bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral white matter vasculature: still uncharted?
Authors: Smirnov Mykyta , Destrieux Christophe , Maldonado Igor Lima
Published: July 2021

White matter vasculature plays a major role in the pathophysiology of permanent neurological deficits following a stroke or progressive cognitive alteration related to small vessel disease. Thus, knowledge of the complex vascularization and functional aspects of the deep white matter territories is paramount to comprehend clinical manifestations of brain ischaemia.

This review provides a structured presentation of the existing knowledge of the vascularization of the human cerebral white matter from seminal historical studies to the current literature. First, we revisit the highlights of prenatal development of the endoparenchymal telencephalic vascular system that are crucial for the understanding of vessel organization in the adult. Second, we reveal the tangled history of debates on the existence, clinical significance and physiological role of leptomeningeal anastomoses. Then, we present how conceptions on white matter vascularization transitioned from the mixed ventriculopetal/ventriculofugal theory, in which a low-flow area was interposed in between concurrent arterial flows, to the purely ventriculopetal theory. The latter model explains variable white matter sensitivity to ischaemia by various organizations of ventriculopetal vessel terminals having different origin/length properties and interconnection patterns. Next, arteries supplying primarily the white matter are described according to their length and overall structure. Furthermore, the known distribution territories, to date, are studied in relation to primary anatomical structures of the human cerebral white matter, emphasizing the sparsity of the ‘ground truth’ data available in the literature. Finally, the implications for both large vessel occlusion and chronic small vessel disease are discussed, as well as the insights from neuroimaging.

All things considered, we identify the need for further research on deep white matter vascularization, especially regarding the arterial supply of white matter fibre tracts.
Digital Reconstruction of the Neuro-Glia-Vascular Architecture
Authors: Zisis Eleftherios , Keller Daniel , Kanari Lida , Arnaudon Alexis , Gevaert Michael , Delemontex Thomas , Coste Benoît , Foni Alessandro , Abdellah Marwan , Calì Corrado , Hess Kathryn , Magistretti Pierre Julius , Schürmann Felix , Markram Henry
Published: July 2021

Astrocytes connect the vasculature to neurons mediating the supply of nutrients and biochemicals. They are involved in a growing number of physiological and pathophysiological processes that result from biophysical, physiological, and molecular interactions in this neuro-glia-vascular ensemble (NGV). The lack of a detailed cytoarchitecture severely restricts the understanding of how they support brain function. To address this problem, we used data from multiple sources to create a data-driven digital reconstruction of the NGV at micrometer anatomical resolution. We reconstructed 0.2 mm3 of the rat somatosensory cortex with 16 000 morphologically detailed neurons, 2500 protoplasmic astrocytes, and its microvasculature. The consistency of the reconstruction with a wide array of experimental measurements allows novel predictions of the NGV organization, allowing the anatomical reconstruction of overlapping astrocytic microdomains and the quantification of endfeet connecting each astrocyte to the vasculature, as well as the extent to which they cover the latter. Structural analysis showed that astrocytes optimize their positions to provide uniform vascular coverage for trophic support and signaling. However, this optimal organization rapidly declines as their density increases. The NGV digital reconstruction is a resource that will enable a better understanding of the anatomical principles and geometric constraints, which govern how astrocytes support brain function.
Modulation of Theta Phase Synchrony during Syllable Processing as a Function of Interactive Acoustic Experience in Infancy
Authors: Ortiz-Mantilla Silvia , Roesler Cynthia P , Realpe-Bonilla Teresa , Benasich April A
Published: July 2021

Plasticity, a prominent characteristic of the infant brain, supports formation of cortical representations as infants begin to interact with and adapt to environmental sensory events. Enhanced acoustic processing efficiency along with improved allocation of attentional resources at 7 months and establishment of well-defined phonemic maps at 9 months have been shown to be facilitated by early interactive acoustic experience (IAE). In this study, using an oddball paradigm and measures of theta phase synchrony at source level, we examined short- and long-term effects of nonspeech IAE on syllable processing. Results demonstrated that beyond maturation alone, IAE increased the efficiency of syllabic representation and discrimination, an effect that endured well beyond the immediate training period. As compared with naive controls, the IAE-trained group at 7, 9, and 18 months showed less theta phase synchrony for the standard syllable and at 7 and 18 months for the deviant syllable. The decreased theta phase synchrony exhibited by the trained group suggests more mature, efficient, acoustic processing, and thus, better cortical representation and discrimination of syllabic content. Further, the IAE modulatory effect observed on theta phase synchrony in left auditory cortex at 7 and 9 months was differentially associated with receptive and expressive language scores at 12 and 18 months of age.
Short physical performance battery vs. 6-minute walking test in hospitalized elderly patients with heart failure
Authors: Kitai Takeshi , Shimogai Takayuki , Tang W H Wilson , Iwata Kentaro , Xanthopoulos Andrew , Otsuka Shuto , Nakada Fumika , Yokoyama Rina , Kamiya Kentaro , Saito Hiroshi , Saito Kazuya , Maekawa Emi , Konishi Masaaki , Ogasahara Yuki , Jujo Kentaro , Wada Hiroshi , Kasai Takatoshi , Momomura Shinichi , Krittanawong Chayakrit , Skoularigis John , Triposkiadis Filippos , Kagiyama Nobuyuki , Furukawa Yutaka , Matsue Yuya
Published: July 2021

Aims

Functional decline due to skeletal muscle abnormalities leads to poor outcomes in patients with acute heart failure (AHF). The 6-minute walking test (6MWT) reliably evaluates functional capacity, but its technical difficulty for the elderly often limits its benefits. Although the Short Physical Performance Battery (SPPB) is a comprehensive measure of physical performance, its role in AHF remains unclear. This study aimed to examine the prognostic significance of SPPB compared to the 6MWT in elderly patients hospitalized for AHF.

