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Introduction This study aimed to determine the prevalence of multidrug-resistant Gram-negative bacteria (GNB) from blood cultures in a tertiary-care hospital and the multiplex PCR assay's ability to detect resistance genes. Methods A total of 388 GNB isolates obtained from hospitalized patients between November 2019 and November 2021 were included in the study. Antimicrobial susceptibility testing was done by VITEK 2 system and broth microdilution method. Beta-lactamase-encoding genes were detected by multiplex PCR assays, BioFire-Blood Culture Identification 2 (BCID2) panel (bioMerieux, France). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically with VITEK AST-GN71 card (bioMerieux, France). The isolates of GNB were classified into multidrug-resistant, extensively-drug-resistant, and pandrug-resistant categories, and their prevalence and distribution in different wards, including coronavirus diseases 2019 (COVID-19) intensive care units (ICU), were calculated. Results Results revealed that all isolates of Acinetobacter baumannii and Pseudomonas aeruginosa were multidrug-resistant as well as 91.6% of Enterobacter cloacae, 80.6% of Proteus mirabilis, and 76.1% of Klebsiella pneumoniae, respectively. In fermentative bacteria, blaOXA-48-like (58.1%), blaNDM (16.1%), blaKPC (9.7%) and blaVIM (6.5%) genes were detected. More than half of Enterobacter cloacae (58.3%) and Klebsiella pneumoniae (53.7%) produced ESBLs. Among non-fermenters, the blaNDM gene was carried by 55% of Pseudomonas aeruginosa and 19.5% of Acinetobacter baumannii. In the COVID-19 ICU, Acinetobacter baumannii was the most common isolate (86.1%). Conclusions This study revealed high proportions of multidrug-resistant blood isolates and various underlying resistance genes in Gram-negative strains. The BCID2 panel seems to be helpful for the detection of the most prevalent resistance genes of fermentative bacteria.Copyright © GERMS 2022.
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Objectives: Opioids play a significant role in the effective management of cancer-related pain. The COVID-19 lock down may have reduced access to opioids and caused a decline in the use of prescription of opioids among cancer survivors. This study compared opioid prescription rates among cancer survivors before and after the onset of COVID-19 pandemic using real-world electronic health records (EHR). Method(s): Cohort analyses of cancer patients using data from EHR database from the TriNetX, a global federated health research network across 76 healthcare organizations. We analyzed changes in prescription opioid use before (March 1, 2018, through March 1, 2019) and after onset of COVID-19 (April 01, 2020, through March 2021) among cancer survivors. The key outcome variable was any opioid prescription within 1 year of cancer diagnosis. One-to-one propensity score matching was used to balance the characteristics (age, sex, race, diagnoses including diabetes, hypertensive diseases, overweight, mood disorders, and visual disturbances) of the two cohorts. Data were analyzed using the TriNetX platform. Result(s): There were 1,502,143 cancer survivors before COVID-19 and 1,412,599 cancer survivors after the onset of COVID-19. The one-to-one propensity-score match yielded 1,382,561 cancer patients, mean age 64 at cancer diagnosis, and 73% were white. Percentage of opioid use among cancer patients declined from 35.6% before the COVID-19 to 35.1% after the onset of the pandemic (OR=0.976, 95% CI 0.971-0.981). Average number of opioid prescriptions within 1 year of cancer diagnosis declined from 5.7 before to 5.3 after the COVID-19 onset (p<0.001). Conclusion(s): Among cancer survivors, a small decline in prescription opioid use was observed after the onset of COVID-19 pandemic. Future studies are needed to distinguish the impact of revised guidelines, opioid prescription policy changes, and COVID-19 lock down on lower rates of prescription opioid use among cancer survivors.Copyright © 2023
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Objective: The current study aimed to describe the clinical characteristics of mild SARS-CoV-2 infected pregnant women with abnormal liver function (ALF), explore the association between ALF with maternal and fetal outcomes. Method(s): This retrospective analysis included 87 pregnant patients with mild SARS-CoV-2 infection admitted and treated from December 1, 2022, to 31, 2022 in the department of Obestircs at Beijing Obstetrics and Gynecology Hospital. We evaluated patients for demographic and clinical features, laboratory parameters and pregnancy complications. Result(s): 27 Patients in this cohort had clinical presentations of ALF. Compared with the control group, the peripheral blood platelet (PLT), D-dimer quantitative determination (D-Dimer), lactate dehydrogenase (LDH), total protein (TP), albumin (ALB), indirect bilirubin (DBIL), gamma- glutamyltranspeptidase (GGT) and total bile acid (TBA) showed significantly differences (p<0.05). 