Immunomodulatory effect of IL-2 induced bone marrow mononuclear cell therapy on control of allergic asthma.

Asthma is a chronic airway disease. Allergic reactions and T helper (h)2 immune response play a key role in asthma occurrence. Cell therapy can control inflammation and remodeling responses in allergic asthma, and cytokines can change this effect. Therefore, in this study, the effect of treated cell therapy with IL-2 to control allergic asthma was studied. Bone marrow cells were extracted and co-cultured with IL-2 and the cells were used via intra-tracheal administration in allergic asthma mice. Levels of IL-4, IL-5, IL-13, Leukotriene B4 and C4, and remodeling factors were measured. At least, a histopathology test of lung tissue was done. Type2 cytokines, leukotrienes, remodeling factors, mucus secretion, goblet cell hyperplasia, peri-bronchial and peri-vascular inflammation were significantly (p˂0.05) decreased by treating with bone marrow-derived mononuclear cells (BMDMCs) and IL-2-BMDMCs. Treatment with IL-2-BMDMCs could significantly decrease IL-13, transforming growth factor (TGF)-ß, HP levels, and mucus secretion (p˂0.05) compared to BMDMCs treatment. In this study, BMDMCs and IL-2-BMDMCs therapy could decrease inflammation, allergic, and remodeling factors in allergic asthma. Cell therapy with BMDMCs had a strong and notable effect on the control of allergic asthma pathophysiology when co-cultured and used with IL-2.

Ranging pattern development of a declining delphinid population: A potential cascade effect of vessel activities.

It is generally accepted that vessel activity causes various behavioral responses of cetaceans and undermines individual fitness. Whether or how it can lead to a demographic response of populations remains rarely examined. In the northern Beibu Gulf, China, vessel activities have sharply increased in the past two decades, while abnormal demographic dynamics was recently noted for the resident Indo-Pacific humpback dolphins. The present study first examined the humpback dolphins' utilization distribution (UD) from 2003 to 2019. Habitat suitability was then modeled with the sighting data collected before the most recent population reduction. Finally, we tried to disentangle the anthropogenic driver of dolphin demography by cross-referring the spatiotemporal development of dolphins' UD, vessel activities, and habitat suitability. Our results showed that the dolphins' UD shrank substantially during the port expansion in the early 2010s, and we suggest that the consequential increase in vessel activities might impose extra marine stressors on the resident humpback dolphins. To reduce the boat interaction, the dolphins steadily shifted their core area to a less suitable area in the east during 2015-2017, when unnaturally low survivals were recorded. Afterward, the dolphin core area partially shifted back to the more suitable area in the west, which corresponded to the improving dolphin survival in 2018. Our finding suggested that the vessel activity may be responsible for the dolphin displacement, while staying in the less suitable area may further lead to a more severe and acute demographic consequence on the population. The underlying and indirect impact of vessel activities as disclosed by the present study is particularly important for port management, marine planning, and conservation practice regarding coastal cetaceans, especially for those resident and endangered populations inhabiting the urbanized coastal areas.

Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial.

BACKGROUND: The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock. METHODS: This single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS. RESULTS: Among 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different (P = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P = 0.94) or the ICU mortality (31.5% vs. 28.8%, P = 0.55) and hospital mortality (34.5% vs. 33.2%, P = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P > 0.05). CONCLUSION: Among adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011 , registration date: March 12, 2019.

The value of urine cell cycle arrest biomarkers to predict persistent acute kidney injury: A systematic review and meta-analysis.

BACKGROUND: The urinary biomarker tissue inhibitor of metalloproteinase-2 (TIMP-2) combined with insulin-like growth factor-binding protein-7 (IGFBP7) has recently been used in the early prediction of persistent acute kidney injury (AKI). However, there is no consensus on the use of urinary TIMP-2 combined with IGFBP7 in predicting persistent AKI. Hence, the present meta-analysis was performed to assess the totality of the current evidence regarding the utilization of urinary TIMP-2 combined with IGFBP7 in predicting persistent AKI. MATERIALS AND METHODS: Relevant studies for this meta-analysis were obtained from the EMBASE, PubMed, Web of Science, and Cochrane Library databases from inception to December 2020. The data on specificity and sensitivity were extracted, and the summary receiver operating characteristic (SROC) curves were constructed. RESULTS: Four studies involving 382 patients were included in this research. The specificity of [TIMP-2] * [IGFBP7] on admission in predicting persistent AKI was 0.68 (95% confidence interval (CI) = 0.50 - 0.82), and the sensitivity was 0.61 (95% CI = 0.46 - 0.75). The area under the curve estimated by SROC was 0.69 (95% CI = 0.65 - 0.73). CONCLUSION: Based on the latest evidence, the present meta-analysis established that urinary TIMP-2 combined with IGFBP7 on admission is a poor predictor of persistent AKI.

