Prediction of preload dependency using phenylephrine-induced peripheral perfusion index during general anaesthesia: a prospective observational study.

BACKGROUND: Tracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke volume is dependent upon preload. Changes in stroke volume induced by phenylephrine administration can be used to predict preload dependency. The change in the peripheral perfusion index derived from photoplethysmography signals reportedly corresponds with changes in stroke volume in situations such as body position changes in the operating room. Thus, the peripheral perfusion index can be used as a non-invasive potential alternative to stroke volume to predict preload dependency. Herein, we aimed to determine whether changes in perfusion index induced by the administration of phenylephrine could be used to predict preload dependency. METHODS: We conducted a prospective single-centre observational study. The haemodynamic parameters and perfusion index were recorded before and 1 and 2 min after administering 0.1 mg of phenylephrine during post-induction hypotension in patients scheduled to undergo surgery. Preload dependency was defined as a stroke volume variation of ≥ 12% before phenylephrine administration at a mean arterial pressure of < 65 mmHg. Patients were divided into four groups according to total peripheral resistance and preload dependency. RESULTS: Forty-two patients were included in this study. The stroke volume in patients with preload dependency (n = 23) increased after phenylephrine administration. However, phenylephrine administration did not impact the stroke volume in patients without preload dependency (n = 19). The perfusion index decreased regardless of preload dependency. The changes in the perfusion index after phenylephrine administration exhibited low accuracy for predicting preload dependency. Based on subgroup analysis, patients with high total peripheral resistance tended to exhibit increased stroke volume following phenylephrine administration, which was particularly prominent in patients with high total peripheral resistance and preload dependency. CONCLUSION: The findings of the current study revealed that changes in the perfusion index induced by administering 0.1 mg of phenylephrine could not predict preload dependency. This may be attributed to the different phenylephrine-induced stroke volume patterns observed in patients according to the degree of total peripheral resistance and preload dependency. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000049994 on 9/01/2023).

Low-Volume Acute Normovolemic Hemodilution Does Not Reduce Allogeneic Red Blood Cell Transfusion in Cardiac Surgery in the Modern Era of Patient Blood Management: A Propensity Score-Matched Cohort Study.

OBJECTIVES: Patients undergoing cardiac surgery often require blood transfusions, which are associated with increased morbidity and mortality. Patient blood management (PBM) strategies, including acute normovolemic hemodilution (ANH), have been implemented to minimize allogeneic transfusion requirements. Older studies suggested that ANH is associated with reduced transfusions; however, its effectiveness in the modern era of PBM remains unclear. DESIGN: This was a retrospective cohort study. SETTING: The study was held at a single university hospital. PARTICIPANTS: 542 patients who underwent elective cardiac surgery with cardiopulmonary bypass (CPB) using low-priming-volume circuits between January 2017 and March 2022. INTERVENTIONS: Patients who received ANH were matched with those who did not receive ANH, using propensity scores. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion of patients who received perioperative red blood cell (RBC) transfusion. Of the 542 eligible patients, 49 ANH cases were propensity-score matched to 97 controls. The median ANH volume was 450 mL (IQR, 400-800 mL). There was no significant difference in perioperative RBC transfusion rates between the 2 groups (24.5% in the ANH group vs 30.9% in the control group, p = 0.42). The odds ratio for perioperative RBC transfusion in the ANH group versus the control group was 0.72 (95% CI, 0.32-1.55, p = 0.42). CONCLUSIONS: Low-volume ANH was not associated with a significant reduction in perioperative allogeneic RBC transfusion during cardiac surgery with CPB using low-priming-volume circuits. The benefits of low-volume ANH in reducing the requirement for RBC transfusion in the modern era of PBM may be smaller than reported previously.

Characteristics of pulmonary artery catheter use in multicenter ICUs in Japan and the association with mortality: a multicenter cohort study using the Japanese Intensive care PAtient Database.

