bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world experience of the role of 18F FDG PET-computed tomography in chronic spinal implant infection
Authors: Brown Philip H. , Carter Joseph R. , Moyade Pamela , Mohammed Mohammed , De Matas Marcus , Vinjamuri Sobhan
Published: May 2020

Objectives

The presence of postinstrumentation back pain in patients after undergoing spinal surgery is a well established phenomenon. So too is the presence of infection, both overt and subclinical which can be a source of pain. The accurate assessment of infection in patients with spinal implants in situ and no overt radiological or biochemical abnormalities frequently presents a diagnostic challenge. We present our experience spanning 5 years of using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F FDG PET)-computed tomography (CT) scans to aid the diagnostic process in treating presumed low-grade chronic implant infection.

Methods

We undertook a retrospective analysis of all patients with spinal implants in place who were referred for 18F FDG PET-CT imaging over a 5-year period. All available images, case notes and laboratory results were reviewed.

Results

Data pertaining to 49 patients were analysed, with infection diagnosed on 18F FDG PET-CT in 24 (45%) of those sent for scanning. Fifteen patients in the cohort underwent revision surgery, and 11 of whom had been diagnosed as infected on PET-CT. Confirmation of infection with positive microbiological sampling occurred in 8/11 giving a positive predictive value of 0.72 in our series.

Conclusion

We present a real-world experience of using 18F FDG PET-CT as a diagnostic tool in the evaluation of patients with chronic pain after undergoing spinal implantation. We have found PET-CT to be a promising modality and would recommend multicentre collaboration to ensure reproducibility across more centres.
Bladder sparing landscape for bacillus Calmette-Guérin unresponsive bladder cancer
Authors: Soria Francesco , Giordano Andrea , Shariat Shahrokh F. , Gontero Paolo
Published: May 2020

Purpose of review

The treatment of bacillus Calmette-Guérin (BCG) unresponsive disease remains a challenge for urooncologists. The search for effective conservative treatments is ongoing and several new agents have been recently tested for this purpose. The aim of this manuscript was to review the last developments in this interesting field.

Recent findings

The advent of systemic immunotherapy in the nonmuscle invasive setting promise to revolutionize the paradigm of treatment of BCG unresponsive disease. The preliminary results of the Keynote-057 trial (3 months complete response of 41% in carcinoma-in-situ patients) have led to the rapid approval of pembrolizumab from the Food and Drug Administration. Interesting results have been reported for gene therapies such as those with CG0700 and Adstiladrin, nonreplicating adenovirus able to increase the ‘in situ’ antitumor activity. However, larger prospective trials with longer follow-up are needed to confirm the initial findings.

In summary, early radical cystectomy remains the standard treatment for BCG unresponsive patients. However, in case of patients unfit for or refusing radical cystectomy, the bladder-sparing options are continuously increasing. Although BCG-reinduction (with or without interferon) and traditional intravesical chemotherapy may represent the past, the present and the future are characterized by device-assisted therapies, systemic immunotherapy, and gene therapy.
Applying the Eosinophilic Esophagitis Endoscopic Reference Scores (EREFS) to Different Aged Children
Authors: Ahuja Neha , Weedon Jeremy , Schwarz Steven M. , Sklar Rachel , Rabinowitz Simon S.
Published: May 2020

Objectives:

The eosinophilic esophagitis (EoE) endoscopic reference score (EREFS) was developed to analyze adults with EoE and has been successfully applied to a pediatric cohort. The present study compares EREFS in younger and older children with EoE.

Methods:

The 99 patients were divided among 3 cohorts: 44 active EoE (EoE‐A); 16 EoE remission (EoE‐R); and 39 controls (esophageal dysfunction but <15 eos/hpf). The cohorts were then subdivided into 2 groups: younger (≤10 years) and older (>10 years) that were compared based on the composite and the individual components of their EREFS.

Results:

EREFS identified EoE‐A in all children with an area under the receiving operating characteristics curve (AUC) of 0.85, in older children with an AUC of 0.90 and in younger children with an AUC of 0.77. Mean EREFS for ≤10 years was 1.26 ± 1.19 and 2.71 ± 1.33 for >10 years (P < 0.01). The 3 most common findings in our entire EoE‐A cohort and in both ages were furrows, edema, and exudates. EREFS in patients with EoE‐A had similar specificities (0.88 vs 0.89) and positive predictive values (0.89 vs 0.91) in both ages.

Conclusions:

The present investigation confirms the utilization of EREFS in Pediatric EoE. Furthermore, EREFS can detect EoE and document response to treatment in both younger and older children. EREFS, however, predicted EoE in the older children with a higher sensitivity (0.89 vs 0.63) and a higher negative predictive value (0.87 vs 0.59) than was seen in the younger cohort.
Venous Thromboembolism After Peripherally Inserted Central Catheters Placement in Children With Acute Leukemia: A Single-center Retrospective Cohort Study
Authors: Ren Yuanyuan , Chang Lixian , Zhao Beibei , Zhang Xiaoyan , Wan Yang , Zhu Xiaofan , Zhang Huimin
Published: May 2020

Objective:

To explore the incidence rate and characteristics of symptomatic venous thromboembolism (VTE) after peripherally inserted central catheters (PICC) placement in children with acute leukemia (AL).

