ABSTRACT
Sulforaphane (SFN) is a bioactive phytonutrient found in cruciferous vegetables. There is a lack of detailed information on the lactational transfer of SFN and SFN metabolites, and potential pharmacological effects on breastfeeding infants. We carried out two maternal supplementation studies in a mouse model, wherein lactating dams received either vehicle, 300 or 600 ppm SFN from postnatal day (PND) 1 to 5, or in a second experiment, vehicle or 600 ppm SFN from PND 1 to 14. The parent compound was only detectable in milk and plasma from dams receiving 600 ppm SFN for five days. The predominant metabolite SFN-N-acetylcysteine (SFN-NAC) was readily detected in milk from dams receiving 300 and 600 ppm SFN for five days or 600 ppm for 14 days. Maternal SFN-NAC plasma levels were elevated in both 600 ppm groups. Maternal hepatic and pulmonary expression of NRF2-related genes, Nqo1, Gsta2, Gstm1, and Gstp1, were significantly increased, generally following a dose-response; however, offspring induction varied. PND5 neonates in the 600-ppm group exhibited significantly elevated expression of Nqo1, Gsta2, and Gstp1 in liver, and Gstm1 and Gstp1 in lung. Findings support maternal dietary supplementation with SFN induces NRF2-related gene expression in neonates via lactational transfer of SFN-NAC. However, NQO1 enzyme activity was not significantly elevated, highlighting the need to optimize dosing strategy. Additionally, in a pilot investigation of lactating women consuming a typical diet, without any purified SFN supplementation, 7 out of 8 breast milk samples showed SFN-NAC above the limit of quantification (LOQ). Notably, the one sample below the LOQ was collected from the only participant who reported no consumption of cruciferous vegetables in the past 24 h. The parent compound was not detected in any of the human breast milk samples. Overall, these data indicate lactational transfer of SFN-NAC at dietary relevant levels. Future studies are needed to evaluate pharmacokinetics and pharmacodynamics of lactational transfer for potential preventive or therapeutic effects in breastfeeding children.
Subject(s)
Acetylcysteine , Lactation , Sulfoxides , Mice , Animals , Child , Infant, Newborn , Humans , Female , Acetylcysteine/pharmacology , Breast Feeding , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Milk, Human/metabolism , Isothiocyanates/pharmacologyABSTRACT
PURPOSE: This study aims to evaluate the factors most associated with early and late complications following microvascular free tissue transfer (MVFTT) after mandibulectomy. METHODS: A retrospective review of patients undergoing MVFTT after segmental mandibulectomy from September 2016 to February 2021 was performed across a single academic institution. Surgical variables were collected, including the location of the resultant mandibular defect (anterior vs posterior) and flap type (osseous or non-osseous). The primary outcome variables included postoperative complications (early, <90 days; and late, >90 days) and the patients' functional status (return to oral intake). Descriptive statistics, chi-square test, Fischer's exact test, and 2-sample t tests were used to analyze differences among variables. RESULTS: We analyzed a cohort of 114 consecutive patients with mandibular defects, comprising 57 anterior and 57 posterior defects. Bony free flaps with hardware were used to reconstruct 98% of anterior defects compared to 58% of posterior defects (P < .001). All soft tissue only flaps did not utilize any hardware during the reconstruction. Anterior defects demonstrated more late complications requiring additional surgery (30% vs 9%, P = .04). A secondary analysis of posterior mandibular reconstructions compared soft tissue only flaps and bony free flaps with hardware and showed equivalent rates of early (12% vs 13%, P > .99) and late (9% vs 8%, P > .99) complications requiring additional surgery while demonstrating a similar return to full oral competence (55% vs 46%, P = .52) and recovery of a 100% oral diet (67% vs 54%, P = .53). CONCLUSION: Osseous free tissue transfer for segmental mandibular defects remains the gold standard in reconstruction. In our patient cohort, anterior mandibular defects are associated with greater late (>90 day) complications requiring additional surgery. Comparable outcomes may be achieved with soft tissue only versus osseous free flap reconstruction of posterior mandibular defects.
Subject(s)
Free Tissue Flaps , Mandibular Osteotomy , Mandibular Reconstruction , Postoperative Complications , Humans , Male , Retrospective Studies , Female , Middle Aged , Mandibular Osteotomy/methods , Postoperative Complications/prevention & control , Aged , Mandibular Reconstruction/methods , Adult , Mandibular Neoplasms/surgery , Mandible/surgery , Plastic Surgery Procedures/methodsABSTRACT
Ewing's sarcoma is a neuroectodermal malignancy classically associated with innocuous and chronic symptomatology. Although tumors typically involve the axial skeleton, some malignancies may be confined to extraosseous tissue only. This report presents the case of a 15-year-old Hispanic male with a tender, slow-growing mass of seven months in the subcutaneous tissue of the right hand. Core needle biopsy and fine needle aspiration confirmed the diagnosis of high-grade extraosseous Ewing's sarcoma and the patient was treated via surgical resection and chemotherapy. Nonspecific findings of Ewing's sarcoma may mimic infection or trauma and contribute to a delay in diagnosis. However, social and economic influences including limited English proficiency and insurance status also critically affect the timing of presentation.