bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cloud Factory II: gravoturbulent kinematics of resolved molecular clouds in a galactic potential
Authors: Izquierdo Andrés F , Smith Rowan J , Glover Simon C O , Klessen Ralf S , Treß Robin G , Sormani Mattia C , Clark Paul C , Duarte-Cabral Ana , Zucker Catherine
Published: November 2020

We present a statistical analysis of the gravoturbulent velocity fluctuations in molecular cloud complexes extracted from our ‘Cloud Factory’ Galactic-scale interstellar medium (ISM) simulation suite. For this purpose, we produce non-local thermodynamic equilibrium 12CO J = 1 − 0 synthetic observations and apply the principal component analysis (PCA) reduction technique on a representative sample of cloud complexes. The velocity fluctuations are self-consistently generated by different physical mechanisms at play in our simulations, which include Galactic-scale forces, gas self-gravity, and supernova feedback. The statistical analysis suggests that, even though purely gravitational effects are necessary to reproduce standard observational laws, they are not sufficient in most cases. We show that the extra injection of energy from supernova explosions plays a key role in establishing the global turbulent field and the local dynamics and morphology of molecular clouds. Additionally, we characterize structure function scaling parameters as a result of cloud environmental conditions: some of the complexes are immersed in diffuse (interarm) or dense (spiral-arm) environments, and others are influenced by embedded or external supernovae. In quiescent regions, we obtain time-evolving trajectories of scaling parameters driven by gravitational collapse and supersonic turbulent flows. Our findings suggest that a PCA-based statistical study is a robust method to diagnose the physical mechanisms that drive the gravoturbulent properties of molecular clouds. Also, we present a new open source module, the pcafactory, which smartly performs PCA to extract velocity structure functions from simulated or real data of the ISM in a user-friendly way.
On rare core collapse supernovae inside planetary nebulae
Authors: Bear Ealeal , Soker Noam
Published: November 2020

We conduct simulations using mesa of the reverse formation of a white dwarf (WD)–neutron star (NS) binary system in which the WD forms before the NS. We conclude that a core collapse supernova (CCSN) explosion might occur inside a planetary nebula (PN) only if a third star forms the PN. In this WD–NS reverse binary evolution, the primary star evolves and transfers mass to the secondary star, forms a PN, and leaves a WD remnant. If the mass-transfer brings the secondary star to have a mass of $\gtrsim 8\, \mathrm{ M}_\odot$ before it develops a helium core, and if the secondary does not suffer an enhanced mass-loss before it develops a massive helium core, e.g. by mass-transfer, it explodes as a CCSN and leaves an NS remnant. The time period from the formation of the PN by the primary to the explosion of the secondary is $\gtrsim 10^6 {~\rm yr}$. By that time, the PN has long dispersed into the interstellar medium. In a binary system with nearly equal-mass components, the first mass-transfer episode takes place after the secondary star has developed a helium core and it ends its life forming a PN and a WD. The formation of a CCSN inside a PN (CCSNIP) requires the presence of a third star. The third star should be less massive than the secondary star but by no more than few ×0.01 M⊙. We estimate that the rate of CCSNIP is ≈10−4 times the rate of all CCSNe.
Exploring the origin of low-metallicity stars in Milky-Way-like galaxies with the NIHAO-UHD simulations
Authors: Sestito Federico , Buck Tobias , Starkenburg Else , Martin Nicolas F , Navarro Julio F , Venn Kim A , Obreja Aura , Jablonka Pascale , Macciò Andrea V
Published: November 2020

The kinematics of the most metal-poor stars provide a window into the early formation and accretion history of the Milky Way (MW). Here, we use five high-resolution cosmological zoom-in simulations (∼ 5 × 106 star particles) of MW-like galaxies taken from the NIHAO-UHD project, to investigate the origin of low-metallicity stars ([Fe/H] ≤ −2.5). The simulations show a prominent population of low-metallicity stars confined to the disc plane, as recently discovered in the MW. The ubiquity of this finding suggests that the MW is not unique in this respect. Independently of the accretion history, we find that ≳90 per cent of the retrograde stars in this population are brought in during the initial build-up of the galaxies during the first few Gyr after the Big Bang. Our results therefore highlight the great potential of the retrograde population as a tracer of the early build-up of the MW. The prograde planar population, on the other hand, is accreted during the later assembly phase and samples the full galactic accretion history. In case of a quiet accretion history, this prograde population is mainly brought in during the first half of cosmic evolution (t ≲ 7 Gyr), while, in the case of an ongoing active accretion history, later mergers on prograde orbits are also able to contribute to this population. Finally, we note that the MW shows a rather large population of eccentric, very metal-poor planar stars. This is a feature not seen in most of our simulations, with the exception of one simulation with an exceptionally active early building phase.
LIN 358: a symbiotic binary accreting above the steady hydrogen fusion limit
Authors: Kuuttila J , Gilfanov M , Woods T E , Seitenzahl I R , Ruiter A J
Published: November 2020

