bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiological Outcomes Associated With Low Leukocyte Counts in Cerebrospinal Fluid
Authors: Wald Mathieu , Merisor Simona , Zachary Pierre , Augereau Olivier , Gravier Simon , Jaulhac Benoit , De Briel Dominique , Velay Aurélie , Gregorowicz Guillaume , Martinot Martin
Published: December 2020

The significance of low leukocyte counts in cerebrospinal fluid (CSF) remains unclear. We performed a 2-year retrospective study to examine microbiological outcomes associated with CSF leukocytes at 6–10/mm3. Of the 178 samples examined, we detected positive results for 11 samples, including 5 cases of tick-borne encephalitis virus infection.
Capital Obsolescence and Agricultural Productivity*
Authors: Caunedo Julieta , Keller Elisa
Published: December 2020

This article argues that accounting for capital-embodied technology greatly increases the importance of capital in explaining cross-country differences in agricultural labor productivity. To do so, we draw on a novel data set of agricultural capital prices. We document that new capital is more expensive in richer countries, both in absolute terms and relative to old capital. A model of endogenous adoption of capital of different quality links these price differences to the path of capital-embodied technology. In particular, our model recovers the level of embodied technology from the price of new capital and the growth rate of embodied technology from the price of new capital relative to old capital. We then measure the stocks of quality-adjusted capital in agriculture for a sample of 16 countries at different stages of development. We find that adjusting for differences in quality almost doubles the importance of capital in accounting for cross-country differences in agricultural labor productivity: from 21% to 37%. In addition, improvements in capital quality have been an important source of agricultural labor productivity growth over the past 25 years, accounting for 21% and 35% of the productivity growth in poor and rich countries, respectively.
Characterization of the Class I MHC Peptidome Resulting From DNCB Exposure of HaCaT Cells
Authors: Bailey Alistair , Nicholas Ben , Darley Rachel , Parkinson Erika , Teo Ying , Aleksic Maja , Maxwell Gavin , Elliott Tim , Ardern-Jones Michael , Skipp Paul
Published: December 2020

Skin sensitization following the covalent modification of proteins by low molecular weight chemicals (haptenation) is mediated by cytotoxic T lymphocyte (CTL) recognition of human leukocyte antigen (HLA) molecules presented on the surface of almost all nucleated cells. There exist 3 nonmutually exclusive hypotheses for how haptens mediate CTL recognition: direct stimulation by haptenated peptides, hapten modification of HLA leading to an altered HLA-peptide repertoire, or a hapten altered proteome leading to an altered HLA-peptide repertoire. To shed light on the mechanism underpinning skin sensitization, we set out to utilize proteomic analysis of keratinocyte presented antigens following exposure to 2,4-dinitrochlorobenzene (DNCB). We show that the following DNCB exposure, cultured keratinocytes present cysteine haptenated (dinitrophenylated) peptides in multiple HLA molecules. In addition, we find that one of the DNCB modified peptides derives from the active site of cytosolic glutathione-S transferase-ω. These results support the current view that a key mechanism of skin sensitization is stimulation of CTLs by haptenated peptides. Data are available via ProteomeXchange with identifier PXD021373.
Synonymous mutations and the molecular evolution of SARS-CoV-2 origins
Authors: Wang Hongru , Pipes Lenore , Nielsen Rasmus
Published: December 2020

Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin-isolated strain, GD410721, in the receptor-binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat-derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead, it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of nonsynonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence is 51.71 years (95% CI, 28.11–75.31) and 37.02 years (95% CI, 18.19–55.85), respectively.
Optimal Crash Cart Configuration for a Surgical NICU
Authors: Lefebvre Maria S. , Milloy Shaunna , Joynt Chloe
Published: December 2020

Background:

Neonates admitted to cardiac and surgical neonatal intensive care units (NICUs) are at an increased risk of requiring emergency lifesaving interventions that require the use of both Neonatal Resuscitation Program (NRP) and Pediatric Advanced Life Support (PALS) algorithms. Clinicians working within the surgical NICU must be able to access emergency equipment and medications quickly in order to respond to critical situations. A crash cart that integrates human factors principles and supports both the NRP and PALS algorithms is necessary to promote patient safety for this high-risk population.

Purpose:

A multidisciplinary quality improvement project constructed an optimal crash cart configuration that embedded human factors principles and supported clinical workflow by reflecting both the NRP and the PALS algorithms in an NICU that cares for cardiac and surgical patients.

Methods:

A crash cart working group including frontline NICU staff, simulation experts, and a human factors specialist was formed within a surgical NICU. Human factors principles were utilized to align the organization of the cart with the NRP and PALS algorithms to increase the efficiency and intuitiveness of the cart. The new crash cart configuration was usability tested through simulation, revised on the basis of clinical feedback, and then implemented in a clinical setting. Data were collected following implementation of the new crash cart to validate that the new configuration was viewed as a significant improvement. The Plan-Do-Study-Act cycle was used to make improvements and capture outcome indicators.

