Serpentine supravenous hyperpigmentation induced by chemotherapy: a systematic review.

Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions.

A Systematic Review of Neurodevelopmental Assessments in Infancy and Early Childhood: Developing a Conceptual Framework, Repository of Measures, and Clinical Recommendations.

The first 6 years of life are when 90% of brain development occurs, setting the foundation for lifelong neurodevelopment. The field of infant and early childhood neurodevelopment has made marginal advancements since introduced in 1988. There remains a gap in knowledge around early neurodevelopmental domains and trajectories given that there are few established assessment procedures for infants and young children and controversies around reserving assessments until school age. Throughout this systematic review, we (1) identified neurodevelopmental assessment measures employed in the literature by domain and age of assessment, (2) compiled a repository of 608 domain-specific neurodevelopmental assessment measures, and (3) established a preliminary conceptual framework for cross-domain neurodevelopmental assessments across infancy and early childhood. This review adhered to PRISMA guidelines and spanned three databases (PsycINFO, MEDLINE, PubMed). Articles were reviewed for (1) infancy and early childhood (0-6 years), (2) neurodevelopmental measures, and (3) English language. This systematic review spanned 795 articles from 1978 to 2020 with international representation. Advancements in assessment methods (e.g. measures, domains, frameworks) are essential for the evaluation of early neurodevelopmental profiles to inform early interventions, thus harnessing the neuroplasticity and dynamic development notable during early childhood. We hope this work catalyzes future research and clinical guidelines around early assessments methods.

Feasibility of Using an Artificial Intelligence-based Telephone Application for Dietary Assessment and Nudging to Improve the Quality of Food Choices of Female Adolescents in Vietnam: Evidence from a Randomized Pilot Study.

Background: Adolescent nutrition has faced a policy neglect, partly owing to the gaps in dietary intake data for this age group. The Food Recognition Assistance and Nudging Insights (FRANI) is a smartphone application validated for dietary assessment and to influence users toward healthy food choices. Objectives: This study aimed to assess the feasibility (adherence, acceptability, and usability) of FRANI and its effects on food choices and diet quality in female adolescents in Vietnam. Methods: Adolescents (N = 36) were randomly selected from a public school and allocated into 2 groups. The control group received smartphones with a version of FRANI limited to dietary assessment, whereas the intervention received smartphones with gamified FRANI. After the first 4 wk, both groups used gamified FRANI for further 2 wk. The primary outcome was the feasibility of using FRANI as measured by adherence (the proportion of completed food records), acceptability and usability (the proportion of participants who considered FRANI acceptable and usable according to answers of a Likert questionnaire). Secondary outcomes included the percentage of meals recorded, the Minimum Dietary Diversity for Women (MDDW) and the Eat-Lancet Diet Score (ELDS). Dietary diversity is important for dietary quality, and sustainable healthy diets are important to reduce carbon emissions. Poisson regression models were used to estimate the effect of gamified FRANI on the MDDW and ELDS. Results: Adherence to the application was 82% and the percentage of meals recorded was 97%. Acceptability and usability were 97%. MDDW in the intervention group was 1.07 points (95% CI: 0.98, 1.18; P = 0.13) greater than that in the control (constant = 4.68); however, the difference was not statistically significant. Moreover, ELDS in the intervention was 1.09 (95% CI: 1.01, 1.18; P = 0.03) points greater than in the control (constant = 3.67). Conclusions: FRANI was feasible and may be effective to influence users toward healthy food choices. Research is needed for FRANI in different contexts and at scale.The trial was registered at the International Standard Randomized Controlled Trial Number as ISRCTN 10681553.

Beyond Infantile Hemangiomas: A Glimpse into Overlapping Rare Syndromes Emphasizing the Vigilant Screening for PHACE and LUMBAR Syndromes.

Infantile hemangiomas are the most common birthmark in newborns. They are clinically diagnosed and usually self-limited. However, there are several exceptions with aggressive types of hemangiomas that can be associated with extracutaneous anomalies, such as PHACE syndrome (posterior fossa anomalies, upper body hemangiomas, arterial anomalies, cardiac anomalies, and eye anomalies) and LUMBAR syndrome (lower body hemangiomas, ulcerations/urogenital anomalies, myelopathies, bony deformities, anorectal malformations/arterial anomalies, and renal anomalies). These two syndromes, described in the literature with distinct features, have rarely been reported in the same patient. We discuss one of the few cases reported with overlapping features of the PHACE and LUMBAR syndromes that initially presented with infantile hemangiomas, as well as other nonspecific skin and systemic findings. Minimal guidance has been described due to the need for more scientific literature. Our aim is to reinforce awareness of these two syndromes and the possibility of an overlap presentation between them. Furthermore, we emphasize the need for an interdisciplinary approach with screening for all known associations to avoid missing essential components of these syndromes that can lead to significant morbidity and lifetime complications.

