Safety and biologic activity of a canine anti-CD20 monoclonal antibody in dogs with diffuse large B-cell lymphoma.

BACKGROUND: To explore the safety and utility of combining low dose single-agent doxorubicin with a canine specific anti-CD20 monoclonal antibody (1E4-cIgGB) in client owned dogs with untreated B-cell lymphoma. ANIMALS: Forty-two client-owned dogs with untreated B-cell lymphoma. METHODS: A prospective, single arm, open label clinical trial of dogs with B-cell lymphoma were enrolled to receive 1E4-cIgGB and doxorubicin in addition to 1 of 3 immunomodulatory regimens. B-cell depletion was monitored by flow cytometry performed on peripheral blood samples at each visit. RESULTS: Dogs demonstrated a statistically significant depletion in CD21+ B-cells 7 days following the first antibody infusion (median fraction of baseline at 7 days = 0.04, P < .01) that persisted throughout treatment (median fraction of baseline at 21 days = 0.01, P < .01) whereas CD5+ T-cells remained unchanged (median fraction of baseline at 7 days = 1.05, P = .88; median fraction of baselie at 7 days = 0.79, P = .42; Figure 1; Supplemental Table 3). Recovery of B-cells was delayed, with at Day 196, only 6/17 dogs (35%) remaining on the study had CD21+ counts >0.5 of baseline, indicating sustained B cell depletion at 4+ months after the final treatment. 1E4-cIgGB was well tolerated with only 1 dog exhibiting a hypersensitivity event within minutes of the last antibody infusion. CONCLUSIONS: The canine 1E4-cIgGB anti-CD20 monoclonal antibody is apparently safe when administered with doxorubicin and effectively depletes B-cells in dogs with DLBCL.

Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma.

Cutaneous T-cell lymphoma (CTCL) is an uncommon type of lymphoma involving malignant skin-resident or skin-homing T cells. Canine epitheliotropic lymphoma (EL) is the most common form of CTCL in dogs, and it also spontaneously arises from T lymphocytes in the mucosa and skin. Clinically, it can be difficult to distinguish early-stage CTCLs apart from other forms of benign interface dermatitis (ID) in both dogs and people. Our objective was to identify novel biomarkers that can distinguish EL from other forms of ID, and perform comparative transcriptomics of human CTCL and canine EL. Here, we present a retrospective gene expression study that employed archival tissue from biorepositories. We analyzed a discovery cohort of 6 canines and a validation cohort of 8 canines with EL which occurred spontaneously in client-owned companion dogs. We performed comparative targeted transcriptomics studies using NanoString to assess 160 genes from lesional skin biopsies from the discovery cohort and 800 genes from the validation cohort to identify any significant differences that may reflect oncogenesis and immunopathogenesis. We further sought to determine if gene expression in EL and CTCL are conserved across humans and canines by comparing our data to previously published human datasets. Similar chemokine profiles were observed in dog EL and human CTCL, and analyses were performed to validate potential biomarkers and drivers of disease. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CD244, CXCL10, and CCL5 in EL in dogs compared to healthy controls. Importantly, CTSW, TRAT1 and KLRK1 distinguished EL from all other forms of interface dermatitis we studied, providing much-needed biomarkers for the veterinary field. XCL1/XCL2 were also highly specific of EL in our validation cohort. Future studies exploring the oncogenesis of spontaneous lymphomas in companion animals will expand our understanding of these disorders. Biomarkers may be useful for predicting disease prognosis and treatment responses. We plan to use our data to inform future development of targeted therapies, as well as for repurposing drugs for both veterinary and human medicine.

Leading the pack: Best practices in comparative canine cancer genomics to inform human oncology.

Pet dogs develop spontaneous cancers at a rate estimated to be five times higher than that of humans, providing a unique opportunity to study disease biology and evaluate novel therapeutic strategies in a model system that possesses an intact immune system and mirrors key aspects of human cancer biology. Despite decades of interest, effective utilization of pet dog cancers has been hindered by a limited repertoire of necessary cellular and molecular reagents for both in vitro and in vivo studies, as well as a dearth of information regarding the genomic landscape of these cancers. Recently, many of these critical gaps have been addressed through the generation of a highly annotated canine reference genome, the creation of several tools necessary for multi-omic analysis of canine tumours, and the development of a centralized repository for key genomic and associated clinical information from canine cancer patients, the Integrated Canine Data Commons. Together, these advances have catalysed multidisciplinary efforts designed to integrate the study of pet dog cancers more effectively into the translational continuum, with the ultimate goal of improving human outcomes. The current review summarizes this recent progress and provides a guide to resources and tools available for comparative study of pet dog cancers.

