The Impact of KPNA2 on Prognosis of Colorectal Cancer Patients: A Meta-Analysis

Background and purpose: Colorectal cancer (CRC) is one of the most common malignant tumors with the highest mortality globally. At present, there is no exact biomarker to predict the prognosis and clinicopathological monitoring of CRC patients. Recent studies on the relationship of Karyopherin α 2 (KPNA2) expression and the prognosis of CRC has gradually become a hot spot while the results are still controversial. The aim of this study was to analyze and assess the prognostic role of KPNA2 in CRC patients. Methods: PubMed, Web of Science, Medline, EMBASE, CNKI, Wanfang, VIP, and Chinese Medical Database were systematically searched. The cohort study of high-level expression of KNPA2 and low-level expression of KPNA2 in CRC patients was included, the relevant data were extracted and the literature quality was evaluated. At the same time, the relationship between KPNA2 expression level and the overall survival (OS), the clinicopathological stage of CRC patients was studied. Meta-analysis was carried out by Stata MP 17.0 (Stata Corporation, College Station, TX, USA) software. Results: A total of 7 cohort studies involving 1166 patients were included. The analysis results showed that higher KPNA2 expression was significantly associated with higher tumor stage (OR=1.90, 95% CI 1.42–2.54), higher degree of tumor invasion (OR=2.14，95% CI 1.55-2.94), more lymph node metastasis (OR=2.20, 95% CI 1.68-2.88) and more distant metastasis (OR=3.66，95% CI 1.81-7.40). Moreover, higher KPNA2 expression was significantly associated with the shorter OS (HR=2.31, 95%CI 1.46-3.68).Conclusion: KPNA2 overexpression is an unfavorable prognostic factor for CRC patients. It could serve as a prognostic biomarker and as a potential therapeutic target for CRC.

Optic Nerve Ultrasound Evaluation in Animals and Normal Subjects

In recent years, ultrasonographic measurement of the optic nerve sheath diameter (ONSD) has been widely used to identify the presence of increased intracranial pressure (ICP). Intracranial hypertension is a life-threatening condition that can be caused by various neurological and non-neurological disorders, and it is associated to poor clinical results. Ultrasonography could be used to qualitatively and efficiently detect ICP increases, but to reach this purpose, clear cut-off values are mandatory. The aim of this review is to provide a wide overview of the most important scientific publications on optic nerve ultrasound normal values assessment published in the last 30 years. A total of 42 articles selected from PubMed medical database was included in this review. Our analysis showed that ocular ultrasonography is considered to be a valuable diagnostic tool, especially when intracranial hypertension is suspected, but unfortunately this research provided conflicting results that could be due to the different ultrasound protocols. This is mainly caused by the use of B scan alone, which presents several limitations. The use of B-scan coupled with the standardized A-scan approach could give more accurate, and reliable ultrasound evaluation, assuring higher data objectivity.

The Use of Prophylaxis Antibiotics to Prevent Acute Pancreatitis Complications: Meta-Analysis of Clinical Trials

Background: Acute pancreatitis (AP) is an inflammation of the pancreas, a serious emergency with no definitive treatment. It may progress to infected necrosis, non-pancreatitis infection, also death that may occur within the first 1 to 2 weeks. The use of prophylactic antibiotics in AP to prevent complications remains a controversy. The objective of this meta-analysis is to assess the benefit of prophylaxis antibiotics administration to prevent the complication.Method: Trials were identified by searching the medical database. Literature range is within the year 1975 to 2021. Review Manager 5.4.1 was used to analyse data extraction and risk of bias of included studies were elaborated. Risk ratio (RR) was calculated with 95% confidence interval (CI). P 0.05 was considered significant.Results: Twenty trials with a total of 1.287 patients of AP were analysed; 646 patients treated with antibiotic prophylaxis and 641 patients treated with placebo. Prophylaxis antibiotics were found to have significant difference between the two groups. The administration of prophylaxis antibiotics lower the risk of non-pancreatic infections (RR = 0.77; 95% CI: 0.62–0.95; p 0.05) and infected pancreatic necrosis (RR = 0.74; 95% CI: 0.58-0.94; p 0.05). Meanwhile, prophylaxis antibiotics were found to be insignificant to lower the risk of mortality (RR = 0.75; 95% CI: 0.54-1.03; p 0.05). Conclusion: Prophylaxis antibiotics lower the risk of non-pancreatic infections and infected pancreatic necrosis, but did not lower the risk of mortality.

