The health risk of social disadvantage is transplantable into a new host.

Low socioeconomic status (SES) is a risk factor for mortality and immune dysfunction across a wide range of diseases, including cancer. However, cancer is distinct in the use of allogeneic hematopoietic cell transplantation (HCT) as a treatment for hematologic malignancies to transfer healthy hematopoietic cells from one person to another. This raises the question of whether social disadvantage of an HCT cell donor, as assessed by low SES, might impact the subsequent health outcomes of the HCT recipient. To evaluate the cellular transplantability of SES-associated health risk, we analyzed the health outcomes of 2,005 HCT recipients who were transplanted for hematologic malignancy at 125 United States transplant centers and tested whether their outcomes differed as a function of their cell donor's SES (controlling for other known HCT-related risk factors). Recipients transplanted with cells from donors in the lowest quartile of SES experienced a 9.7% reduction in overall survival (P = 0.001) and 6.6% increase in treatment-related mortality within 3 y (P = 0.008) compared to those transplanted from donors in the highest SES quartile. These results are consistent with previous research linking socioeconomic disadvantage to altered immune cell function and hematopoiesis, and they reveal an unanticipated persistence of those effects after cells are transferred into a new host environment. These SES-related disparities in health outcomes underscore the need to map the biological mechanisms involved in the social determinants of health and develop interventions to block those effects and enhance the health of both HCT donors and recipients.

Impact of Race and Ethnicity on Outcomes after Umbilical Cord Blood Transplantation.

BACKGROUND: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients. OBJECTIVE: To compare outcomes by social determinants of health. STUDY DESIGN: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, following either a myeloablative (N=1752) or reduced intensity conditioning (N=759) for Acute Myeloid Leukemia, Acute Lymphoid Leukemia, or Myelodysplasia. The primary outcome was 2-year OS. Secondary outcomes included disease free survival, transplant related mortality (TRM), acute and chronic graft vs host disease (GVHD), and GVHD free, relapse free survival (GRFS). RESULTS: For 1705 adults, in univariate analysis, 2-year OS was 41.5% (99% CI, 37.6-45.3) for Whites, 36.1% (99% CI, 28.2-44.5) for Latinx, 45.8% (99% CI, 36.7-55.1) for Blacks, and 44.5% (99% CI, 33.6-55.6) for Asians. In multivariate analysis of adults, Latinx patients had inferior OS compared to black patients (p=0.0005, HR 1.45, 99% CI 1.18-1.79). OS improved over time for all racial/ethnic groups. GVHD rates were comparable among the different racial/ethnic groups. In the 807 children, the 2-year OS in univariate analysis was 66.1% (99% CI, 59.7-72.2) for Whites, 57.1% (99%CI, 49-64.9) for Latinx, 46.8% (99%CI, 35.3-58.4) for Blacks, and 53.8% (99%CI, 32.7-74.2) for Asians. In multivariate analysis, no difference in OS was observed among racial/ethnic groups (p = 0.051). Grade III/IV acute GVHD was higher in Blacks compared with Whites (p= 0.0016, HR 2.25, 99% CI 1.36-3.74) and Latinx (p= 0.0016, HR 2.17, 99% CI 1.43-3.30). There was no survival advantage to receiving a UCB unit from a donor of similar race and ethnicity, for any racial/ethnic groups, for both children and adults. Black and Latinx adult patients were more likely to live in areas defined as high poverty. Patients from high poverty level areas had worse OS (p =0.03), due to a higher rate of TRM (p=0.04). Educational level, and type of insurance did not impact overall survival, GVHD, TRM or other transplant outcomes. Children from areas with a higher poverty level had higher TRM, regardless of race and ethnicity (p=0.02). Public health insurance, such as Medicaid, was also associated with a higher TRM (p=0.02). However, poverty did not impact pediatric OS, DFS, or other post-transplant outcomes. CONCLUSIONS: OS for UCBT has improved over time. In adults, OS is comparable among Whites, Blacks, and Asians and lower for Latinx patients. In children, OS is comparable among Whites, Blacks, Latinx, and Asians, but Grade III/IV acute GVHD was higher in Black patients. There was no survival benefit to matching UCB unit and patient by race and ethnicity for adults and children.