Initial fluid resuscitation (30 mL/kg) in patients with septic shock: More or less?

OBJECTIVES: The 2018 Surviving Sepsis Campaign (SSC) recommends rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock; however, there is limited evidence to support this recommendation. The purpose of this study was to examine the relationship between initial fluid resuscitation doses and prognosis in patients with septic shock. METHODS: This was a multicenter prospective observational study of adult patients with septic shock who were admitted to four intensive care units (ICUs) in a total of three Jiangsu Province teaching hospitals over a 3-year span from May 8, 2018, to June 15, 2021. Each enrolled patients with septic shock was categorized into the low-volume (below 20 mL/kg fluid), medium-volume (20-30 mL/kg fluid) or high-volume (above 30 mL/kg fluid) fluid group according to the initial infusion dose given for fluid resuscitation. Various demographic attributes and other variables were collected from medical records. Logistic regression and Kaplan-Meier curve analysis were used to determine the relationship between initial fluid resuscitation doses and patient outcomes. MEASUREMENTS AND MAIN RESULTS: A total of 302 patients who presented to the ICU were diagnosed with septic shock. The 28-day mortality was highest in the high-volume group (48.3%) and lowest in the medium-volume group (26.3%, P < 0.05). Patients who completed 30 mL/kg initial fluid resuscitation in the first 1-2 h had the lowest 28-day mortality rate (22.8%, P < 0.05). Logistic regression showed that a medium initial fluid volume dose was an independent protective factor, with the odds ratio (OR) indicating significantly decreased mortality (OR, 0.507; 95% confidence interval, 0.310-0.828; P = 0.007; P < 0.05). A Kaplan-Meier curve stratified by initial fluid resuscitation dose was constructed for the probability of 28-day mortality. The medium-volume fluid group showed a significantly lower 28-day mortality rate than the high-volume group or the low-volume group (log-rank test, P = 0.0016). CONCLUSION: In septic shock patients, an initial fluid resuscitation rate of 20-30 mL/kg within the first hour may be associated with reduced 28-day mortality; however, this result needs to be confirmed by further high-quality randomized controlled clinical trials. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OOC-17013223. Registered 2 November 2017, http://www.chictr.org.cn/showproj.aspx?proj=22674.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019-Induced Acute Respiratory Distress Syndrome: A Multicenter Descriptive Study.

OBJECTIVES: Severe acute respiratory distress syndrome is complicated with coronavirus disease 2019 and extracorporeal membrane oxygenation support may be necessary in severe cases. This study is to summarize the clinical features, extracorporeal membrane oxygenation characteristics, and outcomes of patients with severe acute respiratory syndrome coronavirus 2 pneumonia received extracorporeal membrane oxygenation. DESIGN: Descriptive study from two hospitals. SETTING: The ICUs from university hospitals. PATIENTS: Patients with severe acute respiratory syndrome coronavirus 2 pneumonia received mechanical ventilation, including those underwent extracorporeal membrane oxygenation from Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital from January 8, 2020, to March 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical records, laboratory results, ventilator parameters, and extracorporeal membrane oxygenation-related data were abstracted from the medical records. One-hundred twenty-nine critically ill patients with severe acute respiratory syndrome coronavirus 2 pneumonia were admitted to ICU of the two referral hospitals. Fifty-nine patients received mechanical ventilation and 21 of them received extracorporeal membrane oxygenation support (fourteen from Zhongnan hospital and seven from Wuhan pulmonary hospital). Compared to mechanical ventilation patients without extracorporeal membrane oxygenation support, there was a tendency of decline in mortality but with no significant difference (no-extracorporeal membrane oxygenation group 24/38 [63.2%] vs extracorporeal membrane oxygenation group 12/21 [57.1%]; p = 0.782). For those patients with extracorporeal membrane oxygenation, 12 patients died and nine survived by April 7, 2020. Among extracorporeal membrane oxygenation patients, the PaCO2 prior to extracorporeal membrane oxygenation was lower (54.40 mm Hg [29.20-57.50 mm Hg] vs 63.20 mm Hg [55.40-72.12 mm Hg]; p = 0.006), and pH prior to extracorporeal membrane oxygenation was higher (7.38 [7.28-7.48] vs 7.23 [7.16-7.33]; p = 0.023) in survivors than nonsurvivors. CONCLUSIONS: Extracorporeal membrane oxygenation might be an effective salvage treatment for patients with severe acute respiratory syndrome coronavirus 2 pneumonia associated with severe acute respiratory distress syndrome. Severe CO2 retention and acidosis prior to extracorporeal membrane oxygenation indicated a poor prognosis.