Methods and results

We retrospectively analysed 1192 elderly patients with AHF whose SPPB and 6MWT were measured during the hospitalization. The primary outcome measure was defined as a composite of all-cause death and heart failure readmission until 1 year after discharge. Patients with lower SPPB scores (0–6, n = 373) had significantly poorer outcomes than those with higher SPPB scores (7–12, n = 819) even after multivariable adjustment [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01–1.61; P = 0.049], similar to those with shorter 6MWT (<median) than those with longer 6MWT (adjusted HR 1.61, 95% CI 1.27–2.04; P < 0.001). Although both SPPB and 6MWT [net reclassification index (NRI) 0.139, P = 0.036 and NRI 0.350, P < 0.001, respectively] exhibited incremental prognostic value over conventional risk factors of HF, the additive prognostic effect of 6MWT was superior to that of SPPB (NRI 0.300, P < 0.001).

Conclusions

Reduced functional capacity assessed by either the SPPB or 6MWT was associated with worse outcomes in hospitalized elderly patients with AHF. The incremental prognostic value over the conventional risk factors was higher in 6MWT than in SPPB.

Trial Registration

UMIN000023929
Intentional mentoring: maximizing the impact of underrepresented future scientists in the 21st century
Authors: Shuler Haysetta , Cazares Victor , Marshall Andrea , Garza-Lopez Edgar , Hultman Rainbo , Francis Tam'ra-Kay , Rolle Tiffany , Byndloss Mariana X , Starbird Chrystal A , Hicsasmaz Innes , AshShareef Salma , Neikirk Kit , Johnson Pamela E C , Vue Zer , Beasley Heather K , Williams Aislinn , Hinton Antentor
Published: July 2021

Mentoring is a developmental experience intended to increase the willingness to learn and establish credibility while building positive relationships through networking. In this commentary, we focus on intentional mentoring for underrepresented mentees, including individuals that belong to minority racial, ethnic and gender identity groups in Science, Technology, Engineering, Mathematics and Medicine (STEMM) fields. Intentional mentoring is the superpower action necessary for developing harmony and comprehending the purpose and value of the mentor/mentee relationship. Regardless of a mentor's career stage, we believe the strategies discussed may be used to create a supportive and constructive mentorship environment; thereby improving the retention rates of underrepresented mentees within the scientific community.
Testing gene–environment interactions in the presence of confounders and mismeasured environmental exposures
Authors: Cheng Chao , Spiegelman Donna , Wang Zuoheng , Wang Molin
Published: July 2021

Interest in investigating gene–environment (GxE) interactions has rapidly increased over the last decade. Although GxE interactions have been extremely investigated in large studies, few such effects have been identified and replicated, highlighting the need to develop statistical GxE tests with greater statistical power. The reverse test has been proposed for testing the interaction effect between continuous exposure and genetic variants in relation to a binary disease outcome, which leverages the idea of linear discriminant analysis, significantly increasing statistical power comparing to the standard logistic regression approach. However, this reverse approach did not take into consideration adjustment for confounders. Since GxE interaction studies are inherently nonexperimental, adjusting for potential confounding effects is critical for valid evaluation of GxE interactions. In this study, we extend the reverse test to allow for confounders. The proposed reverse test also allows for exposure measurement errors as typically occurs. Extensive simulation experiments demonstrated that the proposed method not only provides greater statistical power under most simulation scenarios but also provides substantive computational efficiency, which achieves a computation time that is more than sevenfold less than that of the standard logistic regression test. In an illustrative example, we applied the proposed approach to the Veterans Aging Cohort Study (VACS) to search for genetic susceptibility loci modifying the smoking-HIV status association.
Monotonicity Formula and Classification of Stable Solutions to Polyharmonic Lane–Emden Equations
Authors: Luo Senping , Wei Juncheng , Zou Wenming
Published: July 2021

In this paper, we consider polyharmonic Lane–Emden equations $$ \begin{equation*} (-\Delta )^m u=|u|^{p-1}u, \ \ \ \mbox{in} \ \ \ {\mathbb R}^n, \end{equation*}$$where $m\geq 3$. We classify the stable or stable outside a compact set solutions when $m=3$ or $4$ for any dimensions and when $m\geq 5$ for large dimensions. In the process, we exhibit the general Joseph–Lundgren exponent (including both local and nonlocal cases) in a concise form and prove related properties. The key ingredient of the proof of the classification is a monotonicity formula for general polyharmonic equations, which may have application in regularity theory for higher-order elliptic equations.
Emergence of resistantCandida glabratain Germany
Authors: Aldejohann Alexander Maximilian , Herz Michaela , Martin Ronny , Walther Grit , Kurzai Oliver
Published: July 2021

Background

Candida glabrata is the second leading fungal pathogen causing candidaemia and invasive candidiasis in Europe. This yeast is recognized for its rapid ability to acquire antifungal drug resistance.

Objectives

We systematically evaluated 176 C. glabrata isolates submitted to the German National Reference Center for Invasive Fungal Infections (NRZMyk) between 2015 and 2019 with regard to echinocandin and fluconazole susceptibility.

