bluuebunny/crossref_metadata_2025 huggingface dataset:
Purulent pericarditis caused by methicillin-sensitive Staphylococcus aureus in an immunocompetent adult after COVID-19 pneumonia: a case report
Authors: Cvetko Tea-Terezija , Ljubic Jelena , Ostricki Branko
Published: March 2023

Background

SARS-CoV-2 has been implicated in many cardiac pathologies, manifesting mainly as acute. However, acute purulent pericarditis is exceedingly rare in the antibiotic era. Though, few studies have associated it with long-COVID, prompt recognition and treatment are crucial.

Case summary

A 61-year-old immunocompetent woman presented with a left lower limb pitting oedema 1 month after COVID-19 pneumonia. Following clinical, laboratory, and imaging work-up, the patient was found to have deep vein thrombosis of the anterior and posterior tibial and gastrocnemius veins. Owning to persistent sinus tachycardia, an additional work-up was performed, which revealed a large pericardial effusion. Pericardiocentesis drained the frank pus, and subsequently, empirical antibiotics therapy was initiated. Pericardial fluid cultures showed methicillin-sensitive Staphylococcus aureus (MSSA). Following the antibiotic treatment with cloxacillin 6 × 2 g IV for 6 weeks, the patient fully recovered.

Discussion

Herein, we report a rare case of bacterial pericarditis caused by MSSA 1 month after COVID-19 pneumonia. Additionally, this condition may arise as a result of immunosuppressive treatment with glucocorticoids during and after COVID-19 pneumonia. However, the causal association has not yet been confirmed.
Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction
Authors: Nurmohamed Nick S , Kraaijenhof Jordan M , Mayr Manuel , Nicholls Stephen J , Koenig Wolfgang , Catapano Alberico L , Stroes Erik S G
Published: March 2023

Given the limited accuracy of clinically used risk scores such as the Systematic COronary Risk Evaluation 2 system and the Second Manifestations of ARTerial disease 2 risk scores, novel risk algorithms determining an individual’s susceptibility of future incident or recurrent atherosclerotic cardiovascular disease (ASCVD) risk are urgently needed. Due to major improvements in assay techniques, multimarker proteomic and lipidomic panels hold the promise to be reliably assessed in a high-throughput routine. Novel machine learning-based approaches have facilitated the use of this high-dimensional data resulting from these analyses for ASCVD risk prediction. More than a dozen of large-scale retrospective studies using different sets of biomarkers and different statistical methods have consistently demonstrated the additive prognostic value of these panels over traditionally used clinical risk scores. Prospective studies are needed to determine the clinical utility of a biomarker panel in clinical ASCVD risk stratification. When combined with the genetic predisposition captured with polygenic risk scores and the actual ASCVD phenotype observed with coronary artery imaging, proteomics and lipidomics can advance understanding of the complex multifactorial causes underlying an individual’s ASCVD risk.
Miriam Camps and European Integration: Blurring the Boundaries between Scholarship and Diplomacy
Authors: Seidel Katja
Published: March 2023

Miriam Camps (1916–1994) was a US diplomat, journalist, economist, and scholar. Involved in the design of early postwar European integration organizations at the State Department in the 1940s, she remained at the center of US foreign policy formulation toward Europe until the late 1960s. Her practical experience as a formal and informal diplomat—from the late 1950s, Camps was affiliated with elite foreign policy think tanks—informed her output as a scholar. Like other female international thinkers and experts, she was well known in her time, but her contribution to both US foreign policy and scholarship on European integration has since been largely overlooked by historians of European integration and international relations scholars. This article explores Camps’ scholarship and her contribution to the field of European Studies. It asks why we know so little about Camps and advocates revisiting early European integration research and integrate individuals with more variegated careers into the founding history of the discipline.
“Mother of the Oceans”: Maritime Governance as a Template for a New Global Order in the International Thought of Elisabeth Mann Borgese (1918–2002)
Authors: Ashworth Lucian M
Published: March 2023

This article explores the international thought of Elisabeth Mann Borgese (1918–2002), a major figure in the third United Nations Conference on the Law of the Sea negotiations and (later in her life) a professor at Dalhousie University. Borgese's analysis of the nature of the Ocean led her to see the emerging system of maritime governance as a template for wider global governance. The fluidity of the Ocean, she argued, blurred terrestrial certainties, while the fundamental interdependence of its ecosystems means that its governance offers a new paradigm that can inform terrestrial governance. The Ocean has always been important, she argued, but that importance is now increasing. Thus, in Borgese's work, the Ocean emerges as more than a passive victim of human exploitation, and becomes a positive influence on humanity's future. Taking her work seriously helps international relations (IR) confront its own failure to engage with global physical realities and would be another step toward rewriting an IR for the Anthropocene.
“Apostates from Realism: Harold and Margaret Sprout, Princeton, and Geopolitics: 1931–1965”
Authors: Specter Matthew
Published: March 2023

By focusing on the joint scholarly work of Harold and Margaret Sprout in the first two-thirds of their academic career, this article aims to recover the work of an important female international thinker from relative obscurity. The Sprouts were important protagonists in the making of a geopolitical strand of realism centered at Princeton University during the war. Historians of realism focused on developments in the mid-1950s centered on Columbia and Chicago have neglected the circle around Edward March Earle at Princeton which gave the Sprouts their start.

