bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current choices of antibiotic treatment for Pseudomonas aeruginosa infections
Authors: Ibrahim Dima , Jabbour Jean-Francois , Kanj Souha S. 
Published: November 2020

Purpose of review

Pseudomonas aeruginosa is one of the most feared nosocomial pathogens. Treatment of P. aeruginosa infections is challenging because of the limited choices of antibiotics and the emergent resistance of the pathogen. The present review aims at addressing the management of P. aeruginosa infections and highlighting the novel antibiotics that show a future promising role.

Recent findings
Novel fluoroquinolones have been recently introduced and show favorable activity. New combinations of β-lactams/β-lactamase inhibitors have been studied in various indications of infections because of P. aeruginosa. Cefiderocol, a new cephalosporin, shows very promising results against P. aeruginosa. Currently, combination therapy is only recommended in limited scenarios. Extended-infusion of β-lactams exhibit clinical benefit. Bacteriophage therapy is a growing field of interest and may have an impactful effect on the treatment of resistant P. aeruginosa.

Summary
Factors that guide clinical decisions for empiric and directed P. aeruginosa therapy include the epidemiology, the patient's risk factors, the site of infection, and the available treatment options. Conventional antipseudomonal antibiotics have been used successfully for a long time, but the increase in worldwide resistance necessitates the need for newer agents. Antimicrobial stewardship is essential to preserve the new drugs and prevent future development of resistance.
Antibiotic treatment of common infections: more evidence to support shorter durations
Authors: Smith Benjamin J. , Heriot George , Buising Kirsty 
Published: November 2020

Purpose of review
Although there is increasing recognition of the link between antibiotic overuse and antimicrobial resistance, clinician prescribing is often unnecessarily long and motivated by fear of clinical relapse. High-quality evidence supporting shorter treatment durations is needed to give clinicians confidence to change prescribing habits. Here we summarize recent randomized controlled trials investigating antibiotic short courses for common infections in adult patients.

Recent findings
Randomized trials in the last five years have demonstrated noninferiority of short-course therapy for a range of conditions including community acquired pneumonia, intraabdominal sepsis, gram-negative bacteraemia and vertebral osteomyelitis.

Summary
Treatment durations for many common infections have been based on expert opinion rather than randomized trials. There is now evidence to support shorter courses of antibiotic therapy for many conditions.
Advocating the Development of Next-Generation, Advanced-Design Low-Field Magnetic Resonance Systems
Authors: Runge Val M. , Heverhagen Johannes T. 
Published: November 2020

Abstract
New next-generation low-field magnetic resonance imaging systems (operating in the range of 0.5 T) hold great potential for increasing access to clinical diagnosis and needed health care both in developed countries and worldwide. The relevant history concerning the choice of field strength, which resulted in 1.5 T still dominating today the number of installed systems, is considered, together with design advances possible because of interval developments, since low field was considered for clinical use in the 1980s, and current research. The potential impact of low-cost, advanced-generation low-field magnetic resonance imaging systems, properly designed, is high in terms of further dissemination of health care—across the gamut from industrial to developing countries—regardless of disease entity and anatomic region of involvement, with major niche applications likely as well.
HLA and AB0 Polymorphisms May Influence SARS-CoV-2 Infection and COVID-19 Severity
Authors: Amoroso Antonio , Magistroni Paola , Vespasiano Francesca , Bella Antonino , Bellino Stefania , Puoti Francesca , Alizzi Silvia , Vaisitti Tiziana , Boros Stefano , Grossi Paolo Antonio , Trapani Silvia , Lombardini Letizia , Pezzotti Patrizio , Deaglio Silvia , Brusaferro Silvio , Cardillo Massimo ,   on behalf of the Italian Network of Regional Transplant Coordinating Centers
Published: November 2020

Background.
SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection.

Methods.
A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002 to March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID+ subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56 304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n = 265, COVID+) or absence (n = 56 039, COVID–) of SARS-CoV-2 infection.