Results:

Evaluation data collected both during usability simulation testing and in situ within the NICU clinical environment indicated that the revised crash cart scored higher on Likert scale response questions than the previous crash cart.

Implications for Practice:

Human factors science, in combination with frontline user engagement, should be utilized to create intuitive crash cart configurations, which are then tested in a simulation environment and evaluated in situ in the NICU.

Implications for Research:

Further research around crash cart design within NICUs that use multiple lifesaving algorithms would add to the paucity of research around the impact of human factors theory in the utilization of lifesaving equipment and medications within this specific population.
Exploratory Factor Analysis for a Nursing Workaround Instrument in Korean and Interpretations of Statistical Decision Points
Authors: Lee Seonah
Published: December 2020

The use of workarounds by nurses is prevalent in clinical settings. Understanding how work processes are adjusted as a result of implementing an electronic medical record is important because of its impact on patient care. The purpose of this study was to conduct an exploratory factor analysis of a 20-item nursing workaround instrument translated into Korean. The responses from 104 nurses were analyzed. Examinations of sample size, factorability of a correlation matrix, the Kaiser-Meyer-Olkin value, the P value of Bartlett test of sphericity, anti-image correlation coefficients, and communality were acceptable to proceed with exploratory factor analysis. The original dimensionality of four groups was retained. However, the number of items loaded onto each group was reduced from five to three. These four factors explained 66% of the total variance between the items. Cronbach's α for the internal consistency reliability of the instrument was .70. The 12-item nursing workaround instrument was specific to an electronic medical record, which was the strongest point of the instrument. Further confirmatory factor analysis of this instrument is needed. This translated instrument is expected to contribute to the proliferation of studies examining nurses' workarounds related to the use of electronic medical records in Korean clinical settings, thereby improving clinical information systems for clinical practice.
Abuse-Deterrent Opioid Formulations and the Opioid Crisis: A Pharmacist's Perspective
Authors: Gadd Shannon , Cox Nicholas , Samuelson James , Kenney Amy , Turner Kyle , Cochran Gerald
Published: December 2020

Background:

For over 20 years, the United States has suffered the detrimental effects of an opioid epidemic. Extended-release opioid products are particularly prone to abuse due to the high amount of opioid present. By bypassing the controlled-release mechanisms and nonoral administration, individuals experience intense and dangerous “highs.” Abuse-deterrent opioid formulations have been recommended as a potential solution to the crisis, but widespread utilization has been stunted and their role in therapy remains unclear owing to limited real-world efficacy data and affordability issues. This review discusses abuse-deterrent opioid formulations, the mechanisms and data underlying available products, and a pharmacist's perspective of their role in the opioid crisis.

Methods:

The authors reviewed PubMed, MEDLINE, and Google Scholar electronic databases for premarketing and postmarketing studies on OxyContin, Xtampza ER, and Hysingla ER.

Results:

Studies showed lower rates of abuse (19% reduction), opioid use disorder (27%), overdose (34%), and fatalities (85%) with the reformulated OxyContin when compared with the original product and comparator opioids. However, these studies revealed the potential for bypassing abuse-deterrent mechanisms and diverting abuse to other drugs. Postmarketing studies are unavailable for Xtampza ER or Hysingla ER, although premarketing studies suggested that some controlled-release properties persist when the product is manipulated, indicating that abuse may be more difficult and less rewarding.

Conclusions:

Abuse-deterrent opioid products may lead to reductions in abuse, overdose, and overdose fatalities. However, cost, loopholes in deterrence mechanism, and possible diversion to other substances hinder their role in the opioid crisis. Multiple approaches must be used to improve opioid safety, and further postmarketing and real-world analyses should be performed on available opioid formulations to assess their impact on abuse-related adverse events.
Microsampling Assays for Pharmacokinetic Analysis and Therapeutic Drug Monitoring of Antimicrobial Drugs in Children: A Critical Review
Authors: Moorthy Ganesh S. , Vedar Christina , Downes Kevin J. , Fitzgerald Julie C. , Scheetz Marc H. , Zuppa Athena F.
Published: December 2020

Background:

With the increasing prevalence of multidrug resistant organisms, therapeutic drug monitoring (TDM) has become a common tool for assuring the safety and efficacy of antimicrobial drugs at higher doses. Microsampling techniques, including dried blood spotting (DBS) and volumetric absorptive microsampling (VAMS), are attractive tools for TDM and pediatric clinical research. For microsampling techniques to be a useful tool for TDM, it is necessary to establish the blood–plasma correlation and the therapeutic window of antimicrobial drugs in the blood.

Methods:

DBS involves the collection of small volumes of blood (30–50 µL per spot) on a filter paper, whereas VAMS allows the accurate and precise collection of a fixed volume of blood (10–30 µL) with microsampling devices. One of the major advantages of VAMS is that it reduces or eliminates the volumetric blood hematocrit (HCT) bias associated with DBS. Liquid chromatography with tandem mass spectrometry is a powerful tool for the accurate quantification of antimicrobial drugs from small volumes of blood specimens.

