Positive association between circulating Caveolin-1 and microalbuminuria in overt diabetes mellitus in pregnancy.

AIMS: Mounting evidence has shown that caveolin-1 plays a pathological role in the progression of albuminuria. Our study aimed to provide clinical evidence showing whether circulating caveolin-1 levels were associated with microalbuminuria (MAU) in women with overt diabetes mellitus in pregnancy (ODMIP). METHODS: A total of 150 pregnant women were enrolled in different groups, including 40 women with ODMIP and MAU (ODMIP + MAU), 40 women with ODMIP, and 70 women without ODMIP (Non-ODMIP). Plasma caveolin-1 levels were determined by ELISA. The presence of caveolin-1 in the human umbilical vein vascular wall was evaluated by immunohistochemical and western blot analysis, respectively. Albumin transcytosis across endothelial cells was measured using an established nonradioactive in vitro approach. RESULTS: Significantly increased levels of plasma caveolin-1 were detected in ODMIP + MAU women. The Pearson's correlation analysis revealed a positive correlation between plasma caveolin-1 levels and Hemoglobin A1c (HbA1c %) as well as with MAU in the ODMIP + MAU group. Simultaneously, experimental knockdown or overexpression of caveolin-1 significantly decreased or increased the level of albumin transcytosis across both human and mouse glomerular endothelial cells (GECs), respectively. CONCLUSIONS: Our data showed a positive association between plasma caveolin-1 levels and microalbuminuria in ODMIP + MAU.

Effects of Three Different Heating Devices on Patients Undergoing Surgery: A Network Meta-Analysis.

PURPOSE: Perioperative hypothermia is a common anesthesia-related complication that can result in negative outcomes. Intraoperative active heating can positively impact these outcomes. Therefore this study aimed to investigate the effectiveness of three common heating devices for controlling hypothermia, improving thermal comfort, and reducing anesthesia recovery time. DESIGN: Systematic review and meta-analysis. METHODS: Seven electronic literature databases were searched from the inception date of the databases to March 18, 2022. RevMan 5.4 and Stata 15.1 were used to perform meta-analyses on the obtained data, and the Cochrane Evaluation Manual was used for quality risk assessment of the included studies. FINDINGS: A total of 18 studies involving 1,511 patients undergoing surgery using heating devices were included. In this meta-analysis, a ranking method known as the Surface Under the Cumulative Ranking Curve (SUCRA) was used. SUCRA provides a numerical measure of the effectiveness of treatments, with higher values indicating superior efficacy. Findings demonstrated that the concurrent use of three heating devices led to an elevation in core body temperatures (SUCRA = 69.2%) and enhanced delayed recovery (SUCRA = 88.6%) as compared to the application of a single device. Furthermore, for thermal comfort, the employment of heating blankets proved to be the most effective (SUCRA = 87.8%). CONCLUSIONS: This study showed the core body temperatures and reductions in delayed recovery were greater when three heating devices were used together as compared to use one of them alone. Heating blankets was the most effective option for improving the thermal comfort of patients. Thus, clinicians should opt for appropriate heating equipment according to the type of surgery and the characteristics and needs of patients. The choice of appropriate heating equipment will ensure surgical safety, improve patient comfort, and reduce surgical risks.

[Research progress on exosomes and exosomal microRNAs in the occurrence and development of diabetic peripheral neuropathy].

Diabetic peripheral neuropathy (DPN) is one of the chronic complications of diabetic neuropathy, and also the main cause of chronic wounds and disability. Exosomes and exosomal-microRNAs (miRNAs) are closely related to DPN and participate in the signal transduction and protein expression of the peripheral nervous system by mediating intercellular communication. However, the specific role and mechanism of EVs and exosomal-miRNAs in the occurrence and development of DPN in high-glucose environments are not fully understood. This article reviews the promotion of EVs and exosomal-miRNAs in the occurrence and development of DPN in inhibiting axon growth, promoting inflammatory response, and inducing vascular injury in a high glucose environment.

ABO Blood Group and Bleeding and Survival in VA-ECMO Patients.