Feasibility and efficacy of a novel audiovisual tool to increase colorectal cancer screening among rural Appalachian Kentucky adults.

Introduction: Residents of Appalachian regions in Kentucky experience increased colorectal cancer (CRC) incidence and mortality. While population-based screening methods, such as fecal immunochemical tests (FITs), can reduce many screening barriers, written instructions to complete FIT can be challenging for some individuals. We developed a novel audiovisual tool ("talking card") to educate and motivate accurate FIT completion and assessed its feasibility, acceptability, and efficacy. Materials and methods: We collected data on the talking card via: (1) cross-sectional surveys exploring perceptions of images, messaging, and perceived utility; (2) follow-up focus groups centered on feasibility and acceptability; and (3) efficacy testing in community-based FIT distribution events, where we assessed FIT completion rate, number of positive vs. negative screens, demographic characteristics of participants, and primary drivers of FIT completion. Results: Across the three study phases, 692 individuals participated. Survey respondents positively identified with the card's sounds and images, found it highly acceptable, and reported high-to-very high self-efficacy and response efficacy for completing FIT, with nearly half noting greater likelihood to complete screening after using the tool. Focus group participants confirmed the acceptability of the individuals featured on the card. Nearly 75% of participants provided a FIT accurately completed it, with most indicating the talking card, either alone or combined with another strategy, helped with completion. Discussion: To reduce CRC screening disparities among Appalachian Kentuckians, population-based screening using contextually relevant implementation strategies must be used alongside clinic-based education. The talking card represents a novel and promising strategy to promote screening uptake in both clinical and community settings.

Weathering the storm when the end of the road is near: A qualitative analysis of supportive care needs during CAR T-cell therapy in pediatrics.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy provides promising outcomes in relapsed/refractory B acute lymphoblastic leukemia (ALL), yet still carries high toxicity rates and relatively poor long-term survival. Efficacy has yet to be demonstrated in other diagnoses while toxicity and risk profiles remain formidable. To date, treatment-related symptom burden is gleaned from clinical trial toxicity reports; the patient perspective remains understudied. METHODS: English- or Spanish-speaking patients (ages 8-25 years) undergoing CAR T-cell therapy for any malignancy and their primary caregivers were recruited from Seattle Children's Hospital (SCH), St. Jude Children's Research Hospital (SJCRH), and the Pediatric Oncology Branch of the National Cancer Institute (NCI). Both patient and caregiver completed semi-structured dyadic interviews 3 months post treatment. We used directed content analysis for codebook development and thematic network analysis for inductive qualitative analysis. RESULTS: Twenty families completed interviews (13 patients, 15 parents). Patients were a median age 16.5 years, predominantly female (65%), White (75%), and diagnosed with ALL (75%). Global themes included "A clear decision," "Coping with symptoms," and "Unforeseen psychosocial challenges." When families were asked to describe the "most challenging part of treatment," most described "the unknown." Most reported "the symptoms really weren't that bad," even among patients hospitalized for severe toxicity events. Fatigue, pain, and nausea were the most prevalent symptoms. Importantly, only one family would have chosen a different therapy, if given another opportunity. CONCLUSIONS: Although physical symptoms were largely tolerable, recognizing supportive care opportunities remains imperative, particularly psychosocial concerns.

A framework and process for community-engaged, mixed-methods cancer needs assessments.

