bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening and Prevention of Preeclampsia
Authors: Poon Liona C. , Sahota Daljit
Published: April 2020

Preeclampsia (PE) is a multisystem disorder of pregnancy classically characterized by hypertension with significant proteinuria after 20 weeks’ gestation. This disorder is one of the leading causes of maternal and perinatal morbidity and mortality. PE can be subdivided into preterm PE (with delivery at <37 weeks’ gestation) and term PE (with delivery at ≥37 weeks’ gestation). Preterm PE is associated with a higher risk of adverse maternal and perinatal outcomes than term PE. Traditional method of screening as recommended by professional guidelines has limited predictive performance and therefore should be updated to reflect recent scientific evidence that the target of screening should be preterm PE, the best way to identify the high-risk group is the Bayes-based method that combines maternal risk factors and biomarkers, the threshold should be set at screen positive rate of 10%, aspirin should be started before 16 weeks’ gestation, and the daily dose should be higher than 100 mg.
Cervical Assessment by Transvaginal Ultrasound for Predicting Preterm Birth in Asymptomatic Women
Authors: Li Jie
Published: April 2020

Preterm birth (PTB) is defined as delivery before completing 37 weeks of gestation. It is the main cause of neonatal morbidity and mortality in the most countries. The inherent cervical length and strength are two main features of the cervix that determine whether or not a pregnant woman is at risk for PTB. Routine transvaginal cervical length screening was recommended for women with singleton pregnancy and history of prior spontaneous PTB, while the issue of universal cervical length screening and the screening in multiple gestations remain an object of debate. Strain sonoelastography and shear-wave sonoelastography have been used to evaluate the cervical stiffness in pregnant women, but the predictive value for PTB still requires further investigations. In this review, we will discuss the measurement methods of cervical length and cervical stiffness, and compare the value of cervical assessment by transvaginal ultrasound for predicting PTB in asymptomatic women.
Protection Against Lethal Multidrug-Resistant Bacterial Infections Using Macrophage Cell Therapy
Authors: Tacke Robert , Sun Josh , Uchiyama Satoshi , Polovina Anya , Nguyen Deborah G. , Nizet Victor
Published: April 2020

Multidrug-resistant (MDR) bacterial infections exert a tremendous burden on the public health system throughout the developing and developed world. Slowing development of novel antibiotic scaffolds, over-prescription of antibiotics, extensive agricultural antibiotic use, and the increasingly complex hospitalized patient populations undergoing treatment, all fuel the rise of highly MDR “superbugs.” Unfortunately, host-directed therapies to boost immune resistance to infection are not currently available for treatment of MDR pathogens. Hematopoietic cells are endowed with a variety of mechanisms to control microbial invasion. Macrophages in particular have long been appreciated as potent antimicrobial immune cells equipped with several receptors that allow for rapid recognition, phagocytosis, and killing of pathogenic microbes, coupled to secretion of immunostimulatory cytokines to further orchestrate a robust multifaceted antibacterial immune response. To investigate the utility of macrophages as a cell therapy for MDR bacterial infections, we developed a therapeutically translatable process to generate, harvest, and cryopreserve monocyte-derived macrophages (ICONIMAC™). These cells effectively killed both Gram-positive and Gram-negative MDR pathogens in vitro, and conferred protection in vivo against experimental lethal peritonitis and lung infection. Our discoveries provide a proof-of-concept for a novel immuno-therapeutic approach against MDR bacterial infections, urgently needed to supplement the diminishing antibiotic pipeline.
Pharmacological and Immunological Aspects of Phage Therapy
Authors: Manohar Prasanth , Tamhankar Ashok. J. , Leptihn Sebastian , Ramesh Nachimuthu
Published: April 2020

Bacteriophages, or viruses of microbes, when used as a medical strategy, might be able to solve the current crisis mankind faces with the increasing number of pathogens being antibiotic-resistant, where chemical drugs seized to show any therapeutic effect. The so-called phage therapy may be one of the most promising alternatives to treat infections caused by antibiotic-resistant bacteria, which are killed after infection by a phage. While phages that destroy the host by lysis are chosen for therapy, many pharmacological and immunological aspects of phages as medicines have not been established so far. The immune system plays an important role in a process called phage acceptance where both, innate and adaptive immune responses of the host are involved. However, not only medical aspects but also social ones such as lacking public awareness or acceptance, and lack of structured regulatory guidelines are challenges that have to be addressed in the near future to establish phage therapy as a reliable and safe alternative for the treatment of infections. This review focuses on the unique pharmacological and immunological aspects of phages used in therapy.
Faropenem Susceptibility of Multidrug-resistant Contemporary Clinical Isolates from Zhejiang Province, China
Authors: Feng Xue-Wen , Shao Jun-Dan , Ji Zhong-Kang , Fang Hong , Ding Cheng , Wang Shu-Ting , Shang-Guan Yan-Wan , Shi Pei , Li Lan-Juan , Xu Kai-Jin
Published: April 2020

