bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective examination of adolescent sleep patterns and behaviors before and during COVID-19
Authors: Becker Stephen P , Dvorsky Melissa R , Breaux Rosanna , Cusick Caroline N , Taylor Katherine P , Langberg Joshua M
Published: February 2021

Study Objectives

To prospectively examine changes in adolescent sleep before and during the COVID-19 pandemic in adolescents with and without ADHD.

Methods

Participants were 122 adolescents (ages 15–17; 61% male; 48% with ADHD). Parents reported on adolescents’ sleep duration and difficulties initiating and maintaining sleep (DIMS); adolescents reported on sleep patterns, sleep duration, delayed sleep/wake behaviors, and daytime sleepiness before (September 2019 to February 2020) and during (May–June 2020) COVID-19. Adolescents also reported on their health behaviors, COVID-19-related negative affect, and difficulties concentrating due to COVID-19.

Results

Parents reported adolescents had more DIMS during COVID-19 than before COVID-19, with clinically elevated rates increasing from 24% to 36%. Both bedtimes and waketimes shifted later during COVID-19, and adolescents reported more delayed sleep/wake behaviors. Adolescents also reported less daytime sleepiness and longer school night sleep duration during COVID-19. In considering differences between adolescents with and without ADHD, adolescents with ADHD did not experience an increase in school night sleep duration and were less likely to obtain recommended sleep duration during COVID-19. In the full sample, controlling for ADHD status, COVID-19-related sadness/loneliness was associated with increases in DIMS, and spending less time outside and more COVID-19-related worries/fears were associated with increases in delayed sleep/wake behaviors during COVID-19.

Conclusions

COVID-19 had negative and positive impacts on adolescent sleep. Adolescents with ADHD did not experience the benefit of increased school night sleep duration during COVID-19 like adolescents without ADHD. Negative affect and health behaviors may be useful intervention targets for reducing negative impacts of COVID-19 for adolescent sleep.
Low-Level Metal Contamination and Chelation in Cardiovascular Disease—A Ripe Area for Toxicology Research
Authors: Ujueta Francisco , Navas-Acien Ana , Mann Koren K , Prashad Rakesh , Lamas Gervasio A
Published: February 2021

Cardiovascular disease remains the leading cause of death worldwide. In spite of cardiovascular prevention, there is residual risk not explicable by traditional risk factors. Metal contamination even at levels previously considered safe in humans may be a potential risk factor for atherosclerosis. This review examines evidence that 2 metals, lead, and cadmium, demonstrate sufficient toxicological and epidemiologic evidence to attribute causality for atherosclerotic disease. Basic science suggests that both metals have profound adverse effects on the human cardiovascular system, resulting in endothelial dysfunction, an increase in inflammatory markers, and reactive oxygen species, all of which are proatherosclerotic. Epidemiological studies have shown both metals to have an association with cardiovascular disease, such as peripheral arterial disease, ischemic heart disease, and cardiovascular mortality. This review also examines edetate disodium-based chelation as a possible pharmacotherapy to reduce metal burden in patients with a history of cardiovascular disease and thus potentially reduce cardiovascular events.
High-Throughput Metabarcoding Characterizes Fungal Endophyte Diversity in the Phyllosphere of a Barley Crop
Authors: Milazzo Carla , Zulak Katherine G. , Muria-Gonzalez M. Jordi , Jones Darcy , Power Matthew , Bransgrove Kaylene , Bunce Michael , Lopez-Ruiz Francisco J.
Published: February 2021

Over the last decade, the microbiome has received increasing attention as a key factor in macroorganism fitness. Sustainable pest management requires an understanding of the complex microbial endophyte communities existing symbiotically within plants and the way synthetic pesticides interact with them. Fungal endophytes are known to benefit plant growth and fitness and may deter pests and diseases. Recent advances in high-throughput sequencing (HTS) have enabled integrative microbiome studies, especially in agricultural contexts. Here, we profile the fungal endophyte community in the phyllosphere of two barley (Hordeum vulgare) cultivars exposed to two systemic foliar fungicides using metabarcoding, an HTS tool that constructs community profiles from environmental DNA. We studied the fungal nuclear ribosomal large subunit D2 and internal transcribed spacer 2 (ITS2) DNA markers through a bioinformatics pipeline introduced here. We found 88 and 128 unique amplicon sequence variants (ASVs) using the D2 and ITS2 metabarcoding assays, respectively. With principal coordinate analysis and permutational analysis of variance, ASV diversity did not change in response to barley cultivar or fungicide treatment; however, the community structure of unsprayed plants did change between two collection times 8 days apart. The workflow described here can be applied to other microbiome studies in agriculture and we hope it encourages further research into crop microbiomes to improve agroecosystem management.
Characterization of PmDGM Conferring Powdery Mildew Resistance in Chinese Wheat Landrace Duanganmang
Authors: Wu Yanan , Yu Xiaoting , Zhang Xu , Yan Lijuan , Gao Li , Hao Yiqing , Wang Xingyu , Xue Shulin , Qu Yunfeng , Hu Tiezhu , Fu Bisheng , Zhou Yun , Li Suoping , Li Hongjie , Li Chunxin , Ma Pengtao , Xu Hongxing
Published: February 2021

Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici, is a devastating disease that threatens yield and quality. Host resistance is considered the most effective and preferred means to control this disease. Wheat landrace Duanganmang (DGM) showed high resistance or near immunity to Blumeria graminis f. sp. tritici mixture from Henan Province, China. DGM was crossed with highly susceptible Chinese wheat landrace Huixianhong (HXH) and cultivar ‘Shimai 15’ (SM15) to produce genetic populations. The resistance of DGM to Blumeria graminis f. sp. tritici isolate E09 was shown to be controlled by a single dominant Mendelian factor, tentatively designated PmDGM. Marker analysis and 55K single nucleotide polymorphism (SNP) array scanning showed that this gene was positioned in the Pm5 interval (2.4 cM or 1.61 Mb) flanked by Xhenu099 and Xmp1158 in the Chinese Spring reference genome. Homology-based cloning and sequence analysis demonstrated that DGM has the identical NLR gene (Pm5e) and RXL gene reported in Fuzhuang 30 (FZ30), conferring and modifying powdery mildew resistance, respectively. However, based on the different reaction patterns to the Blumeria graminis f. sp. tritici isolate B15 between DGM and FZ30, the authors speculate that DGM may have two tightly linked genes that could not be separated in the current mapping population, one of which is PmDGM and the other being Pm5e. Hence, this study provides a valuable resistance resource for improvement of powdery mildew resistance.
Trust in Hospital Physicians Among Patients With Substance Use Disorder Referred to an Addiction Consult Service: A Mixed-methods Study
Authors: King Caroline , Collins Devin , Patten Alisa , Nicolaidis Christina , Englander Honora
Published: February 2021

Background:

Trust is essential in patient-physician relationships. Hospitalized patients with substance use disorders (SUDs) often experience stigma and trauma in the hospital, which can impede trust. Little research has explored the role of hospital-based addictions care in creating trusting relationships with patients with SUDs. This study describes how trust in physicians changed among hospitalized people with SUDs who were seen by an interprofessional addiction medicine service.

Methods:

We analyzed data from hospitalized patients with SUD seen by an addiction consult service from 2015 to 2018. Participants completed surveys at baseline and 30 to 90 days after hospital discharge. Follow-up assessments included open-ended questions exploring participant experiences with hospitalization and the addiction consult service. We measured provider trust using the Wake Forest Trust scale. We modeled trust trajectories using discrete mixture modeling, and sampled qualitative interviews from those trust trajectories.

Results:

Of 328 participants with SUD who had prior hospitalizations but had not previously been seen by an addiction consult service, 196 (59.8%) had both baseline and follow-up trust scores. We identified 3 groups of patients: Persistent-Low Trust, Increasing Trust, and Persistent-High Trust and 4 qualitative themes around in-hospital trust: humanizing care, demonstrating addiction expertise, reliability, and granting agency.

Conclusions:

Most participants retained or increased to high trust levels after hospitalization with an addiction consult service. Addiction consult services can create environments where healthcare providers build trust with, and humanize care for, hospitalized patients with SUD, and can also mitigate power struggles that hospitalized patients with SUD frequently experience.
Transmuscular Quadratus Lumborum and Lateral Femoral Cutaneous Nerve Block in Total Hip Arthroplasty
Authors: Li Jinlei , Dai Feng , Ona Ayala Kimberly E. , Zhou Bin , Schonberger Robert B. , Sharma Avijit
Published: February 2021

Objectives:

Adequate pain control after total hip arthroplasty is essential for patient satisfaction and surgical outcome.

Methods:

A retrospective study with before and after design was performed in 210 elective total hip arthroplasty patients. The control group (N=132) received spinal anesthesia with periarticular injection (PAI) and the treatment group (N=78) received transmuscular quadratus lumborum block and lateral femoral cutaneous nerve block in addition to spinal anesthesia and PAI. The primary outcome was visual analog scale (VAS) pain score on postoperative day (POD) 1, and secondary outcomes included VAS and opioid consumption on each POD, hospitalization cost, length of stay, and discharge acuity.

Results:

The mean VAS and opioid consumption (MME) were significantly lower in the treatment group than that in the control group on POD 1, with VAS difference −1.10 (95% confidence interval, −1.64 to −0.55), false discover rate corrected (P<0.001), and MME difference −26.19 (95% confidence interval, −39.16 to −13.23,P<0.001). A significant difference was also found for both VAS (P=0.007) and opioid consumption (P=0.018) on POD 2 and for opioid consumption on POD 3 (P=0.008). Length of stay (days) in the control group versus the treatment group was 2.50±1.38 versus 1.36±0.95 (P=0.002), and the total cost of hospitalization was over 20% higher in the control group than that in the treatment group (P=0.002).

Discussion:

The addition of transmuscular quadratus lumborum and lateral femoral cutaneous nerve block in total hip arthroplasty provides improved analgesia indicated by lower pain scores and opioid reduction and accelerated recovery with shorter hospitalization and decreased hospitalization cost.
Balanced Opioid-free Anesthesia with Dexmedetomidine versus Balanced Anesthesia with Remifentanil for Major or Intermediate Noncardiac Surgery
Authors: Beloeil Helene , Garot Matthias , Lebuffe Gilles , Gerbaud Alexandre , Bila Julien , Cuvillon Philippe , Dubout Elisabeth , Oger Sebastien , Nadaud Julien , Becret Antoine , Coullier Nicolas , Lecoeur Sylvain , Fayon Julie , Godet Thomas , Mazerolles Michel , Atallah Fouad , Sigaut Stephanie , Choinier Pierre-Marie , Asehnoune Karim , Roquilly Antoine , Chanques Gerald , Esvan Maxime , Futier Emmanuel , Laviolle Bruno ,   POFA Study Group,   SFAR Research Network
Published: February 2021

Background

It is speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support the speculation. The authors hypothesized that opioid-free balanced anesthetic with dexmedetomidine reduces postoperative opioid-related adverse events compared with balanced anesthetic with remifentanil.