Baseline tumor gene expression signatures correlate with chemoimmunotherapy treatment responsiveness in canine B cell lymphoma.

Pet dogs develop spontaneous diffuse large B cell lymphoma (DLBCL), and veterinary clinical trials have been employed to treat canine DLBCL and to inform clinical trials for their human companions. A challenge that remains is selection of treatment to improve outcomes. The dogs in this study were part of a larger clinical trial evaluating the use of combinations of doxorubicin chemotherapy, anti-CD20 monoclonal antibody, and one of three small molecule inhibitors: KPT-9274, TAK-981, or RV1001. We hypothesized that significant differential expression of genes (DEGs) in the tumors at baseline could help predict which dogs would respond better to each treatment based on the molecular pathways targeted by each drug. To this end, we evaluated gene expression in lymph node aspirates from 18 trial dogs using the NanoString nCounter Canine Immuno-oncology (IO) Panel. We defined good responders as those who relapsed after 90 days, and poor responders as those who relapsed prior to 90 days. We analyzed all dogs at baseline and compared poor responders to good responders, and found increased CCND3 correlated with poor prognosis and increased CD36 correlated with good prognosis, as is observed in humans. There was minimal DEG overlap between treatment arms, prompting separate analyses for each treatment cohort. Increased CREBBP and CDKN1A for KPT-9274, increased TLR3 for TAK-981, and increased PI3Kδ, AKT3, and PTEN, and decreased NRAS for RV1001 were associated with better prognoses. Trends for selected candidate biomarker genes were confirmed via qPCR. Our findings emphasize the heterogeneity in DLBCL, similarities and differences between canine and human DLBCL, and ultimately identify biomarkers that may help guide the choice of chemoimmunotherapy treatment in dogs.

Characterizing the Response of Puccinia striiformis f. sp. tritici to Periods of Heat Stress that Are Common in Kansas and the Great Plains Region of North America.

Stripe rust of wheat, caused by Puccinia striiformis f. sp. tritici, is considered a disease of cool environments, and it has been observed that high temperatures can suppress disease development. However, recent field observations in Kansas suggest that the pathogen may be recovering from heat stress more quickly than expected. Previous research indicates that some strains of this pathogen were adapted to warm temperature regimes but did not consider how the pathogen responds to periods of heat stress that are common in the Great Plains region of North America. Therefore, the objectives of this study were to characterize the response of contemporary isolates of P. striiformis f. sp. tritici to periods of heat stress and to look for evidence of temperature adaptations within the pathogen population. These experiments evaluated nine isolates of the pathogen: eight isolates collected in Kansas between 2010 and 2021 and a historical reference isolate. Treatments compared the latent period and colonization rate of isolates given a cool temperature regime (12 to 20°C) and as they recovered from 7 days of heat stress (22 to 35°C). Results documented that contemporary isolates of the pathogen had similar latent periods and colonization rates as the historical reference under the cool temperature regime. Following exposure to 7 days of heat stress, the contemporary isolates had shorter latent periods and higher colonization rates than the historical isolate. There was also variability in how the contemporary isolates recovered from heat stress, with some isolates collected during 2019 to 2021 recovering sooner than those collected just 5 to 10 years ago.

The genomic landscape of canine osteosarcoma cell lines reveals conserved structural complexity and pathway alterations.

The characterization of immortalized canine osteosarcoma (OS) cell lines used for research has historically been based on phenotypic features such as cellular morphology and expression of bone specific markers. With the increasing use of these cell lines to investigate novel therapeutic approaches prior to in vivo translation, a much more detailed understanding regarding the genomic landscape of these lines is required to ensure accurate interpretation of findings. Here we report the first whole genome characterization of eight canine OS cell lines, including single nucleotide variants, copy number variants and other structural variants. Many alterations previously characterized in primary canine OS tissue were observed in these cell lines, including TP53 mutations, MYC copy number gains, loss of CDKN2A, PTEN, DLG2, MAGI2, and RB1 and structural variants involving SETD2, DLG2 and DMD. These data provide a new framework for understanding how best to incorporate in vitro findings generated using these cell lines into the design of future clinical studies involving dogs with spontaneous OS.

