Peri-operative Anticoagulation Strategies, Bleeding and Thrombotic Complications in Pediatric Patients Undergoing Intervention for Congenital Portosystemic Shunts.

BACKGROUND: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications. METHODS: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications. RESULTS: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported. CONCLUSIONS: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively. LEVELS OF EVIDENCE: Level II, retrospective study.

A History of Umbilical Vein Catheterization Does Not Preclude Children from a Successful Meso-Rex Bypass.

INTRODUCTION: Umbilical vein catheterization (UVC) can cause portal venous thrombosis, leading to the development of extrahepatic portal venous obstruction (EHPVO) and portal hypertension (PHT). The feasibility of the Meso-Rex bypass (MRB) for the treatment of EHPVO in patients with a history of UVC has been questioned. We compared the feasibility of performing an MRB in patients with or without a history of previous UVC. METHODS: A retrospective review of patients with EHPVO and known UVC status explored for a possible MRB at our institution was performed (1997-2022). Patients were categorized in two groups: with (UVC(+)) or without (UVC(-)) a history of UVC for comparison. A p-value less than 0.05 was considered significant. RESULTS: One hundred and eighty-seven patients were included (n = 57 in UVC(+); n = 130 in UVC(-)). Patients in the UVC group were significantly younger at surgery and the incidence of prematurity was higher. Other risk factors for the development of EHPVO were similar between the groups, but only history of UVC could predict the ability to receive MRB (odds ratio [OR]: 7.4 [3.5-15.4]; p < 0.001). The success rate of MRB was significantly higher in patients with no history of UVC (28/57 [49.1%] in UVC(+) vs. 114/130 [87.7%] in UVC(-); p < 0.001). However, MRB patency at discharge (25/28 [89.3%] in UVC(+) vs. 106/114 [94.7%] in UVC(-); p = 0.3) was equally high in both groups. CONCLUSION: Our results indicate that a history of UVC is not a contraindication to MRB. Half of the patients were able to successfully receive an MRB. Patients with symptomatic PHT from EHPVO should not be excluded from consideration for MRB based on UVC history.

Outcomes after ABO incompatible pediatric liver transplantation are comparable to ABO identical/compatible transplant.

Background: ABO incompatible (ABOi) liver transplantation (LT) was initially associated with a higher incidence of vascular, biliary, and rejection complications and a lower survival than ABO compatible (ABOc) LT. Various protocols have been proposed to manage anti-isohemagglutinin antibodies and hyperacute rejection. We present our experience with a simplified protocol using only plasmapheresis. Methods: A retrospective review of all patients who received an ABOi LT at our institution was performed. Comparisons were made based on era (early: 1997-2008, modern: 2009-2020) and severity of disease (status 1 vs. exception PELD at transplant). A pair-matched comparison was done to patients who received an ABOc LT. p < 0.05 was considered significant. Results: 17 patients received 18 ABOi LT (3 retransplants). Median age at transplant was 7.4 months (1.1-28.9). 66.7% patients were listed as status 1. Hepatic artery thrombosis (HAT) occurred in one patient (5.6%), there were 2 cases of portal vein thrombosis (PVT) (11.1%), and 2 biliary strictures (11.1%). Patient and graft survival improved in the ABOi modern era, although not significantly. In the pair-matched comparison, complications (HAT p = 0.29; PVT p = 0.37; biliary complications p = 0.15) and survival rates were similar. Patient and graft survivals were 100% in the non-status 1 ABOi patients compared to 67% (p = 0.11) and 58% (p = 0.081) respectively for patients who were transplanted as status 1. Conclusion: ABO incompatible liver transplants in infants with a high PELD score have excellent outcomes. Indications for ABO incompatible transplants should be liberalized to prevent deaths on the waiting list or deterioration of children with high PELD scores.

Fluid balance in pediatric postoperative liver transplant recipients.

