Transplant Eligible and Ineligible Elderly Patients with AML-A Genomic Approach and Next Generation Questions.

The management of elderly patients diagnosed with acute myelogenous leukemia (AML) is complicated by high relapse risk and comorbidities that often preclude access to allogeneic hematopoietic cellular transplantation (allo-HCT). In recent years, fast-paced FDA drug approval has reshaped the therapeutic landscape, with modest, albeit promising improvement in survival. Still, AML outcomes in elderly patients remain unacceptably unfavorable highlighting the need for better understanding of disease biology and tailored strategies.

Evolving Standards of Care in the Management of Localized Colorectal Cancer.

The treatment of patients with localized rectal cancer is complex and requires input from a multidisciplinary team. Baseline local staging and mismatch repair protein testing are vital to develop individualized treatment plans. There are multiple options in terms of treatment modalities and sequencing, including transanal excision, short-course radiation, long-course chemoradiation, chemotherapy doublet or triplet, nonoperative management, and immune checkpoint blockade for patients with mismatch repair deficient tumors.

Overcoming the hurdles: surmounting acquired resistance to anti-EGFR therapy in metastatic colorectal cancer.

Colorectal cancer is the third most prevalent cancer type in the United States, with an alarming incidence and mortality rate, especially among individuals younger than 50 years. The epidermal growth factor receptor (EGFR), essential for cell proliferation and survival, has surfaced as a promising therapeutic target for metastatic colorectal cancer and has demonstrated success in various clinical trials. Monoclonal antibodies such as cetuximab and panitumumab have proven to be effective against EGFR by blocking vital downstream signaling pathways and inhibiting gene transcription and cell proliferation.

A Multicenter Retrospective Chart Review of Clinical Outcomes Among Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer.

Background: On May 28, 2021, the United States Food and Drug Administration (FDA) granted accelerated approval to sotorasib for second-line or later treatment of patients with locally advanced or metastatic KRAS G12C mutant non-small cell lung cancer (NSCLC). This was the first FDA-approved targeted therapy for this patient population. Due to a paucity of real world data describing clinical outcomes in patients with locally advanced or metastatic KRAS G12C mutated NSCLC in the second-line or later, we sought to compile a large, academic medical center-based historical dataset to clarify clinical outcomes in this patient population.

Race & sex disparities related to low-dose computed tomography lung cancer screening eligibility criteria: A lung cancer cases review.

Introduction: The United States Preventive Services Task Force (USPSTF) recommendations do not account for race and sex differences in lung cancer risk. We compared the sensitivity for finding lung cancer cases eligible for lung cancer screening (LCS) by USPSTF 2013 recommendations versus the PLCOm2012 model at an equivalent threshold.

Methods: Using Georgetown University Hospital tumor registry, we identified lung cancer cases (≥55 years old) between 2014 and 2018.

Comprehensive Analysis of R-Spondin Fusions and RNF43 Mutations Implicate Novel Therapeutic Options in Colorectal Cancer.

Purpose: Gene fusions involving R-spondin (RSPOfp) and RNF43 mutations have been shown to drive Wnt-dependent tumor initiation in colorectal cancer. Herein, we aimed to characterize the molecular features of RSPOfp/RNF43 mutated (mut) compared with wild-type (WT) colorectal cancers to gain insights into potential rationales for therapeutic strategies.

Experimental Design: A discovery cohort was classified for RSPOfp/RNF43 status using DNA/RNA sequencing and IHC.

Pembrolizumab-induced cytokine release syndrome in a patient with metastatic lung adenocarcinoma: a case report.

Cytokine release syndrome (CRS) is a well-described immune-related adverse event following chimeric antigen receptor T-cell therapy, but has rarely been reported following anti-programmed death ligand-1 therapy. We report the case of a 55-year-old man with metastatic lung adenocarcinoma who presented with fever, chills and hypotension. Initial labs were notable for highly elevated serum ferritin levels and mildly elevated triglyceride levels.

The role of total ankle replacement in patients with haemophilia and end-stage ankle arthropathy: A review.

Haemophilia is the most common X-linked bleeding disorder, affecting over 1 million individuals throughout the world. Patients are subclassified into mild, moderate and severe disease based on per cent factor activity level. Nearly, all patients with haemophilia develop haemophilic arthropathy (HA) by age 30 and HA is known to have a negative impact on physical health subscores in Haem-A-QOL, a validated quality of life scoring system for patients with haemophilia.

A Prospective Cohort Study of Factors Associated With Place of Death Among Patients With Late-Stage Cancer in Southern Africa.

Context: Identifying factors that affect terminally ill patients' preferences for and actual place of death may assist patients to die wherever they wish.

Objective: The objective of this study was to investigate factors associated with preferred and actual place of death for cancer patients in Johannesburg, South Africa.

Methods: In a prospective cohort study at a tertiary hospital in Johannesburg, South Africa, adult patients with advanced cancer and their caregivers were enrolled from 2016 to 2018.

Epidemiologic trends in neuroendocrine tumors: An examination of incidence rates and survival of specific patient subgroups over the past 20 years.

Introduction: Neuroendocrine tumors (NETs) represent a small proportion of cancers, but are increasing in incidence due to incidental diagnosis. We examined NET incidence and survival over time in a population-based registry.

Materials/methods: We identified all NET cases diagnosed between 1995 and 2014 in the Surveillance, Epidemiology, and End Results database, November 2016 submission.

Magnetic Resonance Imaging-Based Screening for Asymptomatic Brain Tumors: A Review.

Brain tumors comprise 2% of all cancers but are disproportionately responsible for cancer-related deaths. The 5-year survival rate of glioblastoma, the most common form of malignant brain tumor, is only 4.7%, and the overall 5-year survival rate for any brain tumor is 34.

Informal Caregiver Challenges for Advanced Cancer Patients During End-of-Life Care in Johannesburg, South Africa and Distinctions Based on Place of Death.

Context: In sub-Saharan Africa, late diagnosis with cancer is common. Many dying patients rely on family members for care; little is known about the challenges African informal caregivers face.

Objectives: To better understand the challenges of informal caregivers at the end of life in South Africa, both at home and in inpatient facilities.

FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy.

In addition to the infectious consequences of immunodeficiency, patients with Wiskott-Aldrich syndrome (WAS) often suffer from poorly understood exaggerated immune responses that result in autoimmunity and elevated levels of serum IgE. Here, we have shown that WAS patients and mice deficient in WAS protein (WASP) frequently develop IgE-mediated reactions to common food allergens. WASP-deficient animals displayed an adjuvant-free IgE-sensitization to chow antigens that was most pronounced for wheat and soy and occurred under specific pathogen-free as well as germ-free housing conditions.

Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis.

Background: During IgE-mediated immediate hypersensitivity reactions, vascular endothelial cells permeabilize in response to mast cell mediators. We have demonstrated previously that patients and mice with signal transducer and activator of transcription 3 (STAT3) mutations (autosomal dominant hyper-IgE syndrome [AD-HIES]) are partially protected from anaphylaxis.

Objectives: We sought to study the mechanism by which STAT3 contributes to anaphylaxis and determine whether small-molecule inhibition of STAT3 can prevent anaphylaxis.

Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia.

Isolated congenital asplenia (ICA) is characterized by the absence of a spleen at birth in individuals with no other developmental defects. The patients are prone to life-threatening bacterial infections. The unbiased analysis of exomes revealed heterozygous mutations in RPSA in 18 patients from eight kindreds, corresponding to more than half the patients and over one-third of the kindreds studied.