bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying and Quantifying Cannabinoids in Biological Matrices in the Medical and Legal Cannabis Era
Authors: Karschner Erin L , Swortwood-Gates Madeleine J , Huestis Marilyn A
Published: May 2020

Background

Cannabinoid analyses generally included, until recently, the primary psychoactive cannabis compound, Δ9-tetrahydrocannabinol (THC), and/or its inactive metabolite, 11-nor-9-carboxy-THC, in blood, plasma, and urine. Technological advances revolutionized the analyses of major and minor phytocannabinoids in diverse biological fluids and tissues. An extensive literature search was conducted in PubMed for articles on cannabinoid analyses from 2000 through 2019. References in acquired manuscripts were also searched for additional articles.

Content

This article summarizes analytical methodologies for identification and quantification of multiple phytocannabinoids (including THC, cannabidiol, cannabigerol, and cannabichromene) and their precursors and/or metabolites in blood, plasma, serum, urine, oral fluid, hair, breath, sweat, dried blood spots, postmortem matrices, breast milk, meconium, and umbilical cord since the year 2000. Tables of nearly 200 studies outline parameters including analytes, specimen volume, instrumentation, and limits of quantification. Important diagnostic and interpretative challenges of cannabinoid analyses are also described. Medicalization and legalization of cannabis and the 2018 Agricultural Improvement Act increased demand for cannabinoid analyses for therapeutic drug monitoring, emergency toxicology, workplace and pain-management drug testing programs, and clinical and forensic toxicology applications. This demand is expected to intensify in the near future, with advances in instrumentation performance, increasing LC-MS/MS availability in clinical and forensic toxicology laboratories, and the ever-expanding knowledge of the potential therapeutic use and toxicity of phytocannabinoids.

Cannabinoid analyses and data interpretation are complex; however, major and minor phytocannabinoid detection windows and expected concentration ranges in diverse biological matrices improve the interpretation of cannabinoid test results.
Heat, health and hatchlings: associations of in situ nest temperatures with morphological and physiological characteristics of loggerhead sea turtle hatchlings from Florida
Authors: Fleming Kelsey A , Perrault Justin R , Stacy Nicole I , Coppenrath Christina M , Gainsbury Alison M
Published: May 2020

Incubation temperatures, in addition to an embryo’s genetic makeup, are critical in many aspects of adequate sea turtle embryonic development. The effects of high and low incubation temperatures on hatchling quality have been previously examined; however, many of these studies were conducted on relocated or laboratory-reared nests, which do not accurately reflect natural nest temperature fluctuations. To observe the impacts of varying in situ incubation temperatures on loggerhead sea turtle (Caretta caretta) hatchling morphology, various health variables and locomotor performance, temperature data loggers were deployed in 15 loggerhead nests on Juno Beach, Florida, between May and July 2018. Over the course of the study period, 10 morphological traits were measured, blood analytes and heart rate were assessed for the establishment of reference intervals and the self-righting response in seawater was evaluated. Warmer months were associated with smaller body size and higher body condition index, larger umbilical scar size, slower righting time, lower heart rates and higher packed cell volume, hemoglobin, total solids, total white blood cell count, absolute heterophils and absolute basophils. These findings provide evidence that higher in situ incubation temperatures have the potential to adversely affect hatchlings from warmer nests due to increased risk of predation from smaller body sizes, decreased physical responses and overall fitness, altered hemodynamic balance (e.g. dehydration) and potential inflammation and/or stress. With rising temperatures, we predict sea turtle hatchlings may have increasing risks of developing suboptimal physiological features affecting overall fitness and ultimately survival. These results demonstrate that rising environmental temperatures can negatively impact sea turtle hatchlings, thus representing additional stress on sea turtle populations and contributing to our understanding of potential pathophysiological effects of climate change on the delicate life-stage class of the sea turtle hatchling. This information will be useful for formulating effective future sea turtle management plans.
Cylinder mitral and tricuspid valve replacement in neonates and small children
Authors: Myers Patrick O , Dave Hitendu , Kretschmar Oliver , Sologashvili Tornike , Pfister Raymond , Prêtre René
Published: May 2020

OBJECTIVES

Atrioventricular valve replacement in small children is associated with high morbidity and mortality. There are no prostheses available with a diameter ˂15 mm. This study reports our initial experience with a cylinder valve for mitral and tricuspid valve replacement in infants and small children.

METHODS

Our cylinder valve was hand-made for patients requiring atrioventricuclar valve replacement with an annulus of <15 mm. A 12-mm Contegra valve was prepared and placed inside a 14-mm Gore-Tex tube graft and sutured on both extremities.

RESULTS

Eight patients were included, with a median age of 6.9 months (range 1 day to 38 months). Four had mitral and 4 had tricuspid valve replacement. All implants were technically successful, with no significant regurgitation, no stenosis and no left ventricular outflow tract obstruction. There were 3 early deaths from low cardiac output, in patients with significant associated lesions (severe neonatal Ebstein’s, pulmonary artery-intact ventricular septum, biventricular conversion from Norwood stage 1). Two patients required early reintervention: 1 for balloon dilatation for stenosis and 1 for reoperation for paravalvular leak. During follow-up, 2 patients had mitral valve replacement with a 16-mm mechanical valve at 9 and 20 months from the cylinder valve implantation. The remaining 2 patients are alive and well 2 years and 2 months after the procedure.

