bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes insipidus secondary to nivolumab-induced neurohypophysitis and pituitary metastasis
Authors: Fosci Michele , Pigliaru Francesca , Salcuni Antonio Stefano , Ghiani Massimo , Cherchi Maria Valeria , Calia Maria Antonietta , Loviselli Andrea , Velluzzi Fernanda 
Published: February 2021

Summary
A 62-year-old patient with metastatic hypopharyngeal carcinoma underwent treatment with nivolumab, following which he developed symptoms suggestive of diabetes insipidus. Nivolumab was stopped and therapy with methylprednisolone was started. During corticosteroid therapy, the patient presented himself in poor health condition with fungal infection and glycemic decompensation. Methylprednisolone dose was tapered off, leading to the resolution of mycosis and the restoration of glycemic compensation, nevertheless polyuria and polydipsia persisted. Increase in urine osmolarity after desmopressin administration was made diagnosing central diabetes insipidus as a possibility. The neuroradiological data by pituitary MRI scan with gadolinium was compatible with coexistence of metastatic localization and infundibulo-neurohypophysitis secondary to therapy with nivolumab. To define the exact etiology of the pituitary pathology, histological confirmation would have been necessary; however, unfortunately, it was not possible. In the absence of histological confirmation, we believe it is likely that both pathologies coexisted.

Learning points:

A remarkable risk of endocrine immune-related adverse events (irAEs) during therapy with checkpoint inhibitors exsists.

In order to ensure maximum efficiency in the recognition and treatment of endocrine iRAes related to immune checkpoint inhibitors, multidisciplinary management of oncological patients is critical.

The pituitary syndrome in oncological patients who underwent immunotherapy represents a challenge in the differential diagnosis between pituitary metastasis and drug-induced hypophysitis.

This is the first case, described in the literature of diabetes insipidus in a patient suffering from nivolumab-induced infundibulo-neurohypophysitis and anterohypophyseal metastasis.
White adipose tissue-infiltrated CD11b+ myeloid cells are a source of S100A4, a new potential marker of hepatic damage
Authors: Reyes Marjorie , González Lorena , Ibeas Kevin , Cereijo Rubén , Taxerås Siri D , Pellitero Silvia , Martínez Eva , Tarascó Jordi , Moreno Pau , Malagón Paloma , Higueras Carmen , Soria Andrea , Puig-Domingo Manel , Villarroya Francesc , Serra Dolors , Herrero Laura , Sánchez-Infantes David 
Published: February 2021

Context
The endocrine and immunological properties of subcutaneous vs visceral adipose tissue (sWAT and vWAT, respectively) have turned a milestone in the study of metabolic diseases. The cytokine S100A4 is increased in obesity and has a role in adipose tissue dysfunction. However, the cellular source and its potential role in hepatic damage in obesity has not been elucidated.

Objective
We aim to study the regulation of S100A4 in immune cells present in sWAT and vWAT, as well as its potential role as a circulating marker of hepatic inflammation and steatosis.

Design
A cohort of 60 patients with obesity and distinct metabolic status was analyzed. CD11b+ myeloid cells and T cells were isolated from sWAT and vWAT by magnetic-activating cell sorting, and RNA was obtained. S100A4 gene expression was measured, and correlation analysis with clinical data was performed. Liver biopsies were obtained from 20 patients, and S100A4 circulating levels were measured to check the link with hepatic inflammation and steatosis.

Results
S100A4 gene expression was strongly upregulated in sWAT- vs vWAT-infiltrated CD11b+ cells, but this modulation was not observed in T cells. S100A4 mRNA levels from sWAT (and not from vWAT) CD11b+ cells positively correlated with glycemia, triglycerides, TNF-α gene expression and proliferation markers. Finally, circulating S100A4 directly correlated with liver steatosis and hepatic inflammatory markers.

Conclusion
Our data suggest that sWAT-infiltrated CD11b+ cells could be a major source of S100A4 in obesity. Moreover, our correlations identify circulating S100A4 as a potential novel biomarker of hepatic damage and steatosis.
Semen quality and testicular adrenal rest tumour development in 46,XY congenital adrenal hyperplasia: the importance of optimal hormonal replacement
Authors: Rohayem Julia , Bäumer Lena Maria , Zitzmann Michael , Fricke-Otto Susanne , Mohnike Klaus , Gohlke Bettina , Reschke Felix , Jourdan Claus , Müller Herman L , Dunstheimer Désirée , Weigel Johannes , Jorch Norbert , Müller-Rossberg Elke , Lankes Erwin , Gätjen Imke , Richter-Unruh Annette , Hauffa Berthold P , Kliesch Sabine , Krumbholz Aniko , Brämswig Jürgen 
Published: February 2021

Objective
To study the impact of the quality of therapeutic control on fertility and on the prevalence of testicular adrenal rest tumours (TART) in young males with congenital adrenal hyperplasia (CAH).

