Continuous Right Ventricular Pressure Monitoring in Cardiac Surgery.

OBJECTIVE: Right ventricular (RV) dysfunction in cardiac surgery can lead to RV failure, which is associated with increased morbidity and mortality. Abnormal RV function can be identified using RV pressure monitoring. The primary objective of the study is to determine the proportion of patients with abnormal RV early to end-diastole diastolic pressure gradient (RVDPG) and abnormal RV end-diastolic pressure (RVEDP) before initiation and after cardiopulmonary bypass (CPB) separation. The secondary objective is to evaluate if RVDPG before CPB initiation is associated with difficult and complex separation from CPB, RV dysfunction, and failure at the end of cardiac surgery. DESIGN: Prospective study. SETTING: Tertiary care cardiac institute. PARTICIPANTS: Cardiac surgical patients. INTERVENTION: Cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Automated electronic quantification of RVDPG and RVEDP were obtained. Hemodynamic measurements were correlated with cardiac and extracardiac parameters from transesophageal echocardiography and postoperative complications. Abnormal RVDPG was present in 80% of the patients (n = 105) at baseline, with a mean RVEDP of 14.2 ± 3.9 mmHg. Patients experienced an RVDPG > 4 mmHg for a median duration of 50.2% of the intraoperative period before CPB initiation and 60.6% after CPB separation. A total of 46 (43.8%) patients had difficult/complex separation from CPB, 18 (38.3%) patients had RV dysfunction, and 8 (17%) had RV failure. Abnormal RVDPG before CPB was not associated with postoperative outcome. CONCLUSION: Elevated RVDPG and RVEDP are common in cardiac surgery. RVDPG and RVEDP before CPB initiation are not associated with RV dysfunction and failure but can be used to diagnose them.

[Baicalin induces ferroptosis in HepG2 cells by inhibiting ROS-mediated PI3K/Akt/FoxO3a signaling pathway].

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.

The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (223Ra) combined with new-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapies remains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of 223Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bone mCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), five retrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the 223Ra+NHA combination group and the 223Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91-2.34, P = 0.66), but the incidences in both the 223Ra+NHA combination group (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01) and the 223Ra monotherapy group (OR: 2.24, 95% CI: 1.23-4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, in the meta-analysis involving only RCTs, there was no difference between the 223Ra monotherapy group and the NHA monotherapy group (OR: 1.14, 95% CI: 0.22-5.95, P = 0.88), while the difference between the 223Ra+NHA combination group and the NHA monotherapy group remained significant (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-free survival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significant difference. Our results indicate that the combination of 223Ra with NHAs was well tolerated in bone mCRPC patients compared to 223Ra monotherapy, even though the incidence of fracture was higher in patients who received 223Ra than that among those who received NHA monotherapy. More evidence is needed to explore the safety and efficiency of 223Ra combination therapies.

Right Ventricular Outflow Tract Obstruction in Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is a cause of hemodynamic instability that can occur in several situations, including cardiac surgery, lung transplantation, and thoracic surgery, and in critically ill patients. The timely diagnosis of RVOTO is important because it requires specific considerations, including the adverse effects of positive inotropes, and depending on the etiology, the requirement for urgent surgical intervention. METHODS: The objective of this systematic review and meta-analysis was to determine the prevalence of RVOTO in adult patients, and the distribution of all reported cases by etiology. RESULTS: Of 233 available reports, there were 229 case reports or series, and 4 retrospective cohort studies, with one study also reporting a prospective cohort. Of 291 reported cases of RVOTO, 61 (21%) were congenital, 56 (19%) were iatrogenic, and 174 (60%) were neither congenital nor iatrogenic (including intracardiac tumour). The mechanism of RVOTO was an intrinsic obstruction in 169 cases (58%), and an extrinsic obstruction in 122 cases (42%). A mechanical obstruction causing RVOTO was present in 262 cases (90%), and 29 cases of dynamic RVOTO (10%) were reported. In the 5 included cohorts, with a total of 1122 patients, the overall prevalence was estimated to be 4.0% (1%-9%). CONCLUSIONS: RVOTO, though rare, remains clinically important, and therefore, multicentre studies are warranted to better understand the prevalence, causes, and consequences of RVOTO.

