bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of biofilm formation bySporothrix schenckii
Authors: Sánchez-Herrera Rocío , Flores-Villavicencio Lérida Liss , Pichardo-Molina Juan Luis , Castruita-Domínguez José Pedro , Aparicio-Fernández Xochilt , Sabanero López Myrna , Villagómez-Castro Julio Cesar
Published: May 2020

The development of mature biofilms is an aid in numerous aspects of the life cycle of fungi. It is well known that Sporothrix schenckii complex causes a benign subcutaneous mycosis, but recent studies have suggestedthat biofilm formation may be one of the important factors involved in its virulence. Here we report the study of the biomass organization and a model of the stages of S. schenckii biofilm development: adsorption, active adhesion, microcolony formation, maturation, and dispersal of biofilm fragments. During the development, the biofilm is surrounded by extracellular matrix, which contains glycoprotein (mannose rich), carbohydrates, lipids, and nucleic acid. In addition, the extracellular DNA increases in extracellular matrix as a key component to structural integrity and antifungal resistance. The study of S. schenckii biofilm contributes to a better understanding of growth biofilm and physiology, adding new insights into the mechanisms of virulence and persistence of pathogenic microorganisms.
The VANDELS survey: a strong correlation between Ly α equivalent width and stellar metallicity at 3 ≤ z ≤ 5
Authors: Cullen F , McLure R J , Dunlop J S , Carnall A C , McLeod D J , Shapley A E , Amorín R , Bolzonella M , Castellano M , Cimatti A , Cirasuolo M , Cucciati O , Fontana A , Fontanot F , Garilli B , Guaita L , Jarvis M J , Pentericci L , Pozzetti L , Talia M , Zamorani G , Calabrò A , Cresci G , Fynbo J P U , Hathi N P , Giavalisco M , Koekemoer A , Mannucci F , Saxena A
Published: May 2020

We present the results of a new study investigating the relationship between observed Ly α equivalent width (Wλ(Ly α)) and the metallicity of the ionizing stellar population ( Z⋆) for a sample of 768 star-forming galaxies at 3 ≤ z ≤ 5 drawn from the VANDELS survey. Dividing our sample into quartiles of rest-frame Wλ(Ly α) across the range $-58 \,\rm {\mathring{\rm A}} \lesssim$Wλ(Ly α) $\lesssim 110 \,\rm {\mathring{\rm A}}$, we determine  Z⋆ from full spectral fitting of composite far-ultraviolet spectra and find a clear anticorrelation between Wλ(Ly α) and  Z⋆. Our results indicate that  Z⋆ decreases by a factor ≳ 3 between the lowest Wλ(Ly α) quartile (〈Wλ(Ly α)$\rangle =-18\,\rm {\mathring{\rm A}}$) and the highest Wλ(Ly α) quartile (〈Wλ(Ly α)$\rangle =24\,\rm {\mathring{\rm A}}$). Similarly, galaxies typically defined as Lyman alpha emitters (LAEs; Wλ(Ly α) $\gt 20\,\rm {\mathring{\rm A}}$) are, on average, metal poor with respect to the non-LAE galaxy population (Wλ(Ly α) $\le 20\,\rm {\mathring{\rm A}}$) with  Z⋆non-LAE ≳ 2 ×  Z⋆LAE. Finally, based on the best-fitting stellar models, we estimate that the increasing strength of the stellar ionizing spectrum towards lower  Z⋆ is responsible for ${\simeq}15{-}25{{\ \rm per\ cent}}$ of the observed variation in Wλ(Ly α) across our sample, with the remaining contribution (${\simeq}75{-}85{{\ \rm per\ cent}}$) being due to a decrease in the H i/dust covering fractions in low- Z⋆ galaxies.
On building a cluster watchlist for identifying strongly lensed supernovae, gravitational waves and kilonovae
Authors: Ryczanowski Dan , Smith Graham P , Bianconi Matteo , Massey Richard , Robertson Andrew , Jauzac Mathilde
Published: May 2020

Motivated by discovering strongly lensed supernovae, gravitational waves, and kilonovae in the 2020s, we investigate whether to build a watchlist of clusters based on observed cluster properties (i.e. lens-plane selection) or on the detectability of strongly lensed background galaxies (i.e. source-plane selection). First, we estimate the fraction of high-redshift transient progenitors that reside in galaxies that are themselves too faint to be detected as being strongly lensed. We find ∼15–50 per cent of transient progenitors reside in z = 1 − 2 galaxies too faint to be detected in surveys that reach AB ≃ 23, such as the Dark Energy Survey. This falls to ≲10 per cent at depths that will be probed by early data releases of LSST (AB ≃ 25). Secondly, we estimate a conservative lower limit on the fraction of strong-lensing clusters that will be missed by magnitude-limited searches for multiply imaged galaxies and giant arcs due to the faintness of such images. We find that DES-like surveys will miss ∼75 per cent of 1015 M⊙ strong-lensing clusters, rising to ∼100 per cent of 1014 M⊙ clusters. Deeper surveys, such as LSST, will miss ∼40 per cent at 1015 M⊙ and ∼95 per cent at 1014 M⊙. Our results motivate building a cluster watchlist for strongly lensed transients that includes those found by the lens-plane selection.
Two-moment scheme for general-relativistic radiation hydrodynamics: a systematic description and new applications
Authors: Weih Lukas R , Olivares Hector , Rezzolla Luciano
Published: May 2020

