bluuebunny/crossref_metadata_2025 huggingface dataset:
SURG-14. COMPARABLE SURVIVAL OUTCOMES BETWEEN THE ELDERLY AND THEIR YOUNGER COUNTERPARTS AFTER RESECTION OF BENIGN MENINGIOMAS
Authors: Ma Jun , Alattar Ali , Dhawan Sanjay , Jakola Asgeir , Bartek Jr Jiri , Chen Clark
Published: November 2021

OBJECTIVE

Using the Surveillance, Epidemiology and End Results (SEER) database, we characterized the patterns of surgical recommendations and outcomes after benign meningioma resection in the elderly population.

METHODS

27,839 adult meningioma patients were identified in SEER between 1973- 2015 and 6,967 patients were identified between 2016-18. Patients were stratified into four age groups:18-39, 40-59, 60-79, and > 80 years old. The likelihood for recommendation to proceed with resection, extent of resection, and survival outcome were determined using logistic regression models.

RESULTS

In a multi-variate model that accounted for gender, race, marital status, tumor size, and tumor location, the likelihood of recommendation to proceed with benign meningiomas resection decreased with advancing age. Relative to patients age 40-59, the likelihood of recommendation for surgery were 1.130 (95%CI=0.925-1.380, P=0.230), 0.593 (95%CI=0.531-0.662, P< 0.001), and 0.173 (95%CI=0.146-0.205, P< 0.001) for patients age 18-39, 60-79, and >= 80, respectively. A similar trend in the likelihood of gross total resection (GTR) was observed. Relative to patients age 40-59, the likelihood of gross total resection were 1.009 (95%CI=0.913-1.114, P=0.867), 0.903 (95%CI=0.849-0.961, P=0.001), and 0.580 (95%CI=0.512-0.657, P< 0.001) for patients age 18-39, 60-79, and >= 80, respectively. However, survival after meningioma resection did not vary significantly as a function of patient age. Relative to patients age 40-59, the hazard of death after GTR of meningioma resection were 1.324 (95%CI=0.795-2/203, P=0.280), 0.813 (95%CI=0.639-1.035, P=0.092), and 0.913 (95%CI=0.618-1.350, P=0.649) for patients age 60-79, and >= 80, respectively. These results were validated using SEER data from 2016-2018.

CONCLUSION

This analysis provide evidence that surgeons exert caution in surgical resection of benign meningioma in the elderly, with decreased likelihood for recommending surgery in this population. In patients selected for and underwent gross resection, survival outcome in the elderly was comparable to their younger counterparts, suggesting safety of procedure in appropriately selected elderly.
TAMI-05. FATTY ACID SYNTHESIS IS REQUIRED FOR HER2+ BREAST CANCER BRAIN METASTASIS
Authors: Ferraro Gino , Ali Ahmed , Luengo Alba , Deik Amy , Abbott Keene , Bezwada Divya , Blanc Landry , Prideaux Brendan , Jin Xin , Posada Jessica , Amoozgar Zohreh , Ferreira Raphael , Chen Ivy , Naxerova Kamila , Ng Christopher , Westermark Anna , Davidson Shawn , Fukumura Dai , Dartois Véronique , Clish Clary , Heiden Matthew Vander , Jain Rakesh
Published: November 2021

Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive breast cancer and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
TAMI-13. MODULATION OF REDUCTIVE CARBOXYLATION FLUX OF GLUTAMINE IN GLIOBLASTOMA CELLS BY USING OSCILLATING MAGNETIC FIELD
Authors: Pichumani Kumar , Ijare Omkar , Hambarde Shashank , Sharpe Martyn , John Blessy , Baskin David , Helekar Santosh
Published: November 2021

Increased cell proliferation in glioblastoma (GBM) leads to hypoxia in the tumor microenvironment. This is a major concern in GBM patients as it promotes tumor invasion. Glutaminolysis is a hallmark of cancer cells and under hypoxic conditions glutamine metabolism proceeds through reductive carboxylation pathway. Recently, we have shown that oscillating magnetic field (OMF) produces oncolytic effects which can influence cellular metabolism. Here, we have explored the effect of OMF on glutamine metabolism in GBM cells. Patient-derived GBM cells were grown in high glucose (25 mM) DMEM supplemented with 20% fetal bovine serum (FBS), 2.0 mM glutamine and 1.0 mM pyruvate at 37 °C under humidified air and 5% CO2. Cells were divided into 2 groups (Test and Sham; n = 4 each group). When reached confluency (~2.0×106 cells/mL), cells in both groups were treated with 4.0 mM of [U-13C]glutamine in DMEM (supplemented with 20% FBS, and 1.0 mM pyruvate). The “Test” group was subjected to OMF for 3 hours, and the “Sham” group was treated similar to the “Test” group but with non-magnetic rods of the same dimensions as the magnets in the Test group. After 3 h, cells were harvested in 50% methanol analyzed by GC-MS. The 13C-isotopomer analysis showed that glutamine metabolism in GBM cells proceeds through reduction carboxylation, confirmed by the higher levels of M+5 citrate (15.42 ± 1.28 % ) than M+4 citrate (2.05 ± 0.28 %). When GBM cells were treated with OMF, a statistically significant decrease in the citrate M+5 was observed, compared to the “Sham” treated group (15.42 ± 1.28 % vs. 8.89 ± 1.30 %; p = 0.0003). This decrease in M+5 citrate upon OMF treatment clearly indicates that the OMF decreases the reductive carboxylation flux of glutamine in GBM cells which would have therapeutic value in treating GBM patients.
TAMI-28. IDENTIFICATION OF A NEUROLIGIN-3 BINDING PARTNER IN HIGH-GRADE GLIOMAS AND NORMAL PROGENITORS
Authors: Gillespie Shawn , Kim Yoon Seok , Geraghty Anna , Quezada Michael , Reed James , Woo Pamelyn , Monje Michelle
Published: November 2021