Methods

Patients were randomized to receive a standard balanced anesthetic with either intraoperative remifentanil plus morphine (remifentanil group) or dexmedetomidine (opioid-free group). All patients received intraoperative propofol, desflurane, dexamethasone, lidocaine infusion, ketamine infusion, neuromuscular blockade, and postoperative lidocaine infusion, paracetamol, nefopam, and patient-controlled morphine. The primary outcome was a composite of postoperative opioid-related adverse events (hypoxemia, ileus, or cognitive dysfunction) within the first 48 h after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting.

Results

The study was stopped prematurely because of five cases of severe bradycardia in the dexmedetomidine group. The primary composite outcome occurred in 122 of 156 (78%) dexmedetomidine group patients compared with 105 of 156 (67%) in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33; P = 0.031). Hypoxemia occurred 110 of 152 (72%) of dexmedetomidine group and 94 of 155 (61%) of remifentanil group patients (relative risk, 1.19; 95% CI, 1.02 to 1.40; P = 0.030). There were no differences in ileus or cognitive dysfunction. Cumulative 0 to 48 h postoperative morphine consumption (11 mg [5 to 21] versus 6 mg [0 to 17]) and postoperative nausea and vomiting (58 of 157 [37%] versus 37 of 157 [24%]; relative risk, 0.64; 95% CI, 0.45 to 0.90) were both less in the dexmedetomidine group, whereas measures of analgesia were similar in both groups. Dexmedetomidine patients had more delayed extubation and prolonged postanesthesia care unit stay.

Conclusions

This trial refuted the hypothesis that balanced opioid-free anesthesia with dexmedetomidine, compared with remifentanil, would result in fewer postoperative opioid-related adverse events. Conversely, it did result in a greater incidence of serious adverse events, especially hypoxemia and bradycardia.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Comparison of Bone-Conducted Cervical VEMPs Elicited by B71 and B81 Bone Vibrators
Authors: Romero Daniel J. , Piker Erin G. , Thorne Andrew , Clinard Christopher
Published: February 2021

Objective:

A variety of stimulus delivery methods can elicit vestibular evoked myogenic potentials (VEMPs). The current study compared bone conduction (BC) cervical VEMPs (cVEMPs) across two different clinical bone vibrators. It was hypothesized that the B81 transducer would be more effective for producing larger BC-cVEMP peak to peak amplitudes due to its low-frequency advantages in pure-tone audiometry applications.

Design:

Twenty young adults under the age of 40 years with no reported history of hearing or balance disorders participated in the study. BC cVEMPs were elicited using two clinical bone transducers: the Radioear B71 bone vibrator and the Radioear B81 bone vibrator. Both transducers were calibrated using the acoustic method of calibration before data collection, and the linear dynamic range of the transducers was determined. Participants were asked to sit and match a fixed electromyography (EMG) target level of 100 µV, while BC cVEMPs were recorded using stimulus frequencies of 250, 500, and 750 Hz.

Results:

Statistically significant differences in raw amplitude at 250 and 750 Hz between the B71 and B81 were observed; the B71 produced larger peak to peak amplitudes over the B81. At 500 Hz, larger amplitudes were observed with the B71, but results were not statistically significant. The B71 produced significantly lower cVEMP thresholds at all three frequencies. Across both transducers, 500 Hz produced the largest peak to peak amplitude compared with 250 and 750 Hz. Peak to peak amplitude did not increase above 55 dB nHL for 250 and 500 Hz, but amplitude continued to increase at 750 Hz.

Discussion:

The present study found statistically significant differences in BC-cVEMP amplitude and threshold between the B71 and B81, but results were not what we hypothesized. In general, the B71 elicited larger BC-cVEMP amplitudes and lower thresholds compared with the B81. Additionally, 500 Hz was found to be the best frequency for both BC transducers, contrasting previous studies suggesting lower frequencies yield larger BC-cVEMP amplitudes. It is possible that these average differences could also be clinically significant when looking at individual amplitude differences. Larger peak to peak amplitudes at 500 Hz may be partially due to the underlying physical levels used in the current study, as well as the output spectra of the transducers, and may explain the larger response amplitudes observed at 500 Hz compared with 250 Hz.
The Feasibility and Reliability of a Digits-in-Noise Test in the Clinical Follow-Up of Children With Mild to Profound Hearing Loss
Authors: Vroegop Jantien , Rodenburg-Vlot Marian , Goedegebure André , Doorduin Agnes , Homans Nienke , van der Schroeff Marc
Published: February 2021

Objectives:

Speech perception in noise is an important aspect of the rehabilitation of children with hearing loss. We aimed to evaluate the feasibility and reliability of the Dutch digits-in-noise (DIN) test in the clinical follow-up of children with hearing aids (HAs) and/or cochlear implants (CIs). A second aim of the study was to gain insight in the speech perception in noise performance of children with different degrees of hearing loss.

Design:

We retrospectively analyzed DIN test data of Dutch-speaking children with hearing loss (N = 188; 5 to 18 years old). A free-field version of the DIN-test was used. Children with open-set phoneme recognition in quiet of >70% at 65 dB SPL (best aided condition) were included. Ages ranged from 5 to 18 years old. All were experienced HA or CI users and had used their device(s) for at least 1 year before the measurement in the study. The DIN-test was performed in the framework of a clinical rehabilitation program. During testing, children wore their own devices with normal daily programs.

