Amyand Hernia: As Seen on Point-of-Care Emergency Ultrasound.

ABSTRACT: Amyand hernia is a rare type of inguinal hernia defined by the presence of the appendix in the inguinal hernia sac. Clinical diagnosis of Amyand hernia can be challenging because this diagnosis is typically made intraoperatively, often as an incidental finding. Preoperative diagnosis by computed tomography and radiology ultrasound has previously been reported; however, there exists no reports of the diagnosis being made by point-of-care ultrasound. We present a case of Amyand hernia visible on point-of-care ultrasound performed by a pediatric emergency medicine physician.

Optimizing Duration of Empiric Management of Suspected Central Line-Associated Bloodstream Infections in Pediatric Patients with Intestinal Failure.

OBJECTIVES: To assess whether a 24-hour length of hospitalization and empiric antibiotic therapy to exclude central line-associated bloodstream infection (CLABSI) in children with intestinal failure is potentially as safe as 48 hours, which is the duration most commonly used but not evidence based. STUDY DESIGN: A prospective single-institution observational cohort study was conducted among pediatric patients with intestinal failure from July 1, 2015, through June 30, 2018, to identify episodes of suspected CLABSI. The primary end point was time from blood sampling to positive blood culture. Secondary end points included presenting symptoms, laboratory test results, responses to a parent/legal guardian-completed symptom survey, length of inpatient stay, costs, and charges. RESULTS: Seventy-three patients with intestinal failure receiving nutritional support via central venous catheters enrolled; 35 were hospitalized with suspected CLABSI at least once during the study. There were 49 positive blood cultures confirming CLABSI in 128 episodes (38%). The median time from blood sampling to positive culture was 11.1 hours. The probability of a blood culture becoming positive after 24 hours was 2.3%. Elevated C-reactive protein and neutrophil predominance in white blood cell count were associated with positive blood cultures. Estimated cost savings by transitioning from a 48-hour to a 24-hour admission to rule-out CLABSI was $4639 per admission. CONCLUSIONS: A 24-hour duration of empiric management to exclude CLABSI may be appropriate for patients with negative blood cultures and no clinically concerning signs. A multi-institutional study would more robustly differentiate patients safe for discharge after 24 hours from those who warrant longer empiric treatment.

Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy.

Children with hypoplastic lung diseases, such as congenital diaphragmatic hernia, can require life support via extracorporeal membrane oxygenation and systemic anticoagulation, usually in the form of heparin. The role of heparin in angiogenesis and organ growth is inconclusive, with conflicting data reported in the literature. This study aimed to investigate the effects of heparin on lung growth in a model of compensatory lung growth (CLG). Compared to the absence of heparin, treatment with heparin decreased the vascular endothelial growth factor (VEGF)-mediated activation of VEGFR2 and mitogenic effect on human lung microvascular endothelial cells in vitro. Compared to non-heparinized controls, heparinized mice demonstrated impaired pulmonary mechanics, decreased respiratory volumes and flows, and reduced activity levels after left pneumonectomy. They also had lower lung volume, pulmonary septal surface area and alveolar density on morphometric analyses. Lungs of heparinized mice displayed decreased phosphorylation of VEGFR2 compared to the control group, with consequential downstream reduction in markers of cellular proliferation and survival. The use of bivalirudin, an alternative anticoagulant that does not interact with VEGF, preserved lung growth and pulmonary mechanics. These results demonstrated that heparin impairs CLG by reducing VEGFR2 activation. These findings raise concern for the clinical use of heparin in the setting of organ growth or regeneration.

Fueling the FIRES: Hemophagocytic lymphohistiocytosis in febrile infection-related epilepsy syndrome.

OBJECTIVES: Although secondary hemophagocytic lymphohistiocytosis (HLH) has been reported in children with critical illness of various etiologies, it has not been reported in patients with febrile infection-related epilepsy syndrome (FIRES). We describe a series of patients with concurrent HLH and FIRES in an effort to establish common pathophysiologic abnormalities. METHODS: Five patients with FIRES who were assessed for HLH were identified from a neurocritical care database. All were previously healthy and had extensive diagnostic testing. All had clinical deterioration with multiorgan dysfunction prompting HLH screening 20-29 days after hospitalization. Markers for inflammatory dysregulation were assessed in cerebrospinal fluid (CSF) and serum at various time points. Outcomes were assessed 6 months after presentation. RESULTS: Three patients met clinical criteria for secondary HLH. Elevation of specific cytokines/chemokines was variable. CSF neopterin, high mobility group box 1 (HMGB1), and C-X-C motif chemokine ligand 8 (CXCL8) were significantly elevated in all. Interleukin-1ß (IL-1ß) and IL-18 were not elevated in any of the samples. Treatment and outcomes were variable. SIGNIFICANCE: We describe 3 patients with HLH and FIRES. The co-occurrence of these 2 rare disorders suggests the possibility of a common immune dysregulation phenotype prolonging epileptogenesis. HLH screening in critically ill patients with FIRES may yield a broader understanding of shared inflammatory processes.

