A Case of acute Myocardial Infarction in a Patient with Essential Thrombocythaemia Treated with Anagrelide.

Anagrelide is a medication primarily used to manage thrombocytosis, an abnormal increase in platelet levels in the blood. It is often prescribed for patients with myeloproliferative disorders, such as essential thrombocythaemia (ET). Given the heightened susceptibility to thromboembolism associated with this condition, the primary emphasis in treatment revolves around reducing the risk of thrombotic events through the administration of cytotoxic agents. While anagrelide is generally effective in reducing platelet counts, it comes with potential side effects, including an increased risk of certain thrombotic events. Anagrelide acts by inhibiting megakaryocyte maturation and platelet release, thereby reducing platelet production. However, this platelet-lowering effect may be accompanied by an increase in platelet activation and reactivity, which could contribute to a prothrombotic state. We present a case of a 60-year-old female with a history of ET, managed with anagrelide and hydroxyurea therapy, who experienced an acute ST-elevation myocardial infarction. LEARNING POINTS: The dual role of anagrelide: although anagrelide is effective in lowering platelet levels in essential thrombocythaemia, it can increase platelet activation, raising thrombotic risk. Clinicians need to monitor patients closely for thrombotic events.Balancing efficacy and side effects: the risk of severe side effects such as myocardial infarction, as seen in this case report, necessitates a balanced approach in using anagrelide, weighing its benefits against potential risks.

Primary intracranial marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue arising in the lateral ventricle: Case report and review of pathogenesis.

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal subtype of nonHodgkin's lymphoma. Ventricle-predominant PCNSL, arising in the CNS ventricular system, is a rare entity. In over 90% of cases, PCNSL is classified as diffuse large B-cell lymphoma. Rarely, PCNSL may be classified as marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT). Taken together, a primary MALT-type MZBCL arising in a cerebral ventricle is an extremely rare presentation. Case Description: A 69-year-old female presented with a persistent left frontal headache for 1 year. Magnetic resonance imaging revealed an enhancing soft-tissue lesion within the left lateral ventricle, with associated periventricular edema. We performed an excisional biopsy of the tumor, which grossly had the appearance of a meningioma. Histopathology of the tumor was consistent with MZBCL of the MALT type. The patient was treated with Rituximab and Ibrutinib. Six months after surgery, she remained neurologically intact and free of disease. Conclusion: We report the case of a primary MALT-type MZBCL arising in the CNS ventricular system, with characteristics mimicking meningioma. This lymphoma involved the lateral ventricle and likely originated from the choroid plexus. Meningothelial cells and epithelial cells in the choroid plexus may acquire MALT in response to chronic inflammatory stimuli, such as infection or autoimmune disease. In rare cases, MALT lymphoma may develop as part of this pathogenesis.

The Prognostic Significance of Peripheral Blood Biomarkers in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab: A Clinical Study.

Systemic inflammation has long been associated with poor outcomes in many types of solid tumors. Peripheral blood biomarkers, such as absolute lymphocyte count (ALC) and the ratio of absolute neutrophil count to absolute lymphocyte count (ANC/ALC), have been shown to be immune-inflammatory parameters highlighting an individual's immune status. The prognostic role of ALC and ANC/ALC on overall survival (OS) was examined in patients with advanced non-small cell lung carcinoma (NSCLC) receiving pembrolizumab. Of a total of 239 patients, 52% were male, with a median age of 67 years (interquartile range [IQR], 59-73). Most patients had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PD-L1 expression was >50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.8 months (IQR, 2.9-12.7). An ANC/ALC <5 was associated with improved OS at initiation of pembrolizumab (P = .002), whereas an ALC >1.4 deciliter (dL) trended toward improved OS compared with ALC <1.4 dL (P = .053). After adjusting for potential cofounders with a multivariate analysis, a baseline ANC/ALC of 5 or higher was associated with a significantly increased risk of death (HR, 1.93; 95% CI, 1.27-2.93; P = .002). An ANC/ALC <5 at the time of initiation of treatment with pembrolizumab was associated with improved OS in patients with advanced NSCLC. The median ALC and ANC/ALC were significantly lower after 6 weeks of treatment with pembrolizumab.