Results:

This review summarizes the recent liquid chromatography with tandem mass spectrometry assays that have used DBS and VAMS approaches for quantifying antimicrobial drugs. Sample collection, extraction, validation outcomes, including the interassay and intra-assay accuracy and precision, recovery, stability, and matrix effect, as well as the clinical application of these assays and their potential as tools of TDM are discussed herein.

Conclusions:

Microsampling techniques, such as VAMS, provide an alternative approach to traditional plasma sample collection for TDM.
Validation of a Capillary Dry Blood Sample MITRA-Based Assay for the Quantitative Determination of Systemic Tacrolimus Concentrations in Transplant Recipients
Authors: Undre Nasrullah , Dawson Ian , Aluvihare Varuna , Kamar Nassim , Saliba Faouzi , Torpey Nicholas , Anaokar Swapneel , Kazeem Gbenga , Hussain Imran
Published: December 2020

Background:

Tacrolimus is a narrow therapeutic index medication, which requires therapeutic drug monitoring to optimize dosing based on systemic exposure. MITRA microsampling offers a convenient, minimally invasive approach for the collection of capillary blood samples from a finger prick versus conventional venous blood sampling for quantitation of tacrolimus blood concentrations. However, the suitability of MITRA microsampling for the determination of tacrolimus concentrations requires assessment in clinical settings.

Methods:

Paired venous (2 mL) and capillary (10 μL) blood samples were collected pre–tacrolimus dose and 1 and 3 hours postdose during routine outpatient visits from stable adult liver or kidney transplant patients receiving prolonged-release tacrolimus. Tacrolimus concentrations were determined by liquid chromatography–tandem mass spectrometry, and the concentrations obtained by the 2 sampling methods were compared by linear regression and Bland–Altman agreement analyses.

Results:

Samples were available for 82 transplant recipients (kidney, n = 41; liver, n = 41). A high correlation was observed between tacrolimus concentrations in capillary and venous blood samples (Pearson correlation coefficient, 0.97; Lin concordance coefficient, 0.87; slope of the fitted line, >1.0). Tacrolimus concentrations in capillary samples were 22.5% higher on average than in the corresponding venous blood samples (95% limits of agreement, 0.5%–44.6%). Similar results were observed in both transplant subgroups.

Conclusions:

MITRA finger prick sampling provides a convenient alternative to venipuncture for therapeutic drug monitoring in transplant recipients maintained on prolonged-release tacrolimus. When using the finger prick MITRA method, the positive bias in tacrolimus concentrations observed with this technique, when compared with venipuncture, needs to be taken into consideration.
A Patient With AIRE Mutation Who Presented With Severe Diarrhea and Lung Abscess
Authors: Soyak Aytekin Elif , Serin Oguzhan , Cagdas Deniz , Tan Cagman , Aksu Tekin , Unsal Yagmur , Yeni Selma , Orhan Diclehan , Ozon Zeynep Alev , Tezcan Ilhan
Published: December 2020

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) (polyglandular endocrinopathy type 1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). The major clinical features of APECED are hypoparathyroidism, adrenal insufficiency (Addison disease), and chronic mucocutaneous candidiasis. This disease is also associated with multiple other and uncommon autoimmune (autoimmune hepatitis, autoimmune enteropathy, atrophic gastritis with or without pernicious anemia, gonadal failure, diabetes mellitus, hypothyroidism, functional hyposplenism), ectodermal (alopecia and vitiligo), and inflammatory (intestinal lung disease, nephritis) features. Here, we report a case of a 13-year-old Turkish boy who presented wih enteropathy and lung abscess. Molecular genetic analysis demonstrated a homozygous frameshift mutation (p.Asp70fs, c.208_209insCAGG) in exon 2, in AIRE gene. APECED may present with severe, life-threatening infections due to functional hyposplenism. Multidisciplinary approach, careful follow-up, and molecular genetic studies are needed.
Late-onset Hearing Loss From Congenital Cytomegalovirus Infection After Newborn Period in a Highly Immune Population in China
Authors: Wang Chengbin , Liu Xiaolin , Wang Shiwen , Zhang Wenqiang , Wang Haiyan , Ma Wei , Meng Xiangxin , Xu Xingqu , Li Zhan , Pan Qiang , Zhang Shuxia , Wang Ping , Lin Qian , Wang Xiaofang , Amin Minal , Dollard Sheila , Xu Aiqiang , Chung Winnie
Published: December 2020

After following 141 children with likely asymptomatic congenital cytomegalovirus infection in a highly immune population in China, four children (2.8%) were found to have late-onset hearing loss. No maternal or childhood factors, except higher saliva cytomegalovirus viral load at birth (P = 0.03), were associated with increased risk of developing a hearing loss.
Accuracy of new-generation intraocular lens calculation formulas in eyes undergoing combined silicone oil removal and cataract surgery
Authors: Zhang Jiaqing , Wang Wei , Liu Zhenzhen , Yang Guangyao , Qiu Xiaozhang , Xu Jingmin , Jin Guangming , Li Yonghao , Zhang Shaochong , Tan Xuhua , Luo Lixia , Liu Yizhi
Published: December 2020

Purpose:

To compare the performance of new-generation and traditional intraocular lens (IOL) calculation formulas in eyes undergoing combined silicone oil (SO) removal and cataract surgery and to evaluate the prediction accuracy of Wang-Koch (WK) adjustment in SO-filled long eyes.

