Utility of a Benchmarking Report for Balancing Infection Prevention and Antimicrobial Stewardship in Children with Complicated Appendicitis.

OBJECTIVE: To develop a severity-adjusted, hospital-level benchmarking comparative performance report for postoperative organ space infection and antibiotic utilization in children with complicated appendicitis. BACKGROUND: No benchmarking data exist to aid hospitals in identifying and prioritizing opportunities for infection prevention or antimicrobial stewardship in children with complicated appendicitis. METHODS: This was a multicenter cohort study using NSQIP-Pediatric data from 16 hospitals participating in a regional research consortium, augmented with antibiotic utilization data obtained through supplemental chart review. Children with complicated appendicitis who underwent appendectomy from 07/01/2015 to 06/30/2020 were included. Thirty-day postoperative OSI rates and cumulative antibiotic utilization were compared between hospitals using observed-to-expected (O/E) ratios after adjusting for disease severity using mixed effects models. Hospitals were considered outliers if the 95% confidence interval for O/E ratios did not include 1.0. RESULTS: 1790 patients were included. Overall, the OSI rate was 15.6% (hospital range: 2.6-39.4%) and median cumulative antibiotic utilization was 9.0 days (range: 3.0-13.0). Across hospitals, adjusted O/E ratios ranged 5.7-fold for OSI (0.49-2.80, P=0.03) and 2.4-fold for antibiotic utilization (0.59-1.45, P<0.01). Three (19%) hospitals were outliers for OSI (1 high and 2 low performers), and eight (50%) were outliers for antibiotic utilization (5 high and 3 low utilizers). Ten (63%) hospitals were identified as outliers in one or both measures. CONCLUSIONS: A comparative performance benchmarking report may help hospitals identify and prioritize quality improvement opportunities for infection prevention and antimicrobial stewardship, as well as identify exemplar performers for dissemination of best practices.

Postoperative Antibiotics, Outcomes, and Resource Use in Children With Gangrenous Appendicitis.

Importance: Gangrenous, suppurative, and exudative (GSE) findings have been associated with increased surgical site infection (SSI) risk and resource use in children with nonperforated appendicitis. Establishing the role for postoperative antibiotics may have important implications for infection prevention and antimicrobial stewardship. Objective: To compare SSI rates in children with nonperforated appendicitis with GSE findings who did and did not receive postoperative antibiotics. Design, Setting, and Participants: This was a retrospective cohort study using American College of Surgeons' National Surgical Quality Improvement Program (NSQIP)-Pediatric Appendectomy Targeted data from 16 hospitals participating in a regional research consortium. NSQIP data were augmented with operative report and antibiotic use data obtained through supplemental medical record review. Children with nonperforated appendicitis with GSE findings who underwent appendectomy between July 1, 2015, and June 30, 2020, were identified using previously validated intraoperative criteria. Data were analyzed from October 2022 to July 2023. Exposure: Continuation of antibiotics after appendectomy. Main Outcomes and Measures: Rate of 30-day postoperative SSI including both incisional and organ space infections. Complementary hospital and patient-level analyses were conducted to explore the association between postoperative antibiotic use and severity-adjusted outcomes. The hospital-level analysis explored the correlation between postoperative antibiotic use and observed to expected (O/E) SSI rate ratios after adjusting for differences in disease severity (presence of gangrene and postoperative length of stay) among hospital populations. In the patient-level analysis, propensity score matching was used to balance groups on disease severity, and outcomes were compared using mixed-effects logistic regression to adjust for hospital-level clustering. Results: A total of 958 children (mean [SD] age, 10.7 [3.7] years; 567 male [59.2%]) were included in the hospital-level analysis, of which 573 (59.8%) received postoperative antibiotics. No correlation was found between hospital-level SSI O/E ratios and postoperative antibiotic use when analyzed by either overall rate of use (hospital median, 53.6%; range, 31.6%-100%; Spearman ρ = -0.10; P = .71) or by postoperative antibiotic duration (hospital median, 1 day; range, 0-7 days; Spearman ρ = -0.07; P = .79). In the propensity-matched patient-level analysis including 404 patients, children who received postoperative antibiotics had similar rates of SSI compared with children who did not receive postoperative antibiotics (3 of 202 [1.5%] vs 4 of 202 [2.0%]; odds ratio, 0.75; 95% CI, 0.16-3.39; P = .70). Conclusions and Relevance: Use of postoperative antibiotics did not improve outcomes in children with nonperforated appendicitis with gangrenous, suppurative, or exudative findings.

