A Seasonal Variation of Clinical and Neurological Outcomes in Patients with Out-of-Hospital Cardiac Arrest Treated with Extracorporeal Cardiopulmonary Resuscitation: A Secondary Data Analysis of the SaveJ II Study.

The prognosis for patients with out-of-hospital cardiac arrest (OHCA) has been reported to be worse in the cold season. On the other hand, it is unclear whether a similar trend exists in OHCA patients who are treated with extracorporeal cardiopulmonary resuscitation (ECPR). This study was a retrospective multicenter registry study. We examined the association between ECPR and season. We compared the prognosis in four seasonal groups according to the day of occurrence. Multivariable logistic regression analysis was performed for the assessment of clinical and neurological outcomes. A total of 2024 patients with OHCA who received ECRP were included. There were no significant differences in in-hospital mortality (p = 0.649) and in the rate of favorable neurological outcome (p = 0.144). In the multivariable logistic regression, the seasonal factor was not significantly associated with worse in-hospital mortality (p = 0.855) and favorable neurological outcomes (p = 0.807). In this study, there was no seasonal variation in OHCA patients with ECPR.

Impact of Lactate Clearance on Clinical and Neurological Outcomes of Patients With Out-of-Hospital Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation: A Secondary Data Analysis.

OBJECTIVES: Serial evaluations of lactate concentration may be more useful in predicting outcomes in patients with out-of-hospital cardiac arrest (OHCA) than a single measurement. This study aimed to evaluate the impact of lactate clearance (LC) on clinical and neurologic outcomes in patients with OHCA who underwent extracorporeal cardiopulmonary resuscitation (ECPR). DESIGN: Retrospective multicenter observational study. SETTING: Patients with OHCA receiving ECPR at 36 hospitals in Japan between January 1, 2013, and December 31, 2018. PATIENTS: This study evaluated 1227 patients, with lactateinitial assessed upon emergency department admission and lactatesecond measured subsequently. To adjust for the disparity in the time between lactate measurements, the modified 6-hour LC was defined as follows: ([lactateinitial-lactatesecond]/lactateinitial) × 100 × (6/the duration between the initial and second measurements [hr]). The patients were divided into four groups according to the modified 6-hour LC with an equivalent number of patients among LC quartiles: Q1 (LC < 18.8), Q2 (18.8 < LC < 59.9), Q3 (60.0 < LC < 101.2), and Q4 (101.2 < LC). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 30-day survival rates increased as the 6-hour LC increased (Q1, 21.2%; Q2, 36.8%; Q3, 41.4%; Q4, 53.6%; p for trend < 0.001). In the multivariate analysis, the modified 6-hour LC was significantly associated with a 30-day survival rate (adjusted odds ratio [AOR], 1.003; 95% CI, 1.001-1.005; p < 0.001) and favorable neurologic outcome (AOR, 1.002; 95% CI, 1.000-1.004; p = 0.027). CONCLUSIONS: In patients with OHCA who underwent ECPR, an increase in the modified 6-hour LC was associated with favorable clinical and neurologic outcome. Thus, LC can be a criterion to assess whether ECPR should be continued.

Clinical characteristics of pneumothorax and pneumomediastinum in mechanical ventilated patients with coronavirus disease 2019: a case series.

BACKGROUND: Pneumothorax (PTX) and pneumomediastinum (PM) have been reported as potential complications in patients with coronavirus disease 2019 (COVID-19); however, their risk factors and etiology remain unknown. Herein, we investigated the clinical characteristics of mechanically ventilated patients with COVID-19 with PTX or PM. METHODS: We examined patients with severe COVID-19 requiring mechanical ventilation who were admitted to the intensive care unit of a tertiary-level emergency medical center in Tokyo, Japan between April 1, 2020. and October 31, 2021. We collected and analyzed the clinical characteristics of the patients who presented with either PTX or PM during mechanical ventilation. RESULTS: During the study period, a total of 165 patients required mechanical ventilation, and 15 patients with PTX/PM during mechanical ventilation were selected. Three patients with obvious causes were excluded, and the remaining 12 patients were analyzed (7.3%). The mortality rate in these patients was as high as 50%, demonstrating the difficulty of treatment in the presence of PTX/PM. PTX/PM occurred 14.5 days after intubation. A peak pressure of > 30 cmH2O was only apparent in one patient, suggesting that high positive pressure ventilation may be less involved than mentioned in the literature. In addition, the inspiratory effort was not strong in our group of patients. (P0.1 was 2.1 cm H2O [1.0-3.8]). CONCLUSION: Various factors are associated with the development of PTX/PM in patients on mechanical ventilation for COVID-19. We did not find a strong correlation between PTM/PM and barotrauma or strong inspiratory efforts, which have been identified as potential causes in previous studies.