Methods:

The authors performed a retrospective study aiming at children admitted to Pediatric Blood Diseases Center with a new diagnosis of AL and received a PICC insertion, collected the clinical materials of all venous thrombosis cases, and analyzed the incidence rate and characteristics in various types of AL.

Results:

From September 2007 to December 2018, a total of 2423 patients got PICCs at least once, of whom 29 patients experienced thrombosis events and the overall incidence rate of symptomatic VTE after PICC insertion was 1.2%. Deep venous thrombosis accounted for the majority with 75.9%. Seven cases of cerebral venous sinus thrombosis were documented and they all developed in patients with acute lymphoblastic leukemia (ALL). No pulmonary embolism was detected. Patients with acute myeloid leukemia (AML) had an identical risk of thrombosis to patients with acute lymphoblastic leukemia (ALL) (1.7% vs. 1.09%, P>0.05). All thrombi in patients with AML were located on the upper extremity, whereas in the ALL group about half of the thromboembolism developed in other locations. There were no statistical differences between patients in different clinical trials of the ALL group (0.7% vs. 1.6%, P>0.05).

Conclusions:

The incidence rates of symptomatic VTE after PICC placement in children with AL in our center were relatively low and acceptable. For patients with AML, PICC placement plays the most important role in venous thrombosis. However, in patients with ALL, the potential risk factors were more complex.
C-Reactive Protein and Procalcitonin Levels May Not Predict Delirium in Critically Ill Children*
Authors: Dechnik Andzelika , Mauer Elizabeth A. , Gerber Linda M. , Traube Chani
Published: May 2020

Objectives:

The objective of this study was to investigate the relationship between C-reactive protein and procalcitonin and the diagnosis of delirium in critically ill children.

Design:

Retrospective cohort study.

Setting:

Tertiary care urban academic PICU.

Patients:

All PICU patients (ages 0–21 yr) admitted between January 1, 2015, and December 31, 2017, who had a C-reactive protein and/or procalcitonin level drawn within the first 14 days of their PICU stay.

Interventions:

None.

Measurements and Main Results:

Each patient was screened for delirium and/or coma bid using the Cornell Assessment of Pediatric Delirium. Patient information including demographics, delirium status, and laboratory values were extracted from the electronic medical record. Seven-hundred thirty-four patients were enrolled, with C-reactive protein and procalcitonin levels drawn in 664 and 587 patients, respectively. Thirty-seven percent of patients (n = 274) were delirious on at least one study day. In bivariate analysis, C-reactive protein was not related to either delirium or coma. Procalcitonin was highest on days with coma and lowest on days with delirium. There was no statistically significant relationship between inflammatory markers and any subtype of delirium.

Conclusions:

Despite evidence of inflammatory markers being predictive of delirium in adults, in this retrospective pediatric cohort, no association was found between C-reactive protein or procalcitonin levels and development of delirium.
Brief Report: Incidence and Correlates of Pregnancy in HIV-Positive Kenyan Sex Workers
Authors: Lokken Erica M. , Wanje George , Richardson Barbra A. , Mutunga Esther , Wilson Kate S. , Jaoko Walter , Kinuthia John , McClelland Raymond Scott
Published: May 2020

Introduction:

The incidence of pregnancy in female sex workers (FSWs) living with HIV is not well characterized.

Methods:

Current and former FSWs living with HIV and enrolled in a prospective cohort study in Mombasa, Kenya, were followed monthly to ascertain sexual behavior and underwent quarterly pregnancy testing. Pregnancies were considered planned, mistimed, or unwanted according to fertility desires and pregnancy intentions. Cox proportional hazards models were used to estimate hazard ratios (HRs) of the association between characteristics and incident pregnancy.

Results:

Two hundred seventy-nine FSWs were eligible (October 2012–April 2017). Most women had a nonpaying, regular partner (83.2%, 232/279), were not using modern nonbarrier contraception (69.5%, 194/279), and did not desire additional children (70.6%, 197/279). Of 34 first incident pregnancies [5.8/100 person-years (p-y); 95% confidence interval (CI): 4.1 to 8.0], 91.2% (n = 31) were unintended. The incidences of planned (5.7/100 p-y, n = 3), mistimed (10.4/100 p-y, n = 9), and unwanted pregnancies (4.9/100 p-y, n = 22) were similar (P = 0.15). In univariable analysis, oral contraceptive pill use (versus no contraception), having a nonpaying, regular partner, transactional sex, vaginal washing, condomless sex, and higher sex frequency were associated with an increased pregnancy risk. Older age was associated with a lower pregnancy risk. In multivariable analysis, having a nonpaying, regular partner (adjusted HR 4.0, 95% CI: 1.2 to 14.1) and age ≥40 years (aHR 0.2, 95% CI: 0.0 to 0.9) remained significantly associated with a higher and lower pregnancy risk, respectively.

Conclusion:

In this cohort of HIV-positive FSWs, most pregnancies were unintended. Identifying FSWs' fertility desires and pregnancy intentions could facilitate efforts to increase contraceptive use and implement safer conception strategies.
Myocardial Cut-off Sign is a Sensitive and Specific Cardiac Computed Tomography and Magnetic Resonance Imaging Sign to Distinguish Left Ventricular Pseudoaneurysms From True Aneurysms
Authors: Ballard David H. , Jokerst Clinton , Raptis Constantine A. , Pilgram Thomas K. , Woodard Pamela K.
Published: May 2020

Purpose:

The purpose of this study was to describe the myocardial cut-off sign, assess its ability to distinguish left ventricular pseudoaneurysms (LV PSAs) from true aneurysms (LVAs), and compare its performance with other imaging findings and quantitative measurements used to differentiate LV PSAs from LVAs.

