Iron and cardiovascular health: A review.

Iron is an essential element for the biological processes of living organisms, including the production of crucial oxygen-carrying proteins, formation of heme enzymes, and playing roles in electron transfer and oxidation-reduction reactions. It plays a significant role in various cardiovascular functions, including bioenergetics, electrical activity, and programmed cell death. Minor deficiencies of iron have been found to have negative impact on cardiovascular function in patients with heart failure (HF). The contractility of human cardiomyocytes is impaired by iron deficiency (ID), which results in reduced mitochondrial function and lower energy production, ultimately leading to cardiac function impairment, contributing to significant morbidity and mortality in patients with HF. This review discusses iron homeostasis within the human body, as well as ID pathophysiology and its role in HF. Focusing on therapeutic approaches including iron supplementation and/or repletion in patients with ID and HF, comparing results from recent clinical trials. Intravenous (IV) iron therapy has shown promising results in treating ID in HF patients. Large, randomized trials and meta-analysis, like Ferinject Assessment in patients with ID and chronic HF, AFFIRM-AHF, IRONMAN, and HEART-FID have demonstrated the efficacy of IV iron supplementation with IV ferric carboxymaltose or IV ferric derisomaltose in reducing hospitalizations and improving quality of life in patients with Heart Failure with reduced ejection fraction (HFrEF), New York Heart Association (NYHA) II-III. However, survival and mortality have demonstrated no improvement during acute exacerbations of HF or in outpatient management. The potential benefits of IV iron across the entire HF spectrum and its interaction with other HF therapies remain areas of interest for further research.

Deciphering cellular and molecular mechanism of MUC13 mucin involved in cancer cell plasticity and drug resistance.

There has been a surge of interest in recent years in understanding the intricate mechanisms underlying cancer progression and treatment resistance. One molecule that has recently emerged in these mechanisms is MUC13 mucin, a transmembrane glycoprotein. Researchers have begun to unravel the molecular complexity of MUC13 and its impact on cancer biology. Studies have shown that MUC13 overexpression can disrupt normal cellular polarity, leading to the acquisition of malignant traits. Furthermore, MUC13 has been associated with increased cancer plasticity, allowing cells to undergo epithelial-mesenchymal transition (EMT) and metastasize. Notably, MUC13 has also been implicated in the development of chemoresistance, rendering cancer cells less responsive to traditional treatment options. Understanding the precise role of MUC13 in cellular plasticity, and chemoresistance could pave the way for the development of targeted therapies to combat cancer progression and enhance treatment efficacy.

Spurious Presentation of Pulmonary Kaposi Sarcoma as Unresolved Pneumonia Led to Fatal Outcome.

Acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS) is an angioproliferative neoplasia caused by infection with human herpesvirus 8 (HHV-8). It typically presents with mucocutaneous involvement, but it can be disseminated. Initial presentation with primarily pulmonary KS is rare. We present a case of a 32-year-old male with untreated human immunodeficiency virus (HIV) diagnosed 1 year before presentation who developed progressively worsening cough and shortness of breath for 6 months. He was hospitalized twice and treated for unresolved pneumonia in an outside hospital. The patient concomitantly developed purplish nodules on his face, then the upper trunk, back, chest, and thighs bilaterally that gradually increased in size and number. Histopathology findings from skin lesions were consistent for KS. Bronchoscopy found multiple erythematous plaques throughout the tracheobronchial tree with telangiectasias and inflammation suggestive of pulmonary KS. His imaging findings and positive serum HHV-8 polymerase chain reaction (PCR) were consistent with disseminated KS. He started antiretroviral therapy (ART) to treat his HIV infection, followed by liposomal doxorubicin chemotherapy. But both ART and chemotherapy were interrupted due to adherence and insurance issues. The patient was readmitted with acute respiratory failure requiring mechanical ventilation with multiple vasopressors that led to the patient's demise. The late recognition of KS diagnosis and delayed treatment can lead to worse outcomes.

What You See Is Not What You Get: Germ Cell Tumor Mimicking Disseminated Coccidioidomycosis.

We present the case of a 30-year-old man with no prior medical history who presented to the hospital with a myriad of symptoms such as shortness of breath, generalized weakness, lower limb weakness, and urinary retention. He was recently diagnosed with "disseminated coccidioidomycosis" by an outside provider on an outpatient basis and started on fluconazole orally. However, due to a lack of improvement and significant symptoms, he was sent to the hospital to initiate liposomal amphotericin B treatment. After a comprehensive workup, an alternative diagnosis was suspected and eventually confirmed as metastatic germ cell carcinoma. Due to the vast dissemination and his poor functional status despite chemotherapy initiation, the patient elected for palliative care and expired shortly after at hospice. This case demonstrates the similarity of clinical findings between disseminated infections and malignancies.

