bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcatheter versus surgical aortic valve replacement in lower-risk and higher-risk patients: a meta-analysis of randomized trials
Authors: Ahmad Yousif , Howard James P , Arnold Ahran D , Madhavan Mahesh V , Cook Christopher M , Alu Maria , Mack Michael J , Reardon Michael J , Thourani Vinod H , Kapadia Samir , Thyregod Hans Gustav Hørsted , Sondergaard Lars , Jørgensen Troels Højsgaard , Toff William D , Van Mieghem Nicolas M , Makkar Raj R , Forrest John K , Leon Martin B
Published: January 2023

Aims

Additional randomized clinical trial (RCT) data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) is available, including longer term follow-up. A meta-analysis comparing TAVI to SAVR was performed. A pragmatic risk classification was applied, partitioning lower-risk and higher-risk patients.

Methods and results

The main endpoints were death, strokes, and the composite of death or disabling stroke, occurring at 1 year (early) or after 1 year (later). A random-effects meta-analysis was performed. Eight RCTs with 8698 patients were included. In lower-risk patients, at 1 year, the risk of death was lower after TAVI compared with SAVR [relative risk (RR) 0.67; 95% confidence interval (CI) 0.47 to 0.96, P = 0.031], as was death or disabling stroke (RR 0.68; 95% CI 0.50 to 0.92, P = 0.014). There were no differences in strokes. After 1 year, in lower-risk patients, there were no significant differences in all main outcomes. In higher-risk patients, there were no significant differences in main outcomes. New-onset atrial fibrillation, major bleeding, and acute kidney injury occurred less after TAVI; new pacemakers, vascular complications, and paravalvular leak occurred more after TAVI.

Conclusion

In lower-risk patients, there was an early mortality reduction with TAVI, but no differences after later follow-up. There was also an early reduction in the composite of death or disabling stroke, with no difference at later follow-up. There were no significant differences for higher-risk patients. Informed therapy decisions may be more dependent on the temporality of events or secondary endpoints than the long-term occurrence of main clinical outcomes.
Lifestyle habits associated with cardiac conduction disease
Authors: Frimodt-Møller Emilie K , Soliman Elsayed Z , Kizer Jorge R , Vittinghoff Eric , Psaty Bruce M , Biering-Sørensen Tor , Gottdiener John S , Marcus Gregory M
Published: January 2023

Aims

Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. Research to identify modifiable risk factors has been scant.

Methods and results

Data from the Cardiovascular Health Study, a population-based cohort study of adults ≥ 65 years with annual 12-lead electrocardiograms obtained over 10 years, were utilized to examine relationships between baseline characteristics, including lifestyle habits, and conduction disease. Of 5050 participants (mean age 73 ± 6 years; 52% women), prevalent conduction disease included 257 with first-degree atrioventricular block, 99 with left anterior fascicular block, 9 with left posterior fascicular block, 193 with right bundle branch block (BBB), 76 with left BBB, and 102 with intraventricular block at baseline. After multivariable adjustment, older age, male sex, a larger body mass index, hypertension, and coronary heart disease were associated with a higher prevalence of conduction disease, whereas White race and more physical activity were associated with a lower prevalence. Over a median follow-up on 7 (interquartile range 1–9) years, 1036 developed incident conduction disease. Older age, male sex, a larger BMI, and diabetes were each associated with incident conduction disease. Of lifestyle habits, more physical activity (hazard ratio 0.91, 95% confidence interval 0.84–0.98, P = 0.017) was associated with a reduced risk, while smoking and alcohol did not exhibit a significant association.

Conclusion

While some difficult to control comorbidities were associated with conduction disease as expected, a readily modifiable lifestyle factor, physical activity, was associated with a lower risk.
Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity
Authors: Iqbal Farwah , Schlotter Florian , Becker-Greene Dakota , Lupieri Adrien , Goettsch Claudia , Hutcheson Joshua D , Rogers Maximillian A , Itoh Shinsuke , Halu Arda , Lee Lang Ho , Blaser Mark C , Mlynarchik Andrew K , Hagita Sumihiko , Kuraoka Shiori , Chen Hao Yu , Engert James C , Passos Livia S A , Jha Prabhash K , Osborn Eric A , Jaffer Farouc A , Body Simon C , Robson Simon C , Thanassoulis George , Aikawa Masanori , Singh Sasha A , Sonawane Abhijeet R , Aikawa Elena
Published: January 2023

Aims

Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.

Methods and results

An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype.

Conclusion

Sortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.
Evaluation of Associations of Growth Differentiation Factor-11, Growth Differentiation Factor-8, and Their Binding Proteins Follistatin and Follistatin-Like Protein-3 With Dementia and Cognition
Authors: Newman Anne B , Patel Sheena , Kizer Jorge R , Lee Se-Jin , Bhasin Shalinder , Cawthon Peggy , LeBrasseur Nathan , Tracy Russel P , Ganz Peter , Cummings Steven R
Published: January 2023

Background

Studies using heterochronic parabiosis discovered that circulating factors mediate brain aging in animal models.