Materials and Methods:

This retrospective single-center study identified patients with preoperative cardiac computed tomography (CT) or magnetic resonance imaging (MRI) and surgically confirmed LVAs or LV PSAs over a 10-year period. Seventeen LV PSAs (11 MRI, 6 CT) and 18 LVAs (10 MRI, 8 CT) were included. The myocardial cut-off sign was objectively a >50% decrease in aneurysm sac wall thickness measured at 1 cm from the aneurysmal neck (measurements at 2 cm were also assessed) and subjectively an abrupt “cut-off” of myocardium for the aneurysm sac for PSA compared with a gradual tapering of sac wall thickness for LVA. Two radiologists independently evaluated images for the subjective presence of this sign.

Results:

The myocardial cut-off sign was 91% sensitive and 97% specific when measured 1 cm from the aneurysm neck. When measured at 2 cm from the neck, the sign was 100% sensitive and 69% specific. Subjective analysis of whether the myocardium appeared “cut-off” was 94% to 100% sensitive and 78% to 94% specific with excellent agreement for both PSA (κ=0.94) and LVA (κ=0.83).

Conclusions:

The myocardial cut-off sign on cardiac CT and MRI is a sensitive and specific finding of LV PSA. Specificity is improved with objective measurements compared with subjective assessment (97% vs. 78% to 94%). This sign may help radiologists distinguish between LV PSAs and LVAs.
Radiological Simultaneous Portohepatic Vein Embolization (RASPE) Before Major Hepatectomy
Authors: Laurent Christophe , Fernandez Benjamin , Marichez Arthur , Adam Jean-Philippe , Papadopoulos Panteleimon , Lapuyade Bruno , Chiche Laurence
Published: May 2020

Objective:

The aim of this retrospective study was to compare portal vein embolization (PVE) and radiologica simultaneous portohepatic vein embolization (RASPE) for future liver remnant (FLR) growth in terms of feasibility, safety, and efficacy.

Summary of Background Data:

After portal vein embolization (PVE), 15% of patients remain ineligible for hepatic resection due to insufficient hypertrophy of the FLR. RASPE has been proposed to induce FLR growth.

Materials and Methods:

Between 2016 and 2018, 73 patients were included in the study. RASPE was proposed for patients with a ratio of FLR to total liver volume (FLR/TLV) of <25% (RASPE group). This group was compared to patients who underwent PVE for a FLR/TLV <30% (PVE group). Patients in the 2 groups were matched for age, sex, type of tumor, and number of chemotherapy treatments. FLR was assessed by computed tomography before and 4 weeks after the procedure.

Results:

The technical success rate in both groups was 100%. Morbidity post-embolization, and the time between embolization and surgery were similar between the groups. In the PVE group, the FLR/TLV ratio before embolization was 31.03% (range: 18.33%–38.95%) versus 22.91% (range: 16.55–32.15) in the RASPE group (P < 0.0001). Four weeks after the procedure, the liver volume increased by 28.98% (range: 9.31%–61.23%) in the PVE group and by 61.18% (range: 23.18%–201.56%) in the RASPE group (P < 0.0001). Seven patients in the PVE group, but none in the RASPE group, had postoperative liver failure (P = 0.012).

Conclusions:

RASPE can be considered as “radiological associating liver partition and portal vein ligation for staged hepatectomy.” RASPE induced safe and profound growth of the FLR and was more efficient than PVE. RASPE also allowed for extended hepatectomy with less risk of post-operative liver failure.
Assessment of gustatory function in aging people using event-related potentials
Authors: Hu Chunhua , Yao Linyin , Chen Zirong , Sun Zhifu , Zhang Lichuan , Wei Yongxiang
Published: May 2020

Gustatory dysfunctions are more frequent than other chemosensory dysfunctions in aging people. Gustatory event-related potentials (ERPs) has been suggested as a reliable and effective approach for assessing gustatory functions in young and middle subjects, but has rarely been investigated in aging people, leaving influencing factors of ERPs in that population not completely understood. In this study, we analyzed gustatory ERPs results of aging participants and characterized potential impacting factors, including age, sex, BMI, drinking, smoking, hypertension, diabetes, cognition and psychophysical test scores of gustation and olfaction. Our results revealed three components (P1, N1 and P2) in gustatory ERPs upon salty stimulation. Significant differences between responses collected from different recording electrodes were observed: minimum latencies and maximum amplitudes of P1 were detected at frontal electrode, and maximum amplitudes of N1 and P2 were detected at central and centro-parietal electrodes, respectively. Major cortical sources of components P1, N1 and P2 were located at bilateral insula, frontal operculum, and orbitofrontal cortex. Diabetes was positively associated with latencies of P1. Sex was positively associated with amplitudes of P1, N1 and P2. Hypertension was negatively associated with amplitudes of P1 and P2. In conclusion, gustatory ERPs in aging people exhibited a specific topographical distribution, represented by sex-related differences and negative impacts of diabetes and hypertension.
Relationship between symptom dimensions and white matter alterations in untreated patients with obsessive–compulsive disorder: a diffusion tensor imaging study
Authors: Zhu Jiahui , Li Jinhao , Han Yunyi , Liu Wei
Published: May 2020

