Miracle-dz/UniFAR-FTUs huggingface dataset:
A case of dyspepsia and abdominal fullness

A 59-year-old woman presented with a 5-month history of acid reflux symptoms which were initially relieved with a proton pump inhibitor. She complained of no weight loss, anorexia or abdominal pain but could feel a ‘fullness’ in her upper abdomen which prevented her from lying prone. Examination revealed a hard epigastric mass which seemed separate from the liver and spleen. There was no lymphadenopathy or other positive findings. Initial laboratory investigations showed a normal full blood count, urea and electrolytes, bilirubin and …
Toll-like receptors 2/4 agonists: a potential strategy for preventing invasion and metastasis of hepatocellular carcinoma

In their recent study, Mencin and colleagues1 summarised the role of toll-like receptors (TLRs) and TLR ligands in the pathophysiology of some chronic liver diseases, including hepatocellular carcinoma (HCC), and discussed the potential role of TLR agonists, antagonists and probiotics for the treatment of these diseases. As we know, the long-term prognosis of HCC remains unsatisfactory even after surgical resection and chemotherapy because of a high recurrence rate. Invasion, together with metastasis formation, are commonly associated with the HCC recurrence and represent the most common reasons for the poor prognosis. However, fewer agents are currently available to block or postpone HCC progression. Mencin and colleagues discussed the repressive effects of TLR agonists on the replication of hepatitis C virus (HCV) and HBV, which are two risk factors of developing HCC. Regarding our study, we would like to bring to your attention that the TLR 2/4 agonist …
Natural inhibitors of advanced glycation end‐products

Purpose – The purpose of this paper is to focus on some of the reported natural advanced glycation end‐products (AGE) inhibitors providing an outline of AGE‐breakers and the potential anti‐glycation properties of some foodstuffs.Design/methodology/approach – Literature searches were conducted to find a link between common household spices, medicinal herbs, AGE and diabetes which could lead to practical home‐based recommendations for changes in a person's diet.Findings – Findings tend to indicate the potential of some dietary components to prevent and/or inhibit AGE formation. Thus, these dietary agents may be exploited for controlling AGE‐mediated diabetic pathological conditions and as possible natural protector of AGE formation in vivo. Consequently, the quest for new AGE inhibitors is considered of paramount importance which can be of therapeutic potential in patients with diabetes or age‐related diseases.Practical implications – Studies on the inhibition of AGE formation have received increasing recog.
The next thing in prognostic molecular markers: microRNA signatures of cancer

Cancer is known to be a consequence of the accumulation of mutations and epigenetic alterations of oncogenes and tumour suppressor genes, which cooperate to cause a normal cell to transform into a cancer cell. Thus, the clinical behaviour of cancer cells has been logically predicted to reflect the consequences of these mutated and altered genes. This hypothesis has led to the hope that measurement of gene activity or expression can be used as biomarkers to accurately determine which tumours will recur and which are likely to respond to specific treatments. Consequently, for over three decades, there has been an ongoing search to identify mutated or otherwise altered genes that can precisely predict the behaviour of tumours with regards to risk for recurrence and response to chemotherapy. In the May issue of Gut , Li et al reported on the discovery of a microRNA gene expression signature that shows considerable promise for determining the prognosis of individuals with gastric cancer.1 Their identification of this panel of prognostic microRNAs for gastric cancer is one of several recent studies that have found this class of small non-coding RNAs to be useful for predicting the behaviour of a variety of different cancers, including acute myeloid leukaemia, chronic lymphocytic leukaemia, colon cancer, pancreatic cancer, and non-small cell lung cancer.2 These reports highlight that this relatively newly identified class of RNA molecules is showing substantial potential to be used as diagnostic and prognostic biomarkers for cancer. Beyond the promise that microRNAs hold as candidate biomarkers for the early detection and management of cancer, there is also considerable excitement for the use of miRNAs as a novel class of therapeutic targets and as an entirely new class of therapeutic agents for the treatment of cancers. In order to appreciate where our understanding of microRNAs is …
Systemic lupus erythematosus observations of travel burden: A qualitative inquiry

Explorations of travel impediments among patients suffering from rheumatic diseases have been very limited. Research has consistently indicated a shortage of rheumatologists, resulting in patients potentially having to travel long distances for care. The purpose of our study was to explore how systemic lupus erythematosus (SLE) patients experience travel issues differentially by race and socio‐economic status.
Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles

Background Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis. Objective To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed. Results Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10−40 and OR=4.13, p=8.4×10−76, respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk. Conclusions Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.
Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas

Objective The clinicopathological significance of four morphological types of intraductal papillary mucinous neoplasms of the pancreas (IPMNs; gastric, intestinal, pancreatobiliary and oncocytic) was assessed. Design Retrospective multicentre analysis of 283 surgically resected IPMNs. Results Of the 283 IPMNs, 139 were of the gastric type, 101 were intestinal, 19 were pancreatobiliary and 24 were oncocytic. These types were significantly associated with clinicopathological factors including sex (p=0.0032), age (p=0.00924), ectatic duct size (p=0.0245), detection of mural nodules (p=4.09×10−6), histological grade (p<2.20×10−16), macroscopic types with differential involvement of the pancreatic duct system (p=3.91×10−5), invasive phenotypes (p=3.34×10−12), stage (p<2.20×10−16) and recurrence (p=0.00574). Kaplan–Meier analysis showed significant differences in patient survival by morphological type (p=5.24×10−6). Survival rates at 5 and 10 years, respectively, were 0.937 (95% CI 0.892 to 0.984) for patients with gastric-type IPMNs; 0.886 (95% CI 0.813 to 0.965) and 0.685 (95% CI 0.553 to 0.849) for those with intestinal-type IPMNs; 0.839 (95% CI 0.684 to 1.000) and 0.734 (95% CI 0.526 to 1.000) for those with oncocytic-type IPMNs; and 0.520 (95% CI 0.298 to 0.909) and undetermined for those with pancreatobiliary-type IPMNs. Analysis by the Cox proportional hazards model comparing prognostic risks determined by stage and the morphological and macroscopic types indicated that staging was the most significant predictor of survival (p=3.68×10−8) followed by the morphological type (p=0.0435). Furthermore, the morphological type remained a significant predictor in a subcohort of invasive cases (p=0.0089). Conclusion In this multicentre retrospective analysis, the morphological type of IPMN appears to be an independent predictor of patient prognosis.
Polycyclic aromatic hydrocarbon exposure in oesophageal tissue and risk of oesophageal squamous cell carcinoma in north-eastern Iran

Objective To evaluate the association between polycyclic aromatic hydrocarbon (PAH) exposure in oesophageal epithelial tissue and oesophageal squamous cell carcinoma (ESCC) case status in an ESCC case–control study in a high-risk population in north-eastern Iran. Methods Tissue microarrays (TMAs) of non-tumoral oesophageal biopsies from patients with biopsy-proven ESCC and gastrointestinal clinic patients with no endoscopic or biopsy evidence of ESCC (control subjects) in a rural region in north-eastern Iran were immunohistochemically stained. Immunohistochemistry was performed using monoclonal antibodies 8E11 and 5D11 raised against benzo[a]pyrene (B[a]P) diol epoxide (BPDE)-I-modified guanosine and BPDE-I-modified DNA, respectively. Staining intensity was quantified by image analysis and the average staining in three replicates was calculated. The main outcome measure was adjusted ORs with 95% CIs for the association between antibody staining intensity and ESCC case status. Results Cultured ESCC cells exposed to B[a]P in vitro showed dose-dependent staining with 8E11 but not with 5D11. With 8E11, sufficient epithelial tissue was available in the TMA cores to analyse 91 cases and 103 controls. Compared with the lowest quintile of 8E11 staining in the controls, adjusted ORs for the 2nd to 5th quintiles were 2.42, 5.77, 11.3 and 26.6 (95% CI 5.21 to 135), respectively (p for trend <0.001). With 5D11, 89 cases and 101 controls were analysed. No association between staining and case status was observed (ORs for the 2nd to 5th quintiles were 1.26, 0.88, 1.06 and 1.63 (95% CI 0.63 to 4.21), p for trend=0.40). Conclusions Dramatically higher levels of 8E11 staining were observed in non-tumoral oesophageal epithelium from patients with ESCC than from control subjects. This finding strengthens the evidence for a causal role for PAHs in oesophageal carcinogenesis in north-eastern Iran.
Pathophysiological relevance of apical large-conductance Ca2+-activated potassium channels in pancreatic duct epithelial cells