Vascular endothelial growth factor accelerates compensatory lung growth by increasing the alveolar units.

BackgroundDeficiency of vascular endothelial growth factor (VEGF) is associated with hypoplastic lung diseases, such as congenital diaphragmatic hernia. Provision of VEGF has been demonstrated to be beneficial in hyperoxia-induced bronchopulmonary dysplasia, and hence could induce lung growth and improve the outcome in hypoplastic lung diseases. We aimed to determine the effects of exogenous VEGF in a rodent model of compensatory lung growth after left pneumonectomy.MethodsEight-to-ten-week-old C57Bl6 male mice underwent left pneumonectomy, followed by daily intra-peritoneal injections of saline or VEGF (0.5 mg/kg). Lung volume measurement, pulmonary function tests, and morphometric analyses were performed on post-operative day (POD) 4 and 10. The pulmonary expression of angiogenic factors was analyzed by quantitative polymerase chain reaction and western blot.ResultsLung volume on POD 4 was higher in the VEGF-treated mice (P=0.03). On morphometric analyses, VEGF increased the parenchymal volume (P=0.001), alveolar volume (P=0.0003), and alveolar number (P<0.0001) on POD 4. The VEGF group displayed higher levels of phosphorylated-VEGFR2/VEGFR2 (P=0.03) and epidermal growth factor (EGF) messenger RNA (P=0.01).ConclusionVEGF accelerated the compensatory lung growth in mice, by increasing the alveolar units. These changes may be mediated by VEGFR2 and EGF-dependent mechanisms.

Technique and perioperative management of left pneumonectomy in neonatal piglets.

BACKGROUND: Although commonly performed in adult swine, unilateral pneumonectomy in piglets requires significant modifications in the surgical approach and perioperative care because of their smaller size and limited physiological reserve. METHODS: Nineteen neonatal piglets underwent a left pneumonectomy. They were allowed 5-7 d of preoperative acclimation and nutritional optimization. Preoperative weight gain and laboratory values were obtained before the time of surgery. A "ventro-cranial" approach is adopted where components of the pulmonary hilum were sequentially identified and ligated, starting from the most ventral and cranial structure, the superior pulmonary vein. The principle of gentle ventilation was followed throughout the entire operation. RESULTS: The median age of the piglets at the time of surgery was 12 (10-12) d. The median preoperative weight gain and albumin level were 20% (16-26%) and 2.3 (2.1-2.4) g/dL, respectively. The median operative time was 59 (50-70) min. Five of the first nine piglets died from complications, two from poor preoperative nutritional optimization (both with <10% weight gain and 2 g/dL for albumin), one from an intubation complication, one from intra-operative bleeding, and one in the postoperative period from a ruptured bulla. No mortality occurred for the next 10 cases. CONCLUSIONS: Successful outcomes for unilateral pneumonectomy in piglets require special attention to preoperative nutritional optimization, gentle ventilation, and meticulous surgical dissection. Preoperative weight gain and albumin levels should be used to identify appropriate surgical candidates. The "ventro-cranial" approach allows for a technically straightforward completion of the procedure.

Epidemiology and Prognosis of Primary Periocular Sweat Gland Carcinomas.