Setting:

Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Design:

Retrospective consecutive case-series study.

Methods:

New-generation formulas (Barrett Universal II, Emmetropia Verifying Optical, Kane, and Ladas Super formulas) and traditional formulas (Haigis, Hoffer Q, Holladay 1, and SRK/T formulas) were compared. The performance of WK adjustment was assessed in eyes with axial length more than 26 mm. The median absolute error (MedAE) was the main parameter to evaluate the accuracy of formulas.

Results:

A total of 211 participants (211 eyes) who underwent combined SO removal and phacoemulsification with IOL implantation were included. Four new-generation formulas displayed statistically significant lower MedAE (0.32 to 0.35 diopter [D]) and higher percentage of eyes within ±1.00 D of prediction error (85.31% to 87.20%) compared with those of the traditional formulas (MedAE: 0.39 to 0.50 D; ±1.00 D: 81.04% to 81.99%, P < .05). For SO-filled long eyes, all traditional formulas showed hyperopic bias (0.36 to 0.65 D, P < .05), except for Haigis formula (0.28 D, P = .083), and this bias could be corrected by WK adjustment (P > .05). EVO formula displayed the lowest MedAE both in total (0.32 D) and in long eyes (0.33 D).

Conclusions:

New-generation formulas and traditional formulas with WK adjustment showed satisfactory prediction accuracy in eyes undergoing combined SO removal and cataract surgery. EVO formula displayed the highest accuracy.
Surgically induced astigmatism made easy: calculating the surgically induced change in sphere and cylinder for corneal incisional, corneal laser, and intraocular lens–based surgery
Authors: Næser Kristian
Published: December 2020

Net cylinder and spherocylinder formats characterize individual keratometries and prescriptions but must be converted to dioptric vectors to allow for calculations and statistical analyses. Næser's polar value system was specifically developed for the analysis of the surgically induced refractive change along the surgical meridian. This study provides a short description together with a practical manual and a computer program for the use of this dioptric vector method. Measurement techniques, vector equations, statistical methods, and terminology are reviewed. The analysis is identical for corneal and refractive measurements and for corneal incisional, corneal laser, and intraocular lens–based surgery. The choice of appropriate surgical reference meridians for standard surgical procedures is demonstrated. The Excel file may be used by the reader for future studies.
Clinical evaluation of the effectiveness of asymmetric intracorneal ring with variable thickness and width for the management of keratoconus
Authors: Cuiña Sardiña Ricardo , Arango Alexandra , Alfonso Jose F. , Álvarez de Toledo Juan , Piñero David P.
Published: December 2020

Purpose:

To evaluate the short-term clinical outcomes obtained with a new model of asymmetric intracorneal ring segments (ICRS) with variable thickness and base width in keratoconus.

Setting:

Four ophthalmologic centers in Spain.

Design:

Prospective multicenter longitudinal noncomparative clinical trial.

Methods:

Thirty-one keratoconus eyes of 25 patients (aged 15 to 50 years) that underwent implantation of ICRS of variable thickness and base (AJL-pro+) in 4 Spanish centers were enrolled. Visual, refractive, topographic, aberrometric, and pachymetric changes were evaluated during a 3-month follow-up. Complications were also recorded.

Results:

Statistically significant changes after surgery were observed in uncorrected distance visual acuity (P = .002) and corrected distance visual acuity (CDVA) (P = .005), as well as in spherical equivalent (P = .006). At 3 months postoperatively, no loss of 2 or more lines of CDVA was observed, whereas 48.4% (15) of eyes gained ≥1 line. Statistically significant changes were observed in the steepest and mean keratometric values (P ≤ .047) and in the magnitude of astigmatism (P < .001) of both anterior and posterior corneal surfaces. Likewise, a change to a less prolate shape of the anterior surface was found (P = .011). Primary coma was also reduced significantly at 1 month postoperatively (P = .001, mean reduction 40.1%). No serious implant-related complications occurred during the follow-up.

Conclusions:

The implantation of intrastromal asymmetric ring segments of variable thickness and base width in keratoconus corneas induces a significant anterior corneal flattening, leading to refractive changes, a significant reduction of its prolate shape and irregularity, and improvement in patient CDVA.
Intraocular lens implantation in the absence of capsular support: scleral-fixated vs retropupillary iris-claw intraocular lenses
Authors: Forlini Matteo , Bedi Raman
Published: December 2020

