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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.
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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.
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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.
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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).
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Anestesia General , Índice de Perfusión , Humanos , Fenilefrina/farmacología , Gasto Cardíaco , Estudios Prospectivos , Volumen Sistólico , Fluidoterapia , Presión SanguíneaRESUMEN
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.
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Neoplasias Pulmonares , Neoplasias Pancreáticas , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Pulmón , Dosificación Radioterapéutica , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/radioterapiaRESUMEN
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.
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Procedimientos Quirúrgicos Cardíacos , Trasplante de Células Madre Hematopoyéticas , Humanos , Transfusión de Eritrocitos , Estudios de Cohortes , Estudios Retrospectivos , Hemodilución , Puntaje de Propensión , Procedimientos Quirúrgicos Cardíacos/efectos adversosRESUMEN
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.
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Cateterismo de Swan-Ganz , Arteria Pulmonar , Humanos , Catéteres , Cuidados Críticos , Pueblos del Este de Asia , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Japón/epidemiología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Differentiated thyroid cancer (DTC) is the most prevalent endocrine malignancy worldwide and requires effective prognostic markers and therapeutic targets to optimize patient outcomes. This study investigated the potential of human serum albumin (HSA) cysteine-34 (Cys34) redox state as a prognostic indicator and therapeutic avenue for DTC. A retrospective cohort study of 99 patients with DTC undergoing radioactive iodine therapy found that higher concentrations of HSA with the reduced form of Cys34 (i.e., human mercaptalbumin [HMA]) were associated with improved progression-free survival in metastatic DTC. In vitro experiments using a DTC cell line revealed that HMA induced cytotoxic effects by triggering ferroptosis, characterized by lipid peroxidation, intracellular ROS accumulation, and decreased cell viability. Ferroptosis inhibitors rescued cell viability, confirming their role in cytotoxicity. These results implicate the HSA-Cys34 redox state is a promising avenue for precision medicine in DTC, shedding light on the prognostic relevance and therapeutic potential of HMA-induced ferroptosis. They emphasize the opportunity for personalized treatment strategies to advance the management of patients with DTC.
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Adenocarcinoma , Ferroptosis , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/tratamiento farmacológico , Cisteína/metabolismo , Estudios Retrospectivos , Radioisótopos de Yodo/uso terapéutico , Ferroptosis/genética , Albúmina Sérica Humana/metabolismo , Oxidación-ReducciónRESUMEN
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.
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Neoplasias Pulmonares , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Diafragma/diagnóstico por imagen , Tomografía Computarizada Cuatridimensional/métodos , Tomografía Computarizada de Haz Cónico/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Oro , Fantasmas de ImagenRESUMEN
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.
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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.
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BACKGROUND: Perinatal brain injury is multifactorial and primarily associated with brain prematurity, inflammation, and hypoxia-ischemia. Although recent advances in perinatal medicineãhave 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.
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Lesiones Encefálicas , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ratas , Animales , Humanos , Recién Nacido , Infusiones Intravenosas , Ratas Sprague-Dawley , Recien Nacido Prematuro , Lesiones Encefálicas/terapia , Células Madre Mesenquimatosas/fisiología , Modelos Animales de EnfermedadRESUMEN
This study aimed to assess recurrence-free survival (RFS) rates and recurrence-related factors of patients who received adjuvant therapy (AT) with radioactive iodine (RAI) for differentiated thyroid cancer (DTC) following thyroidectomy. We evaluated 284 patients who underwent AT between January 2011 and July 2020 at our hospital. Recurrence was defined as visible recurrent lesions on image analysis or need for repeat surgery with pathologically confirmed recurrent lesions. RFS rate and prognostic factors were statistically evaluated. The median observation period was 30.2 months (range, 5.7-294 months). Overall, 192 patients were female and 92 were male, and the median age was 54 years (range, 9-85 years). Initial assessment revealed 39 recurrence cases. The 3-year RFS rate was 85.8% (95% confidence interval: 81.1-90.9%). Univariate analysis revealed that histology (except for papillary carcinoma), Tg level > 4 ng/dL before AT, and AT result significantly exacerbated the RFS rate. In multivariate analysis, histology and AT result were also important contributors to the worsening RFS rate. Results of AT can be determined relatively early and are important in predicting future recurrence in patients with DTC. Increasing the success rate of AT may lead to an improved prognosis.
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Adenocarcinoma , Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Radioisótopos de Yodo/uso terapéutico , Pronóstico , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patologíaRESUMEN
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).
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Background and purpose: This prospective multicenter phase II study aimed to evaluate the safety and efficacy of dynamic tumor tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring of liver tumors using a gimbal-mounted system. Materials and methods: Patients with < 4 primary or metastatic liver tumors with diameters ≤ 50 mm and expected to have a respiratory motion of ≥ 10 mm were eligible. The prescribed dose was 40 Gy in five fractions. The primary endpoint was local control (LC) at 2 years. The secondary endpoints were overall survival (OS), progression-free survival (PFS), treatment-related toxicity, and tracking accuracy. Results: Between September 2015 and March 2019, 48 patients (48 lesions) with a median age of 74 years were enrolled from four institutions. Of these, 39 were diagnosed with hepatocellular carcinoma and nine with metastatic liver cancer. The median tumor diameter was 17.5 mm. DTT-SBRT was successfully performed in all patients; the median treatment time was 28 min/fraction. The median follow-up period was 36.5 months. The 2-year LC, OS, and PFS rates were 98.0 %, 88.8 %, and 55.1 %, respectively. Disease progression was observed in 33 (68.8 %) patients. One patient (0.2 %) had local recurrence, 31 (64.6 %) developed new hepatic lesions outside the irradiation field, and nine (18.8 %) had distant metastases (including overlap). Grade 3 late adverse events were observed in seven patients (14.5 %). No grade 4 or 5 treatment-related toxicity was observed. The median tracking accuracy was 2.9 mm. Conclusion: Employing DTT-SBRT to treat liver tumors results in excellent LC with acceptable adverse-event incidence.
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Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Femenino , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Progresión , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Quimioradioterapia , Estadificación de NeoplasiasRESUMEN
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.
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Cuerpos Extraños , Potencial Evento Adverso , Humanos , Quirófanos , Radiografía , Estudios RetrospectivosRESUMEN
Polycomb group proteins (PcG), polycomb repressive complexes 1 and 2 (PRC1 and 2), repress lineage inappropriate genes during development to maintain proper cellular identities. It has been recognized that PRC1 localizes at the replication fork, however, the precise functions of PRC1 during DNA replication are elusive. Here, we reveal that a variant PRC1 containing PCGF1 (PCGF1-PRC1) prevents overloading of activators and chromatin remodeling factors on nascent DNA and thereby mediates proper deposition of nucleosomes and correct downstream chromatin configurations in hematopoietic stem and progenitor cells (HSPCs). This function of PCGF1-PRC1 in turn facilitates PRC2-mediated repression of target genes such as Hmga2 and restricts premature myeloid differentiation. PCGF1-PRC1, therefore, maintains the differentiation potential of HSPCs by linking proper nucleosome configuration at the replication fork with PcG-mediated gene silencing to ensure life-long hematopoiesis.
Asunto(s)
Cromatina , Replicación del ADN , Cromatina/genética , Linaje de la Célula/genética , Nucleosomas/genética , Proteínas del Grupo Polycomb , Complejo Represivo Polycomb 2RESUMEN
BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.