Design
Combined cross-sectional and retrospective clinical study.

Methods
Twenty-nine patients and age-matched controls underwent clinical investigation, including semen analysis, testicular and adrenal ultrasound imaging, and serum and hair steroid analysis. The quality of therapeutic control was categorized as ‘poor’, ‘moderate’ or ‘medium’. Evaluation of current control was based on concentrations of 17-hydroxy-progesterone and androstenedione in serum and 3 cm hair; previous control was categorized based on serum 17-hydroxy-progesterone concentrations during childhood and puberty, anthropometric and puberty data, bone age data and adrenal sizes.

Results
Semen quality was similar in males with CAH and controls (P  = 0.066), however patients with ‘poor’ past control and large TART, or with ‘poor’ current CAH control had low sperm counts. Follicle-stimulating hormone was decreased, if current CAH control was ‘poor’ (1.8 ± 0.9 U/L; ‘good’: 3.9 ± 2.2 U/L); P  = 0.015); luteinizing hormone was decreased if it was ‘poor’ (1.8 ± 0.9 U/L; P  = 0.041) or ‘moderate’ (1.9 ± 0.6 U/L; ‘good’: 3.0 ± 1.3 U/L; P  = 0.025). None of the males with ‘good’ past CAH control, 50% of those with ‘moderate’ past control and 80% with ‘poor past control had bilateral TART. The prevalence of TART in males with severe (class null or A) CYP21A2 mutations was 53% and 25% and 0% in those with milder class B and C mutations, respectively.

Conclusions
TART development is favoured by inadequate long-term hormonal control in CAH. Reduced semen quality may be associated with large TART. Gonadotropin suppression by adrenal androgen excess during the latest spermatogenic cycle may contribute to impairment of spermatogenesis.
Recovery of hypothalamus–pituitary–gonadal dysfunction after the treatment of suprasellar germ cell tumors
Authors: Zhang Kun , Wang Linjie , Duan Lian , Yang Hongbo , Pan Hui , Lian Xin , Yao Yong , Zhu Huijuan 
Published: February 2021

Objective
To investigate the incidence of hypothalamus–pituitary–gonadal (HPG) axis initiation/recovery after treatment and to identify predictive risk factors for noninitiation/recovery.

Methods
A total of 127 consecutive suprasellar germ cell tumor (GCT) patients managed at Peking Union Medical College Hospital (2006–2019) were retrospectively analyzed. Prepubertal patients (followed up until 13 years of age for girls and 14 years of age for boys) and patients with HPG dysfunction (followed up for 2 years) were divided into the initiation/recovery and noninitiation/recovery groups.

Results
Of the 127 suprasellar GCT patients, 75 met the follow-up criteria, 28 (37.3%) of whom experienced HPG axis initiation/recovery. Compared to the noninitiation/recovery group, the initiation/recovery group included more males and had shorter delayed diagnosis times, smaller tumor sizes, lower panhypopituitarism rates, thinner pituitary stalk widths, lower visual deficit rates, and higher serum testosterone and estradiol levels. The cutoff values of pituitary stalk width, tumor size, and delayed diagnosis time used to predict noninitiation/recovery were 6.9 mm, 6.9 mm and 1.7 years, respectively. Tumor size ≥6.9 mm (odds ratio (OR) = 7.5, 95% CI: 2.2–25.8, P = 0.001), panhypopituitarism (OR = 5.0, 95% CI: 1.4–17.6, P = 0.013), and delayed diagnosis time ≥1.7 years (OR = 5.7, 95% CI: 1.5–20.7, P = 0.009) were risk factors for noninitiation/recovery.

