[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.

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.

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.

Low HDL-C can be a biomarker to predict persistent severe AKI in septic patients? A retrospective cohort study.

PURPOSES: Low HDL-C is associated with an increased risk of sepsis-associated AKI and subsequent decline in eGFR. HDL-C possesses anti-inflammatory, antioxidant, and endothelial repair-promoting properties. The use of Apo A-I mimetic peptides, which are the main structural components of HDL-C, has been shown to improve renal function in animal models of sepsis. However, the diagnostic value of low HDL-C in persistent sepsis-associated AKI remains unclear. METHODS: This is a retrospective cohort study based on MIMIC IV (V 2.2). The study population consisted of all adult septic patients admitted to the Beth Israel Deaconess Medical Center Intensive Care Unit from 2008 to 2019, with plasma HDL-C measured within 24 h of ICU admission. The primary endpoint was persistent severe sepsis-associated acute kidney injury (SA-AKI) and the secondary endpoint is kidney replacement therapy (KRT). Logistic regression was used to assess the correlation between HDL-C and persistent severe SA-AKI and KRT, and receiver operating characteristic (ROC) curve analysis was performed to evaluate predictive ability. RESULTS: A total of 604 cases of SA-AKI patients were included in the analysis, among which 88 cases (14.5%) experienced persistent severe SA-AKI. The median (IQR) HDL-C level in the group with persistent severe SA-AKI was lower (33.0 [24.0-45.5]) compared to the non-persistent severe SA-AKI group (42.0 [31.0-53.0]). However, HDL-C showed poor discriminatory ability with an AUROC [95%CI] of 0.62 [0.56-0.69]. Clinical prediction models based on serum creatinine concentration, 24-h creatinine change, APSIIIscore, lactate levels, APTT, and heart rate performed well in predicting persistent severe SA-AKI with an AUROC [95%CI] of 0.876 [0.84-0.91]. However, adding HDL-C to this model did not improve predictive performance. CONCLUSIONS: The plasma HDL-C measured within 24 h after admission to the ICU does not provide a good prediction for persistent severe SA-AKI, and it does not improve the clinical predictive ability compared to conventional variables.

[A nonlinear relationship between the hemoglobin level and prognosis of elderly patients with sepsis: an analysis based on MIMIC-IV].

OBJECTIVE: To investigate the correlation of hemoglobin (Hb) level with prognosis of elderly patients diagnosed as sepsis. METHODS: A retrospective cohort study was conducted. Information on the cases of elderly patients with sepsis in the Medical Information Mart for Intensive Care-IV (MIMIC-IV), including basic information, blood pressure, routine blood test results [the Hb level of a patient was defined as his/her maximum Hb level from 6 hours before admission to intensive care unit (ICU) and 24 hours after admission to ICU], blood biochemical indexes, coagulation function, vital signs, severity score and outcome indicators were extracted. The curves of Hb level vs. 28-day mortality risk were developed by using the restricted cubic spline model based on the Cox regression analysis. The patients were divided into four groups (Hb < 100 g/L, 100 g/L ≤ Hb < 130 g/L, 130 g/L ≤ Hb < 150 g/L, Hb ≥ 150 g/L groups) based on these curves. The outcome indicators of patients in each group were analyzed, and the 28-day Kaplan-Meier survival curve was drawn. Logistic regression model and Cox regression model were used to analyze the relationship between Hb level and 28-day mortality risk in different groups. RESULTS: A total of 7 473 elderly patients with sepsis were included. There was a "U" curve relationship between Hb levels within 24 hours after ICU admission and the risk of 28-day mortality in patients with sepsis. The patients with 100 g/L ≤ Hb < 130 g/L had a lower risk of 28-day mortality. When Hb level was less than 100 g/L, the risk of death decreased gradually with the increase of Hb level. When Hb level was ≥ 130 g/L, the risk of death gradually increased with the increase of Hb level. Multivariate Logistic regression analysis revealed that the mortality risks of patients with Hb < 100 g/L [odds ratio (OR) = 1.44, 95% confidence interval (95%CI) was 1.23-1.70, P < 0.001] and Hb ≥ 150 g/L (OR = 1.77, 95%CI was 1.26-2.49, P = 0.001) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (OR = 1.21, 95%CI was 0.99-1.48, P = 0.057). The multivariate Cox regression analysis suggested that the mortality risks of patients with Hb < 100 g/L [hazard ratio (HR) = 1.27, 95%CI was 1.12-1.44, P < 0.001] and Hb ≥ 150 g/L (HR = 1.49, 95%CI was 1.16-1.93, P = 0.002) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (HR = 1.17, 95%CI was 0.99-1.37, P = 0.053). Kaplan-Meier survival curve showed that the 28-day survival rate of elderly septic patients in 100 g/L ≤ Hb < 130 g/L group was significantly higher than that in Hb < 100 g/L, 130 g/L ≤ Hb < 150 g/L and Hb ≥ 150 g/L groups (85.26% vs. 77.33%, 79.81%, 74.33%; Log-Rank test: χ2 = 71.850, P < 0.001). CONCLUSIONS: Elderly patients with sepsis exhibited low mortality risk if their 100 g/L ≤ Hb < 130 g/L within 24 hours after admission to ICU, and both higher and lower Hb levels led to increased mortality risks.