ABO blood group has been shown to be a major determinant of plasma von Willebrand factor (vWF) levels. O blood group is associated with the lowest vWF levels and confers an increased risk of hemorrhagic events, while AB blood group has the highest levels and is associated with thromboembolic events. We hypothesized in extracorporeal membrane oxygenation (ECMO) patients that O blood type would have the highest and AB blood type would have the lowest transfusions, with an inverse relationship to survival. A retrospective analysis of 307 VA-ECMO patients at a major quaternary referral hospital was performed. The distribution of blood groups included 124 group O (40%), 122 group A (40%), 44 group B (14%), and 17 group AB (6%) patients. Regarding usage of packed red blood cells, fresh frozen plasma, and platelets, there was a non-statistically significant difference in transfusions, with group O having the least and group AB having the most requirements. However, there was a statistically significant difference in cryoprecipitate usage when comparing to group O: group A (1.77, 95% CI: 1.05-2.97, P < .05), group B (2.05, 95% CI: 1.16-3.63, P < .05), and group AB (3.43, 95% CI: 1.71-6.90, P < .001). Furthermore, a 20% increase in length of days on ECMO was associated with a 2-12% increase in blood product usage. The cumulative 30-day mortality rate for groups O and A was 60%, group B was 50%, and group AB was 40%; the 1-year mortality rate for groups O and A was 65%, group B was 57%, and group AB was 41%; however, the mortality differences were not statistically significant.

Red blood cell distribution width predicts mortality of adult patients receiving veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Red blood cell distribution width (RDW) is a numerical measure of the variation in the size of circulating red blood cells. Recently, there is increasing interest in the role of RDW as a biomarker for inflammatory states and as a prognostication tool for a wide range of clinical manifestations. The predictive power of RDW on mortality among patients receiving mechanical circulatory support remains largely unknown. METHODS: A retrospective analysis of 281 VA-ECMO patients at a tertiary referral academic hospital from 2009 to 2019 was performed. RDW was dichotomized with RDW-Low <14.5% and RDW-High ≥14.5%. The primary outcome was all-cause mortality at 30 days and 1 year. Cox proportional hazards models were used to examine the association between RDW and the clinical outcomes after adjusting for additional confounders. RESULTS: 281 patients were included in the analysis. There were 121 patients (43%) in the RDW-Low group and 160 patients (57%) in the RDW-High group. Survival to ECMO decannulation [RDW-H: 58% versus RDW-L: 67%, p = 0.07] were similar between the two groups. Patients in RDW-H group had higher 30-days mortality (RDW-H: 67.5% vs RDW-L: 39.7%, p < 0.001) and 1 year mortality (RDW-H: 79.4% vs RDW-L: 52.9%, p < 0.001) compared to patients in the RDW-L group. After adjusting for confounders, Cox proportional hazards model demonstrated that patients with high RDW had increased odds of mortality at 30 days (hazard ratio 1.9, 95% CI 1.2-3.0, p < 0.01) and 1 year (hazard ratio 1.9, 95% CI 1.3-2.8, p < 0.01) compared to patients with low RDW. CONCLUSIONS: Among patients receiving mechanical circulatory support with VA-ECMO, a higher RDW was independently associated with increased 30-days and 1-year mortality. RDW may serve as a simple biomarker that can be quickly obtained to help provide risk stratification and predict survival for patients receiving VA-ECMO.

[Combination of anlotinib and irinotecan in the second-line treatment of metastatic colorectal cancer: a multicenter phase 1/2 trial].