A Case of Disseminated Histoplasmosis From California, in the Setting of Secondary Hemophagocytic Lymphohistiocytosis: A Diagnostic Challenge.

Histoplasma capsulatum is a geographically specific dimorphic fungus that can cause a spectrum of diseases. While most cases are asymptomatic pulmonary infections, in severe cases, particularly in immunocompromised patients, disseminated disease can occur. Histoplasmosis in California is limited to only a few case reports. In this article, we describe a rare case of disseminated histoplasmosis in a non-endemic region presenting with diagnostically challenging symptomatology, including altered mental status, status epilepticus, septic shock, and bilateral adrenal masses.

Immune Thrombocytopenia following COVID-19 Vaccine.

Several vaccines have been developed and are being administered against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Common side effects include fever, chills, headache, myalgia, and soreness at the injection site. However, some rare adverse effects have also been reported. We present a case of induced thrombocytopenia presenting with petechiae and mucosal bleeding which developed as an adverse response after first-dose administration of the Moderna COVID-19 vaccine.

Two Cases of Pelvic Diffuse Large B-Cell Lymphoma.

Primary diffuse large B-cell lymphoma presenting as an extranodal site in the pelvis is rare and can mimic a gynecological malignancy. Although management for diffuse large B-cell lymphoma is standardized and curative, prognosis depends on timely diagnosis and therapy. Diagnosis can be challenging as patients lack classical symptoms of fever, night sweats, weight loss, and lymphadenopathy associated with lymphoma. A multidisciplinary approach is recommended to diagnose and treat judiciously. In this article, we present cases of 2 females who presented with pelvic masses with initial suspicion of a gynecological malignancy but were ultimately diagnosed as diffuse large B-cell lymphoma of the pelvis and managed accordingly.

LECT-2 amyloidosis: what do we know?

Amyloidosis is a rare group of diseases characterized by abnormal folding of proteins and extracellular deposition of insoluble fibrils. It can be localized to one organ system or can have systemic involvement. The kidney is the most common organ to be involved in systemic amyloidosis often leading to renal failure and the nephrotic syndrome. The two most common types of renal amyloidosis are immunoglobulin light chain-derived amyloidosis (AL) and reactive amyloidosis (AA). A novel form of amyloidosis (ALECT2) derived from leukocyte chemotactic factor 2 (LECT-2) and primarily involving the kidneys was first described by Benson et al in 2008. The liver was subsequently identified as the second most common organ involved in ALECT2 amyloidosis. LECT-2 is a unique protein that can form amyloid deposits even in its unmutated form. Patients with ALECT2 present with minimal proteinuria in contrast to other forms of amyloidosis especially AL and AA. They may present with slightly elevated serum creatinine. Nephrotic syndrome and hematuria are rare. ALECT2 can be found in association with other types of amyloidosis as well as malignancies or autoimmune diseases. ALECT2 may be confused with amyloidosis associated with light and heavy chain monoclonal gammopathy if the immunofluorescence is positive with anti-light chain and anti-AA sera. The other organs involved are the duodenum, adrenal gland, spleen, prostate, gall bladder, pancreas, small bowel, parathyroid gland, heart, and pulmonary alveolar septa, but consistently uninvolved organs included brain and fibroadipose tissue. A renal biopsy along with characteristic features found on immunohistochemistry and mass spectrometry is diagnostic of ALECT2. ALECT2 should be suspected when all markers for AL and AA are negative. Proper diagnosis of ALECT2 can determine need for supportive care versus more aggressive interventions.

Neutrophilic Dermatosis in Myelodysplastic Syndrome and Chronic Active Hepatitis C.

In this article, we describe a case of neutrophilic dermatosis of the dorsal hands (NDDH) complicated with myelodysplastic syndrome and chronic active hepatitis C infection. NDDH was first suggested by Galaria et al in 2000. After comparing features of NDDH with Sweet syndrome in terms of encompassing clinical, laboratory, and histological characteristics, it can be concluded that "distributional or localized variant" of Sweet syndrome is classified as NDDH. Early diagnosis and treatment can improve prognosis. Systemic glucocorticoids are the mainstay of treatment.

