bluuebunny/crossref_metadata_2025 huggingface dataset:
The possible long-term periodic variability of the extremely luminous quasar WISE J090924.01+000211.1
Authors: Horiuchi Takashi , Toba Yoshiki , Misawa Toru , Murata Katsuhiro L , Isogai Keisuke , Yatsu Yoichi , Takahashi Ichiro , Sasada Mahito , Niwano Masafumi , Higuchi Narikazu , Hayatsu Shunsuke , Seki Hibiki , Oasa Yumiko , Sato Rikuto
Published: December 2024

The extremely luminous infrared galaxy (ELIRG), WISE J090924.01$+$000211.1 (hereafter WISE J0909$+$0002, $z=1.87$) is an extraordinary object with a quasar aspect. This study performed monitoring observations of WISE J0909$+$0002 with the 105$\:$cm Murikabushi telescope, Okayama and Akeno 50$\:$cm telescopes/MITSuME ($g^{\,\prime}$, $R_{\rm c}$, and $I_{\rm c}$ bands), and the SaCRA 55$\:$cm telescope/MuSaSHI (r, i, and z bands) for three years. We obtain the following results by combining the UV/optical light curves of the CRTS, Pan-STARRS, and ZTF archive data, and our observational data: (1) the light curves of WISE J0909$+$0002 present quasi-periodic (sinusoidal) oscillations with the rest-frame period of $\sim \!660$–$689\:$d; (2) the structure functions of WISE J0909$+$0002 do not show a damped random walk (DRW) trend; (3) the mock DRW light curves present periodic-like trend on rare occasions in 10000 simulations; (4) the relativistic boost scenario is favored, since the relation between variability amplitude and power-law slope ratio is consistent with the theoretical prediction of this scenario, and a substantial parameter space exists between the inclination angles and the black hole mass; (5) the circumbinary disk model is insufficient to explain the spectral energy distribution of our target; (6) the significant radio flux density of WISE J0909+0002 is not detected from the VLA FIRST Survey, thus the radio jet precession scenario is ruled out. The Doppler boost scenario is, from our results, likely as a cause of the periodic variability; consequently the quasi-periodic oscillations in WISE J0909$+$0002 is possibly interpreted by a supermassive black hole binary. Additional observations to investigate the continuity of the periodic trend would bring new insights into mechanisms of the quasi-periodic oscillations and/or ELIRGs.
Versatility of megakaryocytes in homeostasis and disease
Authors: Wang Daosong , Xie Jiayi , Zhao Meng
Published: December 2024

Megakaryocytes (MKs) constitute a small portion of bone marrow cells and are primarily responsible for producing platelets, which are essential for hemostasis and wound healing. Recent studies have revealed that MKs and platelets perform diverse functions in various physiological and pathological contexts. This comprehensive review highlights the functional diversity of MKs beyond thrombopoiesis, including their roles in regulating hematopoietic stem cells, modulating immune responses, contributing to hematological malignancies, and influencing aging processes.
Recent TIPS increases postoperative mortality: A national cohort study
Authors: Tang Helen , Kaplan David E. , Abu-Gazala Samir , Mahmud Nadim
Published: December 2024

Background:

Patients with cirrhosis have an increased risk of postoperative mortality, which is partially attributable to portal hypertension. Preoperative TIPS placement may reduce operative risk. Studies suggesting the benefits of preoperative TIPS are limited by residual confounding and lack of longitudinal laboratory data. To address these limitations, we used granular longitudinal data from the Veterans Health Administration.

Methods:

This retrospective cohort study of Veterans Health Administration patients with cirrhosis who underwent major surgery from 2008 to 2022 identified patients who underwent TIPS placement within 6 months before surgery. Demographics, comorbidities, surgery type, and longitudinal laboratory data were incorporated into a propensity score using 5:1 caliper matching for receipt of TIPS. The propensity-matched cohort included 39 patients with preoperative TIPS and 171 without.

Results:

Baseline characteristics were similar between groups. In Cox regression, recent TIPS was associated with an increased risk of postoperative mortality (HR: 2.69, 95% CI: 1.37–5.30, p = 0.004), redemonstrated in 500 random resampling events (median HR: 1.71). TIPS and non-TIPS patients had similar albumin, bilirubin, and international normalized ratio 6 months before surgery; however, immediately before surgery, TIPS patients had lower albumin (p = 0.009), higher bilirubin (p = 0.001), and higher international normalized ratio (p = 0.001).

Conclusions:

In a propensity-matched analysis of patients with cirrhosis undergoing major surgery, recent TIPS was associated with increased postoperative mortality and worsened liver synthetic function in the immediate preoperative period. TIPS placement should be carefully considered in patients with cirrhosis who may undergo surgery.
The value of fractional flow reserve based on coronary computed tomography angiography with low-dose contrast agent in noninvasive diagnosis of coronary artery disease
Authors: Wang Zengkun , Luan Xiaomei , Zhang Qian , Chu Chu , Xu Xiaodie , Chai Huijing , Song Peiji
Published: December 2024

Aim

The study aimed, using invasive coronary angiography (ICA) as the gold standard, to investigate the noninvasive diagnostic value of flow reserve fraction derived from coronary computed tomography angiography (CCTA) with low-dose contrast agent in coronary artery disease (CAD).

