Indications, Detection, Completion and Retention Rates of Capsule Endoscopy in Two Decades of Use: A Systematic Review and Meta-Analysis.

BACKGROUND: Capsule endoscopy (CE) has become a widespread modality for non-invasive evaluation of the gastrointestinal (GI) tract, with several CE models having been developed throughout the years. The aim of this systematic review and meta-analysis is to evaluate performance measures such as completion, detection and retention rates of CE. METHODS: Literature through to August 2021 was screened for articles regarding all capsule types: small bowel, double-headed capsule for the colon or PillCam®Crohn's capsule, magnetically-controlled capsule endoscopy, esophageal capsule and patency capsule. Primary outcomes included detection rate (DR), completion rate (CR) and capsule retention rate (RR). DR, CR and RR were also analyzed in relation to indications such as obscure GI bleeding (OGIB), known/suspected Crohn's disease (CD), celiac disease (CeD), neoplastic lesions (NL) and clinical symptoms (CS). RESULTS: 328 original articles involving 86,930 patients who underwent CE were included. OGIB was the most common indication (n = 44,750), followed by CS (n = 17,897), CD (n = 11,299), NL (n = 4989) and CeD (n = 947). The most used capsule type was small bowel CE in 236 studies. DR, CR and RR for all indications were 59%, 89.6% and 2%, respectively. According to specific indications: DR were 55%, 66%, 63%, 52% and 62%; CR were 90.6%, 86.5%, 78.2%, 94% and 92.8%; and RR were 2%, 4%, 1%, 6% and 2%. CONCLUSIONS: Pooled DR, CR and RR are acceptable for all capsule types. OGIB is the most common indication for CE. Technological advancements have expanded the scope of CE devices in detecting GI pathology with acceptable rates for a complete examination.

Infliximab-induced hypoglycemia, a rare but relevant side effect.

Tumor necrosis factor (TNF) inhibitors are part of the therapeutic arsenal for many immune-mediated diseases and, especially in inflammatory bowel disease (IBD), have led to a change in the management of this disease.

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.

Does capsule endoscopy impact clinical management in established Crohn's disease?

BACKGROUND: Capsule endoscopy (SBCE) has developed a relevant role in patients with established Crohn's Disease (CD). However, evaluation of the impact in clinical management has been scarce. AIMS: To evaluate therapeutic impact of SBCE in an 11-year real-life cohort of known CD patients. METHODS: Retrospective single center study including all patients with established CD submitted to SBCE procedure from 01/01/2008 to 31/12/2019. Patency capsule was used in selected patients. Small bowel mucosal inflammation was quantified using Lewis score. Therapeutic impact was defined as a change in CD-related treatment recommended based on SBCE results. Patients were assigned to four groups regarding SBCE indication: staging, flare, post-op and remission. RESULTS: From the 432 SBCE performed 87.5% were conclusive. Active disease was present in 63.7 of patients; 41.6% mild inflammation and 21.9% moderate-to-severe activity. A change of management was guided by SBCE in 51.3% of procedures: 199 (46.1%) escalation and 23 (5.3%) de-escalation, with significant changes in all groups. Escalation increased with disease activity: 57.8% in mild and 89.5% in moderate-to-severe disease. De-escalation was conducted in 13.9% procedures with mucosal healing and 1.1% with mild disease. CONCLUSION: SBCE is a useful tool for guiding therapeutic management in CD patients both for treatment escalation and de-escalation.

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.

Bile Processing Protocol for Improved Proteomic Analysis.

One of the critical issues to warrant the success of a proteome-wide analysis is sample preparation. Efficient protein extraction in the absence of interferent material is mandatory to achieve an ample proteome coverage by mass spectrometry. The study of biological fluids is always challenging due to their specific biochemical composition. However, there is increasing interest in their characterization as it will provide proteins that may advice disease setting, state, and progression. In particular, bile is proximal to liver and pancreas, and its study is especially attractive since it might provide valuable information for the clinical management of severe diseases afflicting these organs, which are at an urgent need of new biomarkers. Though previous efforts have been made to optimize protocols to analyze bile proteome, only partial descriptions were achieved due to its complex composition, where proteins represent less than 5% of the organic components. Here we describe a new method that significantly increases the bile proteome coverage while reducing by a factor of six the amount of sample required for the proteomic analysis.