12 cases (44.44%) complicated with pregnancy induced hypertension (PIH), 14 cases (51.85%) complicated with intrahepatic cholestasis of pregnancy (ICP), 2 cases (7.4%) complicated with acute fatty liver during pregnancy (AFLP) and 5 cases (14.81%) complicated with postpartum hemorrhage in patients with abnormal LFT were significantly higher than those in the control group (p<0.05). Compared with the control group, the incidence of premature delivery (22.22%) and fetal distress (37.04%) in the experiment group were significantly higher (p<0.05), and the incidence of neonatal asphyxia was not significantly different (p>0.05). Conclusion(s): Pregnant women are generally susceptible to mild SARS-CoV-2 and may induce ALF. ALF is associated with increased risk of mother and infant. The maternal and infant outcomes of those who terminated pregnancy in time are acceptable. Therefore, pregnant women with COVID-19 who received antiviral treatment should be closely monitored for evaluating liver function and relevant indicators. The long-term outcomes in the future are worth to further study.Copyright © 2023
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Objective To summarize and analyze the features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2). Methods In this study,an analysis was performed for the liver function test results of the locally transmitted or imported pediatric patients with SARS - CoV - 2 infection during isolation who were admitted to Guangzhou Eighth People's Hospital,Guangzhou Medical University,since May 21,2021,and the clinical data and the constituent ratio of liver injury were compared between the pediatric patients infected with Delta variant and those infected with Omicron variant. The independent samples t - test or the Mann - Whitney U test was used for comparison of continuous data between two groups,and the chi - square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results A total of 85 pediatric patients infected with SARS - CoV - 2 were enrolled,among whom there were 32 (37. 6%)pediatric patients infected with Delta variant and 53 (62. 4%)pediatric patients infected with Omicron variant,and there were no significant differences between the two groups in age,sex, body height,body weight,and comorbidities (all P > 0. 05). There were no significant differences between the two groups in alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma - glutamyl transpeptidase,total bilirubin,albumin,and cholinesterase (all P > 0. 05),and the pediatric patients infected with Omicron variant had a significantly higher level of total bile acid (TBA)than those infected with Delta variant (Z = - 2. 336,P = 0. 020). However,the median values of TBA were within the normal range and the ratios of abnormal TBA were no significant difference between the two groups (P > 0. 05). Among the 85 pediatric patients,10 (11. 8%)had a mild increase in liver function parameters,among whom 7 had an increase in TBA,1 had an increase in ALT, 1 had increases in ALT and AST,and 1 had an increase in ALP. The analysis of liver injury in the pediatric patients infected with Delta variant or Omicron variant showed that there was no significant difference in the constituent ratio of liver injury caused by the two variants (6. 3% vs 15. 1%,chi2 = 0. 691,P = 0. 406). Conclusion Mild liver injury is observed in pediatric patients infected with Delta and Omicron variants of SARS - CoV - 2,but further studies are needed to evaluate the long - term influence of such infection on liver function.Copyright © 2022 Editorial Board of Jilin University
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Objectives: Malnutrition is a prevalent condition affecting 30-50% of hospitalized patients. Malnutrition is linked to impairments in health outcomes and increased economic burden on healthcare systems. We assessed the prevalence and burden of malnutrition by examining demographic characteristics, Disease Related Group (DRG) payments and associated claims among Medicare inpatients (65+ years) with and without COVID-19. Method(s): Hospital inpatient COVID-19 claims from the Centers for Medicare & Medicaid Services (CMS) Inpatient Prospective Payment System (IPPS) between October 2020 - September 2021 were analyzed. The International Classification of Diseases, Tenth Revision, and Clinical Modification (ICD-10-CM) were used for malnutrition diagnoses. Demographic variables were compared based on the COVID-19 status;economic burden was analyzed by DRG payment of malnutrition