Methods

We assessed growth differentiation factors (GDF)-11 and GDF-8 using mass spectrometry and inhibitors follistatin and follistatin-like protein-3 (FSTL-3) with ELISA in the Cardiovascular Health Study (CHS; N = 1 506) and the Health, Aging and Body Composition (Health ABC) Study (N = 1 237). CLL-11 and beta-2 microglobulin (β2M) were measured with ELISA in a subset of 400 individuals in Health ABC. Associations were assessed with cognitive function, brain magnetic resonance imaging (MRI) findings (CHS only), and incident dementia using correlations, linear regression, and Cox proportional hazards models.

Results

In CHS, levels of GDF-11, GDF-8, and follistatin were not correlated cross-sectionally with the 3MSE or DSST, brain MRI findings of white matter hyperintensity, atrophy, or small infarcts, nor were they associated with incident dementia. FSTL-3 was modestly correlated with poorer cognitive function, greater white matter hyperintensities, and atrophy on MRI, as well as with incident dementia with an adjusted hazard ratio (HR) of 1.72 (95% CI = 1.13, 2.61) per doubling of FSTL-3. FSTL-3 was not associated with cognition or dementia in Health ABC, but GDF-8 was associated with both. The adjusted HR for incident dementia was 1.50 (95% CI = 1.07, 2.10) per doubling of GDF-8.

Conclusions

Total GDF-11 level was not related to cognition or dementia in older adults. Associations of GDF-8 with cognitive outcomes in Health ABC were not expected, but consistent with animal models. Associations of FSTL-3 with cognition, brain abnormalities, and incident dementia in CHS implicate TGFβ superfamily inhibition in the pathogenesis of dementia.
Everyday Discrimination, Neighborhood Perceptions, and Incidence of Activity Limitations Among Middle-Aged and Older African Americans
Authors: Qin Weidi , Nguyen Ann W , Wang Yi , Hamler Tyrone C , Wang Fei
Published: January 2023

Objectives

This study aims to examine the relationship between everyday discrimination, neighborhood perceptions, and the incidence of daily activity limitations (i.e., activities of daily living [ADL] and instrumental activities of daily living [IADL]) among middle-aged and older African Americans. This study also examines whether neighborhood perceptions moderate the association between discrimination and the incidence of daily activity limitations.

Methods

Data were from the 2006 to 2016 waves of the Health and Retirement Study. African Americans aged 50 or older free of ADL limitations (N = 1,934) and IADL limitations (N = 2,007) at baseline were selected. Cox proportional hazards regression models were performed to test the study aims. Multiple imputations were applied to handle missing data.

Results

One-unit increase in everyday discrimination was associated with a 25% (p < .05) higher risk of ADL limitation onset. Perceived neighborhood social cohesion and physical disadvantage moderated the association between discrimination and IADL limitation onset.

Discussion

Everyday discrimination represents a significant stressor that negatively affects older African Americans’ performance of daily activities. Community-level efforts that improve neighborhood perceptions are needed to alleviate the negative effects of discrimination on the incidence of activity limitations.
Estimation of time-varying causal effects with multivariable Mendelian randomization: some cautionary notes
Authors: Tian Haodong , Burgess Stephen
Published: January 2023

Introduction

For many exposures present across the life course, the effect of the exposure may vary over time. Multivariable Mendelian randomization (MVMR) is an approach that can assess the effects of related risk factors using genetic variants as instrumental variables. Recently, MVMR has been used to estimate the effects of an exposure during distinct time periods.

Methods

We investigated the behaviour of estimates from MVMR in a simulation study for different time-varying causal scenarios. We also performed an applied analysis to consider how MVMR estimates of body mass index on systolic blood pressure vary depending on the time periods considered.

Results

Estimates from MVMR in the simulation study were close to the true values when the outcome model was correctly specified: i.e. when the outcome was a discrete function of the exposure at the precise time points at which the exposure was measured. However, in more realistic cases, MVMR estimates were misleading. For example, in one scenario, MVMR estimates for early life were clearly negative despite the true causal effect being constant and positive. In the applied example, estimates were highly variable depending on the time period in which genetic associations with the exposure were estimated.

Conclusions

The poor performance of MVMR to study time-varying causal effects can be attributed to model misspecification and violation of the exclusion restriction assumption. We would urge caution about quantitative conclusions from such analyses and even qualitative interpretations about the direction, or presence or absence, of a causal effect during a given time period.
In vitro activity of imipenem/relebactam against piperacillin/tazobactam-resistant and meropenem-resistant non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa collected from patients with lower respiratory tract infections in Western Europe: SMART 2018–20
Authors: Karlowsky James A , Lob Sibylle H , Akrich Brune , DeRyke C Andrew , Siddiqui Fakhar , Young Katherine , Motyl Mary R , Hawser Stephen P , Sahm Daniel F
Published: January 2023

Objectives

To describe the in vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales (NME) and Pseudomonas aeruginosa recently isolated from lower respiratory tract infection samples by hospital laboratories in Western Europe.