The aim of the study was explore how the white matter structure changes and obsessive–compulsive disorder (OCD) symptom dimensions are related. We recruited 46 untreated adult patients with OCD, and 46 healthy controls matched for gender, age, and education. The patients were classified according to symptom dimensions assessed by the four-factor model. Diffusion tensor imaging (DTI) was employed to evaluate brain structural alterations in patients with OCD, and DTI data were processed using voxel-based morphometry (VBM) analysis. In comparison with healthy controls, there was a significant decreased fractional anisotropy of patients with OCD in several white matter regions of the cingulate gyrus and left inferior frontal gyrus. When stratified by symptom dimensions, patients presenting with the contamination/cleaning dimension had significantly lower fractional anisotropy in the white matter areas of the right insula and the left thalamus than the healthy controls. Whereas harm/checking symptom dimension patients exhibited a significant decrease of fractional anisotropy in the white matter regions of the right hippocampus. Our study has clear implications for the idea that OCD can be seen as a heterogeneous disorder, and symptom dimensions in patients with OCD are relevant to various white matter alterations patterns.
Icariin improves cognitive deficits by reducing the deposition of β-amyloid peptide and inhibition of neurons apoptosis in SAMP8 mice
Authors: Wu Jie , Qu Jing-Qiu , Zhou Yan-Jun , Zhou Yong-Jian , Li Yuan-Yuan , Huang Nan-Qu , Deng Cheng-Min , Luo Yong
Published: May 2020

Effective therapeutic drugs for prevent or reverse the pathobiology of Alzheimer’s disease (AD) have not been developed. Icariin (ICA), a prenylated flavonol glycoside derived from the traditional Chinese herb Epimedium sagittatum, exerts a variety of pharmacological activities and shows promise in the treatment and prevention of AD. This study investigated the neuroprotective effects of ICA in SAMP8 mice model of aspects of early AD and explored potential underlying mechanisms. Our results showed that intragastric administration of ICA could reverse the learning and memory impairment of SAMP8 mice in the Morris water maze. Western blot of hippocampal specimens revealed that ICA down-regulated the expression of BACE1 to reduce the expression of cytotoxic Aβ1-42. Furthermore, ICA siginificantly increase the Bcl-2/Bax ratio by increasing the expression of anti-apoptotic protein Bcl-2, and decreasing the expression of pro-apoptotic protein Bax, and thus inhibit neurons apoptosis. These findings indicate that ICA could improve cognitive deficits by reducing the deposition of β1-42 and inhibition of neurons apoptosis and provide further evidence for the clinical efficacy of ICA in the treatment of AD.
Monascin exhibits neuroprotective effects in rotenone model of Parkinson’s disease via antioxidation and anti-neuroinflammation
Authors: Lin Qiuyu , Hou Sen , Dai Yuyin , Jiang Nan , Lin Yingjie
Published: May 2020

Increasing evidence verified that oxidative stress and neuroinflammatory response exacerbates motor deficits and increases neuronal loss in several rodent models of Parkinson’s disease. In the present study, we explore the neuroprotective effects of monascin in a rotenone-induced Parkinson’s disease model as well as the underlying mechanisms. Our results showed that monascin remarkedly attenuated behavioral impairments and the depletion of dopaminergic neurons induced by rotenone in the rats. Besides, monascin decreased the levels of pro-inflammatory factors such as interleukin-1β, interleukin-6, tumor necrosis factor-α and oxidative stress marker malondialdehyde while promoted the expression of superoxide dismutase, glutathione peroxidase and other antioxidant factors. Further detection of the expression of related proteins showed that monascin significantly promoted the expression of proliferator-activated receptor-gamma, F-E2-related factor 2 and heme oxygenase-1, but inhibited the expression of NF-κB. What’s more, levels of growth factors that are essential for neuronal and synaptic function were increased under the effects of monascin. All in all, our results revealed that monascin exerted neuroprotective effects in rotenone model of Parkinson’s disease via antioxidation and anti-neuroinflammation.
Ventral motion parallax enhances fruit fly steering to visual sideslip
Authors: Ruiz Carlos , Theobald Jamie C.
Published: May 2020

Flies and other insects use incoherent motion (parallax) to the front and sides to measure distances and identify obstacles during translation. Although additional depth information could be drawn from below, there is no experimental proof that they use it. The finding that blowflies encode motion disparities in their ventral visual fields suggests this may be an important region for depth information. We used a virtual flight arena to measure fruit fly responses to optic flow. The stimuli appeared below (n= 51) or above the fly (n= 44), at different speeds, with or without parallax cues. Dorsal parallax does not affect responses, and similar motion disparities in rotation have no effect anywhere in the visual field. But responses to strong ventral sideslip (206° s−1) change drastically depending on the presence or absence of parallax. Ventral parallax could help resolve ambiguities in cluttered motion fields, and enhance corrective responses to nearby objects.
Internalizing symptoms and working memory as predictors of mathematical attainment trajectories across the primary–secondary education transition
Authors: Evans Danielle , Gaysina Darya , Field Andy P.
Published: May 2020

