Transmural cross-sectional findings and bowel damage assessment in preclinical Crohn's disease: a case-control study.

PURPOSE: Crohn's disease (CD) is a progressive disorder leading to cumulative bowel damage. The Lémann index is a validated tool that can help in monitoring the progression of the disease and evaluating the effectiveness of different therapies. Our aim was to describe the main radiological findings in incidentally diagnosed CD and to evaluate bowel damage in this subgroup compared to patients diagnosed at later stages. METHODS: Patients with an incidental diagnosis of CD during the colorectal cancer screening program were compared to controls with a CD cohort diagnosed after symptomatic onset and matched 1:1 by disease extent. All cross-sectional examinations were centrally read, performing a descriptive analysis of the main findings and calculation of Lémann index. RESULTS: Thirty-eight patients were included: 19 with preclinical CD (median age 55 years (IQR, 54-62), 53% male, 74% non-smokers; 74% B1 and 26% B2) and 19 matched-controls with symptomatic CD. In those with preclinical CD, the most frequent transmural findings on MRE were contrast enhancement (79%), wall thickening (79%), followed by lymphadenopathy (68%), edema (42%), and increased vascularity (42%). Among those with strictures, controls showed a higher rate of preestenotic dilation (100% vs. 0%, p = 0.01). Bowel damage assessment revealed no statistically significant differences in the Lémann index between preclinical CD and controls (p = 0.95). A statistically significant higher score in the colonic/rectum score was observed (p = 0.014). CONCLUSION: Patients with preclinical CD demonstrate similar radiological findings and degree of bowel damage as new-onset symptomatic CD.

Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures.

OBJECTIVE: Despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). DESIGN: A prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. RESULTS: An initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. CONCLUSION: Implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.

HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples.

BACKGROUND: Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations. METHODS: Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR. RESULTS: We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples. CONCLUSIONS: We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.

Characteristics and Progression of Preclinical Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a chronic disease usually diagnosed after the appearance of gastrointestinal symptoms. Little is known about IBD progression during its early and even preclinical phases. We aimed to determine the number of new incidental diagnoses of IBD in an older population, and evaluate disease progression from its early stages. METHODS: We performed a retrospective analysis of 31,005 colonoscopies performed during colorectal cancer screening of patients with positive results from fecal immunochemical tests, at 11 centers in the Basque Country (Spain) from 2009 through 2014. We collected clinical and laboratory data from all asymptomatic individuals suspected to have IBD during screening colonoscopies, with histologic confirmation. RESULTS: Colonoscopy screening led to 79 new diagnoses of ulcerative colitis, 24 of Crohn's disease, and 7 of unclassified colitis (average patient age, 57 y; interquartile range, 52-62 y; 57% male). Eleven patients had symptoms before colonoscopy and were excluded from the analysis. Among those patients who were asymptomatic at diagnosis, 36% developed symptoms after a follow-up period of 25 months (interquartile range, 10.5-42 mo), mostly rectal bleeding and diarrhea. Treatment was prescribed for 81 patients (88%), and 2 cases required surgery. CONCLUSIONS: We analyzed data from a large cohort of patients with IBD diagnosed at early or even preclinical stages, from an older population. New incidental diagnoses of IBD were made in 0.35% of individuals undergoing a population-based screening colonoscopy-most were classified as ulcerative colitis. Approximately one third of patients developed symptoms during the follow-up period.

Comparative study of a responsive insertion technology (RIT) colonoscope versus a variable-stiffness colonoscope.

BACKGROUND AND OBJECTIVES: recently, Olympus developed a new prototype (XCF-Q180AY2L) with responsive insertion technology (RIT), which besides the still known variable stiffness technology, included a passive bending section and a new high force insertion tube. Our objective was to investigate whether the use of this prototype could ease colonoscope insertion, increasing the cecal intubation rate, and/or shortening the cecal intubation time. MATERIAL AND METHODS: the study was designed as a prospective observational study in 305 consecutive patients from a colo-rectal cancer screening program. We compared colonoscopies performed with conventional colonoscopes (CFH180AL/CFQ160L) with those performed with the prototype XCF-Q180AY2L. End points were mean cecal and terminal ileal intubation times, cecum intubation rate, and need for specific maneuvers. All colonoscopies were performedunder sedation with intravenous propofol. Finally, 288 patients were included. RESULTS: no complications were observed. Complete cecal intubation rate was 100 % in both groups. The ileum could be reached in 98.95 % of cases. Mean time required to reach the cecum was shorter in the prototype endoscope group (4.31 min, SD 2.63 min) than in the conventional endoscope group (4.66 min, SD 2.52 min) (p < 0.05). Compared with the standard colonoscope group, we observed in the prototype group less subjective sensation of difficultyin the passage of the sigma (p < 0.01), fewer maneuvers when it proved necessary to straighten the scope (p < 0.01), and less frequent need to modify the stiffness of the endoscope (p < 0.05). CONCLUSION: we concluded that the prototype endoscope (XCFQ180AY2L) facilitated colonoscope insertion, requiring slightly less time to reach the cecum than a standard colonoscope.

