Emodin reduces tumor burden by diminishing M2-like macrophages in colorectal cancer

Emodin, a natural anthraquinone, has been shown to have anti-tumorigenic properties and may be an effective therapy for colorectal cancer (CRC). However, its clinical development has been hampered by a poor understanding of its mechanism of action. The purpose of this study was to 1) evaluate the efficacy of emodin in mouse models of intestinal/colorectal cancer and 2) to examine the impact of emodin on macrophage behavior in the context of CRC. We utilized a genetic model of intestinal cancer (ApcMin/+) and a chemically induced model of CRC (AOM/DSS). Emodin was administered orally (40 mg/kg or 80 mg/kg in AOM/DSS and 80mg/kg in ApcMin/+) 3x/week to observe its preventative effects. Emodin reduced polyp count and size in both rodent models (p<0.05). We further analyzed the colon microenvironment of AOM/DSS mice and found that mice treated with emodin exhibited lower pro-tumorigenic M2-like macrophages and a reduced ratio of M2/M1 macrophages within the colon (p<0.05). Despite this, we did not detect any significant changes in M2-associated cytokines (IL10, IL4, and Tgfb1) nor M1-associated cytokines (IL6, TNFα, IL1β, and IFNγ) within excised polyps. However, there was a significant increase in NOS2 expression (M1 marker) in mice treated with 80 mg/kg emodin (p<0.05). To confirm emodin's effects on macrophages, we exposed bone marrow-derived macrophages (BMDMs) to C26 colon cancer cell conditioned media. Supporting our in vivo data, emodin reduced M2-like macrophages. Overall, these data support the development of emodin as a natural compound for prevention of CRC given its ability to target pro-tumor macrophages.

Successful management of complex scalp wounds with exposed calvarial bones by customized Negative pressure wound therapy (NPWT): Case series and review of the literature

Scalp wounds with exposed calvarial bones continue to be a challenge especially when no local flap options are available and no microvascular flaps can be performed. Our prospective study looked at 19 patients (14 males) where customized negative pressure wound treatment was used till the complex scalp wounds, mostly from animal bites, were covered with healthy granulation and grafted. Scalp wounds ranged from 6 × 4 cm to 17 × 11 cm in size whereas the area of exposed bone ranged from 1 × 2 cm to 10 × 10 cm. No major complication was seen, and wounds were rapidly healed.

A Retrospective Analysis of Clinical Use and Outcomes Using Viable Placental Membrane Allografts in Chronic Wounds

Introduction. Viable placental membrane (vPM) has been shown to decrease time to healing, adverse wound events, and wound-related infections. Wound research exclusion criteria commonly exclude wound types other than diabetic foot ulcers and venous leg ulcers (VLUs), comorbidities including peripheral arterial disease (PAD) and uncontrolled diabetes mellitus (DM), and wounds with exposed bone or tendon. Objective. This retrospective research study evaluated the clinical use and outcomes of the vPM with living mesenchymal stem cells used in chronic wound management in the community hospital outpatient department setting with the goal of comparing real-world use and outcomes of the product with use and outcomes described in the chronic wound literature. Materials and Methods. A retrospective analysis on vPM treatments at a Wisconsin academic health system’s community hospitals. Participants included all patients who received vPM therapy between July 1, 2016, and August 21, 2019. Results. A total of 89 patients received vPM treatment during the study period (mean age, 70 years; 69% male [n = 61], 31% female [n = 28]). Wound types were 54% diabetic or neuropathic foot ulcers (n = 48), 17% VLUs (n = 15), 7% pressure injuries (n = 6), and 22% atypical wounds (n = 20). The average wound duration prior to vPM initiation was 104 days. Average wound size at presentation was 6.9 cm2. Of study participants 54% had PAD (n = 48), 63% had DM (n = 56), 33.7% had DM and PAD (n = 30), and 17% had exposed bone or tendon (n = 15). Average adjusted time to healing after initiation of vPM was 81.2 days. The percentage of wounds healed 12 weeks after initiation of vPM treatment was 57%. Conclusions. Effectiveness of vPM observed in controlled trials also was observed in this real-world study on vPM for multiple wound types, patients with comorbidities including PAD and uncontrolled DM, and wounds with exposed bone or tendon. Results of this study were not statistically different from those reported in the literature. More randomized controlled trials are needed to explore the efficacy of vPM on patient presentations common to wound healing centers.