PURPOSE: Community health needs assessments are required for most state and local public health agencies and non-profit hospitals. Typically based on community health improvement planning models, these assessments encompass overall community health and multiple diseases to inform program planning. National Cancer Institute (NCI)-designated Cancer Centers and community-based cancer-focused programs share the goal of reducing cancer burden in the catchment areas they serve. However, to date, no published models exist to guide cancer-specific needs assessments for a determined geographic area that can inform both public health and research initiatives. The purpose of this article is to outline a cancer needs assessment (CNA) framework and community-engaged, mixed-methods process, along with a case study of how we applied it in Kentucky. METHODS: We convened a steering committee of key organizational partners to provide input throughout the process. We developed a conceptual framework of multi-level determinants affecting cancer-related outcomes. We incorporated both quantitative and qualitative data gathered through a variety of means, including a novel application of group concept mapping to guide definition of priorities. RESULTS: The resulting CNA has helped guide strategic planning and priorities for Kentucky's Cancer Action Plan, Markey Cancer Center, state agencies, and community-based organizations. CONCLUSION: This framework and process can be used collaboratively by cancer center Community Outreach and Engagement offices, public health agencies, oncology programs, and community partners to plan impactful cancer control programs and research in their catchment areas. Universities can also use them to inform the planning of community engagement and health equity research efforts.

The SkillsCenter: Creating scalable research opportunities for STEM students.

Undergraduate students generally need laboratory skills and experience to be accepted into a position within an academic lab or a company. However, those settings are traditionally where students would develop that necessary expertise. We developed a laboratory course paradigm to equip students with the skills they need to access future opportunities.

Perceptions and Current Practices in Patient-Centered Care: A Qualitative Study of Ryan White HIV Providers in South Florida.

Background: Patient-centered care (PCC) improves HIV adherence and retention, though lack of consensus on its conceptualization and understanding how it is interpreted has hindered implementation. Methods: We recruited 20 HIV providers at Ryan White Programs in FL for in-depth interviews. Thematic analysis identified core consistencies pertaining to: 1) provider perceptions, 2) current practices promoting PCC. Results: Provider perceptions of PCC emerged under four domains: 1) holistic, 2) individualized care, 3) respect for comfort and security, and 4) patient engagement and partnership. PCC practices occurred at multiple levels: 1) individual psychosocial and logistical support, 2) interpersonal support within patient-provider relationships through respectful communication and active engagement, and 3) institutional practices including feedback mechanisms, service integration, patient convenience, and diverse staffing. Conclusions: Our findings highlight the central tenets of PCC as respectful, holistic, individualized, and engaging care. We offer an HIV-adapted framework of PCC as a multilevel construct to guide future intervention.

Patient-centered care perspectives among HIV care providersThis study explores HIV care provider perceptions of patient-centered care (PCC) by analyzing common themes that arose in interviews. We found that providers perceived PCC to be holistic, individualized care focused on respecting patient comfort and security and actively engaging them as partners in care. Providers discussed a variety of ways in which they practiced PCC at the individual service level through psychosocial and logistical support, through their interpersonal relationships with respectful communication and trust, and through more structured facility level policies and activities such as greater service integration and employing a diverse staff. PCC is rapidly becoming the new standard of care and this study hopes to offer insight into provider perceptions of PCC and examples of practice in the HIV care field.

Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities.

ABSTRACT: There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Radiographic and Advanced Imaging Evaluation of Posterior Shoulder Instability.

PURPOSE OF REVIEW: Posterior shoulder instability is an uncommon but important cause of shoulder dysfunction and pain which may occur as the result of seizure, high energy trauma, or repetitive stress related to occupational or sport-specific activities. This current review details the imaging approach to the patient with posterior shoulder instability and describes commonly associated soft tissue and bony pathologies identified by radiographs, CT, and MR imaging. RECENT FINDINGS: Advances in MR imaging technology and techniques allow for more accurate evaluation of bone and soft tissue pathology associated with posterior shoulder instability while sparing patients exposure to radiation. Imaging can contribute significantly to the clinical management of patients with posterior shoulder instability by demonstrating the extent of associated injuries and identifying predisposing anatomic conditions. Radiologic evaluation should be guided by clinical history and physical examination, beginning with radiographs followed by CT and/or MRI for assessment of osseous and soft tissue pathology. Synthesis of a patient's clinical history, physical exam findings, and radiologic examinations should guide clinical management.