Methods

A total of 163 patients with clinical symptoms related to CAD were enrolled between 1 January 2022 and 30 January 2023. The patients received CCTA with a low dose of contrast agent to rule out CAD. If significant (CCTA ≥ 50%) stenosis is suspected, ICA is performed to further evaluate the CCTA for coronary lesions. CT-FFR is calculated from the CCTA dataset using a machine learning-based algorithm. Compared with ICA as a reference standard, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of low-dose contrast agent CT-FFR in the diagnosis of myocardial ischemia were calculated. Coronary lesions with CT-FFR ≤0.80 were defined as hemodynamically significant.

Results

Obstructive CAD was excluded by low-contrast CCTA in 87 of 163 patients (53.7%). In the remaining 75 patients (42.35%), at least one coronary artery stenosis was greater than 50%. The accuracy, sensitivity, specificity, PPV, and NPV of low-dose contrast agent CT-FFR on a patient-based evaluation in diagnosing CAD were 93.06, 93.44, 90.01, 98.28, and 71.43%, respectively (Kappa = 0.759). The accuracy, sensitivity, specificity, PPV, and NPV of low-dose contrast agent CT-FFR on a vessel-based evaluation in diagnosing CAD were 86.72, 82.76, 91.58, 92.31, and 81.31%, respectively (Kappa = 0.735). Pearson correlation analysis showed that the ICA examination had a good correlation with CT-FFR value of low-dose contrast media (r = 0.731, P < 0.01). Moreover, in 81.31% of cases, additional analysis of CT-FFR correctly excluded the hemodynamic significance of stenosis.

Conclusion

CT-FFR based on low-dose contrast agent CCTA is a very promising noninvasive approach to exclude hemodynamically significant coronary artery stenosis in patients with suspected coronary heart disease while reducing renal burden and helping to reduce the rate of ICA in this high-risk population.
Effect of PCSK9 inhibitors on major cardiac adverse events and lipoprotein-a in patients with coronary heart disease: a meta-analysis
Authors: Hu Enze , Wan Macao
Published: December 2024

Background

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease due to its unique apo(a) component and its association with atherosclerosis and thrombogenesis. This meta-analysis was conducted to evaluate the effects of PCSK9 inhibitors on major adverse cardiac events (MACE) and Lp(a) levels in patients with coronary heart disease.

Methods

Randomized controlled trials (RCTs) were systematically searched in PubMed, the Cochrane Library, and other databases. Stata 15.1 software was used for data analysis, and a random- or fixed-effects model was selected based on inter-study heterogeneity. Egger’s test was applied to detect publication bias.

Results

A total of 12 RCTs were included, involving 48 116 patients with a mean age of 62 years, comprising 65% males and diverse ethnic backgrounds. The results showed that compared with the control group, PCSK9 inhibitors significantly reduced low-density lipoprotein cholesterol (WMD = −1.24 mmol/L, 95% confidence interval (CI): −1.28 to −1.20), total cholesterol, triglycerides, and Lp(a) levels while increasing high-density lipoprotein cholesterol levels. In terms of safety, there was no increased risk of adverse reactions other than injection site reactions. For MACE, PCSK9 inhibitors significantly reduced the risk of nonfatal myocardial infarction, stroke, and coronary revascularization events (RR = 0.87, 95% CI: 0.84–0.89).

Conclusion

PCSK9 inhibitors not only significantly improve blood lipid profiles and reduce Lp(a) levels but also reduce the risk of MACE in patients with coronary heart disease. Therefore, PCSK9 inhibitors offer an effective and safe treatment option for these patients.
A pilot clinical trial of exercise program for elderly patients with cirrhosis and frailty: comprehensive exercise rehabilitation intervention
Authors: Ma Yanmei , Yuan Yuan , Lu Yang , Li Siyu
Published: December 2024

Background and aim:

Comprehensive exercise rehabilitation has the potential to increase muscle mass and performance by stimulating protein synthesis and accelerating muscle catabolism. We developed the comprehensive exercise rehabilitation intervention (CERI) for elderly patients with cirrhosis, and we aimed to evaluate the safety and efficacy of CERI.

Methods:

Eligible were elderly patients with cirrhosis and frailty. Patients were randomized 1 : 1 to 12 weeks of CERI. Physical function were assessed using the gait speed, grip strength, 5 Sit-down Tests, and Balance Test, respectively.

Results:

Finally, 58 and 58 completed the study in CERI and SOC arms, respectively. The age range is 60–73. After 12 weeks, gait speed improved from 0.89 to 1.06 in CERI participants (Δgait speed 0.17) and 0.87–0.91 (Δgait speed 0.04) in SOC arm (P = 0.001 for Δgait speed difference). Grip strength improved from 15.44 to 15.94 in CERI participants (Δgrip strength 0.50) and 15.52–15.16 (Δgrip strength −0.36) in SOC arm (P = 0.044 for Δgrip strength difference). 5 Sit-down Tests Score improved from 16.17 to 15.46 in CERI participants (Δ5 Sit-down Tests 0.71) and 16.78–16.61 (Δ5 Sit-down Tests 0.17) in SOC arm (P = 0.037 for Δ5 Sit-down Tests difference). Median Balance Test score improved from 26.11 to 28.82 in CERI participants (ΔBalance Test 2.71) and 25.94–26.13 (ΔBalance Test 0.19) in SOC arm (P < 0.001 for ΔBalance Test difference); 92% of CERI participants adhered to the study for 12 weeks. No adverse events were reported by CERI participants.