Results:

The average speech reception threshold (SRT) was −3.6 dB (SD 3.6) for the first list and significantly improved to −4.0 dB (SD 3.1) for the second list. HA users had a 4-dB better SRT compared with CI users. The larger the child’s hearing loss, the worse the SRT is. However, 15% of the children who completed a first list of 24 trials were unable to complete a second list. Mean adaptive staircase trajectories across trials suggested that learning occurred throughout the first list, and that loss of sustained attention contributed to response variability during the second list.

Conclusion:

The DIN test can be used to assess speech perception in noise abilities for children with different degrees of hearing loss and using HAs or CIs. The children with hearing loss required a higher signal-to-noise ratio (SNR) than did normal-hearing children and the required SNR is larger as the hearing loss increases. However, the current measurement procedure should be optimized for use in standard pediatric audiological care, as 15% of the children were unable to conduct a second list after the first list to reach a more stable SNR.
Predicting Depression From Hearing Loss Using Machine Learning
Authors: Crowson Matthew G. , Franck Kevin H. , Rosella Laura C. , Chan Timothy C. Y.
Published: February 2021

Objectives:

Hearing loss is the most common sensory loss in humans and carries an enhanced risk of depression. No prior studies have attempted a contemporary machine learning approach to predict depression using subjective and objective hearing loss predictors. The objective was to deploy supervised machine learning to predict scores on a validated depression scale using subjective and objective audiometric variables and other health determinant predictors.

Design:

A large predictor set of health determinants from the National Health and Nutrition Examination Survey 2015–2016 database was used to predict adults’ scores on a validated instrument to screen for the presence and severity of depression (Patient Health Questionnaire-9 [PHQ-9]). After model training, the relative influence of individual predictors on depression scores was stratified and analyzed. Model prediction performance was determined by prediction error metrics.

Results:

The test set mean absolute error was 3.03 (95% confidence interval: 2.91 to 3.14) and 2.55 (95% confidence interval: 2.48 to 2.62) on datasets with audiology-only predictors and all predictors, respectively, on the PHQ-9’s 27-point scale. Participants’ self-reported frustration when talking to members of family or friends due to hearing loss was the fifth-most influential of all predictors. Of the top 10 most influential audiometric predictors, five were related to social contexts, two for significant noise exposure, two objective audiometric parameters, and one presence of bothersome tinnitus.

Conclusions:

Machine learning algorithms can accurately predict PHQ-9 depression scale scores from National Health and Nutrition Examination Survey data. The most influential audiometric predictors of higher scores on a validated depression scale were social dynamics of hearing loss and not objective audiometric testing. Such models could be useful in predicting depression scale scores at the point-of-care in conjunction with a standard audiologic assessment.
Onset of ulcerative colitis and complete response during the treatment of a metastatic colon cancer: case report and literature review
Authors: Saavedra Cristina , Mesonero Francisco , Perna Cristian , Reguera Pablo , Corral Elena , Ferreiro Reyes , Carrato Alfredo , Pachón Vanessa
Published: February 2021

Colorectal cancer is a common cancer worldwide. Several risk factors have been described, such as age, lifestyle and family history. Inflammatory bowel diseases (IBD) are a well-recognized risk factor for the development of colorectal cancer. However, the onset of an IBD de novo in the context of the treatment of a colorectal neoplasia has not been reported before, except in the context of the treatment with immunocheckpoint inhibitors. Fifty-nine-years old man diagnosed with a metastatic colorectal cancer who received conventional treatment with chemotherapy and an antiangiogenic inhibitor. The patient had a complete response with the therapy after few cycles. Nevertheless, during the treatment, the patient presented with rectal bleeding, and was diagnosed with ulcerative colitis. Although the treatment was discontinued, tumoral complete remission is maintained. The relevance of this case lies in the concurrence of the onset of an autoimmune disease and a complete response of the malignancy. The concurrence of these events has been described previously only with immunotherapy. There are not cases reported involving chemotherapy and antiangiogenic drugs. Other causes of colitis were ruled out due to the unusual presentation of the case.
Successful treatment of Afatinib plus Apatinib using for a lung adenocarcinoma patient with HER-2 V659D mutation: a rare case report
Authors: Sun Chao , Xu Yinghui , Wang Xu , Guo Ye , Qiu Shi , Shao Guoguang , Yang Zhiguang , Liu Yunpeng , Zhang Peng , Ma Kewei
Published: February 2021

Lung cancer is one of the most important and lethal cancers in the world. Human epidermal growth factor 2 (HER2) is a member of the erbB receptor tyrosine kinase family. The incidence of HER2 kinase domain mutations in adenocarcinoma of lung ranges from 1% to 3%. HER2 V659D mutation is located in the trans-membrane domain (TMD) with only a few cases reported before, and importantly, there were no more standard and effective ways for this kind of diseases until now. Afatinib irreversibly blocks all kinase-competent HER family members. Apatinib is one of the small-molecule oral anti-angiogenesis-targeted agents developed firstly in China, and it’s a highly selective inhibition of the activity of VEGFR-2. This report presents an advanced lung adenocarcinoma patient with HER2 V659D mutation who was treated with combination of Afatinib and Apatinib. He achieved good efficacy and tolerable adverse reactions.
Combination of radiation therapy for brain metastasis and anti-PD-1/PD-L1 treatment in non-small cell lung cancer: two cases and review of the literature
Authors: Nigro Olga , Tuzi Alessandro , Coppola Andrea , Tartaro Tiziana , Chini Claudio , Pinotti Graziella
Published: February 2021

