bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcutaneous tunnelling versus conventional insertion of peripherally inserted central catheters in hospitalized patients (TUNNEL-PICC): a study protocol for a randomized controlled trial
Authors: Kwon Yohan , Kim Eung Tae , Cho Soo Buem , Lee Jae Hwan , Shim Dong Jae
Published: September 2022

Background

Peripherally inserted central catheters (PICCs) are now widely used in modern medicine, and associated complications have also increased. Central line-associated bloodstream infection (CLABSI) is the most serious complication because it can cause extended hospital stays and increase costs. Furthermore, it can contribute to dire consequences for critically ill patients. Subcutaneous tunnelling for central venous catheters is an accepted method to reduce the risk of CLABSI. However, it is not generally adopted for PICC placement in most hospitals because its safety and efficacy have not been thoroughly evaluated.

Methods

In this multi-institutional, prospective, non-blinded pragmatic randomized controlled trial, 1694 patients treated at five referral hospitals will be assigned to one of two parallel arms (conventional and tunnelled PICC groups) using computer-generated stratified randomization. The conventional group will undergo PICC placement by routine practice. In the tunnelled PICC (tPICC) group, additional subcutaneous tunnelling will be applied. Patients will be followed until PICC removal or the end of this study. The primary endpoint is whether subcutaneous tunnelling reduced the rate of CLABSI compared to the conventional method. The secondary endpoints are technical success rates, complications including exit-site bleeding or infection, and the procedure time between the groups.

Discussion

Subcutaneous tunnelling is a widely used method to reduce catheter-associated infection. However, it has not been thoroughly applied for PICC. A randomized trial is needed to objectively assess the effects of the subcutaneous tunnel in PICC placement. This TUNNEL-PICC trial will provide evidence for the effectiveness of subcutaneous tunnelling in decreasing the risk of CLABSI.

Trial registration

Clinical Research Information Service (CRiS) KCT0005521
A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis—ICE-COVID
Authors: Jessop Z. M. , Gibson J. , Lim J. Y. , Jovic T. H. , Combellack E. , Dobbs T. D. , Carter K. , Hiles S. , Islam S. , Healy B. , Humphreys I. , Eccles R. , Hutchings H. A. , Whitaker I. S.
Published: September 2022

Introduction

At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2.

Methods and analysis

A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks.

Primary outcome

Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years.

Discussion

This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population.

Trial registration

NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.
Re-analysis on the statistical sampling biases of a mask promotion trial in Bangladesh: a statistical replication
Authors: Chikina Maria , Pegden Wesley , Recht Benjamin
Published: September 2022

A recent randomized trial evaluated the impact of mask promotion on COVID-19-related outcomes. We find that staff behavior in both unblinded and supposedly blinded steps caused large and statistically significant imbalances in population sizes. These denominator differences constitute the rate differences observed in the trial, complicating inferences of causality.
Promoting the adoption of local governmental policy on the reimbursement of chronic disease medicines (PAPMed): study protocol of a field-based cluster randomized trial in rural Nantong, China
Authors: He Zhengting , Cao Xin , Zhao Duan , Tang Zemin , Zhao Jiayu , Beasley Mariel , Renne Angela , Liu Lei , Zhu Shengjie , Gao Yuexia , Yan Lijing L.
Published: September 2022

Background

Among rural Chinese patients with non-communicable diseases (NCDs), low socioeconomic status increases the risk of developing NCDs and associated financial burdens in paying for medicines and treatments. Despite the chronic disease medicine reimbursement policy of the local government in Nantong City, China, various barriers prevent patients from registering for and benefitting from the policy. This study aims to develop a behavior science-based intervention program for promoting the adoption of the policy and to evaluate the effectiveness of the program compared with usual practices.

Methods

Barriers and opportunities affecting stakeholders in adopting the policy were identified through contextual research and summarized through behavior mapping. The intervention is designed to target these barriers and opportunities through behavior science theories and will be evaluated through a 6-month cluster randomized controlled trial in Tongzhou District, Nantong, China. A total of 30 villages from two townships are randomized in a 1:1 ratio to either the intervention or the control arm (usual practices). Village doctors in the intervention arm (1) receive systematic training on policy details, registration procedures, and intervention protocol, (2) promote the policy and encourage registration, (3) follow up with patients in the first, third, and sixth months after the intervention, and (4) receive financial incentives based on performance. The primary outcome is policy registration rate and the secondary outcomes include the number of patients registering for the policy, medical costs saved, frequency of village doctor visits, and health measures such as blood pressure and glucose levels.

Discussion

This study is one of very few that aims to promote adoption of NCDs outpatient medication reimbursement policies, and the first study to evaluate the impact of these policies on patients’ financial and physical wellbeing in China. The simple, feasible, and scalable intervention is designed based on the theories of behavior science and is applicable to similar low-income regions nationwide where outpatient medical costs remain a financial burden for patients.