Subclinical bowel inflammation increases healthcare resources utilization and steroid use before diagnosis of inflammatory bowel disease.

BACKGROUND: Previous data support that the inflammatory process underlying ulcerative colitis (UC) and Crohn's disease (CD) can start years before the diagnosis. The aim of this study was to determine if patients with an incidental diagnosis of UC or CD demonstrate an increase in healthcare utilization in the years preceding the symptomatic onset of the disease. METHODS: We performed a multicenter, retrospective, hospital-based, case-control study. Patients with an incidental diagnosis of UC or CD during the colorectal cancer screening program at 9 hospitals were included. Cases were matched 1:3 and compared separately with two control populations: one including healthy non-IBD subjects adjusted by gender, age, and date, excluding those with visits to Gastroenterology; and a second control cohort of UC/CD patients with symptomatic onset. RESULTS: A total of 124 patients with preclinical inflammatory bowel disease (IBD) were included (87 UC, 30 CD, 7 IBD unclassified; median age 56 years). Patients with preclinical IBD showed an increase in the number of visits to Primary Care up to 3 and 5 years before diagnosis (aIRR 1.59, 95% CI [1.37-1.86], p = 0.001; aIRR 1.43, 95% CI [1.24-1.67], p = 0.01) and more frequent use of steroids (aOR 2.84, 95% CI [1.21-6.69], p = 0.03; aOR 2.25, 95% CI [1.06-4.79], p = 0.04) compared to matched non-IBD healthy controls, respectively. In contrast, patients with a symptomatic onset visited Primary Care less frequently, but they had an increase in the number of visits to Emergency Department, specialist care, sick-leaves, CT/ultrasound examinations, and use of antibiotics or systemic steroids. CONCLUSIONS: There is an increased need for medical assistance and use of systemic steroids during the presymptomatic phase of IBD. These results will help in establishing new tools for early identification of IBD in the future.

Herpetic esophagitis: a case report on an immunocompetent adolescent.

Herpetic esophagitis in immunocompetent individuals is a rare entity that should be suspected clinically by an acute onset of symptoms, and without apparent cause of a symptomatic triad consisting on odynophagia, heartburn and fever. Its occurrence may be due to reactivation of a previous infection or less often a primary infection. Herpes simplex type 1 is the most common cause. Upper endoscopy establishes the diagnosis of suspicion of herpetic esophagitis. It also allows to take multiple biopsy samples and viral culture, leading to a definitive diagnosis. The severity of symptoms is related to the degree of oesophageal involvement. In immunocompromised patients treatment is indicated with acyclovir, but the indication in immunocompetent patients is controversial because the process is time, limited with a low probability of complications. We present a case of acute herpetic esophagitis in an immunocompetent host that debuted acutely with severe upper gastrointestinal tract symptoms, associated with an insidious and nonspecific onset of flu-like symptoms. Endoscopic findings showed a severe involvement in the lower third of the oesophageal mucosa.

[Giant Brunner's gland hamartoma: diagnosis and endoscopic treatment]. / Hamartoma gigante de glándulas de Brunner: diagnóstico y tratamiento endoscópico.

Brunner's gland hamartoma is a polypoid lesion typically composed of an increased quantity of normal-appearing Brunner's glands, accompanied by a variable proportion of smooth muscle. Most of these masses are asymptomatic and behave as benign tumors. Occasionally tumoral growth can provoke gastrointestinal problems which, together with the possibility of malignant transformation, will require resection after a broad differential diagnosis has been made with solitary duodenal mass. Both clinical and radiographic studies are nonspecific and often do not allow diagnosis of these tumors. Basic endoscopic studies (upper endoscopy) with adequate characterization of the lesion by endoscopic ultrasound (EUS) can establish a high diagnostic suspicion and determine the best therapeutic option (endoscopy or surgery). We present a case of giant Brunner's gland hamartoma. The initial manifestation was iron-deficiency anemia with no evidence of bleeding. After adequate characterization of the lesion, EUS allowed complete and safe endoscopic resection, avoiding more invasive surgical treatment.