PURPOSE: To characterize the clinical presentation, management, and outcomes of patients with sweat gland carcinoma of the periocular region. To review the pathologic classification scheme, compare the clinical behavior between subtypes, and discuss treatment recommendations for periocular sweat gland carcinomas. METHODS: Retrospective study from 2 tertiary centers, which are part of the American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database. RESULTS: Twenty-two patients, of whom 13 (59%) were female, were included in the study. The median age was 69 years. The median follow-up time was 23 months. Twenty (91%) patients had lesions that were slow growing and were present for several months to years before diagnosis. Presentation was varied, and pathology included mucinous carcinoma (7; 32%), microcystic adnexal carcinoma (4; 18%), endocrine mucin-producing sweat gland carcinoma (4; 18%), eccrine carcinoma (2; 9%), apocrine carcinoma (2; 9%), poorly differential adnexal carcinoma (2; 9%), and hidroadenocarcinoma (1; 5%). Microcystic adnexal carcinoma tended to present with the largest tumor dimension (range: 25-32 mm) and mucinous carcinoma the smallest (range: 5-13 mm). Treatments included Mohs micrographic excision in 10 patients (45.5%), wide local excision in 10 patients (45.5%), and orbital exenteration in 2 patients (9%). No lesions ≤T2b (by AJCC 7th edition classification for eyelid carcinomas) had local recurrence or nodal metastasis. No patients had distant metastasis. CONCLUSIONS: Sweat gland carcinomas tend to grow slowly and be present for several months to years before diagnosis. Overall, microcystic adnexal carcinoma subtype showed more aggressive clinical behavior than mucinous subtypes. Eyelid carcinomas AJCC category T2b or less were associated with better outcomes.

Orbital sarcomas in retinoblastoma patients: recommendations for screening and treatment guidelines.

PURPOSE OF REVIEW: Retinoblastoma is the most common primary ocular malignancy in children. Although currently retinoblastoma has an excellent survival rate in developed countries, hereditary retinoblastoma survivors as well as those with a history of radiation therapy as children are at an increased risk for second primary tumors (SPTs), and specifically, for orbital sarcomas. Despite the known increased risk for SPTs in retinoblastoma survivors and the associated morbidity and mortality, no screening or treatment guidelines exist. RECENT FINDINGS: Understanding of retinoblastoma tumorigenesis and genomic expression has expanded significantly, and treatment has evolved with a shift away from radiotherapy. Until the last two decades, however, radiation was the therapy of choice for patients with bilateral disease. Because both hereditary retinoblastoma and radiation are independent risk factors for the development of SPTs such as sarcomas and these SPTs are often fatal, appropriate surveillance for retinoblastoma survivors is crucial. SUMMARY: As a result of the excellent survival rates for retinoblastoma patients, it is important to: recognize the risk of sarcoma, particularly in patients with hereditary retinoblastoma and/or prior radiation therapy; establish a screening protocol, such as the one proposed, to maximize early detection; and discuss and develop treatment guidelines for high-risk patients. Future directions of research for these patients will involve the development of molecularly targeted agents and the use of proton radiotherapy.

The Quantitated Internal Suture Browpexy: Comparison of Two Brow-Lifting Techniques in Patients Undergoing Upper Blepharoplasty.

PURPOSE: To describe and evaluate 1) the quantitated internal suture browpexy (ISB), which combines the advantages of a browpexy and "brassiere suture," 2) the endoscopic Endotine browplasty, and 3) to compare these two techniques in patients undergoing simultaneous upper blepharoplasty. METHODS: Retrospective review of patients undergoing bilateral upper blepharoplasty alone, bilateral ISB with upper blepharoplasty, and bilateral Endotine (MicroAire, Charlottesville, VA, U.S.A.) browplasty with upper blepharoplasty by one surgeon was performed. ImageJ 1.47v software (Wayne Rasband, National Institutes of Health, Bethesda, MD, U.S.A.) and standardized photographs were used to measure pre- and postoperative brow position at three positions (central, medial, lateral). Statistical analysis was performed using Sigmaplot version 12.5 for Windows (Systat Software, Inc., San Jose, CA, U.S.A.). RESULTS: Thirty-three patients undergoing ISB with blepharoplasty, 33 undergoing Endotine browplasty with blepharoplasty, and 30 patients undergoing blepharoplasty alone were included. The 3 groups were matched for age and gender. Patients undergoing upper blepharoplasty alone showed statistically significant brow descent at all three brow positions (mean: -1.7 mm [p ≤ 0.04]). The quantitated ISB prevented brow descent but provided minimal brow elevation (mean lateral elevation: right eye (OD) +1.3 mm [p = 0.03]; OS +0.9 mm [p = 0.08]). Endotine browplasty with upper blepharoplasty provided significant brow elevation at all brow positions, particularly laterally (OD +4.0 mm [p < 0.001]; OS +3.5 mm [p < 0.001]). There were no complications. CONCLUSIONS: Upper blepharoplasty alone is associated with brow descent; performing ISB simultaneously effectively prevents this descent. Endotine browplasty with upper blepharoplasty achieves significant brow elevation. Quantitation of the browpexy allows reproducible placement of the suture thereby producing consistent and symmetrical results.

