Codon-Optimized and de novo-Synthesized E-Selectin/AAV2 Dose-Response Study for Vascular Regeneration Gene Therapy.

OBJECTIVE: This study focuses on dose-response investigation using a codon-optimized and de novo-synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug (IND)-enabling of subsequent clinical studies. BACKGROUND: Gene therapy is a potential solution for patients suffering from chronic limb-threatening ischemia (CLTI). Understanding the dose for effective gene delivery is crucial for future IND-enabling studies. METHODS: Expression of the codon-optimized E-Selectin gene was assessed by flow cytometry following in vitro cell transfection assay and RT-qPCR for murine limbs injected in vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose-response studies involved three cohorts of FVB/NJ mice (n=6/group) with escalating log doses of E-Selectin/AAV2 injected intramuscularly (IM) in divided aliquots, ranging from 2×109 VG to 2×1011 VG, into ischemic limbs created by left femoral artery/vein ligation/excision and administration of nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent of gangrene free limb, functional limb recovery and therapeutic angiogenesis were assessed. RESULTS: Codon-optimized E-Sel/AAV2 gene therapy exhibits superior expression level than WT E-Sel/AAV2 gene therapy both in vitro and in vivo. Mice treated with a high dose (2×1011 VG) of E-Sel/AAV2 showed significantly improved perfusion indices, lower Faber's scores, increased running stamina and neovascularization compared with lower doses tested with control groups, indicating a distinct dose-dependent response. No toxicity was detected in any of the animal groups studied. CONCLUSION: E-Sel/AAV2 Vascular Regeneration Gene Therapy (VRGT) holds promise for enhancing the recovery of ischemic hindlimb perfusion and function, with the effective dose identified in this study as 2×1011 VG aliquots injected IM.

Screening and Prophylaxis for Venous Thromboembolism in Pediatric Surgery: A Systematic Review.

OBJECTIVE: The American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee conducted a systematic review to describe the epidemiology of venous thromboembolism (VTE) in pediatric surgical and trauma patients and develop recommendations for screening and prophylaxis. METHODS: The Medline (Ovid), Embase, Cochrane, and Web of Science databases were queried from January 2000 through December 2021. Search terms addressed the following topics: incidence, ultrasound screening, and mechanical and pharmacologic prophylaxis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. Consensus recommendations were derived based on the best available literature. RESULTS: One hundred twenty-four studies were included. The incidence of VTE in pediatric surgical populations is 0.29% (Range = 0.1%-0.48%) and directly correlates with surgery type, transfusion, prolonged anesthesia, malignancy, congenital heart disease, inflammatory bowel disease, infection, and female sex. The incidence of VTE in pediatric trauma populations is 0.25% (Range = 0.1%-0.8%) and directly correlates with injury severity, major surgery, central line placement, body mass index, spinal cord injury, and length-of-stay. Routine ultrasound screening for VTE is not recommended. Consider sequential compression devices in at-risk nonmobile, pediatric surgical patients when an appropriate sized device is available. Consider mechanical prophylaxis alone or with pharmacologic prophylaxis in adolescents >15 y and post-pubertal children <15 y with injury severity scores >25. When utilizing pharmacologic prophylaxis, low molecular weight heparin is superior to unfractionated heparin. CONCLUSIONS: While VTE remains an infrequent complication in children, consideration of mechanical and pharmacologic prophylaxis is appropriate in certain populations. TYPE OF STUDY: Systematic Review of level 2-4 studies. LEVEL OF EVIDENCE: Level 3-4.

Management and Outcomes of Pediatric Lymphatic Malformations: A Systematic Review From the APSA Outcomes and Evidence-Based Practice Committee.