Objective: To evaluate the safety and efficacy of anlotinib plus irinotecan in the second-line treatment of patients with metastatic colorectal cancer (mCRC). Methods: This prospective phase 1/2 study was conducted in 2 centers in China (Cancer Hospital of Chinese Academy of Medical Sciences and Jiangsu Province Hospital). We enrolled patients with mCRC whose disease had progressed after first-line systemic therapy and had not previously treated with irinotecan to receive anlotinib plus irinotecan. In the phase 1 of the trial, patients received anlotinib (8 mg, 10 mg or 12 mg, po, 2 weeks on/1 week off) in combination with fixed-dose irinotecan (180 mg/m(2), iv, q2w) to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). In the phase 2, patients were treated with the RP2D of anlotinib and irinotecan. The primary endpoints were MTD and objective response rate (ORR). Results: From May 2018 to January 2020, a total of 31 patients with mCRC were enrolled. Anlotinib was well tolerated in combination with irinotecan with no MTD identified in the phase 1, and the RP2D was 12 mg. Thirty patients were evaluable for efficacy analysis. Eight patients achieved partial response, and 21 had stable disease, 1 had progressive disease. The ORR was 25.8% and the disease control rate was 93.5%. With a median follow-up duration of 29.5 months, the median progression-free survival and overall survival were 6.9 months (95% CI: 3.7, 9.3) and 17.6 months (95% CI: 12.4, not evaluated), respectively. The most common grade 3 treatment-related adverse events (≥10%) were neutropenia (25.8%) and diarrhea (16.1%). There was no treatment-related death. Conclusion: The combination of anlotinib and irinotecan has promising anti-tumor activity in the second-line treatment of mCRC with a manageable safety profile.

[BCS1Neonatal growth retardation and lactic acidosis initiated by novel mutation sites in L gene].

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.

A conserved acetylation switch enables pharmacological control of tubby-like protein stability.

Tubby-like proteins (TULPs) are characterized by a conserved C-terminal domain that binds phosphoinositides. Collectively, mammalian TULP1-4 proteins play essential roles in intracellular transport, cell differentiation, signaling, and motility. Yet, little is known about how the function of these proteins is regulated in cells. Here, we present the protein-protein interaction network of TULP3, a protein that is responsible for the trafficking of G-protein-coupled receptors to cilia and whose aberrant expression is associated with severe developmental disorders and polycystic kidney disease. We identify several protein interaction nodes linked to TULP3 that include enzymes involved in acetylation and ubiquitination. We show that acetylation of two key lysine residues on TULP3 by p300 increases TULP3 protein abundance and that deacetylation of these sites by HDAC1 decreases protein levels. Furthermore, we show that one of these sites is ubiquitinated in the absence of acetylation and that acetylation inversely correlates with ubiquitination of TULP3. This mechanism is evidently conserved across species and is active in zebrafish during development. Finally, we identify this same regulatory module in TULP1, TULP2, and TULP4 and demonstrate that the stability of these proteins is similarly modulated by an acetylation switch. This study unveils a signaling pathway that links nuclear enzymes to ciliary membrane receptors via TULP3, describes a dynamic mechanism for the regulation of all tubby-like proteins, and explores how to exploit it pharmacologically using drugs.

Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial.

BACKGROUND: Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm-Pac plus cisplatin and solvent-based paclitaxel (sb-Pac) plus cisplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 448 stage IIIB to IV NSCLC patients were randomly assigned (2:1) to receive six 3-week cycles of either pm-Pac (230 mg/m2) plus cisplatin (70 mg/m2; n = 300), followed by dose escalation of pm-Pac to 300 mg/m2 from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m2) plus cisplatin (70 mg/m2; n = 148). The primary end point was objective response rate (ORR) assessed by independent review committees (IRCs). The secondary end points included IRC-assessed progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Patients in the pm-Pac-plus-cisplatin group showed significant improvements in IRC-assessed ORR compared with those in the sb-Pac-plus-cisplatin group (50% versus 26%; rate ratio 1.91; P < 0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and nonsquamous histological types. IRC-assessed median PFS was significantly higher in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group (6.4-month versus 5.3-month; hazard ratio 0.63; P = 0.0001). Median OS was not significantly different between the two groups. The incidence of treatment-related serious adverse events (9% versus 18%; P = 0.0090) was significantly lower in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group. CONCLUSION: Pm-Pac plus cisplatin yielded superior ORR and PFS along with a favorable safety profile and should become an option for patients with advanced NSCLC. CLINICAL TRIAL IDENTIFIER: ClinicalTrials.gov NCT02667743; https://clinicaltrials.gov/ct2/show/NCT02667743.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated with IRF7, BANK1 and TBX21 polymorphisms in two populations.

