bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and preclinical therapeutic outcome metrics for USH2A-related disease
Authors: Toms Maria , Dubis Adam M , de Vrieze Erik , Tracey-White Dhani , Mitsios Andreas , Hayes Matthew , Broekman Sanne , Baxendale Sarah , Utoomprurkporn Nattawan , Bamiou Doris , Bitner-Glindzicz Maria , Webster Andrew R , Van Wijk Erwin , Moosajee Mariya
Published: January 2020

USH2A variants are the most common cause of Usher syndrome type 2, characterized by congenital sensorineural hearing loss and retinitis pigmentosa (RP), and also contribute to autosomal recessive non-syndromic RP. Several treatment strategies are under development; however, sensitive clinical trial endpoint metrics to determine therapeutic efficacy have not been identified. In the present study, we have performed longitudinal retrospective examination of the retinal and auditory symptoms in (i) 56 biallelic molecularly confirmed USH2A patients and (ii) ush2a mutant zebrafish to identify metrics for the evaluation of future clinical trials and rapid preclinical screening studies. The patient cohort showed a statistically significant correlation between age and both rate of constriction for the ellipsoid zone length and hyperautofluorescent outer retinal ring area. Visual acuity and pure tone audiograms are not suitable outcome measures. Retinal examination of the novel ush2au507 zebrafish mutant revealed a slowly progressive degeneration of predominantly rods, accompanied by rhodopsin and blue cone opsin mislocalization from 6 to 12 months of age with lysosome-like structures observed in the photoreceptors. This was further evaluated in the ush2armc zebrafish model, which revealed similar changes in photopigment mislocalization with elevated autophagy levels at 6 days post fertilization, indicating a more severe genotype-phenotype correlation and providing evidence of new insights into the pathophysiology underlying USH2A-retinal disease.
Current status of perioperative chemotherapy for locally advanced gastric cancer and JCOG perspectives
Authors: Terashima Masanori , Yoshikawa Takaki , Boku Narikazu , Ito Seiji , Tsuburaya Akira , Iwasaki Yoshiaki , Fukagawa Takeo , Tokunaga Masanori , Sano Takeshi , Sasako Mitsuru ,   the Stomach Cancer Study Group, Japan Clinical Oncology Group
Published: January 2020

Perioperative treatment for locally advanced gastric cancer has been inconsistent between Japan and the Western countries. In Japan, D2 gastrectomy followed by adjuvant chemotherapy is regarded as standard treatment, while neoadjuvant or perioperative chemotherapy is considered to be a standard in the Western countries. Stomach Cancer Study Group of Japan Clinical Oncology Group (JCOG) has conducted many perioperative chemotherapy trials. After the publishing of positive results of ACTS-GC trial, stage-specific adjuvant chemotherapy protocols are planned. JCOG1104 was conducted as to demonstrate the non-inferiority of four courses of S-1 to standard eight courses of S-1, because the efficacy of S-1 appears to be sufficient in stage II. The trial failed to demonstrate the non-inferiority of four courses of S-1. S-1 for 1 year is still recognized to be a standard for stage II gastric cancer. For stage III, studies with more intensive treatments were planned as the efficacy of S-1 monotherapy seems to be insufficient. As in the Western countries, JCOG planned the perioperative chemotherapy. However, the clinical staging is a serious issue to select optimal patients for perioperative chemotherapy. JCOG conducted a prospective cohort study to evaluate the validity of clinical staging in JCOG1302A. From the results of this study, cT3-4 and cN1–3 are selected as optimal candidate for perioperative chemotherapy. JCOG1509 was conducted to demonstrate the superiority of perioperative chemotherapy to adjuvant chemotherapy in these cohorts. Perioperative chemotherapy for marginally resectable tumours such as linitis plastica or extensive nodal disease and special type of cancer like HER2 positive are also conducted.
Capture and migration of Jupiter and Saturn in mean motion resonance in a gaseous protoplanetary disc
Authors: Chametla Raúl O , D’Angelo Gennaro , Reyes-Ruiz Mauricio , Sánchez-Salcedo F Javier
Published: January 2020

We study the dynamical evolution of Jupiter and Saturn embedded in a gaseous, solar nebula-type disc by means of hydrodynamics simulations with the fargo2d1d code. We study the evolution for different initial separations of the planets’ orbits, ΔaSJ, to investigate whether they become captured in mean motion resonance (MMR) and the direction of the subsequent migration of the planet (inwards or outwards). We also provide an assessment of the planet’s orbital dynamics at different epochs of Saturn’s growth. We find that the evolution of initially compact orbital configurations is dependent on the value of ΔaSJ. This implies that an evolution as that proposed in the Grand Tack model depends on the precise initial orbits of Jupiter and Saturn and on the time-scales for their formation. Capture in the 1:2 MMR and inward or (nearly) stalled migration are highly favoured. Within its limits, our work suggests that the reversed migration, associated with the resonance capture of Jupiter and Saturn, may be a low-probability evolutionary scenario, so that other planetary systems with giant planets are not expected to have experienced a Grand Tack-like evolutionary path.
Detection of gamma-ray transients with wild binary segmentation
Authors: Antier S , Barynova K , Fryzlewicz P , Lachaud C , Marchal-Duval G
Published: January 2020