Characterizing the metabolic role of STAT3 in canine osteosarcoma.

Signal transducer and activator of transcription 3 (STAT3) dysregulation has been characterized in canine OS, with previous data suggesting that constitutive STAT3 activation contributes to survival and proliferation in OS cell lines in vitro. Recently, the contribution of STAT3 to tumour metabolism has been described across several tumour histologies, and understanding the metabolic implications of STAT3 loss may elucidate novel therapeutic approaches with synergistic activity. The objective of this work was to characterize metabolic benchmarks associated with STAT3 loss in canine OS. STAT3 expression and activation was evaluated using western blotting in canine OS cell lines OSCA8 and Abrams. STAT3 was deleted from these OS cell lines using CRISPR-Cas9, and the effects on proliferation, invasion and metabolism (respirometry, intracellular lactate) were determined. Loss of STAT3 was associated with decreased basal and compensatory glycolysis in canine OS cell lines, without modulation of cellular proliferation. Loss of STAT3 also resulted in diminished invasive capacity in vitro. Interestingly, the absence of STAT3 did not impact sensitivity to doxorubicin in vitro. Our data demonstrate that loss of STAT3 modulates features of aerobic glycolysis in canine OS impacting capacities for cellular invasions, suggesting a role for this transcription factor in metastasis.

Changes in attitudes and behaviors supportive of maternal and newborn health in Ethiopia: an evaluative case study.

BACKGROUND: Ethiopia's high neonatal mortality rate led to the government's 2013 introduction of Community-Based Newborn Care (CBNC) to bring critical prevention and treatment interventions closer to communities in need. However, complex behaviors that are deeply embedded in social and cultural norms continue to prevent women and newborns from getting the care they need. A demand creation strategy was designed to create an enabling environment to support appropriate maternal, newborn, and child health (MNCH) behaviors and CBNC. We explored the extent to which attitudes and behaviors during the prenatal and perinatal periods varied by the implementation strength of the Demand Creation Strategy for MNCH-CBNC. METHODS: Using an embedded, multiple case study design, we purposively selected four kebeles (villages) from two districts with different levels of implementation strength of demand creation activities. We collected information from a total of 150 key stakeholders across kebeles using multiple qualitative methods including in-depth interviews, focus group discussions, and illness narratives; sessions were transcribed into English and coded using NVivo 10.0. We developed case reports for each kebele and a final cross-case report to compare results from high and low implementation strength kebeles. RESULTS: We found that five MNCH attitudes and behaviors varied by implementation strength. In high implementation strength kebeles women felt more comfortable disclosing their pregnancy early, women sought antenatal care (ANC) in the first trimester, families did not have fatalistic ideas about newborn survival, mothers sought care for sick newborns in a timely manner, and newborns received care at the health facility in less than an hour. We also found changes across all kebeles that did not vary by implementation strength, including male engagement during pregnancy and a preference for giving birth at a health facility. CONCLUSIONS: Findings suggest that a demand creation approach-combining participatory approaches with community empowering strategies-can promote shifts in behaviors and attitudes to support the health of mothers and newborns, including use of MNCH services. Future studies need to consider the most efficient level of intervention intensity to make the greatest impact on MNCH attitudes and behaviors.

Audit and Feedback: An Evidence-Based Practice Literature Review of Nursing Report Cards.