Acute promyelocytic leukemia presenting as recurrent venous and arterial thrombotic events: a case report and review of the literature.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a translocation of chromosomes 15 and 17, creating an alternation in the retinoic acid receptor-alpha (RAR-alpha) gene. This leads to excessive medullary production of promyelocytic blasts, which are frequently associated with the hemorrhagic complications seen in APL. In contrast, APL-associated thrombosis occurs much less frequently and is an underappreciated life-threatening manifestation of the disease. Most thrombotic events occur during induction chemotherapy with all-transretinoic acid and are rarely seen as the initial presentation on APL. Here we report an exceedingly rare case of a patient with recurrent venous and arterial thrombotic events, including deep vein thrombosis, bilateral segmental pulmonary embolism, an ischemic stroke, splenic infarcts, and renal infarcts, later found to have APL. We aim to discuss the most recent understanding of the pathogenesis of APL-associated thrombosis and to summarize the literature of this rare presentation of APL.

Efficacy of PARP Inhibitors as Maintenance Therapy for Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials.

Background: PARP inhibitors have been recently approved by the FDA for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Their effectiveness is seen when used with androgen deprivation therapy in patients with or without deleterious germline and somatic genetic mutations. Objectives: To identify all the randomized controlled trials (RCTs) in which PARP inhibitors have been assessed in the treatment of mCRPC, and to compare the efficacy of PARP inhibitors in these patients with standard-of-care (S/nonhormonal therapies like abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in terms of progression-free survival (PFS) and overall survival (OS). Search strategy: A systemic review search was conducted using PubMed, Embase, and Central Cochrane Registry. Selection criteria: Randomized clinical trials with PARP inhibitors, with or without antihormonal therapy, as the intervention arm, with SOC as control. Data analysis: HRs were calculated for PFS and OS. For effect sizes, a confidence interval of 95% was used, and for statistical significance, a P value of less than .05 was used. Analysis was done using random effects and fixed models and both were reported. Heterogeneity was evaluated using I2 statistic. Results: Three RCTs were included in the analysis. PARP inhibitors showed a statistically significant improvement in OS when calculated using a fixed model (HR, 0.751; 95% CI, 0.582-0.968) but the improvement was not significant when calculated using a random model (HR, 0.758; 95% CI, 0.565-1.017; I2 = 23). Similarly, the improvement in PFS was statistically significant when calculated using a fixed model (HR, 0.626; 95% CI, 0.521-0.752), and no statistical significance was noted with a random model (HR, 0.674; 95% CI, 0.437-1.039; I2 = 80). Conclusions: PARP inhibitors contributed to significant increases in PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide. This efficacy was pronounced among the patients with deleterious germline or somatic homologous recombination repair gene mutations, although patients without these mutations also showed a better PFS and OS in comparison with SOC therapy.

Neutropenic Enterocolitis Secondary to Sulfasalazine in a Woman With Psoriatic Arthritis.

Neutropenic enterocolitis (NE) also known as typhlitis is a serious condition that has been described in immunosuppressed hosts including patients with leukemia, HIV and in patients on chemotherapy. We present the first case of female on sulfasalazine for psoriatic arthritis, otherwise healthy, who was diagnosed with NE involving the cecum and rectum. This adds up to the cases of NE diagnosed in nononcologic conditions. A 65-year-old female with a history of psoriatic arthritis on sulfasalazine, presented to the emergency department (ED) after an episode of syncope. She was complaining of a fever and mild generalized abdominal pain. Physical exam was remarkable for peri-umbilical tenderness. Severe neutropenia and acute kidney injury were found on blood work. CT scan of the abdomen showed evidence of colitis, involving the cecum, ascending colon and rectum, which in light of neutropenia was consistent with NE. Clostridium difficile colitis was ruled out. Intravenous fluids and broad-spectrum antibiotics were initiated, and sulfasalazine was discontinued. The patient was subsequently afebrile and was out of neutropenia by day 3 without the need for granulocyte-macrophage colony-stimulating factor (GM-CSF). By day 5, the patient was pain free and was discharged. Even though NE is primarily described in the setting of malignancies and chemotherapy, one should keep in mind that this entity can occur in people on any immunosuppressive therapy. Early discontinuation of sulfasalazine and conservative management were essential in the treatment of NE in this case. Whether neutropenia precipitates colitis or the latter causes agranulocytosis by bone marrow suppression through cytokines remains to be proved. The diagnosis of medication-related adverse reactions remains a big challenge for clinicians and therefore requires a high index of suspicion. Resolution of the symptoms can simply occur with the discontinuation of the offending drug and often does not require extensive workup or treatments that might cause harm to the patient's health.