Effect of the Timing of Amubarvimab/Romlusevimab (BRII-196/198) Administration on Progression to Severe Disease in Elderly Patients with COVID-19 Infection: A Retrospective Cohort Study.

Objective: Early intervention with neutralizing antibodies is considered to be effective in preventing disease progression in patients with mild to moderate COVID-19 infection. Elderly patients are the most susceptible and at a higher risk of COVID-19 infection. The present study aimed to assess the necessity and possible clinical benefits of the early administration of Amubarvimab/Romlusevimab (BRII-196/198) in the elderly population. Methods: The present study was designed as a retrospective, multi-center cohort study conducted with 90 COVID-19 patients aged over 60, who were divided into two groups based on the timing of the administration of BRII-196/198 (administration at ≤ 3 days or > 3 days from the onset of infection symptoms). Results: The ≤ 3 days group exhibited a greater positive effect (HR 5.94, 95% CI, 1.42-24.83; P < 0.01), with only 2 patients among 21 patients (9.52%) exhibiting disease progression, compared to the 31 patients among the 69 patients (44.93%) of the > 3 days group who exhibited disease progression. The multivariate Cox regression analysis revealed low flow oxygen support prior to BRII-196/198 administration (HR 3.53, 95% CI 1.42-8.77, P < 0.01) and PLT class (HR 3.68, 95% CI 1.37-9.91, P < 0.01) as independent predictors of disease progression. Conclusions: In elderly patients with mild or moderate COVID-19 disease, who do not require oxygen support and had the risk factors for disease progression to severe COVID-19 disease, the administration of BRII-196/198 within 3 days resulted in a beneficial trend in terms of preventing disease progression.

Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

Development and validation of a nomogram for predicting in-hospital mortality of elderly patients with persistent sepsis-associated acute kidney injury in intensive care units: a retrospective cohort study using the MIMIC-IV database.

OBJECTIVES: To identify the clinical risk factors that influence in-hospital mortality in elderly patients with persistent sepsis-associated acute kidney injury (S-AKI) and to establish and validate a nomogram to predict in-hospital mortality. DESIGN: Retrospective cohort analysis. SETTING: Data from critically ill patients at a US centre between 2008 and 2021 were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database (V.1.0). PARTICIPANTS: Data from 1519 patients with persistent S-AKI were extracted from the MIMIC-IV database. PRIMARY OUTCOME: All-cause in-hospital death from persistent S-AKI. RESULTS: Multiple logistic regression revealed that gender (OR 0.63, 95% CI 0.45-0.88), cancer (2.5, 1.69-3.71), respiratory rate (1.06, 1.01-1.12), AKI stage (2.01, 1.24-3.24), blood urea nitrogen (1.01, 1.01-1.02), Glasgow Coma Scale score (0.75, 0.70-0.81), mechanical ventilation (1.57, 1.01-2.46) and continuous renal replacement therapy within 48 hours (9.97, 3.39-33.9) were independent risk factors for mortality from persistent S-AKI. The consistency indices of the prediction and the validation cohorts were 0.780 (95% CI: 0.75-0.82) and 0.80 (95% CI: 0.75-0.85), respectively. The model's calibration plot suggested excellent consistency between the predicted and actual probabilities. CONCLUSIONS: This study's prediction model demonstrated good discrimination and calibration abilities to predict in-hospital mortality of elderly patients with persistent S-AKI, although it warrants further external validation to verify its accuracy and applicability.

