bluuebunny/crossref_metadata_2025 huggingface dataset:
Association and pathways between shift work and cardiovascular disease: a prospective cohort study of 238 661 participants from UK Biobank
Authors: Ho Frederick K , Celis-Morales Carlos , Gray Stuart R , Demou Evangelia , Mackay Daniel , Welsh Paul , Katikireddi S Vittal , Sattar Naveed , Pell Jill P
Published: June 2021

Background

This study aimed to study the association between shift work and incident and fatal cardiovascular disease (CVD), and to explore modifying and mediating factors.

Methods

This is a population-based, prospective cohort study with a median follow-up of 11 years; 238 661 UK Biobank participants who were in paid employment or self-employed at baseline assessment were included.

Results

Shift workers had higher risk of incident [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.06–1.19] and fatal (HR 1.25, 95% CI 1.08–1.44) CVD compared with non-shift workers, after adjusting for socio-economic and work-related factors. The risk was higher with longer duration of shift work, in women and in jobs with little heavy manual labour. Current smoking, short sleep duration, poor sleep quality, adiposity, higher glycated haemoglobin and higher cystatin C were identified as the main potentially modifiable mediators. Mediators collectively explained 52.3% of the associations between shift work and incident CVDs.

Conclusions

Shift workers have higher risk of incident and fatal CVD, partly mediated through modifiable risk factors such as smoking, sleep duration and quality, adiposity and metabolic status. Workplace interventions targeting these mediators have the potential to alleviate shift workers’ CVD risk.
Intelligent energy optimization system development and validation for German building types
Authors: Gökçe H Ufuk , Gökçe K Umut
Published: June 2021

Cost-effective building energy optimization solutions have a strategic function to assist German and European energy policies for the simple reason that buildings account for 40% of the total energy consumption in Europe. The International Energy Agency considers energy efficiency as the first fuel and a major resource. In this work, a cost-effective building energy optimization system consisting of 14 different wireless network embedded sensors, control units (actuators), wireless communication protocol, multi-dimensional information management system, context sensitive graphical user interfaces and energy optimization software with artificial intelligence-backed control algorithms is examined. The R&D activity is accomplished in the ‘Intelligent Building Energy Management System’ research project, which is funded by the State of Lower Saxony (Germany) in the frame of Innovation Support Program between the years 2014 and 2018. The ‘Energy Optimization System (EOS)’, which is subject to this research, reduces the total energy use and CO2 emissions of buildings through optimization of energy-consuming building systems, such as heating, cooling, lighting systems and home/office appliances with the support of an integrated system solution consisting of artificial intelligence-based software and wireless network embedded hardware. The system is deployed and validated in two appropriately selected test buildings in Germany. It has been recorded that the system provides energy efficiency levels between 29.34% and 38.18% under different seasonal and occupancy conditions in office and residential building types. The developed system can be deployed to all types of historical and new buildings to optimize energy consumption and reduce carbon emissions.
Molecular recognition of a single-chain Fv antibody specific for GA-pyridine, an advanced glycation end-product (AGE), elucidated using biophysical techniques and synthetic antigen analogues
Authors: Kobashigawa Yoshihiro , Ohara Toshiya , Morita Kosuke , Toyota Yuya , Nakamura Teruya , Kotani Shunsuke , Arimori Takao , Yamauchi Soichiro , Liu Chenjiang , Kitazaki Masaya , Wakeyama-Miyazaki Yukari , Suwa Yoshiaki , Uchida-Kamekura Makiyo , Fukuda Natsuki , Sato Takashi , Nakajima Makoto , Takagi Junichi , Yamagata Yuriko , Morioka Hiroshi
Published: June 2021

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by non-enzymatic reaction between reducing-sugar and Arg/Lys in proteins and are involved in various diabetic complications. GA-pyridine is derived from glycolaldehyde and is one of the most cytotoxic AGEs. Here, we established a single-chain Fv (scFv) antibody against GA-pyridine, 73MuL9-scFv, and examined the details of its specificity and antigen recognition by using various techniques involving biophysics, chemical biology and structural biology. We also synthesized several compounds that differ slightly in regard to the position and number of GA-pyridine substituent groups, and revealed that GA-pyridine was specifically bound to 73MuL9-scFv. Thermodynamic analysis revealed that the association of GA-pyridine to 73MuL9-scFv was an exothermic and enthalpy driven reaction, and thus that the antigen recognition involved multiple specific interactions. Crystallographic analysis of the Fv fragment of 73MuL9-scFv revealed that several CH-π and hydrogen bond interactions took place between the Fv-fragment and GA-pyridine, which was consistent with the results of thermodynamic analysis. Further studies using 73MuL9-scFv as a tool to clarify the relevance of GA-pyridine to diabetic complications are warranted.
#4: Antibiotic Durations for Skin and Soft Tissue Infections in Pediatric Urgent Care Clinics
Authors: Hamner Megan , Nedved Amanda , Austin Holly , Wyly Donna , Burns Alaina , King Diana , Lee Brian , El Feghaly Rana E
Published: June 2021

Background

Skin and soft tissue infections (SSTIs) are the second most common diagnosis leading to pediatric antibiotic prescriptions in the outpatient setting after respiratory diagnoses. However, most antibiotic stewardship programs have mainly focused on the latter. Children seen in the ambulatory setting for SSTIs often receive >7 days of antibiotics, although current society guidelines recommend 5–7 days for most diagnoses.