Primary plasma cell leukemia: A case report and review of the literature.

Due to the rarity and fulminant nature of the condition, there are limited data driving dialogue for optimal treatment strategies for plasma cell leukemia (PCL). Additionally, the current diagnostic definition of PCL has not been prospectively studied which may result in delays to initiating early aggressive treatment due to underdiagnosis.

Venous Thrombosis Secondary to Acute Cytomegalovirus Infection in an Immunocompetent Host: Consideration for New Screening Guidelines.

Serious thrombotic complications associated with an acute cytomegalovirus (CMV) infection in immunocompromised and immunocompetent patients are becoming increasingly recognized. While typically asymptomatic and self-limiting, an acute CMV infection appears to demonstrate a rare propensity for a vascular thrombosis, such as deep vein thrombosis (DVT), thrombophlebitis, and pulmonary embolism (PE). It remains unclear whether other predisposing factors play a role in its pathogenesis. We report the case of a young, immunocompetent male with extensive lower extremity DVT who was coincidentally found to be CMV-immunoglobulin M (IgM) seropositive. In light of the increasing prevalence of CMV-associated thrombotic events, we reviewed the current literature on its incidence, pathophysiology, clinical features, and thrombophilia screening to consider the possibility of CMV seropositivity as an independent risk factor for vascular events. This may have repercussions for screening guidelines and preventive strategies in those with active CMV infection.

Composite Diffuse Large B-cell and Mantle Cell Lymphoma: A Case Report.

Composite lymphoma is an extremely rare clinical entity and is characterized by the presence of two different subtypes of lymphoma in the same lymph node. We report a case of composite lymphoma in a 57-year-old male presenting with leg and groin pain. The right inguinal lymph node biopsy showed large and small cells. Immunohistochemistry was consistent with large cells staining for diffuse large B-cell lymphoma (DLBCL) and small cells positive for mantle cell lymphoma (MCL). Polymerase chain reaction (PCR) analysis of immunoglobulin heavy (IGH) chain and immunoglobulin kappa (IGK) light chain gene rearrangements confirmed that the two were clonally unrelated neoplasms. There are only two reported cases of composite lymphoma with this combination in the published English literature. We report the third such case and discuss the pathology, diagnostic challenges and management of composite lymphoma.

Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer.

Suppression of gonadal testosterone synthesis represents the standard first line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer (CRPC), it is possible to detect persistent activation of the androgen receptor (AR) through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17α-hydroxylase and 17,20-lyase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a significant improvement in overall survival (OS) with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone (ACTH), providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-lyase (orteronel, galeterone and VT-464) that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors; recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents; and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone benefit or restore abiraterone activity.

Clinical experience using vitamin d and analogs in the treatment of myelodysplasia and acute myeloid leukemia: a review of the literature.

Despite progress in understanding the biology of acute myeloid leukemia (AML), and despite advances in treatment, the majority of patients with AML die from the disease. The observation that Vitamin D can induce AML blast cells in vitro to differentiate along the monocytic lineage was made 30 years ago; however, it remains to translate this into a clinically meaningful strategy. This is a review of published clinical experience regarding the use of Vitamin D and its analogs, either alone or in combination with other agents, to treat AML. In many of these reports, investigators included patients with myelodysplasia (MDS) as well as AML patients in their treatment cohorts; therefore reports of Vitamin D and its analogs in treating MDS are included. This review documents heterogeneity in selection criteria for patients treated in these studies, the spectrum of Vitamin D analogs used in various studies, and the differing dosing strategies employed by investigators. Despite examples of occasional clinical efficacy, barriers remain to the successful application of Vitamin D in the treatment of MDS and AML. These include the lack of definition of a particularly sensitive target population, and the as yet unknown optimal choice of Vitamin D analog and dosing schedule.