bluuebunny/crossref_metadata_2025 huggingface dataset:
The (In)discreet Charm of the Romans
Authors: Ostrowska Elżbieta
Published: January 2021

Made in 2001 by Jerzy Kawalerowicz, the Polish film Quo vadis represents a vernacular variant of ‘heritage cinema’ which has flourished in the country since 1989. Mostly consisting of adaptations of Polish literary classics, whose action takes place in a relatively distant past, they feature protagonists who are preoccupied by matters such as love, honour, and patriotism that are always linked with Catholicism. As demonstrated in this chapter, Kawalerowicz’s film also condones regressive gender norms, patriarchal order, and the hegemonic discourse of Catholicism. Most importantly, the chapter will argue that Quo vadis follows other novels by Sienkiewicz in developing a vernacular colonial fantasy. In Kawalerowicz’s Quo vadis colonial fantasies merge with contemporary discourse about Poland’s Europeanness. Arguably, Lygia’s romance with Marcus Vinicius, who decides to convert to Christianity, implies a symbolic union between (Eastern European) Poland and the (Western European) Roman Empire. Kawalerowicz’s decision to frame the ancient story with two contemporary images of the Roman Colosseum seems to suggest that, ultimately, Poland has ‘returned to Europe’—as the post-communist slogan claimed. The chapter will also pay special attention to the film’s melodramatic mode of representation and its affective power, as well as to its potential to present a utopian world of moral potency and transparency. Melodrama in Quo vadis provides a textual space through which viewers could channel the emotions they had experienced during the stark time of transition.
Towards an Analyses of the Mega-Political Jurisprudence of the ECOWAS Community Court of Justice
Authors: Akinkugbe Olabisi D.
Published: January 2021

This chapter fills the gap in the judicialization of mega-political disputes before the Economic Community of West African States (ECOWAS) Community Court of Justice (ECOWAS Court). Judicialization of mega-political disputes in this Court has until now been understudied. Although the ECOWAS Court lacks an express mandate to adjudicate over political disputes, the Court has been innovative in assuming jurisdiction over mega-political disputes when these disputes are intertwined with actual or potential human rights violations. The Ugokwe doctrine, enunciated in the case of, Dr. Jerry Ugokwe v. The Federal Republic of Nigeria and Dr. Christian Okeke, established the “cause of action” for the judicialization of mega-political disputes before the ECOWAS Court. By examining cases that have largely remained obscure, the chapter uncovers the judicialization of political disputes, particularly of electoral cases, before the ECOWAS Court. Unlike the traditional scholarship that measures effectiveness based on compliance with the decisions of the courts, the chapter argues that the significance of the mega-political disputes judicialized before Africa’s regional courts derives from the instrumental objectives of the litigants. By incorporating the social, political, and economic contexts that gave rise to the francophone and anglophone cases analyzed, the chapter illuminates the judicialization of mega-political disputes in ways that are not wedded to the traditional analyses of the functions of regional economic courts.
Introduction
Authors: Televantos Andreas
Published: January 2021

This introductory chapter discusses the significance of the Regency era in English commercial law's development. There are two main reasons for this. First, the unstable economic circumstances of the period, and the business failures this caused, brought commercial law issues into sharp focus. The second reason the Regency era was particularly important in the development of commercial law relates to the availability of published legal materials. In the period, cases were continuously reported for the first time, and many new commercial law treatises were published. This story of how the courts responded to the needs of commerce has four sets of main characters, which the chapter describes in depth. It concludes with a quick outline of the basic structure of this book.
Trusts and the Risk of Bankruptcy
Authors: Televantos Andreas
Published: January 2021

This chapter shows how commercial parties could use trusts to control the effects of bankruptcy and evade the doctrine of reputed ownership. Trusts facilitated by improving traders' capacity to pursue their rational self-interest: by acting as a surrogate for a charge or mortgage over personal property. The chapter examines how traders could use trusts to avoid the risk of their debtors' insolvency in three stages. It first examines why and how the doctrine of reputed ownership restricted the ability of traders to take mortgages or charges over personal property, and so limited their autonomy. The chapter then examines why the doctrine did not apply to trusts law — if a trustee had legal title to trust assets, surely he was their ‘reputed owner’? Finally, this chapter shows the role that trusts played in controlling the risk of insolvency in contemporary finance.
Partnership Dissolution and Bankruptcy
Authors: Televantos Andreas
Published: January 2021

This chapter looks at those cases where a partnership failed and looks at the rules governing how its assets would be distributed on the bankruptcy of its partners. This is used as a way of examining the extent to which a partnership was treated as an entity separate from the partners, given contemporary ideas about the importance of traders' personal liability for their business debts. Exactly how partnership law prioritised business creditors' claims over the personal creditors of a partner has to be examined in cases where the firm collapsed. Only in cases of insolvency did the issue of which assets different types of creditor could claim matter. By examining the rights of creditors upon a partnership's insolvency in this way, the extent to which the law encouraged creditors to lend money to partnerships — and so facilitated trade — are examined.
The Timefulness of Creativity in an Accelerating World
Authors: Simpson Barbara , Tracey Rory , Weston Alia
Published: January 2021