BACKGROUND AND PURPOSE: Autoantibodies targeting the GluN1(NR1) subunit of the anti-N-methyl-D-aspartate receptor (NMDAR) cause encephalitis. Although it has been shown that anti-NMDAR encephalitis is associated with human leukocyte antigen (HLA) loci, susceptibility genes for the disease outside the HLA loci remain unidentified. In this study, we aimed to explore the association of anti-NMDAR encephalitis with non-HLA genes. METHODS: Two Chinese anti-NMDAR encephalitis cohorts from Han populations were recruited for this study. The North Chinese case-control set consisted of 98 patients and 460 controls, while the South Chinese case-control set included 78 patients and 541 controls. All participants were genotyped for 28 single nucleotide polymorphisms that are associated with autoimmune disorders or infectious diseases. RESULTS: In two independent case-control sets, we identified significant associations of anti-NMDAR encephalitis with IRF7 rs1131665 (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.99-5.63; P < 0.000001, Padjusted  = 0.00004), BANK1 rs4522865 (OR 1.44, 95% CI 1.15-1.82; P = 0.0017, Padjusted  = 0.0149), and TBX21 rs17244587 (OR 2.03, 95% CI 1.35-3.05; P = 0.00051, Padjusted  = 0.0066). Furthermore, analysis of the three polymorphisms with clinical features of the disease revealed that the IRF7 rs1131665 was associated with tumor status. CONCLUSION: The present study has for the first time identified non-HLA susceptibility genes for anti-NMDAR encephalitis. The association of IRF7, BANK1 and TBX21 with anti-NMDAR encephalitis suggests that B-cell activation, Th1 responses, virus infection and the type I interferon signaling pathway are involved in the pathogenesis of the disease.

Continuous Noninvasive Arterial Pressure Monitoring for Transcatheter Aortic Valve Replacement.

OBJECTIVES: The objective of the present study, which was conducted in patients undergoing transcatheter aortic valve replacement, was to compare continuous noninvasive arterial pressure measured with the ClearSight device (Edwards Lifesciences, Irvine, CA) with invasive radial artery pressure used as the reference method. The authors hypothesized that the ClearSight device is an accurate, precise, safe, and efficient method for arterial blood pressure measurement comparable with an invasive radial arterial line. DESIGN: The study included the retrospective review of 20 consecutive patients scheduled for elective transcatheter aortic valve replacement with the SAPIEN 3 transcatheter heart valve (Edwards Lifesciences) at a single tertiary academic hospital, who underwent monitoring with both the ClearSight device and an invasive radial arterial pressure line. The patients underwent transcatheter aortic valve replacement from October to December 2019. SETTING: Single tertiary academic medical center. PARTICIPANTS: The study comprised 20 patients, with 2,243 unique blood pressure data points. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A statistically significant correlation between the invasive radial arterial pressure line and the ClearSight device was observed for systolic blood pressure (correlation coefficient 0.86; p < 0.001), diastolic blood pressure (correlation coefficient 0.56; p < 0.001), and mean arterial pressure (correlation coefficient 0.78; p < 0.001). Bland-Altman analysis was used to assess the agreement of systolic blood pressure, diastolic blood pressure, and mean arterial pressure between the two methods. Results for systolic blood pressure between the arterial line and ClearSight device were as follows: bias = 9.8 ± 10.1, percentage bias = 7.6%, and mean error = 15.8%. Results for diastolic blood pressure between the arterial line and ClearSight device were as follows: bias = -5.9 ± 7.8, percentage bias = 10.7%, and mean error = 28.4%. Results for mean arterial pressure between the arterial line and ClearSight device were as follows: bias = 0.3 ± 7.4, percentage bias = 0.4%, and mean error = 18.3%. The concordance rates of systolic blood pressure, diastolic blood pressure, and mean arterial pressure were 100%, 95.1%, and 98.8%, respectively. CONCLUSIONS: The accuracy, agreement, and precision of the ClearSight device were convincing for mean arterial pressure, systolic blood pressure, and diastolic blood pressure for patients with severe aortic stenosis undergoing elective transcatheter aortic valve replacement.

Perioperative Outcomes of Thrombectomy Patients Using Venovenous Bypass and Suction Filtration With General Anesthesia.