High-grade gliomas, including diffuse intrinsic pontine glioma, are lethal cancers whose progression is strongly regulated by neuronal activity. One way in which gliomas detect neuronal activity is via interaction with the ectodomain of post-synaptic adhesion protein neuroligin-3 (NLGN3), which is shed from neurons and oligodendrocyte precursors (OPCs) by the ADAM10 sheddase in an activity dependent manner. NLGN3 signaling drives glioma growth, but the cognate binding partner of shed NLGN3 (sNLGN3) on glioma cells is unknown. Here, we employed a proximity labeling technique to identify chondroitin sulfate proteoglycan 4 (CSPG4) as a putative binding partner of sNLGN3 in gliomas. We then confirmed complexing between recombinant proteins with size exclusion chromatography and are determining kinetics and affinity by surface plasmon resonance. When looking for evidence of binding in cells, we were surprised to find that sNLGN3 triggers regulated intramembrane proteolysis (RIP) of CSPG4, leaving no trace of the interaction at the membrane. sNLGN3 binding first induces ADAM10-mediated cleavage and release of the CSPG4 ectodomain, followed by gamma secretase-mediated release of the intracellular domain and downstream signaling in OPCs and gliomas. Pre-treatment of glioma cells or OPCs with an ADAM10 inhibitor entirely blocks sNLGN3-induced CSPG4 shedding. Acute depletion of CSPG4 via CRISPR gene editing renders glioma cells insensitive to the growth-promoting effects of sNLGN3 in vitro. Furthermore, we find that tamoxifen-induced deletion of NLGN3 from murine OPCs reduces the total number of OPCs, suggesting that this signaling axis promotes maintenance of OPC stemness in an autocrine fashion. Indeed, gamma secretase inhibition accelerates OPC differentiation in vitro, pointing towards a fundamental role for sNLGN3-CSPG4 signaling in OPCs and high-grade gliomas. Altogether, our results form a critical missing link in understanding how glioma cells detect a key neuronal activity-regulated signal, suggest intriguing links to OPC biology and identify a therapeutic target to disrupt neuron-glioma interactions.
TAMI-56. TARGETING AMINO ACID METABOLIC VULNERABILITIES IN IDH-MUTANT AND IDH-WILDTYPE GLIOMAS
Authors: Ohba Shigeo , Hirayama Akiyoshi , Hitachi Keisuke , Yamaguchi Hisateru , Mukherjee Joydeep , Pieper Russell , Hirose Yuichi
Published: November 2021

IDH-wildtype glioma and IDH-mutant glioma have different genetical and metabolic background although their histological appearances are similar. The aim of the study is to reveal the difference in metabolites between IDH-wildtype glioma and IDH-mutant glioma, and to find the effective treatment targeting cancer metabolism according to the status of IDH in gliomas. Two artificial cell lines made from normal human astrocyte were used: NHAE6E7hTERTRas (IDH-wildtype) and NHAE6E7hTERTIDHmut (IDH-mutant). Capillary electrophoresis time-of-flight-mass spectrometry (CE-TOFMS) revealed that the amount of asparagine was lower in NHAE6E7hTERTRas cells compared with NHAE6E7hTERTIDHmut cells. L-asparaginase, which converts asparagine into aspartate, was more effective in the former cells than the latter cells. L-asparaginase induced autophagy and inhibition of autophagy by 3-MA suppressed L-asparaginase-induced antitumor effect. Adding asparagine into the culture medium rescued the antitumor effect of L-asparaginase. L-asparaginase increased the expression of asparagine synthetase (ASNS) and genetical or pharmacological inhibition of ASNS enhanced the antitumor effect of L-asparaginase. CE-TOFMS showed the lower amount of glutamine, glutamate and 2-oxoglutarate in NHAE6E7hTERTIDHmut cells than NHAE6E7hTERTRas cells. GLUD1 inhibitor inhibited proliferation by inducing higher ROS level and apoptosis in NHAE6E7hTERTIDHmut cells than NHAE6E7hTERTRas cells. ROS inhibitor, NAC suppressed GLUD1 inhibitor-induced ROS, apoptosis, and cytotoxicity in NHAE6E7hTERTIDHmut cells. Exogeneous dimethyl 2-oxoglutarate rescued the cytotoxicity induced by GLUD1 inhibitor. L-asparaginase and GLUD1 inhibitor will be new therapeutic option for IDH-wildtype glioma and IDH-mutant glioma, respectively.
BRMP-01. Awake cranial surgery with intraoperative language mapping for brain tumors. A single-center experience
Authors: Cervio Andrés , Giovannini Sebastían , Hasdeu Sonia , Pertierra Lucía , Diez Blanca
Published: November 2021

BACKGROUND

Maximal safe resection of brain tumors affecting language areas has been a matter of increasing interest worldwide in the last decades. Functional MRI, tractography, and awake cranial surgery are standard procedures in our department since 2006. The aim of this study was to describe our experience in a series of 58 patients who underwent awake cranial surgery with intraoperative language mapping.

