bluuebunny/crossref_metadata_2025 huggingface dataset:
Mouse model and human patient data reveal critical roles for Pten and p53 in suppressing POLE mutant tumor development
Authors: Park Vivian S , Sun Meijuan J S , Frey Wesley D , Williams Leonard G , Hodel Karl P , Strauss Juliet D , Wellens Sydney J , Jackson James G , Pursell Zachary F
Published: March 2022

Mutations in the exonuclease domain of POLE are associated with tumors harboring very high mutation burdens. The mechanisms linking this significant mutation accumulation and tumor development remain poorly understood. Pole+/P286R;Trp53+/– mice showed accelerated cancer mortality compared to Pole+/P286R;Trp53+/+ mice. Cells from Pole+/P286R mice showed increased p53 activation, and subsequent loss of p53 permitted rapid growth, implicating canonical p53 loss of heterozygosity in POLE mutant tumor growth. However, p53 status had no effect on tumor mutation burden or single base substitution signatures in POLE mutant tumors from mice or humans. Pten has important roles in maintaining genome stability. We find that PTEN mutations are highly enriched in human POLE mutant tumors, including many in POLE signature contexts. One such signature mutation, PTEN-F341V, was previously shown in a mouse model to specifically decrease nuclear Pten and lead to increased DNA damage. We found tumors in Pole+/P286R mice that spontaneously acquired PtenF341V mutations and were associated with significantly reduced nuclear Pten and elevated DNA damage. Re-analysis of human TCGA (The Cancer Genome Atlas) data showed that all PTEN-F341V mutations occurred in tumors with mutations in POLE. Taken together with recent published work, our results support the idea that development of POLE mutant tumors may involve disabling surveillance of nuclear DNA damage in addition to POLE-mediated hypermutagenesis.
Transcriptional regulators of human oncoviruses: structural and functional implications for anticancer therapy
Authors: Nečasová Ivona , Stojaspal Martin , Motyčáková Edita , Brom Tomáš , Janovič Tomáš , Hofr Ctirad
Published: March 2022

Transcription is often the first biosynthetic event of viral infection. Viruses produce preferentially viral transcriptional regulators (vTRs) essential for expressing viral genes and regulating essential host cell proteins to enable viral genome replication. As vTRs are unique viral proteins that promote the transcription of viral nucleic acid, vTRs interact with host proteins to suppress detection and immune reactions to viral infection. Thus, vTRs are promising therapeutic targets that are sequentially and structurally distinct from host cell proteins. Here, we review vTRs of three human oncoviruses: HBx of hepatitis B virus, HBZ of human T-lymphotropic virus type 1, and Rta of Epstein–Barr virus. We present three cunningly exciting and dangerous transcription strategies that make viral infections so efficient. We use available structural and functional knowledge to critically examine the potential of vTRs as new antiviral-anticancer therapy targets. For each oncovirus, we describe (i) the strategy of viral genome transcription; (ii) vTRs’ structure and binding partners essential for transcription regulation; and (iii) advantages and challenges of vTR targeting in antiviral therapies. We discuss the implications of vTR regulation for oncogenesis and perspectives on developing novel antiviral and anticancer strategies.
Synergistic action of WDR5 and HDM2 inhibitors in SMARCB1-deficient cancer cells
Authors: Florian Andrea C , Woodley Chase M , Wang Jing , Grieb Brian C , Slota Macey J , Guerrazzi Kiana , Hsu Chih-Yuan , Matlock Brittany K , Flaherty David K , Lorey Shelly L , Fesik Stephen W , Howard Gregory C , Liu Qi , Weissmiller April M , Tansey William P
Published: March 2022

Rhabdoid tumors (RT) are rare and deadly pediatric cancers driven by loss of SMARCB1, which encodes the SNF5 component of the SWI/SNF chromatin remodeler. Loss of SMARCB1 is associated with a complex set of phenotypic changes including vulnerability to inhibitors of protein synthesis and of the p53 ubiquitin-ligase HDM2. Recently, we discovered small molecule inhibitors of the ‘WIN’ site of WDR5, which in MLL-rearranged leukemia cells decrease the expression of a set of genes linked to protein synthesis, inducing a translational choke and causing p53-dependent inhibition of proliferation. Here, we characterize how WIN site inhibitors act in RT cells. As in leukemia cells, WIN site inhibition in RT cells causes the comprehensive displacement of WDR5 from chromatin, resulting in a decrease in protein synthesis gene expression. Unlike leukemia cells, however, the growth response of RT cells to WIN site blockade is independent of p53. Exploiting this observation, we demonstrate that WIN site inhibitor synergizes with an HDM2 antagonist to induce p53 and block RT cell proliferation in vitro. These data reveal a p53-independent action of WIN site inhibitors and forecast that future strategies to treat RT could be based on dual WDR5/HDM2 inhibition.
Dialysis-network variability in home dialysis use not explained by patient characteristics: a national registry-based cohort study in France
Authors: Couchoud Cécile , Béchade Clémence , Kolko Anne , Baudoin Agnès Caillette , Bayer Florian , Rabilloud Muriel , Ecochard René , Lobbedez Thierry
Published: March 2022

Background

Although associated with better quality of life and potential economic advantages, home dialysis use varies greatly internationally and appears to be underused in many countries. This study aimed to estimate the dialysis-network variability in home dialysis use and identify factors associated with (i) the uptake in home dialysis, (ii) the proportion of time spent on home dialysis and (iii) home dialysis survival (patient and technique).

