Thromboelastographic evaluation after cardiac surgery optimizes transfusion requirements in the intensive care unit: a single-center retrospective cohort study using an inverse probability weighting method.

OBJECTIVE: There are no reports from Japan showing the effects of using the thromboelastography algorithm on transfusion requirements after Intensive Care Unit (ICU) admission, and post-implementation knowledge regarding the thromboelastography algorithm under the Japanese healthcare system is insufficient. Therefore, this study aimed to clarify the effect of the TEG6s thromboelastography algorithm on transfusion requirements for patients in the ICU after cardiac surgery. METHODS: We retrospectively compared the requirements for blood transfusion up to 24 h after ICU admission using the thromboelastography algorithm (January 2021 to April 2022) (thromboelastography group; n = 201) and specialist consultation with surgeons and anesthesiologists (January 2018 to December 2020) (non-thromboelastography group; n = 494). RESULTS: There were no significant between-group differences in terms of age, height, weight, body mass index, operative procedure, duration of surgery or cardiopulmonary bypass, body temperature, or urine volume during surgical intervention. Moreover, there was no significant between-group difference in the amount of drainage at 24 h after ICU admission. However, crystalloid and urine volumes were significantly higher in the thromboelastography group than in the non-thromboelastography group. Additionally, fresh-frozen plasma (FFP) transfusion volumes were significantly lower in the thromboelastography group. However, there were no significant between-group differences in red blood cell count or platelet transfusion volume. After variable adjustment, the amount of FFP used from the operating room to 24 h after ICU admission was significantly reduced in the thromboelastography group. CONCLUSIONS: The thromboelastography algorithm optimized transfusion requirements at 24 h after admission to the ICU following cardiac surgery.

Ceftriaxone-associated Biliary Pseudolithiasis with Elderly Type 1 Diabetes Mellitus: Two Case Reports.

Biliary pseudolithiasis is a ceftriaxone (CTRX)-induced complication, but the risk in cases of elderly type 1 diabetes mellitus (T1DM) is unclear. Case 1: A 78-year-old woman with T1DM complicated by diabetic autonomic neuropathy was admitted with pneumonia and treated with CTRX. On day 8, biliary pseudolithiasis and cholecystitis were observed. Case 2: an 80-year-old woman with T1DM was suspected of having a urinary tract infection and treated with CTRX. After a week, she developed asymptomatic biliary pseudolithiasis with gastroparesis. CTRX-associated biliary pseudolithiasis was thus noted in these cases of elderly T1DM. CTRX should be cautiously administered, especially in elderly T1DM patients with diabetic autonomic neuropathy.

Accuracy of a noninvasive estimated continuous cardiac output measurement under different respiratory conditions: a prospective observational study.

PURPOSE: The estimated continuous cardiac output (esCCO) system was recently developed as a noninvasive hemodynamic monitoring alternative to the thermodilution cardiac output (TDCO). However, the accuracy of continuous cardiac output measurements by the esCCO system compared to TDCO under different respiratory conditions remains unclear. This prospective study aimed to assess the clinical accuracy of the esCCO system by continuously measuring the esCCO and TDCO. METHODS: Forty patients who had undergone cardiac surgery with a pulmonary artery catheter were enrolled. We compared the esCCO with TDCO from mechanical ventilation to spontaneous respiration through extubation. Patients undergoing cardiac pacing during esCCO measurement, those receiving treatment with an intra-aortic balloon pump, and those with measurement errors or missing data were excluded. In total, 23 patients were included. Agreement between the esCCO and TDCO measurements was evaluated using Bland-Altman analysis with a 20 min moving average of the esCCO. RESULTS: The paired esCCO and TDCO measurements (939 points before extubation and 1112 points after extubation) were compared. The respective bias and standard deviation (SD) values were 0.13 L/min and 0.60 L/min before extubation, and - 0.48 L/min and 0.78 L/min after extubation. There was a significant difference in bias before and after extubation (P < 0.001); the SD before and after extubation was not significant (P = 0.315). The percentage errors were 25.1% before extubation and 29.6% after extubation, which is the criterion for acceptance of a new technique. CONCLUSION: The accuracy of the esCCO system is clinically acceptable to that of TDCO under mechanical ventilation and spontaneous respiration.