Cataract surgery via phacoemulsification with intraocular lens (IOL) placement in the capsular bag is the gold standard in the presence of adequate capsular support. However, when capsule and/or zonular fibers are weak or absent, alternate fixation strategies are required. Common alternative options include retropupillary iris-claw IOLs (RP-IC IOLs) and scleral-fixated IOLs (SF IOLs). In the present review of 87 articles with 2174 eyes implanted with RP-IC IOLs and 2980 eyes with SF IOLs, we discuss the published literature with respect to safety and efficacy. Although the studies reporting outcomes of these IOLs have been performed in patients with different concomitant conditions, visual and refractive outcomes were found to be comparable between RP-IC IOLs and SF IOLs. RP-IC IOL implantation seemed to provide equivalent or a potentially lower rate of complications than SF IOL implantation. Data from the literature also suggest that the surgical technique of RP-IC IOL implantation is relatively simpler with correspondingly shorter surgical times.
Quantifying the Degree of Bruise Visibility Observed Under White Light and an Alternate Light Source
Authors: Scafide Katherine N. , Downing Nancy R. , Kutahyalioglu Nesibe S. , Sebeh Yesser , Sheridan Daniel J. , Hayat Matthew J.
Published: December 2020

Background

Documentation of injuries associated with abuse and assault has pivotal impacts on clinical and legal outcomes. Before this study, no reliable and valid tools to consistently document the clinical visibility of bruises existed. The purpose of this study was to systematically evaluate reliability and validity of the Bruise Visibility Scale for documenting bruises visualized in normal (white) light and the Absorption Visibility Scale for documenting bruises visualized using an alternate light source (ALS).

Methods

Bruises were induced using a paintball on the upper arms of 157 participants stratified into six skin color categories. Bruises were visualized 21 times over 4 weeks under white light and 10 ALS wavelength/goggle color combinations. Bruise size was measured using a metric ruler; bruise color was measured using a spectrophotometer. Interrater reliability was calculated using kappa and intraclass correlations coefficients. Construct validity was evaluated using generalized linear mixed modeling of associations between bruise size and color with both visibility scales.

Results

Interrater agreement for bruise detection was over 90% for all but two ALS wavelength/goggle combinations. Kappa values indicated adequate interrater agreement under white light (κ = 0.76) and ALS (κ = 0.78). The visibility scale intraclass correlation coefficients were .91 for normal light and .93 for ALS. Statistical modeling showed greater bruise size was associated with higher visibility using either scale, and greater contrast in color or lightness was associated with higher Bruise Visibility Scale values.

Implications for Practice

Both visibility scales showed satisfactory reliability and validity. Forensic nurses can use the scales to consistently document bruises.
Adrenal insufficiency updates in children
Authors: Ramirez Alcantara Jonanlis , Halper Alyssa
Published: December 2020

Purpose of review

The current article will review the newest diagnostic tools, genetic causes, and treatment of adrenal insufficiency in children.

Recent findings

It is common practice to perform an adrenocorticotropin hormone (ACTH) stimulation test when adrenal insufficiency is suspected. The indications for use of a high-dose or low-dose of synthetic ACTH in children have been refined. In addition, newer studies propose adding 15 and 30-min serum or salivary cortisol levels to the low-dose ACTH stimulation test to correctly identify adrenal insufficiency. Recent identification of genetic mutations in children with non-classic steroidogenic acute regulatory protein and other mutations associated with primary and secondary adrenal insufficiency have expanded the cause and pathophysiology of monogenic adrenal insufficiency. In addition, newer hydrocortisone formulations and delivery methods and medications to use in combination with hydrocortisone are being explored to improve treatment for children with adrenal insufficiency.

Improved diagnostic aids, detection of newer genetic mutations, and better treatment options and delivery systems will help correctly identify and manage children with adrenal insufficiency to improve health outcomes and quality of life.

Video abstract

http://links.lww.com/COE/A21
The role of endoscopic medial maxillectomy in sinus disease
Authors: Govindaraju Revadi , Prepageran Narayanan
Published: December 2020

Purpose of review

The endoscopic medial maxillectomy (EMM) has remained a relevant procedure for certain sinus diseases and at the same time reemerged as a salvage technique or even as a primary procedure for other diseases. Several mucosal-sparing techniques have also been described and the outcome of the surgeries is available for review.

Recent findings

Modifications of the EMM technique in the last two decades, aimed at mucosal preservation of the inferior turbinate, nasolacrimal duct, and medial maxillary wall have been successful in addressing a multitude of diseases. There are also evidences to support adjunct procedures/methods to improve access, healing, and to address associated dysfunction such as impaired mucociliary clearance. Tailored approaches have shown favourable outcomes with a low rate of adverse effects.

The EMM is appropriate for selected indications, in particular lesions causing medial wall destruction or extensive tumour involving the anterior wall or the prelacrimal recess. As for other maxillary sinus diseases including those identified to a limited site, a modified EMM is a reasonable consideration. The choice is appropriate provided instrument access, visualization, the ability for complete resection, postoperative care, and the requirement for surveillance is not compromised. A tailored approach with or without adjunct procedures is recommended.
Treatment of persistent/recurrent nodal disease in nasopharyngeal cancer
Authors: Tsang Raymond K. , Ng Wai-Tong
Published: December 2020

Purpose of review

Persistent or recurrent disease in the neck lymphatics is an unusual pattern of failure in nasopharyngeal carcinoma (NPC) after definitive radiotherapy or chemoradiotherapy. The purpose of this review is to critically synthesize the current knowledge regarding salvage treatment of this unique form of failure in NPC.

