Current and Advanced Applications of Gadoxetic Acid-enhanced MRI in Hepatobiliary Disorders.

Gadoxetic acid is an MRI contrast agent that has specific applications in the study of hepatobiliary disease. After being distributed in the vascular and extravascular spaces during the dynamic phase, gadoxetic acid is progressively taken up by hepatocytes and excreted to the bile ducts during the hepatobiliary phase. The information derived from the enhancement characteristics during dynamic and hepatobiliary phases is particularly relevant in the detection and characterization of focal liver lesions and in the evaluation of the structure and function of the liver and biliary system. The use of new MRI sequences and advanced imaging techniques (eg, relaxometry, multiparametric imaging, and analysis of heterogeneity), the introduction of artificial intelligence, and the development of biomarkers and radiomic and radiogenomic tools based on gadoxetic acid-enhanced MRI findings will play an important role in the future in assessing liver function, chronic liver disease, and focal liver lesions; in studying biliary pathologic conditions; and in predicting treatment responses and prognosis. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion. The initial approach is similar in most cases, but a definitive treatment depends on etiology, that is why etiological investigation is mandatory in all cases. The majority of patients are asymptomatic and diagnosed during routine exams; only a small percentage of patients present with severe manifestations which can affect neurological, muscular, gastrointestinal, renal, and cardiovascular systems. Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms. Critically ill patients should receive treatment as soon as diagnosis is made. Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption such as bisphosphonates and, more recently, denosumab, in refractory cases; also, corticosteroids and calcitonin can be used in specific cases. This review aims to provide a clinical update on current concepts of the pathophysiology of calcium homeostasis, epidemiology, screening, clinical presentation, diagnosis, and management of hypercalcemia.

Buena concordancia entre la elastografía de transición y las pruebas combinadas APRI y FIB-4 en presos con hepatitis C sin enfermedad hepática avanzada / Good agreement between transitional elastography and combined APRI and FIB-4 tests in hepatitis C prisoners without advanced liver disease

Objetivos: Determinar la concordancia entre la elastografía de transición (ET) y los métodos no invasivos (MNI) del índicede relación de niveles de plaquetas y aspartato-aminotransferasa (APRI, aspartate aminotransferase to platelet ratio index) y elíndice de fibrosis 4 (FIB-4) combinados en internos con Hepatitis C crónica (HCC) sin enfermedad hepática avanzada (EHA).Material y método: Estudio multicéntrico y retrospectivo realizado en reclusos con HC de dos prisiones de Barcelona con ETefectuada en 2019. Se comparó el resultado de la ET frente a MNI. Se consideró que no era EHA si la fibrosis era ≤2 (≤12,5 kilopascales [kPa], en ET). Se calculó el grado de fibrosis por métodos no invasivos (MNI) y, en los casos sin EHA, se determinóla concordancia entre ET y MNI mediante el índice kappa (κ).Resultados: Se incluyeron 107 casos, 82 evaluables. Edad media: 42 (desviación estándar [DE]: ±3,2) años. El 96,4% eranhombres, el 51,2% españoles, el 70,7% con antecedente de uso de drogas intravenosas (UDI) y el 39% infectados por VIH. El45,1% de los infectados presentaba genotipo 1. En el 90,2% de los evaluados mediante ET, no se detectó EHA. El índice κ fuede 0,78. Se prescribió tratamiento contra el virus de la hepatitis C (VHC) a 65 (79,3%). El 20,7% no pudo tratarse por falta detiempo para completar el estudio.Conclusiones: La mayoría de los infectados actuales no presentan EHA y, en estos casos, la concordancia MNI/ET es buena.Los MNI pueden utilizarse para acortar el tiempo de evaluación hepática y prescribir antes el tratamiento, sobre todo si el tiempo de estancia en prisión se prevé corto y el riesgo de transmisión es alto. (AU)

