechanisms have utilized primarily in vitro approaches. We have established a DrosophilaPD model based on ingestion of the herbicide paraquat, which recapitulates most behavioral and patho-physiological features of PD, including loss of dopaminergic neurons. Using this model, we have discovered that paraquat ingestion induces nitric oxide synthase (NOS) and a corresponding elevation of NO production in the adult Drosophila brain. Mammalian microglia have been shown to be a source of NOS, recognized as a major component/marker in neuron death, in mammalian PD models. Therefore, the observation of NOS induction during Drosophilaneurodegeneration parallels the mammalian process. The paraquat-induced stimulation of NOS was further confirmed using pharmacological approaches, which demonstrated that inhibition of NOS partially rescued adult Drosophila from the deleterious effects of paraquat. Minocycline, a tetracycline derivative, has been reported to act primarily on microglia, ameliorating excessive activation of NOS, in mammalian neurodegenerative disease models including PD. Similarly, ingestion of minocycline by adult Drosophilaameliorates the effects of paraquat, including reduction of NOS activity and protection of dopaminergic neurons. The paraquat-induced PD model was also employed to identify the mechanisms of action that confer the neuroprotective properties of minocycline. Components of signaling pathways that potentially could mediate DA toxicity in this PD model were tested for their ability to modify the action of minocycline. The discovery of a NOS-dependent paraquat response in flies provides the foundation for future work to explore cellular and molecular mechanisms directing NOS induction and action in Drosophila, which exhibits features resembling neuroinflammation. This research also takes advantage of the ease of genetic and pharmacological methods in the Drosophila model to identify important genetic components of this process. (Published By University of Alabama Libraries