BACKGROUND: As more hospitals transition to electronic health records (EHR) and rely on technology to inform practice, what is done with that information is increasingly important. Performance report cards for physicians and nurses are not new, yet there is little recent evidence on nurse-specific audit and feedback. AIM: The aim of the project was to conduct an evidence-based practice (EBP) review to answer the question, "Does implementing an individualized audit and feedback report tool for nurses improve compliance, adherence, and/or performance of nursing tasks?". METHODS: Evidence was gathered from several databases. Reviewers read and appraised articles that answered the EBP question using the Johns Hopkins Nursing EBP Model. Data were then collated to synthesize and generate recommendations. RESULTS: Of the initial 613 unique articles, eight (two research and six quality improvement) were included. Six articles demonstrated improvements while two did not. Articles analyzed nursing documentation (n = 3), tasks or skills (n = 2), and best practice compliance (n = 3). One manuscript utilized an EHR-generated report; all others were completed by hand. Overall, there was not consistent and compelling evidence to support individualized audit and feedback report tools in nursing. However, several themes emerged related to sustainability, timing of feedback, audit, and feedback in the context of quality improvement, and the methods of acquiring and distributing data. LINKING EVIDENCE TO ACTION: The ubiquity and ease of the EHR make providing automated feedback to nurses tempting, yet it is not supported by the literature. More implementation science research is needed to explore audit and feedback reports in nursing. This article adds to the literature by highlighting a significant lack of consistent and compelling positive results from the well-established quality improvement strategy of audit and feedback in the nursing population. The absence of good data is as telling as its presence.

Structures of five salt forms of disulfonated monoazo dyes.

The structures of five s-block metal salt forms of three disulfonated monoazo dyes are presented. These are poly[di-µ-aqua-diaqua[µ4-3,3'-(diazane-1,2-diyl)bis(benzenesulfonato)]disodium(I)], [Na2(C12H8N2O6S2)(H2O)4]n, (I), catena-poly[[tetraaquacalcium(II)]-µ-3,3'-(diazane-1,2-diyl)bis(benzenesulfonato)], [Ca(C12H8N2O6S2)(H2O)4]n, (II), catena-poly[[[diaquacalcium(II)]-µ-2-(4-amino-3-sulfonatophenyl)-1-(4-sulfonatophenyl)diazenium] dihydrate], {[Na(C12H10N3O6S2)(H2O)2]·2H2O}n, (III), hexaaquamagnesium bis[2-(4-amino-3-sulfonatophenyl)-1-(4-sulfonatophenyl)diazenium] octahydrate, [Mg(H2O)6](C12H10N3O6S2)2·8H2O, (IV), and poly[[{µ2-4-[2-(4-amino-2-methyl-5-methoxyphenyl)diazen-1-yl]benzene-1,3-disulfonato}di-µ-aqua-diaquabarium(II)] dihydrate], {[Ba(C14H13N3O7S2)(H2O)4]·2H2O}n, (V). Compound (III) is that obtained on crystallizing the commercial dyestuff Acid Yellow 9 [74543-21-8]. The Mg species is a solvent-separated ion-pair structure and the others are all coordination polymers with bonds from the metal atoms to sulfonate groups. Compound (I) is a three-dimensional coordination polymer, (V) is a two-dimensional coordination polymer and both (II) and (III) are one-dimensional coordination polymers. The coordination behaviour of the azo ligands and the water ligands, the dimensionality of the coordination polymers and the overall packing motifs of these five structures are contrasted to those of monosulfonate monoazo congers. It is found that (I) and (II) adopt similar structural types to those of monosulfonate species but that the other three structures do not.

A Quality Improvement Initiative to Reduce Surgical Site Infections in Patients Undergoing Delayed Sternal Closure After Pediatric Cardiac Surgery.

Sternal wound infections (SWI) in delayed sternal closure (DSC) patients are a healthcare burden after congenital heart surgery. There are no guidelines specific for pediatric DSC patients to prevent this costly complication. The hypothesis was that the modifications to a bundled approach for DSC patients would decrease the SWI rate. For this prospective cohort study, DSC patients were postoperatively admitted to a pediatric cardiac care unit from February 2017 to January 2018. Using a modified protocol for prevention of SWI, the infection rates pre- and post-modified protocol were compared. The primary outcome measure was SWI. Secondary outcome measures were compliance with modifications. Retrospective review of cases in pre-protocol modification era from January 1, 2014 to December 31, 2016 showed 377 pediatric cardiopulmonary bypass cases and 39 (10.4%) underwent DSC. During the post-protocol modification era, there were 129 cardiopulmonary bypass cases and 17 (13%) DSC cases. The SWI rate in DSC were 7.7% and 0% for pre-intervention and post-intervention, respectively (p = 0.52). The Bayesian confidence interval with Jeffreys prior gives a 95% confidence interval of 1.5% to 18.3% for pre-intervention and 0 to 13.5% for post-intervention. Compliance with the protocol bundle during the post protocol era was 93-100%. Although preliminary results are not statistically significant due to cohort size, the economic burden and increased LOS for each SWI is clinically significant. The early results of reduced infections for DSC patients using a modified bundle approach appear promising. Continued study and a multicenter project would be beneficial.