Lateral Canthal Position Following Lateral Orbitotomy and the Influence of Ocular Proptosis.

PURPOSE: Anecdotal evidence suggests that detachment of the lateral canthal tendon during lateral orbitotomy results in shortening of the horizontal palpebral aperture (HPA) and rounding of the lateral canthal angle (LCA). This study investigated the change in HPA and LCA following lateral orbitotomy and the effect of proptosis on the HPA. METHODS: Retrospective, single surgeon, review of all cases undergoing lateral orbitotomy, comprising of a canthotomy and cantholysis and reconstruction of the lateral canthus using a single suture. The HPA and lateral canthal height (LCH) were measured on pre- and postoperative photographs using ImageJ software. Changes in the LCA and degree of proptosis were also investigated. Exclusion criteria included previous eyelid surgery, acute trauma, and less than 6 months' follow up. RESULTS: There were 41 cases of lateral orbitotomy in 27 patients, 67% female, average age 51 years. Twenty patients had thyroid eye disease of which 14 underwent bilateral surgery; the other 7 patients had a variety of orbital pathologies. Thirteen patients underwent unilateral orbitotomy with the contralateral eye serving as a control. Average follow up was 23 months. Overall, the HPA and proptosis were reduced by 0.6 mm (p = 0.143) and 3.4 mm (p < 0.001), respectively. A 0.2-mm reduction in HPA was observed for every 1-mm reduction in proptosis. A difference in post-orbitotomy HPA was observed between cases and their matched controls (p = 0.016). No rounding of the LCA or significant change in LCH was observed following lateral orbitotomy. CONCLUSIONS: The described technique of lateral orbitotomy and simple reconstruction do not appear to cause lateral canthal drift or rounding. There was no significant change in HPA or LCH. The degree of change of proptosis does appear to influence the change of HPA.

In vitro quantification of specific microRNA using molecular beacons.

MicroRNAs (miRNAs), a class of non-coding RNAs, have become a major focus of molecular biology research because of their diverse genomic origin and ability to regulate an array of cellular processes. Although the biological functions of miRNA are yet to be fully understood, tissue levels of specific miRNAs have been shown to correlate with pathological development of disease. Here, we demonstrate that molecular beacons can readily distinguish mature- and pre-miRNAs, and reliably quantify miRNA expression. We found that molecular beacons with DNA, RNA and combined locked nucleic acid (LNA)-DNA backbones can all detect miRNAs of low (<1 nM) concentrations in vitro, with RNA beacons having the highest detection sensitivity. Furthermore, we found that molecular beacons have the potential to distinguish miRNAs that have slight variations in their nucleotide sequence. These results suggest that the molecular beacon-based approach to assess miRNA expression and distinguish mature and precursor miRNA species is quite robust, and has the promise for assessing miRNA levels in biological samples.

The hybrid lid crease approach to address lateral frontal sinus disease with orbital extension.

OBJECTIVE: This study aimed to describe the hybrid lid crease approach in conjunction with functional endoscopic sinus surgery (FESS) for lateral frontal sinus disease with orbital extension. STUDY DESIGN: Retrospective case review. METHODS: Patients undergoing hybrid lid crease approach with FESS for frontal sinus disease were reviewed retrospectively. Surgical indications consisted of inverting papilloma with extension into the frontal sinus (n = 1) and frontal sinus mucocele (n = 2). Inclusion criteria included presence of disease in the lateral frontal sinus with extension into the orbital space and erosion of the superior orbital rim. Preoperative and postoperative parameters included complete ophthalmologic exam, endoscopic exam, and computed tomography scan. RESULTS: We were able to access the frontal sinus and orbit in all 3 cases and address sinus pathology of the lateral frontal sinus and orbit using the lid crease approach with FESS. All patients had improvement in ophthalmologic symptoms and interval disease resolution and were satisfied with their postoperative lid crease incision. CONCLUSION: The lid crease approach offers direct access to the frontal sinus with minimal dissection through a well-hidden incision. In our case series of lateral frontal sinus pathology with orbital extension, the hybrid lid crease approach with FESS allowed complete eradication of disease without recurrence.

Keloidal scarring in hard palate grafts.