The transition from primary to secondary education is a critical period in early adolescence which is related to increased anxiety and stress, increased prevalence of mental health issues, and decreased maths performance, suggesting it is an important period to investigate maths attainment. Previous research has focused on anxiety and working memory as predictors of maths, without investigating any long-term effects around the education transition. This study examined working memory and internalizing symptoms as predictors of children's maths attainment trajectories (age 7–16) across the transition to secondary education using secondary longitudinal analysis of the Avon Longitudinal Study of Parents and Children (ALSPAC). This study found statistically significant, but very weak evidence for the effect of internalizing symptoms and working memory on maths attainment. Greater parental education was the strongest predictor, suggesting that children of parents with a degree (compared with those with a CSE) gain the equivalent of almost a year's schooling in maths. However, due to methodological limitations, the effects of working memory and internalizing symptoms on attainment cannot be fully understood with the current study. Additional research is needed to further uncover this relationship, using more time-appropriate measures.
High persister cell formation by clinical Staphylococcus aureus strains belonging to clonal complex 30
Authors: Liu Liping , Wang Ying , Bojer Martin Saxtorph , Andersen Paal Skytt , Ingmer Hanne
Published: May 2020

Bacterial persisters form a subpopulation of cells that survive lethal concentrations of antibiotics without being genetically different from the susceptible population. They are generally considered to be phenotypic variants that spontaneously have entered a dormant state with low ATP levels or reduced membrane potential. InStaphylococcus aureus, a serious opportunistic human pathogen, persisters are believed to contribute to chronic infections that are a major global healthcare problem. WhileS. aureuspersisters have mostly been studied in laboratory strains, we have here investigated the ability of clinical strains to form persisters. For 44 clinical strains belonging to the major clonal complexes CC5, CC8, CC30 or CC45, we examined persister cell formation in stationary phase when exposed to 100 times the MIC of ciprofloxacin, an antibiotic that targets DNA replication. We find that while all strains are able to form persisters, those belonging to CC30 displayed on average 100-fold higher persister cell frequencies when compared to strains of other CCs. Importantly, there was no correlation between persister formation and the cellular ATP content of the individual strains, but the group of CC30 strains displayed slightly lower membrane potential compared to the non-CC30 group. CC30 strains have previously been associated with chronic and reoccuring infections and we hypothesize that there could be a correlation between lineage-specific characteristics displayed viain vitropersister assays and the observed clinical spectrum of disease.
The Clinical and Economic Value of a Successful Shutdown During the SARS-CoV-2 Pandemic in Germany
Authors: Gandjour Afschin
Published: May 2020

Background and aim

A shutdown of businesses enacted during the SARS-CoV-2 pandemic can serve different goals, e.g., preventing the intensive care unit (ICU) capacity from being overwhelmed (‘flattening the curve’) or keeping the reproduction number substantially below one (‘squashing the curve’). The aim of this study was to determine the clinical and economic value of a shutdown that is successful in ‘flattening’ or ‘squashing the curve’ in Germany.

Methods

In the base case, the study compared a successful shutdown to a worst-case scenario with no ICU capacity left to treat COVID-19 patients. To this end, a decision model was developed using, e.g., information on age-specific fatality rates, ICU outcomes, and the herd protection threshold. The value of an additional life year was borrowed from new, innovative oncological drugs, as cancer reflects a condition with a similar morbidity and mortality burden in the general population in the short term as COVID-19.

Results

A shutdown that is successful in ‘flattening the curve’ is projected to yield an average health gain between 0.02 and 0.08 life years (0.2 to 0.9 months) per capita in the German population. The corresponding economic value ranges between €1543 and €8027 per capita or, extrapolated to the total population, 4% to 19% of the gross domestic product (GDP) in 2019. A shutdown that is successful in ‘squashing the curve’ is expected to yield a minimum health gain of 0.10 life years (1.2 months) per capita, corresponding to 24% of the GDP in 2019. Results are particularly sensitive to mortality data and the prevalence of undetected cases.

Conclusion

A successful shutdown is forecasted to yield a considerable gain in life years in the German population. Nevertheless, questions around the affordability and underfunding of other parts of the healthcare system emerge.
Risk factors for adverse clinical outcomes in patients with COVID-19: A systematic review and meta-analysis
Authors: Bellou Vanesa , Tzoulaki Ioanna , Evangelou Evangelos , Belbasis Lazaros
Published: May 2020

