Left ventricular remodeling in end-stage liver disease and post-transplant mortality assessed using end-diastolic pressure-volume relation analysis: Observational retrospective study.

BACKGROUND: Diastolic dysfunction is regarded as an important predictor of outcome after liver transplantation (LT). We investigated the influence of liver disease severity on left ventricular diastolic properties using end-diastolic pressure-volume relationship (EDPVR) analysis in patients with end-stage liver disease (ESLD). Association between alterations of the EDPVR and mortality after LT was evaluated. METHODS: In this observational retrospective cohort study, 3,211 patients who underwent LT for ESLD were included in analysis. Variables derived from single-beat EDPVR (diastolic stiffness-coefficient [ß] and end-diastolic volume at an end-diastolic pressure of 20 mmHg [EDVI20] indicating ventricular capacitance) were estimated using preoperative echocardiographic data. Alterations in EDPVR with increased stiffness (ß > 6.16) were categorized into 3 groups; leftward-shifted (EDVI20 <51 mL/m2), rightward-shifted (EDVI20 > 69.7 mL/m2), and intermediate (EDVI20 51-69.7 mL/m2). RESULTS: As the model for ESLD score increases, both EDVI20 and ß gradually increased, which indicated ventricular remodeling with larger capacitance and higher diastolic stiffness. Among patients with increased stiffness (ß > 6.16, n = 1,090), survival rates after LT were lower in leftward-shifted EDPVR than in rightward-shifted EDPVR (73.7% vs 82.9%; log-rank P = 0.002). In the adjusted Cox proportional hazard model, risk of cumulative all-cause mortality at 11 years was the highest in leftward-shifted EDPVR (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.27-2.92), followed by intermediate EDPVR (HR: 1.55; 95% CI: 1.12-2.26), compared with rightward-shifted EDPVR. The SHapley Additive exPlanation model revealed that the variables associated with leftward-shifted EDPVR were diabetes, female sex, old age, and hypertension. CONCLUSIONS: As ESLD advances, diastolic ventricular properties are characterized by increased EDVI20 and ß on rightward-shifted EDPVR, indicating larger capacitance and higher stiffness. However, leftward-shifted EDPVR with left ventricle remodeling failure is associated with poor post-LT survival.

Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

Relationship between Preoperative Echocardiographic Parameters and the Incidence of Postoperative Complications in Patients Undergoing Clipping of Unruptured Intracranial Aneurysms: A Retrospective Cohort Study.

Background and Objectives: Preoperative echocardiography is widely performed in patients undergoing major surgeries to evaluate cardiac functions and detect structural abnormalities. However, studies on the clinical usefulness of preoperative echocardiography in patients undergoing cerebral aneurysm clipping are limited. Therefore, this study aimed to investigate the correlation between preoperative echocardiographic parameters and the incidence of postoperative complications in patients undergoing clipping of unruptured intracranial aneurysms. Materials and Methods: Electronic medical records of patients who underwent clipping of an unruptured intracranial aneurysm from September 2018 to April 2020 were retrospectively reviewed. Data on baseline characteristics, laboratory variables, echocardiographic parameters, postoperative complications, and hospital stays were obtained. Univariable and multivariable logistic regression analyses were performed to identify independent variables related to the occurrence of postoperative complications and prolonged hospital stay (≥8 d). Results: Among 531 patients included in the final analysis, 27 (5.1%) had postoperative complications. In multivariable logistic regression, the total amount of crystalloids infused (1.002 (1.001-1.003), p = 0.001) and E/e' ratio (1.17 (1.01-1.35), p = 0.031) were significant independent factors associated with the occurrence of a postoperative complication. Additionally, the maximal diameter of a cerebral aneurysm (1.13 (1.02-1.25), p = 0.024), total amount of crystalloids infused (1.001 (1.000-1.002), p = 0.031), E/A ratio (0.22 (0.05-0.95), p = 0.042), and E/e' ratio (1.16 (1.04-1.31), p = 0.011) were independent factors related to prolonged hospitalization. Conclusions: Echocardiographic parameters related to diastolic function might be associated with postoperative complications in patients undergoing clipping of unruptured intracranial aneurysms.

