Perioperative therapy in metastatic colorectal cancer: Pattern of use and survival outcomes.

BACKGROUND: Multimodality therapy of metastatic colorectal cancer (mCRC) is currently considered the standard of care. The aim of this study was to evaluate the impact of perioperative therapy on surgical resection in mCRC. METHODS: The National Cancer Database was analyzed for affected patients between 2004 and 2013. Univariate and multivariate analyses were done to identify factors associated with patient outcomes. Kaplan-Meier analysis and Cox proportional hazards models were used for the association between patient characteristics and survival. RESULTS: About 61,940 patients with mCRC were identified. Mean age = 63.4 years (SD ± 14). About 69% had a colon primary and 32% had only one metastatic site. Only 49% of those who underwent surgery for both primary and metastatic sites received postoperative chemotherapy (p < .001). Negative prognostic factors included no chemotherapy received (hazard ratio [HR], 2.32; 2.27-2.37; p < .001), more than three metastatic sites (HR, 2.28; 2.09-2.48; p < .001), year of diagnosis between 2004 and 2008 (HR, 1.71; 1.15-1.20; p < .001) and colon tumor location with right worse than left-sided (HR, 1.21; 1.19-1.24; p < .001). Five-year overall survival for resection of the primary and metastatic site (28.2%) was higher than for no surgical treatment (4.7%). CONCLUSION: Perioperative therapy was associated with improved survival, following resection of metastatic sites or primary tumor.

Mutant selection window of clarithromycin for clinical isolates of Helicobacter pylori.

BACKGROUND: Clarithromycin-resistance is becoming a global health concern in the treatment of Helicobacter pylori (H. pylori). The mutant prevention concentration (MPC) represent the propensities of antimicrobial agents to select resistant mutants. The concentration range between the minimum inhibitory concentration (MIC) and the MPC is defined as mutant selection window (MSW). In this study, we aimed to determine the cause of increasing clarithromycin resistance by investigating the MSW for clinical isolates of H. pylori. RESULTS: A retrospective subgroup, which included 68 clarithromycin-sensitive H. pylori strains, was selected from a double-blind trial. The MICs and MPCs were determined using agar plate assays. Genotypic tests were performed using Sanger sequencing. All isolates were wild-type, and 33.82% (23/68) had a 0.016 mg/L MIC, 45.59% (31/68) had a 0.031 mg/L MIC, 16.18% (11/68) had a 0.062 ≤ MIC ≤ 0.125 mg/L, and 4.41% (3/68) had a 0.25 mg/L MIC. The MPC50/90 (mg/L) of the isolates were: 0.062/0.125, 0.125/0.5, 0.25/0.25 and 1/2, respectively. The MPCs showed a moderate correlation with the MICs (rs = 0.65, P < 0.0001). Using published data and MPC90, we calculated the time inside the MSW (TMSW) for low- and high-dose (200 or 500 mg bid) clarithromycin that were 6 and 0 h, 24 and 4 h, 15 and 2 h, 5 and 17 h for the strains with MICs (mg/L) of 0.016, 0.031, 0.062-0.125, and 0.25, respectively. CONCLUSIONS: This study showed that in the clarithromycin-sensitive clinical isolates of H. pylori, low-dose clarithromycin may lead to decreased drug sensitivity or even clarithromycin resistance; strains with a 0.25 mg/L MIC display a high risk of treatment failure.

Pneumococcal Vaccination Lowers the Risk of Alzheimer's Disease: A Study Utilizing Data from the IBM® MarketScan® Database.

Previous studies demonstrated an association between influenza vaccination and the likelihood of developing Alzheimer's disease. This study was aimed at assessing whether pneumococcal vaccinations are associated with a lower risk of Alzheimer's disease based on analysis of data from the IBM® MarketScan® Database. Vaccinated and unvaccinated matched cohorts were generated using propensity-score matching with the greedy nearest-neighbor matching algorithm. The conditional logistic regression method was used to estimate the relationship between pneumococcal vaccination and the onset of Alzheimer's disease. There were 142,874 subjects who received the pneumococcal vaccine and 14,392 subjects who did not. The conditional logistic regression indicated that the people who received the pneumococcal vaccine had a significantly lower risk of developing Alzheimer's disease as compared to the people who did not receive any pneumococcal vaccine (OR=0.37; 95%CI: 0.33-0.42; P-value < .0001). Our findings demonstrated that the pneumococcal vaccine was associated with a 63% reduction in the risk of Alzheimer's disease among US adults aged 65 and older.

The Efficacy of Long-Term Hydroxychloroquine Use in the Prevention of COVID-19: A Retrospective Cohort Study.

