Cerium oxide nanoparticle conjugation to microRNA-146a mechanism of correction for impaired diabetic wound healing.

Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide nanoparticles (CNP) to microRNA (miR)-146a improves diabetic wound healing. CNP are divalent metal oxides that act as free radical scavenger, while miR146a inhibits the pro-inflammatory NFκB pathway, so CNP-miR146a has a synergistic role in modulating both oxidative stress and inflammation. In this study, we define the mechanism(s) by which CNP-miR146a improves diabetic wound healing by examining immunohistochemical and gene expression analysis of markers of inflammation, oxidative stress, fibrosis, and angiogenesis. We have found that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and lowers inflammation and oxidative stress, ultimately promoting faster closure of diabetic wounds.

Cerium oxide nanoparticle delivery of microRNA-146a for local treatment of acute lung injury.

Acute respiratory distress syndrome (ARDS) is a devastating pulmonary disease with significant in-hospital mortality and is the leading cause of death in COVID-19 patients. Excessive leukocyte recruitment, unregulated inflammation, and resultant fibrosis contribute to poor ARDS outcomes. Nanoparticle technology with cerium oxide nanoparticles (CNP) offers a mechanism by which unstable therapeutics such as the anti-inflammatory microRNA-146a can be locally delivered to the injured lung without systemic uptake. In this study, we evaluated the potential of the radical scavenging CNP conjugated to microRNA-146a (termed CNP-miR146a) in preventing acute lung injury (ALI) following exposure to bleomycin. We have found that intratracheal delivery of CNP-miR146a increases pulmonary levels of miR146a without systemic increases, and prevents ALI by altering leukocyte recruitment, reducing inflammation and oxidative stress, and decreasing collagen deposition, ultimately improving pulmonary biomechanics.

Is Tapering Enteroplasty an Alternative to Resection of Dilated Bowel in Small Intestinal Atresia?

BACKGROUND: Intestinal atresia is a congenital defect resulting in intestinal discontinuity and can be associated with significant morbidity related to intestinal failure. The bowel proximal to the atresia is often significantly dilated and dysfunctional. The treatment approaches of this dilated bowel include resection with primary anastomosis versus tapering enteroplasty with preservation of bowel length. The purpose of this study was to compare these two approaches in regard to bowel function as characterized by the time to full enteral feeding. METHODS: A retrospective review was performed of intestinal atresia repair performed at a tertiary referral pediatric hospital from 2007 to 2017. Length of stay, time to full enteral feeds, and complications were assessed in patients who underwent repair with tapering enteroplasty (n = 8) and compared with those who underwent resection and anastomosis (n = 39). RESULTS: The median age at surgery, gender distribution, weeks gestational age (WGA), location of the atresia, and comorbidities were similar between the two groups. Overall, there was no statistically significant difference in length of stay and time to full enteral feeds between groups. Three of eight (38%) patients in the tapered group and five of 39 patients (13%; P = 0.12) in the nontapered group underwent further surgical exploration because of bowel dysmotility. Factors associated with longer length of hospital stay were abdominal reoperation and WGA, and factors associated with longer time to full enteral feeds were WGA, abdominal reoperation, and gastroschisis. CONCLUSIONS: Tapering enteroplasty at initial operation for intestinal atresias preserves bowel length and has statistically equivalent outcomes to resection and anastomosis in regard to the length of stay and time to full enteral feeds.

Examination of Prenatal Sonographic Findings: Intra-Abdominal Bowel Dilation Predicts Poor Gastroschisis Outcomes.

