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.

Combined use of veno-venous extracorporeal membrane oxygenation and asynchronous independent lung ventilation after thoracic surgery for lung abscess.

We used independent lung ventilation (ILV) during veno-venous extracorporeal membrane oxygenation (V-V ECMO) after lung abscess surgery in a patient with severe hypoxia and air leak. ILV can be effective in V-V ECMO as unilateral lung air leak.

Safety of Supraclavicular Approach for Dual-Lumen Catheter Placement in Veno-Venous Extracorporeal Membrane Oxygenation: A Case Report.

In veno-venous extracorporeal membrane oxygenation (V-V ECMO), the dual-lumen catheter (DLC) facilitates mobility, reduces recirculation, and mitigates the risk of infection. The right internal jugular vein (IJV) is the most common site for DLC insertion. Still, it is often unavailable for various reasons, including local infection, hematoma, or thrombus. A 64-year-old male patient with mantle lymphoma, which was in remission after autogenous blood transplantation, suffered lung damage and refractory pneumothorax from coronavirus disease 2019 (COVID-19) and required V-V ECMO treatment initiated on day 39. The patient was unable to be weaned off V-V ECMO due to uncontrolled high serum carbon dioxide (CO2) concentration and required long-term V-V ECMO treatment for more than 80 days. DLC placement was necessary to implement aggressive rehabilitation, reduce puncture site-induced infections, and reduce recirculation. On day 119, a supraclavicular approach was used for DLC placement under fluoroscopic guidance using ultrasound guidance because a thrombus in the right IJV prevented the DLC insertion at a usual puncture site. Rehabilitation was safely performed at a higher intensity than preoperatively of DLC insertion. Overall, the DLC catheter was maintained for more than 30 days until the patient died due to septic shock by an unknown focus on day 150, with no complications such as bleeding or infection. This case report highlights the significance of using the supraclavicular approach for DLC placement in V-V ECMO in cases where IJV is not possible due to thrombus presence. In conclusion, the supraclavicular approach is safe and feasible for V-V ECMO insertion as an alternative to the IJV.

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.

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.

Heat stroke management during the COVID-19 pandemic: Recommendations from the experts in Japan (2nd edition).

Both coronavirus disease 2019 (COVID-19) and heat stroke have symptoms of fever or hyperthermia and the difficulty in distinguishing them could lead to a strain on emergency medical care. To mitigate the potential confusion that could arise from actions for preventing both COVID-19 spread and heat stroke, particularly in the context of record-breaking summer season temperatures, this work offers new knowledge and evidence that address concerns regarding indoor ventilation and indoor temperatures, mask wearing and heat stroke risk, and the isolation of older adults. Specifically, the current work is the second edition to the previously published guidance for handling heat stroke during the COVID-19 pandemic, prepared by the "Working group on heat stroke medical care during the COVID-19 epidemic," composed of members from four organizations in different medical and related fields. The group was established by the Japanese Association for Acute Medicine Heatstroke and Hypothermia Surveillance Committee. This second edition includes new knowledge, and conventional evidence gleaned from a primary selection of 60 articles from MEDLINE, one article from Cochrane, 13 articles from Ichushi, and a secondary/final selection of 56 articles. This work summarizes the contents that have been clarified in the prevention and treatment of infectious diseases and heat stroke to provide guidance for the prevention, diagnosis, and treatment of heat stroke during the COVID-19 pandemic.

Venovenous Extracorporeal Membrane Oxygenation in Diffuse Alveolar Hemorrhage Secondary to Anti-neutrophil Cytoplasmic Autoantibody-associated Vasculitis: Starting without Systemic Anticoagulation.

Regarding extracorporeal membrane oxygenation (ECMO) support against hemorrhagic conditions, there seems to be a dilemma when deciding between maintaining the circuit patency by systemic anticoagulation and increasing the risk of bleeding. We herein report two cases of diffuse alveolar hemorrhage (DAH) caused by myeloperoxidase (MPO) anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) successfully treated with venovenous (VV)-ECMO support, both initially started without systemic anticoagulation. Under anticoagulation-free ECMO management, we should consider the shortcomings of frequent circuit exchange and hemorrhagic diathesis related to circuit-induced disseminated intravascular coagulation (DIC).

Optimal timing of tracheostomy in patients on veno-venous extracorporeal membrane oxygenation for coronavirus 2019: a case series.

