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Background MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. Methods In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn’s disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. Results In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20–3.27; logrank p = 1.80 × 10–3), in particular CD [HR 2.81; IQR: 1.11–3.53, p = 6.50 × 10–4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. Interpretation We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

Background Return of normal gastrointestinal (GI) function is a critical determinant of recovery after colorectal surgery. The aim of this meta-analysis was to evaluate whether perioperative intravenous (IV) lidocaine benefits return of gastrointestinal function after colorectal resection. Methods A comprehensive search of Ovid Medline, PubMed, Embase, Cochrane library, and clinicaltrials.org was performed on 1st July 2018. A manual search of reference lists was also performed. Inclusion criteria were as follows: randomized controlled trials (RCTs) of intravenous (IV) lidocaine administered perioperatively compared to placebo (0.9% saline infusion) as part of a multimodal perioperative analgesic regimen, human adults (> 16 years), and open or laparoscopic colorectal resectional surgery. Exclusion criteria: non-colorectal surgery, non-placebo comparator, children, non-general anaesthetic, and pharmacokinetic studies. The primary endpoint was time to first bowel movement. Secondary endpoints were time to first passage of flatus, time to toleration of diet, nausea and vomiting, ileus, pain scores, opioid analgesia consumption, and length of stay. Results One hundred and ninety one studies were screened, with 9 RCTs meeting inclusion criteria (405 patients, four laparoscopic and five open surgery studies). IV lidocaine reduced time to first bowel movement compared to placebo [seven studies, 325 patients, mean weighted difference − 9.54 h, 95% CI 18.72–0.36, p = 0.04]. Ileus, pain scores, and length of stay were reduced with IV lidocaine compared with placebo. Conclusions Perioperative IV lidocaine may improve recovery of gastrointestinal function after colorectal surgery. Large-scale effectiveness studies to measure effect size and evaluate optimum dose/duration are warranted. Electronic supplementary material The online version of this article (10.1007/s10151-019-1927-1) contains supplementary material, which is available to authorized users.

Background A liver resection under low central venous pressure (CVP) has become standard practice; however, the benefits beyond a reduction in blood loss are not well reported. Moreover, the precise method to achieve CVP reduction has not been established. A systematic review and meta analysis of randomized controlled trials (RTCs) was performed to assess the effects of CVP on clinical outcome and to identify the optimum method of CVP reduction. Methods EMBASE, Medline, PubMed and the Cochrane database were searched for trials comparing low CVP surgery with controls. The primary outcome was post operative complications within 30 days. Secondary outcomes included estimated blood loss (EBL), blood transfusion rates and length of stay (LOS). Sub group analysis was performed to assess the CVP reduction method on the outcome. Results Eight trials were identified. No difference was observed in the morbidity rate between the high CVP and control groups [odds ratio (OR) = 0.96 (95% confidence interval (CI) 0.66, 1.40) P = 0.84, I 2 = 0%]. EBL [weighted mean difference (WMD) = −308.63 ml (95% CI −474.67, −142.58) P = I 2 = 73%] and blood transfusion rates [OR 0.65 (95% CI 0.44, 0.97) P = 0.040, I 2 = 37%] were significantly lower in the low CVP groups. Neither anaesthetic nor surgical methods of CVP reduction were associated with a reduced post operative morbidity. Conclusion Low CVP surgery is associated with a reduction in EBL; however, this does not translate into an improvement in post operative morbidity. The optimum method of CVP reduction has not been identified.

