Supine transfer test-induced changes in cardiac index predict fluid responsiveness in patients without intra-abdominal hypertension.

BACKGROUND: The reversible maneuver that mimics the fluid challenge is a widely used test for evaluating volume responsiveness. However, passive leg raising (PLR) does have certain limitations. The aim of the study is to determine whether the supine transfer test could predict fluid responsiveness in adult patients with acute circulatory failure who do not have intra-abdominal hypertension, by measuring changes in cardiac index (CI). METHODS: Single-center, prospective clinical study in a 25-bed surgery intensive care unit at the Fudan University Shanghai Cancer Center. Thirty-four patients who presented with acute circulatory failure and were scheduled for fluid therapy. Every patient underwent supine transfer test and fluid challenge with 500 mL saline for 15-30 min. There were four sequential steps in the protocol: (1) baseline-1: a semi-recumbent position with the head of the bed raised to 45°; (2) supine transfer test: patients were transferred from the 45° semi-recumbent position to the strict supine position; (3) baseline-2: return to baseline-1 position; and (4) fluid challenge: administration of 500 mL saline for 15-30 min. Hemodynamic parameters were recorded at each step with arterial pulse contour analysis (ProAQT/Pulsioflex). A fluid responder was defined as an increase in CI ≥ 15% after fluid challenge. The receiver operating characteristic curve and gray zone were defined for CI. RESULTS: Seventeen patients were fluid challenge. The r value of the linear correlations was 0.73 between the supine transfer test- and fluid challenge-induced relative CI changes. The relative changes in CI induced by supine transfer in predicting fluid responsiveness had an area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.72-0.97) and predicted a fluid responder with 76.5% (95% confidence interval 50.1-93.2) sensitivity and 88.2% (95% confidence interval 63.6-98.5) specificity, at a best threshold of 5.5%. Nineteen (55%) patients were in the gray zone (CI ranging from -3 and 8 L/min/m2). CONCLUSION: The supine transfer test can potentially assist in detecting fluid responsiveness in patients with acute circulatory failure without intra-abdominal hypertension. Nevertheless, the small threshold and the 55% gray zone were noteworthy limitation. TRIAL REGISTRATION: Predicting fluid responsiveness with supine transition test (ChiCTR2200058264). Registered 2022-04-04 and last refreshed on 2023-03-26, https://www.chictr.org.cn/showproj.html?proj=166175 .

Characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for immune checkpoint inhibitor-related pneumonitis.

As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis). The incidence of ICI-pneumonitis is higher in reality than in clinical trials. The diagnosis is challenging, mainly based on clinical and imaging features, and requires the exclusion of other causes. The data on the biological mechanisms of ICI-pneumonitis are scarce, resulting in little knowledge of the best treatment for ICI-pneumonitis. Bronchoalveolar lavage (BAL) may be helpful to identify the biological differences or find predictive biomarkers, and may in turn help to develop phenotype-specific targeted drugs to treat ICI-pneumonitis. Herein, we outline the characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for ICI-pneumonitis. Through careful sorting and literature review, we find crosstalk between pathogenic Th17/Th1 cells (i.e., Th17.1) and pro-inflammatory monocytes, and activation of Th17(/Th1)/IL-17A (/IFN-γ) pathways may play a key role in the pathogenesis of ICI-pneumonitis. Disruption of the interaction between pathogenic Th17/Th1 cells and pro-inflammatory monocytes (such as, anti-IL-23) may be a potential treatment for ICI-pneumonitis. We first describe the possible pathophysiological mechanisms of ICI-pneumonitis, hoping to contribute to the optimization of diagnosis and treatment, as well as provide readers with research inspiration.

The diagnostic value of endoplasmic reticulum stress-related specific proteins GRP78 and CHOP in patients with sepsis: a diagnostic cohort study.