Barriers to Prescribing Oral Anticoagulants To Inpatients Aged 80 Years and Older With Nonvalvular Atrial Fibrillation: A Cross-Sectional Study

Background: To investigate the temporal trend of prevalence of anticoagulation treatment and explore the factors associated with under prescription of oral anti-coagulants (OACs) among inpatients aged ≥80 years with nonvalvular atrial fibrillation (NVAF). Methods: We retrospectively reviewed the medical records of inpatients with a discharge diagnosis of NVAF from a medical database. We used the Pearson chi-square or Fisher’s exact test to compare categorical variables between patients with and without OACs prescription. Logistic regression analysis was used to assess the association between risk factors and under prescription of OACs. Results: A total of 4375 patients aged ≥80 years with AF were assessed in the largest academic hospital in China from August 1, 2016, to July 31, 2020, 3165 NVAF patients were included. The prevalence of OACs use was 20.9% in 2017, 28.7% in 2018, 35.6% in 2019, and 43.9% in 2020. Of all participants with CHA2DS2-VASc≥2, 1,027 (32.4%) were prescribed OACs; 33.7% and 31.8% of patients with and without prior stroke received OACs, respectively. Age, clinical department where patients were discharged, use of antiplatelets, and history of stroke and dementia were significantly associated with not prescribing OACs. Conclusions: The prevalence of OACs use increased over the past several years. The rate of prescription of OACs was lower among NVAF patients who were older, prescribed antiplatelets, discharged from non-departmental cardiology, and suffered from comorbidities. This study found the iatrogenic factors affecting the use of OACs in the inpatients aged ≥80 years, providing clues and basis for the standardized use of OACs in the inpatients.

Serum Creatinine Reference Limits in Pediatric Population—A Single Center Electronic Health Record-Based Database in Taiwan

Objective: To assess age- and sex-specific serum creatinine levels in a pediatric population using a hospital-based database in Taiwan.Study Design: Data on serum creatinine levels were obtained from the National Taiwan University Hospital-integrated Medical Database (NTUH-iMD). Due to the possibility of having acute kidney injury or chronic kidney disease, individuals with multiple serum creatinine measurements were excluded, and outliers in each age- and sex-specific group were also subsequently removed. The remaining creatinine measurements in each group were analyzed, and 95% reference limits were established.Results: Serum creatinine data of individuals aged between 1 month and 18 years from May 2011 to January 2018 were retrieved. After applying the exclusion criteria, 27,911 individuals with a single corresponding serum creatinine measurement were enrolled. Creatinine level reference limits for each age- and sex-specific group were generated. The upper reference limits (URLs), which are particularly useful in clinical practice, followed the natural trend of increasing serum creatinine with age.Conclusion: We generated serum creatinine reference limits from a single hospital-integrated medical database in Taiwan for different age- and sex-specific groups of children. Our results will aid physicians in clinical practice regarding renal function evaluation, especially for patients without a recent baseline serum creatinine level.

Protective Effect of Melatonin Administration against SARS-CoV-2 Infection: A Systematic Review

