Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis.

Background: Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. Methods: DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein-protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Results: Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. Conclusion: ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.

Will Proton Pump Inhibitors Increase the Risk of Diabetes Mellitus? A Systemic Review and Meta-Analysis.

BACKGROUND: Proton pump inhibitor use was reported to potentially provide benefits to prevent diabetes mellitus. This study aims to investigate the association between proton pump inhibitor use and the risk of developing diabetes mellitus. METHODS: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42021238481). A systematic literature search was conducted to identify eligible studies up to February 2021. Quality assessment was conducted according to Jadad Scoring Scale and Newcastle-Ottawa Scale. The heterogeneity among studies was tested and estimated by Q test and I2. Pooled hazard ratio with 95% CI was calculated using the random-effects or fixed-effects model depending on the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also performed. RESULTS: Eight studies including 850 019 participants were included. We found that proton pump inhibitor use was associated with a statistically non-significant increased risk of diabetes mellitus (pooled hazard ratio was 1.06, 95% CI = 0.89-1.28, P = .50). In subgroup analysis, 5 studies conducted in North America confirmed the overall result; however, one study conducted in Europe demonstrated a statistically significant increased risk, while one study in Asia revealed a statistically significant decreased risk. CONCLUSION: Proton pump inhibitor use is not associated with either increased or decreased risk of diabetes mellitus. However, more well- designed studies focusing on proton pump inhibitor use and the risk of diabetes mellitus, especially among populations with different backgrounds, are still needed.

Diagnostic Value, Prognostic Value, and Immune Infiltration of LOX Family Members in Liver Cancer: Bioinformatic Analysis.

Background: Liver cancer (LC) is well known for its prevalence as well as its poor prognosis. The aberrant expression of lysyl oxidase (LOX) family is associated with liver cancer, but their function and prognostic value in LC remain largely unclear. This study aimed to explore the function and prognostic value of LOX family in LC through bioinformatics analysis and meta-analysis. Results: The expression levels of all LOX family members were significantly increased in LC. Area under the receiver operating characteristic curve (AUC) of LOXL2 was 0.946 with positive predictive value (PPV) of 0.994. LOX and LOXL3 were correlated with worse prognosis. Meta-analysis also validated effect of LOX on prognosis. Nomogram of these two genes and other predictors was also plotted. There was insufficient data from original studies to conduct meta-analysis on LOXL3. The functions of LOX family members in LC were mostly involved in extracellular and functions and structures. The expressions of LOX family members strongly correlated with various immune infiltrating cells and immunomodulators in LC. Conclusions: For LC patients, LOXL2 may be a potential diagnostic biomarker, while LOX and LOXL3 have potential prognostic and therapeutic values. Positive correlation between LOX family and infiltration of various immune cells and immunomodulators suggests the need for exploration of their roles in the tumor microenvironment and for potential immunotherapeutic to target LOX family proteins.

Does Proton Pump Inhibitor Use Lead to a Higher Risk of Coronavirus Disease 2019 Infection and Progression to Severe Disease? a Meta-analysis.

The findings of previous research on the association between proton pump inhibitor (PPI) use and the treatment and prevention of coronavirus disease 2019 (COVID-19) are inconsistent. Therefore, this meta-analysis was conducted to clarify the outcomes of patients taking PPIs. This analysis included 14 articles with more than 268,683 subjects. PPI use was not associated with increased or decreased risk of COVID-19 infection (odds ratio [OR] 1.64, 95% confidence interval [CI] = 0.54-5.00, P = 0.39) or mortality (OR = 1.91, 95% CI = 0.86-4.24, P = 0.11). However, PPI use increased the risks of severe disease (OR 1.67, 95% CI = 1.37-2.02, P < 0.00001) and secondary infection (OR 4.62, 95% CI = 2.55-8.39, P < 0.00001). In summary, PPI use was not associated with an increased risk of infection and mortality in COVID-19 but appeared to be associated with an increased risk of progression to severe disease and secondary infection. However, more original studies are urgently needed to further clarify the relationship between PPI use and COVID-19.

