5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer.

Immune checkpoint inhibitors (ICIs) drastically improve therapeutic outcomes for lung cancer, but accurately predicting individual patient responses to ICIs remains a challenge. We performed the genome-wide profiling of 5-hydroxymethylcytosine (5hmC) in 85 plasma cell-free DNA (cfDNA) samples from lung cancer patients and developed a 5hmC signature that was significantly associated with progression-free survival (PFS). We built a 5hmC predictive model to quantify the 5hmC level and validated the model in the validation, test, and control sets.

Cell-Free DNA 5-Hydroxymethylcytosine Signatures for Lung Cancer Prognosis.

Accurate prognostic markers are essential for guiding effective lung cancer treatment strategies. The level of 5-hydroxymethylcytosine (5hmC) in tissue is independently associated with overall survival (OS) in lung cancer patients. We explored the prognostic value of cell-free DNA (cfDNA) 5hmC through genome-wide analysis of 5hmC in plasma samples from 97 lung cancer patients.

Thrombopoietin Receptor Agonists for Thrombocytopenia Secondary to HER2-Targeted Antibody Drug Conjugates.

Trastuzumab emtansine and trastuzumab deruxtecan are widely used in breast cancer and other solid tumor malignancies. Thrombocytopenia is a common adverse event associated with the use of these agents that can lead to a treatment delay, reduction in dose intensity, and discontinuation. The role of thrombopoietin receptor agonists (TPO-RA) remains unknown in this setting.

HER2-targeted antibody-drug conjugates for breast cancer: ancestry and dose adjustment for thrombocytopenia.

Background: Thrombocytopenia is a common adverse event on HER2-targeted therapies, fam-trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1). A reported association of Asian ancestry with this event merits investigation to rule out potential confounding.

Methods: Subjects in this retrospective cohort were female patients with HER2 positive breast cancer, of Asian or non-Hispanic White ancestry, who initiated T-DM1 or T-DXd from January 2017 through October 2021.

Difficulties in Defining Oligometastatic Prostate Cancer: Implications for Clinical Trial Accrual and Community Practice Adoption of Metastasis-Directed Therapy Approaches.

Background: Metastasis-directed therapy is widely utilized for oligometastatic prostate cancer patients, but standard imaging does not always identify metastases definitively and, even with PSMA PET, there may be equivocal findings. Not all clinicians have access to detailed imaging review, particularly outside of academic cancer centers, and PET scan access is also limited. We sought to understand how imaging interpretation impacted recruitment to a clinical trial for oligometastatic prostate cancer.

A Practical Guide to Relugolix: Early Experience With Oral Androgen Deprivation Therapy.

Background: Relugolix is the newest form of androgen deprivation therapy (ADT) approved for prostate cancer. However, as an oral drug, several real-world concerns exist, particularly medication compliance, safety with other androgen receptor-targeted agents, and financial burden to patients.

Methods: A single institution retrospective chart review was conducted evaluating all patients who were prescribed relugolix for any prostate cancer indication from January 1, 2021 to January 31, 2022.

Recurrent small bowel obstruction caused by Burkitt lymphoma in an elderly man: a case report and review of the literature.

Background: Acute small bowel obstruction is a common surgical emergency usually caused by abdominal adhesions, followed by intraluminal tumors from metastatic disease. Although lymphomas have been known to cause bowel obstruction, Burkitt lymphoma is seldom reported to induce an obstruction in the adult population.

Case Presentation: A 78-year-old Hispanic man with a history of abdominal interventions presented to our hospital with abdominal pain.

Pancreatic adenocarcinoma with early esophageal metastasis: A case report and review of literature.

Background: Pancreatic adenocarcinoma is an aggressive malignancy with a high propensity to metastasize. Esophageal metastasis manifesting as dysphagia is rarely reported in the literature and has not to our knowledge been reported prior to the appearance of the primary disease.

Case Summary: A patient presented with progressive dysphagia to solids and a persistent earache.

Hyperprogressive NSCLC With Two Immune-Checkpoint Inhibitors.

Introduction: Immune-checkpoint inhibitors (ICIs) are transforming the modern era of cancer therapy. As new treatment options are becoming available, new patterns of disease behavior are manifesting. One such phenomenon, known as hyperprogressive disease (HPD), is a rare complication resulting in exponential disease progression on exposure to an ICI.

A Case of Histiocytic Sarcoma Arising from Mycosis Fungoides.

Histiocytic sarcoma (HS) is an uncommon malignant neoplasm arising from mature histiocytes and most commonly characterized by the immunophenotypic expression of CD68, CD163, or lysozyme. Although rare, HS arising as a second primary malignancy following hematolymphoid neoplasms has been reported. To our knowledge, this is the first reported case of HS occurring as a second primary malignancy in a patient with mycosis fungoides (MF), with the retained immunophenotype markers CD30 and CD4.

Macrophage Activation Syndrome Secondary to Underlying Sarcoidosis.

Hemophagocytic lymphohistiocytosis (HLH) due to an underlying rheumatologic condition is known as macrophage activation syndrome (MAS), a rare and serious complication that often has a delayed diagnosis. MAS can complicate any rheumatologic disease, although it is most prevalent in systemic juvenile idiopathic arthritis. MAS occurring as a sequela of sarcoidosis is seldom reported.

Cryptococcal meningoencephalitis in patients with mantle cell lymphoma on ibrutinib.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, has been increasingly widely used in relapsed and refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia [1, 2]. With its use becoming more common, there have been emerging case reports of opportunistic infections like cryptococcal infections [3-8]. These infections in patients receiving ibrutinib were mostly reported in patients with chronic lymphocytic leukaemia, who have poor immune reconstitution.

Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.

Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection.

HIV-specific Immunity Derived From Chimeric Antigen Receptor-engineered Stem Cells.

The human immunodeficiency virus (HIV)-specific cytotoxic T lymphocyte (CTL) response is critical in controlling HIV infection. Since the immune response does not eliminate HIV, it would be beneficial to develop ways to enhance the HIV-specific CTL response to allow long-term viral suppression or clearance. Here, we report the use of a protective chimeric antigen receptor (CAR) in a hematopoietic stem/progenitor cell (HSPC)-based approach to engineer HIV immunity.

CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection.

Unlabelled: A unique aspect of human monocytes, compared to monocytes from many other species, is that they express the CD4 molecule. However, the role of the CD4 molecule in human monocyte development and function is not known. We determined that the activation of CD4 via interaction with major histocompatibility complex class II (MHC-II) triggers cytokine expression and the differentiation of human monocytes into functional mature macrophages.