Methods

All adults ≥18 years old who had dialysis treatment during 2017–2019 in mainland France were included. Mixed-effects regression models were built to explore factors including patient or residence characteristics and dialysis network associated with variation in home dialysis use.

Results

During 2017–2019, 7728/78 757 (9.8%) patients underwent dialysis at least once at home for a total of 120 594/1 508 000 (8%) months. The heterogeneity at the dialysis-network level and to a lesser extent the regional level regarding home dialysis uptake or total time spent was marginally explained by patient characteristics or residence and dialysis-network factors. Between-network heterogeneity was less for patient and technique survival. These results were similar when the analysis was restricted to home peritoneal dialysis or home hemodialysis.

Conclusions

Variability between networks in the use of home dialysis was not fully explained by non-modifiable patient and residence characteristics. Our results suggest that to increase home dialysis use in France, one should focus on home dialysis uptake rather than survival. Financial incentives and a quality improvement programme should be implemented at the dialysis-network level to increase home dialysis use.
Coronavirus Disease 2019-Associated Pulmonary Aspergillosis: Reframing the Debate
Authors: Clancy Cornelius J , Nguyen M Hong
Published: March 2022

Background

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has been reported in ~5%–10% of critically ill COVID-19 patients. However, incidence varies widely (0%–33%) across hospitals, most cases are unproven, and CAPA definitions and clinical relevance are debated.

Methods

We reframed the debate by asking, what is the likelihood that patients with CAPA have invasive aspergillosis? We use diagnostic test performance in other clinical settings to estimate positive predictive values (PPVs) and negative predictive values (NPVs) of CAPA criteria for invasive aspergillosis in populations with varying CAPA incidence.

Results

In a population with CAPA incidence of 10%, anticipated PPV/NPV of diagnostic criteria are ~30%–60%/≥97%; ~3%–5% of tested cohort would be anticipated to have true invasive aspergillosis. If CAPA incidence is 2%–3%, anticipated PPV and NPV are ~8%–30%/>99%.

Conclusions

Depending on local epidemiology and clinical details of a given case, PPVs and NPVs may be useful in guiding antifungal therapy. We incorporate this model into a stepwise strategy for diagnosing and managing CAPA.
H3K36 demethylase JMJ710 negatively regulates drought tolerance by suppressing MYB48-1 expression in rice
Authors: Zhao Weijie , Wang Xiaoyan , Zhang Qian , Zheng Qian , Yao Haitao , Gu Xiangyang , Liu Dongliang , Tian Xuemin , Wang Xiaoji , Li Yongqing , Zhu Zhengge
Published: March 2022

The homeostasis of histone methylation is maintained by histone methyltransferases and demethylases, which are important for the regulation of gene expression. Here, we report a histone demethylase from rice (Oryza sativa), Jumonji C domain-containing protein (JMJ710), which belongs to the JMJD6 group and plays an important role in the response to drought stress. Overexpression of JMJ710 causes a drought-sensitive phenotype, while RNAi and clustered regularly interspaced short palindromic repeats (CRISPR)-knockout mutant lines show drought tolerance. In vitro and in vivo assays showed that JMJ710 is a histone demethylase. It targets to MYB TRANSCRIPTION FACTOR 48 (MYB48-1) chromatin, demethylates H3K36me2, and negatively regulates the expression of MYB48-1, a positive regulator of drought tolerance. Under drought stress, JMJ710 is downregulated and the expression of MYB48-1 increases, and the subsequent activation of its downstream drought-responsive genes leads to drought tolerance. This research reports a negative regulator of drought stress-responsive genes, JMJ710, that ensures that the drought tolerance mechanism is not mis-activated under normal conditions but allows quick activation upon drought stress.
Ready for a Woman President?
Authors: DeMora Stephanie L , Lindke Christian A , Merolla Jennifer L , Stephenson Laura B
Published: March 2022

Even though a record number of women ran for the Democratic nomination in 2020, Clinton’s loss in 2016 led pundits, party elites, and voters to worry about whether the country would be willing to support a woman for president, and polling organizations regularly asked questions that tapped into such concerns. While the vast majority expressed willingness to vote for a woman for president in polls, people were more skeptical about how their neighbors felt. Our research question cuts to the heart of this issue: How does polling information about comfort with the idea of a woman president affect perceptions of the electability of actual women running for their party’s nomination, and in turn voting decisions? We expect that exposure to signals of low comfort with a woman president will reduce perceptions of electability, and in turn dampen support for women at the nomination stage, but there are competing hypotheses for how signals of high comfort will be received. We further expect that Democratic women will be most affected by such information. We test these expectations with an experiment fielded on the 2019 Cooperative Congressional Election Study (CCES). Our findings have important implications for media coverage of polls related to women running for executive office.
Climate Change Risk and the Cost of Mortgage Credit
Authors: Nguyen Duc Duy , Ongena Steven , Qi Shusen , Sila Vathunyoo
Published: March 2022

We show that lenders charge higher interest rates for mortgages on properties exposed to a greater risk of sea level rise (SLR). This SLR premium is not evident in short-term loans and is not related to borrowers’ short-term realized default or creditworthiness. Further, the SLR premium is smaller when the consequences of climate change are less salient and in areas with more climate change deniers. Overall, our results suggest that mortgage lenders view the risk of SLR as a long-term risk and that attention and beliefs are potential barriers through which SLR risk is priced in residential mortgage markets.
Preferred policy responses to technological change: Survey evidence from OECD countries
Authors: Busemeyer Marius R , Gandenberger Mia , Knotz Carlo , Tober Tobias
Published: March 2022