Effect of Low-Dose Hydrocortisone Therapy in Adult Patients With Septic Shock: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of low-dose hydrocortisone therapy in the management of septic shock remains controversial in critical care for many years. Hence, we performed this meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) to evaluate its effect on clinical outcome among adult patients with septic shock. METHODS: We identified relevant RCTs published from inception to March 7, 2018 comparing low-dose hydrocortisone with placebo or no intervention in adults admitted to the intensive care unit (ICU) for septic shock. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Collaboration's instrument. Trial sequential analysis was used to pool the results from the included studies for the primary outcomes. RESULTS: Thirteen studies were retrieved by our literature search strategy. There were no significant differences in 28-day mortality (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.81-1.00; P = .05) and hospital mortality (OR = 0.91, 95% CI = 0.82-1.02; P = .09) between the 2 groups, which were confirmed by TSA. However, there was a significant improvement in shock reversal in the hydrocortisone group (OR = 1.33, 95% CI = 1.02-1.72; P = .03). Furthermore, subgroup analyses revealed that hydrocortisone plus fludrocortisone statistically reduced the rate of 28-day mortality (OR = 0.79, 95% CI = 0.64-0.97; P = .03), ICU mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .02), and hospital mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .01) in comparison with the placebo, the results were also confirmed by TSA. CONCLUSION: Among adult patients with septic shock, the use of low-dose hydrocortisone compared with control did not confer overall survival benefits, albeit improving shock reversal rate. The benefit of reducing 28-day mortality, ICU mortality, and hospital mortality was observed in combination use of hydrocortisone and fludrocortisone.

Application of high-flow nasal cannula in hypoxemic patients with COVID-19: a retrospective cohort study.

BACKGROUND: It had been shown that High-flow nasal cannula (HFNC) is an effective initial support strategy for patients with acute respiratory failure. However, the efficacy of HFNC for patients with COVID-19 has not been established. This study was performed to assess the efficacy of HFNC for patients with COVID-19 and describe early predictors of HFNC treatment success in order to develop a prediction tool that accurately identifies the need for upgrade respiratory support therapy. METHODS: We retrospectively reviewed the medical records of patients with COVID-19 treated by HFNC in respiratory wards of 2 hospitals in Wuhan between 1 January and 1 March 2020. Overall clinical outcomes, the success rate of HFNC strategy and related respiratory variables were evaluated. RESULTS: A total of 105 patients were analyzed. Of these, 65 patients (61.9%) showed improved oxygenation and were successfully withdrawn from HFNC. The PaO2/FiO2 ratio, SpO2/FiO2 ratio and ROX index (SpO2/FiO2*RR) at 6h, 12h and 24h of HFNC initiation were closely related to the prognosis. The ROX index after 6h of HFNC initiation (AUROC, 0.798) had good predictive capacity for outcomes of HFNC. In the multivariate logistic regression analysis, young age, gender of female, and lower SOFA score all have predictive value, while a ROX index greater than 5.55 at 6 h after initiation was significantly associated with HFNC success (OR, 17.821; 95% CI, 3.741-84.903 p<0.001). CONCLUSIONS: Our study indicated that HFNC was an effective way of respiratory support in the treatment of COVID-19 patients. The ROX index after 6h after initiating HFNC had good predictive capacity for HFNC outcomes.

Effect of transpulmonary pressure-guided positive end-expiratory pressure titration on lung injury in pigs with acute respiratory distress syndrome.