Risk factors for recurrence of suicide attempt via overdose: A prospective observational study.

BACKGROUND: Although the prevalence of drug overdose has gradually increased worldwide, the risk factors associated with the recurrence of suicide attempts via drug overdose have not been well elucidated. In this study, we investigated the clinical course of patients with drug overdose and whether or not patients reattempted suicide via overdose, using telephone interviews, to evaluate the risk factors associated with overdose recurrence. METHODS: This prospective observational study enrolled patients who attempted suicide by drug overdose and were transferred to a tertiary emergency hospital in Japan between January 1, 2015 and July 30, 2021. Recurrence of overdose within 1 year of admission for overdose was designated as the primary outcome. Multivariable logistic regression analysis was performed to assess the independent risk factors for the recurrence of overdose. Furthermore, we compared the difference in the recurrence interval between patients with and without cohabitants using the log-rank test. RESULTS: A total of 94 patients were identified, and recurrence of overdose was observed in 28 patients (29.8%). The median recurrence interval was 6.0 months [IQR (interquartile range), 4.0-7.0 months]. The recurrence rate was significantly higher in patients with a history of schizophrenia than that in patients without a history of schizophrenia (58.3% vs 25.6%, p = 0.048), and significantly lower in patients with cohabitants than that in patients without cohabitants (22.6% vs 43.8%, p = 0.015). The presence of a cohabitant was significantly associated with a longer recurrence interval (p = 0.049). The effect of psychiatric intervention during hospitalization and psychiatric visits after discharge could not be found in this study. CONCLUSIONS: A history of schizophrenia was an independent risk factor for the recurrence of overdose, and the presence of a cohabitant was significantly associated with a lower risk of recurrence. Large-scale, long-term studies are required to confirm the results of this study.

Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

Manual Chest Compression versus Automated Chest Compression Device during Day-Time and Night-Time Resuscitation Following Out-of-Hospital Cardiac Arrest: A Retrospective Historical Control Study.

OBJECTIVE: We assessed the effectiveness of automated chest compression devices depending on the time of admission based on the frequency of iatrogenic chest injuries, the duration of in-hospital resuscitation efforts, and clinical outcomes among out-of-hospital cardiac arrest (OHCA) patients. METHODS: We conducted a retrospective historical control study of OHCA patients in Japan between 2015-2022. The patients were divided according to time of admission, where day-time was considered 07:00-22:59 and night-time 23:00-06:59. These patients were then divided into two categories based on the in-hospital cardiopulmonary resuscitation (IHCPR) device: manual chest compression (mCC) group and automatic chest compression devices (ACCD) group. We used univariate and multivariate ordered logistic regression models adjusted for pre-hospital confounders to evaluate the impact of ACCD use during IHCPR on outcomes (IHCPR duration, CPR-related chest injuries, and clinical outcomes) in the day-time and night-time groups. RESULTS: Among 1101 patients with OHCA (day-time, 809; night-time, 292), including 215 patients who underwent ACCD during IHCPR in day-time (26.6%) and 104 patients in night-time group (35.6%), the multivariate model showed a significant association of ACCD use with the outcomes of in-hospital resuscitation and higher rates of return in spontaneous circulation, lower incidence of CPR-related chest injuries, longer in-hospital resuscitation durations, greater survival to Emergency Department and hospital discharge, and greater survival with good neurological outcome to hospital discharge, though only in the night-time group. CONCLUSIONS: Patients who underwent ACCD during in-hospital resuscitation at night had a significantly longer duration of in-hospital resuscitation, a lower incidence of CPR-related chest injuries, and better outcomes.

