Group Coping Intervention in Patients With Chronic Graft-Versus-Host Disease: A Pilot Randomized Clinical Trial.

BACKGROUND: More than half the long-term survivors of allogeneic hematopoietic cell transplantation develop chronic graft-versus-host disease (GVHD), a debilitating inflammatory syndrome. Supportive interventions to assist survivors in coping with chronic GVHD are critically needed. PATIENTS AND METHODS: We conducted a pilot randomized clinical trial of a multidisciplinary group intervention (Horizons Program; n=39) versus minimally enhanced usual care (n=41) for patients with moderate or severe chronic GVHD. Horizons participants received 8 weekly sessions about GVHD and coping co-led by a transplant clinician and a behavioral health expert via a secure videoconferencing platform. Participants completed the following surveys before randomization, at 10 weeks, and at 18 weeks: Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) for quality of life (QoL), Lee Symptom Scale for symptom burden, and Hospital Anxiety and Depression Scale-Depression Symptoms (HADS) for mood. The primary endpoint was feasibility (≥50% enrollment, ≥80% attendance in half the sessions for the Horizons arm only, and ≥80% retention). We also explored preliminary efficacy of the Horizons intervention on changes in patient-reported outcomes with linear mixed effects models and estimates of effect size at 10 weeks. RESULTS: We enrolled and registered 80 (67.2%) of 119 eligible patients (mean age, 62 years; 48.8% female). Of the participants in the Horizons Program, 84.6% attended at least half the sessions. Of registered participants, 91.3% completed assessment follow-ups (Horizons, 35/39 [89.7%]; minimally enhanced usual care, 38/41 [92.7%]). Horizons participants reported improvements in QoL (b = 2.24; d=0.53), anxiety symptoms (b = -0.10; d=0.34), and depression symptoms (b = -0.71; d=0.44) compared with participants who received minimally enhanced usual care. CONCLUSIONS: Participation in a multidisciplinary group intervention study was feasible for patients with chronic GVHD, with promising signals for improving QoL and mood. A full-scale efficacy trial is needed to confirm effects on patient-reported outcomes.

Clinical Outcomes and Health Care Utilization in Patients With Burkitt Lymphoma.

PURPOSE: Burkitt lymphoma is an aggressive B-cell lymphoma requiring intensive therapy, which places patients at risk for severe toxicity. However, few studies have described these patients' clinical outcomes and health care utilization, particularly among older adults. METHODS: We conducted a retrospective analysis of adults 40 years and older with Burkitt lymphoma at Massachusetts General Hospital and Dana-Farber Cancer Institute from February 1999 to December 2020 (N = 97). We abstracted patient characteristics, clinical outcomes, and health care utilization (unplanned hospitalizations, intensive care unit [ICU] admissions) during therapy from the electronic health record. Using univariate logistic regression, we examined factors associated with rates of unplanned hospitalization and ICU admission during therapy. RESULTS: Among evaluable patients (median age, 69 years; 23.7% female; 19.3% with bone marrow involvement), 45.8% (38 of 83) experienced unplanned hospitalization and 23.2% (19 of 82) experienced ICU admission during therapy. Among those 70 years and older, rates of unplanned hospitalization and ICU admission were 36.8% (14 of 38) and 29.0% (11 of 38), respectively. Bone marrow involvement (odds ratio [OR], 3.00; P = .069) was associated with a nonsignificantly greater likelihood of unplanned hospitalization. Older age (OR, 1.06; P = .039), Charlson comorbidity index >0 (OR, 3.14; P = .038), and hypoalbuminemia (OR, 3.22; P = .035) were associated with greater likelihood of ICU admission. Overall, 8.7% (8 of 92) of patients died during treatment, all of whom were 70 years and older. CONCLUSION: Adults with Burkitt lymphoma experience substantial rates of unplanned hospitalizations and ICU admissions, with older adults at especially high risk for ICU admission and death during treatment. Our findings underscore the need to develop supportive care interventions for patients with Burkitt lymphoma to help improve clinical outcomes and health care utilization.

Quality of Life, Physical Functioning, and Psychological Distress of Older Adults Undergoing Hematopoietic Stem Cell Transplantation.