CONCLUSIONS

Cylinder valve replacement of atrioventricular valves was feasible without any technical issues. It was successful in getting out of a difficult situation and allows for somatic growth and implantation of a reasonably-sized mechanical prosthesis on the annulus.
Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study
Authors: Gao Chao , Cai Yue , Zhang Kan , Zhou Lei , Zhang Yao , Zhang Xijing , Li Qi , Li Weiqin , Yang Shiming , Zhao Xiaoyan , Zhao Yuying , Wang Hui , Liu Yi , Yin Zhiyong , Zhang Ruining , Wang Rutao , Yang Ming , Hui Chen , Wijns William , McEvoy J William , Soliman Osama , Onuma Yoshinobu , Serruys Patrick W , Tao Ling , Li Fei
Published: May 2020

Aims

It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19).

Methods and results

This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17–3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03–4.57, P = 0.041). The mortality rates were similar between the renin–angiotensin–aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28–2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45–0.94, P = 0.20).

Conclusion

While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.
Exploring primary health care professionals’ perceptions about a patient feedback intervention to improve patient safety in Spanish primary health care centres: a qualitative study
Authors: Serrano-Ripoll Maria J , Ripoll Joana , Briones-Vozmediano Erica , Llobera Joan , Fiol-deRoque Maria A , Ricci-Cabello Ignacio
Published: May 2020

Background

Patient feedback interventions are receiving increasing attention given their potential to improve health care provision. However, primary health care (PHC) professionals’ acceptability and perceived utility of this type of interventions remain largely unexplored.

Objectives

The aim of this study was to explore PHC professionals’ perceptions, opinions and suggestions about a patient feedback intervention currently being designed to improve patient safety in Spanish PHC centres.

Methods

We conducted an exploratory qualitative study with 43 PHC professionals. Information was obtained from three semi-structured interviews and four focus groups. All data were audio-recorded, transcribed and analyzed using content analysis by three analysts.

Results

The patient feedback intervention was acceptable to health care professionals, who perceived it as a useful strategy to improve health care processes and activate patients. A number of factors potentially limiting the acceptability and perceived utility of the intervention were identified (low patient safety culture, low patient-centred care orientation and limited credibility of patient feedback data). Recommendations for designing and implementing the proposed intervention in the Spanish PHC centres were identified in relation to the following areas: ‘collection and analysis of feedback data’; ‘feedback display’; ‘feedback delivery’ and; ‘implementation of safety improvement initiatives’.

Conclusions

Although the proposed intervention was generally perceived as useful and acceptable, our study identified a number of tensions about the practical aspects of using the patient-reported data and the credibility of the data and what actions would arise from its use. The intervention has been adapted to address these tensions before its formal evaluation in a randomized clinical trial.
Rethinking liability rules for online hosting platforms
Authors: Buiten Miriam C , de Streel Alexandre , Peitz and Martin
Published: May 2020

With the growing economic and societal importance of online platforms, the question of their liability for illegal content or products they host becomes more important. Based on an analysis of platforms’ incentives, we address the appropriate liability rule for hosting service providers and derive policy recommendations for an efficient liability regime in the European Union. Online hosting platforms may take monitoring efforts on their own initiative that are suboptimal due to the presence of externalities and asymmetric information problems, warranting some form of liability rules. However, for more fundamental reasons of free speech and preventing censorship, policy makers may want to be cautious in entrusting—and burdening—private parties which such an extensive ‘policing’ role. Additionally, higher monitoring requirements may disproportionally burden small entrants. As we argue, since several actors participate to the diffusion of illegal material online, the responsibility of a safe Internet should be shared among all these actors. Concrete regulatory improvements may encourage online hosting platforms to do their part in monitoring proactively and diligently.
Prediction of Breast Cancer Treatment–Induced Fatigue by Machine Learning Using Genome-Wide Association Data
Authors: Lee Sangkyu , Deasy Joseph O , Oh Jung Hun , Di Meglio Antonio , Dumas Agnes , Menvielle Gwenn , Charles Cecile , Boyault Sandrine , Rousseau Marina , Besse Celine , Thomas Emilie , Boland Anne , Cottu Paul , Tredan Olivier , Levy Christelle , Martin Anne-Laure , Everhard Sibille , Ganz Patricia A , Partridge Ann H , Michiels Stefan , Deleuze Jean-François , Andre Fabrice , Vaz-Luis Ines
Published: May 2020

Background

We aimed at predicting fatigue after breast cancer treatment using machine learning on clinical covariates and germline genome-wide data.

Methods

We accessed germline genome-wide data of 2799 early-stage breast cancer patients from the Cancer Toxicity study (NCT01993498). The primary endpoint was defined as scoring zero at diagnosis and higher than quartile 3 at 1 year after primary treatment completion on European Organization for Research and Treatment of Cancer quality-of-life questionnaires for Overall Fatigue and on the multidimensional questionnaire for Physical, Emotional, and Cognitive fatigue. First, we tested univariate associations of each endpoint with clinical variables and genome-wide variants. Then, using preselected clinical (false discovery rate < 0.05) and genomic (P < .001) variables, a multivariable preconditioned random-forest regression model was built and validated on a hold-out subset to predict fatigue. Gene set enrichment analysis identified key biological correlates (MetaCore). All statistical tests were 2-sided.