Symbiotic binaries are long-period interacting binaries consisting of a white dwarf (WD) accreting material from a cool evolved giant star via stellar winds. In this paper, we study the symbiotic binary LIN 358 located in the Small Magellanic Cloud. We have observed LIN 358 with the integral field spectrograph WiFeS and obtained its line emission spectrum. With the help of the plasma simulation and spectral synthesis code cloudy, we have constructed a 2D photoionization model of LIN 358. From comparison with the observations, we have determined the colour temperature of the WD in LIN 358 to be 19 eV, its bolometric luminosity L = (1.02 ± 0.15) × 1038 erg s−1, and the mass-loss rate from the donor star to be 1.2 × 10−6 M⊙ yr−1. Assuming a solar H to He ratio in the wind material, a lower limit to the accreted mass fraction in LIN 358 is 0.31. The high mass accretion efficiency of a wind Roche lobe overflow implies that the WD is accreting above the upper boundary of stable hydrogen fusion and thus growing in mass with the maximal rate of ≈4 × 10−7 M⊙ yr−1. This causes the WD photosphere to expand, which explains its low colour temperature. Our calculations show that the circumstellar material in LIN 358 is nearly completely ionized except for a narrow cone around the donor star, and that the WD emission is freely escaping the system. However, due to its low colour temperature, this emission can be easily attenuated by even moderate amounts of neutral interstellar medium. We speculate that other symbiotic systems may be operating in a similar regime, thus explaining the paucity of observed systems.
The chemotherapeutic agent CX-5461 irreversibly blocks RNA polymerase I initiation and promoter release to cause nucleolar disruption, DNA damage and cell inviability
Authors: Mars Jean-Clément , Tremblay Michel G , Valere Mélissa , Sibai Dany S , Sabourin-Felix Marianne , Lessard Frédéric , Moss Tom
Published: November 2020

In the search for drugs to effectively treat cancer, the last 10 years have seen a resurgence of interest in targeting ribosome biogenesis. CX-5461 is a potential inhibitor of ribosomal RNA synthesis that is now showing promise in phase I trials as a chemotherapeutic agent for a range of malignancies. Here, we show that CX-5461 irreversibly inhibits ribosomal RNA transcription by arresting RNA polymerase I (RPI/Pol1/PolR1) in a transcription initiation complex. CX-5461 does not achieve this by preventing formation of the pre-initiation complex nor does it affect the promoter recruitment of the SL1 TBP complex or the HMGB-box upstream binding factor (UBF/UBTF). CX-5461 also does not prevent the subsequent recruitment of the initiation-competent RPI–Rrn3 complex. Rather, CX-5461 blocks promoter release of RPI–Rrn3, which remains irreversibly locked in the pre-initiation complex even after extensive drug removal. Unexpectedly, this results in an unproductive mode of RPI recruitment that correlates with the onset of nucleolar stress, inhibition of DNA replication, genome-wide DNA damage and cellular senescence. Our data demonstrate that the cytotoxicity of CX-5461 is at least in part the result of an irreversible inhibition of RPI transcription initiation and hence are of direct relevance to the design of improved strategies of chemotherapy.
Sequence variation, common tissue expression patterns and learning models: a genome-wide survey of vertebrate ribosomal proteins
Authors: Kyritsis Konstantinos A , Ouzounis Christos A , Angelis Lefteris , Vizirianakis Ioannis S
Published: November 2020

Ribosomal genes produce the constituents of the ribosome, one of the most conserved subcellular structures of all cells, from bacteria to eukaryotes, including animals. There are notions that some protein-coding ribosomal genes vary in their roles across species, particularly vertebrates, through the involvement of some in a number of genetic diseases. Based on extensive sequence comparisons and systematic curation, we establish a reference set for ribosomal proteins (RPs) in eleven vertebrate species and quantify their sequence conservation levels. Moreover, we correlate their coordinated gene expression patterns within up to 33 tissues and assess the exceptional role of paralogs in tissue specificity. Importantly, our analysis supported by the development and use of machine learning models strongly proposes that the variation in the observed tissue-specific gene expression of RPs is rather species-related and not due to tissue-based evolutionary processes. The data obtained suggest that RPs exhibit a complex relationship between their structure and function that broadly maintains a consistent expression landscape across tissues, while most of the variation arises from species idiosyncrasies. The latter may be due to evolutionary change and adaptation, rather than functional constraints at the tissue level throughout the vertebrate lineage.
Prevalence of Sleep Disordered Breathing in Children With Myelomeningocele
Authors: Rocque Brandon G , Maddox Mary Halsey , Hopson Betsy D , Shamblin Isaac C , Aban Inmaculada , Arynchyna Anastasia A , Blount Jeffrey P
Published: November 2020

BACKGROUND

Retrospective studies have shown high rates of sleep disordered breathing in children with myelomeningocele. However, most patients included in those studies underwent polysomnography because of symptoms, so the prevalence of sleep disordered breathing in this population is unknown.

OBJECTIVE

To determine the prevalence of sleep disordered breathing in children with myelomeningocele using screening polysomnography.

METHODS

In this cross-sectional study, all children with myelomeningocele seen in a multi-disciplinary spina bifida clinic between 2016 and 2020 were referred for polysomnography regardless of clinical symptoms. Included children had not previously undergone polysomnography. The primary outcome for this study was presence of sleep disordered breathing, defined as Apnea-Hypopnea Index (AHI, number of apnea or hypopnea events per hour of sleep) greater than 2.5. Clinical and demographic variables relevant to myelomeningocele were also prospectively collected and tested for association with presence of sleep apnea.

