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1.
Endoscopy ; 56(3): 174-181, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37949103

RESUMEN

BACKGROUND: Device-assisted enteroscopy (DAE) has become a well-established diagnostic and therapeutic tool for the management of small-bowel pathology. We aimed to evaluate the performance measures for DAE across the UK against the quality benchmarks proposed by the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We retrospectively collected data on patient demographics and DAE performance measures from electronic endoscopy records of consecutive patients who underwent DAE for diagnostic and therapeutic purposes across 12 enteroscopy centers in the UK between January 2017 and December 2022. RESULTS: A total of 2005 DAE procedures were performed in 1663 patients (median age 60 years; 53% men). Almost all procedures (98.1%) were performed for appropriate indications. Double-balloon enteroscopy was used for most procedures (82.0%), followed by single-balloon enteroscopy (17.2%) and spiral enteroscopy (0.7%). The estimated depth of insertion was documented in 73.4% of procedures. The overall diagnostic yield was 70.0%. Therapeutic interventions were performed in 42.6% of procedures, with a success rate of 96.6%. Overall, 78.0% of detected lesions were marked with a tattoo. Patient comfort was significantly better with the use of deep sedation compared with conscious sedation (99.7% vs. 68.5%; P<0.001). Major adverse events occurred in only 0.6% of procedures. CONCLUSIONS: Performance measures for DAE in the UK meet the ESGE quality benchmarks, with high diagnostic and therapeutic yields, and a low incidence of major adverse events. However, there is room for improvement in optimizing sedation practices, standardizing the depth of insertion documentation, and adopting marking techniques to aid in the follow-up of detected lesions.


Asunto(s)
Enfermedades Intestinales , Masculino , Humanos , Persona de Mediana Edad , Femenino , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/terapia , Estudios Retrospectivos , Mejoramiento de la Calidad , Endoscopía Gastrointestinal/métodos , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/patología , Enteroscopía de Doble Balón/métodos
2.
Expert Rev Neurother ; 23(4): 413-423, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37021592

RESUMEN

BACKGROUND: The following study evaluated the clinical outcomes of patients enrolled in the UK Medical Cannabis Registry, who were treated with inhaled dried flower (Adven® EMT2, Curaleaf International, Guernsey), and sublingual/oral medium-chain triglyceride-based oils (Adven, Curaleaf International, Guernsey) for chronic pain. METHODS: In this cohort study, the primary outcomes were changes in validated patient reported outcome measures (PROMs) at 1, 3, and 6 months compared to baseline, and adverse event analysis. Statistical significance was defined as p < 0.050. RESULTS: Three hundred and forty-eight (45.7%), 36 (4.7%), and 377 (49.5%) patients were treated with oils, dried flower, or both, respectively. Patients treated with oils or combination therapy recorded improvements within health-related quality of life, pain, and sleep-specific PROMs at 1, 3, and 6 months (p < 0.050). Patients treated with combination therapy recorded improvements in anxiety-specific PROMs at 1, 3, and 6 months (p < 0.050). 1,273 (167.3%) adverse events were recorded, with previously cannabis naïve users, ex-cannabis users, and females more likely to experience adverse events (p < 0.050). CONCLUSIONS: This study observed an association between initiation of CBMP treatment and improved outcomes for chronic pain patients. Prior cannabis use and gender were associated with adverse event incidence. Placebo-controlled trials are still necessary to establish the efficacy and safety of CBMPs for chronic pain.


Asunto(s)
Cannabis , Dolor Crónico , Alucinógenos , Marihuana Medicinal , Femenino , Humanos , Marihuana Medicinal/efectos adversos , Dolor Crónico/tratamiento farmacológico , Calidad de Vida , Estudios de Cohortes , Alucinógenos/uso terapéutico , Aceites/uso terapéutico , Sistema de Registros , Reino Unido
3.
Expert Rev Clin Pharmacol ; 16(3): 257-266, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36848456

