Anticoagulant-Related Nephropathy: A Common, Under-Diagnosed Clinical Entity.

Anticoagulant-related nephropathy (ARN) is a clinical entity consisting of the constellation of acute kidney injury (AKI) and hematuria in patients receiving anticoagulation therapy. It was formerly known as warfarin-induced nephropathy. The underlying pathogenesis remains yet to be fully clarified. Diagnosis is established by kidney biopsy, which has possibly led to underreporting of the disease. Patients usually present with a supratherapeutic INR. Herein, we present a case of acute kidney injury secondary to anticoagulant-related nephropathy.

Infective Endocarditis: A Rare Trigger of Immunoglobulin A Vasculitis in an Adult.

Immunoglobulin A vasculitis (IgA vasculitis) is a small-vessel vasculitis usually triggered by bacterial or viral infections, antibiotics, and vaccinations. Although it is a disease of the pediatric population, it can occur in adults as well. We present a case of IgA vasculitis that was triggered by underlying infective endocarditis (IE). IE is a rare and fatal cause of the vasculitis that requires timely diagnosis and management to prevent catastrophic outcomes. Our patient was treated with antibiotics for IE, which led to the resolution of vasculitis.

A Rare Case of Flavocoxid-Induced Pulmonary Fibrosis.

Pulmonary fibrosis is a chronic progressive interstitial lung disease characterized by repetitive cycles of epithelial cell injury and dysregulated repair. Although most cases of pulmonary fibrosis are idiopathic, a detailed history that includes medications, comorbidities, tobacco use, environmental exposures, and family history should be taken to rule out secondary etiology. We present a case of flavocoxid-induced pulmonary toxicity which progressed from hypersensitivity pneumonitis to pulmonary fibrosis even after discontinuation of the offending drug.

Paraneoplastic Confusion: A Case of Anti-Hu Encephalitis.

Paraneoplastic manifestations are frequently seen in patients with small cell lung carcinoma (SCLC) and can present as diverse clinical entities ranging from endocrinopathies to neurological conditions. Anti-Hu encephalitis is a rare paraneoplastic manifestation most commonly seen in patients with SCLC. This case highlights an SCLC patient who presented with behavioral changes, cognitive deficits, and memory issues, and was found to have anti-Hu encephalitis. The subacute course of this clinical entity should be kept in mind and prompt further investigation in SCLC patients with these symptoms, especially when the laboratory workup of the major culprits is negative or inconclusive.

Thyrotoxic Periodic Paralysis- A Diagnostically Challenging Rare Clinical Entity.

Thyrotoxic periodic paralysis (TPP) is characterized by a classic triad of muscle paralysis, hypokalemia, and hyperthyroidism. The underlying thyroid disorder is often very subtle making it challenging to recognize TPP. It is a completely reversible condition if diagnosed early; however, it is associated with fatal outcomes if delayed.

The Hidden Variable: A Case of Dasatinib-Induced Respiratory Failure.

Tyrosine kinase inhibitors that target the BCR/ABL mutation have been used as therapies of BCR/ABL positive acute lymphoblastic leukemia (ALL) with significant results. Dasatinib is a multitargeted tyrosine kinase inhibitor with significant activity in Philadephia positive ALL which is resistant to imatinib, as well as in treatment-naïve patients. We present a case of an elderly patient with Philadelphia chromosome-positive ALL, who presented with acute hypoxic respiratory failure in the setting of active immunotherapy with dasatinib.

Proteome-based classification of Nonmuscle Invasive Bladder Cancer.