Isolated myeloid sarcoma of lumbar spine without bone marrow involvement: a rare case report and treatment dilemma.

Granulocytic sarcoma, chloroma, myeloblastoma, or here referred as myeloid sarcoma (MS), is a rare extramedullary tumor composed of immature myeloid cells called myeloblasts. MS is seen most commonly in patients with acute myeloid leukemia and less frequently in chronic myeloid leukemia, myelodysplastic syndrome. In rarer instances, MS has been shown to precede the development of myeloid tumors by acute myeloblastic leukemia (AML). In particular, isolated MS involving spine is extremely rare. We herein present a rare case of isolated spinal MS in non-leukemic patient. This is a previously relatively healthy 47-year-old man who presented with signs of lumbar spinal cord compression, initially reported as schwannoma on imaging, later diagnosed with spinal MS on pathology. Further workup did not reveal any evidence of bone marrow or other hematological involvement. The patient successfully treated by L4/L5 laminectomy and debulking with subsequent radiation resulting in substantial decrease in size of tumor with significant improvement in symptoms during follow up. This case not only describes a rare case of isolated MS of lumbar spine, but also highlights the potential treatment challenges of such a rare diagnosis. We review the available literature, discuss available treatment options, and highlight the need for further investigations along with increased clinician awareness.

Non-Hodgkin's Plasmablastic Lymphoma as Initial Presentation of Human Immunodeficiency Virus.

Plasmablastic lymphoma (PBL) is a subtype of non-Hodgkin's lymphoma that manifests in patients with the diagnosis of human immunodeficiency virus (HIV), more prominently in the head, neck, and oral mucosal region. The diagnosis of this rare lymphoma serves as a concomitant diagnosis of acquired immunodeficiency syndrome. The case is of a 33-year-old previously healthy male, with an unknown diagnosis of HIV with a painful right mandibular mass. He was subsequently diagnosed with PBL and HIV. This case of PBL illustrates the importance of linking a rare and potentially life-threatening diagnosis as a possible first manifestation of HIV.

Locus Minoris Resistentiae: Two Cases of Malignant Metastasis and Review of Literature.

Locus minoris resistentiae refers to a region of decreased resistance within the body. This occurs from changes to the microenvironment secondary to previous trauma and results in increased vulnerability. As a result, infection, inflammatory processes, and malignancy may localize to this area. In this article, we describe 2 unique cases of malignancy, primary prostate carcinoma and serous carcinoma of the ovary, both of which disseminated to sites of prior trauma. We review the available literature, discuss proposed pathophysiology, and highlight the need for further investigations along with increased clinician awareness.

A phase I study of intravenous fenretinide (4-HPR) for patients with malignant solid tumors.

BACKGROUND: Fenretinide is a synthetic retinoid that can induce cytotoxicity by several mechanisms. Achieving effective systemic exposure with oral formulations has been challenging. An intravenous lipid emulsion fenretinide formulation was developed to overcome this barrier. We conducted a study to establish the maximum tolerated dose (MTD), preliminary efficacy, and pharmacokinetics of intravenous lipid emulsion fenretinide in patients with advanced solid tumors. METHODS: Twenty-three patients with advanced solid tumors refractory to standard treatments received fenretinide as a continuous infusion for five consecutive days in 21-day cycles. Five different dose cohorts were evaluated between doses of 905 mg/m2 and 1414 mg/m2 per day using a 3 + 3 dose escalation design. A priming dose of 600 mg/m2 on day 1 was introduced in an attempt to address the asymptomatic serum triglyceride elevations related to the lipid emulsion. RESULTS: The treatment-related adverse events occurring in ≥ 20% of patients were anemia, hypertriglyceridemia, fatigue, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) increase, thrombocytopenia, bilirubin increase, and dry skin. Five evaluable patients had stable disease as best response, and no patients had objective responses. Plasma steady-state concentrations of the active metabolite were significantly higher than with previous capsule formulations. CONCLUSION: Fenretinide emulsion intravenous infusion had a manageable safety profile and achieved higher plasma steady-state concentrations of the active metabolite compared to previous capsule formulations. Single-agent activity was minimal but combinatorial approaches are under evaluation.

A Progressive Case of Eosinophilic Myocarditis Due to Eosinophilic Granulomatosis With Polyangiitis in a Caucasian Male.