RESUMEN

BACKGROUND: There is a paucity of high-quality data on patient outcomes and safety after initiating treatment with cannabis-based medicinal products (CBMPs). The aim of this study was to assess the clinical outcomes and safety of CBMPs by analyzing patient-reported outcome measures and adverse events across a broad spectrum of chronic conditions. RESEARCH DESIGN AND METHODS: This study analyzed patients enrolled in the UK Medical Cannabis Registry. Participants completed the EQ-5D-5L to assess health-related quality of life, Generalized Anxiety Disorder-7 (GAD-7) questionnaire to measure anxiety severity, and the Single-item Sleep Quality Scale (SQS) to rate sleep quality at baseline and follow-up after 1, 3, 6, and 12 months. RESULTS: A total of 2833 participants met inclusion criteria. The EQ-5D-5L index value, GAD-7, and SQS all improved at each follow-up (p < 0.001). There was no difference in EQ-5D-5L index values between former or current illicit cannabis consumers and naïve patients (p > 0.050). Adverse events were reported by 474 (16.73%) participants. CONCLUSIONS: This study suggests that CBMPs are associated with an improvement in health-related quality of life in UK patients with chronic diseases. Treatment was tolerated well by most participants, but adverse events were more common in female and cannabis-naïve patients.


Asunto(s)
Cannabis , Alucinógenos , Marihuana Medicinal , Humanos , Femenino , Marihuana Medicinal/efectos adversos , Calidad de Vida , Reino Unido , Encuestas y Cuestionarios , Evaluación de Resultado en la Atención de Salud
4.
Expert Rev Neurother ; 23(3): 281-295, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36803620

RESUMEN

INTRODUCTION: There is growing evidence on the efficacy of cannabis-based medicinal products (CBMPs) for chronic pain (CP). Due to the interaction between CP and anxiety, and the potential impact of CBMPs on both anxiety and CP, this article aimed to compare the outcomes of CP patients with and without co-morbid anxiety following CBMP treatment. METHODS: Participants were prospectively enrolled and categorized by baseline General Anxiety Disorder-7(GAD-7) scores, into 'no anxiety'(GAD-7 < 5) and 'anxiety'(GAD-7 ≥ 5) cohorts. Primary outcomes were changes in Brief Pain Inventory Short-Form, Short-form McGill Pain Questionnaire-2, Pain Visual Analogue Scale, Sleep Quality Scale (SQS), GAD-7 and EQ-5D-5L index values at 1, 3 and 6 months. RESULTS: 1254 patients (anxiety = 711; no anxiety = 543) met inclusion criteria. Significant improvements in all primary outcomes were observed at all timepoints (p < 0.050), except GAD-7 in the no anxiety group(p > 0.050). The anxiety cohort reported greater improvements in EQ-5D-5L index values, SQS and GAD-7(p < 0.050), but there were no consistent differences in pain outcomes. CONCLUSION: A potential association between CBMPs and improvements in pain and health-related quality of life (HRQoL) in CP patients was identified. Those with co-morbid anxiety reported greater improvements in HRQoL.


Asunto(s)
Dolor Crónico , Marihuana Medicinal , Humanos , Calidad de Vida , Marihuana Medicinal/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Estudios de Cohortes , Trastornos de Ansiedad/tratamiento farmacológico , Encuestas y Cuestionarios
5.
Cannabis Cannabinoid Res ; 8(3): 557-566, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35073160

RESUMEN

Introduction: There is a growing body of literature supporting the efficacy of cannabis-based medicinal products (CBMPs). Despite an increase in prescribing globally, there is a paucity of high-quality clinical data on the efficacy of CBMPs for many conditions. This study aims to detail the changes in health-related quality of life (HRQoL) and associated clinical safety in patients prescribed CBMPs for any clinical indication from the UK Medical Cannabis Registry (UKMCR). Methods: An uncontrolled prospective case series of the UKMCR was analyzed. Primary outcomes included change from baseline in patient-reported outcome measures collected across all patients (the Generalized Anxiety Disorder Scale [GAD-7], EQ-5D-5L, and Sleep Quality Scale [SQS]) at 1, 3, and 6 months. Secondary outcomes included the self-reported incidence and severity of adverse events. Statistical significance was defined as p<0.050. Results: Three hundred twelve patients were included in the final analysis, with a mean age of 44.8. The most common primary diagnoses were chronic pain of undefined etiology (n=102, 32.7%), neuropathic pain (n=43, 13.8%), and fibromyalgia (n=31, 9.9%). Before enrolment, 112 (35.9%) patients consumed cannabis daily. The median cannabidiol and (-)-trans-Δ9-tetrahydrocannabinol doses prescribed at baseline were 20.0 mg (0.0-510.0 mg) and 3.0 mg (0.0-660.0 mg), respectively. Statistically significant improvements were observed in GAD-7, EQ-5D-5L Index, EQ-5D Visual Analog Scale and SQS scores at 1, 3, and 6 months (p<0.050). There were 94 (30.1%) reported adverse events, of which nausea (n=12, 3.8%), dry mouth (n=10, 3.2%), dizziness (n=7, 2.2%), and somnolence (n=7, 2.2%) were the most common. Conclusion: This study demonstrated CBMP treatment to be associated with a relatively low incidence of severe adverse events in the medium-term. Positive changes following treatment were observed in general, as well as anxiety and sleep-specific, HRQoL outcomes. Randomized controlled trials are still awaited to assess causation; however, real-world evidence can help inform current clinical practice, future trials, and is an important component of pharmacovigilance.


