A Standardized Step-by-Step Approach for the Diagnosis and Treatment of Sepsis.

Sepsis is the major culprit of death among critically ill patients who are hospitalized in intensive care units (ICUs). Although sepsis-related mortality is steadily declining year-by-year due to the continuous understanding of the pathophysiological mechanism on sepsis and improvement of the bundle treatment, sepsis-associated hospitalization is rising worldwide. Surviving Sepsis Campaign (SSC) guidelines are continuously updating, while their content is extremely complex and comprehensive for a precisely implementation in clinical practice. As a consequence, a standardized step-by-step approach for the diagnosis and treatment of sepsis is particularly important. In the present study, we proposed a standardized step-by-step approach for the diagnosis and treatment of sepsis using our daily clinical experience and the latest researches, which is close to clinical practice and is easy to implement. The proposed approach may assist clinicians to more effectively diagnose and treat septic patients and avoid the emergence of adverse clinical outcomes.

Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation.

Alternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain. Whether AR-V7 can be a driver for CRPC remains controversial as the oncogenic mechanism of AR-V7 activation remains elusive. Here, we found that KDM4B promotes AR-V7 and identified a novel regulatory mechanism. KDM4B is phosphorylated by protein kinase A under conditions that promote castration-resistance, eliciting its binding to the splicing factor SF3B3. KDM4B binds RNA specifically near the 5'-CE3, upregulates the chromatin accessibility, and couples the spliceosome to the chromatin. Our data suggest that KDM4B can function as a signal responsive trans-acting splicing factor and scaffold that recruits and stabilizes the spliceosome near the alternative exon, thus promoting its inclusion. Genome-wide profiling of KDM4B-regulated genes also identified additional alternative splicing events implicated in tumorigenesis. Our study defines KDM4B-regulated alternative splicing as a pivotal mechanism for generating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRPC.

Acute right ventricular dysfunction in severe COVID-19 pneumonia.

To investigate the right heart function in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS), a retrospective analysis of 49 COVID-19 patients with ARDS was performed. Patients were divided into severe group and critically-severe group according to the severity of illness. Age-matched healthy volunteers were recruited as a control group. The cardiac cavity diameters, tricuspid annular plane systolic excursion (TAPSE), tricuspid valve regurgitation pressure gradient biggest (TRPG), pulmonary arterial systolic pressure (PASP), maximum inferior vena cava diameter (IVCmax) and minimum diameter (IVCmin), and inferior vena cava collapse index (ICV-CI) were measured using echocardiography. We found that the TAPSE was significantly decreased in pneumonia patients compared to healthy subjects (P < 0.0001), and it was significantly lower in critically-severe patients (P = 0.0068). The TAPSE was less than 17 mm in three (8.6%) severe and five (35.7%) critically-severe patients. In addition, the TAPSE was significantly decreased in severe ARDS patients than in mild ARDS patients. The IVCmax and IVCmin were significantly increased in critically-severe patients compared to healthy subjects and severe patients (P < 0.01), whereas the ICV-CI was significantly decreased (P < 0.05). COVID-19 patients had significantly larger right atrium and ventricle than healthy controls (P < 0.01). The left ventricular ejection fraction (LVEF) in critically-severe patients was significantly lower than that in severe patients and healthy controls (P < 0.05). Right ventricular function was impaired in critically-severe COVID-19 patients. The assessment and protection of the right heart function in COVID-19 patients should be strengthened.

MicroRNA-223-5p and -3p Cooperatively Suppress Necroptosis in Ischemic/Reperfused Hearts.