Is metformin use associated with a reduced risk of oesophageal cancer? A systematic review and meta-analysis.

OBJECTIVES: Studies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC. METHODS: A comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed. RESULTS: Seven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable. CONCLUSION: Metformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations. PROSPERO REGISTRATION NUMBER: CRD42021237127.

Is endoscopic retrograde appendicitis therapy a better modality for acute uncomplicated appendicitis? A systematic review and meta-analysis.

BACKGROUND: Previous studies had shown endoscopic retrograde appendicitis therapy (ERAT) is an effective treatment for acute appendicitis. However, different studies reported conflicting outcomes regarding the effectiveness of ERAT in comparison with laparoscopic appendectomy (LA). AIM: To compare the effectiveness of ERAT with LA. METHODS: Randomized controlled trials (RCTs) and retrospective studies of ERAT for acute uncomplicated appendicitis were searched in PubMed, Cochrane Library, Web of Science, Embase database, China National Knowledge Infrastructure (CNKI), the WanFang Database, and Chinese Scientific Journals Database (VIP) from the establishment date to March 1 2021. Heterogeneity was assessed using the I-squared statistic. Pooled odds ratios (OR), weighted mean difference (WMD), and standard mean difference (SMD), with 95% confidence intervals (CI) were calculated through either fixed-effects or random-effects model. Sensitivity analysis was also performed. Publication bias was tested by Egger's test, and Begg's test. The quality of included RCT were evaluated by the Jadad scale, while Newcastle-Ottawa scale is adopted for assessing the methodological quality of case-control studies. All statistical analysis was performed using Stata 15.1 statistical software. All statistical analysis was performed using Stata 15.1 statistical software. This study is registered with PROSPERO, CRD42021243955. RESULTS: After screening, 10 RCTs and 2 case-control studies were included in the current systematic review. Firstly, the length of hospitalizations [WMD = -1.15, 95%CI: -1.99, -0.31; P = 0.007] was shorter than LA group. Secondly, the level of post-operative CRP [WMD = -10.06, 95%CI: (-17.39, -2.73); P = 0.007], TNF-α [WMD = -7.70, 95%CI: (-8.47, -6.93); P < 0.001], and IL-6 Levels [WMD = -9.78, 95%CI: (-10.69, -8.88); P < 0.001; P < 0.001] in ERAT group was significantly lower than LA group. Thirdly, ERAT group had a lower incidence of intestinal obstruction than LA group. [OR = 0.19, 95%CI: (0.05, 0.79); P = 0.020]. Moreover, the quality of 10 RCTs were low with 0-3 Jadad scores, while the methodological quality of two case-control studies were fair with a score of 2 (each). CONCLUSION: Compared with LA, ERAT reduces operation time, the level of postoperative inflammation, and results in fewer complications and shorter recovery time, with preserving the appendix and its immune and biological functions.

An unusual presentation of acute deep vein thrombosis after the Moderna COVID-19 vaccine-a case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic of the multisystem disease coronavirus disease-2019 (COVID-19). Since the development of COVID-19 vaccines, there has been extensive monitoring for potential serious side effects. We report an unusual presentation of acute deep vein thrombosis (DVT) in the right upper extremity of a 27-year-old Caucasian female, 3 days after receipt of her second dose of the Moderna COVID-19 vaccine. Her relevant thrombophilia workup was negative on initial presentation. She was treated with rivaroxaban for 3 months and her symptoms of right upper extremity swelling, and pain improved. Considering our case did not have any evidence of thrombocytopenia, we discuss the possible pathophysiology of acute DVT following Moderna COVID-19 vaccine in contrast to adenoviral vector COVID-19 vaccines (ChAdOx1 nCoV-19 and Ad26.COV2.S), including mRNA COVID-19 vaccine binding to pattern recognition receptors (PRR) in the endosomes and cytosol leading to a pro inflammatory cascade and coagulopathy. We highlight the importance of initial workup for acute DVT post COVID-19 vaccination, that should include complete blood count (CBC) with platelet count, international normalized ratio (INR), prothrombin time (PTT), D-dimer levels, fibrinogen levels, platelet factor 4 (PF4)/heparin enzyme-linked immunosorbent assays (ELISA) followed by a confirmatory PF4 platelet activation assay such as serotonin release assay, P-selectin expression assay, or heparin induced platelet aggregation (HIPA) assay, and imaging for thrombosis.

Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer.

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.

Does Famotidine Reduce the Risk of Progression to Severe Disease, Death, and Intubation for COVID-19 Patients? A Systemic Review and Meta-Analysis.

BACKGROUND: Famotidine was reported to potentially provide benefits to Coronavirus Disease 2019 (COVID-19) patients. However, it remains controversial whether it is effective in treating COVID-19. AIMS: This study aimed to explore whether famotidine use is associated with reduced risk of the severity, death, and intubation for COVID-19 patients. METHODS: This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42020213536). A comprehensive search was performed to identify relevant studies up to October 2020. I-squared statistic and Q-test were utilized to assess the heterogeneity. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated through the random effects or fixed effects model according to the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also conducted. RESULTS: Five studies including 36,635 subjects were included. We found that famotidine use was associated with a statistically non-significant reduced risk of progression to severe disease, death, and intubation for Coronavirus Disease 2019 (COVID-19) patients (pooled RR was 0.82, 95% CI = 0.52-1.30, P = 0.40). CONCLUSION: Famotidine has no significant protective effect in reducing the risk of developing serious illness, death, and intubation for COVID-19 patients. More original studies are needed to further clarify whether it is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

Does aspirin reduce the incidence, recurrence, and mortality of colorectal cancer? A meta-analysis of randomized clinical trials.

BACKGROUND: Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of all cancer deaths in the USA. Some evidences are shown that aspirin can reduce the morbidity and mortality of different cancers, including CRC. Aspirin has become a new focus of cancer prevention and treatment research so far; clinical studies, however, found conflicting conclusions of its anti-cancer characteristics. This study is to summarize the latest evidence of correlation between aspirin use and CRC and/or colorectal adenomas. METHODS: Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. The pooled relative risk (RR) with 95% confidence interval (CI) was used to estimate the effect of aspirin on colorectal cancer and/or colorectal adenomas. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: The result showed that aspirin use was not associated with incidence of CRC (RR 0.97; 95% CI 0.84-1.12; P = 0.66; I2 = 34%), aspirin use was found to be associated with reduced recurrence of colorectal adenomas (RR 0.83; 95% CI 0.72-0.95; P = 0.006; I2 = 63%) and reduced mortality of CRC (RR 0.79; 95% CI 0.64-0.97; P = 0.02; I2 = 14%). Subgroup analysis found a statistically significant association in low dose with a pooled RR of 0.85 (95% CI 0.74-0.99; P = 0.03; I2 = 31%). CONCLUSIONS: This meta-analysis of randomized controlled trial data indicates that aspirin reduces the overall risk of recurrence and mortality of CRC and/or colorectal adenomas. Incidence of CRC was also reduced with low-dose aspirin. The emerging evidence on aspirin's cancer protection role highlights an exciting time for cancer prevention through low-cost interventions. TRIAL REGISTRATION: Clinicaltrials.gov no: CRD42020208852; August 18, 2020; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020208852 ).

Is antibiotics use really associated with increased risk of colorectal cancer? An updated systematic review and meta-analysis of observational studies.