Predictability performance of urinary C-C motif chemokine ligand 14 and renal resistive index for persistent sepsis-associated acute kidney injury in ICU patients.

OBJECTIVES: The performance of renal resistance index (RRI) in predicting persistent sepsis-associated acute kidney injury (S-AKI) remains debatable, and the value of urinary C-C motif chemokine ligand 14 (CCL14) in predicting persistent S-AKI has not been validated yet. Therefore, we aimed to determine the applicability of a urinary biomarker CCL14 for the early detection of persistent S-AKI. Furthermore, the use of RRI obtained from renal Doppler ultrasonography was applied to differentiate transient from persistent S-AKI. Finally, we aimed to evaluate the use of these techniques in predicting different subtypes of S-AKI. METHODS: This prospective observational study was conducted at the internal medicine intensive care unit (ICU) of a university hospital. The RRI was determined within 12 h of ICU admission and the urinary CCL14 was evaluated at T0, T6, T12, and T24. The reversibility of renal dysfunction was assessed within 48 h. The receiver operating characteristic curves were then plotted to assess the diagnostic efficacy of the RRI and urinary CCL14 in predicting persistent S-AKI. RESULTS: Out of 48 patients, 23 developed persistent S-AKI upon admission. The RRI was higher in the persistent S-AKI group (P = 0.02) and the RRI ≥ 0.679 could predict persistent S-AKI with an area under the receiver operating characteristic curve of 0.79 (95% CI 0.65-0.93), a sensitivity of 91.30% (95% CI 70-98%), and a specificity of 65.20% (95% CI 43-83%). Urinary CCL14 was not significantly different between the two groups at the tested period, showing poor diagnostic performance at T0, T6, T12, and T24, with areas under the receiver operating characteristic curves of 0.56 (95% CI 0.38-0.73), 0.62 (95% CI 0.46-0.79), 0.52 (95% CI 0.35-0.68), and 0.60 (95% CI 0.43-0.77), respectively. CONCLUSIONS: The RRI obtained from renal Doppler ultrasound is extremely effective in predicting persistent S-AKI in critically ill patients, and urinary CCL14 could not distinguish between transient and persistent S-AKIs.

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.

Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock.