Asunto(s)
Cannabis , Alucinógenos , Marihuana Medicinal , Humanos , Adulto , Marihuana Medicinal/efectos adversos , Calidad de Vida , Dronabinol/efectos adversos , Cannabis/efectos adversos , Evaluación de Resultado en la Atención de Salud , Reino Unido/epidemiología
6.
Expert Rev Gastroenterol Hepatol ; 17(1): 85-98, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36562418

RESUMEN

OBJECTIVES: Cannabis-based medicinal products (CBMPs) have shown promising preclinical activity in inflammatory bowel disease (IBD). However, clinical trials have not demonstrated effects on inflammation. This study aims to analyze changes in health-related quality of life (HRQoL) and adverse events in IBD patients prescribed CBMPs. METHODS: A case series from the UK Medical Cannabis Registry was performed. Primary outcomes included changes from baseline in the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), Generalized Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L Index score at 1 and 3 months. Statistical significance was defined using p < 0.050. RESULTS: Seventy-six patients with Crohn's disease (n = 51; 67.11%) and ulcerative colitis (n = 25; 32.89%) were included. The median baseline SIBDQ score improved at 1 and 3 months. EQ-5D-5L index values, GAD-7, and SQS also improved after 3 months (p < 0.050). Sixteen (21.05%) patients reported adverse events with the majority being classified as mild to moderate in severity. CONCLUSION: Patients treated with CBMPs for refractory symptoms of Crohn's disease and ulcerative colitis demonstrated a short-term improvement in IBD-specific and general HRQoL. Prior cannabis consumers reported greater improvement compared to cannabis-naïve individuals.


Asunto(s)
Cannabis , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Marihuana Medicinal , Humanos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Marihuana Medicinal/efectos adversos , Calidad de Vida , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Cannabis/efectos adversos , Agonistas de Receptores de Cannabinoides/uso terapéutico , Reino Unido
7.
Neuropediatrics ; 54(3): 174-181, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36539215

RESUMEN

BACKGROUND: There is a paucity of high-quality evidence of the efficacy and safety of cannabis-based medicinal products in treatment of treatment-resistant epilepsy (TRE) in children. METHODS: A case series of children (<18 years old) with TRE from the UK Medical Cannabis Registry was analyzed. Primary outcomes were ≥50% reduction in seizure frequency, changes in the Impact of Pediatric Epilepsy Score (IPES), and incidence of adverse events. RESULTS: Thirty-five patients were included in the analysis. Patients were prescribed during their treatment with the following: CBD isolate oils (n = 19), CBD broad-spectrum oils (n = 17), and CBD/Δ9-THC combination therapy (n = 17). Twenty-three (65.7%) patients achieved a ≥50% reduction in seizure frequency. 94.1% (n = 16) of patients treated with CBD and Δ9-THC observed a ≥50% reduction in seizure frequency compared to 31.6% (n = 6) and 17.6% (n = 3) of patients treated with CBD isolates and broad-spectrum CBD products, respectively (p< 0.001). Twenty-six (74.3%) adverse events were reported by 16 patients (45.7%). The majority of these were mild (n = 12; 34.2%) and moderate (n = 10; 28.6%). CONCLUSION: The results of this study demonstrate a positive signal of improved seizure frequency in children treated with Cannabis-based medicinal products (CBMPs) for TRE. Moreover, the results suggest that CBMPs are well-tolerated in the short term. The limitations mean causation cannot be determined in this open-label, case series.


