ABSTRACT
BackgroundThe Coronavirus disease 2019 (COVID-19) pandemic has had significant global impact. While public health interventions and universal health insurance has been credited with minimizing transmission rates in Canada relative to neighboring countries, significant morbidity and mortality have occurred nationwide. We sought to determine factors associated with differences in gastrointestinal outcomes in COVID-19 patients at a Canadian hospital. MethodsWe collected data from 192 hospital records of COVID-19 patients across seven Hamilton Health Sciences hospitals, a network of academic health centres serving one of the largest metropolitan areas in Canada. Statistical and correlative analysis of symptoms, comorbidities, and mortality were performed. ResultsThere were 192 patients. The mean age was 57.6 years (SD=21.0). For patients who died (n=27, 14%), mean age was 79.2 years old (SD=10.6) versus 54 years for survivors (SD=20.1). There was a higher mortality among patients with older age (p=0.000), long hospital stay (p=0.004), male patients (p=0.032), and patients in nursing homes (p=0.000). Patients with dyspnea (p=0.028) and hypertension (p=0.004) were more likely to have a poor outcome. Laboratory test values that were significant in determining outcomes were an elevated INR (p=0.007) and elevated creatinine (p=0.000). Cough and hypertension were the most common symptom and comorbidity, respectively. Diarrhea was the most prevalent (14.5%) gastrointestinal symptom. Impaired liver function was related to negative outcome (LR 5.6; p=0.018). ConclusionsIn a Canadian cohort, elevated liver enzymes, prolonged INR and elevated creatinine were associated with poor prognosis. Hypertension was also linked to a higher likelihood of negative outcome. SUMMARY BOXO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIThe prevalence of gastrointestinal symptoms in COVID-19 patients across Canada is lacking C_LIO_LIGastrointestinal manifestations of COVID-19 are well described, and longterm sequelae of gastrointestinal tract involvement are an ongoing concern C_LI What are the new findings?O_LIThere was a significant prevalence of gastrointestinal symptoms in patients with a confirmed diagnosis of COVID-19 at one of the largest metropolitan regions across Canada C_LIO_LILiver enzyme abnormalities were common in patients at diagnosis C_LIO_LIThis report, over an 8-month period, represents the largest cohort of COVID-19 patients reported in Canada C_LI How might these results impact on clinical practice in the foreseeable future?O_LIBaseline gastrointestinal symptoms and laboratory abnormalities correlate with patient outcome in Canadian COVID-19 patients C_LIO_LIThese results enhance our knowledge of the prevalence of gastrointestinal symptoms and laboratory abnormalities in Canadian patients and offer important baseline data for longitudinal studies in these patients C_LIO_LIOur findings increase our knowledge of the epidemiology of COVID-19 in Canada and allow future comparison with international data C_LI
ABSTRACT
Background/Aims@#To determine whether the expression of tight junction proteins (TJPs) differs depending on the subtype of functional dyspepsia (FD) and sex. @*Methods@#Control (n = 95) and FD (n = 165) groups based on Rome III criteria were prospectively enrolled. Gastric mucosal mRNA expression levels of various TJPs (claudins [CLDN] 1, 2, and 4; zonula occludens-1; occludin [OCLN]) were assessed by reverse transcription polymerase chain reaction. Western blot was performed to determine the levels of various TJPs. Helicobacter pylori infection status was evaluated by histology, rapid urease test, and culture. Questionnaires were analyzed. @*Results@#In all groups irrespective of H. pylori , FD group showed significantly higher CLDN2 mRNA levels than control group (P = 0.048). The level of CLDN4 mRNA expression was significantly lower in female FD group than in male FD group (P = 0.018). In H. pylori uninfected subjects, the level of CLDN1 mRNA expression in female FD group was significantly lower than that of male FD group (P = 0.014). The level of CLDN2 mRNA expression was significantly higher in the male postprandial distress syndrome (P = 0.001) and male epigastric pain syndrome (P = 0.023) groups than in the male control group. In Western blot analysis, the expression of OCLN was significantly elevated 48 hour after the culture with H. pylori strain 43504. @*Conclusions@#H. pylori can affect a variety of TJPs, particularly claudin-4 and occludin. Claudin-2 is thought to be involved in FD irrespective of H. pylori status, especially in the pathophysiology of male FD.
ABSTRACT
Cancer progression is governed by multifaceted interactions of cancer cells with their microenvironment and one of these ways is through secreted compounds. Substances released by gastric cancer cells have not being profiled in a proteome-wide manner. ITRAQ-based tandem mass spectrometry was employed to quantify proteins secreted by HFE145 normal, MKN7 well-differentiated, and MKN45 poorly differentiated gastric cancer cell lines. The expression levels of 237 proteins were found to be significantly different between normal and cancer cells. Further examination of 16 gastric cell lines and 115 clinical samples validated the up-regulation of CTSS expression in gastric cancer. Silencing CTSS expression suppressed the migration and invasion of gastric cancer cells in vitro. Subsequent secretomics revealed that CTSS silencing resulted in changes in expression levels of 197 proteins, one-third of which are implicated in cellular movement. Proteome-wide comparative secretomes of normal and gastric cancer cells were produced that constitute a useful resource for gastric cancer research. CTSS was demonstrated to play novel roles in gastric cancer cell migration and invasion, putatively via a network of proteins associated with cell migration, invasion, or metastasis. Cathepsin S is member of a large group of extracellular proteases, which are attractive drug targets. The implicated role of CTSS in gastric cancer metastasis provides an opportunity to test existing compounds against CTSS for adjuvant therapy and/or treatment of metastatic gastric cancers.