BACKGROUND: Gastroschisis is an anterior abdominal wall defect with variable outcomes. There are conflicting data regarding the prognostic value of sonographic findings. OBJECTIVES: The aim of this study was to identify prenatal ultrasonographic features associated with poor neonatal outcomes. METHOD: A retrospective review of 55 patients with gastroschisis from 2007 to 2017 was completed. Ultrasounds were reviewed for extra-abdominal intestinal diameter (EAID) and intra-abdominal intestinal diameter (IAID), echogenicity, visceral content within the herniation, amniotic fluid index, defect size, and abdominal circumference (AC). Ultrasound variables were correlated with full enteral feeding and the diagnosis of a complex gastroschisis. RESULTS: Bivariate analysis demonstrated an increased time to full enteral feeds with increasing number of surgeries, EAID, and IAID. Additionally, there was a significant relationship between IAID and AC percentile with the diagnosis of complex gastroschisis. On multivariate analysis, only IAID was significant and increasing diameter had a 2.82 (95% CI 1.02-7.78) higher odds of a longer time to full enteral feeds and a 1.2 (95% CI 1.05-1.36) greater odds of the diagnosis of a complex gastroschisis. CONCLUSIONS: Based on these findings, IAID is associated with a longer time to full enteral feeding and the diagnosis of complex gastroschisis.

Pilot Prehabilitation Program for Patients With Esophageal Cancer During Neoadjuvant Therapy and Surgery.

BACKGROUND: Locally advanced esophageal cancer is often treated with neoadjuvant therapy followed by surgery. Many patients present with or experience clinical deconditioning during neoadjuvant therapy. Prehabilitation programs in other areas of surgery have demonstrated improved postoperative outcomes. The aims of this study were to evaluate the feasibility of a pilot prehabilitation program and determine preliminary effects on surgical and cancer-related outcomes. METHODS: A retrospective review of patients treated at a single institution with resectable esophageal cancer was performed (n = 22). Patients in the prehabilitation group received protocol-structured intervention in several clinical domains including nutrition, psychosocial support, and physical exercise. RESULTS: Clinical stage and comorbidities were well matched between groups. The structured prehabilitation program was feasible and well received by participants. Fewer patients required admission during neoadjuvant therapy in the prehabilitation group (27.3% versus 54.5%). Percentage weight loss during treatment was 3.0% in the prehabilitation group versus 4.3% in the control group. Compared with the control group, the prehabilitation group demonstrated 0.0% versus 18.2% 30-d postoperative readmission rate and 18.2% versus 27.3% 90-d postoperative readmission rate. There were no statistically significant differences between groups in regard to complications or mortality. CONCLUSIONS: The pilot prehabilitation program demonstrated feasibility of implementing a structured program for patients receiving neoadjuvant therapy for esophageal cancer. Although the small population limits evaluation of statistical significance, trends in the data suggest a potential benefit of the prehabilitation program on neoadjuvant hospital admission rates, postsurgical readmission rates, and nutritional status.

Sacral agenesis and fecal incontinence: how to increase the index of suspicion.

PURPOSE: Sacral abnormalities range from missing the coccyx, a few sacral vertebrae, or hemi-sacrum, to complete absence with fused iliac bones. The purpose of this study was to review the association between sacral agenesis and fecal incontinence to help inform patient prognosis. METHODS: A retrospective review was performed of patients who presented for bowel management due to sacral agenesis at a tertiary care children's hospital between 2016 and 2017 (n = 10). Data collection included: gender, time of diagnosis, sacral ratio, and associated anomalies. Patients with anorectal malformation and sacrococcygeal teratomas were excluded. RESULTS: Four patients were female. Seven patients had a delayed diagnosis ranging from 22 months of age to 9 years. Most common symptoms included failure of age-appropriate toilet training and severe diaper rash. The sacral ratio was zero (6), 0.3 and 0.4 (2), and hemi-sacrum (2). Associated anomalies were present in five patients. CONCLUSION: Sacral abnormalities should be suspected in patients who present with early severe diaper rash and those who fail to toilet train. An abdominal radiograph can evaluate the sacrum, when the sacral ratio is 0.4 or less, parents should be counseled regarding fecal incontinence and neurogenic bladder.

Systematic review: sacral nerve stimulation in the treatment of constipation and fecal incontinence in children with emphasis in anorectal malformation.