OBJECTIVE: AngioVac (Angiodynamics, Latham, NY) is a novel drainage system that offers a less-invasive approach compared with open surgical thromboembolectomy to remove intracardiac and intravascular thrombotic and embolic material. For this study, the authors' single-center experience with patients undergoing thromboembolectomy using the AngioVac system was reviewed retrospectively to evaluate anesthetic management and postoperative complications. DESIGN: Retrospective, observational study. SETTING: Single institution, quaternary care hospital. PARTICIPANTS: The study comprised 20 consecutive patients whose treatment included the AngioVac between January 2016 and November 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty patients underwent AngioVac suction filtration. The mean age was 56 years, and women comprised 35% of the patient cohort. Indications for AngioVac suction filtration included deep venous thrombosis involving the inferior vena cava (n = 12 [60%]), right atrial mass/thrombus (n = 11 [55%]), right ventricular mass/thrombus (n = 3 [15%]), and pulmonary embolism(n = 2 [10%]). All patients required vasopressor support, and nine patients (45%) required blood transfusion during the procedure. There was no intraoperative death or cardiac arrest associated with the procedure. The 30-day mortality was zero, and in-hospital mortality was 5% (1/20). Significant postoperative complications occurred in 11/20 patients (55%). Postoperative left ventricular dysfunction (36% v 0%; p < 0.05), preoperative shock requiring vasopressors (36% v 0%; p < 0.05), postoperative blood transfusion (100% v 56%; p < 0.05), and having undergone recent surgery (64% v 11%; p < 0.05) were associated with increased odds of experiencing postoperative complications. CONCLUSIONS: The rate of intraoperative complication during AngioVac suction filtration is low, but vasopressors and blood transfusions often are required. Patients at increased risk of developing postoperative complications potentially can be identified as having undergone recent surgery, experiencing preoperative shock requiring vasopressors or postoperative left ventricular dysfunction, and requiring postoperative blood transfusion.

[Employment, turnover intention and the associated factors among public health graduates in China].

Objective: To understand the employment situation of graduates of public health-related majors and explore the associated factors of turnover intention among public health practitioners in China. Methods: In April 2020, the convenient sampling method was used to recruit public health related graduates from 98 universities with public health-related majors from 31 provinces in China (excluding Hong Kong, Macao and Taiwan) and from Chinese Center for Disease Control and Prevention (only including working or unemployed status, no requirement for graduation years). A total of 1 322 questionnaires were collected, of which 1 165 (88.1%) were valid. Through the network questionnaire survey, the information of public health graduates' work situation, job satisfaction and turnover intention were collected. Multivariate logistic regression model was used to analyze the associated factors of turnover intention, and structural equation model was constructed to explore the correlation between turnover intention and job satisfaction. Results: The age of 1 165 graduates was (28.1±4.8) years. Among them, 719 (61.7%) were female and 856 (73.5%) graduates were engaged in public health-related work after graduation. The results of multivariate logistic regression analysis showed that compared with those over 30 years old, graduates under 30 years old had higher turnover intention (OR=2.531, 95%CI: 1.549-4.155). Compared with those with junior or no title, graduates with senior title had higher turnover intention (OR=2.310, 95%CI: 1.047-5.162). The results of structural equation model analysis showed that the four factors of job satisfaction, 'salary and welfare', 'promotion development', 'work itself', and 'internal and external environment', were negatively correlated with turnover intention. The internal and external environment had the greatest impact on turnover intention (total effect =-0.539). Conclusion: Most graduates of public health-related majors are engaged in public health-related work in China. Age, professional title and job satisfaction are the associated factors of turnover intention.

Microstructure evolution and wear behavior of AISI 304 stainless steel after Nd:YAG pulsed laser surface melting.

The microstructure and wear behavior of AISI 304 stainless steel after Nd:YAG pulsed laser surface melting (LSM) were investigated. The microstructural features of the LSM layer were characterized by field emission scanning electron microscope and high-resolution transmission electron microscope. Experimental results showed that the microstructure was obviously refined to the nano- and sub-micrometer scales on the AISI 304 stainless steel surface after LSM treatment. Fine grains with grain size of less than 200 nm were obtained when the applied laser energy densities were in the range of 1.90×107 to 3.52×107J/m2 during LSM. The results indicated that the calculated surface temperature, cooling rate, and measured grain size are closely related to the adopted laser energy densities. The lower the laser energy density is, the lower the surface temperature, and the faster the cooling rate, the finer the grain size. In addition, the microhardness and wear resistance of the stainless steel was significantly improved. Finally, the wear mechanism after LSM process was revealed.