Finding conditions that are conducive to creative practice is a perennial concern in today’s accelerating world, but temporal theories that might shed light onto this problematic still lag behind the day-to-day practicalities of actually doing creative work. This chapter shows that clock time, with its realist focus on the ordered succession of past, present, and future, is inadequate as a basis for understanding the ways in which creative practice is temporally resourced. Drawing on the idealist philosophies of Bergson, Heidegger, and Mead, an alternative becoming temporality characterized by the timefulness of interpenetrating pasts and futures is elaborated. Rather than simply protecting pockets of time for innovation, timefulness evokes mindfulness, carefulness, and playfulness as actions to be nurtured if creativity is to flourish.
Temporal Shaping of Routine Patterning
Authors: Bygballe Lena E. , Swärd Anna R. , Vaagaasar Anne Live
Published: January 2021

This chapter explores how temporality shapes the creation and recreation of routines. Few have explicitly addressed the role temporality plays and how it influences actors’ routine enactment. Based on a process study of a quality routine in a large construction company, the chapter demonstrates how routine patterning is a continuous flow between past, present, and future enactments of the routine. The following key insights are developed: (1) how orientation toward the past can create stability in routine patterning, (2) how temporal conflict in the present performance of the routine and the questioning of temporal assumptions trigger change in routine patterning, and (3) how the shaping of temporal structures can create temporal commons that balance the tensions inherent in temporality, thus allowing for routine patterning and an orientation toward the future. These insights can turn attention away from the time reckoning and sequential understanding inherent in much research on routines.
Gore Mountain Garnet Amphibolite Records UHT Conditions: Implications for the Rheology of the Lower Continental Crust during Orogenesis
Authors: Shinevar William J , Jagoutz Oliver , VanTongeren Jill A
Published: January 2021

The Gore Mountain Garnet Amphibolite (GMGA), part of the Mesoproterozoic Grenville Province in the Adirondack Highlands, NY, USA, is an iconic rock type known for hosting the world’s largest garnets (up to 1 m diameter). We present a new detailed petrographic study of these rocks. Field relations, whole-rock, and mineral major and trace element chemistry suggest that these rocks formed via a prograde hydration reaction of a metagabbro during an increase in pressure and temperature. Laser ablation inductively coupled plasma mass spectrometry U–Pb geochronology applied to zircon interpreted to be metamorphic in origin dates this reaction to 1053·9 ± 5·4 Ma (2σ; MSWD = 0·94), during the Ottawan Orogeny (1090–1020 Ma). Our results on peak metamorphic P–T conditions based on thermobarometry, diffusion models, and thermodynamic modelling indicate that these rocks formed at ultrahigh-temperature (>900 °C) conditions (P = 9–10 kbar, T = 950 ± 40 °C), significantly hotter than previously estimated. Diffusion models pinned by nearby cooling ages require the GMGA to initially cool quickly (9·1 °C Ma–1), followed by slower cooling (2·6 °C Ma–1). The two-stage cooling history for the GMGA could reflect initial advection-dominated cooling followed by conduction-dominated cooling once flow ceases. Our results suggest that the region was hot enough to undergo topography-driven lower crustal flow similar to that hypothesized for modern Tibet for 20–0 Ma (25–0 Ma when the effects of melt are included).
Arabidopsis Ca2+-ATPases 1, 2, and 7 in the endoplasmic reticulum contribute to growth and pollen fitness
Authors: Rahmati Ishka Maryam , Brown Elizabeth , Rosenberg Alexa , Romanowsky Shawn , Davis James A , Choi Won-Gyu , Harper Jeffrey F
Published: January 2021

Generating cellular Ca2+ signals requires coordinated transport activities from both Ca2+ influx and efflux pathways. In Arabidopsis (Arabidopsis thaliana), multiple efflux pathways exist, some of which involve Ca2+-pumps belonging to the Autoinhibited Ca2+-ATPase (ACA) family. Here, we show that ACA1, 2, and 7 localize to the endoplasmic reticulum (ER) and are important for plant growth and pollen fertility. While phenotypes for plants harboring single-gene knockouts (KOs) were weak or undetected, a triple KO of aca1/2/7 displayed a 2.6-fold decrease in pollen transmission efficiency, whereas inheritance through female gametes was normal. The triple KO also resulted in smaller rosettes showing a high frequency of lesions. Both vegetative and reproductive phenotypes were rescued by transgenes encoding either ACA1, 2, or 7, suggesting that all three isoforms are biochemically redundant. Lesions were suppressed by expression of a transgene encoding NahG, an enzyme that degrades salicylic acid (SA). Triple KO mutants showed elevated mRNA expression for two SA-inducible marker genes, Pathogenesis-related1 (PR1) and PR2. The aca1/2/7 lesion phenotype was similar but less severe than SA-dependent lesions associated with a double KO of vacuolar pumps aca4 and 11. Imaging of Ca2+ dynamics triggered by blue light or the pathogen elicitor flg22 revealed that aca1/2/7 mutants display Ca2+ transients with increased magnitudes and durations. Together, these results indicate that ER-localized ACAs play important roles in regulating Ca2+ signals, and that the loss of these pumps results in male fertility and vegetative growth deficiencies.
Meta-analysis of the association between emphysematous change on thoracic computerized tomography scan and recurrent pneumothorax
Authors: Girish M , Pharoah P D , Marciniak S J
Published: January 2021