RESULTS

A total of 117 participants underwent polysomnography (age 1 mo to 21 yr, 49% male). The majority were white, non-Hispanic. Median AHI was 1.9 (interquartile range 0.6-4.2). A total of 49 children had AHI 2.5 or greater, yielding a sleep disordered breathing prevalence of 42% (95% CI 33%-51%). In multivariable logistic regression analysis, children with more rostral neurological lesion levels had higher odds of sleep disordered breathing (OR for thoracic, mid-lumbar, and low-lumbar: 7.34, 3.70, 4.04, respectively, compared to sacral level, P = .043).

CONCLUSION

Over 40% of a sample of children with myelomeningocele, who underwent screening polysomnography, had significant sleep disordered breathing. Routine screening polysomnography may be indicated in this population.
Data-driven prioritization and preclinical evaluation of therapeutic targets in glioblastoma
Authors: Brahm Cyrillo G , Abdul U Kulsoom , Houweling Megan , van Linde Myra E , Lagerweij Tonny , Verheul Henk M W , Westerman Bart A , Walenkamp Annemiek M E , Fehrmann Rudolf S N
Published: November 2020

Background

Patients with glioblastoma (GBM) have a dismal prognosis, and there is an unmet need for new therapeutic options. This study aims to identify new therapeutic targets in GBM.

Methods

mRNA expression data of patient-derived GBM (n = 1279) and normal brain tissue (n = 46) samples were collected from Gene Expression Omnibus and The Cancer Genome Atlas. Functional genomic mRNA profiling was applied to capture the downstream effects of genomic alterations on gene expression levels. Next, a class comparison between GBM and normal brain tissue was performed. Significantly upregulated genes in GBM were further prioritized based on (1) known interactions with antineoplastic drugs, (2) current drug development status in humans, and (3) association with biologic pathways known to be involved in GBM. Antineoplastic agents against prioritized targets were validated in vitro and in vivo.

Results

We identified 712 significantly upregulated genes in GBM compared to normal brain tissue, of which 27 have a known interaction with antineoplastic agents. Seventeen of the 27 genes, including EGFR and VEGFA, have been clinically evaluated in GBM with limited efficacy. For the remaining 10 genes, RRM2, MAPK9 (JNK2, SAPK1a), and XIAP play a role in GBM development. We demonstrated for the MAPK9 inhibitor RGB-286638 a viability loss in multiple GBM cell culture models. Although no overall survival benefit was observed in vivo, there were indications that RGB-286638 may delay tumor growth.

Conclusions

The MAPK9 inhibitor RGB-286638 showed promising in vitro results. Furthermore, in vivo target engagement studies and combination therapies with this compound warrant further exploration.
“Living Well with Chronic Pain”: Integrative Pain Management via Shared Medical Appointments
Authors: Znidarsic Josie , Kirksey Kellie N , Dombrowski Stephen M , Tang Anne , Lopez Rocio , Blonsky Heather , Todorov Irina , Schneeberger Dana , Doyle Jonathan , Libertini Linda , Jamie Starkey , Segall Tracy , Bang Andrew , Barringer Kathy , Judi Bar , Ehrman Jane Pernotto , Roizen Michael F , Golubić Mladen
Published: November 2020

Objective

To evaluate the effectiveness of a multidisciplinary, nonpharmacological, integrative approach that uses shared medical appointments to improve health-related quality of life and reduce opioid medication use in patients with chronic pain.

Design

This is a retrospective, pre–post review of “Living Well with Chronic Pain” shared medical appointments (August 2016 through May 2018).

Setting

The appointments included eight 3-hour-long visits held once per week at an outpatient wellness facility.

Subjects

Patients with chronic, non–cancer-related pain.

Methods

Patients received evaluation and evidence-based therapies from a team of integrative and lifestyle medicine professionals, as well as education about nonpharmacological therapeutic approaches, the etiology of pain, and the relationship of pain to lifestyle factors. Experiential elements focused on the relaxation techniques of meditation, yoga, breathing, and hypnotherapy, while patients also received acupuncture, acupressure, massage, cognitive behavioral therapy, and chiropractic education. Patients self-reported data via the Patient-Reported Outcomes Measurement Information System (PROMIS-57) standardized questionnaire. Use of opioid medications was evaluated in morphine milligram equivalents.

Results

A total of 178 participants completed the PROMIS-57 questionnaire at the first and the last visits. Statistically significant improvements in all domains (Physical Functioning, Anxiety, Depression, Fatigue, Social Roles, Pain Interference, and Sleep Disturbance) were observed (P < 0.001) between the pre-intervention (visit 1) and post-intervention (visit 8) scores. Average opioid use decreased nonsignificantly over the 8-week intervention, but the lower rate of opioid use was not sustained at 6 and 12 months’ follow-up.

Conclusions

Patients suffering from chronic pain who participated in a multidisciplinary, nonpharmacological treatment approach delivered via shared medical appointments experienced reduced pain and improved measures of physical, mental, and social health without increased use of opioid pain medications.
Construct Validity and Reliability of the Japanese Version of the Lumbar Stiffness Disability Index
Authors: Furuya Hidetaka , Ito Takashi , Hirohata Kenji , Mitomo Sho , Yamasaki Koji , Igarashi Hidetoshi , Omori Keita , Hoshino Masahiro , Hart Robert A.
Published: November 2020

Study Design.

Outcome study to determine the construct validity and reliability of the Japanese version of the Lumbar Stiffness Disability Index.

Objective.

