Objective— The mechanism of neovascularization during the proliferative phase of infantile hemangioma is poorly understood. It is known that circulating bone marrow-derived endothelial progenitor cells (EPCs) form new blood vessels in ischemic tissues using mediators regulated by the transcription factor, HIF-1α. Mobilization of EPCs is enhanced by VEGF-A, matrix metalloproteinase (MMP)-9, and estrogen, whereas homing is secondary to localized expression of stromal cell-derived factor-1α (SDF-1α). We examined whether these mediators of EPC trafficking are upregulated during the proliferation of infantile hemangioma. Methods and Results— Surgical specimens and blood samples were obtained from children with proliferating hemangioma and age-matched controls (n=10, each group). VEGF-A and MMP-9 levels were measured in blood, and tissue sections were analyzed for SDF-1α, MMP-9, VEGF-A, and HIF-1α. The role of estrogen as a modulator of hemangioma endothelial cell growth was also investigated. We found that all these mediators of EPC trafficking are elevated in blood and specimens from children with proliferating infantile hemangioma. In vitro, the combination of hypoxia and estrogen demonstrated a synergistic effect on hemangioma endothelial cell proliferation. Conclusions— These findings demonstrate that proliferating hemangiomas express known mediators of vasculogenesis and suggest that this process may play a role in the initiation or progression of this disease.
Objective: Evaluate the factors that influence caregiver-reported completion of nasoalveolar molding (NAM) therapy for patients with cleft lip and palate. Design: An IRB-approved 30-question survey. Setting: Outpatient clinic for patients with cleft lip. Patients: Patients with unilateral or bilateral cleft lip treated with NAM therapy. Interventions: Survey of previous experiences. Main Outcome Measure(s): Rate of noncompletion for patients initiating NAM therapy and identifiable causes. Results: Of 94 patients who underwent NAM, 13 (13.8%) failed to complete NAM therapy. Reasons for incomplete treatment included: obstructive sleep apnea, device intolerance, tape issues, and lack of support. Patients who did not complete NAM therapy were less likely to have primary caregivers >30-year old (P = .045) and more likely to be the first child for the family (P = .021) and have a bilateral cleft (P = .03). Caregivers of NAM patients were less satisfied with the outcome (P < .001) when they did not complete therapy. Conclusion: This study shows that a high number of parents fail to complete this therapy for many reasons, personal and medical. More data are needed to elucidate true prevalence of NAM noncompletion and to establish evidence-based guidelines to reduce barriers to care for completing NAM treatment.
Background: Enhanced recovery after surgery (ERAS) protocols have been adopted for many types of surgery. Postoperative pain following palatoplasty may cause feeding and swallowing difficulty. Our study evaluated the use of ERAS protocols to improve the management of pain following primary palatoplasty as well as in the transition of care from inpatient to outpatient. Methods: An Institutional Review Board approved retrospective analysis was performed for patients who previously underwent primary palatoplasty before ERAS implementation. Separately, an Institutional Review Board approved prospective trial of patients undergoing primary palatoplasty was performed and these patients were managed with ERAS protocols. Data were obtained for length of stay, pain scale scores, milligrams of morphine administered, and inpatient readmissions/emergency department visits. Outpatient medication logs were used to follow pain medicine usage, and a satisfaction survey was administered at the first postoperative visit. Results: Data were obtained retrospectively for 56 patients and prospectively for 57 patients who underwent primary palatoplasty. Patients in the ERAS protocol received significantly less milligrams of morphine on postoperative day 1 through day 4 than those patients in the usual care group P < 0.05. No significant difference was observed for length of stay, oral intake prior to discharge, or inpatient face, legs, activity, cry, consolability pain scale scores. Outpatient medication logs showed a continued decrease in narcotic usage at home with no spike post discharge day 1. Parents reported high satisfaction levels for inpatient pain management (4.66 ± 0.49) and even higher satisfaction levels for understanding (5.0 ± 0) and management of pain at home (4.92 ± 0.29). Return visits to the hospital for pain management following primary palatoplasty decreased from 7.1% (4) following the previous protocol to 0% with the new ERAS protocol (P = 0.057). Conclusion: The ERAS protocols provide improved inpatient pain management following primary palatoplasty as evidence by decreased total narcotic pain medication usage. The use of multimodality therapy and increased patient education regarding non-narcotic medications can improve the transition of care from inpatient to outpatient, without sacrificing patient/parent satisfaction. The results of this study merit future study into more restricted use of opioid pain medications with greater emphasis on the use of multimodal therapeutics as primary agents as opposed to adjuncts.
ALP, alkaline phosphatase; BMP, bone morphogenetic protein; ERK-1, extracellular signal-regulated kinase 1; iCALs, immortalized calvarial cells; IHC, immunohistochemical; MAP, mitogen-activated protein; MSC, mesenchymal stem cell; OCN, osteocalcin; OPN, osteopontin; p38α, p38-reactivating kinase; PBS, phosphate-buffered saline; PEMF, pulsed electromagnetic field.
Our experience shows that LAGB is a safe and effective solution to failed RYGBP.
For Gustilo IIIB fractures that require free-flap coverage, the added bony and soft tissue manipulation required for intramedullary rodding may disrupt the surrounding blood supply and lead to higher rates of complications that threaten the overall success of the reconstruction. Plastic and orthopedic surgeons should discuss the optimal method of bony fixation for complex tibial fractures when a free flap will likely be needed for soft tissue coverage. This integrated team approach may help minimize complications.
This study identifies factors used to choose a cleft team/surgeon. Parents are more concerned with the experience level, reputation, and environment of the cleft team/surgeon than the distance traveled to get to the center.
Rationale: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory checkpoint receptor that is expressed by naïve T-cells in lymph nodes (LNs) to inhibit activation against “self” antigens (Ags). In cancer, anti-CTLA-4 blocks inhibitory action, enabling robust activation of T-cells against tumor Ags presented in tumor draining LNs (TDLNs). However, anti-CTLA-4 is administered intravenously with limited exposure within TDLNs and immune related adverse events (irAEs) are associated with over-stimulation of the immune system.Methods: Herein, we first deliver anti-CTLA-4 in an orthotopic mammary carcinoma murine model using a nanotopographical microneedle-array device to compare its anti-tumor response to that from systemic administration. Additionally, to demonstrate the feasibility of lymphatic delivery in humans using the device, we use near-infrared fluorescence imaging to image delivery of ICG to LNs.Results: Our data show that lymphatic infusion results in more effective tumor growth inhibition, arrest of metastases, increased tumor infiltrating lymphocytes and complete responses when compared to conventional systemic administration. In clinical studies, we demonstrate for the first time that nanotopographic infusion can deliver ICG through the lymphatics directly to the axilla and inguinal LNs of healthy human volunteers.Conclusion: Taken together, these results suggest that regional delivery using a nanotopography-based microneedle array could revolutionize checkpoint blockade immunotherapy by reducing systemic drug exposure and maximizing drug delivery to TDLNs where tumor Ags present. Future work is needed to determine whether lymphatic delivery of anti-CTLA-4 can alleviate irAEs that occur with systemic dosing.
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