In Section I, I use a close reading of archives at Princeton, as well as an unpublished autobiography that the couple wrote before Harold's death in 1980 (amended by Margaret in 1995), to establish the collaborative nature of their scholarship and the challenges Margaret faced as an unsalaried researcher without a formal academic appointment.

In Section II, I trace the Sprouts' work from the 1939–1940 work on naval power through to a critical review of Hans Morgenthau in 1949.

In Section III, I argue that Man-Milieu Relationship Hypotheses (1956) constituted their break with the geopolitical realism that they had championed through the late 1940s. I also show how their work from 1956 to 1965, critical of teleology and reification of large-scale “influences of geography” and “elements of national power” made them pioneers in cognitive foreign policy analysis (like Snyder, Burton, and Sapin, 1954) and forerunners of constructivism. I conclude with some reflections on their marginalization by international relations theory and history alike.
“A Pro-Fascist English Lady”: The International Thought of Muriel Innes Currey
Authors: Allen Kye J
Published: March 2023

This article recovers the activities, international thought, and reception of Muriel Innes Currey during the formative decades of the twentieth century. As both an ardent campaigner on behalf of the League of Nations Union and a fascist sympathizer, the paper highlights the variegated beliefs and tensions encapsulated within Currey's thinking as she attempted to reconcile advocacy for the League of Nations with a peculiar mélange of High Tory conservatism, Italophilic solidarity, and fascist sympathies. The contribution of this study is two-fold. First, building on efforts to excavate the history of women's international thought from undue obscurity, this article expands the referent of analysis to the thought and activity of a hitherto neglected woman, yet one overwhelmingly pro-fascist in orientation. Second, discerning Currey's thought contributes to redressing a double erasure within the history of the discipline: the gendered elision of women's international thinking and the concurrent amnesia surrounding fascism and its place within the then-fledgling discipline of international relations. Currey may have been on the periphery of academia; however, she was nevertheless a thinker who engaged with key questions occupying, and institutions affiliated with, the emergent field.
Thinking Outside of the Box: Transnational Terrorism in Civil Wars
Authors: Soules Michael J
Published: March 2023

Scholars have written on the extensive risks that transnational terrorism entails for militant groups that perpetrate such attacks. However, despite these risks, transnational terrorism has become an increasingly common feature of civil wars. This raises the question: Why do rebel groups launch terrorist attacks outside of the countries they are fighting civil wars in? I argue that weaker rebel groups are more inclined to turn to such tactics because they are desperate, and as a result, are more willing to make the gamble to signal their resolve, impose costs on their enemies, avoid direct military confrontation with domestic security forces, and generate external support. Using data on the transnational terrorist attack patterns of all rebel group–government dyads present in the Uppsala Conflict Data Program (UCDP) Dyadic Dataset from 1970 to 2013, I find that conventionally weak rebel groups are more likely to rely on transnational terrorism.
MR Enterography Scores Correlate with Degree of Mucosal Healing in Pediatric Crohn’s Disease: A Pilot Study
Authors: Gladkikh Maria , Benchimol Eric I , Mack David R , Mojaverian Nassim , Highmore Kerri , Miller Elka , Davila Jorge
Published: March 2023

Objectives

MR enterography (MRE) Index of Activity (MaRIA) and Clermont are validated scores that correlate with Crohn’s disease (CD) activity; however, the Clermont score has not been validated to correlate with the degree of change in mucosal inflammation post induction treatment in children. This pilot study evaluated if MaRIA and Clermont scores can serve as surrogates to ileocolonoscopy for assessing interval change in mucosal inflammation in pediatric CD post-induction treatment.

Methods

Children with known or newly diagnosed ileocolonic CD starting or changing therapy underwent ileocolonoscopy, scored with simple endoscopic score for Crohn’s disease (SES-CD), and MRE on the same day at two time points (Week 0 and 12). Accuracy of global MaRIA and Clermont indices relative to ileocolonoscopy in detecting degree of post-treatment interval change in mucosal inflammation was assessed through correlational coefficients (r). Inter-reader agreement was calculated for imaging scores through intraclass correlation (ICC).

Results

Sixteen children (mean age 11.5 ± 2.8) were evaluated. Global MaRIA/Clermont correlated with SES-CD in detecting the degree of change in mucosal inflammation (r = 0.676 and r = 0.677, P < 0.005, respectively). Correlation for pooled timepoint assessments between SES-CD and global MaRIA/Clermont was moderate (r = 0.546, P < 0.001 and r = 0.582, P < 0.001, respectively). Inter-rater reliability for global MaRIA and Clermont was good (ICC = 0.809 and ICC = 0.768, respectively, P < 0.001).