Methods

From 2018 to 2020, 29 hospital laboratories in six countries in Western Europe participated in the SMART global surveillance programme and contributed 4414 NME and 1995 P. aeruginosa isolates. MICs were determined using the CLSI broth microdilution method and interpreted by EUCAST (2021) breakpoints. β-Lactamase genes were identified in selected isolate subsets (2018–20) and oprD sequenced in molecularly characterized P. aeruginosa (2020).

Results

Imipenem/relebactam (99.1% susceptible), amikacin (97.2%), meropenem (96.1%) and imipenem (95.9%) were the most active agents tested against NME; by country, relebactam increased imipenem susceptibility from <1% (France, Germany, UK) to 11.0% (Italy). A total of 96.0% of piperacillin/tazobactam-resistant (n = 990) and 81.1% of meropenem-resistant (n = 106) NME were imipenem/relebactam-susceptible. Only 0.5% of NME were MBL positive, 0.9% were OXA-48-like-positive (MBL negative) and 2.8% were KPC positive (MBL negative). Amikacin (91.5% susceptible) and imipenem/relebactam (91.4%) were the most active agents against P. aeruginosa; 72.3% of isolates were imipenem-susceptible. Relebactam increased susceptibility to imipenem by 34.4% (range by country, 39.1%–73.5%) in piperacillin/tazobactam-resistant and by 37.4% (3.1%–40.5%) in meropenem-resistant P. aeruginosa. Only 1.8% of P. aeruginosa isolates were MBL positive. Among molecularly characterized imipenem/relebactam-resistant P. aeruginosa isolates from 2020, 90.9% (30/33) were oprD deficient.

Conclusions

Imipenem/relebactam appears to be a potential treatment option for lower respiratory tract infections caused by piperacillin/tazobactam- and meropenem-resistant NME and P. aeruginosa in Western Europe.
Sudden cardiac death in synucleinopathies
Authors: Javanshiri Keivan , Drakenberg Tove , Haglund Mattias , Englund Elisabet
Published: January 2023

The purpose of this study was to investigate the cause of death in subjects with α-synucleinopathies (ASs) and the confirmed presence of cardiac α-synuclein (α-syn), compared to non-AS disorders in a neuropathologically confirmed cohort. In total, 78 neuropathologically confirmed AS cases positive for cardiac α-syn were included in the study. Individuals with other neurocognitive diseases, having no α-syn in the brainstem or above, nor in cardiac nerves, served as controls (n = 53). Data regarding the cause of death, cardiac α-syn, pathological cardiac findings, and cardio- and cerebrovascular disease were assembled from autopsy reports and medical records. In the AS group, there was a significantly higher prevalence of sudden cardiac death ([SCD]; n = 40, 51.3%) compared to the control group (n = 12, 22.6%, p < 0.001). No statistically significant differences between the groups were reported regarding other cardiac conditions on autopsy or regarding cardio- and cerebrovascular disease from the medical records. The most prevalent cause of death in the AS group was SCD, which differed significantly from the control group. This suggests that α-syn deposits in cardiac nerves may cause lethal alterations in cardiac function, warranting further research.
Integrating individual preferences into collective argumentation
Authors: Li Chonghui , Liao Beishui
Published: January 2023

In the field of collective argumentation, multiple agents may have different knowledge representations and individual preferences. In order to obtain a reasonable collective outcome for the group, either individual frameworks should be merged or individual preferences should be aggregated. However, framework merging and preference aggregation are different procedures, leading to disagreements on collective outcomes. In this paper, we figure out a solution to combine framework merging, argumentative reasoning and incomplete preference aggregation together. Furthermore, a couple of rational postulates are proposed to be the criteria for the rationality of collective outcomes obtained based on our approach.
Role of Uterine Telocytes During Pregnancy
Authors: Soliman Soha A , Abd-Elhafeez Hanan H , Abou-Elhamd Alaa S , Kamel Basma Mohamed , Abdellah Nada , Mustafa Fatma El-Zahraa A
Published: January 2023