Lung cancer is the most frequent cause of cancer-related death worldwide and is usually diagnosed in advanced stages. Among those, approximately 7.4% of non-small cell lung cancer (NSCLC) patients will have brain metastasis (BM) at presentation, and 25–30% will develop BM during the course of their disease. To date, patients with BMs are increasingly considered for combined treatment using systemic immune checkpoint inhibition (ICI) and cranial radiation therapy (RT); yet, there is limited data regarding the safety of this approach. Here, we report two cases of NSCLC patients treated with two different types of cranial RT and ICIs.
LncRNA highly upregulated in liver cancer regulates imatinib resistance in chronic myeloid leukemia via the miR-150-5p/MCL1 axis
Authors: Han Yunxia , Ma Zhenzhi
Published: February 2021

Chronic myeloid leukemia (CML) is a type of myeloproliferative neoplasm. Aberrant expression of long noncoding RNA highly upregulated in liver cancer (HULC) has been implicated in tumor progression, including CML. This study aimed to investigate the role of HULC in CML. The levels of HULC, miR-150-5p and myeloid cell leukemia 1 (MCL1) were examined by quantitative real-time PCR or western blot assay. Cell counting kit-8 assay was used to detect cell viability and half inhibition concentration. Cell apoptosis was monitored by flow cytometry and western blot. The interaction among HULC, miR-150-5p and MCL1 was validated by dual-luciferase reporter assay. The expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and phosphorylation-AKT was evaluated using western blot assay. HULC and MCL1 were upregulated, whereas miR-150-5p was downregulated in bone marrow mononuclear cells of CML patients and CML cells. HULC overexpression increased imatinib resistance in K562 cells, and HULC depletion enhanced imatinib sensitivity in imatinib-resistant cells (K562-R). Mechanically, HULC was a sponge of miR-150-5p. HULC contributed to imatinib resistance through regulation of miR-150-5p. MCL1 bound to miR-150-5p and reversed the effect of HULC on imatinib resistance. HULC regulated the PI3K/AKT pathway via the miR-150-5p/MCL1 axis. These findings indicated that HULC enhanced imatinib resistance in CML by modulating the miR-150-5p/MCL1 axis, providing a promising biomarker for CML.
Relatively mild symptoms after chronic overdose with a double-dose encorafenib: a case report
Authors: Mian Paola , Meussen Elvera , Piersma Djura , Lankheet Nienke A. G.
Published: February 2021

Encorafenib (Braftovi) is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation, in combination with binimetinib (Mektovi). According to the product label of encorafenib, there are no specific treatment recommendations in case of an overdose. We report on a 63-year-old man who ingested a double dose (900 mg) of encorafenib for 16 days. He developed overall minor chronic overdose symptoms such as nausea and vomiting grade 1 and muscle pain. Based on the most occurring adverse events of encorafenib, liver values, kidney function parameters and QTc interval were measured. Kidney function parameters were normal, whereas liver values were slightly increased (grade 1) and QTc slightly prolonged. The plasma concentration 3 h after the last dose was 2110 ng/mL. We describe the course of a case with a chronic overdose during 16 days of the double dose of encorafenib as well as the followed approach, which could be taken into account when observing an encorafenib overdose. Providing information in times of Covid-19 is challenging, but remains necessary for good clinical care.
Implementation of a Critical Care Asthma Pathway in the PICU
Authors: Miksa Michael , Kaushik Shubhi , Antovert Gerald , Brown Sakar , Ushay H. Michael , Katyal Chhavi
Published: February 2021

Objectives:

Acute asthma management has improved significantly across hospitals in the United States due to implementation of standardized care pathways. Management of severe acute asthma in ICUs is less well studied, and variations in management may delay escalation and/or deescalation of therapies and increase length of stay. In order to standardize the management of severe acute asthma in our PICU, a nurse- and respiratory therapist–driven critical care asthma pathway was designed, implemented, and tested.

Design:

Cross-sectional study of severe acute asthma at baseline followed by implementation of a critical care asthma pathway.

Setting:

Twenty-six–bed urban quaternary PICU within a children’s hospital.

Patients:

Patients 24 months to 18 years old admitted to the PICU in status asthmaticus. Patients with severe bacterial infections, chronic lung disease, heart disease, or immune disorders were excluded.

Interventions:

Implementation of a nurse- and respiratory therapist–driven respiratory scoring tool and critical care asthma pathway with explicit escalation/deescalation instructions.

Measurements and Main Results:

Primary outcome was PICU length of stay. Secondary outcomes were time to resolution of symptoms and hospital length of stay. Compliance approached 90% for respiratory score documentation and critical care asthma pathway adherence. Severity of illness at admission and clinical baseline characteristics were comparable in both groups. Pre intervention, the median ICU length of stay was 2 days (interquartile range, 1–3 d) with an overall hospital length of stay of 4 days (interquartile range, 3–6 d) (n = 74). After implementation of the critical care asthma pathway, the ICU length of stay was 1 day (interquartile range, 1–2 d) (p = 0.0013; n = 78) with an overall length of stay of 3 days (interquartile range, 2–3.75 d) (p < 0.001). The time to resolution of symptoms was reduced from a median of 66.5 hours in the preintervention group to 21 hours in the postintervention compliant group (p = 0.036).