Recent studies have shown that myocardial ischemia/reperfusion (I/R)-induced necrosis can be controlled by multiple genes. In this study, we observed that both strands (5p and 3p) of miR-223 were remarkably dysregulated in mouse hearts upon I/R. Precursor miR-223 (pre-miR-223) transgenic mouse hearts exhibited better recovery of contractile performance over reperfusion period and lesser degree of myocardial necrosis than wild type hearts upon ex vivo and in vivo myocardial ischemia. Conversely, pre-miR-223 knock-out (KO) mouse hearts displayed opposite effects. Furthermore, we found that the RIP1/RIP3/MLKL necroptotic pathway and inflammatory response were suppressed in transgenic hearts, whereas they were activated in pre-miR-223 KO hearts upon I/R compared with wild type controls. Accordingly, treatment of pre-miR-223 KO mice with necrostatin-1s, a potent necroptosis inhibitor, significantly decreased I/R-triggered cardiac necroptosis, infarction size, and dysfunction. Mechanistically, we identified two critical cell death receptors, TNFR1 and DR6, as direct targets of miR-223-5p, whereas miR-223-3p directly suppressed the expression of NLRP3 and IκB kinase α, two important mediators known to be involved in I/R-induced inflammation and cell necroptosis. Our findings indicate that miR-223-5p/-3p duplex works together and cooperatively inhibits I/R-induced cardiac necroptosis at multiple layers. Thus, pre-miR-223 may constitute a new therapeutic agent for the treatment of ischemic heart disease.

Suppression of Ghrelin Exacerbates HFCS-Induced Adiposity and Insulin Resistance.

High fructose corn syrup (HFCS) is widely used as sweetener in processed foods and soft drinks in the United States, largely substituting sucrose (SUC). The orexigenic hormone ghrelin promotes obesity and insulin resistance; ghrelin responds differently to HFCS and SUC ingestion. Here we investigated the roles of ghrelin in HFCS- and SUC-induced adiposity and insulin resistance. To mimic soft drinks, 10-week-old male wild-type (WT) and ghrelin knockout (Ghrelin-/-) mice were subjected to ad lib. regular chow diet supplemented with either water (RD), 8% HFCS (HFCS), or 10% sucrose (SUC). We found that SUC-feeding induced more robust increases in body weight and body fat than HFCS-feeding. Comparing to SUC-fed mice, HFCS-fed mice showed lower body weight but higher circulating glucose and insulin levels. Interestingly, we also found that ghrelin deletion exacerbates HFCS-induced adiposity and inflammation in adipose tissues, as well as whole-body insulin resistance. Our findings suggest that HFCS and SUC have differential effects on lipid metabolism: while sucrose promotes obesogenesis, HFCS primarily enhances inflammation and insulin resistance, and ghrelin confers protective effects for these metabolic dysfunctions.

Budesonide ameliorates lung injury induced by large volume ventilation.

BACKGROUND: Ventilation-induced lung injury (VILI) is a health problem for patients with acute respiratory dysfunction syndrome. The aim of this study was to investigate the effectiveness of budesonide in treating VILI. METHODS: Twenty-four rats were randomized to three groups: a ventilation group, ventilation/budesonide group, and sham group were ventilated with 30 ml/kg tidal volume or only anesthesia for 4 hor saline or budesonide airway instillation immediately after ventilation. The PaO2/FiO2and wet-to-dry weight ratios, protein concentration, neutrophil count, and neutrophil elastase levels in bronchoalveolar lavage fluid (BALF) and the levels of inflammation-related factors were examined. Histological evaluation of and apoptosis measurement inthe lung were conducted. RESULTS: Compared with that in the ventilation group, the PaO2/FiO2 ratio was significantly increased by treatment with budesonide. The lung wet-to-dry weight ratio, total protein, neutrophil elastase level, and neutrophilcount in BALF were decreased in the budesonide group. The BALF and plasma tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, intercellular adhesion molecule (ICAM)-1, and macrophage inflammatory protein (MIP)-2 levels were decreased, whereas the IL-10 level was increased in the budesonide group. The phosphorylated nuclear factor (NF)-kBlevels in lung tissue were inhibited by budesonide. The histological changes in the lung and apoptosis were reduced by budesonide treatment. Bax, caspase-3, and cleaved caspase-3 were down-regulated, and Bcl-2 was up-regulated by budesonide. CONCLUSIONS: Budesonide ameliorated lung injury induced by large volume ventilation, likely by improving epithelial permeability, decreasing edema, inhibiting local and systemic inflammation, and reducing apoptosis in VILI.

