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.

Therapeutic efficacy of intravenous infusion of mesenchymal stem cells in rat perinatal brain injury.

BACKGROUND: Perinatal brain injury is multifactorial and primarily associated with brain prematurity, inflammation, and hypoxia-ischemia. Although recent advances in perinatal medicine　have improved the survival rates of preterm infants, neurodevelopmental disorders remain a significant complication. We tested whether the intravenous infusion of mesenchymal stem cells (MSCs) had therapeutic efficacy against perinatal brain injury in rats. METHODS: Pregnant rats at embryonic day (E) 18 received lipopolysaccharide and the pups were born at E21. On postnatal day (PND) 7, the left common carotid artery of each pup was ligated, and they were exposed to 8% oxygen for 2 h. They were randomized on PND10, and MSCs or vehicle were intravenously infused. We performed behavioral assessments, measured brain volume using MRI, and performed histological analyses on PND49. RESULTS: Infused MSCs showed functional improvements in our model. In vivo MRI revealed that MSC infusion increased non-ischemic brain volume compared to the vehicle group. Histological analyses showed that cortical thickness, the number of NeuN+ and GAD67+ cells, and synaptophysin density in the non-ischemic hemisphere in the MSC group were greater than the vehicle group, but less than the control group. CONCLUSIONS: Infused MSCs improve sensorimotor and cognitive functions in perinatal brain injury and enhance neuronal growth. IMPACT: Intravenous infusion of MSCs improved neurological function in rats with perinatal brain injury, including motor, sensorimotor, cognitive, spatial, and learning memory. Infused MSCs increased residual (non-ischemic) tissue volume, number of neuronal cells, GABAergic cells, and cortical synapses in the contralesional (right) hemisphere. Intravenous administration of MSC might be suitable for the treatment of perinatal brain injury.

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.

Development of a prediction model for target positioning by using diaphragm waveforms extracted from CBCT projection images.

PURPOSE: To develop a prediction model (PM) for target positioning using diaphragm waveforms extracted from CBCT projection images. METHODS: Nineteen patients with lung cancer underwent orthogonal rotational kV x-ray imaging lasting 70 s. IR markers placed on their abdominal surfaces and an implanted gold marker located nearest to the tumor were considered as external surrogates and the target, respectively. Four different types of regression-based PM were trained using surrogate motions and target positions for the first 60 s, as follows: Scenario A: Based on the clinical scenario, 3D target positions extracted from projection images were used as they were (PMCL ). Scenario B: The short-arc 4D-CBCT waveform exhibiting eight target positions was obtained by averaging the target positions in Scenario A. The waveform was repeated for 60 s (W4D-CBCT ) by adapting to the respiratory phase of the external surrogate. W4D-CBCT was used as the target positions (PM4D-CBCT ). Scenario C: The Amsterdam Shroud (AS) signal, which depicted the diaphragm motion in the superior-inferior direction was extracted from the orthogonal projection images. The amplitude and phase of W4D-CBCT were corrected based on the AS signal. The AS-corrected W4D-CBCT was used as the target positions (PMAS-4D-CBCT ). Scenario D: The AS signal was extracted from single projection images. Other processes were the same as in Scenario C. The prediction errors were calculated for the remaining 10 s. RESULTS: The 3D prediction error within 3 mm was 77.3% for PM4D-CBCT , which was 12.8% lower than that for PMCL . Using the diaphragm waveforms, the percentage of errors within 3 mm improved by approximately 7% to 84.0%-85.3% for PMAS-4D-CBCT in Scenarios C and D, respectively. Statistically significant differences were observed between the prediction errors of PM4D-CBCT and PMAS-4D-CBCT . CONCLUSION: PMAS-4D-CBCT outperformed PM4D-CBCT , proving the efficacy of the AS signal-based correction. PMAS-4D-CBCT would make it possible to predict target positions from 4D-CBCT images without gold markers.

Characteristics of retained foreign bodies and near-miss events in the operating room: a ten-year experience at one institution.

