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The field of abdominal organ transplantation is multifaceted, with the clinician balancing recipient comorbidities, risks of the surgical procedure, and the pathophysiology of immunosuppression to ensure optimal outcomes. An underappreciated element throughout this process is acute pain management related to the surgical procedure. As the opioid epidemic continues to grow with increasing numbers of transplant candidates on opioids as well the increase in the development of enhanced recovery after surgery protocols, there is a need for greater focus on optimal postoperative pain control to minimize opioid use and improve outcomes. This review will summarize the physiology of acute pain in transplant recipients, assess the impact of opioid use on post-transplant outcomes, present evidence supporting nonopioid analgesia in transplant surgery, and briefly address the perioperative approach to the pretransplant recipient on opioids.

Chapter 2 covers U.S. government controls on exports, reexports, and transfers of “U.S.-origin” goods, software, and technology, and the provision of services, that are military in nature. These are governed principally by the Arms Export Control Act of 1976 and the International Traffic in Arms Regulations (ITAR), which are administered by the State Department’s Directorate of Defense Trade Controls (DDTC). The chapter explains: which items are subject to the ITAR; the basis and criteria for the ITAR’s restrictions; the requirement to register with DDTC if you export or manufacture items subject to the ITAR or if you are involved in other activities regulated by the ITAR; how to determine whether your product or technology is covered and, if so, whether you will need a license to export or reexport it; how to get a license if one is required; how to clear and document the actual export; the potential penalties for violating the rules; and reporting requirements related to political contributions, fees, and commissions paid in connection with certain sales, . The chapter also explains how the ITAR relate to the regulatory regimes covered in other parts of the book.

Chapter 4 covers two related sets of U.S. government controls on nuclear-related items that flow from the Atomic Energy Act of 1954 and the Nuclear Non-Proliferation Act of 1978. One, administered by the Nuclear Regulatory Commission (NRC), covers exports of nuclear hardware and nuclear materials. The other, called “Part 810” and administered by the National Nuclear Security Administration (NNSA) of the U.S. Department of Energy, covers assistance by U.S. persons (including transfers of nuclear-related technology) to foreign nuclear activities. The chapter explains: which items and activities are subject to the NRC and NNSA regulations; the basis and criteria for their restrictions; how to determine whether your commodity or activity is covered and, if so, whether you will need a license to export or reexport it; how to get a license if one is required; and the potential penalties for violating the rules. The chapter also explains how the NRC and NNSA rules relate to the regulatory regimes covered in other parts of the book.

Chapter 1 covers U.S. government controls on exports, reexports, and transfers of “U.S.-origin” goods, software, and technology that are commercial, “dual-use” (i.e., having both civilian and military uses), and low-level military in nature. These are governed principally by the Export Control Reform Act of 2018 and the Export Administration Regulations (EAR), which are administered by the Commerce Department’s Bureau of Industry and Security. The chapter explains: what kinds of items are subject to the EAR; the various bases for the EAR’s restrictions; how to determine whether your product or technology is covered and, if so, whether you will need a license to export or reexport it; how to get a license if one is required; how to clear and document the actual export; and the potential penalties for violating the rules. The chapter also explains how the EAR relate to the regulatory regimes covered in other parts of the book.

Chapter 3 covers U.S. government economic sanctions, which may be imposed upon entire countries (as embargoes), specified economic sectors, or individual state or nonstate actors. These comprise approximately thirty different programs that are governed principally by the International Emergency Economic Powers Act (IEEPA), various other sanctions legislation, and the regulations of the U.S. Department of the Treasury’s Office of Foreign Assets Control (OFAC). The chapter explains: which types of transactions are subject to the OFAC regulations; the basis and criteria for those restrictions; how to determine whether your transaction is prohibited without a license and, if so, whether you are likely to get a license for it; how to seek a license if one is required; and the potential penalties for violating the rules. The chapter also explains how the OFAC regulations relate to the regulatory regimes covered in other parts of the book.