Conclusions:

The use of a structured critical care asthma pathway, driven by an ICU nurse and respiratory therapist, is associated with faster resolution of symptoms, decreased ICU, and overall hospital lengths of stay in children admitted to an ICU for severe acute asthma.
Pearls and perils in the management of germ cell tumors
Authors: Wei Cynthia X. , Einhorn Lawrence H. , Adra Nabil
Published: February 2021

Purpose of review

Research and innovation over the past half century have rendered testicular cancer a highly curable malignancy. Challenges and uncertainty remain in several aspects related to the management and surveillance of patients with germ cell tumors (GCT). Long-term effects of treatment on survivors of testicular cancer remain as continued areas of interest. This review aims to highlight pearls and perils in the management of patients with GCT.

Recent findings

Uncertainty remain regarding complex aspects of first-line and salvage treatments of GCT, interpretation of tumor markers in cases of α-fetoprotein levels less than 25 ng/ml, plateau of β-human chorionic gonadotropin (hCG) levels in patients with initial hCG greater than 50 000 mIU/ml, supportive therapies throughout chemotherapy regimens, and long-term survivorship of patients who underwent surgery or received platinum-based chemotherapy. This review aims to highlight challenges that remain in GCT, review the emerging data in these areas, and provide our institutional opinion on the management in several aspects of GCT.

Testicular cancer continues to present challenging clinical scenarios with respect to treatment, surveillance, and long-term management of patients. We review the data and share our institutional knowledge in several challenging areas related to the management of GCT.
miRNA-296-5p functions as a potential tumor suppressor in human osteosarcoma by targeting SND1
Authors: Huang Ya-Zeng , Zhang Jun , Shen Jian-Jian , Zhao Ting-Xiao , Xu You-Jia
Published: February 2021

Background:

The pathogenesis of osteosarcoma (OS) is still unclear, and it is still necessary to find new targets and drugs for anti-OS. This study aimed to investigate the role and mechanism of the anti-OS effects of miR-296-5p.

Methods:

We measured the expression of miR-296-5p in human OS cell lines and tissues. The effect of miR-296-5p and its target gene staphylococcal nuclease and tudor domain containing 1 on proliferation, migration, and invasion of human OS lines was examined. The Student's t test was used for statistical analysis.

Results:

We found that microRNA (miR)-296-5p was significantly downregulated in OS cell lines and tissues (control vs. OS, 1.802 ± 0.313 vs. 0.618 ± 0.235, t = 6.402, P < 0.01). Overexpression of miR-296-5p suppressed proliferation, migration, and invasion of OA cells. SND1 was identified as a target of miR-296-5p by bioinformatic analysis and dual-luciferase reporter assay. Overexpression of SND1 abrogated the effects induced by miR-296-5p upregulation (miRNA-296-5p vs. miRNA-296-5p + SND1, 0.294 ± 0.159 vs. 2.300 ± 0.277, t = 12.68, P = 0.003).

Conclusion:

Our study indicates that miR-296-5p may function as a tumor suppressor by targeting SND1 in OS.
A Systematic Review of Primary, Adjuvant, and Salvage Radiation Therapy for Cutaneous Squamous Cell Carcinoma
Authors: Krausz Aimee E. , Ji-Xu Antonio , Smile Timothy , Koyfman Shlomo , Schmults Chrysalyne D. , Ruiz Emily S.
Published: February 2021

BACKGROUND

The gold standard of treatment for cutaneous squamous cell carcinoma (cSCC) is surgery radiation therapy (RT) is used selectively as definitive treatment for low-risk tumors or as adjuvant/salvage treatment for high-risk tumors. There is a lack of standardized studies evaluating the efficacy of RT in either clinical scenario.

OBJECTIVE

To determine the efficacy of primary and adjuvant/salvage RT for the treatment of cSCC.

MATERIALS AND METHODS

A systematic review of PubMed, Embase, Cochrane, and Web of Science was performed for studies that reported outcomes of cSCC treated with RT to the primary site alone. Outcomes included local control (LC), local recurrence (LR), nodal metastases (NM), distant metastases (DM), disease-specific death (DSD), and recurrence-free survival (RFS).

RESULTS

Forty-six studies with 4,141 tumors were included. Pooled LC and LR rates were 87.3% and 8.6%, respectively. The rates of NM, DM, DSD, and RFS were 4.8%, 3.5%, 5.3%, and 73.5%, respectively. Local recurrence was significantly higher for T3 and T4 tumors, with rates above 25.9%.

CONCLUSION

LR after RT to the primary site increased with increasing tumor stage, highlighting the importance of clear surgical margins for high-risk tumors. Prospective randomized studies characterizing outcomes by tumor stage for RT compared with surgery are needed to inform guidelines.
Simultaneous Determination of 6 Antiretroviral Drugs in Human Hair Using an LC-ESI+-MS/MS Method: Application to Adherence Assessment
Authors: Wu Yan , Chu Liuxi , Yang Haoran , Wang Wei , Zhang Quan , Yang Jin , Qiao Shan , Li Xiaoming , Shen Zhiyong , Zhou Yuejiao , Liu Shuaifeng , Deng Huihua
Published: February 2021

Background:

The determination of antiretroviral drugs in hair is receiving considerable research interest to assess long-term adherence to antiretroviral therapy (ART). Currently in China, lamivudine, zidovudine, nevirapine, efavirenz, ritonavir, and lopinavir are combined as first-line and second-line free therapy regimens and are recommended for people living with HIV (PLWH). Simultaneous determination of the 6 antiretroviral drugs in human hair is important for accurately and widely assessing long-term adherence in Chinese PLWH receiving different ART regimens.