The use of hydroxychloroquine (HCQ) in the prevention or treatment of COVID-19 remains controversial due to the insufficient supporting evidence and clinical studies indicating that it does not reduce COVID-19 mortality. Its potential protective effects against SARS-CoV-2 are still unclear. Big data resources, such as MarketScan database containing over 30 million insured participants annually, have not been used systematically to assess the association between long-term HCQ use and the risk of COVID-19. This retrospective study aimed to determine the protective effect of HCQ using the MarketScan database. We examined COVID-19 incidence from January to September 2020 among adult patients with systemic lupus erythematosus or rheumatoid arthritis who had received HCQ for at least 10 months in 2019 compared to those who did not. Propensity score matching was used to control for confounding variables and make the HCQ and non-HCQ groups comparable in this study. After matching at the ratio of 1:2, the analytical dataset comprised 13,932 patients who received HCQ for over 10 months and 27,754 HCQ-naïve patients. Multivariate logistic regression showed that long-term HCQ use was associated with a lower likelihood of COVID-19 in patients who had been receiving HCQ for over 10 months (OR=0.78, 95% CI: 0.69-0.88). These findings suggest that long-term HCQ use may provide protection against COVID-19.

Using Big Data to Uncover Association Between Sildenafil Use and Reduced Risk of Alzheimer's Disease.

Alzheimer's disease is a chronic neurodegenerative disease with multiple pathogenesis pathways. Sildenafil, one of the phosphodiesterase-5 inhibitors, was proven to have effective benefits in transgenic Alzheimer's disease mice. The purpose of the study was to investigate the relationship between sildenafil use and the risk of Alzheimer's disease based on the IBM® MarketScan® Database covering over 30 million employees and family members per year. Sildenafil and non-sildenafil-matched cohorts were generated using propensity-score matching with the greedy nearest-neighbor algorithm. The propensity score stratified univariate analysis and the Cox regression model showed that sildenafil use was significantly associated with a 60% risk reduction of developing Alzheimer's disease (HR=0.40; 95%CI:0.38-0.44; P<.0001) compared to the cohort of individuals who did not take sildenafil. Sex-stratified analyses revealed that sildenafil was related to a lower risk of Alzheimer's disease in subgroups of both males and females. Our findings demonstrated a significant association between sildenafil use and a lower risk of Alzheimer's disease.

Exercise Exertion Levels Prediction Based on Real-Time Wearable Physiological Signal Monitoring.

The real-time revolutions per minute (RPM) data, ECG signal, pulse rate, and oxygen saturation levels were collected during 16-minute cycling exercises. In parallel, ratings of perceived exertion (RPE) were collected each minute from the study participants. A 2-minute moving window, with one minute shift, was applied to each 16-minute exercise session to divide it into a total of fifteen 2-minute windows. Based on the self-reported RPE, each exercise window was labeled as "high exertion" or "low exertion" classes. The heart rate variability (HRV) characteristics in time and frequency domains were extracted from the collected ECG signals for each window. In addition, collected oxygen saturation levels, pulse rate, and RPMs were averaged for each window. The best predictive features were then selected using the minimum redundancy maximum relevance (mRMR) algorithm. Top selected features were then used to assess the accuracy of five ML classifiers to predict the level of exertion. The Naïve Bayes model demonstrated the best performance with an accuracy of 80% and an F1 score of 79%.

Exercise Exertion Level Prediction Using Data from Wearable Physiologic Monitors.

This study aims to develop machine learning (ML) algorithms to predict exercise exertion levels using physiological parameters collected from wearable devices. Real-time ECG, oxygen saturation, pulse rate, and revolutions per minute (RPM) data were collected at three intensity levels during a 16-minute cycling exercise. Parallel to this, throughout each exercise session, the study subjects' ratings of perceived exertion (RPE) were gathered once per minute. Each 16-minute exercise session was divided into a total of eight 2-minute windows. Each exercise window was labeled as "high exertion," or "low exertion" classes based on the self-reported RPEs. For each window, the gathered ECG data were used to derive the heart rate variability (HRV) features in the temporal and frequency domains. Additionally, each window's averaged RPMs, heart rate, and oxygen saturation levels were calculated to form all the predictive features. The minimum redundancy maximum relevance algorithm was used to choose the best predictive features. Top selected features were then used to assess the accuracy of ten ML classifiers to predict the next window's exertion level. The k-nearest neighbors (KNN) model showed the highest accuracy of 85.7% and the highest F1 score of 83%. An ensemble model showed the highest area under the curve (AUC) of 0.92. The suggested method can be used to automatically track perceived exercise exertion in real-time.

Effect of Hydroxychloroquine on Influenza Prevention.

The aim of this study was to assess whether long-term administration of hydroxychloroquine (HCQ) is protective from influenza in patients with rheumatoid arthritis and systemic lupus erythematosus. Using a propensity score-matched design, patients who were prescribed HCQ for more than 10 months were matched with patients of the same gender, age group, and Charlson Comorbidity Index score who did not receive HCQ. A logistic regression model was used to estimate the association between the HCQ exposure and influenza after adjusting for covariates. We found no evidence that long-term HCQ exposure can provide a protective effect against influenza during an influenza season.

Usability Inspection of a Mobile Cancer Telerehabilitation System.