With advances in therapies for hematologic cancers, older adults increasingly undergo hematopoietic stem cell transplantation (HSCT). Older adults may potentially experience an exaggerated burden of toxicity from HSCT. Studies examining the quality of life (QOL), physical functioning, and psychological symptom trajectory for older adults undergoing HSCT are limited. Our primary aim was to describe the trajectory of QOL, physical functioning, and psychological distress of older adults undergoing HSCT. Secondarily, we aimed to compare the trajectory of QOL, physical functioning, and psychological distress of older and younger adults undergoing HSCT and to evaluate factors associated with QOL trajectory in older adults undergoing HSCT. We conducted secondary analyses of two prospective studies conducted at Massachusetts General Hospital. From 2011 to 2016, we enrolled 250 adults undergoing allogeneic or autologous HSCT. Older age was defined as age ≥65 years. We collected patient-reported outcomes (PROs) within 72 hours of admission for HSCT, at hematologic nadir (2 weeks), and at 6 months after HSCT. To assess QOL, physical functioning, and psychological symptoms, we used the Functional Assessment of Cancer Therapy (FACT)-Bone Marrow Transplant, FACT-Trial Outcome Index, and Patient Health Questionnaire-9, respectively. We used the post-traumatic stress disorder (PTSD) Checklist-Civilian Version to assess PTSD symptoms. We fit linear mixed effects models to characterize trajectories of changes in PROs across timepoints and to evaluate baseline factors associated with QOL trajectories in older adults. Overall 30.4% (76/250) of our cohort was 65 years or older. All older adults undergoing allogeneic HSCT received a reduced intensity conditioning regimen. At 2 weeks after HSCT, older patients experienced a decline in QOL (Δ = -16.6, P < .001), physical functioning (Δ = -15.4, P < .001) and an increase in depression symptoms (Δ = 3.8, P < .001). At 6 months after HSCT, QOL (Δ = 1.4, P = .7), physical functioning (Δ = 1.7, P = .5), and depression symptoms (Δ = 0.4, P = .6) recovered to baseline values. At 6 months after HSCT, the proportion of older patients with PTSD symptoms increased from 5.3% (4/76) at baseline to 13.2% (10/76). There was no significant difference in slopes or trajectories of PROs between older and younger patients. In older adults, baseline psychological distress was associated with significantly worse QOL trajectory (Δ= -21.6, P ≤ .001). Older adults experienced a sharp decline in QOL and physical functioning and an increase in depression symptoms within 2 weeks of HSCT hospitalization. Baseline psychological distress was associated with a pronounced worsening in post-HSCT QOL trajectory. These findings underscore the need for supportive care interventions to improve the experience of older adults undergoing HSCT.

Delirium and Healthcare Utilization in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Delirium, a common neuropsychiatric syndrome among hospitalized patients, has been associated with significant morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Although delirium is often reversible with prompt diagnosis and appropriate management, timely screening of hospitalized patients, including HSCT recipients at risk for delirium, is lacking. The association between delirium symptoms and healthcare utilization among HSCT recipients is also limited. We conducted a retrospective analysis of 502 hospitalized patients admitted for allogeneic or autologous HSCT at 2 tertiary care hospitals between April 2016 and April 2021. We used Natural Language Processing (NLP) to identify patients with delirium symptoms, as defined by an NLP-assisted chart review of the electronic health record (EHR). We used multivariable regression models to examine the associations between delirium symptoms, clinical outcomes, and healthcare utilization, adjusting for patient-, disease-, and transplantation-related factors. Overall, 44.4% (124 of 279) of patients undergoing allogeneic HSCT and 39.0% (87 of 223) of those undergoing autologous HSCT were identified as having delirium symptoms during their index hospitalization. Two-thirds (139 of 211) of the patients with delirium symptoms were prescribed treatment with antipsychotic medications. Among allogeneic HSCT recipients, delirium symptoms were associated with longer hospital length of stay (ß = 7.960; P < .001), fewer days alive and out of the hospital (ß = -23.669; P < .001), and more intensive care unit admissions (odds ratio, 2.854; P = .002). In autologous HSCT recipients, delirium symptoms were associated with longer hospital length of stay (ß = 2.204; P < .001). NLP-assisted EHR review is a feasible approach to identifying hospitalized patients, including HSCT recipients at risk for delirium. Because delirium symptoms are negatively associated with health care utilization during and after HSCT, our findings underscore the need to efficiently identify patients hospitalized for HSCT who are at risk of delirium to improve their outcomes. © 2023 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Coping in caregivers of patients with hematologic malignancies undergoing hematopoietic stem cell transplantation.