Time-saving effect of real-time ultrasound-guided cannulation for extracorporeal cardiopulmonary resuscitation: A multicenter retrospective cohort study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR), a bridge to treatments for cardiac arrest patients, can be technically challenging and requires expertise. While ultrasound guidance is frequently used for vascular access, its effects on cannulation time in patients treated with ECPR are poorly defined. We hypothesized that real-time ultrasound guidance would contribute to faster and safer cannulation for ECPR. METHODS: This nationwide, multicenter, retrospective study analyzed data from 36 Japanese institutions. Patients who were over age 18 years and underwent ECPR between January 1, 2013, and December 31, 2018, were included. Patients who underwent open surgical vascular access were excluded. Cannulation time and outcomes of patients who underwent real-time ultrasound-guided cannulation (i.e., ultrasound-guided group) were compared to those cannulated without the use of real-time ultrasound guidance (control group) using propensity score matching analysis. RESULTS: The ultrasound-guided group comprised 510 cases, whereas the control group comprised 941 cases. Of those, 443 propensity score-matched pairs were evaluated. Cannulation time in the ultrasound-guided group was 2.5 minutes shorter than in the control group [difference, -2.5 minutes; 95% Confidence interval (CI), -3.7 to -1.3, p < 0.001]. The incidence of catheter-related complications and the incidence of the poor neurological outcomes (Cerebral Performance Category ≥3) did not differ between groups [Odds ratio (OR), 1.51; 95% CI, 0.64-3.74; OR, 1.08; 95% CI, 0.83-1.59]. CONCLUSION: Real-time ultrasound-guided cannulation was associated with shorter cannulation time of ECPR.

Large esophageal gastrointestinal stromal tumors resected thoracoscopically after oral imatinib therapy: a report of two cases.

Esophageal gastrointestinal stromal tumors (GISTs) are very rare, accounting for 2-5% of all GISTs. As with other GISTs, the principle of surgical treatment is complete resection with negative margins. In addition to biological grades of GISTs itselves, local recurrence due to capsular damage is a known risk. We describe two cases of massive esophageal GISTs that were successfully resected thoracoscopically after 2 months administration of 400 mg imatinib, with some discussion of the literature. Case 1, the patient was a 51-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtMtAeG, 110 × 95 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 11 months postoperatively. Case 2, the patient was a 70-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtAeG, 90 × 52 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 9 months postoperatively.

Cardiopulmonary Resuscitation: Let's Together Step into a New Era!

Although the out-of-hospital cardiac arrest (OHCA) survival rate has improved due to the spread of cardiopulmonary resuscitation (CPR) techniques and insights, OHCA remains a major public health issue worldwide [...].

Transcriptomic analysis reveals high ITGB1 expression as a predictor for poor prognosis of pancreatic cancer.

Transcriptomic analysis of cancer samples helps identify the mechanism and molecular markers of cancer. However, transcriptomic analyses of pancreatic cancer from the Japanese population are lacking. Hence, in this study, we performed RNA sequencing of fresh and frozen pancreatic cancer tissues from 12 Japanese patients to identify genes critical for the clinical pathology of pancreatic cancer among the Japanese population. Additionally, we performed immunostaining of 107 pancreatic cancer samples to verify the results of RNA sequencing. Bioinformatics analysis of RNA sequencing data identified ITGB1 (Integrin beta 1) as an important gene for pancreatic cancer metastasis, progression, and prognosis. ITGB1 expression was verified using immunostaining. The results of RNA sequencing and immunostaining showed a significant correlation (r = 0.552, p = 0.118) in ITGB1 expression. Moreover, the ITGB1 high-expression group was associated with a significantly worse prognosis (p = 0.035) and recurrence rate (p = 0.028). We believe that ITGB1 may be used as a drug target for pancreatic cancer in the future.

Primary esophageal cancer treated by esophagectomy with distal pancreatectomy: a report of three cases.