BACKGROUND: Trials and study-level meta-analyses have failed to resolve the role of corticosteroids in the management of patients with septic shock. Patient-level meta-analyses may provide more precise estimates of treatment effects, particularly subgroup effects. METHODS: We pooled individual patient data from septic shock trials investigating the adjunctive use of intravenous hydrocortisone. The primary outcome was 90-day all-cause mortality, and it was also analyzed across predefined subgroups. Secondary outcomes included mortality at intensive care unit and hospital discharge, at 28 and 180 days, and vasopressor-, ventilator-, and organ failure­free days. Adverse events included superinfection, muscle weakness, hyperglycemia, hypernatremia, and gastroduodenal bleeding. RESULTS: Of 24 eligible trials (n=8528), 17 (n=7882) provided individual patient data, and 7 (n=5929) provided 90-day mortality. The marginal relative risk (RR) for 90-day mortality of hydrocortisone versus placebo was 0.93 (95% confidence interval [CI], 0.82 to 1.04; P=0.22; moderate certainty). It was 0.86 (95% CI, 0.79 to 0.92) for hydrocortisone with fludrocortisone and 0.96 (95% CI, 0.82 to 1.12) without fludrocortisone. There was no significant differential treatment effect across subgroups. Hydrocortisone was associated with little to no difference in any of the secondary outcomes except vasopressor-free days (mean difference, 1.24 days; 95% CI, 0.74 to 1.73; high certainty). Hydrocortisone may not be associated with an increase in the risk of superinfection (RR, 1.04; 95% CI, 0.95 to 1.15; low certainty), hyperglycemia (RR, 1.05; 95% CI, 0.98 to 1.12; low certainty), or gastroduodenal bleeding (RR, 1.11; 95% CI, 0.83 to 1.48; low certainty). Hydrocortisone may be associated with an increase in the risk of hypernatremia (RR, 2.01; 95% CI, 1.56 to 2.60; low certainty) and muscle weakness (n=2647; RR, 1.73; 95% CI, 1.49 to 1.99; low certainty). CONCLUSIONS: In this patient-level meta-analysis, hydrocortisone compared with placebo was not associated with reduced mortality for patients with septic shock. (Funded by "Programme d'Investissements d'Avenir," a research Professorship from the National Institute of Health and Care Research, Leadership Fellowships from the National Health and Medical Research Council of Australia, and Emerging Leaders Fellowship from the National Health and Medical Research Council of Australia; PROSPERO registration number, CRD42017062198.)

[Effects of vaccination status on the disease severity of patients with coronavirus disease 2019].