U.S. Export Controls and Economic Sanctions is a must for those who deal with U.S. government export control and economic sanctions regulations. Written as a user’s manual rather than an academic or historical treatise, it covers in considerable detail—but in language that is intelligible to non-lawyers as well as lawyers—the Commerce Department’s controls on exports of commercial, “dual-use” (having both commercial and military utility), and low-level military items, the State Department’s controls on higher-level military items, the Treasury Department’s approximately thirty different economic sanctions programs, the Nuclear Regulatory Commission’s controls on nuclear-related commodities, and the Energy Department’s restrictions on assistance to foreign nuclear programs. Given the authors’ decades of experience with these regulations, the book not only explains the legal rules but also offers tips—not necessarily reflected in the regulations themselves—about how to interpret the regulations and deal with the regulators.

Background Angiotensin receptor blocker‐associated enteropathy (ARB‐e) is an increasingly recognised clinical entity with symptoms and histological findings identical to coeliac disease (CD). There is evidence to suggest immune‐mediated mucosal injury in ARB‐e with a high prevalence of DQ2/DQ8; however, as IgA anti‐tissue transglutaminase (anti‐TTG) is usually negative, an insult other than TTG‐mediated injury is suspected. The impact of ARBs on disease activity in patients with CD is not known. Objective To assess the effect of ARB exposure on patients with established CD. Methods A patient record search of 1142 individual patients attending a dedicated coeliac clinic from 2010 to the present identified 59 patients treated with ARB. Those with CD confirmed by serology (TTG + ve/EMA + ve) and histopathology (Marsh criteria) were included (n = 40, 0.52%). Data collected included disease duration, compliance with gluten‐free diet (GFD), reported symptoms (diarrhoea, weight loss and abdominal pain), surrogate markers of absorption (Vitamin D, Iron, Calcium and Haemoglobin), in addition to anti‐TTG titre and histological grade at last follow up. Patients were age and sex‐matched in a 1:2 ratio with CD patients not taking ARBs (controls), with comparable rates of disease duration and compliance with GFD. Results The ARB and control groups were matched in terms of age (mean 66.2 years) and gender (female 63%). Strict compliance with GFD was reported in 55% and 56%, respectively. Persistent symptoms were reported in 10/40 (25%) of the ARB group compared with 7/82 (9%) of controls (p = 0.0181). There were lower rates of mucosal healing (Marsh grade 0) in the ARB group (36% n = 11) compared to controls (55%, n = 33). There was no significant difference in anti‐TTG titres. Surrogate markers of absorption were comparable across the groups, except for Vitamin D which was lower in those taking olmesartan (p = 0.0015). Conclusions ARBs may aggravate the enteropathy and lead to increased symptoms in patients with bone fide diagnosed CD following a GFD., Key summary Summarise the estabished knowledge on this subject Angiotensin receptor blocker‐associated enteropathy (ARB‐e) is an increasingly recognised clinical entity with symptoms and histological findings identical to coeliac disease (CD).The exact cause of mucosal injury in ARB‐e is unknown however there is evidence to suggest immune‐mediated mucosal injury in ARB‐e with a high prevalence of DQ2/DQ8, however as anti‐tissue transglutaminase (TTG) is usually negative, an insult other than TTG‐mediated injury is suspected. The impact of ARBs on disease activity in patients with CD is not known. What are the significance and/or new findins of this study? Coeliac patients who take ARBs are more likely to have persistent symptoms and lower rates of mucosal healing than their age‐matched coeliac controls. This observation appears to be independent of TTG mediated injury, akin to that reported in non‐coeliac populations.ARB use in patients with established coeliac disease may confound the interpretation of clinical and histological response to a gluten‐free diet.

Background Pain continues to be the most common medical concern, and perioperative health care providers are encountering increasing numbers of patients with chronic pain conditions. It is important to have a clear understanding of how long-term use of pain medications impacts anesthesia during the intraoperative and postoperative periods. Objective To review common medications used to treat chronic pain and summarize current recommendations regarding perioperative care. Method We reviewed the literature by searching PubMed and Google Scholar for articles from 2000-2016. The search strategy included searching for the various classes of pain medications and including the terms perioperative, anesthesiology, and recommendations. We also reviewed the reference lists of each article to identify other relevant sources regarding the perioperative management of pain medications. Results After the literature review, we were able to establish the pharmacology, anesthetic interactions, and recommendations for management of each of the common classes of pain medication. Conclusion Management of postoperative pain is an important concern for all perioperative health care providers. Although most pain medications should be continued in the perioperative period, it is important to preoperatively discontinue those that antagonize pain receptors to avoid significant postoperative morbidities associated with poorly managed pain.