Vasculitis is an inflammatory process involving blood vessels of various sizes, including the small vessels in the kidneys to the large vessels, such as the aorta. This inflammatory condition is usually autoimmune in nature and is associated with involvement of many locations, such as the sinuses, lungs, kidneys, and even the heart. Specifically, eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis that may initially hide as asthma, allergic rhinitis, and/or sinusitis. However, it is known to become a lethal disease once progressed to include cardiovascular manifestations. It is important to remember EGPA as a differential for any patient with a history of asthma, allergic rhinitis, and/or sinusitis who also presents with cardiovascular complaints and eosinophilia. Treatment recommendations focus on immunosuppression in such cases. In this article, we discuss the case of a 62-year-old male, with a known history of asthma, who presented to the emergency department with concern for his chest pain and right-sided weakness. He was later diagnosed with EGPA with eosinophilic myocarditis. Diagnosis and treatment are described.

Acute Myelogenous Leukemia With Trisomy 8 and Concomitant Acquired Factor VII Deficiency.

Acquired isolated factor VII deficiency is a rare bleeding disorder and has been reported in 31 cases. This is in contrast to congenital factor VII deficiency, which while also infrequent is the most common rare congenital bleeding disorder. Acquired isolated factor VII deficiency has been described primarily in patients with solid malignancies, sepsis, and in the presence of anti-factor VII autoantibodies. We report a case of acute myelogenous leukemia with an associated trisomy 8 cytogenetic abnormality presenting with factor VII deficiency. The factor VII deficiency cleared after induction chemotherapy and with the disappearance of the cytogenetic and molecular abnormalities. We discuss a possible link between trisomy 8 and vitamin K metabolism, which might result in acquired factor VII deficiency in acute myelogenous leukemia.

Leptomeningeal Carcinomatosis From Carcinoma of Unknown Primary in a Young Patient: A Case Report and a Literature Review.

Leptomeningeal carcinomatosis, leptomeningeal meningitis, or, as referred here, leptomeningeal metastasis (LM), is a rare but frequently fatal complication seen in advanced stage of cancer either locally advanced or after a metastasis of a known primary cancer. We present a rare and uncommon case of leptomeningeal metastases from carcinoma of unknown primary. A 32-year-old female was diagnosed with LM; however, no known primary carcinoma was identified after 2 separate biopsies. The first biopsy of the right pre-tracheal lymph node showed poorly differentiated pan-keratin (AE1 and AE3) and placental alkaline phosphatase with the possibility of germ cell origin. Second cytology of cervical lymphadenopathy was remarkable for cytokeratin 7 and 20, placental alkaline phosphatase, and CDX2 suggestive of germ line tumor with both mucinous ovarian and gastrointestinal carcinomas. Unfortunately, the LM progressed rapidly despite multiple cycles of germ cell origin directed systemic and intrathecal chemotherapy, and the patient opted for hospice care without getting a chance to identify the primary source.

An Unusual Presentation of Spinal Giant Cell Glioblastoma in a 21-Year-Old Female.

Primary spinal cord giant cell glioblastoma multiforme of the thoracic spinal cord is a rarely-diagnosed primary spinal cord tumor in comparison to neoplasms in intracranial locations. In this article, we highlight a young adult who was diagnosed with intramedullary giant cell glioblastoma, IDH wild-type, World Health Organization grade IV/IV of the thoracic spinal cord. This case report describes the treatment approach with a postsurgical combination of radiation therapy and temozolomide, which resulted in the patient to return to her baseline of health only to later develop neurological symptoms significant for a recurrence of malignancy. In a review of the literature of described cases of primary spinal cord glioblastoma multiforme, prognosis continues to be unfavorable as current treatment options of the aggressive malignancy remain absent of a cure.

A Synchronous Diagnosis of Metastatic Male Breast Cancer and Prostate Cancer.

In this article, we present a patient diagnosed synchronously with metastatic male breast cancer and prostate cancer. This is a 63-year-old male and recent immigrant from Nigeria, who sought medical attention for progressively worsening of shortness of breath and acute progression of a chronic right breast mass. An invasive breast carcinoma was diagnosed by the core biopsy of the right breast mass. Within 2 months of his breast cancer diagnosis, the patient also was diagnosed with prostate adenocarcinoma after being worked up for urinary retention. By presenting this patient with a synchronous diagnosis with metastatic male breast cancer and prostate cancer, history of chronic right breast mass, and gynecomastia, we speculate on possible cancer etiologies and risk factors.