CONTEXTE: L'obstruction de la chambre de chasse du ventricule droit (OCCVD) est une cause d'instabilité hémodynamique qui peut survenir dans plusieurs situations, y compris une chirurgie cardiaque, une transplantation pulmonaire ou une chirurgie thoracique, ou encore chez des patients en phase critique. Il est important que le diagnostic d'OCCVD soit posé rapidement, car d'une part cette affection exige la prise en compte d'éléments particuliers, y compris les effets indésirables des agents inotropes positifs et, d'autre part, en fonction de l'étiologie, une intervention chirurgicale d'urgence pourrait être nécessaire. MÉTHODOLOGIE: L'objectif de cette revue systématique associée à une méta-analyse était de déterminer la prévalence de l'OCCVD chez les patients adultes ainsi que la distribution de tous les cas rapportés en fonction de leur étiologie. RÉSULTATS: Sur les 233 rapports disponibles, on comptait 229 études ou séries de cas, et quatre études de cohortes rétrospectives, dont une qui présentait également les résultats d'une cohorte prospective. Sur 291 cas d'OCCVD rapportés, 61 (21 %) étaient d'origine congénitale, 56 (19 %) étaient d'origine iatrogène et 174 (60 %) avaient une origine qui n'était ni congénitale ni iatrogène (dont une tumeur intracardiaque). Le mécanisme de l'OCCVD était une obstruction intrinsèque dans 169 cas (58 %), et une obstruction extrinsèque dans 122 cas (42 %). Une obstruction mécanique causant l'OCCVD était présente dans 262 cas (90 %), et 29 cas d'OCCVD dynamique (10 %) ont été rapportés. Dans les 5 cohortes incluses, comptant au total 1 122 patients, la prévalence globale était estimée à 4,0 % (de 1 % à 9 %). CONCLUSIONS: L'OCCVD, malgré sa rareté, n'en est pas moins importante sur le plan clinique; la réalisation d'études multicentriques serait donc justifiée pour permettre de mieux comprendre la prévalence, les causes et les conséquences de cette affection.

Right Ventricular Outflow Tract Obstruction in the Intensive Care Unit: A Case Report of 2 Patients.

Right ventricular outflow tract obstruction (RVOTO) is a rare cause of hemodynamic instability in the intensive care unit (ICU) after cardiac surgery. We report the first cases of RVOTO diagnosed in the ICU using continuous right ventricular pressure waveform monitoring. Our 2 cases reflect both mechanical and dynamic causes of obstruction, each of which require different approaches to treatment. Inotrope use can exacerbate RVOTO caused by dynamic etiology, whereas surgery is usually the treatment of choice for mechanical obstructions. Inability to recognize RVOTO or the correct etiology can lead to hemodynamic compromise and poor outcomes.

Right Ventricular Epicardial Pacing Postcardiac Surgery Can Cause Dynamic Right Ventricular Outflow Tract Obstruction: A Case Report.

Dynamic right ventricular outflow tract obstruction is rare in the cardiac surgical population. Significant obstruction developing in the perioperative period can contribute to systemic hemodynamic instability. We describe 2 cases of dynamic right ventricular outflow tract obstruction that developed immediately after separation from cardiopulmonary bypass, due to temporary right ventricular epicardial pacing. Both patients had systemic hypotension which improved once ventricular pacing was discontinued. We discuss the recognition of right ventricular outflow tract obstruction as a contributing factor to hemodynamic instability, as well as the importance of identifying the underlying cause such as to institute appropriate management in these patients.

Doppler Interrogation of the Femoral Vein in the Critically Ill Patient: The Fastest Potential Acoustic Window to Diagnose Right Ventricular Dysfunction?