The aim of this study was to evaluate the psychometric measurement properties of the Japanese version of the Lumbar Stiffness Disability Index (J-LSDI) following lumbar spinal surgery in order to assess its construct validity and reliability.

Summary of Background Data.

The LSDI was designed and validated as a tool to assess functional impacts of lumbar spine stiffness and diminished spinal flexibility. A Japanese version has been developed, but its construct validity and reliability have not been evaluated.

Methods.

A Pearson correlation coefficient was calculated using flexion and extension range of motion, Oswestry Disability Index (ODI) and Tampa Scale for Kinesiophobia (TSK) as external standards to evaluate construct validity. An intraclass correlation coefficient (ICC) and a Bland-Altman analysis were used to evaluate test–retest reliability.

Results.

A total of 244 patients following lumbar spinal surgery participated in the study. Fifty one of the 244 patients participated in the reliability study. The ICC of the J-LSDI for test–retest reliability was 0.89 (95% confidence interval, 0.79–0.93). There was no systematic error found in the results of the Bland-Altman analysis. One hundred ninety-three of the 244 patients participated in the validity study. There were significant correlations between the J-LSDI and trunk flexion range of motion (r = −0.66), extension (r = −0.51), ODI (r = 0.62), and TSK (r = 0.38).

Conclusion.

The construct validity and reliability of the Japanese version of the LSDI were confirmed. The J-LSDI can be used to evaluate lumbar stiffness and associated disability in Japanese patients following lumbar spinal surgery.

Level of Evidence: 2
Does a Multidisciplinary Triage Pathway Facilitate Better Outcomes After Spine Surgery?
Authors: Wu Adam , Liu Lucy , Fourney Daryl R.
Published: November 2020

Study Design.

Single-center prospective non-randomized matched cohort comparison.

Objective.

To compare elective lumbar spine surgery outcomes for cases triaged through a multidisciplinary spine pathway versus conventional referral processes.

Summary of Background Data.

Many health care systems have facilitated low back pain (LBP) guidelines into primary care practice by creating local or regional “pathways” with the goal of enhanced quality of care, improved patient satisfaction and optimal resource utilization, particularly for imaging and surgery. Few comparative outcomes exist for LBP pathways, particularly for surgical outcomes.

Methods.

One-hundred-fifty patients (SSP group n = 75; conventional group n = 75) undergoing elective lumbar surgery for degenerative conditions between 2011 and 2016 were analyzed with 1-year follow-up. Patient self-reported outcomes included the Oswestry disability index (ODI), visual analogue pain scores (VAS) for back and leg, and EuroQol Group 5—Dimension self-report (EQ-5D). We also assessed baseline clinical features, indications for surgery, therapies received prior to surgery, type of surgery, wait times, and overall patient satisfaction.

Results.

The groups had equivalent baseline demographics, body mass index, Saskatchewan Spine Pathway (SSP) classification of pain pattern, pain scores, functional scores, quality of life scores, indication for surgery, and type of surgery (instrumented or non-instrumented). There was no difference with respect to wait times to see the surgeon or for surgery. Wait time for magnetic resonance imaging (MRI) was significantly shorter for the SSP group (16.8 vs. 63.0 days, P < 0.001). Patients triaged through the SSP were significantly more likely to utilize multiple nonoperative treatment strategies prior to seeing the surgeon (P < 0.04). Patient satisfaction was significantly higher for SSP patients prior to surgical assessment (P = 0.03) but did not differ between groups after surgery.

Conclusion.

The SSP facilitates significantly shorter wait times for MRI and promotes nonoperative treatment strategies. Preoperative patient satisfaction is significantly higher among SSP patients, but there were no significant differences in surgical outcomes.

Level of Evidence: 3
Time Course of Physical and Mental Well-being Improvements After Cervical Surgery
Authors: Tamai Koji , Suzuki Akinobu , Terai Hidetomi , Hoshino Masatoshi , Toyoda Hiromitsu , Takahashi Shinji , Hori Yusuke , Yabu Akito , Nakamura Hiroaki
Published: November 2020

Study Design.

Retrospective cohort study.

Objective.

To elucidate the postoperative time course of improvements in physical and mental well-being in patients with cervical spondylotic myelopathy (CSM).

Summary of Background Data.

Spinal surgeons should understand the postoperative course in detail. However, data are still needed regarding the time course of improvements in well-being, a fundamental aspect of human life, after cervical surgery for CSM.

Methods.

One hundred consecutive patients who underwent laminoplasty for CSM, with complete clinical data preoperatively and 3 months and 2 years postoperatively, were enrolled. The Short Form-36 physical component summary (PCS) and mental component summary (MCS) scores were used as parameters of physical and mental well-being, respectively, and 4.0 was defined as the minimal clinically important difference (MCID) for both parameters.

Results.

On average, PCS and MCS scores were significantly improved after surgery (P < 0.001, P=0.004, respectively). Moreover, 64 and 48 patients achieved meaningful improvement (>MCID) in PCS and MCS scores at 3 months postoperatively, with maintained improvement (to 2 yr) in 46/64 (71.9%) and 34/48 patients (70.8%), respectively (PCS vs. MCS: P = 0.912). Additionally, 15 of 36 patients (41.7%) and 8 of 52 patients (15.4%) achieved late improvement (meaningful improvement at 2 yr but not at 3 months) in PCS and MCS scores, respectively (PCS vs. MCS: P = 0.007). In multivariate regression analysis, improvement in cJOA score was significantly associated with PCS improvement, but not MCS improvement, at both 3 months and 2 years (P = 0.001, P > 0.001, respectively).

