Impact of endoscopic ultrasound-guided tissue acquisition on prognosis and peritoneal lavage cytology in resectable or borderline resectable pancreatic ductal adenocarcinoma.

OBJECTIVES: This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021. RESULTS: To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (P = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54-1.70, P = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25-2.20, P = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups. CONCLUSIONS: EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC.

Novel weaning assessment for veno-arteriovenous to veno-venous extracorporeal membrane oxygenation using pump-controlled retrograde trial off.

INTRODUCTION: Pump-controlled retrograde trial off (PCRTO) is described as an effective weaning strategy for veno-arterial extracorporeal membrane oxygenation (ECMO) in the guidelines. Contrastingly, there is no established weaning strategy for veno-arteriovenous (V-AV) ECMO. We report a novel application of PCRTO in a patient undergoing V-AV ECMO. CASE REPORT: A 49-year-old man had pneumonia and a history of kidney transplantation. Two days after intubation, respiratory failure progressed and veno-venous (V-V) ECMO was introduced. On day 7 after ECMO, the configuration was changed to V-AV ECMO owing to septic cardiomyopathy due to suspected cholangitis. On day 15, with partial haemodynamic improvement and persistent respiratory failure, PCRTO was performed; the patient was safely returned to V-V ECMO. DISCUSSION: In patients undergoing V-AV ECMO, PCRTO could have the potential to accurately simulate decannulation of the arterial cannula. CONCLUSION: This novel weaning strategy could be considered in patients undergoing V-AV ECMO.

Hyperglycaemia induces metabolic reprogramming into a glycolytic phenotype and promotes epithelial-mesenchymal transitions via YAP/TAZ-Hedgehog signalling axis in pancreatic cancer.

BACKGROUND: Hyperglycaemia is a well-known initial symptom in patients with pancreatic ductal adenocarcinoma (PDAC). Metabolic reprogramming in cancer, described as the Warburg effect, can induce epithelial-mesenchymal transition (EMT). METHODS: The biological impact of hyperglycaemia on malignant behaviour in PDAC was examined by in vitro and in vivo experiments. RESULTS: Hyperglycaemia promoted EMT by inducing metabolic reprogramming into a glycolytic phenotype via yes-associated protein (YAP)/PDZ-binding motif (TAZ) overexpression, accompanied by GLUT1 overexpression and enhanced phosphorylation Akt in PDAC. In addition, hyperglycaemia enhanced chemoresistance by upregulating ABCB1 expression and triggered PDAC switch into pure basal-like subtype with activated Hedgehog pathway (GLI1 high, GATA6 low expression) through YAP/TAZ overexpression. PDAC is characterised by abundant stroma that harbours tumour-promoting properties and chemoresistance. Hyperglycaemia promotes the production of collagen fibre-related proteins (fibronectin, fibroblast activation protein, COL1A1 and COL11A1) by stimulating YAP/TAZ expression in cancer-associated fibroblasts (CAFs). Knockdown of YAP and/or TAZ or treatment with YAP/TAZ inhibitor (K975) abolished EMT, chemoresistance and a favourable tumour microenvironment even under hyperglycemic conditions in vitro and in vivo. CONCLUSION: Hyperglycaemia induces metabolic reprogramming into glycolytic phenotype and promotes EMT via YAP/TAZ-Hedgehog signalling axis, and YAP/TAZ could be a novel therapeutic target in PDAC.

The Impact of Histologic Liver Inflammation on Oncology and the Prognosis of Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: Liver inflammation is a reaction to disease-causing stress in the liver that induces fibrosis and cirrhosis. However, its prognostic impact after hepatectomy remains unclear. This study aimed to evaluate the prognostic and oncologic impacts of liver inflammation on patients after curative hepatectomy for hepatocellular carcinoma (HCC). METHODS: The study enrolled 500 consecutive patients with primary HCC who underwent curative and primary hepatectomy. Patient characteristics and prognoses were evaluated according to histologic liver inflammation assessed by the New Inuyama Classification. RESULTS: Severe liver inflammation (A3) was observed in 97 patients (19.4%) and nonsevere liver inflammation (A0-2) in 403 patients (80.6%). The patients with A3 had a significantly poorer prognosis than those with A0-2 in terms of relapse-free survival (p < 0.0001, log-rank) and overall survival (p = 0.0013, log-rank). The study showed that A3 is an independent poor prognostic factor (hazard ratio, 1.36; 95% confidence interval [Cl], 1.02-1.81; p = 0.039), and that Child-Pugh grade B and multiple tumors are associated with relapse-free survival. Furthermore, The significant predictors of early recurrence (within 2 years after hepatectomy) were A3 (odds ratio, 2.10; 95% CI, 1.25-3.55; p = 0.005), a des-γ-carboxyprothrombin level higher than 40 mAU/mL, and multiple tumors. CONCLUSIONS: Severe liver inflammation was associated with poor short- and long-term prognoses independently of cirrhosis. Controlling liver inflammation in the perioperative period may be essential to improving the prognosis of patients with HCC after hepatectomy.