BACKGROUND: Sacral nerve stimulation (SNS) is frequently used for constipation and fecal incontinence in the adult literature. The purpose of this study is to perform a systemic review of the literature for SNS for constipation and fecal incontinence in children with emphasis in anorectal malformations. METHODS: Systematic literature review was conducted to include all SNS studies in patients < 19 years of age. Studies were separated into those for (1) constipation, (2) bowel and bladder dysfunction, and (3) anorectal malformations. RESULTS: 28 articles were included in the review: (1) 12 constipation (269 patients) and (2) 16 bowel and bladder dysfunction (441 patients). Some studies overlapped groups, as they included some patients with anorectal malformations (4 articles and 29 patients). Constipation studies included slow transit and retention constipation and showed varying degrees of improvement. For bowel and bladder dysfunction, studies also reported varying degrees of improvement using different measures (number of bowel movements per day, transit times, and soiling improvement). There was no specific description of the results in anorectal malformation (ARM) cases and also information regarding specific ARM type, sacral ratio, or presence of tethered cord. CONCLUSIONS: SNS for constipation and urinary problems seems to be promising. Data are limited and heterogeneous, and SNS cannot be definitively encouraged or discouraged in patients with ARM, based on current studies. Future studies should include more objective measurements of bowel outcomes and specify outcomes related to patients with anorectal malformations including information regarding their specific malformation, sacral ratio, and presence of tethered cord. Complications' rate is considerable high.

Differentiating presacral masses in anorectal malformations and isolated sacrococcygeal teratomas.

PURPOSE: Presacral masses associated with anorectal malformations (ARM) are most frequently dermoid or teratomas. Sacrococcygeal teratoma (SCT), in isolation, is a different condition. There are limited data comparing the two. The aim of this study was to compare presacral masses associated with ARM and isolated SCTs. METHODS: A retrospective review was performed from 1979 to 2018. Patients with presacral masses and associated ARM (n = 39) were identified and compared to patients with isolated SCTs (n = 32). RESULTS: Those with presacral mass and ARM had a lower proportion of immature and mixed teratomas by pathology and a longer time to mass resection. They had higher percentages of sacral anomalies (76% versus 9%), tethered cord (50% versus 6%), and other anomalies (51% versus 9%). For long-term bowel function, patients with presacral mass and ARM were more likely to be fecally incontinent and require enemas (59% versus 11%). Regarding isolated SCTs, 4% recurred with a time to recurrence of 7 months. CONCLUSIONS: Compared to patients with isolated SCT, patients with presacral mass and ARM had lower grade tumors. In addition, they had a higher proportion of sacral defects and other congenital defects, as well as worse bowel function outcomes.

MOMS Plus: Single-Institution Review of Outcomes for Extended BMI Criteria for Open Fetal Repair of Myelomeningocele.

BACKGROUND: In utero repair has become an accepted therapy to decrease the rate of ventriculoperitoneal shunting and improve neurologic function in select cases of myelomeningocele. The Management of Myelomeningocele Study (MOMS) trial excluded patients with a BMI >35 due to concerns for increased maternal complications and preterm delivery, limiting the population that may benefit from this intervention. OBJECTIVES: The aim of this study was to evaluate outcomes associated with extending the maternal BMI criteria to 40 in open fetal repair of myelomeningocele. METHOD: Retrospective review of fetal closure of myelomeningocele at a quaternary referral center between 2013 and 2016 with maternal BMI ranging from 35 to 40. RESULTS: Eleven patients with a BMI >35 were identified. The average BMI was 37. The average maternal age at the time of evaluation was 27 years. The average gestational age at fetal surgery was 24 weeks. Gestational age at birth was an average of 32 weeks. There was one perinatal death immediately following the fetal intervention. The shunt rate at 1 year was 45% (5/11 patients). CONCLUSIONS: In this single-institution review of expanded BMI criteria for fetal repair of myelomeningocele, we did not observe any adverse maternal outcomes associated with maternal obesity; however, the gestational age at delivery was 2 weeks earlier compared to the MOMS trial.

Pediatric tracheomalacia and the perioperative anesthetic management of thoracoscopic posterior tracheopexy.