Conclusion.

The overall outcome of physical well-being improvement is decided within 3 months postoperatively, in proportion to the recovery in myelopathy, with a relatively high chance of meaningful improvement over the next 21 months. The outcome of improvement in mental well-being is decided within 3 months postoperatively, independently from the recovery in myelopathy, with a low chance of meaningful improvement over the next 21 months.

Level of Evidence: 3
Machine Learning Predicts the 3D Outcomes of Adolescent Idiopathic Scoliosis Surgery Using Patient–Surgeon Specific Parameters
Authors: Pasha Saba , Shah Suken , Newton Peter
Published: November 2020

Study Design.

Retrospective descriptive, multicenter study.

Objective.

The aim of this study was to predict the three-dimensional (3D) radiographic outcomes of the spinal surgery in a cohort of adolescent idiopathic scoliosis (AIS) as a function preoperative spinal parameters and surgeon modifiable factors.

Summary of Background Data.

Current guidelines for posterior spinal fusion surgery (PSF) in AIS patients are based on two-dimensional classification of the spinal curves. Despite the high success rate, the prediction of the 3D spinal alignment at the follow-ups remains inconclusive. A data-driven surgical decision-making method that determines the combination of the surgical procedures and preoperative patient specific parameters that leads to a specific 3D global spinal alignment outcomes at the follow-ups can lessen the burden of surgical planning and improve patient satisfaction by setting expectations prior to surgery.

Methods.

A dataset of 371 AIS patients who underwent a PSF with two-year follow-up were included. Demographics, 2D radiographic spinal and pelvic measurements, clinical measurements of the trunk shape, and the surgical procedures were collected prospectively. A previously developed classification of the preoperative global 3D spinal alignment was used as an additional predictor. The 3D spinal alignment (vertebral positions and rotations) at two-year follow-up was used as the predicted outcome. An ensemble learner was used to predict the 3D spinal alignment at two-year follow-up as a function of the preoperative parameters with and without considering the surgeon modifiable factors.

Results.

The preoperative and surgical factors predicted three clusters of 3D surgical outcomes with an accuracy of 75%. The prediction accuracy decreased to 64% when only preoperative factors, without the surgical factors, were used in the model. Predictor importance analysis determined that preoperative distal junctional kyphosis, pelvic sagittal parameters, end-instrumented vertebra (EIV) angulation and translation, and the preoperative 3D clusters are the most important patient-specific predictors of the outcomes. Three surgical factors, upper and lower instrumented vertebrae, and the operating surgeon, were important surgical predictors. The role of surgeon in achieving a certain outcome clusters for specific ranges of preoperative T10-L2 kyphosis, EIV angulation and translation, thoracic and lumbar flexibilities, and patient's height was significant.

Conclusion.

Both preoperative patient-specific and surgeon modifiable parameters predicted the 3D global spinal alignment at two-year post PSF. Surgeon was determined as a predictor of the outcomes despite including 20 factors in the analysis that described the surgical moves. Methods to quantify the differences between the implemented surgeon modifiable factors are essential to improve outcome prediction in AIS spinal surgery.

Level of Evidence: 3
Association Between Vertebral Dimensions and Lumbar Modic Changes
Authors: Julin Modarress , Saukkonen Jesperi , Oura Petteri , Junno Juho-Antti , Niemelä Maisa , Määttä Juhani , Niinimäki Jaakko , Jämsä Timo , Korpelainen Raija , Karppinen Jaro
Published: November 2020

Study Design.

Population-based birth cohort study.

Objective.

The aim of this study was to evaluate the relationship between vertebral dimensions and lumbar MC.

Summary of Background Data.

Low back pain (LBP) has become the leading cause of disability worldwide. Modic changes (MC) of the lumbar spine are one potential LBP-associated etiological factor. Mechanical stress is considered to play a key role in the development of MC through damage to endplates. There is speculation that vertebral dimensions play a role in some degenerative changes in the spine. Previous studies have also shown a positive association between moderate-to-vigorous physical activity (MVPA) and both vertebral dimensions and MC. In this study, we aimed to evaluate the relationship between vertebral dimensions and MC.

Methods.

The study population consisted of 1221 participants from the Northern Finland Birth Cohort 1966 who underwent lumbar magnetic resonance imaging (MRI) and physical activity measurements at the age of 46–48. The presence of Type 1 (MC1) and Type 2 (MC2) MC and the height, axial cross-sectional area (CSA), and volume of the L4 vertebra were determined from MRI scans. MVPA (≥3.5 metabolic equivalents) was measured by a wrist-worn accelerometer. We analyzed the association between lumbar MC and vertebral height, CSA, and volume using logistic regression models before and after adjustment for sex, height, weight, smoking, education level, and MVPA.

Results.

Vertebral height was positively associated with the presence of MC2 (odds ratio [OR] 3.51; 95% confidence interval [CI] 1.43–8.65), whereas vertebral CSA was not associated with the presence of lumbar MC. Vertebral volume was positively associated with the presence of any MC (OR 1.04; 95% CI 1.00–1.07), but the association did not persist when analyzing MC1 and MC2 separately.