Prognostic Value of the Preoperative Tumor Marker Index in Resected Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Institution Study.

BACKGROUND: The prediction of prognostic outcomes can provide the most suitable strategy for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the clinical value of the preoperative tumor marker index (pre-TI) in predicting prognostic outcomes after resection for PDAC. METHODS: For 183 patients who underwent pancreatic resection of PDAC, adjusted carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), pancreatic cancer-associated antigen-2 (DUpan-2), and s-pancreas-1 antigen (SPan-1) were retrospectively evaluated, and the positive number of these markers was scored as the pre-TI. RESULTS: A high pre-TI (≥ 2) was significantly associated with a larger tumor and lymph node metastases, and the patients with a high pre-TI had worse prognostic outcomes in terms of both relapse-free survival (RFS) (P < 0.0001, log-rank) and overall survival (OS) (P < 0.0001, Λlog-rank) than the patients with a low pre-TI. The pre-TI was one of the independent factors of a poor prognosis for RFS (hazard ratio [HR], 2.36; P < 0.0001) and OS (HR, 2.27; P < 0.0001). In addition, even for the patients with normal adjusted CA19-9 values (n = 74, 40.4%), those with the high pre-TI had a significantly poorer prognosis than those with a low pre-TI (RFS: P = 0.002, log-rank; OS: P = 0.031, log-rank). CONCLUSIONS: The pre-TI could be a potent predictive marker of prognostic outcomes for patients with resections for PDAC. Patients with a high pre-TI may need additional strategies to improve their prognosis.

Frailty is associated with poor prognosis after resection for pancreatic cancer.

BACKGROUND: With population aging, the number of frail patients with pancreatic cancer has increased. The Clinical Frailty Scale (CFS) is a simple and validated tool to assess frailty, and higher scores predict worse clinical outcomes after cardiovascular surgery. In this retrospective study, we aimed to examine the association of preoperative frailty with prognosis after resection for pancreatic cancer. METHODS: We retrospectively analyzed data from 142 consecutive patients undergoing resection for pancreatic cancer between April 2010 and December 2018. We used the CFS: 1 (very fit) to 9 (terminally ill) to assess frailty and examined associations of the CFS scores with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS: Of the 142 patients, 113 (80%) had CFS scores of ≤ 3, 13 (9.2%) scores of 4, and 16 (11%) scores of ≥ 5. Scores of ≥ 5 on the CFS were associated with worse CSS (univariable HR: 2.62, 95% confidence interval [CI]: 1.19-5.18, P = 0.019; multivariable HR: 2.49, 95% CI 1.05-5.34, P = 0.039) and OS (univariable HR: 2.42, 95% CI 1.19-4.46, P = 0.016; multivariable HR: 2.25, 95% CI 1.05-4.43, P = 0.038). The association between CFS scores and RFS was not significant in multivariable analysis (univariable HR: 2.11, 95% CI 1.08-3.79, P = 0.030; multivariable HR: 1.47, 95% CI 0.71-2.83, P = 0.29). CONCLUSION: Higher scores on the CFS are associated with worse CSS and OS after resection for pancreatic cancer. Preoperative measurement of frailty may improve risk assessment among patients with pancreatic cancer.

Peptide Toxins Targeting KV Channels.

A number of peptide toxins isolated from animals target potassium ion (K+) channels. Many of them are particularly known to inhibit voltage-gated K+ (KV) channels and are mainly classified into pore-blocking toxins or gating-modifier toxins. Pore-blocking toxins directly bind to the ion permeation pores of KV channels, thereby physically occluding them. In contrast, gating-modifier toxins bind to the voltage-sensor domains of KV channels, modulating their voltage-dependent conformational changes. These peptide toxins are useful molecular tools in revealing the structure-function relationship of KV channels and have potential for novel treatments for diseases related to KV channels. This review focuses on the inhibition mechanism of pore-blocking and gating-modifier toxins that target KV channels.