Conclusions

MRE-based global scores correlate with endoscopic indices and may be used to monitor disease changes in children with CD undergoing induction treatment, which can advise the physician if treatment changes should be made.
Predictive value of peripheral blood markers in soft tissue sarcoma patients treated with eribulin
Authors: Ishihara Shin , Ogura Koichi , Maejima Aiko , Shimoi Tatsunori , Sudo Kazuki , Kojima Yuki , Fukushima Suguru , Osaki Shuhei , Kobayashi Eisuke , Iwata Shintaro , Matsui Yoshiyuki , Yonemori Kan , Kawai Akira
Published: March 2023

Objective

eribulin, an anticancer agent that inhibits microtubule growth, along with trabectedin and pazopanib, has been approved for the treatment of advanced soft tissue sarcoma (STS). However, there has been no consensus on the optimal second-line therapy among these three agents following treatment failure with doxorubicin. Recently, the effects of eribulin on the tumor microenvironment and immunity have been reported in breast cancer, and peripheral blood immune markers have also been reported to be a predictor of eribulin efficacy, though this remains unverified in STS. We aimed to evaluate the predictive value of various peripheral blood immune markers in STS patients treated with eribulin.

Methods

we retrospectively reviewed the medical records of STS patients treated with eribulin and examined whether peripheral blood immune markers at different time points could be prognostic factors for STS patients treated with eribulin.

Results

several peripheral blood immune markers were significantly associated with progression-free survival (PFS), specifically neutrophil-to-lymphocyte ratio (NLR) prestart (NLR before the initial administration of eribulin) (P = 0.019) and absolute lymphocyte count (ALC)8D (ALC on Day 8 of the first administration of eribulin) (P = 0.037). NLR prestart (P = 0.001) was significantly associated with overall survival. The combination of NLR prestart and ALC8D determined the PFS of STS patients treated with eribulin.

Conclusions

the combined indicator of low NLR prestart and high ALC8D predicted the survival of patients treated with eribulin as well as the histology of L-sarcoma. Though further validation was needed, this finding would provide valuable prognostic factor that help treatment decision in the absence of consensus on the optimal second-line therapy following doxorubicin treatment in STS patients.
Characterization and CRISPR/Cas9-mediated genetic manipulation of neutrophils derived from Hoxb8-ER-immortalized myeloid progenitors
Authors: Shannon Jeffrey G , Hinnebusch B Joseph
Published: March 2023

Neutrophils represent a first line of defense against a wide variety of microbial pathogens. Transduction with an estrogen receptor–Hoxb8 transcription factor fusion construct conditionally immortalizes myeloid progenitor cells (NeutPro) capable of differentiation into neutrophils. This system has been very useful for generating large numbers of murine neutrophils for in vitro and in vivo studies. However, some questions remain as to how closely neutrophils derived from these immortalized progenitors reflect primary neutrophils. Here we describe our experience with NeutPro-derived neutrophils as it relates to our studies of Yersinia pestis pathogenesis. NeutPro neutrophils have circular or multilobed nuclei, similar to primary bone marrow neutrophils. Differentiation of neutrophils from NeutPro cells leads to increased expression of CD11b, GR1, CD62L, and Ly6G. However, the NeutPro neutrophils expressed lower levels of Ly6G than bone marrow neutrophils. NeutPro neutrophils produced reactive oxygen species at slightly lower levels than bone marrow neutrophils, and the 2 cell types phagocytosed and killed Y. pestis in vitro to a similar degree. To further demonstrate their utility, we used a nonviral method for nuclear delivery of CRISPR/Cas9 guide RNA complexes to delete genes of interest in NeutPro cells. In summary, we have found these cells to be morphologically and functionally equivalent to primary neutrophils and useful for in vitro assays related to studies of bacterial pathogenesis.
Modelling admixture across language levels to evaluate deep history claims
Authors: Hübler Nataliia , Greenhill Simon J
Published: March 2023

The so-called ‘Altaic’ languages have been subject of debate for over 200 years. An array of different data sets have been used to investigate the genealogical relationships between them, but the controversy persists. The new data with a high potential for such cases in historical linguistics are structural features, which are sometimes declared to be prone to borrowing and discarded from the very beginning and at other times considered to have an especially precise historical signal reaching further back in time than other types of linguistic data. We investigate the performance of typological features across different domains of language by using an admixture model from genetics. As implemented in the software STRUCTURE, this model allows us to account for both a genealogical and an areal signal in the data. Our analysis shows that morphological features have the strongest genealogical signal and syntactic features diffuse most easily. When using only morphological structural data, the model is able to correctly identify three language families: Turkic, Mongolic, and Tungusic, whereas Japonic and Koreanic languages are assigned the same ancestry.
Classification in Traditional Nosologies
Authors: Keeley Jared W. , Chung Lisa , Kleva Christopher
Published: March 2023

The classification of psychopathology drives many aspects of the mental health profession. This chapter outlines the major controversies current today in traditional psychiatric classification, including the definition of mental disorder, the organization of classificatory systems, issues concerning comorbidity, measurement issues, and many others. These controversies are tracked historically across the various editions of the American Psychiatric Association’s DSM and the World Health Organization’s ICD and put into their historical context. This chapter argues that the classification of mental disorders is an inherently value-laden and subjective enterprise, but one that is nonetheless integral to the science and practice of mental health.
Depression: Social and Cognitive Aspects
Authors: Ingram Rick E. , Balderas Jessica , Khonle Kendall , Fulton Joe
Published: March 2023