METHODS

Retrospective study of 58 adult patients who underwent awake surgery for brain tumors between January 2006 and January 2021. Preoperative neuropsychological assessment served as inclusion criteria. Language was evaluated according to the BDAE (Boston diagnostic aphasia examination) and WAB (Western aphasia battery) and strength according to the MRC (Medical Research Council) motor scale in the preoperative, immediate postoperative, and 3-months follow up. Functional MRI and tractography depicting white-matter tracts, neuronavigation, cortical and subcortical stimulation were performed in all cases. Conscious sedation was the anesthetic technique (propofol, fentanyl, and NSAIDs). Minimum follow-up was 6 months.

FINDINGS

The average age was 35 years (16–74). The anatomopathological findings were: low-grade glioma in 75,8% (n = 44), high-grade glioma in 15,6% (n = 9) and others in 8,6% (n = 5). No complications were registered during postoperative course. At the immediate postoperative evaluation 65% of patients presented with speech disturbances but at the 3-months follow up speech recovery was observed in all cases. Only 1 patient remained with moderate aphasia. mRS score at 3- months follow up was ≤ 1 in 96% of patients. Two patients had a persistent moderate hemiparesis.

CONCLUSION

Tumor resection in awake patients showed to be a safe procedure, and well tolerated by the patients. Preoperative planning of anatomical and functional aspects and intraoperative neurophysiological assessment are the cornerstones for pursuing maximal safe resection.
CNTM-03. Functional connectivity networks in patients with brain tumors and vascular lesions in the occipital cortex
Authors: Rosengarth Katharina , Hense Katharina , Plank Tina , Greenlee Mark , Wendl Christina , Proescholdt Martin , Schmidt Nils-Ole
Published: November 2021

OBJECTIVE

Space-occupying brain lesions as brain tumors in the occipital lobe have only been sparsely investigated so far, as this localization is extremely rare with only 1% of cases. It is still unclear how this affects the overall organization of the visual system. We investigated functional connectivity of functional networks associated with higher visual processing between patients with occipital space-occupying lesion in the occipital cortex and healthy controls.

METHODS

12 patients with brain tumors, 7 patients with vascular lesions in the occipital cortex and 19 healthy subjects matched for age and sex were included. During functional MRI patients and subjects performed a visual excentricity mapping task. Data analysis was done using CONN toolbox based on Matlab. See-to-ROI connectivities of 23 Regions of Interest (ROIs) implemented in the CONN toolbox which were assigned to the Default Mode, Visual, Salience, Dorsal Attention, and Frontoparietal network were assessed. For each subject, connectivity was calculated using Fischer transformed pairwise correlations. These correlations were first considered separately for each group in one-sample analyses and then compared between the groups.

RESULTS

Main results show, that compared to control subjects and vascular patients, tumor patients showed weaker intra-network connectivity of components of all networks except the default-network. Tumor patients showed even stronger between-network connectivity in the default-mode network compared to the other groups. Weaker connectivity was observed within the salience network in both patient groups compared to controls.

CONCLUSION

The results indicate that in the course of the disease, compensatory countermeasures take place in the brain against a brain tumor or a space-occupying brain lesion with the aim of maintaining the performance level and cognitive processes for as long as possible. However, more research is needed in this area to understand the mechanisms and effects of brain tumors and space-consuming brain lesions on surrounding tissue.
Polluted lake restoration to promote sustainability in the Yangtze River Basin, China
Authors: Qin Boqiang , Zhang Yunlin , Deng Jianming , Zhu Guangwei , Liu Jianguo , Hamilton David P , Paerl Hans W , Brookes Justin D , Wu Tingfeng , Peng Kai , Yao Yizhou , Ding Kan , Ji Xiaoyan
Published: November 2021

China has made a concerted effort to successfully improve water quality of rivers, but lake water quality has not improved. Lakes require controls on both catchment external nutrient loads and in-lake internal loads, where nature-based solutions are coupled with engineered systems to achieve the United Nations Sustainable Development Goals (SDGs).
The Changing Epidemiology and Microbiology of Patients With Prostate Abscess: Increase in Staphylococcal Infection
Authors: McCormick David W , Kaplan Julika , Whigham Cliff , Coburn Michael , Greenberg Stephen B
Published: November 2021

Background

Prostatic abscesses are rare and have been most commonly associated with gram-negative bacteria; however, Staphylococcus aureus has emerged as a leading cause, particularly in persons who are immunocompromised.

Methods

We conducted a retrospective chart review of all patients discharged from Ben Taub Hospital with a diagnosis of prostatic abscess during January 2011–January 2019. Demographic, clinical, microbiologic, and radiographic data were abstracted from the patients’ charts and analyzed for comorbidities, causative organisms, clinical course, and outcomes.

Results

We identified 32 patients with a prostatic abscess during the study period. S. aureus was the most common causative organism (18/32, 56%). Most patients (24/32, 75%) were admitted to a general medicine service, and the median length of stay was 9 days. Twenty-one patients (66%) were treated with a combination of surgical drainage and antibiotic therapy; 11 (34%) were treated with antibiotics alone. All patients treated with antibiotics alone had full clinical recovery. Two patients (6.3%) died, both of whom had septic shock secondary to disseminated S. aureus infection.