Objectives

To determine the baseline percentage of patients receiving antibiotic prescriptions for >7 days for SSTIs in urgent care clinics (UCC)s of a pediatric health system and to evaluate factors that influence providers towards longer durations.

Methods

We built a report that extracted patient encounters from the three UCCs based on International Classification of Diseases (ICD)-10 codes for common SSTIs including impetigo, abscesses, cellulitis, erysipelas, folliculitis, paronychia, and animal bites. Data was pulled from June 2019 through June 2020. The report included patient age, concomitant diagnoses, antibiotics prescribed and their duration. We excluded encounters if the patient was transferred to the emergency department or admitted, the patient was younger than 3 months of age, no antibiotics were prescribed, or if there was a concurrent infectious diagnosis affecting antibiotic duration. We sent a 22-question survey to UCC providers to understand prescribing habits particularly focusing on factors prompting administration of longer antibiotic courses.

Findings

From June 2019-June 2020, we reviewed 2,575 encounters; we excluded 208 of those (8%). 823 (35%) of patients received >7 days of antibiotics for SSTIs while 1181 (50%) received 5–7 days and 35 (1%) received <5 days of antibiotics. 328 (14%) received topical therapy only. Most common antibiotics prescribed included cephalexin, clindamycin, and trimethoprim-sulfamethoxazole. A mild improvement in the 5–7 days duration was noted through our study period (Figure 1). The survey was sent to 50 providers with 27 responding (54% response rate). Of providers surveyed, 5 (19%), 7 (26%), and 8 (29%), expressed being uncomfortable with a 5-day treatment course for cellulitis, erysipelas, and abscesses respectively. Barriers for shorter treatment courses included concern for acute rheumatic fever development, parental pressure, fear of complications, and accustomed antibiotic duration.

Conclusion

A third of children with SSTIs in our UCCs receive long courses of antibiotics. A mild improvement noted in our study period may be due to existing antibiotic stewardship interventions. Specific provider concerns leading to overprescribing will be targeted by quality improvement efforts.
#13: Respiratory and Intestinal Epithelial Cells Exhibit Differential Susceptibility and Innate Immune Responses to Contemporary EV-D68 Isolates
Authors: Freeman Megan Culler , Wells Alexandra I , Ciomperlik-Patton Jessica , Myerburg Michael M , Anstadt Jennifer , Coyne Carolyn B
Published: June 2021

Background

Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and associated with acute flaccid myelitis (AFM), a disease which causes paralysis in previously healthy patients, mostly children. AFM peaked in even numbered years, at least 2014–2018. While 2020 was expected to be a peak AFM year, few cases were seen, likely due to non-specific social distancing measures due to SARS-CoV-2. EV-D68 is primarily described as a respiratory pathogen, in contrast to ‘classic’ enteroviruses that are spread via the fecal-oral route. However, similar to other enteroviruses, EV-D68 has been detected in wastewater, suggesting it might also have an enteric route of transmission.

Methods

We used a panel of EV-D68 isolates, including a historic isolate from 2009 and multiple contemporary isolates from AFM peak years to define dynamics of viral replication and host response to infection. We performed comparative studies in primary human bronchial epithelial cells grown at an air-liquid interface and in primary human stem-cell derived intestinal enteroids. These human primary cell-based models more accurately reflect the cells targeted by EV-D68 in vivo. We defined growth characteristics, temperature sensitivity, infection polarity, and acid sensitivity in these parallel models. We used unbiased Luminex-based multianalyte profiling and bulk RNA-sequencing to define the innate immune response in each model.

Results

Conclusions

Our findings suggest that a subset of contemporary isolates of EV-D68 have the potential to target both the human airway and gastrointestinal tracts as a potential route of infection, identifying a previously unrecognized potential route of infection as well as defining, for the first time, the innate immune response to infection in multiple relevant primary epithelial models.

These findings are highly significant and are the first to characterize the viral replication and host innate immune response to a diverse panel of historic and contemporary EV-D68 isolates in both the respiratory and intestinal tracts.
#17: Disease and Immunoprophylaxis Model of Human Nose Organoids to Study SARS-CoV-2 and RSV Infection
Authors: Rajan Anubama , Marie Aloisio Gina , Weaver Ashley Morgan , Jelinski Joseph , Johnson Hannah , McBride Trevor , Robertson Matthew , Melicoff-Portillo Ernestina , Kanthi Yerramilli Malli Rama , Zeng Xi-Lei , Yu Xiaomin , Stossi Fabio , Coarfa Cristian , Kotkar Shalaka , Blutt Sarah , Estes Mary K , Avadhanula Vasanthi , Piedra Pedro A
Published: June 2021

Background

There is a significant and unmet need for pre-clinical models to predict responsiveness of immunotherapies to both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) infection. Airway organoid models have been recently developed to study respiratory viruses; however, the current methods rely on invasive or biopsy derived samples to generate lung or airway organoids.

Objective

To establish human nose organoids (HNOs) as a model to study SARS-CoV-2 and RSV pathogenesis and test therapeutics.

Methods

We developed a non-invasive method to establish HNOs using stem cells isolated from nasal-wash and mid-turbinate samples. We made air liquid interface (ALI) cultures from undifferentiated 3-dimensional HNOs and differentiated for 21 days to form differentiated nasal epithelium. We inoculated the apical epithelium and assessed SARS-CoV-2 and RSV infection on the apical compartment using real time-polymerase chain reaction, plaque assays and immunofluorescence techniques. We then evaluated the feasibility of HNO-ALI model system to test the efficacy of serum antibodies to prevent SARS-CoV-2 infection and palivizumab monoclonal antibodies to prevent infection using palivizumab sensitive and resistant RSV strains. We introduced the antibodies in the basolateral compartment and monitored its neutralizing capacity on the apical side mimicking the neutralizing effects of antibodies in circulation.