Results

Statistically significant clinical associations were found only with Emotional and Cognitive Fatigue, including receipt of chemotherapy, anxiety, and pain. Some single nucleotide polymorphisms had some degree of association (P < .001) with the different fatigue endpoints, although there were no genome-wide statistically significant (P < 5.00 × 10−8) associations. Only for Cognitive Fatigue, the predictive ability of the genomic multivariable model was statistically significantly better than random (area under the curve = 0.59, P = .01) and marginally improved with clinical variables (area under the curve = 0.60, P = .005). Single nucleotide polymorphisms found to be associated (P < .001) with Cognitive Fatigue belonged to genes linked to inflammation (false discovery rate adjusted P = .03), cognitive disorders (P = 1.51 × 10−12), and synaptic transmission (P = 6.28 × 10−8).

Conclusions

Genomic analyses in this large cohort of breast cancer survivors suggest a possible genetic role for severe Cognitive Fatigue that warrants further exploration.
Distinct Profiles of Attention in Children Born Moderate-to-Late Preterm at 6 Years
Authors: Bogičević Lilly , Verhoeven Marjolein , van Baar Anneloes L
Published: May 2020

Objective

Attention difficulties are commonly reported by caregivers in school-aged children born moderate-to-late preterm (MLPT; 32–36 weeks’ gestation). We aimed to assess distinct aspects of attentional functioning (i.e. orienting, alerting and executive attention, processing speed and behavioral components) in children born MLPT and full term (FT), profiles of attentional functioning, and associated risk factors such as preterm birth.

Methods

Participants were 170 (87 MLPT and 83 FT) children, evaluated on cognitive and behavioral attention aspects at 6 years of age. We used a variable-centered approach to compare attentional functioning of children born MLPT and FT at group level, and a person-centered approach to identify profiles of attentional functioning. Neonatal and demographic characteristics of these profiles were compared.

Results

The variable-centered approach showed that at group level children born MLPT had poorer orienting attention and processing speed, and behavioral attention than children born FT. The person-centered approach revealed four profiles: (a) normal attentional functioning, (b) overall poorer attention, (c) poorer cognitive attention, and (d) behavioral attention problems. Children born MLPT were overrepresented in each of the suboptimal attention profiles, and were more dispersed across profiles than children born FT.

Conclusions

Children born MLPT are at increased risk of difficulties in some attention aspects, but at group level differences with children born FT are small. However, children born MLPT show considerable variation in the nature of attention difficulties and are twice as likely to show a suboptimal attention profile, indicating a cumulation of poorer attention scores.
Cosmic Dawn II (CoDa II): a new radiation-hydrodynamics simulation of the self-consistent coupling of galaxy formation and reionization
Authors: Ocvirk Pierre , Aubert Dominique , Sorce Jenny G , Shapiro Paul R , Deparis Nicolas , Dawoodbhoy Taha , Lewis Joseph , Teyssier Romain , Yepes Gustavo , Gottlöber Stefan , Ahn Kyungjin , Iliev Ilian T , Hoffman Yehuda
Published: May 2020

Cosmic Dawn II (CoDa II) is a new, fully coupled radiation-hydrodynamics simulation of cosmic reionization and galaxy formation and their mutual impact, to redshift z < 6. With 40963 particles and cells in a 94 Mpc box, it is large enough to model global reionization and its feedback on galaxy formation while resolving all haloes above 108 M⊙. Using the same hybrid CPU–GPU code RAMSES–CUDATON as CoDa I in Ocvirk et al. (2016), CoDa II modified and re-calibrated the subgrid star formation algorithm, making reionization end earlier, at z ≳ 6, thereby better matching the observations of intergalactic Lyman α opacity from quasar spectra and electron-scattering optical depth from cosmic microwave background fluctuations. CoDa II predicts a UV continuum luminosity function in good agreement with observations of high-z galaxies, especially at z = 6. As in CoDa I, reionization feedback suppresses star formation in haloes below ∼2 × 109 M⊙, though suppression here is less severe, a possible consequence of modifying the star formation algorithm. Suppression is environment dependent, occurring earlier (later) in overdense (underdense) regions, in response to their local reionization times. Using a constrained realization of lambda cold dark matter constructed from galaxy survey data to reproduce the large-scale structure and major objects of the present-day Local Universe, CoDa II serves to model both global and local reionization. In CoDa II, the Milky Way and M31 appear as individual islands of reionization, i.e. they were not reionized by the progenitor of the Virgo cluster, or by nearby groups, or by each other.
Skeneimorph but not skeneid: systematics and anatomy of Lodderena Iredale, 1924 (Vetigastropoda: Trochoidea)
Authors: Haszprunar Gerhard , Brückner Martin , Ruthensteiner Bernhard
Published: May 2020