To investigate the effect of positive end-expiratory pressure (PEEP) guided by transpulmonary pressure or with maximum oxygenation-directed PEEP on lung injury in a porcine model of acute respiratory distress syndrome (ARDS). The porcine model of ARDS was induced in 12 standard pigs by intratracheal infusion with normal saline. The pigs were then randomly divided into two groups who were ventilated with the lung-protective strategy of low tidal volume (VT) (6 ml/kg), using different methods to titrate PEEP level: transpulmonary pressure (TP group; n = 6) or maximum oxygenation (MO group; n = 6). Gas exchange, pulmonary mechanics, and hemodynamics were determined and pulmonary inflammatory response indices were measured after 4 h of ventilation. The titrated PEEP level in the TP group (6.12 ± 0.89 cmH2O) was significantly lower than that in the MO group (11.33 ± 2.07 cmH2O) (P < 0.05). The PaO2/FiO2 (P/F) after PEEP titration both improved in the TP and MO groups as compared with that at T0 (when the criteria for ARDS were obtained). The P/F in the TP group did not differ significantly from that in the MO group during the 4 h of ventilation (P > 0.05). Respiratory system compliance and lung compliance were significantly improved in the TP group compared to the MO group (P < 0.05). The VD/VT in the TP group was significantly lower than that in the MO group after 4 h of ventilation (P < 0.05). Central venous pressure increased and the cardiac index decreased significantly in the MO group as compared with the TP group (P < 0.05), whereas oxygen delivery did not differ significantly between the groups (P > 0.05). The pulmonary vascular permeability index and the extravascular lung water index in the TP group were significantly lower than those in the MO group (P < 0.05). The TP group had a lower lung wet to dry weight ratio, lung injury score, and MPO, TNF-, and IL-8 concentrations than the MO group (P < 0.05). In summary, in a pig model of ARDS, ventilation with low VT and transpulmonary pressure-guided PEEP adjustment was associated with improved compliance, reduced dead space ventilation, increased cardiac output, and relieved lung injury, as compared to maximum oxygenation-guide PEEP adjustment.

A meta-analysis of the effects of therapeutic hypothermia in adult patients with traumatic brain injury.

PURPOSE: Therapeutic hypothermia management remains controversial in patients with traumatic brain injury. We conducted a meta-analysis to evaluate the risks and benefits of therapeutic hypothermia management in patients with traumatic brain injury. METHODS: We searched the Web of Science, PubMed, Embase, Cochrane (Central) and Clinical Trials databases from inception to January 17, 2019. Eligible studies were randomised controlled trials that investigated therapeutic hypothermia management versus normothermia management in patients with traumatic brain injury. We collected the individual data of the patients from each included study. Meta-analyses were performed for 6-month mortality, unfavourable functional outcome and pneumonia morbidity. The risk of bias was evaluated using the Cochrane Risk of Bias tool. RESULTS: Twenty-three trials involving a total of 2796 patients were included. The randomised controlled trials with a high quality show significantly more mortality in the therapeutic hypothermia group [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.04 to 1.53, p = 0.02]. Lower mortality in the therapeutic hypothermia group occurred when therapeutic hypothermia was received within 24 h (RR 0.83, 95% CI 0.71 to 0.96, p = 0.01), when hypothermia was received for treatment (RR 0.66, 95% CI 0.49 to 0.88, p = 0.006) or when hypothermia was combined with post-craniectomy measures (RR 0.69, 95% CI 0.48 to 1.00, p = 0.05). The risk of unfavourable functional outcome following therapeutic hypothermia management appeared to be significantly reduced (RR 0.78, 95% CI 0.67 to 0.91, p = 0.001). The meta-analysis suggested that there was a significant increase in the risk of pneumonia with therapeutic hypothermia management (RR 1.48, 95% CI 1.11 to 1.97, p = 0.007). CONCLUSIONS: Our meta-analysis demonstrated that therapeutic hypothermia did not reduce but might increase the mortality rate of patients with traumatic brain injury in some high-quality studies. However, traumatic brain injury patients with elevated intracranial hypertension could benefit from hypothermia in therapeutic management instead of prophylaxis when initiated within 24 h.

Effects of restrictive red blood cell transfusion on the prognoses of adult patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