Conclusion:

CERI was safely administered at pilot randomized clinical trial, while all participants showed minimal improvement in gait speed, grip strength, 5 Sit-down Tests, and Balance Test. But multicenter, larger sample clinical trials are needed to track the effects of CERI.
Characteristics and survival of patients with viral versus nonviral associated hepatocellular carcinoma: a multicenter cohort study
Authors: El-Kassas Mohamed , Barakat Eman M.F. , Shousha Hend Ibrahim , Kohla Mohamed , Said Mohamed , Moustafa Ehab Fawzy , Tawheed Ahmed , Shamkh Mostafa Abd Alfattah , Nabeel Mohamed Mahmoud , Elkhateeb Eman , Dabees Hossam , Abdelmalek Mohamed Omar , Sayed Hamdy , Abdallah Nourhan Mohamed , Elbaz Tamer , Rewisha Eman , Nassief Anwar , Riad Ahmed Radwan , Sweedy Ahmad Taha , Askar Safaa Ragab , Abdelmaksoud Ahmed Hosni , Gaber Yasmine , Eysa Basem , Shaker Mohamed , Hashem Mohamed Bassam , Kaddah Mona , Radwan Hend , Hassan Mohammed Sobhi , Lithy Rania , AbouElmaaty Mohamed ElGharib , Abo-Elazm Omnia M. , Abdelaziz Ashraf Omar ,   representing The Egyptian Network for the Study of HCC (ENSH) group
Published: December 2024

Background:

Viral hepatitis B and C are the leading causes of hepatocellular carcinoma (HCC). With obesity, metabolic-related disorders are increasingly associated with a higher incidence of nonviral HCC. This study aimed to investigate the characteristics, tumor features, treatment outcomes, and survival of patients with viral versus nonviral HCC.

Methods:

This multicenter cohort study was conducted at six tertiary care centers. Patients were recruited between February 2007 and June 2022 and follow-up was recorded until death or the study end (July 2023). The patients were divided into viral-related and nonviral HCC groups. We studied baseline patient characteristics, tumor characteristics, treatment, and overall survival (OS).

Results:

This study included 2233 patients, 1913 patients with viral and 320 patients with nonviral HCC. Patients with nonviral HCC presented with more advanced Barcelona Clinic Liver Cancer (BCLC) stages (BCLC stage C or D were present in 26.3% and 53.8% of patients with viral and nonviral HCC, respectively) that affected the median OS (19.167 vs. 13.830 months, P-value <0.001 for viral and nonviral HCC, respectively). The OS did not differ between patients with viral and nonviral HCC treated with resection, percutaneous ablation, trans-arterial chemoembolization, or Sorafinib. The independent factors affecting the survival of nonviral HCC were albumin-bilirubin score (hazard ratio = 2.323, 95% confidence interval (CI): 1.696–3.181, P-value <0.001), tumor size (hazard ratio = 1.085, 95% CI: 1.019–1.156, P-value 0.011), and alpha-fetoprotein (hazard ratio = 1.000, 95% CI: 1.000–1.000, P-value 0.042).

Conclusion:

Patients with nonviral HCC had higher BMI, worse performance status, BCLC stage, and tumor response than those with viral HCC.
The Role of Simulation in Pressure Injury Education
Authors: Sengul Tuba , Senol Celik Sevilay , Kirkland-Kyhn Holly
Published: December 2024

This systematic review aims to evaluate the effectiveness of simulation in enhancing the knowledge and skills required for preventing, managing, and treating pressure injuries (PIs) among nursing students. A systematic review of English articles published between January 1, 2014, and March 31, 2024, was conducted to determine the effectiveness of simulation in PI education. PubMed, Cochrane Library, Medline (OVID), Scopus, Web of Science, CINAHL, and Science Direct databases were searched using the keywords “simulation”, “pressure ulcer”, “pressure injury”, “nursing”, and “nursing education”. The study data were analyzed using the content analysis method. Of the 101 articles retrieved from the databases, 5 met the eligibility criteria. The study found that simulation in PI prevention and management education increased students’ knowledge and skill levels, enhanced their satisfaction and communication skills, and was more effective than traditional didactic education. This systematic review supports the use of simulation as an educational tool for nursing students in preventing, implementing protective interventions, and managing PI. Furthermore, it encourages further research to explore the role and effectiveness of different formats of simulation, particularly high-fidelity simulation, in PI management education and their impact on student achievement and clinical practice.
Tabletop Simulation as an Innovative Tool for Clinical Workflow Testing
Authors: Bissmeyer Heather , Gallegos Cara , Randazzo Shelly , Scheffler Chrissy , Sullivan Lee Lyn , Powell Lindsey
Published: December 2024

Tabletop simulation can be used to support and test system processes for clinical workflows. This paper will describe an innovative approach to testing change in clinical workflows for direct admissions to the operating room and interventional radiology departments in a 700-bed urban hospital in the Pacific Northwest and will highlight the specific benefits to nurse leaders. The simulation exercise involved key stakeholders and subject matter experts from various departments and aimed to evaluate the process workflow, provoke discussion on gaps, uncover improvement opportunities, and formulate recommendations. The simulation experience was broadly acknowledged by those involved as novel, engaging, suitable for complex process changes in health care settings and promoting valuable collaboration.
Return on Investment With Health Care Simulation
Authors: Metcalfe-Smith Russell D.
Published: December 2024