In the context of time domain astronomy, we present an offline detection search of gamma-ray transients using a wild binary segmentation analysis called F-WBSB targeting both short and long gamma-ray bursts (GRBs) and covering the soft and hard gamma-ray bands. We use NASA Fermi/GBM archival data as a training and testing data set. This paper describes the analysis applied to the 12 NaI detectors of the Fermi/GBM instrument. This includes background removal, change-point detection that brackets the peaks of gamma-ray flares, the evaluation of significance for each individual GBM detector, and the combination of the results among the detectors. We also explain the calibration of the ∼ 10 parameters present in the method using one week of archival data. Finally, we present our detection performance result for 60 d of a blind search analysis with F-WBSB by comparing to both the onboard and offline GBM search as well as external events found by others surveys such as Swift-BAT. We detect 42/44 onboard GBM events but also other gamma-ray flares at a rate of 1 per hour in the 4–50 keV band. Our results show that F-WBSB is capable of recovering gamma-ray flares, including the detection of soft X-ray long transients. FWBSB offers an independent identification of GRBs in combination with methods for determining spectral and temporal properties of the transient as well as localization. This is particularly useful for increasing the GRB rate and that will help the joint detection with gravitational-wave events.
The bias of dark matter tracers: assessing the accuracy of mapping techniques
Authors: Pellejero-Ibañez Marcos , Balaguera-Antolínez Andres , Kitaura Francisco-Shu , Angulo Raúl E , Yepes Gustavo , Chuang Chia-Hsun , Reyes-Peraza Guillermo , Autefage Mathieu , Vakili Mohammadjavad , Zhao Cheng
Published: January 2020

We present a comparison between approximated methods for the construction of mock catalogues based on the halo-bias mapping technique. To this end, we use as reference a high-resolution N-body simulation of 38403 dark matter particles on a 400 h−1 Mpc cube box from the Multidark suite. In particular, we explore parametric versus non-parametric bias mapping approaches and compare them at reproducing the halo distribution in terms of the two- and three-point statistics down to $\sim 10^8\, {\rm M}_{\odot }\, h^{-1}$ halo masses. Our findings demonstrate that the parametric approach remains inaccurate even including complex deterministic and stochastic components. On the contrary, the non-parametric one is indistinguishable from the reference N-body calculation in the power spectrum beyond $k=1\, h\, {\rm Mpc}^{-1}$, and in the bispectrum for typical configurations relevant to baryon acoustic oscillation analysis. We conclude that approaches which extract the full bias information from N-body simulations in a non-parametric fashion are ready for the analysis of the new generation of large-scale structure surveys.
l = 1: Weinberg’s weakly damped mode in an N-body model of a spherical stellar system
Authors: Heggie Douglas C , Breen Philip G , Varri Anna Lisa
Published: January 2020

Spherical stellar systems such as King models, in which the distribution function is a decreasing function of energy and depends on no other invariant, are stable in the sense of collisionless dynamics. But Weinberg showed, by a clever application of the matrix method of linear stability, that they may be nearly unstable, in the sense of possessing weakly damped modes of oscillation. He also demonstrated the presence of such a mode in an N-body model by endowing it with initial conditions generated from his perturbative solution. In the present paper we provide evidence for the presence of this same mode in N-body simulations of the King W0 = 5 model, in which the initial conditions are generated by the usual Monte Carlo sampling of the King distribution function. It is shown that the oscillation of the density centre correlates with variations in the structure of the system out to a radius of about 1 virial radius, but anticorrelates with variations beyond that radius. Though the oscillations appear to be continually reexcited (presumably by the motions of the particles) we show by calculation of power spectra that Weinberg’s estimate of the period (strictly, 2π divided by the real part of the eigenfrequency) lies within the range where the power is largest. In addition, however, the power spectrum displays another very prominent feature at shorter periods, around 5 crossing times.
An Augmented q-Factor Model with Expected Growth*
Authors: Hou Kewei , Mo Haitao , Xue Chen , Zhang Lu
Published: January 2020

In the investment theory, firms with high expected investment growth earn higher expected returns than firms with low expected investment growth, holding investment and expected profitability constant. Building on cross-sectional growth forecasts with Tobin’s q, operating cash flows, and change in return on equity as predictors, an expected growth factor earns an average premium of 0.84% per month (t = 10.27) in the 1967–2018 sample. The q5 model, which augments the Hou–Xue–Zhang (2015, Rev. Finan. Stud., 28, 650–705) q-factor model with the expected growth factor, shows strong explanatory power in the cross-section and outperforms the Fama–French (2018, J. Finan. Econom., 128, 234–252) six-factor model.
Mathematically Modeling Anhedonia in Schizophrenia: A Stochastic Dynamical Systems Approach
Authors: Strauss Gregory P , Esfahlani Farnaz Zamani , Granholm Eric , Holden Jason , Visser Katherine Frost , Bartolomeo Lisa A , Sayama Hiroki
Published: January 2020

Objective

Anhedonia, traditionally defined as a diminished capacity for pleasure, is a core symptom of schizophrenia (SZ). However, modern empirical evidence indicates that hedonic capacity may be intact in SZ and anhedonia may be better conceptualized as an abnormality in the temporal dynamics of emotion.

Method

To test this theory, the current study used ecological momentary assessment (EMA) to examine whether abnormalities in one aspect of the temporal dynamics of emotion, sustained reward responsiveness, were associated with anhedonia. Two experiments were conducted in outpatients diagnosed with SZ (n = 28; n = 102) and healthy controls (n = 28; n = 71) who completed EMA reports of emotional experience at multiple time points in the day over the course of several days. Markov chain analyses were applied to the EMA data to evaluate stochastic dynamic changes in emotional states to determine processes underlying failures in sustained reward responsiveness.