Use of Antipseudomonal Antibiotics is not Associated with Lower Rates of Postoperative Drainage Procedures or More Favorable Culture Profiles in Children with Complicated Appendicitis: Results from a Multicenter Regional Research Consortium.

OBJECTIVE: To compare rates of postoperative drainage and culture profiles in children with complicated appendicitis treated with the two most common antibiotic regimens with and without antipseudomonal activity (piperacillin-tazobactam [PT] and ceftriaxone with metronidazole [CM]). SUMMARY OF BACKGROUND DATA: Variation in use of antipseudomonal antibiotics has been driven by a paucity of multicenter data reporting clinically relevant, culture-based outcomes. METHODS: Retrospective cohort study of patients with complicated appendicitis (7/2015-6/2020) using NSQIP-Pediatric data from 15 hospitals participating in a regional research consortium. Operative report details, antibiotic utilization, and culture data were obtained through supplemental chart review. Rates of 30-day postoperative drainage and organism-specific culture positivity were compared between groups using mixed effects regression to adjust for clustering after propensity matching on measures of disease severity. RESULTS: 1002 children met criteria for matching (58.9% received CM and 41.1% received PT). In the matched sample of 778 patients, children treated with PT had similar rates of drainage overall (PT: 11.8%, CM: 12.1%; OR 1.44 [OR:0.71-2.94]) and higher rates of drainage associated with growth of any organism (PT: 7.7%, CM: 4.6%; OR 2.41 [95%CI:1.08-5.39]) and Escherichia coli (PT: 4.6%, CM: 1.8%; OR 3.42 [95%CI:1.07-10.92]) compared to treatment with CM. Rates were similar between groups for drainage associated with multiple organisms (PT: 2.6%, CM: 1.5%; OR 3.81 [95%CI:0.96-15.08]) and Pseudomonas (PT: 1.0%, CM: 1.3%; OR 3.42 [95%CI:0.55-21.28]). CONCLUSIONS AND RELEVANCE: Use of antipseudomonal antibiotics is not associated with lower rates of postoperative drainage procedures or more favorable culture profiles in children with complicated appendicitis.

A Social Media-Based Public Health Campaign to Reduce Indoor Tanning in High-Risk Populations.

Introduction: Indoor tanning beds cause more than 450,000 new skin cancers each year, yet their use remains common, with a global indoor tanning prevalence of 10.4%. Social media provides an opportunity for cost-effective, targeted public health messaging. We sought to direct Instagram users at high risk of indoor tanning to accurate health information about the risks of indoor tanning and to reduce indoor tanning bed use. Methods: We disseminated a public health campaign on Instagram on April 6-27, 2022 with 34 video and still-image advertisements. We had 2 target audiences at high risk of indoor tanning: women aged 18-30 years in Kentucky, Nebraska, Ohio, or Tennessee interested in indoor tanning and men aged 18-45 years in California interested in indoor tanning. To evaluate the impact of the campaign, we tracked online metrics, including website visits, and conducted an interrupted time-series analysis of foot traffic data in our target states for all tanning salons documented on SafeGraph from January 1, 2018 to 3 months after the campaign. Results: Our indoor tanning health information advertisements appeared on Instagram feeds 9.1 million times, reaching 1.06 million individuals. We received 7,004 views of our indoor tanning health information landing page (Average Time on Page of 56 seconds). We did not identify a significant impact on foot traffic data on tanning salons. Conclusions: We show the successful use of social media advertising to direct high-risk groups to online health information about indoor tanning. Future research quantifying tanning visits before and after indoor tanning interventions is needed to guide future public health efforts.

Outcomes and Resource Utilization Associated with Use of Routine Pre-Discharge White Blood Cell Count for Clinical Decision-Making in Children with Complicated Appendicitis: A Multicenter Hospital-Level Analysis.