cases with and without COVID-19. Result(s): Among 7,394,657 Medicare inpatient claims, only 12% had a documented malnutrition diagnosis. Of these patients, 1.2% had COVID-19. Regardless of COVID-19 status, malnourished patients averaged 75 years of age, and were predominantly female (54%) and White (78%) followed by Black (14%), and Hispanic (2%). Sepsis, kidney failure, and urinary tract infection (UTI) were the most common primary diagnoses in malnourished patients, regardless of COVID-19 status. Malnourished patients with COVID-19 had significantly higher DRG payments ($27,407 vs. $18,327) and increased cost of outlier payment ($3,208 vs. $2,049) compared to those without COVID-19, regardless of other diagnoses. Conclusion(s): Malnutrition diagnosis was confirmed in only 12% of the Medicare inpatients, thus suggesting that malnutrition continues to be underdiagnosed and undertreated - evidenced by high rates of hospitalizations/claims and payments in both COVID-19 and non-COVID-19 cases. It is imperative for hospitals to implement nutrition-focused protocols to identify, diagnose and address malnutrition among all Medicare inpatients regardless of COVID-19 status (and especially among patients with sepsis, kidney failure, and UTI). Nutrition-focused protocols can effectively improve patient health outcomes and reduce healthcare costs.Copyright © 2023
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Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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Objective. To study the characteristics of cardiotocography (CTG) and pregnancy outcomes in patients who had a mild coronavirus infection in the third trimester. Patients and methods. The parameters and variations of CTG and pregnancy outcomes were analyzed in 32 low-risk pregnant women who experienced mild COVID-19 in the third trimester (the study group) and in 30 pregnant women (matched pairs) who had no coronavirus infection (the comparison group). Results. A total of 375 CTGs were analyzed: 221 in the study group and 154 in the comparison group. Normal CTG recordings were found in 87% of pregnant women in the study group, which was significantly less frequent than in those without COVID-19 (97%) (p = 0.02), and suspicious CTG in 10 and 1.3%, respectively, which was 3.38-fold more frequent than in the comparison group (p = 0.04). Pathological CTG recordings were observed only in two women in the study group. The features of CTG in women who had a mild form of COVID-19 in the third trimester were a significant decrease in the number of accelerations, short-term variation (STV) in the range of 3 to 5 ms, long-term variation (LTV) <50 ms, a tendency toward tachycardia and low heart rate variability (<5 ms), and prolonged decelerations. The frequency of fetal asphyxia and neonatal morbidity was higher in the study group. Conclusion. COVID-19 even in its mild form may have a negative effect on the fetus, increasing the frequency of fetal hypoxia and neonatal asphyxia.Copyright © 2023, Dynasty Publishing House. All rights reserved.
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Background: The 2019 novel coronavirus disease (COVID-19) has been reported as pandemy and the number of patients continues to rise. Based on recent data, cardiac injury is a prominent feature of the disease, leading to increased morbidity and mortality. In the present study we aimed to evaluate myocardial dysfunction using transthoracic echocardiography (TTE) and tissue Doppler imaging (TDI) in hospitalized COVID-19 patients. Methods and Results: We recruited 30 patients (56.7% male, 55.80 +/- 14.949 years) who were hospitalized with the diagnosis COVID-19 infection. We analyzed left ventricular (LV) and right ventricular (RV) conventional and TDI parameters at the time of hospitalization and during the course of the disease. Patients without any cardiac disease and with preserved LV ejection fraction (EF) were included. TTE examination was performed and all the variables were recorded and analyzed retrospectively. We observed that both LV and RV conventional echocardiographic parameters were similar when the day of admission to the hospital was compared to the 5th day of the disease. Regarding TDI analysis, we demonstrated significant impairment in LV septal and lateral deformation (P < 0.001). In the correlation analysis no marked correlation was observed between impairment in LV deformation and inflammation biomarkers. Conclusion(s): Cardiac involvement is an important feature of the COVID-19 infection but the exact mechanism is still undefined. Echocardiography is an essential technique to describe myocardial injury and provide new concepts for the possible definitions of cardiac dysfunction.Copyright © 2023 The Author(s).