Results.
The cumulative incidence rate of COVID-19 was 0.112% in the Italian population and 0.462% in waitlisted/transplanted patients (OR = 4.2; 95% CI, 3.7-4.7; P < 0.0001). HLA-DRB1*08 was more frequent in COVID+ (9.7% and 5.2%: OR = 1.9, 95% CI, 1.2-3.1; P = 0.003; P
c = 0.036). In COVID+ patients, HLA-DRB1*08 was correlated to mortality (6.9% in living versus 17.5% in deceased: OR = 2.9, 95% CI, 1.15-7.21; P = 0.023). Peptide binding prediction analyses showed that these DRB1*08 alleles were unable to bind any of the viral peptides with high affinity. Finally, blood group A was more frequent in COVID+ (45.5%) than COVID– patients (39.0%; OR = 1.3; 95% CI, 1.02-1.66; P = 0.03).

Conclusions.
Although preliminary, these results suggest that HLA antigens may influence SARS-CoV-2 infection and clinical evolution of COVID-19 and confirm that blood group A individuals are at greater risk of infection, providing clues on the spread of the disease and indications about infection prognosis and vaccination strategies.
Race, Education, and Gender Disparities in Transplantation of Kidneys From Hepatitis C Viremic Donors
Authors: Nguyen Tiffany , Sise Meghan E. , Delgado Cindy , Williams Winfred , Reese Peter , Goldberg David 
Published: November 2020

Background.
Transplantation of kidneys from hepatitis C virus (HCV)-viremic donors into HCV-negative patients followed by direct-acting antiviral therapy was an important breakthrough to increase the number of life-saving kidney transplants. Data suggest that these transplants offer several benefits; however, it is unknown whether adoption of this practice has been shared equitably, especially among disadvantaged groups.

Methods.
We evaluated United Network for Organ Sharing data on HCV-seronegative adult deceased-donor kidney transplant recipients from January 1, 2017, to June 12, 2020. We compared recipients of a kidney from an HCV antibody− (Ab−)/nucleic acid test− (NAT−), HCV Ab+/NAT−, and HCV NAT+ donor. The primary covariates were as follows: (1) race/ethnicity; (2) female sex; and (3) highest level of education. Models included variables associated with being offered an HCV NAT+ kidney. We fit mixed-effects multinomial logistic regression models with the center as a random effect to account for patient clustering.

Results.
Of 48 255 adult kidney-alone deceased-donor kidney transplant HCV-seronegative recipients, 1641 (3.4%) donors were HCV NAT+−, increasing from 0.3% (January 2017–June 2017) to 6.9% (January 2020–June 2020). In multivariable models, racial/ethnic minorities, women, and those with less education were significantly less likely to receive a kidney from an HCV NAT+ donor relative to an HCV Ab−/NAT− and HCV Ab+/NAT− donor. The disparities were most pronounced among Hispanic and Asian patients with less educational attainment (grade school, high school, or some college/tech school).

Conclusions.
Despite an increase in transplants from HCV NAT+ donors, we found substantial racial/ethnic disparities in transplantation of these kidneys. These data highlight how the benefits of a scientific breakthrough are often made less available to disadvantaged patients.
Pharmacokinetics of remdesivir in a COVID-19 patient with end-stage renal disease on intermittent hemodialysis
Authors: Sörgel Fritz , Malin Jakob J. , Hagmann Henning , Kinzig Martina , Bilal Muhammad , Eichenauer Dennis A. , Scherf-Clavel Oliver , Simonis Alexander , Tabei Lobna El , Fuhr Uwe , Rybniker Jan 
Published: November 2020

AbstractRemdesivir, a drug with provisional approval for the treatment of COVID-19, is not recommended in patients with an estimated glomerular filtration rate ≤ 30 mL/min. Here we provide a first detailed pharmacokinetic assessment of remdesivir and its major metabolites in a patient with end stage renal disease on hemodialysis.
A Predictive Model for Severe Covid-19 in the Medicare Population: A Tool for Prioritizing Scarce Vaccine Supply
Authors: Experton Bettina , Tetteh Hassan A. , Lurie Nicole , Walker Peter , Carroll Colin J. , Elena Adrien , Hein Christopher S. , Schwendiman Blake , Vincent Justin L. , Burrow Christopher R. 
Published: November 2020

