Progress towards permanent respiratory support.

PURPOSE OF REVIEW: Although lung transplantation stands as the gold standard curative therapy option for end-stage lung disease, the scarcity of available organs poses a significant challenge in meeting the escalating demand. This review provides an overview of recent advancements in ambulatory respiratory assist systems, selective anticoagulation therapies that target the intrinsic pathway, and innovative surface coatings to enable permanent respiratory support as a viable alternative to lung transplantation. RECENT FINDINGS: Several emerging ambulatory respiratory assist systems have shown promise in both preclinical and clinical trials. These systems aim to create more biocompatible, compact, and portable forms of extracorporeal membrane oxygenation that can provide long-term respiratory support. Additionally, innovative selective anticoagulation strategies, currently in various stages of preclinical or clinical development, present a promising alternative to currently utilized nonselective anticoagulants. Moreover, novel surface coatings hold the potential to locally prevent artificial surface-induced thrombosis and minimize bleeding risks. SUMMARY: This review of recent advancements toward permanent respiratory support summarizes the development of ambulatory respiratory assist systems, selective anticoagulation therapies, and novel surface coatings. The integration of these evolving device technologies with targeted anticoagulation strategies may allow a safe and effective mode of permanent respiratory support for patients with chronic lung disease.

Hemocompatibility Evaluation of a Novel Ambulatory Pulmonary Assist System Using a Lightweight Axial-Flow Pump.

The Pulmonary Assist System (PAS) is currently under development as a wearable respiratory assist system. In this study, the hemocompatibility of the PAS's axial-flow mechanical pump (AFP) was compared to other contemporary mechanical pumps in an acute ovine model. The PAS was attached to a normal sheep in a venovenous configuration using one of three pumps: 1) AFP, 2) ReliantHeart HeartAssist 5 (control), or 3) Abbott Pedimag (control) (n = 5 each). Each sheep was supported on the PAS for 12 hours with two L/minute of blood flow and four L/minute of sweep gas. Hemolysis, coagulation, inflammation, and platelet activation and loss were compared among the groups. In this study, the plasma-free hemoglobin (pfHb) was less than 10 mg/dl in all groups. The pfHb was significantly lower in the AFP group compared to other groups. There was no significant clot formation in the pumps and oxygenators in all groups. Furthermore, no significant differences in coagulation (oxygenator resistance, fibrinopeptide A), inflammation (white blood cell counts, IL-8), and platelet activation and loss (p-selectin, platelet counts) were observed among the groups (all, p > 0.05). This study demonstrates equivalent hemocompatibility of the PAS's AFP to other contemporary mechanical pumps with a reduced level of hemolysis on startup.

Pilot Testing of a Lightweight, Pulmonary Assist System in an Ambulatory Sheep Model of Destination Therapy Respiratory Support.

A new, lightweight (2.3 kg), ambulatory pulmonary assist system (PAS) underwent preliminary evaluation in ambulatory sheep. The PAS was purposefully designed for long-term extracorporeal respiratory support for chronic lung disease and utilizes a novel, small (0.9 m 2 surface area) gas exchanger, the pulmonary assist device, with a modified Heart Assist 5 pump fitting in a small wearable pack. Prototype PAS were attached to two sheep in venovenous configuration for 7 and 14 days, evaluating ability to remain thrombus free; maintain gas exchange and blood flow resistance; avoid biocompatibility-related complications while allowing safe ambulation. The PAS achieved 1.56 L/min of flow at 10.8 kRPM with a 24 Fr cannula in sheep one and 2.0 L/min at 10.5 kRPM with a 28 Fr cannula in sheep 2 without significant change. Both sheep walked freely, demonstrating the first application of truly ambulatory ECMO in sheep. While in vitro testing evaluated PAS oxygen transfer rates of 104.6 ml/min at 2 L/min blood flow, oxygen transfer rates averaged 60.6 ml/min and 70.6 ml/min in studies 1 and 2, due to average hemoglobin concentrations lower than humans (8.9 and 10.5 g/dl, respectively). The presented cases support uncomplicated ambulation using the PAS.

Factor XII Silencing Using siRNA Prevents Thrombus Formation in a Rat Model of Extracorporeal Life Support.

Heparin anticoagulation increases the bleeding risk during extracorporeal life support (ECLS). This study determined whether factor XII (FXII) silencing using short interfering RNA (siRNA) can provide ECLS circuit anticoagulation without bleeding. Adult male, Sprague-Dawley rats were randomized to four groups (n = 3 each) based on anticoagulant: (1) no anticoagulant, (2) heparin, (3) FXII siRNA, or (4) nontargeting siRNA. Heparin was administered intravenously before and during ECLS. FXII or nontargeting siRNA were administered intravenously 3 days before the initiation of ECLS via lipidoid nanoparticles. The rats were placed on pumped, arteriovenous ECLS for 8 hours or until the blood flow resistance reached three times its baseline resistance. Without anticoagulant, mock-oxygenator resistance tripled within 7 ± 2 minutes. The resistance in the FXII siRNA group did not increase for 8 hours. There were no significant differences in resistance or mock-oxygenator thrombus volume between the FXII siRNA and the heparin groups. However, the bleeding time in the FXII siRNA group (3.4 ± 0.6 minutes) was significantly shorter than that in the heparin group (5.5 ± 0.5 minutes, p < 0.05). FXII silencing using siRNA provided simpler anticoagulation of ECLS circuits with reduced bleeding time as compared to heparin. http://links.lww.com/ASAIO/A937.