Hard palate grafts are a commonly accepted treatment for lower eyelid retraction and are typically associated with low complication rates. The authors present a case of bilateral keloidal scarring within hard palate grafts requiring surgical excision. A 72-year-old woman who had undergone bilateral hard palate grafts to her lower eyelids for lower eyelid retraction was referred for the evaluation of ocular irritation. She was diagnosed with bilateral hypertrophy of the grafts with secondary entropion. The grafts were excised; the pathology was consistent with keloidal scarring. To the authors' knowledge, there is no previously reported case of bilateral keloidal scarring in normal donor tissue, which required excision of the hard palate grafts. It is important for oculoplastic surgeons to be aware of this potential complication when considering, discussing, and consenting patients for eyelid reconstruction with hard palate grafting.

Eyelid procedures in patients who have undergone Boston keratoprosthesis surgery.

PURPOSE: Artificial corneas or keratoprostheses such as the Boston keratoprosthesis (KPro) are being used more frequently to provide a clear corneal window in patients with severe corneal disease. A significant percentage of patients who undergo Boston KPro implantation require subsequent eyelid surgery. However, few articles in peer-reviewed literature evaluate the indication and outcome of eyelid procedures after Boston KPro implantation. This study examines the frequency, nature, and outcomes of oculoplastic procedures in patients with Boston KPro implantation. METHODS: A retrospective chart review was conducted of all KPro-1 procedures performed at the University of Illinois at Chicago between December 2006 and September 2010 and all KPro-1 and KPro-2 procedures performed at the University of Iowa between December 2008 and October 2010. RESULTS: One hundred and twenty eyes underwent Boston KPro-1 procedures, and 2 eyes underwent Boston KPro-2 procedures. Twenty-one (17.2%) of the 122 eyes required subsequent eyelid alterations. Chemical burn was the most common preoperative corneal diagnosis (8 of 21; 38.1%). A variety of oculoplastic procedures were performed; the most common procedure was a permanent lateral tarsorrhaphy. Seventeen (81.0%) of 21 KPro eyes that underwent oculoplastic procedures maintained the KPro at an average of 12.4 months of follow up. CONCLUSIONS: A significant number of patients with Boston KPros require subsequent eyelid surgery. With limited existing literature and increasing popularity for using Boston KPros to treat severe corneal disease, it is essential for oculoplastic and corneal surgeons to understand the need for eyelid alterations in these patients and the surgical intricacies surrounding these cases.

Methotrexate as an alternative treatment for orbital angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign disorder that presents as solitary or multiple nodules in the dermis or subcutaneous tissue. Orbital ALHE has been reported on occasion. We report a case of orbital ALHE which was refractory to systemic steroids but effectively treated with low-dose subcutaneous methotrexate. To our knowledge, this is the first reported case of methotrexate as a successful treatment for refractory ALHE.

A Mixed-Method Process Evaluation of an Intervention to Improve Social Reactions to Disclosures of Sexual Assault and Partner Abuse.

Because of the high rates and deleterious consequences of sexual assault (SA) and partner abuse (PA) on college campuses, there is a proliferation of programming to both prevent and respond to these issues. Most research to date, however, presents outcome evaluation data on these programs and neglects to present process evaluation data which are critical for program refinement and dissemination. The purpose of this study was to present process evaluation data (i.e., acceptability and feasibility) specific to a program that endeavored to increase positive and decrease negative social reactions from disclosure recipients to individuals disclosing SA and PA. Participants were 303 students who completed the program and participated in postintervention surveys and a subset of students (n = 18) who completed exit interviews. Results documented that the program was both feasible and acceptable, as evidenced by high satisfaction ratings. Important suggestions were also provided for how to improve the program, such as reducing repetition and making scenarios more realistic. Finally, participants who reported higher program engagement and more program usage generally reported more intentions to provide positive social reactions, less intentions to provide negative social reactions, and less actual negative social reactions. This information is useful not only for adapting the current program discussed herein but also for program developers and preventionists wishing to create similar programming to effectively prevent and improve response to SA and PA.

Clinical variation in surveillance and management of Barrett's esophagus: A cross-sectional study of gastroenterologists and gastrointestinal surgeons.