We provide a systematic description of the steps necessary – and of the potential pitfalls to be encountered – when implementing a two-moment scheme within an implicit–explicit (IMEX) scheme to include radiative-transfer contributions in numerical simulations of general-relativistic (magneto-)hydrodynamics (GRMHD). We make use of the M1 closure, which provides an exact solution for the optically thin and thick limits, and an interpolation between these limits. Special attention is paid to the efficient solution of the emerging set of implicit conservation equations. In particular, we present an efficient method for solving these equations via the inversion of a 4 × 4-matrix within an IMEX scheme. While this method relies on a few approximations, it offers a very good compromise between accuracy and computational efficiency. After a large number of tests in special relativity, we couple our new radiation code, frac, with the GRMHD code bhac to investigate the radiative Michel solution, namely, the problem of spherical accretion on to a black hole in the presence of a radiative field. By performing the most extensive exploration of the parameter space for this problem, we find that the accretion’s efficiency can be expressed in terms of physical quantities such as temperature, T, luminosity, L, and black hole mass, M, via the expression $\varepsilon =(L/L_{\rm Edd})/(\dot{M}/\dot{M}_{\rm Edd})= 7.41\times 10^{-7}\left(T/10^6\, \mathrm{K}\right)^{0.22} \left(L/L_\odot \right)^{0.48} \left(M/M_\odot \right)^{0.48}$, where LEdd and $\dot{M}_{\mathrm{Edd}}$ are the Eddington luminosity and accretion rate, respectively. Finally, we also consider the accretion problem away from spherical symmetry, finding that the solution is stable under perturbations in the radiation field.
What causes the fragmentation of debris streams in TDEs?
Authors: Sacchi Andrea , Lodato Giuseppe , Toci Claudia , Motta Valentina
Published: May 2020

A tidal disruption event (TDE) occurs when a star passes too close to a supermassive black hole and gets torn apart by its gravitational tidal field. After the disruption, the stellar debris form an expanding gaseous stream. The morphology and evolution of this stream are particularly interesting as it ultimately determines the observational properties of the event itself. In this work, we perform 3D hydrodynamical simulations of the TDE of a star modelled as a polytropic sphere of index γ = 5/3 and study the gravitational stability of the resulting gas stream. We provide an analytical solution for the evolution of the stream in the bound, unbound, and marginally bound cases, which allows us to describe the stream properties and analyse the time-scales of the physical processes involved, applying a formalism developed in star formation context. Our results are that, when fragmentation occurs, it is fuelled by the failure of pressure in supporting the gas against its self-gravity. We also show that a stability criterion that includes also the stream gas pressure proves to be far more accurate than one that only considers the black hole tidal forces, giving analytical predictions of the time evolution of the various forces associated with the stream. Our results point out that fragmentation occurs on time-scales longer compared with the observational windows of these events and is thus not expected to give rise to significant observational features.
Black widow evolution: magnetic braking by an ablated wind
Authors: Ginzburg Sivan , Quataert Eliot
Published: May 2020

Black widows are close binary systems in which a millisecond pulsar is orbited by a companion, a few per cent the mass of the sun. It has been suggested that the pulsar’s rotationally powered γ-ray luminosity gradually evaporates the companion, eventually leaving behind an isolated millisecond pulsar. The evaporation efficiency is determined by the temperature Tch ∝ F2/3 to which the outflow is heated by the flux F on a dynamical time-scale. Evaporation is most efficient for companions that fill their Roche lobes. In this case, the outflow is dominated by a cap around the L1 point with an angle θg ∼ (Tch/Tg)1/2, and the evaporation time is tevap = 0.46(Tch/Tg)−2 Gyr, where Tg > Tch is the companion’s virial temperature. We apply our model to the observed black widow population, which has increased substantially over the last decade, considering each system’s orbital period, companion mass, and pulsar spin-down power. While the original black widow (PSR B1957+20) evaporates its companion on a few Gyr time-scale, direct evaporation on its own is too weak to explain the overall population. We propose instead that the evaporative wind couples to the companion’s magnetic field, removes angular momentum from the binary, and maintains stable Roche lobe overflow. While a stronger wind carries more mass, it also reduces the Alfvén radius, making this indirect magnetic braking mechanism less dependent on the flux $t_{\rm mag}\propto t_{\rm evap}^{1/3}$. This reduces the scatter in evolution times of observed systems, thus better explaining the combined black widow and isolated millisecond pulsar populations.
Clinical, molecular, and radiomic profile of gliomas with FGFR3-TACC3 fusions
Authors: Di Stefano Anna Luisa , Picca Alberto , Saragoussi Edouard , Bielle Franck , Ducray Francois , Villa Chiara , Eoli Marica , Paterra Rosina , Bellu Luisa , Mathon Bertrand , Capelle Laurent , Bourg Véronique , Gloaguen Arnaud , Philippe Cathy , Frouin Vincent , Schmitt Yohann , Lerond Julie , Leclerc Julie , Lasorella Anna , Iavarone Antonio , Mokhtari Karima , Savatovsky Julien , Alentorn Agusti , Sanson Marc ,   TARGET study group
Published: May 2020

Background

Actionable fibroblast growth factor receptor 3 (FGFR3)–transforming acidic coiled-coil protein 3 fusions (F3T3) are found in approximately 3% of gliomas, but their characteristics and prognostic significance are still poorly defined. Our goal was to characterize the clinical, radiological, and molecular profile of F3T3 positive diffuse gliomas.

Methods

We screened F3T3 fusion by real-time (RT)-PCR and FGFR3 immunohistochemistry in a large series of gliomas, characterized for main genetic alterations, histology, and clinical evolution. We performed a radiological and radiomic case control study, using an exploratory and a validation cohort.

Results

We screened 1162 diffuse gliomas (951 unselected cases and 211 preselected for FGFR3 protein immunopositivity), identifying 80 F3T3 positive gliomas. F3T3 was mutually exclusive with IDH mutation (P < 0.001) and EGFR amplification (P = 0.01), defining a distinct molecular cluster associated with CDK4 (P = 0.04) and MDM2 amplification (P = 0.03). F3T3 fusion was associated with longer survival for the whole series and for glioblastomas (median overall survival was 31.1 vs 19.9 mo, P = 0.02) and was an independent predictor of better outcome on multivariate analysis.