Importance: COVID-19 is a clinically heterogeneous disease of varying severity and prognosis. Clinical characteristics that impact disease course could offer guidance for clinical decision making and future research endeavors and unveil disease pathways.
Objective: To examine risk factors associated with adverse clinical outcomes in patients with COVID-19.
Data sources: We performed a systematic review in PubMed from January 1 until April 19, 2020.
Study selection: Observational studies that examined the association of any clinical characteristic with an adverse clinical outcome were considered eligible. We scrutinized studies for potential overlap.
Data extraction and synthesis: Information on the effect of clinical factors on clinical endpoints of patients with COVID-19 was independently extracted by two researchers. When an effect size was not reported, crude odds ratios were calculated based on the available information from the eligible articles. Study-specific effect sizes from non-overlapping studies were synthesized applying the random-effects model.
Main outcome and measure: The examined outcomes were severity and progression of disease, admission to ICU, need for mechanical ventilation, mortality, or a composite outcome.
Results: We identified 88 eligible articles, and we performed a total of 256 meta-analyses on the association of 98 unique risk factors with five clinical outcomes. Seven meta-analyses presented the strongest epidemiological evidence in terms of statistical significance (P-value <0.005), between-study heterogeneity (I2 <50%), sample size (more than 1000 COVID-19 patients), 95% prediction interval excluded the null value, and absence of small-study effects. Elevated C-reactive protein (OR, 6.46; 95% CI, 4.85 - 8.60), decreased lymphocyte count (OR, 4.16; 95% CI, 3.17 - 5.45), cerebrovascular disease (OR, 2.84; 95% CI, 1.55 - 5.20), chronic obstructive pulmonary disease (OR, 4.44; 95% CI, 2.46 - 8.02), diabetes mellitus (OR, 2.04; 95% CI, 1.54 - 2.70), hemoptysis (OR, 7.03; 95% CI, 4.57 - 10.81), and male sex (OR, 1.51; 95% CI, 1.30 - 1.75) were associated with risk of severe COVID-19.
Conclusions and relevance: Our results highlight factors that could be useful for prognostic model building, help guide patients' selection for randomized clinical trials, as well as provide alternative treatment targets by shedding light to disease pathophysiology.
High speed large scale automated isolation of SARS-CoV-2 from clinical samples using miniaturized co-culture coupled with high content screening
Authors: Francis Rania , Bideau Marion Le , Jardot Priscilla , Grimaldier Clio , Raoult Didier , Bou Khalil Jacques Yaacoub , Scola Bernard La
Published: May 2020

SARS-CoV-2, a novel coronavirus infecting humans, is responsible for the current COVID-19 global pandemic. If several strains could be isolated worldwide, especially forin-vitrodrug susceptibility testing and vaccine development, few laboratories routinely isolate SARS-CoV-2. This is due to the fact that the current co-culture strategy is highly time consuming and requires working in a biosafety level 3 laboratory. In this work, we present a new strategy based on high content screening automated microscopy (HCS) allowing large scale isolation of SARS-CoV-2 from clinical samples in 1 week. A randomized panel of 104 samples, including 72 tested positive by RT-PCR and 32 tested negative, were processed with our HCS procedure and were compared to the classical isolation procedure. Isolation rate was 43 % with both strategies on RT-PCR positive samples, and was correlated with the initial RNA viral load in the samples, where we obtained a positivity threshold of 27 Ct. Co-culture delays were shorter with HCS strategy, where 80 % of the positive samples were recovered by the third day of co-culture, as compared to only 25 % with the classic strategy. Moreover, only the HCS strategy allowed us to recover all the positive elements after 1 week of co-culture. This system allows rapid and automated screening of clinical samples with minimal operator work load, thus reducing the risks of contamination.
VENTILATORY SUPPORT IN SARS-VOC-2 DURING INTENSIVE THERAPY
Authors: Pereira Rodriguez Javier Eliecer , Quintero Gomez Juan Camilo , Lopez Florez Otilio , Waiss Skvirsky Sandra Sharon , Velasquez Badillo Ximena
Published: May 2020

Introduction: The SARS-CoV-2 disease outbreak has now become a pandemic. Critical patients with COVID-19 require basic and advanced respiratory support. Therefore, the objective was to describe the ventilatory support strategies in SARS-CoV-2 during intensive therapy.
Materials and methods: A systematic review of observational studies of the available scientific literature was performed in accordance with the recommendations of the Cochrane collaboration and the criteria of the PRISMA Declaration.
Results: Fifteen observational studies were included that gave a study population of 4,081 patients. Mechanical ventilation is the main respiratory support treatment for critically ill patients, which should be administered as soon as normal oxygenation cannot be maintained, and despite the fact that there is no current consensus on the parameters of mechanical ventilation, the evidence collected suggests the use of Fio2 on average 50%, PEEP of 14 cmH2O, lung compliance of 29-37 ml per cm of water, driving pressure between 12-14 cm of water and a plateau pressure of 22-25 cm of water. Conclusions: IL-6 is shown as a possible marker of respiratory failure and a worse prognosis as well as obesity. In addition, the use of prone position, neuromuscular blockade, pulmonary vasodilators, ECMO, and mechanical ventilation based on the clinical conditions and needs of the patient with COVID-19 are strategies that could benefit patients entering intensive therapy for SARS-CoV- 2.
Projecting Demand-Supply Gap of Hospital Capacity in India in the face of COVID-19 pandemic using Age-Structured deterministic SEIR model
Authors: Verma Veenapani Rajeev , Saini Anuraag , Gandhi Sumirtha , Dash Umakant , Koya Muhammad Shaffi Fazaludeen
Published: May 2020

BACKGROUND

Due to uncertainties encompassing the transmission dynamics of COVID-19, mathematical models informing the trajectory of disease are being proposed throughout the world. Current pandemic is also characterized by surge in hospitalizations which has overwhelmed even the most resilient health systems. Therefore, it is imperative to assess supply side preparedness in tandem with demand projections for comprehensive outlook.

OBJECTIVE

Hence, we attempted this study to forecast the demand of hospital resources for one year period and correspondingly assessed capacity and tipping points of Indian health system to absorb surges in demand due to COVID-19.

METHODS

We employed age-structured deterministic SEIR model and modified it to allow for testing and isolation capacity to forecast the demand under varying scenarios. Projections for documented cases were made for varying degree of mitigation strategies of a) No-lockdown b) Moderate-lockdown c) Full-lockdown. Correspondingly, data on a) General beds b) ICU beds and c) Ventilators was collated from various government records. Further, we computed the daily turnover of each of these resources which was then adjusted for proportion of cases requiring mild, severe and critical care to arrive at maximum number of COVID-19 cases manageable by health care system of India.