Appropriate surveillance and treatment of Barrett's esophagus (BE) is vital to prevent disease progression and decrease esophageal adenocarcinoma (EAC)-related mortality. We sought to determine the variation in BE care and identify improvement opportunities. 275 physicians (113 general gastroenterologists, 128 interventional gastroenterologists, 34 gastrointestinal surgeons) cared for 3 simulated patients, one each from 3 BE clinical scenarios: non-dysplastic BE (NDBE), BE indefinite for dysplasia (IND), and BE with low grade dysplasia (LGD), and care scores were measured against societal guidelines. Overall quality-of-care scores ranged from 17% to 85% with mean of 47.9% ± 11.8% for NDBE, 50.8% ± 11.7% for IND, and 52.7% ± 12.2% for LGD. Participants appropriately determined risk of progression 20.3% of the time: 14.4% for NDBE cases, 19.9% for LGD cases, and 26.8% for IND cases (P = .001). Treatment and follow-up care scores averaged 12.9% ± 17.5% overall. For the LGD cases, guideline-recommended twice-daily PPI treatment was ordered only 24.7% of the time. Guideline-based follow-up endoscopic surveillance was done in only 27.7% of NDBE cases and 32.7% of IND cases. For the LGD cases, 45.4% ordered endoscopic eradication therapy while 25.1% chose annual endoscopic surveillance. Finally, participants provided counseling on lifestyle modifications in just 20% of cases. Overall care of patients diagnosed with BE varied widely and showed room for improvement. Specific opportunities for improvement were adherence to guideline recommended surveillance intervals, patient counseling, and treatment selection for LGD. Physicians would potentially benefit from additional BE education, endoscopic advances, and better methods for risk stratification.

Common carotid artery imaging after vessel sparing decannulation from Extracorporeal Membrane Oxygenation (ECMO) support.

INTRODUCTION: In 2008, Children's National Hospital adopted a simple vessel sparing technique (VST) for neck extra corporeal membrane (ECMO) cannulation/decannulation that is technically simple and reproducible. In this study, we review a cohort of patients decannulated from venous-arterial (VA) ECMO using a VST with the goal of understanding flow dynamics and anatomic changes of the common carotid artery (CCA) after repair with a VST. METHODS: Patients supported with ECMO at a single, tertiary care center between 2008 and 2019 were identified. Patients were included in the analysis if they survived VA ECMO including VST decannulation and neck vessel imaging was completed with either magnetic resonance angiogram (MRA) or computerized tomography angiogram (CTA) post decannulation. The right CCA was assessed for patency and arteriopathy. Complications and feasibility of repeat ECMO cannulation via the neck vessels were also investigated. RESULTS: Three hundred and nineteen patients were identified as having received ECMO support in either the PICU or CICU between 2008 and 2019, of which 76 survived VA ECMO support via neck cannulation. Neck vessel imaging was obtained in 21 patients. Ten had imaging demonstrating a normal right CCA. The CCA was occluded in 3 and stenotic in 5. Vessel wall defects were present in 4. No definitive complication was associated with any of the arterial abnormalities. Repeat right CCA cannulation was achieved in 6/7 patients who needed additional VA ECMO support. CONCLUSIONS: Repair of the right CCA with a simple VST can be achieved safely and consistently during VA ECMO support in pediatric patients. Vascular imaging of the right CCA was normal in almost half and repeat cannulation was achieved in most when pursued. Stenosis and vessel wall defects were common, thus neck vessel imaging post decannulation may be warranted for all patients with a right CCA repair after ECMO support.

MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity.

Mechanical forces associated with blood flow play an important role in regulating vascular signaling and gene expression in endothelial cells (ECs). MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. miRNAs are known to have an important role in modulating EC biology, but their expression and functions in cells subjected to shear stress conditions are unknown. We sought to determine the miRNA expression profile in human ECs subjected to unidirectional shear stress and define the role of miR-21 in shear stress-induced changes in EC function. TLDA array and qRT-PCR analysis performed on HUVECs exposed to prolonged unidirectional shear stress (USS, 24h, 15 dynes/cm(2)) identified 13 miRNAs whose expression was significantly upregulated (p<0.05). The miRNA with the greatest change was miR-21; it was increased 5.2-fold (p=0.002) in USS-treated versus control cells. Western analysis demonstrated that PTEN, a known target of miR-21, was downregulated in HUVECs exposed to USS or transfected with pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and increased eNOS phosphorylation and nitric oxide (NO(*)) production. These data demonstrate that shear stress forces regulate the expression of miRNAs in ECs, and that miR-21 influences endothelial biology by decreasing apoptosis and activating the NO(*) pathway. These studies advance our understanding of the mechanisms by which shear stress forces modulate vascular homeostasis.