Methods

Susceptibility testing was performed using a reference protocol (EUCAST) and a range of commercial assays. Hot spot regions of the echinocandin target FKS genes were sequenced using Sanger sequencing.

Results

In total, 84 of 176 isolates were initially classified as anidulafungin-resistant based on EUCAST testing. Of those, 71 harboured mutations in the glucan synthase encoding FKS genes (13% in FKS1, 87% in FKS2). Significant differences in anidulafungin MICs were found between distinct mutation sites. 11 FKS wild-type (WT) isolates initially classified as resistant exhibited anidulafungin MICs fluctuating around the interpretation breakpoint upon re-testing with multiple assays. Two FKS WT isolates consistently showed high anidulafungin MICs and thus must be considered resistant despite the absence of target gene mutations. Over one-third of echinocandin-resistant strains displayed concomitant fluconazole resistance. Of those, isolates linked to bloodstream infection carrying a change at Ser-663 were associated with adverse clinical outcome.

Conclusions

Resistant C. glabrata strains are emerging in Germany. Phenotypic echinocandin testing can result in misclassification of susceptible strains. FKS genotyping aids in detecting these strains, however, echinocandin resistance may occur despite a wild-type FKS genotype.
Comparative Effectiveness of Lumen-Apposing Metal Stents and Plastic Stents for the Treatment of Pancreatic Walled-Off Necrosis: A Meta-analysis
Authors: Calo Natalia Causada , Bishay Kirles , Yaghoobi Mohammad , Yuan Yuhong , Mosko Jeffrey , May Gary , Chen Yen-I , Teshima Christopher
Published: July 2021

Background

Plastic stents (PS), lumen-apposing metal stents (LAMS) and biflanged metal stents (BFMS) are used for initial drainage of pancreatic walled-off necrosis (WON). There are no strong evidence to support the use of LAMS/BFMS over PS, and prior systematic reviews lack comparative analyses and also lack both trial data and observational studies for WON efficacy outcomes. The aim of this study is to compare the efficacy and adverse events (AEs) in LAMS/BFMS versus PS in patients with pancreatic WON.

Methods

A comprehensive search up to December 1, 2020, was performed. The primary outcome was clinical improvement after drainage. Secondary outcomes included AEs and technical failure. Pooled odds ratios (OR) with 95% confidence intervals (CI) were reported using random effects models. Heterogeneity was evaluated with the Cochrane I2 statistic. Subgroup and sensitivity analyses were performed. The quality of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

Results

Nine studies (one randomized controlled trial and eight observational) were included for the primary outcome including 493 patients treated with LAMS/BFMS and 514 with PS. LAMS/BFMS were associated with higher odds of clinical improvement compared with PS (OR 2.58; 95% CI 1.81, 3.68; I2 = 1%). This association remained robust in sensitivity analyses. The use of LAMS/BFMS was not associated with higher AEs (OR 1.22; 0.61, 2.46; I2 = 71%). There was no difference in technical failure (OR 1.06; 0.19, 6.00; I2 = 12%).

Conclusions

LAMS/BFMS seem to result in better clinical outcomes compared with PS in patients with pancreatic WON, with comparable AEs and technical failure. Larger randomized controlled trials for this comparison are warranted.
Action-at-a-distance mutations at 5′-GpA-3′ sites induced by oxidised guanine in WRN-knockdown cells
Authors: Suzuki Tetsuya , Masuda Hiroshi , Mori Madoka , Ito Rikako , Kamiya Hiroyuki
Published: July 2021

G:C sites distant from 8-oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) are frequently mutated when the lesion-bearing plasmid DNA is replicated in human cells with reduced Werner syndrome (WRN) protein. To detect the untargeted mutations preferentially, the oxidised guanine base was placed downstream of the reporter supF gene and the plasmid DNA was introduced into WRN-knockdown cells. The total mutant frequency seemed higher in the WRN-knockdown cells as compared to the control cells. Mutation analyses revealed that substitution mutations occurred at the G:C pairs of 5′-GpA-3′/5′-TpC-3′ sites, the preferred sequence for the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3)-family cytosine deaminases, in the supF gene in both control and knockdown cells. These mutations were observed more frequently at G sites than C sites on the DNA strand where the GO base was originally located. This tendency was promoted by the knockdown of the WRN protein. The present results imply the possible involvement of APOBEC3-family cytosine deaminases in the action-at-a-distance (untargeted) mutations at G:C (or G) sites induced by GO and in cancer initiation by oxidative stress.
Venous Causes of Pulsatile Tinnitus: Clinical Presentation, Clinical and Radiographic Evaluation, Pathogenesis, and Endovascular Treatments: A Literature Review
Authors: Essibayi Muhammed Amir , Oushy Soliman H , Lanzino Giuseppe , Brinjikji Waleed
Published: July 2021