PURPOSE: Retained foreign bodies (RFBs) are a major complication of surgical procedures. However, the efficacy of preventive measures is not well defined. This study investigates the characteristics of potential (near miss) and actual RFBs, and the contributions of routine practice for the prevention of RFB events. METHODS: We conducted a retrospective review of incident reports regarding near-miss and RFB events in patients who underwent surgery under general anesthesia in our institution between October 2008 and November 2018. RESULTS: Among 49,831 operations under general anesthesia, there were 106 (2.13/1000) near-miss events and 24 (0.48/1000) RFB events. Counting surgical materials and intraoperative X-rays detected the remaining items before completion of surgery in 59 (56%) and 15 (14%) cases, respectively. The operator or staff noticed the surgical materials in the remaining 32 (30%) near-miss events. RFBs included 4 sponges (17%), 4 instruments (17%), 4 needles (17%), and 12 miscellaneous items (50%). Of these, 12 (50%) RFBs were discovered on postoperative X-rays and 16 (67%) patients required operative removal. Four incidents (17%) with RFBs were attributable to ignoring count discrepancies during surgery. CONCLUSION: The actual incidence of RFB events is higher than previously reported. A standardized counting protocol, communication among staff, and intra- and postoperative X-rays may contribute to the prevention and detection of RFBs.

Intracellular virus sensor MDA5 mutation develops autoimmune myocarditis and nephritis.

Mutations in IFIH1 gene encoding viral RNA sensor MDA5 have been reported responsible for many interferonopathies, including Aicardi-Goutières syndrome (AGS) and monogenic lupus, however, the pathological link between IFIH1 mutations and various autoimmune symptoms remains unclear. Here, we generated transgenic mice expressing human MDA5 R779H mutant (R779H Tg), reported in AGS and monogenic lupus patient. Mice spontaneously developed myocarditis and nephritis with upregulation of type I IFNs in the major organs. R779H Tg Mavs-/- and R779H Tg Ifnar-/- showed no phenotypes, indicating direct MDA5-signaling pathway involvement. Rag-2 deficiency and bone marrow cells transfer from wild type to adult mice did not prevent myocarditis development, while mice with cardiomyocyte-specific expression of hMDA5 R779H showed cardiomegaly and high expression of inflammatory cytokines. Taken together, our study clarifies that type I IFNs production and chemokines from cardiomyocytes starts in neonatal period and is critical for the development of myocarditis. Activated lymphocytes and auto-antibodies exacerbate the pathogenesis but are dispensable for the onset.

Utility of real-time image fusion technology in ultrasonography-guided fiducial marker implantation for stereotactic body radiation therapy for liver tumors.

BACKGROUND: Ultrasonography (US) is useful when implanting fiducial markers in the liver. However, the implant position is sometimes lost. Recently, real-time image fusion technology (Volume Navigation [V-navi]; GE Healthcare, Milwaukee, WI, USA) has been introduced as a technique for using images from different modalities, and its utility for fiducial marker implantation has been hypothesized. PURPOSE: To evaluate the utility of US-guided fiducial marker implantation in the liver using V-navi compared to conventional US. MATERIAL AND METHODS: We retrospectively reviewed 35 patients who underwent fiducial marker implantation for stereotactic body radiation therapy of liver tumors in 2013-2018. To avoid artifacts obscuring the tumor, the target point of implantation was set 10 mm cranial or caudal to the tumor. Marker implantation was then performed using US alone (US group, n = 24) or V-navi with computed tomography (CT) or magnetic resonance imaging (V-navi group, n = 11). Postprocedural CT was evaluated to determine technical success, distances between marker and either tumor surface or target point, and whether marker-induced artifacts obscured the tumor. Complications were also evaluated. Results were compared between groups. RESULTS: Technical success was obtained in 33 patients. Distance between the tumor and marker showed no significant difference between groups. Distance between target point and marker was shorter in the V-navi group (P = 0.0093). Tumor-obscuring artifacts were seen in 12 patients (V-navi group, n = 1; US group, n = 11; P = 0.055). The only complication was minor bleeding in the US group (n = 1). CONCLUSION: V-navi appears useful for US-guided fiducial marker implantation in the liver compared with conventional US.