Objectives

At least a third of patients go on to suffer a recurrence following a first spontaneous pneumothorax. Surgical intervention reduces the risk of recurrence and has been advocated as a primary treatment for pneumothorax. But surgery exposes patients to the risks of anaesthesia and in some cases can cause chronic pain. Risk stratification of patients to identify those most at risk of recurrence would help direct the most appropriate patients to early intervention. Many studies have addressed the role of thoracic computerized tomography (CT) in identifying those individuals at increased risk of recurrence, but a consensus is lacking.

Aim

Our objective was to clarify whether CT provides valuable prognostic information for recurrent pneumothorax.

Design

Meta-analysis.

Methods

We conducted an exhaustive search of the literature for thoracic CT imaging and pneumothorax, and then performed a meta-analysis using a random effects model to estimate the common odds ratio and standard error.

Results

Here, we show by meta-analysis of data from 2475 individuals that emphysematous change on CT scan is associated with a significant increased odds ratio for recurrent pneumothorax ipsilateral to the radiological abnormality (odds ratio 2.49, 95% confidence interval 1.51–4.13).

Conclusions

The association holds true for primary spontaneous pneumothorax when considering emphysematous changes including blebs and bullae. Features, such as bullae at the azygoesophageal recess or increased Goddard score similarly predicted recurrent secondary pneumothorax, as shown by subgroup analysis. Our meta-analysis suggests that CT scanning has value in risk stratifying patients considering surgery for pneumothorax.
Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis
Authors: Ruperto Nicolino , Brunner Hermine I , Ramanan Athimalaipet V , Horneff Gerd , Cuttica Rubén , Henrickson Michael , Anton Jordi , Boteanu Alina Lucica , Penades Inmaculada Calvo , Minden Kirsten , Schmeling Heinrike , Hufnagel Markus , Weiss Jennifer E , Pardeo Manuela , Nanda Kabita , Roth Johannes , Rubio-Pérez Nadina  , Hsu Joy C , Wimalasundera Sunethra , Wells Chris , Bharucha Kamal  , Douglass Wendy , Bao Min , Mallalieu Navita L , Martini Alberto , Lovell Daniel , Benedetti Fabrizio De ,   for the Paediatric Rheumatology INternational Trials Organisation (PRINTO) and the Paediatric Rheumatology Collaborative Study Group (PRCSG)
Published: January 2021

Objectives

To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA).

Methods

In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA.

Results

Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ.

Conclusion

s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279
Causal pathways to health-related quality of life in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort
Authors: Oen Kiem , Tian Jiahao , Loughin Thomas M , Shiff Natalie J , Tucker Lori B , Huber Adam M   , Berard Roberta A , Levy Deborah M , Rumsey Dax G , Tse Shirley M , Chan Mercedes , Feldman Brian M , Duffy Ciaran M , Guzman Jaime ,   for the ReACCh-Out Investigators
Published: January 2021

Objective

Structural equation modelling was applied to data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort to help elucidate causal pathways to decreased health-related quality of life (HRQoL) in children with JIA.

Methods

Based on published literature and clinical plausibility, a priori models were constructed with explicit root causes (disease activity, treatment intensity) and mediators (pain, disease symptoms, functional impairments) leading to HRQoL [measured by the Quality of my Life (QoML) scale and the Juvenile Arthritis Quality of Life Questionnaire (JAQQ)] at five disease stages: (i) diagnosis, (ii) 3–9 months after diagnosis, (iii) flare, (iv) remission on medications, (v) remission off medications. Following structural equation modelling, a posteriori models were selected based on data fit and clinical plausibility.

Results

We included 561, 887, 137, 186 and 182 patients at each stage, respectively. In a posteriori models for active disease stages, paths from disease activity led through pain, functional impairments, and disease symptoms, directly or through restrictions in participation, to decreased QoML scores. Treatment intensity had detrimental effects through psychosocial domains; while treatment side effects had a lesser role. Pathways were similar for QoML and JAQQ, but JAQQ models provided greater specificity. Models for remission stages were not supported by the data.