Objectives: To establish concordance between transient elastography (TE) and non invasive markers (NIM) APRI and FIB-4combination in hepatitis C (HC) patients with non-advanced liver fibrosis (NALF).Material and method: Multi-centre retrospective study carried out at two different Barcelona Prisons HC inmates whohad the TE done at 2019. We compared the ET vs. NIM results. The NALF consideration was ≤2 (≤12.5 Kpa in TE). In theNALF cases was calculated de NIM APRI and FIB-4 and the kappa index agreement was established between TE and NIM.Results: 107 cases were included, but only 82 were assessable. The average age was 42 (DS: ±3.2) years. The 96.5% were men,51.2% spanish, 70.7% drug users and 39% HIV co infected. The 45.1% of those HC infected had genotipe 1. The 90.2%of the evaluated patients by TE the ALD was not detected. The kappa index was 0.78. 65 (79.3%) studied inmates got HCtreatment. The 20.7% could not be treated because the evaluation was not completed. Conclusion: Most of the HC infected inmates have no ALD, and in such cases concordance between NIM/TE is substantial.The NIM can be used to shorten the evaluation time and prescribe the treatment faster, especially if the length of stay inprison is short and risk of transmission is high. (AU)

Avoiding Misdiagnosis of Abdominal Vascular Catastrophes.

Abdominal vascular emergencies are an uncommon entity in emergency medicine, but when they present, they are often catastrophic. These time-sensitive and life-threatening diagnoses are often hidden in nonspecific complaints such as nausea, vomiting, or flank pain, so the emergency physician must remain diligent and consider these in the differential diagnoses. The following is an overview of the more common of these abdominal vascular emergencies, in the hope that they help the Emergency Physician avoid the misdiagnosis and subsequent vascular catastrophe that would follow.

AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review.