Establishment and evaluation of a rat model of extracorporeal membrane oxygenation (ECMO) thrombosis using a 3D-printed mock-oxygenator.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) research using large animals requires a significant amount of resources, slowing down the development of new means of ECMO anticoagulation. Therefore, this study developed and evaluated a new rat ECMO model using a 3D-printed mock-oxygenator. METHODS: The circuit consisted of tubing, a 3D-printed mock-oxygenator, and a roller pump. The mock-oxygenator was designed to simulate the geometry and blood flow patterns of the fiber bundle in full-scale oxygenators but with a low (2.5 mL) priming volume. Rats were placed on arteriovenous ECMO at a 1.9 mL/min flow rate at two different heparin doses (n = 3 each): low (15 IU/kg/h for eight hours) versus high (50 IU/kg/h for one hour followed by 25 IU/kg/h for seven hours). The experiment continued for eight hours or until the mock-oxygenator failed. The mock-oxygenator was considered to have failed when its blood flow resistance reached three times its baseline resistance. RESULTS: During ECMO, rats maintained near-normal mean arterial pressure and arterial blood gases with minimal hemodilution. The mock-oxygenator thrombus weight was significantly different (p < 0.05) between the low (0.02 ± 0.006 g) and high (0.003 ± 0.001 g) heparin delivery groups, and blood flow resistance was also larger in the low anticoagulation group. CONCLUSIONS: This model is a simple, inexpensive system for investigating new anticoagulation agents for ECMO and provides low and high levels of anticoagulation that can serve as control groups for future studies.

Incidence and impact of scheduled endoscopic surveillance on recurrence after curative endoscopic resection for early gastric cancer.

BACKGROUND AND AIMS: The aim of this study was to identify the incidence of recurrent lesions after endoscopic submucosal dissection (ESD) and to determine whether scheduled endoscopic surveillance might control their development and treatment. METHODS: We reviewed the clinical data of patients who underwent gastric ESD between March 2007 and April 2014. RESULTS: A total of 1347 patients who underwent curative ESD for early gastric cancer that met the expanded indication for ESD were analyzed. Of these, recurrence at the previous ESD site occurred in 39 patients, whereas recurrence in the stomach at a site other than the ESD site occurred in 102 patients. Older age, intestinal metaplasia, flat or depressed lesions, and ESD criteria were associated with recurrence in the stomach in places other than the ESD site. The annual incidence was .84% for recurrence at the previous ESD site and 2.48% for recurrence in the stomach at other than the ESD site. In cases of local recurrence and metachronous lesions, there was a significant difference between the short- and long-surveillance interval group (≤12 months vs >12 months) in the proportions of recurrent adenocarcinoma (31.9% vs 60.9%, P = .021), additional gastrectomy (7.1% vs 46.2%, P = .033), and size (8.92 ± 4.17 mm vs 18.08 ± 10.47 mm, P = .010). CONCLUSIONS: Scheduled endoscopy surveillance is necessary for detecting recurrent lesions. In addition, scheduled endoscopy surveillance might help to detect recurrent lesions at a stage early enough for a curative resection.

Sedation methods can determine performance of endoscopic submucosal dissection in patients with gastric neoplasia.

BACKGROUND: Although proper sedation is mandatory for endoscopic procedures such as endoscopic submucosal dissection (ESD), there is no research investigating the effects of sedation on ESD performance and complications. We aimed to evaluate the relationship among sedation methods, clinical outcomes, and complications after ESD for gastric neoplasia. METHODS: We retrospectively reviewed clinical data of 1,367 patients with 1,485 lesions who had undergone ESD for gastric adenoma or early gastric cancer at our tertiary teaching hospital in Seoul, Korea, between January 2008 and May 2011. Of these, 1,035 lesions in 958 patients were included in the intermittent midazolam/propofol injection by endoscopists (IMIE) group, and 450 lesions in 409 patients were included in the continuous propofol infusion with opioid administration by anesthesiologists (CPIA) group. RESULTS: En bloc resection and complete resection rates were higher in the CPIA group than in the IMIE group (CPIA vs. IMIE; en bloc resection, 99.8 and 95.0 %, P < 0.001; complete resection, 94.2 and 88.3 %, P < 0.001). Duration of procedure was shorter in the CPIA group than in the IMIE group (CPIA vs. IMIE; 48.2 ± 32.5 and 57.6 ± 41.3 min, P < 0.001). In multivariate analysis, sedation method was an independent factor associated with en bloc resection and complete resection. Additionally, sedation with CPIA was not a risk factor for bleeding (P = 0.403) or perforation (P = 0.474); however, aspiration pneumonia developed more frequently in patients sedated with CPIA (CPIA vs. IMIE, 4.4 and 1.5 %, P = 0.002). CONCLUSIONS: Sedation with CPIA can improve ESD performance.