Tracheomalacia is a broad term used to describe an abnormally compliant trachea that can lead to exaggerated collapse and obstruction with expiration. We describe the perioperative management of a complex pediatric patient undergoing a posterior tracheopexy which is a relatively new surgical treatment, with a novel surgical approach-thoracoscopy. This procedure has competing surgical and anesthetic needs and presents unique challenges to the physicians involved in caring for these patients. We also review the current literature on pediatric tracheomalacia and examine the newest treatment options to highlight the potential anesthetic challenges and pitfalls associated with management.

Trauma capacity in the central plateau department of Haiti.

BACKGROUND: Surgical burden is a large and neglected global health problem in low- and middle-income countries. With the increasing trauma burden, the goal of this study was to evaluate the trauma capacity of hospitals in the central plateau of Haiti. MATERIALS AND METHODS: The World Health Organization Emergency and Essential Surgical Care survey was adapted with a focus on trauma capacity. Interviewers along with translators administered the survey to key hospital staff. RESULTS: Seven hospitals in the region were surveyed. Of the hospitals surveyed, 3/7 had functioning surgical facilities. None of the hospitals had trauma registries. 71% of the hospitals had no formal trauma guidelines. 2/7 hospitals had a general surgeon available 100% of the time. All surgical facilities had oxygen cylinders available 100% of the time, but three of the primary level hospitals only had it available 51%-90% of the time. Intubation equipment was available at 57% of the facilities. Ventilators were only available in the operating room. Only the largest hospital had a computed tomography scanner. Other hospitals (66%) had a functioning x-ray machine 76%-90% of the time. Hospitals (57%) had an ultrasound machine. The most common reasons for referral were lack of appropriate facilities and supplies at the primary level care centers or lack of trained personnel at higher-level facilities. CONCLUSIONS: Trauma capacity in the central plateau of Haiti is limited. There is a great need for more personnel, trauma training at all staff levels, emergency care guidelines, trauma registries, and imaging equipment and training, specifically in ultrasonography. To accomplish this, coordination is needed between the Haitian government and local and international nongovernmental organizations.

Urologic Presentation of Unicentric Pediatric Castleman Disease in the Setting of Acute Renal Colic.

An 11-year-old otherwise healthy female presented with renal colic and during computed tomography imaging evaluation, she was found to have a right distal ureteral stone with associated hydroureteronephrosis, medially deviated ureter, and 4-cm solid retroperitoneal mass. The mass was palpable on physical exam and was further categorized with magnetic resonance imaging, ultrasound, and laboratory testing. A multidisciplinary team approach, including pediatric surgery, radiology, oncology, and urology, led to the patient undergoing a right retrograde pyelogram, ureteroscopy with stent placement, and laparoscopic excision of retroperitoneal mass. Her pathology revealed lymphoid hyperplasia with histologic features of Castleman disease.

Outcomes of Bariatric Surgery in Older Versus Younger Adolescents.

OBJECTIVES: In this report, we compare weight loss, comorbidity resolution, nutritional abnormalities, and quality of life between younger and older adolescents after metabolic and bariatric surgery. METHODS: From March 2007 to December 2011, 242 adolescents (≤19 years of age) who underwent bariatric surgery at 5 clinical centers in the United States were enrolled in the prospective, multicenter, long-term outcome study Teen-Longitudinal Assessment of Bariatric Surgery. Outcome data from younger (13-15 years; n = 66) and older (16-19 years; n = 162) study participants were compared. Outcomes included percent BMI change, comorbidity outcomes (hypertension, dyslipidemia, and type 2 diabetes mellitus), nutritional abnormalities, and quality of life over 5 years post surgery. RESULTS: Baseline characteristics, except for age, between the 2 cohorts were similar. No significant differences in frequency of remission of hypertension (P = .84) or dyslipidemia (P = .74) were observed between age groups. Remission of type 2 diabetes mellitus was high in both groups, although statistically higher in older adolescents (relative risk 0.86; P = .046). Weight loss and quality of life were similar in the 2 age groups. Younger adolescents were less likely to develop elevated transferrin (prevalence ratio 0.52; P = .048) and low vitamin D levels (prevalence ratio 0.8; P = .034). CONCLUSIONS: The differences in outcome of metabolic and bariatric surgery between younger and older adolescents were few. These data suggest that younger adolescents with severe obesity should not be denied consideration for surgical therapy on the basis of age alone and that providers should consider adolescents of all ages for surgical therapy for obesity when clinically indicated.

