Treatment of Bouveret syndrome with stone fragmentation using an endoscopic submucosal dissection knife.

Video 1Treatment of Bouveret syndrome with stone fragmentation using an endoscopic submucosal dissection knife. A 61-year-old man with a 3-decade history of recurrent cholecystitis presented to the community emergency department with severe right upper quadrant pain. A CT scan was performed and revealed gangrenous cholecystitis with likely cholecystoduodenal fistulous communication.After discussion with the patient and the HPB team, the plan was made to attempt endoscopic extraction of the obstructing stone. This would be performed in the operating room, such that if endoscopic extraction was not possible, surgical management would proceed.During the endoscopy, 1 L of liquid material was suctioned and the retained solids were cleared as best as possible. The large obstructing stone was then seen in the duodenal cap. In the cap, we could appreciate the obstructing stone and the fistulous tract.We then passed a guidewire distal to the stone and advanced a 15- to 20-mm extraction balloon over the guidewire. The balloon was passed distal to the stone and inflated to 20 mm. We then applied firm, steady traction in an attempt to extract the stone.With the double-channel gastroscope, we passed a second wire and extraction balloon distal to the stone to increase the amount of traction that could be applied. Both balloons were inflated distal to the stone, and steady, firm traction was again applied. Unfortunately, this was not successful either.We then decided to use a regular ERCP needle knife to incise the stone. Because the knife was delicate, it was easily deformable, so we decided to switch to a triangle-tip knife.Using the "PreciseSECT" mode on the electrosurgical unit, the stone was repeatedly incised. Particular care was taken to avoid flinging the knife and damaging the duodenal wall.Saline was used as the irrigation solution to ensure electrosurgical conductivity when the current was applied.At this point, we could appreciate fragmentation of the stones after repeated incision.After about 3 hours of stone incision and fragmentation, the guidewire was passed beyond the stone; the extraction balloon was advanced over the wire; and the balloon was again inflated with steady traction applied. This time, the stone was successfully extracted from the stomach.The duodenum was then examined. There were no remaining large pieces of stone or any significant mucosal damage or perforation.Using a mechanical lithotripter, the remaining larger fragments of stone were fragmented and extracted. However, because the stone had a large diameter, lithotripsy at the center was not initially possible, and the smaller lateral aspects had to be performed until the stone was completely fragmented.This case demonstrates the incision and fragmentation of a massive gallstone with the use of an endoscopic submucosal dissection knife and electrosurgical unit.With cautious application of this technique, successful endoscopic management of a large gallstone causing Bouveret syndrome was achieved. This technique avoided open surgical management and allowed for elective cholecystectomy at a later date with less morbidity.

Combatting Sedentary Lifestyles: Can Exercise Prescription in the Emergency Department Lead to Behavioral Change in Patients?

Introduction Emergency department (ED) patients with chronic disease are known to benefit from exercise; however, there are few studies examining the prescription of exercise in the ED. We asked, is exercise prescription in the ED feasible and effective? Methods In this pilot prospective block randomized trial, consented patients were divided into control and intervention groups. The control group received routine care. The intervention group received combined written and verbal prescriptions for moderate exercise of 150 minutes/week. Both groups were followed up by phone at two months. The primary outcome was achieving 150 minutes of exercise per week. Secondary outcomes included change in exercise and differences in reported median weekly exercise. Results Follow-up was completed for 23/28 patients (11 control; 12 intervention). Baseline reported median (with interquartile range) weekly exercise was similar between groups: control 0 (0-0) minutes, intervention 0 (0-45) minutes. There was no difference between groups for the primary outcome at two months (control 3/11; intervention 4/12, relative risk [RR] 1.33 (95% confidence interval [CI] 0.38-4.6; p=1.0). There was a significant increase in median exercise from baseline in both groups, but no difference between the groups (control 75 (10-225) minutes; intervention 120 (52.5-150) minutes; NS). A post hoc comparison of patients actually receiving intervention vs. no intervention revealed a significant increase in patients meeting the primary outcome (no intervention 0/8; intervention 7/15, RR 2.0 (95% CI 1.2-3.4); p=0.05). Conclusion The improvement seen in patients receiving the exercise prescription intervention, and the increase in reported exercise in both groups suggests that exercise prescription for ED patients may be beneficial.

