Use of AgomiR and AntagomiR technologies to alter satellite cell proliferation in vitro, miRNA expression, and muscle fiber hypertrophy in intrauterine growth-restricted lambs.

Introduction: microRNAs (miRNAs) are small non-coding RNAs that work at the posttranscriptional level to repress gene expression. Several miRNAs are preferentially expressed in skeletal muscle and participate in myogenesis. This research was conducted to alter endogenous miRNA expression in skeletal muscle to promote muscle hypertrophy. Methods: Two experiments were conducted using mimic/agomiR or antagomir technologies to alter miRNA expression and examine changes in myoblast proliferation in vitro (experiment 1) and muscle hypertrophy in vivo (experiment 2). In vitro experiments found that antagomiR-22-3p and mimic-127 increased myoblast proliferation compared to other miRNA treatments or controls. These miRNA treatments, antagomiR-22-3p (ANT22) and agomiR-127 (AGO127), were then used for intramuscular injections in longissimus muscle. Results and discussion: The use of antagomiR or mimic/agomiR treatments down-regulated or up-regulated, respectively, miRNA expression for that miRNA of interest. Expression of predicted target KIF3B mRNA for miR-127 was up-regulated and ACVR2a mRNA was up-regulated for miR-22-3p. ANT22 injection also up-regulated the major regulator of protein synthesis (mTOR). Proteomic analyses identified 11 proteins for AGO127 and 9 proteins for ANT22 that were differentially expressed. Muscle fiber type and cross-sectional area were altered for ANT22 treatments to transition fibers to a more oxidative state. The use of agomiR and antagomir technologies allows us to alter miRNA expression in vitro and in vivo to enhance myoblast proliferation and alter muscle fiber hypertrophy in IUGR lambs during early postnatal growth.

Evaluation of the Ventral Hernia Working Group classification for long-term outcome using English Hospital Episode Statistics: a population study.

PURPOSE: The Ventral Hernia Working Group (VHWG) classification of ventral/incisional hernia (IH) was developed by expert consensus in 2010. Subsequently, Kanters et al. have demonstrated the validity of a modified version of the system for predicting short-term outcomes. This study aims to evaluate the modified system for predicting hernia recurrence. METHODS: Patients undergoing IH surgery (defined by OPCS codes) in the England Hospital Episode Statistics (HES) database, from 1997 to 2012, were identified. Baseline demographics at index hernia operation and episodes of further hernia surgery (FHS) were recorded. Risk factors for FHS were identified using cox regression and evaluated against the modified-VHWG grade using receiver-operating characteristics (ROC). RESULTS: The final analysis included 214,082 index IH operations. Of these, 52.6% were female and mean age was 56.59 (SD15.9). An admission for FHS was found in 8.3% cases (17,714 patients). Multi-variate cox regression revealed contaminated hernia (p < 0.0001), pre-existing IBD (p < 0.0001) and hernia comorbidity (p = 0.05) to be significantly related to long-term FHS. Classifying patients using these factors, according to the modified-VHWG classification, revealed that compared to Grade 1, the hazard ratio (HR) of FHS increased in Grade 2 (HR 1.19; p < 0.0001) and further increased in Grade 3 (HR 1.79; p < 0.0001). ROC analysis revealed the area under the curve to be 0.73 (95% CI 0.73-0.74). CONCLUSION: This analysis demonstrates the broad validity of the modified-VHWG classification in discriminating risk for FHS. Inclusion of pre-existing IBD as a factor defining Grade 2 patients would be recommended. This analysis is limited by the absence of certain factors within the HES database, such as BMI.

Review of current practice and outcomes following ileoanal pouch surgery: lessons learned from the Ileoanal Pouch Registry and the 2017 Ileoanal Pouch Report.