ABSTRACTBackgroundRecommendations for prioritizing populations for COVID-19 vaccination have focused on front-line health care personnel and residents in long term care, followed by other individuals at higher risk for severe disease. Existing models for identifying higher risk individuals including those over age 65 lack the needed integration of socio-demographic and clinical risk factors to ensure equitable vaccine allocation.MethodsWe developed a predictive model for severe COVID-19 using clinical data from de-identified Medicare claims for 16 million Medicare fee-for-service beneficiaries, including 1 million COVID-19 cases, and socio-economic data from the CDC Social Vulnerability Index. To identify risk factors for severe COVID-19, we used multivariate logistic regression and random forest modeling. Predicted individual probabilities of COVID-19 hospitalization were then calculated for population risk stratification and COVID-19 vaccine prioritization, and for mapping of population risk levels at the county and zip code levels on a nationwide dashboard.ResultsThe leading Covid-19 hospitalization risk factors driving the risk model were: Non-white ethnicity (particularly North American Native, Black, and Hispanic), end-stage renal disease, advanced age (particularly age over 85), prior hospitalization, leukemia, morbid obesity, chronic kidney disease, lung cancer, chronic liver disease, pulmonary fibrosis or pulmonary hypertension, and chemotherapy. However, previously reported risk factors such as chronic obstructive pulmonary disease and diabetes conferred modest hospitalization risk. Among all social vulnerability factors analyzed, residence in a low-income zip code was the only risk factor independently predicting Covid-19 hospitalization. The mapped hospitalization risk levels showed significant correlations with the cumulative COVID-19 case hospitalization rates at the zip code level in the fifteen most populous U.S. major metropolitan areas.ConclusionThis multi-factor risk model which predicts severe Covid-19and its population risk dashboard can be used to optimize Covid-19 vaccine allocation in the higher risk Medicare population where socio-demographic and comorbidity risk factors need to be considered concurrently.
Genetically downregulated interleukin-6 signaling is associated with a favorable cardiometabolic profile: a phenome-wide association study
Authors: Georgakis Marios K. , Malik Rainer , Li Xue , Gill Dipender , Levin Michael G. , Vy Ha My T. , Judy Renae , Ritchie Marylyn , Verma Shefali S. ,   Regeneron Genetics Center, Nadkarni Girish N. , Damrauer Scott M. , Τheodoratou Evropi , Dichgans Martin 
Published: November 2020

AbstractBackgroundInterleukin-6 (IL6) signaling is a key inflammatory pathway widely implicated in the pathogenesis of multiple diseases including autoimmune, vascular, and metabolic disorders. While IL6-receptor (IL6R) inhibitors are already in use for the treatment of autoimmune diseases, their repurposing potential and safety profile is still debated.MethodsWe used 7 genetic variants at theIL6Rlocus as proxies for IL6 signaling downregulation and explored their effects on 1,428 clinical outcomes in a phenome-wide association study (PheWAS) using data from the UK Biobank (339,256 unrelated individuals). Significant associations were meta-analyzed with data from the Penn Medicine (10,244 individuals) and BioMe (9,054 individuals) Biobanks for validation. We further investigated associations between genetically downregulated IL6 signaling and 366 biomarkers and endophenotypes of human disease in the UK Biobank and other phenotype-specific consortia. All associations were examined by Mendelian randomization (MR) analyses scaled to the effects of tocilizumab, a monoclonal antibody targeting IL6R.ResultsThe PheWAS-MR analyses showed significant associations with 16 clinical outcomes and 17 biomarkers following correction for multiple comparisons. Genetically downregulated IL6 signaling was associated with a lower risk of several atherosclerotic phenotypes including ischemic heart disease (OR: 0.84, 95%CI: 0.77-0.90) and abdominal aortic aneurysm (OR: 0.44, 95%CI: 0.29-0.67). We further found significant associations with lower risk of type 2 diabetes (OR: 0.80, 95%CI: 0.73-0.88), lower glycated hemoglobin A1c (HbA1c) levels (beta: −0.07, 95%CI: −0.08 to −0.05), and higher HDL-cholesterol levels (beta: 0.04, 95%CI: 0.02-0.06). In accord with clinical trials examining pharmacological IL6 blockade, genetically downregulated IL6 signaling was associated with higher risk of neutropenia and bacterial infections (cellulitis and urinary tract infections) and with higher hemoglobin concentrations. We further found significant associations with higher risk of atopic dermatitis and higher levels of the pro-allergic cytokine interleukin-4.ConclusionsGenetic IL6 signaling downregulation associates with a lower risk of vascular outcomes and a more favorable cardiometabolic profile. These findings further support a repurposing of IL6R blockade for lowering cardiovascular risk while also informing on potential side effects.
Performance of EasyBreath® Decathlon Snorkeling mask for Delivering Continuous Positive Airway Pressure
Authors: Noto Alberto , Crimi Claudia , Cortegiani Andrea , Giardina Massimiliano , Benedetto Filippo , Princi Pietro , Carlucci Annalisa , Appendini Lorenzo , Gregoretti Cesare 
Published: November 2020