PCNL vs. two staged RIRS for kidney stones greater than 20 mm: systematic review, meta-analysis, and trial sequential analysis.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is considered the gold standard treatment for kidney stones greater than 20 mm. However, retrograde intrarenal surgery (RIRS) may achieve the same stone-free rate with repeated procedures, and potentially fewer complications. This study aimed to compare the efficacy and safety of PCNL and two-staged RIRS. EVIDENCE ACQUISITION: We conducted a systematic search in PubMed, Embase, Scopus, Cochrane, and Web of Science for studies comparing PCNL and RIRS for kidney stones greater than 20mm. The primary outcome is stone-free rate (SFR) of PCNL and RIRS (repeated once if needed). Secondary outcomes were SFR of PCNL versus RIRS (single procedure), operative time, hospital stay, need for auxiliary procedures, and complications. We performed a subgroup analysis for randomized trials, non-randomized trials, and patients with solitary kidney. We performed a trial sequential analysis for the main outcome. EVIDENCE SYNTHESIS: We included 31 articles, with 1987 patients in the PCNL and 1724 patients in RIRS. We confirmed the traditional result that after a single procedure PCNL has a higher SFR. We also found that comparing the SFR of PCNL and RIRS, repeated up to two times if needed, no difference in SFR was observed. Surprisingly, only 26% (CI95 23%-28%) of the patients required a second RIRS. In the trial sequential analysis, the last point of the z-curve was within futility borders. We observed that PCNL has a higher incidence of complications (RR=1.51; CI95 1.24, 1.83; P<0.0001; I2=28%), specifically CD2 (RR=1.82; CI95 1.30, 2.54; P=0.0004; I2=26%) and longer hospital stay (MD 2.57; 2.18, 2.96; P<0.00001; I2-98%). No difference was observed regarding operative time. CONCLUSIONS: RIRS repeated up to two times is equivalent to PCNL in terms of the SFR and may have the same safety.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Call to Action.

This Call to Action is the eighth and final article in this special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, or FCEI-DHH. Collectively, these articles highlight evidence-informed actions to enhance family well-being and to optimize developmental outcomes among children who are DHH. This Call to Action outlines actionable steps to advance FCEI-DHH supports provided to children who are DHH and their families. It also urges specific actions to strengthen FCEI-DHH programs/services and systems across the globe, whether newly emerging or long-established. Internationally, supports for children who are DHH are often siloed, provided within various independent sectors such as health/medicine, education, early childhood, and social and disability services. With this Call to Action, we urge invested parties from across relevant sectors to join together to implement and improve FCEI-DHH programs/services and systems, build the capacity of early intervention (EI) Providers and other professionals, extend research regarding FCEI-DHH, and fund EI supports, systems, and research, all with the aim of advancing outcomes for families and their children who are DHH.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Methods.

This is the fourth article in a series of eight that comprise a special issue on family-centered early intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, FCEI-DHH. This article describes the co-production team and the consensus review method used to direct the creation of the 10 Principles described in this special issue. Co-production is increasingly being used to produce evidence that is useful, usable, and used. A draft set of 10 Principles for FCEI-DHH and associated Tables of recommended behaviors were developed using the knowledge creation process. Principles were refined through two rounds of eDelphi review. Results for each round were analyzed using measures of overall group agreement and measures that indicated the extent to which the group members agreed with each other. After Round 2, with strong agreement and low to moderate variation in extent of agreement, consensus was obtained for the 10 Principles for FCEI-DHH presented in this special issue. This work can be used to enhance evolution of FCEI-DHH program/services and systems world-wide and adds to knowledge in improvement science.

EHMT2/G9a and EZH2: Epimarkers in testicular germ cell tumors.