AIM: The second Association of Coloproctology of Great Britain and Ireland (ACPGBI) Ileoanal Pouch Registry (IPR) report was released in July 2017 following a first report in 2012. This article provides a summary of data derived from the most recent IPR report (2017 Ileoanal Pouch Report. https://www.acpgbi.org.uk/content/uploads/2016/07/Ileoanal-Pouch-Report-2017-FINAL.compressed.pdf). METHOD: The IPR is an electronic database of voluntarily submitted data including patient demographics, disease, intra-operative and postoperative factors submitted by consultant surgeons or delegates. Data up to 31 March 2017 have been analysed for this report. RESULTS: A total of 5352 pouch operations were carried out at 76 UK and four European centres by 154 surgeons over four decades. Recorded procedures have increased over time but data submission is voluntary and underestimates actual volume. Significant variation exists in institutional volume; 73 centres entered data on patients undergoing pouch surgery during the past 5 years. Of these, 44 centres have submitted ≤ 10 cases, with 10 centres submitting one patient and nine centres two cases. Since 2013, minimal access surgery has been employed in 54% of cases. Rectal dissection was undertaken in the total mesorectal excision plane in 69%. J-pouch configuration was used in 99% of cases and 90% of pouch-anal anastomoses were performed using a stapled technique. Including all years, the IPR rate of pelvic sepsis was 9.4% and the rate of pouch failure was 4.7%. CONCLUSION: The IPR holds the largest voluntary repository of data on ileoanal pouch surgery. The second report from the IPR records marked refinements in surgical technique over time but also highlights wide variation in institutional caseload and outcome across the UK.

Management of early pouch-related septic complications in ulcerative colitis: a systematic review.

AIM: It is well established that ileo-anal pouch-related septic complications (PRSC) increase the risk of pouch failure. There are a number of publications that describe the management of early PRSC in ulcerative colitis (UC) in small series. This article aims to systematically review and summarize the relevant current data on this subject and provide an algorithm for the management of early PRSC. METHOD: A systematic review was undertaken in accordance with PRISMA guidelines. Studies published between 2000 and 2017 describing the clinical management of PRSC in patients with UC within 30 days of primary ileo-anal pouch surgery were included. A qualitative analysis was undertaken due to the heterogeneity and quality of studies included. RESULTS: A total of 1157 abstracts and 266 full text articles were screened. Twelve studies were included for analysis involving a total of 207 patients. The studies described a range of techniques including image-guided, endoscopic, surgical and endocavitational vacuum methods. Based on the evidence from these studies, an algorithm was created to guide the management of early PRSC. CONCLUSION: The results of this review suggest that although successful salvage of early PRSC is improving there is little information available relating to methods of salvage and outcomes. Novel techniques may offer an increased chance of salvage but comparative studies with longer follow-up are required.

Restorative surgery after colectomy for ulcerative colitis in England and Sweden: observations from a comparison of nationwide cohorts.

AIM: A longstanding disparity exists between the approaches to restorative surgery after colectomy for patients with ulcerative colitis (UC) in England and Sweden. This study aims to compare rates of colectomy and restorative surgery in comparable national cohorts. METHOD: The English Hospital Episode Statistics (HES) and Swedish National Patient Register (NPR) were interrogated between 2002 and April 2012. Patients with two diagnostic episodes for UC (age ≥ 15 years) were included. Patients were excluded if they had an episode of inflammatory bowel disease or colectomy before 2002. The cumulative incidences of colectomy and restorative surgery were calculated using the Kaplan-Meier method. RESULTS: A total of 98 691 patients were included in the study, 76 129 in England and 22 562 in Sweden. The 5-year cumulative incidence of all restorative surgery after colectomy in England was 33% vs 46% in Sweden (P-value < 0.001). Of the patients undergoing restorative surgery, 92.3% of English patients had a pouch vs 38.8% in Sweden and 7.7% vs 59.1% respectively had an ileorectal anastomosis (IRA). The 5-year cumulative incidence of colectomy in this study cohort was 13% in England and 6% in Sweden (P-value < 0.001). CONCLUSION: Following colectomy for UC only one-third of English patients and half of Swedish patients underwent restorative surgery. In England nearly all these patients underwent pouches, in Sweden a less significant majority underwent IRAs. It is surprising to demonstrate this discrepancy in a comparable cohort of patients from similar healthcare systems. The causes and consequences of this international variation in management are not fully understood and require further investigation.