Although there are numerous facets of depression, this chapter reviews its social and cognitive aspects. The chapter begins with a brief history of depression and then examines the epidemiology of depression, as well as demographic data related to ethnicity, sex difference, and age and cohort effects. Social and cognitive models and the factors associated with these models, such as life events, are reviewed. Among these models is the idea of stress generation, wherein stress is not brought about by external events but is rather generated by the interpersonal behaviors of depressed individuals. Several cognitive models focus on Beck’s cognitive model of depression, which examines the role of depressogenic schemas in the onset and maintenance of depression. There is also some evidence to suggest that depressive cognition might have a genetic basis, and data on the role of the 5-HTTLPR gene in relation to depressive cognitions is reviewed. Attribution-based models, such as the learned helplessness and learned hopelessness models, are also reviewed, as is the self-regulatory approach to depression proposed by Crevone. The authors conclude by summarizing social and cognitive factors related to depression.
Eating Disorders
Authors: Steiger Howard , Booij Linda , St-Hilaire Annie , Thaler Lea
Published: March 2023

This chapter discusses the psychopathology of the eating disorders (EDs), with emphasis on important shifts in understanding that have occurred over recent decades. The chapter offers a treatment of ED phenomenology, epidemiology, and etiology and provides a review of findings on comorbid syndromes and traits that often accompany an ED. In addition, the chapter reviews etiology, providing a review of the factors that are part of a contemporary, biopsychosocial perspective on ED development. Arguably, a multidimensional perspective informed by findings on the ways in which EDs result from the activation by diverse environmental impacts of an underlying heritable biology helps reduce stigma associated with these disorders and causal misconceptions surrounding them.
Paraphilia, Gender Dysphoria, and Hypersexuality
Authors: Cantor James M.
Published: March 2023

Atypical sexualities span psychopathologies whose physical expression poses risk of physical harm, erotic interests which are physically harmless but may pose social or mental health or social challenges related to stigma or hindrances to finding partners with corresponding interests, and sexualities which represent membership among sexual orientation or gender identity minorities. Some sexual fantasies would pose harm if enacted in the real world but remain in fantasy only. These overlapping contexts pose unique challenges to researchers, as findings become discussed with regard to their potential impact on, for example, insurance payments for treatments, justification for medical sex reassignment of minors, parole and probation terms following sex-related crimes, and so on. The present chapter provides an atheoretical review of the evidence regarding atypical sexualities and identities, their known correlates, their etiologies, and their responses to the available treatment options and social reactions.
Schizotypy and Schizotypic Psychopathology: Theory, Evidence, and Future Directions
Authors: Lenzenweger Mark F.
Published: March 2023

This chapter provides an overview of the concept of schizotypy and its relationship to schizotypic psychopathology as well as schizophrenia. The derivation of the schizotypy model is traced through early clinical observations of the biological relativity of schizophrenia patients as well as schizotypic patients presenting for treatment to modern biological, genetic, psychometric, neurocognitive, and longitudinal follow-up studies. The theoretical formulations of Rado, Meehl, and others are explicated and used as a framework to organize empirical research findings on schizotypic psychopathology. A wide array of results suggests that schizotypy can be defined as the latent liability for schizophrenia, one expressing itself variably from subtle indicators detectable with sensitive laboratory measures through a range of phenotypically discernible schizotypic pathologies. Considerable attention is given to the meaning of the term “schizotypy” and how it is used in psychopathology research, with particular importance placed on the centrality of the liability for schizophrenia concept. Areas in need of additional research are highlighted, and potentially fruitful avenues for such research are suggested.
HPr prevents FruR-mediated facilitation of RNA polymerase binding to the fru promoter in Vibrio cholerae
Authors: Yoon Chang-Kyu , Lee Seung-Hwan , Zhang Jing , Lee Hye-Young , Kim Min-Kyu , Seok Yeong-Jae
Published: March 2023

Phosphorylation state-dependent interactions of the phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS) components with transcription factors play a key role in carbon catabolite repression (CCR) by glucose in bacteria. Glucose inhibits the PTS-dependent transport of fructose and is preferred over fructose in Vibrio cholerae, but the mechanism is unknown. We have recently shown that, contrary to Escherichia coli, the fructose-dependent transcriptional regulator FruR acts as an activator of the fru operon in V. cholerae and binding of the FruR–fructose 1-phosphate (F1P) complex to an operator facilitates RNA polymerase (RNAP) binding to the fru promoter. Here we show that, in the presence of glucose, dephosphorylated HPr, a general PTS component, binds to FruR. Whereas HPr does not affect DNA-binding affinity of FruR, regardless of the presence of F1P, it prevents the FruR–F1P complex from facilitating the binding of RNAP to the fru promoter. Structural and biochemical analyses of the FruR–HPr complex identify key residues responsible for the V. cholerae-specific FruR–HPr interaction not observed in E. coli. Finally, we reveal how the dephosphorylated HPr interacts with FruR in V. cholerae, whereas the phosphorylated HPr binds to CcpA, which is a global regulator of CCR in Bacillus subtilis and shows structural similarity to FruR.
Short-term variability in plankton abundance on the inner shelf off Ubatuba, Brazil
Authors: Penninck Silvana B , Lopes Rubens M
Published: March 2023