BACKGROUND: It has been 50 years since the pulmonary artery catheter was introduced, but the actual use of pulmonary artery catheters in recent years is unknown. Some randomized controlled trials have reported no causality with mortality, but some observational studies have been published showing an association with mortality for patients with cardiogenic shock, and the association with a pulmonary artery catheter and mortality is unknown. The aim of this study was to investigate the utilization of pulmonary artery catheters (PACs) in the intensive care unit (ICU) and to examine their association with mortality, taking into account differences between hospitals. METHODS: This is a retrospective analysis using the Japanese Intensive care PAtient Database, a multicenter, prospective, observational registry in Japanese ICUs. We included patients aged 16 years or older who were admitted to the ICU for reasons other than procedures. We excluded patients who were discharged within 24 h or had missing values. We compared the prognosis of patients with and without PAC. The primary outcome was hospital mortality. We performed propensity score analysis to adjust for baseline characteristics and hospital characteristics. RESULTS: Among 184,705 patients in this registry from April 2015 to December 2020, 59,922 patients were included in the analysis. Most patients (94.0%) with a PAC in place had cardiovascular disease. There was a wide variation in the frequency of PAC use between hospitals, from 0 to 60.3% (median 14.4%, interquartile range 2.2-28.6%). Hospital mortality was not significantly different between the PAC use group and the non-PAC use group in patients after adjustment for propensity score analysis (3.9% vs 4.3%; difference, - 0.4%; 95% CI - 1.1 to 0.3; p = 0.32). Among patients with cardiac disease, those with post-open-heart surgery and those in shock, hospital mortality was also not significantly different between the two groups (3.4% vs 3.7%, p = 0.45, 1.7% vs 1.7%, p = 0.93, 4.8% vs 4.9%, p = 0.87). CONCLUSIONS: The frequency of PAC use varied among hospitals. PAC use for ICU patients was not associated with lower hospital mortality after adjusting for differences between hospitals.

Association between Plasma Ascorbic Acid Levels and Postoperative Delirium in Older Patients Undergoing Cardiovascular Surgery: A Prospective Observational Study.

BACKGROUND: The incidence of delirium is high in older patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Intraoperative tissue hypoperfusion and re-reperfusion injury, which generate reactive oxygen species (ROS), are suggested to induce delirium. Ascorbic acid is an excellent antioxidant and may reduce organ damage by inhibiting the production of ROS. This prospective observational study aimed to measure pre- and postoperative plasma ascorbic acid levels and examine their association with delirium. METHODS: Patients older than 70 years of age scheduled for elective cardiovascular surgery using CPB were enrolled. From September 2020 to December 2021, we enrolled 100 patients, and the data of 98 patients were analyzed. RESULTS: In total, 31 patients developed delirium, while 67 did not. Preoperative plasma ascorbic acid levels did not differ between the non-delirium and delirium groups (6.0 ± 2.2 vs. 5.5 ± 2.4 µg/mL, p = 0.3). Postoperative plasma ascorbic acid levels were significantly different between the groups (2.8 [2.3-3.5] vs. 2.3 [1.6-3.3] µg/mL, p = 0.037). CONCLUSIONS: In patients who undergo cardiovascular surgery with CPB, lower postoperative plasma ascorbic acid levels may be associated with the development of delirium.

A low peripheral perfusion index can accurately detect prolonged capillary refill time during general anesthesia: A prospective observational study.

Background: Capillary refill time (CRT) is the gold standard for evaluating peripheral organ perfusion; however, intraoperative CRT measurement is rarely used because it cannot be conducted continuously, and it is difficult to perform during general anesthesia. The peripheral perfusion index (PI) is another noninvasive method for evaluating peripheral perfusion. The PI can easily and continuously evaluate peripheral perfusion and could be an alternative to CRT for use during general anesthesia. This study aimed to determine the cutoff PI value for low peripheral perfusion status (prolonged CRT) by exploring the relationship between CRT and the PI during general anesthesia. Methods: We enrolled 127 surgical patients. CRT and the PI were measured in a hemodynamically stable state during general anesthesia. A CRT >3 s indicated a low perfusion status. Results: Prolonged CRT was observed in 27 patients. The median PI values in the non-prolonged and prolonged CRT groups were 5.0 (3.3-7.9) and 1.5 (1.2-1.9), respectively. There was a strong negative correlation between the PI and CRT (r = -0.706). The area under the receiver operating characteristic curve generated for the PI was 0.989 (95% confidence interval, 0.976-1.0). The cutoff PI value for detecting a prolonged CRT was 1.8. Conclusion: A PI <1.8 could accurately predict a low perfusion status during general anesthesia in the operating room. A PI <1.8 could be used to alert the possibility of a low perfusion status in the operating room. Trial Registration: University Hospital Medical Information Network (UMIN000043707; retrospectively registered on March 22, 2021, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno = R000049905).

