Liberation from Mechanical Ventilation in Critically Ill Patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.

BACKGROUND: Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. METHOD: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. RESULT: Recommendations for nine population, intervention, comparator, outcome (PICO) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. CONCLUSIONS: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Liberation from mechanical ventilation in critically ill patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.

BACKGROUND: Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. METHODS: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. RESULTS: Recommendations for nine PICO (population, intervention, comparator, and outcome) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. CONCLUSIONS: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis.

BACKGROUND: Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of reactive oxygen species (ROS) from podocytes may participate in the development of glomerular injury and proteinuria. We studied the role of oxidative stress in angiotensin II-induced podocyte apoptosis. METHODS: Mouse podocytes were incubated in media containing various concentrations of angiotensin II at different incubation times and were transfected with NADH/NADPH oxidase 4 (Nox4) or angiotensin II type 1 receptor for 24 hours. The changes in intracellular and mitochondrial ROS production and podocyte apoptosis were measured according to the presence of angiotensin II. RESULTS: Angiotensin II increased the generation of mitochondrial superoxide anions and ROS levels but suppressed superoxide dismutase activity in a dose- and time-dependent manner that was reversed by probucol, an antioxidant. Angiotensin II increased Nox4 protein and expression by a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of Nox4 by small interfering RNA (siRNA) reduced the oxidative stress induced by angiotensin II. Angiotensin II treatment also upregulated AT1R protein. Furthermore, angiotensin II promoted podocyte apoptosis, which was reduced significantly by probucol and Nox4 siRNA and also recovered by angiotensin II type 1 receptor siRNA. CONCLUSION: Our findings suggest that angiotensin II increases the generation of mitochondrial superoxide anions and ROS levels via the upregulation of Nox4 and angiotensin II type 1 receptor. This can be prevented by Nox4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as use of antioxidants.

Successful treatment of propofol-related infusion syndrome in critically ill patient receiving low-dose propofol infusion: a case report.

Propofol is widely used to sedate agitated patients in intensive care units. However, it can cause a rare but fatal complication, propofol-related infusion syndrome (PRIS). The pathophysiology of PRIS is not clear, and there is no definitive diagnosis and treatment. We report a successfully treated case of PRIS in a critically ill patient receiving low-dose propofol infusion. A 59-year-old male patient complaining of sudden chest pain repeatedly collapsed in an ambulance and the emergency room, and veno-arterial extracorporeal membrane oxygenation was delivered. He was diagnosed with a total occluded left anterior descending coronary artery in coronary angiography. On day 20, he showed arrhythmia, increased creatinine kinase (CK), and increased CK-MB and troponin I, accompanied by unstable hemodynamic status despite high-dose vasopressors. He was administered propofol for 20 days at an average dose of 1.3 mg/kg/hr owing to issues with agitation and ventilator synchrony. We strongly suspected PRIS and immediately discontinued propofol infusion, and he was successfully treated with aggressive supportive care. PRIS can occur in patients administered propofol for a prolonged period at low doses. Thus, clinicians should use propofol with caution for PRIS and change to alternative sedatives for long-term sedation.

A Transient Effect of Convalescent Plasma Therapy in a Patient with Severe Covonavirus Disease 2019: A Case Report.

A 65-year-old male patient with an end-stage renal disease was diagnosed with coronavirus disease 2019 (COVID-19) by reverse transcription polymerase chain reaction. The patient complained of cough, sputum, and respiratory distress that worsened three days ago. The patient required mechanical ventilation and extracorporeal mentrane oxygenation. On day 9, convalescent plasma collected from a 34-year old man who recovered from COVID-19 45 days ago was administered. The patient showed immediate clinical improvement. However, on day 14, the patient's clinical course worsened again. On day 19 and day 24, vancomycin-resistant Enterococcus faecium bacteremia and methicillin-resistant Staphylococcus aureus pneumonia were found. After long-term supportive care, he slowly recovered. He was discharged on day 91 without any oxygen requirement. This case report suggests that convalescent plasma therapy might just provide a short-term relief and that persistent effort for critical care is necessary to save patients from severe COVID-19.

2021 KSCCM clinical practice guidelines for pain, agitation, delirium, immobility, and sleep disturbance in the intensive care unit.