Conclusion

Our findings support disease activity and treatment intensity as being root causes of decreased HRQoL in children with JIA, with pain, functional impairments, and participation restrictions being mediators for disease activity; they support psychosocial effects and side effects as being mediators for treatment intensity.
Informed Trading and Momentum in the Corporate Bond Market
Authors: Li Lifang , Galvani Valentina
Published: January 2021

Taking advantage of the different trading behaviors of investors on same-issuer bonds, we show that informed trading lies at the core of the momentum effect for corporate bonds. We split the firm-level bond cross-section into top (nontop) bonds that are characterized by higher (lower) volumes of institution-sized trades. We show that top bonds attract more informed trading and transmit information faster than nontop bonds. We design specific top and nontop bond momentum strategies to capitalize on this informational heterogeneity. The results indicate that fast news spreading yields short-lived momentum in top bonds, whereas momentum in nontop bonds is strong and drawn-out due to slow information diffusion. These differences are concentrated in bond-level information-intensive periods and are not explained by differences in liquidity levels, systematic risk (including liquidity risk), bond characteristics, and market states. In particular, bond-level liquidity affects the momentum effect only by altering the rate at which news spreads.
Known Distribution of the Soybean Cyst Nematode, Heterodera glycines, in the United States and Canada in 2020
Authors: Tylka Gregory L. , Marett Christopher C.
Published: January 2021

In the United States and Canada, the most damaging pathogen of soybean, Glycine max, is the soybean cyst nematode (SCN), Heterodera glycines. Plant health professionals working for universities and state and provincial departments of agriculture in the United States and Canada are queried periodically about counties and rural municipalities that are newly known to be infested with SCN in their states and provinces. Such a census was conducted in 2020, and the results were compared with results of the most recent survey, published in 2017. Between 2017 and 2020, 55 new SCN-infested counties were reported from 11 U.S. states. Also, 24 new SCN-infested counties and rural municipalities were identified in the Canadian provinces of Manitoba, Ontario, and Quebec. A map of the known distribution of SCN in these two countries was updated. The results reveal steady expansion of the distribution of SCN throughout the United States and Canada, and the pest almost certainly will continue to spread among and within soybean-producing areas of these countries in the future. Therefore, continued scouting and soil sampling for detection of new SCN infestations are warranted as the first step toward successfully managing the pathogen.
Low Preoperative Lung Functions in Children With Early Onset Scoliosis Predict Postoperative Length of Stay
Authors: White Klane K. , Bompadre Viviana , Krengel Walter F. , Redding Gregory J.
Published: January 2021

Introduction:

Children with early onset scoliosis (EOS) undergoing spine surgery often have significant respiratory disease. Preoperative risk assessments that predict an increased length of hospital stay (LOS) for this group have not been previously evaluated.

Methods:

A voluntary protocol using preoperative lung function studies began among participants of a multicenter registry in 2016. Preoperative assessments were standardized to include spirometry, blood hemoglobin levels, serum bicarbonate, albumin and prealbumin; radiographic parameters of the spine, C-EOS classification and need for preoperative pulmonary assistance before initial growth friendly device insertion or “definitive” spine fusion. Primary outcome was LOS postoperatively. Data, including age, diagnosis, and type of surgery, was collected prospectively. Secondary outcomes measured included intensive care unit LOS, requirement for new pulmonary assistance on discharge, and pulmonary complications. Groups were compared using the Fisher exact tests.

Results:

Of 525 children enrolled, 101 (20%) had preoperative spirometry. Median age was 8.9 years [interquartile range (IQR): 4.27]. Etiologies for EOS included 29 neuromuscular (28%), 33 idiopathic (32%), 19 syndromic (19%), and 22 congenital (21%) scoliosis. Eighty (78%) had growing rod (GR) insertions; 23 (22%) had spine fusion SF. Eighteen subjects (17%) were hospitalized ≥7 days (median=9 d); 83 had a LOS <7 days (median=3 d). Percentage of forced vital capacity (FVC%) predicted was inversely associated with LOS ≥7 days with a median of 75.3% (IQR: 41.7) for LOS <7 days and 51.7% (IQR: 41.6) (P=0.02). There were no detectable differences in LOS for other preoperative values.

Conclusion:

FVC predicted ≤50% preoperatively in children undergoing initial growth friendly rod insertion or definitive fusion after growth friendly treatment is associated with an increased risk of postoperative hospital stays ≥7 days. As demonstrated in previous studies, severe restrictive lung disease (FVC% predicted at or below 50%) is associated with increased risk of poorer outcomes for EOS patients.
Do Obese Children Have Poor Patient-reported Outcomes After Closed Reduction and Percutaneous Pin Fixation of Supracondylar Humerus Fractures?
Authors: DiBartola Alex C. , Thakur Nikita , Singh Satbir , Quinion Carl D. , Samora Julie Balch
Published: January 2021

Background:

Nearly 1 in 5 American children are obese. The primary purpose of this study is to evaluate the relationship between childhood obesity and perioperative complications, patient-reported outcomes (PRO), and functional recovery after closed reduction and percutaneous pinning (CRPP) of type II and III supracondylar humerus fractures.