AIM: An early tracheostomy is often considered for patients with veno-venous extracorporeal membrane oxygenation (VV-ECMO). However, there is no consensus on the timing of a tracheostomy in patients on VV-ECMO for coronavirus disease 2019 (COVID-19). The present report described the optimal timing of tracheostomy for these patients. METHOD: The present study was a single-center case series. We retrospectively reviewed the medical records of nine consecutive patients who underwent tracheostomy either during or after VV-ECMO treatment in our center between January 1, 2020 and December 31, 2020. RESULTS: All the patients received a percutaneous dilatational tracheostomy, which was performed during VV-ECMO in four patients. Three of these patients experienced hemorrhagic complications, and the remaining patient required a circuit change on the day after the operation. Heparin was discontinued 8 h preoperatively and resumed 1-14 h later. The platelet count was below normal in two patients, but no transfusion was performed. APTT was almost normal, and D-dimer was elevated postoperatively. The remaining five patients received a tracheostomy after weaning off VV-ECMO, and no complication was observed. Eight patients were deeply sedated during VV-ECMO to prioritize lung rest and prevent infecting the healthcare workers. CONCLUSION: In the present study, patients who underwent a tracheostomy during VV-ECMO tended to have more hemorrhagic complications. Because an early tracheostomy during ECMO has little benefit for patients with COVID-19, it should be performed after weaning off VV-ECMO to protect the safety of the healthcare workers concerned.

Feasibility and Safety of Early Oral Feeding in Patients with Gastric Cancer After Radical Gastrectomy.

An enhanced recovery after surgery (ERAS) protocol is useful in patients undergoing colorectal surgery. However, its feasibility for gastric surgery remains unclear. This study aimed to evaluate the feasibility and safety of early oral feeding (EOF) for patients with gastric cancer after radical gastrectomy. The EOF protocol was implemented in 397 patients who underwent radical gastrectomy between 2005 and 2014 at our hospital. The protocol was common in 277 patients after distal gastrectomy (DG) and 120 patients after total gastrectomy (TG). The patients were scheduled to start drinking water in the morning of the first postoperative day and to start thin rice gruel with a liquid nutrition supplement on the second postoperative day. We analyzed the incidence of postoperative complications and surgical outcomes in these patients. Furthermore, we analyzed risk factors for dropout from the EOF protocol. All patients started drinking water, while 26 patients were unable to start eating. The EOF protocol was implemented in 371 patients (93%), and 48 patients stopped eating. Specifically, 227 patients (87%) after DG and 96 patients (88%) after TG followed the EOF protocol perfectly. The incidence of postoperative complications, including anastomotic leakage (n = 0), ileus (n = 22), and pneumonia (n = 11), was 15% and that of clinically significant events (≥ grade 3) was 4.3%. Multivariate analysis showed that the male gender, comorbidities, and intra-operative bleeding are independent risk factors for dropout from the EOF protocol. EOF can be safely implemented in patients after radical gastrectomy.

N-glycan alterations are associated with drug resistance in human hepatocellular carcinoma.

BACKGROUND: Correlations of disease phenotypes with glycosylation changes have been analysed intensively in the tumor biology field. Glycoforms potentially associated with carcinogenesis, tumor progression and cancer metastasis have been identified. In cancer therapy, drug resistance is a severe problem, reducing therapeutic effect of drugs and adding to patient suffering. Although multiple mechanisms likely underlie resistance of cancer cells to anticancer drugs, including overexpression of transporters, the relationship of glycans to drug resistance is not well understood. RESULTS: We established epirubicin (EPI)--and mitoxantrone (MIT)--resistant cell lines (HLE-EPI and HLE-MIT) from the human hepatocellular carcinoma cell line (HLE). HLE-EPI and HLE-MIT overexpressed transporters MDR1/ABCB1 and BCRP/ABCG2, respectively. Here we compared the glycomics of HLE-EPI and HLE-MIT cells with the parental HLE line. Core fucosylated triantennary oligosaccharides were increased in the two resistant lines. We investigated mRNA levels of glycosyltransferases synthesizing this oligosaccharide, namely, N-acetylglucosaminyltransferase (GnT)-IVa, GnT-IVb and alpha1,6-fucosyltransferase (alpha1,6-FucT), and found that alpha1,6-FucT was particularly overexpressed in HLE-MIT cells. In HLE-EPI cells, GnT-IVa expression was decreased, while GnT-IVb was increased. Both GnT-IVs were downregulated in HLE-MIT cells. HLE-MIT cells also showed decreases in fucosylated tetraantennary oligosaccharide, the product of GnT-V. GnT-V expression was decreased in both lines, but particularly so in HLE-MIT cells. Thus both N-glycan and glycosyltransferase expression was altered as cells acquired tolerance, suggesting novel mechanisms of drug resistance. CONCLUSION: N-glycan and glycosyltransferase expression in HLE-EPI and HLE-MIT were analysed and presented that glycans altered according with acquired tolerance. These results suggested novel mechanisms of drug resistance.

