bluuebunny/crossref_metadata_2025 huggingface dataset:
Inotropic agents in cardiogenic shock
Authors: Polyzogopoulou Eftihia , Arfaras-Melainis Angelos , Bistola Vasiliki , Parissis John
Published: June 2020

Purpose of review

Cardiogenic shock is a multifactorial and diverse entity in which inotropes are the cornerstone therapy. Although published clinical trials have focused on pharmacologic treatment of cardiogenic shock, there is lack of an established and widely accepted decision-making algorithm on the use of inotropic agents in cardiogenic shock.

Recent findings

The current review incorporates cardiogenic shock pathophysiology, inotropes and vasopressors pharmacodynamics. It emphasizes on each agent's indications, potential adverse effects, highlights special considerations and fsummarizes the recent guidelines.

Finally, proposes an algorithm of inotropes and vasopressors use and their potential combinations based on the clinical stage of cardiogenic shock. This algorithm can be used as a guide during the initial management of cardiogenic shock while underlying cause investigation is underway.
DNA methylation and incident cardiovascular disease
Authors: Westerman Kenneth E. , Ordovás José M.
Published: June 2020

Purpose of review

DNA methylation is an epigenetic mark that reflects both genetic and environmental influences over the life course and has the potential to be a robust biomarker for cardiovascular disease (CVD) risk. However, standard association studies linking DNA methylation and CVD are susceptible to reverse causation and may not directly translate into useful biomarkers of future disease. Studies of incident CVD represent a crucial tool for improving this evidence base.

Recent findings

Recent investigations have started to provide links between DNA methylation and incident CVD. Epigenome-wide association studies have suggested individual genetic loci in which differential methylation exists prior to disease onset, while multivariate predictive modeling approaches have made progress towards realizing the potential for DNA methylation as a predictive biomarker of CVD risk. Meanwhile, complementary analysis strategies such as Mendelian randomization have provided clues as to the causality of these epigenomic associations.

Taken together, this wave of studies provides the basis for a better understanding of CVD pathophysiology and the development of more confident biomarkers of CVD risk.
Machine-learning algorithms for predicting results in liver transplantation: the problem of donor–recipient matching
Authors: Briceño Javier , Ayllón María Dolores , Ciria Rubén
Published: June 2020

Purpose of review

Classifiers based on artificial intelligence can be useful to solve decision problems related to the inclusion or removal of possible liver transplant candidates, and assisting in the heterogeneous field of donor–recipient (D-R) matching.

Recent findings

Artificial intelligence models can show a great advantage by being able to handle a multitude of variables, be objective and help in cases of similar probabilities. In the field of liver transplantation, the most commonly used classifiers have been artificial neural networks (ANNs) and random forest classifiers. ANNs are excellent tools for finding patterns which are far too complex for a clinician and are capable of generating near-perfect predictions on the data on which they are fit, yielding excellent prediction capabilities reaching 95% for 3 months graft survival. On the other hand, RF can overcome ANNs in some of their limitations, mainly because of the lack of information on the variables they provide. Random forest algorithms may allow for improved confidence with the use of marginal organs and better outcome after transplantation.

ANNs and random forest can handle a multitude of structured and unstructured parameters, and establish non explicit relationships among risk factors of clinical relevance.
Outcome of Core Binding Factor Acute Myeloid Leukemia in Children: A Single-Center Experience
Authors: Mansoor Neelum , Jabbar Naeem , Arshad Uzma , Maqsood Sidra , Habib Muhammad A. , Raza Muhammad R.
Published: June 2020

Childhood acute myeloid leukemia (AML) harboring core binding factor (CBF)–associated translocations are considered as a favorable cytogenetic subgroup. The 2 major subtypes of CBF-AML include t(8;21) and inversion of chromosome 16, accounting for ∼25% of patients. Because of expensive and toxic treatment, which may require hospitalization during the entire course of induction chemotherapy, most of the centers in Pakistan neither workup for this low-risk entity nor offer curative treatment. Therefore, we adopted an approach of screening AML cases for the presence of CBF with the rationale of offering curative treatment to this subgroup. Data of 244 cases were reviewed, and translocations were found in 72 (34%) patients among them, 59 (82%) had t(8;21) and 13 (18%) showed inversion of chromosome 16. The event-free survival with and without abandonment was 36% and 40%, respectively. Among 44 patients who completed treatment, 26 (59%) are leukemia-free, while 18 (41%) relapsed. None of the relapsed patients received salvage chemotherapy or hematopoietic stem cell transplant. Treatment-related mortality and abandonment was found in 24% and 10% of patients, respectively. The frequency of CBF-AML is higher in our study; however, poor outcome demands holistic measures in supportive care to improve the survival.
Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer
Authors: Coleman Robert L. , Spirtos Nick M. , Enserro Danielle , Herzog Thomas J. , Sabbatini Paul , Armstrong Deborah K. , Kim Jae-Weon , Park Sang-Yoon , Kim Byoung-Gie , Nam Joo-Hyun , Fujiwara Keiichi , Walker Joan L. , Casey Ann C. , Alvarez Secord Angeles , Rubin Steve , Chan John K. , DiSilvestro Paul , Davidson Susan A. , Cohn David E. , Tewari Krishnansu S. , Basen-Engquist Karen , Huang Helen Q. , Brady Mark F. , Mannel Robert S.
Published: June 2020