Digging deeper into bile proteome.

The analysis of biological fluids to identify proteins that may indicate a disease setting, state and progression, is an increasingly explored field. Despite the expectatives created, there are several hurdles that must be solved to reach an extensive proteome coverage using mass spectrometry, mainly due to the complex composition of the matrices. In this regard, bile is specially challenging and yet, very attractive, as a proximal fluid that might provide valuable information for the management of liver and pancreas associated diseases. Proteins account for less than 5% of bile organic components and, although optimized protocols for protein extraction have been developed, only partial descriptions of bile proteome have been achieved. In this manuscript a new procedure is described that significantly improves protein recovery from rat bile, which reduces by a factor of six the sample amount required for a typical proteomics analysis. Moreover, the number of proteins reliably identified in a single nanoLC-MS/MS run from 1 µg protein was increased by three-fold. This procedure provides a valuable resource to dig deeper into the molecular composition of bile and open new avenues to identify new hallmarks of disease such as cholangiocarcinoma, hepatocellular carcinoma and pancreatic cancer for their better clinical management.

Cross-sectional survey of the wish to die among palliative patients in Spain: one phenomenon, different experiences.

OBJECTIVE: Cultural backgrounds and values have a decisive impact on the phenomenon of the wish to die (WTD), and examination of this in Mediterranean countries is in its early stages. The objectives of this study were to establish the prevalence of WTD and to characterise this phenomenon in our cultural context. METHODS: A cross-sectional study with consecutive advanced inpatients was conducted. Data about WTD (Assessing Frequency & Extent of Desire to Die (AFFED) interview) and anxiety and depression (Edmonton Symptom Assessment System-revised (ESAS-r)) were collected through two face-to-face clinical encounters. Data were analysed with descriptive statistics, χ2 and analysis of variance. RESULTS: 201 patients participated and 165 (82%) completed both interviews. Prevalence of WTD was 18% (36/201) in the first interview and 16% (26/165) in the second interview (p=0.25). After the first interview, no changes in depression (p=0.60) or anxiety (p=0.90) were detected. The AFFED shows different experiences within WTD: 11% of patients reported a sporadic experience, while 7% described a persistent experience. Thinking about hastening death (HD) appeared in 8 (22%) out of 36 patients with WTD: 5 (14%) out of 36 patients considered this hypothetically but would never take action, while 3 (8%) out of 36 patients had a more structured idea about HD. In this study, no relation was detected between HD and frequency of the appearance of WTD (p=0.12). CONCLUSIONS: One in five patients had WTD. Our findings suggest the existence of different experiences within the same phenomenon, defined according to frequency of appearance and intention to hasten death. A linguistically grounded model is proposed, differentiating the experiences of the 'wish' or 'desire' to die, with or without HD ideation.

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.

The Patient Dignity Inventory: Just another evaluation tool? Experiences with advanced cancer patients.

OBJECTIVE: The Patient Dignity Inventory (PDI) evaluates sources of distress related to the feeling of loss of dignity and was designed for patients at the end of life. The aim of the present work was to generate a better understanding of the experiences of healthcare staff when using the PDI. METHOD: An exploratory qualitative study is presented about the experience of 4 professionals who applied the PDI to 124 advanced-cancer patients. Our study consisted of an analysis of their experiences, taken from information generated in a focus group. A thematic analysis was performed on the information generated at that meeting by two researchers working independently. RESULTS: The initial experiences with the PDI on the part of the professionals led them to systematically administer the questionnaire as part of an interview instead of having patients fill it out themselves in written form. What started out as an evaluation very often led to a profound conversation on the meaning of life, dignity, and other sensitive, key issues related to the process of the illness. SIGNIFICANCE OF RESULTS: The PDI has intrinsic therapeutic value and is useful in clinical practice, and it is also a way of examining issues related to dignity and the meaning of life within the context of advanced-stage illness. There is a need for studies that examine patient experiences through a PDI-based interview.