OBJECTIVE: To evaluate the effect of 2019 novel coronavirus inactivated vaccine on the disease severity of patients with Delta variant of coronavirus disease 2019. METHODS: A retrospective analysis was performed on 704 patients with coronavirus disease 2019 infected with Delta variant who were older than 18 years old and admitted in the coronavirus disease 2019 designated hospital of Yangzhou (Subei Hospital New Area Branch) from July 2021 to September 2021. They were divided into severe (severe, critical) group and non-severe (light, ordinary) group according to the clinical characteristics of patients. According to the vaccination status, they were divided into 0-dose group, 1-dose group and 2-dose group. We evaluated the effects of vaccination on the severity of the disease and the production of antibodies, and analyzed the influencing factors leading to the severe group of coronavirus disease 2019. RESULTS: The proportion of severe group in the 2-dose vaccinated group was significantly lower than that in the 1-dose vaccinated group and 0-dose vaccinated group [3.02% (7/232) vs. 9.48% (22/232), 15.83% (38/240), P < 0.05]. The time from onset to admission (day: 1.97±1.66 vs. 2.66±2.70), age (years: 45.3±12.2 vs. 63.6±17.0), direct bilirubin [DBil (µmol/L): 3.70±1.83 vs. 5.30±5.13], lactate dehydrogenase [LDH (U/L): 240.69±74.29 vs. 256.30±85.18], creatinine [SCr (µmol/L): 63.38±19.86 vs. 70.23±25.43], interleukin-6 [IL-6 (ng/L): 7.32 (1.54, 17.40) vs. 18.38 (8.83, 33.43)], creatine kinase [CK (U/L): 66.00 (43.00, 99.75) vs. 78.00 (54.50, 144.00)] and D-dimer [mg/L: 0.30 (0.08, 0.49) vs. 0.41 (0.23, 0.69)] of patients in the 2-dose group were significantly lower than those in the 0-dose group (all P < 0.05), while platelet [PLT (×109/L): 176.69±60.25 vs. 149.25±59.07], white blood cell count [WBC (×109/L): 5.43±1.77 vs. 5.03±1.88] and lymphocyte [LYM (×109/L): 1.34±0.88 vs. 1.17±0.50] were significantly higher than those in the 0-dose group (all P < 0.05). The titer of immunoglobulin G (IgG) in the 2-dose group was significantly higher than those in the 1-dose group and 0-dose group on the 10th day after admission [U/L: 130.94 (92.23, 326.31), 113.18 (17.62, 136.20), 117.85 (33.52, 156.73), both P < 0.05], and higher than 0-dose group on the 16th day [U/L: 156.12 (120.32, 167.76) vs. 126.52 (61.34, 149.57), P < 0.05]. The proportion of complete 2-dose vaccination [10.45% (7/67) vs. 35.32% (225/637)], LYM (×109/L: 1.09±0.32 vs. 1.25±0.56) and PLT (×109/L: 138.55±68.03 vs. 166.93±59.70) in the severe group were significantly lower than those in the non-severe group (P < 0.05), while the time from onset to admission (day: 3.01±2.99 vs. 2.25±2.09), the length of hospital stay (day: 28±18 vs. 16±6), male proportion [77.61% (52/67) vs. 34.54% (220/637)], age (years: 69.13±12.63 vs. 52.28±16.53), DBil [µmol/L: 4.20 (3.18, 6.65) vs. 3.60 (2.80, 4.90], LDH (U/L: 310.61±98.33 vs. 238.19±72.14), SCr (µmol/L: 85.67±38.25 vs. 65.98±18.57), C-reactive protein [CRP (µmol/L): 28.12 (11.32, 42.23) vs. 8.49 (2.61, 17.58)], IL-6 [ng/L: 38.38 (24.67, 81.50) vs. 11.40 (4.60, 22.07)], CK [U/L: 140.00 (66.00, 274.00) vs. 72.80 (53.00, 11.00)] and the D-dimer [mg/L: 0.46 (0.29, 0.67) vs. 0.35 (0.19, 0.57)] in the severe group were significantly higher than those in the non-severe group (all P < 0.05). Multivariate regression analysis showed that the odds ratio (OR) of severe group was 0.430 (P = 0.010) in the 1-dose group and the 2-dose group compared with the 0-dose group. However, the risk of severe group was 0.381-fold in the 2-dose group compared with the 0-dose group [OR = 0.381, 95% confidence interval (95%CI) was 0.121-1.199] which was not statistically significant, when the age was included in the regression analysis (P > 0.05). PLT (OR = 0.992, 95%CI was 0.986-0.998) were protective factors, but older than 60 years old (OR = 3.681, 95%CI was 1.637-8.278), CK (OR = 1.001, 95%CI was 1.000-1.001), IL-6 (OR = 1.006, 95%CI was 1.002-1.010), SCr (OR = 1.020, 95%CI was 1.007-1.033) were risk factors for severe group (all P < 0.05). CONCLUSIONS: Compared with the 0-dose vaccinated patients, the coronavirus disease 2019 patients infected with delta variant and fully vaccinated with 2-dose 2019 novel coronavirus inactivated vaccine had lower level of IL-6, SCr, CK and D-dimer, and higher PLT, LYM and IgG titer, who were not easy to develop into the severe condition.

[Research progress of ferroptosis in sepsis].

Sepsis is a systemic disease with severe health consequences, and it was redefined in 2016 as a life-threatening organ dysfunction caused by an abnormal host response to infection and is a global public health priority. In recent years, there has been increasing recognition of the role of dysregulated micronutrient iron metabolism in the pathogenesis of sepsis. The concept of ferroptosis, an iron-dependent, non-apoptotic mode of cell death characterized by the accumulation of lipid reactive oxygen species (ROS), was first proposed by Dixon et al. in 2012. As a novel mode of programmed cell death, ferroptosis differs in morphological and biochemical characteristics from various forms of cell death, such as apoptosis, autophagy, necrosis and lysis. Recent studies have shown that ferroptosis plays an important regulatory role in the development of sepsis and has become a research focus and highlight for the diagnosis and prognosis of related diseases. Therefore, this paper reviews the latest developments in ferroptosis in sepsis, in order to further understanding its pathogenesis and providing new therapeutic targets for sepsis-related organ dysfunction.

Interspecies differences in mammalian susceptibility to legacy POPs and trace metals using skin fibroblast cells.