How do the labor market risks associated with technological change affect policy preferences? We argue that higher perceptions of technology-related risks should increase support for compensation and decrease support for social investment. We expect the opposite effect for individuals who use technology constantly at work, have a university degree and earn higher incomes. However, as the perception of technology-related employment risks in the latter group of individuals increases, so does their preference for compensatory and protective policy solutions to technological change. Our expectations are confirmed by novel data from a survey of 24 diverse Organisation for Economic Co-operation and Development (OECD) countries that includes specifically designed questions on technology-related risks and policy preferences. The results suggest that technology-related risks not only correlate with certain demographic and occupational characteristics, but also cross-cut them. Thus, technology-related risks might not only become a source of new cleavages between the losers and winners of technological change, but also the basis for new cross-class coalitions.
Novel Pedicle Navigator Based on Micro Inertial Navigation System (MINS) and Bioelectric Impedance Analysis (BIA) to Facilitate Pedicle Screw Placement in Spine Surgery: Study in a Porcine Model
Authors: Lin Wentao , Xie Faqin , Zhao Shuofeng , Lin Songhui , He Chaoqin , Wang Zhiyun
Published: March 2022

Study Design.

A porcine model.

Objective.

The study aims to design a novel pedicle navigator based on micro-inertial navigation system (MINS) and bioelectrical impedance analysis (BIA) to assist place pedicle screw placement and validate the utility of the system in enhancing pedicle screw placement.

Summary of Background Data.

The incidence of pedicle screw malpositioning in complicated spinal surgery is still high.

Procedures such as computed tomography image-guided navigation, and robot-assisted surgery have been used to improve the precision of pedicle screw placement, but it remains an unmet clinical need.

Methods.

The miniaturized integrated framework containing MINS was mounted inside the hollow handle of the pedicle finder. The inner core was complemented by a high-intensity electrode for measuring bioelectric impedance. Twelve healthy male Wuzhishan minipigs of similar age and weight were used in this experiment and randomized to the MINS-BIA or freehand (FH) group. Pedicle screw placement was determined according to the modified Gertzbein–Robbins grading system on computed tomography images. An impedance detected by probe equal to the baseline value for soft tissue was defined as cortical bone perforation.

Results.

A total of 216 screws were placed in 12 minipigs. There were 15 pedicle breaches in the navigator group and 31 in the FH group; the detection rates of these breaches were 14 of 15 (93.3%) and 25 of 31 (80.6%), respectively, with a statistically significant difference between groups. The mean offsets between the planned and postoperatively measured tilt angles of the screw trajectory were 4.5° ± 5.5° in the axial plane and 4.8° ± 3.3° in the sagittal plane with the navigator system and 7.0° ± 5.1° and 7.7° ± 4.7°, respectively, with the FH technique; the differences were statistically significant.

Conclusion.

A novel and portable navigator based on MINS and BIA could be beneficial for improving or maintaining accuracy while reducing overall radiation exposure.
Management of prostatosymphyseal fistula following photoselective vaporization of the prostate: Case series and systematic review of the literature
Authors: Lundy Scott D. , Hauser Nicholas , Wood Hadley , Fergany Amr , Angermeier Kenneth
Published: March 2022

Background:

This study is aimed to describe our institutional experience and review the literature to date on prostatosymphyseal fistula (PSF), or puboprostatic fistula, following bladder outlet procedures such as transurethral resection of the prostate (TURP) or laser photoselective vaporization of the prostate (PVP).

Materials and methods:

We retrospectively queried our institutional experience for management of PSF following PVP performed for symptomatic benign prostatic hyperplasia. We also performed a systematic literature review for PSF following PVP or TURP. Finally, we describe our surgical approach to the management of this challenging condition.

Results:

We identified 7 cases of PSF following PVP from our institution, as well as an additional 7 cases following PVP and 9 cases following TURP from literature review. The diagnosis of PSF was made between 0.5 and 24 months following PVP, and the most specific symptoms were pubic pain and difficulty ambulating. Most patients requiring several evaluations before the diagnosis was made using appropriate imaging studies. Seventy percent of patients required surgical intervention including fistula repair or prostatectomy. Our surgical approach has evolved, and we now routinely perform robotic fistula repair with Y-V plasty and interposition flap with excellent results.

Conclusions:

Puboprostatic fistula is a rare and poorly described complication of PVP or TURP. To the best of our knowledge, this case series of PSF following PVP represents the largest series to date and doubles the number of reported cases in the literature. Robotic fistula repair with interposition of either peritoneal or perivesical fat flaps appears to be a viable management strategy.
Influences of achieved SBP on age and sex-related left ventricular structural alteration in community hypertensive populations
Authors: Cai Anping , Liu Lin , Zhou Dan , Tang Songtao , Zhou Yingling , Feng Yingqing
Published: March 2022

Objective:

To evaluate age and sex-related left ventricular (LV) structural alteration in community hypertensive populations, and to explore whether achieved systolic blood pressure (SBP) (< 120, < 130 and <140 mmHg) would modify the association between age and sex with LV structural alteration.

Method:

A total of 1419 community hypertensive people (mean age 61 years, women 50.5%) without cardiovascular disease and left ventricular hypertrophy (LVH) at baseline were included. LV structural measures were assessed using transthoracic echocardiography at baseline and at follow-up. Age and sex-related LV structural alteration was evaluated using linear and Cox regression analysis as appropriate.