Tinnitus is an abnormal perception of a sound without external stimulation. Venous pulsatile tinnitus (VPT) is a specific form of tinnitus characterized by an objective and often subjective bruit that occurs as a result of localized venous abnormalities. Clinical evaluation relies on sound quality, duration, and precipitating factors. Idiopathic intracranial hypertension (IIH) and transverse sinus stenosis (TSS) are among the most common causes of VPT. Other causes include sigmoid sinus wall abnormalities (SSWAs), jugular vein anomalies (JVAs), and emissary veins anomalies. These anomalies can be detected on magnetic resonance imaging, magnetic resonance angiography/magnetic resonance venography, and high-resolution temporal bone computed tomography. The pathogenesis behind the VPT includes turbulent blood flow as a result of luminal stenosis or abnormal dilation, amplification of internal sound due to temporal bone defects, and abnormal position of the venous sinus system structures adjacent to the bony structures of the auditive apparatus. Based on these theories, different interventional treatment modalities can be applied to treat the underlying causes. Endovascular treatments have shown high efficacy and safety among those treatments which include stenting of the lateral sinus stenosis in IIH and TSS, coiling of the SSWA and JVA, and embolization of emissary veins anomalies. Further studies are needed to understand the natural history of these anomalies and the efficacy of treatments of VPT, which—unlike other types of tinnitus—can be cured with proper treatment.
Independent Predictors of Revision Lumbar Fusion Outcomes and the Impact of Spine Surgeon Variability: Does It Matter Whether the Primary Surgeon Revises?
Authors: Montenegro Thiago Scharth , Singh Akash , Elia Christopher , Matias Caio M , Gonzalez Glenn A , Saiegh Fadi Al , Philipp Lucas , Hattar Ellina , Hines Kevin , Fatema Umma , Thalheimer Sara , Wu Chengyuan , Prasad Srinivas K , Jallo Jack , Heller Joshua E , Sharan Ashwini , Harrop James
Published: July 2021

BACKGROUND

There is a paucity of information regarding treatment strategies and variables affecting outcomes of revision lumbar fusions.

OBJECTIVE

To evaluate the influence of primary vs different surgeon on functional outcomes of revisions.

METHODS

All elective lumbar fusion revisions, March 2018 to August 2019, were retrospectively categorized as performed by the same or different surgeon who performed the primary surgery. Oswestry Disability Index (ODI) and clinical variables were collected. Multiple logistic regression identified multivariable-adjusted odds ratio (OR) of independent variables analyzed.

RESULTS

Of the 130 cases, 117 (90%) had complete data. There was a slight difference in age in the same (median: 59; interquartile range [IQR], 54-66) and different surgeon (median: 67; IQR, 56-72) groups (P = .02); all other demographic variables were not significantly different (P > .05). Revision surgery with a different surgeon had an ODI improvement (median: 8; IQR, 2-14) greater than revisions performed by the same surgeon (median: 1.5; IQR, −3 to 10) (P < .01). Revisions who achieved minimum clinically important difference (MCID) performed by different surgeon (59.7%) were also significantly greater than the ones performed by the same surgeon (40%) (P = .042). Multivariate analysis demonstrated that a different surgeon revising (OR, 2.37; [CI]: 1.007-5.575, P = .04) was an independent predictor of MCID achievement, each additional 2 years beyond the last surgery conferred a 2.38 ([CI]: 1.36-4.14, P < .01) times greater odds of MCID achievement, and the anterior lumbar interbody fusion approach decreased the chance of achieving MCID (OR, 0.19; [CI]: 0.04-0.861, P = .03).

CONCLUSION

All revision lumbar spinal fusion approaches may not achieve the same outcomes. This analysis suggests that revision surgeries may have better outcomes when performed by a different surgeon.
Missing repeated measures data in clinical trials
Authors: Pugh Stephanie L , Brown Paul D , Enserro Danielle
Published: July 2021

Clinical trials typically collect longitudinal data, data that are collected repeated over time, such as laboratories, scans, or patient-reported outcomes. Due to a variety of reasons, this data can be missing, whether a patient stops attending clinical visits (ie, dropout) or misses assessments intermittently. Understanding the reasons for missing data as well as predictors of missing data can aid in determination of the missing data mechanism. The analysis methods used are dependent on the missing data mechanism and may make certain assumptions about the missing data itself. Methods for nonignorable missing data, which assumes that the missing data depend on the missing data itself, make stronger assumptions and include pattern-mixture models and shared parameter models. Missing data that are ignorable after adjusting for other covariates can be analyzed using methods that adjust for covariates, such as mixed-effects models or multiple imputation. Missing data that are ignorable can be analyzed using standard approaches that require complete case data, such as change from baseline or proportion of patients who declined at a specified time point. In clinical trials, truly ignorable data are rare, resulting in additional analysis methods required for proper interpretation of the results. Conducting several analyses under different assumptions, called sensitivity analyses, can determine the extent of the impact of the missing data.
Microsurgical Resection of Giant Thoraco-Lumbo-Sacral Ependymoma With Hybrid Spinal Reconstruction Using Multilevel Laminoplasty and Up-Front Thoracolumbar Posterior Fixation: 2-Dimensional Operative Video
Authors: Donoho Daniel A , Lazaro Tyler , Snyder Rita , Guerrero Jaime , Bauer David F
Published: July 2021

Extensive multifocal intradural lesions in children present a formidable challenge. This surgical video illustrates our management of a 14-yr=old boy with two intradural mass lesions on magnetic resonance imaging (MRI): one at T2-5 and the other from T12 through the sacral cul-de-sac. In a single procedure, we performed a T2-5 laminectomy and laminoplasty and T12-sacrum laminectomy for tumor resection. For reconstruction, we performed complete laminoplasty at all levels with supplementation at the thoracolumbar junction via T11-L2 posterior spinal fixation and allograft placement for fusion. In this video, we illustrate the microsurgical challenges of intradural tumor resection in both the thoracic cord and amidst the cauda equina. In young patients, prevention of postsurgical spinal deformity is of paramount concern. We discuss considerations for long-segment spinal stabilization in an adolescent and describe our decision-making to perform stabilization at the thoracolumbar junction to supplement laminoplasty while preserving function. The patient and their family consented to the procedure.

