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.

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.

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.

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.

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.

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.

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.

Nationwide Outcomes After Thoracoscopic Versus Open Resection of Congenital Pulmonary Airway Malformations in Newborns.

Purpose: Elective resection of congenital pulmonary airway malformations (CPAM) has been debated for decades and varies significantly between individual surgeons. However, few studies have compared outcomes and costs associated with thoracoscopic and open thoracotomy approaches on a national level. This study sought to compare nationwide outcomes and resource utilization in infants undergoing elective lung resection for CPAM. Materials and Methods: The Nationwide Readmission Database was queried from 2010 to 2014 for newborns who underwent elective surgical resection of CPAM. Patients were stratified by operative approach (thoracoscopic versus open). Demographics, hospital characteristics, and outcomes were analyzed using standard statistical tests. Results: A total of 1716 newborns with CPAM were identified. Elective readmission for pulmonary resection was performed in 12% (n = 198), with 63% of resections completed at a different hospital than the newborn stay. Most resections were thoracoscopic (75%), compared to only 25% via thoracotomy. Infants treated with thoracoscopic resection were more often male (78% versus 62% open, P = .040) and were older at the time of resection. Patients who had an open thoracotomy experienced a higher rate of serious complications (40% versus 10% thoracoscopic, P < .001), including postoperative hemorrhage, tension pneumothorax, and pulmonary collapse. Readmission costs were higher for infants treated via thoracotomy (P < .001). Conclusion: Thoracoscopic lung resection for CPAM is associated with lower cost and fewer postoperative complications than thoracotomy. Most resections are performed at different hospitals than the place of birth, which may affect long-term outcomes from single institutional studies. These findings may be used to address costs and improve future evaluations of elective CPAM resections.

Examination Scores but not Clinical Performance Correlate With Duration of Preclinical Didactic Time: A Synchronous Comparison of Second- Versus Third-Year Medical Students on the Surgery Clerkship.

OBJECTIVE: Numerous institutions have reduced preclinical didactic time to facilitate earlier clinical exposure during the second year of medical education. However, the effects that shortened preclinical education may have on performance in the surgery clerkship are unclear. This study aims to compare the clinical and examination performance of second- (MS2) and third-year (MS3) students synchronously completing an identical surgery clerkship. DESIGN: All students completing the surgery clerkship (identical didactics, examinations, clinical rotations, etc.) were included. MS3s received 24 months of preclinical education, whereas MS2s received 14 months. Performance outcomes included weekly quizzes based on lectures, NBME Surgery Shelf Exam, numeric clinical evaluations, objective structured clinical examination (OSCE) scores, and overall clerkship grades. SETTING: University of Miami Miller School of Medicine. PARTICIPANTS: All second- (MS2) and third-year (MS3) medical students completing the Surgery Clerkship over 1 year (n = 395). RESULTS: There were 199 MS3 (50%) and 196 MS2 (50%) students. MS3s demonstrated higher median shelf exams (77% vs 72% MS2s), weekly quiz score averages (87% vs 80% MS2s), clinical evaluations (96% vs 95% MS2s), and overall clerkship grades (89% vs 87% MS2s), all p < 0.020. There was no difference in median OSCE performance (both 92%; p = 0.499). A greater proportion of MS3 students performed in the highest 50% of weekly quiz scores (57% vs 43% MS2), NBME shelf exams (59% vs 39% MS2), and overall clerkship grades (45% vs 37% MS2), all p < 0.010. No significant difference in the proportion of students placing in the top 50% of clinical parameters including the OSCE (48% MS3 vs 46% MS2; p = 0.106) and clinical evaluations (45% MS3 vs 38%; p = 0.185) was observed. CONCLUSIONS: Although the duration of preclerkship education may correspond to examination scores, MS2s and MS3s perform similarly on clinical metrics. Future strategies to enhance available preclinical didactic time and preparation for examinations are needed.

Nationwide Outcomes of Pancreaticoduodenectomy for Pancreatic Malignancies: Center Volume Matters.

BACKGROUND: Complex surgeries such as pancreaticoduodenectomies (PD) have been shown to have better outcomes when performed at high-volume centers (HVCs) compared to low-volume centers (LVCs). Few studies have compared these factors on a national level. The purpose of this study was to analyze nationwide outcomes for patients undergoing PD across hospital centers with different surgical volumes. METHODS: The Nationwide Readmissions Database (2010-2014) was queried for all patients who underwent open PD for pancreatic carcinoma. High-volume centers were defined as hospitals where 20 or more PDs were performed per year. Sociodemographic factors, readmission rates, and perioperative outcomes were compared before and after propensity score-matched analysis (PSMA) for 76 covariates including demographics, hospital factors, comorbidities, and additional diagnoses. Results were weighted for national estimates. RESULTS: A total of 19,810 patients were identified with age 66 ± 11 years. There were 6,840 (35%) cases performed at LVCs, and 12,970 (65%) at HVCs. Patient comorbidities were greater in the LVC cohort, and more PDs were performed at teaching hospitals in the HVC cohort. These discrepancies were controlled for with PSMA. Length of stay (LOS), mortality, invasive procedures, and perioperative complications were greater in LVCs when compared to HVCs before and after PSMA. Additionally, readmission rates at one year (38% vs 34%, P < .001) and readmission complications were greater in the LVC cohort. CONCLUSIONS: Pancreaticoduodenectomy is more commonly performed at HVCs, which is associated with less complications and improved outcomes compared to LVCs.