The interaction between biological and short-term physical processes affects plankton distribution and composition variability, with consequences for the entire ecosystem. Aspects of the plankton distribution at smaller scales have been understudied, mainly in coastal regions where highly variable conditions promote variations in the biophysical environment. This work aimed to investigate the short-term variations in the distribution of plankton along the inner shelf off Ubatuba, Brazil. We quantified the abundance and diversity of the main planktonic taxa (>100 μm) and their spatiotemporal distribution in winter 2018 and summer 2019 using high-resolution sensors and a shadowgraphic imaging system at cross-shore and fixed stations (12 and 24 h). Summer–winter environmental contrast was evident in the water column stability and plankton abundance. In the summer, higher values of plankton abundance and diversity were obtained. Our results suggested that spatiotemporal variations related to wind-induced mixing and water mass intrusions lead to variabilities in plankton populations on a time scale of a few hours, vertically between depth layers and at spatial scales ˂2 km. This study contributes to the knowledge of the mechanisms of biophysical interactions and their spatiotemporal variation, which is crucial for assessing the effects of climate variability on plankton-mediated ecosystem services.
Depicting pseudotime-lagged causality across single-cell trajectories for accurate gene-regulatory inference
Authors: Reagor Caleb C , Velez-Angel Nicolas , Hudspeth A J
Published: March 2023

Identifying the causal interactions in gene-regulatory networks requires an accurate understanding of the time-lagged relationships between transcription factors and their target genes. Here we describe DELAY (short for Depicting Lagged Causality), a convolutional neural network for the inference of gene-regulatory relationships across pseudotime-ordered single-cell trajectories. We show that combining supervised deep learning with joint probability matrices of pseudotime-lagged trajectories allows the network to overcome important limitations of ordinary Granger causality-based methods, for example, the inability to infer cyclic relationships such as feedback loops. Our network outperforms several common methods for inferring gene regulation and, when given partial ground-truth labels, predicts novel regulatory networks from single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) data sets. To validate this approach, we used DELAY to identify important genes and modules in the regulatory network of auditory hair cells, as well as likely DNA-binding partners for two hair cell cofactors (Hist1h1c and Ccnd1) and a novel binding sequence for the hair cell-specific transcription factor Fiz1. We provide an easy-to-use implementation of DELAY under an open-source license at https://github.com/calebclayreagor/DELAY.
Predictors of Noninvasive Ventilation Failure in the Post-Extubation Period: A Systematic Review and Meta-Analysis*
Authors: Hryciw Brett N. , Hryciw Nicole , Tran Alexandre , Fernando Shannon M. , Rochwerg Bram , Burns Karen E. A. , Seely Andrew J. E.
Published: March 2023

Objectives:

To identify factors associated with failure of noninvasive ventilation (NIV) in the post-extubation period.

Data Sources:

We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to February 28, 2022.

Study Selection:

We included English language studies that provided predictors of post-extubation NIV failure necessitating reintubation.

Data Extraction:

Two authors conducted data abstraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios (ORs) mean difference (MD), respectively. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty.

Data Synthesis:

We included 25 studies (n = 2,327). Illness-related factors associated with increased odds of post-extubation NIV failure were higher critical illness severity (OR, 3.56; 95% CI, 1.96–6.45; high certainty) and a diagnosis of pneumonia (OR, 6.16; 95% CI, 2.59–14.66; moderate certainty). Clinical and biochemical factors associated with moderate certainty of increased risk of NIV failure post-extubation include higher respiratory rate (MD, 1.54; 95% CI, 0.61–2.47), higher heart rate (MD, 4.46; 95% CI, 1.67–7.25), lower Pao
2:Fio
2 (MD, –30.78; 95% CI, –50.02 to –11.54) 1-hour after NIV initiation, and higher rapid shallow breathing index (MD, 15.21; 95% CI, 12.04–18.38) prior to NIV start. Elevated body mass index was the only patient-related factor that may be associated with a protective effect (OR, 0.21; 95% CI, 0.09–0.52; moderate certainty) on post-extubation NIV failure.

Conclusions:

We identified several prognostic factors before and 1 hour after NIV initiation associated with increased risk of NIV failure in the post-extubation period. Well-designed prospective studies are required to confirm the prognostic importance of these factors to help further guide clinical decision-making.
A SCLERAL BUCKLE INFECTION CAUSED BY CUTIBACTERIUM ACNES (FORMERLY PROPIONIBACTERIUM ACNES) AN ATYPICAL, INDOLENT COURSE
Authors: Yehezkeli Veronika , Ayalon Anfisa , Naftali Ben Haim Liron , Rubowitz Alexander
Published: March 2023

Purpose:

To report a case of atypical, indolent presentation of scleral buckle infection, caused by Cutibacterium acnes (formerly known as Propionibacterium acnes).