Esophagectomy and pancreatectomy are recognized as highly invasive procedures with relatively high complication rates; therefore, careful indication decisions are required. The depth of tumors invading adjacent organs, such as the aorta, vertebral body, and trachea, is defined as T4, and are estimated to have a low survival rate even after treatment. Conversely, pancreatic invasion of esophageal cancer is uncommon and not clearly defined as T4. Thus, it is often difficult to decide on a treatment strategy for locally advanced esophageal cancer. In this study, we describe three cases of esophagectomy with combined resection of the pancreas and spleen for esophageal cancer or esophagogastric junction cancer with invasion of the pancreatic body or tail. To the best of our knowledge, this is the first report of esophagectomy and combined resection of the pancreas and spleen in multiple patients from a single institution.

Efficacy of thoracotomy and thoracoscopic-assisted esophageal surgery in conversion and salvage surgeries: a retrospective study.

BACKGROUND: The esophagus has no serosa; therefore, esophageal cancer may quickly invade its adjacent organs. In recent years, reports of conversion surgery (CS) and salvage surgery (SS) have described resection of esophageal cancer previously considered unresectable, with the addition of intensive preoperative chemotherapy or chemoradiotherapy. Currently, there is no established method for determining whether tumor excision is possible. Additionally, differences in surgical approaches between facilities may influence outcome after resection. However, the option for resection is considered a significant factor in determining a patient's prognosis. METHODS: Patients who were diagnosed with advanced-stage (T3 or higher) squamous cell carcinoma of the esophagus and subsequently underwent resection with CS or SS were included in the study. Resection was performed through a small thoracotomy using a thoracoscope. Clinicopathologic factors, such as complete resection rate (R0) and prognosis, were investigated. RESULTS: A total of 49 surgeries were conducted: 39 CS and 10 SS cases. The male-to-female ratio was 37:12. R0:R1:R2 equals 42:3:4, and the R0 resection rate was 85.7%. The 5-year survival rates for CS and SS cases were 69.2% and 32.1%, respectively. The 5-year survival rates for R0, R1, and R2 resections were 63.4%, 0.0%, and 25.0%, and those for R0 and R1 + 2 resections were 63.4% and 14.3%, respectively, indicating that the prognosis for R0 resection cases was significantly better (P = 0.001 and P = 0.001, respectively). Regarding chemotherapy for CS, 29 patients received 5-FU and cisplatin therapy, whereas 10 patients received 5-FU, cisplatin, and docetaxel (DCF) therapy. After 2015, the ratio of DCF was significantly high, and the R0 resection rate was 100% in patients who received DCF therapy. CONCLUSIONS: In this study, a satisfactory R0 rate was achieved using the magnifying effect of the thoracoscope while ensuring safety during thoracotomy. TRIAL REGISTRATION: This was a single-center cohort study wherein clinical data were retrospectively registered. This study was approved by the Chiba Cancer Center review board (H29-262). All procedures adhered to the ethical standards of the responsible committee on human experimentation and the Helsinki Declaration of 1964 and its later amendments.

Extracorporeal cardiopulmonary resuscitation in adult patients with out-of-hospital cardiac arrest: a retrospective large cohort multicenter study in Japan.

BACKGROUND: The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications. METHODS: We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2. RESULTS: A total of 1644 patients with OHCA were included in this study. The patient age was 18-93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45-66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively. CONCLUSIONS: In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%.

Therapeutic anticoagulation using heparin in early phase severe coronavirus disease 2019: A retrospective study.