Increased whole blood viscosity associated with arterial stiffness in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for increased cardiovascular disease. The brachial-ankle pulse wave velocity (baPWV) is a marker for early atherosclerotic changes. Recently, the effect of changed blood rheology on atherosclerosis has received attention. A study confirmed that whole blood viscosity (WBV) is a predictor of cardiovascular events. Therefore, this study aimed to investigate the association of WBV with baPWV in patients with NAFLD. METHODS: In this cross-sectional study, the relationship between WBV and baPWV was investigated in 2032 participants (1035 men and 997 women) with NAFLD in a general health examination. RESULTS: Different metabolic parameters were compared across WBV (3/s) quartiles. The mean values of baPWV gradually increased with WBV (3/s) quartiles. Stepwise multiple linear regression analysis revealed that WBV (3/s) is a significant determinant for increased baPWV both in men and in women (for male, ß = 0.229; P < 0.001; for female, ß = 0.672; P < 0.001). CONCLUSIONS: The findings showed that baPWV elevated as WBV (3/s) increased in NAFLD. Moreover, WBV (3/s) is independently associated with baPWV even after adjusting other cardiovascular risk factors. Early detection of abnormal WBV levels at low shear rate should warrant for early search of undetected arterial stiffness in patients with NAFLD.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Up-regulation of Myocardial Klotho Expression to Promote Cardiac Functional Recovery in Old Mice following Endotoxemia.

Objective: Endotoxemic cardiac dysfunction contributes to greater morbidity and mortality in elderly patients with sepsis. This study tested the hypothesis that Klotho insufficiency in aging heart exaggerates and prolongs myocardial inflammation to hinder cardiac function recovery following endotoxemia. Methods: Endotoxin (0.5 mg/kg, iv) was administered to young adult (3-4 months) and old (18-22 months) mice with or without subsequent treatment with recombinant interleukin-37 (IL-37, 50 µg/kg, iv) or recombinant Klotho (10 µg/kg, iv). Cardiac function was analyzed using a microcatheter 24, 48 and 96 h later. Myocardial levels of Klotho, ICAM-1, VCAM-1 and IL-6 were determined by immunoblotting and ELISA. Results: In comparison to young adult mice, old mice had worse cardiac dysfunction accompanied by greater myocardial levels of ICAM-1, VCAM-1 and IL-6 at each time point following endotoxemia and failed to fully recover cardiac function by 96 h. The exacerbated myocardial inflammation and cardiac dysfunction were associated with endotoxemia-caused further reduction of lower myocardial Klotho level in old mice. Recombinant IL-37 promoted inflammation resolution and cardiac functional recovery in old mice. Interestingly, recombinant IL-37 markedly up-regulated myocardial Klotho levels in old mice with or without endotoxemia. Similarly, recombinant Klotho suppressed myocardial inflammatory response and promoted inflammation resolution in old endotoxemic mice, leading to complete recovery of cardiac function by 96 h. Conclusion: Myocardial Klotho insufficiency in old endotoxemic mice exacerbates myocardial inflammatory response, impairs inflammation resolution and thereby hinders cardiac functional recovery. IL-37 is capable of up-regulating myocardial Klotho expression to improve cardiac functional recovery in old endotoxemic mice.

Successful treatment of near-fatal pulmonary embolism and cardiac arrest in an adult patient with fulminant psittacosis-induced severe acute respiratory distress syndrome after veno-venous extracorporeal membrane oxygenation rescue: A case report and follow-up.

Background: Veno-venous extracorporeal membrane oxygenation (ECMO) was successfully performed for the rescue of an adult patient with severe acute respiratory distress syndrome (ARDS) induced by fulminant psittacosis, and then a near-fatal pulmonary embolism (PE) and cardiac arrest (CA) of the same patient was cured through catheter-directed thrombolysis. Case presentation: A 51-year-old female patient was admitted to the hospital on September 10, 2021 due to slurred speech, weakness in lower limbs, dizziness, and nausea. Subsequently, she developed confusion and was transferred to the intensive care unit (ICU), where she received anti-shock, antibiotics, invasive mechanical ventilation (IMV), and veno-venous ECMO due to the diagnosis of severe pneumonia, severe ARDS, and septic shock based on comprehensive physical examination, laboratory tests, and imaging findings. The metagenomic next-gengeration sequencing (m-NGS) in the bronchoalveolar lavage fluid (BALF) suggested that the pathogen was chlamydia psittaci, so the antibiotics were adjusted to doxycycline combined with azithromycin. After withdrawal from ECMO, ultrasound (US) re-examination of the left lower limb revealed inter-muscular vein thrombosis, following which heparin was replaced by subcutaneous injection of 0.4ml enoxaparin sodium twice daily for anti-coagulation therapy. After withdrawal from IMV, the patient suffered sudden CA and successful cardiopulmonary resuscitation (CPR), and emergency pulmonary angiography (PA) was performed to show bilateral main pulmonary artery embolism. After immediate catheter-directed thrombolysis and placement of an inferior vena cava filter, the patient's condition gradually stabilized. Conclusions: Veno-venous ECMO can be successfully performed as an emergency life-saving treatment for patients with severe ARDS induced by fulminant psittacosis, and during ECMO regular examinations should be conducted to detect and manage thrombosis in time, thereby avoiding the occurrence of near-fatal PE and CA.