Alternative antimicrobial therapies are urgently needed for a variety of multidrug-resistant bacterial pathogens. Faropenem is an orally available β-lactam in the class of carbapenem antibiotics. Thus far, little information is available on faropenem susceptibility of multidrug-resistant clinical isolates from China. Therefore, in the current study 141 contemporary clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA: n = 18), coagulase-negative staphylococci (CNS: n = 16), Enterococcus faecalis (n = 14), Enterococcus faecium (n = 7), Pseudomonas aeruginosa (n = 25), Klebsiella pneumoniae (n = 21), Escherichia coli (n = 20), and Acinetobacter baumannii (n = 20), were collected between March 2018 and March 2019 and tested for susceptibility to faropenem and other antimicrobials using the broth microdilution method. All E. faecium, P. aeruginosa, and A. baumannii isolates were fully resistant to faropenem. However, most of the MRSA, CNS, E. faecalis, K. pneumonia, and E. coli isolates appeared to be susceptible to faropenem, with minimal inhibitory concentration90 values of 4 mg/L, 2 mg/L, 2 mg/L, 4 mg/L, and 2 mg/L, respectively. Therefore, faropenem could be considered as alternative therapy for future treatment of multidrug-resistant MRSA, CNS, E. faecalis, K. pneumonia, and E. coli infections in China.
Allicin and Glycyrrhizic Acid Display Antiviral Activity Against Latent and Lytic Kaposi Sarcoma-associated Herpesvirus
Authors: Xie Yirui , Chen Ying , Guo Yongzheng , Huang Ying , Zhu Biao
Published: April 2020

Kaposi sarcoma-associated herpesvirus (KSHV) triggers the development of Kaposi sarcoma, a skin malignancy that is one of the most widespread defining symptoms in acquired immunodeficiency syndrome patients. KSHV manifests in two distinct cycles, a chronic latent cycle and an acute lytic cycle. Current clinical anti-herpesvirus therapeutic agents are predominantly composed of nucleoside analogues that target viral replication in the lytic cycle only, while KSHV latent genes are at the basis tumorigenesis. Currently, there are no effective therapies targeting latent KSHV infections. Therefore, the aim of this study was to identify putative therapeutic compounds with inhibitory activity against latent KSHV. The KSHV-infected primary effusion lymphoma cell line BC-3 was used to study antiviral activity of glycyrrhizic acid (GA), Allicin, and epigallocatechin-3-gallate (EGCG) against latent and lytic KSHV. Activity of GA, Allicin, EGCG, and the established anti-lytic cycle control compound ganciclovir was quantified by real-time polymerase chain reaction of nuclear and virion KSHV DNA yields after treatment compared with the untreated control. GA and Allicin showed antiviral activity against both latent and lytic KSHV, while EGCG displayed activity against lytic KSHV only. Therefore, GA and Allicin are interesting compounds for further development of anti-KSHV therapy against latent cycle infections.
Role of Outer Membrane Vesicles in Bacterial Physiology and Host Cell Interactions
Authors: Gao Lingyu , van der Veen Stijn
Published: April 2020

Outer membrane vesicles (OMVs) are spherical particles shed from the outer membrane of Gram-negative bacteria, which contain the typical components present in the outer membrane, although enrichment of specific molecules may occur, and furthermore a variety of periplasmic components and occasionally some inner membrane or cytoplasmic fractions. Although the detailed mechanisms of OMV biogenesis are not fully illuminated yet, several models have been proposed that demonstrate OMV biogenesis is an orchestrated well-regulated process. OMV secretion offers a way for both intra- and inter-species bacterial communication and for interaction or modulation of the bacterial environment. Therefore, OMVs have proven to be functionally versatile and important for bacterial physiology and survival of the host environment. In the host, OMVs are internalized via host cell endocytosis pathways, allowing them to subsequently trigger a variety of cellular responses. In this review, we discuss the recent advances in establishing the mechanisms involved in OMV biogenesis and the impact of OMVs on bacterial physiology and intracellular modulation of the host.
Suboptimal Chlamydia trachomatis Detection Method Is Still Widely Used in China: Results of External Quality Assessments from 2013 to 2018
Authors: Han Yan , Yin Yue-Ping , Zhong Ming-Ying , Chen Kai , Shi Mei-Qin , Chen Xiang-Sheng
Published: April 2020

Objective:

Laboratory capacity for Chlamydia trachomatis (C. trachomatis) detection is important in the diagnosis and treatment of C. trachomatis infection, appropriate clinical management of patients, and providing evidence for prevention programs. We conducted this study to assess laboratory capabilities for detecting C. trachomatis in China by analysis of external quality assessment (EQA) results from 2013 to 2018.

Methods:

Overall, 310/1,048 (29.58%) laboratories at national sexually transmitted disease (STD) sentinel site with 252–272 laboratories per time participated in six times of EQA. Each laboratory was requested to test the samples from EQA organization by the common method used, and the test results were reported to EQA organization for assessment. Z test and multinomial logistic regression analyses were used for data analyses.

Results:

Immunochromatographic test, nucleic acid amplification test (NAAT), and ELISA were used and accounted for 76.69%, 21.54%, 1.77%, respectively of all participating laboratories from 2013 to 2018. The total specificity for negative samples was 94.76%, the sensitivity for positive samples with medium and high concentration of C. trachomatis samples were 94.31% and 95.51%, respectively, but the sensitivity for sample with low concentration of C. trachomatis was 36.89%, and the immunochromatographic test had the worst sensitivity for detection of this sample (21.17% [95% CIs: 18.93%–23.60%]) among the three methods. Three factors were found to be significantly associated with the sensitivity of the low-concentration sample: the location of laboratories (East China: adjusted odds ratio [AOR] = 2.98, 95% CIs: 1.69–5.25, P < 0.05; South China: AOR = 3.34, 95% CIs: 1.38–5.48, P < 0.05; Southwest China: AOR = 2.75, 95% CIs: 1.37–5.48, P < 0.05, as compared with Northwest China); the types of hospitals (prevention and control agencies: AOR = 0.56, 95% CIs: 0.40–0.80, P < 0.05, as compared with general hospitals); and the method used (NAAT: AOR = 46.99, 95% CIs: 28.49–77.48, P < 0.050; ELISA: AOR = 5.42, 95% CIs: 2.40–12.25, P < 0.05, as compared with immunochromatographic test).