BACKGROUND: The objective was to explore the hospital-level relationship between routine pre-discharge WBC utilization (RPD-WBC) and outcomes in children with complicated appendicitis. METHODS: Multicenter analysis of NSQIP-Pediatric data from 14 consortium hospitals augmented with RPD-WBC data. WBC were considered routine if obtained within one day of discharge in children who did not develop an organ space infection (OSI) or fever during the index admission. Hospital-level observed-to-expected ratios (O/E) for 30-day outcomes (antibiotic days, imaging utilization, healthcare days, and OSI) were calculated after adjusting for appendicitis severity and patient characteristics. Spearman correlation was used to explore the relationship between hospital-level RPD-WBC utilization and O/E's for each outcome. RESULTS: 1528 children were included. Significant variation was found across hospitals in RPD-WBC use (range: 0.7-100%; p < 0.01) and all outcomes (mean antibiotic days: 9.9 [O/E range: 0.56-1.44, p < 0.01]; imaging: 21.9% [O/E range: 0.40-2.75, p < 0.01]; mean healthcare visit days: 5.7 [O/E 0.74-1.27, p < 0.01]); OSI: 14.1% [O/E range: 0.43-3.64, p < 0.01]). No correlation was found between RPD-WBC use and antibiotic days (r = +0.14, p = 0.64), imaging (r = -0.07, p = 0.82), healthcare days (r = +0.35, p = 0.23) or OSI (r = -0.13, p = 0.65). CONCLUSIONS: Increased RPD-WBC utilization in pediatric complicated appendicitis did not correlate with improved outcomes or resource utilization at the hospital level. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Clinical Research.

Association Between Antibiotic Redosing Before Incision and Risk of Incisional Site Infection in Children With Appendicitis.

OBJECTIVE: To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis. BACKGROUND: Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing before incision. METHODS: This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from July 2016 to June 2020 who received antibiotics upon diagnosis of appendicitis between 1 and 6 hours before incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within 1 hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events. RESULTS: A total of 3533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P <0.001) and iSSI rates were similar between groups [redosed: 1.2% vs non-redosed: 1.3%; odds ratio (OR) 0.84, (95%,CI, 0.39-1.83)]. In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs nonredosed: 2.5%; OR: 0.38, (95% CI, 0.17-0.84)], but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity. CONCLUSIONS: Redosing of antibiotics within 1 hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic.

Association of Gangrenous, Suppurative, and Exudative Findings With Outcomes and Resource Utilization in Children With Nonperforated Appendicitis.

Importance: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis. Objective: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization. Design, Setting, and Participants: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study cohort comprised children (aged ≤18 years) with nonperforated appendicitis who underwent appendectomy from July 1, 2015, to June 30, 2020. Exposures: The presence of GSE findings was established through standardized, keyword-based audits of operative reports by EPSN surgeons. Interrater agreement for the presence or absence of GSE findings was evaluated in a random sample of 900 operative reports. Main Outcomes and Measures: The primary outcome was 30-day postoperative surgical site infections (incisional and organ space infections). Secondary outcomes included rates of hospital revisits, postoperative abdominal imaging, and postoperative length of stay. Multivariable mixed-effects regression was used to adjust measures of association for patient characteristics and clustering within hospitals. Results: Among 6133 children with nonperforated appendicitis, 867 (14.1%) had GSE findings identified from operative report review (hospital range, 4.2%-30.2%; P < .001). Reviewers agreed on presence or absence of GSE findings in 93.3% of cases (weighted κ, 0.89; 95% CI, 0.86-0.92). In multivariable analysis, GSE findings were associated with increased odds of any surgical site infection (4.3% vs 2.2%; odds ratio [OR], 1.91; 95% CI, 1.35-2.71; P < .001), organ space infection (2.8% vs 1.1%; OR, 2.18; 95% CI, 1.30-3.67; P = .003), postoperative imaging (5.8% vs 3.7%; OR, 1.70; 95% CI, 1.23-2.36; P = .002), and prolonged mean postoperative length of stay (1.6 vs 0.9 days; rate ratio, 1.43; 95% CI, 1.32-1.54; P < .001). Conclusions and Relevance: In children with nonperforated appendicitis, findings of gangrene, suppuration, or exudate are associated with increased surgical site infections and resource utilization. Further investigation is needed to establish the role and duration of postoperative antibiotics and inpatient management to optimize outcomes in this cohort of children.

Barriers and facilitators to mobile health and active surveillance use among older adults with skin disease.