(Abstracted from N Engl J Med 2019;381:1929–1939)

The National Comprehensive Cancer Network recommends secondary cytoreduction for ovarian cancer patients with recurrent disease who have received no treatment for a period of 6 months following a complete response from prior chemotherapy. Retrospective reviews and meta-analyses have shown the most benefit from this operation in those with platinum-sensitive disease and those with little or no postoperative residual disease.
Prospective Evaluation of Maternal Sleep Position Through 30 Weeks of Gestation and Adverse Pregnancy Outcomes
Authors: Silver Robert M. , Hunter Shannon , Reddy Uma M. , Facco Francesca , Gibbins Karen J. , Grobman William A. , Mercer Brian M. , Haas David M. , Simhan Hyagriv N. , Parry Samuel , Wapner Ronald J. , Louis Judette , Chung Judith M. , Pien Grace , Schubert Frank P. , Saade George R. , Zee Phyllis , Redline Susan , Parker Corette B.
Published: June 2020

(Abstracted from Obstet Gynecol 2019;134:667–676)

Maternal sleep position has been associated with adverse pregnancy outcomes including fetal growth restriction and stillbirth. Despite prior data suggesting a relation between supine sleep position and adverse pregnancy outcomes, there remains uncertainty in regard to the validity of these findings, due to the potential for recall bias.
A Patient With Acute Cervical Cord Injury and COVID-19
Authors: Pattanakuhar Sintip , Tangvinit Chatchai , Kovindha Apichana
Published: June 2020

During the pandemic of coronavirus disease 2019, it is possible for rehabilitation physicians and personnel to take care of patients with concurrent spinal cord injury and coronavirus disease 2019. Here, we describe a case of acute cervical spinal cord injury resulting in complete tetraplegia C5 American Spinal Injury Association Impairment Scale A with unrecognized, severe acute respiratory syndrome coronavirus 2 infection. This resulted in large-scale quarantines of related surgical and rehabilitation staff, and the unexpected death of the patient despite receiving the treatments according to the standard guideline. Rehabilitation personnel who take care of acute spinal cord injury patients with coronavirus disease 2019 should consider the effect of spinal cord injury on the course of coronavirus disease 2019, the effect of coronavirus disease 2019 and its treatments on the course of spinal cord injury, and risks of severe acute respiratory syndrome coronavirus 2 transmission between patients and rehabilitation staff, to continue providing safe and effective rehabilitation programs.
Pseudologia Fantastica: An Elaborate Tale of Combat-related PTSD
Authors: GREY JESSICA S. , DURNS TYLER , KIOUS BRENT M.
Published: June 2020

Pseudologia fantastica (PF), also known as mythomania or pathologic lying, is a well-known yet controversial phenomenon in psychiatry. There is no firm conceptualization of PF, nor are there any widely accepted diagnostic criteria for PF. The condition may be related to low self-esteem, and it shows some overlap with narcissistic personality disorder and other Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) cluster B personality disorders. Given the mysteriousness and rarity of PF, there is a dearth of information to guide diagnosis and even more limited information about effective treatments. Here, we discuss a case in which an adult male patient exhibited protracted symptoms that were consistent with PF, which consisted of elaborate falsifications pertaining to a history of military service that had duped even close family members. We describe the patient’s presentation and the careful process of confrontation and acquisition of collateral information used to reach the diagnosis, along with the patient’s efforts to avoid accepting the truth by constructing a series of even more elaborate stories. Finally, we underscore the importance of maintaining a therapeutic alliance in caring for patients with PF through frequent displays of uniform positive regard, and we describe the approach to treatment used during the patient’s hospital stay.
The Clinical Efficacy of Surgical Removal of Hepatocellular Carcinoma in Caudate Lobe in the Chinese Population: A Case-control Study
Authors: Zhou Xin-Feng , Xia Qing , Xie Shu-Jie
Published: June 2020

Our aims were to compare the therapeutic efficacy of surgical resection of caudate lobe hepatocellular carcinoma and noncaudal lobe hepatocellular carcinoma in the Chinese population. The study group consisted of 220 patients undergoing caudate lobe hepatectomy during the period spanning from January 2003 to November 2017, and 220 patients with caudate lobe hepatectomy were selected as the control group. There were 142 cases (64.5%) of surgical margin of R0 in patients with caudate lobe liver cancer, and 178 cases (80.9%) of surgical margins in patients with noncaudal lobe liver cancer, and the difference was statistically significant (P<0.01) between the 2 groups. Compared with noncaudal lobe liver cancer patients, caudate lobe liver cancer patients had significantly longer operation time (186.65±81.36 vs. 118.85±69.23, P<0.01), longer vessel block time (29.93±11.96 vs. 22.76±10.74, P<0.01), more intraoperative blood loss (709.73±108.39 vs. 329.74±85.76, P<0.01), and there was no significant difference in the incidence of complications (53.4% vs. 46.6%, P>0.05). Significantly different therapeutic efficacy was found between the caudate lobe hepatocellular carcinoma group and the noncaudal lobe hepatocellular carcinoma group, which may be due to the lack of resection margin of caudate-leaf liver cancer surgery and more intraoperative bleeding.
Design of a Study to Measure Patient-Perspectives in Adverse Event Reporting (the PPAR Study): Supplementary Study to the ASPIRe Trial
Authors: Sung Vivian W. , Menefee Shawn , Dunivan Gena , Richter Holly E. , Moalli Pamela , Weidner Alison , Andy Uduak Umoh , Jelovsek Eric , Mazloomdoost Donna , Whitworth Ryan , Thomas Sonia ,   for the NICHD Pelvic Floor Disorders Network
Published: June 2020

Objectives

The primary objective of this study is to compare patient versus physician rankings of adverse event (AE) and adverse symptom (AS) severity after pelvic reconstructive surgery. Secondary objectives include to estimate the association between patient rankings of AEs/ASs with decision-making and quality-of-life outcomes and to determine whether patient perspective about AE/AS changes over time.

