High Incidence of Barotrauma in Patients With Severe Coronavirus Disease 2019.

OBJECTIVE.: To report the high incidence of barotrauma in critically ill patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19) and to discuss its implications. DESIGN.: Retrospective cohort study. SETTING.: ICU of an academic county hospital in Los Angeles, CA admitted from March 15-June 20, 2020. PATIENTS.: 77 patients with COVID-19 pneumonia. 75 patients met inclusion criteria. RESULTS.: 21% of patients with severe COVID-19 sustained barotrauma (33% of patients receiving IMV, 8% of patients receiving (NIV). There were no differences between the barotrauma and non-barotrauma groups regarding demographics, illness severity, or medications received, nor tidal volume or average/peak airway pressures in those receiving IMV. In the barotrauma group there was a greater proportion of patients receiving therapeutic anticoagulation (81% vs. 47%, p = 0.023) and ventilated using airway pressure release ventilation mode (13% vs. 0%, p = 0.043). Barotrauma was associated with increased likelihood of receiving a tracheostomy (OR 2.58 [0.23-4.9], p = 0.018]), longer median ICU length of stay (17 days vs. 7 days, p = 0.03), and longer median length of hospitalization (26 days vs. 14 days, p < 0.001). There was also a trend toward prolonged median duration of IMV (12.5 days vs 7 days, p = 0.13) and higher average mortality (56% vs 37%, p = 0.25). CONCLUSIONS.: Barotrauma is seen in 5-12% of patients with ARDS receiving IMV and is exceedingly rare in patients receiving NIV. We report a high incidence of barotrauma observed in critically ill patients with COVID-19 requiring either NIV or IMV. While there was a trend toward increased mortality in patients with barotrauma, this did not reach statistical significance. The increased incidence of barotrauma with COVID-19 may be a product of the pathophysiology of this disease state and a heightened inflammatory response causing rampant acute lung injury. Evidence-based medicine and lung-protective ventilation should remain the mainstay of treatment.

COVID-19: the trends of conspiracy theories vs facts.

Coronavirus disease (COVID-19) caused by SARS-CoV-2-a new single-stranded RNA virus with respiratory system proclivity and epithelial cell- is a novel infectious disease that originated in Wuhan, China in December, 2019 and has spread to many countries with the total number of confirmed cases put at 20,259,579 cases as of 12th August, 2020. It is transmitted from human-to-human via droplets. When an infected person coughs or sneezes, these droplets find their way into the mouth or nostrils of another person that is within a close range. Alternatively it can be contracted by touching infected hard surfaces and using the same hands to touch the mouth, nose and eye(s). COVID-19 has been declared a global pandemic by the World Health Organization (WHO) on 11th March, 2020. There is currently no therapeutic substance accepted as a panacea for the prophylaxis of this infectious disease. As a result of this back drop, many nations have instituted fourteen (14) days quarantine for suspected cases, social distancing and border closure in an attempt to curb the spread of COVID-19. There has been several conspirary theories that emanated since the disease was declared a pandemic. This paper provides useful information to serve as reference to those who seek proper understanding of COVID-19 and its deleterious effects in the body, by distiguishing between the factsand the conspiracy theoriesof coronavirus disease.

Bronchoscopy on Intubated COVID-19 Patients is Associated with Low Infectious Risk to Operators at a High-Volume Center Using an Aerosol-minimizing Protocol.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic raised concern for exposure to healthcare providers through aerosol generating procedures, such as bronchoalveolar lavage (BAL). Current society guidelines recommended limiting use of BAL to reduce operators' risk for infection, yet data on the infection rate for providers after BAL is sparse. Since March 2020, our institution used a modified protocol to perform over 450 BALs on intubated COVID-19 patients. We therefore sought to describe the subsequent infectious risks to providers associated with BAL. METHODS: Fifty-two pulmonary and critical care providers (faculty and fellows) at our tertiary-care, urban medical center were surveyed. Survey participants were asked to provide the number of BALs on COVID-19 patients they performed, the number of weeks they cared for intensive care unit (ICU) patients with COVID-19, and the results of any SARS-CoV-2 testing that they received. Participants were asked to assess the difficulty of BAL on intubated COVID-19 patients as compared to routine ICU BAL using a numeric perceived difficulty score ranging from 1 (easier) to 10 (harder). RESULTS: We received forty-seven responses from fifty-two surveyed (90% response rate), with 2 declining to participate. Many respondents (19/45, 42%) spent >5 weeks on an ICU service with COVID-19 patients. The number of BALs performed by providers ranged from 0 to >60. Sixteen of the 35 providers (46%) who performed BALs underwent at least one nasopharyngeal (NP) swab to test for SARS-CoV-2, but none were positive. Twenty-seven of the 35 providers (77%) who performed BALs underwent SARS-CoV-2 serology testing, and only one (3.7%) was positive. Respondents indicated occasionally not being able to follow aerosol-minimizing steps but overall felt BALs in COVID-19 patients was only slightly more difficult than routine ICU BAL. DISCUSSION: At a high-volume center having performed >450 BALs on intubated COVID-19 patients with aerosol-limiting precautions, our survey of bronchoscopists found no positive NP SARS-CoV-2 tests and only one positive antibody test result. While the optimal role for COVID-19 BAL remains to be determined, these data suggest that BAL can be safely performed in intubated COVID-19 patients if experienced providers take precautions to limit aerosol generation and wear personal protective equipment.