Evolution and functionalization of vitellogenin genes in the termite Reticulitermes speratus.

Eusociality has been commonly observed in distinct animal lineages. The reproductive division of labor is a particular feature, achieved by the coordination between fertile and sterile castes within the same nest. The sociogenomic approach in social hymenopteran insects indicates that vitellogenin (Vg) has undergone neo-functionalization in sterile castes. Here, to know whether Vgs have distinct roles in nonreproductive castes in termites, we investigated the unique characteristics of Vgs in the rhinotermitid termite Reticulitermes speratus. The four Vgs were identified from R. speratus (RsVg1-4), and RsVg3 sequences were newly identified using the RACE method. Molecular phylogenetic analysis supported the monophyly of the four termite Vgs. Moreover, the termites Vg1-3 and Vg4 were positioned in two different clades. The  dN/dS ratios indicated that the branch leading to the common ancestor of termite Vg4 was under weak purifying selection. Expression analyses among castes (reproductives, workers, and soldiers) and females (nymphs, winged alates, and queens) showed that RsVg1-3 was highly expressed in fertile queens. In contrast, RsVg4 was highly expressed in workers and female nonreproductives (nymphs and winged adults). Localization of RsVg4 messenger RNA was confirmed in the fat body of worker heads and abdomens. These results suggest that Vg genes are functionalized after gene duplication during termite eusocial transition and that Vg4 is involved in nonreproductive roles in termites.

Effect of intensive insulin therapy on inflammatory response after cardiac surgery using bedside artificial pancreas: A propensity score-matched analysis.

BACKGROUND: Perioperative hyperglycemia leads to poor postoperative clinical outcomes, including compromised immune function, cardiovascular events, and mortality. The optimal perioperative blood glucose levels during cardiac surgery remain unclear. A closed-loop glycemic control system (artificial pancreas, target blood glucose range:120-150 mg/dl) prevents postoperative inflammatory response more effectively than conventional insulin therapy (<200 mg/dl). However, the clinical effects of intensive insulin therapy with strict glycemic control (80-110 mg/dl) are controversial. This study aimed to determine whether intensive insulin therapy would further suppress postoperative inflammatory reactions. METHODS: This study analyzed 262 patients who underwent cardiovascular surgery with cardiopulmonary bypass. The patients were divided into two groups according to their target blood glucose range: 80-110 mg/dl and 120-150 mg/dl. The primary outcome was the difference in the C-reactive protein levels between the two groups. RESULTS: Propensity score matching resulted in 95 patients in each group based on their covariates. There was no difference in the postoperative maximum C-reactive protein levels between the two groups (14.81 ± 5.93 mg/dl vs. 14.34 ± 5.52 mg/dl; p = 0.571) following propensity score matching. Hypoglycemia did not occur during intensive insulin therapy. CONCLUSIONS: Intensive insulin therapy following cardiac surgery with cardiopulmonary bypass did not demonstrate significant advantages in the suppression of postoperative inflammatory reactions compared to that with mild glycemic control. However, intensive insulin therapy using an artificial pancreas was found to be safe, with no hypoglycemic events.

A comprehensive risk assessment for nocturnal hypoglycemia in geriatric patients with type 2 diabetes: A single-center case-control study.

