TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(-) Classical Myeloproliferative Neoplasm.

We investigated the role of toll-like receptors (TLRs) in inflammatory pathways in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-)MPNs). TLR2 expression was increased in ET, PV, and MPN (grouped as (PV + (ET) + MF)), whereas TLR4 was elevated only in MPN. TLR3, 7, and 9 were not elevated. Cultured monocyte-derived dendritic cells and plasma assays in TLR2-elevated patients were found to secrete more cytokines than those from TLR2-normal patients. These facts suggest that TLR2 is the major inflammatory pathways in MPN. We also measured S100A9 and reactive oxygen species (ROS), revealing increased S100A9 in PV, MF, and MPN, while ROS were only increased in MF. These data suggests that MPNs initially involve TLR2, with minor contributions from TLR4, and with S100A9, leading to ROS formation, JAK2 mutation, and progression to MF or leukemia. Furthermore, patients with JAK2 mutations or leukocytosis exhibited higher TLR2 expression. In leukocyte-platelet interactions, cells from MPN patients displayed a stronger response to a TLR2 agonist than TLR4 agonist. A TLR2 inhibitor (but not a TLR4 inhibitor) attenuated this response. Thrombosis incidence was higher in TLR2-elevated patients (29%) than in TLR2-normal patients (19%). These findings suggest that TLR2 likely contributes to thrombosis in MPN.

A Rare Case of Epithelioid Hemangioma Presenting as an Isolated Sacral Mass.

Epithelioid hemangioma (EH) is an uncommon benign vascular tumor of mesenchymal origin. It mainly presents as expanding nodules around the ear, the forehead, and long bones. Only a handful of cases have been found in cervical, thoracic, lumbar, and sacral vertebrae as lytic lesions with pain and neurological impairment. We present the case of a 36-year-old female with an incidental finding of a sacral mass along with inguinal lymphadenopathy on imaging. Initially, there were no symptoms. The mass gradually progressed and later showed an extraosseous extension with involvement of sacral neural foramina and nerve roots causing severe low back pain and weakness of the left lower extremity. Differential diagnoses initially included secondary metastases and chordoma. However, the biopsy of the mass revealed findings consistent with an EH. To our knowledge, this is the first case of EH presenting as an isolated mass in the sacrum and the third case of EH involving the sacrum in continuation with other vertebrae. EH should be in our differential diagnoses when there is a sacral mass.

Presentation and treatment of aggressive, Triple-Negative carcinosarcoma of the breast.

An extremely rare form of breast cancer, breast carcinosarcoma accounts for less than a percent of all breast malignancies and is highly aggressive. Composed of both cancerous epithelial and mesenchymal cell types, breast carcinosarcoma is associated with a poor prognosis compared to more common breast cancers, and typically lack the receptors typical of other breast carcinomas, which minimize potential targets for treatment. In this case report, we discuss a 56-year-old patient affected by carcinosarcoma of the breast at a T2N1 stage, and the decision-making process that factored into her treatment plan.

SMARCA4-Deficient Undifferentiated Tumor of Lung Mass-A Rare Tumor With the Rarer Occurrence of Brain Metastasis: A Case Report and Review of the Literature.

Among thoracic tumors, these include subsets of a relatively newly described and yet to be fully characterized tumor entity: SMARCA4-deficient Undifferentiated Tumor (SMARCA4-dUT). Mutations of SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and loss of BRG1 (Brahma-related gene-1) is the underlying molecular hallmark of SMARCA4-dUT. They mostly involved the mediastinum, lung, and/or pleura showing undifferentiated round cell or rhabdoid morphology associated with aggressive clinical behavior. The pathogenesis of these tumors is still not clear. Morphologically, SMARAC4-dUT is differentiated from SMARCA4-dNSCLC by the presence of squamous and solid components in the latter. Immunohistochemically SMARC4-dUT has characteristic loss of SMARCA4 and SMARCA2 and strong expression of SOX2, CD34, and SALL4. Common sites of metastasis include lymph nodes, bones, and adrenal glands but rarely brain metastasis. We present a unique and rare case of a 76-year-old male with a right lung mass with documented pathology of SMARCA4-dUT and was found to have multiple brain metastases.