Methods

This is a supplementary study, Patient-Perspectives in Adverse Event Reporting (PPAR), to the index trial, ASPIRe (Apical Suspension Repair for Vault Prolapse In a Three-Arm Randomized Trial Design). During the trial, AEs/ASs will be assessed by physicians longitudinally every 6 months, which includes a determination of the AE/AS grade severity. For PPAR, additional patient perspective will be measured for 19 predetermined AEs/ASs at the time of identification and again at 12 and 36 months postoperatively. Decision-making and quality-of-life questionnaires will be collected at these time points. The primary outcome, the overall interrater agreement between patient and physician rankings for AE/AS severity, will be determined using a repeated-measures concordance correlation coefficient.

Results

To date, the index trial has completed enrollment, and follow-up is ongoing.

Conclusions

The PPAR methods for incorporating patient perspective in the measurement of AEs/ASs to determine their agreement with physician ranking, long-term relevance, and impact on treatment decision making and quality of life are described. This will contribute to improved measurements of AEs/ASs in future research with the goal of improving patient counseling and informing expectations and treatment decision making.
The First Injection: Rates of Urinary Retention in Women With Urgency Incontinence Treated With Intravesical OnabotulinumtoxinA Injection
Authors: Squires Natalie A. , Mueller Margaret G. , Lewicky-Gaupp Christina , Collins Sarah A. , Kenton Kimberly S. , Geynisman-Tan Julia
Published: June 2020

Objective

The aim of the study was to describe the rate of symptomatic and asymptomatic urinary retention and catheterization in women undergoing initial intravesical onabotulinumtoxinA (BnTA) injection for urgency urinary incontinence (UUI).

Methods

This retrospective chart review included women receiving initial 100 U of BnTA injection for UUI for 5 years. Straight-catheterized postvoid residuals (PVRs) were performed 2 weeks after the injection. Women without the sensation of incomplete bladder emptying, worsened urgency, inability to void, or suprapubic pain but with PVR of greater than 300 mL were characterized as having asymptomatic retention, whereas women with a PVR of greater than 150 and any of these symptoms were diagnosed with symptomatic retention.

Results

One hundred eighty-seven 187 patients received initial BnTA injection. The majority were postmenopausal (89%) and white (82%) with a mean age of 65 years and body mass index of 30 kg/m2. One-third of the cohort underwent baseline urodynamic studies. At 2 weeks after injection, 163 patients (87%) followed up, and 17 (10%) had either asymptomatic or symptomatic retention (2% and 8%, respectively). There were no differences in demographic or pretreatment urodynamic parameters in women with and without retention except that women who had previous anti–stress urinary incontinence procedures were more likely to experience retention (53% vs 18%, P = 0.002) despite similar baseline PVRs.

Conclusion

We demonstrated that the rate of retention requiring catheterization after 100 U BnTA may be as high as 10% although only 5% develop PVRs for 300 mL and only 2% have asymptomatic retention for 300 mL.
Anterior Bilateral Sacrospinous Ligament Fixation: A Safe Route for Apical Repair
Authors: Solomon Ellen R. , St. Marie Peter , Jones Keisha A. , Harmanli Oz
Published: June 2020

Objectives

Traditionally, sacrospinous ligament fixation is performed unilaterally with a posterior dissection for correction of apical vaginal prolapse. There is limited information on alternative techniques including bilateral application and use of anterior vaginal dissection for this procedure. The objective of this study is to evaluate the anatomic and perioperative outcomes in women who have undergone bilateral sacrospinous ligament fixation through an anterior approach.

Methods

This cohort represents women in our prospective repository who underwent anterior approach bilateral sacrospinous ligament fixation between September 2011 and June 2014. Concomitant procedures were performed as indicated. Pelvic organ prolapse quantification points were measured preoperatively and at 6 weeks and 6 months postoperatively and were compared. Perioperative outcome measures and adverse events were also analyzed.

Results

In this cohort, 144 women underwent anterior approach to bilateral sacrospinous ligament fixation. The patients’ mean age was 57.8 ± 10.9 years, and the average body mass index was 29.6 ± 5.8 kg/m2. In patients who underwent anterior approach bilateral sacrospinous ligament fixation, points Aa, Ba, C, Gh, Ap, and Bp remained at stage I or less when compared with pelvic organ prolapse quantification measurements at the baseline. Perioperative and postoperative complications were minimal, with 1 (0.7%) patient requiring a blood transfusion and 3 (2%) patients suffered from intraoperative lower urinary tract injuries, none of which were attributable to the sacrospinous fixation part of the procedure.