Changes in peripheral perfusion index during intraoperative end-expiratory occlusion tests do not predict the response to fluid administration in patients undergoing lung protective ventilation.

INTRODUCTION: The end-expiratory occlusion test (EEOT) may predict the response to fluid administration in patients undergoing lung-protective ventilation, but arterial catheter insertion is necessary to evaluate changes in stroke volume (SV). The peripheral perfusion index is a potential noninvasive alternative to evaluate SV. The aim of this study is to investigate whether changes in perfusion index during an intraoperative EEOT can predict the response to fluid administration in patients undergoing lung-protective ventilation (tidal volume 7 ml/kg predicted body weight). METHODS: Forty-one elective surgical patients were enrolled. The SV and perfusion index were recorded before (baseline), during a 40-s EEOT and after volume expansion (250 ml of lactated Ringer's solution over 10 min). Patients with an increase in SV greater than 10% after volume expansion were defined as responders. ΔPI (change in perfusion index between baseline and 20 (ΔPI20) or 40 s (ΔPI40) after the beginning of EEOT were calculated using: ΔPI20 (%) = [(PI at 20 s after EEOT beginning - PIbaseline)/PIbaseline] × 100, ΔPI40 (%) = [(PI at 40 s after EEO beginning - PIbaseline)/PIbaseline] × 100). RESULTS: Sixteen patients were responders, and 25 were non-responders. The area under the receiver operating characteristics curves generated for ΔPI20 and ΔPI40 to predict response to a fluid challenge were 0.561 (95% CI 0.374-0.749) and 0.688 (95% CI 0.523-0.852), respectively. CONCLUSION: Changes in perfusion index during intraoperative EEOT in patients undergoing lung-protective ventilation (7 ml/kg) were unable to predict the response to fluid administration.

Correlation between activated clotting time monitoring and heparin concentration measurement in a patient with antiphospholipid syndrome during cardiac valve surgery: a case report.

BACKGROUND: Anticoagulation management of patients with antiphospholipid syndrome (APS) undergoing cardiac surgery is challenging due to the prolongation of activated clotting time (ACT). Currently, no study has compared the utility of ACT monitoring using the Hemochron Jr. Signature+ and that of heparin concentration management using the Hemostasis Management System (HMS) Plus in patients with APS. CASE PRESENTATION: A 71-year-old woman with APS was scheduled to undergo an aortic valve replacement for aortic regurgitation. The ACT was measured using the Hemochron Jr. Signature+, and the heparin concentration was measured concurrently using the HMS Plus. ACT over 480 s corresponded to an adequate heparin concentration during cardiopulmonary bypass. The clinical course was uneventful, and no thrombotic or hemorrhagic complications were observed. CONCLUSION: In the present patient with APS, the Hemochron Jr. Signature+ was useful as an anticoagulation management during cardiac valve surgery.

Genome analysis of three novel lytic Vibrio coralliilyticus phages isolated from seawater, Okinawa, Japan.