Results

Our HNO-ALI cultures consist of well-differentiated, pseudostratified, ciliated, and mucosal respiratory epithelial cells and are susceptible to SARS-CoV-2, RSV A and B infection. SARS-CoV-2 and RSV replicates in the apical ciliated cells of the HNO-ALI cultures, peaks at 4 days, and plateaus at 8 days post infection. Infected HNO-ALI recapitulates aspects of SARS-CoV-2 and RSV disease, including viral shedding, asynchronous cilia beating/ciliary damage, and mucus hyper-secretion. Our model effectively showed protection to infection in a concentration dependent manner of the antibodies used.

Conclusion

We established a non-invasive method to generate HNO-ALI epithelial model as an authentic and an alternative model to 1-D cell culture systems. Our ex-vivo HNO-ALI infection model provides a novel approach for testing therapeutic interventions.
#31: Children with Invasive S. aureus Infection Produce Broadly Neutralizing Antibodies Against Distantly Related Variants of the Cytotoxin LukAB
Authors: Bennett Monique , Kose Nurgun , Perelman Sofya , Crowe James , Torres Victor , Thomsen Isaac
Published: June 2021

Background

Staphylococcus aureus is the most common invasive bacterial pathogen in children, and novel targets of intervention are urgently needed. The two-component leukotoxin, LukAB, is critical for S. aureus targeting and killing of human neutrophils and is abundantly produced in the setting of invasive human infection. LukAB is unique among S. aureus cytotoxins in that it exists in variant form across distantly related strains of clinically relevant S. aureus. The broad diversity of circulating clinical S. aureus strains must be taken into account to successfully develop new anti-staphylococcal preventives or therapeutics. This diversity and ongoing S. aureus evolution may explain previous unsuccessful attempts to intervene against S. aureus at the virulence factor level. We have previously shown that LukAB is ubiquitous among clinical isolates and that children with invasive disease mount a high-titer neutralizing response, but the breadth of function of this response has not previously been explored.

Methods

B-cells were isolated from children with invasive S. aureus infections (e.g. bacteremia or acute hematogenous osteomyelitis). Following EBV-transformation, cell supernatants were screened for LukAB binding and selected for generation of monoclonal hybridomas. MAbs were assessed for binding by ELISA and neutralizing function by in vitro cytotoxicity assays, where neutrophil-like HL-60 cells were cultured in the presence of human mAbs and diverse allelic variants of LukAB. The infecting S. aureus isolates were typed using multilocus sequence typing (MLST) to determine clonal complexes.

Results

34 distinct human anti-LukAB mAbs were generated from 3 children with invasive S. aureus disease. Of these, 22% were isolated following infection with a strain belonging to clonal complex 8 (CC8), consistent with the epidemic USA300 clone, and 78% were generated against CC5 strains. Within this panel, all mAbs potently neutralized LukAB from the same clonal complex as the corresponding infecting isolate, but 23 also demonstrated neutralization against other allelic variants of LukAB. 7 mAbs were capable of broad, potent neutralization against LukAB variants from all clinically relevant clonal complexes tested (CC8, CC30, CC45, CC75, CC1, CC5, and CC398).

Conclusions

A subset of human mAbs isolated from children with invasive S. aureus disease were capable of broad neutralization against distantly related variants of the important toxin LukAB. This has two important implications: First, we found strong evidence of a conserved target (or targets) for antibody-mediated toxin neutralization across diverse strains of S. aureus. Second, this provides additional support for this toxin as a target of intervention, as some previous vaccine attempts were likely unsuccessful due to activity against a narrow subset of circulating S. aureus strains.
#34: Characteristics of Pediatric Patients with Candidemia and Risk Factors for Disseminated Candidiasis
Authors: Leopold K E , Lloyd E C , Weinberg J B
Published: June 2021

Background

Candida species are the most common cause of fungal infection in hospitalized patients. Patients with candidemia are at risk of developing disseminated infection. Studies in adults have described risk factors for disseminated candidiasis in patients with candidemia, but there are fewer such studies in pediatric populations. The objective of the study is to examine the prevalence of disseminated candidiasis in pediatric patients with candidemia and to compare patients with disseminated candidiasis to those with candidemia alone.

Methods

All patients with blood cultures positive for a Candida species from 2007–2018 were identified from the UM Clinical Microbiology Laboratory. Retrospective chart review was conducted to gather demographic, clinical, and microbiologic data. Disseminated candidiasis was defined as ocular infection; endocarditis; renal, hepatic, or splenic involvement; peritonitis; or CNS infection. Patients with disseminated candidiasis were compared to those with candidemia alone using odds ratios.

Results

There were 81 episodes of candidemia during the study period, representing 61 unique patients. The most common comorbidity was intestinal failure (43%), and the presence of a central line (99%) and use of TPN (73%) were both highly prevalent. The most frequently identified Candida species was C. albicans, followed by C. parapsilosis. There were 14 patients (17%) with disseminated candidiasis. The most common site for dissemination was the abdomen (5 patients). Immunosuppressed patients were significantly more likely to have disseminated candidiasis (OR 4.1, 95% CI 1.1–15.3), while those with intestinal failure were significantly less likely to develop disseminated candidiasis (OR 0.07, 95% CI 0.01–0.6). Patients with disseminated candidiasis were significantly more likely to require ICU admission (OR 5.8, 95% CI 1.2–28) and were significantly more likely to die within three months of infection (OR 9.3, 95% CI 2.3–37.6) than those with candidemia alone.