Methods:

Observational case report.

Results:

A 44-year-old healthy woman with a history of scleral buckling procedure for retinal detachment repair 16 years before presentation was admitted with pain and redness in her left eye for 6 weeks. Conjunctival hyperemia and vascular congestion were noted over the scleral buckle in a circular manner without signs of exposure. After removal of the scleral buckle, culture analysis revealed C. acnes. Systemic amoxicillin was administrated. Over a six-month follow-up, the retina remained attached.

Conclusion:

Cutibacterium acnes, known to be associated with chronic postoperative endophthalmitis after cataract surgery, may also lead to scleral buckle infection with an indolent, chronic course.
Trend in the Numbers of Hospitalized Patients With Varicella, Herpes Zoster, and Ischemic Stroke in Japanese Individuals <20 Years of Age Before and After Implementation of Universal Varicella Vaccination
Authors: Ishimaru Soichiro , Michihata Nobuaki , Kawamura Yoshiki , Uda Kazuaki , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo , Yoshikawa Tetsushi
Published: March 2023

Several studies have shown an association between varicella-zoster virus infection and ischemic stroke. We analyzed the trends in the numbers of patients with varicella, herpes zoster and ischemic stroke before and after the universal vaccination program using a Japanese database of hospitalized patients. The number of patients with varicella decreased but those of herpes zoster and ischemic stroke did not change.
Facilitators and Barriers to Providing Clinical Education Experiences Through the Lens of Clinical Stakeholders
Authors: Wilkinson Tawna , Myers Katherine , Bayliss Jamie , Gleeson Peggy , Konecne Janet , Lewis Michele , Thomas Jodi , Pientok Colette , Hoang Thuha
Published: March 2023

Introduction.

Although the provision of clinical education (CE) experiences affords many benefits to clinical stakeholders, little published literature exists regarding the factors influencing decisions of site coordinators of CE (SCCE), clinical administrators, and clinical instructors (CI) to provide CE.

Review of Literature.

Site coordinators of CE and CIs navigate workplace expectations while making decisions about their engagement in CE experiences. The purpose of this study was to determine clinical stakeholders’ perceptions of facilitators and barriers to the provision of CE experiences for entry-level Doctor of Physical Therapy students.

Subjects.

This study used survey data from a previous study on perspectives related to payment for CE experiences. The survey questions analyzed included responses provided by 501 clinical administrators, 445 SCCEs, and 657 CIs.

Methods.

Retrospective analysis of survey data included frequencies and percentages of responses for nominal and categorical data. Open-ended survey questions underwent content analysis to identify overarching concepts and subordinate categories.

Results.

Clinicians are most motivated to serve as CIs by “enjoyment of teaching” (274, 49.4%) and a sense of “professional responsibility” (147, 26.5%). Site coordinators of CEs indicated that the top challenges faced in soliciting CIs were the ability to manage challenging students (347, 69.0%), lack of experience serving as a CI (227, 63.4%), ability to maintain productivity standards (220, 61.5%), and clinician burnout (219, 61.2%). Although all participants agreed that their organization promotes a culture of teaching, clinical administrators agreed at a higher percentage than SCCEs (97.8% vs 94.3%, respectively).

Discussion and Conclusion.

Clinical instructors identified values and benefits that were, at times, in contrast to the organizational culture. The discrepancies in perceptions among stakeholders that were uncovered by this research provide a unique lens that has not been addressed in the literature to date. To provide meaningful support for CIs, it is imperative that directors of CEs, clinical administrators, and SCCEs clearly understand the perceptions of the CI.
Preclinical study in a postoperative pain model to investigate the action of ketamine, lidocaine, and ascorbic acid in reversing fentanyl-induced, non–glutamate-dependent hyperalgesia
Authors: Delgado Marina Ayres , Ferreira Luana Assis , Gomes Bianka Jaciara dos Santos , Leite Isis Katarine Orlandi , Gomez Marcus Vinícius , Castro-Junior Célio
Published: March 2023

Introduction:

Opioid-induced hyperalgesia (OIH) is a paradoxical phenomenon in which exposure to opioids can increase sensitivity to painful stimuli. Currently, several drugs have been used in an attempt to prevent OIH. We design this study to address the effect of preemptive treatment with ketamine, lidocaine, and ascorbic acid in a rat preclinical model of perioperative opioid-induced hyperalgesia.

Methods:

To reproduce OIH in a model of postoperative pain, rats received successive doses of fentanyl subcutaneously and underwent an incision in the paw. In an attempt to prevent OIH, ketamine, lidocaine, and ascorbic acid were administered before treatment with fentanyl. The von Frey test and the hot-plate test were used to evaluate mechanical allodynia and thermal hyperalgesia, respectively, with a follow-up period from 1 hour up to 7 days after surgery. Spinal cord nerve terminals (synaptosomes) were used to assess glutamate release under our experimental conditions.

