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.

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.

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.

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.

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.

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.

Holistic care model of time-sharing management for severe and critical COVID-19 patients.

The rapid global outbreak of coronavirus disease 2019 (COVID-19) and the surge of infected patients have led to the verge of exhaustion of critical care medicine resources worldwide, especially with regard to critical care staff. A holistic care model on time-sharing management for severe and critical COVID-19 patients is proposed, which includes formulation of individualized care objectives and plans, identification of care tasks in each shift and making detailed checklist, and management of quality of care. This study was conducted in the COVID-19 treatment center of Harbin, Heilongjiang Province. The data collected from the treatment center were recorded and analyzed. From the results we can deduce that it is especially suitable for non-intensive care unit (non-ICU) nurses to adapt care management mode of ICU as soon as possible and ensure the quality and efficiency of care during the epidemic. The holistic care model on time-sharing management for severe and critical cases with COVID-19 proposed based on our daily work experiences can assist in improving the quality and efficiency of care, thus reducing the mortality rate of patients in ICU.

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.

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.

Preoperative Mean Platelet Volume and Platelet Distribution Width Predict Postoperative Sepsis in Patients with Colorectal Cancer.

PURPOSE: Mean platelet volume (MPV) and platelet distribution width (PDW) have been used to reflect the platelet activity in clinics. We assessed initial serum MPV and PDW levels in colorectal cancer (CRC) patients, in predicting the development of sepsis in CRC patients postoperatively. PATIENTS AND METHODS: This study included 220 patients diagnosed with CRC. 55 patients were stratified to one group that developed sepsis postoperatively, and 165 patients were stratified to the other group that did not develop sepsis postoperatively. Clinical and laboratory characteristics were collected 3 days before the operation. RESULTS: MPV (p < 0.001) was significantly higher and PDW (p < 0.001) was significantly lower in the sepsis group than in the nonsepsis group. Either MPV or PDW is independently associated with ICU mortality in sepsis patients with CRC. MPV is independently associated with 14-day, 28-day, and 90-day mortality and PDW is independently associated with 90-day mortality in patients with CRC. The prevalence of sepsis increased as MPV tertiles increased (p < 0.001), and the prevalence of sepsis increased as PDW tertiles decreased (p < 0.001). CONCLUSIONS: Serum MPV and PDW levels between CRC patients with/without sepsis postoperatively are significantly different. The initial serum MPV or PDW levels can potentially serve as a predictor of sepsis in CRC patients postoperatively.

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.

Overexpression of connective tissue growth factor is associated with tumor progression and unfavorable prognosis in endometrial cancer.

OBJECTIVES: This study was to explore the prognostic value of connective tissue growth factor (CTGF) expression in endometrial cancer (EC). METHODS: We compared CTGF expression in 198 samples from patients with endometrial cancer and 50 samples from patients with healthy endometrial tissues as determined by immunohistochemistry. RESULTS: Expression of CTGF was significantly higher in endometrial cancers as compared to normal endometrial tissues. Positive CTGF expression displayed a strong association with CA125 level, histological grade, depth of myometrial invasion and the International Federation of Gynecology and Obstetrics (FIGO) stage. Our findings revealed histological grade, depth of myometrial invasion, FIGO stage, vascular/lymphatic invasion, and the CTGF expression are related to 5-year survival in patients with endometrial cancer. Positive CTGF expression, lymph node status, as well as vascular/lymphatic invasion, were identified as independent prognostic factors in endometrial cancer. CONCLUTIONS: Over-expression of CTGF is an independent prognostic factor that will allow the successful differentiation of high-risk population from the group of patients with stage III-IV endometrial cancer. The up-regulation of CTGF may contribute to the progression of endometrial cancer and serve as a new prognostic biomarker in patients with endometrial cancer survival.

Uncoupling Protein 2 Drives Myocardial Dysfunction in Murine Models of Septic Shock.

Cardiac dysfunction is a major component of sepsis-induced multiorgan failure in critical care units. Uncoupling protein 2 (UCP2) involves immune response, regulation of oxidative stress, and maintenance of mitochondrial membrane potential as well as energy production. However, whether and how UCP2 plays roles in the development of septic cardiac dysfunction are largely unknown. Here, intraperitoneal injection of LPS significantly activated UCP2 expression accompanied by a significant decrease of cardiac function and caused a significantly lower survival rate in mice. Of note, knockdown of UCP2 through a cardiotropic adenoassociated viral vector carrying a short hairpin RNA (shRNA) specifically targeting the UCP2 evoked resistance to LPS-triggered septic cardiac dysfunction and lethality in vivo. Moreover, UCP2 deficiency ameliorated the reduced levels of intracellular ATP in the LPS-challenged heart tissues and preserved mitochondrial membrane potential loss in primary adult mouse cardiomyocytes in LPS-challenged animals. Mechanistically, we confirmed that the inhibition of UCP2 promoted autophagy in response to LPS, as shown by an increase in LC3II and a decrease in p62. At last, the autophagy inhibitor 3-MA abolished UCP2 knockdown-afforded cardioprotective effects. Those results indicate that UCP2 drives septic cardiac dysfunction and that the targeted induction of UCP2-mediated autophagy may have important therapeutic potential.

Platelet indices in non-small cell lung cancer patients with brain metastases.

BACKGROUND: Platelets play a crucial role in cancer progression and metastasis. The aim of the present study was to assess the relationship between platelet indices and non-small cell lung cancer (NSCLC) with brain metastases. METHODS: Between January 2015 and December 2017, 232 NSCLC patients with brain metastases and 244 NSCLC patients without metastases were retrospectively analyzed. Patients' clinicopathological characteristics data were collected. RESULTS: Platelet count was increased and mean platelet volume (MPV) was reduced in NSCLC patients with brain metastases compared with NSCLC patients without metastases. In addition, the prevalence of NSCLC decreased as MPV quartiles increased. After adjusting for other risk factors, the ORs (95% CIs) for NSCLC brain metastases according to MPV quartiles were 1.757 (1.024-3.015), 2.097 (1.209-3.635), 1.517 (0.874-2.635), and 1.000, respectively. CONCLUSIONS: MPV is reduced in NSCLC patients with brain metastases compared with NSCLC patients without metastases. Moreover, MPV is found to be independently associated with the presence of NSCLC brain metastases.