The genus Lodderena Iredale, 1924 has been classified in the Skeneidae by most recent authors. However, this family, originally characterized by their minute size, lack of nacre in the teleoconch and a rhipidoglossate radula, is currently considered to be polyphyletic assemblage, and preliminary molecular systematic data suggest exclusion of Lodderena from Skeneidae. In order to shed light on the systematic position of this genus, we provide a detailed description of the anatomy and histology of the type species, Lodderena minima (Tenison-Woods, 1878), and of L. ornata (Olsson & McGinty, 1958). The anatomical data confirm the vetigastropod-trochoid nature of Lodderena but exclude the genus from Skeneidae. Skeneidae are mainly characterized by a propodial penis, a hermaphroditic condition with separated testis and ovary, and a large receptaculum in the mantle roof. In contrast, Lodderena species lack both a copulatory organ and receptaculum, and have a true ovotestis. We also provide a critical review of nominal species in the genus. Based on molecular and morphological evidence, we exclude Lodderena from Skeneidae, instead treating it as a genus incertae sedis within Trochoidea. We discuss the implications of small size for functional morphology and reproduction.
Fluxer: a web application to compute, analyze and visualize genome-scale metabolic flux networks
Authors: Hari Archana , Lobo Daniel
Published: May 2020

Next-generation sequencing has paved the way for the reconstruction of genome-scale metabolic networks as a powerful tool for understanding metabolic circuits in any organism. However, the visualization and extraction of knowledge from these large networks comprising thousands of reactions and metabolites is a current challenge in need of user-friendly tools. Here we present Fluxer (https://fluxer.umbc.edu), a free and open-access novel web application for the computation and visualization of genome-scale metabolic flux networks. Any genome-scale model based on the Systems Biology Markup Language can be uploaded to the tool, which automatically performs Flux Balance Analysis and computes different flux graphs for visualization and analysis. The major metabolic pathways for biomass growth or for biosynthesis of any metabolite can be interactively knocked-out, analyzed and visualized as a spanning tree, dendrogram or complete graph using different layouts. In addition, Fluxer can compute and visualize the k-shortest metabolic paths between any two metabolites or reactions to identify the main metabolic routes between two compounds of interest. The web application includes >80 whole-genome metabolic reconstructions of diverse organisms from bacteria to human, readily available for exploration. Fluxer enables the efficient analysis and visualization of genome-scale metabolic models toward the discovery of key metabolic pathways.
The hyperthermophilic partners Nanoarchaeum and Ignicoccus stabilize their tRNA T-loops via different but structurally equivalent modifications
Authors: Rose Simon , Auxilien Sylvie , Havelund Jesper F , Kirpekar Finn , Huber Harald , Grosjean Henri , Douthwaite Stephen
Published: May 2020

The universal L-shaped tertiary structure of tRNAs is maintained with the help of nucleotide modifications within the D- and T-loops, and these modifications are most extensive within hyperthermophilic species. The obligate-commensal Nanoarchaeum equitans and its phylogenetically-distinct host Ignicoccus hospitalis grow physically coupled under identical hyperthermic conditions. We report here two fundamentally different routes by which these archaea modify the key conserved nucleotide U54 within their tRNA T-loops. In N. equitans, this nucleotide is methylated by the S-adenosylmethionine-dependent enzyme NEQ053 to form m5U54, and a recombinant version of this enzyme maintains specificity for U54 in Escherichia coli. In N. equitans, m5U54 is subsequently thiolated to form m5s2U54. In contrast, I. hospitalis isomerizes U54 to pseudouridine prior to methylating its N1-position and thiolating the O4-position of the nucleobase to form the previously uncharacterized nucleotide m1s4Ψ. The methyl and thiol groups in m1s4Ψ and m5s2U are presented within the T-loop in a spatially identical manner that stabilizes the 3′-endo-anti conformation of nucleotide-54, facilitating stacking onto adjacent nucleotides and reverse-Hoogsteen pairing with nucleotide m1A58. Thus, two distinct structurally-equivalent solutions have evolved independently and convergently to maintain the tertiary fold of tRNAs under extreme hyperthermic conditions.
A case of pyridoxine-dependent epilepsy with novel ALDH7A1 mutations
Authors: Dowa Yuri , Shiihara Takashi , Akiyama Tomoyuki , Hasegawa Kosei , Inoue Fumitaka , Watanabe Mio
Published: May 2020

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal-recessive disorder typically presenting with neonatal seizures and is sometimes difficult to diagnose, because the clinical features mimic those of birth asphyxia. A Japanese newborn boy presented with pulmonary haemorrhage and convulsions on the day of birth. Brain computed tomography showed diffuse, but mild, low-density cerebral white matter and a thin subdural hematoma in the posterior fossa. He did not have thrombocytopenia or coagulopathy. His respiratory status improved with conservative treatment, but his convulsions were persistent even after prescription of several antiepileptic drugs. His serum and cerebrospinal fluid showed decreased vitamin B6 vitamers and increased upstream metabolites of α-aminoadipic semialdehyde dehydrogenase, strongly suggesting a diagnosis of PDE; the epileptic spasms ceased after administration of intravenous pyridoxal phosphate hydrate. Gene analysis revealed novel compound heterozygous mutations in ALDH7A1 that included NM_001182.4:[c.1196G > T] and [c.1200 + 1G > A]. Atypical birth asphyxia with persistent neonatal seizure should prompt vitamin B6/metabolite screening.
An atypical case of ectopic ACTH syndrome in an adolescent boy
Authors: Sharma Shreya , Joshi Rajesh
Published: May 2020