Results

In both studies, Markov models indicated that SZ had deficits in the ability to sustain positive emotion over time, which resulted from failures in augmentation (ie, the ability to maintain or increase the intensity of positive emotion from time t to t+1) and diminution (ie, when emotions at time t+1 are opposite in valence from emotions at time t, resulting in a decrease in the intensity of positive emotion over time). Furthermore, in both studies, augmentation deficits were associated with anhedonia.

Conclusions

These computational findings clarify how abnormalities in the temporal dynamics of emotion contribute to anhedonia.
Modelling Authority: Obstetrical Machines in the Instruction of Midwives and Surgeons in Eighteenth-Century Italy
Authors: Kosmin Jennifer F
Published: January 2020

This article takes the commission of an elaborate and life-like obstetrical machine by the Italian midwifery instructor, Vincenzo Malacarne, in 1791 as a starting point for considering the ways that medical practitioners were renegotiating the relationship between the senses at the end of the eighteenth century. In particular, it focuses on the cultivation of touch as an authoritative and professionalised source of bodily knowledge. The article argues that Malacarne's obstetrical machine reflects an important moment of transition in the way medical practitioners were trained to interact with female patients, in which the manual exploration of a woman’s genitals was re-contextualised as an expression of scientific rationality and medical authority. A close examination of the use of obstetrical machines in midwifery training suggests, moreover, that women, too, whose touch had often been accused of irrationality and ignorance, had to be taught how to perform manual procedures in a rational and scientific manner.
Association Between Inflammatory Biomarkers and Nonspecific Low Back Pain
Authors: Lim Yuan Z. , Wang Yuanyuan , Cicuttini Flavia M. , Hughes Harrison J. , Chou Louisa , Urquhart Donna M. , Ong Pei Xuan , Hussain Sultana Monira
Published: January 2020

Objectives:

Chronic inflammation increases the production of cytokines and activates proinflammatory pathways which may lead to nonspecific low back pain (LBP). We systematically reviewed the literature to investigate whether inflammatory biomarkers are associated with nonspecific LBP.

Materials and Methods:

CINAHL, Medline, and Embase were searched between January 1946 and May 2018. MeSH terms and key words were used to identify studies examining the association between inflammatory biomarkers and LBP. Two reviewers performed the risk of bias assessment and 3 reviewers extracted data independently. Qualitative evidence synthesis was performed.

Results:

Thirteen studies, ranging from fair to low quality, were included. Five studies examined the association between C-reactive protein (CRP)/high-sensitivity CRP and LBP; 6 studies assessed tumor necrosis factors (TNFs); 8 studies assessed interleukins (ILs); and 2 studies assessed fibrinogen. There was evidence for an association of elevated levels of CRP, TNFs, and IL-6 with LBP. There was conflicting evidence for an association between IL-1β, fibrinogen, and LBP.

Discussion:

Our findings support the notion of a positive association between inflammatory biomarkers and nonspecific LBP, specifically for CRP, TNFs, and IL-6. Although further high quality longitudinal studies are needed to confirm these findings and evaluate the magnitude of these associations, our findings suggest a role of inflammation in the pathogenesis of nonspecific LBP.
Early for Everyone
Authors: Quinn Megan , Weiss Alyssa B. , Crist Janice D.
Published: January 2020

Background:

Palliative care (PC) in the neonatal intensive care unit (NICU) is often provided exclusively to infants expected to die. Standards of care support providing PC early after diagnosis with any condition likely to impact quality of life.

Purpose:

To determine the state of early PC practice across populations to derive elements of early PC applicable to neonates and their families and demonstrate their application in practice.

Search Strategy:

Multiple literature searches were conducted from 2016 to 2019. Common keywords used were: palliative care; early PC; end of life, neonate; NICU; perinatal PC; pediatric PC; family-centered care; advanced care planning; palliative care consultant; and shared decision-making.

Findings:

Early PC is an emerging practice in adult, pediatric, and perinatal populations that has been shown to be helpful for and recommended by families. Three key elements of early PC in the NICU are shared decision-making, care planning, and coping with distress. A hypothetical case of a 24-week infant is presented to illustrate how findings may be applied. Evidence supports expansion of neonatal PC to include infants and families without terminal diagnoses and initiation earlier in care.

Implications for Practice:

Involving parents more fully in care planning activities and decision-making and providing structured support for them to cope with distress despite their child's prognosis are essential to early PC.

Implications for Research:

As early PC is incorporated into practice, strategies should be evaluated for feasibility and efficacy to improve parental and neonatal outcomes. Researchers should consider engaging NICU parent stakeholders in leading early PC program development and research.
Outcome Metrics in Pediatric Sports Medicine: Do PROMIS Computer-adaptive Testing Metrics Correlate With Pedi-IKDC?
Authors: Schafer Kevin A. , Minaie Arya , Nepple Jeffrey J.
Published: January 2020

Background:

A modified version of the International Knee Documentation Committee (IKDC), the Pedi-IKDC, is a validated patient-reported outcome measure in pediatric patients with knee pain. However, this questionnaire is lengthy and can fatigue patients, leading to inconsistent outcome collection. Thus, we sought to compare more easily attainable Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing patient reported outcomes to the gold standard Pedi-IKDC.