Variation in practice of pouch surgery in England - using SWORD data to cut to the chase and justify centralization.

AIM: Increasing scrutiny on both individual and unit outcomes after surgical procedures is now expected. In the field of inflammatory bowel disease, this is particularly pertinent for outcomes after ileoanal pouch surgery. METHOD: The Surgical Workload and Outcomes Research Database (SWORD) relies on administrative data derived from Hospital Episode Statistics collected in England. The platform was interrogated for pouch procedures undertaken in England between April 2009 and December 2016 to assess national caseload and, between April 2012 and December 2016, to assess variation in caseload and outcomes after pouch surgery. RESULTS: In England there is a suggestion that numbers of pouch procedures may be decreasing. Over 80% of Trusts offering pouch surgery do so at very low volume with less than five procedures per year. There is also a clear phenomenon of the occasional pouch surgeon with 126 surgeons undertaking just one pouch operation during the study period of almost 5 years. Laparoscopic practice varies but 60% of pouches overall were done via an open approach. Mean length of stay was 10.1 days and average 30-day readmission rates were 27.4%. Outside London there appears to be an increasing trend for higher volume units to do more adult pouch procedures and lower volume units to do fewer. CONCLUSION: Low volume units and occasional pouch surgeons present a strong argument for centralization of pouch surgery. Data from England outside London suggest that this may already be happening.

Systematic review with meta-analysis: the management of chronic refractory pouchitis with an evidence-based treatment algorithm.

BACKGROUND: Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is considered the procedure of choice in patients with ulcerative colitis (UC) refractory to medical therapy. The incidence of pouchitis is 40% at 5 years. Ten to 15% of patients with pouchitis experience chronic pouchitis. AIM: To determine the efficacy of medical therapies for the treatment of chronic refractory pouchitis in patients undergoing IPAA for UC. METHODS: A systematic computer-assisted search of the on-line bibliographic database MEDLINE and EMBASE was performed between 1966 and February 2016. All original studies reporting remission rates following medical treatment for chronic pouchitis were included. All study designs were considered. Remission was defined according to the individual study. Remission endpoints ranged from 15 days to 10 weeks. Chronic pouchitis was defined by each study. RESULTS: Twenty-one papers were considered eligible. Results from all studies combined suggested that overall remission was obtained in 59% of patients (95% CI: 44-73%). Antibiotics significantly induced remission in patients with chronic pouchitis with 74% remission rate (95% CI:56-93%), (P < 0.001). Biologics significantly induced remission in patients with chronic pouchitis with 53% remission rate (95% CI:30-76%), (P < 0.001). Steroids, bismuth, elemental diet and tacrolimus all can induce remission but failed to achieve significance. Faecal microbiota transplantation in a single study was not found to achieve remission. CONCLUSIONS: Treatment of chronic refractory pouchitis remains difficult and is largely empirical. Larger randomised controlled trials will help aid the management of chronic pouchitis.

Laser arytenoidectomy in children with bilateral vocal fold immobility.

Bilateral vocal fold immobility in children is a challenging problem because a balance between good airway and voice quality has to be achieved. Surgery to improve the airway is often postponed or avoided because of fear of losing the voice. In this study our results of laser arytenoidectomy in children are described. This was a retrospective case notes review at a tertiary level paediatric ENT department. The six patients in this case series ranged from nine to 16 years old at the time of laser arytenoidectomy. Post-operative airway and voice quality were assessed. All children in the series had an adequate post-operative airway. Four of these patients had tracheostomies pre-operatively and achieved decannulation. All six patients rated their post-operative voice as better than pre-operatively. This is principally due to increased loudness associated with increased airflow through the larynx, particularly after tracheostomy decannulation. It is recommended that special care should be taken not to disturb the anterior two thirds of the vocal fold during the surgery in order to achieve a good post-operative voice outcome.