ABSTRACTBackgroundDuring the COVID-19 pandemic, the need for noninvasive respiratory support devices has dramatically increased, sometimes exceeding hospital capacity. The full-face Decathlon snorkeling mask, EasyBreath® (EB® mask), has been adapted to deliver continuous positive airway pressure (CPAP) as an emergency respiratory interface. We aimed to assess the performance of this modified EB® mask.MethodsCPAP set at 5, 10, and 15 cmH2O was delivered to 10 healthy volunteers with a high-flow system generator set at 40, 80, and 120 L min-1 and with a turbine-driven ventilator during both spontaneous and loaded (resistor) breathing. Inspiratory CO2 partial pressure (PiCO2), pressure inside the mask, breathing pattern and electrical activity of the diaphragm (EAdi) were measured at all combinations of CPAP/flows delivered, with and without the resistor.ResultsUsing the high-flow generator set at 40 L min-1, the PiCO2 significantly increased and the system was unable to maintain the target CPAP of 10 and 15 cmH2O and a stable pressure within the respiratory cycle; conversely, the turbine-driven ventilator did. EAdi significantly increased with flow rates of 40 and 80 L min-1 but not at 120 L min-1 and with the turbine-driven ventilator.ConclusionsEB® mask can be safely used to deliver CPAP only under strict constraints, using either a high-flow generator at a flow rate greater than 80 L min-1, or a high-performance turbine-driven ventilator.
Role of cytokines and other prophetic variables in the development and progression of disease in patients suffering from COVID-19
Authors: Malik Arif , Iqbal Saima , Waquar Sulayman , Hafeez Muhammad Mansoor 
Published: November 2020

ABSTRACTINTRODUCTIONOutbreak of the novel COVID-19 infection identifies both causative agents that threaten global pandemic in 2003 and 2011. It is an enveloped virus with spike (S) protein attached that facilitates its receptor binding on the surface. Although it has brought about the global interest for the researchers and medical practitioner in the identification of potential targets that may be addressed in order to cope up with the situation. In the current study potential role of cytokines and related inflammatory markers have been identified that interplays in the progression of disease in COVID-19 patients.MATERIALS AND METHODSCurrent study substitutes hundred and fifty (n=150) patients with novel-COVID-19 and hundred (n=100) healthy controls. After getting informed consent serum samples of the participants were collected and analyzed for their significance in the disease progression. Levels of Interleukins i.e., (IL- 1,6,8,10,11) and tumor necrosis factor-alpha (TNF-α) were determined with help of their specific spectrophotometric and ELISA methods.RESULTSFindings of study show significant increase in the levels of interleukins and TNF-α that signifies the presence of “cytokine storm” in worsening the condition in respect to the exposure of COVID-19. Levels of IL-1 and 6 were significantly higher in patients (98.69±39.35pg/ml and 71.95±28.41 pg/ml) as compared to controls (30.06±14.19pg/ml and 9.46±3.43pg/ml) where, (p=0.001 and 0.007). It also suggests that IL-6 is most sensitive test with about (98%) sensitivity in comparison with 96%,95%, 95%,93% and 92% in case of IL-10,1,8,11 and TNF-α respectively.CONCLUSIONCurrent study elucidate the effects of cytokines and respective inflammatory markers in the progression of the COVID-19. Findings show that activation of macrophages and neutrophils have significant role in the worsening of the symptoms and progression of the viral infection. Thus, use of certain blockers in initial stages could serve with potent benefits in coping up the infectious condition.
The Role of Societal Aspects in the Formation of Official COVID-19 Reports: A Data-Driven Analysis
Authors: Tamás Kurbucz Marcell , Katona Attila Imre , Lantos Zoltán , Kosztyán Zsolt Tibor 
Published: November 2020