Three novel Vibrio phages were isolated from seawater in Okinawa. The Vibrio phage RYC infected Vibrio coralliilyticus SWA 07, while Vibrio phages CKB-S1 and CKB-S2 infected the coral pathogen V. coralliilyticus P1 (LMG 23696). The Vibrio phages CKB-S1 and CKB-S2 displayed head-tail structures whereas the Vibrio phage RYC showed a tailless non-enveloped capsid. All these Vibrio phages contained linear and double-stranded DNA. The whole genome sequencing revealed that Vibrio phage RYC has a larger genome size compared to Vibrio phages CKB-S1 and CKB-S2, and six tRNAs genes were found only in Vibrio phage RYC. Genome-wide comparison showed that Vibrio phage CKB-S1 was closely related, but was not identical, to Vibrio parahaemolyticus phages VP16T and VP16C. Meanwhile, the Vibrio phages RYC and CKB-S2 did not show high genome-wide similarity to any phages. These results suggest that the Vibrio phages CKB-S1, CKB-S2 and RYC are novel phages, which need further exploration, especially for their potential applications in phage therapy.

GPAT2, a mitochondrial outer membrane protein, in piRNA biogenesis in germline stem cells.

piRNA (PIWI-interacting RNA) is a germ cell-specific small RNA in which biogenesis PIWI (P-element wimpy testis) family proteins play crucial roles. MILI (mouse Piwi-like), one of the three mouse PIWI family members, is indispensable for piRNA production, DNA methylation of retrotransposons presumably through the piRNA, and spermatogenesis. The biogenesis of piRNA has been divided into primary and secondary processing pathways; in both of these MILI is involved in mice. To analyze the molecular function of MILI in piRNA biogenesis, we utilized germline stem (GS) cells, which are derived from testicular stem cells and possess a spermatogonial phenotype. We established MILI-null GS cell lines and their revertant, MILI-rescued GS cells, by introducing the Mili gene with Sendai virus vector. Comparison of wild-type, MILI-null, and MILI-rescued GS cells revealed that GS cells were quite useful for analyzing the molecular mechanisms of piRNA production, especially the primary processing pathway. We found that glycerol-3-phosphate acyltransferase 2 (GPAT2), a mitochondrial outer membrane protein for lysophosphatidic acid, bound to MILI using the cells and that gene knockdown of GPAT2 brought about impaired piRNA production in GS cells. GPAT2 is not only one of the MILI bound proteins but also a protein essential for primary piRNA biogenesis.

Chloroplast phylogeny indicates that bryophytes are monophyletic.

Opinions on the basal relationship of land plants vary considerably and no phylogenetic tree with significant statistical support has been obtained. Here, we report phylogenetic analyses using 51 genes from the entire chloroplast genome sequences of 20 representative green plant species. The analyses, using translated amino acid sequences, indicated that extant bryophytes (mosses, liverworts, and hornworts) form a monophyletic group with high statistical confidence and that extant bryophytes are likely sisters to extant vascular plants, although the support for monophyletic vascular plants was not strong. Analyses at the nucleotide level could not resolve the basal relationship with statistical confidence. Bryophyte monophyly inferred using amino acid sequences has a good statistical foundation and is not rejected statistically by other data sets. We propose bryophyte monophyly as the currently best hypothesis.

Sequence-specific binding of the Schizosaccharomyces pombe His1 protein to fission yeast telomeric DNA.

Sequence-specific protein-DNA interaction is critical for many important cellular processes such as transcription, DNA replication, and chromosome segregation. Identification of additional proteins that bind to DNA in a sequence-specific manner will contribute to the understanding of the mechanism of molecular recognition between protein and DNA. We found that the ATP phosphoribosyl transferase His1, which catalyzes the first step in histidine biosynthesis, is bound to both single- and double-stranded telomeric DNA. Competition experiments revealed that His1 is bound to a fission yeast telomeric DNA in a sequence-specific manner. Previously identified sequence-specific telomere-binding proteins contain Myb domain. In contrast, Schizosaccharomyces pombe His1 does not contain Myb domain. These findings indicate that His1 has a novel DNA-recognition domain.

Competition between the Rad50 complex and the Ku heterodimer reveals a role for Exo1 in processing double-strand breaks but not telomeres.

