Assessment of Genotoxic Biomarker in Tongue and Buccal Mucosal Epithelial Cells of COVID-19 Patients: An Observational Study.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) is the main host cell receptor for coronavirus disease 2019 (COVID-19) and is highly expressed in the tongue and buccal mucosa. Therefore, the present study was conducted to investigate genotoxic changes in epithelial cells of the buccal and tongue mucosa following COVID-19 infection. MATERIALS AND METHODS: This study included 40 patients aged 25-40 years, divided into two groups: Group 1 (control group) included 20 healthy individuals with no prior history of COVID-19 infection subdivided into Group 1a (buccal mucosa), and Group 1b (tongue mucosa); Group 2 (case group) included 20 patients with a history of mild to moderate COVID-19 infection subdivided into Group 2a (buccal mucosa) and Group 2b (tongue mucosa). Genotoxic biomarkers, such as the number of micronuclei, pyknosis, karyolysis, and karyorrhexis, were assessed in epithelial cells from the buccal mucosa and the ventral surface of the tongue. Analysis of variance was used for intragroup comparisons, followed by post-hoc analysis using Tukey's test. RESULTS: The mean age of the patients was 27.4±6.52 years. Statistically significant differences were observed between cases and controls in the number of micronuclei, pyknosis, karyolysis, and karyorrhexis in the epithelial cells of the buccal and tongue mucosa (p = 0.05). CONCLUSION: SARS-CoV-2 has pronounced genotoxic effects on the epithelium of the ventral surface of the tongue in comparison to the buccal mucosa Therefore, patients with COVID-19 should be monitored regularly to develop future carcinomas, particularly those with habits of smoking, alcohol consumption, and tobacco usage.

Emergency department patient navigators successfully connect patients to care within a rapidly evolving healthcare system.

In the United States, adherence to follow up medical appointments among patients discharged from the emergency department varies between 26% and 56%, depending on the population. It is well known that patients face significant barriers to care within an increasingly complicated system of care. In an effort to better support patients, in 2020, NewYork-Presbyterian Queens implemented a Patient Navigator Program with 7 bilingual Patient Navigators who were trained to deliver culturally sensitive education and support, and to schedule follow up appointments for patients experiencing barriers to care. Between February 2020 and December 2022, 30,164 patients were supported by the 7 Patient Navigators. Ninety-four percent of patients without a primary care provider had a new provider and appointment upon discharge, and 81% of patients attended the appointment scheduled by the Patient Navigator. This study demonstrates that Patient Navigators can work alongside clinical colleagues, and as members of emergency department health care teams, to support patients to connect to care and to attend follow up appointments. It also highlights that Patient Navigators are uniquely qualified to build trust and to support patients to achieve appropriate, continuous care within a rapidly evolving health care system.

Molecular Response Assessment with Immune Adaptive PERCIST in Lung Cancer Patients Treated with Nivolumab: Is It Better Than iRECIST?

Aims We compared the immune response evaluation criteria in solid tumors (iRECIST) with immune adaptive positron emission tomography response criteria in solid tumors (imPERCIST) in lung cancer patients treated with nivolumab. Materials and Methods Twenty lung cancer patients underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan at baseline (PET-0), after four cycles (PET-1) and six to eight cycles (PET-2) of nivolumab were included. Kappa coefficient ( k ) was derived to see the level of agreement in two response criteria. Progression-free survival (PFS) curves were computed by the Kaplan-Meier method and compared with the Log Rank test. Univariate and multivariate regression for the percentage change in the sum of diameters (SoD), standard uptake value maximum (SUVmax), sum of metabolic tumor volume (SoMTV), and sum of total lesion glycolysis (SoTLG) was computed. A p -value less than 0.05 was considered significant. Results Kappa coefficient showed a substantial level of agreement (k 0.769) in two response criteria. Mean PFS in partial response, stable disease, and progressive disease (PD) patients in iRECIST and imPERCIST was 27.3, 17.7, 4.2, and 23.3, 18.8, 3.8 months, respectively. The Kaplan-Meier method with the log rank test showed a significant difference in PFS on intracomparison within both criteria; however, it was not significant on intercomparison. On univariate analysis, the percentage change in SoD, SoMTV, SoTLG was significant. However, on multivariate analysis, only percentage change in SoD was a significant predictor. Conclusions We concluded that imPERCIST was equally effective as currently recommended criteria iRECIST for response evaluation of nivolumab in lung cancer patients.