BACKGROUND: The COVID-19 pandemic has accelerated the adoption of telemedicine, including teledermatology. Monitoring skin lesions using teledermatology may become increasingly important for several skin diseases, including low-risk skin cancers. The purpose of this study was to describe the key factors that could serve as barriers or facilitators to skin disease monitoring using mobile health technology (mHealth) in older adults. METHODS: Older adult dermatology patients 65 years or older and their caregivers who have seen a dermatologist in the last 18 months were interviewed and surveyed between December 2019 and July 2020. The purpose of these interviews was to better understand attitudes, beliefs and behaviours that could serve as barriers and facilitators to the use of mHealth and active surveillance to monitor low-risk skin cancers. RESULTS: A total of 33 interviews leading to 6022 unique excerpts yielded 8 factors, or themes, that could serve as barriers, facilitators or both to mHealth and active surveillance. We propose an integrated conceptual framework that highlights the interaction of these themes at both the patient and provider level, including care environment, support systems and personal values. DISCUSSION AND CONCLUSIONS: These preliminary findings reveal factors influencing patient acceptance of active surveillance in dermatology, such as changes to the patient-provider interaction and alignment with personal values. These factors were also found to influence adoption of mHealth interventions. Given such overlap, it is essential to address barriers and facilitators from both domains when designing a new dermatology active surveillance approach with novel mHealth technology. PATIENT OR PUBLIC CONTRIBUTION: The patients included in this study were participants during the data collection process. Members of the Stanford Healthcare and Denver Tech Dermatology health-care teams aided in the recruitment phase of the data collection process.

Characteristics and in-hospital outcomes of patients requiring aeromedical retrieval for pregnancy, compared to non-retrieved metropolitan cohorts.

BACKGROUND: Limited access to obstetrics and gynaecology (O&G) services in rural and remote Australia is believed to contribute to suboptimal birth outcomes. AIMS: To describe the characteristics of pregnancy aeromedical transfers, in-hospital outcomes, and patient access to O&G services, as compared to whole of Australia data. MATERIALS AND METHODS: We conducted a cohort study of women who required aeromedical retrieval for pregnancy-related issues between the 1 January 2015 and 31 December 2017. RESULTS: Hospital outcome data were collected on 2171 (65.2%) mothers and 2438 (100.0%) babies. The leading retrieval reason was threatened preterm labour and delivery (n = 883; 40.7%). Most patients were retrieved from rural and remote areas (n = 2224; 93.0%). Retrieved patients were significantly younger (28.0 vs 30.0 years, 95% CI 27.7-28.3), more likely to be overweight or obese (52.2% vs 45.1%, 95% CI 47.5-56.9) and to have smoked during their pregnancy (14.0% vs 9.9%, 95% CI 12.5-15.5) compared to Australian pregnant women overall. Over one-third of transferred women gave birth by Caesarean section (n = 812; 37.4%); the median gestational age at birth was 33.0 (95% CI 32.7-33.3) weeks. Early gestation is associated with low birth weights (median = 2579.5 g; 95% CI 2536.1-2622.9), neonatal resuscitation (35.4%, 95% CI 33.5-37.3), and special care nursery admission (41.2%, 95% CI 39.3-43.2). There were 42 (1.7%, 95% CI 1.2-2.2) stillbirths, which was significantly higher than seen Australia-wide (n = 6441; 0.7%). CONCLUSION: This study found that pregnant women retrieved by the Royal Flying Doctor Service were younger, with higher rates of obesity and smoking.

National Survey of Pediatric Intestinal Rehabilitation Programs in the United States.

BACKGROUND: Pediatric intestinal rehabilitation (PIR) programs are associated with improved outcomes in children with intestinal failure but remain heterogeneous nationally. This study characterizes PIR program components to aid those seeking to establish or expand a program. METHODS: Members of the Children's Hospital Association reporting a PIR program to the US News and World Report completed a 14-item questionnaire using the Qualtrics Online Survey Software. Programs were categorized as small or large (≤50 vs >50 patients) and new or established (≤10 vs >10 years). RESULTS: Seventy-one programs were identified and 61 surveys were returned for a response rate of 86%. Majority of programs had gastroenterology, surgery, nutrition, nursing, and social work services involved. Large programs (n = 34; 59%) were more likely to serve as referral centers; have greater participation by nursing, social work, and primary care; have more dedicated time by gastroenterology, surgery, nursing, nutrition, and social work; have more frequent meetings; and have various funding sources (P < .05). CONCLUSION: Critical components of a PIR program include gastroenterology, surgery, and nutrition services with strong nursing and social work support. These data document the components of modern PIR programs, though further studies on the relationship between program structure and patient outcomes are warranted.