Gastrointestinal symptoms in relation to quality of life after metabolic surgery in adolescents.

BACKGROUND: Adolescent obesity is associated with significant co-morbidities, including decreased quality of life (QOL). QOL improves after metabolic and bariatric surgery (MBS), but recent studies have demonstrated that certain gastrointestinal symptoms (GIS) worsen after surgery, including reflux symptoms, nausea, bloating, and diarrhea. OBJECTIVE: The aim of this study was to evaluate QOL and the effect of these symptoms on QOL after bariatric surgery. SETTING: Five academic centers that perform adolescent MBS in the United States. METHODS: We prospectively studied 228 adolescents undergoing MBS using the Teen-Longitudinal Assessment of Bariatric Surgery cohort. GIS and QOL scores were assessed before surgery, at 6 months, and yearly to 5 years after surgery. Analysis involved linear models examining QOL and the association between GIS and QOL adjusting for a priori determined covariates. RESULTS: Adjusting for body mass index change over time, the physical component score (PCS) of the Short Form-36 (SF-36) increased after surgery from 44.2 at baseline to 54.4 at 5 years (P < .0001). The mental component score did not significantly change over time. The SF-36 domains that showed the biggest increase after surgery were physical functioning, physical role functioning, and general health. The SF-36 PCS decreased significantly over time post surgery in those with GIS of reflux, nausea, and diarrhea but remained higher than baseline SF-36 PCS. There was no statistically significant change in mental component score or impact of weight on quality of life-KIDS scores in those with or without GIS. CONCLUSION: QOL, specifically the SF-36 PCS, increases after MBS. Reflux symptoms, nausea, and diarrhea reduce the degree of improvement in QOL in adolescents after MBS. Patients should be monitored and treated for these symptoms to address this decreased QOL.

Nanosilk Increases the Strength of Diabetic Skin and Delivers CNP-miR146a to Improve Wound Healing.

Diabetes mellitus is a metabolic disorder associated with properties and an increased risk of chronic wounds due to sustained pro-inflammatory response. We have previously of radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA (miR)-146a, termed CNP-miR146a, improves diabetic wound healing by synergistically lowering oxidative stress and inflammation, and we sought to evaluate this treatment in a topical application. Silk fibroin is a biocompatible polymer that can be fabricated into nanostructures, termed nanosilk. Nanosilk is characterized by a high strength-to-density ratio and an ability to exhibit strain hardening. We therefore hypothesized that nanosilk would strengthen the biomechanical properties of diabetic skin and that nanosilk solution could effectively deliver CNP-miR146a to improve diabetic wound healing. The ability of nanosilk to deliver CNP-miR146a to murine diabetic wounds and improve healing was assessed by the rate of wound closure and inflammatory gene expression, as well as histologic analysis. The effect of nanosilk on the properties of human diabetic skin was evaluated by testing the biomechanical properties following topical application of a 7% nanosilk solution. Diabetic murine wounds treated with topical nanosilk and CNP-miR146a healed by day 14.5 compared to day 16.8 in controls (p = 0.0321). Wounds treated with CNP-miR146a had higher collagen levels than controls (p = 0.0126) with higher pro-fibrotic gene expression of TGFß-1 (p = 0.0092), Col3α1 (p = 0.0369), and Col1α2 (p = 0.0454). Treatment with CNP-miR146a lowered pro-inflammatory gene expression of IL-6 (p = 0.0488) and IL-8 (p = 0.0009). Treatment of human diabetic skin with 7% nanosilk solution resulted in significant improvement in maximum load and modulus (p < 0.05). Nanosilk solution is able to strengthen the biomechanical properties of diabetic skin and can successfully deliver CNP-miR146a to improve diabetic wound healing through inhibition of pro-inflammatory gene signaling and promotion of pro-fibrotic processes.