DESCRIPTION: The purpose of this Clinical Practice Update Expert Review is to provide clinicians with guidance on the diagnosis and management of atrophic gastritis, a common preneoplastic condition of the stomach, with a primary focus on atrophic gastritis due to chronic Helicobacter pylori infection-the most common etiology-or due to autoimmunity. To date, clinical guidance for best practices related to the diagnosis and management of atrophic gastritis remains very limited in the United States, which leads to poor recognition of this preneoplastic condition and suboptimal risk stratification. In addition, there is heterogeneity in the definitions of atrophic gastritis, autoimmune gastritis, pernicious anemia, and gastric neoplasia in the literature, which has led to confusion in clinical practice and research. Accordingly, the primary objective of this Clinical Practice Update is to provide clinicians with a framework for the diagnosis and management of atrophic gastritis. By focusing on atrophic gastritis, this Clinical Practice Update is intended to complement the 2020 American Gastroenterological Association Institute guidelines on the management of gastric intestinal metaplasia. These recent guidelines did not specifically discuss the diagnosis and management of atrophic gastritis. Providers should recognize, however, that a diagnosis of intestinal metaplasia on gastric histopathology implies the diagnosis of atrophic gastritis because intestinal metaplasia occurs in underlying atrophic mucosa, although this is often not distinctly noted on histopathologic reports. Nevertheless, atrophic gastritis represents an important stage with distinct histopathologic alterations in the multistep cascade of gastric cancer pathogenesis. METHODS: The Best Practice Advice statements presented herein were developed from a combination of available evidence from published literature and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out. These statements are meant to provide practical advice to clinicians practicing in the United States. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Atrophic gastritis is defined as the loss of gastric glands, with or without metaplasia, in the setting of chronic inflammation mainly due to Helicobacter pylori infection or autoimmunity. Regardless of the etiology, the diagnosis of atrophic gastritis should be confirmed by histopathology. BEST PRACTICE ADVICE 2: Providers should be aware that the presence of intestinal metaplasia on gastric histology almost invariably implies the diagnosis of atrophic gastritis. There should be a coordinated effort between gastroenterologists and pathologists to improve the consistency of documenting the extent and severity of atrophic gastritis, particularly if marked atrophy is present. BEST PRACTICE ADVICE 3: Providers should recognize typical endoscopic features of atrophic gastritis, which include pale appearance of gastric mucosa, increased visibility of vasculature due to thinning of the gastric mucosa, and loss of gastric folds, and, if with concomitant intestinal metaplasia, light blue crests and white opaque fields. Because these mucosal changes are often subtle, techniques to optimize evaluation of the gastric mucosa should be performed. BEST PRACTICE ADVICE 4: When endoscopic features of atrophic gastritis are present, providers should assess the extent endoscopically. Providers should obtain biopsies from the suspected atrophic/metaplastic areas for histopathological confirmation and risk stratification; at a minimum, biopsies from the body and antrum/incisura should be obtained and placed in separately labeled jars. Targeted biopsies should additionally be obtained from any other mucosal abnormalities. BEST PRACTICE ADVICE 5: In patients with histology compatible with autoimmune gastritis, providers should consider checking antiparietal cell antibodies and anti-intrinsic factor antibodies to assist with the diagnosis. Providers should also evaluate for anemia due to vitamin B-12 and iron deficiencies. BEST PRACTICE ADVICE 6: All individuals with atrophic gastritis should be assessed for H pylori infection. If positive, treatment of H pylori should be administered and successful eradication should be confirmed using nonserological testing modalities. BEST PRACTICE ADVICE 7: The optimal endoscopic surveillance interval for patients with atrophic gastritis is not well-defined and should be decided based on individual risk assessment and shared decision making. A surveillance endoscopy every 3 years should be considered in individuals with advanced atrophic gastritis, defined based on anatomic extent and histologic grade. BEST PRACTICE ADVICE 8: The optimal surveillance interval for individuals with autoimmune gastritis is unclear. Interval endoscopic surveillance should be considered based on individualized assessment and shared decision making. BEST PRACTICE ADVICE 9: Providers should recognize pernicious anemia as a late-stage manifestation of autoimmune gastritis that is characterized by vitamin B-12 deficiency and macrocytic anemia. Patients with a new diagnosis of pernicious anemia who have not had a recent endoscopy should undergo endoscopy with topographical biopsies to confirm corpus-predominant atrophic gastritis for risk stratification and to rule out prevalent gastric neoplasia, including neuroendocrine tumors. BEST PRACTICE ADVICE 10: Individuals with autoimmune gastritis should be screened for type 1 gastric neuroendocrine tumors with upper endoscopy. Small neuroendocrine tumors should be removed endoscopically, followed by surveillance endoscopy every 1-2 years, depending on the burden of neuroendocrine tumors. BEST PRACTICE ADVICE 11: Providers should evaluate for iron and vitamin B-12 deficiencies in patients with atrophic gastritis irrespective of etiology, especially if corpus-predominant. Likewise, in patients with unexplained iron or vitamin B-12 deficiency, atrophic gastritis should be considered in the differential diagnosis and appropriate diagnostic evaluation pursued. BEST PRACTICE ADVICE 12: In patients with autoimmune gastritis, providers should recognize that concomitant autoimmune disorders, particularly autoimmune thyroid disease, are common. Screening for autoimmune thyroid disease should be performed.

Evaluation of Validity and Efficiency of Diagnostic Criteria in Autoimmune Hepatitis in Children.

BACKGROUND: Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease with various clinical symptoms, but treatment and prevention of hepatic failure and cirrhosis is possible with early diagnosis. However, no specific test has been approved for the diagnosis of AIH. In 2008, the International Autoimmune Hepatitis Group (IAIHG) developed a simplified diagnostic scoring system that has been widely used in practice. Nevertheless, it cannot distinguish AIH from Primary Sclerosing Cholangitis (PSC) and consensus is lacking with respect to its validity, sensitivity, and applicability for children patients. The newer 2018 version also requires validation. The present study intends to evaluate the validity and efficiency of the IAIHG simplified scoring system and new scoring system in children with AIH. METHODS: The present study is a non-interventional case-control study covering 152 patients with hepatic diseases (83 patients with AIH and 69 patients with Wilson disease (WD)). Titers of autoantibodies, IgG levels, hepatic histology, and absence of viral hepatitis were scored and calculated according to IAIHG diagnostic criteria. Statistics software package (SPSS) and draft receiver operating characteristic (ROC) curves was used to analyze data and determine value of diagnostic criteria. RESULT: In our study, both scoring systems' accuracy was good in AIH diagnosis, although new score displays higher sensitivity and specificity, suggestive of greater accuracy and predictive strength. CONCLUSION: Our study is the first validation study of the new scoring system in diagnosing AIH, and further studies require verifying this scoring system.