 Image of the article at 0:51 is from McGirt et al, Short-term progressive spinal deformity following laminoplasty versus laminectomy for resection of intradural spinal tumors: analysis of 239 patients, Neurosurgery, 2010, 66(5), 1005-1012, by permission of the Congress of Neurological Surgeons.
COVID-19 diplomacy: analysis of Serbia COVID-19 vaccine strategy in the western Balkans
Authors: Barovic Alek , Cardenas Nicky C
Published: July 2021

Serbia’s regional influence in the western Balkans enhanced strategic geopolitical partnership with Russia and China during COVID-19 pandemic. This paper critically analyzes Serbia COVID-19 vaccine strategy to the public health in the western Balkans. Importantly, this paper proposes strategic policy by enhancing ‘joint coordinated EU–US-western Balkans COVID-19 vaccine manufacturing production’ to accelerate inoculation, address gaps on vaccine hesitancy and promote long-term post-pandemic recovery plan to build back together and achieve herd immunity.
OBSIDIAN – real-world evidence of originator to biosimilar drug switch in juvenile idiopathic arthritis
Authors: Maccora Ilaria , Lombardi Niccolò , Crescioli Giada , Bettiol Alessandra , Bonaiuti Roberto , Pagnini Ilaria , Maniscalco Valerio , Marrani Edoardo , Mastrolia Maria Vincenza , Ravaldi Claudia , Consolini Rita , Cattalini Marco , Vannacci Alfredo , Simonini Gabriele
Published: July 2021

Objectives

Limited data about use of biosimilars (BIOs) are available in children with JIA. This study therefore aimed to evaluate long-term efficacy and safety of switching from etanercept (ETA) and adalimumab (ADA) originators to their biosimilars (BIOs), in children with JIA, in a real-world setting.

Methods

This is a retro-prospective non-interventional multicentre Italian comparative cohort study. Medical charts of JIA children treated with biosimilars of ETA or ADA were included. Efficacy and safety of TNF-inhibitors therapy was evaluated at last follow-up during originator and at 3, 6 and 12 months following the switch to biosimilar.

Results

A total of 59 children (42 female, median age at onset 88 months) were treated with biosimilar of ETA (21) and ADA (38). Forty-five switched from the originator to the BIO (17 ETA, 28 ADA). At time of switch, 12/17 patients on ETA and 18/28 on ADA were in remission. No significant difference has been found at 3, 6 and 12 months after the switch. Ten patients discontinued biosimilars due to disease remission (4 ETA, 3 ADA), family willing (1 ETA), occurrence of burning at injection site (1 ETA) and persistent activity (1 ADA). No statistically significant difference was observed between originator and BIOs, nor between originator and BIOs, and between ADA and ETA in time to disease remission achievement, time to relapse and number of patients who experienced adverse event (AE).

Conclusion

Our real-life results seem to confirm the efficacy and safety profile of switching from originator of ADA and ETA to their respective BIOs, also in paediatric patients with JIA.
Clinical significance of anti-NOR90 antibodies in systemic sclerosis and idiopathic interstitial pneumonia
Authors: Yamashita Yuta , Yamano Yasuhiko , Muro Yoshinao , Ogawa-Momohara Mariko , Takeichi Takuya , Kondoh Yasuhiro , Akiyama Masashi
Published: July 2021

Objective

Anti-NOR90 antibodies are usually found in patients with SSc; however, their clinical relevance remains obscure. We developed an ELISA for measuring them to investigate the clinical features of patients with anti-NOR90 antibodies.

Methods

Serum samples from 1252 patients with various conditions from Nagoya University Hospital and 244 patients with idiopathic interstitial pneumonia (IIP) from Tosei General Hospital were included. Anti-NOR90 antibodies were assayed by an ELISA using the recombinant protein produced by in vitro transcription/translation.

Results

Five (0.4%) patients in the Nagoya University Hospital cohort had anti-NOR90 antibodies. One patient with diffuse cutaneous SSc, three with limited cutaneous SSc, and one with Raynaud’s disease were positive for anti-NOR90 antibodies. Anti-NOR90 antibodies were found more frequently in patients with systemic scleroderma-spectrum disorders (SSDs) than without SSDs (5/316 vs 0/936, P <0.00101) and were found more frequently in patients with SSc than without SSc (4/249 vs 0/528, P <0.0104) in the systemic autoimmune rheumatic diseases cohort. Three of the four anti-NOR90-positive SSc patients had interstitial lung disease (ILD), and two of those four had cancer. Three (1.2%) patients in the Tosei General Hospital cohort had anti-NOR90 antibodies. All three of the anti-NOR90-positive IIP patients had gastrointestinal tract involvement, and two of those three had cancer or skin lesions observed in SSc.