BACKGROUND: Coeliac disease (CD) is associated with an increased risk of other immune-mediated conditions. Aim: To investigate the prevalence of coexistent immune-mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years. METHODS: Medical record data were collected retrospectively from 749 CD patients in Ireland. Prevalence of autoimmune diseases was compared with previously published results from general populations. Patients were divided into four groups based on the year of diagnosis to analyse changes in the prevalence of autoimmune thyroidal disease over time. RESULTS: Median age at the time of CD diagnosis was 56 years (range 18–91 years). A total of 233 (31.1%) patients had a coexistent immune-mediated condition (IMC). Autoimmune thyroidal diseases were seen in 149 (19.9%) patients, hypothyroidism in 110 (14.7%), type 1 diabetes in 27 (3.6%), psoriasis in 20 (2.7%), inflammatory bowel disease in 14 (1.9%) and rheumatoid arthritis in 12 (1.6%). All conditions were more common in CD patients than in the general population. Type 1 diabetes was diagnosed mainly before CD, whereas there was no such trend in other conditions. Autoimmune thyroidal diseases became less common in female CD patients over time. CONCLUSIONS: Prevalence of autoimmune diseases is increased in adult CD patients compared with the general population. However, concomitant autoimmune thyroidal diseases became less common over time in women.

Since its description in 1974, the Objective Structured Clinical Examination (OSCE) has gained popularity as an objective assessment tool of medical students, residents, and trainees. With the development of the anesthesiology residents’ milestones and the preparation for the Next Accreditation System, there is an increased interest in OSCE as an evaluation tool of the six core competencies and the corresponding milestones proposed by the Accreditation Council for Graduate Medical Education. In this article the authors review the history of OSCE and its current application in medical education and in different medical and surgical specialties. They also review the use of OSCE by anesthesiology programs and certification boards in the United States and internationally. In addition, they discuss the psychometrics of test design and implementation with emphasis on reliability and validity measures as they relate to OSCE.

Background A considerable portion of the US population uses herbal supplements on a daily basis for their various proposed beneficial effects. However, the over-the-counter nature of these medications and lack of knowledge of adverse effect profiles can have unexpected serious impact on the perioperative course. The growing list of supplements presents a pharmacologic conundrum to the anesthesiologist. Objective The study aimed to compile a comprehensive list of vitamins, herbals, and supplements used commonly by patients, describe the risks associated with them, and identify recommendations for perioperative management. Method The current literature on PubMed and Medline was reviewed for the years 2000 through 2016. The reference lists of each selected article were also reviewed for additional sources of information. Results The review identified 23 herbals and supplements that are commonly used and their perioperative considerations. Conclusion The management of herbals and supplements is an issue for the anesthesiologist. Although it would be prudent to stop the use of most substances a week or more preoperatively, the perioperative physician must be wary of the potential for withdrawal.

Celiac disease is an immune-mediated enteropathy characterized with high heterogeneity in presentation among genetically predisposed individuals. In recent years, a change in the phenotypic presentation of celiac disease has been reported. We studied clinical presentation, from 1960 through 2015, in Ireland, which has a high incidence of celiac disease.We performed a retrospective analysis of medical charts from patients diagnosed with celiac disease at 5 secondary referral centers in Ireland from 1960 through 2015 (n = 749; median age, 56 years; age range, 18-91 years). The cohort was divided into 5 groups based on year of diagnosis (≤1985, 1986-1995, 1996-2005, 2006-2010, or 2011 and later). We collected findings from clinical presentation at diagnosis; serology tests; small intestinal biopsy analyses; and patients' demographic, clinical, and family data. Presentations at diagnosis were classified according to the Oslo criteria as follows: classical (patients presenting with malabsorption), nonclassical (no signs or symptoms of malabsorption at presentation), or subclinical (below the threshold of clinical detection). The primary outcome was change in clinical presentation of celiac disease over time.Of the 749 patients studied, 512 were female and 237 were male (ratio of 2.2:1). Female patients were diagnosed at younger ages than male patients (42 vs 47 years, respectively; P = .004), and had more immune-mediated conditions than male patients (35.7% for female patients vs 21.5% for male patients; P.001). For patients diagnosed as adults (after the age of 18 years), the median age of diagnosis increased from 34.0 years during the period ≤1985 to median ages of 44-46 years after 1985 (P.002). A smaller proportion of patients presented with classical features of celiac disease after 2010 (48.4%) than ≤1985 (85.2%); the proportion of patients with nonclassical or subclinical celiac disease increased from 14.8% ≤1985 to 51.6% after 2010 (P = .006 for each). Biopsies categorized as Marsh 3c decreased, from 52.2% in the period 1996-2005 to 22.5% in the period after 2010 (P = .003). The prevalence of associated thyroid disease has decreased during the study period, from 36.6% ≤1985 to 17.1% after 2010 (P = .039), whereas body mass index at diagnosis increased from 21.5 kg/mWe found the clinical presentation of celiac disease changed significantly in Ireland from 1960 through 2015. The age of presentation in adulthood increased over this time period, as did the proportions of patients with nonclassical or subclinical disease.