Methods:

We prospectively collected PROMIS scores and Pedi-IKDC scores in 100 new, consecutive patients presenting with knee pain to a pediatric sports medicine practice. Patients were excluded if they provided an incomplete Pedi-IKDC, had prior ipsilateral lower extremity surgery, or significant associated medical comorbidities. PROMIS domains including Mobility, Pain Interference, and Upper Extremity (control) were compared with the Pedi-IKDC with Pearson correlations. The number of questions in each metric was analyzed. Floor and ceiling effects of each test were also assessed.

Results:

The average age of the study cohort was 14 years (range, 7 to 18  y) with 53% female and 47% male. 70% of patients completed the Pedi-IKDC questionnaire, compared with 100% with PROMIS tests. The average Pedi-IKDC score was 48.8±22.3 (range, 5.4 to 100). Mean scores for Mobility, Pain Interference, and Upper Extremity domains were 38.4±10.1, 53.5±10.3, and 49.7±8.7, respectively. All tests demonstrated similar and acceptable floor and ceiling effects (<15%). The length of the Pedi-IKDC (22 questions) was roughly double that of combined PROMIS Pain Interference and Mobility tests (11.9±2.3 questions). Pedi-IKDC scores correlated with tested PROMIS measures (Mobility/Pain Interference, r=0.42/−0.49). When 7 highly functional patients with significant pain symptoms were removed for a secondary analysis, Mobility and Pain correlations improved to 0.69 and −0.67, respectively.

Conclusions:

PROMIS Mobility and Pain scores demonstrate moderate correlations with the Pedi-IKDC, highlighting these tests are not capturing the same patient experiences. These correlations are weakened by a small group of painful yet highly functioning patients. The Pedi-IKDC was significantly longer and had a much lower completion rate than PROMIS tests, highlighting a need for a validated computer adaptive testing in evaluating pediatric patients with knee pain.

Levels of Evidence:

Level II.
Predicting Radial Head Instability in Multiple Hereditary Exostoses (MHE): A Multicenter Analysis of Risk Factors
Authors: Meza Blake C. , Obana Kyle K. , Talathi Nakul S. , Shah Apurva S. , Lightdale-Miric Nina , Arkader Alexandre
Published: January 2020

Background:

Forearm deformity occurs in one third of patients with multiple hereditary exostoses (MHE). Conservative and surgical treatment are aimed at preventing radial head subluxation and/or dislocation. Dislocation has been associated with isolated distal ulnar lesions, radial bowing, and ulnar shortening. Risk factors for radial head subluxation have not been clearly elucidated. This study aimed to identify risk factors for all radial head instability in MHE, to optimize early detection and prevent frank dislocation.

Methods:

This multicenter retrospective case-control investigation included MHE patients with forearm lesions seen between 2000 and 2017 at 2 tertiary care children’s hospitals. Demographic, clinical factors, radiographic measures, and surgical history were quantified. Comparisons were made between forearms that developed radial head instability versus those that remained stable and between those that progressed to radial head subluxation versus those that progressed to dislocation.

Results:

This study included 171 forearms in 113 patients with MHE, who presented at a mean age of 8.0 years with a median follow-up time of 6.0 years. Nine forearms progressed to radial head subluxation (mean age: 10.2 y), and 24 forearms had radial head dislocation (mean age: 9.9 y). Five subluxations and 3 dislocations occurred despite preventative surgery. Initial radial bowing (7.2% vs. 8.5%, P=0.04), ulnar variance (−5.8% vs. 11.0%, P<0.001), and ulnar shortening (−2.5 vs. 9.1 mm, P=0.04) were predictive of radial head instability. Distal ulnar lesions and more severe ulnar variance (−5.8 vs. −10.6, P<0.001) and shortening (−2.5 vs. 13.2 mm, P=0.02) were associated with an increased risk of radial head subluxation. No significant differences were identified between forearms that progressed to subluxation versus those that progressed to dislocation.

Conclusions:

Distal ulnar lesions and radiographic measures can be used to determine the risk of radial head instability in MHE. Ulnar variance and shortening are early identifiable risk factors for radial head subluxation that can help guide monitoring and treatment. Radial bowing may be a late predictor of instability.

Level of Evidence:

Level III—prognostic.
Open Ankle Arthrodesis: Transfibular Approach
Authors: Sripanich Yantarat , Steadman Jesse , Valderrabano Victor , Barg Alexej
Published: January 2020

Ankle arthrodesis is a well-established surgical treatment for patients suffering from end-stage ankle osteoarthritis. This procedure can be executed by surgeons through various techniques. Among these methods is the open transfibular approach, which is utilized by the senior author as a routine procedure to treat the degenerative articulation. Outcomes of primary open ankle arthrodesis operations and cases necessitating a revision following a primary procedure were assessed through retrospective data and collective experience and were found to be similar to comparable postoperative complication rates.