Results:

Consecutive fentanyl injections increased the postoperative pain as indicated by increased thermal hyperalgesia and allodynia 48 hours after incision. Ketamine, lidocaine, and the combination of ketamine + lidocaine were able to prevent thermal hyperalgesia but not mechanical allodynia. Ascorbic acid did not prevent the hyperalgesia induced by fentanyl. We found no correlation between spinal glutamate release and the pharmacological treatments.

Conclusion:

Fentanyl induced a hyperalgesic effect that last few days in a postoperative model of pain. Hyperalgesic effect was not totally inhibited by ketamine and lidocaine in rats. Increased glutamate release was not the main molecular mechanism of fentanyl-induced hyperalgesia.
Three-Dimensional Surface Analysis for Preoperative Prediction of Breast Volume: A Validation Study
Authors: Stern Carrie S. , Plotsker Ethan L. , Rubenstein Robyn , Mehrara Ellie , Haglich Kathryn , Zoghbi Yasmina , Mehrara Babak J. , Nelson Jonas A.
Published: March 2023

Background:

Few studies have examined whether preoperative three-dimensional (3D) surface imaging can accurately predict breast volume. Reliably predicting breast volume preoperatively can assist with breast reconstruction planning, patient education, and perioperative risk stratification.

Methods:

We conducted a review of patients who underwent mastectomy from 2020–2021 and included all patients who had preoperative VECTRA XT 3D imaging. VECTRA Analysis Module (VAM) and VECTRA Body Sculptor (VBS) were used for volumetric analysis using standard anatomic breast borders. Breast weights were obtained intraoperatively. Predictive accuracy was defined as VAM estimates ±10% of mastectomy specimen weight or ±100 g of mastectomy weight.

Results:

The study included 179 patients (266 breasts). There was no significant difference (p=0.22) between mean mastectomy weight of 620.8 g (SD=360.3 g) and mean VAM estimate of 609.5 g (SD=361.9 g). Mean VBS estimate was 498.9 g (SD=337.6 g), which differed from mean mastectomy weight (p<0.001). When defining predictive accuracy as ±100 g, 58.7% of VAM and 44.4% of VBS estimates were accurate. Body mass index, body surface area, and ptosis grade significantly impacted VAM and VBS breast volume predictions.

Conclusions:

VAM is more accurate at predicting mastectomy weight than VBS, likely due to VAM’s analysis of surface topography rather than discrete surface landmarks. Discrepancies between VECTRA estimates and mastectomy weight were likely due to differences between surgical mastectomy borders and breast borders used in volumetric analysis. Surgeons should consider the physical characteristics of patients when utilizing 3D imaging.
Air versus Saline in Initial Prepectoral Tissue Expansion: A Comparison of Complications and Perioperative Patient-Reported Outcomes
Authors: Plotsker Ethan L. , Coriddi Michelle , Rubenstein Robyn N. , Chu Jacqueline J. , Haglich Kathryn , Disa Joseph J. , Matros Evan , Dayan Joseph H. , Allen Robert , Nelson Jonas A
Published: March 2023

Background:

One option to optimize prepectoral tissue expander fill volume while minimizing stress on mastectomy skin flaps is to use air as an initial fill medium, with subsequent exchange to saline during postoperative expansion. We compared complications and early patient-reported outcomes (PROs) based on fill type in prepectoral breast reconstruction patients.

Methods:

We reviewed prepectoral breast reconstruction patients who underwent intraoperative tissue expansion with air or saline from 2018–2020 to assess fill-type utilization. Primary endpoint was expander loss; secondary endpoints included seroma, hematoma, infection/cellulitis, full-thickness mastectomy skin flap necrosis (MSFN) requiring revision, expander exposure, and capsular contracture. PROs were assessed with BREAST-Q Physical Well-Being of the Chest 2 weeks postoperatively. Propensity-matching was performed as a secondary analysis.

Results:

Of 560 patients (928 expanders) included in our analysis, 372 had devices initially filled with air (623 expanders) and 188 with saline (305 expanders). No differences were observed for overall rates of expander loss (4.7% vs. 3.0%, p=0.290) or overall complications (22.5% vs. 17.7%, p=0.103). No difference in BREAST-Q scores was observed (p=0.142). Utilization of air-filled expanders decreased substantially over the last study year. Following propensity matching, we did not observe differences in loss, other complications, or PROs across cohorts.