Conclusions

Prostatic abscesses are rare and can be difficult to diagnose, leading to significant morbidity and mortality. S. aureus is a frequent causative organism especially in persons with diabetes mellitus or other immunocompromising conditions. Hematogenous spread of S. aureus infection to the prostate appears common. Prostatic abscesses can serve as the nidus of disseminated S. aureus infection.
SARS-CoV-2 Genomic Surveillance Reveals Little Spread From a Large University Campus to the Surrounding Community
Authors: Valesano Andrew L , Fitzsimmons William J , Blair Christopher N , Woods Robert J , Gilbert Julie , Rudnik Dawn , Mortenson Lindsey , Friedrich Thomas C , O’Connor David H , MacCannell Duncan R , Petrie Joshua G , Martin Emily T , Lauring Adam S
Published: November 2021

Background

Coronavirus disease 2019 (COVID-19) has had high incidence rates at institutions of higher education (IHE) in the United States, but the transmission dynamics in these settings are poorly understood. It remains unclear to what extent IHE-associated outbreaks have contributed to transmission in nearby communities.

Methods

We implemented high-density prospective genomic surveillance to investigate these dynamics at the University of Michigan and the surrounding community during the Fall 2020 semester (August 16–November 24). We sequenced complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from 1659 individuals, including 468 students, representing 20% of cases in students and 25% of total cases in Washtenaw County over the study interval.

Results

Phylogenetic analysis identified >200 introductions into the student population, most of which were not related to other student cases. There were 2 prolonged student transmission clusters, of 115 and 73 individuals, that spanned multiple on-campus residences. Remarkably, <5% of nonstudent genomes were descended from student clusters, and viral descendants of student cases were rare during a subsequent wave of infections in the community.

Conclusions

The largest outbreaks among students at the University of Michigan did not significantly contribute to the rise in community cases in Fall 2020. These results provide valuable insights into SARS-CoV-2 transmission dynamics at the regional level.
Lower SARS-CoV-2 viral shedding following COVID-19 vaccination among healthcare workers in Los Angeles, California
Authors: Adamson Paul C , Pfeffer Michael A , Arboleda Valerie A , Garner Omai B , de St. Maurice Annabelle , von Bredow Benjamin , Flint Jonathan , Kruglyak Leonid , Currier Judith S
Published: November 2021

Among 880 healthcare workers with a positive SARS-CoV-2 test, 264 (30.0%) infections were identified following receipt of at least one vaccine dose. Median SARS-CoV-2 cycle threshold values were highest among individuals receiving two vaccine doses, corresponding to lower viral shedding. Vaccination might lead to lower transmissibility of SARS-CoV-2.
High Mortality During the Second Wave of the Coronavirus Disease 2019 (COVID-19) Pandemic in Uganda: Experience From a National Referral COVID-19 Treatment Unit
Authors: Bongomin Felix , Fleischer Brian , Olum Ronald , Natukunda Barbra , Kiguli Sarah , Byakika-Kibwika Pauline , Baluku Joseph Baruch , Nakwagala Frederick Nelson
Published: November 2021

Background

We evaluated clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in the second wave of the pandemic in a national COVID-19 treatment unit (CTU) in Uganda.

Methods

We conducted a retrospective cohort study of COVID-19 patients hospitalized at the Mulago National Referral Hospital CTU between May 1 and July 11, 2021. We performed Kaplan-Meier analysis to evaluate all-cause in-hospital mortality.

Results

Of the 477 participants, 247 (52%) were female, 15 (3%) had received at least 1 dose of the COVID-19 vaccine, and 223 (46%) had at least 1 comorbidity. The median age was 52 (interquartile range, 41–65) years. More than 80% of the patients presented with severe (19%, n=91) or critical (66%, n=315) COVID-19 illness. Overall, 174 (37%) patients died. Predictors of all-cause in-hospital mortality were as follows; age ≥50 years (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2–3.2; P=.011), oxygen saturation at admission of ≥92% (aOR, 0.97; 95% CI, 0.91–0.95; P<.001), and admission pulse rate of ≥100 beats per minute (aOR, 1.01; 95% CI, 1.00–1.02; P=.042). The risk of death was 1.4-fold higher in female participants compared with their male counterparts (hazards ratio, 1.4; 95% CI, 1.0–2.0; P=.025).

Conclusions

In this cohort, where the majority of the patients presented with severe or critical illness, more than one third of the patients hospitalized with COVID-19 at a national CTU died of the illness.
Antibiotic Use in Patients With β-Lactam Allergies and Pneumonia: Impact of an Antibiotic Side Chain–Based Cross-Reactivity Chart Combined With Enhanced Allergy Assessment
Authors: Collins Curtis D , Bookal Renee S , Malani Anurag N , Leo Harvey L , Shankar Tara , Scheidel Caleb , West Nina
Published: November 2021

Background

β-lactam antibiotics with dissimilar R-group side chains are associated with low cross-reactivity. Despite this, patients with β-lactam allergies are often treated with non-β-lactam alternative antibiotics. An institutional β-lactam side chain–based cross-reactivity chart was developed and implemented to guide in antibiotic selection for patients with β-lactam allergies.