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Objectives: The impact of the COVID-19 pandemic on mental health is not yet well-studied. This study's objective is to describe demographic characteristics of the population diagnosed with depression or anxiety, and to compare PHQ9 scores before and after the pandemic. Method(s): A retrospective cohort study was performed using Komodo Health's healthcare claims and EMR data, which included Patient Health Questionnaire-9 (PHQ9) survey responses. The study's baseline and follow-up periods were set as one year before and after 03/01/2020. Patients selected were >=18 years of age, had a MDD, GAD, or other psychiatric diagnosis in both periods, and had taken at least one PHQ9 survey in both periods, resulting in 10,433 patients. Demographic characteristics were described across age, gender, and race/ethnicity, and a subgroup analysis was performed on PHQ9 scores and depression categories using averages (mean, SD) and odds ratios. Result(s): Demographic analysis showed depression severity correlated with patients who were younger, female, and Black or Hispanic. Younger patients (<30) were more likely than older (>=30) to be in the moderately severe category or worse (PHQ9 score >=15) in both time periods (ORs 1.72 and 1.62, p<0.001). This was also true for female as compared to male (ORs 1.45 and 1.49, p<0.001), and Black or Hispanic as compared to White (ORs 1.87 and 1.47, p<0.001). However, mean PHQ9 scores tended to decrease in the follow-up period. The overall mean decreased slightly from 6.28 (SD 6.05) to 5.68 (SD 5.82), which was consistent in nearly all age, gender, and race/ethnicity subcategories. Conclusion(s): While the improvements in average PHQ9 scores were counterintuitive, given the harmful impacts of the pandemic, existing correlations between demographics and depression severity remained. One possible explanation is that this cohort definition selected for patients who received more consistent mental healthcare. Further study will investigate this and other possible factors.Copyright © 2023
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Objectives: Using a historical control or external control arm (ECA) to augment or replace a concurrent control arm in a randomized trial is a hot topic given the challenge of patient recruitment in rare diseases or during COVID-19 pandemic. The FDA released draft guidance in 2021 on effectiveness and safety submissions using real-world evidence. While the guidance focuses mainly on elements of study design and data source selection, there is a lack of consensus in the selection of appropriate statistical methods when constructing an ECA. This study discusses rigorous statistical methodology for ECA-supported trials in regulatory or HTA submissions. Method(s): Targeted literature reviews of statistical simulations comparing methods for ECA in statistical journals were performed. The articles compared commonly used ECA-construction and analysis methods were selected and summarized, including but not limited to propensity score (PS)-based matching, weighting, and stratification, and PS plus Bayesian integrated approaches. Result(s): Type I error, power, bias, and coverage probability are common criteria used to compare different methods. When imbalances only exist in known baseline covariates and the outcome distributions are the same between the trial concurrent control and ECA, the PS method alone or paired with commensurate prior yield almost unbiased estimates, good Type I errors, and coverage probability. PS plus Bayesian approaches have wider interval width and lower power compared with PS-only methods. When there is a change in the outcome distribution over time, the PS (matching or IPTW) and commensurate prior integrated methods yield the smallest biases among all methods. Conclusion(s): PS and Bayesian integrated methods outperformed the PS-only methods in terms of bias and Type I error when outcome distribution changed with current trial control. A "sweet spot" that balances all criteria through trial-specific simulations could provide the ideal setting of trial analyses plan based on specific trial design and scenarios.Copyright © 2023
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Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.