Background: Sepsis is a life-threatening disease with high mortality. Early diagnosis is critical as early treatment improves outcomes. The protein levels of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), markers of endoplasmic reticulum stress (ERS) activation, were reported increasing rapidly and continuously in the serum of patients with sepsis. Therefore, they might serve as a potential biomarker for sepsis diagnosis. This study aimed to analyze the role of GRP78 and CHOP in the diagnosis of patients with sepsis. Methods: This study enrolled a total of 92 infected patients with or without sepsis who were admitted to the intensive care unit (ICU) from February 1, 2018 to September 30, 2018. According to 2016 SCCM/ESICM Sepsis 3.0 diagnostic criteria, patients with sepsis were allocated into group I (sepsis infected group) and patients without sepsis were allocated into group II (non-sepsis infected group). Serum samples were collected on days 1, 2, 3, and 7 after admission to ICU, and the concentrations of GRP78 and CHOP in the serum were analyzed by enzyme-linked immunosorbent assay (ELISA). The diagnostic ability of GRP78, CHOP, and other traditional inflammatory markers was assessed with receiver operating characteristic (ROC)/area under the ROC curves (AUC) analysis. Patients were shortly follow-up for the 28-day mortality. Results: Serum GRP78 and CHOP levels in group I patients were higher than that in group II patients (P=0.021, P=0.00, respectively). When GRP78 was used to diagnose sepsis, the maximum area under the ROC curve (AUC) was 0.771 (95% CI: 0.662-0.880) and the optimal threshold was 157.29 ng/L (sensitivity, 75.0%; specificity, 73.1%) on day 2. When CHOP was used for the diagnosis of sepsis, the maximum AUC was 0.813(95% CI: 0.721-0.906) and the optimal threshold was 4.915 ng/L (sensitivity, 57.7%; specificity, 96.2%) on day 2. Conclusions: Compared with traditional inflammatory markers, ERS-related specific proteins GRP78 and CHOP have better sensitivity and specificity in the diagnosis of sepsis, which is helpful for clinicians in the diagnosis of sepsis.

Changes in the Cardiac Index Induced by Unilateral Passive Leg Raising in Spontaneously Breathing Patients: A Novel Way to Assess Fluid Responsiveness.

Background: Evaluation of fluid responsiveness in intensive care unit (ICU) patients is crucial. This study was to determine whether changes in the cardiac index (CI) induced by a unilateral passive leg raising (PLR) test in spontaneously breathing patients can estimate fluid responsiveness. Methods: This was a prospective study, and 40 patients with spontaneous breathing activity who were considered for volume expansion (VE) were included. CI data were obtained in a semirecumbent position, during unilateral PLR, bilateral PLR, and immediately after VE. If the CI increased more than 15% in response to the expansion in volume, patients were defined as responders. Results: The results showed that a unilateral PLR-triggered CI increment of ≥7.5% forecasted a fluid-triggered CI increment of ≥15% with 77.3% sensitivity and 83.3% specificity with and an area under the receiver operating characteristic (ROC) curve of 0.82 [P < 0.001]. Compared with that for bilateral PLR, the area under the ROC curve constructed for unilateral PLR-triggered changes in CI (ΔCI) was not significantly different (p = 0.1544). Conclusion: ΔCI >7.5% induced by unilateral PLR may be able to predict fluid responsiveness in spontaneously breathing patients and is not inferior to that induced by bilateral PLR. Trial Registration: Unilateral passive leg raising test to assess patient volume responsiveness: Single-Center Clinical Study, ChiCTR2100046762. Registered May 28, 2021.

Identification and application of T3SS translocation signal in Edwardsiella piscicida attenuated carrier as a bivalent vaccine.

Type III secretion system (T3SS)-dependent translocation has been used to deliver heterologous antigens by vaccine carriers into host cells. In this research, we identified the translocation signal of Edwardsiella piscicida T3SS effector EseG and constructed an antibiotic resistance-free balanced-lethal system as attenuated vaccine carrier to present antigens by T3SS. Edwardsiella piscicida LSE40 asd gene deletion mutant was constructed and complemented with pYA3342 harbouring the asd (aspartate ß-semialdehyde dehydrogenase) gene from Salmonella. Fusion proteins composed of EseG N-terminal 1-108 amino acids and the TEM1-ß-lactamase reporter were inserted in plasmid pYA3342. The fusion protein could secrete into the cell culture, translocate into HeLa cells, and localize in the membrane fraction. Then, the double gene deletion mutant LSE40ΔasdΔpurA was constructed as an attenuated vaccine carrier, and Aeromonas hydrophila GapA (glyceraldehyde-3-phosphate dehydrogenase) was fused with the translocation signal, instead of the TEM1-ß-lactamase reporter. The bivalent vaccine could protect blue gourami (Trichogaster trichopterus) against E. piscicida and A. hydrophila, with the relative per cent survival of 80.77% and 63.83%, respectively. These results indicated that EseG N-terminal 1-108 amino acid peptide was the translocation signal of E. piscicida T3SS, which could be used to construct bivalent vaccines based on an attenuated E. piscicida carrier.

Sheaths of Zostera marina L. as ecological indicators of shoot length and the elemental stoichiometry of aboveground tissues.