BACKGROUND: Significant variation in management strategies for lymphatic malformations (LMs) in children persists. The goal of this systematic review is to summarize outcomes for medical therapy, sclerotherapy, and surgery, and to provide evidence-based recommendations regarding the treatment. METHODS: Three questions regarding LM management were generated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Publicly available databases were queried to identify articles published from January 1, 1990, to December 31, 2021. A consensus statement of recommendations was generated in response to each question. RESULTS: The initial search identified 9326 abstracts, each reviewed by two authors. A total of 600 abstracts met selection criteria for full manuscript review with 202 subsequently utilized for extraction of data. Medical therapy, such as sirolimus, can be used as an adjunct with percutaneous treatments or surgery, or for extensive LM. Sclerotherapy can achieve partial or complete response in over 90% of patients and is most effective for macrocystic lesions. Depending on the size, extent, and location of the malformation, surgery can be considered. CONCLUSION: Evidence supporting best practices for the safety and effectiveness of management for LMs is currently of moderate quality. Many patients benefit from multi-modal treatment determined by the extent and type of LM. A multidisciplinary approach is recommended to determine the optimal individualized treatment for each patient.

Fibroblasts in Diabetic Foot Ulcers.

Fibroblasts are stromal cells ubiquitously distributed in the body of nearly every organ tissue. These cells were previously considered to be "passive cells", solely responsible for ensuring the turnover of the extracellular matrix (ECM). However, their versatility, including their ability to switch phenotypes in response to tissue injury and dynamic activity in the maintenance of tissue specific homeostasis and integrity have been recently revealed by the innovation of technological tools such as genetically modified mouse models and single cell analysis. These highly plastic and heterogeneous cells equipped with multifaceted functions including the regulation of angiogenesis, inflammation as well as their innate stemness characteristics, play a central role in the delicately regulated process of wound healing. Fibroblast dysregulation underlies many chronic conditions, including cardiovascular diseases, cancer, inflammatory diseases, and diabetes mellitus (DM), which represent the current major causes of morbidity and mortality worldwide. Diabetic foot ulcer (DFU), one of the most severe complications of DM affects 40 to 60 million people. Chronic non-healing DFU wounds expose patients to substantial sequelae including infections, gangrene, amputation, and death. A complete understanding of the pathophysiology of DFU and targeting pathways involved in the dysregulation of fibroblasts are required for the development of innovative new therapeutic treatments, critically needed for these patients.

Directing Cell Delivery to Murine Atherosclerotic Aortic Lesions via Targeting Inflamed Circulatory Interface using Nanocarriers.

Stem cell therapy holds significant potential for many inflammatory diseases and regenerative medicine applications. However, delivery of therapeutic cells to specific disease sites after systemic administration without indiscriminate trafficking to other non-target tissues is a major limitation of current cell therapies. Here, we describe a novel nanocarrier-directed targeted cell delivery system that enables cell surface coating with dendrimer nanocarriers containing adhesion moieties to serve as a global positioning system "GPS" to guide circulating cells to targeted lesions and mediate the anchoring of cells at the inflammation site. By exploiting cell surface ligands/receptors selectively and/or molecular moieties that are highly expressed on activated endothelium in pathologic disease states, nanocarrier-coated cells containing the counterpart binding receptors/ligands can be enabled to specifically traffic to and dock at vasculature within target lesions. We demonstrate the efficacy of the I-domain fragment of LFA-1 ( id LFA-1) complexed to modified nanocarriers to facilitate homing of mesenchymal stem cells (MSCs) to inflamed luminal endothelial cells on which ICAM-1 is highly expressed in a murine model of aortic atherosclerosis. Our method can overcome challenges imposed by the high velocity and dynamic circulatory flow of the aorta to successfully deliver MSCs to atherosclerotic regions and allow for docking of the potentially therapeutic and immunomodulating cells. This targeted cell-delivery platform can be tailored for selective systemic delivery of various types of therapeutic cells to different disease areas.

Outcomes After Pectus Excavatum Repair: Center Volume Matters.