Methods

This single-center, retrospective cohort study analyzed the impact of the implementation of the cross-reactivity chart for patients with pneumonia. Study time periods were defined as January 2013 to October 2014 prior to implementation of the chart (historical cohort) and January 2017 to October 2018 (intervention cohort) following implementation. The primary outcome was the incidence of β-lactam utilization between time periods. Propensity-weighted scoring and interrupted time-series analyses compared outcomes.

Results

A total of 341 and 623 patient encounters were included in the historical and intervention cohorts, respectively. There was a significantly greater use of β-lactams in the intervention cohort (70.4% vs 89.3%; P < .001) and decreased use of alternative therapy (58.1% vs 36%; P < .001). There was no difference in overall allergic reactions between cohorts (2.4% vs 1.6%; P = .738) or in reactions caused by β-lactams (1.3% vs 0.9%; P = .703). Inpatient mortality increased (0% vs 6.4%; P < .001); however, no deaths were due to allergic reactions. Healthcare facility–onset Clostridioides difficile infections decreased between cohorts (1.2% vs 0.2%; P = .032).

Conclusions

Implementation of a β-lactam side chain–based cross-reactivity chart and enhanced allergy assessment was associated with increased use of β-lactams in patients with pneumonia without increasing allergic reactions.
Phosphatidylinositol 3-phosphate regulates SCAB1-mediated F-actin reorganization during stomatal closure in Arabidopsis
Authors: Yang Yongqing , Zhao Yi , Zheng Wenna , Zhao Yang , Zhao Shuangshuang , Wang Qiannan , Bai Li , Zhang Tianren , Huang Shanjin , Song Chunpeng , Yuan Ming , Guo Yan
Published: November 2021

Stomatal movement is critical for plant responses to environmental changes and is regulated by the important signaling molecule phosphatidylinositol 3-phosphate (PI3P). However, the molecular mechanism underlying this process is not well understood. In this study, we show that PI3P binds to stomatal closure-related actin-binding protein1 (SCAB1), a plant-specific F-actin-binding and -bundling protein, and inhibits the oligomerization of SCAB1 to regulate its activity on F-actin in guard cells during stomatal closure in Arabidopsis thaliana. SCAB1 binds specifically to PI3P, but not to other phosphoinositides. Treatment with wortmannin, an inhibitor of phosphoinositide kinase that generates PI3P, leads to an increase of the intermolecular interaction and oligomerization of SCAB1, stabilization of F-actin, and retardation of F-actin reorganization during abscisic acid (ABA)-induced stomatal closure. When the binding activity of SCAB1 to PI3P is abolished, the mutated proteins do not rescue the stability and realignment of F-actin regulated by SCAB1 and the stomatal closure in the scab1 mutant. The expression of PI3P biosynthesis genes is consistently induced when the plants are exposed to drought and ABA treatments. Furthermore, the binding of PI3P to SCAB1 is also required for vacuolar remodeling during stomatal closure. Our results illustrate a PI3P-regulated pathway during ABA-induced stomatal closure, which involves the mediation of SCAB1 activity in F-actin reorganization.
Effects of compound stimulation of fluid shear stress plus ultrasound on stem cell proliferation and osteogenesis
Authors: Jing Lingzhi , Fan Suna , Yao Xiang , Zhang Yaopeng
Published: November 2021

Bone tissue with strong adaptability is often in a complex dynamical microenvironment in vivo, which is associated with the pathogenesis and treatment of orthopedic diseases. Therefore, it is of great significance to investigate the effects of corresponding compound stimulation on cell behaviors. Herein, a fluid shear stress (FSS) plus ultrasound stimulation platform suitable for cell studies based on a microfluidic chip was constructed and bone marrow mesenchymal stem cell (BMSC) was chosen as a model cell. The proliferation and osteogenesis of BMSCs under the compound stimulation of FSS plus ultrasound in growth medium without any soluble induction factors were firstly investigated. Single FSS stimulation and static culture conditions were also examined. Results illustrated that suitable single FSS stimulation (about 0.06 dyn/cm2) could significantly enhance cell proliferation and osteogenesis simultaneously when compared to the static control, while greater FSS mitigated or even restricted these enhancing effects. Interestingly, ultrasound stimulation combined with this suitable FSS stimulation further accelerated cell proliferation as the intensity of ultrasound increasing. As for the osteogenesis under compound stimulation, it was relatively restricted under lower ultrasound intensity (about 0.075 W/cm2), while promoted when the intensity became higher (about 1.75 W/cm2). This study suggests that both the cell proliferation and osteogenesis are very responsive to the magnitudes of FSS and ultrasound stimulations and can be both significantly enhanced by proper combination strategies. Moreover, these findings will provide valuable references for the construction of effective cell bioreactors and also the treatment of orthopedic diseases.
Multi-asset Noisy Rational Expectations Equilibrium with Contingent Claims
Authors: Chabakauri Georgy , Yuan Kathy , Zachariadis Konstantinos E
Published: November 2021

We study a noisy rational expectations equilibrium in a multi-asset economy populated by informed and uninformed investors and noise traders. The assets can include state contingent claims such as Arrow–Debreu securities, assets with only positive payoffs, options or other derivative securities. The probabilities of states depend on an aggregate shock, which is observed only by the informed investor. We derive a three-factor CAPM with asymmetric information, establish conditions under which asset prices reveal information about the shock, and show that information asymmetry amplifies the effects of payoff skewness on asset returns. We also find that volatility derivatives make incomplete markets effectively complete, and their prices quantify market illiquidity and shadow value of information to uninformed investors.
Analgesic prescribing in patients with inflammatory arthritis in England: an observational study using electronic healthcare record data
Authors: Scott Ian C , Bailey James , White Christopher R , Mallen Christian D , Muller Sara
Published: November 2021

Objectives

International data suggest inflammatory arthritis (IA) pain management frequently involves opioid prescribing, despite little evidence of efficacy, and potential harms. We evaluated analgesic prescribing in English National Health Service-managed patients with IA.