[Effects of extracorporeal membrane oxygenation on hemodynamics in acute right heart failure in dogs].

OBJECTIVE: To investigate the effects of extracorporeal membrane oxygenation (ECMO) on the hemodynamics in dogs with acute right heart failure. METHODS: Ten healthy adult male dogs (weighted 20-25 kg) were randomly divided into two groups: acute right heart failure group (n = 5) and ECMO group (n = 5). Under anesthesia, dogs were underwent thoracotomy, then the catheters were placed in the right atrium, right ventricle, and pulmonary artery, for measuring the relevant pressures, including right arterial pressure (RAP), right ventricular pressure (RVP), and pulmonary artery pressure (PAP). The vascular ultrasound probe were placed on the aorta and pulmonary artery for measuring the cardiac output (CO) and pulmonary artery flow rate (QPA). Then, a baseline measurement was acquired. The femoral artery and femoral vein were cannulated and used for the venoarterial extracorporeal membrane oxygenation (VA-ECMO), and then connected to extracorporeal circuit, which was initially primed. The pulmonary artery was progressively ligated to decrease blood flow until QPA was 60%, 40%, and 0% of baseline in both groups. The above flow conditions were respectively maintained for 30 minutes, after which hemodynamic data were collected. RESULTS: The baseline hemodynamic measurements were not different between acute right heart failure group and ECMO group. After ligating the pulmonary artery, compared with baseline, CO (L/min) decreased significantly at 60% and 40% QPA in acute right heart failure group (1.80 ± 0.19, 1.48 ± 0.22 vs. 3.24 ± 0.23, both P < 0.05), and significantly lower than that of ECMO group (60%QPA: 1.80 ± 0.19 vs. 3.24 ± 0.35; 40%QPA: 1.48 ± 0.22 vs. 3.20 ± 0.37, both P < 0.05). CO was not significantly different from baseline in ECMO group at 60%, 40% and 0% QPA (3.24 ± 0.35, 3.20 ± 0.37, 3.12 ± 0.28 vs. 3.44 ± 0.32, all P>0.05). PAP, RAP and RVP (all mm Hg, 1 mm Hg = 0.133 kPa) were significantly elevated in acute right heart failure group at 60% and 40% QPA compared with baseline (PAP: 36.2 ± 5.3, 39.8 ± 5.4 vs. 17.4 ± 2.7; RAP: 11.2 ± 2.8, 12.8 ± 2.6 vs. 4.4 ± 1.7; RVP: 25.6 ± 4.9, 27.8 ± 4.5 vs. 11.6 ± 1.8, all P < 0.05), and significantly higher than those of ECMO group (60%QPA: PAP 36.2 ± 5.3 vs. 23.2 ± 5.2, RAP 11.2 ± 2.8 vs. 6.2 ± 2.3, RVP 25.6 ± 4.9 vs. 15.2 ± 3.5; 40%QPA: PAP 39.8 ± 5.4 vs. 24.4 ± 4.8, RAP 12.8 ± 2.6 vs. 7.0 ± 2.4, RVP 27.8 ± 4.5 vs. 16.8 ± 4.2, all P < 0.05), whereas mean artery pressure (MAP, mm Hg) was significantly lowered compared with that of baseline (81.2 ± 15.8, 62.2 ± 14.4 vs. 128.6 ± 16.4, both P < 0.05), and it was lower than that of ECMO group (60%QPA: 81.2 ± 15.8 vs. 128.0 ± 26.5; 40%QPA: 62.2 ± 14.4 vs. 124.6 ± 25.4, both P < 0.05). At 60%, 40% and 0% QPA in ECMO group, whereas heart rate (HR, beats/min), PAP, RAP and RVP were slightly increased compared with those of baseline (HR: 161.4 ± 14.8, 160.6 ± 13.1, 157.6 ± 11.9 vs. 152.6 ± 14.5; PAP: 23.2 ± 5.2, 24.4 ± 4.8, 25.2 ± 6.2 vs. 18.8 ± 3.4; RAP: 6.2 ± 2.3, 7.0 ± 2.4, 7.6 ± 4.2 vs. 4.6 ± 1.5; RVP: 15.2 ± 3.5, 16.8 ± 4.2, 16.2 ± 3.3 vs. 12.2 ± 2.3), but MAP was slightly decreased (128.0 ± 26.5, 124.6 ± 25.4, 121.2 ± 21.4 vs. 135.8 ± 22.2), however, all differences were not statistically significant (all P>0.05). CONCLUSION: These findings demonstrate that VA-ECMO could be helpful in improving cardiac function, and maintaining stability of hemodynamics in dogs with acute right heart failure.