Asunto(s)
Cannabis , Epilepsia Refractaria , Epilepsia , Marihuana Medicinal , Niño , Humanos , Adolescente , Marihuana Medicinal/efectos adversos , Dronabinol/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Reino Unido
8.
Methods Appl Fluoresc ; 10(4)2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36214388

RESUMEN

The permeability of the intestinal barrier is altered in a multitude of gastrointestinal conditions such as Crohn's and coeliac disease. However, the clinical utility of gut permeability is currently limited due to a lack of reliable diagnostic tests. To address this issue, we report a novel technique for rapid, non-invasive measurement of gut permeability based on transcutaneous ('through-the-skin') fluorescence spectroscopy. In this approach, participants drink an oral dose of a fluorescent dye (fluorescein) and a fibre-optic fluorescence spectrometer is attached to the finger to detect permeation of the dye from the gut into the blood stream in a non-invasive manner. To validate this technique, clinical trial measurements were performed in 11 healthy participants. First, after 6 h of fasting, participants ingested 500 mg of fluorescein dissolved in 100 ml of water and fluorescence measurements were recorded at the fingertip over the following 3 h. All participants were invited back for a repeat study, this time ingesting the same solution but with 60 g of sugar added (known to transiently increase intestinal permeability). Results from the two study datasets (without and with sugar respectively) were analysed and compared using a number of analysis procedures. This included both manual and automated calculation of a series of parameters designed for assessment of gut permeability. Calculated values were compared using Student's T-tests, which demonstrated significant differences between the two datasets. Thus, transcutaneous fluorescence spectroscopy shows promise in non-invasively discriminating between two differing states of gut permeability, demonstrating potential for future clinical use.


Asunto(s)
Colorantes Fluorescentes , Agua , Fluoresceína , Voluntarios Sanos , Humanos , Permeabilidad , Espectrometría de Fluorescencia , Azúcares
9.
Scand J Gastroenterol ; 57(9): 1138-1146, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35450506

RESUMEN

BACKGROUND: Colonoscopy proficiency is significantly influenced by skills achieved during training. Although assessment scores exist, they do not evaluate the impact of visual search strategies and their use is time and labour intensive. Eye-tracking has shown significant differences in visual gaze patterns (VGPs) between expert endoscopists with varying polyp detection rates, so may provide a means of automated assessment and guidance for trainees. This study aimed to assess the feasibility of eye-tracking as a novel assessment method for trainee endoscopists. METHODS: Eye-tracking glasses were used to record 26 colonoscopies from 12 endoscopy trainees who were assessed with directly observed procedural scores (DOPS), devised by the Joint Advisory Group (JAG) on GI endoscopy, and a visual analogue score of overall competence. A 'total weighted procedure score' (TWPS) was calculated from 1 to 20. Primary outcomes of fixation duration (FixD) and fixation frequency (FixF) were analysed according to areas of interest (AOIs) with the bowel surface and lumen represented by three concentric rings. Correlation was assessed using Pearson's coefficient. Significance was set at p<.050. RESULTS: Trainees displayed a significant positive correlation between TWPS and FixD (R = 0.943, p<.0001) and FixF (R = 0.936, p<.0001) in the anatomical bowel mucosa peripheries. Conversely, they had significant negative correlations between TWPS and the anatomical bowel lumen (FixD: R= -0.546, p=.004; FixF: R= -0.568, p=.002). CONCLUSIONS: Higher objective performance scores were associated with VGPs focussing on bowel mucosa. This is consistent with prior analysis showing peripheral VGPs correspond with higher polyp detection rates. Analysis of VGPs, therefore, has potential for training and assessment in colonoscopy.


Asunto(s)
Pólipos del Colon , Colonoscopía , Gastroenterólogos , Mucosa Intestinal , Competencia Clínica , Pólipos del Colon/diagnóstico por imagen , Colonoscopía/métodos , Medidas del Movimiento Ocular , Gastroenterólogos/educación , Humanos
10.
Expert Rev Clin Pharmacol ; 15(4): 473-485, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34937477