Determining maternal risk factors for gastroschisis using colorado's birth registry database.

AIM OF STUDY: Gastroschisis is a congenital abdominal wall defect which results in herniation of abdominal contents. The objective of this study was to determine the maternal risk factors for gastroschisis in Colorado. METHODS: A case-control study was performed using the Birth Registry database from 2007 to 2016. The outcome was gastroschisis, and the main variable was maternal age which was divided into <21, 21-30, and >30 years of age. Descriptive analysis, bivariate analysis, and logistic regression was performed. RESULTS: There were 236 cases of gastroschisis compared to 944 controls. Maternal age did vary significantly between groups (23.4 ±â€¯5 years (cases) vs. 28.7 ±â€¯5.9 years (controls); p < 0.0001). Unadjusted analysis demonstrated that those with young maternal age (<21 years of age) had a 14.14 (95% CI 8.44-23.67) higher odds of gastroschisis compared to those >30 years of age. Independent risk factors for gastroschisis were exposure to prenatal and first trimester cigarettes, prenatal and first trimester alcohol, and chlamydia infection. The odds (4.41, 95% CI 1.36-14.26) of gastroschisis were highest in those with first trimester cigarette exposure and young maternal age (p = 0.03). CONCLUSIONS: Young maternal age, cigarette exposure, alcohol exposure, and chlamydia infection increase the odds of gastroschisis. The interaction between young maternal age and first trimester cigarette exposure significantly increases the odds of gastroschisis. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level III.

A congenital cystic pulmonary airway malformation occurring together with both an extralobar pulmonary sequestration and an esophageal duplication cyst.

A foregut duplication cyst occurring together with both a congenital cystic pulmonary airway malformation and extralobar pulmonary sequestration is an unusual combination. Prenatal ultrasound, MRI, and postnatal CT are helpful for operative planning. Surgical resection is the definitive management for all three anomalies.

Excess skin problems among adolescents after bariatric surgery.

BACKGROUND: Bariatric surgery results in significant and durable weight loss and improved health in severely obese adolescents. An important adverse consequence of the massive weight loss after bariatric surgery is excess skin and soft tissue. The prevalence and clinical characteristics of excess skin-related symptoms have been described in adults undergoing bariatric surgery but not in adolescents. Although the higher skin elasticity of adolescents may result in fewer excess skin problems compared with adults, this hypothesis remains untested. OBJECTIVES: The purpose of the present study was to describe the natural history of excess skin and its associated complications among severely obese adolescents undergoing bariatric surgery. SETTING: University Hospitals, United States. METHODS: We evaluated data from the Teen-Longitudinal Assessment of Bariatric Surgery cohort, a prospective, multiinstitutional study of adolescents (13-19 yr) undergoing bariatric surgery. Abdominal pannus severity (graded 0-5) and excess skin symptoms were evaluated preoperatively and for the first 5 years after bariatric surgery. RESULTS: Among the 217 study participants, 198 (90%) had an abdominal pannus and 16 (7%) reported pannus-related symptoms at the time of bariatric surgery. Preoperative symptoms included intertriginous infections (n = 12, 75%), recurrent cellulitis (n = 5, 31%), and superficial cutaneous ulcerations (n = 1, 6%). Participants with a higher pannus grade preoperatively experienced both a greater reduction in pannus severity (P < .0001) and a higher incidence of pannus-related symptoms (P = .002) postoperatively. Changes in pannus severity occurred during the first 24 months after bariatric surgery; mean pannus severity remained unchanged beyond 24 months. CONCLUSIONS: Severely obese adolescents who undergo bariatric surgery often present with an abdominal pannus at the time of surgery with associated symptoms. Higher preoperative pannus grade is associated with more pannus related symptoms after surgery. Counseling about need for body contouring surgery should be considered in this group.