Methods:

Retrospective review of patients treated operatively with CRPP of Wilkins modification of the Gartland classification type II and III supracondylar humerus fractures was performed over a 1-year timeframe (July 1, 2016 to July 1, 2017). One hundred forty-four patients under the age of 16 treated were identified. Obesity was defined as body mass index (BMI) at or above the 95th percentile for age. Obesity as a risk factor for poor outcomes was assessed. The primary outcome measure was postoperative PRO [quick-DASH, Patient Reported Outcomes Measurement Information System (PROMIS)-UE, PROMIS Global Health, and PROMIS Pain scores].

Results:

Mean age at surgery was 5.9 years (SD=2.1, 1.07 to 12.2) and mean age at final follow-up (3.3 y) was 8.8 (SD=2.14, 4 to 16). Mean patient BMI was 17.2 (SD=4.48, 12.4 to 56.2). Sixty-six patients were female (45.8%) and 78 patients were male (54.2%). In all, 31 of 144 patients (21.5%) met criteria for obesity. Obesity (95th percentile for BMI or above) was not associated with a higher rate of complications overall (χ2=1.29, P=0.256), range of motion loss (χ2=0.2, P=0.655) or requirement of postoperative physical therapy (χ2=0.17, P=0.678). Seventy-five patients were available and willing to participate in the outcomes score assessments. Mean follow-up for this cohort of 75 patients was 3.3 years (SD=0.31, 2.85 to 3.88). There were no differences in PROMIS pain, PROMIS upper extremity function, PROMIS general health, or quick-DASH scores when comparing obese with nonobese patients.

Conclusions:

Obesity is a growing concern in the United States and its effect on long-term outcomes after CRPP of supracondylar humerus fractures is unknown. The present study demonstrates no difference in complications or PRO among obese patients compared with nonobese patients.

Level of Evidence:

Level IV—retrospective cohort study.
A Post Hoc Analysis of Osmotherapy Use in the Erythropoietin in Traumatic Brain Injury Study—Associations With Acute Kidney Injury and Mortality
Authors: Skrifvars Markus B. , Bailey Michael , Moore Elizabeth , Mårtensson Johan , French Craig , Presneill Jeffrey , Nichol Alistair , Little Lorraine , Duranteau Jacques , Huet Olivier , Haddad Samir , Arabi Yaseen M. , McArthur Colin , Cooper David James , Bendel Stepani , Bellomo Rinaldo
Published: January 2021

OBJECTIVES:

Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown.

DESIGN:

A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use.

SETTING:

Twenty-nine university-affiliated teaching hospitals in seven countries.

PATIENTS:

A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2–4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9–2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1–4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02–3.2; p = 0.04) were associated with time to death.

CONCLUSIONS:

In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.
Congenital vascular lesions, could MAPK and PI3K inhibitors pave the way to new therapies?
Authors: Bisdorff-Bresson Annouk , Eyries Mélanie , Boccara Olivia
Published: January 2021

Purpose of review

Superficial vascular anomalies are a heterogeneous group of malformative and tumoral lesions, developed from various types of abnormal lymphatic and/or blood vessels. They are mostly benign but their clinical evolution can lead to dramatic cosmetic concern, functional impairment and even life-threatening conditions. Until recently, treatments relied on invasive procedures such as embotherapy/sclerotherapy and/or surgery. Recent molecular findings pave the way of new medical therapies.

Recent findings

Two main signaling pathways PI3K-AKT-mTOR and RAS-MAPK-ERK are now identified to encounter for the causative pathogenic genetic variants of most vascular anomalies. Involved genes are also responsible for several common neoplasms for which targeted therapies are already available or under development. Repurposing treatment strategy is considered for vascular anomalies treatment with promising results.

The mTOR inhibitor sirolimus is the most used targeted therapy so far but new molecules are tested currently.
Extramedullary Blast Crisis of Chronic Myelogenous Leukemia With a Skin Lesion: A Case Report and Literature Review
Authors: Qi Jing , Zhang Fan , Liu Yinhua , Yao Junping , Xu Youhai , He Hesheng
Published: January 2021

Extramedullary blast crisis of chronic myeloid leukemia (CML) is defined as extramedullary disease composed of blasts regardless of the proliferation of blasts in the bone marrow. The commonly affected sites are the lymph node, central nervous system, bone, skin, and soft tissue. However, skin infiltration of CML patients as the initial presentation while their bone marrow is still in the chronic phase is extremely rare. In this article, we present a case of a 51-year-old woman who was admitted to our hospital complaining about a skin nodule in her right calf and easy fatigability for 1 week. The peripheral blood and bone marrow analysis both supported the diagnosis of CML in the chronic phase, whereas the excisional biopsy specimen obtained from her right calf showed immature cells infiltration, and fluorescence in situ hybridization test was positive for p210 BCR/ABL1 gene rearrangement. Based on the presence of extramedullary myeloid sarcoma, the patient was diagnosed with extramedullary myeloid blast crisis of CML despite the chronic phase in the bone marrow.
Efficacy and Safety of a New Botulinum Toxin (HU-014) Versus Existing Onabotulinumtoxin A in Subjects With Moderate to Severe Glabellar Lines
Authors: Yoo Kwang Ho , Lee Yang Won , Lee Ji Su , Kwon Soon Hyo , Huh Chang Hun , Kim Beom Joon
Published: January 2021

BACKGROUND

Recently, the safety of a new botulinum toxin (HU-014) was confirmed through animal experiments. The evaluation of the efficacy and safety of this newly introduced botulinum toxin is required considering the risk of adverse events (AEs) and need for standardization before its universal use.