BACKGROUND: Testicular germ cell tumors remain the most frequent solid malignancies in young males. Despite excellent prognosis, the fact that only 60% of patients at diagnosis have elevated serum tumor markers (dependent on stage and histology) and the poor quality of life of patients who develop resistance to chemotherapy cannot be neglected. Consequently, it is mandatory to bring out novel biomarkers. OBJECTIVES: The main goal was to evaluate EZH2 and EHMT2/G9a immunoexpression in a well-characterized patients' cohort of primary and metastatic testicular germ cell tumors, seeking associations with clinicopathological features and discovering differential immunoexpression patterns among specific subtypes. MATERIALS AND METHODS: First, an in silico analysis of the Cancer Genome Atlas database was performed regarding EZH2 and EHMT2/G9a. Then, immunohistochemistry for EZH2 and EHMT2/G9a was carried out in a cohort of testicular germ cell tumor patients, comprising 155 chemo-naïve primary tumors and 11 chemo-treated metastases. Immunoexpression was evaluated using a digital pathology analysis software. RESULTS: Higher EZH2 and EHMT2/G9a expression levels were found in non-seminoma in the in silico analysis, particularly in embryonal carcinoma. Through digital pathology analysis, non-seminomas showed significantly higher EZH2 and EHMT2/G9a immunoexpression, with embryonal carcinoma showing higher expression. Moreover, mixed tumors with 50% or more of embryonal carcinoma component revealed the highest nuclei positivity for both biomarkers. Cisplatin-exposed metastases demonstrated a higher EZH2-positive nuclei and H-score, as well as higher EHMT2/G9a-positive nuclei. DISCUSSION AND CONCLUSION: Overall, our data suggest that EZH2 and EHMT2/G9a might be associated with greater aggressiveness and, eventually, involved in the metastatic setting, paving the way for testing targeted therapies.

Pulmonary Vein Isolation in Elderly Patients ≥ 75 Years: A Propensity Score-Matched Analysis With Focus on Differences Among Atrial Fibrillation Types.

BACKGROUND: Age is a major risk factor for development of atrial fibrillation (AF) and associated with increased recurrence rates in the setting of rhythm control. Current data tend to support catheter ablation in elderly patients, but uncertainties exist regarding efficacy and safety of ablation in elderly patients. METHODS: This was a prospective single-centre observational study with propensity score matching (PSM) to investigate the influence of age on efficacy and safety of cryoballoon ablation (CBA) stratified by age (< 75 years vs ≥ 75 years) and AF phenotype (paroxysmal vs persistent). Primary efficacy endpoint was recurrence of atrial arrhythmia after a 90-day blanking period. Safety endpoints were death, stroke, or procedure-associated complications. RESULTS: Consecutive patients (n = 953) underwent CBA for first-time AF ablation. Median follow-up was 18 months. By means of PSM, 268 matches were formed. At 1 year, primary efficacy endpoint occurred in 22.4% of young vs 33.2% of elderly patients, including both AF phenotypes (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47-0.90; P = 0.01). AF relapse occurred in 19.7% of young vs 28.5% of elderly patients with paroxysmal (HR, 0.63; 95% CI, 0.40-0.99; P = 0.046) compared with 25.9% (30 of 116, young) vs 38.8% (45 of 116, elderly) patients with persistent AF (HR, 0.62; 95% CI, 0.39-0.97; P = 0.038). No difference was observed regarding the incidence of safety endpoints between young and elderly patients (P = 0.38). CONCLUSIONS: CBA is associated with higher recurrence rates in elderly (≥ 75 years) than in younger patients, with highest recurrence rates in elderly patients with persistent AF.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Introduction.

This article is the first of eight articles in this special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH), or FCEI-DHH. In 2013, a diverse panel of experts published an international consensus statement on evidence-based Principles guiding FCEI-DHH. Those original Principles have been revised through a coproduction process involving multidisciplinary collaborators and an international consensus panel, utilizing the best available evidence and current understanding of how to optimally support children who are DHH and their families. This revision (referred to as expanded Principles) was motivated by the need to incorporate (a) input from family leaders and DHH leaders, (b) broader international and cultural perspectives, (c) new empirical evidence, and (d) research in human development. This Introduction provides an overview of the rationale, purposes, and main content areas to be addressed throughout the special issue.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Foundation Principles.