We revised and expanded the "2010 Guideline for the Use of Sedatives and Analgesics in the Adult Intensive Care Unit (ICU)." We revised the 2010 Guideline based mainly on the 2018 "Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) in Adult Patients in the ICU," which was an updated 2013 pain, agitation, and delirium guideline with the inclusion of two additional topics (rehabilitation/mobility and sleep). Since it was not possible to hold face-to-face meetings of panels due to the coronavirus disease 2019 (COVID-19) pandemic, all discussions took place via virtual conference platforms and e-mail with the participation of all panelists. All authors drafted the recommendations, and all panelists discussed and revised the recommendations several times. The quality of evidence for each recommendation was classified as high (level A), moderate (level B), or low/very low (level C), and all panelists voted on the quality level of each recommendation. The participating panelists had no conflicts of interest on related topics. The development of this guideline was independent of any industry funding. The Pain, Agitation/Sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep Disturbance panels issued 42 recommendations (level A, 6; level B, 18; and level C, 18). The 2021 clinical practice guideline provides up-to-date information on how to prevent and manage pain, agitation/sedation, delirium, immobility, and sleep disturbance in adult ICU patients. We believe that these guidelines can provide an integrated method for clinicians to manage PADIS in adult ICU patients.

Local complications are related to poor long-term outcome in patients undergoing curative gastrectomy for advanced gastric cancer.

Purpose: The present study was performed to investigate the effects of local complications (LC) on long-term survival and cancer recurrence in patients undergoing curative gastrectomy for gastric cancer. Methods: We analyzed 2,627 patients after curative gastrectomy for gastric cancer between January 2001 and December 2006. Patients were classified into groups no complications (NC), LC, or systemic complications (SC). Results: Among the 2,627 patients, 475 patients developed complications (LC group [n=374, 14.2%] and SC group [n=101, 3.9%]). The 5-year cancer-specific survival rate was significantly poorer in the LC group compared to the NC and SC groups (LC, 78.0%; NC, 85.4%; SC, 80.2%; P=0.007). The occurrence of LC was identified as a significant independent prognostic factor for overall and cancer-specific survival (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.46-2.97; P=0.001 and HR, 1.77; 95% CI, 1.12-2.81; P=0.015). The tumor recurrence rates were higher in the LC group than the in other two groups (LC, 23.5%; NC, 15.4%; SC, 15.8%; P<0.001). The occurrence of LC was an independent predictor of tumor recurrence in patients undergoing curative gastrectomy for gastric cancer (HR, 1.55; 95% CI, 1.11-2.17; P=0.011). Conclusion: LC are associated with adverse long-term outcomes in patients after curative gastrectomy for advanced gastric cancer.

Characteristics of pediatric rhabdomyolysis and the associated risk factors for acute kidney injury: a retrospective multicenter study in Korea.

BACKGROUND: The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. METHODS: This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. RESULTS: Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. CONCLUSIONS: Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Implementing a multidisciplinary care bundle to reduce colon surgical site infections.

PURPOSE: The aim of this study was to investigate how rates of surgical site infections (SSI) were changed over 2 years after applying colon SSI bundle in patients who underwent colon surgery. METHODS: The multidisciplinary working group developed a care bundle consisting of 8 components, including several recommendations of Surgical Care Improvement Project and monitoring of medical/surgical hand washing. We implemented the care bundle for each patient who underwent colon surgery from April 2013 to December 2014. RESULTS: Overall bundle compliance was 87.9% before implementation, 88.2% in 2013, and 90.5% in 2014. In particular, compliance of the following 3 components was substantial improved during the project period; discontinuation of prophylactic antimicrobial agent within 24 hours of surgery (from 88.3% to 100%), surgical hand washing (from 50.0% to 78.9%), and medical hand washing (from 74.7% to 82.8%). The rate of SSI was 8.0% (12/150) during 3 months before implementation, 3.3% (16/480) from April to December in 2013, and 2.3% (14/607) in 2014. CONCLUSION: After implementation of multidisciplinary care bundle, the compliance of each component was increased and rates of SSIs were significantly decreased compared to those before the quality improvement project.

Autophagy Precedes Apoptosis in Angiotensin II-Induced Podocyte Injury.