Delivering simulation across a health system can engage the entire workforce by moving beyond traditional educational delivery and focusing on broader organizational needs specific to a particular organization. The commonly known use of simulation as a form of life support education has progressed to include fully immersive simulation experiences focusing on team-based communication, leadership, fellowship, and clinical care. It continues beyond this point with the inclusion of patient safety strategies, root cause analysis investigation, leadership, and management training, and recently, it has included environments that catalyze innovation in complex healthcare systems. The focus on pure fiscal elements of simulation-based approaches does not give a health system the accurate nontangible benefits simulation can provide, and importantly, acknowledging that each location has differing needs is essential when considering what investment should be made and where. A small community hospital will have vastly different needs from specialty hospitals that deliver specialist care. It must also be understood that every simulation center, to some extent, will always be unique, as it should. The commonly quoted statement “when you have seen one simulation center, you have seen one simulation center” really does reflect the reality of this established and rapidly growing specialty. In this article, we reflect on the traditional use of simulation and discuss some wider uses that may engage a wider audience and, importantly, provide a greater return on investment for your facility, making the case for investment more reasonable and impactful to each part of a busy health system.
Increased Intracranial Pressure in Myelin-Oligodendrocyte Glycoprotein Antibody–Associated Disease
Authors: Rempe Torge , Elfasi Aisha , Alkabie Samir , Christy Alison , Rodriguez Elsa , Castrodad-Molina Rhaisa , Buchowicz Bryce , Cuascut Fernando X. , Hutton George , Kinkel Revere , Graves Jennifer
Published: December 2024

Objectives:

To assess characteristics of increased intracranial pressure (ICP) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Methods:

This is a multicenter retrospective review of 84 MOGAD cases at the University of Florida, Baylor College of Medicine, the University of California San Diego, and Providence Health and Services, Portland, Oregon, to identify cases with a documented increased opening pressure >25 cm H2O. A literature review was conducted to identify previously reported MOGAD cases with an opening pressure >25 cm H2O.

Results:

Of 28 MOGAD cases with available opening pressures, 6 (21.4%) patients (age: 5 to 36 y; 2/6 females) had documented increased ICP with an opening pressure of 26 to 46 cm H2O and optic nerve head edema on funduscopic examination. The increased ICP occurred in the setting of bilateral optic neuritis in all cases. In 5/6 patients, this was the initial presentation of the disorder. Anti-MOG titers were 1:40 (n = 1), 1:100 (n = 4), and 1:1000 (n = 1). In our literature review, we identified 13 additional MOGAD cases with ICP elevations in the setting of meningo-cortical presentations (n = 10), as well as bilateral optic neuritis (n = 3).

Conclusions:

Increased ICP may occur in MOGAD and may be more common in patients with optic neuritis or meningoencephalitis.
Spectrum of Intracranial Hemorrhages in Cerebral Venous Thrombosis
Authors: Jha Shreyashi , Kulanthaivelu Karthik , Raja Pritam , Kenchiah Raghavendra , Ramakrishnan Subasree , Kulkarni Girish Baburao , Asranna Ajay
Published: December 2024

Objective:

We aim to provide a pictorial representation of the broad spectrum of intracranial hemorrhages associated with cerebral venous thrombosis (CVT), emphasizing atypical locations and rare intracerebral hemorrhage (ICH) types. We also hypothesize the pathophysiology leading to atypical locations of the ICH in CVT and the outcomes with anticoagulation therapy.

Background:

ICH complicates about 40% of cases with CVT and is known to cause various types of ICH, including subarachnoid hemorrhage (SAH) and subdural hemorrhage (SDH). A combination of hemorrhages is also reported.

Methods:

Patients with computed tomography and magnetic resonance imaging findings consistent with CVT examined between January 2011 and June 2014 were included in this retrospective review. Demographic and clinical data and imaging findings were reviewed with particular attention to the type and location of ICH and sinus involvement. Treatment details and 3-month outcomes, assessed using the modified Rankin Scale, were analyzed.

Results:

Eleven patients (9 males), ranging in age from 22 years to 58 years, were included. The most common clinical presentations were headache (n = 8) and seizures (n = 7). Intraparenchymal hemorrhages were most common (n = 7), followed by SDH and SAH (n = 4), intraventricular hemorrhage (IVH; n = 3), and juxtacortical hemorrhage (n = 1). All patients who received anticoagulation therapy (n = 11) experienced complete resolution of their symptoms, and the median modified Rankin Scale was 0.

Conclusions:

The spectrum of intracranial hemorrhages seen in association with CVT is broad, encompassing atypical locations like basal ganglia, external capsule, and cerebellar hemispheres, and involves multiple intracranial compartments—IVH, SAH, and SDH. While SAH and SDH are seen with superior sagittal sinus thrombosis, ICH is common with lateral sinus thrombosis, and IVH with deep venous thrombosis.
Ergonomic Considerations in Robotic-assisted Microsurgery
Authors: Struebing Felix , Kneser Ulrich , Bigdeli Amir , Gazyakan Emre , Weigel Jonathan , Vollbach Felix Hubertus , Boecker Arne
Published: December 2024

Objective:

Microsurgery necessitates precision and skill, with conventional methods often leading to surgeon discomfort due to prolonged static postures. The introduction of robot-assisted microsurgery using the Symani surgical system and a three-dimensional exoscope aims to enhance surgical precision while mitigating these ergonomic issues.

Methods:

This prospective, single-center clinical study involved 50 preclinical training sessions and 87 robot-assisted microsurgical procedures at the authors' institution, covering a wide array of interventions from free flap reconstructions to nerve and lymphatic surgeries. Ergonomic assessment was conducted using the Localized Experienced Discomfort (LED) questionnaire, completed post-procedure. The study adhered to the Helsinki Declaration and received local ethics committee approval.

Results:

The neck and back region experienced the most discomfort (P < 0.0001). Notably, operations performed with an exoscope showed significantly lower discomfort scores, particularly in the occipital and neck regions, compared with those using traditional microscopes (P < 0.05). Preclinical and clinical LED scores did not show a significant difference (P < 0.05). Using a Pearson correlation analysis, a correlation between LED scores and operating time was found.