In vitro models to evaluate ingestible devices: Present status and current trends.

Orally ingestible medical devices offer significant opportunity in the diagnosis and treatment of gastrointestinal conditions. Their development necessitates the use of models that simulate the gastrointestinal environment on both a macro and micro scale. An evolution in scientific technology has enabled a wide range of in vitro, ex vivo and in vivo models to be developed that replicate the gastrointestinal tract. This review describes the landscape of the existing range of in vitro tools that are available to characterize ingestible devices. Models are presented with details on their benefits and limitations with regards to the evaluation of ingestible devices and examples of their use in the evaluation of such devices is presented where available. The multitude of models available provides a suite of tools that can be used in the evaluation of ingestible devices that should be selected on the functionality of the device and the mechanism of its function.

Integrative Effects and Vagal Mechanisms of Transcutaneous Electrical Acustimulation on Gastroesophageal Motility in Patients With Gastroesophageal Reflux Disease.

INTRODUCTION: Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD. METHODS: Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively. RESULTS: Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD health-related quality of life (P = 0.028) and improved nutrient drink-induced fullness (P < 0.001) and belching (P < 0.001) in patients with GERD. Although only acute TEA significantly enhanced LES pressure (P < 0.05), both acute and chronic TEA remarkedly increased DCI (P < 0.05) and reduced the incidence of ineffective esophageal contractions during wet swallows (P = 0.02). In addition, chronic TEA significantly increased gastric accommodation and the percentage of postprandial normal GSW compared with sham-TEA and baseline. Concurrently, TEA-enhanced vagal activity (P = 0.02) and the vagal activity positively correlated with LES pressure (r = 0.528; P = 0.003) and DCI (r = 0.522; P = 0.003). DISCUSSION: The TEA treatment performed in this study improves reflux-related symptoms, increases DCI, reduces the incidence of ineffective esophageal contractions during wet swallows, and improves gastric accommodation and slow waves. The improvement in GERD symptoms might be attributed to the integrative effects of TEA on these gastroesophageal functions mediated via the vagal mechanism.

Nutrient Drinking Test as Biomarker in Functional Dyspepsia.

INTRODUCTION: Functional dyspepsia (FD) is a prevalent condition with multifactorial pathophysiology, including impaired gastric accommodation (GA), hypersensitivity to gastric distention, and delayed gastric emptying. Drink tests (DT) have been proposed as a potential biomarker for the presence and severity of gastric sensorimotor dysfunction. Thus, we aimed to summarize the state of knowledge on different DT and their potential as a biomarker for FD. METHODS: A PubMed and MEDLINE search was conducted for English language articles, reviews, meta-analyses, case series, and randomized controlled trials, including also published meeting abstracts. RESULTS: Several DT have been described in literature (e.g., different type of liquid, number of calories used, pace of drinking, and subject's awareness of the amount of liquid drunk). FD patients ingest significantly less volume in the different variants of the tests. The slow nutrient ("satiety drinking") test (SDT) studies show the most consistent separation between health and FD and correlation with GA. However, sensitivity to distention may be correlated with rapid DT. SDTs were used to evaluate the effect of several pharmacological agents, often showing concordance between their effects on GA and tolerated nutrient volume. This correlation was not found mainly for agents with central actions. DISCUSSION: An SDT is a potential diagnostic biomarker in FD, reflecting GA. Additional studies are required to confirm its role as a predictive biomarker for treatment outcome in FD.