Contamination Assessment of Heavy Metals in Agricultural Soil, in the Liwa Area (UAE).

The Liwa area is a primary food production area in the United Arab Emirates (UAE) and has intensively been used for agriculture. This study investigates the pollution levels with heavy metals in agricultural soils from the Liwa area. Thirty-two soil samples were analyzed for Mn, Zn, Cr, Ni, Cu, Pb, Cd, Co, and As. Results revealed that heavy metal levels varied in the ranges 220.02-311.21, 42.39-66.92, 43.43-71.55, 32.86-52.12, 10.29-21.70, 2.83-8.84, 0.46-0.69, 0.03-0.37 mg/kg for Mn, Zn, Cr, Ni, Cu, Pb, Cd, Co, and As, respectively. All samples presented low As concentrations with an average of 0.01 mg/kg. The variations in bulk metal contents in the soil samples were related to multiple sources, including agrochemicals, atmospheric dust containing heavy metals, and traffic-related metals. Enrichment factor analysis indicates that Cd, Ni, Zn, and Cr were highly enriched in soils, and they could originate from non-crustal sources. Based on the geo-accumulation index (Igeo), the soil samples appeared uncontaminated with Mn, Cr, Zn, Pb, Co, As, Cu, uncontaminated to moderately contaminated with Ni and moderately contaminated with Cd. The contamination factors suggest low contamination, except for Ni, which showed moderate contamination. The average pollution load index (PLI) revealed unpolluted to low pollution of all soil samples. The ecological risk assessment (PERI) showed that all heavy metals posed a low risk, except for Cd which exhibited a high ecological risk.

Assessment of Metals Concentrations in Soils of Abu Dhabi Emirate Using Pollution Indices and Multivariate Statistics.

The aim of this study was twofold. Firstly, we performed a land capability class determination of the agricultural soils from the Abu Dhabi Emirate, the United Arab Emirates, based on the concentrations of 17 chemical elements determined in the soil samples collected from 84 locations. Secondly, we assess the soil pollution with different metals, using several pollution indices. The results of Principal Component Analysis (PCA) shows that four principal components (PCs) are responsible for describing the total metals concentrations' variance, the highest contribution on PC1 being that of Mn, and Cr, on PC2 that of Fe, on PC3 that of Cu, and on PC4 that of Al. After determining the optimal number of clusters, we classified the sites into three clusters, while the studied metals were grouped function on their concentrations. Then, we used five indices to assess the pollution level of the soil at the study sites and in the clusters. The geo-accumulation index (Igeo) indicates uncontamination/moderately contamination with Cu in cluster 1, uncontaminated/moderately contaminate soils with Cd, Cu, and Ni in cluster 2, and uncontaminated/moderately contaminated soil with Cu and moderately contaminated with Pb, Zn, and Ni in cluster 3. By comparison, the enrichment factors overestimate the pollution of the studied sites. The pollution load index (PLI) indicates a baseline level of pollution at 14 sites and the deterioration of the soil quality at four sites. The Nemerow pollution index provides similar results as PLI.

Crisis clinical pathway for COVID-19.

The pandemic of COVID-19 has been particularly severe in the New York City area, which has had one of the highest concentrations of cases in the USA. In March 2020, the EDs of New York-Presbyterian Hospital, a 10-hospital health system in the region, began to experience a rapid surge in patients with COVID-19 symptoms. Emergency physicians were faced with a disease that they knew little about that quickly overwhelmed resources. A significant amount of attention has been placed on the problem of limited supply of ventilators and intensive care beds for critically ill patients in the setting of the ongoing global pandemic. Relatively less has been given to the issue that precedes it: the demand on resources posed by patients who are not yet critically ill but are unwell enough to seek care in the ED. We describe here how at one institution, a cross-campus ED physician working group produced a care pathway to guide clinicians and ensure the fair and effective allocation of resources in the setting of the developing public health crisis. This 'crisis clinical pathway' focused on using clinical evaluation for medical decision making and maximising benefit to patients throughout the system.