Solitary osteolytic skull metastasis as the only recurrence of advanced gastric cancer: a case report and literature review.

Bone metastases from gastric cancer are very rare, and skull metastases develop in only 11.2% among patients who develop bone metastases from gastric cancer. We report a case of solitary osteolytic skull metastasis as the only recurrence of advanced gastric cancer. A 67-year-old man was referred to us with a two-month history of headache and progressive scalp swelling in the left parietal region. A right hemiparesis developed a week before admission. Thirteen months previously, he had undergone radical total gastrectomy with Roux-en-Y reconstruction. Pathological analysis indicated well-differentiated adenocarcinoma of the gastric cardia (stage IIIA: pT3N2M0). Brain magnetic resonance imaging showed a large skull metastasis in the left parietal region (approximately 65 × 54 mm). An extensive search did not reveal any other tumors. Gross total tumor resection was performed, and the biopsy revealed an adenocarcinoma, suggesting metastasis of the gastric cancer.

[Network Meta-analysis of six Chinese patent medicines for replenishing Qi and activating blood in treatment of chronic heart failure].

The efficacy of six commonly used Chinese patent medicines for replenishing Qi and activating blood in the treatment of chronic heart failure was evaluated systematically by network Meta-analysis. Randomized controlled trials(RCTs) about the treatment of chronic heart failure were searched against CNKI, Wanfang, SinoMed, PubMed, and Cochrane library. Network Meta-analysis was performed in Stata 16. A total of 154 RCTs involving 15 620 patients were eventually included. The network Meta-analysis showed that Qili Qiangxin Capsules+conventional western medicine had the highest total effective rate, followed by Tongxinluo Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, Naoxintong Capsules+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Yangxinshi Tablets+conventional western medicine, and conventional western medicine. As for left ventricular ejection fraction(LVEF), Yangxinshi Tablets+conventional western medicine had the highest value, followed by Shexiang Tongxin Drop Pills+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Tongxinluo Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, Naoxintong Capsules+conventional western medicine, and conventional western treatments. As for N-terminal pro-B type natriuretic peptide(NT-proBNP), Qishen Yiqi Drop Pills+conventional western medicine was the most effective treatment, followed by Yangxinshi Tablets+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Tongxinluo Capsules+conventional western medicine, and conventional the most effective treatment was. As for left ventricular end-diastolic diameter(LVEDD), Naoxintong Capsules+conventional western medicine was the best therapy, followed by Tongxinluo Capsules+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Yangxinshi Tablets+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, and conventional western medicine. In summary, the combination of Chinese patent medicines for replenishing Qi and activating blood with western medicines is superior to conventional western medicine alone in the treatment of chronic heart failure. It effectively improves cardiac function indicators such as LVEF, NT-proBNP, and LVEDD, and thus is worthy of popularization in clinical practice. The results of this study provide evidence-based options for the clinical treatment of chronic cardiac failure by combining the Chinese patent medicines for replenishing Qi and activating blood with western medicine.

Glucose deprivation-induced endoplasmic reticulum stress response plays a pivotal role in enhancement of TRAIL cytotoxicity.

Abnormalities of the tumor vasculature result in insufficient blood supply and development of a tumor microenvironment that is characterized by low glucose concentrations, low extracellular pH, and low oxygen tensions. We previously reported that glucose-deprived conditions induce metabolic stress and promote tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cytotoxicity. In this study, we examined whether the metabolic stress-associated endoplasmic reticulum (ER) stress response pathway plays a pivotal role in the enhancement of TRAIL cytotoxicity. We observed no significant cytotoxicity when human colorectal cancer SW48 cells were treated with various doses of TRAIL (2-100 ng/ml) for 4 h or glucose (0-25 mM) for 24 h. However, a combination of TRAIL and low glucose-induced dose-dependent apoptosis through activation of caspases (-8, -9, and -3). Studies with activating transcription factor 4 (ATF4), C/EBP-homologous protein (CHOP), p53 upregulated modulator of apoptosis (PUMA), or death receptor 5 (DR5)-deficient mouse embryonic fibroblasts or HCT116 cells suggest that the ATF4-CHOP-PUMA axis and the ATF4-CHOP-DR5 axis are involved in the combined treatment-induced apoptosis. Moreover, the combined treatment-induced apoptosis was completely suppressed in BH3 interacting-domain death agonist (Bid)- or Bcl-2-associated X protein (Bax)-deficient HCT116 cells, but not Bak-deficient HCT116 cells. Interestingly, the combined treatment-induced Bax oligomerization was suppressed in PUMA-deficient HCT116 cells. These results suggest that glucose deprivation enhances TRAIL-induced apoptosis by integrating the ATF4-CHOP-PUMA axis and the ATF4-CHOP-DR5 axis, consequently amplifying the Bid-Bax-associated mitochondria-dependent pathway.