Endometrial remolding and angiogenesis are critical events that occur during pregnancy in order to establish uteroplacental vascular communication. This study investigated the role of uterine telocytes (TCs) in pregnancy. We analyzed the distribution of TCs and morphological changes in the endometrium of the gravid rabbit uterus at different stages of pregnancy: after ovulation, pre-implantation (day 7), post-implantation (days 8 and 9), and mid-pregnancy (day 14) and late (days 21–28) pregnancy. TCs gradually increased with the progression of pregnancy. They had distinctive telopodes (TPs) and podoms, with intranucleolar chromatin. The TCs established contact with decidual cells, growing a glandular epithelium, blood vessels, and immune cells, such as lymphocytes, neutrophils, and macrophages. The TCs underwent morphological changes at the post-implantation phase. They acquired thick and voluminous TPs, formed an extensive three-dimensional (3D) labyrinth at mid-pregnancy, and exhibited irregular-shaped nuclei and a dilated rough endoplasmic reticulum at late pregnancy. They also acquired a convoluted contour-formed complex network. Scanning electron microscopy (SEM) showed an extensive 3D network in the endometrium, forming a condensed sheath at late pregnancy. Transmission electron microscopy and SEM detected fenestrated TPs, and TCs were identified by CD34 and vascular endothelial growth factor expression. TCs also expressed matrix metalloproteinase-9 and transforming growth factor beta-1. Results suggested that TCs might play an essential role in maternal placenta formation, especially decidualization, regulation of uterine gland development, and neovascularization of maternal uterine blood vessels.
Electron-Beam-Induced Carbon Contamination in STEM-in-SEM: Quantification and Mitigation
Authors: Hugenschmidt Milena , Adrion Katharina , Marx Aaron , Müller Erich , Gerthsen Dagmar
Published: January 2023

Contamination is an undesired side effect in many electron microscopy studies that covers structures of interest and degrades resolution. Although contamination has been studied for decades, open questions remain regarding favorable imaging conditions for contamination minimization and the efficiency of contamination-mitigation strategies. This work focuses on electron-beam-induced carbon contamination in scanning transmission electron microscopy at electron energies of 30 keV and below. A reliable method to measure contamination thicknesses was developed in this work and enables the identification of imaging conditions that minimize contamination. Thin amorphous carbon films were used as test samples. The variation of important imaging parameters shows that the contamination thickness increases with the reduction of the electron energy to about 1 keV but decreases below 1 keV. Contamination increases with the beam current but saturates at high currents. Applying a given dose with a high dose rate reduces contamination. Among the tested contamination-mitigation methods, plasma cleaning and beam showering are most effective. Most experiments in this work were performed with focused scanning illumination. Experiments were also carried out with a stationary defocused beam for comparison with a theoretical contamination model with good agreement between measured and calculated contamination thickness.
The Micro-CT Analysis of the Structural Parameters of Collagen-based Porous Scaffolds: The Influence of Image Processing and Binarization
Authors: Bartoš Martin , Suchý Tomáš , Luňáčková Jitka , Soukup Petr
Published: January 2023

The micro-CT evaluation of structural parameter values is dependent on the processing of the image prior to its analysis. However, the degree of bias introduced by the image-processing process is generally unknown. The micro-CT analysis of three basic parameters (volume, surface, and pore size) was performed for 20 collagen-based porous scaffolds. The image data were processed using various approaches (noise reduction, binarization), analyzed and results were compared. A high degree of variability was observed in the values of the structural parameters. The differences between the mean values were as follows: 190% (volume), 160% (surface density), and 210% (pore size). Significant differences were observed with respect to the noise reduction in terms of the pore size values (frequently in excess of 300%). Our study proved the significant dependence of image processing on the results obtained. The data presented can be used as an estimate for the introduced bias. We suggest improvements in terms of the selection of the image-processing approach based on a combination of subjective selection (the standard method) and numerical analysis based on the consistency of the results. Although we focused on tissue engineering scaffolds, the principles are similar for all fields of the micro-CT application.
Operando Liquid-Phase TEM Experiments for the Investigation of Dissolution Kinetics: Application to Li-Ion Battery Materials
Authors: Poulizac Julie , Boulineau Adrien , Billy Emmanuel , Masenelli-Varlot Karine
Published: January 2023

We present here a novel and universal sample preparation method for liquid-phase transmission electron microscopy (TEM) experiments involving powder materials. Thanks to this new protocol, we demonstrate the ability to study the dissolution of cathode materials by sulfuric acid using operando TEM. Based on ultramicrotomy, this method has been developed to avoid compatibility issues between sample size and liquid cell geometry. The observation parameters have been optimized to get the best contrast in scanning TEM (STEM) images. The reaction kinetics have been investigated by image analysis and compared to those obtained ex situ. By taking into account the sample geometry and the reacting surfaces in both experiments, we show that the reaction kinetics are equivalent and could be overlaid. This proves that the protocol developed enables real operando experiments, as it provides quantitative data at the nanoscale that are representative of the bulk specimen. The main challenges of such a protocol for operando liquid-phase TEM, as well as the accuracy of the image analysis method used, are also discussed.
Assessing the Accuracy of Mass Attenuation Coefficients for Soft X-ray EPMA
Authors: Llovet Xavier , Pöml Philipp , Moy Aurélien , Fournelle John H
Published: January 2023