Conclusion:

Immunochromatographic test is widely used for C. trachomatis antigen in China; however, based on its suboptimal detection sensitivity, methods with high sensitivity such as NAAT-based point-of-care diagnostic method are recommended to apply for C. trachomatis detection, and efforts should be performed to promote the high-sensitivity methods among laboratories.
Epidemiological Characteristics of Leprosy in China, 2018
Authors: Wang Le , Sun Pei-Wen , Yu Mei-Wen , Gu Heng , Wang Hong-Sheng , Chen Xiang-Sheng
Published: April 2020

Objective:

To describe the epidemiological characteristics of leprosy in China in 2018 and provide the essential evidences for leprosy control.

Methods:

We collected data of leprosy cases nationwide from Leprosy Management Information System in China (LEPMIS) except Hong Kong, Macao, and Taiwan. And then we performed a descriptive and comparative analysis.

Results:

A total of 521 new leprosy cases were detected nationwide in 2018, with a case detection rate of 0.037/100,000. The proportion of children under 15 years of age, multi-bacillary (MB) cases, and cases with WHO grade 2 disability (G2D) were 1.3%, 89.4%, and 19.0%, respectively. There were 2,479 registered cases of leprosy in China by the end of 2018, accounting for a prevalence rate of 0.178/100,000, with 43 replase cases. Southwest China separately accounted for 312/521 (59.9%) newly detected cases and 1180/2479 (47.6%) registered cases of leprosy in China.

Conclusion:

China is a low endemic country for leprosy and the detection rate was much lower than the global average. Southwest China is still the key regions for leprosy control, including Yunnan, Guizhou, and Sichuan. In addition, leprosy in low endemic provinces also needs to be focused.
Erosive Pustular Dermatosis of the Scalp After Excision and Skin Grafting of Scalp Squamous Cell Carcinoma
Authors: He Xun , Wang Chao-Qun , Lu Wei , Gong Yu-Gang , Sha Xiao-Wei , Shen Zhu
Published: April 2020

Introduction:

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon condition with unknown etiology. The clinical exclusive diagnosis needs to be differentiated from similar diseases.

Here, we present a case of EPDS after surgical treatment of scalp squamous cell carcinoma.

Case presentation:

A 68-year-old woman presented with an eight-month history of a chronic scalp eruption. She had been diagnosed as squamous cell carcinoma by biopsy nine months ago, and had been treated by surgical excision and skin grafting. One month later, she was referred for evaluation of the newly enlarged lesion which was observed at the skin grafting site. She was diagnosed of EPDS based on characteristics of lesions, clinicopathological findings and laboratory data. The condition had clinically improved with systemic steroid therapy and topical tacrolimus for two weeks. Relapses occurred after complete withdrawal of both treatments. After repeating the above therapy and applying topical tacrolimus as maintenance therapy, the condition was well controlled at the one-year follow-up.

Discussion:

EPDS is an uncommon inflammatory dermatosis with main incidence rate of elderly patients and female predominance. The diagnosis of EPDS cant be made only by histopathological examination, which is helpful for differential diagnosis. Microbiological investigations commonly remain negative. For the high risk of relapse, it is important for clinicians to be aware of maintenance treatment and a long- term management.

Conclusion:

It should be recognized by clinicians that EPDS is an uncommon and relapse disease, leading to serious cosmetic problems. The treatment lacks evidence-based medicine data, clinician should choose the appropriate therapy according to the condition of patients.
Effects of Honokiol on Activation of Transient Receptor Potential Channel V1 and Secretion of Thymic Stromal Lymphopoietin in HaCaT Keratinocytes
Authors: Xie Bo , Song Sha-Sha , Wang Yong-Fang , Wu Jian-Bing , Li Xin-Yu
Published: April 2020

Objective:

This study was performed to investigate the effects of honokiol on the activation of transient receptor potential channel V1 (TRPV1) and the secretion of thymic stromal lymphopoietin (TSLP) in a human benign epidermal keratinocyte line (HaCaT).

Methods:

HaCaT keratinocytes were cultivated and divided into six groups: capsaicin-induced model control group, capsazepine control group, solvent control group, and three honokiol treatment groups (7.81, 15.63, and 31.25 mg/L of honokiol). The effect of honokiol on calcium (Ca2+) influx was measured by a Ca2+ fluorescence imaging system. The fluorescence intensity (F) of cells was measured. The rate of change in F (ΔF/F
0) was calculated, and the ΔF/F
0–time curve was constructed. HaCaT keratinocytes were stimulated with polyinosinic:polycytidylic acid, recombinant human tumor necrosis factor α, and recombinant human interleukin 4. Different concentrations of honokiol (15.63, 7.81, and 3.91 mg/L) were added to the cells in the respective honokiol groups; 20 mg/L of dexamethasone or 0.5% dimethyl sulfoxide was added to the cells in the positive control group or solvent control group. The TSLP concentration in the HaCaT keratinocytes of each group was detected by enzyme-linked immunosorbent assay. Statistical analysis was performed by one-way analysis of variance and Dunnett t test.