Recent findings

Surgery in the form of radical neck dissection has been established as the standard salvage treatment with 5-year regional control of 60--86%. Recent shift in paradigm has resulted in the use of modified or selective neck dissection as salvage surgery in some centers. Risk factors for poor survival outcome include recurrent nodal disease, number of involved lymph nodes, extracapsular extension, high lymph node ratio, and positive resection margin. There are no well controlled studies on the role of additional radiotherapy or chemotherapy to improve local control or survival after salvage neck dissection in this group of patients with regional failure.

There is limited literature regarding the extent of surgical dissection in treating nodal persistent or recurrent disease. Prospective studies are also needed to determine whether adjuvant therapy improves treatment outcomes.
Diagnostic testing for SARS-CoV-2/COVID19
Authors: Spearman Paul
Published: December 2020

Purpose of review

SARS-CoV-2 is the novel human coronavirus responsible for the COVID19 pandemic. Accurate detection of infection with SARS-CoV-2 is an essential component of efforts to treat individual patients and to contain spread of the virus in the community. The purpose of this review is to describe current diagnostic modalities for SARS-CoV-2 and outline their use. Special considerations for pediatric age groups are included.

Recent findings

RNA PCR from the upper respiratory tract remains the gold standard for detection of infection with SARS-CoV-2. Antigen testing is being widely deployed as a faster and more convenient alternative to PCR, but is less sensitive and should only be used for diagnosis early after symptom onset. Serologic assays can document prior infection and are helpful in diagnosing multisystem inflammatory syndrome in children. Serologic testing should not be used to diagnose acute or active infection. Immune assays are likely to provide a useful measure of protection against COVID19 in the future as knowledge of protective responses improves.

A variety of SARS-CoV-2 diagnostics have recently been developed and deployed. Clinicians should understand the appropriate use and interpretation of RNA PCR, antigen testing and immune assays for SARS-CoV-2 in order to diagnose and treat patients in this evolving pandemic.
Advances in the classification and treatment of pediatric brain tumors
Authors: Fangusaro Jason , Bandopadhayay Pratiti
Published: December 2020

Purpose of review

Recent genetic and molecular findings have impacted the diagnosis, prognosis, and in some instances, treatment strategies for children with pediatric central nervous system tumors. Herein, we review the most up-to-date molecular findings and how they have impacted tumor classification and clinical care.

Recent findings

It is now recognized that aberrations of the mitogen-activated protein kinase pathway are present in the majority of pediatric low-grade glioma. Also, there has been the identification of recurrent histone H3 K27M mutations in diffuse intrinsic pontine and other midline gliomas. Medulloblastoma is now divided into four molecular subgroups with distinct characteristics and prognoses. The classification of other unique embryonal tumors is also highlighted. Finally, we present the newest classification of ependymoma; supratentorial ependymomas comprise two subtypes based on expression of the chromosome 11 Open Reading Frame 95–reticuloendotheliosis Viral Oncogene Homolog A or yes-associated protein 1 fusion, whereas posterior fossa ependymomas are divided into two distinct molecular subgroups, posterior fossa-A and posterior fossa-B.

These advances in the molecular classification of pediatric central nervous system tumors have not only assisted in diagnoses, but they have led to a new era of tumor classification and prognostication. They also have served as drivers for the evaluation of new targeted therapies based upon molecular aberrations with the hope for improved survival outcomes for our patients.
COVID-19 vaccine development: a pediatric perspective
Authors: Kamidani Satoshi , Rostad Christina A. , Anderson Evan J.
Published: December 2020

Purpose of review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes coronavirus disease 2019 (COVID-19), has caused substantial morbidity and mortality. Operation Warp Speed aims to accelerate the development of a safe and effective vaccine by early 2021. Multiple vaccine candidates with reassuring safety and efficacy profiles have advanced to phase 3 clinical trials in adults. The purpose of this review is to describe the burden of COVID-19 in children, to update pediatricians about adult COVID-19 vaccine clinical trials, to discuss the importance of COVID-19 vaccine trials in children and to instill confidence in the established vaccine development and licensure processes.

Recent findings

Children of all ages are at risk for SARS-CoV-2 infection and severe disease manifestations. Children are also susceptible to downstream effects of COVID-19, including social isolation and interruption in education. Developing a pediatric COVID-19 vaccine could prevent disease, mitigate downstream effects and enable children to re-engage in their world.

Children could benefit both directly and indirectly from vaccination. In light of the safety and immunogenicity results from recent adult COVID-19 vaccine clinical trials, children should have the opportunity to be included in clinical trials in parallel to ongoing adult phase 3 clinical trials in a manner that is careful, methodical and transparent.
Profiling the liver graft
Authors: Celaj Stela , Levitsky Josh
Published: December 2020

Purpose of review

Achieving operational tolerance remains a priority in liver transplantation. Although several biomarkers of tolerance and rejection have been identified, few have been reproducible and validated across centers, and therefore have yet to reach clinical practice. Here we summarize findings from prior seminal studies and review current developments in profiling the liver allograft.