PURPOSE: Pectus excavatum (Pectus) repair may be offered for those with significant cardiopulmonary compromise or severe cosmetic defects. The influence of hospital center volume on postoperative outcomes in children is unknown. This study aimed to investigate the outcomes of children undergoing Pectus repair, stratified by hospital surgical volume. METHODS: The Nationwide Readmission Database was queried (2016-2020) for patients with Pectus (Q67.6). Patients were stratified into those who received repair at high-volume centers (HVCs; ≥20 repairs annually) versus low-volume centers (LVCs; <20 repairs annually). Demographics and outcomes were analyzed using standard statistical tests. RESULTS: A total of 9414 patients with Pectus underwent repair during the study period, with 69% treated at HVCs and 31% at LVCs. Patients at LVCs experienced higher rates of complications during index admission, including pneumothorax (23% vs. 15%), chest tube placement (5% vs. 2%), and overall perioperative complications (28% vs. 24%) compared to those treated at HVCs, all p < 0.001. Patients treated at LVCs had higher readmission rates within 30 days (3.8% vs. 2.8% HVCs) and overall readmission (6.8% vs. 4.7% HVCs), both p < 0.010. Among readmitted patients (n = 547), the most frequent complications during readmission for those initially treated at LVCs included pneumothorax/hemothorax (21% vs. 8%), bar dislodgment (21% vs. 12%), and electrolyte disorders (15% vs. 9%) compared to those treated at HVCs. CONCLUSION: Pediatric Pectus repair performed at high-volume centers was associated with fewer index complications and readmissions compared to lower-volume centers. Patients and surgeons should consider this hospital volume-outcome relationship. TYPE OF STUDY: Retrospective Comparative. LEVEL OF EVIDENCE: III.

Improper Restraint Use in Fatal Pediatric Motor Vehicle Collisions.

PURPOSE: Motor vehicle collisions (MVC) are the second leading cause of death in children and adolescents, but appropriate restraint use remains inadequate. Our previous work shows that about half of pediatric MVC victims presenting to our trauma center were unrestrained. This study evaluates restraint use among children and adolescents who did not survive after MVC. We hypothesize that restraint use is even lower in this population than in pediatric MVC patients who reached our trauma center. METHODS: We reviewed the local Medical Examiner's public records for fatal MVCs involving decedents <19 years old from 2010 to 2021. When restraint use was not documented, local Fire Rescue public records were cross-referenced. Patients were excluded if restraint use was still unknown. Age, demographics, and restraint use were compared using standard statistical methods. RESULTS: Of 199 reviewed cases, 92 met selection criteria. Improper restraint use was documented in 72 patients (78%). Most decedents were White (72% versus 28% Black) and male (74%), with a median age of 17 years [15-18]. Improper restraint use was more common among Black (92% vs 73% White, p = 0.040) and male occupants (85% vs 58% female, p = 0.006). Improper restraint use was lower in the Hispanic population (73%) compared to non-Hispanic individuals (89%), but this difference was not statistically significant (p = 0.090). CONCLUSION: Most pediatric patients who die from MVCs in our county are improperly restrained. While male and Black patients are especially high-risk, the overall dismal rates of restraint use in our pediatric population present an opportunity to improve injury prevention measures. TYPE OF STUDY: Retrospective Comparative Study. LEVEL OF EVIDENCE: Level III.

Nationwide Outcomes After Neoadjuvant Chemotherapy for Locally Advanced Sigmoid Colon Cancer-A Propensity Score-Matched Analysis.

BACKGROUND: The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration. METHODS: The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study. RESULTS: There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P < .001) and high-volume centers (27%, P < .001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC (P < .001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P < .001). There was no difference in survival (P = .20), R0 resection (P = .090), or 30-day readmission rates (P = .30) in the NAC cohort compared to the non-NAC cohort. CONCLUSIONS: Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort.

Admission to a Verified Pediatric Trauma Center is Associated With Improved Outcomes in Severely Injured Children.