Background Acute pancreatitis is among the few inflammatory diseases for which no specific pharmacological treatment is available. It has previously been shown that bile acids alter pancreatic ductal secretion and these effects are probably involved in the pathogenesis of bile-induced pancreatitis. Objective To understand the mechanism responsible for bile-induced hypersecretion and, in particular, to identify the molecular target for bile acids in native pancreatic duct epithelial cells (PDECs). Methods Patch clamp recordings and spectrofluorimetry were used to measure whole cell currents and rates of HCO3− secretion, respectively, from isolated guinea pig pancreatic ducts. Expression of ion channels and receptors was investigated by immunohistochemistry/immunofluorescence of intact pancreatic tissue. Results Exposing PDECs to chenodeoxycholate (CDC, 100 μM) reversibly increased whole cell K+ currents and hyperpolarised cell membrane potential. Bile acid-stimulated K+ currents were inhibited by Ba2+ (2 mM), iberiotoxin (100 nM), and suppressed by strong intracellular Ca2+ buffering. Luminally applied iberiotoxin also blocked CDC-stimulated HCO3− secretion from microperfused ducts; however, the inhibitor did not influence the stimulatory effect of secretin, carbachol or luminally applied ATP. The specific large-conductance Ca2+-activated potassium (BK) channel activator, NS11021, induced a similar increase in HCO3− secretion to CDC. Immunohistochemical analysis showed strong BK channel protein expression on the apical membrane of PDECs, while the G-protein-coupled bile acid receptor-1 was not detected in PDECs, but was present in acinar cells. Conclusion It was shown for the first time that BK channels (i) are expressed at the apical membrane of guinea pig PDECs; (ii) have a crucial role in regulating HCO3− secretion and (iii) are also essential for the bile acid-induced hypersecretion and, therefore, underlie the response of the pancreas to this noxious agent.
Acute-on-chronic liver failure: an early biopsy is essential?

In patients with cirrhosis, an innocent precipitating event can often lead to acute clinical deterioration which culminates in multiple organ failure and very high rates of mortality, a condition referred to as acute-on-chronic liver failure (ACLF). 1 The definition, natural history and the pathophysiological basis of this condition is being intensely discussed and studied by numerous groups across the world and has led to the development of the Asian, European and American study groups to try and answer the many questions that this intriguing condition raises. The paper by Katoonizadeh et al 2 explores the important question of the histological characteristics of this syndrome ( see page 1561 ). In order to limit the heterogeneity, the authors appropriately limited their observations to patients with alcoholic liver disease. They included two groups of patients: an ACLF group comprising patients with underlying alcoholic cirrhosis who, within a short period of 4–8 weeks, developed end-organ dysfunction following a precipitating event; these patients were biopsied within 48–72 h of admission. The second group they studied were patients with chronic decompensated cirrhosis (CHD) who underwent liver biopsy as part of assessment for liver transplantation. The study group included 102 eligible patients (54 with ACLF and 48 with CHD). The data confirm that mortality of patients with ACLF is extremely high, with an in-hospital mortality of 46% compared with 10% for patients with CHD. The presence of clinical indicators of systemic inflammatory …
Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma

Background and aims Golgi protein 73 (GP73) as a potential serum marker for hepatocellular carcinoma (HCC) has not been validated in large cohort studies. Furthermore, its significance in the assessment of tumour recurrence after HCC resection remains unknown. The aim of this study was to determine the value of serum GP73 in the diagnosis of HCC. Methods Serum GP73 and alpha-fetoprotein (AFP) were compared in a total of 4217 human subjects in this multicentre study, including 1690 healthy adults, 337 hepatitis B virus (HBV) carriers, 512 patients with cirrhosis, 789 patients with HCC, 61 patients with other malignant liver lesions, 206 patients with benign liver lesions and 622 patients with 14 different kinds of non-liver cancers. The main outcome measures were the specificity and sensitivity of GP73 in patients at risk for the development of HCC. Results Using 8.5 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 74.6% (95% CI 71.5% to 77.6%) and 97.4% (95% CI 96.8 to 98.3%), compared with 58.2% (95% CI 55.2% to 62.1%) and 85.3% (95% CI 83.4% to 88.1%) for AFP (p<0.001) using 35 ng/ml as a cut-off value. The GP73 level was significantly increased in patients with HCC compared with healthy controls (14.7 vs 1.2, p<0.001). Although GP73 levels in HBV carriers (2.9) and patients with cirrhosis (4.7) were somewhat elevated, they were much lower than that in patients with HCC (p<0.001). GP73 decreased following surgical resection of HCC lesions and increased with tumour recurrence. Fourteen types of non-liver cancers were analysed; all the benign and other malignant liver lesions had moderate elevations of GP73, albeit at a much lower level than in HCC. Conclusions GP73 is an accurate serum marker for the detection of HCC and its recurrence after surgery, with higher sensitivity and specificity than AFP. Clinical implementation of serum GP73 measurement as a standard test for HCC is recommended.
Colorectal cancer screening: Will global warming affect the accuracy of FIT testing?

Colorectal cancer screening with tests that identify occult blood in faeces are currently the cornerstone of the screening programmes in most developed countries.1 The first generation of this class of tests has been proven in several randomised controlled trials to significantly reduce mortality from colorectal cancer when performed every 1–2 years after the age of 50 years.2–5 It has further been shown to be associated with reduced incidence of colorectal cancer, presumably due to additional detection of premalignant lesions.6 However, the old school of faecal occult blood tests (FOBTs), even though proven effective, suffers from less than optimal sensitivity and leaves much to be desired in terms of improved detection qualities. Newer faecal-based tests can be divided into three groups: (1) guaiac tests of higher sensitivity, such as Hemoccult Sensa; (2) high-sensitivity immunological tests and (3) stool-based genetic tests.7 8 Of these, the genetic tests are still at relatively early stages of development and scientifically are not ready yet for prime-time use, in spite of some recent suggestions in this direction.9–11 Both newer techniques of the detection of faecal occult blood, sensitive guaiac and immunological tests, have been demonstrated in several studies to have a sensitivity rate which is at least twice higher than the old generation tests …
Vitreous microRNA levels as diagnostic biomarkers for vitreoretinal lymphoma.