Results:

Per 10 years increase in age was associated with positive alteration of LV mass (LVM) index (coefficient-β: 2.63) and LV mass-to-volume (LVMV) ratio (coefficient-β: 0.04). Female sex was associated with positive alteration of LVM index (coefficient-β: 4.87) and LVMV ratio (coefficient-β: 0.05). After a median follow-up of 4years, compared to men, women had a higher rate of LVH (36.8% vs. 11.5%, P 
< 0.001). The association between age and incident LVH was nonsignificant when achieved SBP <120 mmHg. The association between female sex and LVM index alteration was nonsignificant when achieved SBP <120mmHg and <130mmHg.

Conclusion:

Age and female sex were associated with a phenotype of LV remodeling which was featured by increased LVM index and concentric remodeling. Women had a higher risk of developing LVH. A lower achieved SBP conferred greater effects on mitigating age and sex-related LV structural alteration.

Video abstract:

http://links.lww.com/HJH/B907
.
CENTRAL RETINAL ARTERY OCCLUSION AS PRESENTATION OF BARTONELLA ENDOCARDITIS
Authors: Chebolu Apoorv P. , Wallsh Josh O. , Falk Naomi , Bhatnagar Pawan
Published: March 2022

Background/Purpose:

To describe a rare ocular presentation of a systemic illness and the important lifesaving diagnosis made by a complete eye examination.

Methods:

The patient was evaluated with a comprehensive ophthalmic examination and followed closely in the outpatient setting with optical coherence tomography, fluorescein angiography, and color fundus photos.

Results:

A 66-year-old man presented with acute vision loss of the left eye. A complete eye examination revealed that he had a central retinal artery occlusion. Systemic workup revealed that he had a mitral valve vegetation and blood cultures grew Bartonella henselae. His kidney biopsy showed membranoproliferative glomerulonephritis, which is often seen with septic emboli. Furthermore, the patient lacked any ocular inflammatory signs. This constellation of findings was diagnostic for a thromboembolic etiology causing his central retinal artery occlusion. At follow-up, the optical coherence tomography demonstrated inner retinal hyperreflectivity and the fluorescein angiogram showed segmented flow and no neovascularization. On follow-up, the patient had a stable examination with light perception vision and completed antibiotic therapy for bartonella endocarditis.

Conclusion:

The detection of a fatal systemic illness was made promptly with a thorough ocular examination. We highlight the importance of a multidisciplinary approach in making a lifesaving diagnosis.
Occlusive retinal vasculitis: novel insights into causes, pathogenesis and treatment
Authors: Arepalli Sruthi R. , Thomas Akshay S.
Published: March 2022

Purpose of review

Occlusive retinal vasculitis (ORV) has a large differential diagnosis and varied therapeutic approaches. This review highlights existing and novel causes and treatment options for ORV.

Recent findings

Mutations in CAPN5, TREX1, and TNFAIP3 have been associated with dominantly inherited forms of ORV. Various intraocular therapeutics have been shown to occasionally cause ORV; the most recent medications associated with ORV are vancomycin and brolucizumab. In cases of ORV linked to Behçet's disease, clinical trials support the use of tumor necrosis factor alpha inhibitors.

Identification of the underlying etiology of ORV is critical to help guide treatment. Treatment in ORV involves both treatment any underlying infection or autoimmune condition, cessation of the any offending causative agent and local treatment of neovascular complications.
Ophthalmologists' attitudes toward immediate sequential bilateral cataract surgery: Dutch national survey
Authors: Spekreijse Lindsay S. , Veldhuizen Claudette A. , Henry Ype P. , van den Biggelaar Frank J.H.M. , Dirksen Carmen D. , Nuijts Rudy M.M.A.
Published: March 2022

Purpose:

To evaluate current practice patterns of immediate sequential bilateral cataract surgery (ISBCS) in the Netherlands and assess ophthalmologists' attitudes toward performing ISBCS in future cataract care.

Setting:

Dutch ophthalmic society members.

Design:

Cross-sectional study (national survey).

Methods:

An electronic survey on ISBCS was sent as part of an annual survey on cataract practice patterns to members of the Dutch ophthalmic society. Questions regarding current ISBCS practice patterns, willingness to perform ISBCS routinely in future care, reasons for performing ISBCS, and reasons for not performing ISBCS were included. Data were analyzed using descriptive statistics.

Results:

237 (45.6%) of 520 survey recipients responded to the overall survey. Data on the ISBCS questions were available from 227 respondents. 62 ophthalmologists (27.3%) currently performed ISBCS, predominantly in low patient volumes (90.3% on 1 to 5 patients per month). However, 108 (47.6%) of 227 ophthalmologists considered performing ISBCS routinely in future practice. Procedures for which ISBCS was mainly considered included age-related cataract surgery using topical and general anesthesia. Availability of separate products and instruments for both eyes and patient advantages were considered of high importance when performing ISBCS. Main reasons for not performing ISBCS included the risk for endophthalmitis and potential medicolegal aspects.

Conclusions:

Although ISBCS is currently not a routine procedure in the Netherlands, it is considered by almost 50% of surgeons. To improve implementation on a national level, potential barriers identified in this survey (fear of bilateral endophthalmitis, potential medicolegal issues, and a lack of availability of separate products for both eyes) should be addressed.
To Use the Back-up Cochlear Implant or Not? Using Intra-operative Impedance to Guide Your Decisions
Authors: Mehta Nishchay , Chu Philip , Birman Catherine S.
Published: March 2022

Introduction:

Intra-operative electrophysiological testing is being increasingly used to determine device functionality. Impedance abnormalities (open or short circuits) measured at time of surgery pose a dilemma: is it likely to resolve or is it a permanent fault? There is little in the literature on how to manage these intraoperative finding and if, at time of surgery, the back-up device should be used.