Recent findings

Substantial efforts and progress have been made in the recent years towards the discovery of reliable biomarkers that can predict and guide successful immunosuppression withdrawal. Recent studies have also investigated the transcriptomic signatures underlying not only acute rejection but also subclinical inflammation and chronic allograft injury.

As new genomic and sequencing technologies continue to develop, clinical trials are underway to validate biomarkers of tolerance, as well as better understand the mechanisms of both acute and subclinical rejection, with the goal of maximizing allograft survival. Altogether, this will hopefully enable the implementation of immunosuppression withdrawal protocols into clinical practice and make operational tolerance reliably attainable in the near future.
Prostate cancer and human papillomavirus infection: a recent literature review
Authors: Mahmoudi Samira , Jafari-Sales Abolfazl , Nasiri Rozita , Baghi Hossein Bannazadeh
Published: December 2020

Aim:

Prostate cancer is one of the most frequent cancers in men and it is reported that about one in nine men experience the disease in their lifetime. It has been found that in some cases, HPV can be a culprit for prostate cancer. The present meta-analysis study aims to examine whether human papillomavirus (HPV) serves as a foundation of human prostate cancer.

Methods:

Related studies to HPV and prostate cancer from 1990 to 2020 were sought in PubMed and Google Scholar. Earlier published expert reviews and systematic meta-analysis were utilized as a supplementary source to recognize appropriate articles. Finally, data from 54 articles, with 7072 prostate cancer cases, were pooled and analyzed.

Results:

The pooled rating for the odds ratio was 17.42%. Stratified pooled analyses were subsequently performed according to the HPV detection of geographical regions, publication years, the number of prostate cases, and HPV-positive cases.

Conclusion:

The meta-analysis confirmed the variant frequencies of HPV positivity in prostate cancer of different geographic zones. It has been found that there can be a potential link between HPV and prostate cancer. Yet, further investigations of this cancer relating to HPV may be necessary.
Integrating Education and Competency for Safe Patient Care
Authors: Coughlin Vincenza , Easter Tara , Geraghty Gail
Published: December 2020

In an effort to streamline educational initiatives at our institution, we developed the Nursing Education and Competency Algorithm and the Nursing Education and Competency Advisory Panel. The Nursing Education and Competency Algorithm serves as a framework in differentiating education and competency through standardization of practice. Utilizing the algorithm assists in distinguishing initiatives as one time, on-going, or if they are specific to a specialty. The Nursing Education and Competency Advisory Panel serves as a vetting structure to improve collaboration through decision-making and shared governance.
Physical Medicine and Rehabilitation Milestone Evaluation Project
Authors: Kohar Audrey , Tran Duc , Perret Danielle , Chi Bradley , Kim Mary , Bagay Leslie , Hata Justin , Cuccurullo Sara J.
Published: December 2020

This tri-institutional study describes the outcomes of utilization of newly developed, standardized, rotation-specific evaluations for faculty assessment of resident achievement of the physical medicine and rehabilitation milestones. Thirty-six physical medicine and rehabilitation faculty, representing three distinct academic institutions, completed a prestudy survey on the adequacy of the rotation-generic resident evaluation tools historically in use at each institution. During the 2016–2017 academic year, faculty in all three institutions consistently used a new set of rotation-specific milestone-incorporated evaluation tools. The same faculty completed surveys assessing the new evaluation tools 6 and 12 months later. Ordinal logistic regression was used to compare survey results before and after implementation of the rotation-specific milestone-incorporated evaluation tools. Results demonstrate high tool satisfaction scores, and a statistically significant improvement in the adequacy and specificity of the new evaluation tools compared with the old ones. There was also a statistically significant improvement in both faculty understanding of the milestones and faculty ability to assess the milestones with use of the new tools compared with the old ones. The implementation of standardized physical medicine and rehabilitation rotation-specific milestone-incorporated faculty-of-resident evaluation tools across three institutions improves faculty ability to assess resident overall performance specifically related to resident achievement of the milestones in each rotation.
Risks of metabolic syndrome and diabetes with integrase inhibitor-based therapy
Authors: Shah Shahini , Hill Andrew
Published: December 2020

Purpose of review

A growing body of evidence suggests that integrase inhibitors (INSTIs) are significantly associated with weight gain and obesity. Obesity is a significant risk factor for metabolic syndrome and diabetes. This article comprehensively reviews recent available evidence weight gain and the risks of metabolic syndrome and diabetes associated with INSTIs.

Recent findings

Recent evidence continues to contribute to the evidence for weight gain associated with INSTIs, especially when used with newer nucleoside reverse transcriptase inhibitor, tenofovir alafenamide (TAF). Although the literature suggests a neutral effect on lipids, there is evidence that INSTIs are associated with metabolic syndrome due to treatment-emergent obesity. The literature for short-term treatment-emergent diabetes and insulin resistance remains inconsistent, but there is some evidence that weight gain could lead to an increased risk of developing diabetes in the future.