Conclusion:

The authors' study’s findings, in conjunction with existing literature, herald a promising shift towards more ergonomic microsurgical practices through the use of robotic assistance and three-dimensional mesoscopic systems. Continued research and innovation in this direction are not only anticipated but necessary for the evolution of microsurgical techniques and the well-being of surgeons in the field.
Predicting Sepsis Induced Hypotension Patient Attributes for Restrictive vs Liberal Fluid Strategy
Authors: Upadhyaya Pulakesh , Wang Jeffrey , Mathew Daniel T. , Ali Ayman , Tallowin Simon , Gann Eric , Lisboa Felipe A. , Schobel Seth A. , Elster Eric A. , Buchman Timothy G. , Dente Christopher J. , Kamaleswaran Rishikesan
Published: December 2024

Background

Patients with sepsis-induced hypotension are generally treated with a combination of intravenous fluids and vasopressors. The attributes of patients receiving a liberal compared to a restrictive fluid strategy have not been fully characterized. We use machine learning (ML) techniques to identify key predictors of restrictive versus liberal fluids strategy, and the likelihood of receiving each strategy in distinct patient phenotypes.

Methods

We performed a retrospective observational study of patients at Emory University Hospital from 2014-2021 that were hypotensive, met Sepsis-3 criteria, and received at least 1 L of intravenous crystalloid fluids. We excluded patients with non-septic etiologies of hypotension. Supervised ML techniques were used to identify key predictors for the two strategies. Additionally, subset analyses were performed on patients with pneumonia, congestive heart failure (CHF), or chronic kidney disease (CKD). Using unsupervised ML techniques, we also identified three distinct sepsis-induced hypotension phenotypes and evaluated their likelihood of receiving either strategy.

Results

We identified N = 15292 patients and randomly split them into training (N = 12233) and validation (N = 3059) datasets. XGBoost was the most accurate model (AUC:0.84) for predicting the strategies. While worse oxygenation was the strongest predictor of utilizing a restrictive fluid strategy, top predictors of a liberal fluid strategy included higher pulse and blood urea nitrogen. In subset analyses, CHF, CKD and pneumonia were predictive of restrictive fluid strategy. We identified three distinct sepsis-induced hypotension phenotypes; 1) mild organ injury; 2) severe hypoxemia; and 3) renal dysfunction.

Conclusions

We identified key predictors of restrictive versus liberal fluids strategy and distinct patient phenotypes for sepsis-induced hypotension.
Prophylactic Vancomycin Leads to Fewer Device Removals in Sacral Neuromodulation
Authors: Ohene-Agyei Jada A. , Wang Xi , Sahil Suman , Cheng An-Lin , Shepherd Jonathan P , Sutkin Gary
Published: December 2024

Importance

Sacral neuromodulation (SNM) requires removal for infectious complications in 3–11%.

Objective

The objective of this study was to examine the effect of preoperative antibiotic choice on all-cause SNM device removal rates.

Study Design

This was a retrospective cohort analysis, using the Health Facts Database, representing more than 750 hospitals. We included female patients undergoing SNM implantation from 2010 to 2018. Univariate and multivariate logistic regression identified factors associated with removal. Thirty-five comorbidities were evaluated. Those with P < 0.2 on univariate analysis were included in the multivariate analysis. We decided a priori to include prophylactic antibiotic choice in the final model.

Results

Of 1,433 patients, 170 (11.9%) had device removal. Patients were 63.0 ± 14.9 years old, predominantly Caucasian (90.0%), treated in urban hospitals (94.1%), and married (54.2%). A total of 11.8% were obese, and 18.0% smoked. Those in the removal cohort were more likely from the Northeastern United States; 52.3% received first-gen cephalosporins (CPSN), 7.4% second- or third-generation CPSNs, 9.1% vancomycin, 13.4% aminoglycosides, 4.6% clindamycin, and 13.3% fluoroquinolones. Compared to vancomycin, more removals were associated with first-generation CPSNs (odds ratio [OR] = 3.1, 95% confidence interval [1.4, 6.8]); clindamycin (OR = 3.2, [1.2, 8.4]); second/third-generation CPSNs (OR = 3.1, [1.3, 7.6]); and aminoglycosides (OR = 3.1, [1.3, 7.4]). Additionally, patients treated in the Northeast were more likely to undergo removal (OR = 1.9, [1.0, 3.7]).

Conclusions

Vancomycin as a prophylactic antibiotic was associated with fewer device removals compared to most antibiotics in this retrospective cohort analysis. While prospective trials could confirm this benefit, low removal rates may make this impractical.
Integrated vascular training may not prepare graduates to care for vascular trauma patients
Authors: Kundi Rishi , Dhillon Navpreet K. , Ley Eric J. , Scalea Thomas M.
Published: December 2024

BACKGROUND

Vascular surgery board eligibility may be secured through 5+0 integrated programs (IV) as well as 5+2 general surgery/vascular fellowship pathway (VF). We hypothesized that IV graduates accrue less experience relevant to vascular trauma than VF graduates. We assessed the first decade of IV graduate experience and compared it to contemporaneous VF graduates.

METHODS

The 2013–2022 Accreditation Council for Graduate Medical Education case log data were collected for IV and VF graduates. Vascular fellows' data were combined with synchronousgeneral surgery residency data. Open vascular cases were classed as cerebrovascular, upper extremity, thoracic, abdominopelvic, infrainguinal, and infrapopliteal. Nonvascular open cases were categorized as neck, thoracic, and abdominopelvic. Nonoperative trauma and critical care data were recorded.