F3T3 positive gliomas had specific MRI features, affecting preferentially insula and temporal lobe, and with poorly defined tumor margins. F3T3 fusion was correctly predicted by radiomics analysis on both the exploratory (area under the curve [AUC] = 0.87) and the validation MRI (AUC = 0.75) cohort. Using Cox proportional hazards models, radiomics predicted survival with a high C-index (0.75, SD 0.04), while the model combining clinical, genetic, and radiomic data showed the highest C-index (0.81, SD 0.04).

Conclusion

F3T3 positive gliomas have distinct molecular and radiological features, and better outcome.
Bridging the treatment gap in infant medulloblastoma: molecularly informed outcomes of a globally feasible regimen
Authors: Baroni Lorena V , Sampor Claudia , Gonzalez Adriana , Lubieniecki Fabiana , Lamas Gabriela , Rugilo Carlos , Bartels Ute , Heled Ayala , Smith Kyle S , Northcott Paul A , Bouffet Eric , Alderete Daniel , Ramaswamy Vijay
Published: May 2020

Background

Infant medulloblastoma represents an enormous challenge in neuro-oncology, due to their simultaneous high-risk of recurrence and high risk of severe neurodevelopmental sequelae with craniospinal irradiation. Currently infant medulloblastoma are treated with intensified protocols, either comprising intraventricular methotrexate or autologous transplant, both of which carry significant morbidity and are not feasible in the majority of the world. We sought to evaluate the molecular predictors of outcome in a cohort of infants homogeneously treated with induction chemotherapy, focal radiation and maintenance chemotherapy.

Methods

In a retrospective analysis, 29 young children treated with a craniospinal irradiation sparing strategy from Hospital Garrahan in Buenos Aires were profiled using Illumina HumanMethylationEPIC arrays, and correlated with survival.

Results

Twenty-nine children (range, 0.3–4.6 y) were identified, comprising 17 sonic hedgehog (SHH), 10 Group 3/4, and 2 non-medulloblastomas. Progression-free survival (PFS) across the entire cohort was 0.704 (95% CI: 0.551–0.899). Analysis by t-distributed stochastic neighbor embedding revealed 3 predominant groups, SHHβ, SHHγ, and Group 3. Survival by subtype was highly prognostic with SHHγ having an excellent 5-year PFS of 100% (95% CI: 0.633–1) and SHHβ having a PFS of 0.56 (95% CI: 0.42–1). Group 3 had a PFS of 0.50 (95% CI: 0.25–1). Assessment of neurocognitive outcome was performed in 11 patients; the majority of survivors fell within the low average to mild intellectual disability, with a median IQ of 73.5.

Conclusions

We report a globally feasible and effective strategy avoiding craniospinal radiation in the treatment of infant medulloblastoma, including a robust molecular correlation along with neurocognitive outcomes.
The Application of Regional Cerebral Oxygenation Monitoring in the Prediction of Cerebral Hypoperfusion During Carotid Endarterectomy
Authors: Yu Bin , Peng Yuming , Qiao Hui , Liu Bin , Wang Mingran , Yang Xiaocui , Han Ruquan
Published: May 2020

Background:

The aim of this study was to assess the diagnostic ability of near-infrared spectroscopy-monitored regional cerebral oxygen saturation (rSO2) to detect cerebral hypoperfusion during internal carotid artery (ICA) clamping compared with motor and somatosensory evoked potential (EP) monitoring.

Methods:

This prospective study recruited consecutive patients undergoing carotid endarterectomy under general anesthesia. Significant EP changes (defined as >50% decrease in ipsilateral somatosensory EP amplitude or disappearance of contralateral motor EP on >2 consecutive stimulations) during ICA clamping were considered a warning sign for cerebral hypoperfusion. If significant EP changes occurred, the amplitude of the EPs and simultaneous rSO2 values were recorded before therapeutic intervention. The relationship between reductions in rSO2 and EP amplitudes was analyzed using Spearman rank-correlation analysis. Receiver operating characteristic curve analysis was used to calculate the optimal cutoff value for the relative reduction in rSO2. False-positive rates were evaluated according to immediate postoperative motor outcomes.

Results:

A total of 203 patients were included for analysis, of whom 23 developed significant EP changes during ICA clamping. There was a positive relationship between decreases in EP amplitude and rSO2 (R
2=0.15, P=0.02). A rSO2 reduction ≥16% from baseline had the optimal diagnostic performance for the detection of cerebral hypoperfusion (area under the receiver operating characteristic curve=0.82; 95% confidence interval: 0.76-0.87). The false-positive rate was 8.9%.

Conclusions:

Decreases in rSO2 correlated with decreases in EP amplitude during ICA clamping. A relative reduction in rSO2 ≥16% could serve as a warning for clamping-associated cerebral hypoperfusion. The 8.9% false-positive rate is a potential clinical limitation of the use of rSO2 to predict postoperative neurological deficits.
Close to Home
Authors: Ziegler Tammy Ruiz , Kuebelbeck Amy
Published: May 2020

Background:

Advances in prenatal testing and diagnosis have resulted in more parents learning during pregnancy that their child may die before or shortly after birth. These advances in testing and diagnosis have also resulted in more parents choosing, despite the diagnosis, to continue their pregnancies and pursue a palliative approach to their infant's short life. Perinatal hospice and palliative care is a growing model of care developed in response to these parents' previously unmet needs. A seldom-discussed opportunity to provide this care exists in outlying community hospitals, which are ideally placed to provide care close to home for families who have chosen comfort measures and time with their child.