Do all epistaxis patients with a nasal pack need admission? A retrospective study of 116 patients managed in accident and emergency according to a peer reviewed protocol.

INTRODUCTION: Epistaxis is the most common nasal emergency and if nasal packing is required this commonly results in admission. METHODS: A literature search could find no published (UK) protocols for the management of this common condition in accident and emergency (A&E) departments. This paper presents a retrospective review of 116 patients with epistaxis, following implementation of the new peer reviewed protocol in June 2004. RESULTS: Apart from cautery, 62 had nasal packing inserted. Only 17 required admission. Forty-six patients were discharged with nasal packing in situ and only seven (16 per cent) returned due to bleeding. The overall return rate was 11 per cent. DISCUSSION: We feel this is a safe and logical protocol. Compared to mandatory admission after nasal pack insertion, we saved 39 admissions in five months. There were also the added benefits to patients of being able to recuperate at home rather than in hospital and avoidance of the risk of hospital acquired infection.

Whole genomewide linkage screen for neural tube defects reveals regions of interest on chromosomes 7 and 10.

Neural tube defects (NTDs) are the second most common birth defects (1 in 1000 live births) in the world. Periconceptional maternal folate supplementation reduces NTD risk by 50-70%; however, studies of folate related and other developmental genes in humans have failed to definitively identify a major causal gene for NTD. The aetiology of NTDs remains unknown and both genetic and environmental factors are implicated. We present findings from a microsatellite based screen of 44 multiplex pedigrees ascertained through the NTD Collaborative Group. For the linkage analysis, we defined our phenotype narrowly by considering individuals with a lumbosacral level myelomeningocele as affected, then we expanded the phenotype to include all types of NTDs. Two point parametric analyses were performed using VITESSE and HOMOG. Multipoint parametric and nonparametric analyses were performed using ALLEGRO. Initial results identified chromosomes 7 and 10, both with maximum parametric multipoint lod scores (Mlod) >2.0. Chromosome 7 produced the highest score in the 24 cM interval between D7S3056 and D7S3051 (parametric Mlod 2.45; nonparametric Mlod 1.89). Further investigation demonstrated that results on chromosome 7 were being primarily driven by a single large pedigree (parametric Mlod 2.40). When this family was removed from analysis, chromosome 10 was the most interesting region, with a peak Mlod of 2.25 at D10S1731. Based on mouse human synteny, two candidate genes (Meox2, Twist1) were identified on chromosome 7. A review of public databases revealed three biologically plausible candidates (FGFR2, GFRA1, Pax2) on chromosome 10. The results from this screen provide valuable positional data for prioritisation of candidate gene assessment in future studies of NTDs.

Laryngeal ultrasound to assess vocal fold paralysis in children.

The purpose of this study was to assess the practicality and validity of laryngeal ultrasound to establish vocal fold movement in children with suspected vocal fold palsy. Fifty-five consecutive patients (age range three days to 12 years) with suspected vocal fold palsy underwent both laryngoscopy and laryngeal ultrasound. Ultrasonographic findings correlated with endoscopic findings in 81.2 per cent of cases. This, however, rose to a concordance rate of 89.5 per cent in patients aged over 12 months. Laryngeal ultrasound is well-tolerated, safe and non-invasive and the authors feel that it is a useful adjunct to endoscopy in the diagnosis of vocal fold palsy.

No association between the APOE gene and autism.

Autism is a neurodevelopmental disorder characterized by stereotypic and repetitive behavior and interests, together with social and communicative deficiencies. The results of several genomic screens suggest the presence of an autism susceptibility locus on chromosome 19p13.2-q13.4. The apolipoprotein E (APOE) gene on chromosome 19 encodes for a protein, apoE, whose different isoforms (E2, E3, E4) influence neuronal growth. APOE participates in lipid transport and metabolism, repair, growth, and maintenance of axons and myelin during neuronal development. The APOE protein competes with the Reelin protein for VLDL/APOER2 receptor binding. Several studies have reported evidence for an association between autism and the Reelin gene. Based on these data we tested for association between APOE and autism using family-based association methods in a data set of 322 autism families. Three promoter, one intronic, and one 3' UTR single nucleotide polymorphisms (SNPs) in the APOE gene (-491a/t, -427c/t, -219g/t, 113c/g, and 5361c/t) as well as the APOE functional polymorphism (E2, E3, E4) were examined and failed to reveal significant evidence that autism is associated with APOE.