Trial registration

ClinicalTrials.govhttps://clinicaltrials.gov/ct2/show/NCT04731194?term=PAPMed&draw=2&rank=1, registered on 29 January 2021; Chinese Clinical Trial Registry http://www.chictr.org.cn/showproj.aspx?proj=65987, registered on 14 January 14 2021.
Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial
Authors: Franco-Moreno Anabel , Acedo-Gutiérrez María Soledad , Martín Nicolás Labrador-San , Hernández-Blanco Clara , Rodríguez-Olleros Celia , Ibáñez-Estéllez Fátima , Suárez-Simón Ana , Balado-Rico Mateo , Romero-Paternina Ana Rocío , Alonso-Menchén David , Escolano-Fernández Belén , Piniella-Ruiz Esther , Alonso-Monge Ester , Notario-Leo Helena , Bibiano-Guillén Carlos , Peña-Lillo Gabriela , Antiqueira-Pérez Armando , Romero-Pareja Rodolfo , Cabello-Clotet Noemí , Estrada-Pérez Vicente , Troya-García Jesús , de Carranza-López María , Escobar-Rodríguez Ismael , Vallejo-Maroto Nacho , Torres-Macho Juan
Published: September 2022

Background

Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death.

Methods/design

This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of < 0.80 × 109/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment.

Discussion

If our hypothesis is correct, the results of this study will provide additional insights into the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease.

Trial registration

ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.
Investigation of selected physico-chemical quality parameters in industrial wastewater by electrocoagulation process, Ethiopia
Authors: Tibebe Dessie , Negash Almaz , Mulugeta Marye , Kassa Yezbie , Moges Zerubabel , Yenealem Dereje
Published: September 2022

Nowadays, there are more than fourteen major state and private owned textile industries and garment factories in Ethiopia. However, these textile effluents are directly discharged without treatment to the surrounding environment, as a result, the pollutants bring serious problem to the surrounding community including health such as skin diseases, asthma, abortion, carcinogenic effect, biodiversity loss and mutagenic effect on the. The main objective of this study is characterization and treatment of the textile effluent using aluminum electrodes in the electrocoagulation process. EC experimental setups were designed and different parameters were optimized. Electrocoagulation treatment process eliminates physicochemical quality indicators such as pH, electrical conductivity (EC); turbidity, biological oxygen demand (BOD), ammonia; nitrate, nitrite, total nitrogen (TN) and phosphate were determined using standard procedures. From the result, the maximum removal efficiency of phosphate, ammonia, TN, electrical conductivity, turbidity and BOD were obtained 97, 87, 88, 89, 99 and 66%, respectively. Analyses of the electrochemically generated sludge by X-ray Diffraction, Scanning Electron Microscope (SEM), and Fourier Transform Infrared Spectroscopy (FTIR) revealed that the expected crystalline aluminum oxides (bayerite (Al(OH)3 diaspore (AlO(OH)) were found in the sludge. The amorphous phase was also found in the floc. Therefore, a treatment technology was good and encourages the community to apply the technique for the treatment of textile effluent before discharging into the environment.
The lymphatic vascular system: much more than just a sewer
Authors: Wilting Jörg , Becker Jürgen
Published: September 2022

Almost 400 years after the (re)discovery of the lymphatic vascular system (LVS) by Gaspare Aselli (Asellius G. De lactibus, sive lacteis venis, quarto vasorum mesaraicorum genere, novo invento Gasparis Asellii Cremo. Dissertatio. (MDCXXIIX), Milan; 1628.), structure, function, development and evolution of this so-called ‘second’ vascular system are still enigmatic. Interest in the LVS was low because it was (and is) hardly visible, and its diseases are not as life-threatening as those of the blood vascular system. It is not uncommon for patients with lymphedema to be told that yes, they can live with it. Usually, the functions of the LVS are discussed in terms of fluid homeostasis, uptake of chylomicrons from the gut, and immune cell circulation. However, the broad molecular equipment of lymphatic endothelial cells suggests that they possess many more functions, which are also reflected in the pathophysiology of the system. With some specific exceptions, lymphatics develop in all organs. Although basic structure and function are the same regardless their position in the body wall or the internal organs, there are important site-specific characteristics. We discuss common structure and function of lymphatics; and point to important functions for hyaluronan turn-over, salt balance, coagulation, extracellular matrix production, adipose tissue development and potential appetite regulation, and the influence of hypoxia on the regulation of these functions. Differences with respect to the embryonic origin and molecular equipment between somatic and splanchnic lymphatics are discussed with a side-view on the phylogeny of the LVS. The functions of the lymphatic vasculature are much broader than generally thought, and lymphatic research will have many interesting and surprising aspects to offer in the future.
A dark and stormy night: Reallocation storms in edge computing
Authors: Lovén Lauri , Peltonen Ella , Ruha Leena , Harjula Erkki , Pirttikangas Susanna
Published: September 2022

