Delirium in Children Undergoing Hematopoietic Cell Transplantation: A Multi-Institutional Point Prevalence Study.

Delirium occurs frequently in adults undergoing hematopoietic cell transplantation, with significant associated morbidity. Little is known about the burden of delirium in children in the peri-transplant period. This study was designed to determine delirium rates, define risk factors (demographic and treatment related), and establish feasibility of multi-institutional bedside screening for delirium in children undergoing hematopoietic cell transplant.

Immunotherapy breaches low-sugar dieting of tumor Treg cells.

Glycolysis supports effector T cell function but is detrimental to the immunosuppressive activity of regulatory T cells. In a recent issue of Nature, two papers address a role for glucose and lactate availability within the tumor microenvironment for the balance of pro- and anti-tumoral effects of T cells and the efficacy of neoadjuvant cancer immunotherapy.

A unified atlas of CD8 T cell dysfunctional states in cancer and infection.

CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across experimental and clinical settings. By carrying out a unified analysis of over 300 assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) experiments from 12 studies of CD8 T cells in cancer and infection, we defined a shared differentiation trajectory toward dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell states across models.

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance.

Activation of the STAT5 transcription factor downstream of the Interleukin-2 receptor (IL-2R) induces expression of Foxp3, a critical step in the differentiation of regulatory T (Treg) cells. Due to the pleiotropic effects of IL-2R signaling, it is unclear how STAT5 acts directly on the Foxp3 locus to promote its expression. Here, we report that IL-2 - STAT5 signaling converged on an enhancer (CNS0) during Foxp3 induction.

Treating breast implant-associated anaplastic large cell lymphoma.

Each year, hundreds of thousands of women undergo aesthetic or reconstructive breast implant surgery. Clinicians and patients must be aware of the benefits and risks of this surgery. Recently, the FDA suggested a recall of certain textured breast implants because of a link between these implants and a rare form of lymphoma, now referred to as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

What Should Clinicians Do When a Patient's Autonomy Undermines Her Being Treated Equitably?

Language and cultural barriers can impede communication between patients and clinicians, exacerbating health inequity. Additional complications can arise when family members, intending to protect their loved ones, ask clinicians to lie or not disclose to patients their diagnoses, prognoses, or intervention options. Clinicians must express respect for patients' and families' cultural, religious, and social norms regarding health care decision making, but they might also be ethically troubled by some decisions' effects on patients' health outcomes.

Immune Escape in Prostate Cancer: Known and Predicted Mechanisms and Targets.

Complex immune evasion mechanisms and lack of biomarkers predicting responsiveness to immune checkpoint blockade therapies compromise immunotherapy's therapeutic efficacy for patients with prostate cancer. The authors review established and nominated immune evasion mechanisms in prostate cancer and discuss how the precise treatment strategies can be developed to improve efficacy of immunotherapy.

Targeting Phosphatidylserine Enhances the Anti-tumor Response to Tumor-Directed Radiation Therapy in a Preclinical Model of Melanoma.

Phosphatidylserine (PS) is exposed on the surface of apoptotic cells and is known to promote immunosuppressive signals in the tumor microenvironment (TME). Antibodies that block PS interaction with its receptors have been shown to repolarize the TME into a proinflammatory state. Radiation therapy (RT) is an effective focal treatment of isolated solid tumors but is less effective at controlling metastatic cancers.

Highly accurate diagnosis of papillary thyroid carcinomas based on personalized pathways coupled with machine learning.

Thyroid nodules are neoplasms commonly found among adults, with papillary thyroid carcinoma (PTC) being the most prevalent malignancy. However, current diagnostic methods often subject patients to unnecessary surgical burden. In this study, we developed and validated an automated, highly accurate multi-study-derived diagnostic model for PTCs using personalized biological pathways coupled with a sophisticated machine learning algorithm.

The Transcription Factor Foxp3 Shapes Regulatory T Cell Identity by Tuning the Activity of trans-Acting Intermediaries.

Regulatory T (Treg) cell identity is defined by the lineage-specifying transcription factor (TF) Foxp3. Here we examined mechanisms of Foxp3 function by leveraging naturally occurring genetic variation in wild-derived inbred mice, which enables the identification of DNA sequence motifs driving epigenetic features. Chromatin accessibility, TF binding, and gene expression patterns in resting and activated subsets of Treg cells, conventional CD4 T cells, and cells expressing a Foxp3 reporter null allele revealed that the majority of Foxp3-dependent changes occurred at sites not bound by Foxp3.