BACKGROUND: Previous studies have shown improved survival for severely injured adult patients treated at American College of Surgeons verified level I/II trauma centers compared to level III and undesignated centers. However, this relationship has not been well established in pediatric trauma centers (PTCs). We hypothesize that severely injured children will have lower mortality at verified level I/II PTCs compared to centers without PTC verification. METHODS: All patients 1-15 years of age with ISS >15 in the 2017-2019 American College of Surgeons Trauma Quality Programs (ACS TQP) dataset were reviewed. Patients with pre-hospital cardiac arrest, burns, and those transferred out for ongoing inpatient care were excluded. Logistic regression models were used to assess the effects of pediatric trauma center verification on mortality. RESULTS: 16,301 patients were identified (64 % male, median ISS 21 [17-27]), and 60 % were admitted to verified PTCs. Overall mortality was 6.0 %. Mortality at centers with PTC verification was 5.1 % versus 7.3 % at centers without PTC verification (p < 0.001). After controlling for injury mechanism, sex, age, pediatric-adjusted shock index (SIPA), ISS, arrival via interhospital transfer, and adult trauma center verification, pediatric level I/II trauma center designation was independently associated with decreased mortality (OR 0.72, 95 % CI 0.61-0.85). CONCLUSIONS: Treatment at ACS-verified pediatric trauma centers is associated with improved survival in critically injured children. These findings highlight the importance of PTC verification in optimizing outcomes for severely injured pediatric patients and should influence trauma center apportionment and prehospital triage. LEVEL OF EVIDENCE: Level IV - Retrospective review of national database.

Uncovering Risk Factors and Outcomes of Pulmonary Embolism in a Nationwide Cohort of Hospitalized Children.

PURPOSE: The incidence of pulmonary embolism (PE) in hospitalized children has increased in recent years. This study sought to characterize factors and outcomes associated with PE using a national pediatric cohort. METHODS: The Nationwide Readmissions Database was queried (2016-2018) for patients (<18 years) with a diagnosis of PE. Index and prior hospitalizations (PHs) within 1 year were analyzed. A binary logistic regression utilizing 37 covariates (demographics, procedures, comorbidities, etc.) was constructed to examine a primary outcome of in-hospital mortality. RESULTS: 3440 patients were identified (57% female) with the majority >12 years old (77%). One-third had a known deep vein thrombosis (69% lower and 31% upper extremity). Nineteen percent underwent central venous catheter (CVC) placement. Twenty-one percent had a PH within 1 year. Nine percent underwent an operation with the majority being cardiothoracic (5%). Overall mortality was 5%. Neurocranial surgery, cardiothoracic surgery, and CVC placement were associated with the highest odds of inpatient mortality after logistic regression. CONCLUSION: Pediatric patients with PE have a high rate of PHs, CVC placement, and inpatient operations, which may be associated with higher mortality. This information can be utilized to improve screening measures and clinical suspicion for PE in hospitalized children.

Contemporary Trends in Laparoscopy and Ovarian Sparing Surgery for Ovarian Torsion in the Pediatric Population.