Methods

Repeated cross-sectional analyses in the Consultations in Primary Care Archive (primary care consultation and prescription data in nine general practices from 2000 to 2015) evaluated the annual prevalence of analgesic prescriptions in: (i) IA cases (RA, PsA or axial spondyloarthritis [SpA]), and (ii) up to five age-, sex- and practice-matched controls. Analgesic prescriptions were classified into basic, opioids, gabapentinoids and oral NSAIDs, and sub-classified into chronic and intermittent (≥3 and 1–2 prescriptions per calendar year, respectively).

Results

In 2000, there were 594 cases and 2652 controls, rising to 1080 cases and 4703 controls in 2015. In all years, most (65.3–78.5%) cases received analgesics, compared with fewer (37.5–41.1%) controls. Opioid prescribing in cases fell between 2000 and 2015 but remained common with 45.4% (95% CI: 42.4%, 48.4%) and 32.9% (95% CI: 29.8%, 36.0%) receiving at least 1 and ≥3 opioid prescriptions, respectively, in 2015. Gabapentinoid prescription prevalence in cases increased from 0% in 2000 to 9.5% (95% CI: 7.9%, 11.4%) in 2015, and oral NSAID prescription prevalence fell from 53.7% (95% CI: 49.6%, 57.8%) in 2000 to 25.0% (95% CI: 22.4%, 27.7%) in 2015. Across years, analgesic prescribing was commoner in RA than PsA/axial SpA, and 1.7–2.0 times higher in cases than controls.

Conclusions

Analgesic prescribing in IA is common. This is at variance with existing evidence of analgesic efficacy and risks, and guidelines. Interventions are needed to improve analgesic prescribing in this population.
The White View of Black America: Three Forms of Prejudice
Authors: Chatterjee Esha
Published: November 2021

This paper examines the contemporary racial attitudes of white American adults towards black Americans, using data from the General Social Surveys and classifies these attitudes using latent class analysis. The purpose of the analysis is to resolve ongoing debates between (a) those who contend that overt forms of racism have largely been replaced by more socially acceptable forms of racism, and (b) those who contend that overt forms of racism are still so strong in the United States that even the survey form can successfully detect them. Consistent with the second of these two views, a full 55.6 percent of the population adopts a pattern of responses consistent with deeply essentialist accounts of racial inequality.
The efficacy of peer-led oral health programs based on Social Cognitive Theory and Health Belief Model among Hong Kong adolescents: a cluster-randomized controlled trial
Authors: Xiang Bilu , Wong Hai Ming , McGrath Colman P J
Published: November 2021

Oral diseases are preventable through the building of good oral health behaviors. Theory-based behavior change was key to the efficacy of oral health promotion since conventional promotion strategies achieved only short-lived and limited improvements. The objective of the study was to investigate the efficacy of a peer-led oral health intervention based on the health belief model (HBM) and the social cognitive theory (SCT) on oral self-care behaviors among Hong Kong adolescents. One thousand one hundred and eighty-four adolescents in 12 schools participated and were randomly assigned to either intervention or control group, utilizing a cluster-randomized controlled trial design. Brushing/flossing frequency, HBM/SCT constructs, oral health knowledge, and dental anxiety were measured at baseline and 6-month follow-up. Changes in behaviors were assessed using mixed-effects model and the mediators of behavioral change were identified with parallel multiple mediation analysis. At 6 months, the intervention group showed a significant increase in the frequency of brushing and flossing compared with the control group. Self-efficacy was identified as mediator between treatment condition and behavioral changes of brushing and flossing. Combining theories of HBM and SCT is a promising avenue for efficacy in oral health behaviors. The effects were mediated through cognitive variables, which provided guidance for both theory and health intervention development.
Process evaluation of a medical assistant health coaching intervention for type 2 diabetes in diverse primary care settings
Authors: Clark Taylor L , Fortmann Addie L , Philis-Tsimikas Athena , Bodenheimer Thomas , Savin Kimberly L , Sandoval Haley , Bravin Julia I , Gallo Linda C
Published: November 2021