BACKGROUND/AIMS: Angiotensin II (Ang II) induces podocyte injury resulting in apoptosis in vitro and in vivo. However, the relationship between autophagy and apoptosis in Ang II-induced podocyte injury is unknown and the role of Ang II-induced autophagy in podocyte survival or death remains unclear. We investigated the sequential relationship between autophagy and apoptosis in Ang II-induced podocytes as well as the role of phosphatidylinositide 3-kinase (PI3-kinase). METHODS: Mouse podocytes were incubated in media containing various concentrations of Ang II and at different incubation times. The changes of podocyte autophagy and apoptosis were observed by electron microscopy, confocal imaging, western blotting, and FACS assay according to the presence of Ang II. RESULTS: Ang II enhanced the podocyte expression of the autophagic proteins, LC3A/B-II and beclin-1, and also increased the number of autophagosomes compared with control cells at early phase of 12 hours in a dose-dependent manner. This effect was inhibited by pretreatment with 3-methyladenine (3-MA), a PI3-kinase class III inhibitor. Thereafter, the Ang II-induced enhancement in autophagy decreased, whereas, podocyte apoptosis appeared later at 24 hours in concentration- and time-dependent manners in FACS and TUNEL assays. 3-MA and LY294002, a pan PI3-kinase inhibitor, further increased Ang II-induced podocyte apoptosis. Suppression of autophagy by Atg5 siRNA could induce podocyte apoptosis and further augment high-dose Ang II-induced podocyte apoptosis. CONCLUSION: These findings suggest that Ang II promotes autophagy in podocytes before apoptosis as an early adaptive cytoprotective mechanism for podocyte survival after Ang II treatment, and the transitional imbalance between autophagy and apoptosis causes podocyte injury.

Ginseng Total Saponin Attenuates Podocyte Apoptosis Induced by Diabetic Conditions Through the Recovery of CD2-Associated Protein.

CD2-associated protein (CD2AP), an adaptor protein, plays several important roles in podocyte function, linking slit diaphragms to actin-based cytoskeleton and sending survival signals. Here, we investigated whether ginseng total saponin (GTS) had a protective role in the changes of podocyte CD2AP protein and podocyte apoptosis under in vitro diabetic conditions. Conditionally immortalized mouse podocytes cultured with normal glucose (5 mM) or high glucose (30 mM) and with or without advanced glycosylation end products were treated with GTS. We found that CD2AP co-localized with the F-actin fibers in podocyte cytoplasm using confocal imaging; however, diabetic conditions caused the podocytes to diminish and conglomerate CD2AP stainings in the peripheral cytoplasm, which were recovered by GTS. Diabetic conditions also suppressed CD2AP protein levels at 6 and 24 h in western blotting. These phenotypical changes of CD2AP protein were mitigated by GTS. Diabetic conditions also induced podocyte apoptosis at 24 h, which were attenuated by GTS. These findings provide a novel mechanism that diabetic conditions induce quantitative and qualitative changes of podocyte CD2AP protein and apoptosis, which would be restored by GTS.

Puromycin aminonucleoside triggers apoptosis in podocytes by inducing endoplasmic reticulum stress.

Background: Puromycin aminonucleoside (PAN) is a known podocytotoxin. PAN-induced nephrosis is a widely used animal model for studying human idiopathic nephrotic syndrome. Abnormal protein accumulation associated with podocyte-specific endoplasmic reticulum (ER) stress damages cells structurally and functionally, which in turn induces apoptosis and severe proteinuria. In the present study, we investigated the effect of PAN on ER stress and apoptosis in podocytes in vitro. Methods: Mouse podocytes were cultured and treated with various concentrations of PAN. ER stress markers were then evaluated by western blotting, and apoptosis was evaluated by fluorescence-activated cell sorting (FACS) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. Results: PAN treatment increased ER stress markers such as activating transcription factor (ATF) 6α and caspase-12 in a dose-dependent manner at 12 and 24 hours, respectively. These markers were reduced by chemical chaperones, such as sodium 4-phenylbutyric acid and tauroursodeoxycholic acid. PAN treatment also increased 78 kD glucose-regulated protein (GRP78)/binding immunoglobulin protein (BiP) at the earlier stage of 12 hours. PAN significantly induced podocyte apoptosis in concentration- and time-dependent manners, as seen using FACS and TUNEL assays. This result was improved by Nox4 siRNA, ATF6 siRNA, and chemical chaperones. LY294002, a PI3-kinase inhibitor, significantly boosted ER stress and apoptosis. PAN-induced ER stress increased oxidative stress and subsequently induced apoptosis, and could be mitigated by inhibition of PI3-kinase signaling. Conclusion: Our findings suggest that PAN induces ER stress in podocytes mainly through the GRP78/BiP, ATF6α, and caspase-12 pathways, which trigger apoptosis via induction of oxidative stress. This stress is mitigated by inhibiting PI3-kinase signaling.