Cancer rehabilitation (CR) has been shown to address physical impairments and progressive disablement experienced by patients with cancer. Access to CR is limited by multiple barriers. Previous studies demonstrated that telemedicine approaches may facilitate access to rehabilitation services however usability and acceptance of cancer telerehabilitation has not been systematically evaluated. This goal of this study was usability inspection of a mobile cancer telerehabilitation system based on cognitive walkthroughs and heuristics evaluations, supplemented by surveys to capture health literacy, patient engagement, and acceptance. The System Usability Scale provided a standardized reference for usability and satisfaction, and the mean result of 83.2±16.9 placed this mobile interface in the top 10th percentile. A semi-structured qualitative interview provided actionable feedback, which informed the next iteration of this project. Overall, this mobile telerehabilitation system was considered by cancer patients easy-to-use, satisfying, and engaging with 91% of participants planning to use it in the future.

Exploring Determinants of Longevity of Biomedical Databases.

The maintenance of biomedical databases requires ongoing and systematic efforts in keeping them up-to-date which may affect long-term sustainability. Since research has become more reliant on publicly available biomedical data collections, it is important to understand factors affecting their longevity. The aim of this article was to explore potential determinants of biomedical database longevity. To build an analytical dataset, we used Database journal that have been created as an open access platform for presenting biological databases. A stratified analysis of all the original databases published in Database journal between 2009 and 2016 was conducted depending on their accessibility status. Overall, 35% of 518 analyzed databases were not accessible in 2020. We showed that databases with higher citation counts from institutions with higher scientific output were significantly more likely to be currently accessible. Databases from researchers with higher h-index were more likely to be accessible. Further investigation is warranted to identify factors affecting longevity of high impact databases.

The Efficacy of an Ultrasound-Guided Improved Puncture Path Technique of Nerve Block/Pulsed Radiofrequency for Pudendal Neuralgia: A Retrospective Study.

Objectives: To investigate the efficacy and safety of an improved ultrasound-guided pulsed radiofrequency (PRF) and nerve block (NB) for patients with pudendal neuralgia (PN). Methods: This retrospective analysis included 88 adults with PN treated in the Pain Department of Southwest Hospital from November 2011 to June 2021, with treatment including NB (n = 40) and PRF (n = 48). The primary outcome variable was pain severity, measured by a standardized visual analog scale (VAS). VAS values were collected at 1, 3, 7, and 14 days and 1 and 3 months after patients were treated with NB or PRF. Results: Compared with patients treated with NB (n = 40) and those treated with PRF (n = 48), no significant difference in pain reduction was observed in the short term (p = 0.739 and 0.981, at 1 and 3 days, respectively); however, in the medium and long term (1 to 3 months), there were statistically significant improvements in the PRF group over the NB group (p < 0.001). Moreover, it was noted that the average pain severity of primary PN and PN due to sacral perineurial cyst was significantly reduced with PRF therapy in the medium and long term when compared to other secondary PNs, including surgery, trauma, and diabetes. Discussion: The ultrasound-guided, improved, and innovative PRF/NB puncture path technique allows for gentler stimulation and faster identification of the pudendal nerve. The PRF technique may provide better treatments for primary PN and sacral perineurial cyst causing secondary PN in the medium and long term.

CXCR4/CX43 Regulate Diabetic Neuropathic Pain via Intercellular Interactions between Activated Neurons and Dysfunctional Astrocytes during Late Phase of Diabetes in Rats and the Effects of Antioxidant N-Acetyl-L-Cysteine.

Growing evidence suggests that the interactions between astrocytes and neurons exert important functions in the central sensitization of the spinal cord dorsal horn in rodents with diabetes and neuropathic pain (DNP). However, it still remains unclear how signal transmission occurs in the spinal cord dorsal horn between astrocytes and neurons, especially in subjects with DNP. Chemokine CXC receptor 4 (CXCR4) plays critical roles in DNP, and connexin 43 (CX43), which is also primarily expressed by astrocytes, contributes to the development of neuropathy. We thus postulated that astrocytic and neuronal CXCR4 induces and produces inflammatory factors under persistent peripheral noxious stimulation in DNP, while intercellular CX43 can transmit inflammatory stimulation signals. The results showed that streptozotocin-induced type 1 diabetic rats developed heat hyperalgesia and mechanical allodynia. Diabetes led to persistent neuropathic pain. Diabetic rats developed peripheral sensitization at the early phase (2 weeks) and central sensitization at the late phase (5 weeks) after diabetes induction. Both CXCR4 and CX43, which are localized and coexpressed in neurons and astrocytes, were enhanced significantly in the dorsal horn of spinal cord in rats undergoing DNP during late phase of diabetes, and the CXCR4 antagonist AMD3100 reduced the expression of CX43. The nociceptive behavior was reversed, respectively, by AMD3100 at the early phase and by the antioxidant N-acetyl-L-cysteine (NAC) at the late phase. Furthermore, rats with DNP demonstrated downregulation of glial fibrillary acidic protein (GFAP) as well as upregulation of c-fos in the spinal cord dorsal horn at the late phase compared to the controls, and upregulation of GFAP and downregulation of c-fos were observed upon treatment with NAC. Given that GFAP and c-fos are, respectively, makers of astrocyte and neuronal activation, our findings suggest that CXCR4 as an inflammatory stimulation protein and CX43 as an intercellular signal transmission protein both may induce neurons excitability and astrocytes dysfunction in developing DNP.