Efficacy of peroral endoscopic myotomy compared with other invasive treatment options for the different esophageal motor disorders

Introduction: Peroral endoscopic myotomy (POEM) has been performed since 2008 on more than 5,000 patients. It has proven to be highly effective in the treatment of achalasia and has shown promising outcomes for other esophageal motility spastic disorders. Methods: A literature review of the efficacy of POEM compared to the previous invasive treatments for different esophageal motility disorders was performed. The application in the pediatric and elderly populations and its role as a rescue therapy after other procedures are also outlined. Results: Short-term outcomes are similar to laparoscopic Heller myotomy (LHM) and pneumatic endoscopic dilation (PD) (clinical success > 90%) for achalasia subtypes I and II. Mid-term outcomes are comparable to LHM and overcome results obtained after PD (> 90% vs ~50%). With regard to type III achalasia, POEM efficacy is 98% compared to 80.8% for LHM and the PD success remains at 40%. With regard to spastic esophageal disorders (SED), POEM has an effectiveness of 88% and 70% for distal esophageal spasm (DES) and jackhammer esophagus (JE) respectively. A response of 95% in patients with sigmoid esophagus has been reported. POEM has been performed in pediatric and elderly populations and has obtained a higher efficacy than PD in pediatric series (100% vs 33%) without greater adverse events. Previous treatments do not seem to hinder POEM results with excellent response rates, including 97% in post LHM and 100% in a re-POEM series. Final considerations: POEM has shown excellent short and mid-term results for all subtypes of achalasia but long-term results are not yet available. The promising results in SED may make POEM the first-line treatment for SED. A high-safety profile and efficacy have been shown in elderly and pediatric populations. Previous treatments do not seem to diminish the success rate of POEM. Core tip: POEM has emerged as an efficient treatment option for all subtypes of achalasia and other scenarios (including previous treatments and elderly and pediatric populations). Short and midterm results are comparable to LHM and are better than PD data. The clinical response rate of DES and JE may make POEM the first-line treatment for SED (AU)

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Efficacy of peroral endoscopic myotomy compared with other invasive treatment options for the different esophageal motor disorders.

INTRODUCTION: Peroral endoscopic myotomy (POEM) has been performed since 2008 on more than 5,000 patients. It has proven to be highly effective in the treatment of achalasia and has shown promising outcomes for other esophageal motility spastic disorders. METHODS: A literature review of the efficacy of POEM compared to the previous invasive treatments for different esophageal motility disorders was performed. The application in the pediatric and elderly populations and its role as a rescue therapy after other procedures are also outlined. RESULTS: Short-term outcomes are similar to laparoscopic Heller myotomy (LHM) and pneumatic endoscopic dilation (PD) (clinical success > 90%) for achalasia subtypes I and II. Mid-term outcomes are comparable to LHM and overcome the results obtained after PD (> 90% vs ~50%). With regard to type III achalasia, POEM efficacy is 98% compared to 80.8% for LHM and the PD success remains at 40%. With regard to spastic esophageal disorders (SED), POEM has an effectiveness of 88% and 70% for distal esophageal spasm (DES) and jackhammer esophagus (JE) respectively. A response of 95% in patients with sigmoid esophagus has been reported. POEM has been performed in pediatric and elderly populations and has obtained a higher efficacy than PD in pediatric series (100% vs 33%) without greater adverse events. Previous treatments do not seem to hinder POEM results with excellent response rates, including 97% in post LHM and 100% in a re-POEM series. Final considerations: POEM has shown excellent short and mid-term results for all subtypes of achalasia but long-term results are not yet available. The promising results in SED may make POEM the first-line treatment for SED. A high-safety profile and efficacy have been shown in elderly and pediatric populations. Previous treatments do not seem to diminish the success rate of POEM. Core tip: POEM has emerged as an efficient treatment option for all subtypes of achalasia and other scenarios (including previous treatments and elderly and pediatric populations). Short and mid-term results are comparable to LHM and are better than PD data. The clinical response rate of DES and JE may make POEM the first-line treatment for SED.

Gallbladder perforation after closed thoracoabdominal trauma, diagnosed and treated by ERCP.