RESUMEN

OBJECTIVES: To explore pain-specific, general health-related quality of life (HRQoL), and safety outcomes of chronic pain patients prescribed cannabis-based medicinal products (CBMPs). METHODS: A case series was performed using patients with chronic pain from the UK Medical Cannabis Registry. Primary outcomes were changes in Brief Pain Inventory short-form (BPI), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2), Visual Analogue Scale-Pain (VAS), General Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5L, at 1, 3, and 6 months from baseline. Statistical significance was defined at p-value<0.050. RESULTS: 190 patients were included. Median initial Δ9-tetrahydrocannabinol and cannabidiol daily doses were 2.0mg (range:0.0-442.0mg) and 20.0mg (range:0.0-188.0mg) respectively. Significant improvements were observed within BPI, SF-MPQ-2, GAD-7, SQS, EQ-5D-5 L index, and VAS measures at all timepoints (p<0.050). Seventy-five adverse events (39.47%) were reported, of which 37 (19.47%) were rated as mild, 23 (12.11%) as moderate, and 14 (7.37%) as severe. Nausea (n=11; 5.8%) was the most frequent adverse event. CONCLUSION: An association was identified between patients with chronic pain prescribed CBMPs and improvements in pain-specific and general HRQoL outcomes. Most adverse events were mild to moderate in severity, indicating CBMPs were well tolerated. Inherent limitations of study design limit its overall applicability.


Asunto(s)
Dolor Crónico , Marihuana Medicinal , Analgésicos , Enfermedad Crónica , Dolor Crónico/tratamiento farmacológico , Humanos , Marihuana Medicinal/efectos adversos , Calidad de Vida , Sistema de Registros , Encuestas y Cuestionarios , Reino Unido
11.
Neuropsychopharmacol Rep ; 41(3): 362-370, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33988306

RESUMEN

AIM: Cannabis-based medicinal products (CBMPs) are prescribed with increased frequency, despite a paucity of high-quality randomized controlled trials. The aim of this study is to analyze the early outcomes of the first series of patients prescribed CBMPs in the UK with respect to effects on health-related quality of life and clinical safety. METHODS: A prospective case series was performed using the UK Medical Cannabis Registry. Primary outcomes were change in patient-reported outcomes measures (EQ-5D-5L, General Anxiety Disorder-7 (GAD-7) and Single-Item Sleep Quality Scale (SQS)) at 1 and 3 months from baseline. The secondary outcome was the incidence of adverse events. Statistical significance was defined by a P-value <.050. RESULTS: There were 129 patients included in the final analysis with a mean age of 46.23 (±14.51) years. The most common indication was chronic pain of undefined etiology (n = 48; 37.2%). The median initial cannabidiol and (-)-trans-Δ9-tetrahydrocannabinol daily dose was 20.0 mg (Range: 0.0-768.0 mg) and 3.9 mg (Range: 0.0-660.0 mg), respectively. Statistically significant improvements in health-related quality of life were demonstrated at 1 and 3 months in GAD-7, SQS, EQ-5D-5L pain and discomfort subscale, EQ-5D-5L anxiety and depression subscale, EQ-VAS and EQ-5D-5L index values(P < .050). There were 31 (24.03%) total reported adverse events. CONCLUSION: This study suggests that CBMP therapy may be associated with an improvement in health-related quality-of-life outcomes as self-reported by patients. CBMPs are also demonstrated to be relatively safe in the short to medium-term. These findings must be treated with caution given the limited scope of this initial analysis, with no placebo or an active comparator, with further research required.


Asunto(s)
Marihuana Medicinal , Estado de Salud , Humanos , Marihuana Medicinal/efectos adversos , Persona de Mediana Edad , Calidad de Vida , Sistema de Registros , Calidad del Sueño , Reino Unido/epidemiología
12.
Gastrointest Endosc ; 93(4): 888-898.e1, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32763242

RESUMEN

BACKGROUND AND AIMS: Definitive chemoradiotherapy (CRT) is increasingly used as a nonsurgical treatment for esophageal cancer. In Japanese studies, salvage endoscopic resection (ER) has emerged as a promising strategy for local failure after definitive CRT. We aimed to evaluate the safety and efficacy of salvage ER in a Western setting. METHODS: Gastroenterologists from Europe and the United States were invited to submit their experience with salvage endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) after definitive CRT. Participating gastroenterologists completed an anonymized database, including patient demographics, clinicopathologic variables, and follow-up on survival and recurrence. RESULTS: Gastroenterologists from 10 endoscopic units in 6 European countries submitted information on 25 patients. A total of 35 salvage ER procedures were performed, of which 69% were ESD and 31% EMR. Most patients had squamous cell carcinoma (64%) of the middle or lower esophagus (68%) staged as cT2-3 (68%) and cN+ (52%) before definitive CRT. The median time from end of definitive CRT to ER was 22 months (interquartile range, 6-47). The en-bloc resection rate was 92% for ESD and 46% for EMR. During a median of 24 months (interquartile range, 12-59) of follow-up after salvage ER, 52% developed a recurrence (11 locoregional, 2 distant). The 5-year recurrence-free survival, overall survival, and disease-specific survival were 36%, 52%, and 79%, respectively. No major intra- or postprocedural adverse events, such as bleeding or perforation, were reported. CONCLUSIONS: In carefully selected esophageal cancer patients, salvage ER is technically feasible after definitive CRT. Further prospective research is recommended to validate the safety and effectivity of salvage ER for the management of local failure.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Quimioradioterapia , Neoplasias Esofágicas/terapia , Europa (Continente) , Humanos , Recurrencia Local de Neoplasia/terapia , Estudios Retrospectivos , Resultado del Tratamiento
13.
Sci Rep ; 10(1): 16169, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32999336