Management of procedural pain in the intensive care unit.

Pain is a common experience for inpatients, and intensive care unit (ICU) patients undergo more pain than other departmental patients, with an incidence of 50% at rest and up to 80% during common care procedures. At present, the management of persistent pain in ICU patients has attracted considerable attention, and there are many related clinical studies and guidelines. However, the management of transient pain caused by certain ICU procedures has not received sufficient attention. We reviewed the different management strategies for procedural pain in the ICU and reached a conclusion. Pain management is a process of continuous quality improvement that requires multidisciplinary team cooperation, pain-related training of all relevant personnel, effective relief of all kinds of pain, and improvement of patients' quality of life. In clinical work, which involves complex and diverse patients, we should pay attention to the following points for procedural pain: (1) Consider not only the patient's persistent pain but also his or her procedural pain; (2) Conduct multimodal pain management; (3) Provide combined sedation on the basis of pain management; and (4) Perform individualized pain management. Until now, the pain management of procedural pain in the ICU has not attracted extensive attention. Therefore, we expect additional studies to solve the existing problems of procedural pain management in the ICU.

[Clinical observation of passive leg raising combined with non invasive cardiac output monitoring system in predicting volume responsiveness].

OBJECTIVE: To investigate whether passive leg raising (PLR) combined with ultrasonic cardiac output monitoring system (USCOM) could be used to predict the hemodynamic response to volume expansion (VE) in patients with spontaneous respiration. METHODS: The study was performed with prospective , cohort study method. Thirty three patients with spontaneous breathing activity who were admitted to the intensive care unit (ICU) from October 2009 to April 2010 were included. Measurements of stroke volume (SV) were obtained with transthoracic echocardiography (TTE) and USCOM. Patients were considered to be responders to VE if SV(TTE) increased ≥ 15%. Based on the responsiveness of VE, all the patients were divided into responders and non responders. The change in SV (ΔSV) after the experiment and its correlation were observed. RESULTS: A total of 36 fluid load tests in 33 patients were evaluated resulting in 24 responders and 12 non responders. There was no significant difference between two groups in the clinical data and hemodynamics parameters at incipient stage when head side of bed was raised for 45 degrees angle.After PLR, the ΔSV(TTE) and ΔSV(USCOM) in responder group were significantly higher than those in non responder group [ΔSV(TTE): (21.7 ± 13.2)% vs. (4.8 ± 9.4)%,ΔSV(USCOM):(23.5 ± 13.0)% vs. (4.6 ± 8.9)%, both P <0.01], with positive correlation between ΔSV( TTE) and ΔSV(USCOM) ( r =0.792, P <0.01). After VE, the ΔSV(TTE)and ΔSV(USCOM) in responder group were significantly higher than those in non responder group [ΔSV(TTE): (27.3 ± 14.1)%vs.(7.2 ± 8.4)%,ΔSV(USCOM): (25.4 ± 13.8)% vs. (6.7 ± 8.6)%, both P <0.01], with positive correlation between ΔSV(TTE) and ΔSV(USCOM) ( r =0.855, P <0.01). The ΔSV(TTE) ≥ 15% during PLR was predictive of response to VE with a sensitivity of 100.0% [95% confidence interval (95% CI) 85.0-100.0] and a specificity of 83.3% (95% CI 68.4-98.2). The ΔSV(USCOM)≥ 15% during PLR was predictive of response to VE with a sensitivity of 83.3% (95% CI 66.1-100.0) and a specificity of 94.4% (95% CI 83.9-100.0). There was no difference between the area under the receiver operating characteristic (ROC) curve for PLR induced ΔSV(TTE)and ΔSV(USCOM) (0.95 ± 0.04 vs. 0.93 ± 0.05, P>0.05). CONCLUSION: PLR combined with USCOM can predict the hemodynamic response to VE in spontaneously breathing patients, and the procedure can be used to guide fluid therapy in spontaneously breathing patients.