Conclusions

Anterior approach bilateral sacrospinous ligament fixation is a safe and effective procedure for reestablishing apical support in a patient with apical vaginal prolapse.
Does a Hysterectomy Hurt? Comparing Narcotic Requirements and Pain Scores in Patients Undergoing Apical Prolapse Repair With or Without Hysterectomy
Authors: Gillingham Akira , Kenton Kimberly , Geynisman-Tan Julia , Brown Oluwateniola , Collins Sarah A. , Lewicky-Gaupp Christina , Mueller Margaret G.
Published: June 2020

Objective

The aim of the study was to compare narcotic requirements with early postoperative pain scores in women undergoing apical prolapse surgery with or without hysterectomy.

Methods

All cases of apical prolapse repair at our institution in 2016 were identified. The following was abstracted from the health record: demographics, comorbidities, procedure details, baseline and postoperative care unit (PACU) pain scores, and operating room (OR) and PACU narcotic doses. Doses were converted to morphine milligram equivalents (MME) for analysis. Correlations are reported using Pearson ρ.

Results

One hundred fifty-six cases were identified. Seventy-eight percent of participants were white and the mean ± SD age was 59 ± 11 years. One hundred seventeen patients (75%) underwent laparoscopic/robotic sacrocolpopexy, 35 (22%) native tissue vaginal repairs, and 4 (3%) open sacrocolpopexy. One hundred twenty-two patients (78%) underwent concomitant hysterectomy: 93 (76%) were laparoscopic, 25 (20%) vaginal, and 4 (4%) abdominal.

The groups were similar, with the exception of younger age and longer OR time in the hysterectomy group. Hysterectomy by any route was not associated with increased OR MMEs (29 vs 22, P = 0.22), PACU MMEs (13 vs 13, P = 0.54), 4-hour PACU pain scores (2.5 vs 2.0, P = 0.22), or 6-hour PACU pain scores (2.6 vs 2.3, P = 0.54). After controlling for age and OR time, there remained no differences in these variables. Likewise, when analyzing laparoscopic or vaginal groups separately on multivariate regression, there were no differences in MMEs or postoperative pain scores in patients with and without concomitant hysterectomy.

Conclusions

Concomitant hysterectomy at the time of prolapse repair does not increase pain medication requirements or patient-reported postoperative pain scores.
Genomic instability and cancer: lessons from
Drosophila
Authors: Gerlach Stephan U. , Herranz Héctor
Published: June 2020

Cancer is a genetic disease that involves the gradual accumulation of mutations. Human tumours are genetically unstable. However, the current knowledge about the origins and implications of genomic instability in this disease is limited. Understanding the biology of cancer requires the use of animal models. Here, we review relevant studies addressing the implications of genomic instability in cancer by using the fruit fly,
Drosophila melanogaster
, as a model system. We discuss how this invertebrate has helped us to expand the current knowledge about the mechanisms involved in genomic instability and how this hallmark of cancer influences disease progression.
Resistant maltodextrin intake reduces virulent metabolites in the gut environment: randomized control study in a Japanese cohort
Authors: Nishimoto Yuichiro , Mizuguchi Yoshinori , Mori Yuka , Ito Masaki , Miyazato Shoko , Kishimoto Yuka , Yamada Takuji , Fukuda Shinji
Published: June 2020

Objective

In recent years, there have been many reports on the effects of prebiotics on intestinal health. In particular, consuming resistant maltodextrin (RMD) has been reported to be beneficial. However, there has been no comprehensive quantification of the effect of RMD on the intestinal environment. Therefore, this study aimed to quantify the effects of RMD on the intestine, especially the intestinal microbiome and metabolome profiles.

Design

A randomized, double-blind controlled trial was conducted in 29 Japanese subjects with relatively high hemoglobin A1c (HbA1c). Subjects consumed RMD or placebo twice per day for 24 weeks. Blood and fecal samples were collected before and after intake. The intestinal environment was assessed by a metabologenomics approach combined with 16S rRNA gene-based microbiome and mass spectrometry-based metabologenomics analyses.

Results

The intake of RMD increased the levels of Bifidobacterium and Fusicatenibacter, and decreased deoxycholate. In addition, intake of the RMD lowered the levels of some virulent metabolites, such as imidazole propionate and trimethylamine, in subjects with an initially high amount of those metabolites.

Conclusion

RMD may have beneficial effects on the gut environment such as commensal microbiota modulation and reduction of virulence metabolites, known as a causative factor in metabolic disorders. However, its effect partially depends on the gut environmental baseline.
Increased expression of ACE2, the SARS-CoV-2 entry receptor, in alveolar and bronchial epithelium of smokers and COPD subjects
Authors: Jacobs Merel , Van Eeckhoutte Hannelore P , Wijnant Sara RA , Janssens Wim , Joos Guy F , Brusselle Guy G , Bracke Ken R
Published: June 2020

Rationale

Smokers and patients with chronic obstructive pulmonary disease (COPD) are at increased risk for severe Coronavirus Disease 2019 (COVID-19).

Objectives

We investigated the expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptor ACE2 and the protease TMPRSS2 in lung tissue from never smokers and smokers with and without COPD.