Intravenous (IV) lidocaine has analgesic and anti-inflammatory properties. This study aims to evaluate the efficacy of IV lidocaine in controlling postoperative pain following laparoscopic surgery. A meta-analysis of randomised controlled trials (RCTs) comparing IV lidocaine versus placebo/routine treatment for postoperative analgesia following laparoscopic surgery. The primary outcome was opiate requirement at 24 h. Secondary outcomes included cumulative opiate requirement, numerical pain scores (2, 12, 24, 48 h at rest and on movement), recovery indices (nausea and vomiting, length of stay, time until diet resumption, first flatus and bowel movement) and side effects (cardiac/neurological toxicity). Subgroup analyses were performed according to operation type and to compare IV lidocaine with intraperitoneal lidocaine. Fourteen RCTs with 742 patients were included. IV lidocaine was associated with a small but significant reduction in opiate requirement at 24 h compared with placebo/routine care. IV lidocaine was associated with reduced cumulative opiate requirement, reduced pain scores at rest at 2, 12 and 24 h, reduced nausea and vomiting and a shorter time until resumption of diet. The length of stay did not differ between groups. There was a low incidence of IV lidocaine-associated toxicity. In subgroup analyses, there was no difference between IV and intraperitoneal lidocaine in the measured outcomes. IV lidocaine has a multidimensional effect on the quality of recovery. IV lidocaine was associated with lower opiate requirements, reduced nausea and vomiting and a shorter time until resumption of diet. Whilst IV lidocaine appears safe, the optimal treatment regimen remains unknown. Statistical heterogeneity was high.

BACKGROUND Acute appendicitis remains the most common indication for emergency abdominal surgery in the United Kingdom. Although laparoscopic appendicectomy has demonstrable advantages over open appendicectomy, uptake has not been universal. The aims of this study were to describe trends in laparoscopic appendicectomy in a District General Hospital in Scotland. METHODS Retrospective review of appendix histopathology records within NHS Fife between 2003 and 2010. Note review of cases of acute appendicitis managed with laparoscopic appendicectomy was performed. Perioperative variables in perforated and nonperforated appendicitis were compared. A multivariate logistic regression analysis to determine factors associated with developing complications was performed. RESULTS Between 2003 and 2010, 237 laparoscopic appendicectomies were performed. The rate of laparoscopic appendicectomy increased from 2.5% in 2003 to 78% in 2010. In 50% of cases, the trainee surgeon was the primary operator. Complications occurred in 9.6% and the mortality rate was 0.4%. No factors on multivariate logistic regression predicted development of complications. CONCLUSIONS We describe a change in practice towards laparoscopic appendicectomy for the treatment of acute appendicitis over a 7-year period. Furthermore, laparoscopic appendicectomy is associated with acceptable morbidity rates.

In the past decade, there have been fundamental advances in our understanding of genetic factors that contribute to the inflammatory bowel diseases (IBDs) Crohn’s disease and ulcerative colitis. The latest international collaborative studies have brought the number of IBD susceptibility gene loci to 163. However, genetic factors account for only a portion of overall disease variance, indicating a need to better explore gene-environment interactions in the development of IBD. Epigenetic factors can mediate interactions between the environment and the genome; their study could provide new insight into the pathogenesis of IBD. We review recent progress in identification of genetic factors associated with IBD and discuss epigenetic mechanisms that could affect development and progression of IBD.

Aim Reduced opioid use in the immediate postoperative period is associated with decreased complications. This study aimed to determine the effect of transversus abdominis plane (TAP) block on morphine requirements 24 h after abdominal surgery. Secondary outcomes included the effect of TAP block on morphine use 48 h after surgery, incidence of postoperative nausea and vomiting (PONV) and impact on reported pain scores (visual analogue scale). Method A systematic review of the literature was conducted for randomised controlled trials (RCTs) evaluating the effects of TAP block in adults undergoing abdominal surgery. For continuous data, weighted mean differences (WMD) were formulated; for dichotomous data, odds ratios (OR) were calculated. Results were produced with a random effects model with 95% confidence intervals (CI). Results Nine studies, including published and unpublished data, containing a total of 413 patients were included. Of these 205 received a TAP block and 208 a placebo. Cumulative morphine utilization was statistically significantly reduced at 24 h. [WMD = 23.71 mg (38.66–8.76); P = 0.002] and 48 h [WMD = 38.08 mg (18.97–57.19); P

INTRODUCTION Reducing exogenously administered opioids in the post-operative period is associated with early return of bowel function and decreased post-operative complication rates. We evaluated the effectiveness of a surgeon-delivered open transversus abdominis plane (TAP) block as a method to reduce post-operative opioid requirements, sedation and inpatient stay. METHODS The patient cohort was identified from those who had undergone a right hemicolectomy for colonic cancer. Patients received either an open TAP block and post-operative patient controlled anaesthesia (PCA) (n=20) or were part of a control group who received subcutaneous local anaesthetic infiltration and PCA (n=16). RESULTS PCA morphine use was reduced within the first 24 hours post-operatively in the TAP block group compared with controls (42.1mg vs 72.3mg, p=0.002). Sedation was also reduced significantly in the early post-operative period (pCONCLUSIONS Open TAP blocks are safe and reduce post-operative opioid requirements and sedation after right hemicolectomies. They should be considered as part of a multimodal enhanced recovery approach to patients undergoing abdominal surgery via a transverse incision.

INTRODUCTION Parastomal herniation occurs in 30–50% of colostomy formations. The aim of this study was to radiologically evaluate the mechanical defects at stoma sites in patients who had previously undergone a permanent colostomy with or without mesh at the index operation for colorectal cancer. METHODS A study was performed of all colorectal cancer patients (n=41) having an end colostomy between 2002 and 2010, with or without Prolene® mesh plication, with blinded evaluation of the annual follow-up staging computed tomography (CT) for stomal characteristics. The presence of parastomal hernias, volume, dimensions, grade of the parastomal hernia and abdominal wall defect size were measured by two independent radiologists, and compared with demographic and operative variables. RESULTS In those patients with radiological evidence of a parastomal hernia, Prolene® mesh plication significantly reduced the incidence of bowel containing parastomal hernias at one year following the procedure (pCONCLUSIONS Prophylactic mesh placement at the time of the index procedure reduces the diameter of abdominal wall aperture and the incidence of parastomal hernias containing bowel. Future studies should use both objective radiological as well as clinical endpoints when assessing parastomal hernia development with and without prophylactic mesh.

Transcalcaneal talonavicular dislocation is a rare injury, with very few reported cases. Of these, most have been the result of high-energy mechanisms such as road traffic collisions or falls from a height. The management of this injury is challenging, and treatment is fraught with a high rate of disability, infection, and amputation. We describe the successful management of the first reported case of a low-energy transcalcaneal talonavicular dislocation in a 71-year-old female. Combined external and internal fixation was used to reduce and maintain the injury, with a resultant good functional and complication-free outcome at 1 year after the injury. Our experience highlights the prevalence of these devastating injuries caused by relatively benign mechanisms in an increasingly older population with osteoporotic bone. It also indicates that operative stabilization of a low-energy injury can be more successful than that with the traditional high-velocity trauma.

Article first published online 17 April 2015. Supplemental Digital Content is Available in the Text., Background: Glycobiology is an underexplored research area in inflammatory bowel disease (IBD), and glycans are relevant to many etiological mechanisms described in IBD. Alterations in N-glycans attached to the immunoglobulin G (IgG) Fc fragment can affect molecular structure and immunological function. Recent genome-wide association studies reveal pleiotropy between IBD and IgG glycosylation. This study aims to explore IgG glycan changes in ulcerative colitis (UC) and Crohn's disease (CD). Methods: IgG glycome composition in patients with UC (n = 507), CD (n = 287), and controls (n = 320) was analyzed by ultra performance liquid chromatography. Results: Statistically significant differences in IgG glycome composition between patients with UC or CD, compared with controls, were observed. Both UC and CD were associated with significantly decreased IgG galactosylation (digalactosylation, UC: odds ratio [OR] = 0.71; 95% confidence interval [CI], 0.5–0.9; P = 0.01; CD: OR = 0.41; CI, 0.3–0.6; P = 1.4 × 10−9) and significant decrease in the proportion of sialylated structures in CD (OR = 0.46, CI, 0.3–0.6, P = 8.4 × 10−8). Logistic regression models incorporating measured IgG glycan traits were able to distinguish UC and CD from controls (UC: P = 2.13 × 10−6 and CD: P = 2.20 × 10−16), with receiver–operator characteristic curves demonstrating better performance of the CD model (area under curve [AUC] = 0.77) over the UC model (AUC = 0.72) (P = 0.026). The ratio of the presence to absence of bisecting GlcNAc in monogalactosylated structures was increased in patients with UC undergoing colectomy compared with no colectomy (FDR-adjusted, P = 0.05). Conclusions: The observed differences indicate significantly increased inflammatory potential of IgG in IBD. Changes in IgG glycosylation may contribute to IBD pathogenesis and could alter monoclonal antibody therapeutic efficacy. IgG glycan profiles have translational potential as IBD biomarkers.

Novel local anesthetic blocks have become increasingly popular in the multimodal pain management following abdominal surgery, but have not been evaluated in a procedure-specific manner in colorectal surgery.This study aims to evaluate the efficacy of novel local anesthetic techniques in colorectal surgery.Electronic literature search of PubMed, EMBASE, and Cochrane databases (date range, January 1990 to February 2013) STUDY SELECTION: Randomized controlled trials comparing a novel local anesthetic technique with placebo/routine analgesia in adults undergoing open or laparoscopic colonic or rectal resection were selected.This is a meta-analysis of randomized controlled trials evaluating novel local anesthetic wound infiltration techniques such as wound catheter, transversus abdominis plane block, and intraperitoneal instillation in colorectal surgical procedures. The comparator group was defined as placebo/routine analgesia.The primary outcome was opiate requirement at 24 hours. Secondary outcomes included opiate requirements at 48 hours, pain numerical rating score at 24 and 48 hours at rest and on movement, recovery (length of stay, nausea and vomiting, time until bowel movement and diet resumption), and complications. Subgroup analysis was performed to evaluate specific local anesthetic techniques and open and laparoscopic surgery.Twelve randomized controlled trials compared local anesthetic techniques with placebo/routine analgesia. Local anesthetic techniques demonstrated a significant reduction in opiate requirement at 48 hours. Local anesthetic techniques were also associated with lower pain scores on movement at 24 and 48 hours, shorter length of stay, and earlier resumption of diet.The diverse study design led to statistical heterogeneity in several analyses.Novel local anesthetic wound infiltration techniques in colorectal surgery appear to reduce opiate requirements, to reduce pain scores, and to improve recovery in comparison with placebo/routine analgesia.

BackgroundLocal anaesthetic wound infiltration techniques reduce opiate requirements and pain scores. Wound catheters have been introduced to increase the duration of action of local anaesthetic by continuous infusion. The aim was to compare these infiltration techniques with the current standard of epidural analgesia.MethodsA meta-analysis of randomized clinical trials (RCTs) evaluating wound infiltration versus epidural analgesia in abdominal surgery was performed. The primary outcome was pain score at rest after 24 h on a numerical rating scale. Secondary outcomes were pain scores at rest at 48 h, and on movement at 24 and 48 h, with subgroup analysis according to incision type and administration regimen (continuous versus bolus), opiate requirements, nausea and vomiting, urinary retention, catheter-related complications and treatment failure.ResultsNine RCTs with a total of 505 patients were included. No differences in pain scores at rest 24 h after surgery were detected between epidural and wound infiltration. There were no significant differences in pain score at rest after 48 h, or on movement at 24 or 48 h after surgery. Epidural analgesia demonstrated a non-significant a trend towards reduced pain scores on movement and reduced opiate requirements. There was a reduced incidence of urinary retention in the wound catheter group.ConclusionWithin a heterogeneous group of RCTs, use of local anaesthetic wound infiltration was associated with pain scores comparable to those obtained with epidural analgesia. Further procedure-specific RCTs including broader measures of recovery are recommended to compare the overall efficacy of epidural and wound infiltration analgesic techniques.

Background: Although endoscopy is the gold standard for the assessment of activity in Crohn's disease (CD), it should be integrated with clinical, laboratory, and radiological data. In particular, it is still unclear when MRI should be performed. Aim: To evaluate the advantages and limitations of endoscopy and MRI to assess disease activity and severity in a series of CD patients. Material and methods: 50 consecutive patients with endoscopically provenCD underwentMRI enterography for the staging at diagnosis or follow-up. Endoscopic activity was measured by SES-CD (range 0-40) with active mild,moderate ad severe disease defined as a scores 4-10,11-19 and >20 respectively. MRI activity was measured by a validated quantitative score which integrates both mural and extramural involvement (Magnetic Resonance Enterography global score,MEGS,range 0-296), with active disease present for a ≥ 1 score. CDAI, CRP and fecal calprotectin (FC) were measured in all participants (positivity cut-off respectively >0,50 mg/dl and >150 μg/gr). Results: We enrolled 20 males and 30 females (diagnosis in 62%, follow-up in 38%), mean age 38±15 years,mean disease duration 5,4±5 years. SES-CD and MEGS were well correlated (r=0,42, p=0.001); both SESCD andMEGS show correlation with clinical (CDAI r=0,51,r=0,59, p

Importance The optimal analgesic technique following open abdominal surgery within an enhanced recovery protocol remains controversial. Thoracic epidural is often recommended; however, its role is increasingly being challenged and alternative techniques are being suggested as suitable replacements. Objective To determine by meta-analysis whether epidurals are superior to alternative analgesic techniques following open abdominal surgery within an enhanced recovery setting in terms of postoperative morbidity and other markers of recovery. Data Sources A literature search was performed of EMBASE, Medline, PubMed, and the Cochrane databases from 1966 through May 2013. Study Selection All randomized clinical trials comparing epidurals with an alternative analgesic technique following open abdominal surgery within an enhanced recovery protocol were included. Data Extraction and Synthesis All studies were assessed by 2 independent reviewers. Study quality was assessed using the Cochrane bias assessment tool and the Jadad and Chalmers modified bias risk assessment tools. Dichotomous data were analyzed by random or fixed-effects odds ratios. Qualitative analysis was performed where appropriate Results Seven trials with a total of 378 patients were identified. No significant difference in complication rate was detected between epidurals and alternative analgesic methods (odds ratio, 1.14; 95% CI, 0.49-2.64; P = .76). Subgroup analysis showed fewer complications in the patient-controlled analgesia group compared with epidural analgesia (odds ratio, 1.97; 95% CI, 1.10-3.53; P = .02). Following qualitative assessment, epidural analgesia was associated with faster return of gut function and reduced pain scores; however, no difference was observed in length of stay. Conclusions and Relevance Epidurals may be associated with superior pain control but this does not translate into improved recovery or reduced morbidity when compared with alternative analgesic techniques when used within an enhanced recovery protocol.

The bottom line Crohn’s disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract. Although the disease most commonly presents at a young age, it can affect people of all ages. Patients often present with persistent diarrhoea, abdominal pain, and weight loss. Crohn’s disease has a global impact on patients’ education, work, and social and family life. High quality multidisciplinary care, of which primary care is a key aspect, can attenuate relapse, prevent long term complications, and improve quality of life. In this review we provide a practical approach to the diagnosis, management, and long term care of patients with Crohn’s disease. #### Sources and selection criteria We carried out an electronic search of PubMed, the Cochrane Library, and Ovid databases for articles using the term “Crohn’s disease”. We limited studies to those in adults and focused on high quality randomised control trials, meta-analyses, and systematic reviews. Crohn’s disease is an idiopathic, chronic relapsing immune mediated disease, the pathogenesis of which remains incompletely understood, although the condition is thought to arise from environmental priming and …