Purpose:

This article reviews the definition and utility of perinatal palliative care, the population it serves, attempts to support a rational for development of community-based programs, and describes one community hospital's experience with perinatal palliative care in their community.*

Methods/Search Strategy:

This article describes the development and processes of a perinatal palliative care program at a community hospital in Fredericksburg, Virginia.

Implications for Practice:

Perinatal palliative care can be developed with the assistance of already existing training materials, resources, and staff. While the cohort of patients may be small, implementing perinatal palliative care in a community setting may result in wider availability of this care and more accessible options for these families.

Implications for Research:

Research possibilities include developing a template for creating a perinatal palliative care program at community hospitals that could be replicated elsewhere; assessing parental satisfaction and quality indicators of perinatal palliative care at community hospitals and at referral hospitals; and assessing outcomes in various settings.
The Use of Inhaled Nitric Oxide in Congenital Diaphragmatic Hernia
Authors: Novotny Ashley M.
Published: May 2020

Background:

Congenital diaphragmatic hernia (CDH) is a complex congenital defect of the diaphragm that allows abdominal contents to herniate into the chest cavity, altering pulmonary development, and leading to pulmonary hypoplasia and hypertension. Patient presentation is variable in severity, making management difficult. Many common management strategies have improved the survival rate of infants with CDH, including gentle ventilation and permissive hypercapnia. Inhaled nitric oxide (iNO) is a potent, pulmonary vasodilator that has shown to improve oxygenation while decreasing pulmonary pressure in infants with pulmonary hypertension. While many institutions utilize iNO in the treatment of pulmonary hypertension, the role of iNO as a treatment for CDH is controversial.

Purpose:

The purpose of this literature review is to establish a better understanding of CDH including embryology, patient presentation, and management strategies, and to analyze the use and effect of iNO on patients in this population.

Methods/Search Strategy:

A systemic search of PubMed, CINHAL, and Medline was performed to identify research articles studying the use of iNO on patients with pulmonary hypertension secondary to CDH.

Findings/Results:

Three studies were utilized in this review to assess the current use and effectiveness of iNO in patients with CDH.

Implications for Practice:

This review summarized the pathophysiology, embryology, patient presentation, and management strategies, as well as reviewed literature on the effectiveness of iNO on pulmonary hypertension secondary to CDH.

Implications for Research:

Further research is indicated to determine alternative treatment modalities and establish evidence-based practice protocols to standardize care in infants with CDH.
Physiological Stability in Very Preterm Infants During Skin-to-Skin Contact as Assessed by Near-Infrared Spectroscopy
Authors: Blomqvist Ylva Thernström , Karlsson Victoria , Dawit Feven , Sindelar Richard , Ågren Johan
Published: May 2020

Background:

Skin-to-skin contact (SSC) has been demonstrated to allow adequate thermal stability in high-technology settings with extremely preterm infants, while other aspects on how SSC influences basic physiological parameters have been less extensively investigated.

Purpose:

To evaluate physiological stability during SSC and incubator care in a group of preterm infants born at a gestational age (GA) of 32 weeks or less and receiving respiratory support.

Methods:

Descriptive, observational study including 10 preterm infants (GA 22-32 weeks, postnatal age 2-48 days) were evaluated during SSC compared with flanking time periods in the incubator. Cerebral and systemic regional oxygen saturation (rSao
2), pulse oximetry (Spo
2), heart rate (HR), and body temperature were recorded, and the fractional tissue oxygen extraction (fTOE) was calculated.

Results:

A total of 16 periods of SSC (mean duration 3 hours 30 minutes) were evaluated, 9 during nasal continuous positive airway pressure and 7 during mechanical ventilation. Cerebral rSao
2 was 68% ± 4% (SE) and 69% ± 4% during incubator care and SSC, respectively (P = .56). Somatic rSao2 was 64% ± 4% during incubator care and 66% ± 4% during SSC (P = .54). Also, fTOE, HR, and Spo
2 was similar during the 2 modes of care. Body temperature increased during SSC (P < .01).

Implications for Practice:

The present study reveals no differences in cerebral and somatic tissue oxygenation between periods of SSC and care in the incubator. The findings indicate that SSC supports physiological stability also during management of very preterm infants receiving respiratory support.

Implications for Research:

Further studies directed to further optimize SSC performance should enable its safe implementation at gradually lower gestational and postnatal ages.
Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas
Authors: Simon James A. , Al-Hendy Ayman , Archer David F. , Barnhart Kurt T. , Bradley Linda D. , Carr Bruce R. , Dayspring Thomas , Feinberg Eve C. , Gillispie Veronica , Hurtado Sandra , Kim JinHee , Liu Ran , Owens Charlotte D. , Muneyyirci-Delale Ozgul , Wang Alice , Watts Nelson B. , Schlaff William D.
Published: May 2020

OBJECTIVE:

To investigate the safety and efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy for up to 12 months in women with heavy menstrual bleeding associated with uterine leiomyomas.

METHODS:

Elaris UF-EXTEND was a phase 3 extension study that evaluated an additional 6 months (up to 12 months total) of elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg and norethindrone acetate 0.5 mg once daily) in women who completed an initial 6 months of the same treatment in one of two preceding phase 3 studies. The primary endpoint was the percentage of women with both less than 80 mL menstrual blood loss during final month and a 50% or greater reduction in menstrual blood loss from baseline to final month. Safety evaluations included adverse events and bone mineral density changes. The planned sample size of UF-EXTEND was based on estimated rollover and discontinuation rates in the two preceding studies.