Imaging features of perinephric myxoid pseudotumors of fat.

OBJECTIVE: Retrospectively evaluate multimodality imaging features of perinephric myxoid pseudotumor of fat (PMPTF). METHODS: Institutional cases of PMPTF with CT, MRI and/or ultrasound evaluation from 1/1/2020 to 9/1/2023 were retrospectively reviewed. Patient demographics and clinical history were reviewed, and imaging features recorded. RESULTS: 14 patients with pathologically-proven PMPTF were identified (11 M, 3 F; mean age 66.7 ± 17.0 years; range 40-87 years). Three patients (18%) had bilateral lesions; a total of 17 PMPTFs were reviewed. 15/17 (88%) were biopsy-proven; two cases were diagnosed by imaging only in patients with a contralateral biopsy-proven PMPTF. All evaluable specimens were negative for MDM2 amplification. 11/17 (65%) occurred in patients with renal disease, including 4/17 (24%) in patients with renal transplant. 100% (17/17) had CT, 11/17 (65%) MRI, and 6/17 (35%) ultrasound. The mean largest lesion dimension was 10.9 ± 4.6 cm (range 4.3-17.0 cm). Of cases involving native kidneys, 7/13 (54%) presented as multifocal perinephric masses and 5/13 (38%) as a solitary perinephric mass. All four transplant cases presented as infiltrative-appearing masses involving the renal sinus with lesser perinephric involvement. 14/17 (82%) lesions contained macroscopic fat on CT and MRI and 3/17 (18%) showed no macroscopic fat, all involving renal transplants. All cases with MRI demonstrated T2 hyperintensity with signal dropout on opposed-phase imaging. 11/13 (85%) PMPTF showed no or equivocal CT enhancement. Enhancement was better seen on MRI in all cases evaluated by both CT and MRI. Of the six PMPTFs imaged by ultrasound, four (67%) were heterogeneously hypoechoic and two (33%) had mixed regions of hypo-, iso- and hyperechogenicity relative to adjacent renal parenchyma. CONCLUSIONS: PMPTF is a rare, benign, and underrecognized lesion that may mimic malignancy, particularly retroperitoneal well-differentiated liposarcoma. The imaging features of this unusual pseudosarcoma differ in native and transplanted kidneys. Improved awareness of this entity will facilitate appropriate patient management and avoid unnecessary intervention.

Exploiting high-energy hydration sites for the discovery of potent peptide aldehyde inhibitors of the SARS-CoV-2 main protease with cellular antiviral activity.

Small-molecule antivirals that prevent the replication of the SARS-CoV-2 virus by blocking the enzymatic activity of its main protease (Mpro) are and will be a tenet of pandemic preparedness. However, the peptidic nature of such compounds often precludes the design of compounds within favorable physical property ranges, limiting cellular activity. Here we describe the discovery of peptide aldehyde Mpro inhibitors with potent enzymatic and cellular antiviral activity. This structure-activity relationship (SAR) exploration was guided by the use of calculated hydration site thermodynamic maps (WaterMap) to drive potency via displacement of waters from high-energy sites. Thousands of diverse compounds were designed to target these high-energy hydration sites and then prioritized for synthesis by physics- and structure-based Free-Energy Perturbation (FEP+) simulations, which accurately predicted biochemical potencies. This approach ultimately led to the rapid discovery of lead compounds with unique SAR that exhibited potent enzymatic and cellular activity with excellent pan-coronavirus coverage.

Examining the role of social relationships on health and health behaviors in African American men with prostate cancer: a qualitative analysis.