AIMS: To evaluate the overall association between clinically significant nocturnal hypoglycemia (CsNH) and risk factors in geriatric patients with type 2 diabetes. METHODS: Overall, 606 geriatric with type 2 diabetes were evaluated for CsNH using Freestyle Libre Pro® (Abbott Diabetes Care, Tokyo, Japan) during October 2018-February 2020. We defined CsNH as blood glucose level <54 mg/dL (3.0 mmol/L). We investigated clinical characteristics and efficacies of hypoglycemic agents and insulin and analyzed CsNH risk factors using univariate and multivariate logistic regression analyses. RESULTS: We enrolled 152 patients each for the CsNH and non-nocturnal hypoglycemia groups. Insulin use (OR = 3.77 [95 % CI: 1.92-7.67]; P = 0.0002), age (OR = 1.06 [95 % CI: 1.01-1.12]; P = 0.0492), estimated glomerular filtration rate (OR = 0.97 [95 % CI: 0.95-0.98]; P = 0.0492), and fasting blood glucose level (OR = 0.94 [95 % CI: 0.91-0.94]; P < 0.0001) were independent CsNH risk factors. The combined results demonstrated a higher predictability of CsNH than each of the individual risk factors. CONCLUSIONS: We identified risk factors that could help predict CsNH in geriatric patients with type 2 diabetes and demonstrated a comprehensive risk factor assessment.

Machine-learning-based quality-level-estimation system for inspecting steel microstructures.

Quality control of special steel is accomplished through visual inspection of its microstructure based on microscopic images. This study proposes an 'automatic-quality-level-estimation system' based on machine learning. Visual inspection of this type is sensory-based, so training data may include variations in judgments and training errors due to individual differences between inspectors, which makes it easy for a drop in generalization performance to occur due to overfitting. To deal with this issue, we here propose the preprocessing of inspection images and a data augmentation technique. Preprocessing reduces variation in images by extracting features that are highly related to the level of quality from inspection images. Data augmentation, meanwhile, suppresses the problem of overfitting when training with a small number of images by taking into account information on variation in judgment values obtained from on-site experience. While the correct-answer rate for judging the quality level by an inspector was about 90%, the proposed method achieved a correct-answer rate of 92.5%, which indicates that the method shows promise for practical applications.

Genomic and transcriptomic analyses of the subterranean termite Reticulitermes speratus: Gene duplication facilitates social evolution.

Termites are model social organisms characterized by a polyphenic caste system. Subterranean termites (Rhinotermitidae) are ecologically and economically important species, including acting as destructive pests. Rhinotermitidae occupies an important evolutionary position within the clade representing a transitional taxon between the higher (Termitidae) and lower (other families) termites. Here, we report the genome, transcriptome, and methylome of the Japanese subterranean termite Reticulitermes speratus Our analyses highlight the significance of gene duplication in social evolution in this termite. Gene duplication associated with caste-biased gene expression was prevalent in the R. speratus genome. The duplicated genes comprised diverse categories related to social functions, including lipocalins (chemical communication), cellulases (wood digestion and social interaction), lysozymes (social immunity), geranylgeranyl diphosphate synthase (social defense), and a novel class of termite lineage-specific genes with unknown functions. Paralogous genes were often observed in tandem in the genome, but their expression patterns were highly variable, exhibiting caste biases. Some of the assayed duplicated genes were expressed in caste-specific organs, such as the accessory glands of the queen ovary and the frontal glands of soldier heads. We propose that gene duplication facilitates social evolution through regulatory diversification, leading to caste-biased expression and subfunctionalization and/or neofunctionalization conferring caste-specialized functions.

Surgical Site Infections and Inflammatory Reaction After Cardiac Surgery; Bedside Artificial Pancreas Versus Conventional Insulin Therapy: A Propensity Score-Matched Analysis.