Methods

In a cross-sectional, observational study we measured mRNA expression of ACE2 and TMPRSS2 by RT-PCR in lung tissue samples from 120 well phenotyped subjects. Next, protein levels of ACE2 were visualized by immunohistochemistry on paraffin sections from 87 subjects and quantified in alveolar and bronchial epithelium. Finally, primary human bronchial epithelial cells (HBECs) were cultured at air liquid interface and exposed to air or cigarette smoke.

Results

ACE2 mRNA expression was significantly higher in lung tissue from current smokers and subjects with moderate to very severe COPD and correlated with physiological parameters of airway obstruction and emphysema. Pulmonary expression levels of TMPRSS2 were significantly higher in patients with (very) severe COPD and correlated significantly with ACE2 expression. Importantly, protein levels of ACE2 were elevated in both alveolar and bronchial epithelium of current smokers and subjects with moderate to very severe COPD. Finally, TMPRSS2 mRNA expression increased inin vitrocultured HBECs upon acute exposure to cigarette smoke.

Conclusions

We demonstrate increased expression of ACE2 in lungs of smokers and COPD subjects, which might facilitate host cell entry of SARS-CoV-2. These findings help identifying populations at risk for severe COVID-19.
Reinstatement of cortical outcome representations during higher-order learning
Authors: Luettgau Lennart , Porcu Emanuele , Tempelmann Claus , Jocham Gerhard
Published: June 2020

Naturalistic learning scenarios are characterized by infrequent experience of external feedback to guide behavior. Higher-order learning mechanisms like second-order conditioning (SOC) may allow stimuli that were never experienced together with reinforcement to acquire motivational value. Despite its explanatory potential for real-world learning, surprisingly little is known about the neural mechanism underlying such associative transfer of value in SOC. Here, we used multivariate cross-session, cross-modality searchlight classification on functional magnetic resonance imaging data obtained from humans during SOC. We show that visual first-order conditioned stimuli (CS) reinstate cortical patterns representing previously paired gustatory outcomes in the lateral orbitofrontal cortex (OFC). During SOC, this OFC region showed increased functional covariation with amygdala, where neural pattern similarity between second-order CS and outcomes increased from early to late stages of SOC. Our data suggest a mechanism by which motivational value is conferred to stimuli that were never paired with reinforcement.
Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon
Authors: Chamieh Amanda , Afif Claude , El-Hajj Gerard , Zmerli Omar , Djaffar-Jureidini Isabelle , Raad Roy A. , Ashou Raja , Juvelekian Georges , Rolain Jean-Marc , Azar Eid
Published: June 2020

1.

1.1.

Background/Purpose

We share our experience in COVID-19 pneumonia management at Saint George Hospital University Medical Center (SGHUMC) in Lebanon. In the absence of a standard of care, early diagnosis and opt-in therapy with Hydroxychloroquine and Azithromycin were offered.

1.2.

Methods

We reviewed records of COVID-19 pneumonia patients from March 16-April 26 2020. Based on NEWS score, we stratified patients as A: low B: medium, and C: high clinical severity and obtained pharmacotherapy data. Chest-CT-severity-score (CTSS) was used. We defined clinical cure as resolution of symptoms and biomarkers and virologic cure as a PCR above 35 cycles(Ct).

1.3.

Results

We recorded 21 COVID-19 pneumonia patients of whom 19 opted for treatment. Clinical symptoms and laboratory markers at presentation did not significantly correlate with severity. Lower initial viral load significantly correlated with lower levels of clinical and radiological severity (p=0.038). Virologic cure, Ct>35, by day 10, was only 33% in high severity significantly less than categories A and B. We observed 100% clinical cure at day 10 in Category-A, 67% in B, and 33% in C(p<0.05). Patients with the lowest severity had the fastest virologic cure in a mean of 5.8 days from diagnosis, shortest hospitalization and earlier radiological improvement(p<0.005). Ultimately, 18 patients were discharged home in good condition and one remains in the ICU.

1.4.

Conclusion

Viral dynamics matter in COVID-19 pneumonia. An early control of replication may be crucial in averting complications. Early administration of Hydroxychloroquine and Azithromycin potentially explains our 94.7% success rate in treating a fairly complex cohort of COVID-19 pneumonia.
Early CPAP reduced mortality in covid-19 patients. Audit results from Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust
Authors: Ashish Abdul , Unsworth Alison , Martindale Jane , Sedda Luigi , Sundar Ramachandran , Farrier Martin
Published: June 2020

COVID-19 infection typically causes pneumonia with bilateral changes on Chest radiograph. There is significant hypoxia and use of oxygen for patients admitted to hospital is standard. The use of Continuous Positive Airway Pressure (CPAP) in patients with COVID-19 has now become established as a common clinical practice based on recent experience. It is given as part of “best endeavours” treatment in the absence of sufficient evidence to guide best practice. The use of CPAP as a step up in clinical care is now common but has a poor evidence base.

Using routinely collected data, the use of CPAP as a supportive non-invasive ventilatory treatment is described in 35 patients with COVID infection. Patients given early CPAP and in particular within 48 hours of admission, are shown to have a better outcome (a significant probability of lower mortality) than patients who received late CPAP (more than 48 hours after admission).