Efficient resource usage in edge computing requires clever allocation of the workload of application components. In this paper, we show that under certain circumstances, the number of superfluous workload reallocations from one edge server to another may grow to a significant proportion of all user tasks—a phenomenon we present as a reallocation storm. We showcase this phenomenon on a city-scale edge server deployment by simulating the allocation of user task workloads in a number of scenarios capturing likely edge computing deployments and usage patterns. The simulations are based on a large real-world data set of city-wide Wi-Fi network connections, with more than 47M connections over ca. 560 access points. We study the occurrence of reallocation storms in three common edge-based reallocation strategies and compare the latency–workload trade-offs related to each strategy. As a result, we find that the superfluous reallocations vanish when the edge server capacity is increased above a certain threshold, unique for each reallocation strategy, peaking at ca. 35% of the peak ES workload. Further, while a reallocation strategy aiming to minimize latency consistently resulted in the worst reallocation storms, the two other strategies, namely a random reallocation strategy and a bottom-up strategy which always chooses the edge server with the lowest workload as a reallocation target, behave nearly identically in terms of latency as well as the reallocation storm in dense edge deployments. Since the random strategy requires much less coordination, we recommend it over the bottom-up one in dense ES deployments. Moreover, we study the conditions associated with reallocation storms. We discover that edge servers with the very highest workloads are best associated with reallocation storms, with other servers around the few busy nodes thus mirroring their workload. Further, we identify circumstances associated with an elevated risk of reallocation storms, such as summertime (ca. 4 times the risk than on average) and on weekends (ca. 1.5 times the risk). Furthermore, mass events such as popular sports games incurred a high risk (nearly 10 times that of the average) of a reallocation storm in a MEC-based scenario.
Improving datacenter utilization through containerized service-based architecture
Authors: Mulahuwaish Aos , Korbel Shane , Qolomany Basheer
Published: September 2022

The modern datacenter's computing capabilities have far outstripped the applications running within and have become a hidden cost of doing business due to how software is architected and deployed. Resources are over-allocated to monolithic applications that sit idle for large parts of the day. If applications were architected and deployed differently, shared services could be used for multiple applications as needed. When combined with powerful orchestration software, containerized microservices can both deploy and dynamically scale applications from very small to very large within moments—scaling the application not only across a single datacenter but across all datacenters where the application(s) are deployed.

In this paper, we analyze data from an application(s) deployed both as a single monolithic codebase and as a containerized application using microservice-based architecture to calculate the performance and computing resource waste are both architected and deployed. A modern approach is offered as a solution as a path from how to go from a monolithic codebase to a more efficient, reliable, scalable, and less costly deployment model.
A pan-cancer analysis of the oncogenic role of leucine zipper protein 2 in human cancer
Authors: Feng Dechao , Shi Xu , Zhu Weizhen , Zhang Facai , Li Dengxiong , Han Ping , Wei Qiang , Yang Lu
Published: September 2022

In this study, we aimed to perform a pan-cancer analysis of leucine zipper protein 2 (LUZP2). A standardized TCGA pan-cancer dataset was downloaded. Differential expression, clinical prognosis, genetic mutations, immune infiltration, epigenetic modifications, tumor stemness and heterogeneity were analyzed. We conducted all analyses through software R 3.6.3 and its suitable packages. Compared to normal samples, we observed that the LUZP2 mRNA expression was significantly upregulated in LGG, PRAD, LUSC and downregulated in KIRC and other eleven cancer species patients. In terms of overall survival, low-expression of LUZP2 was significantly associated with poor prognosis in lower grade glioma (LGG), lung squamous cell carcinoma (LUSC), kidney renal clear cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). For progression-free survival, we observed that downregulation of LUZP2 was significantly related to LGG, KIRC, LUSC, and PRAD. Our results observed negative correlations of the stemness of LGG and PRAD with the mRNA expression of LUZP2, whose downregulation was closely associated with poor prognosis. The mutation frequencies of LGG, PRAD, KIRC, and LUSC were 0.4%, 0.4%, 0.3%, and 2.1%, respectively. We detected that the LUZP2 level was negatively associated with TILs in most cancers, including LGG, LUSC, PRAD, and KIRC, while the LUZP2 methylation showed the opposite results. In conclusion, the results of our initial pan-cancer investigation provided a somewhat thorough understanding of the functions of LUZP2 on KIRC, LGG, PRAD, and LUSC.
A systematic review of empirical evidence for landscape-level fuel treatment effectiveness
Authors: McKinney Shawn T. , Abrahamson Ilana , Jain Theresa , Anderson Nathaniel
Published: September 2022

Background

Adverse effects of wildfires can be mitigated within fuel treatments, but empirical evidence of their effectiveness across large areas is needed to guide design and implementation at the landscape level. We conducted a systematic literature review of empirically based studies that tested the influence of landscape-level fuel treatments on subsequent wildfires in North America over the past 30 years to evaluate how treatment type and configuration affect subsequent wildfire behavior or enable more effective wildfire response.

