Hospitalised patients with cirrhosis often require admission to intensive care (ITU), usually for management of secondary complications such as GI bleeding, sepsis, or organ failure. Prognosis of these patients is poor. Despite demonstration of modest improvements in recent years, overall in-hospital mortality in this group remained 54.6% in a recent study.1 Our study aimed to explore the characteristics and outcomes of cirrhotic patients admitted to ITU, and whether this was comparable to published data. We also aimed to explore whether parameters such as APACHE 2 score and admission blood lactate differ between those who survived their ITU stay and those that did not, and if this may help predict discharge.
Methods
A retrospective analysis was performed of patients admitted to the Whittington hospital ITU from January 2011-June 2013. Information regarding patients with a diagnosis of cirrhosis was gathered from the Intensive Care National Audit and Research unit (ICNARC) database, and discharge summaries.
Results
We identified 60 patients with cirrhosis, 3.07% of total ITU admissions, mean age 54.8 years (range 19–78). 49/60 patients had alcoholic cirrhosis, 5/60 had non-alcoholic steatohepatitis related cirrhosis. Primary reason for admission included GI bleed (24/60, 40%), pneumonia (16/60, 26.7%), other sepsis (10/60, 16.7%), encephalopathy (8/60, 13.3%). Overall mortality figures were 41.7% in-ITU, 48.3% at 30 days, and 70% at 1 year. In-ITU mortality for patients requiring only ventilatory support was 48.9%, those requiring inotropic support was 61.2% and those requiring renal support 64.2%. 24/60 patients required all 3 methods of support, 66.7% of those died in ITU and 75% at 30 days. 23 patients were admitted with sepsis and decompensated liver disease, 65% died in ITU and 73.9% at 30 days. Mean APACHE 2 scores for patients that died in ITU vs. those discharged from ITU were 23 (range 9–30) and 20 (range 8–36) respectively, with a statistically significant difference between the two groups (p = 0.036). Mean admission serum lactate for patients who died in ITU vs. those discharged from ITU was 7.6 (range 1–23) and 4.6 (range 1–17) respectively, demonstrating a statistically significant difference (p = 0.015).
Conclusion
As expected for a non liver-specialist unit, most patients had alcohol related cirrhosis. Mortality was high but comparable to other published data. The worst outcomes were seen in patients with sepsis and decompensated liver disease, and those requiring organ support. Admission lactate levels and APACHE 2 scores were significantly lower in patients successfully discharged from ITU; admission lactate could potentially aid prediction of successful discharge. Further study is needed.
Gastric adenocarcinoma is a disease that is often detected late, at a stage when curative treatment is unachievable. This must be addressed through changes in our approach to the identification of patients at increased risk by improving the detection and risk assessment of premalignant changes in the stomach, including chronic atrophic gastritis and intestinal metaplasia. Current guidelines recommend utilising random biopsies in a pathology-led approach in order to stage the extent and severity of gastritis and intestinal metaplasia. This random method is poorly reproducible and prone to sampling error and fails to acknowledge recent advances in our understanding of the progression to gastric cancer as a non-linear, branching evolutionary model. Data suggest that recent advances in endoscopic imaging modalities, such as narrow band imaging, can achieve a high degree of accuracy in the stomach for the diagnosis of these premalignant changes. In this review, we outline recent data to support a paradigm shift towards an endoscopy-led approach to diagnosis and staging of premalignant changes in the stomach. High-quality endoscopic interrogation of the chronically inflamed stomach mucosa, supported by targeted biopsies, will lead to more accurate risk assessment, with reduced rates of under or missed diagnoses.