Although the analysis is affected by a small sample size, the results have shown good evidence that supports the early use of CPAP in patients with COVID-19 infection.
Estimated Sp02/Fio2 ratio to predict mortality in patients with suspected COVID-19 in the Emergency Department: a prospective cohort study
Authors: von Vopelius-Feldt Johannes , Watson Daniel , Swanson-Low Carla , Cameron James
Published: June 2020

Background
This study examined whether the presence and severity of Type 1 Respiratory Failure (T1RF), as measured by the ratio of pulse oximetry to estimated fraction of inspired oxygen (SpO2/eFiO2 ratio), is a predictor of in-hospital mortality in patients presenting to the ED with suspected COVID19 infection.

Methods
We undertook a prospective observational cohort study of patients admitted to hospital with suspected COVID-19 in a single ED in England. We used univariate and multiple logistic regression to examine whether the presence and severity of T1RF in the ED was independently associated with in-hospital mortality.

Results
180 patients with suspected COVID19 infection met the inclusion criteria for this study, of which 39 (22%) died. Severity of T1RF was associated with increased mortality with odds ratios (OR) and 95% confidence intervals of 1.58 (0.49 to 5.14), 3.60 (1.23 to 10.6) and 18.5 (5.65 to 60.8) for mild, moderate and severe T1RF, respectively. After adjusting for age, gender, pre-existing cardiovascular disease, neutrophil-lymphocyte ration (NLR) and estimated glomerular filtration rate (eGFR), the association remained, with ORs of 0.63 (0.13 to 3.03), 3.95 (0.94 to 16.6) and 45.8 (7.25 to 290). The results were consistent across a number of sensitivity analyses.

Conclusions
Severity of T1RF in the ED is an important prognostic factor of mortality in patients admitted with suspected COVID19 infection. Current prediction models frequently do not include this factor and should be applied with caution. Further large scale research on predictors of mortality in COVID19 infection should include SpO2/eFiO2 ratios or a similar measure of respiratory dysfunction.
Dynamic regulation of translation quality control associated with ribosome stalling
Authors: Goldman Daniel H. , Livingston Nathan M. , Movsik Jonathan , Wu Bin , Green Rachel
Published: June 2020

Translation of problematic mRNA sequences induces ribosome stalling. Collided ribosomes at the stall site are recognized by cellular quality control machinery, resulting in dissociation of the ribosome from the mRNA and subsequent degradation of the nascent polypeptide and in some organisms, decay of the mRNA. However, the timing and regulation of these processes are unclear. We developed a SunTag-based reporter to monitor translation in real time on single mRNAs harboring difficult-to-translate poly(A) stretches. This reporter recapitulates previous findings in human cells that an internal poly(A) stretch reduces protein output ∼10-fold, while mRNA levels are relatively unaffected. Long-term imaging of translation indicates that poly(A)-containing mRNAs are robustly translated in the absence of detectable mRNA cleavage. However, quantification of ribosome density reveals a ∼3-fold increase in the number of ribosomes on poly(A)-containing mRNAs compared to a control mRNA, consistent with queues of many stalled ribosomes. Using single-molecule harringtonine runoff experiments, we observe the resolution of these queues in real-time by the cellular quality control machinery, and find that rescue is very slow compared to both elongation and termination. We propose that the very slow clearance of stalled ribosomes provides the basis for the cell to distinguish between transient and deleterious stalls, and that the human quality control apparatus predominantly targets the nascent protein rather than the mRNA.
Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19
Authors: Jahromi Reza , Mogharab Vahid , Jahromi Hossein , Avazpour Arezoo
Published: June 2020

Our surrounding environment, especially often-touched contaminated surfaces, plays an important role in the transmission of pathogens in society. The shortage of effective sanitizing fluids, however, became a global challenge quickly after the coronavirus disease-19 (COVID-19) outbreak in December 2019. In this study, we present the effect of surfactants on coronavirus (SARS-CoV-2) virucidal efficiency in sanitizing fluids. Sodium dodecylbenzenesulfonate (SDBS), sodium laureth sulfate (SLS), and two commercial dish soap and liquid hand soap were studied with the goal of evaporation rate reduction in sanitizing liquids to maximize surface contact time. Twelve fluids with different recipes composed of ethanol, isopropanol, SDBS, SLS, glycerin, and water of standardized hardness (WSH) were tested for their evaporation time and virucidal efficiency. Evaporation time increased by 17-63% when surfactant agents were added to the liquid. In addition, surfactant incorporation enhanced the virucidal efficiency between 15-27% according to the 4-field test in the EN 16615:2015 European Standard method. Most importantly, however, we found that surfactant addition provides a synergistic effect with alcohols to inactivate the SARS-CoV-2 virus. This study provides a simple, yet effective solution to improve the virucidal efficiency of commonly used sanitizers.
Endotoxemia and circulating bacteriome in severe COVID-19 patients
Authors: Sirivongrangson Phatadon , Kulvichit Win , Payungporn Sunchai , Pisitkun Trairak , Chindamporn Ariya , Peerapornratana Sadudee , Pisitkun Prapaporn , Chitcharoen Suwalak , Sawaswong Vorthon , Worasilchai Navaporn , Kampunya Sarinya , Putcharoen Opass , Thawitsri Thammasak , Leelayuwatanakul Nophol , Kongpolprom Napplika , Phoophiboon Vorakamol , Sriprasart Thitiwat , Samransamruajkit Rujipat , Tungsanga Somkanya , Tiankanon Kanitha , Lumlertgul Nuttha , Leelahavanichkul Asada , Sriphojanart Tueboon , Tantawichien Terapong , Thisyakorn Usa , Chirathaworn Chintana , Praditpornsilpa Kearkiat , Tungsanga Kriang , Eiam-Ong Somchai , Sitprija Visith , Kellum John A. , Srisawat Nattachai
Published: June 2020

Purpose

When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium are injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19.