Results

We identified 2240 papers, but only 26 met our inclusion criteria. Wildfire sizes ranged from 96 to 186,874 ha and total treated area ranged from 8 to 53,423 ha. Total treated area within a wildfire perimeter was highly correlated with wildfire area (r= 0.89,n= 93 wildfires), and the average proportion of wildfire area that was treated was 22%. All studies demonstrated wildfire behavior changes within treatment boundaries (i.e., site-level effect), but only 12 studies provided evidence that treatments influence wildfires outside of treatment boundaries (i.e., landscape-level effect). These 12 landscape-level papers showed effects on fire severity, fire progression, and fire extent, but were dissimilar in design and analysis approaches, constraining the ability to generalize about the type and configuration of fuel treatments to maximize effectiveness.

Conclusions

It is clear that the state of knowledge based on empirical evidence is at its infancy. This is likely because of the vast challenges associated with designing and implementing sampling designs that account for combinations of spatial and temporal configurations prior to wildfire occurrence. We also suspect part of the reason empirical evidence is lacking is because the distinction between site-level and landscape-level effects is not well recognized in the literature. All papers used the term landscape, but rarely defined the landscape, and some specified identifying landscape-level effects that were truly site-level effects. Future research needs to develop innovative ways to interpret the role of fuel treatments at the landscape level to provide insight on strategic designs and approaches to maximize fuel treatment effectiveness.
Unit group of some finite semisimple group algebras
Authors: Arvind Namrata , Panja Saikat
Published: September 2022

We provide the structure of the unit group of$${\mathbb {F}}_{p^k}S_n$$FpkSn, where$$p>n$$p>nis a prime and$$S_n$$Sndenotes the symmetric group onnletters. We also provide the complete characterization of the unit group of the group algebra$${\mathbb {F}}_{p^k}A_6$$FpkA6for$$p\ge 7$$p≥7, where$$A_6$$A6is the alternating group on 6 letters.
Comparative analysis of imaging diagnostic models for tubular basophilia and mineralization of kidney
Authors: Byun Jong Su , Lee Ji Hyun , Kang Jin Seok , Han Beom Seok
Published: September 2022

Background

Now that it is possible to efficiently classify and save tissue images of laboratory animals using whole-slide imaging, many diagnostic models are being developed through transfer learning with Convolutional Neural Network (CNN). In this study, transfer learning was performed to gain toxicopathological knowledge using CNN models such as InceptionV3 and Xception. For the classification of tubular basophilia and mineralization, two representative background lesions that commonly occur in toxicological studies, accuracies of diagnosis were compared using MobileNetV2, Xception and InceptionV3. For the simultaneous detection of the two lesions, the accuracy was analysed using You Only Look Once version 4 (YOLOv4).

Results

The accuracy of the classification models was as follows: MobileNetV2 (epoch 50, accuracy: 98.57%) > Xception (epoch 70, accuracy: 97.47%) > InceptionV3 (epoch 70, accuracy: 89.62%). In the case of object detection, the accuracy of YOLOv4 was 98.62% at epoch 3000.

Conclusions

Among the classification models, MobileNetV2 had the best accuracy despite applying a lower epoch than InceptionV3 and Xception. The object detection model, YOLOv4, accurately and simultaneously diagnosed tubular basophilia and mineralization, with an accuracy of 98.62% at epoch 3000.
Assessment of the Clinical Utility of PretreatmentDPYDTesting for Patients Receiving Fluoropyrimidine Chemotherapy
Authors: Hertz Daniel L.
Published: September 2022

PURPOSE

Patients who carry pathogenic variants in DPYD have higher systemic fluoropyrimidine (FP) concentrations and greater risk of severe and fatal FP toxicity. Pretreatment DPYD testing and DPYD-guided FP dosing to reduce toxicity and health care costs is recommended by European clinical oncology guidelines and has been adopted across Europe, but has not been recommended or adopted in the United States. The cochairs of the National Comprehensive Cancer Network Guidelines for colon cancer treatment explained their concerns with recommending pretreatment DPYD testing, particularly the risk that reduced FP doses in DPYD carriers may reduce treatment efficacy.