Characteristics and Clinical Outcomes of Critically Ill Cancer Patients Admitted to Korean Intensive Care Units.

BACKGROUND: The objective of this study was to investigate the characteristics and clinical outcomes of critically ill cancer patients admitted to intensive care units (ICUs) in Korea. METHODS: This was a retrospective cohort study that analyzed prospective collected data from the Validation of Simplified Acute Physiology Score 3 (SAPS3) in Korean ICU (VSKI) study, which is a nationwide, multicenter, and prospective study that considered 5,063 patients from 22 ICUs in Korea over a period of 7 months. Among them, patients older than 18 years of age who were diagnosed with solid or hematologic malignancies prior to admission to the ICU were included in the present study. RESULTS: During the study period, a total of 1,762 cancer patients were admitted to the ICUs and 833 of them were deemed eligible for analysis. Six hundred fifty-eight (79%) had solid tumors and 175 (21%) had hematologic malignancies, respectively. Respiratory problems (30.1%) was the most common reason leading to ICU admission. Patients with hematologic malignancies had higher Sequential Organ Failure Assessment (12 vs. 8, P<0.001) and SAPS3 (71 vs. 69, P<0.001) values and were more likely to be associated with chemotherapy, steroid therapy, and immunocompromised status versus patients with solid tumors. The use of inotropes/vasopressors, mechanical ventilation, and/or continuous renal replacement therapy was more frequently required in hematologic malignancy patients. Mortality rates in the ICU (41.7% vs. 24.6%, P<0.001) and hospital (53.1% vs. 38.6%, P=0.002) were higher in hematologic malignancy patients than in solid tumor patients. CONCLUSIONS: Cancer patients accounted for one-third of all patients admitted to the studied ICUs in Korea. Clinical characteristics were different according to the type of malignancy. Patients with hematologic malignancies had a worse prognosis than did patients with solid tumor.

C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation.

Hypertrophy is a prominent feature of damaged podocytes in diabetic kidney disease (DKD). mTORC1 hyperactivation leads to podocyte hypertrophy, but the detailed mechanism of how mTORC1 activation occurs under pathological conditions is not completely known. Moreover, reduced nephrin tyrosine phosphorylation has been observed in podocytes under pathological conditions, but the molecular mechanism linking nephrin phosphorylation and pathology is unclear so far. In this study, we observed a significant increase in C1-Ten level in diabetic kidney and in high glucose-induced damaged podocytes. C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1. Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo. These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity. We suggest that C1-Ten contributes to the pathogenesis of DKD by inducing podocyte hypertrophy under high glucose conditions.

Montelukast improves the changes of cytoskeletal and adaptor proteins of human podocytes by interleukin-13.

OBJECTIVE AND DESIGN: Interleukin-13 (IL-13) has recently been reported to be a potential cytokine in the pathogenesis of minimal-change nephrotic syndrome (MCNS). However, the mechanistic insights associated with podocyte dysfunction mediated by IL-13-induced changes in various slit diaphragm (SD) and cytoskeletal molecules have not yet been shown in cultured human podocytes in vitro. MATERIALS: Human conditionally immortalized podocytes were used. TREATMENT: Podocytes were incubated with various concentrations of IL-13 during the indicated time periods (6, 12, and 24 h) and montelukast was administered with the dose of 0.1 µg. RESULTS: Treatment of IL-13 resulted in a progressive decrease in distinct processes or projections of the human podocytes and high dose of IL-13 increased podocyte permeability in vitro at 6 h. IL-13 had a substantial impact on the redistribution and rearrangement of zonula occludens (ZO)-1, synaptopodin, α-actinin, CD2-associated protein (CD2AP) in podocytes and disrupted the cytoskeletal connections in a concentration-dependent manner on confocal microscopy. IL-13 also down-modulated ZO-1, synaptopodin, α-actinin, CD2AP, and p130Cas at protein levels and upregulated ß-catenin and B7-1 in podocytes. Furthermore, we demonstrated that down-modulated changes in various SD and cytoskeletal structures of human podocytes induced by IL-13 was significantly restored after treatment with montelukast with upregulation of B7-1. CONCLUSION: Our results suggest that targeting IL-13 may be one of the important cytokines in the pathogenesis of MCNS and targeting IL-13 could be one of the potential therapeutic strategies in MCNS.