Development and validation of new diagnostic criteria for atopic dermatitis in children of China.

BACKGROUND: In previous epidemiological study, the prevalence of atopic dermatitis (AD) was 12.94% among children aged 1-7 years by clinical diagnosis, whereas that was 4.76% and 3.51% using U.K., and Hanifin and Rajka diagnostic criteria. OBJECTIVE: We aimed to propose new diagnostic criteria for children and evaluate its efficiency in different populations. METHODS: We screened atopic features and analysed their correlation with AD using data from a previous study. A new set of diagnostic criteria for children in China was proposed and validated in 1031 children in outpatient clinics and 538 children in a birth cohort survey. Clinical diagnosis and atopic feature evaluation were performed face to face by dermatologists specialized in AD. Three criteria were compared for diagnostic efficiency using the clinical diagnosis as the reference. RESULTS: The new diagnostic criteria for children were based on (i) pruritus; (ii) 'typical morphology and distribution' or 'atypical morphology and distribution with xerosis'; and (iii) a chronic or chronically relapsing course. Compared to classical diagnostic criteria, the sensitivity of the new diagnostic criteria was significantly higher in the epidemiological survey and the clinical setting, especially obvious among mild and moderate AD. In the birth cohort, the new criteria showed similar sensitivity and specificity. CONCLUSION: The new criteria for children yielded higher sensitivity for the diagnosis of AD in the epidemiological survey and clinical setting, particularly for mild and moderate AD. Among the birth cohort with a complete medical history, three criteria showed similar sensitivity and specificity.

Rescue Echocardiography/Ultrasonography in the Management of Combined Cardiac Surgical and Medical Patients in a Cardiac Intensive Care Unit.

OBJECTIVES: Rescue point-of-care ultrasound (r-POCUS) in critical care medicine has revolutionized the management of critically ill patients with hemodynamic instability. However, clinical studies on its use among high-risk cardiac patients still are limited. The authors aimed to assess the utility of r-POCUS for managing high-risk cardiac patients in a mixed cardiac-surgical and cardiac-medical intensive care unit (ICU) in a quaternary care hospital by reviewing the indications and findings of r-POCUS and subsequent effect on patient management. DESIGN: Retrospective observational study. DESIGN: Single institution, quaternary care hospital. PARTICIPANTS: The study comprised 189 consecutive r-POCUS examinations performed in a cardiac medical and surgical ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: r-POCUS was performed on 141 patients. Common indications for r-POCUS included hypotension (n = 93 [49%]), assessment of extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (n = 33 [17%]), arrhythmias (n = 13 [7%]), abnormal pulmonary artery catheter values (n = 11 [6%]), and ischemic electrocardiogram changes (n = 10 [5%]). Cardiac pathology was positive in 129 (68%) of the rescue examinations. Common reported pathologies included left ventricular dysfunction (n = 47 [25%]), right ventricular dysfunction (n = 52 [28%]), hypervolemia (n = 13 [7%]), hypovolemia (n = 25 [13%]), pericardial effusion/tamponade (n = 21 [11%]), and ECMO/ventricular assist device cannula malposition (n = 9 [5%]). Seventy-five percent of the rescue examinations resulted in medical and surgical interventions, including fluid resuscitation (n = 25 [13%]), diuresis (n = 14 [7%]), ionotropic support (n = 23 [12%]), surgical intervention in the operating room (n = 21 [11%]), surgical intervention at the bedside (n = 8 [4%]), ECMO initiation (n = 15 [8%]), and ECMO/ventricular assist device cannula/setting adjustment (n = 12 [6%]). CONCLUSION: In this retrospective study, r-POCUS performed by attending intensivists resulted in diverse findings and was associated with rapid changes in clinical management of patients in a high-acuity, mixed cardiac-surgical and cardiac-medical ICU.

Implementing a Cardiac Enhanced Recovery After Surgery Protocol: Nuts and Bolts.