PURPOSE: Restrictive red blood cell transfusion strategies remain controversial in patients undergoing cardiac surgery. We performed a meta-analysis to assess the prognostic benefits of restrictive red blood cell transfusion strategies in patients undergoing cardiac surgery. METHODS: We identified randomized clinical trials through the 9th of December 2017 that investigated a restrictive red blood cell transfusion strategy versus a liberal transfusion strategy in patients undergoing cardiac surgery. Individual patient data from each study were collected. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Risk of Bias Tool. A trial sequential analysis (TSA)-adjusted random-effects model was used to pool the results from the included studies for the primary outcomes. RESULTS: Seven trials involving a total of 8886 patients were included. The TSA evaluations suggested that this meta-analysis could draw firm negative results, and the data were sufficient. There was no evidence that the risk of 30-day mortality differed between the patients assigned to a restrictive blood cell transfusion strategy and a liberal transfusion strategy (odds ratio (OR) 0.98; 95% confidence interval (CI) 0.77 to 1.24; p = 0.87). Furthermore, the study suggested that the restrictive transfusion strategy was not associated with significant increases in pulmonary morbidity (OR 1.09; 95% CI 0.88 to 1.34; p = 0.44), postoperative infection (OR 1.11; 95% CI 0.95 to 1.3; p = 0.58), acute kidney injury (OR 1.03; 95% CI 0.92 to 1.14; p = 0.71), acute myocardial infarction (OR 1.01; 95% CI 0.80 to 1.27; p = 0.78), or cerebrovascular accidents (OR 0.97; 95% CI 0.72 to 1.30; p = 0.66). CONCLUSIONS: Our meta-analysis demonstrates that the restrictive red blood cell transfusion strategy was not inferior to the liberal strategy with respect to 30-day mortality, pulmonary morbidity, postoperative infection, cerebrovascular accidents, acute kidney injury, or acute myocardial infarction, and fewer red blood cells were transfused.

Effect of levosimendan on prognosis in adult patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Small trials suggest that levosimendan is associated with a favorable outcome in patients undergoing cardiac surgery. However, recently published larger-scale trials did not provide evidence for a similar benefit from levosimendan. We performed a meta-analysis to assess the survival benefits of levosimendan in patients undergoing cardiac surgery and to investigate its effects in subgroups of patients with preoperative low-ejection fraction (EF). METHODS: We identified randomized clinical trials through 20 April 2017 that investigated levosimendan therapy versus control in patients undergoing cardiac surgery. Individual patient data from each study were compiled. Meta-analyses were performed for primary outcomes, secondary outcomes and serious adverse events, and subgroup analyses according to the preoperative EF of enrolled patients were also conducted. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: Seventeen studies involving a total of 2756 patients were included. Levosimendan therapy was associated with a significant reduction in 30-day mortality (RR 0.67; 95% CI, 0.49 to 0.93; p = 0.02) and reduced the risk of death in single-center trials (RR 0.49; 95% CI, 0.30 to 0.79; p = 0.004) and in subgroup trials of inferior quality (RR 0.39; 95% CI, 0.17 to 0.92; p = 0.02); however, in multicenter and in high-quality subgroup-analysis trials, no significant difference in mortality was observed between patients who received levosimendan therapy and controls (p > 0.05). However, in high-quality subgroup trials, levosimendan therapy was associated with reduced mortality in patients in a preoperative low-EF subgroup (RR 0.58; 95% CI, 0.38 to 0.88; p = 0.01). Similarly, only patients in the preoperative low-EF subgroup benefited in terms of reduced risk of renal replacement therapy (RR 0.54; 95% CI, 0.34 to 0.85; p = 0.007). Furthermore, levosimendan therapy was associated with a significant reduction in intensive care unit (ICU) length of stay (MDR -17.19; 95% CI, -34.43 to -2.94; p = 0.02). CONCLUSIONS: In patients undergoing cardiac surgery, the benefit of levosimendan in terms of survival was not shown in multicenter or in high-quality trials; however, levosimendan therapy was associated with reduced mortality in patients with preoperative ventricular systolic dysfunction.

Global end-diastolic volume index vs CVP goal-directed fluid resuscitation for COPD patients with septic shock: a randomized controlled trial.

PURPOSE: This study aimed to investigate the clinical effects of early goal-directed therapy according to the global end-diastolic volume index (GEDI) on chronic obstructive pulmonary disease (COPD) patients with septic shock. METHODS: A total of 71 COPD patients with septic shock were randomly assigned to 2 groups. In the control group (n = 37), fluid resuscitation was performed based on the central venous pressure. In the study group (n = 34), fluid resuscitation was performed until GEDI reached 800 mL/m2. The following indices were observed for the 2 groups: 6- and 24-hour fluid volumes, norepinephrine dosage, 24-hour blood lactate clearance rate, duration of mechanical ventilation, intensive care unit (ICU) length of stay, ICU mortality, and 90-day survival rate. RESULTS: At both 6- and 24-hour measurements, the fluid volume was lower and norepinephrine dosage was higher in the control group than in the study group (P < .05). The blood lactate clearance rate was lower, the duration of mechanical ventilation was longer, and the length of stay in the ICU was longer in the control group than in the study group (P < .05). No significant difference in mortality or 90-day survival rate was found between the 2 groups. CONCLUSIONS: The GEDI goal-directed fluid resuscitation shows better clinical effects than that shown by central venous pressure for COPD patients with septic shock; however, it cannot reduce the mortality rate.

