Early progression and transformation of a splenic diffuse red pulp small B-cell lymphoma with NOTCH1, ARID2, CREBBP, and TNFRSF14 gene mutations.

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is a rare entity. Diagnosis is typically achieved with splenectomy and most patients remain in remission after this intervention. Hemoglobin value less than 10 g/dL and NOTCH1, TP53, and MAP2K1 gene mutations at diagnosis have been associated with worse outcome. Progression after splenectomy of SDRPL is possible, although transformation to aggressive lymphoma has rarely been reported. We herein report the case of a patient formerly diagnosed with SDRPL with gene mutations involving CREBBP, NOTCH1, ARID2, and TNFRSF14 who transformed to diffuse large B-cell lymphoma six months after splenectomy.

Systemic Lupus Erythematosus in Disguise: Acute Pancreatitis as Initial Presentation.

Macrophage activation syndrome (MAS) can rarely coexist with lupus pancreatitis. We report on a 20-year-old woman with abdominal pain, nausea, and vomiting. Laboratories were notable for pancytopenia, elevated liver enzymes, elevated ferritin, lipase, and triglycerides. Chest and abdominal computerized tomography (CT) scans revealed bilateral axillary lymphadenopathy, patchy lower lobe consolidations, small pleural effusions, ascites, and splenomegaly. Peritoneal fluid cytology showed lymphocytes and histiocytes with hemophagocytic changes. Immunological workup met the criteria for systemic lupus erythematosus (SLE). Pulse-dosed steroids relieved her condition. Given the high mortality rate associated with MAS, early detection of concomitant pancreatitis and MAS in the context of underlying SLE is critical.

PI3K Isoforms in CD8+ T Cell Development and Function.

CD8+ T cells are an essential part of the immune system and play a vital role in defending against tumors and infections. The phosphoinositide-3-kinase (PI3K), especially class I, is involved in numerous interrelated signaling pathways which control CD8+ T cell development, maturation, migration, activation, and differentiation. While CD8+ T lymphocytes express all class I PI3K isoforms (PI3Kα, PI3Kß, PI3Kδ, and PI3Kγ), isoform-specific functions, especially for PI3Kα and PI3Kß have not been fully elucidated. A few studies suggest the important role of p110δ and p110γ in CD8+ T cell activation, signaling, chemotaxis and function and several clinical trials are currently testing the effect of isoform-specific inhibitors in various types of cancers, including Indolent Non-Hodgkin Lymphoma, Peripheral T cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, non-small cell lung carcinoma (NSCLC), head & neck cancer, and breast cancer. This chapter summarizes current knowledge of the roles of various PI3K isoforms and downstream signaling pathways in regulating CD8+ T cell fate, including cell proliferation, migration, and memory generation. We also discuss certain clinical trials employing PI3K inhibitors for cancer therapy, their limitations, and future perspectives.

Factors Affecting Compliance to Anti-Vascular Endothelial Growth Factor Treatment of Diabetic Macular Edema in a Cohort of Jordanian Patients.

PURPOSE: To determine compliance rates and characteristics and to investigate factors affecting patients' adherence to treatment with anti-vascular endothelial growth factors (anti-VEGFs) for diabetic macular edema (DME) in a cohort of Jordanian patients. METHODS: A retrospective case series wherein the files of DME patients treated with anti-VEGFs were reviewed and analyzed for factors affecting treatment compliance was undertaken. Demographic, clinical and ocular characteristics were recorded. All patients were also interviewed by phone using a structured questionnaire. Univariate and multivariate analyses were performed to determine factors associated with compliance. RESULTS: A total of 117 patients (65 males 52 females) were included in this study with a mean age of 62.93 years (±9.75). Approximately, 85% of patients were compliant to their treatment and follow-up plan during the first year of management. Subjective perception of visual improvement after receiving three loading doses was the only independent variable with a unique statistically significant contribution to compliance. All other studied factors in this group of patients were not significantly associated with patient compliance. CONCLUSION: VEGF suppression via the intravitreal route to treat DME is a long-term process that requires caregiver dedication but also proper patient compliance. Addressing real-life barriers in those patients may help guide future strategies to improve the treatment experience, lower the financial burden and contribute to better outcomes. Patients' perceptions of possible treatment outcomes at the short term may influence their long-term commitment to therapy.