Level of Evidence: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Gut microbial species and metabolic pathways associated with response to treatment with immune checkpoint inhibitors in metastatic melanoma
Authors: Wind Thijs T. , Gacesa Ranko , Vich Vila Arnau , de Haan Jacco J. , Jalving Mathilde , Weersma Rinse K. , Hospers Geke A.P.
Published: January 2020

In patients with metastatic cancer, gut microbiome composition differs between responder and non-responders to immune checkpoint inhibitors. However, there is little consensus on the microbiome taxa associated with response or lack of response. Additionally, recognized confounders of gut microbiome composition have generally not been taken into account. In this study, metagenomic shotgun sequencing was performed on freshly frozen pre-treatment stool samples from 25 patients (12 responders and 13 non-responders) with unresectable metastatic melanoma treated with immune checkpoint inhibitors. We observed no significant differences in alpha-diversity and bacterial prevalence between responders and non-responders (P > 0.05). In a zero-inflated multivariate analysis, correcting for important confounders such as age, BMI and use of antibiotics, 68 taxa showed differential abundance between responders and non-responders (false-discovery rate < 0.05). Cox-regression analysis showed longer overall survival for carriers of Streptococcus parasanguinis [hazard ratio (HR): 6.9] and longer progression-free survival for carriers of Bacteroides massiliensis (HR: 3.79). In contrast, carriership of Peptostreptococcaceae (unclassified species) was associated with shorter overall survival (HR 0.18) and progression-free survival (HR 0.11). Finally, 17 microbial pathways differentially abundant between responder and non-responders were observed. These results underline the association between gut microbiome composition and response to immune checkpoint inhibitor therapy in a cohort of patients with cutaneous melanoma.
Parental preconception and prenatal urinary bisphenol A and paraben concentrations and child behavior
Authors: Skarha Julianne , Messerlian Carmen , Bellinger David , Mínguez-Alarcón Lidia , Romano Megan E. , Ford Jennifer B. , Williams Paige L. , Calafat Antonia M. , Hauser Russ , Braun Joseph M.
Published: January 2020

Background:

Epidemiologic studies suggest that prenatal urinary bisphenol A (BPA) concentrations are associated with childhood behavior problems, but there is limited research on prenatal paraben concentrations. In rodent offspring, preconception maternal BPA exposure caused behavioral problems and paraben exposure impacted sperm quality. However, the effects of parental preconception and prenatal BPA and paraben exposure on children’s neurodevelopment are unknown.

Methods:

The Environment and Reproductive Health (EARTH) Study is a prospective cohort of couples from a fertility clinic at Massachusetts General Hospital. The Centers for Disease Control and Prevention (CDC) quantified BPA, butylparaben, ethylparaben, methylparaben, and propylparaben concentrations in multiple urine samples collected before conception and during pregnancy. From the eligible parents (N = 220), we enrolled 158 children between 2 and 9 years of age. The parents completed the Behavior-Assessment-System-for-Children-2 (BASC-2). We estimated covariate-adjusted associations of average parental preconception and prenatal ln-transformed urinary BPA and sum of paraben concentrations (∑paraben) with BASC-2 scores using linear regression with generalized estimating equations.

Results:

Median urinary BPA and Σparaben concentrations were 1.2 and 189 μg/L in mothers preconception and 1.7 and 25 μg/L in fathers preconception, respectively. Among all children, parental BPA and ∑paraben concentrations were not associated with BASC-2 behavioral symptoms index, internalizing, or externalizing problems scores. Point estimates ranged from −1.5 to 1.4 with wide 95% confidence intervals that included the null value.

Conclusion:

In this fertility clinic cohort, parental preconception and maternal prenatal BPA and paraben concentrations were not associated with problem behaviors among children. However, our small sample sizes reduced the precision of our results.
Renal denervation in patients with end-stage renal disease and resistant hypertension on long-term haemodialysis
Authors: Scalise Filippo , Sole Andrea , Singh Gurbhej , Sorropago Antonio , Sorropago Giovanni , Ballabeni Cinzia , Maccario Massimo , Vettoretti Simone , Grassi Guido , Mancia Giuseppe
Published: January 2020

Introduction:

Recent randomized controlled trials have confirmed the ability of renal denervation to lower blood pressure (BP) in patients, resistant to the BP-lowering effect of multiple antihypertensive drug administration. Evidence is limited, however, in patients with end-stage renal disease (ESRD) and haemodialysis, a condition in which a persistent BP elevation, despite administration of many antihypertensive drugs, is common. Aim of the present study was to test the BP-lowering efficacy of renal denervation in patients with resistant hypertension and ESRD on haemodialysis. BP was measured repeatedly in the office and over the 24 h during 1-year follow-up.

Methods and results:

The study was conducted from February 2017 to January 2018 at the Policlinico of Monza, Monza, Italy. We included 24 men and women aged at least 20 years (mean 55 ± 16) who had ESRD, were on long-term haemodialysis and exhibited resistant hypertension, that is, elevated office and ambulatory BP values, despite multidrug antihypertensive treatment (n = 5.4 ± 1). We excluded patients with renal artery stenosis, malignancy, and a probable life expectancy less than 1 year. Twelve patients were included in the renal denervation and 12 in the medical treatment (control) group. All patients underwent office and 24 h ambulatory BP measurements at baseline and at 1, 6 and 12 months during the follow-up. In the renal denervation group, baseline office and 24 h mean SBP were 180 ± 112 and 175 ± 11 mmHg, respectively, the corresponding values in the control group being 181 ± 19 and 181 ± 20 mmHg. Most of the other baseline characteristics were also similar or only slightly different between groups, including the mean number of administered antihypertensive drugs at baseline. SBP showed an early and persistent reduction after renal denervation (office SBP: 165 ± 13; 150 ± 7 and 149 ± 11mmHg; 24 h SBP 163 ± 20, 148 ± 10 and 149 ± 17 mmHg after 1, 6 and 12 months, respectively). The BP-lowering effect was almost always present and statistically significant during both the day and night. DBP changes followed a similar pattern whereas heart rate never showed any significant change. No significant periprocedural complication of renal denervation was seen. The mean number of administered drugs did not show any significant BP change during the study.