BACKGROUND: Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients. METHODS: We performed a retrospective cohort study of first-time pediatric LT recipients at a quaternary care children's hospital. Patients were stratified into three groups based on their FB in the first 72 h postoperatively: <10%, 10-20%, and > 20%. Outcomes were pediatric intensive care unit (PICU) and hospital length of stay, ventilator-free days (VFD) at 28 days, day 3 severe acute kidney injury, and postoperative complications. Multivariate analyses were adjusted for age, preoperative admission status, and Pediatric Risk of Mortality (PRISM)-III score. RESULTS: We included 129 patients with median PRISM-III score of 9 (interquartile range, IQR 7-15) and calculated Pediatric End-stage Liver Disease score of 15 (IQR 2-23). A total of 37 patients (28.7%) had 10-20% FB, and 26 (20.2%) had >20% FB. Greater than 20% FB was associated with an increased likelihood of an additional PICU day (adjusted incident rate ratio [aIRR] 1.62, 95% CI: 1.18-2.24), an additional hospital day (aIRR 1.39, 95% CI: 1.10-1.77), and lower likelihood of a VFD at 28 days (aIRR 0.85, 95% CI: 0.74-0.97). There were no differences between groups in the likelihood of postoperative complications. CONCLUSIONS: In pediatric LT recipients, >20% FB at 72 h postoperatively is associated with increased morbidities, independent of age and severity of illness. Additional studies are needed to explore the impact of fluid management strategies on outcomes.

Identification of Early Clinical and Histological Factors Predictive of Kasai Portoenterostomy Failure.

Background: It is impossible to predict which patients with biliary atresia (BA) will fail after Kasai portoenterostomy (KPE). We evaluated the predictive nature of pre-KPE clinical and histological factors on transplant-free survival (TFS) and jaundice clearance. Methods: A retrospective review of patients who received a KPE at our institution (1997−2018) was performed. Primary outcomes were two-year TFS, five-year TFS, and jaundice clearance 3 months after KPE. p < 0.05 was considered significant. Results: Fifty-four patients were included in this study. The two-year TFS was 35.1%, five-year TFS was 24.5%, and 37% patients reached a direct bilirubin (DB) ≤ 2.0 mg/dL 3 months post KPE. The median age at biopsy was younger in the five-year TFS (39.0 (24.5−55.5) vs. 56.0 days (51.0−67.0), p = 0.011). Patients with DB ≤ 1.0 mg/dL 3 months after KPE were statistically younger at biopsy (DB ≤ 1.0 44.0 (26.0−56.0) vs. DB > 1.0 56.0 days (51.0−69.0), p = 0.016). Ductal plate malformation was less frequent in the five-year TFS (16/17, 94.1%, vs. 1/17, 5.9%, p = 0.037). Portal fibrosis (19/23, 82.6%, vs. 4/23, 17.4%, p = 0.028) and acute cholangitis (6/7, 85.7%, vs. 1/7, 14.3%, p = 0.047) occurred less frequently in two-year TFS. Conclusion: Older age at biopsy, acute cholangitis, portal fibrosis, and ductal plate malformation were associated with lower native liver survival. Evaluation in a larger study population is needed to validate these results.

Early thrombotic and hemorrhagic complications associated with a risk-adjusted postoperative anticoagulation protocol after pediatric liver transplantation.

BACKGROUND: Systemic anticoagulation after pediatric liver transplantation (pLT) is believed to reduce the incidence of vascular thrombosis, but it may also cause an increase in hemorrhagic complications. PROCEDURE: A 5-year retrospective review of pLT done at our institution was performed (2014-2018). The occurrence of early hemorrhagic and thrombotic complications was compared when using low-dose or high-dose anticoagulation after transplant (p < .05 considered significant). RESULTS: Sixty-nine patients received 73 transplants during the study period. Median age at transplant was 2.3 years (40 days to 18.5 years). Low-dose anticoagulation was utilized in 71% cases. Additionally, six patients were converted from low-dose to high-dose anticoagulation because of a thrombotic event or concerns for suboptimal vascular inflow. Postoperative anticoagulation was discontinued in 18 occurrences due to bleeding (low dose 19%, high dose 47% vs. low dose to high dose 17%, p = .085). Surgical take back for bleeding occurred in 17 occasions (low dose 13.5%, high dose 53% vs. low dose to high dose 33%, p = .005). The overall incidence of hepatic artery thrombosis (HAT) and portal vein thrombosis were each 5.5%, respectively. While patient survival was not statistically different between groups, graft survival was significantly lower in the high-dose group (low dose 93%, high dose 73% vs. low dose to high dose 100%, p = .046). However, graft losses from HAT were similar between groups (low dose 2%, high dose 7% vs. low dose to high dose 0%, p = .56). CONCLUSION: The use of a standardized risk-adjusted anticoagulation protocol after pLT is associated with a low occurrence of thrombotic and hemorrhagic complications. High-dose anticoagulation leads to more bleeding, but those risks outweigh the risks of possible graft loss.

Primary Liver Transplantation vs. Transplant after Kasai Portoenterostomy for Infants with Biliary Atresia.