Exploration of transmission chain and prevention of the recurrence of coronavirus disease 2019 in Heilongjiang Province due to in-hospital transmission.

The coronavirus disease 2019 (COVID-19) epidemic is a major public health emergency characterized by fast spread, a wide range of infections, and enormous control difficulty. Since the end of December 2019, Wuhan has become the first core infection area of China's COVID-19 outbreak. Since March 2020, the domestic worst-hit areas have moved to the Heilongjiang Province due to the increased number of imported COVID-19 cases. Herein, we reported the major COVID-19 outbreak, which caused a rebound of the epidemic in Harbin, China. After the rebound, different levels of causes for the recurrence of COVID-19, including city-level, hospital-level, and medical staff-level cause, were investigated. Meanwhile, corresponding countermeasures to prevent the recurrence of the epidemic were also carried out on the city level, hospital level, and medical staff level, which eventually showed the effect of infection control function in a pandemic. In this study, we described the complete transmission chain, analyzed the causes of the outbreak, and proposed corresponding countermeasures from our practical clinical experience, which can be used as a valuable reference for COVID-19 control.

Standardization of critical care management of non-critically ill patients with COVID-19.

The large global outbreak of coronavirus disease 2019 (COVID-19) has seriously endangered the health care system in China and globally. The sudden surge of patients with severe acute respiratory syndrome coronavirus 2 infection has revealed the shortage of critical care medicine resources and intensivists. Currently, the management of non-critically ill patients with COVID-19 is performed mostly by non-intensive care unit (ICU) physicians, who lack the required professional knowledge, training, and practice in critical care medicine, especially in terms of continuous monitoring of the respiratory function, intervention, and feedback on treatment effects. This clinical problem needs an urgent solution. Therefore, here, we propose a series of clinical strategies for non-ICU physicians aimed at the standardization of the management of non-critically ill patients with COVID-19 from the perspective of critical care medicine. Isolation management is performed to facilitate the implementation of hierarchical monitoring and intervention to ensure the reasonable distribution of scarce critical care medical resources and intensivists, highlight the key patients, timely detection of disease progression, and early and appropriate intervention and organ function support, and thus improve the prognosis. Different management objectives are also set based on the high-risk factors and the severity of patients with COVID-19. The approaches suggested herein will facilitate the timely detection of disease progression, and thus ensure the provision of early and appropriate intervention and organ function support, which will eventually improve the prognosis.

Remote nursing training model combined with proceduralization in the intensive care unit dealing with patients with COVID-19.

The shortage of personal protective equipment and lack of proper nursing training have been endangering health care workers dealing with coronavirus disease 2019 (COVID-19). In our treatment center, the implementation of a holistic care model of time-sharing management for severe and critical COVID-19 patients has further aggravated the shortage of intensive care unit (ICU) professional nurses. Therefore, we developed a short-term specialized and targeted nursing training program to help ICU nurses to cope with stress and become more efficient, thus reducing the number of nurses required in the ICU. In order to avoid possible human-to-human spread, small teaching classes and remote training were applied. The procedural training mode included four steps: preparation, plan, implementation, and evaluation. An evaluation was conducted throughout the process of nursing training. In this study, we documented and shared experiences in transitioning from traditional face-to-face programs to remote combined with proceduralization nursing training mode from our daily work experiences during the COVID-19 pandemic, which has shown to be helpful for nurses working in the ICU.