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mRNA is a new class of drugs that has the potential to revolutionize the treatment of brain tumors. Thanks to the COVID-19 mRNA vaccines and numerous therapy-based clinical trials, it is now clear that lipid nanoparticles (LNPs) are a clinically viable means to deliver RNA therapeutics. However, LNP-mediated mRNA delivery to brain tumors remains elusive. Over the past decade, numerous studies have shown that tumor cells communicate with each other via small extracellular vesicles, which are around 100 nm in diameter and consist of lipid bilayer membrane similar to synthetic lipidbased nanocarriers. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain tumors without undue toxicity. We synthesized LNPs using four components similar to the formulation used in the mRNA COVID19 vaccines (Moderna and Pfizer): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. For the in vitro screen, we tested ten classes of helper lipids based on their abundance in extracellular vesicle membranes, commercial availability, and large-scale production feasibility while keeping rest of the LNP components unchanged. The transfection kinetics of GFP mRNA encapsulated in LNPs and doped with 16 mol% of helper lipids was tested using GL261, U87 and SIM-A9 cell lines. Several LNP formations resulted in stable transfection (upto 5 days) of GFP mRNA in all the cell lines tested in vitro. The successful LNP candidates (enabling >80% transfection efficacy) were then tested in vivo to deliver luciferase mRNA to brain tumors via intrathecal administration in a syngeneic glioblastoma (GBM) mouse model, which confirmed luciferase expression in brain tumors in the cortex. LNPs were then tested to deliver Cre recombinase mRNA in syngeneic GBM mouse model genetically modified to express tdTomato under LoxP marker cassette that enabled identification of LNP targeted cells. mRNA was successfully delivered to tumor cells (70-80% transfected) and a range of different cells in the tumor microenvironment, including tumor-associated macrophages (80-90% transfected), neurons (31- 40% transfected), neural stem cells (39-62% transfected), oligodendrocytes (70-80% transfected) and astrocytes (44-76% transfected). Then, LNP formulations were assessed for delivering Cas9 mRNA and CD81 sgRNA (model protein) in murine syngeneic GBM model to enable gene editing in brain tumor cells. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~94% of brain tumor cells in vivo. In conclusion, we have developed a library of safe LNPs that can transfect GBM cells in vivo with high efficacy. This technology can potentially be used to develop novel mRNA therapies for GBM by delivering single or multiple mRNAs and holds great potential as a tool to study brain tumor biology.
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BACKGROUND: Pregnant women are vulnerable against COVID-19 infection due to physiological and immunological changes. COVID-19 in pregnancy affects fetal well-being with a potential for vertical infection. AIM: This study aims to determine the incidence of vertical infection and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants born to mothers with positive COVID-19 infection. MATERIALS AND METHODS: Amniotic fluid, swabs of the newborn's nasopharynx and oropharynx, and swabs of the placenta were examined using reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. Serological examination was performed by Electro-Chemiluminescence Immunoassay on infant's blood. RESULT(S): Four of 33 pregnant women gave birth to infants positive SARS-CoV-2 infection. RT-PCR examination of all amniotic fluid and placental swabs was negative for SARS-CoV-2. Four of 33 infants (12.1%) showed negative polymerase chain reaction (PCR) results but positive SARS-CoV-2 antibodies, another 4 newborns (12.1%) showed positive PCR results, but no SARS-CoV-2 antibodies detected. The remaining 25 babies (75.8%) showed both negative PCR and serologic results. CONCLUSION(S): No evidence of vertical transmission found in this study.Copyright © 2023 Cut Meurah Yeni, Zinatul Hayati, Sarjani M. Ali, Hasanuddin Hasanuddin, Rusnaidi Rusnaidi, Cut Rika Maharani.
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With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest. Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A highthroughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail. The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.