Methods

We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on day 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1→3)-β-D-Glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome.

Results

Of the 19 patients, 14 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime.

Conclusions

Bacterial DNA and toxins were discovered in virtual all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease
Efficacy and Safety of Leflunomide for Refractory COVID-19: An Open-label Controlled Study
Authors: Wang Qiang , Guo Haipeng , Li Yu , Jian Xiangdong , Hou Xinguo , Zhong Ning , Fei Jianchun , Su Dezhen , Bian Zhouyan , Zhang Yi , Hu Yingying , Sun Yan , Yu Xueyuan , Li Yuan , Jiang Bei , Li Yan , Qin Fengping , Wu Yingying , Gao Yanxia , Hu Zhao
Published: June 2020

OBJECTIVE

To evaluate the safety and efficacy of leflunomide for the treatment of refractory COVID-19 in adult patients.

DESIGN

Open-label controlled study

SETTING

A designated hospital for patients with refractory COVID-19 in Wuhan, China.

PARTICIPANTS

27 hospitalized adult patients (≥18 years of age) with radiologically confirmed pneumonia and SARS-CoV-2 positive for more than 28 days despite standard care were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC.

MAIN OUTCOME MEASURES

The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate.

RESULTS

Twelve patients enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide versus 16.7% for grp 1 patients (2/12) (P=0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12, IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (P=0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 versus 8.3% (1/12) for grp 1 (P=0.001). The 30-day discharge rate was 100% (15/15) for the grp 2 versus 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported.

CONCLUSION

Leflunomide is effective in enhancing SARS-CoV-2 clearance and hospital discharge in refractory COVID-19 patients. The addition of leflunomide to SOC did not increase adverse events versus SOC. These preliminary observations underscore a need for a randomized clinical study of leflunomide in SARS-CoV-2 infection.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Based on the large numbers of global infected patients of SARS-CoV-2, there will be many patients on persist viral positive which is named refractory covid-19. Specific medication for the treatment of the refractory covid-19 has been approved.

Leflunomide has been widely used in rheumatoid arthritis and psoriatic arthritis with good safety and tolerance. Recently, it is found an activity of anti-SARS-CoV-2 in vitro and the effective concentration of leflunomide is within the recognized therapeutic level for rheumatoid arthritis.

WHAT THIS STUDY ADDS

Leflunomide is effective in enhancing SARS-CoV-2 clearance and hospital discharge in refractory COVID-19 patients. The safety and tolerability of the 14-28-day course of treatment with leflunomide is acceptable.
The COVID-19 Critical Care Consortium observational study: Design and rationale of a prospective, international, multicenter, observational study
Authors: Li Bassi Gianluigi , Suen Jacky Y. , Barnett Adrian G. , Corley Amanda , Millar Jonathan E. , Fanning Jonathon P. , Lye India , Colombo Sebastiano , Wildi Karin , Livingstone Samantha , Abbate Gabriella , Hinton Samuel , Liquet Benoit , Shrapnel Sally , Dalton Heidi J. , Fraser John F.
Published: June 2020

Importance

There is a paucity of data that can be used to guide the management of critically ill patients with coronavirus disease 2019 (COVID-19). Global collaboration offers the best chance of obtaining these data, at scale and in time. In the absence of effective therapies, insights derived from real-time observational data will be a crucial means of improving outcomes.

Objective

In response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a research and data-sharing collaborative has been assembled to harness the cumulative experience of intensive care units (ICUs) worldwide. The resulting observational study provides a platform to rapidly disseminate detailed data and insights.

Design

The COVID-19 Critical Care Consortium observational study is an international, multicenter, prospective, observational study of patients with confirmed or suspected SARSCoV-2 infection admitted to ICUs.

Setting

This is an evolving, open-ended study that commenced on January 1st, 2020 and currently includes more than 350 sites in over 48 countries. The study enrolls patients at the time of ICU admission and follows them to the time of death, hospital discharge, or 28 days post-ICU admission, whichever occurs last.

Participants

All subjects, without age limit, requiring admission to an ICU for SARS-CoV-2 infection, confirmed by real-time polymerase chain reaction (PCR) and/or next-generation sequencing or with high clinical suspicion of the infection. Patients admitted to an ICU for any other reason are excluded.

Main outcomes and measures

Key data, collected via an electronic case report form devised in collaboration with the ISARIC/SPRINT-SARI networks, include: patient demographic data and risk factors, clinical features, severity of illness and respiratory failure, need for non-invasive and/or mechanical ventilation and/or extracorporeal membrane COVID–19 CCC observational study protocol oxygenation (ECMO), and associated complications, as well as data on adjunctive therapies. Final outcomes of in-hospital death, discharge or continuing admissions at 28 days.