Colorectal polyps are usually asymptomatic and are found opportunistically. Individuals with adenomata are at increased risk for cancer and therefore guidelines exist for surveillance of these lesions including those of the British Society of Gastroenterology (BSG). Deviation from these guidelines is common and increases the workload of endoscopy. We examined those individuals waiting for endoscopy for polyp surveillance to see whether strict adherence to BSG guidelines could facilitate opportunities for screening. A total of 413 patients with earlier colonic polyps were examined, of whom 50 patients were excluded based on having alternative indications for surveillance, 179 (49.3%) were appropriately scheduled for surveillance and 184 patients (55.9%) were scheduled incorrectly. Seventy-nine patients (30%) could have been discharged; of these, 59 had hyperplastic polyps. Of the remaining 105 inappropriate triages under surveillance at the wrong interval, seven patients were scheduled for too infrequent surveillance and 98 were too frequent. A total of 284 patients with adenomatous polyps were under surveillance of whom 11 patients (3.8%) were in the high-risk category and all were appropriately scheduled, and 75 patients (26.4%) were in the intermediate-risk category, of whom 48 were appropriately scheduled, 20 were incorrectly triaged as high risk and seven were triaged as low risk. A total of 198 (69.7%) patients were in the low-risk category, 117 of these were correctly triaged, 15 were incorrectly triaged as high risk and 66 were classified as intermediate risk. Over a five-year period, 318 unnecessary colonoscopies are being performed. On the basis of the data obtained from a population-based colorectal screening programme using immunohistochemical-faecal occult blood testing in our department another 1516 patients could be screened annually without requiring any additional endoscopy resources, if strict adherence to guidelines was assured.

Since the discovery of Helicobacter pylori in the early 1980s several treatment regimens have been developed to effectively treat this infection. International guidelines have allowed consensus on the best management and improved eradication rates. In recent years increasing antimicrobial resistance and falling eradication rates highlight the need for updated guidelines. In this article we review the most recent European management guidelines and in view of the unavailability of some drugs consider new treatment regimens for the management of H. pylori in Ireland.

The explosive development of gastroenterology and gastrointestinal endoscopy over the past few years, with clinical trials of powerful new drugs and top-quality endoscopes and accessories, has led to a huge increase in the diagnostic and therapeutic potential of modern gastroenterology. At the same time the percentage of elderly people in Europe has increased, patients attending gastrointestinal endoscopy units are expecting to undergo painless endoscopy procedures, and palliative endoscopic therapy is increasingly being used for patients with lethal gastrointestinal diseases. This new environment presents a number of ethical issues and necessitates an updated consensus applicable in the clinical practice of gastroenterology. The European Society of Gastrointestinal Endoscopy (ESGE) and the Organisation Mondiale d’Endoscopie Digestive (OMED), in collaborationwith the United European Gastroenterology Federation (UEGF), organized the Second European Symposium on Ethics in Gastroenterology and Digestive Endoscopy on the island of Kos, Greece, in July 2006. Twenty-three expert gastroenterologists, surgeons, and scientists from the biomedical industry participated in four workshops, aiming to formulate a consensus statement after presentation of the topics, discussion, and voting in a plenary session. We are happy to present these consensus reports here in Endoscopy and hope that they will help our colleagues in their clinical practice. Workshop 1: Patient satisfaction with endoscopy !