METHODS

This special article uses previously published frameworks for assessing the clinical utility of cancer biomarker tests, including for germline indicators of toxicity risk, to assess the clinical utility of pretreatment DPYD testing, with a particular focus on the risk of reducing treatment efficacy.

RESULTS

There is no direct evidence of efficacy reduction, and the available indirect evidence demonstrates that DPYD-guided FP dosing results in similar systemic FP exposure and toxicity compared with standard dosing in noncarriers, and is well calibrated to the maximum tolerated dose, strongly suggesting there is minimal risk of efficacy reduction.

CONCLUSION

This article should serve as a call to action for clinicians and clinical guidelines committees in the United States to re-evaluate the clinical utility of pretreatment DPYD testing. If clinical utility has not been demonstrated, further dialogue is needed to clarify what additional evidence is needed and which of the available study designs, also described within this article, would be appropriate. Clinical guideline recommendations for pretreatment DPYD testing would increase clinical adoption and ensure that all patients receive maximally safe and effective FP treatment.
Electrosorption-induced deformation of a porous electrode with non-convex pore geometry in electrolyte solutions: A theoretical study
Authors: Kolesnikov Andrei L. , Mazur Daria A. , Budkov Yury A.
Published: September 2022

Porous carbon is well known as a good candidate for the development of electrochemical double-layer capacitors. Predominantly, many conventional carbons are microporous and often well described by the assumption of slit pore geometry. However, there is a class of carbons that is significantly different from the others, namely templated mesoporous carbons. In this work, we study electrosorption-induced deformation in CMK-3–like mesopores having non-convex geometry. Our mean-field approach is based on the modified Poisson-Boltzmann equation taking into account the excluded volume of the ions within the hard-sphere model. We assume that the deformation is caused by two effects: ion osmotic pressure and electrostatic interactions of the electric double layers on charged rods. We estimated the pore-load modulus of the CMK-3–like material and found an agreement with the previously obtained values by small-angle neutron scattering (SANS) data analysis. Additionally, we studied the differential capacitance in the non-convex pore geometry and found that the behavior of the differential capacitance profiles was similar to that of the profiles obtained for flat electric double layers: the crowding regime at rather high electric potentials and more pronounced profile asymmetry with increasing differences in the ionic sizes.
Controllability analysis of the small-world network of neural populations
Authors: Liu Xian , Li Ren-Jie , Zhao Yun
Published: September 2022

Controllability analysis of brain networks is the theoretical foundation for neuromodulation feasibility. This paper presents a new framework for studying controllability of certain brain networks on the basis of neural mass models, the minimum driver node, the linearization technique and a controllability index. Firstly, a WS small-world network of Jansen-Rit's neural populations is established to mathematically model complicated neural dynamics. Secondly, an analytical method of analyzing controllability is built based on the bipartite graph maximum matching algorithm, the linearization technique and the matrix condition number. The bipartite graph maximum matching algorithm is applied to determine the minimum driver node sets for the established network while the matrix condition number is applied to define the controllability index which qualitatively evaluates the degree of the controllability of the established network. Finally, the effectiveness of the proposed analytical method is demonstrated by the influence of important parameters on the controllability and the comparison with an existing method. The proposed framework provides theoretical foundation for the study of neuromodulation feasibility, and the results are expected to lead us to better modulate neurodynamics by optimizing network dynamics or designing optimal stimulation protocols.
New Horizons: Revival of Lipoprotein (a) as a Risk Factor for Cardiovascular Disease
Authors: Nestel Paul , Loh Wann Jia , Ward Natalie C , Watts Gerald F
Published: September 2022

The status of lipoprotein (a) [Lp(a)] as a cardiovascular risk factor has been resurrected by advances in genetics. Mendelian randomization studies show a causal link of Lp(a) with coronary artery disease (CAD), peripheral artery disease (PAD), and calcific aortic valve stenosis (CAVS). The genetics of Lp(a) is complex and extends beyond the kringle-IV type 2, as it is also dependent on ancestry. The plasma concentration of Lp(a) is determined by the hepatic production of apolipoprotein(a) [apo(a)] component of Lp(a), supporting the use of nucleic acids that inhibit the messenger RNA (mRNA) gene transcript for apo(a). Analytical barriers to measurement of Lp(a) are being addressed using isoform independent assays and a traceable standard. The association of Lp(a) and atherosclerotic cardiovascular disease is higher for myocardial infarction than PAD and CAVS. Increased risk of type 2 diabetes mellitus associated with low Lp(a) levels is perplexing and requires further investigation. The greatest advancement in Lp(a)-lowering therapies is based on using RNA therapeutics that are now being investigated in clinical trials. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition lowers Lp(a) modestly, but whether cardiovascular benefit is independent of low-density lipoprotein lowering remains unclear. Opportunistic and selective testing for Lp(a) is supported by moderate evidence, with the case for universal screening premature. Modification of behavioral and clinical risk factors may be targeted to mitigate Lp(a)-mediated risk of cardiovascular disease. Clinical practice guidelines have been developed to address gaps in care of high Lp(a), but full implementation awaits the findings of clinical outcome trials using RNA-directed therapies currently underway.
Pro-Con Debate: The Clinical (Ir)relevance of the Lower Limit of Cerebral Autoregulation for Anesthesiologists
Authors: Czosnyka Marek , Santarius Thomas , Donnelly Joseph , van den Dool Rokus E. C. , Sperna Weiland Nicolaas H.
Published: September 2022