FINDINGS

Our results revealed pervasive deficits in the capacity of public health system to absorb surge in demand during peak of epidemic. Also, continuing strict lockdown measures was found to be ineffective in suppressing total infections significantly, rather would only push the peak by a month. However, augmented testing of 500,000 tests per day during peak (mid-July) under moderate lockdown scenario would lead to more reported cases (5,500,000–6,000,000), leading to surge in demand for hospital resources. A minimum allocation of 10% public resources and 30% private resources would be required to commensurate with demand under that scenario. However, if the testing capacity is limited to 200,000 tests per day under same scenario, documented cases would plummet by half.
Altruism and Vaccination Intentions: Evidence from Behavioral Experiments
Authors: Cucciniello Maria , Pin Paolo , Imre Blanka , Porumbescu Greg , Melegaro Alessia
Published: May 2020

Vaccine hesitancy has been on the rise throughout much of the world for the past two decades. At the same time, existing pro-vaccination public health communication strategies have proven ineffective.
We present a novel approach to increase vaccination intentions, which appeals to individuals' other-regarding preferences. Specifically, we assess how vaccination intentions are influenced by the presence of people who cannot vaccinate, such as the immunosuppressed, newborns or pregnant women, using a game where there is a passive player whose welfare depends on the decisions of other, active players.
Results from a survey experiment targeting parents and from a laboratory experiment provide support for a twofold positive effect of the presence of the passive player on vaccination intentions.
These findings suggest messages that invoke altruistic, other-regarding preferences may be an effective approach to increasing vaccination intentions.
Our findings could be extended to other campaigns where the population is invited to adopt behaviors that can help the most susceptible people, as is the case of the self-quarantine measures adopted during the outbreak of CoVID-19 at the beginning of 2020. If the attention of people is focused on the positive effect that they can have on those that cannot protect themselves, then the message may be more effective and people may be more responsive.
Characteristics and outcome of SARS-CoV-2 infection in cancer patients.
Authors: Basse Clemence , Diakite Sarah , Servois Vincent , Frelaut Maxime , Noret Aurelien , Bellesoeur Audrey , Moreau Pauline , Massiani Marie-Ange , Bouyer Anne-Sophie , vuagnat perrine , Malak SAndra , Bidard Francois-Clement , Vanjak Dominique , Kriegel Irene , Burnod Alexis , Bilger Geoffroy , Ramtohul Toulsie , Dhonneur Gille , Bouleuc Carole , Cassoux Nathalie , Paoletti Xavier , Bozec Laurence , Cottu Paul
Published: May 2020

Abstract
Background: Concerns have emerged about the higher risk of fatal COVID-19 in cancer patients. In this paper, we review the experience of a comprehensive cancer center.
Methods: A prospective registry was set up at Institut Curie at the beginning of the COVID-19 pandemic. All cancer patients with suspected or proven COVID-19 were entered and actively followed for 28 days.
Results: Among 9,842 patients treated at Institut Curie between mid-March and early May 2020, 141 (1.4%) were diagnosed with COVID-19, based on RT-PCR testing and/or CT-scan. In line with our case-mix, breast cancer (40%) was the most common tumor type, followed by hematological and lung malignancies (both 13%). Patients with active cancer therapy or/and advanced cancer accounted for 88% and 69% of patients, respectively. At diagnosis, 79% of patients had COVID-19 related symptoms, with an extent of lung parenchyma involvement ≤50% in 90% of patients. Blood count variations and C-reactive protein elevation were the most common laboratory abnormalities. Antibiotics and antiviral agents were administered in 48% and 7% of patients, respectively. At the time of analysis, 26 patients (18%) have died from COVID-19, and 81 (57%) were cured. Independent prognostic factors at the time of COVID-19 diagnosis associated with death or intensive care unit admission were extent of COVID-19 pneumonia and decreased O2 saturation.
Conclusions: COVID-19 incidence and presentation in cancer patients appear to be very similar to those in the general population. The outcome of COVID-19 is primarily driven by the initial severity of infection rather than patient or cancer characteristics.
Disparities in COVID-19 Reported Incidence, Knowledge, and Behavior
Authors: Alsan Marcella , Stantcheva Stefanie , Yang David , Cutler David
Published: May 2020

Background

Data from the COVID-19 pandemic in the United States show large differences in hospitalizations and mortality across race and geography. However, there is limited data on health information, beliefs, and behaviors that might indicate different exposure to risk.

Methods

A sample of 5,198 respondents in the United States (80% population representative, 20% oversample of hotspot areas in New York City, Seattle, New Orleans, and Detroit) was conducted from March 29th to April 13th to measure differences in knowledge, beliefs and behavior regarding COVID-19. Linear regression was used to understand racial, geographic, political, and socioeconomic differences in COVID-19 reported incidence knowledge, and behaviors after adjusting for state-specific and survey date fixed effects.

Results

The largest differences in COVID-19 knowledge and behaviors are associated with race/ethnicity, gender, and age. African-Americans, men, and people <55 years old are less likely to know how the disease is spread, less likely to know symptoms of COVID-19, wash their hands less frequently, and leave the home more often. Differences by income, political orientation, and living in a hotspot area are much smaller.