Introduction: Primary liver transplants (pLT) in patients with biliary atresia (BA) are infrequent, since most babies with BA undergo a prior Kasai portoenterostomy (KPE). This study compared transplant outcomes in children with BA with or without a prior KPE. We hypothesized that pLT have less morbidity and better outcomes compared to those done after a failed KPE. Methods: A retrospective review of patients with BA transplanted at our institution was performed. Patients were included if they received a pLT or if they were transplanted less than 2 years from KPE. Outcomes were compared between those groups. Comparisons were also made based on era (early: 1997−2008 vs. modern: 2009−2020). p < 0.05 was considered significant. Results: Patients who received a pLT were older at diagnosis (141.5 ± 46.0 vs. KPE 67.1 ± 25.5 days, p < 0.001). The time between diagnosis and listing for transplant was shorter in the pLT group (44.5 ± 44.7 vs. KPE 140.8 ± 102.8 days, p < 0.001). In the modern era, the calculated PELD score for the pLT was significantly higher (23 ± 8 vs. KPE 16 ± 8, p = 0.022). Two waitlist deaths occurred in the KPE group (none in pLT, p = 0.14). Both the duration of transplant surgery and transfusion requirements were similar in both groups. There was a significant improvement in graft survival in transplants after KPE between eras (early era 84.3% vs. modern era 97.8%, p = 0.025). The 1-year patient and graft survival after pLT was 100%. Conclusions: Patient and graft survival after pLT are comparable to transplants after a failed KPE but pLT avoids a prior intervention. There was no significant difference in pre- or peri-transplant morbidity between groups other than wait list mortality. A multicenter collaboration with more patients may help demonstrate the potential benefits of pLT in patients predicted to have early failure of KPE.

Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement.

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed­from diagnosis to LT­with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016−2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population.

Psychosocial Stressors and Adaptive Coping Strategies in Couples After a Diagnosis of Young-Onset Dementia.

BACKGROUND AND OBJECTIVES: Diagnoses of young-onset dementias (YODs) are devastating for persons with dementia and spousal caregivers yet limited work has examined both partners' perceptions of challenges and coping after diagnosis. This qualitative study investigated the psychosocial stressors and adaptive coping strategies in couples diagnosed with YOD to inform the development of psychosocial support resources. RESEARCH DESIGN AND METHODS: We conducted live video dyadic interviews with couples (persons with YOD and spousal caregivers together; N = 23 couples). We transcribed interviews and coded data based on a hybrid deductive-inductive approach, with the structure of the coding framework informed by the stress and coping framework, and all codes derived from the data. We derived themes and subthemes related to psychosocial stressors and adaptive coping. RESULTS: We identified 5 themes related to psychosocial stressors: the impact of diagnosis, social and family relationships, changing roles and responsibilities, planning for an uncertain future, and couple communication and relationship strain. We identified 7 themes related to adaptive coping strategies: processing emotions and cultivating acceptance, promoting normalcy, efforts to preserve persons with YOD's independence and identity, collaborative and open communication, social support, meaning-making, humor, and positivity, and lifestyle changes and self-care. DISCUSSION AND IMPLICATIONS: We replicated several themes regarding stressors and adaptive coping strategies from prior YOD research and identified novel themes and subthemes related to dyadic stressors, sources of couples' relationship strain, and the ways in which couples effectively cope with YOD. Findings inform the development of dyadic interventions to reduce YOD-related distress for both persons with dementia and spousal caregivers.

Dating Violence, Protection Orders, and Gender Inequality: A Cross-state Analysis of Policy Formulation and Implementation.

Teen dating violence (TDV) is a public health crisis that organizations and individuals in several fields are working to prevent and address. State lawmakers are a group with substantial power to address TDV and intimate partner violence (IPV) through policies including Civil Protection Order (CPO) statutes. Understanding the factors that influence how state legislators craft TDV and IPV policies and how those policies are implemented can lead to policy processes that better serve survivors. Past research suggests the level of gender inequality in a state may be an important influence on TDV policies. This study used a case study approach to compare the processes of adding individuals in dating relationships to CPO statutes in a subset of states (n = 3) with high, middle, and low levels of gender inequality. Results did not suggest that gender inequality was related to variation between states but rather that it was a larger factor that creates the need for TDV policies at all. Relationships between the state IPV coalitions and lawmakers and the historical moment that laws were considered emerged as important factors in interstate variation. Future research can build on these results by further exploring the role of gender inequality in policy processes with additional states or policies and by examining the factors identified here in greater depth. Implications for practice are also discussed.

Internal split liver transplants reduce the waiting list time for teenagers with a low calculated Model for End-stage Liver Disease score.