Single gallbladder injury after abdominal trauma is a rare finding. Early diagnosis of this disease is often difficult due to the variability of symptoms and unspecific results in the usual radiological tests. The usual management in patients with vesical trauma is surgery. We report a case of a patient with a gallbladder perforation after closed thoracoabdominal trauma diagnosed and treated with ERCP and a conservative management with good clinical evolution.

Perforación vesicular tras traumatismo toracoabdominal cerrado diagnosticado y tratado mediante CPRE / Gallbladder perforation after closed thoracoabdominal trauma, diagnosed and treated by ERCP

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'Dignity therapy', a promising intervention in palliative care: A comprehensive systematic literature review.

BACKGROUND: Dignity therapy is psychotherapy to relieve psychological and existential distress in patients at the end of life. Little is known about its effect. AIM: To analyse the outcomes of dignity therapy in patients with advanced life-threatening diseases. DESIGN: Systematic review was conducted. Three authors extracted data of the articles and evaluated quality using Critical Appraisal Skills Programme. Data were synthesized, considering study objectives. DATA SOURCES: PubMed, CINAHL, Cochrane Library and PsycINFO. The years searched were 2002 (year of dignity therapy development) to January 2016. 'Dignity therapy' was used as search term. Studies with patients with advanced life-threatening diseases were included. RESULTS: Of 121 studies, 28 were included. Quality of studies is high. Results were grouped into effectiveness, satisfaction, suitability and feasibility, and adaptability to different diseases and cultures. Two of five randomized control trials applied dignity therapy to patients with high levels of baseline psychological distress. One showed statistically significant decrease on patients' anxiety and depression scores over time. The other showed statistical decrease on anxiety scores pre-post dignity therapy, not on depression. Nonrandomized studies suggested statistically significant improvements in existential and psychosocial measurements. Patients, relatives and professionals perceived it improved end-of-life experience. CONCLUSION: Evidence suggests that dignity therapy is beneficial. One randomized controlled trial with patients with high levels of psychological distress shows DT efficacy in anxiety and depression scores. Other design studies report beneficial outcomes in terms of end-of-life experience. Further research should understand how dignity therapy functions to establish a means for measuring its impact and assessing whether high level of distress patients can benefit most from this therapy.

Síndrome hemolítico urémico como forma de presentación de cáncer de próstata diseminado / Advanced prostate cancer presented with hemolytic uremic syndrome

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Prevalence of Elevated Blood Lead Levels and Risk Factors Among Residents Younger Than 6 Years, Puerto Rico--2010.

CONTEXT: Limited data exist about blood lead levels (BLLs) and potential exposures among children living in Puerto Rico. The Puerto Rico Department of Health has no formal blood lead surveillance program. OBJECTIVES: We assessed the prevalence of elevated BLLs (≥5 micrograms of lead per deciliter of blood), evaluated household environmental lead levels, and risk factors for BLL among children younger than 6 years of age living in Puerto Rico in 2010. METHODS: We used a population-based, cross-sectional sampling strategy to enroll an island-representative sample of Puerto Rican children younger than 6 years. We estimated the island-wide weighted prevalence of elevated BLLs and conducted bivariable and multivariable linear regression analyses to ascertain risk factors for elevated BLLs. RESULTS: The analytic data set included 355 households and 439 children younger than 6 years throughout Puerto Rico. The weighted geometric mean BLL of children younger than 6 years was 1.57 µg/dL (95% confidence interval [CI], 1.27-1.88). The weighted prevalence of children younger than 6 years with BLLs of 5 µg/dL or more was 3.18% (95% CI, 0.93-5.43) and for BLLs of 10 µg/dL or more was 0.50% (95% CI, 0-1.31). Higher mean BLLs were significantly associated with data collection during the summer months, a lead-related activity or hobby of anyone in the residence, and maternal education of less than 12 years. Few environmental lead hazards were identified. CONCLUSIONS: The prevalence of elevated BLLs among Puerto Rican children younger than 6 years is comparable with the most recent (2007-2010) US national estimate (BLLs ≥5 µg/dL = 2.6% [95% CI = 1.6-4.0]). Our findings suggest that targeted screening of specific higher-risk groups of children younger than 6 years can replace island-wide or insurance-specific policies of mandatory blood lead testing in Puerto Rico.