Conclusions

The prevalence of disseminated candidiasis in patients with candidemia was 17%. Immunosuppression was positively associated and intestinal failure was negatively associated with the development of disseminated candidiasis. Patients with disseminated candidiasis had worse outcomes (including ICU admission and death) than those with candidemia alone. Our data suggest that immunosuppressed patients with candidemia should be thoroughly evaluated for signs of disseminated candidiasis.
#41: Mechanistic Immune Correlates of Protection Following Vaccination Against Rift Valley Fever Virus
Authors: Doyle Joshua D , Barbeau Dominique J , Cartwright Haley N , McElroy Anita K
Published: June 2021

Background

Rift Valley fever virus (RVFV) is a zoonotic arbovirus endemic to large areas of Africa and the Arabian peninsula that causes a significant annual burden of disease in ruminant animals, and is associated with periodic outbreaks in human populations. RVFV causes a wide spectrum of disease in infected patients ranging from a self-limiting febrile illness to hepatitis, encephalitis, hemorrhagic fever, and death. Despite the significant economic and public health impact of RVFV, there are no currently available vaccines or therapeutics available for RVFV.

Methods

Previous work has established that vaccination with an attenuated strain of RVFV, RVFV-ΔNSs, confers protection against subsequent lethal challenge in a murine model of infection. To characterize mechanistic immune correlates of protection, we vaccinated C57BL/6 mice with RVFV-ΔNSs then depleted vaccinated mice of various memory lymphocyte subsets, including CD4+, CD8+, CD4+/CD8+ T-cells before challenging mice with a lethal dose of WT RVFV. To assess for the role of antibodies in providing protection, we depleted mice of their B cells prior to vaccination with RVFV-ΔNSs, confirmed the lack of RVFV specific antibodies, and then challenged them with lethal WT RVFV. To determine the minimal immunologic factors required for protection, we vaccinated a series of donor mice, transferred either immunoglobulins or splenocytes to naïve recipient mice, then challenged them with WT RVFV.

Results

Vaccination with RVFV-ΔNSs protected mice from subsequent challenge, and this protection was not abrogated by depletion of CD4+, CD8+, or combined CD4+ and CD8+ lymphocytes, suggesting that RVFV-specific T-cells are dispensable for protection in the presence of virus specific antibodies. Vaccinated mice depleted of CD20+ B-cells were also protected against WT challenge, suggesting that B-cells/antibodies are also dispensable for protection in the presence of an intact T-cell response. Passive transfer of antibodies from vaccinated mice to recipient mice protected them against subsequent WT challenge, demonstrating that antibodies are sufficient for protection. Adoptive transfer of total splenocytes protected mice against subsequent WT challenge, indicating that lymphocytes are also sufficient to mediate protection.

Conclusions

In this study we defined the mechanistic immune correlates of protection following vaccination with attenuated RVFV-ΔNSs against WT RVFV in a murine model. Here, we have shown that both humoral and cellular immunity are sufficient to mediate protection in recipient animals, and can compensate for each other when one is missing. These results further our understanding of the protective immunologic response to infection by RVFV, and will help inform further vaccine development efforts against this important emerging pathogen.
#51: Neurotropic Astrovirus-VA1: Identifying the distinctions from classical genotypes
Authors: Davis Amy E , Hargest Virginia , Tan Shaoyuan , Jia Qidong , Cortez Valerie , Schultz-Cherry Stacey
Published: June 2021

Background

Human astroviruses (HAstV) are a leading cause of acute gastroenteritis in children, particularly those under the age of 2 or with immunosuppressive conditions. Indeed, our studies suggest that children with hematological malignancies are at high risk of infection. However, it has become increasingly clear that HAstV infections can also be associated with respiratory and even central nervous system (CNS) diseases. In the last decade, there have been at least 12 cases of astrovirus-induced CNS disease resulting in encephalitis and meningitis, including 2 St Jude patients. The CNS-associated infections are overwhelmingly fatal and are primarily caused by a novel astrovirus genotype, VA1, that is genetically more similar to animal astroviruses that also induce CNS-associated infections. The recent ability to propagate the VA1 strain in cell lines affords us the opportunity to better understand VA1 infection and how it compares to the better-studied HAstV1 strain.

Methods

Viral kinetics were determined by infection of human intestinal adenocarcinoma Caco-2 cells with either HAstV1 or VA1 and monitored for 24 hours post-infection (hpi). Infected cells were identified via immunofluorescent microscopy using antibodies against double-stranded RNA and viral capsid. Epithelial permeability of astrovirus-infected Caco-2 cells was measured using transepithelial electrical resistance (TER) and monitored for 24hpi. Nitazoxanide efficacy was identified by immunofluorescent analysis as described previously.

Results

Our findings demonstrate that HAstV1 and VA1 replicate in intestinal epithelial cells without inducing cell death or a pro-inflammatory cytokine response. However, these two strains have distinct replication kinetics. VA1 appears to have an ~8 hour lag in the expression of dsRNA and capsid protein compared to HAstV1 and does not require exogenous proteases to process the viral outer coat (capsid) protein, Additionally, we demonstrated that the increase in epithelial barrier permeability associated with HAstV1-infection is not found in VA1-infected cells, which is intriguing and may explain why HAstV1 is more likely to cause diarrhea. Of clinical importance, we have revealed a similar susceptibility of VA1 to the antiviral drug, nitazoxanide, which we have recently demonstrated its effectiveness inhibiting classical HAstV strains.