Clinical Assessment of 5-Fluorouracil/Leucovorin, Nab-Paclitaxel, and Irinotecan (FOLFIRABRAX) in Untreated Patients with Gastrointestinal Cancer Using UGT1A1 Genotype-Guided Dosing.

PURPOSE: 5-Fluorouracil (5-FU)/leucovorin, irinotecan, and nab-paclitaxel are all active agents in gastrointestinal cancers; the combination, FOLFIRABRAX, has not been previously evaluated. UDP Glucuronosyltransferase 1A1 (UGT1A1) clears SN-38, the active metabolite of irinotecan. UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity and predisposes to toxicity. We performed a trial to assess the safety and tolerability of FOLFIRABRAX with UGT1A1 genotype-guided dosing of irinotecan. PATIENTS AND METHODS: Patients with previously untreated, advanced gastrointestinal cancers received FOLFIRABRAX with prophylactic pegfilgrastim every 14 days. UGT1A1 *1/*1, *1/*28, and *28/*28 patients received initial irinotecan doses of 180, 135, and 90 mg/m2, respectively. 5-FU 2,400 mg/m2 over 46 hours, leucovorin 400 mg/m2, and nab-paclitaxel 125 mg/m2 were administered. Doses were deemed tolerable if the dose-limiting toxicity (DLT) rate during cycle 1 was ≤35% in each genotype group. DLTs were monitored using a sequential procedure. RESULTS: Fifty patients enrolled, 30 pancreatic, 9 biliary tract, 6 gastroesophageal, and 5 others. DLTs occurred in 5 of 23 (22%) *1/*1 patients, 1 of 19 (5%) *1/*28 patients, and 0 of 7 *28/*28 patients. DLTs were all grade 3: diarrhea (3 patients), nausea (2 patients), and febrile neutropenia (1 patient). The overall response rate was 31%. Response rates in pancreatic, gastroesophageal, and biliary tract cancers were 34%, 50%, and 11%, respectively. Eighteen patients (36%) received therapy for at least 24 weeks. CONCLUSIONS: FOLFIRABRAX with genotype-guided dosing of irinotecan is tolerable in patients with advanced gastrointestinal cancer and UGT1A1*1*1 or UGT1A1*1*28 genotypes. Too few *28/*28 patients were enrolled to provide conclusive results. Responses occurred across multiple tumor types.

Facilities that service economically advantaged neighborhoods perform surgical metastasectomy more often for patients with colorectal liver metastases.

BACKGROUND: Metastasectomy of isolated colorectal liver metastases (CRLM) requires significant clinical expertise and may not be readily available or offered. The authors hypothesized that hospitals that treat a greater percentage of patients from higher income catchment areas are more likely to perform metastasectomies regardless of patient or tumor characteristics. METHODS: Using the National Cancer Data Base, the authors classified facilities into facility income quartiles (FIQs) based on the percentage of patients from the wealthiest neighborhoods (by zip code). Quartile 1 included facilities with <2.1% of the patients residing within the highest income zip codes, quartile 2 included facilities with 2.2% to 15.6% of patients residing within the highest income zip codes, quartile 3 included facilities with 15.7% to 40.2% of patients residing within the highest income zip codes, and quartile 4 included facilities with 40.3% to 90.5% of patients residing within the highest income ZIP codes. Patient, tumor, and facility characteristics were analyzed using a multivariate logistic regression to identify associations between metastasectomy and FIQ. RESULTS: Patients with CRLM were more likely to undergo metastasectomy at facilities in the highest FIQ compared with the lowest FIQ (18% vs 11% in FIQ4; P = .001). This trend was not observed in the resection of primary tumors for nonmetastatic CRLM (rates of 95% vs 93%; P = .94). After adjusting for individual insurance status, distance traveled, zip code-level individual income, tumor, and host, patients who were treated at the highest FIQ facilities were found to be more likely to undergo metastasectomy (odds ratio, 1.29; 95% CI, 1.02-1.72 [P = .03]). CONCLUSIONS: Metastasectomy for CRLM is more likely to occur at facilities that serve a greater percentage of patients from high-income catchment areas, regardless of individual patient characteristics. This disparity uniquely affects those patients with advanced cancers for which specialized expertise for therapy is necessary.