Conclusions
Among suprasellar GCT patients, nearly one-third of prepubertal patients and patients with HPG dysfunction experience HPG axis initiation/recovery after treatment. Tumor size ≥6.9 mm, panhypopituitarism, and delayed diagnosis time ≥1.7 years were identified as predictive risk factors for noninitiation/recovery.
Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS‐CoV‐2 spike protein
Authors: Lupala Cecylia S. , Li Xuanxuan , Lei Jian , Chen Hong , Qi Jianxun , Liu Haiguang , Su Xiao‐Dong 
Published: February 2021

BackgroundA novel coronavirus (the SARS‐CoV‐2) has been identified in January 2020 as the causal pathogen for COVID‐19, a pandemic started near the end of 2019. The Angiotensin converting enzyme 2 protein (ACE2) utilized by the SARS‐CoV as a receptor was found to facilitate the infection of SARS‐CoV‐2, initiated by the binding of the spike protein to human ACE2.MethodsUsing homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure and dynamics of the ACE2 in complex with the receptor binding domain (RBD) of the SARS‐CoV‐2 spike protein.ResultsThe predicted model is highly consistent with the experimentally determined structures, validating the homology modeling results. Besides the binding interface reported in the crystal structures, novel binding poses are revealed from all‐atom MD simulations. The simulation data are used to identify critical residues at the complex interface and provide more details about the interactions between the SARS‐CoV‐2 RBD and human ACE2.ConclusionSimulations reveal that RBD binds to both open and closed state of ACE2. Two human ACE2 mutants and rat ACE2 are modeled to study the mutation effects on RBD binding to ACE2. The simulations show that the N‐terminal helix and the K353 are very important for the tight binding of the complex, the mutants are found to alter the binding modes of the CoV2‐RBD to ACE2.
Forecasting the development of the COVID‐19 epidemic by nowcasting: when did things start to get better?
Authors: Zhang Yuehui , Chen Lin , Shi Qili , Luo Zhongguang , Shen Libing 
Published: February 2021

BackgroundNow the coronavirus disease 2019 (COVID‐19) epidemic becomes a global phenomenon and its development concerns billions of peoples’ lives. The development of the COVID‐19 epidemic in China could be used as a reference for the other countries’ control strategy.MethodsWe used a classical susceptible‐infected‐recovered (SIR) model to forecast the development of the COVID‐19 epidemic in China by nowcasting. The linear regression analyses were employed to predict the COVID‐19 epidemic’s inflexion point. Finally, we used a susceptible‐exposed‐infected‐recovered (SEIR) model to simulate the development of the COVID‐19 epidemic in China throughout 2020.ResultsOur nowcasts show that the COVID‐19 transmission rate started to slow down on January 30. The linear regression analyses further show that the inflexion point of this epidemic would arrive between February 17 and 18. The final SEIR model simulation forecasted that the COVID‐19 epidemic would probably infect about 82,000 people and last throughout 2020 in China. We also applied our method to USA’s and global COVID‐19 data and the nowcasts show that the development of COVID‐19 pandemic is not optimistic in the rest of 2020.ConclusionThe COVID‐19 epidemic’s scale in China is much smaller than the previous estimations. After implemented strict control and prevention measures, such as city lockdown, it took a week to slow down the COVID‐19 transmission and about four weeks to really mitigate the COVID‐19 prevalence in China.
Associations among Toddlers’ and Preschoolers’ Sleep Problems, Emotional Reactivity, Sleep Regime and Parental Applied Rules for Screen-Based Media Use
Authors: Baukienė Edita , Jusienė Roma 
Published: February 2021

Background. Children’s sleep problems are associated with temperament. One of the dimensions of temperament – higher emotional reactivity – is defined as a risk factor for children’s emotional, behavioral, and sleep problems. Screen-based media use is a very common phenomenon among children that relates to sleep problems. Still there is a gap of research explaining the interactions between children’s sleep problems, temperament, and parental discipline (sleep regime and rules for screen-based media use). The aim of this study is to evaluate the relations between preschool children’s sleep problems and parents’ discipline (sleep regime and rules for screen-based media use), and the role of children’s emotional reactivity. Methods. This research is a part of the longitudinal study “Electronic Media Use and Young Children’s Health” conducted in the year 2017–2018 and funded by the Research Council of Lithuanian (agreement no. GER-006/2017). Participants are 876 children aged 2 to 5 years old and their parents. Children’s sleep problems and emotional reactivity were assessed using the Child Behavior Checklist (CBCL/1½-5). Information about rules for screen-based media use and sleep regime was obtained using the parent-report questionnaire. Results. Sleep problems are related to emotional reactivity, sleep regime, and rules for screen media use. Children without regular sleep regime and without constant rules for screen-based media use have higher sleep problems and emotional reactivity. The results of the regression analysis show that emotional reactivity, together with sleep regime and rules for screen-based media use, significantly explain one-fifth to one-third of children’s sleep problems at different ages of the preschool period. However, the prognostic value of emotional reactivity and parental discipline varies according to a child’s age, as they are significant predictors of sleep problems among two, three and four-year-olds, but no longer explain sleep problems of five-year-olds. The path analysis confirmed that emotional reactivity, directly and through mediating variables, e.g., parental reported child’s sleep regime and rules for screen-based media use, is significantly associated with children’s sleep problems. Conclusions. Emotional reactivity should be considered as a significant risk factor in the relation between children’s sleep problems, sleep regime and parental applied rules for screen-based media use. These results are important while identifying children at higher risk for sleep problems. The results also support that parental discipline, such as sleep regime and rules for screen-based media use, are significant for preventing sleep problems in children with higher emotional reactivity.
Enteral Nutrition Improves Vital Signs in Children With Bronchiolitis on Noninvasive Ventilation
Authors: Sochet Anthony A. , Nunez Miranda , Wilsey Michael J. , Morrison John M. , Bessone Stacey K. , Nakagawa Thomas A. 
Published: February 2021