The use of Enhanced Recovery After Surgery (ERAS) protocols among various surgical subspecialties is increasing, including in cardiac surgery. The goal of these protocols is to optimize patient outcomes and satisfaction and improve the value of healthcare delivered. Cardiac ERAS protocols are divided into the following 3 stages of perioperative care: preoperative, intraoperative, and postoperative. ERAS strategies have been shown to work synergistically to reduce the length of hospital stay, postoperative complications, hospital cost, and opioid consumption; increase patient satisfaction; and result in less and early extubation. The ERAS team should consist of clinicians involved in the patient's care throughout the entire ERAS process. A cardiac ERAS program is an example of value-based care applied to a specific surgical specialty with goals to improve patient satisfaction, provide earlier recovery, and reduce hospital cost. This narrative review details the updates and gaps in the literature regarding the efficacy and utility of an ERAS protocol in cardiac surgery, outlines the individual components of a cardiac surgery ERAS protocol, and describes the implementation science that can be used to execute a cardiac ERAS protocol successfully.

Extracorporeal Cardiopulmonary Resuscitation: Outcomes and Complications at a Quaternary Referral Center.

OBJECTIVE: At a quaternary care center that regularly performs and cares for patients undergoing extracorporeal cardiopulmonary resuscitation (eCPR), a database of all adult patients who underwent eCPR with venoarterial extracorporeal membrane oxygenation (ECMO) over a 10-year period was reviewed. Seventy-one eCPR patients were analyzed to compare outcomes and complication rates. The authors hypothesized that evidence of end-organ injury, such as the need for continuous renal replacement therapy, in their institution's eCPR population would be associated with increased in-hospital mortality. DESIGN: Retrospective chart review of prospectively collected data at a quaternary care center. SETTING: Single quaternary academic referral center for ECMO. PARTICIPANTS: The study comprised adult patients who underwent venoarterial ECMO for eCPR from 2009-2019 and for whom demographic data, survival data, and complication rates were available. INTERVENTIONS: None-this was a retrospective chart review. MEASUREMENTS AND MAIN RESULTS: eCPR survival was 53.5% (38 of 71), and hospital survival was 33.8% (24 of 71). The most common complications were hemorrhage (26 of 67), renal failure (19 of 67), and neurologic injury (14 of 67). Of 19 patients requiring renal replacement therapy, only 1 survived to hospital discharge (5.3%) versus 23 of 48 patients without renal failure (47.9%) surviving to discharge (p = 0.001). CONCLUSIONS: In this cohort of 71 patients who underwent eCPR, outcomes were promising; however, complication rates were high, and renal failure in particular demonstrated an extremely high mortality. These are single-institution results that should be followed up with larger multicenter cohorts of eCPR patients.

[Expression of anaplastic lymphoma kinase clone 1A4 in pediatric medulloblastoma and its significance].

Objective: To investigate the immunohistochemical staining of anaplastic lymphoma kinase (ALK; clone 1A4) in pediatric medulloblastoma (MB). Methods: Molecular subtyping was performed based on the NanoString and sequencing techniques for 44 pediatric MB cases at Children's Hospital, Zhejiang University School of Medicine from 2014 to 2017. ALK expression was detected with EnVision immunhistochemistry using ALK clone 1A4 on whole section. Statistical analyses were performed to evaluate the correlation of protein expression with molecular subgroups. Results: The age ranged from 0.5 to 13.0 years with an average age of 5.8 years. There were 28 males and 16 females, and 31 classic, 5 desmoplastic nodular, 3 extensive nodular and 5 large cell/anaplastic MBs. Except three cases was unable classified, 41 MBs were classified into the four molecular groups: 5 in WNT group, 12 in SHH group, 9 in Group 3 and 15 in Group 4. Thirteen of 44 MB cases were positive staining for ALK, and the positive rate was 29.5%. Six cases were strong reaction, and 7 cases were weak. The expression of ALK at the protein level was associated with the WNT group (P<0.01). The characteristic perinuclear dot-like staining was only showed in WNT group. Conclusions: The ALK immunhistochemistry using antibody clone 1A4 is a useful marker for the molecular subgroup detection of MB. The strong staining and perinuclear dot-like staining indicate as WNT group.

[Analysis of treatment modalities and prognosis of patients with gallbladder cancer in China from 2010 to 2017].

Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.