Methods:

We routinely undertake impedance testing twice intraoperatively, as well as at switch on, 1 and 3 months postoperatively. Retrospective impedance thresholds were analysed for one surgeon's cases between January 2018 and December 2019.

Results:

There were 235 cochlear implants performed for 217 patients (5,020 electrode contacts) analysed. Thirty-three electrodes had abnormal impedance thresholds on first intraoperative cycle of testing, 76% resolving with the second testing cycle electrode contacts that demonstrated abnormal impedance during both intraoperative test cycles were 16.54 times (95%CI 2.55–107.13, p = 0.003) more likely to be abnormal at three months. Fifty percent resolved by switch on. The intraoperative abnormalities made up 26% of electrode abnormalities seen at 3 months postoperatively.

Discussion:

This study demonstrates the utility of 2 cycles of intraoperative impedance testing, with persistently abnormal electrodes having 16 times the likelihood of persistent abnormalities of impedance, and 50% resolution. These persistent intra-operative abnormal electrodes are responsibly for 26% of electrode abnormalities at 3 months. This information is useful for the surgeon when considering use of the backup cochlear implant device.
Optical Clearing Agents for Optical Imaging Through Cartilage Tympanoplasties: A Preclinical Feasibility Study
Authors: Wang Junzhe , Chawdhary Gaurav , Yang Xiaojie , Morin Francis , Khalid-Raja Mamoona , Farrell Joshua , MacDougall Dan , Chen Fangyi , Morris David P. , Adamson Robert B. A.
Published: March 2022

Hypothesis:

Optical clearing agents (OCAs) can render cartilage tympanoplasty grafts sufficiently transparent to permit visualization of middle ear structures in an operated ear using optical coherence tomography (OCT) imaging.

Methods:

Pieces of human tragal cartilage were treated with glycerol, a commonly used OCA. A reference reflector was imaged with OCT through the tympanoplasty as it cleared and the optical attenuation of the graft was measured. The reversibility of clearing and the dimensional changes associated with glycerol absorption were also measured. In a separate experiment, a human cadaveric temporal bone was prepared to simulate an ossiculoplasty surgery with cartilage replacement of the tympanic membrane. A partial ossicular replacement prosthesis (PORP) inserted in the ear was imaged with OCT through a 0.4mm cartilage graft optically cleared with glycerol.

Main Outcome Measure:

The optical attenuation of 0.4mm cartilage grafts decreased at 2.3+/−1.1 dB/min following treatment with glycerol, reaching a total decrease in attenuation of 13.6+/−5.9 dB after 7 minutes. The optical and dimensional effects of glycerol absorption were reversable following saline washout. In the temporal bone preparation, treatment of a cartilage graft with glycerol resulted in a 13 dB increase in signal-to-noise ratio and a 13 dB increase in contrast for visualizing the PORP through the graft with OCT.

Conclusions:

Optical clearing agents offer a potential pathway towards optical coherence tomography imaging of the middle ear in post-surgical ears with cartilage grafts.
Extracorporeal Membrane Oxygenation as a Bridge to Surgical Repair of Postinfarct Ventricular Septal Defect
Authors: Doi Atsuo , Negri Justin C. , Marasco Silvana F. , Gooi Julian H. , Zimmet Adam , Pellegrino Vincent A. , Nanjayya Vinodh B. , McGloughlin Steve A. , McGiffin David C.
Published: March 2022

Postinfarct ventricular septal defect (PIVSD) is associated with high mortality and the management of these patients has been a challenge with little improvement in outcomes. We commenced a protocol of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for those patients who present in cardiogenic shock with the aim to improve end-organ function before definitive surgical repair to reduce postoperative mortality. This study reviewed the results of this strategy. This was a single-center, retrospective review of all patients who were admitted to our institution with PIVSD in cardiogenic shock from September 2015 to November 2019. Clinical and investigative data were evaluated. Eight patients were referred with PIVSD during this period in cardiogenic shock. One patient had an anterior PIVSD and the other seven had inferior PIVSD. Six patients underwent surgical repair at a median (interquartile range, IQR) of 7 (5–8) days after initiation of VA ECMO. Two patients did not undergo surgical repair. Five patients survived after surgery and one patient died postoperatively due to multiorgan failure.

Preoperative use of VA ECMO is a feasible strategy for PIVSD and may improve the results of repair.
Potential of the EVAHEART 2 Double-Cuff Tipless Inflow Cannula for Prevention of Thromboembolic Events
Authors: Ushijima Tomoki , Tanoue Yoshihisa , Sonoda Hiromichi , Kan-o Meikun , Oda Shinichiro , Kimura Satoshi , Hashimoto Toru , Fujino Takeo , Shiose Akira
Published: March 2022