OBJECTIVES: Perioperative hyperglycemia is associated with poor postoperative recovery, including compromised immune function and increased risk of infection. A closed-loop glycemic control system (artificial pancreas) has demonstrated strict safe perioperative glycemic control without hypoglycemia risk. The authors hypothesized that the artificial pancreas would reduce surgical site infections (SSIs) and postoperative inflammatory reactions. This study aimed to assess the effect of the artificial pancreas on SSIs and C-reactive protein (CRP) levels after cardiac surgery. DESIGN: A single-center retrospective, propensity score-matched analysis. SETTING: A university hospital. PARTICIPANTS: In total, 295 patients who underwent cardiovascular surgery with cardiopulmonary bypass were included. INTERVENTIONS: Patients were divided into two groups: artificial pancreas (target blood glucose: 120-150 mg/dL) and intravenous insulin infusion (conventional insulin therapy, target blood glucose: <200 mg/dL). MEASUREMENTS AND MAIN RESULTS: The differences in the incidence of SSIs and CRP levels between the two groups were assessed. After 1:1 propensity score matching based on their covariates, 101 matched patients were selected from each group. The incidence of SSIs was reduced by 3%, 5% (conventional insulin therapy), and 2% (artificial pancreas), but the reduction was not statistically significant (p = 0.45). The postoperative maximum CRP level was significantly lower in the artificial pancreas group than in the conventional insulin therapy group, mean (standard deviation)14.53 (5.64) mg/dL v 16.57 (5.58) mg/dL; p = 0.01. CONCLUSIONS: The artificial pancreas did not demonstrate a significant reduction in the incidence of SSIs. However, the artificial pancreas was safe and suppressed postoperative inflammation compared with conventional insulin therapy.

Interference of a ventricular assist device with magnetic navigation during insertion of Sherlock 3CG™, a bedside peripherally inserted central catheter.

Recently, the Sherlock 3CG™ Tip Confirmation System, including a magnetic tracking system and an intracavitary electrocardiography guidance system, has been introduced for bedside peripherally inserted central catheter (PICC) insertion. Magnetic field sources interfere with the magnetic tracking system. Electromagnetic interference of the ventricular assist device (VAD) has already been reported with various devices but not on Sherlock 3CG™. We assessed the availability of the magnetic tracking system in patients with and without a VAD during Sherlock 3CG™ insertion and evaluated the rate of optimal PICC tip position. We retrospectively reviewed 99 patients who had undergone PICC insertion using Sherlock 3CG™ on the bedside at our institutional intensive care unit from February 2018 to December 2020. Patients were divided into groups with and without a VAD. The availability of magnetic navigation and the success rate of optimal catheter tip position in each group were assessed. Among 87 cases analyzed, there were 12 and 75 cases with a VAD and without a VAD, respectively. The availability of magnetic navigation during Sherlock 3CG™ insertion was significantly lower in the group with a VAD [4/12 (33%) with VAD vs. 72/75 (96%) without VAD, P < 0.001]. In addition, the rate of optimal PICC tip position was also significantly lower in the group with a VAD [6/12 (50%) vs. 63/75 (84%), P = 0.015] The VAD significantly led to magnetic tracking system failure due to its electromagnetic interference during Sherlock 3CG™ insertion and significantly reduced the success rate of PICC insertions in the optimal position.

Surfactant-Free Decellularization of Porcine Aortic Tissue by Subcritical Dimethyl Ether.

Porcine aortic tissue was decellularized by subcritical dimethyl ether (DME) used as an alternative to the surfactant sodium dodecyl sulfate. The process included three steps. For the first step, lipids were extracted from the porcine aorta using subcritical DME at 23 °C with a DME pressure of 0.56 MPa. Next, DME was evaporated from the aorta under atmospheric pressure and temperature. The second step involved DNA fragmentation by DNase, which was primarily identical to the common method. For the third step, similar to the common method, DNA fragments were removed by washing with water and ethanol. After 3 days of DNase treatment, the amount of DNA remaining in the porcine aorta was 40 ng/dry-mg, which was lower than the standard value of 50 ng/mg-dry. Hematoxylin and eosin staining showed that most cell nuclei were removed from the aorta. These results demonstrate that subcritical DME eliminates the need to utilize surfactants.

Impact of Perioperative Steroid Administration in Patients Undergoing Major Hepatectomy with Extrahepatic Bile Duct Resection: A Randomized Controlled Trial.

