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British Journal of Anaesthesia Jun 2024
PubMed: 38944552
DOI: 10.1016/j.bja.2024.05.014 -
Journal of Cardiothoracic and Vascular... Apr 2024Carotid artery stenting (CAS) may be performed by transfemoral or transcervical (TCAR) approaches and with a variety of anesthetic techniques. No current literature...
OBJECTIVES
Carotid artery stenting (CAS) may be performed by transfemoral or transcervical (TCAR) approaches and with a variety of anesthetic techniques. No current literature clearly supports one anesthetic method over another. We therefore sought to evaluate the outcomes of CAS procedures based on anesthetic approach.
DESIGN
Retrospective cohort study.
SETTING
American College of Surgeons National Surgical Quality Improvement Program database from 2011 to 2018.
PARTICIPANTS
All individuals undergoing CAS during the study period.
INTERVENTIONS
Anesthetic type (locoregional versus general [GA]).
MEASUREMENTS AND MAIN RESULTS
Locoregional anesthesia for CAS was used for 754 (65.5%) patients, with the remainder under GA. Demographic variables were comparable, as were the incidence of symptomatic presentation, high-risk anatomy or physiology, severity of the stenosis, and presence/severity of contralateral carotid disease. There was no difference in composite outcome (stroke, myocardial infarction [MI], and death) (7.0% v 6.1%, p = 0.53). The GA group had lower odds ratio of MI (0.12, p = 0.0362) but higher odds ratio of death (3.33, p = 0.008) and postoperative pneumonia (3.87, p = 0.0083), although on multivariable analysis the risk of death appeared confounded by respiratory variables. Multivariable and propensity score-weighted analyses did not identify a significant association of GA with the composite outcome.
CONCLUSIONS
In patients undergoing CAS in the National Surgical Quality Improvement Program, GA was not associated with the composite outcome but was associated with increased rates of postoperative pneumonia and decreased rates of MI. Further investigation should attempt to better clarify these relationships.
PubMed: 38944543
DOI: 10.1053/j.jvca.2024.04.023 -
Biochemical Pharmacology Jun 2024The approval of immune checkpoint inhibitors (ICIs) has revolutionized the management of metastatic renal cell carcinoma (RCC), introducing several ICI-based...
The approval of immune checkpoint inhibitors (ICIs) has revolutionized the management of metastatic renal cell carcinoma (RCC), introducing several ICI-based combinations as the new standard of care for affected patients. Nonetheless, monotherapy with antiangiogenic tyrosine kinase inhibitors (TKIs), such as pazopanib or sunitinib, still represents a first-line treatment option for selected patients belonging to the favorable risk group according to the International mRCC Database Consortium (IMDC) model. After TKI monotherapy, the main second-line option is represented by ICI monotherapy with the anti-Programmed Death Receptor 1(PD-1) nivolumab To date, the expected clinical outcomes are similar with pazopanib or sunitinib and there is no clear indication for selecting one TKI over the other. Moreover, their impact on subsequent ICI treatment outcomes is not well defined, yet. Based on these premises, we investigated the immunomodulatory activity of these drugs in vitro and in vivo.Both TKIs induced Programmed Cell Death Ligand-1 (PD-L1) expression and soluble PD-L1 release in RCC cells, and hampered T cell activation, reducing cytokine production and the proportion of activated T cells. Nevertheless, in a syngeneic co-culture system with peripheral blood mononuclear cells (PBMCs) and tumor cells, incubation with anti-PD-1 antibody following TKIs treatment significantly restored T cell function, potentiating the cytotoxic effects against tumor cells. Pazopanib and sunitinib followed by anti-PD-1 antibody produced a comparable inhibition of tumor growth in a RCC syngeneic mouse model. Our findings suggest that pazopanib and sunitinib, showing similar immunomodulatory effects, may have a comparable impact on the subsequent effectiveness of PD-1/PD-L1 blockade.
PubMed: 38944394
DOI: 10.1016/j.bcp.2024.116397 -
Journal of Infection and Chemotherapy :... Jun 2024Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are...