Development and Validation of Test for "Leaky Gut" Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults.

BACKGROUND: Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion. AIMS: The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: Sixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12C-mannitol, 13C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13C-mannitol and lactulose. RESULTS: Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D. CONCLUSIONS: Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.

Application of Artificial Intelligence for Diagnosis and Risk Stratification in NAFLD and NASH: The State of the Art.

The diagnosis of nonalcoholic fatty liver disease and associated fibrosis is challenging given the lack of signs, symptoms and nonexistent diagnostic test. Furthermore, follow up and treatment decisions become complicated with a lack of a simple reproducible method to follow these patients longitudinally. Liver biopsy is the current standard to detect, risk stratify and monitor individuals with nonalcoholic fatty liver disease. However, this method is an unrealistic option in a population that affects about one in three to four individuals worldwide. There is an urgency to develop innovative methods to facilitate management at key points in an individual's journey with nonalcoholic fatty liver disease fibrosis. Artificial intelligence is an exciting field that has the potential to achieve this. In this review, we highlight applications of artificial intelligence by leveraging our current knowledge of nonalcoholic fatty liver disease to diagnose and risk stratify NASH phenotypes.

A Diagnostic Score for Acute Small Bowel Obstruction.

BACKGROUND/AIM: The diagnosis of acute small bowel obstruction (ASBO) may be difficult and the decision to operate is based on clinical findings. So far, the diagnostic scores (DSs) for ASBO detection have been rarely evaluated. PATIENTS AND METHODS: A cohort of 1,333 acute abdominal pain (AAP) patients with 54 ASBO patients, were included in the study. The most significant diagnostic findings (in multivariate logistic regression analysis) were used to construct DS formulas for ASBO diagnosis with location of pain at diagnosis (LP+) and without location of pain at diagnosis (LP-). Meta-analytical techniques were used to calculate the summary sensitivity (Se) and specificity (Sp) estimates for each data sets (history-taking, findings, and DS formulas). RESULTS: In SROC analysis, the AUC values for i) clinical history-taking, ii) diagnostic findings and tests, iii) DSLP- and iv) DSLP+ were as follows: i) AUC=0.638 (95%CI=0.600-0.676); ii) AUC=0.694 (95%CI=0.630-0.724), iii) AUC=0.962 (95%CI=0.940-0.986), and for iv) AUC=0.971 (95%CI=0.952-0.988). In roccomp analysis for the AUC values, the differences are significant as follows: between i) and ii) p=0.312; between i) and iii) p<0.0001; between i) and iv) p<0.0001; between ii) and iii) p<0.0001; between ii) and iv) p<0.0001; and between iii) and iv) p=0.317. CONCLUSION: The present study is the first to provide data that the DS could be used for clinical diagnosis of ASBO without radiological or laboratory analyses, to reach a high diagnostic accuracy in AAP patients.

Noninvasive early diagnosis of intestinal diseases based on artificial intelligence in genomics and microbiome.

The maturing development in artificial intelligence (AI) and genomics has propelled the advances in intestinal diseases including intestinal cancer, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). On the other hand, colorectal cancer is the second most deadly and the third most common type of cancer in the world according to GLOBOCAN 2020 data. The mechanisms behind IBD and IBS are still speculative. The conventional methods to identify colorectal cancer, IBD, and IBS are based on endoscopy or colonoscopy to identify lesions. However, it is invasive, demanding, and time-consuming for early-stage intestinal diseases. To address those problems, new strategies based on blood and/or human microbiome in gut, colon, or even feces were developed; those methods took advantage of high-throughput sequencing and machine learning approaches. In this review, we summarize the recent research and methods to diagnose intestinal diseases with machine learning technologies based on cell-free DNA and microbiome data generated by amplicon sequencing or whole-genome sequencing. Those methods play an important role in not only intestinal disease diagnosis but also therapy development in the near future.