Conclusion:

In ESRD patients under long-term haemodialysis in whom BP was markedly elevated despite administration of many antihypertensive drugs, renal denervation lowered both ambulatory and office BP. The reduction persisted over a 1-year follow-up.
Usefulness of Prestorage Corneal Swab Culture in the Prevention of Contaminated Corneal Tissue in Corneal Transplantation
Authors: Szigiato Andrei-Alexandru , Anderson Maude , Mabon Michèle , Germain Marc , Durr Georges M. , Labbé Annie-Claude
Published: January 2020

Purpose:

To assess the efficacy of the prestorage corneal swab (PCS) culture to screen for corneal graft contamination after storage in Optisol-GS.

Methods:

A retrospective analysis of all PCS cultures was performed at the Eye Bank of Québec in Hôpital Maisonneuve-Rosemont from September 2013 to June 2016. Whole corneal culture was performed on rejected grafts because of a positive PCS, and a contamination rate was calculated. In addition, contamination rates of corneoscleral rims were compared between corneas tested with PCS and those of imported corneas which did not have PCS.

Results:

Among the 1966 PCS cultures performed, 814 (41.4%) were positive for growth. Pathogenic bacteria were present in 144 (7.3%) corneas, including Staphylococcus aureus (n = 96, 11.8% of all positive cultures), Enterobacteriaceae (n = 14, 1.7%), and Pseudomonas aeruginosa (n = 6, 0.7%). After preservation in Optisol-GS, only 7 (6.9%) corneas remained contaminated (95% confidence interval 5.1–9.3). The sensitivity of the PCS culture was 87.5% (95% confidence interval 47.4–99.7). There was no significant difference in corneoscleral rim contamination between corneas tested with PCS (1/388; 0.2%) compared with imported, nonswabbed corneas (3/214; 1.4%) (P = 0.131). Therefore, the cost to recover the loss of tissue rejected because of false-positive PCS by purchasing corneal tissue was calculated to be $142,884 (CAD) per year.

Conclusions:

Despite the high sensitivity of PCS cultures, there was no significant reduction of infection after corneal transplantation using this technique. In consequence, 93% of the corneas possibly suitable for transplantation were rejected. This suggests that the PCS culture alone is a poor test for detecting clinically relevant corneal contamination.
Congenital Cytomegalovirus and Autoimmune Neutropenia
Authors: Penner Justin , Chan Claire S.-Y. , Burns James E. , Ali Sakina , Lyall Hermione
Published: January 2020

Background:

Congenital cytomegalovirus (CCMV) accounts for high rates of infant morbidity and mortality. Neutropenia is a common finding in CCMV infection, of which the age of presentation overlaps with autoimmune neutropenia (AIN). AIN represents one of the most common forms of chronic neutropenia in childhood.

Methods:

A literature search exploring biologic associations between CCMV and AIN was conducted: PubMed (MEDLINE), Ovid and Web of Science. We further describe 2 cases of concurrent CCMV and AIN. Both cases were confirmed with the indirect granulocyte immunofluorescence test and alternative etiologies for neutropenia excluded.

Results:

Our 2 patients represent confirmed cases of AIN in infants with CCMV. One patient demonstrated neutropenia while undergoing treatment with Valganciclovir, while the other was never treated. With interruption of Valganciclovir in infant A, neutrophil counts (ANC) did not improve and upon resumption of treatment ANC remained static.

Conclusions:

Further studies examining a possible biologic link between CCMV and AIN are advocated for. We encourage clinicians to actively consider AIN in the differential diagnosis of all infants with CCMV presenting with neutropenia.
PD-L1 and PD-L2 Expression Levels Are Low in Primary and Secondary Adenoid Cystic Carcinomas of the Orbit: Therapeutic Implications
Authors: Wolkow Natalie , Jakobiec Frederick A. , Afrogheh Amir H. , Kidd Martin , Eagle Ralph C. , Pai Sara I. , Faquin William C.
Published: January 2020

Purpose:

To determine if there is a biologic rationale for using checkpoint inhibitor drugs targeting programmed cell death ligand 1 (PD-L1) and PD-L2 in the treatment of adenoid cystic carcinoma of the orbit.

Methods:

Twenty-three cases of adenoid cystic carcinoma involving the orbit (13 primary lacrimal gland, 5 secondarily extending into the orbit, and 5 unspecified) were examined histopathologically. Immunohistochemistry for PD-L1, PD-L2, and CD8 was performed. Charts were reviewed for clinical correlations.

Results:

Expression of PD-L1 and of PD-L2 was overall low in adenoid cystic carcinoma (mean expression 1.4 ± 0.9 of 5 for PD-L1, mean 0.83 ± 1.1 of 5 for PD-L2), and tumor-infiltrating CD8-positive T-lymphocytes were sparse (mean 1.1 ± 0.51 of 3). Only 13 of the 23 (57%) cases expressed PD-L1 as a combined positive score ≥1 of cells. No associations were found between expression levels of these markers and patient sex, tumor site of origin, Tumor, Node, Metastasis stage, or patient outcome. A significant association was observed between stromal PD-L1 expression and tumor histopathologic subtype (p = 0.05), and between tumor PD-L1 expression and prior exposure to radiation (p = 0.03).