Long-term outcome of early gastric cancer after endoscopic submucosal dissection: expanded indication is comparable to absolute indication.

BACKGROUND: Endoscopic submucosal dissection has become widely used for early gastric cancer with an expanded indication, although there is no strong consensus. We aimed to compare the clinical and long-term oncological outcome after endoscopic submucosal dissection according to indication. METHODS: Retrospective review of 1152 patients with 1175 lesions who had undergone endoscopic submucosal dissection for early gastric cancer at tertiary educational hospital in Korea, between March 2005 and November 2011. Of these, 366 and 565 lesions were included in the absolute and expanded indication groups, respectively. RESULTS: En bloc resection rates were not significantly different between the absolute and expanded indication groups. The complete resection rate was higher in the absolute indication group versus the expanded indication group (94.8% vs. 89.9%, respectively; P=0.008). In the expanded indication group, complete resection rate was higher in the differentiated versus undifferentiated tumour subgroups (92.9% vs. 78.4%, respectively; P<0.001). Recurrence rates were 7.7% in the absolute indication group vs. 9.3% in the expanded indication group (P=0.524). Disease-free survival was not significantly different between the two indication groups (P=0.634). CONCLUSIONS: Endoscopic submucosal dissection for early gastric cancer with expanded indication is a feasible approach to disease management. Periodic endoscopic follow-up is necessary to detect cancer recurrence.

Risk factors and prognosis of pulmonary complications after endoscopic submucosal dissection for gastric neoplasia.

BACKGROUND: Hospital-acquired pneumonia after an endoscopic submucosal dissection (ESD) can prolong the patient's stay in the hospital, leading to greater healthcare costs. However, little is known of the characteristics and risk factors associated with this complication. AIMS: To analyze the clinical features of pneumonia after ESD and to suggest a treatment plan. METHODS: This was a retrospective study in which the cases of 1,661 consecutive patients who underwent ESD for 1,725 lesions between January 2008 and June 2011 were reviewed. RESULTS: Of the 1,661 patients who underwent ESD during the study period, 38 were subsequently diagnosed with pneumonia, and an additional 18 patients exhibited lung consolidation, based on chest radiography, without respiratory signs or symptoms. The remaining 1,605 patients showed neither lung consolidation on chest radiography nor respiratory signs/symptoms. Continuous propofol infusion with intermittent or continuous administration of an opioid [odds ratio (OR) 4.498, 95 % confidence interval (CI) 2.267-8.923], a procedure time of >2 h (OR 2.900, 95 % CI 1.307-6.439), male gender (OR 2.835, 95 % CI 1.164-6.909), and age >75 years (OR 2.765, 95 % CI 1.224-6.249) were independent risk factors for pneumonia after ESD. In patients with only lung consolidation (without respiratory signs and symptoms), the length of hospital stay and prognosis were not affected by antibiotics use. CONCLUSIONS: Deep sedation under continuous propofol infusion with opioid injection during ESD may be a risk factor for pneumonia.

Participation and conflict in the decision-making process for endoscopic resection or surgical gastrectomy for early gastric cancer.

BACKGROUND: This study was to evaluate the participation role and conflict of patients during the decision-making process for endoscopic or surgical treatment for early gastric cancer (EGC). METHODS: In this prospective observational study, the sequential survey for patients under consideration for treatment of differentiated EGC was performed at the tertiary referral center. RESULTS: Among the 82 responders, 63.4% preferred endoscopic resection. The total decisional conflict scores were high and significantly different between groups that preferred endoscopic resection or surgical treatment (44.8 vs. 51.6, P = 0.016). Values assigned to the two treatment attributes "preservation of stomach (OR = 0.51)" and "bother in case of incomplete resection (OR = 2.13)" clearly discriminated between patients reaching a final decision of surgical gastrectomy or endoscopic resection. Regarding the participation role, a shared role was more frequent in the group with preference for endoscopic treatment before consultation (42.3% vs. 24.0%, P = 0.045). However, at the time of therapeutic decision, the passive role was most remarkable, both for the endoscopic (53.2%) and surgical (71.4%) groups. CONCLUSION: Despite the high overall decisional conflict, patients with preference for endoscopic treatment tended to be more autonomous. After consultation, all patients exhibited a passive participation role in the decision-making process.