RESULTS:

From September 2016 to March 2019, 433 women were enrolled in UF-EXTEND. Of these women, 218 received up to 12 months of elagolix with add-back therapy; the mean±SD age of this group was 42.4±5.4 years and 67.3% were black. The percentage of women who met the primary endpoint in this elagolix with add-back group was 87.9% (95% CI [83.4–92.3]). The most frequently reported adverse events with up to 12 months of elagolix plus add-back therapy were hot flush (6.9%), night sweats (3.2%), headache (5.5%), and nausea (4.1%). Mean percent decreases in bone mineral density from baseline to extension month 6 were significantly less with elagolix plus add-back therapy than with elagolix alone {between-group difference in lumbar spine: −3.3 (95% CI [−4.1 to −2.5])}.

CONCLUSION:

Up to 12 months of elagolix with add-back therapy provided sustained reduction in menstrual blood loss in women with uterine leiomyomas, with the addition of add-back therapy attenuating the hypoestrogenic effects of elagolix alone. No new or unexpected safety concerns were associated with an additional 6 months of elagolix with addback therapy.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02925494.

FUNDING SOURCE:

AbbVie Inc funded this study.
Vanishing Twins Conceived Through Fresh In Vitro Fertilization
Authors: Harris Amy L. , Sacha Caitlin R. , Basnet Kristen M. , James Kaitlyn E. , Freret Taylor S. , Kaimal Anjali J. , Yeh John , Souter Irene , Roberts Drucilla J. , Toth Thomas L.
Published: May 2020

OBJECTIVE:

To characterize the obstetric outcomes and placental pathology in live births arising from vanishing twin pregnancies compared with nonreduced in vitro fertilization (IVF) pregnancies.

METHODS:

This is a retrospective cohort study of live births resulting from fresh embryo transfers after IVF cycles with autologous oocytes from 2004 through 2017 at a large academic fertility center. Clinical information and pathology reports were reviewed. Placental diagnoses were coded using established nosology by expert placental pathologists. Analysis of variance, Kruskal-Wallis, Pearson's χ2, and Fisher exact tests were used, as appropriate, to compare pathology categories between pregnancy outcomes. Mixed effects logistic regression models were generated to reveal the association between pregnancy outcome and placenta pathology, controlling for pregnancies arising in the same woman and various suspected confounders.

RESULTS:

Of 905 fresh autologous IVF cycles with placental pathology available for review, we identified 73 vanishing twin pregnancies (8.1%), 556 singleton pregnancies (61.4%), and 276 twin pregnancies (30.5%). Vanishing twin syndrome was not associated with preterm delivery, route of delivery, growth restriction or other obstetric outcomes as compared with IVF singleton pregnancies. However, vanishing twin syndrome pregnancies showed distinctive placental pathologies including an increased rate of small placentas (less than the 10th percentile by weight), with more anatomical abnormalities than IVF singleton pregnancies (odds ratio 1.73, 95% CI 0.94–3.19; adjusted odds ratio 2.15, 95% CI 1.08–4.28). The frequency of placental vascular and inflammatory pathologies associated with IVF vanishing twin syndrome pregnancies were similar to that of IVF singleton pregnancies. Loss of a twin after 8 weeks of gestation was not associated with greater risks of placental pathologies.

CONCLUSION:

In vitro fertilization pregnancies affected by vanishing twin syndrome did not have significant differences in obstetric or perinatal outcomes as compared with twin or singleton gestations. However, early twin loss was potentially associated with differences in placental development associated with a higher rate of small placentas and other anatomic pathologies.
Provisional Minifragment Plate Fixation of Acetabular Fractures—A Technical Trick
Authors: Shannon Steven F. , Stevens Kali N. , Nascone Jason W. , O'Toole Robert V. , Eglseder W. Andrew , Sciadini Marcus F.
Published: May 2020

Acetabular fractures may not always be amenable to classic clamp-assisted reductions and interfragmentary lag screw fixation. The routine clamp-assisted reductions with limited osseous territory availability can inhibit typical 3.5-mm reconstruction plate application. Provisional minifragment plate fixation of these fracture patterns with subsequent clamp removal allows for definitive plate application. The provisional minifragment plates may also be retained to theoretically augment fixation. The authors present a step-by-step technique and clinical series of 57 patients demonstrating provisional minifragment fixation of elementary (n = 8) and associated (n = 49) acetabular fractures.
Hansen Disease (Leprosy) and Armadillo Exposure in Arkansas: A Case Series
Authors: Carlock Sarah , Fulton Edward H. , Rosenbaum Eric , Mukasa Leonard , Gardner Jerad M. , Shalin Sara C. , Kaley Jennifer R.
Published: May 2020

Background:

Although most cases of Hansen disease (HD) in the United States are imported from endemic areas, a subset of cases are relate to exposure to nine-banded armadillos. Several recent cases of HD in Arkansas occurred in patients who had not traveled to endemic areas and who reported variable degrees of armadillo exposure.

Objective:

The purpose of this study was to report 6 cases of HD diagnosed in Arkansas between 2004 and 2016. The secondary purpose was to explore the correlation between exposure to the nine-banded armadillo as it pertains to transmission of the disease.

Methods:

The referring clinician of each patient was contacted to gather information regarding the patient's clinical presentation, armadillo exposure, and travel history. In addition, the Arkansas Department of Health was consulted to review the demographics of individuals diagnosed with HD in the past 15 years and to review the distribution of HD throughout the state of Arkansas.

Results:

Six domestic cases of HD were associated with both direct and indirect exposure to armadillos.

Limitations:

Armadillo exposure may be underreported in patients with HD because of fear of stigmatization and/or lack of access to care.