OBJECTIVES:
In children hospitalized for bronchiolitis, enteral nutrition (EN) practices during noninvasive ventilation (NIV) vary widely. We sought to assess the potential impact of EN by observing changes in physiometric indices (heart rate [HR] and respiratory rate [RR]) before and after EN initiation.

METHODS:
We performed a retrospective cohort study in children &lt;2 years of age hospitalized for bronchiolitis receiving NIV from 2017 to 2019 in a quaternary ICU. The primary outcome was patient HR and RR before and after EN initiation. Descriptive data included demographics, anthropometrics, comorbidities, NIV parameters, EN characteristics, and general hospital outcomes. Analyses included paired comparative and descriptive statistics.

RESULTS:
Of the 124 children studied, 85 (69%) were permitted EN at a median of 12 (interquartile range [IQR]: 7 to 29) hours. The route was oral (76.5%), nasogastric (15.3%), or postpyloric (8.2%) and was predominantly started during high-flow nasal cannula (71%) at flow rates of 1 (IQR: 0.7 to 1.4) L/kg per minute. After EN initiation, reductions in the median RR (percentage change: −11 [IQR: −23 to 3]; P &lt; .01) and HR (percentage change: −5 [IQR: −12 to 1]; P &lt; .01) were noted. Those permitted EN were younger (5 [IQR: 2 to 11] vs 11 [IQR: 3 to 17] months; P &lt; .01) and more likely to have bronchopulmonary dysplasia (19% vs 5%; P = .04). Malnutrition rates, comorbidities, admission timing, flow rates, length of stay, and NIV duration did not differ for those provided or not provided EN. No aspiration events were observed.

CONCLUSIONS:
Reductions between pre- and postprandial RR after EN initiation among children hospitalized for bronchiolitis on NIV were observed without clinically significant aspiration. These findings support existing data that suggest that EN is safe during NIV and may lessen distress in some patients.
Validation of Administrative Codes for Palliative Care Consultation Among Critically Ill Children
Authors: O’Keefe Siobhán , Czaja Angela S. 
Published: February 2021

OBJECTIVES:
To determine the validity of palliative care (PC) administrative codes (V66.7 and Z51.5) among critically ill pediatric patients.

METHODS:
In this single-center retrospective cohort study, we included all hospitalizations with a PICU admission between March 2016 and March 2018. Sensitivity, specificity, and positive and negative predictive values of the relevant codes were estimated by using a gold standard of a local PC registry.

RESULTS:
During the study period, 4670 hospitalizations were included. The median admission age was 5 years (interquartile range 1.5–12.9) with 55% having at least 1 complex chronic condition. The median length of PICU stay was 1.8 days (interquartile range 1–3.4) and mortality was low (1.3%). A total 182 (3.9%) hospitalizations had evidence of a PC consultation. Administrative codes for PC had a sensitivity of 11% (95% confidence interval [CI] 6.8%–16.5%) and a specificity of 99.8% (95% CI 99.6%–99.9%). The positive and negative predictive values were 66.7% (95% CI 47.2%–82.7%) and 96.5% (95% CI 95.9%–97.0%), respectively.