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is exceedingly rare in children and scarcely reported. Pancreatic neuroendocrine tumours (NETs) can rarely lead to secretion of ectopic ACTH. A 14-year-old boy presented with hyperpigmentation, hypertension and intermittent abdominal pain, and was diagnosed with endogenous hypercortisolism. An incidental pancreatic mass discovered on routine ultrasonogram (USG) revealed the source of ACTH. He underwent successful excision of the mass with resolution of hypercortisolism. The histopathology revealed a Pancreatic NET and immunohistochemistry was positive for ACTH stain.
Metastatic breast cancer presenting as acute liver injury: diagnostic dilemma in the setting of suspected hemochromatosis
Authors: Chandradevan Raguraj , Takeda Hironobu , Hayes Benjamin , Faulkner Kalli , Darrow Matthew
Published: May 2020

A 70-year-old female with a history of lobular carcinoma of the breast, status post-mastectomy followed by adjuvant radio-chemotherapy in remission for 4 years was admitted with the features of acute liver failure (ALF). Iron studies revealed a hemochromatosis picture and the CT and MRI scans of the abdomen suggested cirrhosis. An extensive workup failed to identify an etiology. A trans-jugular liver biopsy was obtained and revealed poorly differentiated carcinoma consistent with the metastasis of breast primary. The patient’s condition deteriorated and died within a week following the onset of acute hepatic failure. DNA testing revealed that the patient was heterozygous for H63D mutation. In cases of ALF with the suspicion of malignancy, liver biopsy should be obtained to evaluate an infiltrative hepatic disease.
Serum levels of galectin-3 in idiopathic inflammatory myopathies: a potential biomarker of disease activity
Authors: Watanabe Eri , Kato Kazunori , Gono Takahisa , Chiba Emiko , Terai Chihiro , Kotake Shigeru
Published: May 2020

Objectives

Galectin-3 is involved in various biological activities, including immune activations and fibrosis. Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases of unknown aetiology, often complicated by interstitial lung disease (ILD). The aim of this study was to evaluate the expression of galectin-3 in sera and tissues of patients with IIM and assess the associations of galectin-3 with patient characteristics and disease activity.

Results

Serum galectin-3 levels were significantly higher in IIM patients than in healthy controls. The serum galectin-3 levels positively correlated with serum levels of inflammatory markers and proinflammatory cytokines/chemokines and the Myositis Intention-to-Treat Activity Index. Stratification analysis revealed that patients with IIM-associated ILD (IIM-ILD) had significantly higher levels of serum galectin-3 than those without IIM-ILD. In addition, patients with acute/subacute interstitial pneumonia had significantly higher levels of serum galectin-3 than those with chronic interstitial pneumonia. Furthermore, serum galectin-3 levels in IIM-ILD patients correlated with the radiological assessments of parenchymal lung involvement and treatment response. Immunohistochemical analysis revealed that galectin-3 was expressed in inflammatory cells of myositis and dermatitis sections, whereas in ILD sections, galectin-3 was expressed in interstitial fibrosis and inflammatory cells.

Conclusion

Galectin-3 may be involved in the pathogenesis of inflammatory and fibrotic conditions in IIM and can serve as a potential biomarker of disease activity, especially in patients with IIM-ILD.
Perioperative anaphylaxis: diagnostic challenges and management
Authors: Savic Louise C. , Garvey Lene Heise
Published: May 2020

Purpose of review

Perioperative hypersensitivity reactions can pose diagnostic and management challenges for the anaesthetist. Difficulties in diagnosing hypersensitivity reactions in the perioperative setting are highlighted and recommendations from recent guidelines on the acute management of life-threatening anaphylaxis are presented.

Recent findings

Anaesthetists play a key role in investigating perioperative hypersensitivity reactions. During a suspected perioperative hypersensitivity event, a serum tryptase level should be measured to help with subsequent allergy investigation. Moreover, anaesthetists can ensure that a high-quality referral is made to allergy clinics by providing thorough documentation of the events, detailing symptoms, treatments, and the chronology of drug administrations.

Perioperative hypersensitivity reactions are rare but can be life-threatening. A high index of suspicion should be maintained for their successful management. Whenever a perioperative hypersensitivity reaction is suspected, close collaboration between anaesthetist and the allergy team investigating the patient is paramount, in order for the patient to be appropriately investigated and have an uneventful anaesthetic in the future.
Simulation in obstetric anesthesia: an update
Authors: Marynen Frederik , Van Gerven Elke , Van de Velde Marc
Published: May 2020

Purpose of review

Simulation training (crew resource management training and scenario training) has become an important tool in the education of anesthesiologists. This review summarizes recent research performed in this area, focusing more specifically on obstetric anesthesia.

Recent findings

Simulation training is becoming more integrated in the modern education of anesthesiologists. Research regarding the most effective way to perform simulation training in terms of learning outcomes and long-term skill retention has started to appear. Scenarios which are played independently and that allow for simulated mortality, as well as relaxation techniques before debriefing might have positive effects in this regard. Furthermore, simulation has been investigated as a tool to improve patient safety in low-resource settings. In addition, simulation training in the domain of obstetrics has been rapidly expanding and has an important role in this field of medicine as well.