The susceptibility to trace metals and legacy POPs is different between terrestrial and marine mammals. In this study, we established the first cell line from Indo-Pacific finless porpoises and compared the cellular responses of skin fibroblast cells from Pygmy killer whales, Pantropic spotted dolphins, Indo-Pacific finless porpoises, mice, and humans following exposure to copper, methylmercury, cadmium, PCB126, PCB153, and BDE47 to better understand the interspecies sensitivities of mammals to chemical pollutants. We conducted a risk assessment by comparing no-observed effect concentrations (NOEC), lowest-observed effect concentrations (LOEC), and half maximal effective concentrations (EC50) from cell viability assays and previously reported pollutant body burdens in mammals. Based on the in vitro data, Indo-Pacific finless porpoises were more sensitive to copper and methylmercury than other mammals. PCB153 exposure reduced cell viability in all mammals except humans, while PCB126 was more potent, with 13.33 µg/mL exposure reducing cell viability in all mammals. In contrast, BDE47 exposure reduced cell viability only in terrestrial mammals in addition to pantropic spotted dolphin. Based on the in vitro data and the natural context of metal concentrations, both methylmercury and cadmium posed a higher risk to cetaceans than human, while copper posed a lower risk to cetaceans. All three legacy POPs (PCB126, PCB153, and BDE47) posed minor risk to cetaceans for short-term exposure. This study demonstrated that a species-specific in vitro model may provide more accurate information on the potential risk of pollutants to mammals. However, due to the bioamplification of POPs and their potential impact on the endocrine system and immune system of cetaceans, risk assessment with long-term exposure with more in vitro models should be further studied.

Leclercia adecarboxylata infective endocarditis in a man with mitral stenosis: A case report and review of the literature.

BACKGROUND: Infective endocarditis (IE) is a rare disease with a high mortality rate. Leclercia adecarboxylata (L. adecarboxylata) is a movable Gram-negative bacillus of enterobacteriaceae, and it can rarely be a pathogen which often affects immunodeficient patients. There are about three cases of immunocompetent patients with monomicrobial L. adecarboxylata infection. There are only three reported cases of IE caused by L. adecarboxylata in the world. The mitral valve is often affected in IE, and the prognosis for IE with mitral valve lesions is often poor. CASE SUMMARY: A 51-year-old man was found to have moderate to severe mitral stenosis on echocardiography. He came to our Cardiothoracic Surgery Department for surgical management. A diastolic murmur was heard on auscultation of the heart in the mitral region. On the second day of hospitalisation, he presented with slurred speech, reduced muscle strength in the left limb, and acute cerebral infarction on cranial computed tomography. Surgical treatment was decided to postpone. On the ninth day of admission, the patient developed a sudden high fever and shock and was transferred to the Cardiac Intensive Care Unit, where echocardiogram revealed an anterior mitral valve leaflet vegetation. After empirical anti-infective treatment with vancomycin (1g q12h), an emergency valve replacement was performed. Bacterial culture identified L. adecarboxylata. Anti-infective treatment with piperacillin-tazobactam (4.5g q8h) was added for 4 wk. Follow-up echocardiography showed normal bioprosthetic valve function after mitral valve replacement. CONCLUSION: We report the first case of L. adecarboxylata IE in China, and clinicians should pay attention to this pathogen.

[Study on the relationship between ventricular function parameters obtained by echocardiography and prognosis of patients with sepsis].