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.

Regulation of Fetal Genes by Transitions among RNA-Binding Proteins during Liver Development.

Transcripts of alpha-fetoprotein (Afp), H19, and insulin-like growth factor 2 (Igf2) genes are highly expressed in mouse fetal liver, but decrease drastically during maturation. While transcriptional regulation of these genes has been well studied, the post-transcriptional regulation of their developmental decrease is poorly understood. Here, we show that shortening of poly(A) tails and subsequent RNA decay are largely responsible for the postnatal decrease of Afp, H19, and Igf2 transcripts in mouse liver. IGF2 mRNA binding protein 1 (IMP1), which regulates stability and translation efficiency of target mRNAs, binds to these fetal liver transcripts. When IMP1 is exogenously expressed in mouse adult liver, fetal liver transcripts show higher expression and possess longer poly(A) tails, suggesting that IMP1 stabilizes them. IMP1 declines concomitantly with fetal liver transcripts as liver matures. Instead, RNA-binding proteins (RBPs) that promote RNA decay, such as cold shock domain containing protein E1 (CSDE1), K-homology domain splicing regulatory protein (KSRP), and CUG-BP1 and ETR3-like factors 1 (CELF1), bind to 3' regions of fetal liver transcripts. These data suggest that transitions among RBPs associated with fetal liver transcripts shift regulation from stabilization to decay, leading to a postnatal decrease in those fetal transcripts.

PLD4 is a genetic determinant to systemic lupus erythematosus and involved in murine autoimmune phenotypes.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by autoantibody production and widespread inflammation damaging many organs. Previous genome-wide association studies (GWASs) have revealed over 80 genetic determinants of SLE, but they collectively explain a fraction of the heritability, and only a few were proven in vivo for the involvement in SLE. We conducted a meta-analysis of SLE GWAS in the Japanese population, followed by functional analyses of a susceptibility gene with use of mutant mice. METHODS: We conducted a meta-analysis of two GWASs comprising a total of 1363 cases and 5536 controls using the 1000 Genome Project data as an imputation reference. Enrichment analyses for functional annotations were conducted. We examined Phospholipase D4 (Pld4) mutant mice to assess functional involvement of a genetic determinant. RESULTS: We found a total of 14 significant loci, which included rs2582511 in AHNAK2/PLD4 recently reported in a Chinese study and a novel locus of rs143181706 in MAMLD1 (p=7.9×10-11 and 3.7×10-8, respectively). PLD4 risk allele was associated with anti-dsDNA antibody production. Enrichment analysis of genetic signals revealed involvement of a wide range of immune-related cells and pathways. Pld4 mutant mice revealed remarkably low body weight. The mice demonstrated autoimmune phenotypes compatible with SLE, including splenomegaly and lymphadenopathy, expansion of B cells and hypersecretion of BAFF and production of autoantibodies especially anti-nuclear antibody and anti-dsDNA antibody. CONCLUSIONS: We found a novel susceptibility gene to SLE. Pld4 mutant mice revealed autoimmune phenotypes suggesting functional involvement of PLD4 with the basics of SLE.

Suvorexant is associated with a low incidence of delirium in critically ill patients: a retrospective cohort study.