Bronchoscopy on Intubated COVID-19 Patients is Associated with Low Infectious Risk to Operators at a High-Volume Center Using an Aerosol-minimizing Protocol

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic raised concern for exposure to healthcare providers through aerosol generating procedures, such as bronchoalveolar lavage (BAL). Current society guidelines recommended limiting use of BAL to reduce operators risk for infection, yet data on the infection rate for providers after BAL is sparse. Since March 2020, our institution used a modified protocol to perform over 450 BALs on intubated COVID-19 patients. We therefore sought to describe the subsequent infectious risks to providers associated with BAL. MethodsFifty-two pulmonary and critical care providers (faculty and fellows) at our tertiary-care, urban medical center were surveyed. Survey participants were asked to provide the number of BALs on COVID-19 patients they performed, the number of weeks they cared for intensive care unit (ICU) patients with COVID-19, and the results of any SARS-CoV-2 testing that they received. Participants were asked to assess the difficulty of BAL on intubated COVID-19 patients as compared to routine ICU BAL using a numeric perceived difficulty score ranging from 1 (easier) to 10 (harder). ResultsWe received forty-seven responses from fifty-two surveyed (90% response rate), with 2 declining to participate. Many respondents (19/45, 42%) spent >5 weeks on an ICU service with COVID-19 patients. The number of BALs performed by providers ranged from 0 to >60. Sixteen of the 35 providers (46%) who performed BALs underwent at least one nasopharyngeal (NP) swab to test for SARS-CoV-2, but none were positive. Twenty-seven of the 35 providers (77%) who performed BALs underwent SARS- CoV-2 serology testing, and only one (3.7%) was positive. Respondents indicated occasionally not being able to follow aerosol-minimizing steps but overall felt BALs in COVID-19 patients was only slightly more difficult than routine bronchoscopy. DiscussionAt a high-volume center having performed >450 BALs on intubated COVID-19 patients with aerosol-limiting precautions, our survey of bronchoscopists found no positive NP SARS-CoV-2 tests and only one positive antibody test result. While the optimal role for COVID-19 BAL remains to be determined, these data suggest that BAL can be safely performed in intubated COVID-19 patients if experienced providers take precautions to limit aerosol generation and wear personal protective equipment.

Characterizing the impact of health literacy, computer ability, patient demographics, and portal usage on patient satisfaction with a patient portal.

OBJECTIVE: We sought to measure patient portal satisfaction with patient portals and characterize its relationship to attitude towards computers, health literacy, portal usage, and patient demographics. MATERIALS AND METHODS: We invited 13 040 patients from an academic medical center to complete a survey measuring satisfaction, perceived control over computers, and health literacy using validated instruments (End User Computing Satisfaction, Computer Attitude Measure, and Brief Health Literacy Screen). We extracted portal usage and demographic information from the medical center data warehouse. RESULTS: A total of 6026 (46.2%) patients completed the survey. The median (IQR) scores for satisfaction, computer control, and health literacy were 87% (20%), 86% (22%), and 95% (15%), respectively. The normalized mean (SD) usage of messaging, lab, appointment, medication, and immunization functions were 6.6 (2.6), 4.6 (2.4), 3.1 (1.7), 1.5 (1.2), and 0.88 (0.91) times, respectively. Logistic regression yielded significant odds ratios [99% CI] for computer control (3.6 [2.5-5.2]), health literacy (12 [6.9-23]), and immunization function usage (0.84 [0.73-0.96]). DISCUSSION: Respondents were highly satisfied and had high degrees of computer control and health literacy. Statistical analysis revealed that higher computer control and health literacy predicted higher satisfaction, whereas usage of the immunization function predicted lower satisfaction. Overall, the analytical model had low predictive capability, suggesting that we failed to capture the main drivers of satisfaction, or there was inadequate variation in satisfaction to delineate its contributing factors. CONCLUSION: This study provides insight into patient satisfaction with and usage of a patient portal. These data can guide the development of the patient portal, with the ultimate goal of increasing functionality and usability to enhance the patient experience.