This article is the fifth in a series of eight articles that comprise a special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, or FCEI-DHH. The 10 FCEI-DHH Principles are organized conceptually into three sections (a) Foundation Principles, (b) Support Principles, and (c) Structure Principles. Collectively, they describe the essential Principles that guide FCEI for children who are DHH and their families. This article describes the Foundation Principles (Principles 1 and Principle 2). The Foundation Principles emphasize the essential elements of ensuring that families with children who are DHH can access early intervention (EI) and other appropriate supports, as well as highlight the need for provision of EI that is family-centered. Implementation of these FCEI-DHH Principles is intended to improve the lives and the outcomes of children who are DHH and their families around the globe.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Cultural & Global Implications.

This article is the third in a series of eight articles that comprise this special issue on family-centered early intervention for children who are deaf or hard of hearing and their families (FCEI-DHH). It highlights the origins of FCEI-DHH in Western contexts and well-resourced locations and emphasizes the role of culture(s) in shaping FCEI-DHH. This article also cautions against the direct application of the 10 FCEI-DHH Principles presented in this issue across the globe without consideration of cultural implications. Cultural perceptions of decision-making processes and persons who can be decision-makers in FCEI-DHH are explored. Deaf culture(s) and the benefits of exposure to DHH adults with diverse backgrounds are introduced. Structural inequities that impact families' access to FCEI-DHH programs/services and systems, within and among nations and regions, are noted. The need to consider the cultural influences on families is emphasized; this applies to all levels of FCEI, including the development of systems through implementation of supports.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Support Principles.

This article is the sixth in a series of eight articles that comprise a special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, or FCEI-DHH. The Support Principles article is the second of three articles that describe the 10 Principles of FCEI-DHH, preceded by the Foundation Principles, and followed by the Structure Principles, all in this special issue. The Support Principles are composed of four Principles (Principles 3, 4, 5, and 6) that highlight (a) the importance of a variety of supports for families raising children who are DHH; (b) the need to attend to and ensure the well-being of all children who are DHH; (c) the necessity of building the language and communication abilities of children who are DHH and their family members; and (d) the importance of considering the family's strengths, needs, and values in decision-making.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Guiding Values.

This article is the second of eight articles in this special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, or FCEI-DHH. Five foundational values that guide FCEI-DHH are described, providing an evidence-informed, conceptual context for the 10 FCEI-DHH Principles and other articles presented in this issue. These values are applicable for Early Intervention (EI) Providers and other professionals on FCEI teams, as well as for FCEI-DHH programs/services and systems. The five key values include (1) being family-centered, (2) responding to diversity, (3) involving invested parties, especially families and individuals who are DHH, (4) supporting holistic child development, and (5) ensuring fundamental human rights. These evidence-informed values are considered essential to the effective provision of FCEI-DHH supports.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Structure Principles.

This article is the seventh in a series of eight articles that comprise a special issue on family-centered early intervention for children who are deaf or hard of hearing and their families, or FCEI-DHH. This article, Structure Principles, is the third of three articles (preceded by Foundation Principles and Support Principles) that describe the 10 FCEI-DHH Principles. The Structure Principles include 4 Principles (Principle 7, Principle 8, Principle 9, and Principle 10) that highlight (a) the importance of trained and effective Early Intervention (EI) Providers, (b) the need for FCEI-DHH teams to work collaboratively to support families, (c) the considerations for tracking children's progress through developmental assessment, and (d) the essential role of progress monitoring to continuously improve systems.

Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

Expanding Behavioral and Occupational Health Research in Military Police.

INTRODUCTION: It is important to understand the behavioral and occupational health needs of military police personnel, a high-risk and understudied population. MATERIALS AND METHODS: The incidence rates of behavioral and occupational conditions were examined from the years of 2005 to 2021 from the Defense Medical Epidemiology Database. Single-sample chi-square analyses were performed to analyze the differences in the incidence rates across demographic groups relative to population density. RESULTS: There were moderate-to-large increases in sleep-related disorders and mood or stress-related disorders. There were also patterns of overrepresentation or underrepresentation in diagnoses of various conditions by sex, age group, marital status, race, service branch, and pay grade. CONCLUSIONS: It is important to provide tailored resources and programming to employees in high-stress settings to help prevent or manage behavioral and occupational health conditions and reduce the stigma surrounding the utilization of such resources and programs.

Intestinal damage is required for the pro-inflammatory differentiation of commensal CBir1-specific T cells.