Appraisal of Cardiac Ejection Fraction With Liver Disease Severity: Implication in Post-Liver Transplantation Mortality.

BACKGROUND AND AIMS: Enhanced sympathetic nervous activation and peripheral vasodilation in end-stage liver disease (ESLD) may limit the importance of left ventricular ejection fraction (LVEF) as an influential prognosticator. We sought to understand the LVEF and cardiac dimensions in ESLD patients in order to define the LVEF threshold to predict all-cause mortality after liver transplantation (LT). APPROACH AND RESULTS: Data were collected prospectively from the Asan LT Registry between 2008 and 2016, and outcomes were retrospectively reviewed. LVEF, end-diastolic volume index (EDVI), and end-diastolic elastance (Eed) were measured by preoperative echocardiography. Of 2,799 patients, 452 (16.2%) had LVEF ≤ 60%, with 29 (1.0%) having LVEF < 55% and 269 (9.6%) had LVEF ≥ 70%. Over a median of 5.4-year follow-up, 329 (11.8%) patients died: 104 (3.7%) died within 90 days. LVEF (range, 30%-81%) was directly proportionate to Model for End-stage Liver Disease (MELD) scores, an index of liver disease severity, in survivors but showed a fixed flat-line pattern in nonsurvivors (interaction P = 0.004 between groups), with lower EDVI (P = 0.013) and higher Eed (P = 0.001) in the MELD ≥ 20 group. Patients with LVEF ≤ 60% had higher 90-day (13% vs. 7.4%; log rank, P = 0.03) and median 5.4-year (26.7% vs. 16.2%; log rank, P = 0.003) mortality rates in the MELD ≥ 20 group, respectively, compared to those with LVEF > 60%. Specifically, in the MELD > 35 group, median 5.4-year mortality rate was 53.3% in patients with LVEF ≤ 60% versus 24% in those with LVEF > 60% (log rank P < 0.001). By contrast, mortality rates of LVEF ≤ 60% and > 60% were similar in the MELD < 20 group (log rank P = 0.817). CONCLUSIONS: LVEF ≤ 60% is strongly associated with higher post-LT mortality rates in the MELD ≥ 20 group, indicating the need to appraise both LVEF and liver disease severity simultaneously. Enhanced diastolic elastance with low EDVI provides insights into pathogenesis of low LVEF in nonsurvivors with MELD ≥ 20.

BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis.

Ferroptosis is considered a distinctive form of cell death compared to other types of death such as apoptosis. It is known to result from iron-dependent accumulation of lipid peroxides rather than caspase activation. However, we reported recently that ferroptosis interplays with apoptosis. In this study, we investigated a possible mechanism of this interplay between ferroptosis and apoptosis. Results from our studies reveal that combined treatment of the ferroptotic agent erastin and the apoptotic agent TRAIL effectively disrupted mitochondrial membrane potential (ΔΨm) and subsequently promoted caspase activation. The alterations of mitochondrial membrane potential are probably due to an increase in oligomerization of BAX and its accumulation at the mitochondria during treatment with erastin and TRAIL. Interestingly, the combined treatment-promoted apoptosis was effectively inhibited in BAX-deficient HCT116 cells, but not BAK-deficient cells. These results indicate that the BAX-associated mitochondria-dependent pathway plays a pivotal role in erastin-enhanced TRAIL-induced apoptosis.

Intramuscular dexmedetomidine and oral chloral hydrate for pediatric sedation for electroencephalography: A propensity score-matched analysis.

