Multicentricity in Renal Cell Carcinoma

Objective: To find the incidence of multicentric renal cell carcinoma and its possible relationship to the other clinical and pathologic findings. Methods: A total of 40 patients with renal cell carcinoma underwent radical nephrectomy between March 1994 and January 1996 at Hacettepe University, School of Medicine, Department of Urology. All of the materials were examined grossly and histologically by the same pathologist. Results: Among 40 kidneys 4 had satellite carcinoma (10%), 3 of them had been shown by preoperative imaging techniques, 1 was found histopathologically. Conclusion: If preoperative imaging techniques do not show additional lesion in the kidney besides the small early stage primary in incidentally discovered patients, the incidence of satellite renal cell carcinoma is low enough to justify nephron sparing surgery.     

Machine Learning Techniques to Explore Clinical Presentations of COVID-19 Severity and to Test the Association With Unhealthy Opioid Use: Retrospective Cross-sectional Cohort Study

BackgroundThe COVID-19 pandemic has exacerbated health inequities in the United States. People with unhealthy opioid use (UOU) may face disproportionate challenges with COVID-19 precautions, and the pandemic has disrupted access to opioids and UOU treatments. UOU impairs the immunological, cardiovascular, pulmonary, renal, and neurological systems and may increase severity of outcomes for COVID-19.ObjectiveWe applied machine learning techniques to explore clinical presentations of hospitalized patients with UOU and COVID-19 and to test the association between UOU and COVID-19 disease severity.MethodsThis retrospective, cross-sectional cohort study was conducted based on data from 4110 electronic health record patient encounters at an academic health center in Chicago between January 1, 2020, and December 31, 2020. The inclusion criterion was an unplanned admission of a patient aged ≥18 years; encounters were counted as COVID-19-positive if there was a positive test for COVID-19 or 2 COVID-19 International Classification of Disease, Tenth Revision codes. Using a predefined cutoff with optimal sensitivity and specificity to identify UOU, we ran a machine learning UOU classifier on the data for patients with COVID-19 to estimate the subcohort of patients with UOU. Topic modeling was used to explore and compare the clinical presentations documented for 2 subgroups: encounters with UOU and COVID-19 and those with no UOU and COVID-19. Mixed effects logistic regression accounted for multiple encounters for some patients and tested the association between UOU and COVID-19 outcome severity. Severity was measured with 3 utilization metrics: low-severity unplanned admission, medium-severity unplanned admission and receiving mechanical ventilation, and high-severity unplanned admission with in-hospital death. All models controlled for age, sex, race/ethnicity, insurance status, and BMI.ResultsTopic modeling yielded 10 topics per subgroup and highlighted unique comorbidities associated with UOU and COVID-19 (eg, HIV) and no UOU and COVID-19 (eg, diabetes). In the regression analysis, each incremental increase in the classifier’s predicted probability of UOU was associated with 1.16 higher odds of COVID-19 outcome severity (odds ratio 1.16, 95% CI 1.04-1.29; P=.009).ConclusionsAmong patients hospitalized with COVID-19, UOU is an independent risk factor associated with greater outcome severity, including in-hospital death. Social determinants of health and opioid-related overdose are unique comorbidities in the clinical presentation of the UOU patient subgroup. Additional research is needed on the role of COVID-19 therapeutics and inpatient management of acute COVID-19 pneumonia for patients with UOU. Further research is needed to test associations between expanded evidence-based harm reduction strategies for UOU and vaccination rates, hospitalizations, and risks for overdose and death among people with UOU and COVID-19. Machine learning techniques may offer more exhaustive means for cohort discovery and a novel mixed methods approach to population health.     

Anti-Inflammatory and Antioxidant Effects of Carvacrol on N-Methyl-N′-Nitro-N-Nitrosoguanidine (MNNG) Induced Gastric Carcinogenesis in Wistar Rats

Carvacrol is a dietary polyphenol from Lamiaceae plants that has been shown to possess a wide range of biological activities including antioxidant and antitumor effects. This study aimed to investigate its anti-inflammatory and antioxidant effects on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) induced gastric carcinogenesis in Wistar rats. Forty-nine rats were randomly assigned to four treatment and three control groups. Over 60 days, MNNG (200 mg/kg BW) was orally applied to animals of groups 1–5 while the rats in groups 2–5 also received different doses of carvacrol (10, 25, 50, and 100 mg/kg BW, respectively) until the end of the experiment. Group 6 rats were treated with 100 mg/kg BW carvacrol and no MNNG whereas group 7 was the control group without any treatment. After the euthanasia of all rats, the inflammatory cytokines and oxidative stress parameters were assessed in the blood and tissues. The expression of caspase 9, Bax, and Bcl-2 proteins in the stomach tissues were investigated through histopathological examinations. Statistically significant differences were observed in the body weight, oxidative stress, and inflammation parameters of groups 1 to 6 compared to group 7 (p ≤ 0.001). Animals in MNNG groups 2 and 3 treated with the low dose carvacrol (10 and 25 mg/kg BW) showed significantly reduced oxidative stress, inflammation, and apoptotic effect compared to animals of the MNNG groups receiving increased doses of carvacrol (50 and 100 mg/kg BW) or no carvacrol. Rats exposed to MNNG exhibited gastric cancer cells in several areas. In the MNNG group receiving 100 mg/kg BW carvacrol, the inflammatory cell infiltration was observed in gastric mucosal and submucosal areas whereas MNNG rats supplemented with 10 and 25 mg/kg BW carvacrol showed no pathological alterations of the gastric cells. The results of this study indicate that significant antioxidant and anti-inflammatory effects induced by carvacrol at doses of 10 and 25 mg/kg BW interfered with gastric carcinogenesis induced by MNNG in Wistar rats as well as provide hepatoprotection. However, high doses of carvacrol (50 and 100 mg/kg BW) increased oxidative stress, inflammation, and apoptosis.     

Guidelines and considerations for conducting experiments using tissue microarrays

Tissue microarrays (TMAs) represent a powerful method for undertaking large‐scale tissue‐based biomarker studies. While TMAs offer several advantages, there are a number of issues specific to their use which need to be considered when employing this method. Given the investment in TMA‐based research, guidance on design and execution of experiments will be of benefit and should help researchers new to TMA‐based studies to avoid known pitfalls. Furthermore, a consensus on quality standards for TMA‐based experiments should improve the robustness and reproducibility of studies, thereby increasing the likelihood of identifying clinically useful biomarkers. In order to address these issues, the National Cancer Research Institute Biomarker and Imaging Clinical Studies Group organized a 1‐day TMA workshop held in Nottingham in May 2012. The document herein summarizes the conclusions from the workshop. It includes guidance and considerations on all aspects of TMA‐based research, including the pre‐analytical stages of experimental design, the analytical stages of data acquisition, and the postanalytical stages of data analysis. A checklist is presented which can be used both for planning a TMA experiment and interpreting the results of such an experiment. For studies of cancer biomarkers, this checklist could be used as a supplement to the REMARK guidelines.