Results:

The capsazepine-induced Ca2+ fluorescence intensity in HaCaT keratinocytes was significantly inhibited in the 31.25 mg/L honokiol group; ΔF/F
0 at 45 second was 0.76 in the model control group and 0 in the 31.25 mg/L honokiol group. The TSLP level in the 15.63 and 7.81 mg/L honokiol groups was lower than that in the solvent control group (t = 7.382, P = 0.003, and t = 2.766, P = 0.023, respectively), while the TSLP level in the 3.91 mg/L honokiol group was not significantly different from that in the solvent control group (t = 1.872, P = 0.124).

Conclusions:

Honokiol inhibited the Ca2+ influx induced by capsazepine (TRPV1 agonist) in HaCaT keratinocytes. Honokiol has an inhibitory effect on TSLP secretion in HaCaT keratinocytes.
Tinea of Vellus Hair Caused by Trichophyton violaceum in a Child: A Case Report
Authors: Song Ge , Liang Guan-Zhao , Liu Wei-Da
Published: April 2020

Introduction:

Tinea of vellus hair is a rare dermatophytosis, caused by dermatophyte infection in the vellus hair. The clinical symptoms of tinea of vellus hair are more serious and the conventional topical treatment are often ineffective.

Here, we report a case of tinea of vellus hair caused by Trichophyton violaceum in a child.

Case presentation:

A 7-year-old boy presented with a localized, scaly, and itchy erythema on his left cheek for two months. He once used a topical corticosteroid but without any clinical improvement, the erythema was progressively enlarging and spread to the left eyebrow. He denied any contact with animals. Direct microscopy found abundant spores and hyphae on the vellus hair; T. violaceum was identified by culture and PCR examination. The patient was diagnosed with tinea of vellus hair and cured after treating with oral terbinafine 125 mg/day and topical treatment for two weeks. There was no recurrence during the follow-up period.

Discussion:

The clinical symptoms of tinea of vellus hair are often atypical and easy to be misdiagnosed. Timely fungal examination is necessary for suspicious patients and confirmed patients should be treated with oral antifungal drugs.

Conclusion:

The diagnosis and treatment of tinea of vellus hair need to be paid more attention in clinical works.
Acrodermatitis Continua of Hallopeau With Excellent Response to Topical Calcipotriol/Betamethasone Ointment: A Report of Two Cases
Authors: Zhao Yu-Kun , Wu Hui-Hui , Liu Juan-Hua , Luo Di-Qing
Published: April 2020

Introduction:

Acrodermatitis continua of Hallopeau (ACH) is an uncommon chronic cutaneous disorder. Up to date, its treatment is still difficult and frustrating although various topical and systemic agents alone or in different combinations have been tried with variable benefits.

Herein, we report two cases of ACH successfully treated with calcipotriol/betamethasone ointment.

Case presentation:

Two cases of ACH were characterized by thumb involvement alone and showed an excellent response to calcipotriol/betamethasone ointment (1 g: calcipotriol 50 µg and betamethasone 0.5 mg).

Discussion:

Treatment of ACH is challenging for physicians. Multiple systemic therapies and topical drugs have been applied, however, no universally effective treatment regimen has yet been established for long-lasting remission. Combination of calcipotriol and betamethasone is more effective in treating psoriasis than the individual components alone, and the current 2 cases with ACH were reported to be treated successfully by the calcipotriol/betamethasone ointment.

Conclusion:

Topical calcipotriol/betamethasone compound is an optional agent for the treatment of ACH with a novel effect.
Nail Changes as the Initial Sign of Psoriasis: A Case Report
Authors: Zhang Jing , Chen Xue-Yan , Man Xiao-Yong , Zheng Min
Published: April 2020

Introduction:

Nail psoriasis has a profound negative influence on quality of life and has a more closely relationship with psoriatic arthritis. However, patients with nail changes only were often overlooked with the diagnosis of psoriasis. It is necessary to pay more attention to nail psoriatic changes.

Herein, we report a 24-year-old male patient with nail changes as the initial sign of psoriasis who was finally diagnosed with nail psoriasis.

Case presentation:

The nails presented with white streaks, deformations, and had been missed for 8 months. Physical examination further revealed one erythematous scaly plaque on the buttock, anusand scalp respectively with positive Auspitz sign. Combined with the negative fungal microscopic, dermoscopic results and pathological results, the diagnosis of nail psoriasis was made. Oralacitretin (30 mg/day) and topical calcipotriene liniment was prescribed for 3 months followed with etanercept (50 mg once per week), and the nail symptoms were well controlled.

Discussion:

Nail psoriasis is usually noticed after the occurrence of skin lesions, but may occur simultaneously with or before skin psoriasis. Occasionally, nail involvement is the only manifestation of psoriasis. Nail lesions maybe one of the strongest clinical predictors of psoriatic and it has a profound negative influence on quality of life, so that timely recognition and proper treatment are improtant.