Conclusion.

Vertebral height was associated with the presence of MC2. Further studies are needed to clarify the role of vertebral dimensions as independent risk factors for MC.

Level of Evidence: 3
Critical Care Management of the Patient with Clostridioides difficile
Authors: Adelman Max W. , Woodworth Michael H. , Shaffer Virginia O. , Martin Greg S. , Kraft Colleen S.
Published: November 2020

OBJECTIVES:

To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients.

DATA SOURCES:

We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles.

STUDY SELECTION:

We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence.

DATA EXTRACTION:

We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review.

DATA SYNTHESIS:

C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk.

CONCLUSIONS:

Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.
Peristomal Punctate Pemphigus
Authors: Henning Ania , Bartenstein Diana , Kroshinsky Daniela , Nazarian Rosalynn M.
Published: November 2020

Cutaneous reactions surrounding abdominal stoma sites are typically irritant, allergic, infectious, traumatic or pathergic in etiology. Pemphigus, which encompasses a group of vesiculobullous autoimmune skin disorders, is seldom encountered as a peristomal dermatosis. Direct immunofluorescence (DIF) studies of pemphigus generally show continuous intercellular net-like depositions of IgG. However, punctate or dot-like intercellular deposition of IgG can also be seen in cases of pemphigus. The punctuate pattern is underreported in the literature and little is known about its implication. We describe a case of a 58-year-old Caucasian man with a history of bowel obstruction, status postcolostomy, who presented with a sharply demarcated, erythematous, crusted plaque surrounding his abdominal stoma. The patient endorsed persistent pruritus. A punch biopsy of the lesion was performed for clinical suspicion of fungal infection versus irritant dermatitis. Histopathology revealed a predominantly subcorneal acantholytic dermatitis. Periodic acid-Schiff with diastase and Grocott methenamine silver histochemical stains were negative for fungi. DIF was positive for IgG and C3 detected in a punctate intercellular pattern. In conjunction with the patient's clinical presentation and DIF, a diagnosis of peristomal pemphigus foliaceous was rendered. Herein, we describe a case of punctate pemphigus presenting as a peristomal dermatosis and include a review of the literature to raise awareness of this phenomenon.
Evidence for Pharmacogenomic Effects on Risperidone Outcomes in Pediatrics
Authors: Rossow Katelyn M. , Oshikoya Kazeem A. , Aka Ida T. , Maxwell-Horn Angela C. , Roden Dan M. , Van Driest Sara L.
Published: November 2020

Objective:

To determine the association between genetic variants reported to affect risperidone and adverse events (AEs) in children and adolescents.

Methods:

Individuals aged 18 years or younger with ≥4 weeks of risperidone exposure in a deidentified DNA biobank were included. The primary outcome was AE frequency as a function of genotype. Individuals were classified according to metabolizer status for CYP2D6, CYP3A4, and CYP3A5; wild type, heterozygote, or homozygote for specific single nucleotide variants for DRD2, DRD3, HTR2A, and HTR2C; and wild type versus nonwild type for multiple uncommon variants in ABCG2, ABCB1, and HTR2C. Tests of association of each classification to AEs were performed using a Fisher exact test and logistic regression, and statistically significant classifications were included in a final logistic regression.

Results:

The final cohort included 257 individuals. AEs were more common in CYP2D6 poor/intermediate metabolizers (PMs/IMs) than normal/rapid/ultrarapid metabolizers (NMs/RMs/UMs) in univariate and multivariate analysis. HTR2A-rs6311 heterozygotes and homozygotes had fewer AEs than wild types in logistic regression but not in univariate analysis. In the final multivariable model adjusting for age, race, sex, and risperidone dose, AEs were associated with CYP2D6 (adjusted odds ratio [AOR] 2.6, 95% CI 1.1–5.5, for PMs/IMs vs. NMs/RMs/UMs) and HTR2A-rs6311 (AOR 0.6, 95% CI 0.4–0.9, for each variant allele), both consistent with previous studies.

Conclusion:

Children and adolescents who are CYP2D6 PMs/IMs may have an increased risk for risperidone AEs. Of the genes and variants studied, only CYP2D6 has consistent association and sufficient data for clinical use, whereas HTR2A-rs6311 has limited data and requires further study.
No Excess of Mathematics Anxiety in Adolescents Born Very Preterm
Authors: Trickett Jayne , Gilmore Camilla , Cragg Lucy , Clayton Sarah , Marlow Neil , Simms Victoria , Spong Rebecca , Johnson Samantha
Published: November 2020

Objective:

To assess whether adolescents born very preterm (VP; <32 weeks' gestation) have an excess of mathematics anxiety compared with their classmates born at term.

Methods:

This cohort study included 127 adolescents born VP (51% male, mean age 13.9 years, SD 0.7) and 95 term-born classmates (56% male, mean age 13.7 years, SD 0.7) who completed the Wechsler Individual Achievement Test Second UK Edition and the Mathematics Anxiety Scale-UK at the age of 11 to 15 years. Self-reported trait anxiety was assessed using a composite of 3 items from the Strengths and Difficulties Questionnaire.

Results:

Adolescents born VP had significantly poorer mathematics attainment than adolescents born at term (difference in means: −0.64 SD; 95% confidence interval −0.95 to −0.34). However, there were no between-group differences in self-reported mathematics anxiety or trait anxiety. There were significant moderate associations between mathematics anxiety and mathematics attainment for adolescents born VP (rho: −0.45) and at term (rho: −0.54), after controlling for trait anxiety.