Intravascular Large B-cell Lymphoma Presenting as Pulmonary Ground-glass Nodules That Progressed Slowly over Several Months with No Overt Symptoms.

A 74-year-old man with no overt symptoms was referred for a chest computed tomography (CT) that revealed multiple bilaterally pulmonary ground-glass nodules (GGNs) with subtle changes in size over eight months. Surgical lung biopsies were performed in the left upper lobe. A pathologic study confirmed the intravascular large B-cell lymphoma (IVLBCL). This lesion was a nodule-like cluster of atypical cells, meaning that it had been localized for several months. Pulmonary IVLBCL may form focal lesions presenting as GGN on chest CT and progress slowly without apparent symptoms.

Chest CT findings in severe acute respiratory distress syndrome requiring V-V ECMO: J-CARVE registry.

BACKGROUND: Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. METHODS: This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. RESULTS: The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19-2.63], p = 0.005 and 1.97 [1.02-3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14-0.52], p < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. CONCLUSIONS: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO.

Cushing Index Based on Cushing Signs to Predict In-Hospital Death and Early Intervention for Minor Head Injury.

A considerable number of patients with mild traumatic brain injury have been known to "talk and die." Serial neurological examinations, however, have been the only method of determining the necessity of repeat computed tomography (CT), and no validated method has been available to predict early deterioration of minor head injury. This study aimed to evaluate the association between hypertension and bradycardia, a classic sign of raised intracranial pressure (Cushing reflex) on hospital arrival and determine the clinical consequences of minor head injury after blunt trauma. We created a new Cushing Index (CI) by dividing the systolic blood pressure by the heart rate (equaling the inverse number of the Shock Index, a score for hemodynamic stability) and hypothesized that a high CI would predict surgical intervention for deterioration and in-hospital death among patients with minor head injury. To test our hypothesis, a retrospective observational study was conducted using a nationwide trauma database. Accordingly, adult blunt trauma with minor head injury (defined as a Glasgow Coma Scale of 13-15 and Abbreviated Injury Scale score of ≥2 in the head) who were transported directly from the scene by ambulances were included. Among the 338,744 trauma patients identified in the database, 38,844 were eligible for inclusion. A restricted cubic spline regression curve for risks of in-hospital death was created using the CI. Thereafter, the thresholds were determined based on inflection points of the curve, and patients were divided into low-, intermediate-, and high-CI groups. Patients with high CI showed significantly higher in-hospital mortality rates compared with those with intermediate CI (351 [3.0%] vs. 373 [2.3%]; odds ratio [OR] = 1.32 [1.14-1.53]; p < 0.001). Patients with high index also had a higher incidence of emergency cranial surgery within 24h after arrival than those with an intermediate CI (746 [6.4%] vs. 879 [5.4%]; OR = 1.20 [1.08-1.33]; p < 0.001). In addition, patients with low CI (equal to high Shock Index, meaning hemodynamically unstable) showed higher in-hospital death compared with those with intermediate CI (360 [3.3%] vs. 373 [2.3%]; p < 0.001). In conclusion, a high CI (high systolic blood pressure and low heart rate) on hospital arrival would be helpful in identifying patients with minor head injury who might experience deterioration and need close observation.

Midterm Clinical Outcomes for Deferred Coronary Revascularization on the Basis of Resting Full-Cycle Ratio and Fractional Flow Reserve Measurements.

The midterm prognosis of patients with deferred revascularization based on resting full-cycle ratio (RFR) or fractional flow reserve (FFR) is not well established. We investigated the midterm clinical outcomes of 137 consecutive patients with deferred revascularization of 177 coronary arteries based on RFR and FFR. Patients were classified into 3 groups (concordant normal, concordant abnormal, discordant FFR and RFR), using known cutoffs for FFR (≤0.80) and RFR (≤0.89). All-cause mortality occurred in 9 (6.6%) and major adverse cardiac events (MACEs) in 16 patients (11.7%). Concordant abnormal, age, body mass index (BMI), and current or history of cancer were associated with increased risks of all-cause mortality. In a multivariable model, current or history of cancer was significantly associated with all-cause death (hazard ratio [HR] 6.8, p = 0.02). Concordant abnormal, current or history of cancer, BMI, and left ventricular ejection fraction were associated with increased risk of MACE, and all predictors correlated significantly with MACE (abnormal concordance: HR 4.2, p = 0.043; current or history of cancer: HR 4.0, p = 0.047; BMI: HR 0.8, p = 0.020; left ventricular ejection fraction: HR 0.9, p = 0.017). Although these results support performing percutaneous coronary intervention according to evidence-based RFR or FFR thresholds, deferred lesions with discordant FFR and RFR results were not associated with worse prognosis.