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Objectives: The coronavirus disease 2019 (COVID-19) pandemic has imposed significant burden on Brazil's health system. The present study aims to describe patients' demographic and clinical characteristics, vaccine uptake and assess healthcare resource utilization (HCRU) and costs associated with acute COVID-19 in Brazil during the Omicron predominant period. Method(s): A population-based retrospective study was conducted using the National Health Data Network (RNDS), National Vaccination Campaign against COVID-19 data and surveillance data in public setting. Individuals with positive COVID-19 test results between January-April 2022 were identified. Patients' demographics, comorbidities, vaccination status, HCRU for those who were admitted to hospitals and their associated costs were described by age groups. Result(s): A total of 8,160,715 COVID-19 cases were identified and 2.7% were aged <5 years, 11.6% were 5-19 years, 76.9% were 20-64 years and 8.7% were >= 65 years. The presence of comorbidity was 23.1% with a higher prevalence of comorbidities in the elderly (61.8% for 65-74 years and 71.2% for >=75 years). Regarding COVID -19 vaccination uptake, among those aged <=19 years, 20-64 years and >=65 years, 40.6%, 86.5% and 92.2% had primary series, respectively. Among adults, the booster uptake was 47.3% and 75.8% for those aged 20-64 years and >= 65 years, respectively. Among those with confirmed COVID-19, regardless of vaccination status, 87% were being symptomatic and 1.7% were hospitalized (3.8% in aged <5 years, 4.2% in 5-19 years, 34.3% in 20-64 years and 57.6% in >= 65 years). Among hospitalized patients, 32,6% were admitted to ICU and 80% required mechanical ventilation support. The average cost per day in normal wards and ICU without ventilation was R$291,89 and R$923,90, respectively. Conclusion(s): Our results quantify the public health and economic burden of COVID-19 in Brazil, suggesting substantial healthcare resources required to manage the COVID-19 pandemic.Copyright © 2023
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Objectives: The COVID pandemic has imposed significant direct medical cost and resource use burden on healthcare systems. This study described the patient demographic and clinical characteristics, healthcare resource utilization and costs associated with acute COVID in adults in England. Method(s): This population-based retrospective study used linked primary care (Clinical Practice Research Datalink, CPRD, Aurum) and secondary care (Hospital Episode Statistics) data to identify: 1) hospitalized (admitted within 12 weeks of a positive COVID-19 PCR test between August 2020 and March 2021) and 2) non-hospitalized patients (positive test between August 2020 and January 2022 and managed in the community). Hospitalization and primary care costs, 12 weeks after COVID diagnosis, were calculated using 2021 UK healthcare reference costs. Result(s): We identified 1,706,368 adult COVID cases. For hospitalized (n=13,105) and non-hospitalized (n=1,693,263) cohorts, 84% and 41% considered high risk for severe COVID using PANORAMIC criteria and 41% and 13% using the UKHSA's Green Book for prioritized immunization groups, respectively. Among hospitalized cases, median (IQR) length of stay was 5 (2-7), 6 (4-10), 8 (5-14) days for 18-49 years, 50-64 years and >= 65 years, respectively;6% required mechanical ventilation support, and median (IQR) healthcare costs (critical care cost excluded) per-finished consultant episode due to COVID increased with age (18-49 years: 4364 (1362-4471), 50-64 years: 4379 (4364-5800), 65-74 years: 4395 (4364-5800), 75-84 years: 4473 (4364-5800) and 85+ years: 5800 (4370-5807). Among non-hospitalized cases, older adults were more likely to seek GP consultations (13% of persons age 85+, 9% age 75-84, 7% age 65-74, 5% age 50-64, 3% age 18-49). Of those with at least 1 GP visit, the median primary care consultation total cost in the non-hospitalized cohort was 16 (IQR 16-31). Conclusion(s): Our results quantify the substantial economic burden required to manage adult patients in the acute phase of COVID in England.Copyright © 2023