Conclusion:

Adolescents born VP do not have heightened mathematics anxiety compared with their term-born classmates, despite poorer attainment in mathematics. Improving domain-general cognitive skills and scaffolding learning in the classroom may be more promising avenues for intervention than attempting to reduce mathematics anxiety.
The Expert in the Room: Parental Advocacy for Children with Sex Chromosome Aneuploidies
Authors: Richardson Jordan P. , Riggan Kirsten A. , Allyse Megan
Published: November 2020

Objective:

Owing to fragmentation in the medical system, many parents of children with disabilities report taking on a care coordinator and advocate role. The parental advocacy and care coordination requirements are further amplified in this population because of a lack of awareness about sex chromosome aneuploidies (SCAs) in medical and social services settings, as well as the complex needs of affected children. This burden disproportionately affects mothers and low-resource families as a result of gendered ideas of parenthood and social stratification in resource access. The aim of this study is to understand the unique parental burdens of SCAs and family support needs.

Methods:

We conducted 43 interviews with individuals with SCAs and/or their parents and qualitatively coded and analyzed the transcripts for themes relating to parent advocacy, medical services, social and educational services, and coping.

Results:

Our findings indicate that parents must repeatedly advocate for their concerns about their child to be taken seriously before diagnosis and continue to advocate for services and interventions throughout childhood and adolescence. Parents also report the need to educate health care professionals about their child's medical condition. A majority of the parent participants were women, and single mothers reported high levels of emotional burden.

Conclusion:

Parents of children with SCAs shoulder additional roles of medical advocate and care coordinator. This causes excessive burden on families but also disadvantages families in which parents are unable to act as an advocate for their child.
Long-term Results of a Combined Procedure of Cataract Surgery and Descemet Membrane Endothelial Keratoplasty With Stromal Rim
Authors: Studeny Pavel , Hlozankova Katerina , Krizova Deli , Netukova Magdalena , Veith Miroslav , Mojzis Peter , Piñero David P.
Published: November 2020

Purpose:

To evaluate the long-term results of combining cataract surgery, intraocular lens (IOL) implantation, and Descemet membrane endothelial keratoplasty with peripheral stromal support (DMEK-S).

Methods:

The outcomes of 107 eyes of 37 patients who had undergone a combination of cataract surgery, IOL implantation, and DMEK-S between October 2007 and February 2015 were retrospectively evaluated. The average follow-up duration was 18.2 ± 18.3 months (range, 6–84 months). Changes in uncorrected and corrected distance visual acuity, spherical equivalent, and corneal endothelial cell density were analyzed. Intraoperative and postoperative complications were also recorded.

Results:

The mean logMAR uncorrected distance visual acuity improved from 0.92 ± 0.60 preoperatively to 0.33 ± 0.33, 0.28 ± 0.25, 0.24 ± 0.20, and 0.27 ± 0.27 at 6, 12, 24, and 36 months postoperatively (P < 0.001), respectively. The mean logMAR corrected distance visual acuity improved from 0.62 ± 0.65 preoperatively to 0.17 ± 0.29, 0.13 ± 0.21, 0.07 ± 0.16, and 0.11 ± 0.23 at 6, 12, 24, and 36 months postoperatively (P < 0.001), respectively. The mean endothelial cell density decreases were 50.7% ± 21.1%, 50.8% ± 19.8%, 60.7% ± 16.6%, 62.2% ± 11.8%, and 61.8% ± 20.0% at 6, 12, 24, 36, and 48 months after surgery, respectively. Similar trends, although with slightly better visual outcomes, were found in the subgroup of patients without other eye diseases. The mean final deviation from intended spherical equivalent was 0.77 ± 1.19 D, representing a hyperopic shift.

Conclusions:

A combined procedure of cataract surgery, IOL implantation, and DMEK-S is an effective method of treatment in patients with combined corneal disease and cataract, maintaining visual rehabilitation in the long term. Future developments should be performed to minimize the incidence of complications.
Telemedicine in Oculoplastics: The Real-Life Application of Video Consultation Clinics
Authors: Jamison Aaron , Diaper Charles , Drummond Suzannah , Tejwani Deepak , Gregory Maria Elena , Cauchi Paul , Crofts Kevin , Chadha Vikas
Published: November 2020

Purpose:

Our oculoplastic service piloted a new video consultation (VC) clinic in response to the COVID-19 pandemic. Data were collected to determine whether specific patients are better suited to VC, and to quantify the true benefit of VC in patients that successfully attended.

Methods:

Data were collected prospectively on predetermined data collection forms, including consultation duration, diagnosis, management plan, and issues that arose.

Results:

37.8% of new referrals and 60.9% of return patients were vetted as suitable for VC. Of those invited to attend, 83.4% agreed to a VC appointment. Of the patients appointed to a VC clinic, 71.7% (new)/75% (return) successfully completed VC, 14.9%/15.8% attempted a VC which ultimately failed, and 13.4%/9.2% did not attend. VC successfully prevented face-to-face consultation in 81.3% of new cases and 91.1% of returns. Ectropion, entropion and dermatochalasis (new referrals), and postoperative follow-up (return patients) were well suited to VC, while patients with “watery eye” (new), and lid or conjunctival lesions (return), often required face-to-face consultation. Problems (most common issues with patients connecting to the consultation, video quality, and audio quality) were encountered during 50.3% of calls, although 82.6% of attempted calls were ultimately successful. Age was not associated with the proportion of calls that were successful.

