All-trans retinoic acid induces durable tumor immunity in IDH-mutant gliomas by rescuing transcriptional repression of the CRBP1-retinoic acid axis.

Diffuse gliomas are epigenetically dysregulated, immunologically cold, and fatal tumors characterized by mutations in isocitrate dehydrogenase (IDH). Although IDH mutations yield a uniquely immunosuppressive tumor microenvironment, the regulatory mechanisms that drive the immune landscape of IDH mutant (IDHm) gliomas remain unknown. Here, we reveal that transcriptional repression of retinoic acid (RA) pathway signaling impairs both innate and adaptive immune surveillance in IDHm glioma through epigenetic silencing of retinol binding protein 1 (RBP1) and induces a profound anti-inflammatory landscape marked by loss of inflammatory cell states and infiltration of suppressive myeloid phenotypes. Restorative retinoic acid therapy in murine glioma models promotes clonal CD4 + T cell expansion and induces tumor regression in IDHm, but not IDH wildtype (IDHwt), gliomas. Our findings provide a mechanistic rationale for RA immunotherapy in IDHm glioma and is the basis for an ongoing investigator-initiated, single-center clinical trial investigating all-trans retinoic acid (ATRA) in recurrent IDHm human subjects.

Evaluation of the effects of repeated disinfection on medical exam gloves: Part 2. Changes in mechanical properties.

Many healthcare professionals have been forced, under acute shortages, to extend medical exam gloves beyond their intended single use. Despite limited available literature, the CDC proposed a set of guidelines for repeated exam gloves use, indicating a maximum number of treatments for three widely available disinfectants. This study examines how these treatments affect the mechanical properties of latex and nitrile gloves. Furthermore, an acceptability threshold is proposed for changes in tensile property, specifically elastic modulus, as an indication of degradation. This proposed criterion was also applied to similar studies available in the literature to determine applicability and aid in recommendation development. Three different latex glove brands and three nitrile brands were exposed to repeated treatments of an alcohol-based hand rub, diluted bleach, or soap and water. Tensile tests of samples cut from untreated and treated gloves were performed to assess the change in elastic modulus induced by each treatment. The findings suggest that latex gloves performed well within the CDC recommended guidelines of six repeated treatments for an ethanol-based hand rub and 10 repeated treatments of either dilute bleach or soap and water. Nitrile exam gloves, on the other hand, showed significant changes in elastic modulus, with more inconclusive results among brands. This was especially true for treatment with dilute bleach and soap and water. Further research is needed to investigate the effects of disinfection products on the mechanical integrity of nitrile exam gloves. The results support the use of five repeated treatments of ethanol-based hand rub for nitrile exam gloves, a lower threshold than currently recommended by the CDC. This research also supports that the CDC recommendation of 10 repeated treatment with soap and water is appropriate for latex exam gloves, but not for nitrile exam gloves. Occupational safety and health professionals involved in the selection of disposable exam gloves for infection control should consider the compatibility of the glove polymer type with available disinfectants, especially if extended use with repeated disinfection becomes necessary.

Impact of ketamine as an adjunct sedative in acute respiratory distress syndrome due to COVID-19 Pneumonia.

PURPOSE: Deep sedation is sometimes needed in acute respiratory distress syndrome. Ketamine is a sedative that has been shown to have analgesic and sedating properties without having a detrimental impact on hemodynamics. This pharmacological profile makes ketamine an attractive sedative, potentially reducing the necessity for other sedatives and vasopressors, but there are no studies evaluating its effect on these medications in patients requiring deep sedation for acute respiratory distress syndrome. MATERIALS AND METHODS: This is a retrospective, observational study in a single center, quaternary care hospital in southeast Texas. We looked at adults with COVID-19 requiring mechanical ventilation from March 2020 to September 2020. RESULTS: We found that patients had less propofol requirements at 72 h after ketamine initiation when compared to 24 h (median 34.2 vs 54.7 mg/kg, p = 0.003). Norepinephrine equivalents were also significantly lower at 48 h than 24 h after ketamine initiation (median 38 vs 62.8 mcg/kg, p = 0.028). There was an increase in hydromorphone infusion rates at all three time points after ketamine was introduced. CONCLUSIONS: In this cohort of patients with COVID-19 ARDS who required mechanical ventilation receiving ketamine we found propofol sparing effects and vasopressor requirements were reduced, while opioid infusions were not.

The Influence of Baseline Hemoglobin A1c on Digital Health Coaching Outcomes in Adults With Type 2 Diabetes: Real-World Retrospective Cohort Study.