The use of soft X-rays in electron probe microanalysis (EPMA) has gained renewed interest over the past decades due to the advent of new detector technologies. Because X-ray absorption is the dominant correction for soft X-rays, a reliable set of mass attenuation coefficients (MACs) is needed for accurate composition determination. Although several MAC tabulations cover the soft X-ray range, the accuracy of such tabulations below 1 keV is not firmly established. In this study, we assess the accuracy of MAC tabulations in the soft X-ray region by comparing tabulated values for Be, B, C, N, O, and F Kα X-rays with experimental data available in the literature. We find that the 1993 semi-empirical MAC compilation of Henke et al. [(1993). Low-energy X-ray interaction coefficients: Photoabsorption, scattering, transmission and reflection at E=50−30000 eV, Z=1−92. Atom Data Nucl Data Tables54, 181–342] and the more recent theoretical MAC calculations of Sabbatucci and Salvat [(2016). Theory and calculation of the atomic photoeffect. Rad Phys Chem121, 122–140] perform slightly better than the rest of the considered tabulations. The Sabbatucci–Salvat dataset also provides the best agreement with the few existing experimental measurements for Al L2,3M X-rays.
Scoping Review of Postvention for Mental Health Providers Following Patient Suicide
Authors: Daly Kelly A , Segura Anna , Heyman Richard E , Aladia Salomi , Slep Amy M Smith
Published: January 2023

Introduction

As suicides among military personnel continue to climb, we sought to determine best practices for supporting military mental health clinicians following patient suicide loss (i.e., postvention).

Materials and Methods

We conducted a scoping review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Our initial search of academic databases generated 2,374 studies, of which 122 were included in our final review. We categorized postvention recommendations based on the socioecological model (i.e., recommendations at the individual provider, supervisory/managerial, organizational, and discipline levels) and analyzed them using a narrative synthesizing approach.

Results

Extracted recommendations (N = 358) comprised those at the provider (n = 94), supervisory/managerial (n = 90), organization (n = 105), and discipline (n = 69) levels.

Conclusions

The literature converges on the need for formal postvention protocols that prioritize (1) training and education and (2) emotional and instrumental support for the clinician. Based on the scoped literature, we propose a simple postvention model for military mental health clinicians and recommend a controlled trial testing of its effectiveness.
Blastomycosis in New England: 5 Cases and a Review
Authors: Ross John J , Koo Sophia , Woolley Ann E , Zuckerman Richard A
Published: January 2023

The geographic range of blastomycosis is thought to include New England, but documentation is sparse. We report 5 cases of infection with Blastomyces dermatitidis that were likely acquired in New England between 2011 and 2021. Our experience suggests that chart coding for the diagnosis of blastomycosis is imprecise and that mandatory reporting might help resolve uncertainties about the prevalence and extent of blastomycosis.
Lateral medullary infarction presenting only with dermatomal sensory disturbance: a case report
Authors: Aratake Yuriko , Inoue Manabu
Published: January 2023

The triad of Horner’s syndrome, ataxia and sensory disturbances clinically identifies patients with lateral medullary infarct (LMI). However, dermatomal temperature and pain sensory loss have rarely been reported in patients with LMI. We describe the case of a patient with LMI presenting solely with temperature and pain sensory disorder below the C5 sensory level. Magnetic resonance imaging findings demonstrated a small superficial infarction in the right lateral medulla oblongata, indicating that the sensory deficit was caused by a restricted infarction of the lateral spinothalamic tract. We emphasize the importance of adding LMI to a differential diagnosis of acute dermatomal sensory disturbance without other major symptoms of LMI, such as cranial nerve abnormalities, ataxia and Horner’s syndrome.
Left lung aplasia with patent ductus arteriosus in a term newborn baby: a case report
Authors: Aslamzai Mansoor , Mukhlis Abdul Hakim , Hakimi Turyalai , Froogh Basir Ahmad
Published: January 2023

Pulmonary aplasia is a very rare congenital anomaly identified by the absence of lung parenchyma or vessels. This malformation mostly accompanies other anomalies, and chest computed tomography (CT) is a useful diagnostic tool. We present a rare case of left lung aplasia with patent ductus arteriosus and neonatal sepsis in a term newborn baby who had respiratory distress. The clinical features were observed during the first week of life, and the diagnosis of these anomalies was established by clinical, laboratory, chest x-ray, thoracic CT and echocardiographic findings. After the management of neonatal sepsis and patent ductus arteriosus, he was discharged from the hospital in good condition. Since the index case of lung aplasia was associated with congenital heart disease and had strong parental consanguinity, a genetic basis may have been involved in the pathogenesis of pulmonary aplasia.
Pleomorphic adenoma of nasal septum, an unusual site: a case report from Nepal
Authors: Aryal Gyan Raj , Shrestha Nischal , Basnet Meenakshi , Shrestha Oshan , Sharma Pratikshya
Published: January 2023