Conclusion

Overall, our studies highlight that VA1 pathogenesis is distinct from HAstV1, which could explain the differences in vivo. Future studies will be necessary to investigate viral replication and pathogenesis in distinct neuronal cells and in vivo.
#54: Sensitivity and Specificity of Procalcitonin vs C Reactive Protein in Identifying Pediatric Bacterial infections
Authors: Kim Sara , Bhatt Avni , Carr Silvana , Saccoccio Frances , Lew Judy
Published: June 2021

Background

Procalcitonin (PCT) and c-reactive protein (CRP) have been utilized in children to assess risk for serious bacterial infections. However, there have been different cut-offs reported for PCT and CRP, which yield different sensitivity and specificity. This study aims to compare the sensitivity and specificity of PCT and CRP in detecting serious bacterial infections (SBIs), specifically urinary tract infections, bacteremia and meningitis.

Methods

In this retrospective, single center cohort study from January 2018 to June 2019, we analyzed children with a fever greater than 38C with both PCT and CRP value within 24 hours of admission. Each patient had a blood, urine and/or cerebrospinal fluid culture collected within 48 hours of admission. No antibiotics were administered from the admitting hospital prior to collection of the PCT or CRP. Our gold standard was a positive culture obtained from blood, cerebrospinal fluid, or urine. The statistical analysis included categorical variables as percentages and compared them using the Fisher exact test. The optimal cutoff values for PCT or CRP were based on ROC curve analysis and Youden Index. Sensitivity and specificity analysis were based on literature review cut offs and ROC curves cut offs.

Results

Among 202 children, we had 45 culture positive patients (11 urinary tract infections, 4 meningitis, and 32 bacteremia). The patients with culture positivity had higher PCT levels (7.9 ng/mL vs 2.5 ng/mL, P=0.0111), CRP levels (110.9 mg/L vs 49.6 mg/L, P<0.0001) and temperature (39.2C vs 39C, P<0.0052). The area under the curve (AUC) comparing culture positivity vs negativity for all culture types was 0.72 (p<0.0001) for PCT and 0.66 (p=0.001) for CRP. In Figure 1, the AUC for culture positive bacteremia was 0.68 (p=0.0011) for PCT and 0.70 (p=0.0003). The AUC for culture positive urinary tract infections (UTI) only was 0.86 (p=0.0001) for PCT and 0.70 (p=0.3607). For the cut-off value for PCT at 0.5 ng/mL, the sensitivity and specificity was 64% (95% confidence interval [CI] 0.5–0.77) and 70% (95% CI 0.62–0.77) respectively in identifying children with bacterial infection. For the cut-off value for CRP at 20 mg/L, the sensitivity and specificity was 67% (95% CI 0.52–0.79) and 52% (95% CI 0.44–0.59) respectively in identifying children with bacterial infection.

Conclusion

In this study, PCT and CRP are nearly equivalent classifiers for detecting SBIs as a group and bacteremia, but PCT is statistically better for urinary tract infections; however, the clinical utility is unknown.
#7: Clinical Characteristics of Children with COVID-19: A Multicenter Study in the United Arab Emirates
Authors: Ennab Farah , ElSaban Mariam , Khalaf Eman , Tabatabaei Hanieh , Amar H K , Devi Bindu Radha , Hanif Kashif , Elhassan Hiba , Saravanan Ketharanathan , Cremonesini David , Popatia Rizwana , Malik Zainab A , Ho Samuel B , Abusamra Rania
Published: June 2021

Background

To date, coronavirus disease-2019 (COVID-19) has infected over 82 million people globally. The first confirmed case in the United Arab Emirates (UAE)was reported on 29th January 2020. Current data suggests that children with COVID-19 have a mild disease course. There is a lack of extensive published data about COVID-19 infection among children in the Arabian Gulf region.

Methods

This cross-sectional multicenter study included children with confirmed COVID-19 infection admitted between March 1st and June 15th, 2020 to three large hospitals in Dubai, UAE. Serial nasal swabs for COVID-19 polymerase chain reaction (PCR) testing were collected during hospitalization. We investigated patients’ demographics,clinical characteristics, radiological and laboratory investigations during their inpatient hospital course.

Results

111 children were included in our study and represented 22 nationalities. Fifty-nine (53.2%) were boys. The mean age was 7 years (±5.3), and 15.3% of children were younger than 1 year. Only 4 (3.6%) children had pre-existing asthma, all of whom had an uneventful clinical course. At presentation 43 (38.7%) were asymptomatic, 68 (61.2%) had mild or moderate symptoms and none had severe illness requiring intensive care. Fever (20.7%), cough (19.8%) and rhinorrhea (15.3%) were the most common presenting symptoms, most of which resolved by day 5 of hospitalization. Most of our patients had a normal chest x-ray. The most common laboratory abnormalities on admission included variations in neutrophil count (24.7%), aspartate transaminase (22.5%), alkaline phosphatase (36.7%) and lactate dehydrogenase (42.5%). Children were infrequently prescribed targeted medications, with only 4 (3.6%) receiving antibiotics. None of the 52 patients tested for viral co-infections were positive. COVID-19 PCR turned negative at a median of 10 days [6–14 days] after the first positive test. Overall, there was no significant difference in time to negative PCR between symptomatic and asymptomatic children.