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Objectives: To evaluate COVID-19 vaccines in primary prevention against infections and lessening the severity of illness following the most recent outbreak of the SARS-CoV-2 Omicron variant in Shanghai. Method(s): To investigate whether inactivated vaccines were effective in protecting against COVID-19 infections, we estimated the odds ratio (OR) of the vaccination in COVID-19 cases vs. matched community-based healthy controls. To evaluate the potential benefits of vaccination in lowering the risk of symptomatic infection (vs. asymptomatic), we estimated the relative risk (RR) of symptomatic infections among diagnosed patients. We also applied the multivariate stepwise Logistic regression analyses to measure the risk of disease severity (symptomatic vs. asymptomatic and moderate/severe vs. mild) in COVID-19 patient cohort with vaccination status as an independent variable while controlling for potential confounding factors. Result(s): Out of the 153,544 COVID-19 patients included in the analysis, 118,124 (76.9%) patients had been vaccinated and 143,225(93.3%) were asymptomatic patients. Of the 10,319 symptomatic patients, 10,031(97.2%), 281(2.7%) and 7(0.1%) experienced mild, moderate, and severe infections, respectively. There is no evidence that the vaccination helped protect from infections (OR=0.82, p=0.613). The vaccination, however, offered a small but significant protection against symptomatic infections (RR=0.92, p < 0.001) and halved the risk of moderate/severe infections (OR=0.48, 95% CI: 0.37 - 0.61). Older age (> 60 years) and malignant tumors were significantly associated with moderate/severe infections. Gender also appeared to be a risk factor for symptomatic infections, with females being associated with a lower risk for moderate/severe illness. Conclusion(s): Inactivated COVID-19 vaccines helped provide a small but significant protection against symptomatic infections and halved risk of moderate/severe illness among symptomatic patients. The vaccination was not effective in blocking COVID-19 Omicron variant community spread.Copyright © 2023
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Objectives: This study aimed to determine disease severity, clinical features, clinical outcome in hospitalized patients with the Omicron variant and evaluate the effectiveness of one-dose, two-dose, and three-dose inactivated vaccines in reducing viral loads, disease course, ICU admissions and severe diseases. Method(s): Retrospective cohort analysis was performed on 5,170 adult patients (>=18 years) identified as severe acute respiratory syndrome coronavirus 2 positive with Reverse Transcription Polymerase Chain Reaction admitted at Shanghai Medical Center for Gerontology between March 2022 and June 2022. COVID-19 vaccination effectiveness was assessed using logistic regression models evaluating the association between the risk of vaccination and clinical outcomes, adjusting for confounders. Result(s): Among 5,170 enrolled patients, the median age was 53 years, and 2,861 (55.3%) were male. 71.0% were mild COVID-19 cases, and cough (1,137 [22.0%]), fever (592 [11.5%]), sore throat (510 [9.9%]), and fatigue (334 [6.5%]) were the most common symptoms on the patient's first admission. Ct values increased generally over time and 27.1% patients experienced a high viral load (Ct value< 20) during their stay. 105(2.0%) of these patients were transferred to the intensive care unit after admission. 97.1% patients were cured or showed an improvement in symptoms and 0.9% died in hospital. The median length of hospital stay was 8.7+/-4.5 days. In multivariate logistic analysis, booster vaccination can significantly reduce ICU admissions and decrease the severity of COVID-19 outcome when compared with less doses of vaccine (OR=0.75, 95%CI, 0.62-0.91, P<=0.005;OR=0.99, 95%CI, 0.99-1.00, p<0.001). Conclusion(s): In summary, the most of patients who contracted SARSCoV-2 omicron variant had mild clinical features and patients with vaccination took less time to lower viral loads. As the COVID-19 pandemic progressed, an older and less vaccinated population was associated with higher risk for ICU admission and severe disease.Copyright © 2023