Commensal-specific clusters of differentiation (CD)4+ T cells are expanded in patients with inflammatory bowel disease (IBD) compared to healthy individuals. How and where commensal-specific CD4+ T cells get activated is yet to be fully understood. We used CBir1 TCR-transgenic CD4+ T cells, specific to a commensal bacterial antigen, and different mouse models of IBD to characterize the dynamics of commensal-specific CD4+ T-cells activation. We found that CBir1 T cells proliferate following intestinal damage and cognate antigen presentation is mediated by CD11c+ cells in the colon-draining mesenteric lymph nodes. Using assay for transposase-accessible chromatin sequencing and flow cytometry, we showed that activated CBir1 T cells preferentially acquire an effector rather than regulatory phenotype, which is plastic over time. Moreover, CBir1 T cells, while insufficient to initiate intestinal inflammation, contributed to worse disease outcomes in the presence of other CD4+ T cells. Our results suggest that the commensal-specific T-cell responses observed in IBD exacerbate rather than initiate disease.

Feasibility of laparoscopic stapled partial cystectomy in canine cadavers.

OBJECTIVE: To describe a technique for laparoscopic partial cystectomy and evaluate sealing of canine urinary bladder tissue with an endoscopic stapler. STUDY DESIGN: Prospective, cadaveric study. SAMPLE POPULATION: Eleven canine cadavers. METHODS: Laparoscopic partial cystectomy was performed with an endoscopic gastrointestinal anastomosis (GIA) stapler. Leak testing and urodynamic evaluation was performed to measure intravesical pressure at initial leakage and catastrophic failure or the maximum pressure at which intravesical pressure plateaued. Surgical time, complications, and site of leakage were also recorded. RESULTS: Laparoscopic partial cystectomy was successfully performed in 10 of 11 cadavers. Median procedure time was 13.6 min (10.1-15.2 min). Median intravesical pressure at initial leakage was 31 mmHg (28-56 mmHg) with a median increase from initial pressure of 15 mmHg (11-37 mmHg). No catastrophic failure of the cystectomy site was observed during leak testing. Intravesical pressure plateaued at a median of 52 mmHg (39-73 mmHg), which was a median of 13 mmHg (8-23 mmHg) higher than intravesical pressure at initial leakage. The median total volume infused at the time of plateau of intravesical pressure was 89 mL (58-133 mL). CONCLUSION: Laparoscopic stapled partial cystectomy was feasible in canine cadavers. Endoscopic GIA staplers appear to seal the canine urinary bladder with minimal leakage. CLINICAL SIGNIFICANCE: Use of an endoscopic GIA stapler may provide a minimally invasive option for partial cystectomy in dogs. Further evaluation for application to clinical cases is warranted.

A gene therapy targeting medium-chain acyl-CoA dehydrogenase (MCAD) did not protect against diabetes-induced cardiac pathology.

Diabetic cardiomyopathy describes heart disease in patients with diabetes who have no other cardiac conditions but have a higher risk of developing heart failure. Specific therapies to treat the diabetic heart are limited. A key mechanism involved in the progression of diabetic cardiomyopathy is dysregulation of cardiac energy metabolism. The aim of this study was to determine if increasing the expression of medium-chain acyl-coenzyme A dehydrogenase (MCAD; encoded by Acadm), a key regulator of fatty acid oxidation, could improve the function of the diabetic heart. Male mice were administered streptozotocin to induce diabetes, which led to diastolic dysfunction 8 weeks post-injection. Mice then received cardiac-selective adeno-associated viral vectors encoding MCAD (rAAV6:MCAD) or control AAV and were followed for 8 weeks. In the non-diabetic heart, rAAV6:MCAD increased MCAD expression (mRNA and protein) and increased Acadl and Acadvl, but an increase in MCAD enzyme activity was not detectable. rAAV6:MCAD delivery in the diabetic heart increased MCAD mRNA expression but did not significantly increase protein, activity, or improve diabetes-induced cardiac pathology or molecular metabolic and lipid markers. The uptake of AAV viral vectors was reduced in the diabetic versus non-diabetic heart, which may have implications for the translation of AAV therapies into the clinic. KEY MESSAGES: The effects of increasing MCAD in the diabetic heart are unknown. Delivery of rAAV6:MCAD increased MCAD mRNA and protein, but not enzyme activity, in the non-diabetic heart. Independent of MCAD enzyme activity, rAAV6:MCAD increased Acadl and Acadvl in the non-diabetic heart. Increasing MCAD cardiac gene expression alone was not sufficient to protect against diabetes-induced cardiac pathology. AAV transduction efficiency was reduced in the diabetic heart, which has clinical implications.