Simulation training has acquired a central role in modern education of anesthesiologists. Further research regarding elements to optimize simulation training in terms of learning outcomes and long-term skill retention is desirable. In addition, little data exist concerning the effect of simulation training on possible improvement of patient outcomes in anesthesia.
Hyper-Selective Posterior Fusion in Lenke 5C Adolescent Idiopathic Scoliosis
Authors: Shu Shibin , Zhang Tianyuan , Jing Wenting , Zhang Yuancheng , Gu Qi , Zhu Zezhang , Liu Zhen , Qiu Yong , Sun Xu , Wang Bin , Bao Hongda
Published: May 2020

Study Design.

A prospective analysis.

Objective.

To investigate whether the hyper-selective posterior fusion (upper instrumented vertebra [UIV] as the vertebra one level below the upper end vertebra [UEV], lower instrumented vertebra [LIV] as the lower end vertebra [LEV]) was applicable in posterior fusion of Lenke 5C adolescent idiopathic scoliosis (AIS) patients and what could be the indication of hyper-selective fusion.

Summary of Background Data.

The improper UIV selection in selective fusion could lead to progressive thoracic compensatory curve, shoulder imbalance, and even coronal imbalance. However, few studies analyzed the clinical outcome of hyper-selective fusion.

Methods.

A prospective analysis of 80 patients with Lenke 5C AIS who underwent selective fusion was performed. According to the relationship between UEV and UIV, the patients were divided into UEV group (UIV = UEV) and UEV-1 group (UIV = UEV-1). Radiographic parameters and the incidence of postoperative proximal decompensation were compared. The Scoliosis Research Society (SRS)-22 scores were used to evaluate clinical outcomes between two groups.

Results.

Thirteen patients (27%) in UEV group and six (18.75%) in UEV-1 group showed proximal decompensation during follow-up, and the incidence was equivalent (P = 0.280). Within the UEV-1 group, the patients with proximal decompensation showed similar Risser grade, baseline thoracic Cobb angle, and main Cobb angle (P = 0.611, 0.435, 0.708, respectively). However, the baseline L-T apical vertebral translation (AVT) ratio was significantly larger in patients with proximal decompensation (P = 0.028). Meanwhile, patients with proximal decompensation in UEV group showed significantly smaller preoperative UIV translation and lumbar AVT but similar postoperative UIV tilt.

Conclusion.

Hyper-selective posterior fusion strategy could be performed in Lenke 5C patients with Risser more than grade 2 and with thoracic compensatory curve over 15°. The UIV in patients with small baseline thoracic curve, represented by larger baseline lumbar-thoracic AVT ratio, should be selected as UEV to prevent proximal decompensation.

Level of Evidence: 4
Use of granulocyte-colony stimulating factors in older patients: a review of recently published data
Authors: Klastersky Jean A. , Dal Lago Lissandra , Lalami Yassine
Published: May 2020

Purpose of review

This review presents the analysis of recently published studies about the benefit from granulocyte-colony stimulating factors (G-CSF) in older cancer patients receiving chemotherapy.

Recent findings

During the last years, no major study aiming to confirm the clinical benefit of G-CSF prophylaxis in older patients treated with chemotherapy has been published. Nonetheless, all the data made recently available confirm that age, especially if other comorbid conditions are present as well, is a major risk factor for febrile neutropenia occurrence and that G-CSF prophylaxis can reduce significantly that risk.

New modalities of administering G-CSF prophylaxis might be considered in older people in the future. Among these approaches, the ‘same day’ administration of prophylaxis and chemotherapy and the development of less-expensive approaches for G-CSF prophylaxis, such as the use of biosimilars are studied.
Efficacy and Safety of the 532-nm KTP and Long-Pulsed 1064-nm Neodymium-doped Yttrium Aluminum Garnet Laser for Treatment of Vascular Malformations
Authors: Eichenfield Dawn Z. , Ortiz Arisa E.
Published: May 2020

BACKGROUND

Pulsed dye lasers (PDLs) are well-established for treatment of capillary malformations but are unable to penetrate the depth needed to treat deeper vascular lesions. A combined approach using a deeper penetrating wavelength with a “superficial” wavelength could more comprehensively treat vascular malformations than PDL alone.

OBJECTIVE

To evaluate the safety and efficacy of the long-pulsed 1064-nm neodymium:yttrium–aluminum–garnet (LP 1064-nm Nd:YAG) in conjunction with the 532-nm potassium titanyl phosphate (532-nm KTP) laser wavelengths for treatment of capillary venous and venous malformations.

METHODS

In this retrospective single-center study, we queried patient records who underwent treatment with the 532-nm KTP and LP 1064-nm Nd:YAG laser wavelengths. A blinded panel of 3 physicians evaluated improvement in lesion color, elevation, texture, and overall architecture on a four-point scale: 0% to 25%; 26% to 50%, 51% to 75%, and 76% to 100%.

RESULTS

Our cohort consisted of 23 cases. Sixteen cases had sufficient information for clinical assessment. Treatment number and parameters varied depending on lesion, skin type, and end point. Clinical assessment of treatment effectiveness revealed average scores of 51% to 75% improvement for color, elevation, texture, and overall architecture.