Introduction: according to the World Health Organization (WHO), COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, responsible for an increasing number of cases and deaths. From a preventive and therapeutic point of view, there are two concerns that affect institutions and healthcare professionals: global immunization (which is still far from being achieved) and the availability of drugs capable of preventing its consequences in the infected patient. In this sense, the role that melatonin can play is has been assessed in the recent literature. Justification and Objectives: the serious health, social and economic consequences of COVID-19 have forced an urgent search for preventive methods, such as vaccines, among others, and therapeutic methods that could be alternatives to the drugs currently used. In this sense, it must be accepted that one of the most recommended has been the administration of melatonin. The present study proposes to carry out a systematic review of its possible role in the treatment and/or prevention of COVID-19. Material and methods: a systematic review of the literature related to the prevention of COVID-19 through the administration of melatonin was carried out, following the sequence proposed by the Prisma Declaration regarding the identification and selection of documents, using the specialized health databases Trip Medical Database, Cochrane Library, PubMed, Medline Plus, BVS, Cuiden and generic databases such as Dialnet, Web of Science and Google Scholar for their retrieval. Appropriate inclusion and exclusion criteria are described for the articles assessed. The main limitation of the study has been the scarcity of works and the lack of defining a specific protocol in terms of dosage and administration schedule. Results: once the selection process was completed, and after an in-depth critical analysis, 197 papers were selected, and 40 of them were finally used. The most relevant results were: (1) melatonin prevents SARS-CoV-2 infection, (2) although much remains to be clarified, at high doses, it seems to have a coadjuvant therapeutic effect in the treatment of SARS-CoV-2 infection and (3) melatonin is effective against SARS-CoV-2 infection. Discussion: until group immunization is achieved in the population, it seems clear that we must continue to treat patients with SARS-CoV-2 infection, and, in the absence of a specific and effective antiviral therapy, it is advisable to continue researching and providing drugs that demonstrate validity based on the scientific evidence. In this regard, we believe that the available studies recommend the administration of melatonin for its anti-inflammatory, antioxidant, immunomodulatory, sleep-inducing, CD147, Mpro, p65 and MMP9 protein suppressing, nephrotoxicity-reducing and highly effective and safe effects. Conclusions: (1) melatonin has anti-inflammatory, antioxidant, immunomodulatory, and Mpro and MMP9 protein-inhibitory activity. (2) It has been shown to have a wide margin of safety. (3) The contributions reviewed make it an effective therapeutic alternative in the treatment of SARS-CoV-2 infection. (4) Further clinical trials are recommended to clearly define the administration protocol.

Prognostic Performance of Alternative Lymph Node Classification Systems for Patients with Medullary Thyroid Cancer: A Single Center Cohort Study

Background Lymph node ratio (LNR) and the log odds of positive lymph nodes (LODDS) have been proposed as alternative lymph node (LN) classification schemes. Various cut-off values have been defined for each system, with the question of the most appropriate for patients with medullary thyroid cancer (MTC) still remaining open. We aimed to retrospectively compare the predictive impact of different LN classification systems and to define the most appropriate set of cut-off values regarding accurate evaluation of overall survival (OS) in patients with MTC. Methods 182 patients with MTC who were operated on between 1985 and 2018 were extracted from our medical database. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 28 LNR and 28 LODDS classifications and compare them with the N category according to the 8th edition of the AJCC/UICC TNM classification in terms of discriminative power. Regression models were adjusted for age, sex, T category, focality, and genetic predisposition. Results High LNR and LODDS are associated with advanced T categories, distant metastasis, sporadic disease, and male gender. In addition, among 56 alternative LN classifications, only one LNR and one LODDS classification were independently associated with OS, regardless of the presence of metastatic disease. The C-statistic demonstrated comparable results for all classification systems showing no clear superiority over the N category. Conclusion Two distinct alternative LN classification systems demonstrated a better prognostic performance in MTC patients than the N category. However, larger scale studies are needed to further verify our findings.

PP152 Epigenetic In Vitro Diagnostic Test For Early Diagnosis In Lung Cancer: An Early Assessment