Body contouring in adolescents after bariatric surgery.

BACKGROUND: Bariatric surgery leads to sustained weight loss and resolution of obesity-associated co-morbidities in severely obese adolescents. However, one consequence of massive weight loss is excess skin and soft tissue. Many details regarding the timing, outcomes, and barriers associated with body contouring surgery (BCS) in youth who have undergone bariatric surgery are unknown. OBJECTIVES: Describe the incidence and effect of BCS following bariatric surgery among adolescents. SETTING: University Hospitals. METHODS: Teen-Longitudinal Assessment of Bariatric Surgery is a prospective multi-institutional study of 242 adolescents who underwent bariatric surgery from 2007 to 2012. Utilization of BCS was analyzed in this population with comparison of anthropometrics and excess skin-related symptoms between those who did and those who did not undergo BCS. RESULTS: Among the 198 study participants with BCS data available, 25 (12.6%) underwent 41 body contouring procedures after bariatric surgery. The most common BCS was panniculectomy (n = 23). Presence of pannus-related symptoms at baseline and the magnitude of weight loss within the first year after bariatric surgery were independently associated with subsequent panniculectomy (P = .04 and P = .03, respectively). All adolescents who underwent panniculectomy experienced resolution of pannus-related symptoms. At 5 years after bariatric surgery, 74% of those who did not undergo panniculectomy reported an interest in the procedure, and 58% indicated that cost/insurance coverage was the barrier to obtaining BCS. CONCLUSION: Few adolescents who underwent bariatric surgery later underwent BCS procedures. Panniculectomy effectively treated pannus-related symptoms. Disparities in access to surgical care for adolescents who desire BCS warrants further investigation.

Injectable, self-healable zwitterionic cryogels with sustained microRNA - cerium oxide nanoparticle release promote accelerated wound healing.

Diabetics are prone to chronic wounds that have slower healing, and methods of accelerating the wound closure and to ensure protection from infections are critically needed. MicroRNA-146a gets dysregulated in diabetic wounds and injection of this microRNA combined with reactive oxygen species-scavenging cerium oxide nanoparticles (CNPs) can reduce inflammation and improve wound healing; however, a better delivery method than intradermal injections is needed. Here we demonstrate a biomaterial system of zwitterionic cryogels (gels formed below freezing temperatures) laden with CNP-miR146a that are topically applicable, injectable, self-healable, and provide sustained release of the therapeutic molecules. These cryogels are comprised of CBMA or SBMA and HEMA, and do not contain chemical crosslinkers. Properties of the gels can be manipulated by changing monomer type and ratio. These materials have demonstrated efficacy and viability in vivo with a diabetic mouse wound healing model. Overall, these materials have a high potential for application in wound treatments due to their ease of production, antifouling characteristics, durability, topical application, and sustained release mechanics. STATEMENT OF SIGNIFICANCE: This work presents the development of zwitterionic cryogels with unique physical properties including injectability and self-healing, that also offer highly sustained release of nanoparticles over time to improve wound healing in a diabetic mouse model. The nanoparticles are made of cerium oxide, which is known to scavenge reactive oxygen species and reduce oxidative stress, and these particles have been further tagged with a microRNA146a that has been shown to reduce inflammation. Zwitterionic materials are known for their superior antifouling properties and good biocompatibility and ability to incorporate bioactive factors. Given these properties, the use of these materials as wound healing dressings would be exciting, yet to date it has been difficult to prolong the release of bioactive factors from them due to their hydrophilicity. Previously we developed zwitterionic cyrogels with very sustained protein release over time, but those materials were quite brittle and difficult to handle. Here, we demonstrate for the first time that by removing the crosslinker molecule from our reaction and polymerizing gels under cryo-conditions, we are able to form zwitterionic cryogels that are injectable, self-healing, and with sustained release profiles. The sustained release of miRNA146a-tagged cerium oxide nanoparticles from these gels is demonstrated to speed up diabetic wound healing time and significantly reduce inflammation.