CONCLUSIONS:
Among critically ill children, PC administrative codes had high specificity but poor sensitivity. The potential for underascertainment of this resource should be considered in future research using administrative data.
Risk Factors for Adverse Events in Children Receiving Outpatient Parenteral Antibiotic Therapy
Authors: Townsley Elizabeth , Gillon Jessica , Jimenez-Truque Natalia , Katz Sophie , Garguilo Kathryn , Banerjee Ritu 
Published: February 2021

BACKGROUND:Outpatient parenteral antibiotic therapy (OPAT) can decrease length of hospital stay but is associated with adverse events (AEs). The purpose of this study was to quantify and identify risk factors for OPAT-associated AEs in children.METHODS:Retrospective single-center study of children ≤21 years old discharged on OPAT from January 2016 to April 2019 with infectious diseases follow-up. Demographic and clinical factors and medication and central venous catheter (CVC)–associated AEs were assessed through chart review. Univariable and multivariable analyses were performed.RESULTS:Among 181 OPAT courses, an AE occurred in 70 (39%). Medication AEs occurred in 30 of 181 courses (16.6%). Children residing in an urban area had a 4.5 times higher risk of having a medication-related AE compared with those in a rural area (odds ratio: 4.51; 95% confidence interval: 1.60–12.77; P = .005). CVC AEs occurred in 47 of 181 courses (26%). Every additional day of OPAT increased the odds of having a CVC-related AE by 4% (odds ratio: 1.04; 95% confidence interval: 1.01–1.07; P = .003). Twenty (11.1%) courses resulted in readmission to the hospital because of an AE.CONCLUSIONS:In this cohort, 39% of children experienced an OPAT-associated AE, and CVC AEs were more common than medication AEs. Longer duration of intravenous therapy and urban residence were independently associated with OPAT-associated AEs, highlighting the importance of converting to oral antibiotic therapy as soon as feasible to reduce OPAT-associated AEs.
Pediatric Faculty and Trainee Attitudes Toward the COVID-19 Pandemic
Authors: Kazmerski Traci M. , Friehling Erika , Sharp Eleanor A. , Muzumdar Ishan , Corbera-Hincapie Montserrat , Dewar Stephanie , Nowalk Andrew , Srinath Arvind , Muzumdar Hiren 
Published: February 2021

OBJECTIVES:
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented event in modern medicine. In this study, we evaluate pediatric faculty and trainee attitudes and perspectives related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their roles in the COVID-19 pandemic.

METHODS:
We surveyed a pediatric hospital’s faculty and trainees (n = 701) in April 2020 about their concerns related to SARS-CoV-2, trust in current recommendations, and attitudes toward trainee roles. We used descriptive statistics to analyze results and compared across sex and roles using logistic regression.

RESULTS:
Among 320 respondents (46% response rate), 73% were concerned with personal risk of SARS-CoV-2 infection and 88% were concerned with loved ones’ risk. Twenty-four percent were concerned because of personal risk factors. Nearly half expressed concerns as their family’s major provider and about salary changes (48% and 46%). Seventy-nine percent were concerned about lack of personal protective equipment and 43% about redeployment. Respondents endorsed varying levels of trust in recommendations related to COVID-19. Nearly three-fourths (72%) felt trainees are essential personnel. The majority were receptive to returning to usual patient care and training as the pandemic progresses. Significant differences exist across sex and roles related to levels of concern, trust, and trainee roles.

CONCLUSIONS:
In this study, we assess the concerns and perspectives of pediatric faculty and trainees related to the COVID-19 pandemic. Most view trainees as essential personnel and recognize the importance of direct patient care in their training. These results can be used to inform policy changes and trainee roles as the COVID-19 pandemic progresses.
Quantifying Electronic Health Record Data: A Potential Risk for Cognitive Overload
Authors: Gal Dana B. , Han Brian , Longhurst Chistopher , Scheinker David , Shin Andrew Y. 
Published: February 2021

OBJECTIVES:
To quantify and describe patient-generated health data.

METHODS:
This is a retrospective, single-center study of patients hospitalized in the pediatric cardiovascular ICU between February 1, 2020, and February 15, 2020. The number of data points generated over a 24-hour period per patient was collected from the electronic health record. Data were analyzed by type, and frontline provider exposure to data was extrapolated on the basis of patient-to-provider ratios.

RESULTS:
Thirty patients were eligible for inclusion. Nineteen were hospitalized after cardiac surgery, whereas 11 were medical patients. Patients generated an average of 1460 (SD 509) new data points daily, resulting in frontline providers being presented with an average of 4380 data points during a day shift (7:00 am to 7:00 pm). Overnight, because of a higher patient-to-provider ratio, frontline providers were exposed to an average of 16 060 data points. There was no difference in data generation between medical and surgical patients. Structured data accounted for &gt;80% of the new data generated.

CONCLUSIONS:
Health care providers face significant generation of new data daily through the contemporary electronic health record, likely contributing to cognitive burden and putting them at risk for cognitive overload. This study represents the first attempt to quantify this volume in the pediatric setting. Most data generated are structured and amenable to data-optimization systems to mitigate the potential for cognitive overload and its deleterious effects on patient safety and health care provider well-being.