A 32-year-old man, who had developed fulminant myocarditis leading to asystole, underwent implantation of an EVAHEART 2 left ventricular assist system with a double-cuff tipless inflow cannula and a concurrent Fontan operation. Approximately 2 years after the simultaneous EVAHEART 2 implantation and the Fontan operation, the patient underwent heart transplantation. There was no device-related thromboembolism or pump malfunction under adequate antithrombotic management during the postoperative support period. Computed tomography showed no malposition of the inflow cannula irrespective of the left ventricular chamber size. Macroscopically, the left ventricular cavity of the excised heart revealed a smooth inflow ostium with appropriate intimal proliferation and without pannus or wedge thrombus formation. These findings suggest the utility of the double-cuff tipless inflow cannula for long-term clinical applications, which may lead to favorable outcomes during long-term patient management. The double-cuff tipless inflow cannula, which does not protrude into the left ventricular cavity, potentially contributes to the prevention of suction events and the collision of the inflow cannula with the interventricular septum and left ventricular free wall. Further investigation is required to confirm the role of the unique EVAHEART 2 inflow cannula in reducing thromboembolic events.
Transapical Cannulation With a Dual Lumen Cannula for Mechanical Circulatory Support in Cardiogenic Shock
Authors: Singh Ramesh , Chandel Abhimanyu , Paras Jen , Lee Thomas Brad , Tang Daniel G. , Shah Palak , Desai Mehul
Published: March 2022

Temporary mechanical circulatory support can be delivered through a variety of techniques, including percutaneous left ventricular assist devices, surgically implanted rotary pumps, and veno-arterial extracorporeal membrane oxygenation. However, limitations include the effects of high afterload, intravascular hemolysis, patient vascular anatomy, surgical morbidity, and limited patient mobility which can hinder patient recovery. We describe a series of patients managed with transapical left ventricular mechanical circulatory support using a dual lumen cannula for the management of cardiogenic shock as a bridge to recovery or definitive decision. This support strategy may represent an additional option in the care for patients with cardiogenic shock that can provide full temporary anterograde mechanical circulatory support while potentially improving patient mobility and minimizing device-related complications.
Comprehensive Monitoring in Patients With Dual Lumen Right Atrium to Pulmonary Artery Right Ventricular Assist Device
Authors: Usman Asad A. , Spelde Audrey E. , Ibrahim Michael , Cevasco Marisa , Bermudez Christian , MacKay Emily , Khandhar Sameer , Szeto Wilson , Vernick William , Gutsche Jacob
Published: March 2022

Right ventricular assist devices (RVADs) can be used in patients with acute right heart failure. A novel device that has recently been deployed is the right atrium to pulmonary artery (RA-PA) dual lumen single cannula (DLSC). One of the limitations is that it occupies a large proportion of the right ventricular outflow tract and PA; therefore, standard continuous hemodynamic monitoring with a pulmonary artery catheter is commonly not used. Serial echocardiography is pivotal for device deployment, monitoring device position, assessing RV readiness for decannulation, and surveilling for short-term complications. We performed a retrospective case series of 24 patients with RA-PA DLSC RVAD assessing echocardiographic RV progression and vasoactive infusion requirements. The overall survival was 66.6%. The average vasoactive infusion score at the time of cannulation was 24.9 ± 43.9, at decannulation in survivors 4.6 ± 4.9 vs. 25.4 ± 21.5 in nonsurvivors, and 2.7 ± 4.9 at 48 hours post decannulation. On echocardiography, the average visual estimate of RV systolic function encoded (0 = none and 5 = severe) in survivors was 3.9 ± 1.2, 2.8 ± 1.6, 2.5 ± 1.7, and 2.8 ± 1.9, respectively, and in nonsurvivors 3.8 ± 1.6 and 3.4 ± 1.8, respectively. This demonstrated an RV systolic function improvement over time in survivors as opposed to nonsurvivors. This was also demonstrated in RV size visual estimate, respectively. Quantitatively, at the predefined four timepoints, the RV:LV, tricuspid annular plane systolic excursion, and fractional area change all improve over time and there is statistically significant difference in survivors versus nonsurvivors. In this study, we describe a cohort of patients treated with RA-PA DLSC RVAD. We illustrate the critical nature of echocardiographic measures to rate the progression of RV function, improvement in vasoactive infusion requirements, and ventilator parameters with the RA-PA DLSC.
Driveline Infection in Left Ventricular Assist Device Patients: Effect of Standardized Protocols, Pathogen Type, and Treatment Strategy
Authors: Lumish Heidi S. , Cagliostro Barbara , Braghieri Lorenzo , Bohn Bruno , Mondellini Giulio M. , Antler Karen , Feldman Vivian , Kleet Audrey , Murphy Jennifer , Tiburcio Melie , Fidlow Kathryn , Jennings Douglas , Sayer Gabriel T. , Takeda Koji , Naka Yoshifumi , Demmer Ryan T. , Aaron Justin G. , Uriel Nir , Colombo Paolo C. , Yuzefpolskaya Melana
Published: March 2022