Conclusions

Although anti-NOR90 antibodies are rarely found in clinics, our ELISA is useful for their detection. Further studies are needed to confirm the association of anti-NOR90 antibodies with ILD and cancer in SSc and IIP patients.
Sequential Post-Heading Applications for Controlling Wheat Blast: A 9-Year Summary of Fungicide Performance in Brazil
Authors: Ascari João P. , Barro Jhonatan P. , Santana Flávio M. , Padua José M. V. , Maciel João L. N. , Lau Douglas , Torres Gisele A. M. , Sbalcheiro Cheila C. , Seixas Claudine D. S. , Goulart Augusto C. P. , Sussel Angelo A. B. , Schipanski Carlos A. , Chagas Débora F. , Coelho Maurício A. O. , Montecelli Tatiane D. N. , Amaral Daniel R. , Custódio Adriano A. P. , Moreira Lucas S. O. , Utiamada Carlos M. , Venâncio Wilson S. , Goussain Rita C. S. , Alves Kaique S. , Del Ponte Emerson M.
Published: July 2021

Wheat blast, caused by Pyricularia oryzae Triticum lineage, is a major constraint to wheat production, mainly in the tropics of Brazil, where severe epidemics have been more frequent. We analyzed disease and wheat yield data from 42 uniform field trials conducted over 9 years (2012 to 2020) to assess whether the percent control and yield response were influenced by fungicide type, region (tropical or subtropical), and year. Six treatments were selected, all evaluated in at least 19 trials. Two fungicides were applied as solo active ingredients (MANCozeb, and TEBUconazole), and four were premixes (AZOXystrobin plus TEBU, TriFLoXystrobin plus PROThioconazole, TFLX plus TEBU, and PYRAclostrobin plus EPOXiconazole). Percent control, calculated from back-transforming estimates by a meta-analysis network model fitted to the log of the means, ranged from 43 to 58%, with all but PYRA plus EPOX showing efficacy >52% on average, not differing among them. The variation in both efficacy and yield response was explained by region, and all but TEBU performed better in the subtropics than in the tropics. Yield response from using three sequential sprays was approximately two times greater in the subtropics (319 to 532 kg/ha) than in the tropics (149 to 241.3 kg/ha). No significant decline in fungicide efficacy or yield response was observed in 9 years of study for any of the fungicides. These results reinforce the need to improve control by adopting an integrated management approach in the tropics given poorer performance and lower profitability, especially for the premixes, than in the subtropics.
Changing Trends in Corneal Transplantation in Aotearoa/New Zealand, 1991 to 2020: Effects of Population Growth, Cataract Surgery, Endothelial Keratoplasty, and Corneal Cross-Linking for Keratoconus
Authors: Chilibeck Corina M. , Brookes Nigel H. , Gokul Akilesh , Kim Bia Z. , Twohill Helen C. , Moffatt S. Louise , Pendergrast David G. , McGhee Charles N. J.
Published: July 2021

Purpose:

The purpose of this study was to identify trends in the primary indication for keratoplasty in New Zealand/Aotearoa (NZ) after significant population growth, increase in the number of cataract surgeries per population, widespread adoption of endothelial keratoplasty, and introduction of corneal cross-linking for keratoconus.

Methods:

Statistical analysis of the New Zealand National Eye Bank's prospective database of all keratoplasties was performed between January 1991 and January 2020. Indications for keratoplasty were isolated for the primary diagnosis.

Results:

In total, 6840 corneas were transplanted with mean 236 ± 57.5 transplants/year, increasing from 2.55 to 6.06 per 100,000 NZ population/year. Over the past decade, the number of transplant recipients aged 60 years or older has increased and recipients aged 20 to 39 years have plateaued. In 2019, for the first time, regraft became the most common indication (30.9%), followed by keratoconus (27.9%) and corneal dystrophy (18.8%), with a steady decline in bullous keratopathy. Proportions of the keratoplasty technique changed dramatically: penetrating keratoplasty fell from 91.4% in 2006 to 55.0% in 2019, Descemet’s stripping endothelial keratoplasty increased from 0% to 29.5%, anterior lamellar keratoplasty increased from 2.5% to 5.7%, and Descemet membrane endothelial keratoplasty increased from 0% to 9.1%.

Conclusions:

Keratoplasty trends in Aotearoa/NZ have changed considerably because of the evolution of phacoemulsification and keratoplasty techniques. Unlike proportions observed overseas, NZ still performs penetrating keratoplasties in over half of all transplants. Corneal cross-linking may be having an early effect of reducing keratoplasty rates for keratoconus.
Holistic Review in Doctor of Physical Therapy Admissions Can Lead to Enhanced Diversity in Admitted Students
Authors: Canham Lara E. , Mañago Mark M. , Dannemiller Lisa , Rapport Mary Jane
Published: July 2021

Background and Purpose.

Despite an increase in the number of physical therapist education programs and applicants, there is limited diversity represented in the physical therapy profession. This case report describes the development and implementation of a holistic review rubric with the goal of increasing diversity in 1 entry-level physical therapist education program.

Case Description.

The University of Colorado Physical Therapy Program developed a holistic review rubric, based on literature review and conversations with other programs, with a focus on the specific mission/values/goals of the program. Admissions decisions for the 2018–19 admissions cycle were based on holistic rubric scores in addition to the traditionally used cognitive measures and interview recommendations.

Outcomes.

The Program received 919 verified applications, 713 met the eligibility requirements and were reviewed using the holistic rubric, 193 were invited to interview, and 71 matriculated. Overall, the Program admitted a greater proportion of diverse students as compared with the total Program applicant pool in the following categories: 1) race/ethnicity, 2) socioeconomic status, and 3) other unique characteristics (first-generation college student, military experience, and rural). Second, compared with the Physical Therapy Centralized Application Service data, the Program admitted an increased proportion of diverse students. Third, the 193 applicants who were interviewed by the Program based on the holistic review compared with the top 193 applicants based on cumulative grade point average had an increased proportion of diverse students.