CONCLUSION

This study illustrates that 2 wavelengths, 532-nm KTP to target superficial components and LP 1064-nm Nd:YAG for deeper components, can safely and effectively treat both capillary venous and venous malformations.
The effect of SLC6A3 variable number of tandem repeats and methylation levels on individual susceptibility to start tobacco smoking and on the ability of smokers to quit smoking
Authors: Tiili Emmi M. , Mitiushkina Natalia V , Sukhovskaya Olga A. , Imyanitov Evgeny N. , Hirvonen Ari P.
Published: May 2020

Objective

Nicotine acts through the dopamine pathway in the brain affecting reward processing through cigarette consumption. Thus, both genetic and epigenetic factors related to dopamine metabolism may influence individual’s smoking behavior.

Materials and methods

We studied variations of two variable numbers of tandem repeats (VNTRs), 40 and 30 bp in length, in SLC6A3 gene together with six DNA methylation sites located in a first intron of the gene in relation to several smoking-related phenotypes in a study population consisting of 1230 Whites of Russian origin.

Results

Both the 5R allele of 30 bp VNTR and the 9R allele of 40 bp VNTR in SLC6A3 were associated with a reduced risk to tobacco smoking [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.37–0.75; OR 0.62, 95% CI 0.43–0.88]. Although the carriers of 9R allele also had high Fagerström test for nicotine dependence scores (OR 1.65, 95% CI 1.04–2.60), they were still more likely to succeed in smoking cessation (OR 0.59, 95% CI 0.40–0.88). Also, current smokers had more than 2.5-fold likelihood to have increased SLC6A3 methylation levels than former smokers (OR 2.72, 95% CI 1.63–4.53).

Conclusion

The SLC6A3 5R of 30 bp and 9R of 40 bp VNTR variants may lead to a reduced risk to start smoking through decreased dopamine availability, and can also affect the success in subsequent smoking cessation attempts. Moreover, the elevated mean methylation values in the first intron of SLC6A3 may be related to nicotine dependence via a more active dopamine transporter.
Cost-effective minimally invasive gynecologic surgery: emphasizing surgical efficiency
Authors: Misal Meenal , Delara Ritchie , Wasson Megan N.
Published: May 2020

Purpose of review

The United States has the highest healthcare costs among developed countries. This review evaluates surgical practices and equipment choices during endoscopic hysterectomy, highlighting opportunities for the gynecologic surgeon to reduce costs and maximize surgical efficiency.

Recent findings

There are opportunities to economize at every step of the endoscopic hysterectomy. When surgeons are provided education about instrumentation costs, the cost of hysterectomy has been shown to decrease. Colpotomy has been found to be the rate-limiting step in laparoscopic hysterectomy; use of a uterine manipulator likely saves time and money. When evaluating the economic impact of route of surgery, the cost differential between laparoscopic and robotic-assisted hysterectomy has decreased. Robotic-assisted hysterectomy may be more cost-effective in some cases, such as for larger uteri. From a systems-level perspective, dedicating a specific operating room team to the gynecology service can decrease operative time.

The gynecologic surgeon is best equipped to control surgery-related costs by making choices that improve surgical efficiency and decrease operating room time. If a costlier piece of equipment leads to a more efficient case, the choice may be more cost-effective. There are multiple systems-level changes that can be implemented to decrease surgery-related costs.
Multifocal arterial disease: clinical implications and management
Authors: Paraskevas K.I. , Geroulakos G. , Veith F.J. , Mikhailidis D.P.
Published: May 2020

Purpose of review

Vascular disease often affects more than one territory. Atherosclerosis is a global disease affecting multiple organs/systems. Cardiovascular risk factors are associated with an increased risk for the development of arterial disease in all vascular beds but differ in their individual impacts for each vascular bed. We discuss the various options to identify and manage multifocal arterial disease.

Recent findings

Coronary artery disease may coexist with carotid artery stenosis, abdominal aortic aneurysms, and/or peripheral artery disease (PAD). Atherosclerotic renal artery stenosis and renal function impairment may complicate PAD. Recent studies have confirmed that patients with multivascular bed disease have higher risk than patients with monovascular disease. In addition to the specific surgical/endovascular therapeutic options available, aggressive medical treatment and vascular disease prevention strategies should be rigorously implemented to best manage the overall atherosclerotic burden.

A holistic approach is essential to reduce the cardiovascular morbidity and mortality rates of vascular patients. Preventive measures should complement surgical/endovascular procedures so as to improve outcomes.
Additional prognostic value of electrocardiographic left ventricular hypertrophy in traditional cardiovascular risk assessments in chronic kidney disease
Authors: Tanaka Fumitaka , Komi Ryosuke , Nakamura Motoyuki , Tanno Kozo , Onoda Toshiyuki , Ohsawa Masaki , Sakata Kiyomi , Omama Shinichi , Ogasawara Kuniaki , Ishibashi Yasuhiro , Yonekura Yuki , Itai Kazuyoshi , Kuribayashi Toru , Kikuchi Yawara , Ishigaki Yasushi , Okayama Akira , Asahi Koichi
Published: May 2020

Background:

Left ventricular hypertrophy (LVH) is a common predictor of the cardiovascular prognosis in chronic kidney disease (CKD). However, whether or not electrocardiography-derived LVH (ECG-LVH) has prognostic value in patients with various degrees of CKD and improves the cardiovascular risk stratification based on traditional risk factors remains unclear.