Conclusions:

Direct exposure to armadillos does not appear to be required for transmission of HD making a soil-mediated mechanism of indirect exposure plausible.
Epithelioid Fibrous Histiocytoma With Dot-Like Perinuclear ALK Expression and PRKAR2A-ALK Fusion
Authors: Dawson Kellen , Bridge Julia A. , Sumegi Janos , Royce Thomas , Gardner Jerad M. , Shalin Sara C.
Published: May 2020

Epithelioid fibrous histiocytoma (EFH) is a rare, benign, cutaneous neoplasm. This fibrohistiocytic tumor was once believed to be a variant of fibrous histiocytoma, but EFH is now known to be a distinct entity based on the presence of
ALK
gene rearrangements in most cases. The pattern of immunohistochemical expression of ALK in EFH in the literature thus far describes both granular cytoplasmic staining and nuclear staining. We present a case of EFH with dot-like Golgi pattern perinuclear ALK expression, a previously undescribed staining pattern. We surmised this unique staining pattern could be due to a novel fusion partner, and using FISH, we confirmed a rearrangement of the
ALK
(2p23) locus. Further investigation with whole transcriptome sequencing led to the discovery of
PRKAR2A-ALK
fusion, and the function of this fusion partner reflects a Golgi-predominant localization of the protein. Attention to the distinct immunohistochemical pattern of ALK expression may provide clues to the function of the fusion partner.
Workshop on normal reference ranges for estradiol in postmenopausal women, September 2019, Chicago, Illinois
Authors: Santen Richard J. , Pinkerton JoAnn V. , Liu James H. , Matsumoto Alvin M. , Lobo Roger A. , Davis Susan R. , Simon James A.
Published: May 2020

The North American Menopause Society (NAMS) organized the Workshop on Normal Ranges for Estradiol in Postmenopausal Women from September 23 to 24, 2019, in Chicago, Illinois. The aim of the workshop was to review existing analytical methodologies for measuring estradiol in postmenopausal women and to assess existing data and study cohorts of postmenopausal women for their suitability to establish normal postmenopausal ranges. The anticipated outcome of the workshop was to develop recommendations for establishing normal ranges generated with a standardized and certified assay that could be adopted by clinical and research communities. The attendees determined that the term reference range was a better descriptor than normal range for estradiol measurements in postmenopausal women. Twenty-eight speakers presented during the workshop.
BETA-PERIPAPILLARY ATROPHY AND GEOGRAPHIC ATROPHY IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENTS TRIALS
Authors: Kolomeyer Anton M. , Smith Eli , Daniel Ebenezer , Ying Gui-Shuang , Pan Wei , Pistilli Max , Grunwald Juan , Maguire Maureen G. , Kim Benjamin J. ,   for the CATT Research Group
Published: May 2020

Purpose:

To determine associations between beta-peripapillary atrophy (B-PPA) and incidence and growth of geographic atrophy (GA) in eyes treated with anti–vascular endothelial growth factor agents in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

Methods:

We included 245 cases with incident GA and 245 controls matched by baseline demographics and characteristics associated with development of GA in the CATT. Baseline color images were graded for the type of B-PPA, defined as presence of hypopigmentation with visible choroidal vessels and sclera that is adjacent to the optic disk. Beta-peripapillary atrophy was further classified as scleral ring, sclera, sclera/choroidal blood vessels, or combination. Areas of each type of B-PPA and the circumferential extent of B-PPA were measured.

Results:

Beta-peripapillary atrophy was present in 58% of eyes developing GA and in 52% without GA (P = 0.17). The greater circumferential extent of sclera/choroidal blood vessels B-PPA in relation to the optic disk was associated with incident GA (P = 0.02) and the GA size at first observation (P = 0.047). Beta-peripapillary atrophy was not associated with GA growth rates (P>0.05). Patients without B-PPA had a higher number of GA-associated risk alleles of ARMS2 (P = 0.0003) and HTRA1 (P = 0.001).

Conclusion:

The extent of sclera/choroidal blood vessel B-PPA was associated with the GA incidence and size but not with the growth rate in eyes treated for neovascular age-related macular degeneration. Beta-peripapillary atrophy and GA may share some common pathophysiologic pathways unrelated to the GA-associated risk alleles evaluated.
CLINICAL PREDICTORS OF TUBERCULAR RETINAL VASCULITIS IN A HIGH-ENDEMIC COUNTRY
Authors: Kaza Hrishikesh , Tyagi Mudit , Pathengay Avinash , Basu Soumyava
Published: May 2020

Purpose:

To determine clinical signs suggestive of tubercular etiology in retinal vasculitis.

Methods:

A retrospective comparative study of patients who presented with retinal vasculitis at three tertiary care centers in India. All patients underwent detailed clinical evaluation and tailored laboratory investigations for etiological diagnosis. Tubercular etiology was diagnosed on basis on the presence of retinal periphlebitis in association with ancillary evidence of systemic tuberculosis and exclusion of nontuberculosis entities. Patients with tubercular (Group A) and nontubercular (Group B) etiology were compared for demographic characteristics, supportive diagnostic evidence, and specific ocular signs. Statistical analysis was performed at 5% confidence levels.

Results:

Of the 114 patients diagnosed with retinal vasculitis, Group A had 69 patients (100 eyes) and Group B had 45 patients (75 eyes). Active or healed subvascular lesions (P ≤ 0.0001), focal vascular tortuosity (P ≤ 0.0001), and occlusive vasculitis (P = 0.002) were significantly more common in Group A patients than in Group B patients. All three were independent predictors of tubercular etiology on multivariate regression analysis.

Conclusion:

The presence of healed or active subvascular lesions, focal vascular tortuosity, and occlusive vasculitis could be predictive of tubercular etiology in retinal vasculitis.
Outcomes of Ahmed Glaucoma Valve Implantation With Viscoelastic Fill at Both Beginning and End of Surgery
Authors: Dugan Connor , Zheng Cindy X. , Lin Michael M. , Ustaoglu Melih , Zhang Qiang (Ed) , Hamershock Rose A. , Moster Stephen J. , Moster Marlene R.
Published: May 2020

Précis:

Intracameral injection of viscoelastic at the beginning of Ahmed FP7 implantation did not reduce early postoperative complication rates.