Swainsonine reduces 5-fluorouracil tolerance in the multistage resistance of colorectal cancer cell lines.

BACKGROUND: Drug resistance is a major problem in cancer chemotherapy. Acquisition of chemo-resistance not only reduces the effectiveness of drugs, but also promotes side effects and markedly reduces the patient's quality of life. However, a number of resistance mechanisms have been reported and are thought to be the reason for the difficulties in solving drug-resistance problems. RESULT: To investigate the mechanisms of drug resistance, a set of cell lines with different levels of sensitivity and possessing different mechanisms of resistance to 5-fluorouracil (5-FU) was established from a colorectal cancer cell line. The expression of thymidylate synthase, orotic acid phosphoribosyltransferase and dihydropyrimidine dehydrogenase, which are well known to be related to drug resistance, differed among these cell lines, indicating that these cell lines acquired different resistance mechanisms. However, swainsonine, an inhibitor of N-glycan biosynthesis, reduced 5-FU-tolerance in all resistant cells, whereas the sensitivity of the parental cells was unchanged. Further analysis of the N-glycan profiles of all cell lines showed partial inhibition of biosynthesis and no cytotoxicity at the swainsonine dosage tested. CONCLUSION: These observations suggest that N-linked oligosaccharides affect 5-FU resistance more widely than do drug-resistance related enzymes in colorectal cancer cells, and that the N-glycan could be a universal target for chemotherapy. Further, swainsonine may enhance the performance of chemotherapy by reducing tolerance.

Accurate evaluation of axillary sentinel lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid in breast cancer: a preliminary clinical trial.

Breast cancer is the most common type of cancer in women. The 5-year survival rate in patients with breast cancer ranges from 74 to 82 %. Sentinel lymph node biopsy has become an alternative to axillary lymph node dissection for nodal staging. We evaluated the detection of the sentinel lymph node and metastasis of the lymph node using contrast enhanced ultrasonography with Sonazoid. Between December 2013 and May 2014, 32 patients with operable breast cancer were enrolled in this study. We evaluated the detection of axillary sentinel lymph nodes and the evaluation of axillary lymph nodes metastasis using contrast enhanced computed tomography, color Doppler ultrasonography and contrast enhanced ultrasonography with Sonazoid. All the sentinel lymph nodes were identified, and the sentinel lymph nodes detected by contrast enhanced ultrasonography with Sonazoid corresponded with those detected by computed tomography lymphography and indigo carmine method. The detection of metastasis based on contrast enhanced computed tomography were sensitivity 20.0 %, specificity 88.2 %, PPV 60.0 %, NPV 55.6 %, accuracy 56.3 %. Based on color Doppler ultrasonography, the results were sensitivity 36.4 %, specificity 95.2 %, PPV 80.0 %, NPV 74.1 %, accuracy 75.0 %. Based on contrast enhanced ultrasonography with Sonazoid, the results were sensitivity 81.8 %, specificity 95.2 %, PPV 90.0 %, NPV 90.9 %, accuracy 90.6 %. The results suggested that contrast enhanced ultrasonography with Sonazoid was the most accurate among the evaluations of these modalities. In the future, we believe that our method would take the place of conventional sentinel lymph node biopsy for an axillary staging method.

Accurate diagnosis of axillary lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid.

Axillary lymph node enlargement following sentinel lymph node biopsy (SLNB) is often difficult to accurately diagnose. In keeping with the characteristically tortuous and aberrant pattern of tumor neovasculature, metastatic lymph nodes exhibit peripheral and mixed vascularity, resulting in a microvasculature that is often difficult to visualize. Contrast-enhanced ultrasonography (CEUS) with Sonazoid, a new generation contrast agent for ultrasonography, allows for the visualization of lymph node microvessels and may enable a more accurate evaluation of lymph node metastasis. This is a case report of axillary lymph node enlargement following SLNB, in which CEUS with Sonazoid resulted in an accurate diagnosis. On the basis of our experience with this case, we have initiated a clinical trial to evaluate the detection of lymph node metastasis through the use of CEUS in breast cancer patients.