Pleomorphic adenoma is the commonest benign salivary glands tumor. Major salivary glands are mainly involved, and there is very low reported incidence of such tumor in minor salivary glands of nasal cavity. We report a case of 69-year-old woman who complaint of chronic left nasal obstruction and recurrent scanty bleeding from left nostril for last 2 months. On anterior Rhinoscopy examination, there was a pinkish non-tender mass in left nasal cavity arising from cartilaginous part of nasal septum. Intranasal endoscopic excision was done under general anesthesia and histopathological examination of excised tissue revealed pleomorphic adenoma. Patient was discharged after 3 days. There was no recurrence at sixth month of follow-up.
Progressively confluent monkeypox lesions with necrosis
Authors: Smith Kolton , Tyson Kelly , Hossain Raeesa , Young Alexandra , Melnick Jillian
Published: January 2023

Human monkeypox virus became a burgeoning global health issue when outbreaks were identified in over 100 countries beginning in early 2022. We describe the case of a 38-year-old male with acquired immunodeficiency syndrome who presented one month after the development of painful anal lesions, subsequently confirmed to be monkeypox. The patient was unsuccessfully treated outpatient with multiple courses of oral tecovirimat before presenting to the emergency department for continual lesion progression. Given his AIDS, the patient was at-risk for poor response to oral treatment due to the potential for malabsorption from disruptions in his gut microbiome as well as inability to consume the recommended 25 grams of fat per dose needed for absorption. The identification of patients at-risk for severe disease is imperative as this population may be better suited for intravenous tecovirimat treatment due to the difficult parameters required for optimal absorption of oral therapy.
Cerebral venous sinus thrombosis after COVID-19 vaccination: a case report and literature review
Authors: Elfil Mohamed , Aladawi Mohammad , Balian Dmitry , Fahad Ismail , Zhou Daniel J , Villafuerte-Trisolini Brian , Diesing Thomas Scott
Published: January 2023

As COVID-19 vaccines became widely available, there have been reports of neurovascular complications. In this article, we aim to report a case of cerebral venous sinus thrombosis (CVST) induced by COVID-19 vaccination, with a literature review on similar cases as well as the potential pathophysiological mechanisms. Our case is a healthy male who developed headache, vomiting, photophobia and diplopia after receiving the Ad26.COV2.S vaccine. Fundus examination showed papilledema, and magnetic resonance imaging of the brain and cerebral veins showed CVST involving the superior sagittal sinus and right transverse sinus extending into the right jugular vein. Hypercoagulability workup was unremarkable, and the patient received immunotherapy and anticoagulation. Following this treatment, symptoms resolved, and he had no residual neurologic deficits. Developing neurologic manifestations, especially severe headaches with papilledema, after COVID-19 vaccination should warrant neuroimaging. Early recognition and management of CVST are essential for good clinical outcomes.
Cardiogenic shock secondary to stress-induced cardiomyopathy precipitated by severe diabetic ketoacidosis
Authors: Gurreri Riley , Poommipanit Paul , Alghamdi Abdullah
Published: January 2023

Stress-induced cardiomyopathy is caused by neurohormonal release of catecholamines. Although diabetic ketoacidosis (DKA) is a well-known complication of diabetes, diabetes mellitus is usually protective of stress-induced cardiomyopathy. Stress-induced cardiomyopathy secondary to DKA is extremely rare; however, cardiogenic shock is a potential complication of stress-induced cardiomyopathy. We present a rare case describing diabetic ketoacidosis leading to profound acidosis causing stress-induced cardiomyopathy and cardiogenic shock that is successfully managed with venoarterial extracorporeal membrane oxygenation in adults.
Combating the challenges of COVID-19 pandemic: Insights into molecular mechanisms, immune responses and therapeutics against SARS-CoV-2
Authors: Negi Kriti , Agarwal Meetu , Pahuja Isha , Bhardwaj Bhavya , Rawat Mansi , Bhaskar Ashima , Dwivedi Ved Prakash
Published: January 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes lethal coronavirus disease (COVID-19). SARS-CoV-2 has been the chief source of threat to public health and safety from 2019 to the present. SARS-CoV-2 caused a sudden and significant rise in hospitalization due to respiratory issues and pneumonia. We are consistently uncovering new information about SARS-CoV-2, and yet so much is to explore to implement efficient interventions to combat the emergent variants and spread of the ongoing pandemic. Information regarding the existing COVID-19 pandemic is streamlining continuously. However, clinical symptoms of SARS-CoV-2 infections spanning from asymptomatic infection to severe death-instigating disease remain consistent with preliminary reports. In this review, we have briefly introduced highlights of the COVID-19 pandemic and features of SARS-CoV-2. We have focused on current knowledge of innate and adaptive immune responses during SARS-CoV-2 infections and persisting clinical features of recovered patients. Furthermore, we have discussed how these immune responses are not tightly regulated and imbalance can direct the latter phases of COVID-19, long-COVID symptoms, and cause detrimental immunopathogenesis. COVID-19 vaccines are also discussed in detail to describe the efforts going around the world to control and prevent the infection. Overall, we have summarized the current knowledge on the immunology of SARS-CoV-2 infection and the utilization of that knowledge in the development of a suitable COVID-19 therapeutics and vaccines.
Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays in ICU Admitted Patients*
Authors: Roh David J. , Chang Tiffany R. , Kumar Aditya , Burke Devin , Torres Glenda , Xu Katherine , Yang Winni , Cottarelli Azzurra , Moore Ernest , Sauaia Angela , Hansen Kirk , Velazquez Angela , Boehme Amelia , Vrosgou Athina , Ghoshal Shivani , Park Soojin , Agarwal Sachin , Claassen Jan , Connolly E. Sander , Wagener Gebhard , Francis Richard O. , Hod Eldad
Published: January 2023