BACKGROUND: Benzodiazepine use is a risk factor for the development of delirium in adult intensive care unit (ICU) patients. Suvorexant is an alternative to benzodiazepines to induce sleep, but the incidence of delirium in critically ill patients is unknown. We undertook this retrospective study to investigate the incidence of delirium in patients who receive suvorexant in the ICU. METHODS: This retrospective cohort study was conducted in a closed 12-bed ICU at a tertiary teaching hospital. Patients admitted to the ICU for 72 h or longer between January and June 2015 were evaluated for delirium using the Confusion Assessment Method for the Intensive Care Unit tool. We evaluated the incidence of delirium in patients who received suvorexant and those who did not. To adjust for confounding factors, multivariable logistic regression analysis was conducted. RESULTS: Study subjects included 118 patients, with a median age of 72 years and a median Acute Physiology and Chronic Health Evaluation II score of 18 points. Eighty-two patients (69.5%) were admitted after cardiovascular surgery. In the suvorexant group, there were fewer post-cardiovascular surgical patients and more medical patients. The duration of mechanical ventilation during ICU stay was longer in the suvorexant group, and sedatives and sleep inducers other than suvorexant were used more frequently in the suvorexant group. The incidence of delirium was 43.8% in the suvorexant group and 58.8% in the non-suvorexant group (P = 0.149). After adjustment for risk factors using multivariable logistic regression analysis, suvorexant was associated with a lower incidence of delirium (odds ratio = 0.23, 95% confidence interval: 0.07-0.73; P = 0.012). CONCLUSIONS: Suvorexant was associated with decreased odds of transitioning to delirium in critically ill patients. The use of suvorexant may lower the incidence of delirium in ICU patients. Future prospective studies are warranted.

Low-dose immunoglobulin G is not associated with mortality in patients with sepsis and septic shock.

BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655-1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively). CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality. TRIAL REGISTRATION: University Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.

Wearing masks is easy but taking them off is difficult - A situation in Japan during COVID-19 pandemic and after.

Background: Masks are well accepted in Japan, where they were already part of daily life even before the COVID-19 pandemic. Unlike many other countries where mask mandates were lifted as soon as the pandemic was under control, Japan was one of the last countries to ease mask-wearing guidelines. Even after the formal announcement to allow masks-off in mid-March 2023, many Japanese still voluntarily wear masks. In this work, possible reasons for this extreme "mask-affinity" of Japanese people were studied by exploring various information sources including tweets (now known as X posts) and subsequent text-analysis, online news, and medical literature. Methods: An observational study was conducted based on tweets prospectively collected during 5 months from June 26th, 2022 to November 26th, 2022. Tweets with the hashtag "mask (in Japanese)" were collected weekly via the Twitter application programming interface by using R version 4.0.3 to gauge public opinions. The word clouds to allow intuitive understanding of the key words were drawn from the tokenized text. Results: The data collection period included the 7th flareups of the newly infected cases i.e. "the 7th surge". In total, 161,592 tweets were collected. Word clouds for 1) before the 7th surge based on 18,000 tweets on June 26th and 2) during/after the 7th surge based on 143,592 tweets between July-November were created with the R package "wordcloud2". The results indicated that the people wanted to take off masks due to the heat in summer, then shifted again toward mask-wearing along with the 7th surge but with a certainly growing "no-mask" sentiment. Conclusions: Subsequent review of domestic information sources suggested that various factors, not only well-known peer pressure, may have contributed the public's mask affinity in Japan. This work revealed an aspect of Japanese struggle toward adaptation to life in an unexpected pandemic by focusing on masks as our closest daily adjunct over the past 3 years of isolation.Trial registration: not applicable.

Andexanet Alfa for Edoxaban Reversal and Associated Thromboelastography Changes in Surgical Pulmonary Embolectomy.

Andexanet alfa neutralizes factor Xa inhibitors in critical bleeding situations. However, in cardiac surgery with cardiopulmonary bypass (CPB), heparin resistance induced by andexanet alfa should be a concern, and the lack of point-of-care monitoring of plasma concentration of factor Xa inhibitors makes it difficult to decide when to administer andexanet alfa. A 69-year-old man underwent emergency surgery for acute pulmonary thromboembolism. The patient had been on edoxaban until the day before the surgery. Withdrawal from CPB required venoarterial extracorporeal membrane oxygenation due to right heart failure, followed by severe bleeding that required massive transfusion. Despite adequate coagulation factor replacement, bleeding persisted and citrated kaolin-reaction time (CK-R) on thromboelastography (TEG) was prolonged. Administering andexanet alfa achieved excellent hemostasis without any thrombosis and normalized the prolonged CK-R of TEG. This is the first report of a change in TEG findings before and after administration of andexanet alfa in a cardiac surgery patient taking factor Xa inhibitor. Monitoring CK-R in TEG may help evaluate the anticoagulant effect of factor Xa inhibitors and the reversal effect of andexanet alfa.