OBJECTIVE: To investigate the epidemiological characteristics of septic cardiomyopathy and explore the relationship between the relevant indexes measured by echocardiography and the prognosis of patients with sepsis. METHODS: A case-control study was conducted. The data of patients with sepsis admitted to the department of critical care medicine of Jiangsu Subei People's Hospital Affiliated to Yangzhou University and the department of critical care medicine of Beijing Electric Power Hospital of State Grid Corporation of China from June 2018 to June 2021 were enrolled. The general information and 28-day prognosis were recorded. At the same time, ultrasonic parameters obtained by transthoracic echocardiography within 24 hours after intensive care unit (ICU) admission were recorded. The differences in ultrasound indexes between the death group and the survival group on 28 days were compared. Parameters with significant statistical differences between the death group and the survival group were included in the Logistic regression analysis to find the independent risk factors for the prognosis of patients with sepsis, the predictive value of each index for the prognosis of patients with sepsis was evaluated by receiver operator characteristic curve (ROC curve). RESULTS: A total of 145 patients with sepsis were enrolled, including 106 patients with septic shock. Among the 145 patients, septic cardiomyopathy was found in 73 patients, with the incidence of 50.3%. The incidence of left ventricular diastolic dysfunction cardiomyopathy was 41.4% (n = 60), the incidence of left ventricular systolic dysfunction cardiomyopathy was 24.8% (n = 36), and the incidence of right ventricular systolic dysfunction cardiomyopathy was 12.4% (n = 18). At 28 days, 98 patients survived and 47 died, with the mortality of 32.4%. The peak e' velocity by tissue Doppler imaging (e') and right ventricular myocardial systolic tricuspid annulus velocity (RV-Sm) of the death group were significantly lower than those of the survival group [e' (cm/s): 7.81±1.12 vs. 8.61±1.02, RV-Sm (cm/s): 12.12±2.04 vs. 13.73±1.74, both P < 0.05], left ventricular ejection fraction (LVEF) and left ventricular systolic mitral annulus velocity (LV-Sm) in the death group were slightly higher than those in the survival group [LVEF: 0.550±0.042 vs. 0.548±0.060, LV-Sm (cm/s): 8.92±2.11 vs. 8.23±1.71], without significant differences (both P > 0.05). Parameters with significant statistical differences between the two groups were included in the Logistic regression analysis and showed that e' and RV-Sm were independent risk factors for the 28-day prognosis of patients with sepsis [e': odds ratio (OR) = 0.623, 95% confidence interval (95%CI) was 0.410-0.947, P = 0.027; RV-Sm: OR = 0.693, 95%CI was 0.525-0.914, P = 0.010]. ROC curve analysis showed that the area under the ROC curve (AUC) of e' for predicting the 28-day prognosis of patients with sepsis was 0.657, 95%CI was 0.532-0.781, P = 0.016, the best cut-off value was 8.65 cm/s, the sensitivity was 62.1%, and the specificity was 73.4%. The AUC of RV-Sm for predicting the 28-day prognosis of patients with sepsis was 0.641, 95%CI was 0.522-0.759, P = 0.030, the best cut-off value was 14.80 cm/s, the sensitivity was 96.6%, and the specificity was 26.6%. CONCLUSIONS: The incidence of septic cardiomyopathy is high. The LVEF measured by early echocardiography has no predictive value for 28-day prognosis in septic patients, while RV-Sm and e' are important predictors for 28-day prognosis.

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.

Case Report: Extracorporeal Membrane Oxygenation Followed by Intra-Aortic Balloon Counterpulsation Successfully Treated Cardiac Arrest Caused by Anomalous Origin of a Left Coronary Artery From the Right Coronary Sinus.

Background: Anomalous origin of a coronary artery (AOCA) is defined as the failure of the coronary artery to originate from the normal coronary sinus. The anomalous origin of the left coronary artery arising from the right coronary sinus is rare, dangerous and at risk of malignant arrhythmia, sudden death, and high mortality. Case Presentation: In this study, we present a 14-year-old adolescent male who went to a hospital with transient unconsciousness after exercise, who subsequently developed cardio arrest due to malignant arrhythmia. He was admitted to the intensive care unit, and who subsequently received successful veno-arterial extracorporeal membrane oxygenation (VA ECMO) assisted circulation followed by intra-aortic balloon counterpulsation (IABP). Echocardiography and cardiac CTA were also performed, further confirming that the abnormal left coronary artery originated from the right coronary sinus. The patient subsequently underwent heart surgery. Conclusion: The successful treatment of the patient in this report was attributed to the immediately VA ECMO, supplemented by IABP. Establishing clear diagnosis is a process of multidisciplinary joint diagnosis, which provides a reference for clinicians when encountering similar cases.

[Effects of different crystalloid resuscitation on renal function in septic shock rabbits under the guidance of pulse indicator continuous cardiac output].