PURPOSE: Cancer survivor cohort studies document the positive impact of health behaviors on cancer survivorship by influencing quality of life, comorbidity burden, and cancer recurrence. Social networks can be instrumental in supporting health behavior changes. This study used qualitative interviews to explore how social networks may impact health and health behaviors of African American Prostate Cancer Survivors (AAPCS) enrolled in Men Moving Forward (MMF), a lifestyle intervention designed with and for AAPCS. Specifically, we sought to understand how different relationships within social networks influence health and health behaviors, and to identify potential mechanisms for this influence. METHODS: Eighteen men who completed the MMF intervention participated in a semi-structured interview which explored social connections, health and health behaviors, stress, and the cancer experience. Interviews were recorded and transcribed, and thematic analysis was performed by two coders. RESULTS: Participants described robust social networks of friends and family. Four distinct yet overlapping themes were identified that described how relationships influence health and health behaviors among AAPCS: (1) provision of knowledge, (2) health and behavior history, (3) encouragement and support, and (4) shared behavior. CONCLUSIONS: These results provide initial insight into the types of relationships that influence health, and the intersecting and multifaceted mechanisms through which this influence occurs.

Understanding motivations and resilience-associated factors to promote timely linkage to HIV care: a qualitative study among people living with HIV in western Kenya.

Understanding motivations and resilience-associated factors that help people newly diagnosed with HIV link to care is critical in the context of universal test and treat. We analyzed 30 in-depth interviews (IDI) among adults aged 18 and older in western Kenya diagnosed with HIV during home-based counseling and testing and who had linked to HIV care. A directed content analysis was performed, categorizing IDI quotations into a table based on linkage stages for organization and then developing and applying codes from self-determination theory and the concept of resilience. Autonomous motivations, including internalized concerns for one's health and/or to provide care for family, were salient facilitators of accessing care. Controlled forms of motivation, such as fear or external pressure, were less salient. Social support was an important resilience-associated factor fostering linkage. HIV testing and counseling programs which incorporate motivational interviewing that emphasizes motivations related to one's health or family combined with a social support/navigator approach, may promote timely linkage to care.

Experiences of racial discrimination and adverse gene expression among black individuals in a level 1 trauma center sample.

Up to 40 % of individuals who sustain traumatic injuries are at risk for posttraumatic stress disorder (PTSD) and the conditional risk for developing PTSD is even higher for Black individuals. Exposure to racial discrimination, including at both interpersonal and structural levels, helps explain this health inequity. Yet, the relationship between racial discrimination and biological processes in the context of traumatic injury has yet to be fully explored. The current study examined whether racial discrimination is associated with a cumulative measure of biological stress, the gene expression profile conserved transcriptional response to adversity (CTRA), in Black trauma survivors. Two-weeks (T1) and six-months (T2) post-injury, Black participants (N = 94) provided a blood specimen and completed assessments of lifetime racial discrimination and PTSD symptoms. Mixed effect linear models evaluated the relationship between change in CTRA gene expression and racial discrimination while adjusting for age, gender, body mass index (BMI), smoking history, heavy alcohol use history, and trauma-related variables (mechanism of injury, lifetime trauma). Results revealed that for individuals exposed to higher levels of lifetime racial discrimination, CTRA significantly increased between T1 and T2. Conversely, CTRA did not increase significantly over time in individuals exposed to lower levels of lifetime racial discrimination. Thus, racial discrimination appeared to lead to a more sensitized biological profile which was further amplified by the effects of a recent traumatic injury. These findings replicate and extend previous research elucidating the processes by which racial discrimination targets biological systems.

Interdisciplinary rehabilitation for persisting post-concussion symptoms after mTBI: N=15 single case experimental design.