BACKGROUND: To date, five randomized controlled trials have assessed the clinical benefit of perioperative steroid administration in hepatectomy; however, all of these studies involved a substantial number of 'minor' hepatectomies. The benefit of steroid administration for patients undergoing 'complex' hepatectomy, such as major hepatectomy with extrahepatic bile duct resection, is still unclear. This study aimed to evaluate the clinical benefit of perioperative steroid administration for complex major hepatectomy. METHODS: Patients with suspected hilar malignancy scheduled to undergo major hepatectomy with extrahepatic bile duct resection were randomized into either the control or steroid groups. The steroid group received hydrocortisone 500 mg immediately before hepatic pedicle clamping, followed by hydrocortisone 300 mg on postoperative day (POD) 1, 200 mg on POD 2, and 100 mg on POD 3. The control group received only physiologic saline. The primary endpoint was the incidence of postoperative liver failure. RESULTS: A total of 94 patients were randomized to either the control (n = 46) or steroid (n = 48) groups. The two groups had similar baseline characteristics; however, there were no significant differences between the groups in the incidence of grade B/C postoperative liver failure (control group, n = 8, 17%; steroid group, n = 4, 8%; p = 0.188) and other complications. Serum bilirubin levels on PODs 2 and 3 were significantly lower in the steroid group than those in the control group; however, these median values were within normal limits in both groups. CONCLUSION: Perioperative steroid administration did not reduce the risk of postoperative complications, including liver failure following major hepatectomy with extrahepatic bile duct resection.

Lidocaine inhibits vascular endothelial growth factor-A-induced angiogenesis.

PURPOSE: Angiogenesis is closely related to the pathophysiology of diseases such as cancer or ischemia. Here, we investigated the effect of lidocaine at clinically effective blood concentrations on vascular endothelial growth factor A (VEGF-A)-induced angiogenesis. In addition, we aimed to clarify the mechanisms by which lidocaine could inhibit angiogenesis. METHODS: Angiogenesis was analyzed using commercially available in vitro assay kits in human umbilical vein endothelial cells (HUVECs)/normal human dermal fibroblast co-culture systems. The effects of lidocaine on cytotoxicity, VEGF-induced cell migration, and VEGF-induced cell proliferation were examined in HUVECs using lactate dehydrogenase cytotoxic, Boyden chamber, and WST-8 assays, respectively. The VEGF signaling pathway via VEGF receptor 2 (VEGFR-2) was analyzed by western blotting. RESULTS: Lidocaine elicited a significant dose-dependent, angiogenesis-inhibitory effect at a concentration range of 1-10 µg/ml. At this concentration range, cell death was not observed. Lidocaine, at a concentration of 10 µg/ml, significantly inhibited cell proliferation but not cell migration, induced by VEGF-A in HUVECs. Furthermore, lidocaine, in a dose-dependent manner, significantly inhibited the VEGF-A-induced phosphorylation of VEGFR-2 at 3 and 10 µg/ml. CONCLUSION: We demonstrated that lidocaine has an anti-angiogenesis effect on clinically effective blood concentrations without causing cell death. This finding could represent a new avenue for future research into anesthesia, cancer-related analgesia, and revascularization therapy.

Transbronchial biopsy of peripheral lung lesions using fluoroscopic guidance combined with an enhanced ray-summation display.

The aim of this study was to investigate the effectiveness of guidance assistance during transbronchial biopsy (TBB) to achieve an appropriate pathway to small and peripheral pulmonary lesions (PPLs) using a combination of fluoroscopy and specialized ray-summation (Ray-sumTBB) images, which were processed from preprocedural lung computed tomography (CT) images. To improve the visibility of the correct pathway to the PPLs, three-dimensional spatial resolution enhancement and CT number conversion processes were applied to the original CT images. The Ray-sumTBB images reconstructed from the processed CT images were used as additional guides. We compared the rates of successful tumor localization and biopsy (arrival rate) between the trial (with Ray-sumTBB) and control (without Ray-sumTBB) groups. The fluoroscopy and examination times were also compared. The arrival rate of the trial group (73.1%) was significantly better than that of the control group (42.3%) (p = 0.048). The fluoroscopy and examination times did not differ significantly between the trial and control groups. No complications were identified in the trial group. Our results suggest that Ray-sumTBB improves the diagnostic accuracy of TBB.

