Doxorubicin, an anthracycline antibiotic, is a commonly used anticancer drug. In spite of its widespread usage, its therapeutic effect is limited by its cardiotoxicity. On the cellular level, Doxorubicin-induced cardiotoxicity manifests as stress induced premature senescence. Previously, we demonstrated that plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of serine proteases, is an important biomarker and regulator of cellular senescence and aging. Here, we tested the hypothesis that pharmacological inhibition of cellular PAI-1 protects against stress- and aging-induced cellular senescence and delineated the molecular basis of protective action of PAI-1 inhibition. Results show that TM5441, a potent small molecule inhibitor of PAI-1, effectively prevents Doxorubicin-induced senescence in cardiomyocytes, fibroblasts and endothelial cells. TM5441 exerts its inhibitory effect on Doxorubicin-induced cellular senescence by decreasing reactive oxygen species generation, induction of antioxidants like catalase and suppression of stress-induced senescence cadre p53, p21, p16, PAI-1 and IGFBP3. Importantly, TM5441 also reduces replicative senescence of fibroblasts. Together these results for the first time demonstrate the efficacy of PAI-1 inhibitor in prevention of Doxorubicin-induced and replicative senescence in normal cells. Thus PAI-1 inhibitor may form an important adjuvant component of chemotherapy regimens, limiting not only Doxorubicin-induced cardiac senescence but also ameliorating the prothrombotic profile.

Radiation therapy (RT) is a common adjunct therapy in oncology. However, it carries a significant risk of lymphedema when utilized in some anatomic locations. Recent studies have provided insight into lymphedema pathophysiology, diagnostic techniques, and RT. This review will examine the role of RT in upper and lower extremity lymphedema. Radiation's role in increasing the risk of lymphedema through decreased lymphatic proliferation potential, interstitial fibrosis compressing lymphatic vessels, and mechanical insufficiency of the lymphatic system will be reviewed.

No abstract

With the increase in the elderly population in the United States, the number of people seeking care for trauma injuries is expected to increase. However, nationwide studies on epidemiological profile of elderly facial fractures remain sparse. The authors present the epidemiological measures of elderly facial fractures on national scale. Characteristics of facial fractures among younger adults (18-64 years old) and the elderly population (65-74 years old, 75-84 years old and 85 years and above) have been examined using the 2016 American College of Surgeons-Trauma Quality Improvement Program databank. Variables studied included facial fracture patterns, mechanisms of injury, treatment variables, and demographic descriptive data. Of 104,183 elderly trauma patients, 3415 presented with facial fractures, making up 3.3% (versus 6.5% in younger adults). Majority of facial fractures in 85 and over group (60.7%) were experienced by females, compared to only 19.5% in the younger adult group. Most common mechanism of injury in the elderly was falls, versus motor vehicle trauma in younger adults. The most common type of facial fractures among both groups were nasal fractures. Elderly patients presented with fewer zygoma, mandibular and nasal fractures when compared to younger adults, whereas showing more maxillary/ malar and orbital bone fractures. Elderly patients experienced less operative management (4.3%-8.2%) compared to younger adults (15.6%). Concurrently, mortality rates were higher in the elderly patients (9.9%-11.8%) when compared to the younger adults (8.0%). Elderly patients presented with different causes of injury, distribution of fractures, and rates of operative management compared to younger adults.

Background: Trauma involving the facial bones has been shown to be associated with high severity in previous studies. Characteristics of facial fractures in adults have been well described in the adult population, less so in the pediatric literature. Our investigation aims to define these epidemiological measures and risk factors for poor outcomes using the most recent data. Methods: The 2016 Trauma Quality Improvement Program data bank was examined to study facial fracture pattern, mechanism of injury, and demographic descriptive data to characterize pediatric trauma patients. Multivariable regression analysis was performed to assess risk factors for morbidity and mortality in pediatric facial fracture patients. Results: Of 51,168 total pediatric trauma patients, 2917 (5.7%) presented with facial fractures. Motor vehicle trauma was the most common mechanism of injury. Maxillary/malar fractures was the most common fracture type overall. Mandibular fractures were most common in the 0 to 1 age category while nasal bone fractures were more common in older patients. Patients with mandible fractures experienced the highest rate of operative management. Zygoma fracture was highly associated with concomitant traumatic brain injury. Multivariable regression analysis showed that fracture of the zygoma, concomitant traumatic brain injury, and cervical spine injury were risk factors for increased mortality. Conclusion: Facial fractures are a rare but significant form of trauma in the pediatric population. Our data suggests a slight change in fracture patterns compared to previous studies. Zygoma fractures, traumatic brain injury, and cervical spine injury are risk factors of increased mortality that clinicians should be aware of.

Psychiatric well‐being impacts on general satisfaction and quality of life. This study explored how the presence of psychiatric diagnoses affects patient‐reported outcomes in breast reconstruction and on selection of reconstructive modality. Patients who received breast reconstruction at a tertiary hospital between 2013 and 2018 and completed the BREAST‐Q survey were included. BREAST‐Q module scores were compared between patients who had a psychiatric diagnosis at presentation and the remaining cohort using t tests. General linear models (GLMs) were used to control for confounding factors. A chi‐squared test was used to assess the effect on reconstructive modality, and binary logistic regression was used to control for confounding factors. Of the 471 patients included, 93 (19.7%) had at least one psychiatric diagnosis. Cohorts did not differ significantly by age, BMI, race, ASA classification, or insurance status. Patients with a psychiatric diagnosis experienced a decrease in BREAST‐Q scores for the Psychosocial Wellbeing (B = 9.16, P = .001) and Sexual Wellbeing (B = 9.29, P = .025) modules. On binary logistic regression, patients with a psychiatric diagnosis were less likely to receive autologous reconstruction compared with implant reconstruction (OR = 0.489, P = .010). The presence of psychiatric diagnoses is an independent predictor of decreased BREAST‐Q. Furthermore, there is a significant disparity in modality of reconstruction given to patients with psychiatric diagnoses. Further study is needed to evaluate interventions to improve satisfaction among at‐risk populations and evaluate the reason for low autologous reconstruction in this population.

Lymphedema may be characterized by a progressive clinical course and limitations in improvement despite multi-modality treatment. In westernized countries, it most commonly presents as an undesirable complication of cancer treatment, particularly breast cancer. In the past several decades, surgical treatments for lymphedema have advanced, alongside developments in microsurgery. Lymphovenous anastomosis (LVA) and lymph node transplantation are physiological therapies that may reduce lymphedema through addressing its route cause. Ablative techniques such as liposuction and subcutaneous excision aid in resolving the accumulation of proteinaceous adipose and fibrotic tissue seen in advanced lymphedema.The goal of this review is to examine the outcomes and limitations of current surgical techniques used in lymphedema management.

No abstract