Conclusions:

Checkpoint inhibitor drugs may have limited impact in the treatment and clinical course of orbital adenoid cystic carcinoma based on the low frequency of CD8 infiltrate and low expression of PD-L1 and PD-L2. Pretreatment with radiation, however, may improve tumor response to checkpoint inhibitor drugs.
Adenovirus infection and subsequent risk of Kawasaki disease: A population-based cohort study
Authors: Huang Shih-Hui , Chen Chun-Yu , Weng Ken-Pen , Chien Kuang-Jen , Hung Yao-Min , Hsieh Kai-Sheng , Lin Chu-Chuan , Cheng Ming-Fang , Lin Cheng-Li , Wei James Cheng-Chung
Published: January 2020

Background:

The relationship between adenovirus infection and Kawasaki disease (KD) is unclear. The purpose of this study was to determine the relationship between adenovirus infection and KD using a cohort study in Taiwan.

Methods:

We used Taiwan National Health Insurance data (from 2000 to 2008) to conduct a population-based cohort study, analyzing children that was under 18 years of age. In total, 5280 children had adenovirus infection, and 5280 children without adenovirus infection were matched and followed up. Subsequent KD was the major outcome event. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence intervals (CIs) of developing KD associated with adenovirus infection.

Results:

There was a significantly higher cumulative incidence of KD in the adenovirus-infected cohort than that in the control cohort (log-rank test, p < 0.001). In the adenovirus-infected cohort, overall incidence of KD was 5.29 times higher than that of the control cohort (adjusted HR 5.29, 95% CI: 2.48–11.3). Increased KD risk was associated with previous adenovirus infection in children aged 3–5 years, in female patients, in those with a low urbanization level, and in those with allergies.

Conclusion:

An association between previous adenovirus infection and KD was identified in Taiwanese children, but other potential risk factors were not fully analyzed. The relationship between infection and KD requires further study.
Tranexamic acid is effective in decreasing postoperative intraarticular bleeding in arthroscopic knee surgery
Authors: Rodriguez-Merchan E.C.
Published: January 2020

Arthroscopic knee surgery to perform partial meniscectomy and anterior cruciate ligament (ACL) reconstruction is frequent and effective, although a possible complication is postoperative hemarthrosis. When intraarticular bleeding occurs, in addition to the associated pain, the patient usually requires joint aspiration (arthrocentesis) to avoid loss of range of motion (ROM). Sometimes this complication ends up associated with a poor result of surgery due to a loss of ROM. The aim of this narrative review of the literature is to attempt to clarify whether tranexamic acid (TXA) should be utilized in arthroscopic ACL reconstruction and arthroscopic meniscectomy and by what route (intraarticular or intravenous). A number of studies seem to favor the use of intravenous TXA in patients undergoing ACL reconstruction and arthroscopic synovectomy to diminish articular postoperative bleeding and its consequences (pain, swelling, loss of ROM, and the need for arthrocentesis). Regarding the use of intraarticular TXA, one in-vitro study has indicated that TXA in high concentrations is cytotoxic to chondrocytes. Common sense leads me to conclude that until better designed studies can confirm that intraarticular TXA is not cytotoxic to chondrocytes, its use should not be advised. Currently, for patients undergoing arthroscopic ACL reconstruction and arthroscopic meniscectomy, it seems safer to use intravenous TXA.
Clinical nutrition for the gastroenterologist: the physiologic rationale for providing early nutritional therapy to the hospitalized patient
Authors: McClave Stephen A. , Omer Endashaw
Published: January 2020

Purpose of review

Conflicting reports in the literature have been misinterpreted by clinicians, who conclude that nutritional therapy for the hospitalized patient is of marginal value. The true benefit of such therapy is derived from the provision of early enteral nutrition. This article describes the physiologic response to enteral feeding, which accounts for the outcome benefits, and illustrates how use of the gut alters immune responses and the intestinal microbiota.

Recent findings

The provision of early enteral nutrition has been shown to reduce infection and mortality in high-risk hospitalized patients (compared with not providing such therapy). Early feeding maintains gut integrity, reduces permeability, promotes tolerance and appropriate immune responses, and supports commensalism of the intestinal microbiota. Early enteral nutrition influences cross-talk signaling between luminal bacteria and the intestinal epithelium. Failure to utilize the gut in acute illness can amplify the systemic inflammatory response syndrome and worsen disease severity, while at the same time promoting antibiotic resistance and increased septic morbidity.

Appropriate nutritional therapy does change outcomes in the hospitalized patient, especially for those who are at risk on the basis of disease severity and/or poor nutritional status. Greatest benefit is seen from those therapeutic regimens that specifically target gut defenses and the intestinal microbiome.
Nurses' Perceptions of the Palliative Care Needs of Neonates With Multiple Congenital Anomalies
Authors: Şener Taplak Ayşe , Gürol Ayşe , Polat Sevinç
Published: January 2020

This study was conducted to determine neonatal intensive care unit (NICU) nurses' opinions about the palliative care needs of neonates with multiple congenital anomalies. The study sample consisted of the 20 nurses who agreed to participate in the study and worked in the NICU between November and December 2017. A one-to-one interview method was utilized using a semistructured interview form. Written consent was obtained from participants and reconfirmed verbally prior to data collection. In the study, most of the nurses stated that the therapeutic medical treatment should not be started for dying neonates with multiple congenital anomalies. It was also found that nurses did not have enough palliative care knowledge for neonates. The palliative care needs of the neonates with multiple congenital anomalies in NICUs were found to be pain management, infection care, enhancing quality of life by avoiding unnecessary medical practices, skin care, the care of the baby in the ventilator, timely application of the treatment of neonates, and supporting family.
Parasitic skin infections: neglected diseases or just challenging for diagnosis?
Authors: Gardini Giulia , Tomasoni Lina Rachele , Castelli Francesco
Published: January 2020

Purpose of review

The aim of the article is to review the most recent evidence concerning parasitic skin infections.