Conclusion:

Nail psoriasis can cause substantial physical and psychological impairment. However, nail involvement is an often overlooked feature of psoriasis. More attention should be paid to nail psoriatic changes and the administration of appropriate treatment.
Eosinopenia Phenotype in Patients with Coronavirus Disease 2019: A Multi-center Retrospective Study from Anhui, China
Authors: Cheng Yusheng , Zhou Yun , Zhu Mengde , Zha Lei , Lu Zhiwei , Ding Zhen , Jianghua Yang , Yang Gang
Published: April 2020

Background

Coronavirus disease 19 (COVID-19) has become a global unprecedented pandemic infecting more than one millon people, which is declared by WHO as a international public health emergency. Eosinopenia may predict a poor prognosis of COVID-19. However, to date, there is no detailed analysis of the clinical characteristics of COVID-19 patients with eosinopenia.

Research question

The aim of this study was to describe clinical characteristics of COVID-19 patients with eosinopenia.

Study Design and Methods

This was a multi-center retrospective study conducted in three tertiary hospitals. A total of 59 patients with COVID-19 were reviewed from January 23, 2020 to March 10, 2020. We described clincial characteristics of patients with COIVD-19 and eosinopenia phenotype.

Results

The median age of patients with COVID-19 was 39 years old, and 32 (54,2%) were male. Patients with severe type had higher proportions of dyspnea (50%) and gastrointestinal symptoms (50%) compared with mild or moderate patients. Laboratory findings indicated that lower counts of lymphocyte and eosnophils were observed in patients with severe type. Cough, sputum, and fatigue were more common symptoms in eosinopenia patients compared with non-eosinopenia patients. High proportion of comorbidities was observed in eosinopenia patients. Laboratory findings indicated that lymphocyte counts (median: 101 cells/μl) in eosinopenia patients were significantly less than those of non-eosinopenia patients (median: 167 cells/μl, p<0.001). The use of corticosteroids therapy in COVID-19 patients with eosinopenia were notably higher than those in patients with non-eosinopenia (50% vs 13.8%, respectively, p=0.005). Compared with parameters in non-eosinopenia patients, eosinopenia patients were more inclined to have less lymphocyte counts (OR value 6.566, 95%CI[1.101-39.173], p=0.039).

Interpretation

Eosinopenia are very common in COVID-19 patient, particularly in severe patients. Common symptoms included fever, cough, sputum, and fatigue are frequent in eosinopenia patients. Eosinopenia may represent a novel phenotype in COVID-19, which needs further investigation.
Relative disease burdens of COVID-19 and seasonal influenza in New York City, February 1 - April 18, 2020
Authors: Faust Jeremy Samuel , Rio Carlos del
Published: April 2020

Comparisons between the mortality burdens of COVID-19 and seasonal influenza often fail to account for the fact that the United States Centers for Disease Control and Prevention (CDC) reports annual influenza mortality estimates which are calculated based upon a series of assumptions about the underreporting of flu deaths. COVID-19 deaths, in contrast, are being reported as raw counts. In this report, we compare COVID-19 death counts to seasonal influenza death counts in New York City during the interval from February 1 - April 18, 2020. Using this approach, COVID-19 appears to have caused 21.4 times the number of deaths as seasonal influenza during the same period. We also assessed excess mortality in order to verify this finding. New York City has had approximately 13,032 excess all-cause mortality deaths during this time period. We assume that most of these deaths are COVID-19 related. We therefore calculated the ratio of excess deaths (i.e. assumed COVID-19 deaths) to seasonal influenza deaths during the same time interval and found a similar ratio of 21.1 COVID-19 to seasonal influenza deaths. Our findings are consistent with conditions on the ground today. Comparing COVID-19 deaths with CDC estimates of yearly influenza-related deaths would suggest that, this year, seasonal influenza has killed approximately the same number of Americans as COVID-19 has. This does not comport with the realities of the pandemic we see today.
A predictive model to estimate survival of hospitalized COVID-19 patients from admission data
Authors: Levy Todd J. , Richardson Safiya , Coppa Kevin , Barnaby Douglas P. , McGinn Thomas , Becker Lance B. , Davidson Karina W. , Hirsch Jamie S. , Zanos Theodoros P. ,   And the Northwell COVID-19 Research Consortium, Cohen Stuart L. , Debnath Shubham , Dominello Andrew J. , Falzon Louise , Gitman Michael , Kim Eun-Ji , Makhnevich Alexander , Mogavero Jazmin N. , Molmenti Ernesto P. , Paradis Marc d. , Tóth Viktor
Published: April 2020

Objective

Our primary objective was to use initial data available to clinicians to characterize and predict survival for hospitalized coronavirus disease 2019 (COVID-19) patients. While clinical characteristics and mortality risk factors of COVID-19 patients have been reported, a practical survival calculator based on data from a diverse group of U.S. patients has not yet been introduced. Such a tool would provide timely and valuable guidance in decision-making during this global pandemic.

Design

We extracted demographic, laboratory, clinical, and treatment data from electronic health records and used it to build and test the predictive accuracy of a survival probability calculator referred to as “the Northwell COVID-19 Survival (‘NOCOS’) calculator.”

Setting

13 acute care facilities at Northwell Health served as the setting for this study.

Participants

5,233 hospitalized COVID-19–positive patients served as the participants for this study.

Main outcome measures

The NOCOS calculator was constructed using multivariate regression with L1 regularization (LASSO) to predict survival during hospitalization. Model predictive performance was measured using Receiver Operating Characteristic (ROC) curves and the Area Under the Curve (AUC) of the calculators.