Novel Gene-Modified Mesenchymal Stem Cell Therapy Reverses Impaired Wound Healing in Ischemic Limbs.

OBJECTIVE: Here, we report a new method to increase the therapeutic potential of mesenchymal stem/stromal cells (MSCs) for ischemic wound healing. We tested biological effects of MSCs modified with E-selectin, a cell adhesion molecule capable of inducing postnatal neovascularization, on a translational murine model. BACKGROUND: Tissue loss significantly worsens the risk of extremity amputation for patients with chronic limb-threatening ischemia. MSC-based therapeutics hold major promise for wound healing and therapeutic angiogenesis, but unmodified MSCs demonstrate only modest benefits. METHODS: Bone marrow cells harvested from FVB/ROSA26Sor mTmG donor mice were transduced with E-selectin-green fluorescent protein (GFP)/AAV-DJ or GFP/AAV-DJ (control). Ischemic wounds were created via a 4 mm punch biopsy in the ipsilateral limb after femoral artery ligation in recipient FVB mice and subsequently injected with phosphate-buffered saline or 1×10 6 donor MSC GFP or MSC E-selectin-GFP . Wound closure was monitored daily for 7 postoperative days, and tissues were harvested for molecular and histologic analysis and immunofluorescence. Whole-body DiI perfusion and confocal microscopy were utilized to evaluate wound angiogenesis. RESULTS: Unmodified MSCs do not express E-selectin, and MSC E-selectin-GFP gain stronger MSC phenotype yet maintain trilineage differentiation and colony-forming capability. MSC E-selectin-GFP therapy accelerates wound healing compared with MSC GFP and phosphate-buffered saline treatment. Engrafted MSC E-selectin-GFP manifest stronger survival and viability in wounds at postoperative day 7. Ischemic wounds treated with MSC E-selectin-GFP exhibit more abundant collagen deposition and enhanced angiogenic response. CONCLUSIONS: We establish a novel method to potentiate regenerative and proangiogenic capability of MSCs by modification with E-selectin/adeno-associated virus. This innovative therapy carries the potential as a platform worthy of future clinical studies.

Primary Spontaneous Pneumothorax Outcomes in Children: A National Analysis.

OBJECTIVE: Considerable variation in primary spontaneous pneumothorax (PSP) management exists in the pediatric population. This study aims to compare nationwide outcomes of children with PSP. METHODS: The Nationwide Readmissions Database (2016 to 2018) was used to identify patients 1 to 18 years old with PSP. Trauma, secondary pneumothoraces, and elective admissions were excluded. Demographics and complications were compared among patients undergoing initial nonoperative management (NOM; observation or percutaneous drainage) or operative resection using standard statistical tests. RESULTS: A total of 3,890 patients were identified with PSP (median age, 16 [interquartile range 14 to 17] years). Most (78%) underwent NOM, of which 17% failed requiring operative resection. Of the intent-to-treat cohort, 28% failed NOM during index admission or required repeat percutaneous drainage or operative resection on readmission. Patients treated by NOM had higher 30-day and overall readmission rates compared with operative resection (all P < 0.001). Ipsilateral recurrent pneumothorax was higher in those receiving NOM (13% vs 3%, P < 0.001). Patients from the lowest median household income quartile more frequently received NOM compared with the highest income quartile (82% vs 76%) with more readmissions. CONCLUSIONS: Patients with PSP who underwent initial NOM experienced higher readmission rates than those receiving operative resection. Furthermore, socioeconomic status was associated with the utilization of nonoperative versus operative management.

Peripheral vascular bypass with cadaveric arterial allograft in a toddler with femoral mycotic aneurysm.

Mycotic aneurysms are exceedingly rare in the pediatric population. The optimal surgical treatment for children with this disease is unclear as aneurysm resection and vascular reconstruction are uncommonly performed in young children. We present a unique case of a 21-month-old child with a complex cardiac history who presented with limb ischemia and was discovered to have thrombosis of the common femoral and superficial femoral artery. Groin exploration revealed a left common femoral and superficial femoral artery mycotic aneurysm that was successfully repaired with excision of the mycotic aneurysm, external iliac to profunda femoral artery vascular bypass using cryopreserved arterial allograft and femoral vein reconstruction. This case demonstrates successful vascular reconstruction can be performed in a young child with an Aspergillus mycotic aneurysm using cadaveric arterial allograft.