AbstractThis paper investigates the role of socioeconomic considerations in the formation of official COVID-19 reports. To this end, we employ a dataset that contains 1,159 preprocessed indicators from the World Bank Group GovData360 and TCdata360 platforms and an additional 8 COVID-19 variables generated based on reports from 138 countries. During the analysis, a rank-correlation-based complex method is used to identify the time- and space-varying relations between pandemic variables and the main topics of World Bank Group platforms. The results not only draw attention to the importance of factors such as air traffic, tourism, and corruption in report formation but also support further discipline-specific research by mapping and monitoring a wide range of such relationships. To this end, an R Notebook is attached that allows for the customization of the analysis and provides up-to-date results.
Frequency and profile of objective cognitive deficits in hospitalized patients recovering from COVID-19
Authors: Jaywant Abhishek , Vanderlind W. Michael , Alexopoulos George S. , Fridman Chaya B. , Perlis Roy H. , Gunning Faith M. 
Published: November 2020

AbstractBackgroundCognitive impairment is common following critical illness. A number of case reports and case series have suggested that cognitive deficits occur in patients with COVID-19. This study evaluated the frequency, severity, and profile of cognitive dysfunction in hospitalized patients recovering from COVID-19.MethodsWe obtained and analyzed cross-sectional neuropsychological data from a cohort of N=57 patients participating in inpatient rehabilitation. Our primary outcome measure was the Brief Memory and Executive Test (BMET). We calculated the frequency of impairment based on clinician diagnosis and by the BMET subtests using age-normed classification of impairment. We explored associations with intubation and extubation as markers of illness severity and complications, as well as psychiatric diagnosis.OutcomesOur sample was 75% male, 61% non-white, with a mean age of 64.5 (SD = 13.9) years. Patients were evaluated at a mean of 43.2 days post-admission. 88% had documented hypoxemic respiratory failure and 77% required intubation. 81% of patients had cognitive impairment, ranging from mild to severe. Deficits were most common in working memory (55% of patients impaired), set-shifting (47%), divided attention (46%), and processing speed (40%). Executive dysfunction was not significantly associated with intubation length or the time from extubation to assessment, nor was it associated with the presence of a psychiatric diagnosis.InterpretationMedically stable inpatients recovering from COVID-19 commonly have deficits in attention and executive functions. These deficits were not significantly correlated with length of intubation or time since extubation. Findings provide an early benchmark for studying the evolution of cognitive difficulties after COVID-19 and suggest that easy to disseminate interventions that remediate attention and executive dysfunctions may be important in this population.FundingThe authors have no funding for this study to report.
Gastroenterological and Hepatic Manifestations of Patients with COVID-19, Prevalence, Mortality by Country, and Intensive Care Admission Rate: Systematic Review and Meta-analysis
Authors: Shehab Mohammad , Alrashed Fatema , Shuaibi Sameera , Alajmi Dhuha , Barkun Alan 
Published: November 2020

AbstractBackground & AimsPatient infected with the SARS-COV2 usually report fever and respiratory symptoms. However, multiple gastrointestinal (GI) manifestations such as diarrhea and abdominal pain has been described. The aim of this study was to evaluate the prevalence of GI, liver function test (LFT) abnormalities, and mortality of COVID-19 patients.MethodsWe performed a systematic review and meta-analysis of published studies that included cohort of patients infected with SARS-COV2 from December 1st, 2019 to July 1st, 2020. We collected data from the cohort of patients with COVID-19 by conducting a literature search using PubMed, Embase, Scopus, and Cochrane according to the preferred reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms, LFTs abnormalities and performed subanalyses to investigate the relationship between gastrointestinal symptoms, geographic location, fatality, and ICU admission.ResultsThe available data of 17,802 positive patients for SARS-COV2 from 120 studies were included in our analysis. The most frequent manifestations were diarrhea (13.3%, 95% CI 12-16), nausea (9.1%, 95% CI 9-13) and elevated LFTs (23.7%, 95% CI 21- 27). The overall and GI fatality were 7.2% (95% CI 6 -10), and 1% (95% CI 1- 4) respectively. Subgroup analysis showed non statistically significant associations between GI symptoms/LFTs abnormalities and ICU admissions (OR=3.41, 95% CI 0.87 – 13.4). The GI mortality rate was 0.58% in China and 3.5% in the United States (95% CI 2 - 5).ConclusionDigestive symptoms and LFTs abnormalities are common in COVID-19 patients. Our subanalysis shows that the presence of gastrointestinal and liver manifestations does not appear to affect mortality, or ICU admission rate. However, the mortality rate was higher in the United States compared to China.