RESUMEN

Gastro-intestinal function plays a vital role in conditions ranging from inflammatory bowel disease and HIV through to sepsis and malnutrition. However, the techniques that are currently used to assess gut function are either highly invasive or unreliable. Here we present an alternative, non-invasive sensing modality for assessment of gut function based on fluorescence spectroscopy. In this approach, patients receive an oral dose of a fluorescent contrast agent and a fibre-optic probe is used to make fluorescence measurements through the skin. This provides a readout of the degree to which fluorescent dyes have permeated from the gut into the blood stream. We present preliminary results from our first measurements in human volunteers demonstrating the potential of the technique for non-invasive monitoring of multiple aspects of gastro-intestinal health.


Asunto(s)
Tracto Gastrointestinal/diagnóstico por imagen , Enfermedades Inflamatorias del Intestino/diagnóstico por imagen , Espectrometría de Fluorescencia/métodos , Medios de Contraste , Colorantes Fluorescentes , Humanos
14.
Cancer Res ; 80(13): 2764-2774, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32345674

RESUMEN

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging (MSI) can support objective diagnosis in minutes using a routine frozen tissue section. However, whether MSI can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here, we used desorption electrospray ionization-MSI (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariate models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (AUC = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in premalignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened glycerophospholipid chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of premalignant tissues and unveils mechanisms of phospholipidomic reprogramming. SIGNIFICANCE: These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite, as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.


Asunto(s)
Adenocarcinoma/patología , Neoplasias Esofágicas/patología , Lipidómica , Lipogénesis , Fosfolípidos/análisis , Adenocarcinoma/metabolismo , Estudios de Cohortes , Neoplasias Esofágicas/metabolismo , Humanos , Espectrometría de Masas en Tándem , Células Tumorales Cultivadas
15.
Gut ; 69(9): 1708, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31395746
17.
Mucosal Immunol ; 12(5): 1212-1219, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31239514

RESUMEN

Gut-associated lymphoid tissue (GALT) is a key location for the HIV reservoir. The observation that B-cell-T-cell doublets are enriched for CD32a (a low-affinity IgG receptor) in peripheral blood raises interesting questions, especially as these cells have been associated with HIV DNA in some studies. We sought to determine if similar doublets were present in GALT, the significance of these doublets, and their implications for the HIV reservoir. Given the importance of GALT as a reservoir for HIV, we looked for expression of CD32 on gut CD4 T cells and for evidence of doublets, and any relationship with HIV DNA in HIV + individuals initiated on antiretroviral therapy (ART) during primary HIV infection (PHI). Tonsil tissue was also available for one individual. As previously shown for blood, CD32high CD4 cells were mainly doublets of CD4 T cells and B cells, with T-cell expression of ICOS in tonsil and gut tissue. CD4 T cells associated with CD32 (compared with 'CD32-' CD4 cells) had higher expression of follicular markers CXCR5, PD-1, ICOS, and Bcl-6 consistent with a T follicular helper (TFH) phenotype. There was a significant correlation between rectal HIV DNA levels and CD32 expression on TFH cells. Together, these data suggest that CD32high doublets are primarily composed of TFH cells, a subset known to be preferentially infected by HIV.