Team-based models that use medical assistants (MAs) to provide self-management support for adults with type 2 diabetes (T2D) have not been pragmatically tested in diverse samples. This cluster-randomized controlled trial compares MA health coaching with usual care in adults with T2D and poor clinical control (“MAC Trial”). The purpose was to conduct a multi-method process evaluation of the MAC Trial using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Reach was assessed by calculating the proportion of enrolled participants out of the eligible pool and examining representativeness of those enrolled. Key informant interviews documented adoption by MA Health Coaches. We examined implementation from the research and patient perspectives by evaluating protocol adherence and the Patient Perceptions of Chronic Illness Care (PACIC-SF) measure, respectively. Findings indicate that the MAC Trial was efficient and effective in reaching patients who were representative of the target population. The acceptance rate among those approached for health coaching was high (87%). Both MA Health Coaches reported high satisfaction with the program and high levels of confidence in their role. The intervention was well-implemented, as evidenced by the protocol adherence rate of 79%; however, statistically significant changes in PACIC-SF scores were not observed. Overall, if found to be effective in improving clinical and patient-reported outcomes, the MAC model holds potential for wider-scale implementation given its successful adoption and implementation and demonstrated ability to reach patients with poorly controlled T2D who are at-risk for diabetes complications in diverse primary care settings.
Identifying a system-neutral meaning of a title transfer financial collateral arrangement in the Financial Collateral Directive
Authors: Ezike Obiora
Published: November 2021

European Union (EU) directives adopt a functional method. This implies that they are drafted on the assumptions that implementing laws are functionally equivalent and, crucially, that the concepts they contain are system neutral without doctrinal commitment. This article primarily tests these assumptions by exploring the definition of title transfer financial collateral arrangements (TTFCA) in the Financial Collateral Directive. It is argued that the Directive offers a stable meaning of a TTFCA that can be identified in most systems, although, in some cases, there are slight conceptual tensions that require a more contextual, rather than a functional, perspective.
A New Framework for Practice–Academic Partnerships During the Pandemic—and into the Future
Authors: Spector Nancy M. , Buck Michelle , Phipps Sarah
Published: November 2021

During the COVID-19 pandemic, many health care facilities closed their doors to nursing students, depriving them of the experience of caring for patients, a foundation of nursing education. The purpose of this article is to report on how the National Council of State Boards of Nursing convened nurse leaders from around the country to explore this problem and develop possible solutions.

Coming together virtually, these leaders recommended a national model, the practice–academic partnership, to provide nursing students with in-person clinical experiences during the pandemic. This model is unique in its recognition of the important role of nursing regulatory bodies in these partnerships. The practice–academic partnership model creates clinical education opportunities for students during a public health crisis, such as the COVID-19 pandemic. Further, the model could be applied to meet the chronic challenges nursing education programs have often faced in securing clinical sites, even in the absence of a global or national public health emergency. We provide the context in which the practice–academic partnership model was developed, along with keys to its successful implementation and suggestions for its evaluation. We also discuss the implications of using this model once the pandemic ends.
Cohort Studies
Authors: Capili Bernadette , Anastasi Joyce K.
Published: November 2021

Editor's note: This is the seventh article in a series on clinical research by nurses. The series is designed to give nurses the knowledge and skills they need to participate in research, step by step. Each column will present the concepts that underpin evidence-based practice—from research design to data interpretation. The articles will be accompanied by a podcast offering more insight and context from the authors. To see all the articles in the series, go to http://links.lww.com/AJN/A204.
Pain as an Early Indicator of Pressure Ulcer Risk
Authors: Todd Betsy
Published: November 2021

Pain may be an important factor to consider when assessing patients for the development of pressure ulcers, but more research is needed to assess the characteristics associated with pain as a symptom preceding these injuries.
The USPSTF Recommends Earlier Screening for Prediabetes and Type 2 Diabetes
Authors: Todd Betsy
Published: November 2021

Screening is recommended for overweight or obese adults beginning at age 35.

Earlier screening should be considered in populations with a disproportionately high prevalence of diabetes.
Again in a Heartbeat
Authors: Kessler Jeanne
Published: November 2021

When a mother's mental state rapidly worsens during the pandemic, her daughter brings her home.
Impact of the COVID-19 Pandemic on the Future of Nursing Education
Authors: Leaver Cynthia A. , Stanley Joan M. , Goodwin Veenema Tener
Published: November 2021

Nursing is the largest health profession, with nearly 4 million providers practicing across acute, primary, and public health care settings. In response to the pandemic, nursing schools halted on-site course delivery and redesigned programs to attenuate risks to students and faculty. Key challenges faced by schools included financial cutbacks, rapid increases in online learning technology, maintaining student academic progression, disruption to clinical learning opportunities, and meeting accreditation standards, while addressing the stress and loss experienced by faculty, staff, and students. Despite challenges, nursing organizations provided guidance for decision making, new learning resources, and faculty development opportunities. Schools of nursing leveraged their resources to redesign nursing curricula, strengthen partnerships for student clinical experiences, and address needs of the community.

Nursing education will look different from its prepandemic profile in the future. Lessons learned during the pandemic point to gaps in nursing education, particularly related to disaster and public health preparedness, health equity, and technology. The American Association of Colleges of Nursing’s new Essentials—standards for professional nursing education—were finalized during the pandemic and reflect these lessons. The need for nurse scientists to conduct emergency response research was made evident. The importance of strong academic–practice partnerships was highlighted for rapid communication, flexibility, and responses to dynamic environments. For the future, nursing education and practice must collaborate to ensure that students and practicing nurses are prepared to address emergencies and pandemics, as well as the needs of vulnerable populations.
Synergistic Effect of Ketamine and Buprenorphine Observed in the Treatment of Buprenorphine Precipitated Opioid Withdrawal in a Patient With Fentanyl Use
Authors: Hailozian Christian , Luftig Joshua , Liang Amy , Outhay Melena , Ullal Monish , Anderson Erik S. , Kalmin Mariah , Shoptaw Steve , Greenwald Mark K. , Herring Andrew A.
Published: November 2021

Background

Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine’s high-affinity blockade at mu-opioid receptors (μORs). Buprenorphine’s partial agonism (low intrinsic efficacy) at μORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N-methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct μOR binding, synergistically potentiates the effectiveness of buprenorphine μOR signaling, reverses (resensitizes) fentanyl induced μOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine’s rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described.