In this Pro-Con commentary article, we discuss whether the lower limit of cerebral autoregulation is clinically relevant for anesthesiologists. The central question regarding this issue is whether mean arterial blood pressure below the lower limit of autoregulation is detrimental for the brain. The Pro side argues that continuous monitoring of cerebral autoregulation has revealed an association between going below the lower limit and mortality in the critically ill patient. Conversely, the Con side argues that cerebral autoregulation is only one of various defense mechanisms of the brain that protect against cerebral hypoperfusion, and that cerebral autoregulation may be more important to protect against intracranial hypertension.
A Call to Action: A Specialty-Specific Course to Support the Next Generation of Clinician Scientists in Anesthesiology
Authors: Cavallone Laura F. , Duggan Elizabeth W. , Berger Jeffrey S.
Published: September 2022

Clinical production pressure is a significant problem for faculty of anesthesiology departments who seek to remain involved in research. Lack of protected time to dedicate to research and insufficient external funding add to this long-standing issue. Recent trends in funding to the departments of anesthesiology and their academic output validate these concerns. A 2022 study examining National Institutes of Health (NIH) grant recipients associated with anesthesiology departments across 10 years (2011–2020) outlines total awarded funds at $1,676,482,440, with most of the funds awarded to only 10 departments in the United States. Of note, the total 1-year NIH funding in 2021 for academic internal medicine departments was 3 times higher than the 10-year funding of anesthesiology departments. Additionally, American Board of Anesthesiology (ABA) diplomats represent a minority (37%) of the anesthesiology researchers obtaining grant funding, with a small number of faculty members receiving a prevalence of monies. Overall, the number of publications per academic anesthesiologist across the United States remains modest as does the impact of the scholarly work. Improving environments in which academic anesthesiologists thrive may be paramount to successful academic productivity. In fact, adding to the lack of academic time is the limited bandwidth of senior academic physicians to mentor and support aspiring physician scientists. Given then the challenges for individual departments and notable successes of specialty-specific collaborative efforts (eg, Foundation for Anesthesia Education and Research [FAER]), additional pooled-resource approaches may be necessary to successfully support and develop clinician scientists. It is in this spirit that the leadership of Anesthesia & Analgesia and The Journal of Education in Perioperative Medicine, unified with the Association of University Anesthesiologists, aim to sponsor the Introduction to Clinical Research for Academic Anesthesiologists (ICRAA) Course. Directed toward early career academic anesthesiologists who wish to gain competency specifically in the fundamentals of clinical research and receive mentorship to develop an investigative project, the yearlong course will provide participants with the skills necessary to design research initiatives, ethically direct research teams, successfully communicate ideas with data analysts, and write and submit scientific articles. Additionally, the course, articulated in a series of interactive lectures, mentored activities, and workshops, will teach participants to review articles submitted for publication to medical journals and to critically appraise evidence in published research.

It is our hope that this initiative will be of interest to junior faculty of academic anesthesiology departments nationally and internationally.
Ketamine and the At-Risk Brain
Authors: Nathan Naveen
Published: September 2022

Postoperative cognitive dysfunction and delirium are undesirable consequences of surgery and anesthesia that regrettably do not have consistent predictive markers. Nor do they have reliable prophylactic or treatment methodologies. In an effort to better understand how anesthetic drugs alter the rate of postoperative delirium, Chang et al explore how patients with preoperative cognitive impairment respond to the influence of intraoperative ketamine. Patients aged 65 or older presenting for spine surgery lasting over three hours were assessed and divided into those with and without baseline cognitive impairment. Both groups either received intraoperative ketamine or did not. All patients who received intraoperative ketamine demonstrated an increase in power spectral density via electroencephalographic assessment. However, patients with preoperatively established cognitive impairment displayed a significantly diminished electroencephalographic response to ketamine. Furthermore, this subgroup also suffered an increased incidence of postoperative delirium. What is the interpretation of this finding? An accompanying editorial elegantly describes how disorders of cognition result from both predisposing and precipitating factors. In this case, patients with known cognitive impairment were more likely to endure delirium when exposed to ketamine. Is it possible that ketamine and other drugs could be used as agents to stratify cognitive risk? Should we definitively avoid such drugs as potentiators of cognitive dysfunction? A variety of contextual limitations must be entertained when interpreting the results of this study as summarized in this infographic. These are also elaborated in greater detail in both the primary article as well as its attendant editorial. The reader is encouraged to review both in their entirety for an in-depth scope of understanding.
Vanishing Sands
Authors: Pilkey Orrin H. , Longo Norma J. , Neal William J. , Rangel-Buitrago Nelson G. , Pilkey Keith C. , Hayes Hannah L.
Published: September 2022