The Impact of Pediatric Surgical Specialty Meetings: A 5-year Analysis of Presented Abstracts.

BACKGROUND: Abstracts presented at the American Academy of Pediatrics Section on Surgery (AAP) and American Pediatric Surgical Association (APSA) meetings can be taken as a reasonable representation of academic activity in pediatric surgery. We sought to assess ongoing trends in pediatric surgical research by analyzing the scientific content of each association's yearly meeting. METHODS: Abstracts presented at AAP and APSA between 2009 and 2013 were identified from the final printed programs (n = 910). Video abstracts (n = 34) were excluded. Collected data included title, authors, classification (basic science/clinical), presentation type (podium/poster), and topic. Publication as a journal article was determined using the abstract title/authors in a PubMed search. Journal impact factors were recorded for each journal and a composite impact factor (CIF) was calculated by dividing the sum of impact factors by the published articles per meeting. RESULTS: Number of abstracts presented, percentage published, abstract classifications, and presentation type remained consistent over the study period. The AAP meetings accepted a higher percentage of clinical abstracts: AAP 72.3 ± 3.4% versus APSA 65.9 ± 1.3%. The five most popular topics at both meetings were oncology, congenital diaphragmatic hernia, necrotizing enterocolitis, trauma, and appendicitis. The publication rate for clinical and basic science abstracts did not vary significantly over the study period, whereas CIFs were higher for basic science publications nearly every year. The percentage of podium abstracts published was significantly greater than poster abstracts, but no statistical difference in CIF was seen between podium- and poster-associated publications. CONCLUSIONS: Abstracts accepted and presented at the two major pediatric surgical specialty meetings more commonly involve clinical studies with a trend away from basic science. Despite this, basic science abstracts tended to be published in higher impact journals. This study attempts to quantify the quality of pediatric surgical research and serves as a baseline for future comparison.

The 5-HT4 Receptor Agonist Prucalopride Stimulates Mucosal Growth and Enhances Carbohydrate Absorption in the Ileum of the Mouse.

BACKGROUND: Enteric serotonin may function as a mucosal growth factor. Previous work demonstrated increased crypt cell proliferation and intestinal mucosal surface area with potentiation of serotonin. While an indirect mechanism was postulated to explain these effects, the presence of 5-HT4 receptors on enterocytes raises the possibility of a direct action of serotonin. We hypothesized that a 5-HT4 specific agonist, prucalopride, would stimulate intestinal mucosal growth and enhance absorptive function in the murine small intestine. METHODS: Adult wild-type mice were treated parenterally with prucalopride for 14 days via surgically implanted osmotic pumps. In vivo D-xylose absorption was assessed by oral gavage and serum D-xylose measurements. On day 14, glucose absorption was assessed by instilling a glucose solution into isolated segments of small intestine. The bowel was harvested and examined for morphologic parameters and crypt cell proliferation. RESULTS: Villus height, crypt depth, and crypt proliferation were significantly increased in the distal small bowel of prucalopride-treated mice compared with control animals. Crypt depth was also increased in the proximal and middle small intestine in treated mice. There was no difference in D-xylose absorption throughout the study period; however, glucose absorption was significantly increased in the distal small intestine of prucalopride-treated mice. CONCLUSION: Parenteral administration of the 5-HT4 receptor specific agonist, prucalopride, results in morphologic and functional changes in the murine small intestine that are most prominent in the distal small bowel. While further studies are necessary to delineate the mechanism, it is plausible that the effects are mediated by 5-HT4 receptors on enterocytes.

Liver Injury and Endotoxemia in Male and Female Alcohol-Dependent Individuals Admitted to an Alcohol Treatment Program.