IntroductionLung cancer is a leading cause of morbidity and mortality, and early diagnosis is essential for patient survival. Epigenetics is an innovative discipline that provides biomarkers to aid in early diagnosis, patient risk classification, or outcome prediction. Each type of tumor may present specific patterns of gene methylation, the analysis of which may be useful as a diagnostic tool. The aim of this study was to conduct an early assessment of novel in vitro diagnostic (IVD) tests based on the identification of DNA hypermethylation epigenetic signatures developed for the early detection of lung cancer.MethodsWe identified this technology through the Early Awareness and Alert System “SINTESIS-new technologies” of the Agencia de Evaluación de Tecnologías Sanitarias - Instituto de Salud Carlos III. A literature search of PubMed, the Trip Medical Database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials was conducted. Studies published up to November 2019 were reviewed.ResultsThree tests were identified. Epi proLung® analyzes the hypermethylation status of SHOX2/PTGER4 genes in blood samples using polymerase chain reaction (PCR) and showed good discrimination capacity with respect to healthy controls (area under the curve [AUC] = 0.91) and patients with non-malignant lung diseases (AUC = 0.86). The Epi proLung BL Reflex Assay® for determining the hypermethylation state of the SHOX2 gene in bronchoalveolar lavage samples by PCR had modest sensitivity (69%, 95% confidence interval [CI]: 64–75) and high specificity (96%, 95% CI: 97–100). A test in development for determining the hypermethylation state of BCAT1/CDO1/TRIM58/ZNF177 genes in aspirated or bronchoalveolar lavage samples by pyrosequencing yielded a sensitivity of 85 percent and a specificity of 81 percent, with an AUC of 0.91 at the optimal cutoff point.ConclusionsThe evidence for the three tests showed promising results in terms of diagnostic validity. However, although personalized medicine is becoming increasingly widespread in the field of cancer diagnosis, more studies are needed to evaluate the clinical utility of these diagnostic tests, either as a complementary or a screening test, and the economic impact of their use.

Association between SGLT2 Inhibitors vs DPP-4 Inhibitors and Risk of Pneumonia Among Patients with Type 2 Diabetes

Context Patients with diabetes are at a higher risk of pneumonia and pneumonia mortality. Sodium-glucose co-transporter 2 inhibitors (SGLT2is), the latest class of glucose-lowering agents, were shown to reduce the risk of pneumonia in clinical trials. However, the real-world effectiveness of SGLT2is on the risk of pneumonia is largely unknown. Objective To investigate the associations between SGLT2is use and the risk of pneumonia and pneumonia mortality compared to dipeptidyl peptidase-4 inhibitors (DPP4is) using an electronic medical database in Hong Kong. Design A retrospective cohort study. The “prevalent new-user” design was adopted to account for the previous exposure to the study drugs being compared. Propensity score (PS) matching (1:4) was used to balance the baseline characteristics of the two groups. Setting and participants Electronic health data of type 2 diabetes patients using SGLT2is and DPP4is between 2015 and 2018 was collected from the Clinical Data Analysis and Reporting System (CDARS). Main Outcome Measures Pneumonia incidence and mortality. Results The PS-matched cohort consisted of 6,664 users of SGLT2is and 26,656 users of DPP4is, with a mean follow-up of 3.8 years. Poisson regression showed that SGLT2is use was associated with lower risk of pneumonia compared to DPP4is with an absolute rate difference of 4.05 per 1000 person-years (95% CI: 2.61-5.51). The corresponding IRR was 0.71 (95% CI: 0.62-0.81). Similar reduction in risk of pneumonia death was observed (HR: 0.57; 95% CI: 0.42-0.77). Conclusion Compared to DPP4is, SGLT2is use was associated with a reduced risk of pneumonia and pneumonia mortality in a real-world setting.

Increased risk of stroke in patients with diffuse idiopathic skeletal hyperostosis: a nationwide population-based cohort study

Diffuse idiopathic skeletal hyperostosis (DISH) is frequently an incidental finding during X-ray examination. Although it has been shown to be associated with several chronic diseases, the hazard of cerebrovascular disease has seldom been explored. Our study aimed at determining the risk of stroke conferred by DISH, which is a retrospective cohort study adopting the largest medical database in Taiwan. Patients with a diagnosis of DISH at least three times from 2005 to 2010 were identified as the study group, and those in the control group were selected by matching age and gender. Patients were followed up until the end of 2015 to trace the incidence of stroke. Cox regression analysis was performed to compute the hazard ratio of stroke. Among the included 5300 patients, 1060 had a diagnosis of DISH. Significantly higher prevalence rates of stroke, hypertension, diabetes, and hyperlipidemia were noted in these patients. Overall, DISH conferred a 1.68 times higher risk of developing stroke. The significantly higher hazard ratio could be identified in both genders whether hypertension existed or not. Even in those without comorbidities, DISH still conferred a significantly higher risk of cerebrovascular disease in the future, which should never be ignored when encountered during clinical practice.