The effectiveness of guidelines in reducing inappropriate CT scans of the paranasal sinuses.

An effective system for scoring pathological changes on CT scans of the paranasal sinuses has been developed by Lund & Mackay. We have performed an audit using 100 outpatients with nasal symptoms and found that adherence to guidelines prior to ordering CT scans of the paranasal sinuses correlates with an increased average Lund & Mackay score. Using these guidelines has also reduced the number of inappropriate CT scan requests.

Acute abdominal symptoms and signs in children and young adults with spina bifida: ten years' experience.

BACKGROUND/PURPOSE: Diagnosis and management of the acute abdomen in patients with spina bifida (SB) can be problematic. There are at least 4 clinical factors that can predispose to the development of acute abdominal symptoms and signs, and patients with a thoracic level lesion can have a partially insensate abdomen. The authors analyzed their accumulated experience to determine the annual incidence of acute abdominal signs and symptoms in children and young adults with spina bifida, the differential diagnosis, the operative management, and the outcome. The pertinent literature was reviewed. METHODS: Cases were ascertained during a 10-year period at 1 institution and reviewed retrospectively. RESULTS: Twenty-two episodes of acute abdominal symptoms and signs in 19 children and young adults with SB were ascertained over 10 years at 1 institution, for an annual incidence of 0.74%. More patients had a thoracic level lesion (n = 12; 60%) than in the clinic population as a whole (27%; P =.04), but the gender distribution was similar (58% girls), as was the prevalence of ventriculoperitoneal shunts (VPS; 95%). The median age was 13 years (range, 1 year to 26 years). Hospitalization was necessary for 19 (86%) of the 22 episodes. The duration of symptoms before diagnosis was a median of 3 days (range, 1 to 14 days). Most patients (82%) presented with abdominal pain. Fever was present in 27%, shock in 23%, and peritoneal signs in 23%. There were 14 different final diagnoses, 10 (71%) of which were associated with a predisposing factor. Of the 22 episodes, 18 (82%) could be attributed to an underlying factor: (1) neurogenic bladder (9; 41%); (2) neurogenic bowel (3; 14%); (3) VPS (4; 18%); (4) complications from previous surgery (2; 9%). Thirteen patients (59%) underwent a total of 20 surgical procedures of 12 different kinds. Despite awareness of the complexities involved, 3 patients (14%) died: 1 from complications resulting from bladder perforation; 1 from urosepsis and shock; and 1 from peritonitis caused by VPS infection. CONCLUSION: The differential diagnosis of the acute abdomen in patients with SB is broad, conditions requiring surgery are frequently diagnosed, and the mortality rate is substantial, despite aggressive management.

Pediatric traumatic atlanto-occipital dislocation: five cases and a review.

Traumatic atlanto-occipital dislocation (AOD) has been thought to be a rare and fatal injury. Recently, more survivors, especially children, have been reported. During a 10-year period, the authors have encountered five children with traumatic AOD. A retrospective review of traumatic AOD in children from 1985 to 1995 was performed. Clinical presentation, initial radiologic findings, and final outcome were emphasized. Distance from the dens to the basion and the ratio of Powers were measured from initial lateral cervical spine radiographs. The average distance from the dens to the basion was 9.8 mm. The average ratio of Powers was 1.38. There were three survivors, two having a concomitant spinal cord injury. All survivors underwent a posterior occipitovertebral fusion. Three cases initially went undiagnosed. The diagnosis of AOD by lateral cervical spine radiographs can be difficult. The authors recommend detailed measurements of the initial cervical spine radiographs in pediatric patients at risk for traumatic AOD.