Quality Improvement in the Emergency Department: A Project to Reduce Door-to-Electrocardiography Times for Patients Presenting With Chest Pain.

INTRODUCTION: The American Heart Association/American College of Cardiology guidelines recommend obtaining electrocardiography for patients who present to the emergency department with chest pain in less than 10 minutes of arrival. Reducing door-to-electrocardiography time is an important step in adhering to the recommended door-to-balloon times (≤ 90 minutes) for patients who present with ST-segment elevation myocardial infarction. METHODS: Based on lean sigma principles, a protocol was implemented in an adult emergency department that included deferring nurse triage for patients with complaints of chest pain, chest tightness, and chest pressure and providing them with a red heart symbol as an indicator for clinical technicians to prioritize their electrocardiography order. Pre- and postintervention data were collected over a 12-month period. RESULTS: Before the intervention, the mean door-to-electrocardiography time was 17 minutes for patients with chest pain (n = 893). After the intervention, the mean door-to-electrocardiography time for patients with chest pain significantly decreased to 7 minutes (n = 1,057) (t = 10.47, P ≤ 0.001). Initially, the percentage of compliance with door-to-electrocardiography standard of 10 minutes was 31% and improved to 83% after implementation of the new protocol. DISCUSSION: Implementation of the optimized door-to-electrocardiography protocol decreased the time for obtaining diagnostics and improved compliance with the American Heart Association/American College of Cardiology guidelines, potentially decreasing door-to-balloon times for patients who presented with ST-segment elevation myocardial infarction.

Molecular Biology and Evolution of Cancer: From Discovery to Action.

Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay cancer evolution-and progression-require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform cancer biology in new and meaningful ways. We also highlight current challenges to applying these concepts, and propose ways in which incorporating these concepts could identify new therapeutic modes and vulnerabilities in cancer.

Improving Cancer Drug Discovery by Studying Cancer across the Tree of Life.

Despite a considerable expenditure of time and resources and significant advances in experimental models of disease, cancer research continues to suffer from extremely low success rates in translating preclinical discoveries into clinical practice. The continued failure of cancer drug development, particularly late in the course of human testing, not only impacts patient outcomes, but also drives up the cost for those therapies that do succeed. It is clear that a paradigm shift is necessary if improvements in this process are to occur. One promising direction for increasing translational success is comparative oncology-the study of cancer across species, often involving veterinary patients that develop naturally-occurring cancers. Comparative oncology leverages the power of cross-species analyses to understand the fundamental drivers of cancer protective mechanisms, as well as factors contributing to cancer initiation and progression. Clinical trials in veterinary patients with cancer provide an opportunity to evaluate novel therapeutics in a setting that recapitulates many of the key features of human cancers, including genomic aberrations that underly tumor development, response and resistance to treatment, and the presence of comorbidities that can affect outcomes. With a concerted effort from basic scientists, human physicians and veterinarians, comparative oncology has the potential to enhance the cost-effectiveness and efficiency of pipelines for cancer drug discovery and other cancer treatments.

Optimization of Electronic Medical Records for Data Mining Using a Common Data Model.

The increasing use of electronic health records (EHRs) in veterinary medicine creates an opportunity to utilize the high volume of electronic patient data for mining and data-driven analytics with the goal of improving patient care and outcomes. A central focus of the Clinical and Translational Science Award One Health Alliance (COHA) is to integrate efforts across multiple disciplines to better understand shared diseases in animals and people. The ability to combine veterinary and human medical data provides a unique resource to study the interactions and relationships between animals, humans, and the environment. However, to effectively answer these questions, veterinary EHR data must first be prepared in the same way it is now commonly being done in human medicine to enable data mining and development of analytics to facilitate knowledge formation and solutions that advance our understanding of disease processes, with the ultimate goal of improving outcomes for veterinary patients and their owners. As a first step, COHA member institutions implemented a Common Data Model to standardize EHR data. Herein we present the approach executed within the COHA framework to prepare and optimize veterinary EHRs for data mining and knowledge formation based on the adoption of the Observational Health Data Sciences and Informatics' Observational Medical Outcomes Partnership Common Data Model.

