Objective

Caregivers for patients undergoing hematopoietic cell transplantation (HCT) are susceptible to significant psychosocial distress. This cross-sectional study aimed to describe psychosocial support services offered and used by caregivers of pediatric primary immune deficiency (PID) during HCT at 35 hospitals across North America.

Method

Caregivers of pediatric patients with PID were recruited by e-mail to participate in an anonymous 140-question survey instrument between April and May 2016 (N = 171).

Result

Of those meeting inclusion criteria (53%), family counseling services were only offered to fewer than half of caregivers (42%). Of the survey participants not offered counseling services, the majority desired family counseling (70%) and sibling counseling (73%). That said, when offered counseling, utilization rates were low, with 22% of caregivers using family counseling and none using sibling counseling.

Significance of results

These results indicate the need to offer and tailor counseling services for families throughout the HCT process. Further research should focus on reducing barriers to utilization of counseling services such as offering bedside counseling services, online modalities, and/or financial assistance.

Objective

Caregivers for patients undergoing hematopoietic cell transplantation (HCT) are susceptible to significant psychosocial distress. This cross-sectional study aimed to describe psychosocial support services offered and used by caregivers of pediatric primary immune deficiency (PID) during HCT at 35 hospitals across North America.

Method

Caregivers of pediatric patients with PID were recruited by e-mail to participate in an anonymous 140-question survey instrument between April and May 2016 (N = 171).

Result

Of those meeting inclusion criteria (53%), family counseling services were only offered to fewer than half of caregivers (42%). Of the survey participants not offered counseling services, the majority desired family counseling (70%) and sibling counseling (73%). That said, when offered counseling, utilization rates were low, with 22% of caregivers using family counseling and none using sibling counseling.

Significance of results

These results indicate the need to offer and tailor counseling services for families throughout the HCT process. Further research should focus on reducing barriers to utilization of counseling services such as offering bedside counseling services, online modalities, and/or financial assistance.

Precise editing of human genomes in pluripotent stem cells by homology-driven repair of targeted nuclease-induced cleavage has been hindered by the difficulty of isolating rare clones. We developed an efficient method to capture rare mutational events, enabling isolation of mutant lines with single-base substitutions without antibiotic selection. This method facilitates efficient induction or reversion of mutations associated with human disease in isogenic human induced pluripotent stem cells.

Background

Caregivers of children with primary immunodeficiency disorders (PIDs) experience significant psychological distress during their child's hematopoietic cell transplantation (HCT) process.

Objectives

This study aims to understand caregiver challenges and identify areas for health care system-level improvements to enhance caregiver well-being.

Methods

In this mixed-methods study caregivers of children with PIDs were contacted in August to November 2017 through online and electronic mailing lists of rare disease consortiums and foundations. Caregivers were invited to participate in an online survey assessing sociodemographic variables, the child's medical characteristics, psychosocial support use, and the World Health Organization-5 Well-Being Index. Open-ended questions about health care system improvements were included. Descriptive statistics and linear multivariate regression analyses were conducted. A modified content analysis method was used to code responses and identify emergent themes.

Results

Among the 80 caregiver respondents, caregivers had a median age of 34 years (range, 23-62 years) and were predominantly female, white, and married with male children given a diagnosis of severe combined immune deficiency. In the adjusted regression model lower caregiver well-being was significantly associated with lower household income and medical complications. Challenges during HCT include maintaining relationships with partners and the child's healthy sibling or siblings, managing self-care, and coping with feelings of uncertainty. Caregivers suggested several organizational-level solutions to enhance psychosocial support, including respite services, online connections to other PID caregivers, and bedside mental health services.

Conclusions

Certain high-risk subpopulations of caregivers might need more targeted psychosocial support to reduce the long-term effect of the HCT experience on their well-being. Caregivers suggested several organizational-level solutions for provision of this support.

OBJECTIVE:To determine if traumatic renal injuries or computed tomography (CT) findings are predictive of hypertension (HTN) development following injury. METHODS:A retrospective review of a renal trauma database was performed from 1995 to 2015. Renal injuries were graded by the American Association for the Surgery of Trauma system, with high-grade defined as IV or V. Nonrenal genitourinary trauma (ie bladder, penile, urethral, and testicular) patients were selected as controls. Patients with a diagnosis of HTN before their trauma or those lacking follow-up were excluded. Risk factors associated with HTN following trauma were identified using multivariable regression with propensity scoring. RESULTS:In total, 163 patients had a renal injury and 60 had nonrenal, genitourinary injuries. The median age was 31 years (interquartile range 23-43) with median follow-up of 4.7 years (interquartile range 1.9-8.5). Twenty-three (14%) patients with renal trauma were newly diagnosed with HTN on follow-up, compared with 2 (3%) in the control groups. (P = .02) After propensity quartile adjustment, patients with high-grade trauma had higher odds of developing HTN compared with low-grade renal trauma patients and controls (adjusted odds ratio 3.5, 95% confidence interval 1.3-9.3, P = .01). Patients with a midpole medial laceration and medial blood on CT had higher odds of developing HTN compared with patients without these characteristics (odds ratio 5.36, 95% confidence interval 1.3-22.6, P = .02). CONCLUSION:Increasing renal trauma grade is a risk factor for future development of HTN. CT findings at trauma presentation may be useful in stratifying patients who are at increased risk.

Background

Caregivers of children with primary immunodeficiency disorders (PIDs) experience significant psychological distress during their child's hematopoietic cell transplantation (HCT) process.