BACKGROUND
Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are often treated with steroids, require intensive care unit (ICU) treatment, and may therefore be at risk for HCMV infection. However, which factors predispose severely ill patients with COVID-19 to HCMV infection and the prognostic value of such infections remain largely unexplored. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe or critical COVID-19 and evaluate the relationship between HCMV infection and mortality.
METHODS AND FINDINGS
We used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and their contribution to mortality in patients with COVID-19. Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3-1.7% depending on the definition of HCMV infection. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV infection. Furthermore, HCMV infection was associated with patient mortality independent of the observed risk factors for death.
CONCLUSIONS
HCMV infection is a notable complication in patients with severe or critical COVID-19 who are admitted to the ICU or receive steroids, immunosuppressants, and blood transfusion and can significantly increase mortality risk.
PubMed: 38944381
DOI: 10.1016/j.jiac.2024.06.015 -
Journal of Theoretical Biology Jun 2024The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a...
The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing the finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.
PubMed: 38944380
DOI: 10.1016/j.jtbi.2024.111893 -
Comparative Biochemistry and... Jun 2024Di-2-ethylhexyl phthalate (DEHP) is the most commonly preferred synthetic organic chemical in plastics and its products for making them ductile, flexible and durable. As...
Concerted monoamine oxidase activity following exposure to di-2-ethylhexyl phthalate is associated with aggressive neurobehavioral response and neurodegeneration in zebrafish brain.
Di-2-ethylhexyl phthalate (DEHP) is the most commonly preferred synthetic organic chemical in plastics and its products for making them ductile, flexible and durable. As DEHP is not chemically bound to the macromolecular polymer of plastics, it can be easily leached out to accumulate in food and environment. Our recent report advocated that exposure to DEHP significantly transformed the innate bottom-dwelling and scototaxis behaviour of zebrafish. Our present study aimed to understand the possible role of DEHP exposure pertaining towards the development of aggressive behaviour and its association with amplified monoamine oxidase activity and neurodegeneration in the zebrafish brain. As heightened monoamine oxidase (MAO) is linked with genesis of aggressive behaviour, our observation also coincides with DEHP-persuaded aggressive neurobehavioral transformation in zebrafish. Our preliminary findings also showed that DEHP epitomized as a prime factor in transforming native explorative behaviour and genesis of aggressive behaviour through oxidative stress induction and changes in the neuromorphology in the periventricular grey zone (PGZ) of the zebrafish brain. With the finding demarcating towards heightened chromatin condensation in the PGZ of zebrafish brain, our further observation by immunohistochemistry showed a profound augmentation in apoptotic cell death marker cleaved caspase 3 (CC3) expression following exposure to DEHP. Our further observation by immunoblotting study also demarcated a temporal augmentation in CC3 and tyrosine hydroxylase expression in the zebrafish brain. Therefore, the gross findings of the present study delineate the idea that chronic exposure to DEHP is associated with MAO-instigated aggressive neurobehavioral transformation and neurodegeneration in the zebrafish brain.
PubMed: 38944366
DOI: 10.1016/j.cbpc.2024.109970 -
Developmental Biology Jun 2024During neural development, sculpting of early formed circuits by cell death and synaptic pruning is necessary to generate a functional and efficient nervous system. This...
During neural development, sculpting of early formed circuits by cell death and synaptic pruning is necessary to generate a functional and efficient nervous system. This allows for the establishment of rudimentary circuits which necessitate early organism survival to later undergo subsequent refinement. These changes facilitate additional specificity to stimuli which can lead to increased behavioral complexity. In multiple species, Rohon-Beard neurons (RBs) are the earliest mechanosensory neurons specified and are critical in establishing a rudimentary motor response circuit. Sensory input from RBs gradually becomes redundant as dorsal root ganglion (DRG) neurons develop and integrate into motor circuits. Previous studies demonstrate that RBs undergo a dramatic wave of cell death concurrent with development of the DRG. However, contrary to these studies, we show that neurogenin1 (ngn1) RBs do not undergo a widespread wave of programmed cell death during early zebrafish development and instead persist until at least 15 days post fertilization. Starting at 2 dpf, we also observed a dramatic medialization and shrinkage of ngn1 RB somas along with a gradual downregulation of ngn1 in RBs. This alters a fundamental premise of early zebrafish neural development and opens new avenues to explore mechanisms of RB function, persistence, and circuit refinement.