The Mre11-Rad50-Nbs1(Xrs2) complex and the Ku70-Ku80 heterodimer are thought to compete with each other for binding to DNA ends. To investigate the mechanism underlying this competition, we analyzed both DNA damage sensitivity and telomere overhangs in Schizosaccharomyces pombe rad50-d, rad50-d pku70-d, rad50-d exo1-d, and pku70-d rad50-d exo1-d cells. We found that rad50 exo1 double mutants are more methyl methanesulfonate (MMS) sensitive than the respective single mutants. The MMS sensitivity of rad50-d cells was suppressed by concomitant deletion of pku70+. However, the MMS sensitivity of the rad50 exo1 double mutant was not suppressed by the deletion of pku70+. The G-rich overhang at telomere ends in taz1-d cells disappeared upon deletion of rad50+, but the overhang reappeared following concomitant deletion of pku70+. Our data suggest that the Rad50 complex can process DSB ends and telomere ends in the presence of the Ku heterodimer. However, the Ku heterodimer inhibits processing of DSB ends and telomere ends by alternative nucleases in the absence of the Rad50-Rad32 protein complex. While we have identified Exo1 as the alternative nuclease targeting DNA break sites, the identity of the nuclease acting on the telomere ends remains elusive.

RNA editing in hornwort chloroplasts makes more than half the genes functional.

RNA editing in chloroplasts alters the RNA sequence by converting C-to-U or U-to-C at a specific site. During the study of the complete nucleotide sequence of the chloroplast genome from the hornwort Anthoceros formosae, RNA editing events have been systematically investigated. A total of 509 C-to-U and 433 U-to-C conversions are identified in the transcripts of 68 genes and eight ORFs. No RNA editing is seen in any of the rRNA but one tRNA suffered a C-to-U conversion at an anticodon. All nonsense codons in 52 protein-coding genes and seven ORFs are removed in the transcripts by U-to-C conversions, and five initiation and three termination codons are created by C-to-U conversions. RNA editing in intron sequence suggests that editing can precede intercistronic processing. The sequence complementary to the edited site is proposed as a distant cis-recognition element.

The complete nucleotide sequence of the hornwort (Anthoceros formosae) chloroplast genome: insight into the earliest land plants.

It is generally believed that bryophytes are the earliest land plants. However, the phylogenetic relationships among bryophytes, including mosses, liverworts and hornworts, are not clearly resolved. To obtain more information on the earliest land plants, we determined the complete nucleotide sequence of the chloroplast genome from the hornwort Anthoceros formosae. The circular double-stranded DNA of 161 162 bp is the largest genome ever reported among land plant chloroplasts. It contains 76 protein, 32 tRNA and 4 rRNA genes and 10 open reading frames (ORFs), which are identical with the chloroplast genome of the other green plants analyzed. The major difference is a larger inverted repeat than that of the liverwort Marchantia, Anthoceros contains an excess of ndhB and rps7 genes and the 3' exon of rps12. The genes matK and rps15, commonly found in the chloroplast genomes of land plants, are pseudogenes. The intron of rrn23 is the first finding in the known chloroplast genomes of land plants. A striking feature of the hornwort chloroplast is that more than half of the protein-coding genes have nonsense codons, which are converted into sense codons by RNA editing. Maximum-likelihood (ML) analysis, based on 11 518 amino acid sites of 52 proteins encoded in the chloroplast genomes of the green plants, placed liverworts as the sister to all other land plants.

Kinetic analysis of the effect of (-)-epigallocatechin gallate on the DNA scission induced by Fe(II).

The DNA strand scission induced by Fe(II) in a citrate buffer solution and the effect of (-)-epigallocatechin gallate (EGCg) were kinetically analyzed. The rate of consumption of dissolved oxygen by Fe(II) in each of these solutions was measured and paralleled that DNA scission. Coordinated EGCg accelerated these reactions. Curves of the time-course characteristics of DNA scission were simulated by using the rate constant of oxygen consumption and by assuming that scission with the hydroxyl radical (OH), which was formed from the dissolved oxygen, proceeded competitively with the scavenging of OH by citrate, Cl- ions and EGCg added. Free EGCg acted as a DNA scission inhibitor to scavenge OH, in contrast to the case of the coordinated one. This analysis is useful for estimating the rate constant of the reaction between an antioxidant and OH, and might provide a new method for measuring the OH-scavenging activity.