Asunto(s)
Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/fisiología , Ganglios Linfáticos Agregados/metabolismo , Ganglios Linfáticos Agregados/virología , Receptores de IgG/genética , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Colaboradores-Inductores/virología , Adulto , Anciano , Terapia Antirretroviral Altamente Activa , Linfocitos B/inmunología , Linfocitos B/metabolismo , Biomarcadores , Recuento de Linfocito CD4 , Femenino , Expresión Génica , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Ganglios Linfáticos Agregados/inmunología , Receptores de IgG/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Carga Viral
18.
Gut ; 68(5): 776-789, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30792244

RESUMEN

This is the first UK national guideline to concentrate on acute lower gastrointestinal bleeding (LGIB) and has been commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). The Guidelines Development Group consisted of representatives from the BSG Endoscopy Committee, the Association of Coloproctology of Great Britain and Ireland, the British Society of Interventional Radiology, the Royal College of Radiologists, NHS Blood and Transplant and a patient representative. A systematic search of the literature was undertaken and the quality of evidence and grading of recommendations appraised according to the GRADE(Grading of Recommendations Assessment, Development and Evaluation) methodology. These guidelines focus on the diagnosis and management of acute LGIB in adults, including methods of risk assessment and interventions to diagnose and treat bleeding (colonoscopy, computed tomography, mesenteric angiography, endoscopic therapy, embolisation and surgery). Recommendations are included on the management of patients who develop LGIB while receiving anticoagulants (including direct oral anticoagulants) or antiplatelet drugs. The appropriate use of blood transfusion is also discussed, including haemoglobin triggers and targets.


Asunto(s)
Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Adulto , Anciano , Algoritmos , Femenino , Gastroenterología , Hemorragia Gastrointestinal/etiología , Humanos , Masculino , Persona de Mediana Edad , Sociedades Médicas , Reino Unido
19.
Endoscopy ; 50(7): 701-707, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29415286

RESUMEN

BACKGROUND: The adenoma detection rate (ADR) is an important quality indicator in colonoscopy. The aim of this study was to evaluate the changes in visual gaze patterns (VGPs) with increasing polyp detection rate (PDR), a surrogate marker of ADR. METHODS: 18 endoscopists participated in the study. VGPs were measured using eye-tracking technology during the withdrawal phase of colonoscopy. VGPs were characterized using two analyses - screen and anatomy. Eye-tracking parameters were used to characterize performance, which was further substantiated using hidden Markov model (HMM) analysis. RESULTS: Subjects with higher PDRs spent more time viewing the outer ring of the 3 × 3 grid for both analyses (screen-based: r = 0.56, P = 0.02; anatomy: r = 0.62, P < 0.01). Fixation distribution to the "bottom U" of the screen in screen-based analysis was positively correlated with PDR (r = 0.62, P = 0.01). HMM demarcated the VGPs into three PDR groups. CONCLUSION: This study defined distinct VGPs that are associated with expert behavior. These data may allow introduction of visual gaze training within structured training programs, and have implications for adoption in higher-level assessment.


Asunto(s)
Pólipos del Colon/diagnóstico por imagen , Colonoscopía , Movimientos Oculares , Fijación Ocular , Adulto , Humanos , Persona de Mediana Edad
20.
J Clin Gastroenterol ; 52(10): e82-e86, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28644314

RESUMEN

BACKGROUND AND AIMS: Data have emerged supporting the right-lateral starting position in reducing time to cecum and improving patient comfort for minimally sedated colonoscopy. We aimed to test whether prone starting position results in similar advantages in procedure time and patient tolerability in comparison to traditional left-sided starting position. MATERIALS AND METHODS: We conducted a randomized controlled trial in which patients were randomized to begin in either the prone or left-lateral (LL) position. A total of 181 adult patients undergoing scheduled colonoscopy were stratified by age, gender, body mass index, and experience of the endoscopist. Patients were then randomized 1:1 in permuted blocks. The primary outcome measure was time to cecal intubation and secondary outcome measures included patient comfort that was measured by visual analog scale. RESULTS: There was no benefit from prone starting positioning over conventional left-sided starting positioning. Further, prone starting position led to an increase in time to reach cecum (701 vs. 511 s; P=0.01). This could be in part explained by an increased time to reach transverse colon in patients positioned prone (332 vs. 258 s; P=0.06). Comfort levels were similar between patients positioned prone and LL (4 vs. 4 visual analog scale; P=0.6) although endoscopists found colonoscopies in which patients started prone more technically challenging than if started LL (5 vs. 4; P=0.002). CONCLUSIONS: Prone starting position did not improve time to reach cecum or patient comfort for minimally sedated patients undergoing colonoscopy. The ClinicalTrials.gov identifier is NCT02305706.


Asunto(s)
Colonoscopía/métodos , Posicionamiento del Paciente , Ciego/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
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