PubMed: 38944329
DOI: 10.1016/j.ydbio.2024.06.020 -
Chemico-biological Interactions Jun 2024The toxicity of silica nanoparticles (SiNPs) to lung is known. We previously demonstrated that exposure to SiNPs promoted pulmonary impairments, but the precise...
The toxicity of silica nanoparticles (SiNPs) to lung is known. We previously demonstrated that exposure to SiNPs promoted pulmonary impairments, but the precise pathogenesis remains elucidated. Ferroptosis has now been identified as a unique form of oxidative cell death, but whether it participated in SiNPs-induced lung injury remains unclear. In this work, we established a rat model with sub-chronic inhalation exposure of SiNPs via intratracheal instillation, and conducted histopathological examination, iron detection, and ferroptosis-related lipid peroxidation and protein assays. Moreover, we evaluated the effect of SiNPs on epithelial ferroptosis, possible mechanisms using in vitro-cultured human bronchial epithelial cells (16HBE) cells, and also assessed the ensuing impact on fibroblast activation for fibrogenesis. Consequently, fibrotic lesions occurred in the rat lungs, concomitantly by enhanced lipid peroxidation, iron overload, and ferroptosis. Consistently, the in vitro data showed SiNPs triggered oxidative stress and caused the accumulation of lipid peroxides, resulting in ferroptosis. Importantly, the mechanistic investigation revealed miR-21-5p as a key player in the epithelial ferroptotic process induced by SiNPs via targeting GCLM for GSH depletion. Of note, ferrostatin-1 could greatly suppress ferroptosis and alleviate epithelial injury and ensuing fibroblast activation by SiNPs. In conclusion, our findings first revealed SiNPs triggered epithelial ferroptosis through miR-21-5p/GCLM signaling and thereby promoted fibroblast activation for fibrotic lesions, and highlighted the therapeutic potential of inhibiting ferroptosis against lung impairments upon SiNPs exposure.
PubMed: 38944326
DOI: 10.1016/j.cbi.2024.111121 -
The French Journal of Urology Jun 2024Enhanced recovery after surgery (ERAS) is a combination of multimodal pathways to improve surgical outcomes. Recommendations for radical cystectomy have been published...
BACKGROUND
Enhanced recovery after surgery (ERAS) is a combination of multimodal pathways to improve surgical outcomes. Recommendations for radical cystectomy have been published by the ERAS society for the cystectomy but a lack of evidence is observed for urological procedures such as nephrectomy (Ne) and radical prostatectomy (RP). The aim of our study was to evaluate the impact of enhanced recovery protocol implementation for Ne ad RP at our academic institution.
METHODS
We performed a retrospective, monocentric, comparative analysis, pre and post implementation of an enhanced recovery protocol for patients undergoing robotic-assisted radical prostatectomy or nephrectomy (partial or total) for cancer. The primary endpoint was the mean length of stay (LOS). Secondary endpoints included 30-days readmission, postoperative complications, 90 days survival, and oncologic outcome at 6 months.
RESULTS
We included 264 patients between January, 2019, and December, 2020. Statistical analysis was performed separately by type of surgery. The LOS of patients included in the ERP protocol was decreased on average by 1,3 days IC95% [ -2.50; -0.08], p<0.001 for nephrectomies and by 2.2 days IC95% [-3.72; -0.62] p<0.001 for prostatectomies, compared to non-ERP patients. There were no more re-admisson, death or oncologic recurrence.
CONCLUSION
In our experience, ERP for oncological nephrectomy and prostatectomy reduced the length of stay, without increasing postoperative complications and readmission.
PubMed: 38944244
DOI: 10.1016/j.fjurol.2024.102674 -
Spanish Journal of Psychiatry and... Jun 2024
PubMed: 38944243
DOI: 10.1016/j.sjpmh.2024.06.003