OBJECTIVE

The aim of this multicenter, double-blind, randomized, parallel, active-controlled phase III clinical trial was to investigate the noninferiority of HU-014 versus existing onabotulinumtoxin A for the treatment of moderate to severe glabellar lines.

METHODS

In total, 267 subjects were randomized to either the test (HU-014) or control (onabotulinumtoxin A) group. At the baseline and at weeks 4, 8, 12, and 16, investigator's live assessment, independent photographic assessment, subjects' improvement assessment, subjects' satisfaction assessment, and safety assessment were performed.

RESULTS

At week 4, the response rate was 90.15% and 92.31% in the test and control groups, respectively, as per investigator's live assessment while frowning, without a significant difference. Both groups also showed no significant differences in response rates in the other assessments. In addition, no serious AEs were reported.

CONCLUSION

HU-014 was noninferior to existing onabotulinumtoxin A in the treatment of glabellar lines at a 1:1 dose ratio, and both products were well tolerated.
Pulse-Dye Laser Followed by Betamethasone-Calcipotriol and Fractional Ablative CO2-Laser-Assisted Delivery for Nail Psoriasis
Authors: Shehadeh Waseem , Matz Hagit , Ellenbogen Eran , Sprecher Eli , Artzi Ofir
Published: January 2021

BACKGROUND

Nail psoriasis is a common and potentially debilitating condition for which no effective and safe nonsystemic therapy is currently available. Recently, laser-assisted drug delivery (LADD) is being increasingly used to facilitate transcutaneous penetration of topical treatments.

OBJECTIVES

We set to assess the efficacy and safety of combined pulse-dye laser and fractional CO2 laser-assisted betamethasonecalcipotriol gel delivery for the treatment of nail psoriasis.

MATERIAL AND METHODS

We conducted a prospective, intrapatient comparative study in a series of 22 patients with bilateral fingernail psoriasis. Nails on the randomized hand were treated with 3 monthly sessions of pulse-dye laser to the proximal and lateral nail folds followed by fractional ablative CO2 laser to the nail plate. Between treatments and one month following the last treatment, the participants applied betamethasone propionate-calcipotriol gel once daily to the nail plate. Clinical outcome was ascertained using nails photography, the Nail Psoriasis Severity Index (NAPSI) and patient satisfaction.

RESULTS

Seventeen completed the study. Three participants withdrew from the study because of treatment-associated pain. Treatment was associated with a statistically significant improvement of the NAPSI scale (p < .002). Patient satisfaction was high.

CONCLUSION

Combined PDL and fractional ablative CO2-LADD of betamethasone-calcipotriol gel should be considered for the treatment of nail psoriasis.
Safety and Efficacy of Dermal Fillers in Patients With Connective Tissue Disease: A Review
Authors: Gonzalez Cristian D. , Pamatmat Jarod John , Goff Heather W.
Published: January 2021

BACKGROUND

Dermal fillers such as hyaluronic acid, poly-l-lactic acid, and polymethyl-methacrylate are often used to treat cutaneous defects such as lipoatrophy. However, concern exists regarding their use in patients with a connective tissue disease (CTD) because of a theoretical risk of disease reactivation or exacerbation. Evidence regarding their use in patients with CTD also remains limited.

OBJECTIVE

This review intends to summarize and evaluate the available literature regarding the use of dermal fillers in patients with CTD.

MATERIALS AND METHODS

A literature search until May 2020 was conducted through PubMed, Ovid MEDLINE, and Ovid Embase to identify articles discussing the treatment of cutaneous defects secondary to CTD. Articles discussing the use of autologous fat transfer alone were excluded.

RESULTS

Twenty-three articles were reviewed. The amount of available evidence varies between the type of CTD and type of filler with morphea having the most published evidence out of the CTDs discussed and hyaluronic acid having the most published evidence out of the fillers discussed. Most studies demonstrated positive results with no report of disease reactivation or exacerbation.

CONCLUSION

Despite limited available evidence, dermal fillers seem to be safe as an adjunctive treatment for cutaneous defects in patients with CTD.
Treatment of Cutaneous Squamous Cell Carcinoma In Situ With Curettage Followed by Topical Imiquimod 5% Cream
Authors: Ondo Andrew L. , Kerner James D. , Kerner Jacob V. , Ondo Isaac P. , Trainor Patrick , Shanler Stuart D.
Published: January 2021

BACKGROUND

Treatment strategies for cutaneous squamous cell carcinoma in situ (cSCCIS) are many but reported cure rates are variable and few studies report 5-year follow-up data.