BACKGROUND: Interactions between the liver, the gut, and the immune system are critical components of alcoholic liver disease (ALD). The aim of this study was to explore the associations between alcohol-induced liver injury, endotoxemia, and inflammation at admission and over time during abstinence, as well as to examine the sex-related differences in these parameters in alcohol-dependent individuals admitted to an alcohol treatment program. METHODS: A cohort of 48 otherwise healthy participants with alcohol use disorder, but no clinical signs of alcoholic liver injury (34 males [M]/14 females [F]) admitted to an alcohol detoxification program, was stratified into 2 groups based on baseline plasma alanine aminotransferase (ALT) levels (as a marker of liver injury). Group 1 (ALT < 40 U/l, 7M/8F) and Group 2 (ALT ≥ 40 U/l, 27M/6F) were identified. Plasma biomarkers of liver damage, endotoxemia, and inflammation were examined at baseline, day 8, and day 15 of the admission. The drinking history was also evaluated. RESULTS: Sixty-nine percent of patients had elevated ALT and other markers of liver damage, including aspartate aminotransferase and cytokeratin 18 (CK18 M65 and CK M30) at baseline, indicating the presence of mild ALD. Elevated CK18 M65:M30 ratio suggested a greater contribution of necrotic rather than apoptotic hepatocyte cell death in the liver injury observed in these individuals. Females showed greater elevations of liver injury markers compared to males, although they had fewer drinks per day and shorter lifetime duration of heavy drinking. Liver injury was associated with systemic inflammation, specifically, elevated plasma tumor necrosis factor-alpha levels. Compared to patients without liver injury, patients with mild ALD had greater endotoxemia (increased serum lipopolysaccharide levels), which decreased with abstinence and this decrease preceded the drop in CK18 M65 levels. CONCLUSIONS: The study documented the association of mild alcohol-induced liver injury and endotoxemia, which improved with 2 weeks of abstinence, in a subset of individuals admitted to an alcohol detoxification program.

Correlation of Erythrocyte Sedimentation Rate and C-Reactive Protein With Pediatric Inflammatory Bowel Disease Activity.

We aimed to examine correlation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with diagnosis of inflammatory bowel disease and with clinical, endoscopic, histological, and radiographic disease activity during follow-up. We reviewed charts of 135 children with inflammatory bowel disease and correlated their ESR and CRP values with disease activity in various encounters during 5 years. Normal ESR and CRP values were observed in up to 28% of children with Crohn disease and 42% of children with ulcerative colitis at diagnosis, respectively. Correlation of ESR and CRP with Crohn disease clinical, endoscopic, and histologic activity during follow-up depended on their value at diagnosis and mode of analysis (continuous or dichotomous). Both markers were not useful in predicting clinical, endoscopic, or histologic ulcerative colitis disease activity and radiographic small bowel Crohn disease during follow-up.

Treating multi-level cervical disc disease with hybrid surgery compared to anterior cervical discectomy and fusion: a systematic review and meta-analysis.

PURPOSE: The traditional surgical approach to treat multi-level cervical disc disease (mCDD) has been anterior cervical discectomy and fusion (ACDF). There has been recent development of other surgical approaches to further improve clinical outcomes. Collectively, when elements of these different approaches are combined in surgery, it is known as hybrid surgery (HS) which remains a novel treatment option. A systematic review and meta-analysis was conducted to compare the outcomes of HS versus ACDF for the treatment of mCDD. METHODS: Relevant articles were identified from six electronic databases from their inception to January 2016. RESULTS: From 8 relevant studies identified, 169 patients undergoing HS were compared with 193 ACDF procedures. Operative time was greater after HS by 42 min (p < 0.00001), with less intraoperative blood loss by 26 mL (p < 0.00001) and shorter return to work by 32 days (p < 0.00001). In terms of clinical outcomes, HS was associated with greater C2-C7 range of motion (ROM) preservation (p < 0.00001) and less functional impairment (p = 0.008) after surgery compared to ACDF. There was no significant difference between HS and ACDF with respect to postoperative pain (p = 0.12). The postoperative course following HS was not significantly different to ACDF in terms of length of stay (p = 0.24) and postoperative complication rates (p = 0.18). CONCLUSIONS: HS is a novel surgical approach to treat mCDD, associated with a greater operative time, less intraoperative blood loss and comparable if not superior clinical outcomes compared to ACDF. While it remains a viable consideration, there is a lack of robust clinical evidence in the literature. Future large prospective registries and randomised trials are warranted to validate the findings of this study.