Early initiation of low-dose hydrocortisone treatment for septic shock in adults: A randomized clinical trial.

BACKGROUND: Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock. However, the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear. Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone. Thus we designed a placebo-controlled, randomized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome. METHODS: A total of 118 patients with septic shock were recruited in the study. All eligible patients were randomized to receive hydrocortisone (n=58) or normal saline (n=60). The study medication (hydrocortisone and normal saline) was initiated simultaneously with vasopressors. The primary end-point was 28-day mortality. The secondary end-points were the reversal of shock, in-hospital mortality and the duration of ICU and hospital stay. RESULTS: The proportion of patients with reversal of shock was similar in the two groups (P=0.602); There were no significant differences in 28-day or hospital all-cause mortality; length of stay in the ICU or hospital between patients treated with hydrocortisone or normal saline. CONCLUSION: The early initiation of low-dose of hydrocortisone did not decrease the risk of mortality, and the length of stay in the ICU or hospital in adults with septic shock. TRIAL REGISTRATION: www.clinicaltrials.govNCT02580240.

Humpback Dolphins in Hong Kong and the Pearl River Delta: Status, Threats and Conservation Challenges.

In coastal waters of the Pearl River Delta (PRD) region, the Indo-Pacific humpback dolphin (Sousa chinensis) is thought to number approximately 2500 individuals. Given these figures, the putative PRD population may appear strong enough to resist demographic stochasticity and environmental pressures. However, living in close proximity to the world's busiest seaport/airport and several densely populated urban centres with major coastal infrastructural developments comes with challenges to the long-term survival of these animals. There are few other small cetacean populations that face the range and intensity of human-induced pressures as those present in the PRD and current protection measures are severely inadequate. Recent mark-recapture analyses of the animals in Hong Kong waters indicate that in the past two decades the population parameters have not been well understood, and spatial analyses show that only a very small proportion of the dolphins' key habitats are given any form of protection. All current marine protected areas within the PRD fail to meet a minimum habitat requirement that could facilitate the population's long-term persistence. Demographic models indicate a continuous decline of 2.5% per annum, a rate at which the population is likely to drop below the demographic threshold within two generations and lose 74% of the current numbers within the lifespan of three generations. In Hong Kong, the case of humpback dolphins represents a particularly explicit example of inadequate management where a complete revision of the fundamental approach to conservation management is urgently needed.

Improved sepsis bundles in the treatment of septic shock: a prospective clinical study.

BACKGROUND: Sepsis bundles can decrease mortality in patients with severe sepsis or septic shock. However, current methods of measuring pressure, such as central venous pressure, are inadequate. This study investigated the effect of improved sepsis bundles informed by pulse-indicated continuous cardiac output. METHODS: We compared the outcome of treatment with sepsis bundles informed by either conventional pressure measurements or pulse-indicated continuous cardiac output. Patients in 2 groups received fluid resuscitation, standard antibiotics, and oxygen therapy. RESULTS: A total of 105 patients with septic shock were randomly divided into 2 groups: the conventional sepsis bundle group (n = 52) or the improved sepsis bundle group (ISBG, n =53). The ISBG significantly reduced the mean Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores. Significantly fewer ISBG-treated patients received vasoactive drugs compared to conventional sepsis bundle group-treated patients. In addition, patients in the ISBG exhibited a significantly increased arterial blood lactate clearance rate and required less total fluid resuscitation and a shorter duration of mechanical ventilation and stay in the intensive care unit. CONCLUSIONS: Pulse-indicated continuous cardiac output-directed sepsis bundles can reduce the severity of septic shock, provide more accurate fluid resuscitation, and reduce the duration of mechanical ventilation and stay in the intensive care unit.

[Effect of transpulmonary pressure-directed mechanical ventilation on respiration in severe acute pancreatitis patient with intraabdominal hypertension].