Purpose:

To evaluate early postoperative complication rates after a modified technique in which the anterior chamber (AC) is filled with viscoelastic at the beginning of Ahmed FP7 implantation before conjunctival peritomy.

Subjects and Methods:

A retrospective chart review was performed of eyes that underwent Ahmed FP7 implantation with or without viscoelastic fill to ~20 mm Hg by finger tension by a single surgeon (M.R.M). Viscoelastic prevented the AC from becoming shallow at any time during surgery, and additional viscoelastic was injected into the AC at the end of surgery to achieve a final intraocular pressure (IOP) of 20 mm Hg.

Results:

A total of 159 eyes of 159 patients were included. Mean age was 76.4±10.4 years. Mean preoperative IOP was 30.3±9.7 mm Hg on 2.7±1.2 glaucoma medications. On postoperative day 1, there was an IOP spike ≥30 mm Hg in 0% of patients. Within the first postoperative month, hypotony (<5 mm Hg) occurred in 19 (21.8%) eyes that received viscoelastic fill compared with 5 (13.2%) eyes that did not receive viscoelastic fill (P=0.26). During the early postoperative period (≤3 mo), there was no difference in AC depth, microhyphema, choroidal effusion, or leakage between the 2 groups (P≥0.30 for all). There was a higher rate of layered hyphemas in the viscoelastic-fill group at postoperative week 1 (P=0.01). At 3-month follow-up, mean IOP was 14.9±5.5 mm Hg on 1.6±0.8 medications in the viscoelastic-fill group and 16.0±5.2 mm Hg on 1.0±1.2 medications in the nonviscoelastic-fill group (IOP P=0.35). Compared with baseline, change in IOP at 3 months was similar between both groups (P=0.15). Rates of additional medications and procedures did not differ between the 2 groups at any postoperative visit.

Conclusions:

Early intracameral injection of viscoelastic during Ahmed glaucoma valve implantation did not reduce early postoperative complication rates.
A Case of Critically Ill Infant of Coronavirus Disease 2019 With Persistent Reduction of T Lymphocytes
Authors: Qiu Liru , Jiao Rong , Zhang Aiming , Chen Xi , Ning Qin , Fang Feng , Zeng Fang , Tian Niannian , Zhang Yi , Huang Yafei , Sun Ziyan , Dhuromsingh Menaka , Li Hao , Li Yang , Xu Rongrong , Chen Yu , Luo Xiaoping
Published: May 2020

Background:

The outbreak of coronavirus disease 2019 (COVID-19) is becoming a global threat. However, our understanding of the clinical characteristics and treatment of critically ill pediatric patients and their ability of transmitting the coronavirus that causes COVID-19 still remains inadequate because only a handful pediatric cases of COVID-19 have been reported.

Methods:

Epidemiology, clinical characteristics, treatment, laboratory data and follow-up information and the treatment of critically ill infant were recorded.

Results:

The infant had life-threatening clinical features including high fever, septic shock, recurrent apnea, petechiae and acute kidney injury and persistent declined CD3+, CD4+ and CD8+ T cells. The duration of nasopharyngeal virus shedding lasted for 49 days even with the administration of lopinavir/ritonavir for 8 days. The CD3+, CD4+ and CD8+ T cells was partially recovered 68 days post onset of the disease. Accumulating of effector memory CD4+ T cells (CD4+TEM) was observed among T-cell compartment. The nucleic acid tests and serum antibody for the severe acute respiratory syndrome coronavirus 2 of the infant’s mother who kept intimate contact with the infant were negative despite no strict personal protection.

Conclusions:

The persistent reduction of CD4+ and CD8+ T cells was the typical feature of critically ill infant with COVID-19. CD4+ and CD8+ T cells might play a key role in aggravating COVID-19 and predicts a more critical course in children. The prolonged nasopharyngeal virus shedding was related with the severity of respiratory injury. The transmission of SARS-CoV-2 from infant (even very critical cases) to adult might be unlikely.
Rapid Rehabilitation With Skin-Muscle Sparing Orbital Exenteration: A Single-Center Series
Authors: Jayaprakasam Anuradha , Vahdani Kaveh , Rose Geoffrey E. , Saleh George M. , Hussain Badrul , Verity David H. , Collin J. Richard O.
Published: May 2020

Aims:

To examine the features and clinical management of patients who underwent skin-muscle sparing orbital exenteration in a tertiary referral center.

Patients and Method:

Retrospective case-note review for patients undergoing skin-muscle sparing orbital exenteration at Moorfields Eye Hospital between 1997 and 2012. Patient demographics, clinical features, histopathology, clearance, surgery, adjuvant therapy, and outcomes were analyzed.

Results:

Seventy-four patients (33 male; 45%) had skin-muscle sparing orbital exenteration at a median age of 63.8 years (median 65.5, range 13–96 years) for malignancies primarily arising in the eyelids (34 cases; 46%), orbit (25 cases; 34%) or conjunctiva (15 cases; 20%). The commonest pathologies were sebaceous carcinoma (20 cases; 27%), melanoma (19 cases; 26%), squamous cell carcinoma (12 cases; 16%), and basal cell carcinoma (9 cases; 12%). The patients had very rapid rehabilitation with primary closure of skin-muscle flaps over the cavity, either directly (63/74 patients; 85%), or with addition of local flaps. Local radiotherapy had been given before exenteration to 18 (24%) patients, was administered after exenteration in 19 (26%) patients, and both before and after surgery in 5 (7%); those having postoperative radiotherapy were referred at 2–3 weeks after exenteration, and the initial prosthetics fitting was started at 3–6 weeks after surgery. Thirty-eight (51%) patients died during a follow-up of 1–164 months (mean 55, median 47 months); 20/38 (53%) died from metastases—although 9/20 had known metastatic disease prior to palliative exenteration. Three patients were alive with apparently inactive metastases at 30, 39, and 140 months after surgery.