PURPOSE: Although total oophorectomy (TO) was historically performed in cases of nonviable-appearing ovaries, considerable evidence has demonstrated equivalent outcomes after ovarian sparing surgery (OSS) as well as long-term fertility preservation benefits. This study sought to compare outcomes of OSS and TO for patients with ovarian torsion. METHODS: Females <21 years old admitted for ovarian torsion were identified from the Nationwide Readmissions Database (2016-2018) and stratified by OSS or TO. Propensity score-matched analysis (PSMA) utilizing >50 covariates (demographics, medical comorbidities, ovarian diagnoses, etc.) was constructed between those receiving TO and OSS. RESULTS: There were 3,161 females (median 15 [12-18] years) with ovarian torsion, and concomitant pathologies included cysts (42%), benign masses (25%), and malignant masses (<1%). Open approaches were more common (52% vs. 48% laparoscopic), and ovarian resection (OSS or TO) was performed in 87% (39% OSS and 48% TO). OSS was more commonly performed with laparoscopic detorsions (60% vs. 40% TO), while TO was more frequent in open operations (59% vs. 41% TO; both p < 0.001). No differences in overall readmissions (7% OSS vs. 8% TO) or readmissions for recurrent torsion (<1% overall) and ovarian masses (<1%) were observed (both groups <1%; p = 0.612). After PSMA, laparoscopy was still utilized less frequently with TO (39% vs. 53%; p < 0.001) despite similar rates of malignant masses. CONCLUSIONS: Overall, these data offer additional support for the current practice guidelines that give preference to OSS as the primary method of treatment for pediatric ovarian torsion in the majority of cases. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Retrospective Comparative Study.

Immediate Versus Delayed Surgical Management of Infant Cryptorchidism With Inguinal Hernia.

INTRODUCTION: Cryptorchidism is commonly treated with orchiopexy at 6-12 months of age, often allowing time for undescended testicle(s) (UT) to descend spontaneously. However, when an inguinal hernia (IH) is also present, some surgeons perform orchiopexy and inguinal hernia repair (IHR) immediately rather than delaying surgery. We hypothesize that early surgical intervention provides no benefit for newborns with both IH and UT. METHODS: The Nationwide Readmissions Database was used to identify newborns with diagnoses of both IH and UT from 2010 to 2014. Patients were stratified by management: IHR performed on initial admission (Repair) or not (Deferral). Demographics, outcomes, and complications were compared. Results were weighted for national estimates. RESULTS: We analyzed 1306 newborns (64% premature) diagnosed with both IH and UT. IHR was performed at index admission in 30%. Repair was more common in premature babies (43% vs. 8% full-term, p < 0.001) and patients with congenital anomalies (33% vs. 27% without congenital anomaly, p = 0.012). There was no difference in readmission rates. Repair patients had higher rates of orchiectomy than did Deferral. No Deferral patients were readmitted for bowel resection, and <1% were readmitted for orchiectomy or hernia incarceration. CONCLUSION: In newborns with UT and IH, immediate repair is not associated with improved outcomes. Even with incarceration on initial presentation, rates of readmission with incarceration or bowel compromise for patients who undergo Deferral of surgery are minimal. Moreover, Repair newborns have higher rates of orchiectomy. We found no benefit to early operative intervention; thus, we recommend waiting until 6-12 months of age to reassess for surgery. LEVEL OF EVIDENCE: Level III TYPE OF STUDY: Retrospective Comparative Study.

Outcomes Among Malnourished Patients With Crohn's Disease Undergoing Elective Ileocecectomy: A Nationwide Analysis.

BACKGROUND: Crohn's patients' nutritional status can be suboptimal given disease pathophysiology; the effect of a malnourished state prior to elective surgery on post-operative outcomes remains to be more clearly elucidated. This study aims to characterize the effect of malnutrition on post-operative outcomes and readmission patterns for Crohn's patients undergoing elective ileocecectomy using a nationally representative cohort. METHODS: The colectomy-targeted National Surgical Quality Improvement Program Database (2016-2020) was used to identify patients with Crohn's disease without systemic complications who underwent elective ileocecectomy; emergency surgeries were excluded. Malnourished status was defined as pre-operative hypoalbuminemia <3.5 g/dL, weight loss >10% in 6 months, or body mass index <18.5 kg/m2 prior to surgery. RESULTS: Of 1464 patients (56% female) who met inclusion criteria, 1137 (78%) were well-nourished and 327 (22%) were malnourished. Post-operatively, malnourished patients had more organ space surgical site infections (SSI) (9% vs 4% nourished groups, P < .001) and more bleeding events requiring transfusion (9% vs 3% nourished, P < .001). 30-day unplanned readmission was higher in the malnourished group (14% vs 9% nourished, P = .032). Index admission length of stay was significantly longer in the malnourished group (4 days [3-7 days] vs the nourished cohort: 4 days [3-5 days], P < .001). DISCUSSION: Poor nutritional status is associated with organ space infections and bleeding as well as longer hospitalizations and more readmissions in Crohn's patients undergoing elective ileocecectomy. A detailed nutritional risk profile and nutritional optimization is important prior to elective surgery.