OBJECTIVE

To evaluate the treatment of cSCCIS by curettage followed by topical imiquimod 5% cream (C&I).

METHODS

We evaluated all immunocompetent patients with biopsy proven cSCCIS treated by C&I between January 2008 and December 2012.

RESULTS

A total of 861 patients with 1,198 cSCCIS were treated, with median follow-up of 71 months. The mean tumor diameter was 10.2 mm. The average duration of treatment with imiquimod 5% cream was 21 days. Kaplan–Meier estimated recurrence-free survival at 5-year follow-up was 99.71% with 95% CI (99.38%, 100.00%). A follow-up questionnaire returned by 45% of patients revealed that 94% were satisfied with their treatment. Six hundred eleven patients developed a new nonmelanoma skin cancer (NMSC) during the follow-up period, and 91% (556/611) of patients chose this combination treatment for at least one new NMSC.

CONCLUSION

The combination treatment for cSCCIS of C&I had less than 1% cumulative probability of treatment failure at 5 years. Patients tolerated the treatment well, with the majority choosing this method of treatment for at least one new NMSC.
A Pragmatic Approach to the Treatment of Women With Type 2 Diabetes in Pregnancy
Authors: BENDER WHITNEY , DURNWALD CELESTE
Published: January 2021

Type 2 diabetes mellitus (DM) is a growing problem among reproductive-aged women. Contemporary trends in obesity and delayed child-bearing are expected to result in an increasing number of pregnancies affected by type 2 DM. Women with known type 2 DM can greatly benefit from preconception care as improved periconception glycemic control and weight loss can decrease the neonatal and maternal risks associated with type 2 DM and pregnancy. Antenatal mainstays of management include frequent blood glucose monitoring, insulin therapy, optimization of coexisting medical conditions, and fetal surveillance. Careful attention to postpartum glucose control, infant feeding choices, and contraceptive counseling are important aspects of immediate postpartum care.
Menstrual Dysfunction in PCOS
Authors: WALKER KARRIE , DECHERNEY ALAN H. , SAUNDERS RHIANA
Published: January 2021

Menstrual irregularities due to anovulation or severe oligoovulation are a key feature of polycystic ovary syndrome for many women. First-line intervention should entail dietary and lifestyle modifications for overweight or obese polycystic ovary syndrome women. For women not seeking fertility, combination low-dose hormonal contraception are the most effective and first-line choice for regulating menstrual cycles. This option, as well as progestin-only options, have the important added benefit of reducing risks of endometrial hyperplasia and cancer. Metformin is an appropriate medical option to improve ovulation rates for women who cannot take combined hormone contraception or whom are attempting conception.
Educating Trainees to Manage Pregnant Women With Obesity: A Primer
Authors: Reilly Justine , Burrell Dayna
Published: January 2021

This review is intended to outline essential resources for trainees in order to optimize education on the care of pregnant patients with obesity. Addressing provider biases, exploring ethical considerations of care and streamlining screening and counseling of patients with obesity will provide an excellent framework for our trainees to care for women with obesity from preconception to postpartum care and beyond.
AUTOLOGOUS POSTERIOR CAPSULE FLAP TRANSPLANTATION IN THE MANAGEMENT OF REFRACTORY MACULAR HOLE IN A PSEUDOPHAKIC EYE
Authors: Yuguchi Takaaki , Ogura Shuntaro , Hirano Yoshio , Suzuki Norihiro , Yasukawa Tsutomu , Ogura Yuichiro
Published: January 2021

Purpose:

To report a case of refractory macular hole (MH) in pseudophakic eye treated with autologous posterior capsule flaps transplantation.

Methods:

Case report.

Results:

A 48-year-old man visited our hospital with visual loss in the right eye because of unclosed MH. The patient had undergone two previous surgeries in another hospital, that is, the first included a cataract surgery, vitrectomy, and internal limiting membrane peeling with sulfur hexafluoride (SF6) gas tamponade, and the second included an ineffective autologous internal limiting membrane flap technique and massaging the edges of the MH with a soft-tipped flute needle followed by the same gas, but the MH remained open. In our hospital, posterior capsule flaps were acquired from the same eye, inserted into the MH, and the same gas tamponade was performed, which was about four months after the disease onset (3 months after the prior second surgery). The patient kept face-down position for a week after the surgery and the MH was closed, which remained for over 12 months. The visual acuity improved from 20/250 to 20/60, and the retinal sensitivities around the MH gradually improved.