OBJECTIVE: To assess the effect of mehanical ventilation (MV) guided by transpulmonary pressure (Ptp) on respiratory mechanics and gas exchange in severe acute pancreatitis patient with intraabdominal hypertension. METHODS: Twelve severe acute pancreatitis patient with intraabdominal hypertension and acute respiratory distress syndrome(ARDS) underwent mechanical ventilation were involved from Jan to Dec 2013. PEEP levels were set to achieve a Ptp of 0 to 10 cm of water at end expiration. We also limited tidal volume to keep Ptp at less than 25 cm of water at end inspiration. Respiratory mechanics and gas-exchange were measured. RESULTS: Plat pressure (Pplat) increased and the compliance of chest wall (Ccw) decreased when intraabdominal pressure (IAP) increased. Pplat correlated with IAP positively (r2=0.741 9, P<0.05) and Ccw correlated with IAP negtively (r2=0.722 2, P<0.05), respectively.There were not corrletions between IAP and end-expiratory Ptp (Ptp-e) and end-inspiratory Ptp (Ptp-i) (P>0.05). Compared with baseline, after guiding MV with Ptp, the Level of PEEP (14.6±4.2) cmH2O vs (8.3±2.0) cmH2O, and Ptp-e (1.5±0.5) cmH2O vs (-2.3±1.4) cmH2O increased (P<0.05) and Ptp-i did not increase significantly (P>0.05). Ptp-e correlated with PEEP (r2=0.549, P<0.05) and end-expiratory esophageal pressure (Pes-e) (r2=0.260, P<0.05). Ptp-i correlated with Pplat (r2=0.523, P<0.05) and end-inspiratory esophageal pressure (Pes-i) (r2=0.231, P<0.05), but did not correlate with Tidal volume(VT) (r2=0.052 4, P>0.05). Compared with baseline, lung compliance (CL) (48.1±10.3) cmH2O vs (25.7±6.4) cmH2O and oxygenation index (PaO2/FiO2) (235±48) mmHg vs (160±35) mmHg improved obviously (P<0.05), dead space fraction (VD/VT) (0.48±0.07) vs (0.59±0.06) decreased (P<0.05), but Ccw and respiratory compliance(Cr) didn't improve (P>0.05). CONCLUSIONS: Transpulmonary pressure-directed mechanical ventilation in ARDS secondary to severe acute pancreatitis patient with intraabdominal hypertension could not only recruit the collapsed alveoli, improve lung compliance, increase oxygenation index and decrease dead space ventilation but also monitor lung stress to avoid alveoli overinflation, which might be lung protective.

Case report: Inhaled nitric oxide rescued a hypoxemia patient caused by dermatomyositis complicated with interstitial pneumonia.

Interstitial pneumonia is the most common and serious secondary lesion of dermatomyositis. In some cases, patients may develop severe acute pneumonia that can quickly progress to respiratory failure, resulting in high mortality rates. A 57-year-old woman with dermatomyositis and interstitial pulmonary fibrosis experienced severe hypoxemia due to pulmonary infection. Despite receiving various treatments after entering the intensive care unit (ICU), such as anti-infection therapy, lung recruitment, prone position ventilation, sedative and muscle relaxation, the patient's oxygen saturation continued to decline. Electrical impedance tomography (EIT) monitoring revealed that prone position could not improve ventilation homogeneity. However, the patient's ventilation/perfusion (V/Q) matching significantly improved 10 min after initiation of supine position ventilation combined with inhalation of nitric oxide (iNO). The patient's PaO2/FiO2 (P/F) ratio increased from 86 mmHg to 150 mmHg at 30 min post-treatment. iNO treatment continued for 2 days. Then the patient's condition improved and she was successfully weaned off the ventilator with rigorous monitoring and symptomatic care. The implementation of mechanical ventilation combined with iNO therapy rapidly improved V/Q matching and oxygenation in a patient with hypoxemia caused by dermatomyositis complicated with interstitial pneumonia. This approach successfully avoided the need for invasive extracorporeal membrane oxygenation (ECMO) support.

[Construction of a risk predictive model of acute kidney injury based on urinary tissue inhibitor of metalloproteinase 2 and insulin-like growth factor-binding protein 7 and its early predictive value in critically ill patients].