Objectives

This study aims to understand caregiver challenges and identify areas for health care system-level improvements to enhance caregiver well-being.

Methods

In this mixed-methods study caregivers of children with PIDs were contacted in August to November 2017 through online and electronic mailing lists of rare disease consortiums and foundations. Caregivers were invited to participate in an online survey assessing sociodemographic variables, the child's medical characteristics, psychosocial support use, and the World Health Organization-5 Well-Being Index. Open-ended questions about health care system improvements were included. Descriptive statistics and linear multivariate regression analyses were conducted. A modified content analysis method was used to code responses and identify emergent themes.

Results

Among the 80 caregiver respondents, caregivers had a median age of 34 years (range, 23-62 years) and were predominantly female, white, and married with male children given a diagnosis of severe combined immune deficiency. In the adjusted regression model lower caregiver well-being was significantly associated with lower household income and medical complications. Challenges during HCT include maintaining relationships with partners and the child's healthy sibling or siblings, managing self-care, and coping with feelings of uncertainty. Caregivers suggested several organizational-level solutions to enhance psychosocial support, including respite services, online connections to other PID caregivers, and bedside mental health services.

Conclusions

Certain high-risk subpopulations of caregivers might need more targeted psychosocial support to reduce the long-term effect of the HCT experience on their well-being. Caregivers suggested several organizational-level solutions for provision of this support.

Background

Epidemiological studies have shown that bicycle trauma is associated with genitourinary (GU) injuries. Our objective is to characterize GU-related bicycle trauma admitted to a level I trauma center.

Materials and methods

We queried a prospective trauma registry for bicycle injuries over a 20-year period. Patient demographics, triage data, operative interventions and hospital details were collected.

Results

In total, 1659 patients were admitted with major bicycle trauma. Of these, 48 cases involved a GU organ, specifically the bladder (n=7), testis (n=6), urethra (n=3), adrenal (n=4) and/or kidneys (n=36). The median age of cyclists with GU injuries was 29 (range 5-70). More men were injured versus women (35 versus 13). GU-related bicycle trauma involved a motor vehicle in 52% (25/48) of injuries. The median injury severity score for GU-related bicycle trauma was 17 (range 1-50). The median number of concomitant organ injuries was 2 (range 0-6), the most common of which was the lungs (13/48, 27%) and ribs (13/48, 27%). The majority of GU injured cyclists were admitted to an ICU (15/48, 31%) or hospital floor (12/48, 25%). Operative intervention for a GU-related trauma was low (12/48, 25%). The most common GU organ injured was the kidney (36/48, 75%) however most were managed nonoperatively (33/36, 92%). Bladder injuries most often required operative intervention (6/7, 86%). Mortality following GU-related bicycle trauma was low (2/48, 4%).

Conclusions

In a large series of bicycle trauma, GU organs were injured in 3% of cases. The majority of cases were managed non-operatively and mortality was low.

Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype. To model BAG3 cardiomyopathy in a human system, we generated an isogenic series of human induced pluripotent stem cells (iPSCs) with loss-of-function mutations in BAG3. Heterozygous BAG3 mutations reduced protein expression, disrupted myofibril structure, and compromised contractile function in iPSC-derived cardiomyocytes (iPS-CMs). BAG3-deficient iPS-CMs were particularly sensitive to further myofibril disruption and contractile dysfunction upon exposure to proteasome inhibitors known to cause cardiotoxicity. We performed affinity tagging of the endogenous BAG3 protein and mass spectrometry proteomics to further define the cardioprotective chaperone complex that BAG3 coordinates in the human heart. Our results establish a model for evaluating protein quality control pathways in human cardiomyocytes and their potential as therapeutic targets and susceptibility factors for cardiac drug toxicity.

Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype. To model BAG3 cardiomyopathy in a human system, we generated an isogenic series of human induced pluripotent stem cells (iPSCs) with loss-of-function mutations in BAG3. Heterozygous BAG3 mutations reduced protein expression, disrupted myofibril structure, and compromised contractile function in iPSC-derived cardiomyocytes (iPS-CMs). BAG3-deficient iPS-CMs were particularly sensitive to further myofibril disruption and contractile dysfunction upon exposure to proteasome inhibitors known to cause cardiotoxicity. We performed affinity tagging of the endogenous BAG3 protein and mass spectrometry proteomics to further define the cardioprotective chaperone complex that BAG3 coordinates in the human heart. Our results establish a model for evaluating protein quality control pathways in human cardiomyocytes and their potential as therapeutic targets and susceptibility factors for cardiac drug toxicity.

Contractile motion is the simplest metric of cardiomyocyte health in vitro, but unbiased quantification is challenging. We describe a rapid automated method, requiring only standard video microscopy, to analyze the contractility of human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CM). New algorithms for generating and filtering motion vectors combined with a newly developed isogenic iPSC line harboring genetically encoded calcium indicator, GCaMP6f, allow simultaneous user-independent measurement and analysis of the coupling between calcium flux and contractility. The relative performance of these algorithms, in terms of improving signal to noise, was tested. Applying these algorithms allowed analysis of contractility in iPS-CM cultured over multiple spatial scales from single cells to three-dimensional constructs. This open source software was validated with analysis of isoproterenol response in these cells, and can be applied in future studies comparing the drug responsiveness of iPS-CM cultured in different microenvironments in the context of tissue engineering.