EUS and ERCP: A rationale categorization of a productive partnership.

ERCP and EUS are complementary techniques in the management of biliary and pancreatic diseases. Combination of these two techniques can reach different levels of complexity with increasing rates of adverse events. In this article we propose a categorization of the relationship between EUS and ERCP based on whether EUS indicates, complements, facilitates or replaces ERCP. It has implications for the complexity of the technique, the training of the endoscopist and the necessary hospital resources. This classification can also be useful in planning endoscopist training and patient management.

Advanced airway management: a descriptive analysis of complications and factors associated with first-attempt intubation failure in prehospital emergency care. / Análisis descriptivo de pacientes que requirieron manejo avanzado de vía aérea en emergencias prehospitalarias: complicaciones y factores asociados al fracaso en el primer intento de intubación.

OBJECTIVES: To analyze the characteristics of prehospital emergency airway management, including complications; to explore predictors of first-attempt failure of orotracheal intubation. MATERIAL AND METHODS: Observational retrospective cohort study of patients requiring orotracheal intubation by the prehospital emergency services of Castile-La Mancha between June 1, 2017, and January 1, 2021. We analyzed patient and procedure characteristics and complications using logistic regression analysis to detect factors that could predict firstattempt intubation failure. RESULTS: A total of 425 patients were included; 417 (98.1%) were intubated successfully, including 326 (76.7%) on the first attempt. Complications occurred in 183 intubations in 94 patients (22.1%). Predictors of first-attempt failure were age over 55 years (odds ratio [OR], 1.94; 95% CI, 1.10-4.23), body mass index over 30 (OR, 9.14; 95% CI, 4.40-19.00), oxygen saturation less than 90% (OR, 3.33; 95% CI, 1.06-10.58), a Glasgow Coma Score between 9 and 13 (OR, 1.58; 95% CI, 1.28-6.9), intubation in a public place (OR, 2.99; 95% CI, 1.42-6.29), intubation done in any other than standing position (OR, 2.09; 95% CI, 1.08-7.25), direct laryngoscopy (OR, 2.39; 95% CI, 1.20- 6.55), use of a stylet (OR, 1.80; 95% CI, 1.40-3.78), and a Cormack-Lehane classification of 2 or higher (OR, 6.50; 95% CI, 3.96-30.68). CONCLUSION: Orotracheal intubation is generally accomplished on the first attempt. Factors associated with first-attempt failure can facilitate tailored approaches to upper airway management.

OBJETIVO: Analizar las características del manejo de la vía aérea (VA) en emergencias prehospitalarias, sus complicaciones y establecer factores predictores de fracaso en el primer intento de intubación orotraqueal (FIPI). METODO: Estudio observacional de cohortes retrospectivo de pacientes que precisaron intubación orotraqueal por el servicio de emergencias prehospitalarias de Castilla La Mancha, desde el 01-06-2017 hasta el 01-01-2021. Se analizaron características de los pacientes, del procedimiento y sus complicaciones, se realizó una regresión logística para detectar factores predictores de FIPI. RESULTADOS: . Se incluyeron 425 pacientes, 417 (98,1%) fueron intubados con éxito y 326 (76,7%) en el primer intento. Se registraron 183 complicaciones en 94 pacientes (22,1%). Los factores predictores de FIPI fueron la edad > 55 años (OR = 1,94; IC 95% 1,10-4,23), índice de masa corporal > 30 (OR = 9,14; IC 95% 4,40-19,00); saturación de oxígeno 90% (OR = 3,33; IC 95% 1,06-10,58); puntuación en la Glasgow Coma Scale entre 9 y 13 (OR = 1,58; IC 95% 1,28-6,9); intubación realizada en vía pública (OR = 2,99; IC 95% 1,42-6,29); posición distinta a la bipedestación (OR = 2,09; IC 95% 1,08-7,25); laringoscopia directa (OR = 2,39; IC 95% 1,20-6,55); uso de estilete (OR = 1,80; IC 95% 1,40-3,78); y clasificación Cormack-Lehane $ 2 (OR = 6,50; IC 95% 3,96-30,68). CONCLUSIONES: El procedimiento de intubación se realizó de forma habitual en el primer intento. Existen factores asociados a FIPI que permiten individualizar el manejo de la VA.