BACKGROUND: Despite clinical guidelines recommending an interdisciplinary approach to persisting post-concussion symptom (PPCS) management, evaluations of interdisciplinary interventions remain scant. OBJECTIVES: This pilot study aimed to explore the feasibility and preliminary efficacy of an interdisciplinary intervention for PPCSs. METHOD: A single-case experimental design with randomisation to multiple baselines (2, 4, or 6 weeks) was repeated across 15 participants (53% female) with mild traumatic brain injury (mean age 38.3 years, SD 15.7). The 12-week treatment incorporated psychology, physiotherapy, and medical interventions. Feasibility outcomes included recruitment and retention rates, adverse events, treatment adherence and fidelity. Patient-centred secondary outcomes included the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), assessed 3 times per week during the baseline and treatment phases, and at the 1- and 3-month follow-ups. Other secondary outcomes included measures of mood, sleep and fatigue, physical functioning, health-related quality of life, illness perceptions, and goal attainment. Changes in PPCSs were evaluated using systematic visual analysis and Tau-U. Clinically significant changes in secondary outcomes were explored descriptively. RESULTS: 16/26 individuals assessed for eligibility were enroled (61% recruitment rate); 15 completed the post-treatment follow-ups, and 13 completed the 1- and 3-month follow-up assessments (81% retention rate). High treatment adherence and competence in delivering treatments was observed. Moderate-large effect sizes for reducing PPCSs were observed in 12/15 cases, with 7/15 reaching statistical significance. Improvements were maintained at the 1- and 3-month follow-ups and were accompanied by reductions in fatigue, sleep difficulties, and mood symptoms, and changes in illness perceptions. All participants had clinically significant improvements in at least 1 outcome, with 81% of individual therapy goals achieved. CONCLUSIONS: This pilot study provided preliminary support for a subsequent randomised controlled trial (RCT), with satisfactory recruitment, retention, treatment compliance, and treatment fidelity. Improvement was evident on participant outcomes including symptom reduction and goal attainment, suggesting that progressing to a phase-II RCT is worthwhile. Findings highlight the potential benefit of individualized interdisciplinary treatments.

Moving forward on the road to recovery after concussion: participant experiences of interdisciplinary intervention for persisting post-concussion symptoms.

PURPOSE: Many factors contribute to persisting post-concussion symptoms (PPCSs), necessitating multi-modal treatment. Quantitative investigations have shown the potential of interdisciplinary intervention to reduce the burden of PPCSs and facilitate return to activities. There are often varied responses to intervention, warranting further investigation of potential factors underlying treatment response. This study aimed to explore participant experiences of i-RECOveR, an interdisciplinary intervention for PPCSs and its impact on symptoms, daily function, and concussion beliefs. MATERIALS AND METHOD: Semi-structured interviews were conducted 1-month post-treatment via videoconferencing with 13 individuals (61% female) with mild traumatic brain injury (Mage=39.77 years, SD = 16.27) who participated in i-RECOveR. Interview transcripts were analysed thematically. RESULTS: Three themes reflected participants' treatment journeys from concussion to life after treatment: (1) Dissatisfaction with Previous Consultations, reflected personal experiences prior to commencing treatment; (2) Perceived Active Ingredients of Intervention, reflected participant experiences of i-RECOveR; and (3) Impact of Interdisciplinary Intervention, reflected a range of positive changes after completing i-RECOveR. CONCLUSIONS: Findings highlight current gaps in the acute management of concussion and provide end-user insights into the facilitators and barriers of treatment engagement and response. Responses also highlight the potential positive impact of interdisciplinary treatments. Clinician perspectives should be explored in future research.

Access to additional training in concussion care and referral pathways may help medical practitioners manage patients after concussion.Clinicians working with individuals with persisting post-concussion symptoms should develop an understanding of the individual's perceived control over their symptoms, and work with them toward increasing autonomy and control and recognition that symptoms are often multifactorial in nature.Persisting post-concussion symptom rehabilitation may be improved by taking an interdisciplinary approach that is integrated individualised, and is specialised for concussion.Telehealth and hybrid treatment models are well tolerated by individuals with persisting post-concussion symptoms and may facilitate treatment engagement, especially for individuals with mild traumatic brain injury who report disabling symptoms made worse by travelling to in-person treatments.

Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis.

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

Racial and Socioeconomic Disparities in Long-Term Outcomes in ≥1 Year Allogeneic Hematopoietic Cell Transplantation Survivors: A CIBMTR Analysis.