Conclusion:

Tissue expanders initially filled with air appear to have no significant advantage over saline-filled expanders in maintaining mastectomy skin flap viability or PROs, including after propensity matching. These findings can help guide choice of initial tissue expander fill-type.
The Diagnosis and Management of Advanced Endolymphatic Sac Tumor
Authors: Zhang De-Jun , Fu Ze-Ming , Guo Fang , Wan Yi-Ning , Guan Guo-Fang
Published: March 2023

Endolymphatic sac tumor (ELST) is a group of low-grade malignant tumors originating from the endolymphatic sac of the inner ear. It is rare in the clinic and has the biological characteristics of slow growth and local aggression. Due to the lack of specificity in the clinical manifestations of patients with ELST, many cases have entered the advanced stage at the time of diagnosis. However, there are still great challenges in the treatment of advanced ELSTs. Here, the authors describe a case of advanced ELST, which relapsed after 2 operations. This time, the authors chose the transotic approach for tumor resection, which achieved the goal of complete resection of the tumor, and the patient recovered smoothly after surgery. There were no surgical complications and no tumor recurrence after the follow-up. Through literature review and our own experience, the authors suggest that complete surgical resection is the first choice for both primary and recurrent advanced ELSTs. The choice of a reasonable surgical approach is the key to ensuring complete resection of the tumor, while preoperative angiography and embolization, fine treatment of important structures during surgery, and postoperative long-term follow-up are equally important for patients with advanced ELST to obtain a good prognosis.
Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery
Authors: Dhiman Ankit , Kothary Vishesh , Witmer Hunter D. D. , Bregio Celyn , Sood Divya , Ong Cecilia T. , Polite Blase , Eng Oliver S. , Shergill Ardaman , Turaga Kiran K.
Published: March 2023

Objective:

To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

Background:

Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection.

Methods:

Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen.

Results:

One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable (P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06–12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA.

Conclusions:

This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.
Understanding Variation in In-hospital Mortality After Major Surgery in the United States
Authors: Martins Russell Seth , Chang Yu-Hui , Etzioni David , Stucky Chee-Chee , Cronin Patricia , Wasif Nabil
Published: March 2023

Objectives:

We aimed to quantify the contributions of patient characteristics (PC), hospital structural characteristics (HC), and hospital operative volumes (HOV) to in-hospital mortality (IHM) after major surgery in the United States (US).

Background:

The volume-outcome relationship correlates higher HOV with decreased IHM. However, IHM after major surgery is multifactorial, and the relative contribution of PC, HC, and HOV to IHM after major surgery is unknown.

Study Design:

Patients undergoing major pancreatic, esophageal, lung, bladder, and rectal operations between 2006 and 2011 were identified from the Nationwide Inpatient Sample linked to the American Hospital Association survey. Multilevel logistic regression models were constructed using PC, HC, and HOV to calculate attributable variability in IHM for each.

Results:

Eighty thousand nine hundred sixty-nine patients across 1025 hospitals were included. Postoperative IHM ranged from 0.9% for rectal to 3.9% for esophageal surgery. Patient characteristics contributed most of the variability in IHM for esophageal (63%), pancreatic (62.9%), rectal (41.2%), and lung (44.4%) operations. HOV explained < 25% of variability for pancreatic, esophageal, lung, and rectal surgery. HC accounted for 16.9% and 17.4% of the variability in IHM for esophageal and rectal surgery. Unexplained variability in IHM was high in the lung (44.3%), bladder (39.3%), and rectal (33.7%) surgery subgroups.

Conclusions:

Despite recent policy focus on the volume-outcome relationship, HOV was not the most important contributor to IHM for the major organ surgeries studied. PC remains the largest identifiable contributor to hospital mortality. Quality improvement initiatives should emphasize patient optimization and structural improvements, in addition to investigating the yet unexplained sources contributing to IHM.
Does the Tacrolimus Trough Level Adequately Predict Drug Exposure in Patients Requiring a High Tacrolimus Dose?
Authors: Haverals Lien , Roosens Laurence , Wouters Kristien , Marquet Pierre , Monchaud Caroline , Massart Annick , Abramowicz Daniel , Hellemans Rachel
Published: March 2023

Background.

Tacrolimus (Tac) has a narrow therapeutic range. Dosing is generally targeted at Tac trough levels (C
0), notwithstanding conflicting reports on the correlation between Tac C
0 and systemic exposure measured by the area-under-the-concentration-over-time curve (AUC). The Tac dose required to meet the target C
0 varies highly among patients. We hypothesized that patients requiring a relatively high Tac dose for a certain C
0 may show a higher AUC.

Methods.

We retrospectively analyzed data from 53 patients in which a 24-h Tac AUC24 estimation was performed at our center. Patients were divided into those taking a low (≤0.15 mg/kg) or high (>0.15 mg/kg) once-daily Tac dose. Multiple linear regression models were used to investigate if the association between C
0 and AUC24 changes according to dose level.

Results.

Despite the large difference in mean Tac dose between the low- and high-dose group (7 versus 17 mg/d), C
0 levels were similar. However, the mean AUC24 was substantially higher in the high-dose group (320 ± 96 h·μg/L versus 255 ± 81 h·μg/L, P < 0.001). This difference remained significant after adjusting for age and race. For a same C
0, every 0.01 mg/kg increase in Tac dose resulted in an AUC24 increase of 3.59 h·μg/L.

Conclusions.

This study challenges the general belief that C
0 levels are sufficiently reliable to estimate systemic drug exposure. We demonstrated that patients requiring a relatively high Tac dose to attain therapeutic C
0 levels have higher drug exposure and could therefore potentially be overdosed.