Introduction Iron deficiency anaemia (IDA) is a common complication of Crohn’s disease (CD) and Ulcerative Colitis (UC), with estimated prevalence between 36%–76%. Both IDA and its treatment can be associated with significant disease morbidity, particularly fatigue. This 12 month pilot investigation, preceding a wider UK audit, aims to utilise the IBD Registry Web Tool to capture the prevalence of IDA in an outpatient setting and the consistency and quality of treatment patients receive, which are currently uncertain. Method In a Joint Working project between the IBD Registry and Pharmacosmos, patients were recruited at 5 hospitals: UCLH, Southampton, UHSM, James Cook, and Luton and Dunstable. At each site, 20 consecutive patients were recruited until 10 patients with CD and 10 with UC were enrolled, giving a total of 100 patients for the study. Patients gave permission for their data including demographics, disease activity scores, IBD Control Questionnaire, and blood parameters relating to IDA to be used by the Anaemia Service Evaluation and IBD Registry. Results We report baseline data for patients at enrolment. Average age was 44 years 11mos (19–90 years). Mean HBI score was 3.7 based on 57 recorded scores and UCDAI was 2.4 from 13 patients. Using the Physician’s Global Assessment, 3.7% had severe, 13.4% moderate, 26.8% mildly active and 56.1% quiescent disease. 18 patients were anaemic; 9 men and 9 women, with mean Hb114.4±13.7 g/L and 110.9±4.2 g/L respectively. 9 additional patients were iron deficient without anaemia. In anaemic patients, mean ferritin and CRP were 100.3 µg/L and 12.1 mg/L respectively. Ferritin and CRP were 69.9 µg/L and 7.7 mg/L in non-anaemic patients. Mean patient-reported IBD control-8 scores (range 0–16) were 11.47 (anaemic) and 11.45 (non-anaemic). 52 patients reported fatigue while 26 missed activities due to their disease. Conclusion In this pilot study, once patients were consented and entered on the IBD Registry Web Tool, adding blood results and disease scores was straightforward. This could easily be done in an outpatient clinic setting once the clinician is familiar with the process. This initial data set confirms the feasibility of effectively monitoring anaemia with the IBD Registry to enhance detection of under-recognised symptoms such as fatigue and help improve patient care. Our initial experience suggests that the IBD Registry serves as a reliable and meaningful way of capturing quality improvement data regarding IDA and its treatment in IBD. Disclosure of Interest None Declared
GAstric GLands (GAGL) dataset. - v.1 GAGL 'minimal dataset' (a part of GAGL dataset) consists of 9 downsampled WSI including 3 normal, 3 gastric atrophic and 3 intestinal metaplasia cases. The minimal dataset could be used for the validation of the study findings of the following study: A digital pathology workflow for the segmentation and classification of gastric glands: Study of gastric atrophy and intestinal metaplasia cases. GAGL dataset consists of 85 WSI, collected from 20 patients. Gastric tissues were collected at University College London Hospital NHS trust, with ethical approval (research ethics committee (REC) reference: 15/YH/0311, & 19/LO/0089), with informed consent taken for prospective tissue collection. Samples were collected prospectively from patients undergoing gastrectomy for cancer, or sleeve gastrectomy for weight loss, with archival tissue used from endoscopic surveillance biopsies. Tissue underwent routine Hematoxylin & Eosin (H&E) staining. More specifically, the dataset includes 14 normal, 26 GA and 45 IM images. Please cite as: To be confirmed.
Gastric cancer is one of the most frequent causes of cancer-related deaths worldwide. Gastric atrophy (GA) and gastric intestinal metaplasia (IM) of the mucosa of the stomach have been found to increase the risk of gastric cancer and are considered precancerous lesions. Therefore, the early detection of GA and IM may have a valuable role in histopathological risk assessment. However, GA and IM are difficult to confirm endoscopically and, following the Sydney protocol, their diagnosis depends on the analysis of glandular morphology and on the identification of at least one well-defined goblet cell in a set of hematoxylin and eosin (H&E) -stained biopsy samples. To this end, the precise segmentation and classification of glands from the histological images plays an important role in the diagnostic confirmation of GA and IM. In this paper, we propose a digital pathology end-to-end workflow for gastric gland segmentation and classification for the analysis of gastric tissues. The proposed GAGL-VTNet, initially, extracts both global and local features combining multi-scale feature maps for the segmentation of glands and, subsequently, it adopts a vision transformer that exploits the visual dependences of the segmented glands towards their classification. For the analysis of gastric tissues, segmentation of mucosa is performed through an unsupervised model combining energy minimization and a U-Net model. Then, features of the segmented glands and mucosa are extracted and analyzed. To evaluate the efficiency of the proposed methodology we created the GAGL dataset consisting of 85 WSI, collected from 20 patients. The results demonstrate the existence of significant differences of the extracted features between normal, GA and IM cases. The proposed approach for gland and mucosa segmentation achieves an object dice score equal to 0.908 and 0.967 respectively, while for the classification of glands it achieves an F1 score equal to 0.94 showing great potential for the automated quantification and analysis of gastric biopsies.