BACKGROUND: Although several reports recommend the use of systemic anticoagulation therapy in patients with severe coronavirus disease 2019 (COVID-19) pneumonia, appropriate target population and timing of administration are unknown. We assessed association between therapeutic anticoagulation administration with unfractionated heparin and outcomes in patients with severe COVID-19 pneumonia, assuming that anticoagulant administration effects are influenced by therapy timing. METHODS: This retrospective observational study included severe COVID-19 patients requiring mechanical ventilation in a tertiary emergency critical care hospital intensive care unit (ICU) in Japan from May 1, 2020 to September 30, 2021. All included patients were divided into early and late-phase administration groups based on therapeutic anticoagulant administration timing (≤5 and >5 days, respectively, after commencing oxygen therapy). Primary outcomes (in-hospital mortality and adverse events related to anticoagulation therapy) and secondary outcomes [veno-venous extracorporeal membrane oxygenation (ECMO), ventilator-free days (VFD), and ICU-free days] were compared between groups using univariate and multivariate models. RESULTS: Of 198 included patients 104 (52.5%) and 94 (47.5%) were in early-phase and late-phase administration groups, respectively. Although background characteristics were similar between the groups, the early-phase administration group had a significantly lower in-hospital mortality rate (3.8% vs. 27.7%; p < 0.001), lower adverse event rates (1.9% vs. 12.8%; p < 0.001), significantly longer VFD and ICU-free days, and lower ECMO rates, than the late-phase administration group, in the multivariate model. CONCLUSIONS: Late administration of therapeutic-dose anticoagulation in patients with severe COVID-19 pneumonia was significantly associated with worse outcomes than early administration.

Machine learning with imaging features to predict the expression of ITGAV, which is a poor prognostic factor derived from transcriptome analysis in pancreatic cancer.

Radiogenomics has attracted attention for predicting the molecular biological characteristics of tumors from clinical images, which are originally a collection of numerical values, such as computed tomography (CT) scans. A prediction model using genetic information is constructed using thousands of image features extracted and calculated from these numerical values. In the present study, RNA sequencing of pancreatic ductal adenocarcinoma (PDAC) tissues from 12 patients was performed to identify genes useful in evaluating clinical pathology, and 107 PDAC samples were immunostained to verify the obtained findings. In addition, radiogenomics analysis of gene expression was performed by machine learning using CT images and constructed prediction models. Bioinformatics analysis of RNA sequencing data identified integrin αV (ITGAV) as being important for clinicopathological factors, such as metastasis and prognosis, and the results of sequencing and immunostaining demonstrated a significant correlation (r=0.625, P=0.039). Notably, the ITGAV high­expression group was associated with a significantly worse prognosis (P=0.005) and recurrence rate (P=0.003) compared with the low­expression group. The ITGAV prediction model showed some detectability (AUC=0.697), and the predicted ITGAV high­expression group was also associated with a worse prognosis (P=0.048). In conclusion, radiogenomics predicted the expression of ITGAV in pancreatic cancer, as well as the prognosis.

A right pulmonary vein abnormality treated with 3D CT assistance in thoracoscopic surgery for esophageal cancer: a case report.

BACKGROUND: Anomalous bifurcation of the right superior pulmonary vein is an important anomaly that should be recognized not only in respiratory and cardiac surgeries, but also in esophageal surgery for the safe performance of surgery. We report a case in which thoracoscopic esophagectomy was safely performed using preoperative three-dimensional computed tomography (3D CT) imaging. CASE PRESENTATION: An 81-year-old male patient received an upper gastrointestinal endoscopy, which revealed a 20-cm incisor at the entrance, 43-cm EGJ, and 30-mm large type 1 + IIc lesion between the 23-cm and 26-cm incisors; biopsy showed squamous cell carcinoma (SCC). Contrast-enhanced CT showed wall thickening in the anterior wall of the upper thoracic esophagus, without evidence of multi-organ invasion or lymph node metastasis. In addition, a break in the right pulmonary vein passing dorsal to the right main bronchus and flowing directly into the left atrium was observed, and 3D CT was performed preoperatively to confirm the 3D positioning. Positron emission tomography (PET)-CT showed a high degree of accumulation (SUVmax 19.95) in the upper thoracic esophagus. The patient was diagnosed with upper thoracic esophageal cancer, cT2N0M0 cStage II, and underwent thoracoscopic subtotal esophagectomy (three-region dissection) and gastric tube reconstruction. The dorsal inflow of the pulmonary vein in the right main bronchus, which was recognized on preoperative CT, was confirmed and preserved. The pathological diagnosis was basaloid squamous cell carcinoma, pT1b(SM1)N0(0/58)M0 pStage I. The postoperative course was uneventful, and the patient was discharged on postoperative day 20. CONCLUSIONS: The anomalous bifurcation of the pulmonary vein in the right upper lobe area required attention because of its potential to cause massive bleeding and difficulty in securing the operative field if misidentified and damaged during surgery. Although it is not frequently encountered, it is the bifurcation anomaly that esophageal surgeons must bear in mind due to its severe consequences. Preoperative image-reading and intraoperative manipulation of this vessel are imperative for surgical safety.

Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-label Multicenter Prospective Trial (JASPAC05).

OBJECTIVE: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC. SUMMARY OF BACKGROUND DATA: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established. METHODS: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m 2 bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sided α = 0.05 and ß = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively. RESULTS: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively. CONCLUSIONS: S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC. TRIAL REGISTRATION: UMIN000009172.

Concordance of human equilibrative nucleoside transporter-1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial.

BACKGROUND: Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. AIM: We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis. METHODS: The subjects of this study were totally 332 whose formalin-fixed paraffin-embedded specimens and/or unstained sections were obtained. The individual H-scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively. RESULTS: The highest concordance rate (79.8%) was obtained when the cut-off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H-score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p < .001). In contrast, agent for adjuvant chemotherapy was not significant predictor for the patients with high hENT1 expression regardless of the kind of antibody. CONCLUSION: The present study suggests that the two antibodies for evaluating hENT1 expression are equivalent depending on the cut-off point and suggests that S-1 is the first choice of adjuvant chemotherapy for pancreatic cancer with low hENT1 expression, whereas either S-1 or GEM can be introduced for the pancreatic cancer with high hENT1 expression, no matter which antibody is used.

Dielectric Blood Coagulometry for the Early Detection of Sepsis-Induced Disseminated Intravascular Coagulation: A Prospective Observational Study.

OBJECTIVES: To evaluate the utility of dielectric blood coagulometry for early sepsis-induced disseminated intravascular coagulation diagnosis. DESIGN: Single-center, prospective observational study. SETTING: Patients with sepsis or septic shock at the Tokyo Medical and Dental University Hospital of Medicine between September 2019 and September 2020. PATIENTS: The patients were divided into three groups according to the timing of disseminated intravascular coagulation diagnosis based on the Disseminated Intravascular Coagulation score by the Japanese Association for Acute Medicine: 1) no disseminated intravascular coagulation group, 2) late-diagnosed disseminated intravascular coagulation group: not diagnosed with disseminated intravascular coagulation on day 1 but diagnosed within 48 hours after admission, and 3) disseminated intravascular coagulation group: diagnosed with disseminated intravascular coagulation on day 1. The study evaluated 80 patients (no disseminated intravascular coagulation, 31 [38.8%]; late-diagnosed disseminated intravascular coagulation, 34 (42.5%); disseminated intravascular coagulation, 15 [18.8%]). MEASUREMENTS AND MAIN RESULTS: We compared the clinical severity scores and mortality of the groups and assessed the correlation between the dielectric blood coagulometry-derived coagulation marker, thrombin levels, and Disseminated Intravascular Coagulation score using Spearman rank correlation. The mortality rate was 0% (0/31) in the no disseminated intravascular coagulation group, 35.3% (12/34) in the late-diagnosed disseminated intravascular coagulation group, and 33.3% (5/15) in the disseminated intravascular coagulation group. Although the Disseminated Intravascular Coagulation score on day 1 did not reflect disseminated intravascular coagulation in approximately 70% of patients who developed disseminated intravascular coagulation by day 2, dielectric clot strength measured by dielectric blood coagulometry on day 1 strongly correlated with disseminated intravascular coagulation development by day 2 (Spearman ρ = 0.824; p < 0.05) and with thrombin level on day 1 (Spearman ρ = 0.844; p < 0.05). CONCLUSIONS: Dielectric blood coagulometry can be used to detect early-phase disseminated intravascular coagulation in patients with sepsis and is strongly correlated with thrombin levels. Larger studies are needed to verify our results for developing clinical applications.