Discussion and Conclusion.

Although this case report reflects only 1 admission cycle at 1 institution, the initial data suggest that the use of a holistic review may increase diversity in entry-level Doctor of Physical Therapy programs, as compared with using more traditional admissions methods with the goal of leading to increased diversity within the physical therapist profession.
Endoscopic Stapedotomy: A Systematic Review
Authors: Hoskison Emma E. , Harrop Elizabeth , Jufas Nicholas , Kong Jonathan H. K. , Patel Nirmal P. , Saxby Alexander J.
Published: July 2021

Objectives:

Stapes surgery has evolved from its origins in 1956. Microscopic assisted stapedotomy remains the most common technique but the introduction of endoscopic ear surgery has led to some units using this new approach. The endoscope delivers a wide angled, contextual view of the stapes, and associated pathology. This systematic review provides a critical analysis of the current published endoscopic data, allowing comparison to the established microscopic technique.

Data sources:

Six databases (PubMed, Medline, Cochrane database, AMED, EMBASE, and CINAHL) were searched for studies within the last 10 years.

Study selection and data extraction:

English language articles including 5 or more cases were included. Primary outcomes included audiological results and reported complications. Data was extracted according to PRISMA guidelines.

Results:

Thirteen papers were identified comprising 361 endoscopic stapes surgeries. Postoperative temporary facial nerve weakness was reported in 3 patients (0.8%) which all resolved within 4 weeks. Chorda tympani injury occurred in 21 cases (5.8%) and vertigo in 61 (16.9%). The audiometric outcomes of endoscopic stapes surgery were available for 259 patients and showed air bone gap closure rates of 71.4% (0–10 dB), 25.9% (11–20 dB), 2.3% (21–30 dB), and 0.4% (>30 dB).

Conclusions:

Endoscopic stapes surgery has similar audiometric outcomes compared to the traditional microscopic approach with air bone gap closure values of <20 dB in 97.3% of cases. However, the complication rates of chorda tympani damage, postoperative dysguesia, and tympanic membrane perforation for endoscopic stapes surgery are high. Caution should therefore be taken before undertaking stapes surgery with the endoscopic technique. Further studies are required to prove superiority over well established existing microsurgical methods.
Iatrogenic Third Window After Retrosigmoid Approach to a Vestibular Schwannoma Managed with Cochlear Implantation
Authors: Deep Nicholas L. , Kay-Rivest Emily , Roland J. Thomas
Published: July 2021

Objective:

To present a case of an iatrogenic inner ear third window after vestibular schwannoma microsurgery.

Patients:

A 42-year-old male presented 9-months after left-sided retrosigmoid approach for an intracanalicular vestibular schwannoma with hearing-preservation attempt performed elsewhere. Immediately postoperatively, he developed the following disabling and persistent symptoms on the ipsilateral side: autophony, pulsatile tinnitus, high-pitched ringing tinnitus, and hearing his footsteps. He denied vertigo. Otoscopy was normal. Tuning fork (512-Hz) lateralized to the left and Rinne was negative on the left. Audiogram demonstrated a severe mixed hearing loss and 10% aided word-recognition score. High-resolution CT demonstrated violation of the common crus and dehiscence of bone along the medial vestibule suggestive of an iatrogenic inner ear third window.

Interventions:

Labyrinthectomy and concurrent cochlear implantation.

Main outcome measures:

Resolution of third window symptoms, open-set speech recognition, tinnitus suppression.

Results:

Patient reported immediate resolution of third window symptoms after labyrinthectomy and cochlear implantation. He demonstrates open-set word recognition of 64% at 1-year postoperatively and tinnitus suppression with his cochlear implant on.

Conclusions:

Iatrogenic third window symptoms can occur after hearing-preservation vestibular schwannoma microsurgery. Patients with sufficient hearing preservation who are disabled by third window symptoms yet lack sound clarity and useful hearing may be considered for labyrinthectomy and concurrent cochlear implantation. This intervention effectively extinguishes third window symptoms by destroying residual auditory function and simultaneously provides an opportunity to restore useful hearing and suppress tinnitus, thereby enhancing overall quality of life.
Combination of Direct Oval Window Vibroplasty With Customized Partial Ossicular Replacement Prosthesis (PORP): A Novel Reconstruction Technique to Rehabilitate Mixed Hearing Loss
Authors: Grueninger Ivo , Canis Martin , Spiegel Jennifer L. , Müller Joachim
Published: July 2021

Objective:

Hearing rehabilitation with an active middle ear implant (AMEI) in patients with mixed hearing loss (MHL) after multiple ear surgeries is surgically challenging and requires individual solutions in some cases. Our objective was to introduce a feasible novel technique for direct oval window vibroplasty (OW vibroplasty) using a partial ossicular replacement prosthesis (PORP) to ensure stability and enable active and passive sound transmission.

Design:

Four patients with MHL following multiple middle ear surgeries and indication for an AMEI received direct OW vibroplasty in combination with a customized PORP between the enwrapped actuator and reconstructed tympanic membrane (TM).

Results:

Postoperative bone conduction was stable in all patients. All patients benefitted from the AMEI in combination with PORP with a mean functional gain of 31.5 ± 17.0 dB. Mean aided postoperative pure tone average was 27.3 ± 2.6 dB. Speech discrimination in quiet at 65 dB with the German Language Freiburg Monosyllabic Test improved for all patients to 68.8 ± 6.3% and in noise with the German Language Oldenburger Sentence Test to –10.4 ± 3.3 dB SNR. No complications were observed.