Conclusion

This pediatric study of COVID-19 presents a first look into the burden of COVID-19 infection among children in the UAE. Patients had various laboratory abnormalities despite clinical stability. We conclude that a large percentage of children with COVID-19 infection experience no symptoms, and severe disease is uncommon in the UAE. Ongoing surveillance, contact tracing and public health measures will be essential in containing future outbreaks.
#29: Analysis of Mortality Due to Infections in Pediatric Patients in the Oncology Unit of a Third Level Hospital in La Paz, Bolivia
Authors: Marisol Trujillo-Gutierrez , Pablo Rodriguez-Auad Juan
Published: June 2021

Background

In recent decades, advances in cancer treatment have made it possible to improve the prognosis of hemato-oncological patients, however, mortality is still high in developing countries. One of the most important causes of morbidity and mortality during the treatment of children with cancer is infectious complications, especially in the induction phase. The multiple interventions that are carried out during treatment, such as the use of catheters, increase the risk of developing these infections, which can be more frequent if the recommended strategies to prevent them are not applied. The objective of this study was to investigate what were the causes of death in children with cancer at our institution.

Methods

The medical records of deceased patients were analyzed in the onco-hematology unit of the Children′s Hospital “Dr. Ovidio Aliaga Uria” in the city of La Paz, Bolivia. The causes of mortality, the stage of chemotherapy in which the death occurred, its relationship with infections and the microorganism identified during 2020 were classified.

Results

During 2020, 19 deaths were found in cancer patients, the mean age was 8.5 years and of which 52% were male. Regarding the basic diagnosis, there was a higher proportion of hematological diseases 68% and solid tumors 32%. Among the causes of death, 58% were due to their underlying pathology where most of the patients were in palliative care or in relapse and 42% were due to infectious causes, of which 62% were in induction phase of chemotherapy. Among the 8 patients who died from infections, the following causes were found: 50% neutropenic colitis, 25% bacteremia and 25% necrotizing fasciitis; in 7 (87.5%) patients the microorganism was isolated in blood culture, these were E. coli 43%, Klebsiella spp 43% and Bacillus spp 14%. Gram negative bacilli (GNB) represented 86% of the isolates and 50% were producers of extended spectrum beta-lactamases (ESBL).

Conclusions

Considering that infections are preventable and are among the most important causes of mortality in children with cancer in our hospital, it is essential that infection control teams are developed that apply evidence-based strategies to prevent these infections and thus achieve a reduction in morbidity and mortality, applying programs with training of human resources and equipment to reduce these deaths.
#32: Single Center Experience with the Use of Convalescent Plasma Transfusion (CPT) for COVID-19 + Patients in Argentina
Authors: Gómez Sergio Miguel
Published: June 2021

Background

COVID-19 pandemic challenged health sanitary systems worldwide. 1.65 million cases have been reported in Argentina with 43.635 deaths. CPT emerged as a possible and feasible treatment. Transfusion cardiovascular overload (TACO), acute lung injury (TRALI) and anaphylactic reactions (AR) have raised safety concerns; in the other hand, it is still unknown its efficacy but preliminary reports have claimed that if it is delivered early, mortality or morbidity could be decreased. Pediatric use of CPT is emerging from adults’ studies.

Objective

To review clinical outcomes, laboratory parameters and side effects of CPT in a single center in Argentina and determine the mortality rate.

Methods

This is a single-center single-arm exploratory-descriptive prospective study, starting on May 1, 2021 until October 31, 2021. A protocol developed for donation of CPT included those individuals with SARS-CoV-2 RT- PCR positive in respiratory secretions and SARS-CoV-2 antibody positive by immunochromatography o chemiluminescence, with a titer by ELISA (Covidar®) > 1:400 and 200 – 250 mL were considered 1 Unit. Recipients weighing <70 kg received 1 unit, and those recipients weighing >70kg received 2 units. CPT was prescribed within 14 days of starting SARS-CoV-2 symptoms. All patients received dexamethasone and standard support measures. We used percentages and frequencies for reporting the results of this study. Categorical variables were compared with Chi2 and numeric Fisher/Mann Whitney. Time dependent survival variables were calculated with Kaplan Meier method. SPPS 20 software was used for data processing.

Results

The CPT recipients median age (IQR) was 47 years of age (range 43–59 years); 65.5 % were; 12,5% had either hypertension or obesity, 3.1% chronic obstructive lung disease; 30% had diabetes. The median temperature at diagnosed was (IQR) 37.7°C (range 36.6°C - 38.9°C). A total of 39 CPT units were infused in 32 patients. 25 patients (78%) received 1 unit, 6 patients (19%) received 2 units and 1 patient (3%) received 3 units (3%). Donor median (IQR), SARS-CoV-2 antibody titer was 1:400 (range 400–1600); median time (IQR) to transfusion was 1 day (range 1–4). Coverage was 100%.

Outcomes

29 patients (91%) survived and 3 (9%) died for COVID-19. Only 3 patients (8%) developed moderate/reversible side effects: allergic reaction (2 pts) and TRALI(1pt) At a median time of 100 days, the median survival was 85% (0.5) and the mortality rate was 19 % (0.6).