OBJECTIVES:

Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU.

DESIGN:

Observational cohort study and separate in vitro laboratory study.

SETTING:

Multicenter tertiary referral ICUs.

PATIENTS:

Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory study was performed utilizing ICH patient blood samples.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Relationships between baseline hemoglobin and ROTEM/TEG results were separately assessed across patient cohorts using Spearman correlations and linear regression models. A separate in vitro study assessed ROTEM tracing changes after serial hemoglobin modifications from ICH patient blood samples. In both our ROTEM (n = 34) and TEG (n = 239) ICH cohorts, hemoglobin concentrations directly correlated with coagulation kinetics (ROTEM r: 0.46; p = 0.01; TEG r: 0.49; p < 0.0001) and inversely correlated with clot strength (ROTEM r: –0.52, p = 0.002; TEG r: –0.40, p < 0.0001). Similar relationships were identified in perioperative ICU admitted patients (n = 121). We continued to identify these relationships in linear regression models. When manipulating ICH patient blood samples to achieve lower hemoglobin concentrations in vitro, we similarly identified that lower hemoglobin concentrations resulted in progressively faster coagulation kinetics and greater clot strength on ROTEM tracings.

CONCLUSIONS:

Lower hemoglobin concentrations have a consistent, measurable impact on ROTEM/TEG testing in ICU admitted patients, which appear to be artifactual. It is possible that patients with low hemoglobin may appear to have normal viscoelastic parameters when, in fact, they have a mild hypocoagulable state. Further work is required to determine if these tests should be corrected for a patient’s hemoglobin concentration.
Mean Arterial Pressure Targets and Patient-Important Outcomes in Critically Ill Adults: A Systematic Review and Meta-Analysis of Randomized Trials*
Authors: Carayannopoulos Kallirroi Laiya , Pidutti Andrew , Upadhyaya Yashita , Alshamsi Fayez , Basmaji John , Granholm Anders , Alhazzani Waleed , Lewis Kimberley
Published: January 2023

OBJECTIVE:

To conduct a systematic review and meta-analysis to determine whether targeting a higher mean arterial pressure (MAP) compared with a lower MAP in adults with shock results in differences in patient important outcomes.

DATA SOURCES:

We searched MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov through May 2021.

STUDY SELECTION:

Titles and abstracts were screened independently and in duplicate to identify potentially eligible studies, then full text for final eligibility. We included parallel-group randomized controlled trials in adult patients with a diagnosis of shock requiring vasoactive medications. The higher MAP group was required to receive vasoactive medications to target a higher MAP as established by study authors, whereas the lower MAP group received vasoactive medications to target lower MAP.

DATA EXTRACTION:

In triplicate, reviewers independently extracted data using a prepiloted abstraction form. Statistical analyses were conducted using the RevMan software Version 5.3.

DATA SYNTHESIS:

Six randomized controlled trials (n = 3,690) met eligibility criteria. Targeting a higher MAP (75–85 mm Hg) compared with lower MAP of 65 mm Hg resulted in no difference in mortality (relative risk [RR], 1.06; 95% CI, 0.98–1.15; I
2 = 0%; p = 0.12; moderate certainty. Targeting a higher MAP resulted in no difference in the risk of undergoing renal replacement therapy (RR, 0.96; 95% CI, 0.83–1.11; I
2 = 24%; p = 0.57; moderate certainty); however, a subgroup analysis comparing patients with and without chronic hypertension demonstrated that a higher MAP may reduce the risk of undergoing renal replacement therapy (RR, 0.83; 95% CI, 0.71–0.98; I
2 = 0%; p = 0.02).