In vitro protamine addition for coagulation assessment using TEG 6s system during cardiopulmonary bypass: a pilot study.

OBJECTIVE: Systemic heparinization during cardiopulmonary bypass (CPB) can significantly affect thromboelastography (TEG). This study investigated the feasibility of adding protamine in vitro to allow assessment of coagulation status using the TEG 6s system during CPB. METHODS: In this prospective observational study, 21 patients undergoing elective cardiac valve surgery were evaluated. During CPB, protamine was added in vitro to the heparinized blood of these patients at a concentration of 0.05 mg/mL and analyzed with the TEG 6s (Pre). The TEG parameters were compared to those analyzed after CPB withdrawal and systemic protamine administration (Post). RESULTS: The citrated kaolin maximal amplitude (CK-MA) and the citrated functional fibrinogen maximal amplitude (CFF-MA) exhibited strong correlations between Pre and Post measurements (r = 0.790 and 0.974, respectively, P < 0.001 for both), despite significant mean differences (-2.23 mm for CK-MA and -0.68 mm for CFF-MA). Bland-Altman analysis showed a clinically acceptable agreement between Pre and Post measurement of CK-MA and CFF-MA (the percentage error was 10.6% and 12.2%, respectively). In contrast, the citrated kaolin reaction time (CK-R) showed no significant correlation between Pre and Post measurements (r = 0.328, P = 0.146), with a mean difference of 1.42 min (95% CI: -0.45 to 3.29). CONCLUSIONS: In vitro protamine addition allows assessment of coagulation status during CPB using the TEG 6s system. CK-MA and CFF-MA measured during CPB using this method revealed a strong correlation and agreement with post-CPB measurements, suggesting that our method potentially facilitates early prediction of post-CPB coagulation status and decision-making on transfusion strategies. CLINICAL TRIAL REGISTRATION: The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, registration number: UMIN000041097, date of registration: July 13, 2020, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046925 ) before the recruitment of participants.

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

Comparison of Sedation With Ketamine-Propofol Versus Propofol-Fentanyl for Elderly Patients Undergoing Prostate Biopsy: A Retrospective Observational Study.

BACKGROUND: Procedural sedation is increasingly used for elderly patients, but there is no established ideal method for elderly patients who are prone to respiratory and circulatory depression. This study aims to investigate the association of respiratory complications and the combination of ketamine-propofol versus fentanyl-propofol in elderly patients undergoing prostate biopsy requiring deep sedation. METHODS: This was a single-center, retrospective, observational study conducted from April 2020 to March 2021. We included male patients aged 65 years and older scheduled for prostate biopsy under procedural sedation. Ketamine-propofol and fentanyl-propofol were administered at the discretion of the anesthesiologist. The primary outcome was the need for assisted ventilation. The secondary outcome was the duration of oxygen saturation (SpO2) below 90%. RESULTS: We enrolled 120 patients over 65 years, and 92 patients were included in the final analysis. The anesthesiologist administered an initial dose of ketamine and propofol of 1:1 to 1:4 of 1.0 mg kg-1 (interquartile range: 0.98 to 1.17) or administered an initial dose of fentanyl of 0.05 to 0.1 mg and a target-controlled infusion of propofol of 2.8 µg ml-1 (interquartile range: 2.0 to 3.0) followed by additional doses at the discretion of the anesthesiologist. Ketamine-propofol was associated with a reduced need for assisted ventilation and a shorter duration of SpO2 below 90% than propofol-fentanyl (95.7% vs. 4.3%, P < 0.05; 0.64 minutes vs. 0.17 minutes, P = 0.26). CONCLUSIONS: Ketamine-propofol is associated with a significantly reduced need for assisted ventilation compared to propofol-fentanyl during procedural sedation and analgesia for procedures requiring deep sedation for the elderly.

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).