Laboratory features:

Conclusion

CPT was feasible to deliver and could be implemented in a less resourced country in a timely fashion. All our patients could afford plasma therapy. No severe adverse events were reported. Pediatric studies can be based on the results of this type of study. Research should focus now on a control case cohort study to determine efficacy of CPT.
Writing about Polyphony, Talking about Civilization: Charles Burney’s Musical ‘Corns and Acorns’
Authors: Semi Maria
Published: June 2021

In the eighteenth century polyphony—from simply being a term denoting a musical technique—became an evaluative-descriptive concept, following this path in association with the idea of civilization. Retracing Burney’s steps as a music historian and a music critic, the article shows how the Musical Doctor adopted a specific kind of narrative developed by Scottish conjectural historians that saw history as unfolding through several specific stages, progressively abandoning simplicity for the complexities of civilization. This seemingly linear narrative is complicated both by showing how making every music fit into this linear scheme was not easy, and by bringing forth the arguments developed especially by Scottish literati in order to explain why their native musical tradition could be considered equal or superior to Western art-music. The discourse, with Rousseauian echoes, that allowed the association between simplicity and positive values that were to be opposed to the excesses and depravity of civilized life, was articulated through the intellectual tools developed during the debate about luxury that raged through the eighteenth century. Nestled in the luxury debate, the non-literate music tradition that in non-Western locations had been considered as an instance of ‘barbarism’ now stood for a noble ‘simplicity’, whose value consequently reversed making artlessness a possible element of sublime beauty. The contradictions in Burney’s attitude towards non-Western musics and national European musics—on the one hand tirelessly collecting information about music-making from any corner of the world and on the other hand promoting only those values that made multi-part music the emblem of musical civilization—will serve to explain the interplay between ideas related to polyphony, civilization, and national musics in the eighteenth century.
The parental experience and perceptions of blenderized tube feeding for children with medical complexity
Authors: Soscia Joanna , Adams Sherri , Cohen Eyal , Moore Clara , Friedman Jeremy N , Gallagher Kelsey , Marcon Margaret , Nicholas David , Weiser Natalie , Orkin Julia
Published: June 2021

Objectives

Parents of children with medical complexity are often expected to implement complicated plans of care, such as enteral tube feeding, to support the health of their child. Enteral feeding can have psychosocial implications for the parent, child, and family. Blenderized tube feeding (BTF) refers to the administration of pureed food and drinks through a feeding tube. Little is known regarding parents’ experiences with BTF. Therefore, the purpose of this qualitative study was to understand the lived experience of BTF from the parent’s perspective.

Methods

This qualitative study was a grounded theory analysis utilizing semi-structured interviews of parents who provided at least 50% of their child’s diet through BTF. Participants were recruited using purposive sampling from the Complex Care Program at a tertiary care paediatric centre. Interviews were conducted until thematic saturation was achieved. Themes were identified using constant comparative analysis of transcribed interviews.

Results

Parents (n=10) felt that BTF positively affected the experience of tube feeding and enhanced their child’s health and wellbeing. Parents described BTF as a means of self-empowerment and a mechanism to normalize feeding and care for the entire family. Despite reporting BTF as more time consuming than formula feeding, all parents were satisfied with having made the change, and planned on continuing the diet.

Conclusion

BTFs can improve the experience of tube feeding and positively address some of the negative psychosocial implications of enteral tube feeding, providing a sense of normalcy and control for parents caring for a child with medical complexity.
Deformation effect on nuclear density profile and radius enhancement in light- and medium-mass neutron-rich nuclei
Authors: Horiuchi Wataru , Inakura Tsunenori
Published: June 2021

The mass number dependence of nuclear radii is closely related to the properties of nuclear matter. It is known that most nuclei exhibit some deformation. We discuss how the nuclear density profile is modified by nuclear deformation to elucidate the enhancement mechanism of nuclear radii through a systematic investigation of neutron-rich Ne, Mg, Si, S, Ar, Ti, Cr, and Fe isotopes. Skyrme–Hartree–Fock calculations are performed in a 3D Cartesian grid to describe the nuclear deformation in a non-empirical way. The role of nuclear deformation in nuclear density profiles is explored in comparison to calculations with a spherical limit. We find correlations between nuclear deformation and the internal nuclear density. The evolution of nuclear radii appears to follow the core swelling mechanism recently proposed in spherical nuclei [W. Horiuchi and T. Inakura, Phys. Rev. C 101, 061301(R) (2020)], and the radius is further enhanced by nuclear deformation. This study demands further theoretical and experimental investigations for the internal density.
WALANT Hand Surgery Does Not Require Postoperative Opioid Pain Management
Authors: Dar Qurratul-Ain , Avoricani Alba , Rompala Alexander , Levy Kenneth H. , Shah Neil V. , Choueka David , White Colin M. , Koehler Steven M.
Published: June 2021

Background:

Currently, opioids are the standard of care for postoperative pain management. Avoiding unnecessary opioid exposure in patients is of current interest because of widespread abuse.

Methods:

This is a prospective cohort study in which wide-awake, local anesthesia, no-tourniquet (WALANT) technique was used for 94 hand/upper extremity surgical patients and compared to patient cohorts undergoing similar procedures under monitored anesthesia care. Patients were not prescribed opioids postoperatively but were instead directed to use over-the-counter pain relievers. Pain scores on a visual analogue scale were collected from patients preoperatively, and on postoperative days 1 and 14. WALANT visual analogue scale scores were compared to those of the two patient cohorts who either did or did not receive postoperative opioids after undergoing similar procedures under monitored anesthesia care. Electronic medical records and New York State’s prescription monitoring program, Internet System for Tracking Over-Prescribing, were used to assess prescription opioid-seeking. Information on sex, age, comorbidity burden, previous opioid exposure, and insurance coverage was also collected.