TRANSLATOR Database-A Vision for a Multi-Institutional Research Network.

The formation of the CTSI One Health Alliance (COHA) network has generated the infrastructure necessary to support "Big Data" collaborative comparative and translational research in veterinary medicine. We describe the first step in the design, implementation, and dissemination of a collaborative information technology infrastructure that will serve the public and clinicians (COHA public/member based web site at https://ctsaonehealthalliance.org/) and its research focused COHA Research Workbench application. The core research infrastructure, TRANSLATOR (TRanslational ANimal Shared ColLAboraTive Observational Research), represents the foundation of a federated research-capable network to enable pooling large datasets from both electronic health records and publications. The public facing COHA website is a mechanism for both the dissemination of knowledge to the public and to foster collaborations amongst veterinary clinician scientists and the greater medical research community.

Safety and toxicity of combined oclacitinib and carboplatin or doxorubicin in dogs with solid tumors: a pilot study.

BACKGROUND: Oclacitinib is an orally bioavailable Janus Kinase (JAK) inhibitor approved for the treatment of canine atopic dermatitis. Aberrant JAK/ Signal Transducer and Activator of Transcription (STAT) signaling within hematologic and solid tumors has been implicated as a driver of tumor growth through effects on the local microenvironment, enhancing angiogenesis, immune suppression, among others. A combination of JAK/STAT inhibition with cytotoxic chemotherapy may therefore result in synergistic anti-cancer activity, however there is concern for enhanced toxicities. The purpose of this study was to evaluate the safety profile of oclacitinib given in combination with either carboplatin or doxorubicin in tumor-bearing dogs. RESULT: Oclacitinib was administered at the label dose of 0.4-0.6 mg/kg PO q12h in combination with either carboplatin at 250-300 mg/m2 or doxorubicin at 30 mg/m2 IV q21d. Nine dogs were enrolled in this pilot study (n = 4 carboplatin; n = 5 doxorubicin). No unexpected toxicities occurred, and the incidence of adverse events with combination therapy was not increased beyond that expected in dogs treated with single agent chemotherapy. Serious adverse events included one Grade 4 thrombocytopenia and one Grade 4 neutropenia. No objective responses were noted. CONCLUSIONS: Oclacitinib is well tolerated when given in combination with carboplatin or doxorubicin. Future work is needed to explore whether efficacy is enhanced in this setting.

Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2.

Osteosarcoma (OS) is a rare, metastatic, human adolescent cancer that also occurs in pet dogs. To define the genomic underpinnings of canine OS, we performed multi-platform analysis of OS tumors from 59 dogs, including whole genome sequencing (n = 24) and whole exome sequencing (WES; n = 13) of primary tumors and matched normal tissue, WES (n = 10) of matched primary/metastatic/normal samples and RNA sequencing (n = 54) of primary tumors. We found that canine OS recapitulates features of human OS including low point mutation burden (median 1.98 per Mb) with a trend towards higher burden in metastases, high structural complexity, frequent TP53 (71%), PI3K pathway (37%), and MAPK pathway mutations (17%), and low expression of immune-associated genes. We also identified novel features of canine OS including putatively inactivating somatic SETD2 (42%) and DMD (50%) aberrations. These findings set the stage for understanding OS development in dogs and humans, and establish genomic contexts for future comparative analyses.

Lived experience of young widowed individuals: A qualitative study.

Young widowhood is a unique experience that has received little in-depth attention in research and clinical settings. The present study examined the lived experiences of young men and women who had lost a spouse. Eleven men and women between the ages of 18 and 49 were interviewed about their experiences postloss using phenomenological methods. After coding the interviews, three themes emerged: (1) relationship prior to death, (2) coping, and (3) concerns. Clinical implications included the need for more accessible resources for young widowed individuals, such as therapeutic services, finances, and childcare.