Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in ...mainland China, as well as the independent predictors of mortality.
We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included.
A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratioOR, 1.068; 95% confidential intervalCI, 1.027-1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691-4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142-5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141-4.420) were significantly associated with mortality.
Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.
Exposure to the toxic herbicide paraquat (PQ) can lead to the active absorption and enrichment of alveolar epithelial cells, resulting in pulmonary fibrosis and respiratory failure. At present, no ...effective clinical treatment is available. Notably, however, patients infected with human acquired immunodeficiency virus (HIV) (with T lymphocyte deficiency) do not show pulmonary fibrosis after PQ poisoning, suggesting that T lymphocytes may be involved in the occurrence and pathological development of lung fibers following PQ exposure, although relevant studies remain limited. Here, we found that the degree of pulmonary fibrosis induced by intragastric administration of PQ in congenital immunodeficiency BALB/C (nu/nu) nude (T lymphocyte loss) mice was lower than that in normal mice. However, pulmonary fibrosis was aggravated after transplantation of BALB/C (nu/nu) T lymphocytes into congenital immunodeficiency mice. This study is the first to report on the involvement of T lymphocytes in the occurrence and pathological development of lung fibers induced by PQ exposure. Thus, T cells may be an important cellular target for the clinical treatment of pulmonary fibrosis caused by PQ.
•We report on the involvement of T lymphocytes in the occurrence and pathological development of PQ-induced lung fibrosis.•PQ-induced pulmonary fibrosis was lower in T lymphocyte-deficient nude mice than in normal mice.•Pulmonary fibrosis was aggravated after transplantation of BALB/C (nu/nu) T lymphocytes into congenital immunodeficient mice.•T cells may be an important cellular target for the clinical treatment of pulmonary fibrosis caused by PQ poisoning.
Human umbilical cord mesenchymal stem cells (HUC-MSCs) are pluripotent stem cells with anti-inflammatory and immunomodulatory properties used in the treatment of acute lung injury (ALI). However, the ...treatment of ALI using exosomes derived from HUC-MSCs (HUC-MSC-exos) primed with interferon-gamma (IFN-γ-exos) has not been described. This study investigated the effects of IFN-γ-exos on ALI.
IFN-γ primed and unprimed HUC-MSC-exos (IFN-γ-exos and CON-exos, respectively) were extracted, identified, and traced. A549 cells and mice subjected to lipopolysaccharide (LPS)-induced inflammation were treated with IFN-γ-exos or CON-exos. Viability; interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and reactive oxygen species (ROS) levels; NF-κB p65, and NLRP3 expression and histology and lung injury scores were measured in cell, supernatant or lung tissue.
Indoleamine 2,3-dioxygenase (IDO) mRNA expression was elevated in HUC-MSCs primed with 5 ng/mL IFN-γ (
<0.001), and IFN-γ-exos and CON-exos were successfully extracted. LPS-induced inflammation resulted in decreased cell viability in A549 cells, and increased IL-1β, IL-6, TNF-α and ROS levels and NF-κB p65 and NLRP3 expression in A549 cells and mice(
<0.05 to
<0.001). Treatment with IFN-γ-exos and CON-exos increased cell viability and decreased the concentrations of IL-1β, and ROS, expression of NF-κB p65 and NLRP3, and the lung injury score, and these effects were more obvious for IFN-γ-exos(
<0.05 to
<0.001).
IFN-γ-exos reduced oxidative stress and inflammatory responses in LPS-induced A549 cells and mice. The result demonstrated the therapeutic potential of IFN-γ-exos in LPS-induced ALI.
Coronavirus disease 2019 (COVID-19) is a highly infectious epidemic disease that has seriously affected human health worldwide. To date, however, there is still no definitive drug for the treatment ...of COVID-19. Cell-based therapies could represent a new breakthrough. Over the past several decades, mesenchymal stromal cells (MSCs) have proven to be ideal candidates for the treatment of many viral infectious diseases due to their immunomodulatory and tissue repair or regeneration promoting properties, and several relevant clinical trials for the treatment of COVID-19 have been registered internationally. Herein, we systematically summarize the clinical efficacy of MSCs in the treatment of COVID-19 based on published results, including mortality, time to symptom improvement, computed tomography (CT) imaging, cytokines, and safety, while elaborating on the possible mechanisms underpinning the effects of MSCs, to provide a reference for subsequent studies.
•Cerebral I/R can result in decreased SIRT6 expression.•SIRT6 can ameliorate brain damage.•SIRT6 can activate NRF2 and reduce oxidative stress.•NRF2 Knockout can exacerbate brain damage.•NRF2 ...Knockout can abolish the neuroprotective effects of SIRT6 in cerebral I/R.
Sirtuin 6 (SIRT6), a member of the sirtuin family of NAD(+)-dependent deacetylases, has been shown to produce beneficial effects in myocardial ischemia/reperfusion (I/R). However, the role of SIRT6 in cerebral I/R is largely unclear. In this study, we investigated the effects of SIRT6 overexpression in regulating I/R injury in a mouse cerebral I/R model in vivo and in oxygen-glucose-deprivation/reoxygenation (OGD/R)-stimulated neuro-2a neuroblastoma cells in vitro. We found that cerebral I/R (1 h/24 h) resulted in decreased SIRT6 expression in the cerebral cortex (P < 0.01). SIRT6 overexpression in the brain by in vivo gene transfer enhanced the antioxidant NRF2 signaling (P < 0.05), reduced oxidative stress (P < 0.05), and attenuated cerebral I/R-induced brain tissue damage and neurological deficits (P < 0.05). These neuroprotective effects of SIRT6 overexpression were abolished in NRF2 knockout mice. In neuro-2A neuroblastoma cells, SIRT6 overexpression increased total and nuclear NRF2 levels (P < 0.05), reduced oxidative stress (P < 0.05), and attenuated OGD/R-induced cell death (P < 0.05); these protective effects were blocked by NRF2 knockdown (P < 0.05). Moreover, in OGD/R-stimulated neuro-2A cells, SIRT6 overexpression produced similar protective effects to those induced by the antioxidant NAC, but no added benefits were detected when SIRT6 overexpression was used in combination with NAC (P > 0.05). These findings provide evidence that SIRT6 can protect the brain from cerebral I/R injury by suppressing oxidative stress via NRF2 activation. Thus, SIRT6 may serve as a potential therapeutic target for ischemic stroke.