Conclusions:

This novel technique of direct OW vibroplasty extends the portfolio of reconstructive middle ear procedures by combining an intraoperatively customized “off-the-shelf” PORP as a coupler between floating mass transducer (FMT) and a cartilage TM. We found satisfying functional hearing results. Benefits of the reported technique comprise 1) stabilization and optimized coupling of the reconstruction, 2) possibility of passive sound transmission, 3) general feasibility due to great availability of a regular PORP, and 4) flexibility in bridging of large gaps between TM and actuator.
Cochlear Implant Outcomes in Elderly Recipients During the COVID-19 Pandemic
Authors: Knickerbocker Alissa , Bourn Stephanie , Goldstein Mary Rose , Jacob Abraham
Published: July 2021

Objective:

To evaluate the potential significance of social distancing and quarantine precautions for COVID-19 on speech outcomes, missed appointments, wear time, and exposure to various sound environments in the first 6 months following activation for elderly cochlear implant (CI) recipients.

Study Design:

Retrospective cohort.

Setting:

Tertiary private practice.

Patients:

Fifty cochlear implant recipients ≥65 years were evaluated. A Control Group consisted of 26 patients implanted between November 2, 2018 and February 18, 2019 while the Pandemic Group included 24 patients implanted between November 1, 2019 and February 17, 2020.

Intervention:

Rehabilitative.

Main Outcome Measures:

Preoperative and 6-month postoperative AzBio sentence scores in quiet were compared between groups along with the number of missed appointments as well as datalogged information regarding average CI wear time and average hours in various sound environments such as quiet, speech, and speech-in-noise.

Results:

The Control Group averaged 36.5% improvement for AzBio in quiet scores while the Pandemic Group averaged only 17.2% improvement, a difference that was both statistically and clinically significant (p = 0.04; g = 0.64). Patients in the Pandemic Group were nearly twice as likely to miss CI programming appointments than the Control Group. The Pandemic Group wore their CI 1.2 less hours per day on average, and while the Pandemic Group spent similar times in quiet and speech environments to the Control Group, the Pandemic Group spent less time in speech with presence of background noise.

Conclusions:

While social distancing and quarantine measures are crucial to limiting spread of COVID-19, these precautions may have negatively impacted early speech performance for elderly cochlear implant recipients. Missed CI programming appointments, decreased sound processor wear time, and reduced exposure to complex listening environments such as speech in the presence of background noise were more common in the Pandemic Group than in the Control Group operated the year prior.
Absence of exaggerated pharmacology by recombinant ADAMTS13 in the rat and monkey
Authors: Rossato Paolo , Glantschnig Helmut , Leidenmühler Peter , Kopic Alexandra , Ruthsatz Tanja , Majer Bernhard , Schuster Maria , Scheiflinger Friedrich , Höllriegl Werner
Published: July 2021

Insufficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motif repeats-13) is the cause of thrombotic thrombocytopenic purpura (TTP) and contributes in microangiopathy in sickle cell disease (SCD). Recombinant ADAMTS13 effectively cleaves prothrombotic ultra-large von Willebrand factor (VWF) multimers. It is being tested as replacement therapy for TTP, and at supra-physiologic concentrations, for moderating vaso-occlusive crisis in SCD. Deficiencies of VWF, or concomitant treatment with antithrombotic drugs, could pose risks for increased bleeds in these patient populations. The purpose of the experiments was to evaluate the potential of exaggerated pharmacology and temporary bleeding risks associated with rADAMTS13 administration. We utilized safety studies in monkey and tested the effects of administering maximum-feasible doses of rADAMTS13 on nonclinical safety and spontaneous or aggressive bleeds in the rat model. Evaluation of pharmacokinetics, toxicity profiles, and challenge in a tail-tip bleeding model show that treatment with rADAMTS13 did not increase bleeding tendency, either alone, or in combination with enoxaparin or acetylsalicylic-acid. These novel findings demonstrate absence of rADAMTS13 exaggerated pharmacology without spontaneous or aggravated bleeds even at supra-physiologic (>100-fold) plasma concentrations.
The impact of resource limitations on care delivery and outcomes: routine variation, the coronavirus disease 2019 pandemic, and persistent shortage
Authors: Anesi George L. , Kerlin Meeta Prasad
Published: July 2021

Purpose of review

Resource limitation, or capacity strain, has been associated with changes in care delivery, and in some cases, poorer outcomes among critically ill patients. This may result from normal variation in strain on available resources, chronic strain in persistently under-resourced settings, and less commonly because of acute surges in demand, as seen during the coronavirus disease 2019 (COVID-19) pandemic.

Recent findings

Recent studies confirmed existing evidence that high ICU strain is associated with ICU triage decisions, and that ICU strain may be associated with ICU patient mortality. Studies also demonstrated earlier discharge of ICU patients during high strain, suggesting that strain may promote patient flow efficiency. Several studies of strain resulting from the COVID-19 pandemic provided support for the concept of adaptability – that the surge not only caused detrimental strain but also provided experience with a novel disease entity such that outcomes improved over time. Chronically resource-limited settings faced even more challenging circumstances because of acute-on-chronic strain during the pandemic.

The interaction between resource limitation and care delivery and outcomes is complex and incompletely understood. The COVID-19 pandemic provides a learning opportunity for strain response during both pandemic and nonpandemic times.