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Cardiac fibrosis is a central determinant of heart failure progression and arises from pathological remodeling characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix deposition. In contrast, physiological remodeling permits adaptive cardiac growth without net fibrosis. Pregnancy represents an underexplored physiological model of reversible cardiac remodeling. In response to hemodynamic load, the maternal heart undergoes hypertrophic growth that resolves postpartum, constituting a natural paradigm of fibrosis-resistant cardiac adaptation. Pregnancy and lactation are accompanied by profound endocrine and immune reprogramming of maternal tissues. We propose that this hormonal milieu orchestrates coordinated crosstalk among endothelial cells, fibroblasts, and immune cell populations to suppress profibrotic pathways and preserve extracellular matrix homeostasis. Candidate regulators include estrogen, progesterone, prolactin family peptides, relaxin, oxytocin, and components of the renin–angiotensin–aldosterone system. During the postpartum and lactational period, prolactin and oxytocin may further promote reverse remodeling. These hormones likely act by modulating local cytokine and growth factor networks that otherwise drive fibroblast activation. By focusing on non-myocyte cardiac cells and extracellular matrix dynamics, this review positions pregnancy as a translational model to uncover endogenous anti-fibrotic mechanisms and identify novel therapeutic strategies for cardiac fibrosis.

Purpose Body image distress (BID) among head and neck cancer (HNC) survivors is a debilitating toxicity associated with depression, anxiety, stigma, and poor quality of life. BRIGHT ( B uilding a R enewed I ma G e after H ead & neck cancer T reatment) is a brief cognitive behavioral therapy (CBT) that reduces BID for these patients. This study examines the mechanism underlying BRIGHT. Methods In this randomized clinical trial, HNC survivors with clinically significant BID were randomized to receive five weekly psychologist-led video tele-CBT sessions (BRIGHT) or dose-and delivery matched survivorship education (attention control [AC]). Body image coping strategies, the hypothesized mediators, were assessed using the Body Image Coping Skills Inventory (BICSI). HNC-related BID was measured with the Inventory to Measure and Assess imaGe disturbancE–Head and Neck (IMAGE-HN). Causal mediation analyses were used to estimate the mediated effects of changes in BICSI scores on changes in IMAGE-HN scores. Results Among 44 HNC survivors with BID allocated to BRIGHT ( n = 20) or AC ( n = 24), mediation analyses showed that BRIGHT decreased avoidant body image coping (mean change in BICSI-Avoidance scale score) from baseline to 1-month post-intervention relative to AC ( p = 0.039). Decreases in BICSI-Avoidance scores from baseline to 1-month resulted in decreases in IMAGE-HN scores from baseline to 3 months ( p = 0.009). The effect of BRIGHT on IMAGE-HN scores at 3 months was partially mediated by a decrease in BICSI-Avoidance scores ( p = 0.039). Conclusions This randomized trial provides preliminary evidence that BRIGHT reduces BID among HNC survivors by decreasing avoidant body image coping. Further research is necessary to confirm these results and enhance the development of interventions targeting relevant pathways to reduce BID among HNC survivors. Trial registration ClinicalTrials.gov identifier NCT03831100 .

Purpose Body image distress (BID) among head and neck cancer (HNC) survivors leads to depression, social isolation, stigma, and poor quality of life. BRIGHT ( B uilding a R enewed I ma G e after H ead and neck cancer T reatment) is a brief, tailored cognitive behavioral therapy (CBT) that reduces HNC-related BID. This trial examines the effect of BRIGHT on psychosocial outcomes among HNC survivors with BID. Methods In this pilot randomized trial, HNC survivors with clinically significant BID were randomized to 5 weekly psychologist-led tele-CBT sessions (BRIGHT) or dose and delivery-matched survivorship education (attention control [AC]). Secondary psychosocial outcomes were assessed using validated patient-reported outcomes at baseline and 1 and 3-month post-intervention. Results Among 44 HNC survivors with BID, BRIGHT resulted in a greater reduction in depression relative to AC (mean model-based 1-month difference in Δ PROMIS SF v1.0-Depression 8a score, −3.4; 90% CI, −6.4 to −0.4; 3-month difference, −4.3; 90% CI, −7.8 to −0.8). BRIGHT also decreased shame and stigma relative to AC (mean model-based 3-month difference in Δ Shame and Stigma Scale score, −9.7; 90% CI, −15.2 to −4.2) and social isolation (mean model-based 3-month difference in Δ PROMIS SF v2.0 Social Isolation 8a score, −2.9; 90% CI, −5.8 to −0.1). Conclusions In this planned secondary analysis of a pilot RCT, BRIGHT improved a broad array of psychosocial outcomes among HNC survivors with BID. Trial registration ClinicalTrials.gov identifier: NCT03831100 . Implications for Cancer Survivors These promising preliminary data suggest the need for a large efficacy trial evaluating the effect of BRIGHT on psychosocial outcomes among HNC survivors with BID.

Mutations in the HFE gene are associated with hemochromatosis. In this large study of an ethnically and racially diverse population, homozygosity for C282Y mutations in the HFE gene was more common in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Most C282Y homozygotes had elevated serum ferritin levels and transferrin saturation. In this large study of an ethnically and racially diverse population, homozygosity for C282Y mutations in the HFE gene was more common in non-Hispanic whites (0.44 percent) than in Native Americans, Hispanics, blacks, Pacific Islanders, or Asians. Iron overload can be associated with a wide range of genetic and environmental factors and can lead to parenchymal damage of organs. Homozygosity for the C282Y mutation of the HFE gene is associated with susceptibility to iron overload and is a common genetic mutation, occurring in 0.3 to 0.5 percent of white persons of northern European descent. 1 , 2 Phlebotomy treatment can prevent some of the major complications of iron overload, and patients have normal life expectancy if they are treated before organ damage occurs. 3 Iron overload can occur in nonwhites and may be related to as-yet-undiscovered genetic mutations, environmental factors, . . .