Policies and procedures governing patient portal use at an Academic Medical Center.

BACKGROUND AND OBJECTIVE: Patient portal use has increased over the last two decades in response to consumer demand and government regulation. Despite growing adoption, few guidelines exist to direct successful implementation and governance. We describe the policies and procedures that have governed over a decade of continuous My Health at Vanderbilt (MHAV) patient portal use. METHODS: We examined MHAV usage data between May 2007 and November 2017. We classified patient portal activity into eight functional categories: Appointment, Billing, Document Access, Genetics, Health Result, Immunization, Medication, and Messaging. We describe our operating policies and measure portal uptake, patient account activity, and function use over time. RESULTS: By the end of the study period, there were 375 517 registered accounts. Policies made MHAV available to competent adults and adolescents 13 and over. Patients signed up for a limited access account online, which could be upgraded to a full-access account after identity verification. Patients could assign proxy accounts to family and caregivers, which permitted nonpatient access to select MHAV functions. Laboratory and radiology results were accessible via MHAV. Results were classified into three groups based on sensitivity, which govern the length of delay before results appeared in MHAV. DISCUSSION AND CONCLUSION: Patient portals offer significant opportunity to engage patients in their healthcare. However, there remains a need to understand how policies can promote uptake and use. We anticipate that other institutions can apply concepts from our policies to support meaningful patient portal engagement.

Updated guidelines on digital media use by children.

Given the speed at which mobile media has grown recently, the updated American Academy of Pediatrics guidelines for digital technology use by children are a welcome addition to the toolbox of pediatric healthcare providers. This article discusses the changes to the guidelines as well as other useful current research not specifically included in those guidelines.

Minor Salivary Gland Changes in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma - A Histopathological Study.

INTRODUCTION: The most common etiology for Oral Squamous Cell Carcinoma (OSCC) is tobacco and tobacco related products which cause nuclear damage to the keratinocytes. The chemical carcinogens not only affect the lining of oral epithelium but also affect the lining epithelium of the excretory ducts of the salivary glands. Thus, there is a possibility of epithelial dysplasia of the salivary duct epithelium which may lead to potential malignant transformation. AIM: The study was performed to see the changes in the minor salivary glands and excretory ducts in cases of oral epithelial dysplasia and OSCC. MATERIALS AND METHODS: A total of 278 archival cases of mild, moderate and severe epithelial dysplasia, carcinoma in situ, OSCC including verrucous carcinoma were histopathologically evaluated to observe changes in the excretory ducts and the minor salivary glands. RESULTS: In the study there were 56.5% males and 43.5% females. The age group that was most commonly affected in both the sexes was 50-60 yr old. Buccal mucosa was the most common site of involvement. Ductal changes observed in the excretory duct include simple hyperplasia, metaplastic changes such as mucous, oncocytic & squamous, and infiltration of inflammatory cells and malignant cells. Acinar changes observed were degeneration, squamous metaplasia, myoepithelial cell proliferation and inflammatory cell infiltration. Both the excretory ducts and ducts within the gland showed dysplasia. CONCLUSION: According to observations in our study it is suggested that histopathological interpretation for oral mucosal lesions especially oral epithelial dysplasias and OSCC should also include changes related to salivary gland tissue to provide a better treatment plan and prevent recurrence of the malignant tumours.

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. METHODS: We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. RESULTS: Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. CONCLUSIONS: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).

The Trade-Off between Dietary Salt and Cardiovascular Disease; A Role for Na/K-ATPase Signaling?

It has been postulated for some time that endogenous digitalis-like substances, also called cardiotonic steroids (CTS), exist, and that these substances are involved in sodium handling. Within the past 20 years, these substances have been unequivocally identified and measurements of circulating and tissue concentrations have been made. More recently, it has been identified that CTS also mediate signal transduction through the Na/K-ATPase, and consequently been implicated in profibrotic pathways. This review will discuss the mechanism of CTS in renal sodium handling and a potential "trade-off" effect from their role in inducing tissue fibrosis.