Using intent to get ahead of pediatric cranial firearm injuries.

OBJECTIVE: Pediatric firearm injuries (PFI) are a public health crisis. Little is known about how injury intent may influence the outcome of pediatric cranial firearm injuries (PCFI). The current study sought to compare demographics and outcomes of PCFI based on intent of injury. METHODS: The Nationwide Readmission Database (2010-2014) was queried to identify patients <18 years old with PCFI. Demographics and outcomes were compared by injury intent (assault, self-inflicted, unintentional), and results were weighted for national estimates to create a population-based cohort study. RESULTS: There were 1,365 cases of PCFI identified for an incidence of 11% of all PFI. The majority of patients were male (83 %), >13 years (81 %), and had an injury severity score >15 (79 %). Overall PCFI mortality was 43 %, compared to 6 % for all PFI. Assault was the most common intent (51 %), followed by self-inflicted (25 %), and unintentional (24 %). Assault was more likely to occur in patients from low-income households (61 % vs. 31 % self-inflicted vs. 42 % unintentional), p < 0.001. Unintentional injuries occurred in those <13 years old (40 % vs. 12 % assault vs. 16 % self-inflicted) and more often resulted in facial fracture (19 % vs. 11 % vs. 13 %), all p < 0.001. Readmission rate within the year was 21 %. The majority (56 %) of readmissions were unplanned, and the rate was highest for assault (77 % vs. <1 % self-inflicted vs. 44 % unintentional, p < 0.001). CONCLUSIONS: PCFI are associated with significant morbidity and mortality. Demographics and outcomes vary by intent of injury; knowledge of these patterns can direct future interventions to reduce injuries and impact outcomes.

Rural Melanoma Patients Have Less Surgery and Higher Melanoma-Specific Mortality.

BACKGROUND: Melanoma causes most skin cancer-related deaths, and disparities in mortality persist. Rural communities, compared to urban, face higher levels of poverty and more barriers to care, leading to higher stage at presentation and shorter survival in melanoma. To further evaluate these disparities, we sought to assess the association between rurality and melanoma cause-specific mortality and receipt of recommended surgery in a national cohort. METHODS: Patients with primary non-ocular, cutaneous melanoma from the SEER database, 2000-2017, were included. Outcomes included melanoma-specific survival and receipt of recommended surgery. Rurality was based on Rural-Urban Continuum Codes. Variables included age, sex, race, ethnicity, income, and stage. Multivariate regression models assessed the effect of rurality on survival and receipt of recommended surgery. RESULTS: 103,606 patients diagnosed with non-ocular cutaneous primary melanoma met criteria during this period. 93.3% (n = 96620) were in urban areas and 6.7% (n = 6986) were in rural areas. On multivariate regression controlling for age, sex, race, ethnicity, and stage patients living in a rural area were less likely to receive recommended surgery (aOR .52, 95% CI: .29-.90, P = .02) and had increased hazard of melanoma-specific mortality (aHR 1.19, 95% CI: 1.02-1.40, P = .03) even after additionally controlling for surgery receipt. CONCLUSION: Using a large national cohort, our study found that rural patients were less likely to receive recommended surgery and had shorter melanoma cause-specific survival. Our findings highlight the importance of access to cancer care in rural areas and how this ultimately effects survival for these patients.

Augmented Safety Profile of Ultrasound-Guided Gluteal Fat Transfer: Retrospective Study With 1815 Patients.