Spot protein-creatinine ratio and spot albumin-creatinine ratio in the assessment of pre-eclampsia: a diagnostic accuracy study with decision-analytic model-based economic evaluation and acceptability analysis.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) guidelines highlighted the need for 'large, high-quality prospective studies comparing the various methods of measuring proteinuria in women with new-onset hypertensive disorders during pregnancy'. OBJECTIVES: The primary objective was to evaluate quantitative assessments of spot protein-creatinine ratio (SPCR) and spot albumin-creatinine ratio (SACR) in predicting severe pre-eclampsia (PE) compared with 24-hour urine protein measurement. The secondary objectives were to investigate interlaboratory assay variation, to evaluate SPCR and SACR thresholds in predicting adverse maternal and fetal outcomes and to assess the cost-effectiveness of these models. DESIGN: This was a prospective diagnostic accuracy cohort study, with decision-analytic modelling and a cost-effectiveness analysis. SETTING: The setting was 36 obstetric units in England, UK. PARTICIPANTS: Pregnant women (aged ≥ 16 years), who were at > 20 weeks' gestation with confirmed gestational hypertension and trace or more proteinuria on an automated dipstick urinalysis. INTERVENTIONS: Women provided a spot urine sample for protein analysis (the recruitment sample) and were asked to collect a 24-hour urine sample, which was stored for secondary analysis. A further spot sample of urine was taken immediately before delivery. MAIN OUTCOME MEASURES: Outcome data were collected from hospital records. There were four index tests on a spot sample of urine: (1) SPCR test (conducted at the local laboratory); (2) SPCR test [conducted at the central laboratory using the benzethonium chloride (BZC) assay]; (3) SPCR test [conducted at the central laboratory using the pyrogallol red (PGR) assay]; and (4) SACR test (conducted at the central laboratory using an automated chemistry analyser). The comparator tests on 24-hour urine collection were a central test using the BZC assay and a central test using the PGR assay. The primary reference standard was the NICE definition of severe PE. Secondary reference standards were a clinician diagnosis of severe PE, which is defined as treatment with magnesium sulphate or with severe PE protocol; adverse perinatal outcome; one or more of perinatal or infant mortality, bronchopulmonary dysplasia, necrotising enterocolitis or grade III/IV intraventricular haemorrhage; and economic cost and outcomes. Health service data on service use and costs followed published economic models. RESULTS: In total, 959 women were available for primary analysis and 417 of them had severe PE. The diagnostic accuracy of the four assays on spot urine samples against the reference standards was similar. The three SPCR tests had sensitivities in excess of 90% at prespecified thresholds, with poor specificities and negative likelihood ratios of ≥ 0.1. The SACR test had a significantly higher sensitivity of 99% (confidence interval 98% to 100%) and lower specificity. Receiver operating characteristic (ROC) curves were similar (area under ROC curve between 0.87 and 0.89); the area under the central laboratory's SACR curve was significantly higher (p = 0.004). The central laboratory's SACR test was the most cost-effective option, generating an additional 0.03 quality-adjusted life-years at an additional cost of £45.07 compared with the local laboratory's SPCR test. The probabilistic analysis showed it to have a 100% probability of being cost-effective at the standard willingness-to-pay threshold recommended by NICE. LIMITATIONS: Implementation of NICE guidelines has led to an increased intervention rate in the study population that affected recruitment rates and led to revised sample size calculations. CONCLUSIONS: Evidence from this clinical study does not support the recommendation of 24-hour urine sample collection in hypertensive pregnant women. The SACR test had better diagnostic performance when predicting severe pre-eclampsia. All four tests could potentially be used as rule-out tests for the NICE definition of severe PE. FUTURE WORK: Testing SACR at a threshold of 8 mg/mmol should be studied as a 'rule-out' test of proteinuria. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82607486. FUNDING: This project was funded by the National Institute Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 61. See the NIHR Journals Library website for further project information.

Action on Pre-eclampsia: Crisis and recovery.

This is a review of the antenatal guidelines developed under the auspices of the charity Action on Preeclampsia since 2001. They are evidence-based and cover the screening and diagnosis of preeclampsia. They include a risk assessment early in pregnancy, referral for specialist input, a two tier schedule of assessment based on risk, signs and symptoms, referral for step-up care and confirmation of diagnosis, including blood tests. They describe methods for improving reliability of proteinuria testing, and reducing errors in the measurement of blood pressure. Management flowcharts are provided.

Regulation of the 14-3-3-binding protein p39 by growth factors and nutrients in rat PC12 pheochromocytoma cells.

Unstimulated PC12 pheochromocytoma cells contain many proteins that bound to 14-3-3s in competition with a 14-3-3-binding peptide. Additional proteins, including one of 39 kDa (p39), became capable of binding to 14-3-3s in phosphatidylinositol 3-kinase-dependent responses to epidermal growth factor or nerve growth factor in vivo. The growth factor regulation was unaffected by inhibitors of the mitogen- or stress-activated protein kinase pathways, or by glucose starvation, but was blocked by amino acid starvation and only partially blocked by rapamycin. p39 in extracts of unstimulated, nutrient-fed cells, but not nutrient-starved cells, was able to bind to 14-3-3s after phosphorylation by protein kinase B (PKB) in vitro. Nutrient starvation did not affect the growth factor-stimulated activation of PKB in vivo. Either cycloheximide (CHX) or the cysteine protease inhibitor, MG132, restored the responsiveness of p39 to growth factors in nutrient-starved cells. In contrast, MG132 could not replace amino acids in supporting the growth factor-stimulated phosphorylation of two downstream targets of mTOR (mammalian target of rapamycin), namely eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and p70 S6 kinase. CHX permitted complete growth factor-stimulated phosphorylation of both 4E-BP1 and p70 S6 kinase in nutrient- starved cells; however, unlike p39, phosphorylation of these proteins was blocked by rapamycin. These findings implicate PKB (or an enzyme with similar specificity) in the growth factor-triggered phosphorylation of p39. In addition, amino acid starvation induces a CHX- and MG132-sensitive pathway that targets p39 and appears to be distinct from the mechanism of regulation of 4E-BP1 and p70 S6 kinase.