Estimation of plasma lipids and its significance on histopathological grades in oral cancer: Prognostic significance an original research.

BACKGROUND OBJECTIVES: Alterations in the lipid profile have long been associated with various cancers because lipids play a key role in maintenance of cell integrity. This study was to estimate the plasma lipid levels in patients with oral cancer and to correlate the values with the histopathological grades. MATERIALS AND METHODS: The study group included 50 patients with oral cancer aged between 20 and 60 years who had visited the Department of Oral Medicine and Radiology during the period of September 2005 to July 2007. After the histotopathological confirmation, their plasma lipid levels were estimated using auto analyzer and the data was statistically analyzed. RESULTS: The study revealed a significant decrease in the total plasma lipid levels in patients with oral cancer in comparison with the standard values. Comparing the plasma lipid levels with the histopathological grades, we observed a significant variation in the levels of total cholesterol, very low density lipoprotein, low-density lipoprotein, high-density lipoprotein and triglycerides. CONCLUSION: The variation in the levels of plasma cholesterol and other lipid constituents in patients with cancer might be due to their increased utilization by neoplastic cells for new membrane biosynthesis. This study was an attempt to estimate the plasma lipids in oral cancer patients and its significance on histopathological grades. We observed a relationship between lower plasma lipids and oral cancer. The result of our study strongly warrants an in-depth research with larger samples and a longer follow-up to consider the low plasma lipid status in oral cancer patients as a useful indicator to assess the course and prognosis of the disease.

Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences.

During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life.

Development of amperometric α-ketoglutarate biosensor based on ruthenium-rhodium modified carbon fiber enzyme microelectrode.

A rapid and highly sensitive miniaturized amperometric biosensor for the detection of α-ketoglutarate (α-KG) based on a carbon fiber electrode (CFE) is presented. The biosensor is constructed by immobilizing the enzyme, glutamate dehydrogenase (GLUD) on the surface of single carbon fiber modified by co-deposition of ruthenium (Ru) and rhodium (Rh) nanoparticles. SEM and EDX shed useful insights into the morphology and composition of the modified microelectrode. The mixed Ru/Rh coating offers a greatly enhanced electrocatalytic activity towards the detection of ß-nicotinamide adenine dinucleotide (NADH), with a substantial decrease in overpotential of ∼ 400 mV compared to the unmodified CFE. It also imparts higher stability with minimal surface fouling, common to NADH oxidation. Further modification with the enzyme, GLUD leads to effective amperometric biosensing of α-KG through monitoring of the NADH consumption. A very rapid response to dynamic changes in the α-KG concentrations is observed with a response time of 6s. The current response is linear between 100 and 600 µM with a sensitivity of 42 µAM(-1) and a detection limit of 20 µM. This proof of concept study indicates that the GLUD-Ru/Rh-CFE biosensor holds great promise for real-time electrochemical measurements of α-KG.

The use of insects in forensic investigations: An overview on the scope of forensic entomology.

Forensic entomology is the study of insects/arthropods in criminal investigation. Right from the early stages insects are attracted to the decomposing body and may lay eggs in it. By studying the insect population and the developing larval stages, forensic scientists can estimate the postmortem index, any change in position of the corpse as well as the cause of death. Forensic odontologists are called upon more frequently to collaborate in criminal investigations and hence should be aware of the possibilities that forensic entomology have to offer and use it as an adjunct to the conventional means of forensic investigation.

Using biological performance similarity to inform disaccharide library design.

Designing better small-molecule discovery libraries requires having methods to assess the consequences of different synthesis decisions on the biological performance of resulting library members. Since we are particularly interested in how stereochemistry affects performance in biological assays, we prepared a disaccharide library containing systematic stereochemical variations, assayed the library for different biological effects, and developed methods to assess the similarity of performance between members across multiple assays. These methods allow us to ask which subsets of stereochemical features best predict similarity in patterns of biological performance between individual members and which features produce the greatest variation of outcomes. We anticipate that the data-analysis approach presented here can be generalized to other sets of biological assays and other chemical descriptors. Methods to assess which structural features of library members produce the greatest similarity in performance for a given set of biological assays should help prioritize synthesis decisions in second-generation library development targeting the underlying cell-biological processes. Methods to assess which structural features of library members produce the greatest variation in performance should help guide decisions about what synthetic methods need to be developed to make optimal small-molecule screening collections.