BACKGROUND: Intramuscular dexmedetomidine can be used for pediatric sedation without requiring intravenous access and has advantages for electroencephalography by inducing natural sleep pathway, but only a limited number of studies compared the efficacy of intramuscular dexmedetomidine with oral chloral hydrate. AIMS: To compare the efficacy and safety of intramuscular dexmedetomidine and oral chloral hydrate used for sedation during electroencephalography in pediatric patients. METHODS: We reviewed the medical records of pediatric patients who underwent sedation for electroencephalography between January 2015 and December 2016. Initial doses of dexmedetomidine and chloral hydrate were 3 mcg/kg and 50 mg/kg, respectively; second doses (1 mcg/kg and 50 mg/kg, respectively) were administered if adequate sedation was not achieved. Demographic data, time of sedative administration, time of sedation and awakening, and time of arrival at recovery room and discharge were analyzed. RESULTS: Out of a total of 1239 patients, 125 patients had received dexmedetomidine and 1114 had received chloral hydrate. After 1:1 propensity score matching, the dexmedetomidine and chloral hydrate groups each had 118 patients. Testing completion rate with a single dose of medication was higher in the dexmedetomidine group (91.5% vs 71.2%; mean difference [95% CI] 20.3 [10.8-29.9]; P < .0001; Pearson chi-square value = 16.09). Sedation onset time was shorter in the dexmedetomidine group as well (16.6 ± 13.0 minutes vs 41.5 ± 26.8 minutes; mean difference [95% CI] 24.8 [19.1-30.6]; P < .0001; T = 8.27). On the contrary, the duration of recovery was longer in the dexmedetomidine group (35.5 ± 40.2 minutes vs 18.5 ± 30.7 minutes; mean difference [95% CI] 18.6 [8.8-28.5]; P = .0002; T = -2.82). Total residence time was not significantly different between the two groups (125.8 ± 40.6 minutes vs 122.1 ± 42.2 minutes, mean difference [95% CI] 5.21 [6.1-16.5], P = .3665 T = 0.04). CONCLUSIONS: Intramuscular dexmedetomidine showed higher sedation success rate and shorter time to achieving the desired sedation level compared with oral chloral hydrate and thus may be an effective alternative for oral chloral hydrate in pediatric patients requiring sedation for electroencephalography.

Real-Time Monitoring of Blood Pressure Using Digitalized Pulse Arrival Time Calculation Technology for Prompt Detection of Sudden Hypertensive Episodes During Laryngeal Microsurgery: Retrospective Observational Study.

BACKGROUND: Laryngeal microsurgery (LMS) is often accompanied by a sudden increase in blood pressure (BP) during surgery because of stimulation around the larynx. This sudden change in the hemodynamic status is not immediately reflected in a casual cuff-type measurement that takes intermittent readings every 3 to 5 min. OBJECTIVE: This study aimed to investigate the potential of pulse arrival time (PAT) as a marker for a BP surge, which usually occurs in patients undergoing LMS. METHODS: Intermittent measurements of BP and electrocardiogram (ECG) and photoplethysmogram (PPG) signals were recorded during LMS. PAT was defined as the interval between the R-peak on the ECG and the maximum slope on the PPG. Mean PAT values before and after BP increase were compared. PPG-related parameters and the correlations between changes in these variables were calculated. RESULTS: BP surged because of laryngoscopic manipulation (mean systolic BP [SBP] from 115.3, SD 21.4 mmHg, to 159.9, SD 25.2 mmHg; P<.001), whereas PAT decreased significantly (from mean 460.6, SD 51.9 ms, to 405.8, SD 50.1 ms; P<.001) in most of the cases. The change in SBP showed a significant correlation with the inverse of the PAT (r=0.582; P<.001). Receiver-operating characteristic curve analysis indicated that an increase of 11.5% in the inverse of the PAT could detect a 40% increase in SBP, and the area under the curve was 0.814. CONCLUSIONS: During LMS, where invasive arterial catheterization is not always possible, PAT shows good correlation with SBP and may, therefore, have the potential to identify abrupt BP surges during laryngoscopic manipulations in a noninvasive manner.

Ferroptosis-inducing agents enhance TRAIL-induced apoptosis through upregulation of death receptor 5.