BACKGROUND: Digital health coaching is an increasingly common diabetes self-management support strategy for individuals with type 2 diabetes and has been linked to positive mental and physical health outcomes. However, the relationship between baseline risk and outcomes is yet to be evaluated in a real-world setting. OBJECTIVE: The purpose of this real-world study was to evaluate trends in digital health coaching outcomes by baseline hemoglobin A1c (HbA1c) to better understand which populations may experience the greatest clinical and psychosocial benefit. METHODS: A retrospective cohort study design was used to evaluate program effect in a convenience sample of participants in a 12-week digital health coaching program administered by Pack Health. Participants were referred through their health care provider, payer, or employer. The program included patient-centered lifestyle counseling and psychosocial support delivered via telephone, text, and/or email. Self-reported HbA1c and weight were collected at baseline and completion. Physical and mental health were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form and the Diabetes Distress Scale-2. Changes in HbA1c, weight, BMI, and physical and mental health were analyzed within three participant cohorts stratified by baseline HbA1c level. RESULTS: Participants with complete HbA1c data sets (n=226) were included in the analysis. The sample population was 71.7% (162/226) female, with 61.5% (139/226) identifying as white and 34.1% (77/226) as black. Most participants (184/226, 81.4%) reported a baseline HbA1c ≥7%, and 20.3% (46/226) were classified as high risk (HbA1c >9%). Across HbA1c cohorts, the mean baseline BMI was 35.83 (SD 7.79), and the moderate-risk cohort (7% ≤ HbA1c ≤ 9%) reported the highest mean value (36.6, SD 7.79). At 12 weeks, patients reported a significant decrease in HbAlc, and high-risk participants reduced their levels by the greatest margin (2.28 points; P<.001). Across cohorts, BMI improved by 0.82 (P<.001), with the moderate-risk cohort showing the greatest reduction (-0.88; P<.001). Overall, participants reported significant improvements for PROMIS scores, with the greatest change occurring in the high-risk cohort for whom physical health improved 3.84 points (P<.001) and mental health improved 3.3 points (P<.001). However, the lowest-risk cohort showed the greatest improvements in diabetes distress (-0.76; P=.005). CONCLUSIONS: Acknowledging the limitations in this real-world study design, the results reported here suggest that adults with type 2 diabetes with a high baseline HbA1c or high BMI may benefit the most from patient-centered digital health coaching programs when compared to their lower risk counterparts. While all participants improved in physical and mental health categories, participants with high HbA1c experienced the greatest HbA1c reduction and individuals with the highest baseline BMI lost the most weight. These results may be used to inform referrals for patients who are more likely to benefit from digital health coaching.

Perspectives on life following a traumatic spinal cord injury.

BACKGROUND: Persons living with traumatic Spinal Cord Injury (SCI) face challenges when returning to their communities. The Spain Rehabilitation Center at the University of Alabama at Birmingham is developing a continuum of care for SCI patients. The perspectives of individuals with SCI are critical to designing a person-centered approach to the continuum. OBJECTIVE: This study sought to explore the lived experiences of individuals with SCI after their injury, as well as obtain the perspectives of therapists working with SCI patients. METHODS: Ten persons ranging in age from 23 to 65 years old and living with SCI were recruited to participate in in-depth interviews. We utilized a grounded theory approach to develop descriptive codes and themes. RESULTS: Our analysis highlighted domains that are critical to the lives of individuals with SCI including: planning for life after SCI, intrinsic motivation, environmental barriers, financial barriers, role of family, friends, and social networks, and relationships with medical providers. A key theme was the need for more information about how to manage their health condition, including the development of plans that are tailored to their specific needs. CONCLUSIONS: Individuals with an SCI need access to a continuum of care that addresses both medical and social needs.

Defining Plasma MicroRNAs Associated With Cognitive Impairment In HIV-Infected Patients.

Human Immunodeficiency Virus (HIV)-infected individuals are at increased risk for developing neurocognitive disorders and depression. These conditions collectively affect more than 50% of people living with HIV/AIDS and adversely impact adherence to HIV therapy. Thus, identification of early markers of neurocognitive impairment could lead to interventions that improve psychosocial functioning and slow or reverse disease progression through improved treatment adherence. Evidence has accumulated for the role and function of microRNAs in normal and pathological conditions. We have optimized a protocol to profile microRNAs in body fluids. Using this methodology, we have profiled plasma microRNA expression for 30 age-matched, HIV-infected (HIV(+) ) patients and identified highly sensitive and specific microRNA signatures distinguishing HIV(+) patients with cognitive impairment from those without cognitive impairment. These results justify follow-on studies to determine whether plasma microRNA signatures can be used as a screening or prognostic tool for HIV(+) patients with neurocognitive impairment. J. Cell. Physiol. 231: 829-836, 2016. © 2015 Wiley Periodicals, Inc.

Primary chondrosarcoma of the breast: report of a case and review of the literature.

Sarcomas of the breast are rare, comprising 1% of all breast tumors. Primary chondrosarcomas of the breast account for an extremely rare subset of such tumors, with few reports in the literature. We report the case of a 52 year-old woman with a primary chondrosarcoma of the breast and review the current literature.