Conclusions:

VC is a useful tool for oculoplastic patients, irrespective of age, as long as the patient’s notes/referrals are carefully vetted to determine suitability. Patients with ectropion, entropion and dermatochalasis, and postoperative reviews are better suited to VC than those with “watery eye,” lid lesions, and conjunctival lesions.
Low-dose Bleomycin Injections for Orbital Lymphatic and Lymphatic-Venous Malformations: A Multicentric Case Series Study
Authors: Prat Daphna , Gomel Nir , Zloto Ofira , Anne Musika , BenSaid Ahmed , Bhattacharjee Kasturi , Yassur Iftach , Sagiv Oded , Ben Simon Guy J.
Published: November 2020

Purpose:

Orbital lymphatic malformations (LM) are associated with ocular morbidity and facial disfigurement. Surgery is challenging and may not be effective. We describe the outcome of bleomycin injections for venous LM and lymphatic-venous malformation (LVM) malformations of the orbit in 5 tertiary referral centers between January 2010 and December 2018.

Methods:

Multicenter retrospective case series, 5 oculoplastic referral centers: Sheba and Rabin Medical Centers, Israel; Mulago Hospital, Uganda; Sri Sankaradeva Nethralaya, India; and Clinique Ophtalmologique de Tunis, Tunisia. All patients diagnosed with orbital LM/LVM were assigned to successive (range 1–6) intralesional 5 international units bleomycin injections. They all underwent complete ophthalmic and orbital evaluations, orbital imaging, and ancillary testing as needed. Clinical photographs were assessed pre- and posttreatment along with objective assessments of clinical improvement. Additional injections were provided in cases of incomplete response.

Results:

A total of 21 patients (17 women, mean ± standard deviation age 18 ± 13 years, range 2–48 years) underwent bleomycin injections. The mean injection dose was 12 ± 10 international units in 1–3 injections. There was a dramatic improvement in lesion size, appearance, proptosis, and ocular motility in 20/21 patients (95%) after a mean follow-up of 18 months. Visual acuity slightly improved after treatment (20/50–20/30; P = 0.076). No side effects were noted after bleomycin injections.

Conclusions:

Bleomycin injections for LM/LVM of the orbit are effective; local or systemic side effects were not seen in this series. To the best of our knowledge, this is the largest reported series of this treatment.
Quantitative Assessment of Orbital Decompression Surgery Using Photogrammetric Stereoimaging
Authors: Murta Fabiola , Hyer Jonathan N. , Haridas Anjana , Rose Geoffrey E. , Ezra Daniel G.
Published: November 2020

Purpose:

To evaluate periorbital volume changes, using quantitative photogrammetric stereoimaging, after bony orbital decompression for thyroid eye disease (TED) and compare this to changes in Hertel exophthalmometry. Tissue volumes of the upper and lower eyelids were also assessed independently.

Design:

Prospective, nonrandomized, nonconsecutive series of patients.

Subjects:

Adults with inactive TED who had elected to undergo bony orbital decompression at Moorfields Eye Hospital between 2015 and 2017.

Methods:

With their eyes gently closed, patients with inactive TED underwent imaging using the VECTRA M3 system (Canfields Imaging, Fairfield, NJ), both before and at least 3 months after orbital decompression. Proptosis was assessed by Hertel exophthalmometry. Using the manufacturer’s software, changes in periorbital volumes between the preoperative and postoperative images were calculated for the upper and lower eyelids. The Pearson product-moment correlation coefficient was used to assess the linear relationship between changes in periorbital volume and exophthalmometry.

Main Outcome Measures:

Change in stereoimaging volumes of the upper and lower eyelids, and clinical proptosis as measured with Hertel exophthalmometry.

Results:

Thirty-three patients (11 males; 33%) underwent lateral decompression (39 orbits in 26 patients), lateral decompression with complete ethmoidectomy (3 orbits in 3 patients), combined decompression of lateral wall, medial wall, and medial half of floor (10 orbits in 6 patients), or bilateral lateral, medial, and complete floor decompression (1 patient). The corresponding average volumetric changes were 1.74 ml (median 1.64; range 0.39–3.73 ml), 3.38 ml (median 3.38, range 1.89–4.88 ml), 4.05 ml (median 3.53, range 1.72–6.43 ml), and 4.52 ml (range 4.36–4.68 ml), respectively. Similarly, the average reduction in proptosis was 3.6 mm (median 3; range 1.5–7 mm), 5.3 mm (median 5; range 5–6 mm), 7.4 mm (7.5; range 6–9 mm), and 9 mm (range 8–10 mm). Periorbital volume changes were related to the reduction in exophthalmometry (r = 0.713, p < 0.0001), and reduction of lower eyelid volume did not increase further with more than two-wall decompression.

Conclusion:

Graded orbital decompression reduces both proptosis and the upper and lower eyelid tissue volumes, the eyelid changes being likely to influence decisions about future restorative eyelid surgery. The significant changes in eyelid profiles underlines the established principle of thyroid periocular rehabilitation, namely decompression, then strabismus surgery, and finally eyelid surgery.