Driveline infection (DLI) is common after left ventricular assist device (LVAD). Limited data exist on DLI prevention and management. We investigated the impact of standardized driveline care initiatives, specific pathogens, and chronic antibiotic suppression (CAS) on DLI outcomes. 591 LVAD patients were retrospectively categorized based on driveline care initiatives implemented at our institution (2009–2019). Era (E)1: nonstandardized care; E2: standardized driveline care protocol; E3: addition of marking driveline exit site; E4: addition of “no shower” policy. 87(15%) patients developed DLI at a median (IQR) of 403(520) days. S. aureus and P. aeruginosa were the most common pathogens. 31 (36%) of DLI patients required incision and drainage (I&D) and 5 (5.7%) device exchange. P. aeruginosa significantly increased risk for initial I&D (HR 2.7, 95% CI, 1.1–6.3) and recurrent I&D or death (HR 4.2, 95% CI, 1.4–12.5). Initial I&D was associated with a significant increased risk of death (HR 2.92 (1.33–6.44); P = 0.008) when compared to patients who did not develop DLI. Implementation of standardized driveline care protocol (E2) was associated with increased 2-year freedom from DLI compared to nonstandardized care (HR 0.36, 95% CI, 0.2–0.6, P < 0.01). Additional preventive strategies (E3&E4) showed no further reduction in DLI rates. 57(65%) DLI patients received CAS, 44% of them required escalation to intravenous antibiotics and/or I&D. Presence of P. aeruginosa DLI markedly increased risk for I&D or death. Conditional survival of patients progressing to I&D is diminished. Standardized driveline care protocol was associated with a significant reduction in DLI, while additional preventive strategies require further testing.
Shaping the Nursing Profession Postpandemic Through Reconstructed Leadership Practices
Authors: Grubaugh Martha , Bernard Noreen
Published: March 2022

Responding to and navigating the COVID-19 pandemic were demanding and all-consuming for executive nurse leaders. Long-term pandemic challenges will continue and therefore it is important for nurse leaders to develop their reflective practice to increase role competency, gain wisdom, and advance the profession. The complex postpandemic world requires nurse leaders to show up differently, stop ineffective practices, continue best practices, and implement new ideas to improve performance and outcomes. This article offers a framework for leadership reflection, through role negotiation technique, to identify lessons from the lived nurse executive experience of the COVID-19 pandemic. Specific focus is placed on communication, teamwork, professional governance, posttraumatic growth, gratitude, diversity/equity/inclusion, and social determinants of health. These concepts, along with specific tactics, will help leaders set priorities, aid nursing leadership practice, identify meaningful goals and desired outcomes, and effectively lead to advance the nursing profession postpandemic.
Breaking Down Institutional Barriers to Advanced Practice Registered Nurse Practice
Authors: Kleinpell Ruth , Myers Carole R. , Likes Wendy , Schorn Mavis N.
Published: March 2022

Advanced practice registered nurses (APRNs) significantly contribute to health promotion, disease prevention, and disease management. Yet, barriers to APRN practice exist, including regulatory, state, and institutional barriers, that hinder their ability to practice to the full extent of their education, licensure, and certification. Nurse leaders can play an important role in helping reduce unnecessary institutional barriers to APRN practice.
Cone-Beam Computed Tomography-Based Spatial Prediction of Drug Dose After Transarterial Chemoembolization Using Radiopaque Drug-Eluting Beads in Woodchuck Hepatocellular Carcinoma
Authors: Mikhail Andrew S. , Pritchard William F. , Negussie Ayele H. , Inkiyad Gazi , Long Dilara J. , Mauda-Havakuk Michal , Wakim Paul G. , van der Sterren William , Levy Elliot B. , Lewis Andrew L. , Karanian John W. , Wood Bradford J.
Published: March 2022

Objectives

The aims of this study were to develop a model to estimate drug dose delivered to tumors after transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEBs) based on DEB density on cone-beam computed tomography (CT) and to evaluate drug penetration into tissue in a woodchuck hepatoma model.

Materials and Methods

Transarterial chemoembolization was performed in woodchucks with hepatocellular carcinoma (N = 5) using DEBs (70–150 μm, LC Bead LUMI) loaded with doxorubicin. Livers were resected 45 minutes after embolization, immediately frozen, and cut using liver-specific, 3D-printed sectioning molds. Doxorubicin levels in tumor specimens were measured by high-performance liquid chromatography and correlated with DEB iodine content that was measured using prototype cone-beam CT-based embolization treatment planning software. Doxorubicin penetration into tissue surrounding DEBs was assessed by fluorescence microscopy of tumor sections. Fluorescence intensity was converted into doxorubicin concentration using calibration standards. Intensity-thresholded color heatmaps were generated representing extravascular drug penetration.

Results

Consistent segmentation of DEBs on cone-beam CT was achieved using a semiautomated intensity thresholding method. A positive linear correlation (0.96) was found between DEB iodine content measured on cone-beam CT and the amount of doxorubicin measured in tumor specimens. Prediction of doxorubicin levels in tumor sections that were not included in model development was accurate, with a root-mean-square error of 0.08 mg of doxorubicin. Tumor penetration of eluted doxorubicin resulted in concentration gradients where drug content decreased with increasing distance from blood vessels containing DEBs. Drug penetration was greater for blood vessels containing DEB clusters compared with single DEB, with higher doxorubicin concentrations extending further away from the vessels.

Conclusions

Estimation of drug dose delivered during transarterial chemoembolization in a woodchuck hepatocellular carcinoma model was possible using DEB radiopacity on cone-beam CT as a surrogate marker. Doxorubicin penetration was greatest adjacent to vessels containing DEB clusters compared with single DEB. Intraprocedural estimation of the spatial distribution of drug dose within the tumor could enable real-time adjustments to DEB delivery, to maximize treatment coverage or identify regions of tumor at risk for undertreatment.
New-Generation Low-Field Magnetic Resonance Imaging of Hip Arthroplasty Implants Using Slice Encoding for Metal Artifact Correction
Authors: Khodarahmi Iman , Brinkmann Inge M. , Lin Dana J. , Bruno Mary , Johnson Patricia M. , Knoll Florian , Keerthivasan Mahesh B. , Chandarana Hersh , Fritz Jan
Published: March 2022

Objectives

Despite significant progress, artifact-free visualization of the bone and soft tissues around hip arthroplasty implants remains an unmet clinical need. New-generation low-field magnetic resonance imaging (MRI) systems now include slice encoding for metal artifact correction (SEMAC), which may result in smaller metallic artifacts and better image quality than standard-of-care 1.5 T MRI. This study aims to assess the feasibility of SEMAC on a new-generation 0.55 T system, optimize the pulse protocol parameters, and compare the results with those of a standard-of-care 1.5 T MRI.