A prospective compound screening contest identified broader inhibitors for Sirtuin 1.

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified.

Learning-to-rank technique based on ignoring meaningless ranking orders between compounds.

Learning-to-rank, which is a machine-learning technique for information retrieval, was recently introduced to ligand-based virtual screening to reduce the costs of developing a new drug. The quality of a rank prediction model depends on experimental data such as the compound activity values used for learning. However, activity values that contain a large error could lead to the observation of meaningless order relations at a certain rate. This motivated us to develop a novel learning-to-rank method that ignores two meaningless types of order ranking: those between compounds with similar activity and those between inactive compounds. We evaluated the proposed method using five high-throughput screening assay datasets from the PubChem BioAssay database. The results demonstrated that the proposed method could improve the accuracy of the prediction results by ignoring meaningless ranking orders to overcome the virtual screening problem. We confirmed that, although the proposed method is based on a simple idea, it facilitates accurate virtual screening. The source code is publicly available at https://github.com/akiyamalab/SPDRank.

Fibrinogen levels measured by the dry hematology method are lower than those measured by the Clauss method under a high concentration of heparin.

The activity of fibrinogen has been reported to decrease soon after the onset of major bleeding and to be an important determinant of the final extent of bleeding and postoperative outcome. A device that measures the perioperative fibrinogen level using the dry hematology (DH) method has recently become available. The aim of this study was to compare perioperative fibrinogen levels measured by the DH method with those measured by the conventional Clauss method and to assess the effects of heparin on these measurements. The study included 206 samples from 36 patients undergoing major surgery who received high-dose heparin (HH group, 23 samples), low-dose heparin (LH group, 57 samples), or no heparin (C group, 126 control samples). Each sample was measured using the DH and Clauss methods. After excluding samples outside the effective measurement range, the three study groups (HH group, n=23; LH group, n=49; C group, n=115) were compared. The mean fibrinogen level measured by the DH method in the HH group (87.9 ± 3.1%) was significantly lower than that measured by the Clauss method. There were no significant differences between the fibrinogen measurements obtained by the two methods between the LH and C groups. In patients on high-dose heparin, the mean fibrinogen level measured by the DH method was significantly lower than that measured by the Clauss method. When hemorrhage requires emergency treatment, a method that can measure the fibrinogen level rapidly is important. The DH method may be useful for decision-making with regard to perioperative coagulation factor replacement.

QEX: target-specific druglikeness filter enhances ligand-based virtual screening.

Druglikeness is a useful concept for screening drug candidate compounds. We developed QEX, which is a new druglikeness index specific to individual targets. QEX is an improvement of the quantitative estimate of druglikeness (QED) method, which is a popular quantitative evaluation method of druglikeness proposed by Bickerton et al. QEX models the physicochemical properties of compounds that act on each target protein based on the concept of QED modeling physicochemical properties from information on US Food and Drug Administration-approved drugs. The result of the evaluation of PubChem assay data revealed that QEX showed better performance than the original QED did (the area under the curve value of the receiver operating characteristic curve improved by 0.069-0.236). We also present the c-Src inhibitor filtering results of the QEX constructed using Src family kinase inhibitors as a case study. QEX distinguished the inhibitors and non-inhibitors better than QED did. QEX works efficiently even when datasets of inactive compounds are unavailable. If both active and inactive compounds are present, QEX can be used as an initial filter to enhance the screening ability of conventional ligand-based virtual screenings.