Conclusions

There are wide gaps in COVID-19 reported incidence, knowledge regarding disease spread and symptoms, and in social distancing behavior. The findings suggest more effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.
Temporal Changes Guided by Mesenchymal Stem Cells on a 3D Microgel Platform Enhances Angiogenesis In Vivo at a Low-Cell Dose
Authors: Thomas Dilip , Marsico Grazia , Mohd Isa Isma Liza , Thirumaran Arun , Chen Xizhe , Lukasz Bart , Fontana Gianluca , Rodriguez Brian , Marchetti-Deschmann Martina , O’Brien Timothy , Pandit Abhay
Published: May 2020

Therapeutic factors secreted by mesenchymal stem cells (MSCs) promote angiogenesisin vivo. However, delivery of MSCs in the absence of a cytoprotective environment offers limited efficacy due to low cell retention, poor graft survival and the non-maintenance of a physiologically relevant dose of growth factors at the injury site. The delivery of stem cells on an extracellular matrix (ECM)-based platform alters cell behaviour including migration, proliferation and paracrine activity, which are essential for angiogenesis. We demonstrate the biophysical and biochemical effects of pre-conditioning human MSCs for 96 hours on a three-dimensional ECM-based microgel platform. By altering the macromolecular concentration surrounding cells in the microgels, the pro-angiogenic phenotype of hMSCs can be tuned in a controlled manner through cell-driven changes in extracellular stiffness and ‘outside-in’ integrin signaling. The microgels tested at a low-cell dose (5×104cells) in a pre-clinical hindlimb ischemia model showed accelerated formation of new blood vessels with a reduced inflammatory response impeding progression of tissue damage. Molecular analysis revealed that several key mediators of angiogenesis were upregulated in the low-cell dose microgel group, providing a mechanistic insight of pathways modulatedin vivo. Our research adds to current knowledge in cell encapsulation strategies by highlighting the importance of preconditioning or priming the capacity of biomaterials through cell-material interactions. Obtaining therapeutic efficacy at a low-cell dose in the microgel platform is a promising clinical route that would aid faster tissue repair and reperfusion in ‘no-option’ patients suffering from peripheral arterial diseases such as Critical Limb Ischemia (CLI).
Rod signals are routed through specific Off cone bipolar cells in primate retina
Authors: McLaughlin Amanda J. , Percival Kumiko A. , Gayet-Primo Jacqueline , Puthussery Teresa
Published: May 2020

Adapting between scotopic and photopic illumination involves switching the routing of retinal signals between rod and cone-dominated circuits. In the daytime, cone signals pass through parallel On and Off cone bipolar cells, that are sensitive to increments and decrements in luminance, respectively. At night, rod signals are routed into these cone-pathways via a key glycinergic interneuron, the AII amacrine cell (AII-AC). In primates, it is not known whether AII-ACs contact all Off-bipolar cell types indiscriminately, or whether their outputs are biased towards specific Off-bipolar cell types. Here, we show that the rod-driven glycinergic output of AII-ACs is strongly biased towards a subset of macaque Off-cone bipolar cells. The Off-bipolar types that receive this glycinergic input have sustained physiological properties and include the Off-midget bipolar cells, which provide excitatory input to the Off-midget ganglion cells (parvocellular pathway). The kinetics of the glycinergic events are consistent with the involvement of the α1 glycine receptor subunit. Taken together with results in mouse retina, our findings point towards a conserved motif whereby rod signals are preferentially routed into sustained Off signaling pathways.

Significance Statement

Visual signals pass through different retinal neurons depending on the prevailing level of illumination. Under night-time light levels, signals from rods pass through the AII amacrine cell, an inhibitory interneuron that routes rod signals into On and Off bipolar cells to detect increments and decrements in light intensity, respectively. Here, we show in primate retina that the output of AII amacrine cells is strongly biased towards specific Off bipolar cell types, which suggests that rod signals reach the brain via specific neural channels. Our results further our understanding of how visual signals are routed through visual circuits during night-time vision.
Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19
Authors: Larsen Mads Delbo , de Graaf Erik L. , Sonneveld Myrthe E. , Plomp H. Rosina , Linty Federica , Visser Remco , Brinkhaus Maximilian , Šuštić Tonći , de Taeye Steven W. , Bentlage Arthur E.H. , Nouta Jan , Natunen Suvi , Koeleman Carolien A. M. , Sainio Susanna , Kootstra Neeltje A. , Brouwer Philip J.M. , Sanders Rogier W. , van Gils Marit J. , de Bruin Sanne , Vlaar Alexander P.J. ,   Amsterdam UMC COVID-19 biobank study group, Zaaijer Hans L. , Wuhrer Manfred , van der Schoot C. Ellen , Vidarsson Gestur
Published: May 2020

IgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc-tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated binding and killing activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG which are of minor abundance in humans (∼6% of total IgG) are specifically formed against surface epitopes of enveloped viruses after natural infections or immunization with attenuated viruses, while protein subunit immunization does not elicit this low fucose response. This can give beneficial strong responses, but can also go awry, resulting in a cytokine-storm and immune-mediated pathologies. In the case of COVID-19, the critically ill show aggravated afucosylated-IgG responses against the viral spike protein. In contrast, those clearing the infection unaided show higher fucosylation levels of the anti-spike protein IgG. Our findings indicate antibody glycosylation as a potential factor in inflammation and protection in enveloped virus infections including COVID-19.