Caregivers of patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) must cope with substantial caregiving burden, high rates of psychological distress, and diminished quality of life (QOL). However, data describing coping strategies before HSCT and the association between coping, QOL, and psychological outcomes in this population are lacking. We conducted a secondary analysis of data collected during a multisite randomized clinical trial of a supportive care intervention in HSCT recipients and their caregivers. Caregivers completed the Brief COPE, Hospital Anxiety and Depression Scale, and the Caregiver Oncology Quality of Life Questionnaire to measure coping strategies, psychological distress, and QOL, respectively. We grouped coping into 2 higher-order domains: approach-oriented (ie, emotional support and active coping) and avoidant (ie, self-blame and denial). We used the median split method to describe the distribution of coping and multivariate linear regression models to assess the relationship between coping and caregiver outcomes. We enrolled 170 caregivers, with a median (range) age of 53 (47-64) years. Most were White (87%), non-Hispanic (96%), and female (77%). Approach-oriented coping was associated with less anxiety (ß = -0.210, P = .003), depression symptoms (ß = -0.160, P = .009), and better QOL (ß = 0.526, P = .002). In contrast, avoidant coping was associated with more anxiety (ß = 0.687, P<.001), depression symptoms (ß = 0.579, P < .001), and worse QOL (ß = -1.631, P < .001). Our findings suggest that coping is related to distress and QOL among caregivers of HSCT recipients even before transplant. Hence, caregivers of patients with hematologic malignancies undergoing HSCT may benefit from resources that facilitate adaptive coping with the demands of caregiving.

Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

BACKGROUND: Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. METHODOLOGY/PRINCIPAL FINDINGS: Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. CONCLUSIONS/SIGNIFICANCE: Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

Variation in oxytocin is related to variation in affiliative behavior in monogamous, pairbonded tamarins.

Oxytocin plays an important role in monogamous pairbonded female voles, but not in polygamous voles. Here we examined a socially monogamous cooperatively breeding primate where both sexes share in parental care and territory defense for within species variation in behavior and female and male oxytocin levels in 14 pairs of cotton-top tamarins (Saguinus oedipus). In order to obtain a stable chronic assessment of hormones and behavior, we observed behavior and collected urinary hormonal samples across the tamarins' 3-week ovulatory cycle. We found similar levels of urinary oxytocin in both sexes. However, basal urinary oxytocin levels varied 10-fold across pairs and pair-mates displayed similar oxytocin levels. Affiliative behavior (contact, grooming, sex) also varied greatly across the sample and explained more than half the variance in pair oxytocin levels. The variables accounting for variation in oxytocin levels differed by sex. Mutual contact and grooming explained most of the variance in female oxytocin levels, whereas sexual behavior explained most of the variance in male oxytocin levels. The initiation of contact by males and solicitation of sex by females were related to increased levels of oxytocin in both. This study demonstrates within-species variation in oxytocin that is directly related to levels of affiliative and sexual behavior. However, different behavioral mechanisms influence oxytocin levels in males and females and a strong pair relationship (as indexed by high levels of oxytocin) may require the activation of appropriate mechanisms for both sexes.

CCAAT/enhancer-binding protein-beta participates in insulin-responsive expression of the factor VII gene.

Expression of the human coagulation factor VII (FVII) gene by hepatoma cells was modulated in concert with levels of glucose and insulin in the culture medium. In low glucose medium without insulin, amounts of both FVII mRNA and secreted FVII protein were coordinately increased; in the presence of glucose with insulin, both were decreased. Analysis of the FVII promoter showed that these effects could be reproduced in a reporter-gene system, and a small promoter element immediately upstream of the translation start site of the gene, which mediated these effects, was identified. Mutation of this element largely abrogated the glucose/insulin-responsive change in expression of the reporter gene. Several members of the CCAAT/enhancer-binding protein family were found to be capable of binding the identified sequence element but not the mutated element. The expression of a FVII minigene directed by a segment of the native FVII promoter responded to co-expressed activating and inhibiting forms of CCAAT/enhancer-binding protein beta.