Conclusion:

An autologous posterior capsule flaps transplantation was effective in the management of refractory MH to not only close the MH but also improve the visual outcomes.
Malignant Conversion of Eyelid Capillary Hemangioma to Cutaneous Angiosarcoma
Authors: Heinze Kevin , Pham Chau , Lin Amy , Setabutr Pete
Published: January 2021

Angiosarcomas represent a rare aggressive malignancy of endothelial cell origin that carry a poor prognosis. Here, the authors report the case of a 71-year-old male presenting with a well-differentiated angiosarcoma of the right upper eyelid which arose at the site of a congenital eyelid hemangioma. The patient had undergone multiple surgical resections of the hemangioma previously without adjunctive radiation therapy. This lends evidence to the potential for malignant transformation of benign hemangiomas, and long-term monitoring of benign cutaneous vascular lesions should be considered.
A Predictive Model for the Diagnostic and Therapeutic Yield of Colonoscopy Performed for Lower Gastrointestinal Bleeding
Authors: Chung Waihong , Rich Harlan , Wands Jack
Published: January 2021

Background:

Although colonoscopy is routinely performed for the management of lower gastrointestinal bleeding (LGIB), the quality of evidence supporting its use is poor and its yield for active bleeding or malignancy is low in practice.

Methods:

We conducted a retrospective analysis of all adult patients who underwent colonoscopies for LGIB at our hospital system between January 1, 2015, and December 31, 2019. A statistical model was built on a cohort of 5195 cases using multiple logistic regressions to predict the detection of various colonoscopy findings and the use of different colonoscopy maneuvers. The model was converted into a risk scoring system, named the TYPICAL Index, and was validated against a separate cohort of 914 cases.

Results:

Active bleeding was only seen in 3.8% of colonoscopies performed for LGIB and endoscopic hemostasis was applied in 43.7% of actively bleeding lesions. Malignant-appearing lesions were detected in 2.5% of LGIB procedures and all cases of proximal colonic mass were identified in subjects age above 60. The TYPICAL Index, derived from age, gender, hemoglobin, creatinine, international normalized ratio, and prior colonoscopy for LGIB has a concordance statistic of 0.71 and a negative predictive value of 93.8% for potential bleeding sources requiring hemostasis, malignant-appearing lesions, or active bleeding on colonoscopy when applied using a threshold of 6.

Conclusions:

Active bleeding and malignancies are rarely encountered and endoscopic hemostasis is seldom required during colonoscopy performed for LGIB. We developed and validated a risk scoring system to identify cases of low predicted diagnostic and therapeutic yield and to guide clinical decision-making.
Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection
Authors: Du Charles , Luo Yuying , Walsh Samantha , Grinspan Ari
Published: January 2021

Goals:

We performed a systematic review with meta-analysis to examine the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules for recurrent Clostridioides difficile infection (rCDI).

Background:

FMT through colonoscopy is established as effective and safe in treating multiple recurrences of CDI, but consensus has not been established on delivery through oral capsules.

Study:

A systematic literature search was performed with multiple databases including MEDLINE and EMBASE to identify original studies including at least 10 patients that investigated the role of oral FMT capsules to treat rCDI. Cure rates were pooled by a random effects model and publication bias was assessed with the Egger test. Secondary analyses assessed for differences between capsule preparation (frozen vs. lyophilized stool) and delivery modality (capsule vs. colonoscopy).

Results:

Fifteen studies (12 case series and 3 randomized controlled trials) encompassing 763 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols. Meta-analysis of proportions showed efficacy of oral FMT capsules to be 0.821 (95% confidence interval: 0.762-0.874). No evidence for publication bias was found (P=0.51). Secondary analyses did not find significant differences in efficacy. Fourteen adverse events leading to death or hospitalization were noted, none of which were attributed to FMT.

Conclusions:

Oral FMT capsules for rCDI are promising because of ease of administration and noninvasive delivery. We found an overall efficacy of 82.1% with a low rate of serious adverse events. Further studies are needed to optimize protocols and outcomes.
Primary biliary cholangitis: treatment
Authors: Cazzagon Nora , Floreani Annarosa
Published: January 2021

Purpose of review

To discuss the most recent data regarding treatment of patients with primary biliary cholangitis (PBC) with inadequate response to ursodeoxycholic acid (UDCA).

Recent findings

Patients with PBC at high-risk of progressive disease are younger, have advanced fibrosis and showed inadequate response to UDCA after 12 months of treatment. These patients need a second-line treatment in addition to UDCA. The goal of therapy should be the normalization of ALP and bilirubin below 0.6 the upper limit of normal. Obeticholic acid (OCA) has proven to be effective in improving surrogate markers of prognosis in PBC, also in real-life cohort. Pruritus is the most frequent adverse event during treatment with OCA. Bezafibrate is another option in patients with inadequate response to UDCA as it was proven to improve surrogate endpoints, pruritus and even, clinical outcome compared with UDCA monotherapy. Finally, budesonide may be considered in patients with marked portal inflammation. Triple therapy with UDCA, OCA and bezafibrate may be considered in patients showing inadequate response to dual therapy.

Patients with PBC need to be evaluated at baseline, and on-treatment, for the risk of progressive disease and eventually treated with second-line therapies in addition to UDCA.