To the editor: Primary vitreoretinal lymphoma (PVRL) is often associated with primary central nervous system lymphoma (PCNSL) and is a rare high-grade diffuse large-cell B-cell lymphoma occurring within the vitreous and/or retina. [1][1][⇓][2]-[3][3] Overlapping clinical signs observed in PVRL
Optimal treatment of metastatic pancreatic cancer

Approximately 60% of patients with pancreatic cancer have metastatic disease at the time of diagnosis.1 Gemcitabine, which has been shown to improve overall survival (OS) and clinical response compared with 5-fluorouracil (5-FU), is standard treatment with a median survival of 6 months and a 1 year survival rate of only 20%. 2 The addition of other drugs to gemcitabine to improve outcome has been generally unsuccessful with the exception of erlotinib, an oral human epidermal growth factor 1 receptor/epidermal growth factor receptor ( HER1/EGFR ) tyrosine kinase inhibitor. The combination of erlotinib with gemcitabine resulted in an improved 1 year survival compared with gemcitabine alone (23% vs 17%, p=0.023). 3 Data from a phase III trial evaluating gemcitabine with capecitabine (GEM-CAP) showed an improvement in response and progression-free survival with GEM-CAP over single-agent gemcitabine, and pooling of these results with two other randomised controlled trials in a meta-analysis resulted in a survival advantage with GEM-CAP.4 At this year's American Society of Clinical Oncology annual meeting, the interim analysis from the randomised phase III PRODIGE 4/ACCORD 11 trial comparing FOLFIRINOX (5-FU/leucovorin, irinotecan and oxaliplatin) with gemcitabine as first-line treatment for fit patients with metastatic pancreatic adenocarcinoma was presented.5 These preliminary results were encouraging, with a significantly longer OS, progression-free survival and improved response rate associated with the experimental arm compared with gemcitabine alone. Although …
Financial challenges and complexity in the management of an intensive care/coronary care unit: a case study

This case study, written by the manager of an intensive/coronary care unit of an Ontario hospital, demonstrates the difficulties faced by health care managers in controlling costs and dealing with complexity in the current health care and hospital environment. The case describes actions taken to reduce staffing expenditures in an intensive care unit through a rearrangement of nursing duties and the introduction of a different level of nursing staff to take over some of the nursing duties previously carried out by registered nurses. Although the actions were unsuccessful, the careful documentation and analysis of the results of the actions brings to the fore the multi‐faceted nature of the problems faced by hospitals in managing their costs and at the same time meeting their medical mandate. Concludes by pointing to the ongoing nature of the cost problem as nursing professionals are caught in the squeeze between providing the service they are trained for, and their need for appropriate compensation under conditions of increasing work pressure.
Handoffs During Nursing Shift Changes in Acute Care

Handoffs during the nursing shift change were directly observed on two acute care wards each of a private and public hospital, for a total of 236 patient updates by 49 nurses during 14 shift changes. Data from the three wards which conducted audio-taped updates were transcribed. The transcriptions and field notes were analyzed for the existence and frequency of 21 strategies used in high reliability organizations. In addition, we iteratively categorized the interruptions, questions, and statements made during the updates. Finally, we iteratively categorized stances towards decisions communicated during the updates. Implications of the findings are discussed.
Telomere length and angiogenic cytokines in knee osteoarthritis

Dear Editor, The publication on ‘Telomere length and angiogenic cytokines in knee osteoarthritis (OA)’ from Thailand is very interesting. Poonpet et al. concluded that “Telomere length was shortened in knee OA patients compared to healthy controls. Plasma HGF [hepatocyte growth factor], VEGF [vascular endothelial growth factor] and G-CSF [granulocyte colony stimulating factor] were negatively correlated with leukocyte RTL [relative telemore length], suggesting involvement of telomere shortening and these cytokines in knee OA’. The important concern is on the possible confounding factor that might affect the observation on leukocyte telomere length. In Thailand, there is a common genetic inherited disease, b-thalassemia/HbE. The prevalence of this genetic disorder is very high and it has also been reported regarding the ‘accelerated telomere shortening’ in this population. Hence, the observation by Poonpet et al. cannot be validated without control of the possible confounding common genetic disorder.