BACKGROUND: Gluteal augmentation with autologous fat transfer is one of the fastest growing aesthetic surgical procedures worldwide over the past decade. However, this procedure can be associated with high mortality from fatal pulmonary fat embolism events caused by intramuscular injection of fat. Ultrasound-guided fat grafting allows visualization of the transfer in the subcutaneous space, avoiding intramuscular injection. OBJECTIVES: The aim of this study was to assess the safety and efficacy of gluteal fat grafting performed with ultrasound-guided cannulation. METHODS: A retrospective chart review of all patients undergoing ultrasound-guided gluteal fat grafting at the authors' center between 2019 and 2022 was performed. All cases were performed by board-certified and board-eligible plastic surgeons under general anesthesia in ASA Class I or II patients. Fat was only transferred to the subcutaneous plane when over the gluteal muscle. Patients underwent postoperative follow-up from a minimum of 3 months up to 2 years. Results were analyzed with standard statistical tests. RESULTS: The study encompassed 1815 female patients with a median age of 34 years. Controlled medical comorbidities were present in 14%, with the most frequent being hypothyroidism (0.7%), polycystic ovarian syndrome (0.7%), anxiety (0.6%), and asthma (0.6%). Postoperative complications occurred in 4% of the total cohort, with the most common being seroma (1.2%), local skin ischemia (1.2%), and surgical site infection (0.8%). There were no macroscopic fat emboli complications or mortalities. CONCLUSIONS: These data suggest that direct visualization of anatomic plane injection through ultrasound guidance is associated with a low rate of complications. Ultrasound guidance is an efficacious adjunct to gluteal fat grafting and is associated with an improved safety profile that should be considered by every surgeon performing this procedure.

Timing of Pediatric Incarcerated Inguinal Hernia Repair: A Review of Nationwide Readmissions Data.

INTRODUCTION: In pediatric patients, incarcerated inguinal hernias are often repaired on presentation. We hypothesize that in appropriate patients, repair may be safely deferred. METHODS: The Nationwide Readmissions Database was used to identify pediatric patients (aged < 18 y) with incarcerated inguinal hernia from 2010 to 2014. Patients were stratified by management approach (Early Repair versus Deferral). Overall frequencies of these operative strategies were calculated. Propensity score matching was then performed to control for patient age, comorbidities, perinatal conditions, and congenital anomalies. Outcomes including complications, surgical procedures, and readmissions were compared. Outpatient surgeries were not assessed. RESULTS: Among 6148 total patients with incarcerated inguinal hernia, the most common strategy was to perform Early Repair (88% versus 12% Deferral). Following propensity score matching, the cohort included 1288 patients (86% male, average age 1.7 ± 4.1 years). Deferral was associated with equivalent rates of readmission within one year (13% versus 15%, P = 0.143), but higher readmissions within the first 30 days (7% versus 3%, P = 0.002) than Early Repair. Deferral patients had lower rates of orchiectomy (2% versus 5%, P = 0.001), wound infections (< 2% versus 2%, P = 0.020), and other infections (7% versus 15%, P < 0.001). The frequency of other complications including bowel resection, oophorectomy, testicular atrophy, sepsis, and pneumonia were equivalent between groups. Three percent of Deferrals had a diagnosis of incarceration on readmission. CONCLUSIONS: Deferral of incarcerated inguinal hernia repair at index admission is associated with higher rates of hospital readmissions within the first 30 days but equivalent readmission within the entire calendar year. These patients are at risk of repeat incarceration but have significantly lower rates of orchiectomy than their counterparts who undergo inguinal hernia repair at the index admission. We propose that prospective studies be performed to identify good candidates for Elective Deferral following manual reduction and overnight observation. Such studies must capture outpatient surgical outcomes.

Targeted cell delivery of mesenchymal stem cell therapy for cardiovascular disease applications: a review of preclinical advancements.

