A Case of a Micronesian Woman in Hawai'i with Lymphoma and the Role of Implicit Bias in Medicine Affecting Her Care.

Medically indigent patients, patients of color, those with insufficient health insurance, or patients with severe diseases have a high rate of poor health care quality caused by unconscious implicit and explicit biases. Awareness of the relationship between unconscious implicit bias and negative health care outcomes is increasing in the health care community. The objective of this case study was to examine implicit biases that negatively affected the patient care of a young Micronesian woman with a severe cutaneous disease in Hawai'i. Her medical care and death may have been affected by a combination of implicit biases, including bias based on her race, type of health insurance, and underlying disease. Implicit biases and their role in health care disparities are often unintentional and not obvious. Increased awareness by health care providers may help to avoid inequities in clinical decision-making and improve outcomes.

Severe Mpox Infections in People With Uncontrolled Human Immunodeficiency Virus.

In the current mpox outbreak, infections are usually self-limited. We describe 3 patients with uncontrolled HIV and mpox infections lasting months, causing debilitating lesions, complications, and death, despite initiating anti-mpox and antiretroviral therapy. Delayed treatment of mpox with antiviral agents may contribute to poor outcomes in severely immunocompromised patients.

CoNaMad-Cohorte de Nacimiento de Madre de Dios/Madre de Dios Birth Cohort to Study Effects of in-utero Trace Metals Exposure in the Southern Peruvian Amazon.

Background: In-utero exposure to mercury and other trace metals pose a significant threat to child health and development, but exposures and health impacts in artisanal and small-scale gold mining (ASGM) environments are poorly defined. Objectives: We describe the CONAMAD study design, a prospective birth cohort consisting of multiparous women (18 and over) living in rural and peri-urban Peruvian Amazon communities exposed to ASGM. Methods: Pregnant women are enrolled from health posts across four zones of Madre de Dios, Peru. Data are collected at enrollment, childbirth, and (planned) 36-48 months. At enrollment, hair samples for mercury assessment, demographic and clinical data are obtained. At birth, we obtain venous and cord blood, placenta, hair, toenails, and saliva. Findings: Two hundred seventy mothers were enrolled at an average 20 weeks gestational age with no differences in maternal characteristics across zones. Two hundred fifteen mothers were successfully followed at birth. We obtained 214 maternal and cord blood samples, 211 maternal and 212 infant hair samples, 212 placenta samples, 210 infant saliva samples, and 214 infant dried blood spots. Data collected will allow for testing our primary hypotheses of maternal malnutrition modifying ratios of cord:maternal blood total mercury (tHg), cord blood:maternal hair tHg, and infant:maternal hair tHg, and whether chemical mixtures (Hg, Pb, Cd) have synergistic effects on infant neurodevelopment. Conclusions: CONAMAD is designed to collect and store samples for future processing and hypothesis testing associated with in-utero mercury exposure and child development. We have completed the exposure assessments and will conduct a follow-up of mothers to evaluate early child development outcomes, including developmental delay and growth. These data offer insights into disease mechanisms, exposure prevention, and policy guidance for countries where ASGM is prevalent.

Resolution of Pembrolizumab-Associated Steroid-Refractory Lichenoid Dermatitis with Cyclosporine.

Checkpoint inhibitors such as pembrolizumab, an anti-PD-1 monoclonal antibody, are a promising new category of oncological therapeutics, associated with a higher risk of immune-related adverse events including dermatological, autoimmune and endocrine sequelae. Here, we present a case of a woman 76 years of age with stage IV lung adenocarcinoma who developed a severe and steroid-refractory lichenoid dermatitis associated with pruritus on pembrolizumab. This eruption resolved completely with a short course of oral cyclosporine. Cyclosporine is a promising and effective treatment option for checkpoint inhibitor-related severe cutaneous eruptions.

Implementation of personalized music listening for assisted living residents with dementia.

Personalized music listening (PML) has been touted as a safe and inexpensive means of improving the quality of life, mood, and behavior of persons with dementia. A PML program was implemented in an assisted living facility and evaluated across the five dimensions of the RE-AIM framework: reach, effectiveness, adoption, implementation, and maintenance. The first 17 residents invited to participate were enrolled and followed over eight months. Effectiveness was evident in staff-reported mood improvement in 62% of encounters. Adoption was evident in qualitative feedback collected from medication technicians. Implementation was facilitated by low costs, engagement of external volunteers, highlighting outcomes that are relevant to staff, and attention to playlists over time. Maintenance required continued engagement of volunteers, ongoing fundraising, attention to facility staff engagement, and iterative adjustments to the program framework as staffing changes occurred. PML was found to be a meaningful intervention that is possible at a reasonable cost.

Epidermal growth factor regulates hematopoietic regeneration after radiation injury.

The mechanisms that regulate hematopoietic stem cell (HSC) regeneration after myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow serum of mice bearing deletion of Bak and Bax in TIE2-expressing cells in Tie2Cre; Bak1(-/-); Bax(flox/-) mice. These mice showed radioprotection of the HSC pool and 100% survival after a lethal dose of total-body irradiation (TBI). Bone marrow HSCs from wild-type mice expressed functional EGF receptor (EGFR), and systemic administration of EGF promoted the recovery of the HSC pool in vivo and improved the survival of mice after TBI. Conversely, administration of erlotinib, an EGFR antagonist, decreased both HSC regeneration and the survival of mice after TBI. Mice with EGFR deficiency in VAV-expressing hematopoietic cells also had delayed recovery of bone marrow stem and progenitor cells after TBI. Mechanistically, EGF reduced radiation-induced apoptosis of HSCs and mediated this effect through repression of the proapoptotic protein PUMA. Our findings show that EGFR signaling regulates HSC regeneration after myelosuppressive injury.

Pleiotrophin regulates the retention and self-renewal of hematopoietic stem cells in the bone marrow vascular niche.

The mechanisms through which the bone marrow (BM) microenvironment regulates hematopoietic stem cell (HSC) fate remain incompletely understood. We examined the role of the heparin-binding growth factor pleiotrophin (PTN) in regulating HSC function in the niche. PTN(-/-) mice displayed significantly decreased BM HSC content and impaired hematopoietic regeneration following myelosuppression. Conversely, mice lacking protein tyrosine phosphatase receptor zeta, which is inactivated by PTN, displayed significantly increased BM HSC content. Transplant studies revealed that PTN action was not HSC autonomous, but rather was mediated by the BM microenvironment. Interestingly, PTN was differentially expressed and secreted by BM sinusoidal endothelial cells within the vascular niche. Furthermore, systemic administration of anti-PTN antibody in mice substantially impaired both the homing of hematopoietic progenitor cells to the niche and the retention of BM HSCs in the niche. PTN is a secreted component of the BM vascular niche that regulates HSC self-renewal and retention in vivo.