Methods:

A total of 7206 participants at least 40 years of age who were free from cardiovascular events in a general population were followed for the incidence of cardiovascular events. CKD was confirmed by either the presence of a reduced estimated glomerular filtration rate (eGFR) (<60 ml/min per 1.73 m2) or albuminuria, defined as a urinary albumin-to-creatinine ratio (UACR) of at least 30 mg/g Cr.

Results:

A total of 1886 (26.2%) had CKD, of which 1471 (78.0%) had a preserved eGFR (CKD stage 1–2). After an average 11.3 years of follow-up, the adjusted hazard ratio for the incidence of cardiovascular events significantly increased for ECG-LVH according to the Sokolow--Lyon voltage, Cornell voltage, or Cornell voltage product among participants with CKD (hazard ratio 1.47, P = 0.002), in contrast to those without CKD (hazard ratio 1.15, P = 0.210). The inclusion of any ECG-LVH parameters improved the accuracy of reclassification in any risk prediction model based on the eGFR, UACR, or Framingham 10-year risk score in the CKD participants (net reclassification improvement = 0.13–0.32, all P values <0.040).

Conclusion:

In patients with CKD stage 1–5, ECG-LVH is useful for predicting the risk of future cardiovascular events and adds prognostic information to traditional cardiovascular risk assessments.
Concomitant hypertension is associated with abnormal left ventricular geometry and lower systolic myocardial function in overweight participants: the FAT associated CardiOvasculaR dysfunction study
Authors: Herfindal Bertina , Gerdts Eva , Kringeland Ester Anne , Saeed Sahrai , Midtbø Helga , Halland Hilde
Published: May 2020

Objective:

We studied the impact of concomitant hypertension on left ventricular (LV) systolic myocardial function and geometry in apparently healthy women and men with increased BMI.

Material and methods:

We performed a cross-sectional analysis of 535 participants (59% women) with BMI greater than 27 kg/m2 without known cardiovascular disease enrolled in the FAT associated CardiOvasculaR dysfunction (FATCOR) study. Hypertension was defined as use of antihypertensive treatment or elevated 24-h ambulatory blood pressure. Abnormal LV geometry was identified as increased relative wall thickness and/or LV mass index. Systolic myocardial function was assessed by midwall shortening (MWS) and speckle tracking peak global longitudinal strain (GLS).

Results:

Hypertensive participants were older (49 vs. 46 years), had higher BMI and waist circumference, higher prevalences of diabetes and abnormal LV geometry (29 vs. 16%), and lower GLS (−19 vs. −20%) and MWS (16.3 vs. 17.1%) compared with normotensive participants (all P < 0.01). In multivariable linear regression analyses, hypertension was associated with lower GLS (β=0.11, P = 0.035) and lower MWS (β=0.09, P = 0.029) independent of sex, diabetes, LV hypertrophy, ejection fraction, and waist circumference. Hypertension was also associated with presence of abnormal LV geometry [odds ratio 1.74 (95% confidence interval 1.04–2.89), P = 0.035) independent of the same confounders. When replacing waist circumference with BMI in the models, hypertension retained its association with lower myocardial function, whereas the association with abnormal LV geometry was attenuated.

Conclusion:

In participants with increased BMI without known clinical cardiovascular disease, concomitant hypertension was associated with lower systolic myocardial function and more abnormal LV geometry.

Clinical trial registration: URL: http://www.clinicaltrials.gov NCT02805478.
Obstructive sleep apnoea syndrome and left ventricular hypertrophy: a meta-analysis of echocardiographic studies
Authors: Cuspidi Cesare , Tadic Marijana , Sala Carla , Gherbesi Elisa , Grassi Guido , Mancia Giuseppe
Published: May 2020

Aim:

We investigated the association between obstructive sleep apnoea (OSA) and subclinical cardiac organ damage through a meta-analysis of echocardiographic studies that provided data on left ventricular hypertrophy (LVH), assessed as a categorical or continuous variable.

Design:

The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language articles published from 1 January 2000 to 15 August 2019. Studies were detected by using the following terms: ‘obstructive sleep apnea’, ‘sleep quality’, ‘sleep disordered breathing’, ‘cardiac damage’, ‘left ventricular mass’, ‘left ventricular hypertrophy’, and ‘echocardiography’.

Results:

Meta-analysis included 5550 patients with OSA and 2329 non-OSA controls from 39 studies. The prevalence of LVH in the pooled OSA population was 45% (CI 35--55%). Meta-analysis of studies comparing the prevalence of LVH in participants with OSA and controls showed that OSA was associated with an increased risk of LVH (OR = 1.70, CI 1.44–2.00,P < 0.001). LV mass was significantly increased in patients with severe OSA as compared with controls (SMD 0.46 ± 0.08, CI 0.29–0.62,P < 0.001) or with mild OSA. This was not the case for studies comparing patients with unselected or predominantly mild OSA and controls (0.33 ± 0.17, CI −0.01 to 0.67,P = 0.057).

Conclusion:

The present meta-analysis expands previous information on the relationship between OSA and echocardiographic LVH, so far based on individual studies. The overall evidence strongly suggests that the likelihood of LVH increases with the severity of OSA, thus exhibiting a continuous relationship.