Yolk Sac Tumor in the Anterior Mediastinum Presenting as Acute Pericarditis.

BACKGROUND Mediastinal masses can originate from anatomical structures normally located in the mediastinum, or from structures that travel through the mediastinum during embryogenesis. Initial presenting symptoms usually vary from shortness of breath, cough, chest pain, and superior vena cava syndrome to nonspecific constitutional symptoms (eg, fever, weight loss, fatigue). However, the initial presentation of a mediastinal mass with acute pericarditis has not been reported in the literature as far as we know. CASE REPORT A 20-year-old man presented to the Cardiology Clinic with chest pain and new pericardial effusion on echocardiography, both fulfilling the diagnostic criteria of acute pericarditis. The patient also had venous engorgement on the neck, and a chest X-ray followed by computed tomography imaging showed a large mediastinal mass. The serum tumor marker a-fetoprotein (AFP) was markedly elevated. The biopsy and immunohistochemistry revealed a high-grade malignant neoplasm - yolk sac tumor, which is a type of non-seminomatous germ cell tumor. The acute pericarditis resolved after administration of NSAID and colchicine. The patient was then started on chemotherapy. CONCLUSIONS The discussed case shows the rare presentation of an anterior mediastinal mass with acute pericarditis. This emphasizes the importance of a thorough review of systems and critical analysis of every sign and symptom at the time of initial presentation, which helps the physician to obtain appropriate imaging studies early in the course, leading to an early diagnosis and treatment of the disease, such as in this case of an extremely rare germ cell tumor.

Intraoral myeloid sarcoma presenting as toothache and gingival mass.

A female patient in her 70s with a medical history of myelodysplastic neoplasm presented to the outpatient department with a 4-month history of toothache, painful gingival swelling and loose teeth that required extractions. Intraoral examination revealed a swelling in the lower anterior portion of the mandible, which displaced her teeth. Incisional biopsy of the gingival lesion revealed dense aggregates of atypical round cells which stained positive for CD43, CD45, CD33 and myeloperoxidase, consistent with myeloid sarcoma. Subsequent bone marrow biopsy displayed hypercellular marrow with immature myeloid elements and 21% myeloblasts by flow cytometry, compatible with diagnosis of acute myeloid leukaemia (AML). The patient initially went into remission after treatment but later died of AML relapse after 18 months.

Observational Study of Thrombotic Events in a Random Cohort of Hospitalized COVID-19 Patients at a Community-Based Hospital of New York City During the Beginning of the 2020 Pandemic.

Coronavirus disease 2019 (COVID-19) continues to pose an unprecedented challenge for the entire world and the healthcare system. Different theories have been proposed elucidating the pathophysiological mechanisms attributing to high mortality and morbidity in COVID-19 infection. Out of them, thrombosis and procoagulant state have managed to earn the maximum limelight. We conducted an observational study based on data from randomly selected 349 hospitalized patients with COVID-19 infection in a community-based hospital in New York City during the first wave of the COVID-19 viral surge in March 2020. The main objective of our study was to assess the risk and occurrence of thrombotic events (both venous and arterial) among the hospitalized patients including the intensive care unit (ICU) and non-ICU admissions with confirmed COVID-19 infection. The primary outcome in our study was defined as the thrombotic events that included myocardial infarction (MI), deep venous thrombosis (DVT), cerebrovascular accidents (CVA), and pulmonary embolism (PE). The study correlated the association of thrombotic events with the level of biomarkers of interest: D-dimer >1000 ng/ml, troponin-I >1 ng/ml, or both. The association of D-dimers and troponin-I with thrombotic events was measured using both univariate and multivariate Cox proportional hazard (PH) regression analysis. Out of a total of 349 patients, 78 patients (22.35%) were found to have elevated biomarkers (D-dimer >1000 ng/ml and/or troponin-I >1 ng/ml) and were categorized as a high-risk group. Eighty-nine patients developed thrombotic complications (evidence of more than one thrombotic event was found in several patients). Two-hundred seventy-one (77.65%) patients had no documentation of thrombosis. The incidence of thrombotic events included myocardial infarction (MI; N=45; 12.8%), cerebrovascular accidents (CVA; N=16; 4.5%), deep venous thrombosis (DVT; N=16; 4.5%), and pulmonary embolism (PE; N=9; 2.57%).