Ferroptosis is considered genetically and biochemically distinct from other forms of cell death. In this study, we examined whether ferroptosis shares cell death pathways with other types of cell death. When human colon cancer HCT116, CX-1, and LS174T cells were treated with ferroptotic agents such as sorafenib (SRF), erastin, and artesunate, data from immunoblot assay showed that ferroptotic agents induced endoplasmic reticulum (ER) stress and the ER stress response-mediated expression of death receptor 5 (DR5), but not death receptor 4. An increase in the level of DR5, which is activated by binding to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and initiates apoptosis, was probably responsible for synergistic apoptosis when cells were treated with ferroptotic agent in combination with TRAIL. This collateral effect was suppressed in C/EBP (CCAAT-enhancer-binding protein)-homologous protein (CHOP)-deficient mouse embryonic fibroblasts or DR5 knockdown HCT116 cells, but not in p53-deficient HCT116 cells. The results from in vitro studies suggest the involvement of the p53-independent CHOP/DR5 axis in the synergistic apoptosis during the combinatorial treatment of ferroptotic agent and TRAIL. The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor-bearing mice.

Risk stratification of myocardial injury after liver transplantation in patients with computed tomographic coronary angiography-diagnosed coronary artery disease.

We aimed to determine if the severity of computed tomographic coronary angiography (CTCA)-diagnosed coronary artery disease (CAD) is associated with postliver transplantation (LT) myocardial infarction (MI) within 30 days and early mortality. We retrospectively evaluated 2118 consecutive patients who underwent CAD screening using CTCA. Post-LT type-2 MI, elicited by oxygen supply-and-demand mismatch within a month after LT, was assessed according to the severity of CTCA-diagnosed CAD. Obstructive CAD (>50% narrowing, 9.2% prevalence) was identified in 21.7% of patients with 3 or more known CAD risk factors of the American Heart Association. Post-LT MI occurred in 60 (2.8%) of total patients in whom 90-day mortality rate was 16.7%. Rates of post-LT MI were 2.1%, 3.1%, 3.4%, 4.3%, and 21.4% for normal, nonobstructive CAD, and 1-, 2-, and 3-vessel obstructive CAD, respectively. Two-vessel or 3-vessel obstructive CAD showed a 4.9-fold higher post-LT MI risk compared to normal coronary vessels. The sensitivity and negative predictive value of obstructive CAD in detecting post-LT MI were, respectively, 20% and 97.5%. In conclusion, negative CTCA finding in suspected patients can successfully exclude post-LT MI, whereas proceeding with invasive angiography is needed to further risk-stratify in patients with significant CTCA-diagnosed CAD. Prognostic role of CTCA in predicting post-LT MI needs further research.

Neutrophil-to-lymphocyte ratio is a predictor of early graft dysfunction following living donor liver transplantation.

BACKGROUND & AIMS: Early allograft dysfunction (EAD) is predictive of poor graft and patient survival following living donor liver transplantation (LDLT). Considering the impact of the inflammatory response on graft injury extent following LDLT, we investigated the association between neutrophil-to-lymphocyte ratio (NLR) and EAD, 1-year graft failure, and mortality following LDLT, and compared it to C-reactive protein (CRP), procalcitonin, platelet-to-lymphocyte ratio and the Glasgow prognostic score. METHODS: A total of 1960 consecutive adult LDLT recipients (1531/429 as development/validation cohort) were retrospectively evaluated. Cut-offs were derived using the area under the receiver operating characteristic curve (AUROC), and multivariable regression and Cox proportional hazard analyses were performed. RESULTS: The risk of EAD increased proportionally with increasing NLR, and the NLR AUROC was 0.73, similar to CRP and procalcitonin and higher than the rest. NLR ≥ 2.85 (best cut-off) showed a significantly higher EAD occurrence (20.5% vs 5.8%, P < 0.001), higher 1-year graft failure (8.2% vs 4.9%, log-rank P = 0.009) and higher 1-year mortality (7% vs 4.5%, log-rank P = 0.039). NLR ≥ 2.85 was an independent predictor of EAD (odds ratio, 1.89 [1.26-2.84], P = 0.002) after multivariable adjustment, whereas CRP and procalcitonin were not. Increasing NLR was independently associated with higher 1-year graft failure and mortality (both P < 0.001). Consistent results in the validation cohort strengthened the prognostic value of NLR. CONCLUSIONS: Preoperative NLR ≥ 2.85 predicted higher risk of EAD, 1-year graft failure and 1-year mortality following LDLT, and NLR was superior to other parameters, suggesting that preoperative NLR may be a practical index for predicting graft function following LDLT.