In a time of accelerating sea level rise and increasingly intensifying storms, the world’s sandy beaches and dunes have never been more crucial to protecting coastal environments. Yet, in order to meet the demands of large-scale construction projects, sand mining is stripping beaches and dunes, destroying environments, and exploiting labor in the process. The authors of Vanishing Sands track the devastating impact of legal and illegal sand mining over the past twenty years, ranging from Africa, Asia, and the Caribbean to South America and the eastern United States. They show how sand mining has reached crisis levels: beach, dune, and river ecosystems are in danger of being lost forever, while organized crime groups use deadly force to protect their illegal mining operations. Calling for immediate and widespread resistance to sand mining, the authors demonstrate that its cessation is paramount for not only saving beaches, dunes, and associated environments but also lives and tourism economies everywhere.
Intellectual Property Protection in Neurosurgery: An Overview
Authors: Dykeman David J. , Schmitz Olivia , Dagi T. Forcht
Published: September 2022

This is the first article of a series that will cover strategies for the protection of neurosurgical inventions and devices through patent law. Advances in neurosurgical techniques have always been accompanied by advances in neurosurgical technology. Indeed, continuous technological innovation has been a characteristic of the profession. Intellectual property protection serves as an important incentive to innovation. The protection of intellectual property related to neurosurgery presents several issues that deserve careful consideration for neurosurgical innovation.
Retrieval of a Fractured Marathon Microcatheter Entrapped in Onyx Using a Novel Stentriever-Assisted Technique
Authors: Jackson Lachlan , Ma Alice , Faulder Kenneth
Published: September 2022

BACKGROUND AND IMPORTANCE:

Endovascular embolization using Onyx has been a major advancement in the treatment of cerebrovascular malformations. Microcatheter entrapment in Onyx is a procedural complication which can pose a thromboembolic risk to patients. There have been 4 retrieval techniques for intact microcatheters entrapped in Onyx previously described in the literature, which are summarized in this report. We present the first case using a novel stentriever-assisted technique to successfully and safely retrieve a fractured microcatheter entrapped in Onyx.

CLINICAL PRESENTATION:

An adult patient with a Cognard IIa + b dural arteriovenous fistula (dAVF) underwent Onyx embolization. The microcatheter became entrapped and fractured while initially attempting removal. A stentriever was used off label to capture the fractured microcatheter and then a larger caliber microcatheter was railroaded over it. Retrieval of the fractured microcatheter by the stentriever was then facilitated by counter traction on the Onyx cast using the larger microcatheter.

CONCLUSION:

This novel stentriever-assisted technique is a safe and effective rescue maneuver for retrieving a fractured microcatheter trapped in Onyx during embolization of dAVF. There is a need for further research and development of novel devices for retrieval of entrapped microcatheters.
Endoscopic Transorbital Approach to the Middle Fossa: Qualitative and Quantitative Anatomic Study
Authors: Guizzardi Giulia , Mosteiro Alejandra , Hoyos Jhon , Ferres Abel , Topczewski Thomaz , Reyes Luis , Alobid Isam , Matas Jessica , Cavallo Luigi Maria , Cappabianca Paolo , Enseñat Joaquim , Prats-Galino Alberto , Di Somma Alberto
Published: September 2022

BACKGROUND:

The endoscopic superior eyelid transorbital route to the skull base is gaining progressive popularity in the neurosurgical community.

OBJECTIVE:

To evaluate the anatomy of the middle cranial fossa from this novel ventral perspective to reach the skull base through the transorbital route and to show limits for possible safe middle fossa drilling from the transorbital route.

METHODS:

Anatomic study was performed; 5 cadaveric specimens (ie, 10 sides) and 2 dry skulls (ie, 4 sides) were dissected.

RESULTS:

To obtain a functional result, there are boundaries that correspond to neurovascular structures that traverse, enter, or leave the middle fossa that must be respected: inferiorly, the lateral pterygoid muscle; medially, the Gasserian ganglion and the lateral border of the foramen rotundum; laterally, the foramen spinosum with the middle meningeal artery; superiorly, the lesser sphenoid wing; posteriorly, the anterior border of the foramen ovale. Average bone resected was 6.49 ± 0.80 cm3 which is the 63% of total middle fossa floor. The mean axial surgical length calculated was 3.85 cm (3.18-5.19 cm) while the mean sagittal surgical length was 5.23 cm (4.87-6.55 cm). The mean horizontal angle of approach was 38.14° (32.87°-45.63°), while the mean vertical angle of approach was 18.56° (10.81°-26.76°).