High Incidence of Thrombotic Thrombocytopenic Purpura Exacerbation Rate Among Patients With Morbid Obesity and Drug Abuse.

This study aims to identify the baseline patient characteristics, clinical presentation, and response to treatment of 11 patients who were diagnosed with thrombotic thrombocytopenic purpura (TTP) between 2014 and 2020 at Brookdale University Hospital Medical Center, Brooklyn, NY. Laboratory and clinical parameters were recorded for 29 patients who received plasmapheresis in this time period. Of 29 patients, 11 had confirmed TTP and one was diagnosed with hereditary TTP. Young, black, and female patients made up the majority of our patient population. A high prevalence of obesity and drug abuse were seen among our patients. Five out of 11 were obese and four of them were morbidly obese; six out of 11 patients were positive for the drug screen including cannabinoids (3), opiates (2), benzodiazepines (1), PCP (1), and methadone (1). Four patients with a positive drug screen had acute kidney injury (AKI), and plasmapheresis helped them enhance their kidney function. We observed a high incidence of AKI and high TTP exacerbation rates in patients who were drug abusers and those who were morbidly obese. There is a paucity of data on the relationship of TTP with obesityor drug abuse and this needs further study.

Hematological manifestations and complications of COVID-19.

The virus SARS-CoV-2 commonly causes self-resolving, flu-like illnesses in the majority of patients, but a critical illness can be seen in 5% of cases - especially in the elderly population or in patients with multiple comorbidities. When COVID-19 is severe, it can cause pneumonia and hypoxemic respiratory failure, and can progress to viremia involving multiple organ systems. It causes significant cytopenia, mainly severe lymphopenia, and excessive exhaustion of CD8+ T cells, resulting in an immunocompromised state and cytokine storm. Furthermore, COVID-19 can commonly be complicated with acute thrombotic events, including venous thromboembolism, acute stroke, acute myocardial infarction, clotting of hemodialysis and extracorporeal membrane oxygenation (ECMO) catheters, and acute limb ischemia. This makes SARS-COV-2 a unique virus with an undiscovered pathophysiology. Therefore, patients with COVID-19 need close monitoring of their symptoms and laboratory parameters, and early hospitalization and treatment in severe cases. Early identification of severe cases and the abovementioned complications of COVID-19 could decrease the morbidity and mortality caused by the disease. In the study, we summarize what is currently known about the hematological manifestations and complications of COVID-19.

The Association Between Anemia of Chronic Inflammation and Alzheimer's Disease and Related Dementias.

BACKGROUND: Dementia is a spectrum of neurological diseases characterized by memory impairment and cognitive decline with the pathogenesis and effective management remaining elusive. Several studies have identified a correlation between anemia and Alzheimer's disease and related dementias (ADRD); however, anemia subtypes and association with ADRD have yet to be studied conclusively. OBJECTIVE: To study an association between ADRD and anemia of chronic inflammation. METHODS: We conducted a retrospective case-control study of the patients, diagnosed with ADRD at Brookdale Hospital. Pair-wise comparisons between means of controls and cases in terms of iron studies and laboratory results were performed using a Mann-Whitney U test. Pair-wise comparisons between anemia subgroups (moderate and severe) were performed using a Two Sample proportion Z-Test, where for each couple of normally distributed population. RESULTS: There was a total of 4,517 (1,274 ADRD group; 3,243 Control group) patients. There was significant difference in hemoglobin 10.15 versus 11.04 [p-value <0.001]. Iron studies showed a significant difference in ferritin 395±488.18 versus 263±1023.4 [p < 0.001], total iron binding capacity 225±84.08 versus 266±82.30 [p < 0.001] and serum iron level 64±39.34 versus 53±41.83 [p < 0.001]. Folic acid and vitamin B12 levels were normal in both groups. Severe and moderate anemia in the ADRD group were respectively 6.2% [95% CI: 4.2-8.4] and 13% [95% CI: 9.8-16.2] higher. Overall, incidence of moderate-to-severe anemia was found to be 19% higher in ADRD group [95% CI: 15.8-22.1]. CONCLUSION: We demonstrated an association between ADRD and anemia of chronic inflammation independent of age, renal function, and HgbA1C levels.