Genetics of hereditary nephrotic syndrome: a clinical review.

Advances in podocytology and genetic techniques have expanded our understanding of the pathogenesis of hereditary steroid-resistant nephrotic syndrome (SRNS). In the past 20 years, over 45 genetic mutations have been identified in patients with hereditary SRNS. Genetic mutations on structural and functional molecules in podocytes can lead to serious injury in the podocytes themselves and in adjacent structures, causing sclerotic lesions such as focal segmental glomerulosclerosis or diffuse mesangial sclerosis. This paper provides an update on the current knowledge of podocyte genes involved in the development of hereditary nephrotic syndrome and, thereby, reviews genotype-phenotype correlations to propose an approach for appropriate mutational screening based on clinical aspects.

Clinical outcomes after rescue extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to have survival benefit in patients who had in-hospital cardiac arrest (IHCA). However, limited data are available on the role of extracorporeal membrane oxygenation (ECMO) for out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate clinical outcomes and predictors of in-hospital mortality in patients who had OHCA and who underwent ECPR. METHODS: From January 2004 to December 2013, 235 patients who received ECPR were enrolled in a retrospective, single-centre, observational registry. Among those, we studied 35 adult patients who had OHCA. The primary outcome was in-hospital mortality. RESULTS: Among 35 patients with a median age of 55 years (IQR 45-64), 29 (82.9%) of whom were male, ECMO implantation was successful in all and 10 patients (28.6%) lived to be discharged from the hospital. In 18 cases (51.4%), first monitored rhythms were identified as ventricular tachycardia/ventricular fibrillation, that is, shockable rhythm. There were no differences between in-hospital survivors and non-survivors regarding median time of arrest to cardiopulmonary resuscitation (CPR) (survivors: 23.5 min (IQR 18.8-27.3) vs non-survivors: 20.0 min (IQR 15.0-24.5); p=0.41) and median time of CPR to ECMO pump-on (survivors: 61.0 min (IQR 39.8-77.8) vs non-survivors 50.0 min (IQR 44.0-72.5); p=0.50). In 23 cases (65.7%), ischaemic heart disease was diagnosed and successful revascularisation was achieved in a significantly higher proportion of the survivor group (8/10 (80.0%)) than the non-survivor group (8/25 (32.0%)) (p=0.02). Witnessed arrest (HR=3.96; 95% CI 1.38 to 11.41; p=0.01), bystander CPR (HR=4.05; 95% CI 1.56 to 10.42; p=0.004) and successful revascularisation (HR=2.90; 95% CI 1.23 to 6.86; p=0.02) were independent predictors of survival-to-discharge in patients who had OHCA in univariate Cox regression analysis. CONCLUSION: Survival rate for ECPR in the setting of OHCA remains poor. Our findings suggest that ECMO implantation should be very carefully considered in highly selected patients who had OHCA with little no-flow time and a reversible cause.

CD2-associated protein/phosphoinositide 3-kinase signaling has a preventive role in angiotensin II-induced podocyte apoptosis.

Angiotensin II (Ang II) works as a paracrine or autocrine cytokine agent to regulate renal functions and promotes podocytes dysfunction directly or indirectly, causing proteinuria. The glomerular slit diaphragm (SD) serves as a size-selective barrier and is linked to the actin-based cytoskeleton by adaptor proteins, including CD2-associated protein (CD2AP). Therefore, damages to CD2AP affect not only the function of the SD, but also directly disrupt the podocyte cytoskeleton, leading to proteinuria. In addition, CD2AP can facilitate the nephrin-induced phosphoinositide 3-kinase (PI3-K)/Akt signaling, which protects podocytes from apoptosis. Here we found that CD2AP staining was located diffusely but predominantly in the peripheral cytoplasm and CD2AP co-localized with nephrin in mouse podocytes; however, Ang II decreased CD2AP staining diffusely and induced a separation from concentrated nephrin. Ang II notably reduced CD2AP expression in time- and concentration-dependent manners, and this was significantly recovered by losartan. Ang II induced podocyte apoptosis in time- and concentration-dependent manners in TUNEL and FACS assays. LY294002, a PI3-K inhibitor, further reduced CD2AP expression and increased podocyte apoptosis, which was augmented by siRNA for CD2AP. Thus, Ang II induces the relocalization and reduction of CD2AP via AT1R, which would cause podocyte apoptosis by the suppression of CD2AP/PI3-K signaling.