Results:

Decreased pain was reported by WALANT patients 14 days postoperatively compared to preoperatively and 1 day postoperatively, with a total group mean pain score of 0.37. This is lower than mean scores of monitored anesthesia care patients with and without postoperative opioids. Only two WALANT patients (2.1 percent) sought opioid prescriptions from outside providers. There was little evidence suggesting factors including sex, age, comorbidity burden, previous opioid exposure, or insurance status alter these results.

Conclusion:

WALANT may be a beneficial technique hand surgeons may adopt to mitigate use of postoperative opioids and reduce risk of abuse in patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Usefulness of Model-Based Iterative Reconstruction in Brain CT as Compared With Hybrid Iterative Reconstruction
Authors: Sekino Hirofumi , Ishii Shiro , Kuroiwa Daichi , Fujimaki Hideki , Sugawara Shigeyasu , Suenaga Hiroki , Hakozaki Motoharu , Yamakuni Ryo , Watanabe Hirotake , Hasegawa Osamu , Ito Hiroshi
Published: June 2021

Objective

The aim of this study was to compare the contrast of gray to white matter between forward-projected model-based iterative reconstruction solution (FIRST) and hybrid iterative reconstruction (IR) by measuring computed tomography value of brain parenchyma.

Methods

Computed tomography values of the gray and white matter in 15 areas of 21 patients (7 males, 14 females; average age, 49.5 ± 10.7 years) were measured and compared between FIRST and hybrid IR with filtered back projection (FBP) using 2 different reconstruction kernels FC21 and FC26.

Results

The ratio of gray to white matter obtained using FIRST (1.25 ± 0.08) was significantly higher than that obtained using FBP with both kernel FC21 (1.13 ± 0.03) and kernel FC26 (1.22 ± 0.06).

Conclusions

FIRST increases the contrast between the gray and white matter, and decreases noise in brain computed tomography compared with FBP with hybrid IR.
The Effects of the Fat Distribution of Body, Skeletal Muscle Mass and Muscle Quality on Acute Pancreatitis Severity: A Retrospective Cross-Sectional Study
Authors: Akturk Yeliz , Ozbal Gunes Serra , Hekimoglu Baki
Published: June 2021

Objective

We aim to investigate a possible relationship between acute pancreatitis (AP) and body fat and muscle parameters in computed tomography (CT).

Methods

Computed tomography images of 107 patients with AP were scored in terms of AP severity using the modified CT severity index. Muscle mass, muscle mass index, visceral and subcutaneous adipose tissue area, multifidus muscle/fat attenuation ratio, total psoas index (TPI) and Hounsfield units average calculation (HUAC) values were performed.

Results

Total psoas index and HUAC of mild AP cases were significantly higher than those with moderate and severe AP. The TPI of patients with severe pancreatic necrosis were found to be significantly lower than those without necrosis. Hounsfield units average calculation of cases without necrosis were significantly higher than those with severe necrosis in the pancreas.

Conclusions

Our study indicated that lower volume and density of psoas muscle associated with worse CT severity score and larger pancreatic necrosis in patients with AP.
Thirty-Day Hospital Readmissions for Acute Gout in the United States
Authors: Kichloo Asim , Edigin Ehizogie , Jamal Shakeel , El-amir Zain , Aucar Maria Isabel , Wani Farah , Eseaton Precious O. , Annapureddy Narender , Cabling Marven G. , Manadan Augustine M.
Published: June 2021

Background/Objective

The aims of this study were to describe the rates and characteristics of nonelective 30-day readmission among adult patients hospitalized for acute gout and to assess predictors of readmission.

Methods

We analyzed the 2017 Nationwide Readmission Database. Gout hospitalizations were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification code. Hospitalizations for adult patients were included. We excluded planned or elective readmissions. We utilized χ2 tests to compare baseline characteristics between readmissions and index hospitalizations. We used multivariate Cox regression to identify independent predictors of readmissions.

Results

A total of 11,727 index adult hospitalizations with acute gout listed as the principal diagnosis were discharged alive and included. One thousand five hundred ninety-four (13.6%) readmissions occurred within 30 days. Acute gout was the most common reason for readmission. Readmissions had higher inpatient mortality (2.4% vs 0.1%, p < 0.0001), greater mean age (68.1 vs 67.0 years, p = 0.021), and longer hospital length of stay (5.9 vs 3.8 days, p < 0.0001) compared with index hospitalizations. Charlson Comorbidity Index scores of ≥2 (score 2: adjusted hazards ratio [AHR], 1.67; p = 0.001; score ≥3: AHR, 2.08; p < 0.0001), APR-DRG (All Patients Refined Diagnosis Related Groups) severity levels ≥2 (level 2: AHR, 1.43; p = 0.044; level 3: AHR, 1.83; p = 0.002; level 4: AHR, 2.38; p = 0.002), admission to metropolitan hospital (AHR, 1.83; p = 0.012), atrial fibrillation (AHR, 1.31; p = 0.004), and anemia (AHR, 1.30; p = 0.001) were significantly associated with 30-day readmissions.

Conclusions

Acute gout readmissions were associated with worse outcomes compared with index hospitalizations. Charlson Comorbidity Index scores ≥2, APR-DRG severity levels ≥2, admission to metropolitan hospital, atrial fibrillation, and anemia were significant predictors of readmission.