Immunotherapeutic strategies in breast cancer: A clinical update.

Immunotherapy has been incorporated into the standard of care for a wide range of malignancies. The study of tumor-infiltrating lymphocytes has emphasized the importance of the host antitumor immune response in the natural history of breast cancer. Recent clinical trials have used immunotherapeutic approaches to augment this response and improve outcomes for patients with breast cancer.

Deep Learning to Estimate RECIST in Patients with NSCLC Treated with PD-1 Blockade.

Real-world evidence (RWE), conclusions derived from analysis of patients not treated in clinical trials, is increasingly recognized as an opportunity for discovery, to reduce disparities, and to contribute to regulatory approval. Maximal value of RWE may be facilitated through machine-learning techniques to integrate and interrogate large and otherwise underutilized datasets. In cancer research, an ongoing challenge for RWE is the lack of reliable, reproducible, scalable assessment of treatment-specific outcomes.

Enhancing mucosal immunity by transient microbiota depletion.

Tissue resident memory CD8 T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice.

Necrotizing fasciitis: A comprehensive review.

Necrotizing soft-tissue infections (NSTIs) are rare but rapidly progressive, life-threatening bacterial infections with high morbidity and mortality. NSTIs include necrotizing forms of fasciitis, myositis, and cellulitis. This article focuses on necrotizing fasciitis (NF) and discusses NF classifications, clinical features, diagnostic approaches, evidence-based treatments, and nursing interventions.

An Evidence-Based Approach to Increasing Nurses' Publication Rates.

Background: Writing for publication in peer-reviewed journals is one of the most important types of writing that nurses engage in. It is essential for advancing the nursing profession, health care organizations, and individual nurses. Despite its importance, however, the rate of publication remains very low among nurses.

COVID-19 in patients with lung cancer.

Background: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic.

Patients And Methods: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020.

Optimizing Tissue Use: A Step-wise Approach to Diagnosing Squamous Cell Lung Carcinoma on Small Biopsies.

Background: Histologic subtyping of lung cancer has significant implications for treatment planning. Accurate diagnosis based on cytology/small biopsy specimens is challenging and frequently determined by morphology, as material is often not sufficient for immunohistochemical studies (IHC). We investigated the concordance between the rates of diagnosis from cytology/small biopsies compared with surgical specimens in patients with squamous cell lung cancer (SCC) and the utility of IHC for diagnostic precision in lung cancer subtyping.

Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers.

The coronavirus disease 2019 (COVID-19) pandemic has led to dramatic changes in oncology practice. It is currently unknown whether programmed death 1 (PD-1) blockade therapy affects severity of illness from COVID-19 in patients with cancer. To address this uncertainty, we examined consecutive patients with lung cancers who were diagnosed with COVID-19 and examined severity on the basis of no or prior receipt of PD-1 blockade.

Reducing Waste and Increasing Sustainability in Health Care Settings.

Since the 1960s, plastic has been used in the production of medical equipment and products that improve patient comfort, safety, and treatment. Yet an unwelcome challenge has emerged in the years since: how to safely dispose of this material without negatively affecting human health and the environment. Working with medical devices and supplies that are constructed using plastics, nurses are at the forefront of this issue and must identify solutions, collaborate with other health care workers, and lead efforts to establish more sustainable options.

18F-FDG PET Imaging Features of Patients With Autoimmune Lymphoproliferative Syndrome.

Introduction: Autoimmune lymphoproliferative syndrome (ALPS) is a rare immune dysregulatory condition, usually presenting in childhood with massive lymphadenopathy, splenomegaly, and an increased incidence of lymphoma. Methods to differentiate between benign ALPS adenopathy and lymphoma are needed. To this end, we evaluated the usefulness of FDG PET.

Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity.

Dendritic cells (DCs) play a critical role in orchestrating adaptive immune responses due to their unique ability to initiate T cell responses and direct their differentiation into effector lineages. Classical DCs have been divided into two subsets, cDC1 and cDC2, based on phenotypic markers and their distinct abilities to prime CD8 and CD4 T cells. While the transcriptional regulation of the cDC1 subset has been well characterized, cDC2 development and function remain poorly understood.