OBJECTIVE: To study the effect of different crystalloid resuscitation on renal function in septic shock rabbits, and to provide a theoretical basis for the choice of crystalloid for clinical fluid resuscitation. METHODS: Thirty-six healthy male New Zealand white rabbits were divided into six groups by random number table: control group, model group, and four crystalloid groups including normal saline (NS) group, lactate Ringer solution (LR) group, acetate Ringer solution (AR) group, and sodium potassium magnesium calcium glucose injection (SPMCG) group, with 6 rabbits in each group. Rabbits were infused with Escherichia coli lipopolysaccharide (LPS) 500 µg/kg via the marginal ear vein (infused at a constant speed within 20 minutes), and then continued to infuse in an increase of 300 µg/kg every 10 minutes, the maximum dose was 2 mg/kg, until the mean arterial pressure (MAP) dropped to 60% of the basal value, the septic shock model was considered to be successfully reproduced. The rabbits in the control group were not injected with LPS, and other operations were the same as in the model group. Different crystalloid groups were given crystal solution immediately after modeling for resuscitation (predetermined fluid volume 60 mL/kg, transfusion within 3 hours). The volume stress test was performed every hour to guide the fluid volume, and the stroke volume index increase rate (ΔSVI) < 15% was the end point of resuscitation. The control group and the model group were given NS 4 mL×kg-1×h-1 to maintain the physiological requirement. All groups were given tracheotomy and mechanical ventilation, and the hemodynamic changes were monitored by pulse-indicated continuous cardiac output (PiCCO). The dynamic changes of hemodynamic indexes, arterial blood gas analysis, electrolytes, blood glucose and renal function biomarkers were monitored before modeling, immediately after modeling and 3, 6, and 12 hours after resuscitation. RESULTS: (1) Hemodynamic indicators: after modeling, the MAP in the model group and the four fluid resuscitation groups decreased significantly, the cardiac index (CI) increased, and the systemic vascular resistance index (SVRI), global end-diastolic volumn index (GEDVI) decreased. After different crystalloid resuscitation at different time points, MAP, SVRI, and GEDVI increased in the four crystalloid groups. (2) Arterial blood gas analysis, electrolytes, blood glucose: blood lactic acid (Lac) in the model group and the four fluid resuscitation groups increased after model success. After fluid resuscitation, the Lac of each crystalloid group began to decrease and reached to the lowest at 12 hours. Compared with the LR, AR and SPMCG groups, the pH value decreased in the NS group at 6 hours and 12 hours of fluid resuscitation (6 hours: 7.29±0.00 vs. 7.40±0.02, 7.35±0.02, 7.37±0.02; 12 hours: 7.27±0.02 vs. 7.38±0.02, 7.39±0.02, 7.35±0.01; all P < 0.05). After fluid resuscitation, blood Cl- levels at 3, 6, and 12 hours in the NS group were significantly higher than those in the LR, AR and SPMCG groups (mmol/L: 113.4±0.6 vs. 101.4±3.6, 108.0±1.1, 106.0±0.8 at 3 hours; 115.1±2.0 vs. 101.1±2.7, 109.0±2.2, 105.3±0.6 at 6 hours; 116.9±0.1 vs. 104.2±4.4, 107.6±1.7, 108.7±0.6 at 12 hours; all P < 0.05). There was no significant difference in blood glucose at each time point among the four crystalloid groups. (3) Biomarkers of renal function: blood and urine neutrophil gelatinase associated lipocalin (NGAL) and cystatin C (Cys C) were significantly increased in the model group and four fluid resuscitation groups. After fluid resuscitation, blood, urine NGAL and Cys C decreased. There was no significant difference in blood, urine NGAL and Cys C at all the time points among the different fluid resuscitation groups. CONCLUSIONS: In the rabbit model of septic shock induced by Escherichia coli LPS, hyperchloremia and acidosis occurred after NS resucitation, but did not occur during the recovery of LR, AR and SPMCG. There was no difference in the effects of different crystalloid resuscitation on renal function in septic shock rabbits.