Results

Patient age, serum blood urea nitrogen, Emergency Severity Index, red cell distribution width, absolute neutrophil count, serum bicarbonate, and glucose were identified as the optimal predictors of survival by multivariate LASSO regression. The predictive performance of the NOCOS calculator had an AUC of 0.832, reaching 0.91 when updated for each patient daily, with stability assessed and maintained for 14 consecutive days. This outperformed other established models, including the Sequential Organ Failure Assessment (SOFA) score (0.732).

Conclusions

We present a practical estimate of survival probability that outperforms other general risk models. The seven early predictors of in-hospital survival can help clinicians identify patients with increased probabilities of survival and provide critical decision support as COVID-19 spreads across the U.S.

Trial registration

N/A
Clinical evaluation of an immunochromatographic IgM/IgG antibody assay and chest computed tomography for the diagnosis of COVID-19
Authors: Imai Kazuo , Tabata Sakiko , Ikeda Mayu , Noguchi Sakiko , Kitagawa Yutaro , Matsuoka Masaru , Miyoshi Kazuyasu , Tarumoto Norihito , Sakai Jun , Ito Toshimitsu , Maesaki Shigefumi , Tamura Kaku , Maeda Takuya
Published: April 2020

Background

We evaluated the clinical performance of an immunochromatographic (IC) IgM/IgG antibody assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and chest computed tomography (CT) for the diagnosis of Coronavirus disease 2019 (COVID-19).

Methods

We examined 139 serum specimens collected from 112 patients with COVID-19 and 48 serum specimens collected from 48 non-COVID-19 patients. The presence of IgM/IgG antibody for SARS-CoV2 was determined using the One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test. Chest CT was performed in COVID-19 patients on admission.

Findings

Of the139 COVID-19 serum specimens, IgM was detected in 27.8%, 48.0%, and 95.8% of the specimens collected within 1 week, 1–2 weeks, and >2 weeks after symptom onset and IgG was detected in 3.3%, 8.0%, and 62.5%, respectively. Among the 48 non-COVID-19 serum specimens, 1 generated a false-positive result for IgM. Thirty-eight of the 112 COVID-19 patients were asymptomatic, of whom 15 were positive for IgM, and 74 were symptomatic, of whom 22 were positive for IgM and 7 were positive for IgG. The diagnostic sensitivity of CT scan alone and in combination with the IC assay was 57.9 % (22/38) and 68.4% (26/38) for the asymptomatic patients and 74.3% (55/74) and 82.4% (61/74) for the symptomatic patients, respectively.

Conclusion

The IC assay had low sensitivity during the early phase of infection, and thus IC assay alone is not recommended for initial diagnostic testing for COVID-19. If RT-qPCR is not available, the combination of chest CT and IC assay may be useful for diagnosing COVID-19.
Untangling factors associated with country-specific COVID-19 incidence, mortality and case fatality rates during the first quarter of 2020
Authors: Shagam Lev
Published: April 2020

At early stages of the COVID-19 pandemic which we are experiencing, the publicly reported incidence, mortality and case fatality rates (CFR) vary significantly between countries. Here we aim to untangle factors that are associated with the differences during the first quarter of the year 2020. Number of performed COVID-19 tests has a strong correlation with country-specific incidence (p < 2 × 10−16) and mortality rate (p = 5.1 × 10−8). Using multivariate linear regression we show that incidence and mortality rates correlate significantly with GDP per capita (p = 2.6 × 10−15 and 7.0 × 10−4, respectively), country-specific duration of the outbreak (2.6 × 10−4 and 0.0019), fraction of citizens over 65 years old (p = 0.0049 and 3.8 × 10−4) and level of press freedom (p = 0.021 and 0.019) which cumulatively explain 80% of variability of incidence and more than 60% of variability of mortality of the disease during the period analyzed. Country hemisphere demonstrated significant correlation only with mortality (p = 0.17 and 0.036) whereas population density (p = 0.94 and p = 0.75) and latitude (p = 0.61 and 0.059) did not reach significance in our model. Case fatality rate is shown to rise as the outbreak progresses (p=0.028). We rank countries by COVID-19 mortality corrected for incidence and the factors that were shown to affect it, and by CFR corrected for outbreak duration, yielding very similar results. Among the countries where the outbreak started after the 15th of February and with at least 1000 registered patients during the period analyzed, the lowest corrected CFR are seen in Israel, South Africa and Chile. The ranking results should be considered with caution as they do not consider all confounding factors or data reporting biases.
Merging the Traditional with the NewCME-accredited Twitter Journal Clubs
Authors: Desai Tejas
Published: April 2020

Twitter journal clubs are increasingly popular amongst healthcare providers. Most journal clubs rely on voluntary physician participation. Offering continuing medical education credit may incentivize and improve these journal clubs.

In this investigation a series of 5 consecutive publication-sponsored Twitter journal clubs were analyzed in calendar year 2016, in which the latter 3 journal clubs offered CME credit. Various quality metrics were measured and analyzed to identify sustainable improvements in those journal clubs that offered CME credit.

Overall, Twitter journal clubs that offered CME credit performed better in certain quality metrics, to wit activity, originality, and evidence-based tweeting, but fared poorly in number of and type of participant interactions.