Materials and Methods

Titanium (Ti) and cobalt-chromium total hip arthroplasty implants embedded in a tissue-mimicking American Society for Testing and Materials gel phantom were evaluated using turbo spin echo, view angle tilting (VAT), and combined VAT and SEMAC (VAT + SEMAC) pulse sequences. To refine an MRI protocol at 0.55 T, the type of metal artifact reduction techniques and the effect of various pulse sequence parameters on metal artifacts were assessed through qualitative ranking of the images by 3 expert readers while taking measured spatial resolution, signal-to-noise ratios, and acquisition times into consideration. Signal-to-noise ratio efficiency and artifact size of the optimized 0.55 T protocols were compared with the 1.5 T standard and compressed-sensing SEMAC sequences.

Results

Overall, the VAT + SEMAC sequence with at least 6 SEMAC encoding steps for Ti and 9 for cobalt-chromium implants was ranked higher than other sequences for metal reduction (P < 0.05). Additional SEMAC encoding partitions did not result in further metal artifact reductions. Permitting minimal residual artifacts, low magnetic susceptibility Ti constructs may be sufficiently imaged with optimized turbo spin echo sequences obviating the need for SEMAC. In cross-platform comparison, 0.55 T acquisitions using the optimized protocols are associated with 45% to 64% smaller artifacts than 1.5 T VAT + SEMAC and VAT + compressed-sensing/SEMAC protocols at the expense of a 17% to 28% reduction in signal-to-noise ratio efficiency. B1-related artifacts are invariably smaller at 0.55 T than 1.5 T; however, artifacts related to B0 distortion, although frequently smaller, may appear as signal pileups at 0.55 T.

Conclusions

Our results suggest that new-generation low-field SEMAC MRI reduces metal artifacts around hip arthroplasty implants to better advantage than current 1.5 T MRI standard of care. While the appearance of B0-related artifacts changes, reduction in B1-related artifacts plays a major role in the overall benefit of 0.55 T.
Schneiderian Membrane Regeneration After Lateral Bony Window Repositioning in Modified Endoscopic-Assisted Maxillary Sinus Surgery: Transmission Electron Microscopy Evaluation
Authors: Han Jeong Joon , Sodnom-Ish Buyanbileg , Eo Mi Young , Kim Yoon Joo , Oh Ji Hye , Yang Hoon Joo , Kim Soung Min
Published: March 2022

Purpose:

Regeneration of Schneiderian membrane (SM) and restoration of physiologic function of a maxillary sinus are essential for successful treatment of odontogenic maxillary sinusitis (OMS). In the present study, the surgical procedures of modified endoscopic sinus surgery (MESS) for treatment of OMS were described with special focus on regeneration of SM and favorable bone healing in the lateral bony window repositioning procedure.

Methods:

The regeneration of the SM after MESS was assessed based on clinical, histological, and ultrastructural findings. The study included 66 patients who received MESS with repositioning of the lateral bony window for treatment of OMS.

Results:

In the inflamed maxillary sinus membrane, squamous metaplasia was observed with infiltration of inflammatory cells including neutrophils, eosinophils, and plasma cells. Although partial loss of the cilia was observed in the epithelium, the majority of epithelial cells was ciliated. Clinically acceptable partial or complete bone healing was observed without occurrence of postoperative maxillary cyst or invasion of soft tissue into the sinus cavity for all patients at an average of 1.4 ± 1.2 years after MESS. On histopathological and ultrastructural examinations of the healed soft tissue, significant inflammatory features were not found, and fibroblasts with abundant collagen fibers were the main findings.

Conclusions:

These results indicate that repositioning of the lateral bony window leads to regeneration of the SM and favorable bone regeneration without occurrence of complications associated with transmaxillary approaches and can contribute to maintaining normal physiological function of the maxillary sinus.
Lambdoid Craniosynostosis in an Infant With Congenital Cystic Adenomatoid Malformation (CCAM)
Authors: Blum Jessica D. , Villavisanis Dillan F. , Adzick N. Scott , Taylor Jesse A.
Published: March 2022

Both congenital cystic adenomatoid malformation (CCAM) and lambdoid craniosynostosis are exceedingly rare, with estimated incidences of around 1 in 30,000 live births for each. Herein, we present a case of a patient with prenatally diagnosed CCAM requiring 4 doses of prenatal steroids and ultimately thoracotomy with right lower lobectomy. The operation was uncomplicated, and genome-wide analysis of SNPs revealed no pathologic abnormalities. Development was normal until head shape changes were noted at 5 months of age at which point evaluation by a craniofacial surgeon and 3D CT imaging revealed left-sided lambdoid craniosynostosis. The patient underwent uncomplicated posterior and middle vault expansion and remodeling of his lambdoid synostosis at 11 months of age. This paper explores the etiopathogenesis of CCAM and lambdoid craniosynostosis in an attempt to identify common pathways involved in the development of these exceedingly rare diseases which, to date, have not been described in the peer-reviewed literature.