Conclusion:

Direct closure of skin-and-muscle flaps is achievable in almost all undergoing orbital exenteration. In contrast to skin-grafting, free myocutaneous flaps or secondary intention healing, this allows early referral if adjunctive orbital radiotherapy is needed, and the initial fitting of prosthetics can be within weeks of surgery. The technique also avoids the much greater donor-site morbidity of other reconstructive techniques, such as local or free myocutaneous flaps.
Evaluating the effect of intravitreal triamcinolone–moxifloxacin during cataract surgery on central macular edema in patients with preexisting diabetic retinopathy
Authors: Angkadjaja Julia , Chu Joshua , Sierpina David I. , Peng Jiahao , Rauser Michael
Published: May 2020

Purpose:

To evaluate the effect of intravitreal triamcinolone acetonide–moxifloxacin at the time of cataract surgery on central macular edema in patients with preexisting diabetic retinopathy.

Setting:

Loma Linda University Eye Institute, California, USA.

Design:

Retrospective observational clinical study.

Methods:

Retrospective chart review included 75 eyes of 64 patients who had cataract surgery between February 2015 and October 2018 performed by 2 surgeons. Intravitreal injection of triamcinolone–moxifloxacin (15 mg/1 mg/mL, 0.2 mL injection with 3.0 mg triamcinolone acetonide and 0.2 mg moxifloxacin) was given at the time of surgery. Visual acuity and central macular thickness (CMT) with optical coherence tomography were recorded at preoperative and postoperative visits.

Results:

Mean visual acuity (logarithm of the minimum angle of resolution) at 4 to 6 weeks, 6 to 12 weeks, and 12 weeks or more postoperatively was 0.32, 0.35, and 0.43, respectively. Baseline mean CMT of 75 eyes was 294 μm (SD = 72). Mean CMT 4 to 6 weeks postoperatively for 46 eyes decreased from 299 μm (78) to 297 μm (79), with a mean decrease of 2 μm (50) (P = .97). Mean CMT 6 to 12 weeks postoperatively for 34 eyes increased from 317 μm (88) to 344 μm (111), with a mean increase of 26 μm (98) (P = .021). Mean CMT 12 weeks or more for 60 eyes increased from 295 μm (72) to 328 μm (108), with a mean increase of 33 μm (85) (P = .0023).

Conclusions:

Triamcinolone acetonide–moxifloxacin maintained stability of postoperative CMT in patients undergoing cataract surgery with preexisting diabetic retinopathy in the short term, with the greatest effect at 4 to 6 weeks postoperatively.
Acute visceral pain relief mediated by A3AR agonists in rats: involvement of N-type voltage-gated calcium channels
Authors: Lucarini Elena , Coppi Elisabetta , Micheli Laura , Parisio Carmen , Vona Alessia , Cherchi Federica , Pugliese Anna M. , Pedata Felicita , Failli Paola , Palomino Seph , Wahl Jared , Largent-Milnes Tally M. , Vanderah Todd W. , Tosh Dilip K. , Jacobson Kenneth A. , Salvemini Daniela , Ghelardini Carla , Di Cesare Mannelli Lorenzo
Published: May 2020

Pharmacological tools for chronic visceral pain management are still limited and inadequate. A3 adenosine receptor (A3AR) agonists are effective in different models of persistent pain. Recently, their activity has been related to the block of N-type voltage-gated Ca2+ channels (Cav2.2) in dorsal root ganglia (DRG) neurons. The present work aimed to evaluate the efficacy of A3AR agonists in reducing postinflammatory visceral hypersensitivity in both male and female rats. Colitis was induced by the intracolonic instillation of 2,4-dinitrobenzenesulfonic acid (DNBS; 30 mg in 0.25 mL 50% EtOH). Visceral hypersensitivity was assessed by measuring the visceromotor response and the abdominal withdrawal reflex to colorectal distension. The effects of A3AR agonists (MRS5980 and Cl-IB-MECA) were evaluated over time after DNBS injection and compared to that of the selective Cav2.2 blocker PD173212, and the clinically used drug linaclotide. A3AR agonists significantly reduced DNBS-evoked visceral pain both in the postinflammatory (14 and 21 days after DNBS injection) and persistence (28 and 35 days after DNBS) phases. Efficacy was comparable to effects induced by linaclotide. PD173212 fully reduced abdominal hypersensitivity to control values, highlighting the role of Cav2.2. The effects of MRS5980 and Cl-IB-MECA were completely abolished by the selective A3AR antagonist MRS1523. Furthermore, patch-clamp recordings showed that A3AR agonists inhibited Cav2.2 in dorsal root ganglia neurons isolated from either control or DNBS-treated rats. The effect on Ca2+ current was PD173212-sensitive and prevented by MRS1523. A3AR agonists are effective in relieving visceral hypersensitivity induced by DNBS, suggesting a potential therapeutic role against abdominal pain.
Commentary on “Health Spending Under Single-Payer Approaches”
Authors: Ginsburg Paul B.
Published: May 2020

One of the most controversial areas in discussions of single-payer approaches for the United States, such as “Medicare for All,” concerns its implications for costs. Confusion over differences between federal and total spending and effects of lower patient cost sharing gets in the way of “apples-to-apples” comparisons. Key areas with potential to lower costs are lower administrative costs and lower provider prices. But cost reduction would likely be smaller than some envision, especially in the price area because of the need for a long process to gradually allow providers to adjust to lower prices and Americans' unique attitudes toward regulation.