350 Cross Over Septal Flap Technique for Choanal Atresia Surgery: Two Centre Series with Outcomes

Introduction Choanal atresia (CA) is a congenital obstruction of the posterior nasal aperture due to nasal cavity canalisation failure. Endoscopic endonasal surgery has led to successful CA repair and fewer complications compared to open surgery. We describe our surgical technique that uses septal mucosal flaps without need for stenting or subsequent intubation. Method A multicentre retrospective review of patients who underwent surgery using the cross over septal technique. Patient demographics and outcomes were recorded. Flap design: bilateral vertical septal mucosa incisions are performed on either side of the posterior third of the septum to form two mucoperiosteal flaps. The posterior vomer and atretic plates are removed. One flap is pedicled superiorly and rotated over the bare sphenoid rostral bone. The contralateral flap is pedicled inferiorly and rotated to cover exposed bone of nasal cavity floor. Lateral nasal wall mucosal integrity is maintained. This technique is used both for unilateral and bilateral atresia. Results Twelve patients from 2013 to 2020 were included. Age range was 0.07-50 years, male to female ratio of 1:5. Ten patients had unilateral CA, two had bilateral. Nine had bony CA, the remainder mixed. 5 patients (mean age 2.8 years) underwent second-look endoscopy under sedation an average 36 days following primary surgery. Conclusions The cross over technique for CA has low morbidity and 100% success in our multicentre series. Use of mucoperiosteal flaps to cover the exposed bone, removal of vomer and minimal instrumentation to the lateral nasal wall are the best ways to avoid postoperative stenosis.

Surgical Technique for Complex Syndactyly in Apert Syndrome : A Serial Case

Complex syndactyly in Apert syndrome, especially complicated with synonychia and synostosis, is a surgical challenge. The incidence of Apert Syndrome is reported to be approximately 1 per 100.000 to 160.000 live births and its incidence in Indonesia is not yet known. It is practically symmetrical causing significant dysfunction and infection if not treated properly. The goals in the treatment are separation of independent digits without disturbing function and growth, creation of a lined commissure, provision of skin cover for the denuded nail edge and exposed bone, and to create aesthetically pleasing individual fingertips with proper nails, nail folds and adequate pulp fullness. Many variations of surgical release of the first web space and of the remaining syndactyly have been described. Various approaches to the bony deformity of the thumb have also been described. All previously described techniques advocate releasing a single side of a digit at any given surgery to maintain the vascularity of that digit. This is due to the unreliability of the vascular branching pattern to the digits. In this serial case, we reported 5 cases of Apert syndrome. We described the clinical findings, incision design, immediate and post-surgery follow ups. The results were uneventful, with satisfying function and aesthetic appearance.

18F-Fluoride PET/CT Imaging of Medication-Related Osteonecrosis of the Jaw in Conservative Treatment—A Case Report

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect in antiresorptive treatment. Treatment of MRONJ is considered primarily conservative with oral mouth rinses and antibiotics but may demand surgery, depending on the complaints and general condition of the patient, the extent of the necrosis, and the overall prognosis with respect to the underlying disease. A 77 year old female patient with invasive ductal breast cancer and bone metastases was treated with intravenous bisphosphonate (BP) zoledronic acid. During therapy, she developed MRONJ in the mandible with severe pain. Clinical examination revealed confluent exposed bone of the lower left jaw and a fistula at the right molar region. The panoramic radiograph revealed a mandibular osseous involvement with diffuse radiopaque areas between radiolucent areas. For preoperative planning, 18F-fluoride positron emission tomography/computed tomography (PET/CT) of the jaw was performed, showing substantially increased 18F-fluoride uptake in regions 38 to 47 of the mandible with a focal gap in region 36 (area of clinically exposed bone). CT revealed medullary sclerosis and cortical thickening with confluent periosteal reaction and focal cortical erosion in the regions 37 to 42, whereas the regions 43 to 47 were only subtly sclerotic without cortical thickening. After systemic antibiotic therapy with sultamicillin following significant symptom and pain relief, 18F-fluoride PET/CT imaging was performed again after 5 months. No changes in either CT and PET were observed in regions 38 to 42, whereas the bony sclerosis was slightly increased in regions 43 to 47 with a slight reduction of 18F-fluoride uptake. 18F-fluoride PET/CT showed no significant changes assessing the extent of MRONJ prior and after systemic antibiotic therapy, providing no evidence that conservative treatment reduced the extent of the MRONJ-affected jawbone. The additional information of 18F-fluoride PET enables to identify the true extent of MRONJ which may be underestimated by CT imaging alone. Patients with MRONJ undergoing conservative treatment could benefit because additional imaging may be avoided as the pre-therapeutic 18F-fluoride PET/CT delivers all information needed for further treatment. Our findings support the recommendation of a surgical approach as long-term antibiotics cannot downsize the extent of MRONJ.

146 The Use of Biodegradable Temporizing Matrix

Biodegradable temporizing matrix is a synthetic polyurethane dermal substitute that may have advantages over similar templates, which are mainly associated with its increased resistance to bacteria and infectious complications. It can be used to temporize large wounds in major burns, and to cover ungraftable beds, such as exposed bone or tendon. It has also been postulated to minimize the risk of scar contractures, which may warrant further studies. By means of a case report, this video illustrates its employment, showing the treatment stages of application, delamination, and grafting, as well as early postoperative results.