Twitter journal clubs are in their infancy and physician participation remains steady. Offering CME credit improves certain quality metrics within these journal clubs. This investigation should encourage more publications to sponsor CME-accredited Twitter journal clubs.
Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank
Authors: Niedzwiedz Claire L , O’Donnell Catherine A , Jani Bhautesh Dinesh , Demou Evangelia , Ho Frederick K , Celis-Morales Carlos , Nicholl Barbara I , Mair Frances , Welsh Paul , Sattar Naveed , Pell Jill P , Katikireddi S Vittal
Published: April 2020

Background

Understanding of the role of ethnicity and socioeconomic position in the risk of developing SARS-CoV-2 infection is limited. We investigated this in the UK Biobank study.

Methods

The UK Biobank study recruited 40-70 year olds in 2006-2010 from the general population, collecting information about self-defined ethnicity and socioeconomic variables (including area-level socioeconomic deprivation and educational attainment). SARS-CoV-2 test results from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to assess risk ratios (RRs) between the exposures and dichotomous variables for: being tested, having a positive test and testing positive in hospital. We also investigated whether ethnicity and socioeconomic position were associated with having a positive test amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size), behavioural risk factors and baseline health.

Results

Among 428,225 participants in England, 1,474 had been tested and 669 tested positive between 16 March and 13 April 2020. Black, south Asian and white Irish people were more likely to have confirmed infection (RR 4.01 (95%CI 2.92-5.12); RR 2.11 (95%CI 1.43-3.10); and RR 1.60 (95% CI 1.08-2.38) respectively) and were more likely to be hospital cases compared to the White British. While they were more likely to be tested, they were also more likely to test positive. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 2.26 (95%CI 1.76-2.90); and RR 1.91 (95%CI 1.53-2.38) respectively).

Conclusions

Some minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study which was not accounted for by differences in socioeconomic conditions, measured baseline health or behavioural risk factors. An urgent response to addressing these elevated risks is required.
The Potential Impact of Interruptions to HIV Services: A Modelling Case Study for South Africa
Authors: Jewell Britta , Smith Jennifer , Hallett Timothy
Published: April 2020

The numbers of deaths caused by HIV could increase substantially if the COVID-19 epidemic leads to interruptions in the availability of HIV services. We compare publicly available scenarios for COVID-19 mortality with predicted additional HIV-related mortality based on assumptions about possible interruptions in HIV programs. An interruption in the supply of ART for 40% of those on ART for 3 months could cause a number of deaths on the same order of magnitude as the number that are anticipated to be saved from COVID-19 through social distancing measures. In contrast, if the disruption can be managed such that the supply and usage of ART is maintained, the increase in AIDS deaths would be limited to 1% over five years, although this could still be accompanied by substantial increases in new HIV infections if there are reductions in VMMC, oral PrEP use, and condom availability.
Short term Biological Variation of Differential Count in Healthy Subjects in a South Asian Population
Authors: Gupta Arvind Kumar , Arathi K. , Tayal Sakshi Garg , Mehan Anoushika , Sahay Rishabh , Kumar Utpal , Anthony Michael Leonard , Singh Neha , Chandra Harish , Chowdhury Nilotpal
Published: April 2020

Introduction

Estimates of Within-Subject and between subject biological variation in South Asia are sorely lacking. Therefore, we attempted to estimate the short-term estimates of the same for Differential Counts (DC).

Methods

The study was conducted on twenty eight healthy volunteers (15 males and 13 females). After morning collection of blood in K3-EDTA vials analysis was conducted in triplicate on the Sysmex XN-1000 analyzer for six consecutive days. The Within subject, between subject and analytical coefficient of variation of the DC was calculated from the results by nested repeated measures ANOVA after outlier exclusion. The Reference change values (RCV) were also calculated.

Results

The within-subject variation for Eosinophil Count in our group from South Asia was greater than the published European and American studies. The between-subject variation in monocytes and basophils were also increased. Males and females showed similar biological variation for DC. The Within-subject variation of other parameters (Neutrophils, Lymphocytes, Monocytes and Basophils) were similar or showed only mild differences to the published studies.

Conclusion

The markedly different within-subject variation for Eosinophil counts suggest that the RCV for DC in South Asians need to be different from the published data in order to have clinical relevance. The Within-subject variation values of the other parameters seem transportable from the published European and American studies, but small differences found mean that further regional estimates need to be found for robust evidence of the same.
A systematic review and meta-analysis of Anakinra, Sarilumab, Siltuximab and Tocilizumab for Covid-19
Authors: Khan Fasihul , Stewart Iain , Fabbri Laura , Moss Samuel , Robinson Karen A. , Smyth Alan , Jenkins Gisli
Published: April 2020

Background

There is accumulating evidence for an overly activated immune response in severe Covid-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of Covid-19.

Methods

Electronic databases were searched on 7thJanuary 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of Covid-19. The primary outcomes were severity on an ordinal scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality.

Results

71 studies totalling 22,058 patients were included, six were randomised trials. Most explored outcomes in patients who received tocilizumab (59/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (RR 0.83 95%CI 0.72;0.96 I2= 0.0%), but conclusive benefit was not demonstrated for other outcomes. In retrospective studies, tocilizumab was associated with less severe outcomes on an ordinal scale (Generalised odds ratio 1.34 95%CI 1.10;1.64, I2=98%) and adjusted mortality risk (HR 0.52 95%CI 0.41;0.66, I2=76.6%). The mean difference in duration of hospitalisation was 0.36 days (95%CI -0.07;0.80, I2=93.8%). There was substantial heterogeneity in retrospective studies, and estimates should be interpreted cautiously. Other immunomodulatory agents showed similar effects to tocilizumab, but insufficient data precluded meta-analysis by agent.