Racial/ethnic minorities have demonstrated worse survival after allogeneic hematopoietic cell transplantation (HCT) compared to whites. Whether the racial disparity in HCT outcomes persists in long-term survivors and possibly may be even exacerbated in this population, which frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study, we compared long-term outcomes among 1-year allogeneic HCT survivors by race/ethnicity and socioeconomic status (SES). The Center for International Blood and Marrow Transplant Research database was used to identify 5473 patients with acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, or myelodysplastic syndromes who underwent their first allogeneic HCT between 2007 and 2017 and were alive and in remission for at least 1 year after transplantation. The study was restricted to patients who underwent HCT in the United States. SES was defined using patient neighborhood poverty level estimated from the recipient's ZIP code of residence; a ZIP code with ≥20% of persons below the federal poverty level was considered a high poverty area. The primary outcome was to evaluate the associations of race/ethnicity and neighborhood poverty level with overall survival (OS), relapse, and nonrelapse mortality (NRM). Cox regression models were used to determine associations of ethnicity/race and SES with OS, relapse, and NRM. Standardized mortality ratios were calculated to compare mortality rates of the study patients and their general population peers matched on race/ethnicity, age, and sex. The study cohort was predominately non-Hispanic white (n = 4385) and also included non-Hispanic black (n = 338), Hispanic (n = 516), and Asian (n = 234) patients. Overall, 729 patients (13%) resided in high-poverty areas. Significantly larger proportions of non-Hispanic black (37%) and Hispanic (26%) patients lived in high-poverty areas compared to non-Hispanic whites (10%) and Asians (10%) (P < .01). Multivariable analysis revealed no significant associations between OS, PFS, relapse, or NRM and race/ethnicity or poverty level when adjusted for patient-, disease- and transplantation-related covariates. Our retrospective cohort registry study shows that among adult allogeneic HCT recipients who survived at least 1 year in remission, there were no associations between race/ethnicity, neighborhood poverty level, and long-term outcomes.

Prevalence of Sleep Aid Medication Use in Patients Receiving a Hematopoietic Cell Transplant on an Inpatient Unit.

BACKGROUND AND OBJECTIVES: There is a lack of research regarding the use of sleep aids after hematopoietic stem cell transplantation (HCT). We describe the prevalence of sleep aid administration in the HCT unit and identify associations with patient or clinical characteristics. PATIENTS AND METHODS: In this retrospective analysis of sequential inpatient HCTs from July 1 to December 31, 2016 we describe whether and when patients were prescribed sleep aid medications. Chi-square tests determined significant differences between patient characteristics, sleep aid prescription, and time of prescription. RESULTS: Of the 225 patients identified, 193 (86%) were prescribed sleep aids. Significantly more women received prescriptions for sleep aids (90.4%) than men (81%; P = .047). One hundred patients (44%) received prescriptions exclusively while in the hospital. CONCLUSION: Findings show a high prevalence of sleep medication use in patients undergoing inpatient HCT, primarily during hospitalization. Future efforts toward standardized recommendations to optimize peri-transplant sleep would help clinicians and patients.

Inflammatory cytokines and depression symptoms following hematopoietic cell transplantation.

Increased synthesis and release of inflammatory signalling proteins is common among individuals with hematologic malignancies undergoing hematopoietic cell transplantation (HCT) due to intensive conditioning regimens and complications such as graft-versus-host-disease and infections. Prior research indicates that inflammatory responses can activate central nervous system pathways that evoke changes in mood. This study examined relationships between markers of inflammatory activity and depression symptoms following HCT. Individuals undergoing allogeneic (n = 84) and autologous (n = 155) HCT completed measures of depression symptoms pre-HCT and 1, 3, and 6 months post-HCT. Proinflammatory (IL-6, TNF-α) and regulatory (IL-10) cytokines were assessed by ELISA in peripheral blood plasma. Mixed-effects linear regression models indicated that patients with elevated IL-6 and IL-10 reported more severe depression symptoms at the post-HCT assessments. These findings were replicated when examining both allogeneic and autologous samples. Follow-up analyses clarified that relationships were strongest for neurovegetative, rather than cognitive or affective, symptoms of depression. These findings suggest that anti-inflammatory therapeutics targeting an inflammatory mediator of depression could improve quality of life of HCT recipients.