Discussion

This large-scale, observational study of COVID-19 in the critically ill will provide rapid international characterization. Open-ended accrual will increase the power to answer hypothesis-led questions over time. Several sub-studies have already been initiated, examining hemostasis, neurological, cardiac, and long-term outcomes.
Is India heading towards a new high? : An optimistic approach to estimate ending life-cycle and cumulative cases by the end of the major COVID-19 pandemic wave in India and some of its states
Authors: Gupta P. , Sharma K. K. , Joshi S.D. , Goyal S.
Published: June 2020

Projecting the COVID-19 curve parameters such as ending-lifecycle and cumulative cases are helpful in guiding the policy makers to mitigate the outbreak. However, overestimating these parameters may put the public and policy makers in a muddle. In this paper, an optimistic scenario is simulated, wherein the dynamics of the COVID-19 curve is allowed to spread to such an extent that the projections of the COVID-19 parameters do not take excessively high values. Based on this scenario, the ending life-cycle and cumulative cases for India and some of its states, are predicted. Our study, suggests that the fall of the peak amplitude (95%) of the major COVID-19 wave in India may take place by the 8th of September 2020 with a total count of 655000 cases. Simulation results, also indicate that Maharashtra, Tamil Nadu, Delhi, Gujarat, Uttar Pradesh, Bihar, Madhya Pradesh, and Rajasthan may end up with 263700, 18140, 50600, 21130, 24420, 44170, 27080, and 28200 cumulative cases respectively.
Large-scale color biases in the retinotopic functional architecture are region specific and shared across human brains
Authors: Bannert Michael M. , Bartels Andreas
Published: June 2020

Despite the functional specialization in visual cortex, there is growing evidence that the processing of chromatic and spatial visual features is intertwined. While past studies focused on visual field biases in retina and behaviour, large-scale dependencies between coding of color and retinotopic space are largely unexplored in the cortex. Here we asked whether spatial color biases are shared across different human observers, and whether they are idiosyncratic for distinct areas. We tested this by predicting the color a person was seeing using a linear classifier that has never been trained on chromatic responses from that same brain, solely by taking into account: (1) the chromatic responses in other individuals’ brains and (2) commonalities between the spatial coding in brains used for training and the test brain. We were able to predict the color (and luminance) of stimuli seen by an observer based on other subjects’ activity patterns in areas V1-V3, hV4 and LO1. In addition, we found that different colors elicited systematic, large-scale retinotopic biases that were idiosyncratic for distinct areas and common across brains. The area-specific spatial color codes and their conservation across individuals suggest functional or evolutionary organization pressures that remain to be elucidated.

Significance statement

Does a color elicit comparable neural activity in two different observers? We addressed these questions, which involved the central test to predict what color someone is seeing based on their brain activity if it is only known how other brains respond to color. We estimated the commonalities across brains in the way they respond to achromatic, spatial stimulation, which allowed us to retinotopically align different brain responses to each other in a common response space. In this space derived without any color responses we could decode across brains what color an observer was seeing and found that spatial color biases differed between areas. Our results demonstrate systematic dependencies between chromatic and visual field representations that are area-specific and preserved across observers.
Patient ancestry significantly contributes to molecular heterogeneity of systemic lupus erythematosus
Authors: Catalina Michelle D. , Bachali Prathyusha , Yeo Anthony E. , Geraci Nicholas S. , Petri Michelle A. , Grammer Amrie C. , Lipsky Peter E.
Published: June 2020

Gene expression signatures can stratify patients with heterogeneous diseases, such as Systemic Lupus Erythematosus (SLE), yet understanding the contributions of ancestral background to this heterogeneity is not well elucidated. We hypothesized that ancestry would significantly influence gene expression signatures and measured 34 gene modules in 1566 SLE patients of african (AA), european (EA) or native american (NAA) ancestry to determine the impact of ancestry on gene expression. Healthy subject ancestry-specific gene expression provided the transcriptomic background upon which the SLE patient signatures were built. Although standard therapy affected every gene signature, and significantly increased myeloid cell signatures, logistic regression analysis determined that ancestral background significantly changed 23/34 gene signatures. Additionally, the strongest association to gene expression changes was autoantibodies and this also had etiology in ancestry; the AA predisposition to have both RNP and dsDNA autoantibodies compared to EA predisposition to have only antidsDNA. A machine learning approach was used to determine a gene signature characteristic to distinguish AA SLE and was most influenced by genes characteristic of the perturbed B cell axis in AA SLE patients.
Summer vacation and COVID-19: effects of metropolitan people going to summer provinces
Authors: Britton Tom , Ball Frank
Published: June 2020

Many countries are now investigating what the effects of summer vacation might be on the COVID-19 pandemic. Here one particular such question is addressed: what will happen if large numbers of metropolitan people visit a less populated province during the summer vacation? By means of a simple epidemic model, allowing for both short and long-term visitors to the province, it is studied which features are most influential in determining if such summer movements will result in large number of infections among the province population. The method is applied to the island of Gotland off the South East coast of Sweden. It is shown that the amount of mixing between the metropolitan and province groups and the fraction of metropolitan people being infectious upon arrival are most influential. Consequently, minimizing events gathering both the province and metropolitan groups and/or reducing the number of short-term visitors could substantially decrease spreading, as could measures to lower the fraction initially infectious upon arrival.