OBJECTIVE: To establish a risk predictive model nomogram of acute kidney injury (AKI) in critically ill patients by combining urinary tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7), and to verify the predictive value of the model. METHODS: A prospective observational study was conducted. The patients with acute respiratory failure or circulatory disorder admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from November 2017 to April 2020 were enrolled. The patients were enrolled within 24 hours of ICU admission, and their general conditions and relevant laboratory test indicators were collected. At the same time, urine was collected to determine the levels of biomarkers TIMP2 and IGFBP7, and TIMP2×IGFBP7 was calculated. Patients were divided into non-AKI and AKI groups according to whether grade 2 or 3 AKI occurred within 12 hours after enrollment. The general clinical data and urinary TIMP2×IGFBP7 levels of patients between the two groups were compared. The indicators with P < 0.1 in univariate analysis were included in the multivariate Logistic regression analysis to obtain the independent risk factors for grade 2 or 3 AKI within 12 hours in critical patients. An AKI risk predictive model nomogram was established, and the application value of the model was evaluated. RESULTS: A total of 206 patients were finally enrolled, of whom 54 (26.2%) developed grade 2 or 3 AKI within 12 hours of enrollment, and 152 (73.8%) did not. Compared with the non-AKI group, the patients in the AKI group had higher body mass index (BMI), pre-enrollment serum creatinine (SCr), urinary TIMP2×IGFBP7 and proportion of using vasoactive drugs, and additional exposure to AKI (use of nephrotoxic drugs before enrollment) was more common. Multivariate Logistic regression analysis showed that BMI [odds ratio (OR) = 1.23, 95% confidence interval (95%CI) was 1.10-1.37, P = 0.000], pre-enrollment SCr (OR = 1.01, 95%CI was 1.00-1.02, P = 0.042), use of nephrotoxic drugs (OR = 2.84, 95%CI was 1.34-6.03, P = 0.007) and urinary TIMP2×IGFBP7 (OR = 2.19, 95%CI was 1.56-3.08, P = 0.000) was an independent risk factor for the occurrence of grade 2 or 3 AKI in critical patients. An AKI risk predictive model nomogram was constructed based on the independent risk factors of AKI. Bootstrap validation results showed that the model had good discrimination and calibration in internal validation. Receiver operator characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) of urinary TIMP2×IGFBP7 alone in predicting grade 2 or 3 AKI within 12 hours in critical patients was 0.74 (95%CI was 0.66-0.83), the optimal cut-off value was 1.40 (µg/L) 2/1 000 (sensitivity was 66.7%, specificity was 85.0%), and the predictive performance of the model incorporating urinary TIMP2×IGFBP7 was significantly better than that of the model without urinary TIMP2×IGFBP7 [AUC (95%CI): 0.85 (0.79-0.91) vs. 0.77 (0.70-0.84), P = 0.005], net reclassification index (NRI) was 0.29 (95%CI was 0.08-0.50, P = 0.008), integrated discrimination improvement (IDI) was 0.13 (95%CI was 0.07-0.19, P < 0.001). CONCLUSIONS: The AKI risk predictive model based on urinary TIMP2×IGFBP7 has high clinical value and is expected to be used to early predict the occurrence of AKI in critically ill patients.

The influence of gender on the epidemiology of and outcome from sepsis associated acute kidney injury in ICU: a retrospective propensity-matched cohort study.

PURPOSES: The influence of gender on the epidemiology of and outcome from SA-AKI in ICU has not been fully clarified. Our aim is to elucidate these differences. METHODS: This study included adult patients with sepsis in MIMIC IV (V 2.2), and propensity matching analysis, cox regression and logistic regression were used to analyze gender differences in incidence, mortality and organ support rate. RESULTS: Of the 24,467 patients included in the cohort, 18,128 were retained after propensity score matching. In the matched cohort, the incidence of SA-AKI in males is higher than that in females (58.6% vs. 56.2%; P = 0.001).males were associated with a higher risk of SA-AKI (OR:1.07(1.01-1.14), P = 0.026;adjusted OR:1.07(1.01-1.14), P < 0.033).In SA-AKI patients, males were associated with a lower risk of ICU mortality(HR:0.803(0.721-0.893), P < 0.001;adjusted HR:0.836(0.746-0.937), P = 0.002) and in-hospital mortality(HR: 0.820(0.748-0.899), P < 0.001;adjusted HR:0.853(0.775-0.938), P = 0.003).there were no statistically significant differences between male and female patients in 1-year all-cause mortality (36.9% vs. 35.8%, P = 0.12), kidney replacement therapy rate (7.8% vs.7.4%, P = 0.547), mechanical ventilation rate 64.8% vs.63.9%, P = 0.369), and usage of vasoactive drugs (55.4% vs. 54.6%, P = 0.418). CONCLUSIONS: Gender may affect the incidence and outcomes of SA-AKI, further research is needed to fully understand the impact of gender on SA-AKI patients.