RESULTS

There were 1,224 VF and 397 IV graduates. In 2012, 8.3% of graduating vascular surgeons trained in IV programs. By 2022, this proportion was 32.6%. The number of IV programs increased by 4.4 programs per year over the study period (p < 0.05), whereas VF programs remained unchanged. Integrated vascular chiefs logged significantly more lower extremity cases, and VFs logged more upper extremity cases (p < 0.05). IV graduates reported a fraction of the VF open nonvascular cases. Integrated vascular graduates logged 5% of the abdominopelvic, 18% of the thoracic, and 3% of the neck cases of VFs (p < 0.05). Vascular fellows' critical care and nonoperative trauma were each higher than those of IV fellows (p < 0.05). Integrated vascular graduates logged six vascular repairs for every vascular exposure.

CONCLUSION

The proportion of vascular surgeons trained through IV programs has nearly quadrupled. Integrated vascular graduates have a fraction of the experience in critical care, trauma, and nonvascular surgery compared with VF graduates. Relative inexperience with open surgical anatomy and with critically ill patients may limit IV graduates' ability to care for the patient with vascular trauma.

LEVEL OF EVIDENCE

Diagnostic Test/Criteria; Level IV.
Lung contusion complicated by pneumonia worsens lung injury via the inflammatory effect of alveolar small extracellular vesicles on macrophages and epithelial cells
Authors: Nakatsutsumi Keita , Choi Wooil , Johnston William , Pool Katie , Park Dong Jun , Weaver Jessica L. , Coimbra Raul , Eliceiri Brian , Costantini Todd W.
Published: December 2024

BACKGROUND

Lung contusion (LC) complicated by pneumonia is associated with a higher risk of acute lung injury (ALI) mediated by activation of immune cells and injury to the lung epithelium. Small extracellular vesicles (sEVs) are essential mediators of cellular crosstalk; however, their role in the development of postinjury ALI remains unclear. We hypothesized that LC complicated by pneumonia increases the pro-inflammatory effect of alveolar sEVs on macrophages and the cytotoxicity of alveolar sEVs to pulmonary epithelial cells, worsening the severity of ALI.

METHODS

Studies in C57BL/6 mice were designed with four groups: sham, LC, Pneumonia (Pneu), and LC + Pneu. Lung contusion was induced by a cortical controlled impactor, while pneumonia was conducted by intratracheal injection of 105 cfu Pseudomonas aeruginosa. Bronchoalveolar lavage fluid (BAL) was harvested 24 hours postinfection, and sEVs were purified by centrifugation and size exclusion chromatography. To evaluate the effect of alveolar sEV on cells, sEVs from each group were cocultured with macrophages (RAW 264.7) to assess cytokine release and lung epithelial cells (MLE 12) to assess epithelial cytotoxicity.

RESULTS

The LC + Pneu group severely injured lungs histologically and increased the susceptibility to the bacteria. The LC + Pneu group showed higher concentrations of proteins, macrophage inflammatory protein 1-alpha (MIP1α), and intercellular adhesion molecule 1 (ICAM-1) in BAL. MIP1α and ICAM-1 expression in the macrophages increased after incubation with sEVs from the LC + Pneu group. Moreover, the sEVs demonstrated higher cytotoxicity to epithelial cells and increased apoptosis in epithelial cells after incubation with sEVs from the LC + Pneu group.

CONCLUSION

Lung contusion complicated by pneumonia increased the pro-inflammatory effect of alveolar sEVs on macrophages and the cytotoxicity of alveolar sEVs to pulmonary epithelial cells, worsening the severity of ALI. These results demonstrate the potential importance of alveolar sEVs in lung inflammation following a bacterial infection after trauma.
Dynamic changes in bleeding sites: Evaluating contrast extravasation on computed tomography and angiography in pelvic fractures
Authors: Inamasu Fumi , Matsumoto Shokei , Senoo Satomi , Shimizu Masayuki
Published: December 2024

BACKGROUND

Contrast extravasation (“blush”) on contrast-enhanced computed tomography (CECT) indicates active bleeding, but diagnostic angiography (AG) following CECT sometimes differs from the CECT findings in patients with pelvic fractures. This study aimed to evaluate the concordance rate between blush on CECT and AG based on pelvic anatomical location.

METHODS

This retrospective single-center study included patients (18 years or older) with pelvic fractures between 2015 and 2023 who had AG after CECT. Angiography was performed in patients with blush or hematoma on CECT, or unstable hemodynamics due to pelvic fracture. Pelvic bleeding regions were categorized separately into left and right as anterior internal iliac artery and posterior internal iliac artery based on pelvic arterial anatomy. The concordance rate between blush on CECT and AG was assessed using the k statistic.

RESULTS

A total of 87 patients with pelvic fractures were included. Among these, 75 (86%) had blush on CECT, and 12 (14%) had no blush on CECT. The concordance rate was 83% (95% confidence interval, 0.03–0.57; k = 0.30) when assessed on an individual patient basis and 53% (95% confidence interval, 0.24–0.44; k = 0.34) when evaluated by anatomical regions on a unilateral half of the pelvis. The concordance rate for the anatomical hemipelvis evaluation was significantly lower compared with the individual evaluation (p < 0.001). Thirty-three percent of patients with unilateral blush on CECT showed new contralateral blushes during AG.