Longer term studies are required to understand the metabolic impact of INSTIs, secondary to weight gain. Evidence suggests that INSTIs, when used with TAF, contribute to metabolic syndrome and may have long-term risks of diabetes. INSTIs, when used with tenofovir disoproxil fumarate, have fewer metabolic implications. Clinicians must monitor for weight gain and metabolic effects, especially in those with underlying risk factors.
Morphological Basis for Airway Surgical Intervention in Apert Syndrome
Authors: Lu Xiaona , Forte Antonio Jorge , Park Kitae Eric , Allam Omar , Alperovich Michael , Steinbacher Derek M. , Tonello Cristiano , Alonso Nivaldo , Persing John A.
Published: December 2020

Objective

Previous studies have explored the restricted nasopharyngeal airway in Apert syndrome patients. This study aims to investigate the segmented airway volume changes with age and directly analyze their correlations with subcranial dimensions and angulations.

Methods

Ninety-seven preoperative computed tomography scans (Apert, n = 44; control, n = 53) were included in this study, and divided into 5 age-related subgroups. Computed tomography scans were measured using Mimics and 3-matics software.

Results

Before 6 months of age, the nasal cavity in Apert syndrome is reduced by 47% (P= 0.002), which gradually approximates normal thereafter; however, there remained a 30% reduction, compared with controls. It is highly correlated with the anteroposterior length of subcranial space, and the position of maxilla and palate. The pharyngeal airway volume in Apert syndrome patients, younger than 6 months, was larger than normal by 129% (P= 0.013). However, between 2 and 6 years of age, the pharyngeal airway becomes smaller than normal, with a 57% (P= 0.010) reduction in childhood and 52% (P= 0.005) in adolescence. It is closely correlated with the intercondylar and intergonial widths.

Conclusions

Airway compromise in Apert syndrome patients is attributable more to the nasal cavity in infants, but in the older child, it is the pharyngeal region. The restricted nasal airway in Apert syndrome is correlated with the subcranial space length and width, but independent of cranial base flexion. The pharyngeal airway volume in Apert syndrome is not as highly correlated with craniofacial morphology. Rather, it is impacted by the growth of mandible, which often requires surgical intervention later in childhood.
Dyslexia in the 21st century
Authors: Shaywitz Sally E. , Shaywitz Jonathan E. , Shaywitz Bennett A.
Published: December 2020

Purpose of review

Within the past decade tremendous advances have occurred in our understanding of dyslexia.

Recent findings

Reliable data now validate the definition of dyslexia as an unexpected difficulty in reading in an individual who has the ability to be a much better reader. That dyslexia is unexpected is now codified in US federal law (PL 115–391). Replicated studies using functional brain imaging have documented a neural signature for dyslexia. Epidemiologic, longitudinal data now demonstrate that dyslexia is highly prevalent, affecting 20% of the population, affecting boys and girls equally. These data further demonstrate that the achievement gap between dyslexic and typical readers is now evident as early as first grade and persists. Evidence-based, efficient, inexpensive screening tools now offer the possibility of universal screening to identify children at risk for dyslexia as early as first grade. Specialized schools which focus on dyslexic students provide welcoming communities, ensuring that dyslexic children will not only survive but thrive.

Taken together, these findings indicate that we must act and act now to ensure that this 21st century knowledge of dyslexia is disseminated to educators, policy makers, and most of all to parents of dyslexic children.
Systematic review of the association between rotavirus infection, or rotavirus vaccination and coeliac disease
Authors: Inns Thomas , Fleming Kate M , Iturriza-Gomara Miren , Hungerford Daniel
Published: December 2020

Background

There is some evidence that rotavirus infection leads to an increased risk of coeliac disease (CD), and some immunological and biological plausibility for the human immune system recognising rotavirus particles and gluten proteins in a similar way. It is therefore plausible that rotavirus vaccine could have a role in preventing CD. However, such evidence has not previously been summarised in a systematic way to present a coherent picture. We conducted this systematic literature review to address this gap in the evidence. The aim of this research was to determine the nature of any association between rotavirus infection, or rotavirus vaccination, and risk of CD.

Methods

We searched Scopus, MEDLINE, Europe PMC and medRxiv for studies published between 01 January 1980 and 31 July 2020, using terms related to CD and rotavirus. Publications were screened independently by two reviewers using exclusion criteria. We extracted data from included papers using a standardized data extraction form and assessed risk of bias using the Newcastle-Ottawa Scale. Outcomes were descriptions of the settings and methods reported in included papers, and any estimates of effect.

Results

After exclusions, we reviewed five papers of which two used the exposure of rotavirus infection and three used the exposure of rotavirus vaccination. One paper found that rotavirus infection increased the risk of CD and that this was statistically significant. None of the three publications studying the association between rotavirus vaccination and CD were graded as high quality. All found a protective effect of RotaTeq® rotavirus vaccination, but this was only statistically significant in two studies.

Conclusions

Few studies have been published on this research question. Those that have been published are not of sufficient quality and did not use comparable methods. Due to differences in study results there remains uncertainty regarding the relationship between rotavirus infection, vaccination and CD.