Case Description

We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, “microdose”). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use.

Conclusions

This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed.
Racial-ethnic Differences in Reasons for Misuse of Prescription Medications Among US Adults
Authors: Cury James D. , Sharma Vinita , Falise Alyssa M. , Terry Ellen L. , Lopez-Quintero Catalina
Published: November 2021

Objectives

This study aims to investigate racial-ethnic differences in reasons for misuse of prescription medications among a nationally representative sample of US adults.

Methods

We analyzed data from the 2015–2019 National Surveys on Drug Use and Health. The study population includes US adults (18–49 years old) who reported misuse of 3 types of prescription drugs (stimulants [n = 6139], sedatives and tranquilizers [n = 5643], and pain relievers [n = 8780]) for 3 reasons: medical-only (eg, to help with pain), recreational-only (eg, to get high), or combined medical and recreational reasons. Multinomial logistic regressions assessed the association between reasons of misuse of prescription medications and self-identified race-ethnicity.

Results

Misuse of the 4 types of prescription medications was primarily motivated by medical reasons (63%–80%). Compared to non-Hispanic Whites, non-Hispanic Blacks (nHB), and Hispanics (H) were less likely to report misuse of pain relievers for combined (nHB: adjusted relative risk ratio [aRRR] = 0.6, 95% confidence interval [CI]: 0.4, 0.7; H; aRRR = 0.7, 95% CI: 0.5, 0.9) or recreational reasons (nHB: aRRR = 0.8, 95% CI: 0.6, 1.0; H; aRRR = 0.7, 95% CI: 0.6, 0.9) rather than medical-only reasons. The odds of misuse of sedatives and tranquilizers for recreational-only reasons as opposed to medical-only reasons were higher among nHB (aRRR = 1.9, 95% CI: 1.3, 2.7) and H (aRRR = 1.9, 95% CI: 1.4, 2.4) than among non-Hispanic Whites.

Conclusions

The increased misuse of prescription pain relievers for medical reasons among racial-ethnic minority groups demonstrates a continued need to investigate underlying structural factors driving these behaviors. The higher odds of sedative and tranquilizer misuse for recreational purposes among racial-ethnic minority groups warrant further investigation.
Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)
Authors: Bauer Michael , Weyland Andreas , Marx Gernot , Bloos Frank , Weber Stephan , Weiler Norbert , Kluge Stefan , Diers Anja , Simon Tim Philipp , Lautenschläger Ingmar , Gründling Matthias , Jaschinski Ulrich , Simon Philipp , Nierhaus Axel , Moerer Onnen , Reill Lorenz , Jörres Achim , Guo Renfeng , Loeffler Markus , Reinhart Konrad , Riedemann Niels ,   for the SepNet-Study Group
Published: November 2021

IMPORTANCE:

Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction.

OBJECTIVES:

This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal antibody against C5a, in patients with severe sepsis or septic shock.

DESIGN:

Multicenter, randomized, and placebo-controlled study.

SETTING AND PARTICIPANTS:

Eleven multidisciplinary ICUs across Germany. Adult patients with severe sepsis or septic shock and with early onset of infection-associated organ dysfunction.

MAIN OUTCOMES AND MEASURES:

Patients were randomly assigned in a ratio of 2:1 to three subsequent dosing cohorts for IV vilobelimab or placebo receiving either 2 × 2 mg/kg (0 and 12 hr), 2 × 4 mg/kg (0 and 24 hr), and 3 × 4 mg/kg (0, 24, and 72 hr). Co-primary endpoints were pharmacodynamics (assessed by C5a concentrations), pharmacokinetics (assessed by vilobelimab concentrations), and safety of vilobelimab. Preliminary efficacy was evaluated by secondary objectives.

RESULTS:

Seventy-two patients were randomized (16 patients for each vilobelimab dosing cohort and eight patients for each placebo dosing cohort). Vilobelimab application was associated with dosing dependent decrease in C5a compared with baseline (p < 0.001). Duration of C5a decrease increased with more frequent dosing. Membrane attack complex lysis capacity measured by 50% hemolytic complement was not affected. Vilobelimab was well tolerated with similar safety findings in all dose cohorts. No vilobelimab-specific adverse events emerged. For vilobelimab-treated patients, investigators attributed less treatment-emergent adverse events as related compared with placebo. Dosing cohorts 2 and 3 had the highest ICU-free and ventilator-free days. There was no difference in mortality, vasopressor-free days, or renal replacement therapy-free days between the groups.

CONCLUSIONS AND RELEVANCE:

Administration of vilobelimab in patients with severe sepsis and septic shock selectively neutralizes C5a in a dose-dependent manner without blocking formation of the membrane attack complex and without resulting in detected safety issues. The data warrant further investigation of C5a inhibition in sepsis.