PURPOSE: The association between antibiotics and colorectal cancer (CRC) risk has drawn increasing attention but remains controversial. This study was performed to clarify the association. METHODS: A systematic review and meta-analysis was performed on seven electronic databases. The pooled odds ratios (OR) with a 95% confidence interval (CI) were calculated to estimate the association using the fixed-effects model or the random-effects model. RESULTS: Ten studies that contained 4,853,289 participants were included in our study. We found that antibiotics use was associated with a higher risk of CRC (OR 1.09, 95%CI 1.02-1.17, I2 = 92.8%). More than 60 days of antibiotics use and 5 prescriptions of antibiotics were significantly associated with a higher risk of CRC. Sub-analysis on different types of antibiotics found that anti-anaerobic antibiotics, penicillins, and quinolones use led to increased risk of CRC (OR 1.22, 95% CI 1.04-1.44, I2 = 89.1%; OR 1.09, 95% CI 1.04-1.13, I2 = 69.2%; OR 1.15, 95% CI 1.03-1.35, I2 = 88.2%; respectively) and colon cancer (OR 1.28, 95% CI 1.04-1.58, I2 = 98.5%; OR 1.09, 95% CI 1.05-1.12, I2 = 0; OR 1.09, 95% CI 1.04-1.15, I2 = 0; respectively). However, antibiotics use was not significantly associated with rectal cancer (OR 1.03, 95% CI 0.92-1.16, I2 = 77.6%). CONCLUSION: It needs attention that antibiotics use is associated with a higher risk of CRC, especially for colon cancer. Clinicians should be aware of the potential risk of CRC when prescribing anti-anaerobic antibiotics, penicillins, and quinolones in the future. Further studies are needed to assess any potential differences by tumor sites and class of antibiotics.

The Prevention and Management of Contrast-induced Acute Kidney Injury: A Mini-review of the Literature.

Contrast-induced acute kidney injury, also called contrast-induced nephropathy, is one of the main causes of acute renal failure/acute kidney injury (AKI) in hospitalized patients within 48 to 72 hours of contrast media administration during various radiologic procedures. Several factors can be responsible for contrast-induced acute tubular necrosis (ATN); however, patient and procedure-related factors play the lead role in determining the development of contrast-induced nephropathy. There is no definitive treatment and hydration remains the mainstay preventive strategy. This article will review the incidence, criteria for definitive diagnosis, and an effective approach on how to prevent contrast-induced nephropathy in a clinical setup.

Managing Chronic Pain in the Elderly: An Overview of the Recent Therapeutic Advancements.

A majority of the elderly suffer from chronic pain that significantly alters their daily activities and imposes an enormous burden on health care. Multiple comorbidities and the risk of polypharmacy in the elderly make it a challenge to determine the appropriate drug, dosage, and maintenance of therapy. Opioids are the most commonly used agents for this purpose in the elderly. The aim of this article is to discuss both the current well-established therapies used for managing chronic pain in the elderly and also the emerging newer therapies.

American Heart Association High Blood Pressure Protocol 2017: A Literature Review.

Hypertension is the most prevalent clinical symptom arising from various cardiovascular disorders. Likewise, it is considered a precursor or sequelae to the development of acute coronary artery disease and congestive heath failure (CHF). Hypertension has been considered a cardinal criterion to determine cardiovascular function. According to the World Health Organization (WHO) global observatory data, hypertension causes more than 7.5 million deaths a year, about 12.8% of the total human mortality. Similarly, the Center for Disease Control (CDC) states that 35% of the American adults have been estimated to have a persistently high blood pressure, which makes it about one in every three adults. Hypertension is a modifiable symptom that can be managed through pharmacological and non-pharmacological methods and standard protocols set forth by the American Heart Association (AHA). With new findings from various clinical trials related to the management of hypertension, new developments and recommendations have been made to update the previously established protocols for hypertension. This article aims to discuss and dissect the modern updates of hypertension management as comprehensively elaborated in the 2017 Hypertension Clinical Practice Guidelines.

Management of Orthostatic Hypotension: A Literature Review.

In the older population, especially the hospitalized patients who are prone to dehydration and hypovolemia, orthostatic hypotension (OH) presents as a debilitating disease. How different pharmacological and non-pharmacological interventions affect the incapacitating symptoms (falls and episodes of syncope), morbidity, and mortality related to OH has become a topic of debate. OH can predispose to ischemic heart disease (IHD). A non-pharmacological approach consisting of mobilization, early lifestyle changes, and therapeutic maneuvers is the first choice in the management of these patients. Individuals with persistent symptoms require pharmaceutical therapy to increase blood volume and peripheral vascular resistance. This article summarizes the management of OH that is vital to cope with the needs of the growing geriatric populations.