Normal aging is associated with less lateralised task-related activation of the primary motor cortices. It has been hypothesized, but not tested, that this phenomenon is mediated transcallosaly. We have used Transcranial Magnetic Stimulation to look for age-related changes in interhemispheric inhibition (IHI). Thirty healthy individuals (aged 19-78 years) were studied using a paired-pulse protocol at rest and during a low-strength isometric contraction with the right hand. The IHI targeting the right motor cortex was assessed at two intervals, 10 ms (IHI10) and 40 ms (IHI40). The corticospinal excitability of the left hemisphere was assessed by means of input-output curves constructed during voluntary construction. Age was not correlated with IHI10 or IHI40 at rest. During muscle contraction IHI tended to increase at both intervals. However, this increase in IHI during the active condition (changeIHI) was less evident with advancing age for the 40 ms interval (r = 0.444, P = 0.02); in fact a degree of disinhibition was often present. There was no correlation between age and changeIHI10. Age was negatively correlated with the area under the recruitment curve (r = -0.585, P = 0.001) and the size of the maximum MEP collected (r = -0.485, P = 0.007). ChangeIHI and measures of corticospinal excitability were not intercorrelated. In conclusion, task-related increases in interhemispheric inhibition seem to diminish with advancing age. This phenomenon is specific for long-latency IHI and may underlie the age-related bihemispheric activation seen in functional imaging studies. The mechanism underlying changes in IHI with advancing age and the association with changes in corticospinal excitability need further investigation.
Tumours arise within complex 3D microenvironments, but the routine 2D analysis of tumours often underestimates the spatial heterogeneity. In this paper, we present a methodology to reconstruct and analyse 3D tumour models from routine clinical samples allowing 3D interactions to be analysed at cellular resolution. Our workflow involves cutting thin serial sections of tumours followed by labelling of cells using markers of interest. Serial sections are then scanned, and digital multiplexed data are created for computational reconstruction. Following spectral unmixing, a registration method of the consecutive images based on a pre-alignment, a parametric and a non-parametric image registration step is applied. For the segmentation of the cells, an ellipsoidal model is proposed and for the 3D reconstruction, a cubic interpolation method is used. The proposed 3D models allow us to identify specific interaction patterns that emerge as tumours develop, adapt and evolve within their host microenvironment. We applied our technique to map tumour-immune interactions of colorectal cancer and preliminary results suggest that 3D models better represent the tumor-immune cells interaction revealing mechanisms within the tumour microenvironment and its heterogeneity.
Introduction Patients with chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are at risk of developing gastric adenocarcinoma. Their diagnosis and management currently rely on histopathological guidance after random endoscopic biopsy sampling (Sydney biopsy strategy). This approach has significant flaws such as under-diagnosis, poor reproducibility and poor correlation between endoscopy and histology. This prospective, international multicentre study aims to establish whether endoscopy-led risk stratification accurately and reproducibly predicts CAG and IM extent and disease stage. Methods and analysis Patients with CAG and/or IM on standard white light endoscopy (WLE) will be prospectively identified and invited to undergo a second endoscopy performed by an expert endoscopist using enhanced endoscopic imaging techniques with virtual chromoendoscopy. Extent of CAG/IM will be endoscopically staged with enhanced imaging and compared with standard WLE. Histopathological risk stratification through targeted biopsies will be compared with endoscopic disease staging and to random biopsy staging on WLE as a reference. At least 234 patients are required to show a 10 % difference in sensitivity and accuracy between enhanced imaging endoscopy-led staging and the current biopsy-led staging protocol of gastric atrophy with a power (beta) of 80 % and a 0.05 probability of a type I error (alpha). Ethics and dissemination The study was approved by the respective Institutional Review Boards (Netherlands: MEC-2018-078; UK: 19/LO/0089). The findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NTR7661; Pre-results.
AIMTo assess clinical outcomes for submucosal (T1b) oesophageal adenocarcinoma (OAC) patients managed with either surgery or endoscopic eradication therapy. METHODSPatients found to have T1b OAC following endoscopic resection between January 2008 to February 2016 at University College London Hospital were retrospectively analysed.Patients were split into low-risk and high-risk groups according to established histopathological criteria and were then further categorised according to whether they underwent surgical resection or conservative management.Study outcomes include the presence of lymphnode metastases, disease-specific mortality and overall survival. RESULTSA total of 60 patients were included; 22 patients were surgically managed (1 low-risk and 21 high-risk patients) whilst 38 patients were treated conservatively (12 low-risk and 26 high-risk).Overall, lymph node metastases (LNM) were detected in 10 patients (17%); six of these patients had undergone conservative management and LNM were detected at a median of 4 mo after endoscopic mucosal resection (EMR).All LNM occurred in patients with highrisk lesions and this represented 21% of the total high-risk lesions.Importantly, there was no statistically significant difference in tumor-related deaths between those treated surgically or conservatively (P = 0.636) and disease-specific survival time was also comparable between the two treatment strategies (P = 0.376). CONCLUSIONT1b tumours without histopathological high-risk markers of LNM can be treated endoscopically with good outcomes.In selected patients, endoscopic therapy may be appropriate for high-risk lesions.
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