The discovery of Helicobacter pylori was one of the most notable in gastroenterology – and indeed medicine. The century before Marshall and Warren's discovery is peppered with isolated accounts of spiral-shaped bacteria in the stomach. The discovery of H. pylori , and the recognition of its importance, came about as a consequence of combined clinical, pathological and microbiological work. The discovery has transformed the treatment of peptic ulcers and other related diseases.

Gastric adenocarcinoma occurs via a sequence of molecular events known as the Correa's Cascade which often progresses over many years. Gastritis, typically caused by infection with the bacterium H. pylori, is the first step of the cascade that results in gastric cancer; however, not all cases of gastritis progress along this carcinogenic route. Despite recent antibiotic intervention of H. pylori infections, gastric adenocarcinoma remains the second most common cause of cancer deaths worldwide. Intestinal metaplasia is the next step along the carcinogenic sequence after gastritis and is considered to be a precursor lesion for gastric cancer; however, not all patients with intestinal metaplasia develop adenocarcinoma and little is known about the molecular and genetic events that trigger the progression of intestinal metaplasia into adenocarcinoma. This review aims to highlight the progress to date in the genetic events involved in intestinal-type gastric adenocarcinoma and its precursor lesion, intestinal metaplasia. The use of technologies such as whole genome microarray analysis, immunohistochemical analysis and DNA methylation analysis has allowed an insight into some of the events which occur in intestinal metaplasia and may be involved in carcinogenesis. There is still much that is yet to be discovered surrounding the development of this lesion and how, in many cases, it develops into a state of malignancy.

Confocal laser endomicroscopy (CLE) is an advanced imaging technique which combines conventional white light endoscopy (WLE) with an integrated or probe based confocal microscope. This allows microscopic examination of the surface epithelium and in vivo diagnosis during endoscopy. Established CLE applications include the diagnosis of Barrett's oesophagus, gastric intestinal metaplasia, coeliac disease and microscopic colitis. CLE can differentiate hyperplastic from adenomatous polyps in the colon and may obviate the need to biopsy all polyps at endoscopy. CLE is particularly helpful in surveillance endoscopy in inflammatory bowel disease where it has been shown to reduce the number of biopsies required and improve the detection of dysplasia. The future of CLE may be with new contrast agents to allow for molecular tagging and improved endoscopic diagnoses. The aim of this review is to describe the technology and techniques involved in CLE, and discuss the evolving applications in obtaining "virtual biopsy" throughout the GI tract.

Background Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance). The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. Methods We have evaluated six candidate genes in one of these regions (11q23), namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. Results Promotor SNPs (-607, -137) in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P < 0.05). Follow-up analyses of an extended sample supported the same, moderate effect (P < 0.05) for one of these. Haplotype analysis of IL18-137/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C/-137C (P < 0.0001), which was independently associated in two case-control comparisons. This same haplotype has been noted in rheumatoid arthritis. Conclusion Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine's role in maintaining inflammation in active CD.

Antibiotic resistance has resulted in unsatisfactory eradication results with dual and now triple therapy in many countries. Newer antibiotics and changes in dosing and duration of therapy may overcome resistant strains but may only provide limited improvement in eradication rates. Sequential therapy with amoxicillin (1 g twice a day) and a proton pump inhibitor (PPI) (twice a day) given for 5 days followed by a PPI plus clarithromycin (500 mg twice a day) and tinidazole (500 mg twice a day) for 5 days is now a first-line therapy for Helicobacter pylori in some countries. Standard triple therapy is effective in regions where clarithromycin resistance is low. Levofloxacin based triple therapy is an effective alternative to quadruple therapy in second-line treatment. Adjuvant therapy may reduce side-effects and improve compliance. Molecular and genomic research on H. pylori may result in the development of targeted antibiotic therapy; however, more research is required in this field. Further research in vaccination is also necessary before this can become an option in clinical practice.

Helicobacter pylori infection causes a broad spectrum of clinical diseases and the clinical manifestations of the infection depend on host, environmental, and bacterial factors. These factors have an impact on the pattern and severity of gastritis and ultimately determine the clinical outcome of H. pylori infection. Better staging of gastritis may help to identify patients at risk of gastric cancer. In this article we will examine the complex interaction between host, environmental, and bacterial factors in the pathogenesis of H. pylori infection.