CONCLUSION:

Detailed anatomy of the middle cranial fossa is presented, and herewith we demonstrated that from the endoscopic superior eyelid transorbital approach removal of middle cranial fossa floor is possible when anatomic landmarks are respected.
Quantitative Anatomic Comparison of Endoscopic Transnasal and Microsurgical Transcranial Approaches to the Anterior Cranial Fossa
Authors: Agosti Edoardo , Saraceno Giorgio , Rampinelli Vittorio , Raffetti Elena , Veiceschi Pierlorenzo , Buffoli Barbara , Rezzani Rita , Giorgianni Andrea , Hirtler Lena , Alexander Alex Yohan , Deganello Alberto , Piazza Cesare , Nicolai Piero , Castelnuovo Paolo , Locatelli Davide , Peris-Celda Maria , Fontanella Marco Maria , Doglietto Francesco
Published: September 2022

BACKGROUND:

Several microsurgical transcranial approaches (MTAs) and endoscopic transnasal approaches (EEAs) to the anterior cranial fossa (ACF) have been described.

OBJECTIVE:

To provide a preclinical, quantitative, anatomic, comparative analysis of surgical approaches to the ACF.

METHODS:

Five alcohol-fixed specimens underwent high-resolution computed tomography. The following approaches were performed on each specimen: EEAs (transcribriform, transtuberculum, and transplanum), anterior MTAs (transfrontal sinus interhemispheric, frontobasal interhemispheric, and subfrontal with unilateral and bilateral frontal craniotomy), and anterolateral MTAs (supraorbital, minipterional, pterional, and frontotemporal orbitozygomatic approach). An optic neuronavigation system and dedicated software (ApproachViewer, part of GTx-Eyes II—UHN) were used to quantify the working volume of each approach and extrapolate the exposure of different ACF regions. Mixed linear models with random intercepts were used for statistical analyses.

RESULTS:

EEAs offer a large and direct route to the midline region of ACF, whose most anterior structures (ie, crista galli, cribriform plate, and ethmoidal roof) are also well exposed by anterior MTAs, whereas deeper ones (ie, planum sphenoidale and tuberculum sellae) are also well exposed by anterolateral MTAs. The orbital roof region is exposed by both anterolateral and lateral MTAs. The posterolateral region (ie, sphenoid wing and optic canal) is well exposed by anterolateral MTAs.

CONCLUSION:

Anterior and anterolateral MTAs play a pivotal role in the exposure of most anterior and posterolateral ACF regions, respectively, whereas midline regions are well exposed by EEAs. Furthermore, certain anterolateral approaches may be most useful when involvement of the optic canal and nerves involvement are suspected.
Use of Spinal Anesthesia in Lower Thoracic Spine Surgery: A Case Series
Authors: Wang Andy Y. , Liu Penny , Balonov Konstantin , Riesenburger Ron , Kryzanski James
Published: September 2022

BACKGROUND:

Spinal anesthesia is a safe and effective alternative to general anesthesia for patients undergoing lumbar spine surgery, and numerous reports have demonstrated its advantages. To the best of our knowledge, no group has specifically reported on the use of spinal anesthesia in thoracic-level spine surgeries because there is a hypothetical risk of injuring the conus medullaris at these levels. With the advantages of spinal anesthesia and the desire for many elderly patients to avoid general anesthesia, our group has uniquely explored the use of this modality on select patients with thoracic pathology requiring surgical intervention.

OBJECTIVE:

To investigate the feasibility of performing thoracic-level spinal surgeries under spinal anesthesia and report our experience with 3 patients.

METHODS:

A retrospective chart review of medical records was undertaken, involving clinical notes, operative notes, and anesthesia records.

RESULTS:

Three spinal stenosis patients underwent thoracic laminectomy under spinal anesthesia. Two surgeries were performed at the T11-T12 level and 1 at the T12-L1 level. The average age was 82 years, average American Society of Anesthesiologists score was 3.3, and 1 identified as female. Two cases used hyperbaric 0.75% bupivacaine dissolved in dextrose, and 1 used isobaric 0.5% bupivacaine dissolved in water.

CONCLUSION:

Spinal anesthesia is feasible for thoracic-level spine procedures, even in elderly patients with comorbidities. We describe our cases and technique for safely achieving a thoracic level of analgesia, as well as discuss recommendations, adverse events, and considerations for the use of spinal anesthesia during lower thoracic-level spine operations.