TCTP regulates spindle microtubule dynamics by stabilizing polar microtubules during mouse oocyte meiosis.

Dynamic changes in spindle structure and function are essential for maintaining genomic integrity during the cell cycle. Spindle dynamics are highly dependent on several microtubule-associated proteins that coordinate the dynamic behavior of microtubules, including microtubule assembly, stability and organization. Here, we show that translationally controlled tumor protein (TCTP) is a novel microtubule-associated protein that regulates spindle dynamics during meiotic maturation. TCTP was expressed and widely distributed in the cytoplasm with strong enrichment at the spindle microtubules during meiosis. TCTP was found to be phosphorylated during meiotic maturation, and was exclusively localized to the spindle poles. Knockdown of TCTP impaired spindle organization without affecting chromosome alignment. These spindle defects were mostly due to the destabilization of the polar microtubules. However, the stability of kinetochore microtubules attached to chromosomes was not affected by TCTP knockdown. Overexpression of a nonphosphorylable mutant of TCTP disturbed meiotic maturation, stabilizing the spindle microtubules. In addition, Plk1 was decreased by TCTP knockdown. Taken together, our results demonstrate that TCTP is a microtubule-associating protein required to regulate spindle microtubule dynamics during meiotic maturation in mouse oocytes.

Peroxiredoxins are required for spindle assembly, chromosome organization, and polarization in mouse oocytes.

Peroxiredoxins (Prxs) are highly conserved antioxidant enzymes and are implicated in multiple biological processes; however, their function in oocyte meiosis has not been studied. Here we show that inhibition of Prx I and II results in spindle defects, chromosome disorganization, and impaired polarization in mouse oocytes. Prx I was specifically localized at the spindle, whereas Prx II was enriched at the oocyte cortex and chromosomes. Inhibition of Prx activity with conoidin A disturbed assembly of the microtubule organizing center (MTOC) through Aurora A regulation, leading to defects in spindle formation. Moreover, conoidin A impaired actin filament and cortical granule (CG) distribution, disrupting actin cap and CG formation, respectively. Conoidin A also increased DNA damage without significantly increasing reactive oxygen species (ROS) levels, suggesting that the effects of conoidin A on meiotic maturation are not likely associated with ROS scavenging pathways. Therefore, our data suggest that Prxs are required for spindle assembly, chromosome organization, and polarization during meiotic maturation.

Eccentric localization of catalase to protect chromosomes from oxidative damages during meiotic maturation in mouse oocytes.

The maintenance of genomic integrity and stability is essential for the survival of every organism. Unfortunately, DNA is vulnerable to attack by a variety of damaging agents. Oxidative stress is a major cause of DNA damage because reactive oxygen species (ROS) are produced as by-products of normal cellular metabolism. Cells have developed eloquent antioxidant defense systems to protect themselves from oxidative damage along with aerobic metabolism. Here, we show that catalase (CAT) is present in mouse oocytes to protect the genome from oxidative damage during meiotic maturation. CAT was expressed in the nucleus to form unique vesicular structures. However, after nuclear envelope breakdown, CAT was redistributed in the cytoplasm with particular focus at the chromosomes. Inhibition of CAT activity increased endogenous ROS levels, but did not perturb meiotic maturation. In addition, CAT inhibition produced chromosomal defects, including chromosome misalignment and DNA damage. Therefore, our data suggest that CAT is required not only to scavenge ROS, but also to protect DNA from oxidative damage during meiotic maturation in mouse oocytes.

Dynamics of histone H3 phosphorylation at threonine 3 during meiotic maturation in mouse oocytes.