CONCLUSION

The location of active bleeding often differs between CECT and AG, indicating that bleeding may change intermittently and at various sites over time. This suggests the importance of evaluating both sides of the pelvic arteries during AG rather than solely relying on CECT findings.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Physical oceanographic factors controlling the ocean circulation-induced magnetic field
Authors: Trossman David S. , Tyler Robert H. , Pillar Helen R.
Published: December 2024

Oceanic tidal constituents and depth-integrated electrical conductivity (ocean conductivity content, or OCC) extracted from electromagnetic (EM) field data are known to have a strong potential for monitoring ocean heat content, which reflects the Earth’s energy imbalance. In comparison to ocean tide models, realistic ocean general circulation models have a greater need to be baroclinic; therefore, both OCC and depth-integrated conductivity-weighted velocity (

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) data are required to calculate the ocean circulation-induced magnetic field (OCIMF). Owing to a lack of

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observations, we calculate the OCIMF using an ocean state estimate. There are significant trends in the OCIMF primarily owing to responses in the velocities to external forcings and the warming influence on OCC between 1993 and 2017, particularly in the Southern Ocean. Despite being depth-integrated quantities, OCC and

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(which primarily determine the OCIMF in an idealized EM model) can provide a strong constraint on the baroclinic velocities and ocean mixing parameters when assimilated into an ocean state estimation framework. A hypothetical fleet of full-depth EM-capable floats would therefore help improve the accuracy of the OCIMF computed with an ocean state estimate, which could potentially provide valuable guidance on how to extract the OCIMF from satellite magnetometry observations.

This article is part of the theme issue ‘Magnetometric remote sensing of Earth and planetary oceans’.
Satellite monitoring of long period ocean-induced magnetic field variations
Authors: Finlay Christopher C. , Velímský Jakub , Kloss Clemens , Blangsbøll Rasmus M.
Published: December 2024

Satellite magnetic field observations have the potential to provide valuable information on dynamics, heat content and salinity throughout the ocean. Here, we present the expected spatio-temporal characteristics of the ocean-induced magnetic field (OIMF) at satellite altitude on periods of months to decades. We compare these to the characteristics of other sources of Earth’s magnetic field, and discuss whether it is feasible for the OIMF to be retrieved and routinely monitored from space. We focus on large length scales (spherical harmonic degrees up to 30) and periods from one month up to 5 years. To characterize the expected ocean signal, we make use of advanced numerical simulations taking high-resolution oceanographic inputs and solve the magnetic induction equation in three dimensions, including galvanic coupling and self-induction effects. We find the time-varying ocean-induced signal dominates over the primary source of the internal field, the core dynamo, at high spherical harmonic degree with the cross-over taking place at degrees 13–19 depending on the considered period. The ionospheric and magnetospheric fields (including their Earth-induced counterparts) have most power on periods shorter than one month and are expected to be mostly zonal in magnetic coordinates at satellite altitude. Based on these findings, we discuss future prospects for isolating and monitoring long period OIMF variations using data collected by present and upcoming magnetic survey satellites.

This article is part of the theme issue ‘Magnetometric remote sensing of Earth and planetary oceans’.
Harnessing electromagnetic data for tsunami source estimation: a comprehensive review
Authors: Baba Toshitaka , Lin Zhiheng , Minami Takuto , Toh Hiroaki
Published: December 2024

Ocean-bottom pressure gauges are widely used for tsunami observations due to their established accuracy and stability. Recent advancements reveal that the magnetic field fluctuates when a large tsunami passes over the ocean, suggesting potential alternatives to pressure gauges in the form of ocean-bottom electromagnetometers (OBEMs). This article offers a comprehensive synthesis of recent findings concerning tsunami magnetic fields and their utility in tsunami source estimation. In addition, we scrutinize the effectiveness of tsunami observations employing OBEMs. Despite the promise of electromagnetometers, it is worth noting that the background noise inherent in electromagnetic observations tends to be approximately 10 times greater than that of pressure observations within the critical tsunami frequency bands. The Earth’s magnetic field sporadically disrupts tsunami magnetic fields, presenting a potential limitation to the utility of electromagnetometers in tsunami detection when compared with pressure gauges. Nevertheless, our investigation underscores the potential of electromagnetic observations in detecting tsunamis propagating over the ocean at magnitudes of a few centimetres. An invaluable advantage of electromagnetometers over pressure monitoring lies in their capability to observe tsunami velocity fields, suggesting a promising avenue for further research and development in tsunami observation technology.

This article is part of the theme issue ‘Magnetometric remote sensing of Earth and planetary oceans’.
Convergent cellular adaptation to a quiescence-like state in response to freeze-thaw stress
Authors: Tvishamayi Charuhansini , Ali Farhan , Chaturvedi Nandita , Madhu-Kumar Nithila , Rashida Zeenat , Ray Ankita , Thutupalli Shashi
Published: December 2024

Rapid freeze-thaw is an extreme mechano-chemical perturbation that results in very low survival of many organisms (as low as a fraction of a percent). Here, using experimental evolution, we show that the budding yeast,Saccharomyces cerevisiaecan adapt to freeze-thaw stress in a stereotyped manner, with survival increasing nearly two orders of magnitude from ≈2% to ≈70% in about 25 cycles of stress exposure. Adapted cells exhibit reduced membrane damage, smaller sizes, higher mass densities, and a lower prevalence of budding. Rheological measurements show that the adapted cells are stiffer and exhibit lower particle mobilities within the cytoplasm. Whole genome sequencing indicates that increased survival is not accompanied by specific (unique) genetic changes, but rather is associated with multiple, distinct genotypes. Concomitant with mechanical changes in the adapted cells, the basal intracellular level of trehalose, a sugar speculated to play a physical role in maintaining membrane and cytoplasmic integrity, exhibits a three-fold increase. Together, these cellular attributes strongly correlate with the entry of cells into a quiescence-like state. A quantitative model that incorporates selection based on cellular quiescence recapitulates the adaptation dynamics,i.e. increase in survival and trehalose levels, seen in experiments. Finally, we find that the evolved mechano-chemical phenotypes are similar even when we use qualitatively different freeze-thaw selection protocols for the evolution, hinting at a convergent adaptation.
Correcting errors in PCR-derived libraries for rare allele detection by reconstructing parental and daughter strand information
Authors: Lim Hyeonseob , Jun Soyeong , Kim Taehoon , Lee Ji Hyun , Bang Duhee
Published: December 2024