Biological and Clinical Impacts of Glucose Metabolism in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type as it is prone to metastases and is difficult to diagnose at an early stage. Despite advances in molecular detection, its clinical prognosis remains poor and it is expected to become the second leading cause of cancer-related deaths. Approximately 85% of patients develop glucose metabolism disorders, most commonly diabetes mellitus, within three years prior to their pancreatic cancer diagnosis. Diabetes, or glucose metabolism disorders related to PDAC, are typically associated with insulin resistance, and beta cell damage, among other factors. From the perspective of molecular regulatory mechanisms, glucose metabolism disorders are closely related to PDAC initiation and development and to late invasion and metastasis. In particular, abnormal glucose metabolism impacts the nutritional status and prognosis of patients with PDAC. Meanwhile, preliminary research has shown that metformin and statins are effective for the prevention or treatment of malignancies; however, no such effect has been shown in clinical trials. Hence, the causes underlying these conflicting results require further exploration. This review focuses on the clinical significance of glucose metabolism disorders in PDAC and the mechanisms behind this relationship, while also summarizing therapeutic approaches that target glycolysis.

Clinical Impact of Chronic Pulmonary Aspergillosis in Patients with Nontuberculous Mycobacterial Pulmonary Disease and Role of Computed Tomography in the Diagnosis.

Objective Chronic pulmonary aspergillosis (CPA) is an important complication of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnosis is challenging, as both CPA and NTM-PD present as chronic cavitary disease. The present study evaluated the impact of CPA on the survival of patients with NTM-PD and revealed the key computed tomography findings for a prompt diagnosis. Methods We retrospectively reviewed patients newly diagnosed with NTM-PD in Tenri Hospital (Tenri City, Nara Prefecture, Japan) between January 2009 and March 2018; the patients were followed up until May 2021. Clinical and radiological characteristics were assessed, and patients with CPA were identified. Results A total of 611 patients were diagnosed with NTM-PD. Among them, 38 (6.2%), 102 (17%), and 471 (77%) patients were diagnosed with NTM-PD with CPA, cavitary NTM-PD without CPA, and non-cavitary NTM-PD without CPA, respectively. The 5-year survival rate of the NTM-PD with CPA group (42.8%; 95% confidence interval: 28.7-64.0%) was lower than that of the cavitary NTM-PD without CPA group (74.4%; 95% confidence interval: 65.4-84.6%). A multivariate analysis revealed that fungal balls and cavities with adjacent extrapleural fat were significant predictive factors for NTM-PD with CPA. Conclusion NTM-PD with CPA patients exhibited a worse prognosis than cavitary NTM-PD without CPA patients. Therefore, an unerring diagnosis of CPA is essential for managing patients with NTM-PD. Computed tomography findings, such as fungal balls and cavities with adjacent extrapleural fat, may be valuable diagnostic clues when CPA is suspected in patients with NTM-PD.

A Laparoscopically Treated Case of Peritoneal Dissemination Mimicking Liver Metastases from Distal Cholangiocarcinoma Four Years After the Initial Pancreaticoduodenectomy.

BACKGROUND/AIM: Operable peritoneal dissemination from distal cholangiocarcinoma after pancreaticoduodenectomy is rare. Furthermore, peritoneal dissemination mimicking liver metastasis has scarcely been reported. CASE REPORT: An 81-year-old woman received pancreaticoduodenectomy for distal cholangiocarcinoma. She was diagnosed with stage IIA (T3a N0 M0) and received curative resection. She did not receive adjuvant chemotherapy. As a result of the examination in our department, she showed two tumors, 20 mm and 8 mm in segments 7/8 and 7, respectively, in the subphrenic liver surface four and half years after the initial pancreaticoduo-denectomy. The larger tumor was slow-growing, and cystic degeneration was inside. Plain computed tomography imaging revealed an isodense tumor with a marginal high ring and weak early enhancement, and prolonged peripheral enhancement was recognized at the marginal portion. Magnetic resonance imaging showed a heterogeneous mass with peripheral hypointensity ring that may be caused by fibrous tissue. Although the smaller tumor was diagnosed only after admission, it presented similar imaging findings to the larger tumor. The preoperative diagnosis was suspected to be liver metastases from DCC or inflammatory pseudotumor. Laparoscopic partial liver resection with diaphragm dissection was performed for both tumors. Pathologically, the tumors were diagnosed as peritoneal dissemination from distal cholangiocarcinoma. In the disseminated cancer cells, the expression of Ki67 was decreased, which was suspected to be one of the reasons for the long recurrence-free interval. The patient is doing well without any recurrence three months after the second operation. CONCLUSION: Laparoscopic surgery can provide excellent results for diagnosing and treating unknown subphrenic tumors.