Conclusion

Tocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in Covid-19 is insufficient, with further studies urgently needed for conclusive findings.
A draft genome of grass pea (Lathyrus sativus), a resilient diploid legume
Authors: Emmrich Peter M. F. , Sarkar Abhimanyu , Njaci Isaac , Kaithakottil Gemy George , Ellis Noel , Moore Christopher , Edwards Anne , Heavens Darren , Waite Darren , Cheema Jitender , Trick Martin , Moore Jonathan , Webb Anne , Caiazzo Rosa , Thomas Jane , Higgins Janet , Swarbreck David , Kumar Shiv , Mundree Sagadevan , Loose Matt , Yant Levi , Martin Cathie , Wang Trevor L.
Published: April 2020

We have sequenced the genome of grass pea (Lathyrus sativus), a resilient diploid (2n=14) legume closely related to pea (Pisum sativum). We determined the genome size of the sequenced European accession (LS007) as 6.3 Gbp. We generated two assemblies of this genome, i) EIv1 using Illumina PCR-free paired-end sequencing and assembly followed by long-mate-pair scaffolding and ii) Rbp using Oxford Nanopore Technologies long-read sequencing and assembly followed by polishing with Illumina paired-end data. EIv1 has a total length of 8.12 Gbp (including 1.9 billion Ns) and scaffold N50 59,7 kbp. Annotation has identified 33,819 high confidence genes in the assembly. Rbp has a total length of 6.2 Gbp (with no Ns) and a contig N50 of 155.7 kbp. Gene space assessment using the eukaryote BUSCO database showed completeness scores of 82.8 % and 89.8%, respectively.
The flagellar motor ofVibrio alginolyticusundergoes major structural remodeling during rotational switching
Authors: Carroll Brittany L. , Nishikino Tatsuro , Guo Wangbiao , Zhu Shiwei , Kojima Seiji , Homma Michio , Liu Jun
Published: April 2020

The bacterial flagellar motor is an intricate nanomachine that switches rotational directions between counterclockwise (CCW) and clockwise (CW) to direct the migration of the cell. The cytoplasmic ring (C-ring) of the motor, which is composed of FliG, FliM, and FliN, is known for controlling the rotational sense of the flagellum. However, the mechanism underlying rotational switching remains elusive. Here, we deployed cryo-electron tomography to visualize the C-ring in two rotational biased mutants (CCW-biasedfliG-G214S and CW-lockedfliG-G215A) inVibrio alginolyticus. Sub-tomogram averaging was utilized to resolve two distinct conformations of the C-ring. Comparison of the C-ring structures in two rotational senses provide direct evidence that the C-ring undergoes major structural remodeling during rotational switch. Specifically, FliG conformational changes elicit a large rearrangement of the C-ring that coincides with rotational switching, whereas FliM and FliN form a spiral-shaped base of the C-ring, likely stabilizing the C-ring during the conformational remodeling.
The Murphy number: how pitch moment of inertia dictates quadrupedal walking and running energetics
Authors: Polet Delyle T.
Published: April 2020

Most quadrupedal mammals transition from a four-beat walk to a two-beat run (e.g. trot), but some transition to a four-beat run (e.g. amble). Recent analysis shows that a two-beat run minimizes work only for animals with a small pitch moment of inertia (MOI), though empirical MOI were not reported. It also remains unclear whether MOI affects gait energetics at slow speeds. Here I show that a particular normalization of the pitch moment of inertia (the Murphy number) has opposite effects on walking and running energetics. During walking, simultaneous fore and hindlimb contacts dampen pitching energy, favouring a four-beat gait that can distribute expensive transfer of support. However, the required pitching of a four-beat walk becomes more expensive as Murphy number increases. Using trajectory optimization of a simple model, I show that both the walking and slow running strategies used by dogs, horses, giraffes and elephants can be explained by work optimization under their specific Murphy numbers. Rotational dynamics have been largely ignored as a determining factor in quadrupedal locomotion, but appear to be a central factor in gait selection.
Flow-cell based technology for massively parallel characterization of base-modified DNA aptamers
Authors: Wu Diana , Feagin Trevor , Mage Peter , Rangel Alexandra , Wan Leighton , Kong Dehui , Li Anping , Coller John , Eisenstein Michael , Soh H. Tom
Published: April 2020

Aptamers incorporating chemically modified bases can achieve superior affinity and specificity compared to natural aptamers, but their characterization remains a labor-intensive, low-throughput task. Here we describe the ‘non-natural aptamer array’ (N2A2) system, in which a minimally modified Illumina MiSeq instrument is used for the high-throughput generation and characterization of large libraries (∼106) of base-modified DNA aptamer candidates on the basis of both target affinity and specificity. We first demonstrate the capability to screen multiple different base modifications to identify the optimal chemistry for high-affinity target binding. We next use N2A2 to generate aptamers that can maintain excellent specificity even in complex samples, with equally strong target affinity in both buffer and diluted human serum. Given that N2A2 requires only minor mechanical modifications to the MiSeq, we believe N2A2 offers a broadly accessible tool for generating high-quality affinity reagents for diverse applications.