Various histone residues are post-translationally modified during the cell cycle. Among these, histone H3 phosphorylation at threonine 3 (H3T3ph) is newly characterized and has been considered to be crucial for chromosome dynamics during mitosis. However, little is known about the role of H3T3ph during mouse oocyte maturation. In the present study, we examined H3T3ph expression and localization during oocyte meiosis. Our results showed that H3T3ph was tightly associated with condensed chromosomes during meiotic maturation. H3T3ph along the chromosome arms was dissociated at anaphase/telophase I, but centromeric H3T3ph remained intact. Moreover, the inhibition of H3T3ph with the small molecule inhibitors CHR-6494 and 5-Itu impaired segregation of homologous chromosomes during meiosis. Partial inhibition of H3T3ph revealed that centromeric Aurora B/C kinase is sufficient to complete meiosis I, but Aurora B/C kinase along the chromosome arms is required to ensure accurate homologous chromosome segregation. Therefore, our results demonstrate that H3T3ph is a universal regulator of chromosome dynamics during oocyte meiosis and mitosis.

Association between De Ritis ratio and intraoperative blood transfusion in patients undergoing surgical clipping of unruptured intracranial aneurysms: a single center, retrospective, propensity score-matched study.

BACKGROUND: Although elective surgery for unruptured intracranial aneurysms (UIA) has increased, few studies have evaluated the risk factors for transfusion during UIA surgery. We evaluated the association between the preoperative De Ritis ratio (aspartate transaminase/alanine transaminase) and the incidence of intraoperative transfusion in patients who had undergone surgical UIA clipping. METHODS: Patients who underwent surgical clipping of UIA were stratified into two groups according to the preoperative De Ritis ratio cutoff levels (< 1.54 and ≥ 1.54), and the propensity score (PS)-matching analysis was performed to compare the incidence of intraoperative transfusion. Logistic regression analyses were performed to determine the risk factors for intraoperative transfusion. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were performed to verify the improvement in the intraoperative transfusion predictive model upon addition of the De Ritis ratio. RESULTS: Intraoperative transfusion incidence was 15.4% (77/502). We observed significant differences in the incidence of intraoperative transfusion (16.2% vs. 39.7%, P = 0.004) between the groups after matching. In the logistic regression analyses, the De Ritis ratio ≥ 1.54 was an independent risk factor for transfusion (odds ratio [OR]: 3.04, 95% CI [1.53, 6.03], P = 0.002). Preoperative hemoglobin (Hb) value was a risk factor for transfusion (OR: 0.33, 95% CI [0.24, 0.47], P < 0.001). NRI and IDI analyses showed that the De Ritis ratio improved the intraoperative blood transfusion predictive models (P = 0.031 and P = 0.049, respectively). CONCLUSIONS: De Ritis ratio maybe a significant risk factor for intraoperative transfusion in UIA surgery.

Treatment Strategy of Unruptured Intracranial Aneurysms in Octogenarian Patients: A Single-Institution Experience.

AIM: To share our clinical insights into octogenarian patients with unruptured intracranial aneurysms (UIAs) and evaluate the treatment strategies for this demographic. MATERIAL AND METHODS: A retrospective analysis was conducted on data from 134 patients with a follow-up exceeding 6 months, all enrolled in this study. We assessed the incidence rates (IRs) of aneurysm growth and rupture, along with potential predictors of aneurysm growth. RESULTS: Among the 134 patients, 99 (73.9%) underwent conservative management, 25 (18.7%) received coiling, and 10 (7.5%) underwent clipping. The mean age of the cohort was 81.8 years. The middle cerebral artery was the most common location for aneurysms. The mean aneurysm size was 4.9 mm, with sizes significantly larger in the treatment groups (coiling and clipping) compared to the observation group (4.4 mm in the observation group; 5.9 and 7.4 mm in the coiling and clipping groups, respectively). The proportion of aneurysms with a daughter sac was higher in the treatment groups compared to the observation group (6.1% vs. 44% [coiling] and 50% [clipping]). The IR of aneurysm growth was 5.9 per 100 person-years, and that of aneurysm rupture was 0.8 per 100 person-years. No factors were statistically significant for aneurysm growth. CONCLUSION: Age alone, especially in individuals over 80 years old, may not be a contraindication for UIA treatment. We recommend considering treatment in octogenarians with high-risk aneurysm features, such as a large aneurysm and the presence of a daughter sac, as the complication rates are low.

Correlations between heart sound components and hemodynamic variables.

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.