EUS is superior to secretin-enhanced cholangio-MRI to establish the etiology of idiopathic acute pancreatitis.

Background and study aims The etiology of idiopathic acute pancreatitis (IAP) should always be defined. Our aim was to compare the diagnostic value of endoscopic ultrasound (EUS) versus secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) in patients with IAP. Patients and Methods Patients admitted to a single tertiary care University hospital with IAP were invited to participate in the study. Enrolled patients underwent EUS and S-MRCP in a single-blinded comparative study. EUS and S-MRCP were performed no sooner than 4 weeks after discharge. The diagnostic yield of EUS and S-MRCP and demographic variables were included in the analysis. Additional follow-up, results of subsequent serology, radiographic exams, and relevant histological analysis were considered in determination of the final diagnosis. Results A total of 34 patients were enrolled; EUS was normal in six, cholelithiasis was defined in 15, choledocholithiasis in two, pancreas divisum in three, branch-type intraductal papillary mucinous tumor (IPMT) in three, and chronic pancreatitis in five. S-MRCP identified choledocholithiasis in one, divisum in four, branch-type IPMT in three, chronic pancreatitis in two; 24 subjects diagnosed as normal by S-MRCP. Diagnostic correlation between EUS and S-MRCP was slight (kappa = 0.236, 95 % confidence interval: 0.055-0.416). EUS provided a statistically significantly higher diagnostic yield than S-MRCP: 79.4 % (CI95 %: 65 %-94 %) vs 29.4 % (CI95 %: 13 %-46 %) (P = 0.0002). The sensitivity, specificity, and positive and negative predictive values of EUS and S-MRCP were 90 %, 80 %, 96 %, 57 % and 33 %, 100 %, 100 % and 16 %, respectively. Conclusion The diagnostic yield of EUS is higher than S-MRCP in patients with IAP.

Early microscopic findings in preclinical inflammatory bowel disease.

BACKGROUND: The immune response involved in the pathogenesis of Inflammatory Bowel Disease (IBD) may be present years before the diagnosis, but the characteristics of the disease during the preclinical period have been scarcely investigated. AIM: To describe the microscopic findings of preclinical IBD and its relationship with the natural history of the disease. METHODS: Medical records from all patients with an incidental diagnosis of IBD during a screening colonoscopy were included in this multicentric and retrospective study. We assessed 15 histologic items in the biopsy samples at diagnosis, and the Geboes score was calculated in patients with Ulcerative Colitis (UC). The main outcome was the development of gastrointestinal symptoms during follow-up. RESULTS: We included 110 patients (79 UC, 24 Crohn's Disease (CD) and 7 with unclassified disease). In UC the most common histologic findings were acute or chronic inflammatory infiltrate and crypt epithelial polymorphs, while in CD we observed acute or chronic neutrophilic infiltrate and epithelial irregularity. Granuloma were only observed in 4% of CD patients. Crypt distortion and the infiltration of neutrophils in the epithelium were associated with a higher risk of developing symptomatic disease. CONCLUSIONS: Preclinical IBD shows specific microscopic findings and they are associated with the progression to symptomatic disease.

Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach.

Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (1H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.

Quantifying the Economic and Cultural Biases of Social Media through Trending Topics.

Online social media has recently irrupted as the last major venue for the propagation of news and cultural content, competing with traditional mass media and allowing citizens to access new sources of information. In this paper, we study collectively filtered news and popular content in Twitter, known as Trending Topics (TTs), to quantify the extent to which they show similar biases known for mass media. We use two datasets collected in 2013 and 2014, including more than 300.000 TTs from 62 countries. The existing patterns of leader-follower relationships among countries reveal systemic biases known for mass media: Countries concentrate their attention to small groups of other countries, generating a pattern of centralization in which TTs follow the gradient of wealth across countries. At the same time, we find subjective biases within language communities linked to the cultural similarity of countries, in which countries with closer cultures and shared languages tend to follow each other's TTs. Moreover, using a novel methodology based on the Google News service, we study the influence of mass media in TTs for four countries. We find that roughly half of the TTs in Twitter overlap with news reported by mass media, and that the rest of TTs are more likely to spread internationally within Twitter. Our results confirm that online social media have the power to independently spread content beyond mass media, but at the same time social media content follows economic incentives and is subject to cultural factors and language barriers.