Methods:

Six drugs were extracted from 10-mg hair samples incubated in methanol for 16 hours at 37°C and then analyzed by liquid chromatography with tandem mass spectrometry using a mobile phase of 95% methanol, with an electrospray ionization source in multiple reaction monitoring and positive mode.

Results:

The LC-ESI+-MS/MS method exhibited a linear range (R
2 > 0.99) within 6–5000, 10–5000, 6–50,000, 12–50,000, 8–5000, and 8–12,500 pg/mg for lamivudine, zidovudine, nevirapine, efavirenz, ritonavir, and lopinavir. For all 6 drugs, the limits of quantification ranged between 6 and 12 pg/mg. The intraday and interday coefficients of variation were within 15%, and the recoveries ranged from 91.1% to 113.7%. Furthermore, the other validation parameters (ie, selectivity, matrix effect, stability, and carryover) met the acceptance criteria stipulated by guidelines of the US Food and Drug Administration and European Medicines Agency. Significant intergroup differences were observed between high-adherence and low-adherence groups, with high intercorrelations in the hair content of the 6 drugs.

Conclusions:

The developed method demonstrated good reliability, to comprehensively and accurately assess adherence in PLWH receiving different ART regimens.
Two Cases of Preaxial Polydactyly of the Foot: Important Implications for Plastic Surgeons
Authors: Silverstein Max L. , Burke Leah W. , Laub Donald R.
Published: February 2021

Although polydactyly is quite common in general, preaxial polydactyly of the foot is rare (0.4 per 10,000 patients) and specifically associated with certain congenital abnormalities and syndromes, which can include craniosynostosis, corpus callosum agenesis, and renal malformations. We present 2 recent cases of preaxial polydactyly of the foot that highlight the importance of maintaining a high level of suspicion for associated abnormalities in these patients. The first patient, who presented with supernumerary preaxial digits on both feet, pre- and postaxial polydactyly of the hands, was also macrocephalic and hyperteloric; this presentation strongly suggested a diagnosis of Greig cephalopolysyndactyly, a GLI3-variant syndrome. The second patient, who had 2 preaxial digits on one foot, was found to also have a horseshoe kidney, a malformation that has been associated with limb defects as part of an acrorenal syndrome. These cases emphasize the importance of a thorough clinical approach to patients with preaxial polydactyly of the foot. Although many patients with this anomaly may be well known to geneticists, a child may be referred to a plastic surgeon for reconstruction of what is thought to be an isolated cosmetic or local functional issue. Plastic surgeons should be aware of the complex nature of preaxial polydactyly of the foot and potential syndromic presentation.
Characterization of Inflammatory and Fibrotic Aspects of Tissue Remodeling of Acellular Dermal Matrix in a Nonhuman Primate Model
Authors: Ji HaYeun , Sukarto Abby , Deegan Daniel , Fan Frank
Published: February 2021

Background:

Human acellular dermal matrices (hADMs) are applied in various soft tissue reconstructive surgeries as scaffolds to support tissue remodeling and regeneration. To evaluate the clinical efficacy of hADM implants, it is integral that the hADM does not induce a host chronic inflammatory response leading to fibrotic encapsulation of the implant. In this study, we characterized the inflammatory and fibrosis-related tissue remodeling response of 2 commercial hADM products (SimpliDerm and AlloDerm RTU) in a nonhuman primate model using histology and gene expression profiling.

Methods:

Eighteen African green monkeys with abdominal wall defects were applied to evaluate the performance of SimpliDerm and AlloDerm RTU implants (N = 3) at 2, 4, and 12-weeks post-implantation. Using histology and gene expression profiling, tissue responses such as implant integration, degradation, cell infiltration, immune response, neovascularization, and pro-fibrotic responses over time were evaluated.

Results:

SimpliDerm showed a lower initial inflammatory response and slower implant degradation rate than AlloDerm RTU evidenced by histomorphological analysis. These factors led to a more anti-inflammatory and pro-remodeling microenvironment within SimpliDerm, demonstrated by lower TNFα levels and lower expression levels of pro-fibrotic markers, and promoted tissue repair and regeneration by 3-months post-implantation.

Conclusions:

Overall, histology and gene expression profiling analyses shown in this study demonstrated an effective model for analyzing hADM performance in terms of host inflammatory and fibrotic response. Further studies are warranted to fully evaluate the utility of this novel hADM in the clinical setting and verify the prognosis of our pre-clinical analysis model.
Analysis of Environmental Data to Support Quantification of Historical Releases from a Former Uranium Processing Facility in Apollo, Pennsylvania
Authors: Mohler H. Justin , Rood Arthur S. , Grogan Helen A. , Caffrey Emily A. , Till John E.
Published: February 2021