Molecular barcoding methods enable high-sensitivity detection of circulating tumor DNA that is rarely present in liquid biopsy samples. Many methods involve ligation of molecular barcodes to DNA prior to hybridization capture, enabling recovery of starting molecules. Development of polymerase chain reaction (PCR)-based methods could facilitate more cost- and labor- effective detection; however, tracking molecular identity can be difficult, as new barcodes overwrite old barcodes in each cycle. We developed a sensitive genotyping method based on a peer-to-peer network-derived identifier for error reduction in amplicon sequencing (SPIDER-seq) and enable molecular identity tracking with PCR-derived libraries using overwritten barcodes. SPIDER-seq detected mutations at frequences as low as 0.125% after only two consecutive general PCR cycles and systematically analyzed the error pattern in the peer-to-peer network. Our method could facilitate the rapid detection of mutations associated with various cancers.
Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs
Authors: Ghosh Soumita , Lahens Nick , Barekat Kayla , Tang Soon-Yew , Theken Katherine N. , Ricciotti Emanuela , Sengupta Arjun , Joshi Robin , Bushman Frederic D. , Weljie Aalim , Grosser Tilo , FitzGerald Garret A
Published: December 2024

Non-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by side effects in the gastrointestinal and cardiovascular systems. We compared the effects of naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase -2 (Cox-2) inhibitor, in humans. Our findings showed a decrease in tryptophan and kynurenine levels in plasma of volunteers treated with naproxen. We further validated this result in mice. Additionally, we find that the depression of tryptophan was independent of both Cox-1 and Cox-2 inhibition, but rather was due to the displacement of bound tryptophan by naproxen. Supplementation of tryptophan in naproxen-treated mice rescued fecal blood loss and inflammatory gene expression driven by IL-1β in the heart.
Combined analysis of chromatin accessibility, promoter interactions and whole genome sequencing solved the missing heritability in gastric cancer
Authors: São José C. , Ferreira M. , Cordova L. , Pedro A. , Senz J. , Garcia-Pelaez J. , Lobo S. , Gullo I. , André A. , Kaurah P. , Puntieri F. , Glaser J. , Huntsman D. , Mundlos S. , Schrader K. , Oliveira C.
Published: December 2024

Missing heritability in hereditary diffuse gastric cancer (HDGC) ranges from 60 to 90%. These HDGC-like families, despite complying with HDGC clinical criteria, lackCDH1andCTNNA1actionable germline variants, and are not offered HDGC-targeted life-saving disease prevention measures. Herein, we explored novel HDGC predisposition mechanisms affecting theCDH1-regulatory network. We called single-nucleotide (SNV) and copy-number variants (CNV) from 19 HDGC-like probands from whole-genome sequencing data and performed gene-ontology analysis. Chromatin enhancer marks andCDH1promoter interactions were evaluated in normal stomach by ChIP-seq, ATAC-seq and 4C-seq, variant causality was assessed by RT-PCR, immunohistochemistry and microsatellite instability (MSI) analysis in tumours. Functional analysis was performed using CRISPR-Cas9, RT-PCR and flow cytometry in cell lines, and enhancer assays using mouse embryos. Within theCDH1topologically associating domain (TAD), we found two deletions in Family F4 and F9. F4 carried a heterozygousCDH320kb-CNV triggeringCDH1mRNA/protein loss in homozygosity by CRISPR-Cas9 editing, similarly to aCDH1coding deletion. This 20kb sequence encloses two hypomorphic tissue-specific regulatory elements (REs), each contributing 50% toCDH1expression regulation. F9 carried a heterozygous 39bp-intergenic CNV downstream ofCDH1, triggeringCDH1mRNA/protein loss by CRISPR-Cas9. F15, presenting gastric but not colorectal cancer, carried anMLH1heterozygous 2.7Kb germline CNV overlapping a stomach-specific RE found by ChIP-seq. The gastric tumour of mixed histology displayed Microsatellite instability (MSI), reducedMLH1mRNA and protein, and reducedCDH1and E-cadherin protein. CRISPR-Cas9 clones mimicking theMLH1heterozygous CNV, triggered loss ofMLH1andCDH1/E-cadherin mRNA and protein, similar to a coding deletion. Beyond theCDH1TAD and tumour risk syndrome genes, multiple deletions of stomach accessible chromatin sequences were found in particularly young-affected individuals from additional 6 families. This oligogenic pattern impaired specifically mucin genes and multiple immune-related pathways. Herein, we pinpointed novel mechanisms behind HDGC predisposition. One involves deletions ofCDH1-REs in the TAD or stomach-specificCDH1-REs in theMLH1locus. The second involves multiple deletions of stomach REs affecting mucin and immune-related genes, favouring a gastric immune-deficient phenotype. Altogether, by combining stomach-specific chromatin accessibility and promoter interactions with whole genome sequencing, we solved the missing heritability in 47% of HDGC-like families within our cohort.