CONCLUSIONS:

In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in mortality when a higher MAP is targeted in critically ill adult patients with shock. Further studies are needed to determine the impact of mean arterial pressure on need for renal replacement therapy in this population.
Precision Effects of Glibenclamide on MRI Endophenotypes in Clinically Relevant Murine Traumatic Brain Injury
Authors: Zusman Benjamin E. , Wu Yijen , Kochanek Patrick M. , Vagni Vincent E. , Janesko-Feldman Keri , Gerzanich Volodymyr , Simard J. Marc , Karahalios Katherine , Mihaljevic Sandra , Raikwar Sudhanshu , Rani Anupama , Rulney Jarrod , Desai Shashvat M. , Catapano Joshua , Jha Ruchira M.
Published: January 2023

OBJECTIVES:

Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion.

DESIGN:

Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult).

SETTING:

Preclinical laboratory.

SUBJECTS:

Adult male C57BL/6J mice (n = 54).

INTERVENTIONS:

Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 μg/kg)/high-dose glibenclamide (10 μg/mouse). Seven-day subcutaneous infusions (0.4 μg/hr) were continued.

MEASUREMENTS AND MAIN RESULTS:

Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10–6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial.

CONCLUSIONS:

High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.
Development of Moral Injury in ICU Professionals During the COVID-19 Pandemic: A Prospective Serial Interview Study
Authors: Kok Niek , Zegers Marieke , Fuchs Malaika , van der Hoeven Hans , Hoedemaekers Cornelia , van Gurp Jelle
Published: January 2023

OBJECTIVES:

During the COVID-19 pandemic, ICU professionals have faced moral problems that may cause moral injury. This study explored whether, how, and when moral injury among ICU professionals developed in the course of the COVID-19 pandemic.

DESIGN:

This is a prospective qualitative serial interview study.

SETTING:

Two hospitals among which one university medical center and one teaching hospital in the Netherlands.

SUBJECTS:

Twenty-six ICU professionals who worked during the COVID-19 pandemic.

INTERVENTIONS:

None.

MEASUREMENTS MAIN RESULTS:

In-depth interviews with follow-up after 6 and 12 months. In total, 62 interviews were conducted. ICU professionals narrated about anticipatory worry about life and death decisions, lack of knowledge and prognostic uncertainty about COVID-19, powerlessness and failure, abandonment or betrayal by society, politics, or the healthcare organization, numbness toward patients and families, and disorientation and self-alienation. Centrally, ICU professionals describe longitudinal processes by which they gradually numbed themselves emotionally from patients and families as well as potentially impactful events in their work. For some ICU professionals, organizational, societal, and political responses to the pandemic contributed to numbness, loss of motivation, and self-alienation.

CONCLUSIONS:

ICU professionals exhibit symptoms of moral injury such as feelings of betrayal, detachment, self-alienation, and disorientation. Healthcare organizations and ICU professionals themselves should be cognizant that these feelings may indicate that professionals might have developed moral injury or that it may yet develop in the future. Awareness should be raised about moral injury and should be followed up by asking morally injured professionals what they need, so as to not risk offering unwanted help.
Efficacy and Toxicity of Combined Inhibition of EGFR and VEGF in Patients With Advanced Non–small Cell Lung Cancer Harboring Activating EGFR Mutations
Authors: Deluce Jasna , Maj David , Verma Saurav , Breadner Daniel , Boldt Gabriel , Raphael Jacques
Published: January 2023

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways have demonstrated promising results for treatment of advanced non–small cell lung cancer. We conducted a systematic review and meta-analysis to assess the efficacy and toxicity of the combined treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF blockade for patients with advanced non–small cell lung cancer harboring activating EGFR mutations, in comparison to EGFR TKIs alone. The electronic databases were searched for relevant randomized trials between 2000 and 2022. The primary endpoints were overall survival (OS) and progression-free survival. Secondary endpoints included objective response rate (ORR), disease control rate, and grade ≥3 adverse events (AEs). The pooled hazard ratios (HR) and odds ratios were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. A total of 1528 patients from 8 trials were evaluated for analyses. The combination treatment decreased the risk of disease progression by 37% (HR=0.63; 95% CI, 0.56 to 0.72) but had no added benefit on OS compared with EGFR inhibition alone (HR=0.90; 95% CI, 0.76 to 1.05). There was no significant difference in objective response rate or disease control rate between treatments. There was a significantly increased number of AEs reported in the dual treatment arm (odds ratio=3.02; 95% CI, 1.71 to 5.31), with proteinuria and hypertension being the most significantly increased AEs. This meta-analysis suggests combined inhibition of EGFR and VEGF pathways significantly improves progression-free survival, with no OS benefit, and increases AEs. Mature OS data are needed along with results from more trials exploring this strategy with third-generation EGFR TKIs to strengthen these results.