4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites.

Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax.

An assessment of norepinephrine mediated hypertrophy to apoptosis transition in cardiac cells: a signal for cell death.

OBJECTIVES: Heart is an organ which is under a constant work load that generates numerous stress responses. Heart failure is associated with increased plasma norepinephrine (NE) and hypertrophic cell death. Within the current study we try to understand the concentration dependent molecular switch from hypertrophy to apoptosis under stress. METHODS: The effect of increasing concentration of NE on cell death was studied using MTT assay based on which further experimental conditions were decided. Trypan Blue staining and TUNEL assay were done at selected concentrations of NE. Cellular and nuclear morphology at these concentrations was studied using Haematoxylin-Eosin, DAPI and PI stains. The molecular switch between hypertrophy and cell death was studied by expression analysis of ß-MyHC and TNF-α. Rhodamine and DCFH-DA staining were done to evaluate the role of mitochondria and ROS under these conditions. Role of caspases under these transitions was also evaluated. RESULT: NE shows steep falls in cell viability at 50 µM and 100 µM concentrations. The cellular and nuclear morphology is altered at these concentrations along with alterations at molecular level showing a shift from hypertrophy towards cell death. Altered mitochondrial membrane potential and increase in ROS support this which leads to caspase dependent activation of cell death. CONCLUSION: We show that at 50 µM NE, there occurs a transition from cellular hypertrophy towards death. This could be beneficial to prevent hypertrophy induced cardiac cell death and evaluating cardio protective therapeutic targets in vitro.

Direct observation evaluations by emergency medicine faculty do not provide data that enhance resident assessment when compared to summative quarterly evaluations.

OBJECTIVES: The purpose of this study was to compare quarterly global evaluations with direct observation evaluations to determine if direct observation evaluations provide unique data compared to those obtained from quarterly global evaluations. METHODS: This observational, cohort study was performed at a 3-year emergency medicine (EM) residency program with 10 residents per year. Faculty used an online Web-based evaluation system to complete quarterly global evaluations and patient-specific direct observation evaluations. Two scores were collected for each resident within each quarterly evaluation period: 1) the quarterly evaluation score was the mean score across all faculty who performed a quarterly evaluation and, 2) the direct observation score was the mean score across all faculty who performed a direct observation evaluation. Pearson correlation coefficients were performed across these two groups of evaluations. RESULTS: Over the 4-year period of the study 296 complete data sets were available for the analysis. When the quarterly evaluation score was correlated with the direct observation score for each resident at the same evaluation period, we found a very high correlation for each of the eight evaluation questions (r = 0.95-0.96, p < 0.0001). When these evaluations were stratified based on the number of direct observation evaluations that were performed during the evaluation period of interest, the correlation between the quarterly evaluation and the direct observation scores increased as the number of direct observations in the evaluation period increased. The evaluation scores from the faculty who had performed both direct observation and quarterly evaluation methods during the same resident evaluation period were highly correlated even with small numbers of evaluators. CONCLUSIONS: Direct observations are highly correlated with quarterly evaluations when there are greater than three direct observation evaluations completed; however, this correlation drops significantly when the number of direct observations is lower. Direct observation evaluations provide similar data when compared with data obtained from quarterly global evaluations.

Other paradigms: better treatments are identified by better trials: the value of randomized phase II studies.

The emergence of many newer, molecularly targeted anticancer drugs requires that we rethink the way that we conduct phase II trials in oncology. In particular, we can no longer afford to advance drugs (or combinations) to phase III trials with a high risk of failure to improve on outcomes. Drawing on phase II trials of therapeutics for other chronic and progressive diseases in medicine, we find that a randomized design is essential not only for selecting agents for further study but also for optimizing the design (dose, patient population, and endpoints) of the subsequent phase III trials. We use the example of advanced nonsmall cell lung cancer to demonstrate how randomized phase II trials have already made an impact in oncology, whereas single-arm phase II trials have led to negative phase III trials in the same disease. Finally, we make the case that randomized phase II trials are feasible, as long as reasonable statistical standards are applied.