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Objective. To assess the relationship between the severity of COVID-19 in patients without significant baseline cardiovascular pathology and various echocardiographic parameters of myocardial dysfunction. Material and methods. 46 patients with COVID-19 were included in our study: 33 patients of moderate severity and 13 - with severe disease. On days 1 and 9 upon admission, all patients underwent an echocardiographic study with standard assessment of the both ventricles function, as well as an assessment of their global longitudinal strain (GLS). Comparison of the studied parameters was carried out both between groups of patients and within each group in dynamics. Results. On day 1patients in the severe group had higher values of the systolic gradient on the tricuspid valve (22.0 [21.0;26.0] vs 30.0 [24.0;34.5] mm Hg, p = 0.02), systolic excursion of the plane of the tricuspid ring (2.3 [2.1;2.4] vs 2.0 [1.9;2.2] mm, p = 0.016), E/e' ratio (9.5 [7.7;8.9] vs 7.5 [6.8;9.3], p = 0.03). At day 9 among patients in the severe group, there was a decrease in end-diastolic (111.0 [100.0;120.0] vs 100.0 [89.0;105.0] ml, p = 0.03) and of end-systolic (35.5 [32.0;41, 2] vs 28.0 [25.0;31.8] ml, p < 0.01) volumes of the left ventricle. There was a decrease in GLS of the both ventricles compared to general accepted values. In dynamics, there was an increase in the GLS of the right ventricle in both groups, but it was more pronounced among severe group of patients (day 1 -18.5 [-15.2;-21.1] vs -20.2 [-15.8.1;-21.1] %, p = 0.03). The troponin levels were in the normal range. Conclusion. In COVID-19 patients without significant baseline cardiovascular pathology, there is a transient decrease in longitudinal strain of both ventricles, even in the absence of clinical and laboratory signs of acute myocardial injury.Copyright © Creative Cardiology 2021.
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Introduction: The COVID-19 pandemic has required clinical teams to function with an unprecedented amount of uncertainty, balancing complex risks and benefits in a highly fluid environment. This is especially the case when considering the delivery of a pregnant woman critically unwell with COVID-19. This is one maternal critical care team's reflections on establishing best practice and a shared mental model when undertaking a Caesarean section in critically unwell patients with COVID-19. Objective(s): We describe our experience of balancing the risks and streamlining the process of this high-risk intervention. Method(s): We used our standard clinical governance forums across four specialties (Obstetrics, Intensive care, Anaesthetics and Neonatology) to identify key challenges and learning points. We developed a working group to combine our learning and develop a shared mental model across the involved teams. Result(s): 1. The decision to deliver must be multidisciplinary involving Obstetrics, Intensive care, Anaesthetics, Neonatology and the patient according to their capacity to participate. The existing structure of twice daily ITU ward rounds could be leveraged as a 'pause' moment to consider the need for imminent delivery and review the risk-benefit balance of continued enhanced pharmacological thromboprophylaxis. 2. We identified a range of scenarios that our teams might be exposed to: 3. Perimortem Caesarean section 4. Critically unwell - unsafe to move to theatre 5. Critically unwell - safe to move to theatre 6. Recreating an obstetric theatre in the ICU Advantages Avoids moving a critically unstable patient, although our experience is increasing moving patients for ECMO. Some forms of maximal non-invasive therapy such as High Flow Nasal Oxygen may require interruption to move to theatre with resultant risk of harm or be difficult to continue in transport mode through a bulky ICU ventilator e.g. CPAP Disadvantages Significant logistics and coordination burden: multiple items of specialist equipment needing to be brought to the ICU. Human factors burden: performing a caesarean section in an unfamiliar environment is a significant increase in cognitive load for participating teams. Environmental factors: ICU side rooms may offer limited space vs the need to control the space if performed on an open unit. Delivering a Neonate into a COVID bubble. Conclusion(s): Developing a shared mental model across the key teams involved in delivering an emergency caesarean section in this cohort of critically unwell patients has enabled our group to own a common understanding of the key decisions and risks involved. We recommend a patient centred MDT decision making model, with a structure for regular reassessment by senior members of the teams involved. In most circumstances the human factors and logistical burden of recreating an operating theatre in the ICU outweighs the risk of transport to theatre. Pre-defined checklists and action cards mitigate the cognitive and logistical burden when multiple teams do perform an operative delivery in ICU. Action cards highlight key aspects of routine obstetric care to be replicated in the ICU environment.