OBJECTIVES: To report the use of common femoral vein Doppler interrogation as a simple technique to diagnose right ventricular dysfunction. DESIGN: Case report. SETTING: Cardiac surgical ICU. PATIENTS: Postoperative cardiac surgical patients. INTERVENTIONS: Common femoral pulsed-wave and color Doppler examination associated with hepatic, portal, and renal venous Doppler measurement were obtained in both patients and before and after treatment in patient number 1. In addition, right ventricular pressure waveform examination was obtained in patient number 2. MEASUREMENTS AND MAIN RESULTS: The technique to obtain common femoral venous Doppler is described. Two cases of patients presenting with right ventricular dysfunction and fluid overload with portal and renal venous congestion in the perioperative period undergoing complex multivalvular cardiac surgery are presented. Hemodynamic waveform monitoring was performed alongside echocardiographic, hepatic, and renal venous flow Doppler assessment, and spectral Doppler profiles of the common femoral veins were examined. Those findings were useful in confirming our diagnosis and guiding our response to treatment. An algorithm was developed and tested on two additional hemodynamically unstable patients. CONCLUSIONS: Doppler examination of the common femoral vein is a simple, fast, and noninvasive technique that could be useful to rule in the presence of right ventricular dysfunction with venous congestion and help guide the management of such patients.

Insight into the Superior Lithium Storage Properties of Ultrafine CoO Nanoparticles Confined in a 3 D Bimodal Ordered Mesoporous Carbon CMK-9 Anode.

Ultrafine CoO particles immobilized into the mesopores of three-dimensional cubic bimodal ordered mesoporous carbon CMK-9 is successfully prepared by using a combination of nanocasting and wet-impregnation methods. It is found that the cubic bimodal interconnected mesoporous framework of CMK-9 plays a crucial role in achieving the excellent electrochemical performances by assisting the rapid mass and charge transfer. Among the prepared nanocomposites, CoO(10)@CMK-9 delivers a discharge capacity of 830 mAh g-1 after 200 cycles at a current density of 100 mA g-1 in lithium-ion batteries. At a higher current density of 1000 mA g-1 , the anode presents an outstanding discharge capacity of 636 mAh g-1 after 200 cycles. In sodium-ion batteries, the anode provides a discharge capacity of 296 mAh g-1 after 250 cycles at a current density of 100 mA g-1 . The remarkable performances of CoO(10)@CMK-9 demonstrate the promising potentials of the nanocomposite as the anode for rechargeable batteries.

Carboxyl-terminal modulator protein positively regulates Akt phosphorylation and acts as an oncogenic driver in breast cancer.

Akt activation has been implicated broadly in tumorigenesis, but the basis for its dysregulation in cancer cells is incompletely understood. In this study, we sought to clarify a regulatory role for the Akt-binding carboxy-terminal modulator protein (CTMP), which has been controversial. In evaluating CTMP expression in paired normal-tumor specimens of 198 patients with breast cancer, we found that CTMP was upregulated in breast tumors, where it was associated with poor patient survival. Notably, CTMP expression also correlated positively with Akt phosphorylation in breast cancer clinical specimens and cell lines. Furthermore, ectopic expression of CTMP promoted cell proliferation and enhanced the tumorigenic properties of estrogen-dependent breast cancer cells. This effect was correlated with increased sensitivity to insulin-induced Akt phosphorylation, which is mediated primarily by the phosphoinositide 3-kinase-Akt pathway. In contrast, short hairpin RNA-mediated silencing of endogenous CTMP decreased the proliferation of estrogen-dependent or estrogen-independent breast cancer cells. Mechanistic investigations defined the N-terminal domain of CTMP at amino acids 1 to 64 as responsible for Akt binding. Taken together, our results firmly corroborate the concept that CTMP promotes Akt phosphorylation and functions as an oncogenic molecule in breast cancer.