DNA/RNA-based classification of bladder cancer (BC) supports the existence of multiple molecular subtypes, while investigations at the protein level are scarce. Here, we aimed to investigate if Nonmuscle Invasive Bladder Cancer (NMIBC) can be stratified to biologically meaningful groups based on the proteome. Tissue specimens from 117 patients at primary diagnosis (98 with NMIBC and 19 with MIBC), were processed for high-resolution proteomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomics output was subjected to unsupervised consensus clustering, principal component analysis (PCA) and investigation of subtype-specific features, pathways, and gene sets. NMIBC patients were optimally stratified to three NMIBC proteomic subtypes (NPS), differing in size, clinicopathologic and molecular backgrounds: NPS1 (mostly high stage/grade/risk samples) was the smallest in size (17/98) and overexpressed proteins reflective of an immune/inflammatory phenotype, involved in cell proliferation, unfolded protein response and DNA damage response, whereas NPS2 (mixed stage/grade/risk composition) presented with an infiltrated/mesenchymal profile. NPS3 was rich in luminal/differentiation markers, in line with its pathological composition (mostly low stage/grade/risk samples). PCA revealed a close proximity of NPS1 and conversely, remoteness of NPS3 to the proteome of MIBC. Proteins distinguishing these two extreme subtypes were also found to consistently differ at the mRNA levels between high and low-risk subtypes of the UROMOL and LUND cohorts. Collectively, our study identifies three proteomic NMIBC subtypes and following a cross-omics validation in two independent cohorts, shortlists molecular features meriting further investigation for their biomarker or potentially therapeutic value.

Metaplastic breast carcinoma: Current therapeutic approaches and novel targeted therapies.

Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer consisting of various combinations of malignant epithelial and mesenchymal cells. Its aggressive growth pattern combined with its histological heterogeneity account for MBC's characteristic resistance to systemic therapies, which subsequently leads to increased risk of recurrence and breast cancer mortality compared with other invasive mammary carcinomas. The aim of this review is to discuss the current therapeutic approaches, both in loco-regional as well as in systemic management of MBC. With the accumulation of knowledge from histopathologic assessment and the increasing identification of underlying molecular aberrations, emerging, novel targeted therapies will enable physicians to implement a more individualized and efficacious therapeutic strategy, leading hopefully to an improvement in the poor prognosis of MBC.

Impact of advanced glycation end products (AGEs) signaling in coronary artery disease.

Coronary artery disease remains the leading cause of mortality in adult diabetic population with however, a high predominance also in non-diabetic subjects. In search of common molecular mechanisms and metabolic by-products with potential pathogenic role, increased advanced glycation end products (AGEs) present a critical biomarker for CAD development in both cases. Interaction of AGEs with their transmembrane cell receptor, RAGE in endothelial and smooth muscle cells as well as in platelets, activates intracellular signaling that leads to endothelial injury, modulation of vascular smooth muscle cell function and altered platelet activity. Furthermore, tissue accumulation of AGEs affects current treatment approaches being involved in stent restenosis. The present review provides an update of AGE-induced molecular mechanisms involved in CAD pathophysiology while it discusses emerging therapeutic interventions targeting AGE reduction and AGE-RAGE signaling with beneficial clinical outcome.

Critical Role of IL-8 Targeting in Gliomas.

BACKGROUND: Glioma is a heterogeneous, highly complicated central nervous system (CNS) tumor with uncertain mechanism of initiation and progression, resulting in an unfavorable outcome. An extended network of cytokines is recognized as a major regulator of glioma pathogenesis, either promoting or inhibiting glioma progression based on their type and specificity. Interleukin-8 (IL-8) has been revealed as a critical regulator of CNS function and development with participation in many CNS disorders including gliomas. OBJECTIVE: The aim of the present review is to address the role of IL-8 in glioma pathogenesis focusing on the implicated molecular pathways as well as on its potential targeting for glioma therapy. METHODS AND RESULTS: PubMed-Medline, SCOPUS, and Google Scholar databases were searched for pre-clinical and clinical studies related to IL-8 implication in gliomagenesis and IL-8 targeting strategies for gliomas. Literature data indicate that IL-8 participates in glioma angiogenesis and cell migration and it can serve as a potential biomarker, for early diagnosis, follow-up and response to therapy. CONCLUSION: Several promising approaches that target directly or indirectly IL-8 effects in gliomas are currently in progress while more-in-depth studies are needed to validate its biomarker role and elucidate the underlying molecular mechanisms.