Cardiovascular diseases (CVD) continue to be the leading cause of morbidity and mortality globally and claim the lives of over 17 million people annually. Current management of CVD includes risk factor modification and preventative strategies including dietary and lifestyle changes, smoking cessation, medical management of hypertension and cholesterol lipid levels, and even surgical revascularization procedures if needed. Although these strategies have shown therapeutic efficacy in reducing major adverse cardiovascular events such as heart attack, stroke, symptoms of chronic limb-threatening ischemia (CLTI), and major limb amputation significant compliance by patients and caregivers is required and off-target effects from systemic medications can still result in organ dysfunction. Stem cell therapy holds major potential for CVD applications but is limited by the low quantities of cells that are able to traffic to and engraft at diseased tissue sites. New preclinical investigations have been undertaken to modify mesenchymal stem cells (MSCs) to achieve targeted cell delivery after systemic administration. Although previous reviews have focused broadly on the modification of MSCs for numerous local or intracoronary administration strategies, here we review recent preclinical advances related to overcoming challenges imposed by the high velocity and dynamic flow of the circulatory system to specifically deliver MSCs to ischemic cardiac and peripheral tissue sites. Many of these technologies can also be applied for the targeted delivery of other types of therapeutic cells for treating various diseases.

Outcomes of Incidental Appendectomy During Ovarian Operations in a National Pediatric Cohort.

INTRODUCTION: The utility of incidental appendectomy (IA) during many ovarian operations has not been evaluated in the pediatric population. This study sought to compare outcomes after ovarian surgery with IA in the pediatric population. METHODS: Females (≤20 y old) undergoing ovarian surgeries (oophorectomy, detorsion and/or drainage) were identified from the Nationwide Readmissions Database (2016-2018). Those with appendicitis were excluded. A propensity score-matched analysis (PSMA) with 46 covariates (demographics, comorbidities, hospitalization factors, etc.) was performed between those receiving ovarian surgery with or without IA. RESULTS: There were 13,202 females (median age 17 [IQR 14-20] y old) who underwent oophorectomy (90%), detorsion (26%), and/or ovarian drainage (13%). There were more episodes of torsion in the PSMA cohort receiving ovarian surgery alone (17% versus 10% IA; P = 0.016), while other indications (ovarian mass, cyst) were similar. Open (66% versus 34% laparoscopic) IAs were more frequent. Length of stay (LOS) was longer for those undergoing IA (3 [2-4] versus 2 [2-4] days ovarian surgery alone; P < 0.001). There was a higher rate of postoperative GI complications in the IA cohort. Subgroup analysis of those undergoing laparoscopic operations demonstrated no difference in LOS or postoperative complications between patients undergoing IA or not. CONCLUSIONS: These data indicate that IA in pediatric ovarian operations is associated with longer LOS and higher GI postoperative complications. However, laparoscopic IA was not associated with higher cost, complications, LOS, or readmissions. This suggests that IA performed during ovarian surgeries in select patients may be cost-effective and worthy of future study.

Endoscopic Management of a Double Duodenal Web: A Case Report of a Rare Alimentary Anomaly.

Duodenal webs are a rare clinical entity with the presentation of a double duodenal web being exceedingly uncommon. Management of duodenal webs traditionally involves duodenal web excision with duodenoduodenostomy, which is usually performed via a laparoscopic or an open approach. We report the case of a 6-month-old child who presented with progressively worsening bilious emesis with imaging findings concerning for a duodenal web. Endoscopic evaluation was performed that identified 2 webs in the fourth portion of the duodenum. These were managed completely endoscopically with balloon dilation. Although surgery is the mainstay of treatment of duodenal webs, this patient was successfully managed by endoscopic intervention without the need for open or laparoscopic excision, which has not been previously described for double duodenal webs. This work demonstrates the safety and efficacy of endoscopic management for infants with this anomaly.