Statins exert anti-growth effects by suppressing YAP/TAZ expressions via JNK signal activation and eliminate the immune suppression by downregulating PD-L1 expression in pancreatic cancer.

Statins are cholesterol-lowering agents that act as inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzymeA (HMG CoA) reductase. Recently, statins have received a lot of attention, especially regarding how statins act on the immune system. Here, the clinical impact of statin intake was examined in patients with resected pancreatic cancer, and the underlying mechanisms were investigated in vitro and in vivo. We found that statin intake was associated with favorable prognostic outcomes in patients with resectable pancreatic cancer. Statins, especially lipophilic statins, exert anti-proliferative effects on pancreatic cancer cells in vitro (simvastatin > fluvastatin > atorvastatin > rosuvastatin > pravastatin). Simvastatin had an anti-proliferative effect on pancreatic cancer cells with decreased the yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression by activating the JNK pathway, and simvastatin treatment with oxaliplatin revealed additive anti-growth effects. Furthermore, lipophilic and hydrophilic statins suppressed programmed cell death ligand 1 (PD-L1) expression by downregulating TAZ. Simvastatin treatment with an anti-PD-1 drug (BP0273) provided immediate anti-growth effects compared to controls, such as anti-PD-1 only and simvastatin only, and suppressed progressive disease during the early period of anti-PD-1 treatment in vivo. In conclusion, Statins display two distinct anti-cancer effects (direct anti-growth effect and elimination of immune suppression by downregulating PD-L1 expression) by targeting YAP/TAZ expression.

Cancer-associated fibroblasts reuse cancer-derived lactate to maintain a fibrotic and immunosuppressive microenvironment in pancreatic cancer.

Glycolysis is highly enhanced in pancreatic ductal adenocarcinoma (PDAC) cells; thus, glucose restrictions are imposed on nontumor cells in the PDAC tumor microenvironment (TME). However, little is known about how such glucose competition alters metabolism and confers phenotypic changes in stromal cells in the TME. Here, we report that cancer-associated fibroblasts (CAFs) with restricted glucose availability utilize lactate from glycolysis-enhanced cancer cells as a fuel and exert immunosuppressive activity in the PDAC TME. The expression of lactate dehydrogenase A (LDHA), which regulates lactate production, was a poor prognostic factor for patients with PDAC, and LDHA depletion suppressed tumor growth in a CAF-rich murine PDAC model. Coculture of CAFs with PDAC cells revealed that most of the glucose was taken up by the tumor cells and that CAFs consumed lactate via monocarboxylate transporter 1 to enhance proliferation through the TCA cycle. Moreover, lactate-stimulated CAFs upregulated IL-6 expression and suppressed cytotoxic immune cell activity synergistically with lactate. Finally, the LDHA inhibitor FX11 reduced tumor growth and improved antitumor immunity in CAF-rich PDAC tumors. Our study provides insight regarding the crosstalk among tumor cells, CAFs, and immune cells mediated by lactate and offers therapeutic strategies for targeting LDHA enzymatic activity in PDAC cells.

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial.

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.

Pump-controlled retrograde trial off for weaning from venoarterial extracorporeal membrane oxygenation in an adult patient with pulmonary embolism.

Background: Although pump-controlled retrograde trial off (PCRTO) is a practical method for weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO), its advantages and safety for patients with pulmonary embolism are not yet reported. Case Presentation: A 62-year-old man with coronavirus disease 2019 experienced sudden cardiac arrest, and VA-ECMO was introduced. After confirming a massive acute pulmonary embolism, unfractionated heparin treatment was initiated. On day 6, the patient was confirmed stable with a flow rate of 1.0 L/min. However, decannulation led to cardiac arrest and reintroduction of VA-ECMO. After further treatment, a residual thrombus was observed, and pulmonary arterial pressure remained high. On day 23, ECMO was decannulated successfully after a weaning test with PCRTO, which simulated ECMO withdrawal by generating a partial arteriovenous shunt. Conclusion: PCRTO is a feasible weaning strategy and can be considered for patients with uncertain cardiorespiratory recovery.