Management of Recurrent Sigmoid Volvulus in the Pediatric Population.

Sigmoid volvulus is a rare etiology of bowel obstruction in the pediatric population that can be easily misdiagnosed, leading to delayed treatment and potential complications. Given that sigmoid volvulus is a common cause of bowel obstruction in the adult population and the significant lack of literature on its management in children, treatment strategies for pediatric patients often follow standardized protocols for adults. We report the case of a 15-year-old boy who presented with recurrent episodes of sigmoid volvulus over a 1-month period. Computed tomography demonstrated a sigmoid volvulus without evidence of ischemia or bowel infarction. Colonoscopy demonstrated a descending megacolon, and bowel transit studies demonstrated normal transit time. Acute episodes were managed conservatively with colonoscopic decompression. After a complete study, laparoscopic sigmoidectomy was performed. This work demonstrates the importance of early recognition and treatment of sigmoid volvulus in the pediatric population to limit recurrent episodes.

Outcomes After Ladd Procedures for Intestinal Malrotation in Newborns with Heterotaxy Syndrome.

PURPOSE: Intestinal malrotation may be asymptomatic in patients with heterotaxy syndrome (HS), and whether these newborns benefit from prophylactic Ladd procedures is unknown. This study sought to uncover nationwide outcomes of newborns with HS receiving Ladd procedures. METHODS: Newborns with malrotation were identified from the Nationwide Readmission Database (2010-2014) and stratified into those with and without HS utilizing ICD-9CM codes for situs inversus (759.3), asplenia or polysplenia (759.0), and/or dextrocardia (746.87). Outcomes were analyzed using standard statistical tests. RESULTS: 4797 newborns with malrotation were identified, of which 16% had HS. Ladd procedures were performed in 70% overall and more common in those without heterotaxy (73% vs. 56% HS). Ladd procedures in newborns with heterotaxy were associated with higher complications compared to those without HS including surgical site reopening (8% vs. 1%), sepsis (9% vs. 2%), infections (19% vs. 11%), venous thrombosis (9% vs. 1%), and prolonged mechanical ventilation (39% vs. 22%), all p < 0.001. HS newborns were less frequently readmitted with bowel obstructions (0% vs. 4% without HS, p < 0.001) with no readmissions for volvulus in either group. CONCLUSION: Ladd procedures in newborns with heterotaxy were associated with increased complications and cost without differences in rates of volvulus and bowel obstruction on readmission. TYPE OF STUDY: Retrospective Comparative. LEVEL OF EVIDENCE: III.

Nationwide Outcomes of Immediate Versus Staged Surgery for Newborns with Rectosigmoid Hirschsprung Disease.

PURPOSE: Debate exists on whether patients with Hirschsprung Disease (HD) should undergo immediate resection during their newborn hospitalization or undergo a staged procedure. This study sought to compare postoperative outcomes among newborns receiving immediate versus staged surgery for rectosigmoid HD. METHODS: The Nationwide Readmission Database was queried (2016-2018) for newborns with HD who underwent surgical resection during their newborn hospitalization (immediate) versus planned readmission (staged). Those who did not receive rectal biopsy or had long-segment or total colonic HD were excluded. A propensity score-matched analysis (PSMA) of patients receiving either surgery was constructed utilizing >70 comorbidities. Outcomes were analyzed using standard statistical tests. RESULTS: 1,048 newborns with HD were identified (56% immediate vs. 44% staged). Staged resection was associated with higher total hospitalization cost ($56,642 vs. $50,166 immediate), p = 0.014. After PSMA, the staged cohort was more likely to require home healthcare at discharge and experience unplanned readmission (40% vs. 23%). These patients experienced more gastrointestinal complications (40% vs. 22%) on readmission, especially Hirschsprung-associated enterocolitis (35% vs. 20%). CONCLUSION: Newborns receiving staged procedures for HD experience higher rates of unplanned readmission complications and incur higher hospitalization costs. This information should be utilized to defray healthcare utilization costs for newborns with HD. TYPE OF STUDY: Retrospective Comparative. LEVEL OF EVIDENCE: III.

Mesenchymal stem cell-based therapy for non-healing wounds due to chronic limb-threatening ischemia: A review of preclinical and clinical studies.