Cell and nanoparticle transport in tumour microvasculature: the role of size, shape and surface functionality of nanoparticles.

Through nanomedicine, game-changing methods are emerging to deliver drug molecules directly to diseased areas. One of the most promising of these is the targeted delivery of drugs and imaging agents via drug carrier-based platforms. Such drug delivery systems can now be synthesized from a wide range of different materials, made in a number of different shapes, and coated with an array of different organic molecules, including ligands. If optimized, these systems can enhance the efficacy and specificity of delivery compared with those of non-targeted systems. Emerging integrated multiscale experiments, models and simulations have opened the door for endless medical applications. Current bottlenecks in design of the drug-carrying particles are the lack of knowledge about the dispersion of these particles in the microvasculature and of their subsequent internalization by diseased cells (Bao et al. 2014 J. R. Soc. Interface 11, 20140301 (doi:10.1098/rsif.2014.0301)). We describe multiscale modelling techniques that study how drug carriers disperse within the microvasculature. The immersed molecular finite-element method is adopted to simulate whole blood including blood plasma, red blood cells and nanoparticles. With a novel dissipative particle dynamics method, the beginning stages of receptor-driven endocytosis of nanoparticles can be understood in detail. Using this multiscale modelling method, we elucidate how the size, shape and surface functionality of nanoparticles will affect their dispersion in the microvasculature and subsequent internalization by targeted cells.

Near infrared (NIr) light increases expression of a marker of mitochondrial function in the mouse vestibular sensory epithelium.

Strategies for attenuating decline in balance function with increasing age are predominantly focused on physical therapies including balance tasks and exercise. However, these approaches do not address the underlying causes of balance decline. Using mice, the impact of near infrared light (NIr) on the metabolism of cells in the vestibular sensory epithelium was assessed. Data collected shows that this simple and safe intervention may protect these vulnerable cells from the deleterious effects of natural aging. mRNA was extracted from the isolated peripheral vestibular sensory epithelium (crista ampullaris and utricular macula) and subsequently transcribed into a cDNA library. This library was then probed for the expression of ubiquitous antioxidant (SOD-1). Antioxidant gene expression was then used to quantify cellular metabolism. Using transcranial delivery of NIr in young (4 weeks) and older (8-9 months) mice, and a brief treatment regime (90 sec/day for 5 days), this work suggests NIr alone may be sufficient to improve mitochondrial function in the vestibular sensory epithelium. Since there are currently no available, affordable, non-invasive methods of therapy to improve vestibular hair cell function, the application of external NIr radiation provides a potential strategy to counteract the impact of aging on cellular metabolism inthe vestibular sensory epithelium.

Targeted delivery of chemotherapy agents using a liver cancer-specific aptamer.

BACKGROUND: Using antibody/aptamer-drug conjugates can be a promising method for decreasing toxicity, while increasing the efficiency of chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the antitumor agent Doxorubicin (Dox) was incorporated into the modified DNA aptamer TLS11a-GC, which specifically targets LH86, a human hepatocellular carcinoma cell line. Cell viability tests demonstrated that the TLS11a-GC-Dox conjugates exhibited both potency and target specificity. Importantly, intercalating Dox into the modified aptamer inhibited nonspecific uptake of membrane-permeable Dox to the non-target cell line. Since the conjugates are selective for cells that express higher amounts of target proteins, both criteria noted above are met, making TLS11a-GC-Dox conjugates potential candidates for targeted delivery to liver cancer cells. CONCLUSIONS/SIGNIFICANCE: Considering the large number of available aptamers that have specific targets for a wide variety of cancer cells, this novel aptamer-drug intercalation method will have promising implications for chemotherapeutics in general.

Cyclooxygenase-2 and Akt mediate multiple growth-factor-induced epithelial-mesenchymal transition in human hepatocellular carcinoma.

BACKGROUND AND AIM: Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma (HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies. METHODS: The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor ß-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined. RESULTS: LH86 cells display epithelial morphology. Transforming-growth-factor-ß-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin E2 (PGE2), Akt and phosphorylated Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT. CONCLUSIONS: Multiple growth factors induce EMT in HCC. COX-2 and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC.