Search

Background & Aims: Although basal cell hyperplasia is a histologic hallmark of eosinophilic esophagitis (EoE), little is known about the capabilities of epithelial renewal and differentiation in the EoE inflammatory milieu. In murine esophageal epithelium, there are self-renewing and slowly proliferating basal stem-like cells characterized by concurrent expression of CD73 (5'-nucleotidase ecto) and CD104 (integrin β4). Here, we investigated CD73+CD104+ cells within the basal population of human esophageal epithelium and clarified the biological significance of these cells in the EoE epithelium. Methods: We performed flow cytometry on esophageal biopsy samples from EoE and non-EoE patients to determine the quantity of CD73+CD104+ cells in the epithelium. Simulating the EoE milieu we stimulated primary patient-derived and immortalized cell line–derived esophageal organoids with interleukin (IL)4 and IL13 and analyzed by flow cytometry, immunohistochemistry, and quantitative reverse-transcription polymerase chain reaction. We performed single-cell RNA sequencing on primary organoids in the setting of IL13 stimulation and evaluated the CD73+CD104+ population. We performed fluorescent-activated cell sorting to purify CD73+CD104+ and CD73- CD104+ populations and seeded these groups in organoid culture to evaluate the organoid formation rate and organoid size. We used RNA interference to knock down CD73 in esophageal organoids to evaluate organoid formation rates and size. We evaluated the effects of signal transducer and activator of transcription 6 (STAT6) signaling inhibition by RNA interference, a STAT6 inhibitor, AS1517499, as well as the proton pump inhibitor omeprazole. Results: EoE patients showed decreased epithelial CD73+CD104+ cell content. IL4 and IL13 stimulation depleted this population in 3-dimensional organoids with a recapitulation of basal cell hyperplasia as corroborated by single-cell RNA sequencing of the organoids, which suggests depletion of CD73+CD104+ cells. The CD73+CD104+ population had enhanced organoid formation compared with the CD73-CD104+ population. Similarly, knock-down of CD73 resulted in decreased organoid formation rate. Genetic and pharmacologic inhibition of STAT6 prevented T helper 2 cytokine-induced depletion of CD73+CD104+ cells. Lastly, omeprazole treatment prevented the effects of IL4 and IL13 on the CD73+CD104+ population. Conclusions: This study addressed the role of CD73+CD104+ cells in epithelial renewal and homeostasis in the context of EoE. The depletion of the CD73+CD104+ self-renewal population by helper T cell 2 cytokines in EoE milieu may be perpetuating epithelial injury. Future therapies targeting epithelial restitution in EoE could decrease the need for immune modulation and steroid therapy.

Background: Short-latency afferent inhibition (SAI) results when somatosensory afferent input inhibits the corticospinal output from primary motor cortex (M1). The present study examined SAI in the flexor carpi radialis (FCR) muscle in individuals with spinal cord injury (SCI) and uninjured controls. Methods: Short-latency afferent inhibition (SAI) was evoked by stimulating the median nerve at the elbow at intervals of 15, 20 and 25 ms in advance of a transcranial magnetic stimulation (TMS) pulse over M1. SAI was tested with the FCR at rest and also during ~20% of maximum voluntary contraction. Corticospinal output was assessed through measuring both motor thresholds and motor evoked potential (MEP) recruitment curves. The afferent volley was assessed via the N20-P25 amplitude of the somatosensory evoked potential (SEP) and the amplitude of sensory nerve action potentials (SNAP) recorded over the median nerve at the elbow. Results: SAI is reduced in SCI in both the contracted and non-contracted FCR muscle. MEP recruitment curves and thresholds were decreased in SCI only in the active state and not the resting state. N20-P25 amplitude was similar between groups in both the resting and active states although SNAP was significantly reduced in SCI at rest. Conclusions: We conclude that reduced SAI in SCI is likely attributed to neuroplasticity altering the intrinsic M1 circuitry mediating SAI and/or reduced afferent input traversing a direct thalamocortical route to M1. These data provide a new avenue of research aimed at identifying therapeutic approaches to alter SAI to improve upper limb function in individuals with SCI.

Background and Aim: Serrated polyposis syndrome (SPS) is now known to be the commonest polyposis syndrome. Previous analyses for germline variants have shown no consistent positive findings. To exclude other polyposis syndromes, 2019 British Society of Gastroenterology (BSG) guidelines advise gene panel testing if the patient is under 50 years, there are multiple affected individuals within a family, or there is dysplasia within any of the polyps., Methods: A database of SPS patients was established at the Oxford University Hospitals NHS Foundation Trust. Patients were referred for genetic assessment based on personal and family history and patient preference. The majority were tested for a hereditary colorectal cancer panel including MUTYH, APC, PTEN, SMAD4, BMPR1A, STK11, NTLH1, POLD1, POLE, GREM1 (40-kb duplication), PMS2, and Lynch syndrome mismatch repair genes., Results: One hundred and seventy-three patients were diagnosed with SPS based on World Health Organization 2019 criteria between February 2010 and December 2020. The mean age of diagnosis was 54.2 ± 16.8 years. Seventy-three patients underwent genetic testing and 15/73 (20.5%) were found to have germline variants, of which 7/73 (9.6%) had a pathogenic variant (MUTYH n = 2, SMAD4 n = 1, CHEK2 n = 2, POLD1 n = 1, and RNF43 n = 1). Only 60% (9/15) of these patients would have been recommended for gene panel testing according to current BSG guidelines., Conclusions: A total of 20.5% of SPS patients tested were affected by heterozygous germline variants, including previously unreported associations with CHEK2 and POLD1. This led to a change in management in seven patients (9.6%). Current recommendations may miss SPS associated with germline variants, which is more common than previously anticipated., (© 2022 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Magnetic resonance imaging (MRI) assesses pulmonary hypoplasia in fetal congenital diaphragmatic hernia (CDH). Neonatal mortality may occur with CDH., Objective: To quantify MRI parameters associated with neonatal survival in fetuses with isolated CDH., Materials and Methods: Fetal MRI for assessing CDH included region of interest (ROI) measurements for total lung volume (TLV), herniated liver volume, herniated other organ volume and predicted lung volume. Ratios of observed lung volume and liver up volume to predicted lung volume (observed to predicted TLV, percentage of the thorax occupied by liver) were calculated and compared to neonatal outcomes. Analyses included Wilcoxon rank sum test, multivariate logistic regression and receiver operating characteristic (ROC) curves., Results: Of 61 studies, the median observed to predicted TLV was 0.25 in survivors and 0.16 in non-survivors (P=0.001) with CDH. The median percentage of the thorax occupied by liver was 0.02 in survivors and 0.22 in non-survivors (P<0.001). The association of observed to predicted TLV and percentage of the thorax occupied by liver with survival for gestational age (GA) >28 weeks was greater compared to GA ≤28 weeks. The ROC analysis demonstrated an area under the curve of 0.96 (95% confidence interval 0.91-1.00) for the combined observed to predicted TLV, percentage of the thorax occupied by liver and GA., Conclusion: The percentage of the thorax occupied by liver and observed to predicted TLV was predictive of neonatal survival in fetuses with CDH., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To compare prevalence and severity of multi-compartment pelvic floor dysfunction between supine magnetic resonance defecography with defecation (MRD) and supine dynamic MRI during Valsalva, both with and without rectal distention., Methods: This was an IRB-approved, HIPAA-compliant retrospective review of consecutive patients referred for MR Defecography. MRD protocol included imaging at rest, during pre-defecation Valsalva (Pre-DV), defecation (Def), and post-defecation Valsalva (Post-DV). The Post-DV images were performed after complete evacuation either during the defecation acquisition or, in cases where patient was unable to defecate during the examination, in a conventional toilet. Size of cystocele, vaginal prolapse, anorectal (AR) descent, and enterocele were measured on all acquisitions relative to the pubococcygeal line. Rectocele size was recorded in anteroposterior dimension. The presence or absence of rectal intussusception (RI) was documented. The prevalence, absolute size, and grades of prolapse, rectocele, and RI were compared between the acquisitions using pair-wise ANOVA, Friedman, Dunn pair-wise, and Cochran-Mantel-Haenszel tests., Results: 30 patients were included in the final analysis. Higher prevalence of cystocele, vaginal prolapse, enterocele, AR descent grade 2 or higher, rectocele grade 2 or higher, and RI were seen on Def compared to Post-DV and Pre-DV. Cystocele, vaginal prolapse, enterocele, AR descent, and rectocele sizes were significantly larger on Def compared to Post-DV by 0.7-1.95 cm (p ≤ 0.007). Prolapse in all compartments and rectocele size were significantly larger on Def compared to Pre-DV (p < 0.0001). Cystocele, vaginal prolapse, and enterocele sizes were significantly larger on Post-DV compared to Pre-DV (p < 0.0001). There were significant differences in grading of all types of prolapse and rectocele between the various acquisitions of MRD (p < 0.0001). Cystocele, AR descent, and rectocele grades were significantly higher on Def compared to Post-DV (p range ≤ 0.0002). Grading of all types of prolapse and rectocele was significantly higher on Def compared to Pre-DV (p < 0.0001). Cystocele, vaginal prolapse, and enterocele grades were all significantly higher on Post-DV compared to Pre-DV (p  ≤ 0.0007)., Conclusion: Defecation images during supine MRD elicit higher prevalence and size of prolapse of all pelvic compartments in comparison to both pre- and post-defecation Valsalva images. Post-defecation Valsalva images show larger size of anterior and middle compartment prolapse than pre-defecation Valsalva images. Functional evaluation of pelvic floor dysfunction with MRI should include image acquisition during defecation. If Valsalva images are acquired, these should be performed after the defecation acquisition and without rectal distention.

As fetal gestational age increases, other modalities such as ultrasound have demonstrated increased levels of heterogeneity in the normal placenta. In this study, we introduce and apply ROI-based texture analysis to a retrospective fetal MRI database to characterize the second-order statistics of placenta and to evaluate the relationship between heterogeneity and gestational age. Positive correlations were observed for several Haralick texture metrics derived from fetal-brain specific T2-weighted and gravid uterus T1-weighted and T2-weighted images, confirming a quantitative increase in placental heterogeneity with gestational age. Our study shows the importance of identifying baseline MR textural changes at certain gestational ages from which placental diseased states may be compared. Specifically, when evaluating for placental invasion or insufficiency, findings should be evaluated in the context of the normal placental aging process, which occurs throughout gestation., Competing Interests: The authors have declared that no competing interests exist.

Objective: The purpose of this study is to determine which MRI parameters of fetal head and neck masses predict high-morbidity neonatal outcomes, including ex utero intrapartum treatment (EXIT) procedure., Materials and Methods: This retrospective study (2004-2016) included parameters of polyhydramnios (based on largest vertical pocket), mass effect on the trachea, mass midline extension, and morphologic grade and size of masses. The morbid cohort included those requiring an EXIT procedure, difficult intubation at delivery, or lethal outcome. Predictive modeling with a multivariable logistic regression and ROC analysis was then performed., Results: Of 36 fetuses, five were delivered by EXIT procedures, there was one neonatal death within 12 hours after delivery, and another neonate required multiple intubation attempts. The remaining 29 fetuses were delivered at outside institutions with no interventions or neonatal morbidity. The largest vertical pocket and mass effect on the trachea were selected as independent predictors by the logistic regression. The cross-validated ROC AUC was 0.951 (95% CI, 0.8795-1)., Conclusion: The largest vertical pocket measurement and mass effect on the trachea were the most contributory MRI parameters that predicted significant morbidity in fetuses with masses of the face and neck, along with other significant parameters. These parameters predict significant morbid neonatal outcomes, including the need for EXIT procedures.

Background and Objectives: Age and frailty have been correlated with poor clinical outcomes in cancer. Core muscle index (CMI) and nutritional status are integral in assessing frailty. We explored the effect of pre-operative serum albumin and body composition on clinical outcomes in patients with epithelial ovarian cancer (EOC)., Methods: We identified stage III-IV EOC patients undergoing primary cytoreductive surgery from 2007 to 2015. Data were abstracted from medical records. Body composition measurements were obtained from pre-operative imaging. Psoas muscle cross-sectional area was normalized to height 2 to determine CMI. Sarcopenia was defined as CMI below the population mean. The influence of sarcopenia on short-term morbidity was evaluated. Relationships among body composition measurements and albumin were assessed with Spearman correlations. Patient characteristics and body composition measurements between patients with and without sarcopenia were compared with parametric and non-parametric statistical methods. Kaplan-Meier survival curves were compared using log-rank., Results: 102 women met inclusion criteria. Sarcopenia correlated with albumin (P = 0.0002). Sarcopenia was not associated with short-term morbidity or time to recurrence. Sarcopenia was associated with nearly a fourfold increased risk of death when hypoalbuminemia was present (P = 0.02)., Conclusions: Pre-operative sarcopenia in combination with hypoalbuminemia was associated with significantly worse survival., (© 2018 Wiley Periodicals, Inc.)

Background and aims: Radical endoscopic excision of Barrett's epithelium performing 4 - 6 endoscopic resections during the same endoscopic session results in complete Barrett's eradication but has a high stricture rate (40 - 80 %). Therefore radiofrequency ablation is preferred after endoscopic mucosal resection (EMR) of visible nodules. We investigated the clinical outcome of non-radical, stepwise endoscopic mucosal resection with a maximum of two endoscopic resections per endoscopic session. Methods: We analysed our prospectively maintained database of patients undergoing esophageal EMR for early neoplasia in Barrett's esophagus from 2009 to 2014. EMR was performed using a maximum of two band ligation mucosectomies per endoscopic session; thereafter, follow-up was 3-monthly and EMR was repeated as required for Barrett's eradication. Results: In total, 118 patients underwent staging EMR for early Barrett's neoplasia. Subsequently, 27 patients underwent surgery/chemotherapy due to deep submucosal or more advanced tumor stages or were managed conservatively. The remaining 91 patients with high grade dysplasia (48), intramucosal (38) or submucosal cancer (5) in the resected nodule underwent further endoscopic therapy with a mean follow-up of 24 months. Remission of dysplasia/neoplasia was achieved in 95.6 % after 12 months treatment. Stepwise endoscopic Barrett's resection resulted in complete Barrett's eradication in 36/91 patients (39.6 %) in a mean of four sessions; 40/91 patients (44.0 %) had a short circumferential Barrett's segment (< 3 cm). In this group, repeated EMR achieved complete Barrett's excision in 85.0 %. One patient developed a stricture (1.1 %), one a delayed bleeding, and there were no perforations. Conclusion: In patients with a short Barrett's segment, non-radical endoscopic Barrett's resection at the time of scheduled endoscopy follow-up allows complete Barrett's eradication with very low stricture rate.

Purpose: To compare saline infusion sonography (SIS) to tissue obtained from SIS-guided endometrial sampling (SISES) to determine sensitivity and specificity for benign and malignant conditions of the endometrium., Methods: Added value of SISES after SIS was evaluated over 5 years. SIS and SISES techniques have been previously described. Women with abnormal uterine bleeding and endometrial findings underwent SIS. Criteria for SISES included atypical polypoid mass, focal irregularity or global endometrial thickening, nondiagnostic SIS, discordance between SIS and endometrial biopsy, or request from the primary team. Final surgical pathology was compared with SIS and SISES., Results: One-hundred twenty-three SIS patients had SISES. SIS alone had a sensitivity of 100%, specificity of 42%, positive predictive value of 16%, and negative predictive value of 100%. A total of 120 patients had final clinical or surgical outcomes. Specificity was greatly improved with addition of SISES (95.5%, p < 0.001). Combination of SIS with SISES detected all 12 premalignant and malignant endometrial lesions. Three cases had small foci of hyperplasia (n = 2) or atypia (n = 1) in polyps on final surgical pathology, which were not prospectively identified on SISES., Conclusions: SISES significantly improves the specificity in the diagnosis of endometrial lesions. False-negative findings of SISES in polyps in postmenopausal women with bleeding suggest the need for surgical removal in this setting. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:416-422, 2016., (© 2016 Wiley Periodicals, Inc.)

Pelvic floor dysfunction encompasses an extremely common set of conditions, with various surgical and nonsurgical treatment options. Surgical options include injection of urethral bulking agents, native tissue repair with or without bioabsorbable or synthetic graft material, placement of synthetic midurethral slings or use of vaginal mesh kits, and mesh sacrocolpopexy procedures. Numerous different synthetic products with varied imaging appearances exist, and some of these products may be difficult to identify at imaging. Patients often present with recurrent or new symptoms after surgery; and depending on the presenting complaint and the nature of the initial intervention, imaging with ultrasonography (US), magnetic resonance (MR) imaging, voiding cystourethrography, or computed tomography (CT) may be indicated. US and MR imaging can both be used to image urethral bulking agents; US is often used to follow potential changes in bulking agent volume with time. Compared with MR imaging, US depicts midurethral slings better in the urethrovaginal space, and MR imaging is better than US for depiction of the arms in the retropubic space and obturator foramen. Mesh along the vaginal wall may be depicted with both US and MR imaging; however, the distal arms of the mesh traversing the sacrospinous ligaments or within the ischiorectal fossae (ischioanal fossae) are better depicted with MR imaging. Scarring can mimic slings and mesh at both US and MR imaging. MR imaging is superior to US for depiction of sacrocolpopexy mesh and associated complications. Voiding cystourethrography and CT are used less commonly because they rarely allow direct depiction of implanted material. Online supplemental material is available for this article. (©)RSNA, 2016.

Background and Aim: Endoscopic mucosal resection (EMR) has become the standard treatment for early oesophageal neoplasia. The mucosal defect caused by EMR usually takes several weeks to heal. Despite guidelines on high-risk endoscopic procedures in patients on anticoagulation, evidence is lacking whether EMR is safe in such patients. We investigated the immediate and delayed bleeding risk in patients undergoing diagnostic or therapeutic oesophageal EMR comparing patients requiring warfarin anticoagulation with a control group., Methods: Warfarin was stopped 5 days before the planned EMR and restarted on the evening following the procedure. Patients with high-risk conditions, such as recent pulmonary thromboemboli, received bridging with low molecular weight heparin. All EMRs were performed when the INR was <1.5. Bleeding events on the day of the EMR and within 3 months post-procedure were documented., Results: One hundred and seventeen consecutive patients with early oesophageal neoplasia were included. Sixty-eight EMRs were performed in 15 patients requiring anticoagulation. One patient on warfarin was readmitted 10 days after EMR with haematemesis and melaena. Out of 400 EMRs in 102 controls, 26 immediate bleeding events occurred requiring endoscopic intervention. One delayed bleeding event (melaena) occurred in the control group. The number of bleeding events did not differ between groups [p = 0.99; odds ratio 1.01 (0.30-3.44)], neither for acute (p = 0.76) nor delayed bleeding (p = 0.24)., Conclusion: EMR of early oesophageal neoplasia can be safely performed in patients requiring anticoagulation when warfarin is discontinued 5 days before the endoscopic intervention and reinstituted on the evening of the procedure day.

Fetal magnetic resonance (MR) imaging plays an increasing and valuable role in antenatal diagnosis and perinatal management of fetal gastrointestinal (GI) abnormalities. Advances in MR imaging data acquisition and use of motion-insensitive techniques have established MR imaging as an important adjunct to obstetric ultrasonography (US) for fetal diagnosis. In this regard, MR imaging provides high diagnostic accuracy for antenatal diagnosis of common and uncommon GI pathologic conditions. In the setting of fetal GI disease, T1-weighted images demonstrate the amount and distribution of meconium, which is crucial to the diagnostic capability of fetal MR imaging. Specifically, knowledge of the T1 signal intensity characteristics of fetal meconium, the normal pattern of meconium with advancing gestational age, and the expected caliber of small and large bowel in the fetus is key to diagnosis of abnormalities of the GI tract. Use of ultrafast T2-weighted sequences for evaluation of the expected location and morphology of fluid-containing structures, including the stomach and small bowel, in the fetal abdomen further aids in diagnostic confidence. Uncommonly encountered fetal GI pathologic conditions, especially cloacal dysmorphology, may demonstrate characteristic MR imaging patterns, which may add additional information to that from fetal US, allowing improved fetal and neonatal management. This article discusses common indications for fetal MR imaging of the GI tract, imaging protocols for fetal GI MR imaging, the normal appearance of the fetal GI tract with advancing gestational age, and the imaging appearances of common fetal GI abnormalities, as well as uncommon fetal GI conditions with characteristic appearances. (©)RSNA, 2016.

Purpose: To evaluate effects of altering rectal contrast volume on defecatory effort during magnetic resonance defecography (MRD)., Methods: We assessed defecation qualitatively and quantitatively as a function of rectal distention (group A: 180 cc, n=31; group B: 120 cc, n=31). Quantitative evaluation comprised measuring rectal area on midline sagittal images pre- and post-defecation., Results: Resting rectal area was significantly higher for group A than for group B (35.2 vs. 28.3 cm(2), P<.0001). Post-defecation rectal area and change in area (pre- to post-defecation) were not significantly different. Subjective evaluation showed no significant difference., Conclusion: Decreasing rectal gel volume from 180 to 120 cc did not compromise defecation performance during MRD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Ovarian preservation is an option for some premenopausal patients with early stage endometrial cancer. Studies have shown that ovarian preservation in selected patients does not negatively impact survival outcomes. The objective of this study is to determine the frequency and characteristics of ovarian involvement when endometrial cancer is clinically confined to the uterus., Methods: Patients with endometrioid adenocarcinoma of uterus treated at our institution between 2000 and 2013 were identified. Patients with ovarian metastasis or synchronous primary ovarian cancer were included. Patients were excluded if there was gross extrapelvic disease on examination or imaging., Results: Seven hundred and fifty-nine patients were found to have endometrial cancer with the disease confined to the pelvis (stages I, II, and III). Fifteen patients (2%) had ovarian metastasis. Twenty-three patients (3%) had synchronous uterine and ovarian cancer. Most ovarian lesions (32 out of 38) were either enlarged or had abnormal appearing surface involvement. Six patients had microscopic ovarian involvement, accounting for 0.8% of the endometrial cancer patients with pelvis-confined disease. All of the patients were greater than 50 years of age. For those patients with microscopic ovarian metastasis, all had FIGO grade 3 disease, deep myometrial invasion, and extrauterine involvement of either cervix or lymph nodes., Conclusions: Microscopic ovarian involvement occurred in 0.8% of patients with endometrial cancer. For premenopausal patients with endometrial cancer, normal appearing ovaries may be considered for preservation in the absence of extrauterine spread, grade 3 disease and deep myometrial invasion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

CCL19 and CCL21 are chemokines involved in the trafficking of immune cells, particularly within the lymphatic system, through activation of CCR7. Concurrent expression of PSGL-1 and CCR7 in naive T-cells enhances recruitment of these cells to secondary lymphoid organs by CCL19 and CCL21. Here the solution structure of CCL19 is reported. It contains a canonical chemokine domain. Chemical shift mapping shows the N-termini of PSGL-1 and CCR7 have overlapping binding sites for CCL19 and binding is competitive. Implications for the mechanism of PSGL-1's enhancement of resting T-cell recruitment are discussed.

Background: Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding., Methods: In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532., Findings: Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=0·04). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in the restrictive policy vs 83% (25) in the liberal policy (difference 14%; 95% CI 7-21; p=0·005). Mean last recorded haemoglobin concentration was 116 (SD 24) g/L for patients on the restrictive policy and 118 (20) g/L for those on the liberal policy (difference -2·0 [95% CI -12·0 to 7·0]; p=0·50). Fewer patients received RBCs on the restrictive policy than on the liberal policy (restrictive policy 133 [33%] vs liberal policy 247 [46%]; difference -12% [95% CI -35 to 11]; p=0·23), with fewer RBC units transfused (mean 1·2 [SD 2·1] vs 1·9 [2·8]; difference -0·7 [-1·6 to 0·3]; p=0·12), although these differences were not significant. We noted no significant difference in clinical outcomes., Interpretation: A cluster randomised design led to rapid recruitment, high protocol adherence, separation in degree of anaemia between groups, and non-significant reduction in RBC transfusion in the restrictive policy. A large cluster randomised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding., Funding: NHS Blood and Transplant Research and Development., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: Data on costs associated with acute upper gastrointestinal bleeding (AUGIB) are scarce. We provide estimates of UK healthcare costs, indirect costs and health-related quality of life (HRQoL) for patients presenting to hospital with AUGIB., Setting: Six UK university hospitals with >20 AUGIB admissions per month, >400 adult beds, 24 h endoscopy, and on-site access to intensive care and surgery., Participants: 936 patients aged ≥18 years, admitted with AUGIB, and enrolled between August 2012 and March 2013 in the TRIGGER trial of AUGIB comparing restrictive versus liberal red blood cell (RBC) transfusion thresholds., Primary and Secondary Outcome Measures: Healthcare resource use during hospitalisation and postdischarge up to 28  days, unpaid informal care, time away from paid employment and HRQoL using the EuroQol EQ-5D at 28  days were measured prospectively. National unit costs were used to value resource use. Initial in-hospital treatment costs were upscaled to a UK level., Results: Mean initial in-hospital costs were £2458 (SE=£216) per patient. Inpatient bed days, endoscopy and RBC transfusions were key cost drivers. Postdischarge healthcare costs were £391 (£44) per patient. One-third of patients received unpaid informal care and the quarter in paid employment required time away from work. Mean HRQoL for survivors was 0.74. Annual initial inhospital treatment cost for all AUGIB cases in the UK was estimated to be £155.5 million, with exploratory analyses of the incremental costs of treating hospitalised patients developing AUGIB generating figures of between £143 million and £168 million., Conclusions: AUGIB is a large burden for UK hospitals with inpatient stay, endoscopy and RBC transfusions as the main cost drivers. It is anticipated that this work will enable quantification of the impact of cost reduction strategies in AUGIB and will inform economic analyses of novel or existing interventions for AUGIB., Trial Registration Number: ISRCTN85757829 and NCT02105532., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aim: To investigate the outcome of repeating endoscopic retrograde cholangiopancreaticography (ERCP) after initially failed precut sphincterotomy to achieve biliary cannulation., Methods: In this retrospective study, consecutive ERCPs performed between January 2009 and September 2012 were included. Data from our endoscopy and radiology reporting databases were analysed for use of precut sphincterotomy, biliary access rate, repeat ERCP rate and complications. Patients with initially failed precut sphincterotomy were identified., Results: From 1839 consecutive ERCPs, 187 (10%) patients underwent a precut sphincterotomy during the initial ERCP in attempts to cannulate a native papilla. The initial precut was successful in 79/187 (42%). ERCP was repeated in 89/108 (82%) of patients with failed initial precut sphincterotomy after a median interval of 4 d, leading to successful biliary cannulation in 69/89 (78%). In 5 patients a third ERCP was attempted (successful in 4 cases). Overall, repeat ERCP after failed precut at the index ERCP was successful in 73/89 patients (82%). Complications after precut-sphincterotomy were observed in 32/187 (17%) patients including pancreatitis (13%), retroperitoneal perforations (1%), biliary sepsis (0.5%) and haemorrhage (3%)., Conclusion: The high success rate of biliary cannulation in a second attempt ERCP justifies repeating ERCP within 2-7 d after unsuccessful precut sphincterotomy before more invasive approaches should be considered.

Background: Proximal esophageal heterotopic gastric mucosa or so-called inlet patch in the cervical oesophagus is easily missed on endoscopic examination because of its localisation, usually just below the upper oesophageal sphincter. We evaluated the clinical use of narrow band imaging for detection of inlet patches., Methods: In this prospective, controlled observational study, 1407 subsequent patients underwent oesophagogastroduodenoscopy with or without narrow band imaging on withdrawal of the endoscope in the cervical oesophagus., Results: One endoscopist who was not aware of the prospective observation documented 6 (1.17%) cases of inlet patches in 515 oesophagogastroduodenoscopies compared to 4 cases out of 382 (1.05%) performed by the endoscopist who paid special attention to the presence of inlet patches but did not routinely apply narrow band imaging (OR 0.89, CI 95% 0.25-3.20, p=0.85). In comparison, 17 cases of inlet patches out of 510 (3.33%) were detected by the endoscopist who routinely applied narrow band imaging. The detection rate of proximal oesophageal heterotopic gastric mucosa using narrow band imaging was significantly higher compared to white light endoscopy only (OR 3.06, CI 95% 1.39-6.73, p=0.005)., Conclusions: Withdrawal of the endoscope from the cervical oesophagus using narrow band imaging increased the detection of inlet patches about three-fold compared to standard white light endoscopy., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Evaluation of acute abdominal and pelvic pain in pregnancy presents a diagnostic challenge for clinicians and radiologists alike. The differential diagnosis includes obstetric and nonobstetric conditions unique to pregnancy, in addition to causes of acute abdominal and pelvic pain unrelated to the pregnancy. The clinical presentation and course of disease may be altered in pregnancy, and several pathologies are exacerbated by pregnancy. Discriminating clinical features in the diagnosis of abdominal and pelvic pain are often confounded by expected anatomic and physiologic changes in pregnancy. Moreover, while diagnostic pathways may be altered in pregnancy, the necessity for a timely and accurate diagnosis must be underscored, as delay in treatment may result in an undesirable increase in morbidity and/or mortality for both the patient and fetus. Advances in magnetic resonance imaging (MRI) through faster acquisition and motion-insensitive techniques, coupled with increased awareness and education regarding the value of MRI in diagnosing a wide range of pathology, have established MRI as a valuable strategy in the investigation of acute abdominal and pelvic pain in the pregnant patient. This review presents a practical approach to common obstetric and nonobstetric causes of acute abdominal and pelvic pain during pregnancy, as well as safety considerations for performing MRI in this patient population.

Background and Aim: Postpolypectomy haemorrhage (PPH) is a known adverse event that can occur following polypectomy, occurring in 0.3-6.1% of cases. Previous meta-analysis has included small polyps, which are less likely to bleed, and less amenable to some methods of mechanical haemostasis. No comprehensive cost-benefit analysis of this topic is available. The aim of this study was to perform a meta-analysis of randomized trials and a cost-benefit analysis of prophylactic haemostasis in PPH., Methods: A total of 3092 abstracts from prospective trials conducted in human colonoscopic polypectomy were screened. Outpatients undergoing polypectomy in seven suitable studies (1426 episodes), without polyposis syndromes or bleeding diathesis, were identified. The interventions of prophylactic haemostatic measures (clips, loops, and/or adrenaline injection) to prevent PPH were assessed. The main outcome measurements were PPH measured by haematochezia or drop in haematocrit >10% or haemoglobin >1 g/dl. Risk ratio and number needed to treat (NNT) were generated using meta-analysis., Results: Comparing any prophylactic haemostasis to none, the pooled risk ratio for PPH was 0.35 (0.21-0.57; p < 0.0001), NNT was 13.6, and cost to prevent one PPH was USD652. Using adrenaline alone vs. no prophylactic haemostasis revealed a pooled risk ratio of 0.37 (0.20-0.66; p = 0.001), NNT 14.0, cost to prevent one PPH USD382. Any prophylactic mechanical haemostasis compared to adrenaline produced a RR for PPH of 0.28 (0.14-0.57; p < 0.0001), NNT 12.3, and cost to prevent one PPH USD1368., Conclusions: Adrenaline injection or mechanical haemostasis reduces the risk of PPH. Routine prophylactic measures to reduce PPH for polyps larger than 10 mm are potentially cost effective, although more thorough cost-benefit modelling is required.

Acute upper gastrointestinal bleeding (AUGIB) is the commonest reason for hospitalization with hemorrhage in the UK and the leading indication for transfusion of red blood cells (RBCs). Observational studies suggest an association between more liberal RBC transfusion and adverse patient outcomes, and a recent randomised trial reported increased further bleeding and mortality with a liberal transfusion policy. TRIGGER (Transfusion in Gastrointestinal Bleeding) is a pragmatic, cluster randomized trial which aims to evaluate the feasibility and safety of implementing a restrictive versus liberal RBC transfusion policy in adult patients admitted with AUGIB. The trial will take place in 6 UK hospitals, and each centre will be randomly allocated to a transfusion policy. Clinicians throughout each hospital will manage all eligible patients according to the transfusion policy for the 6-month trial recruitment period. In the restrictive centers, patients become eligible for RBC transfusion when their hemoglobin is <8 g/dL. In the liberal centers patients become eligible for transfusion once their hemoglobin is <10 g/dL. All clinicians will have the discretion to transfuse outside of the policy but will be asked to document the reasons for doing so. Feasibility outcome measures include protocol adherence, recruitment rate, and evidence of selection bias. Clinical outcome measures include further bleeding, mortality, thromboembolic events, and infections. Quality of life will be measured using the EuroQol EQ-5D at day 28, and the costs associated with hospitalization for AUGIB in the UK will be estimated. Consent will be sought from participants or their representatives according to patient capacity for use of routine hospital data and day 28 follow up. The study has ethical approval for conduct in England and Scotland. Results will be analysed according to a pre-defined statistical analysis plan and disseminated in peer reviewed publications to relevant stakeholders. The results of this study will inform the feasibility and design of a phase III randomized trial., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Purpose: Children with shunted hydrocephalus have been undergoing surveillance neuroimaging, generally in the form of head CT, for evaluation of ventricular size. As the life expectancy of these children has improved due to better shunt technology and medical care, risks related to the ionizing radiation incurred during multiple head CT examinations that they are expected to undergo throughout their lifetime have become a concern. The purpose of this study is to estimate the LAR of developing fatal cancer due to head CT for ventricular size assessment in children with shunted hydrocephalus and to assess the impact of instituting a rapid brain MR imaging protocol in reducing radiation exposure., Materials and Methods: Retrospective review of medical records yielded 182 patients who underwent neuroimaging for assessment of ventricular size. Available neuroimaging studies (head CT and rapid brain MR) were counted and annual neuroimaging frequency was calculated. It was assumed that these patients undergo a similar number of neuroimaging studies annually through 20 years of age. A risk estimate was calculated based on the BEIR VII report and effective doses obtained using the International Commission on Radiologic Protection Report 103 organ weighting factors., Results: The mean annual neuroimaging study frequency was 2.1. Based on the average age of 1.89 years, it was assumed neuroimaging surveillance commences in the second year of life. LAR was calculated assuming that a patient undergoes neuroimaging in the form of head CT at this frequency (2/year) through 20 years of age. Assuming 2 scans are performed per year and the low-dose head CT protocol is used, approximately 1 excess lifetime fatal cancer would be generated per 230 patients; with standard head CT, there would be 1 excess lifetime fatal cancer per 97 patients., Conclusions: Children with shunted hydrocephalus are at increased risk of developing fatal cancer if they are to undergo surveillance using head CT. Implementation of a rapid brain MR imaging protocol with no radiation detriment will reduce this risk.

Background: Extracorporeal shock wave lithotripsy (ESWL) of pancreatic duct stones followed by ERCP with mechanical clearance of the pancreatic duct and subsequent stenting is an established treatment option for chronic calcific pancreatitis., Objective: To test the efficacy of a modified transportable mini-lithotripter for ESWL of pancreatic duct stones., Design: Prospective single-center study., Setting: University hospital., Patients: This study involved 32 patients with obstructive chronic calcific pancreatitis and pain in whom previous endoscopic stone removal and pancreatic duct decompression had failed., Interventions: ESWL followed by ERCP for stone clearance of the pancreatic duct and mechanical removal of stones or stenting., Main Outcome Measurements: Endoscopic duct clearance and/or stent insertion, pain and quality-of-life scores., Results: A median of 4 ESWL sessions (interquartile range 2.75-8.5) with a median of 6800 shock waves (4225-15,425) were required. Pain relief after ESWL only was noted in 24 patients (75.0%), whereas no change in the intensity of pain was reported by 7 patients (21.9%), and pain was worse in 1 patient. All patients underwent ERCP and stent placement, resulting in complete resolution of pain in 17 patients (53.1%) and pain improvement in 28 patients (87.5%). The quality-of-life score was significantly improved after ESWL and endoscopic clearance or stenting in all patients., Limitations: Uncontrolled study., Conclusions: ESWL with the mini-lithotripter results in fragmentation of pancreatic duct calculi. ESWL in conjunction with endoscopic clearance of the pancreatic duct and stenting is associated with significant improvement in clinical outcome and quality of life in patients with obstructive calcific chronic pancreatitis., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background and Aim: Recurrent stent obstruction necessitating reintervention is problematic and incompletely understood. The aim of the present study was to identify factor(s) predisposing to reintervention., Methods: Retrospective review of patients (n = 117) referred to a single major endoscopic referral centre for palliative enteral stenting from 1999 to 2006. Twelve were excluded due to inadequate follow-up data (n = 7) or initial radiographic documentation (n = 5). A total of 105 patients (gastroduodenal n = 57, colonic n = 48) were therefore analyzed. The primary outcome of interest was recurrent obstruction necessitating reintervention. Kaplan-Meier analysis of potential factors predisposing to reintervention, including stent angulation (mild [<15°], moderate [15°-90°], severe [>90°]) was completed for 98 patients (technically successful enteral stenting)., Results: Technical and clinical success were achieved in 98 of 105 (93.3%) and 92 of 98 (93.9%) cases, respectively. Post-stenting median survival was 97.5 days (range 3-1054). Eighteen patients (18.4%) required reintervention for stent obstruction at a median time to reintervention of 85 days (range 7-481). Increased stent angulation (severe vs mild hazard ratio 6.73 (95% confidence interval 1.59-27.59), P = 0.009) was the only statistically significant factor in multivariate analysis predicting reintervention., Conclusions: Despite its limitation as a retrospective review, this study found that reintervention for stent obstruction is necessary in almost one in five cases, and increasing severity of stent angulation is the most important risk factor., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Objectives: Patients with Barrett's high-grade dysplasia (HGD) or early esophageal adenocarcinoma (EAC) that is shown on biopsy alone continue to undergo esophagectomy without more definitive histological staging. Endoscopic resection (ER) may provide more accurate histological grading and local tumor (T) staging, definitive therapy, and complete Barrett's excision (CBE); however, long-term outcome data are limited. Our objective was to demonstrate the effect on histological grade or local T stage, efficacy, safety and long-term outcome of ER for Barrett's HGD/EAC and of CBE in suitable patients., Methods: This prospective study at two Australian academic hospitals involved 75 consecutive patients over 7 years undergoing ER for biopsy-proven HGD or EAC, using multiband mucosectomy or cap technique. In addition, CBE by 2-3-stage radical mucosectomy was attempted for all Barrett's segments

Background: In the absence of precut needle-knife sphincterotomy (NKS), failure of biliary cannulation may occur in up to 10% of cases. There are few prospective evaluations of the safety and efficacy of NKS, and studies of its early use in difficult cannulation have been inconclusive. Whether precut NKS after failure of primary biliary cannulation is independently associated with post-ERCP pancreatitis (PEP) remains controversial., Objective: To examine the relationship between NKS and PEP., Design: Analysis of prospectively collected data from two randomized trials of ERCP techniques, with PEP as the primary endpoint measure., Setting: Tertiary-care academic medical center., Patients: This study involved 732 patients from two successive, prospective, randomized trials of naïve papilla cannulation between November 2001 and April 2006. Patients with pancreatic or ampullary cancer were excluded., Intervention: Naïve papilla cannulation, NKS, primary guidewire versus contrast-assisted cannulation, and glyceryl trinitrate patch versus placebo., Main Outcome Measurements: PEP and procedure-related complications., Results: NKS was performed in 94 of 732 patients (12.8%) and was successful in achieving bile duct access in 80 of 94 patients (85%). Cannulation success in the entire group was 717 of 732 patients (97.7%). The overall frequency of PEP following NKS was 14.9% (14 of 94 patients) compared with 6.1% (39 of 638 patients) without NKS (P < .001). The incidence of PEP increased with an increasing number of attempts at cannulating the papilla. Pancreatic stents were inserted in 22 patients, 5 of whom developed pancreatitis. In multivariate analysis, independent predictors of PEP were as follow: female sex (odds ratio [OR] = 3.5, P = .028), suspected sphincter of Oddi dysfunction (SOD) (OR = 9.7, P < .001), partial pancreatic drainage (OR = 4.8, P = .011), 10 to 14 attempts at papilla cannulation (OR = 4.4, P = .031), and >/=15 attempts at papilla cannulation (OR = 9.4, P = .013). NKS was not an independent predictor of PEP. There were no perforations, no major bleeding, and no cases of severe pancreatitis in the NKS group., Limitations: Nonrandomized for NKS intervention., Conclusions: The number of attempts at cannulating the papilla is independently associated with PEP, and the risk increases with an increasing number of attempts. NKS is not an independent predictor of PEP.

Background and Study Aims: Small flat nonpolypoid lesions of the colorectum can be technically difficult to target and completely remove; techniques such as hot biopsy forceps electrocauterization are associated with serositis, delayed bleeding, and perforation. This study aimed to describe a novel technique for the removal of such lesions and demonstrate its safety and efficacy., Patients and Methods: Patients aged 18 - 80 years with flat nonpolypoid lesions (Paris-Japanese classification 0-IIa and 0-IIb, measuring less than 10 mm) identified at colonoscopy were included in this prospective study. The lesions were removed by the suction pseudopolyp technique (SPT): the lesion is aspirated into the suction channel of the colonoscope and continuous suction applied for 5 seconds whilst the colonoscope is gently retracted. On release of the suction, the resulting pseudopolyp containing the lesion and a margin of normal tissue is easily ensnared and resected. The primary outcomes were endoscopic completeness of polyp resection and complication rate., Results: Over a 12-month period, 1231 polyps were removed during 2656 colonoscopies; 126 polyps (in 101 patients) met inclusion criteria. Complete endoscopic resection was achieved in 100 % of the polyps, without immediate or delayed complication. Of the resected lesions, 57 % had malignant potential (adenomas 47 % and sessile serrated lesions 10 %); a higher proportion of lesions removed from the right colon had malignant potential compared with those from the left colon (75 % vs. 41 %, P = 0.0066)., Conclusions: Diminutive flat lesions of the colorectum are predominantly adenomas and sessile serrated lesions. SPT is a safe, effective, and reproducible therapy for removal of these lesions., (Georg Thieme Verlag KG Stuttgart New York.)

Background and Study Aims: Inadvertent injection of contrast agent into the pancreatic duct is believed to be an important contributor to pancreatitis occurring after endoscopic retrograde cholangiopancreatography (post-ERCP pancreatitis, PEP). Our aim was to examine whether primary deep biliary cannulation with a guide wire is associated with a lower rate of PEP than conventional contrast-assisted cannulation., Patients and Methods: From August 2003 to April 2006 all patients with an intact papilla who were referred for ERCP were eligible. Patients with pancreatic or ampullary cancer were excluded. Patients were randomized to undergo sphincterotomy biliary cannulation using either contrast injection or a guide wire. The ERCP fellow attempted initially for 5 minutes. If unsuccessful, the consultant attempted for 5 minutes using the same technique, followed by crossover to the other technique in the same sequence and then needle-knife sphincterotomy where appropriate. Patients were assessed clinically after the procedure, then followed up with telephone interviews after 24 hours and 30 days, and serum amylase and lipase tests after 24 hours., Results: Out of 1654 patients undergoing ERCP, 413 were included in the study. PEP occurred in 29/413 (7.0 %): 16 in the guide-wire arm, 13 in the contrast arm ( P = 0.48). The overall cannulation success rate was 97.3 %. Cannulation was successful without crossover in 323/413 patients (78.2 %): 167/202 (81.4 %) in the guide-wire arm and 156/211 (73.9 %) in the contrast arm ( P = 0.03). Multivariate analysis demonstrated female sex (OR = 2.7, P = 0.04), suspected sphincter of Oddi dysfunction (OR = 5.5, P = 0.01), and complete filling of the pancreatic duct with contrast agent (OR = 3.5, P = 0.02) to be independently associated with PEP. The risk of PEP increased incrementally with each attempt at the papilla (OR 1.4 per attempt, P = 0.04) to greater than 10 % after four or more attempts., Conclusions: The guide-wire technique improves the primary success rate for biliary cannulation during ERCP but does not reduce the incidence of PEP compared to the conventional contrast technique. The incidence of PEP increases incrementally with each attempt at the papilla.

Anogenital distance (AGD) and the ratio of the second (index) to fourth (ring) digit lengths (2D:4D) are two widely used indicators of prenatal androgen exposure. The former is commonly used in rodent models, while the latter is principally used in human studies. We investigated variation in these two traits in C57BL/6J mice to test the hypothesis that variation in these two traits reflect a common underlying variable, presumably testosterone exposure. AGD is a sexually dimorphic trait used to sex young rodents. This distance typically increases and becomes more male-like in female pups when their uterine neighbors are male. 2D:4D is sexually dimorphic in a number of species, including humans and other great apes. Lower digit ratios may be associated with greater exposure to androgens during fetal development in humans. We found the expected sexual dimorphism in AGD, but no significant sex difference in 2D:4D, and no correlation between 2D:4D and AGD. Gestating next to males increased a pup's 2D:4D ratio, but it had no effect on AGD. The lack of correlation between 2D:4D and AGDs in this mouse strain suggests that these two measures do not reflect a common influence of androgen exposure. The possible roles of temporal and localized effects of masculinization are discussed.

Objective: The objective of the study was to examine diagnosis and outcome in a series of patients with small bowel tumors detected by capsule endoscopy (CE) in three Australian centers., Methods: Review of prospectively collected data from 416 CEs identified 27 tumors in 26 patients. Clinical parameters, tumor histology, and follow-up are reported., Results: Twenty-seven tumors were identified in 26 patients (mean age 61 +/- 13.7 yr). Indications for CE were obscure gastrointestinal (GI) bleeding (21), suspected tumor (3), abdominal pain (1), diarrhea (1). Prior radiology found a possible lesion in 8 of 23 (35%). Nine tumors were proven benign: hamartoma (4), cystic lymphangioma (1), primary amyloid (1), lipoma (1). Two lesions were non-neoplastic: heterotopic gastric mucosa and inflammatory fibroid polyp. Seventeen tumors were malignant: five adenocarcinomas, six carcinoids, two melanoma metastases, two gastrointestinal stromal tumors (GIST), one colon carcinoma metastasis, one non-Hodgkin's lymphoma. Tumors were surgically resected in 23 patients. Resection was considered curative in 12 (52%). Mean duration of follow-up was 26 +/- 13.7 months. Of the five patients with primary adenocarcinoma only one remains disease free. Three of the six with carcinoid tumors have had no recurrence up to 51 months postresection. Both patients with GIST are disease free. Anemia resolved after surgery in the patients with melanoma., Conclusions: Small bowel tumors are a significant finding at CE and are often missed by other methods of investigation. In many patients, detection of a tumor alters management and improves outcome. Even in malignant lesions, treatment is potentially curative in the absence of metastatic disease.

Digit ratio (2D:4D) is a trait, which is sexually differentiated in a variety of species. In humans, males typically have shorter second digits (2Ds) (index fingers) compared to fourth digits (4Ds) (ring fingers) whereas females' fingers are more equal in length. Smaller, more masculine, digit ratios are thought to be associated with higher prenatal testosterone levels, greater sensitivity to prenatal androgens or both. Men with more masculine digit ratios have shown increased ability, achievement and speed in sports and tend to report that they are more physically aggressive. Previous research has shown the same sexually differentiated pattern in the hind paws of laboratory mice as in human hands, males have lower 2D:4D than females. We measured hind paw digit ratio in mice of eight inbred strains. These measurements were made while blind to strain, sex and whether the paw was from the left or right side. We found large differences in digit ratio between the strains and suggest that inbred mice are a promising system for investigating the correlation between digit ratio and behavioral traits.

Finger length ratio (2D:4D) is a sexually dimorphic trait. Men have relatively shorter second digits (index fingers) than fourth digits (ring fingers). Smaller, more masculine, digit ratios are thought to be associated with either higher prenatal testosterone levels or greater sensitivity to androgens, or both. Men with more masculine finger ratios are perceived as being more masculine and dominant by female observers, and tend to perform better in a number of physical sports. We hypothesized that digit ratio would correlate with propensity to engage in aggressive behavior. We examined the relationship between trait aggression, assayed using a questionnaire, and finger length ratio in both men and women. Men with lower, more masculine, finger length ratios had higher trait physical aggression scores (r(partial) = -0.21, N = 134, P = 0.028). We found no correlation between finger length ratio and any form of aggression in females. These results are consistent with the hypothesis that testosterone has an organizational effect on adult physical aggression in men.

Many mechanisms, including alterations in muscle metabolism, cellular damage, decreased blood volume, and hepatic disfunction, are influential in producing the observed progressive rise in the concentration of amino acids in arterial and venous blood during persisting hypovolemic shock. The rapid rise of venous and arterial concentrations of amino acids and the increase in venoarterial concentration difference suggest that hypovolemia causes a net release from muscle of a potential substrate for energy metabolism. The blood flow through peripheral tissues, however, is reduced to such an extent during hypovolemic shock that the net rate of release of amino acids is not greater than preshock release and may be less. Therefore, the homeostatic advantages served by the alteration in protein metabolism during the more chronic stresses of starvation or after injury may not obtain during acute hypovolemia.

To determine the best antibiotic regimen to employ in patients undergoing laparotomy for trauma, a randomized prospective study was designed comparing cefoxitin alone with a triple-drug regime of an aminoglycoside, ampicillin, and clindamycin. One hundred nineteen consecutive patients sustaining abdominal trauma (97 penetrating; 22 blunt) were divided by date of admission to a 24-hour course of antibiotics. The overall infection rate was 16.0%, with 14.5% of the cefoxitin-treated patients, and 18.0% of the triple-drug-treated patients developing an infectious complication. Excluding remote site infections, the abdominal wound and intraperitoneal infection rates were 13.0% for cefoxitin-treated patients, and 12.0% for triple-drug-treated patients. There was one instance of oliguric renal failure questionably related to an aminoglycoside. It is concluded that a 24-hour course of cefoxitin is a safe and effective prophylactic antibiotic regime in patients undergoing laparotomy for trauma.

The main clinical types of epilepsy and their treatment are described. The treatment of choice in petit mal epilepsy is trimethadione (Trimedone) 0.3 g., three to six times a day, or acetazolamide (Diamox) 125-250 mg., three to four times a day. Phenobarbital is usually given as well to prevent grand mal seizures. Diphenylhydantoin sodium (Dilantin Sodium), 100 mg., and/or phenobarbital, 30-100 mg., three to four times a day, is recommended in patients with focal and grand mal epilepsy. Psychomotor automatisms are a form of focal seizure. Primidone (Mysoline), in doses of 125-250 mg. two to three times a day, is a very useful anticonvulsant in patients with myoclonic features, psychomotor automatisms and grand mal seizures. Primidone should be started in small doses. Drug reactions, especially cerebellar ataxia in the case of diphenylhydantoin and blood dyscrasias in the case of some drugs, should be recognized. Excessive drowsiness can be avoided by proper dosage and proper timing of drug administration. Patients should be seen regularly at least two to three times a year. The objective of treatment is to achieve optimum control of seizures by using the appropriate drug in adequate dosage. Social adaptation is good in the majority of patients, who should be encouraged to carry on their life independently, usually free to marry and have children. Attention to special occupational hazards has to be considered. Education of employers and employees is often necessary. Special work arrangements are occasionally indicated for selected patients. Patients should be seizure-free for two to three years before permission is given to drive an automobile.