Progressive peripheral arterial disease (PAD) can result in chronic limb-threatening ischemia (CLTI) characterized by clinical complications including rest pain, gangrene and tissue loss. These complications can propagate even more precipitously in the setting of common concomitant diseases in patients with CLTI such as diabetes mellitus (DM). CLTI ulcers are cutaneous, non-healing wounds that persist due to the reduced perfusion and dysfunctional neovascularization associated with severe PAD. Existing therapies for CLTI are primarily limited to anatomic revascularization and medical management of contributing factors such as atherosclerosis and glycemic control. However, many patients fail these treatment strategies and are considered "no-option," thereby requiring extremity amputation, particularly if non-healing wounds become infected or fulminant gangrene develops. Given the high economic burden imposed on patients, decreased quality of life, and poor survival of no-option CLTI patients, regenerative therapies aimed at neovascularization to improve wound healing and limb salvage hold significant promise. Cell-based therapy, specifically utilizing mesenchymal stem/stromal cells (MSCs), is one such regenerative strategy to stimulate therapeutic angiogenesis and tissue regeneration. Although previous reviews have focused primarily on revascularization outcomes after MSC treatments of CLTI with less attention given to their effects on wound healing, here we review advances in pre-clinical and clinical studies related to specific effects of MSC-based therapeutics upon ischemic non-healing wounds associated with CLTI.

Underutilization of laparoscopy for ovarian surgeries in the pediatric population: A nationwide analysis.

PURPOSE: Oophorectomy and ovarian detorsion are some of the most frequent operations performed in the female pediatric population. Despite the advent of laparoscopy, many surgeons continue to utilize open surgical approaches in these patients. This study sought to compare nationwide trends and postoperative outcomes in laparoscopic and open ovarian operations in the pediatric population. METHODS: Females less than 21 years old who underwent ovarian operations (oophorectomy, detorsion, and/or drainage) from 2016 to 2017 were identified from the Nationwide Readmissions Database. Patients were stratified by surgical approach (laparoscopic or open). Hospital characteristics and outcomes were compared using standard statistical tests. RESULTS: There were 13,202 females (age 17 [14-20] years) who underwent open (59%) or laparoscopic (41%) ovarian operations. The most common indications for surgery were ovarian mass (48%), cyst (36%), and/or torsion (19%) for which oophorectomy (88%), detorsion (26%), and drainage (13%) were performed most frequently. The open approach was utilized more frequently for oophorectomy (95% vs. 77% laparoscopic) and detorsion (33% vs. 16% laparoscopic), both p < 0.001. A greater proportion of laparoscopic procedures were performed at large (67% vs. 61% open), teaching (82% vs. 76% open) hospitals in patients with private insurance (47% vs. 42% open), all p < 0.001. Patients undergoing open procedures had significantly higher index length of stay (LOS) and rates of wound infections. Thirty-day and overall readmission rates, as well as overall readmission costs, were higher in patients who received open surgeries. CONCLUSIONS: Despite fewer overall complications, decreased cost, fewer readmissions, and shorter LOS, laparoscopic approaches are underutilized for pediatric ovarian procedures. TYPE OF STUDY: Retrospective Comparative. LEVEL OF EVIDENCE: Level III.

Nationwide outcomes of newborns with rectosigmoid versus long-segment Hirschsprung disease.

PURPOSE: Hirschsprung Disease (HD) is a common congenital intestinal disorder. While aganglionosis most commonly affects the rectosigmoid colon (rectosigmoid HD), outcomes for patients in which aganglionosis extends to more proximal segments (long-segment HD) remain understudied. This study sought to compare postoperative outcomes among newborns with rectosigmoid and long-segment HD. METHODS: The Nationwide Readmission Database was queried from 2016 to 2018 for newborns with HD. Newborns were stratified into those with rectosigmoid or long-segment HD. Those who received no rectal biopsy or pull-through procedure during their newborn hospitalization were excluded. A propensity score-matched analysis (PSMA) of newborns with either type of HD was constructed utilizing 17 covariates including demographics, comorbidities, and congenital-perinatal conditions. RESULTS: There were 1280 newborns identified with HD (82% rectosigmoid HD, 18% long-segment HD). Patients with rectosigmoid HD had higher rates of laparoscopic resections (35% vs. 12%) and less frequently received a concomitant ostomy (14% vs. 84%), both p < 0.001. Patients with long-segment HD were more likely to have a delayed diagnosis (12% vs. 5%) and require multiple bowel operations (19% vs. 4%), both p < 0.001. They experienced higher rates of complications, including small bowel obstructions (10% vs. 1%), infections (45% vs. 20%), and Hirschsprung-associated enterocolitis (11% vs. 5%), all p < 0.001. After PSMA, newborns with long-segment HD were found to have a longer length of stay and higher hospitalization costs. CONCLUSION: Newborns with long-segment HD experience significant delays in diagnosis, surgery, and complications compared to those with rectosigmoid HD. This information should be utilized to improve healthcare delivery for this patient population. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: III.