This paper describes how environmental measurement data were used to help quantify the spatial impact and behavior of uranium released to the environment from a uranium manufacturing facility in Apollo, PA. The Apollo facility released enriched uranium to the environment while it operated between 1957 and 1983. Historical monitoring data generated by the site, along with other independent data sources, provided a long-term record documenting the presence and behavior of uranium in the local environment. This record of evidence, together with reconstructed estimates of facility releases, has been used to estimate environmental concentrations during facility operations and potential exposures to members of the public. Historical environmental measurement data were also used to confirm predictions of deposition and concentrations in air. The data are used here to derive atmospheric deposition velocities for the uranium emissions. Based on the spatial pattern of measurements and calculated deposition velocities around the facility, the released material contained larger particles that deposited close to the facility, and the released material remains largely in the surface layers of the soil, indicating limited downward mobility. Evidence of measurable impacts was determined to extend a relatively short distance (<500 m) from the facility. The soil data collected around Apollo are also compared to findings related to uranium mobility at another facility where uranium was released to the environment, and similar behavior was observed at both sites.
Radiation Safety for Yttrium-90-polymer Composites (RadioGel™) in Therapy of Solid Tumors
Authors: Fisher Darrell R.
Published: February 2021

Yttrium-90 (90Y)-polymer composite (RadioGel™) is a new cancer therapeutic agent for treating solid tumors by direct interstitial injection. The 90Y-composite comprises insoluble, microscopic yttrium-phosphate particles carried by a sterile, injectable water-polymer (hydrogel) solution that can be placed directly by needle injection into solid tumors. The yttrium-90-RadioGel™ agent was designed to provide a safe, effective, localized, high-dose beta radiation for treating solid tumors. The properties of 90Y-RadioGel™ also make it a relatively safe agent for health care personnel who prepare, handle, and administer the material. The purpose of this work was to demonstrate and characterize radiation safety of the injectable 90Y-RadioGel™ therapeutic agent. Safety in the patient is defined by its ability to target precisely and remain confined within tumor tissue so that radiation doses are imparted to the tumor and not to normal organs and tissues. Radiation safety for health care personnel is defined by the low radiation doses received by persons who prepare and administer the agent. These safety features were demonstrated during experiments, first involving laboratory rabbits and second in cat and dog animal patients that were treated clinically for sarcoma tumors. This paper focuses mainly on the rabbit tissue biodistribution study; follow-on clinical application in cat and dog subjects confirmed the rabbit results. Implanted VX2 liver tumors in the hind limbs of 26 New Zealand White rabbits were treated using tracer amounts of either (a) 90Y-RadioGel™ or (b) 90Y-microparticles in phosphate-buffered saline (PBS) without the gel carrier. Tumor and margin injections were interstitial. Rabbits were euthanized at 48 h or 10 d following injection. Blood and tissues (tumor or tumor margins, liver, lymph nodes, rib bone, kidney, spleen) were collected for liquid scintillation counting using wet-ash procedures. Biodistribution was also analyzed at 10 d post-injection using micro-computed tomography. Thirteen cat and dog subjects were also treated clinically for sarcomas. Liquid scintillation counting at 48 h post-injection of tumors or margins with 90Y-RadioGel™ showed that significant radioactivity was measurable only at the site of administration and that radioactivity above detector background was not found in blood or peripheral organs and tissues. At 10 d post-injection, microCT showed that yttrium phosphate microparticles were confined to the injection site. Yttrium-90 remained where placed and did not migrate away in significant amounts from the injection site. Radiation doses were confined mainly to tumors and margin tissues. During preparation and administration, radiation doses to hands and body of study personnel were negligible. This work showed that 90Y-RadioGel™ can be safely prepared and administered and that radiation doses to cancer patients are confined to tumor and margin tissues rather than to critical normal organs and tissues.
Dose Estimation of Landfill Disposal of Removed Soil Generated Outside Fukushima Prefecture
Authors: Shimada Asako , Sawaguchi Takuma , Takeda Seiji
Published: February 2021

Dose estimation was conducted by assuming landfill disposal of removed soil generated outside the Fukushima Prefecture by each local town and in a lump sum. Because the radioactivity of removed soil is lower than that of specified waste that was generated at Fukushima Prefecture and the radioactivity concentration is 100,000 Bq kg−1 or less, simple landfill covered with 30 cm of non-contaminated soil was used. The exposure doses of loading/unloading, transportation, and landfill workers and the public residing near the repository site were estimated. Furthermore, migration of cesium into groundwater because of precipitation and using the contaminated groundwater for drinking and agricultural water was evaluated, and exposure doses regarding farmers and the ingestion of agricultural products were estimated. It was confirmed that estimated exposure doses during landfill were less than 1 mSv y−1, and those for after landfill were 0.01 mSv y−1.
External Dose to Recovery Teams Following a Wide-area Nuclear or Radiological Release Event
Authors: Kaminski Michael D. , Sanders Keith , Hepler Katherine , Magnuson Matthew , Slagley Jeremy
Published: February 2021

The common radionuclide 137Cs is a gamma-ray source term for nuclear reactor accidents, nuclear detonations, and potential radionuclide dispersal devices. For wide-area contamination events, one remediation option integrates water washing activities with on-site treatment of water for its immediate reuse. This remediation option includes washing building and roadways via firehose, collecting the wash water, and passing the contaminated water through chemical filtration beds. The primary objective of this study was to quantify the dose incurred to workers performing a remediation recovery effort for roadways and buildings following a wide-area release event. MicroShield® was employed to calculate the dose to workers at the roadway level and to calculate total dose rates while performing washing activities. This study finds that for a realistic contamination scenario for a wide area of a large urban environment, decontamination crews would be subjected to <220 μSv per person, much less than the 50,000 μSv limit for occupational dose. By extrapolation, one decontamination team of 48 people could continue washing operations on a total of 2.8 km2 before reaching their incurred annual dose limits. Though it is unrealistic to assign one team that entire area, we can conclude external dose will not limit worker deployment given the range of contamination levels adopted in this study.