BACKGROUND: Split liver transplantation allows for the simultaneous transplantation of two patients, typically a child and an adult, with a single organ. We report our experience with "internal splits" in which 10 pediatric patients from our institution were transplanted with five organs. We hypothesized that this would reduce the WL time for teenagers with a low calculated MELD score. METHODS: A retrospective chart review of those 10 patients was done. Their WL time was compared with local, regional, and national data. P < .05 was considered significant. RESULTS: The median age of the five primary recipients to whom the liver was first allocated was 2.3 years (0.7-7.4) (median weight 10.4 kg (8.4-17.7)). They received a segment 2-3 graft. Five "secondary" recipients (median age 17.4 years (16.6-18.9); median weight 66.2 kg (53.7-70.0)) were identified on our WL to receive the trisector graft. At transplant, their median calculated MELD score was 11 (8-20). Their mean WL time (241.6 ± 218.9 days) was significantly shorter than local (480.6 ± 833.6 days), regional (370.4 ± 563.4 days), and national patients (245.6 ± 465.4 days) with MELD ≤ 20 (P = .047). There was no significant difference between their WL time and that of patients with a MELD 8 ≤ x≤31 (equivalent to their median exception score, P = .63). Patient and graft survival was 100% for all 10 patients. CONCLUSION: In our experience, simultaneous internal split liver transplantation allowed teenagers with a low calculated MELD score to be transplanted faster than patients with a similar score. Promoting the use of internal split liver transplantation could help reduce the pediatric waitlist mortality.

The evolution of early liver biopsy findings in babies with jaundice may delay the diagnosis and treatment of biliary atresia.

BACKGROUND: The early diagnosis of biliary atresia (BA) is associated with a better outcome after portoenterostomy. However, very early liver biopsy findings may appear atypical for BA and delay diagnosis. Repeat biopsy histology may change rapidly to show more typical features. METHODS: Between 1997 and 2018, 6 babies with jaundice had more than one biopsy to establish diagnosis. Clinical and histologic data were collected. chi-Square was used for analysis (p < 0.05 significant). RESULTS: Five patients had two biopsies, and one had three. Median age at first, second, and third biopsy was 40 (13-57), 68.5 (35-78), and 133 days, respectively. Biopsy readings showed no portal edema initially (0/6), but in all 6 on repeat biopsy (p = 0.001). Bile duct proliferation was seen in 6/6 final biopsies, but in only 1/6 initially (p = 0.003). All patients underwent a portoenterostomy (median age 75 days (43-113)). Median delay between initial biopsy and Kasai was 29 days (14-67). Transplant free survival (n = 5 patients) ranged from 184 to 716 days (median 309 days). One patient died before being transplanted. CONCLUSION: Early biopsies may not display characteristic findings of BA, but these can appear quickly on subsequent evaluation. The interval needed to repeat a biopsy may have an adverse effect on bile drainage. LEVEL OF EVIDENCE: IV.

Diagnostic evaluation and monitoring of patients with posterior cortical atrophy.

Posterior cortical atrophy (PCA) is a progressive neurocognitive syndrome, most commonly associated with the loss of complex visuospatial functions. Diagnosis is challenging, and international consensus classification and nomenclature for PCA subtypes have only recently been reached. Presently, no established treatments exist. Efforts to develop treatments are hampered by the lack of standardized methods to monitor illness progression. Although measures developed from work with Alzheimer's disease and other dementias provide a foundation for diagnosing and monitoring progression, PCA presents unique challenges for clinicians counseling patients and families on clinical status and prognosis, and experts designing clinical trials of interventions. Here, we review issues facing PCA clinical research and care, summarize our approach to diagnosis and monitoring of disease progression, and outline ideas for developing tools for these purposes.

Liver histopathology in patients with hepatic masses and the Abernethy malformation.

BACKGROUND/PURPOSE: The Abernethy malformation (AM) is a congenital venous malformation in which the splanchnic venous return bypasses the liver and drains directly into the systemic circulation. This deprives the liver of hepatotrophic growth factors and allows metabolic products of digestion to enter the systemic veins without the benefit of passing through the liver. The histologic features of liver biopsies in children with an AM were reviewed. METHODS: A retrospective review of liver biopsies in patients with AM between 1997 and 2017 was performed. Patients were divided into two groups for comparison of histologic features: presence (M+) or absence (M-) of a coexistent liver mass on imaging. Biopsies were reviewed by a pediatric pathologist. Chi-square test was used for statistical analysis between groups. Significance was assigned to p values <0.05. RESULTS: Eighteen liver biopsies were reviewed. Masses were present in only 6 patients who had a liver biopsy. Masses were observed with similar frequencies in either type of the Abernethy malformation (I or II). Nine of 12 M- patients and 3/6 M+ patients had the type I AM. Histologically, all patients were noted to have small or absent portal veins. Isolated capillaries were seen more frequently in patients with a known liver mass (p = 0.045), while crowding of portal tracts was more commonly seen in patients without a liver mass (p = 0.019). CONCLUSION: Liver biopsies in patients with AM demonstrate abnormal vascular and parenchymal histologic features. Livers with coexistent masses were more commonly found to have features suggesting an increased dependence on arterial blood supply. LEVEL OF EVIDENCE: III.