Mechanisms of Renal-Splenic Axis Involvement in Acute Kidney Injury Mediated by the α7nAChR-NF-κB Signaling Pathway.

This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.

[Clinical observation of the effect of nalmefene in treatment of septic shock].

OBJECTIVE: To study the effect of nalmefene in treatment of patients with septic shock. METHODS: Twenty patients, suffering from septic shock, admitted to the intensive care unit (ICU) from December, 2008 to June, 2009, were randomly divided into treatment group and control group. Following the international guidelines for management of severe sepsis and septic shock 2008 as the routine anti-shock therapy, nalmefene was administered early in the treatment group, while in the control group same amount of normal saline was given as a placebo. Hemodynamics, acute physiology and chronic health evaluation II (APACHE II) score and 28-day mortality were observed in patients. RESULTS: Compared with control group, mean arterial pressure (MAP, mm Hg, 1 mm Hg=0.133 kPa) in treatment group was significantly higher at 2, 6, 12, 24 hours (control group: 59.67+/-3.56, 60.50+/-2.67, 60.68+/-4.97, 61.09+/-4.92; treatment group: 65.83+/-5.76, 70.83+/-5.76, 83.63+/-5.87, 82.85+/-8.36, all P<0.05), while heart rate (HR, beat per min) decreased significantly (control group: 119.79+/-8.03, 118.56+/-11.48, 116.35+/-12.48, 114.68+/-8.91; treatment group: 103.33+/-10.87, 92.29+/-12.55, 90.49+/-17.29, 86.66+/-11.53, all P<0.05). In treatment group, cardiac index (CI, Lxmin(-1) xm(-2)) at 6, 12, 24 hours was significantly higher (control group: 3.63+/-0.13, 3.67+/-0.31, 3.76+/-0.23; treatment group: 4.01+/-0.45, 4.22+/-0.39, 4.45+/-0.32, all P<0.05). Compared with control group, urine output (mlxkg(-1) xmin(-1)) in treatment group was significantly increased at 12 hours and 24 hours (control group: 0.53+/-0.39, 0.51+/-0.40; treatment group: 0.85+/-0.25, 1.06+/-0.58, both P<0.05), while lactic acid (mmol/L) decreased significantly (control group: 5.54+/-3.98, 4.91+/-2.98; treatment group: 1.51+/-0.83, 1.14+/-0.62, both P<0.05). The APACHE II score of the treatment group lowered significantly, and it was significantly lower than the control group at 24 hours (16.1+/-1.9 vs. 21.7+/-5.2, P<0.05). Compared between the two groups, the 28-day mortality showed no significant difference (20% vs. 40%, P=0.629). CONCLUSION: Based on the conventional anti-shock therapy, early use of nalmefene can improve the hemodynamics, which is conducive to ameliorate septic shock, however, there is no significant effect on 28-day mortality.

Erratum to "An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation".

[This corrects the article DOI: 10.1155/2020/2398420.].

An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation.

Mitochondria play an essential role in energy metabolism. Oxygen deprivation can poison cells and generate a chain reaction due to the free radical release. In patients with sepsis, the kidneys tend to be the organ primarily affected and the proximal renal tubules are highly susceptible to energy metabolism imbalances. Dynamin-related protein 1 (DRP1) is an essential regulator of mitochondrial fission. Few studies have confirmed the role and mechanism of DRP1 in acute kidney injury (AKI) caused by sepsis. We established animal and cell sepsis-induced AKI (S-AKI) models to keep DRP1 expression high. We found that Mdivi-1, a DRP1 inhibitor, can reduce the activation of the NOD-like receptor pyrin domain-3 (NLRP3) inflammasome-mediated pyroptosis pathway and improve mitochondrial function. Both S-AKI models showed that Mdivi-1 was able to prevent the mitochondrial content release and decrease the expression of NLRP3 inflammasome-related proteins. In addition, silencing NLRP3 gene expression further emphasized the pyroptosis importance in S-AKI occurrence. Our results indicate that the possible mechanism of action of Mdivi-1 is to inhibit mitochondrial fission and protect mitochondrial function, thereby reducing pyroptosis. These data can provide a potential theoretical basis for Mdivi-1 potential use in the S-AKI prevention.