Recent findings

Parasitic skin infections are increasingly reported worldwide. Special at-risk categories are migrants, returning travelers, and immunocompromised individuals, who are at higher risk to present disseminated disease. The number of reported cases is growing even outside the endemic areas as a consequence of international travels, migration flows, increasing immunocompromised population, climate change, and natural disasters.

Skin parasitoses are neglected infections. Funding assigned to prevent and treat them is limited, even if they affect millions of persons worldwide. Diagnosis could be a challenge for clinicians of high-income countries who are facing an increasing number of such infections related to great epidemiological events.
The Potential of Integrated Nurse-Led Models to Improve Care for People With Functional Gastrointestinal Disorders
Authors: Linedale Ecushla C. , Mikocka-Walus Antonina , Gibson Peter R. , Andrews Jane M.
Published: January 2020

Functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia are extremely common, debilitating, and costly. Although diagnostic guidelines and effective management options exist, management is suboptimal, with long waiting lists, delayed diagnosis, and poor patient outcomes. The aim of this systematic review was to explore and evaluate evidence for existing models of care for functional gastrointestinal disorders. Thirty-eight studies pertaining to the diagnosis or management of functional gastrointestinal disorders were found; however, only 6 investigated a full model of care. Five studies assessed a nurse-led model and 1 a structured gastroenterologist consultation. Nurse-led models were cheaper to current treatments and resulted in symptomatic improvement, high patient satisfaction, reduced healthcare usage, and improved psychosocial functioning and quality of life, whereas standard gastroenterological care did not alleviate pain or improve quality of life. There is minimal research trialing integrated models of care for the diagnosis and management of functional gastrointestinal disorders. This represents a lost opportunity for timely and effective healthcare provision to a large patient group. Although low in quality, preliminary data suggest that integrated nurse-led models of care are economically viable and may facilitate timely diagnosis and management and improve patient outcomes. Furthermore, studies to robustly evaluate the efficacy, safety, and acceptability of such models are needed.
Medication Adherence Across the Life Span in Inflammatory Bowel Disease
Authors: Knowles Simon R. , Alex George
Published: January 2020

This article reviews the differences and similarities in medication adherence between adolescent and adult cohorts with inflammatory bowel disease. The review covers the rates of medication adherence, as well as predictors, consequences, and related interventions. Rates of adherence were more favorable among adolescents (65%–90%) than among adults (55%–70%). Major risk factors for poor adherence in adolescents include low medication knowledge, not establishing good medication habits initially, and peer victimization with low social support. For adults, nonadherence is more frequently unintentional (e.g., forgetting) and occurs more often in the context of a poor-quality patient–physician relationship, low medication knowledge, infrequent/missed appointments, busy lifestyle, and concurrent mental health concerns. Nonadherence to medication is associated with worsening of symptoms and risk of relapse in adults and adolescents. Nurses can play a significant role in influencing adherence to medication in patients with inflammatory bowel disease. In particular, nurses can help to impart knowledge on the importance of medication and identify factors that may help or hinder an individual in terms of adherence. Based on the current review, implications for practice and recommendations for nurses to promote medication adherence across both adolescent and adult cohorts are provided. Limitations of the currently available evidence and suggestions for future research are discussed.
Prevalence of Female Urinary Incontinence in Crossfit Practitioners and Associated Factors: An Internet Population-Based Survey
Authors: Poli de Araújo Maita , Brito Luiz Gustavo Oliveira , Rossi Fabiana , Garbiere Maria Luiza , Vilela Maria Eduarda , Bittencourt Vitor Ferraz
Published: January 2020

Objectives

CrossFit comprises a set of high-intensity, high-impact exercises that includes movements that may increase intra-abdominal pressure and cause involuntary loss of urine. There is scant literature about the prevalence of urinary incontinence (UI) in female crossfitters, as well as its associated factors.

Methods

A population-based Internet survey stored in a website created with information on the benefits and risks of CrossFit for women’s health (https://crosscontinencebr.wixsite.com/crosscontinencebr) invited female crossfitters. In total, 551 women answered an online questionnaire, and the demographic variables (age, marital status, and parity), anthropometric data (weight, height, and body mass index), and the presence of UI during exercises were also investigated. The prevalence of UI and its associated factors were calculated using a logistic regression model. The significance level was set at 5%.

Results

The overall prevalence of UI during CrossFit exercises was 29.95%, and most women with UI reported loss of urine during at least one exercise (16.70%). Women with UI were older (33.77 ± 8.03 years) than those without UI (30.63 ± 6.93 years; P < 0.001). Double under (20.15%) and single under (7.99%) were the exercises that were most frequently associated with UI and also the only variables that remained in the final model that caused UI. The duration of CrossFit practice, number of days per week practicing CrossFit, daily time practice, previous vaginal delivery, and mean birth weight were not statistically associated with UI.

Conclusions

One-third of female crossfitters presented with UI during exercise. Double under was the exercise that was the most associated with UI.