Intravenous epoprostenol improves oxygenation index in patients with persistent pulmonary hypertension of the newborn refractory to nitric oxide.

OBJECTIVES: Evaluate the short-term effects of IV epoprostenol in neonates with persistent pulmonary hypertension (PPHN) of the newborn. STUDY DESIGN: We reviewed 36 patients with inhaled nitric oxide (iNO) refractory PPHN placed on IV epoprostenol from 2010 to 2015. Patients were categorized as responders or non-responders (who either died or required extracorporeal membranous oxygenation). RESULTS: There were 15 responders and 21 non-responders. Pulmonary hypoplasia was the etiology of PPHN for 57% of non-responders vs. 13% of responders. Median oxygenation index (OI) was similar at baseline (41.8 non-responders vs. 36.5 responders, p = 0.41) with responders having a significantly lower OI by 4 h of treatment (42.3 vs. 23.1, p = 0.002). Epoprostenol responders had a median OI decrease of 11.6 within 4 h (p = 0.017) with a significant response persisting through 24 h. CONCLUSION: In infants with iNO-refractory PPHN, initiation of IV epoprostenol was associated with a significant and rapid OI reduction among responders.

Benefits of training family caregivers on experiences of closure during end-of-life care.

Caregiving at Life's End (CGLE) is a program for family caregivers caring for someone during the last years of life that focuses on the emotional, spiritual, and practical aspects of life and relationship completion and closure. This study evaluated the effectiveness of CGLE in improving three major outcomes: comfort with caregiving, closure, and caregiver gain. Family caregivers (n=2,025) participated in programs facilitated by health and human service professionals (n=142) who completed a CGLE train-the-trainer workshop conducted by The Hospice Institute of the Florida Suncoast. The caregivers completed training rosters and pre- and/or post-surveys. Group differences are reported in baseline characteristics and change in three outcomes for caregivers who completed 1) both pre- and post-survey, 2) pre-survey only, and 3) post-survey only. For those who completed both surveys (n=926), paired t-tests and multiple linear regression tested the impact of program length on caregiver outcomes. Caregivers participated in, on average, four sessions and 7.7 hours of training. The majority of caregivers were Caucasian (88%), female (81%), and on average, 60 years old. Significant improvement was found in all three outcomes (P<0.001). The program length made a difference for improvement in comfort with caregiving and closure but not in caregiver gain. Caregivers who are caring for someone during the last years of life benefit from a program that focuses on the life-changing or transformative aspects of caregiving in the last years of life, as well as practical aspects of caregiving. The ability to support caregivers in this relatively low impact intervention can be used in hospice and nonhospice settings.

Validation of the caregiving at life's end questionnaire.

The researchers in this study developed and validated a questionnaire to measure the needs of end-of-life (EOL) caregivers. The model is used to facilitate meaningful and supportive experiences for both the patient and caregiver The questionnaire was developed using existing scales of meaning, self-acceptance, burden, and gain as well as new scales of caregiver comfort, importance of caregiving tasks, and caregiver closure. The sample included 34 current and 17 bereaved caregivers affiliated with The Hospice Institute of the Florida Suncoast. The scales performed well in terms of concurrent validity, internal consistency, and reliability.

Transformative aspects of caregiving at life's end.

We do not know to what extent the needs of caregivers involved with patients at the end of life are being met by care providers and whether caregiving at life's end can be a positive experience. We used the Hospice Experience Model of Care as a framework for understanding the effect of transformative tasks on caregiving at life's end. We compared current and bereaved caregivers and then, holding background characteristics constant, tested the independent effects of three transformative mediators: self-acceptance, meaning, and closure, as well as comfort with caregiving on several stressors when explaining differences in caregiver burden and gain. Transformative aspects of caregiving do not mediate the stressors associated with burden but do mediate one stressor associated with caregiver gain. Two mediators reduce caregiver burden and all four of the mediators improve caregiver gain. Caregivers who are able to attend to these transformative aspects find more gain in the caregiving experience.