Acute kidney injury (AKI) is widespread in the intensive care unit (ICU) and affects patient prognosis. According to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, the absolute and ...relative increases of serum creatinine (Scr) are classified into the same stage. Whether the prognosis of the two types of patients is similar in the ICU remains unclear.
According to the absolute and relative increase of Scr, AKI stage 1 and stage 3 patients were divided into stage 1a and 1b, stage 3a and 3b groups, respectively. Their demographics, laboratory results, clinical characteristics, and outcomes were analyzed retrospectively.
Of the 345 eligible cases, we analyzed stage 1 because stage 3a group had only one patient. Using 53 or 61.88 µmol/L as the reference Scr (Scr
ref
), no significant differences were observed in ICU mortality (P
53
=0.076, P
61.88
=0.070) or renal replacement therapy (RRT) ratio, (P
53
=0.356, P
61.88
=0.471) between stage 1a and 1b, but stage 1b had longer ICU length of stay (LOS) than stage 1a (P
53
<0.001, P
61.88
=0.032). In the Kaplan-Meier survival analysis, no differences were observed in ICU mortality between stage 1a and 1b (P
53
=0.378, P
61.88
=0.255). In a multivariate analysis, respiratory failure HR = 4.462 (95% CI 1.144-17.401), p = 0.031 and vasoactive drug therapy HR = 4.023 (95% CI 1.584-10.216), p = 0.003 were found to be independently associated with increased risk of death.
ICU LOS benefit was more prominent in KDIGO
SCr
AKI stage 1a patients than in stage 1 b. Further prospective studies with a larger sample size are necessary to confirm the effectiveness of reclassification.
Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare ...workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients.
Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control.
Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.
The COVID-19 cases increased very fast in January and February 2020. The mortality among critically ill patients, especially the elder ones, is relatively high. Considering many patients died of ...severe inflammation response, it is urgent to develop effective therapeutic strategies for these patients. The human umbilical cord mesenchymal stem cells (hUCMSCs) have shown good capabilities to modulate the immune response and repair the injured tissue. Therefore, investigating the potential of hUCMSCs to the treatment of COVID-19 critically ill patients is necessary.
A 65-year-old woman felt fatigued and had a fever with body temperature of 38.2C, coughed up white foaming sputum. After 1 day, she had chest tightness with SPO2 of 81%, and blood pressure of 160/91 mm Hg.
According to the guideline for the diagnosis and treatment of 2019 novel coronavirus infected pneumonia (Trial 4th Edition), COVID-19 was diagnosed, based on the real-time RT-PCR test of SARS-CoV-2.
After regular treatment for 12 days, the inflammation symptom of the patient was still very severe and the potential side effects of corticosteroid were observed. Then, allogenic hUCMSCs were given 3 times (5 × 10 cells each time) with a 3-day interval, together with thymosin α1 and antibiotics daily injection.
After these treatments, most of the laboratory indexes and CT images showed remission of the inflammation symptom. The patient was subsequently transferred out of ICU, and the throat swabs test reported negative 4 days later.
These results indicated the clinical outcome and good tolerance of allogenic hUCMSCs transfer.
To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic.
A survey conducted in 21 intensive care units in 17 provinces in China.
Out of 733 ...questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001).
Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.
Acute respiratory failure (ARF) is still one of the most severe complications in immunocompromised patients. Our previous systematic review showed noninvasive mechanical ventilation (NIV) reduced ...mortality, length of hospitalization and ICU stay in AIDS/hematological malignancy patients with relatively less severe ARF, compared to invasive mechanical ventilation (IMV). However, this systematic review was based on 13 observational studies and the quality of evidence was low to moderate. The efficacy of NIV in more severe ARF and in patients with other causes of immunodeficiency is still unclear. We aim to determine the efficacy of the initial ventilation strategy in managing ARF in immunocompromised patients stratified by different disease severity and causes of immunodeficiency, and explore predictors for failure of NIV.
The VENIM is a multicentre randomized controlled trial (RCT) comparing the effects of NIV compared with IMV in adult immunocompromised patients with severe hypoxemic ARF. Patients who meet the indications for both forms of ventilatory support will be included. Primary outcome will be 30-day all-cause mortality. Secondary outcomes will include in-hospital mortality, length of stay in hospital, improvement of oxygenation, nosocomial infections, seven-day organ failure, adverse events of intervention, et al. Subgroups with different disease severity and causes of immunodeficiency will also be analyzed.
VENIM is the first randomized controlled trial aiming at assessing the efficacy of initial ventilation strategy in treating moderate and severe acute respiratory failure in immunocompromised patients. The result of this RCT may help doctors with their ventilation decisions.
ClinicalTrials.gov NCT02983851 . Registered 2 September 2016.
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