Given a large quantity of epiphytes and other material attached on eelgrass leaf blades, we explored the relationship between eelgrass sheaths and different-aged leaf blades (1st, 2nd, 3rd, and 4th leaf blade) on nutrient content and their ratios (C, N, P, C/N, C/P, and N/P) to identify whether eelgrass sheaths could be used to instead of leaf blades in terms of nutrient content. In addition, we explored the relationship between eelgrass sheath length and shoot length. Results showed that there were significant relationships between the sheath and leaf blades in terms of N and P content and their ratios. For length analysis, there was a significant relationship between sheath length and shoot length, and shoot length was approximately four to five times (mean 4.4659) longer than sheath length, such that shoot length can be estimated by sheath length. These significant relationships suggest that eelgrass sheath could be used as a suitable predictor of leaf blade in length and nutrient stoichiometry, thus eelgrass sheath could be used as an indicator for further eelgrass nutrient monitoring and research.

Plant morphology and seed germination responses of seagrass (Zostera japonica) to water depth and light availability in Ailian Bay, northern China.

Poor water quality and light reduction owing to anthropogenic impacts are the most widespread causes behind marine submerged angiosperm (seagrass) declines, worldwide. Seagrasses could respond to sustained environmental stresses, such as increasing water depth and light reduction, through morphological changes, particularly shoot density and/or biomass reductions. The seagrass Zostera japonica Asch. and Graebn. has been introduced to the Pacific Coast of North America, but it is widely threatened in its native northwestern Pacific Coast range alongside the east coast of China. The main aims of this study were to determine: 1) the depth limit of Z. japonica growth in its native range, and 2) how light availability affects the growth and recruitment of Z. japonica. To achieve these aims, we investigated the temporal responses of Z. japonica shoots and seeds from an intertidal donor site, Swan Lake, to light availability at water depths ranging from 1 to 6 m using in situ suspended cultures deployed in the experimental site, Ailian Bay, off the coast of Weihai City, China. The results showed that the transplanted Z. japonica shoots and seeds could survive for the duration of their annual growth cycle, permanently underwater, at a depth ≤2 m. There was a significant inverse relationship between water depth and time to complete shoot loss, despite temporally varying water clarity levels. Due to the local turbidity of the waters in Ailian Bay, a depth of 2 m yielded sufficient light deprivation (5%-37% surface irradiance) to negatively affect the seagrass shoot density. Our results suggest that this intertidal species can potentially persist in shallow subtidal areas following transplantation with shoots and seeds. The findings may also serve as useful information for local seagrass distribution limits, and will facilitate their habitat establishment and restoration efforts.

Myositis-myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis associated with anti-programmed cell death-1 (sintilimab) therapy for lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have improved clinical outcomes with a number of advanced malignancies. However, diverse immune-related adverse events (iRAEs) occurred with the widespread use of ICIs, some of which are rarely and life-threatening. Here we report a 66-year-old patient with lung adenocarcinoma who received two doses of sintilimab, a human monoclonal antibody against programmed cell death-1 (PD-1), experienced a fatal storm of iRAEs. He was admitted to the intensive care unit (ICU) by immune induced-myositis/myocarditis and rhabdomyolysis. Despite immediate immunosuppressive therapy with methylprednisolone (MP) and immunoglobulin intravenously, he developed into myositis-myasthenia gravis (MG) overlap syndrome complicated with myasthenia crisis. We commenced plasma exchange (PLEX), mechanical ventilation, immunosuppressive therapy, as well as other supportive therapies. Three months later, the patient's serum creatine phosphate kinase (CPK) and anti-acetylcholine receptor antibody (anti-AChR-Ab) returned to normal despite tumor progression. Herein we discuss the incidence, operating mechanism and management strategies of the fatal iRAEs. Early admission to the ICU and multidisciplinary collaborative treatment for unstable patients with iRAEs could help to achieve a favorable outcome.

In situ Responses of the Eelgrass Zostera marina L. to Water Depth and Light Availability in the Context of Increasing Coastal Water Turbidity: Implications for Conservation and Restoration.

Accelerating losses of seagrass meadows has led to efforts to restore these highly productive and beneficial ecosystems globally. Depth and light availability are critical determinants of seagrass restoration success. Eelgrass (Zostera marina L.) is the dominant seagrass species in the temperate northern hemisphere, but its global distribution has reduced dramatically. The main aims of this study were to determine: (1) the depth limit for Z. marina survival in Ailian Bay, north China, and (2) how light availability affects the growth and recruitment of Z. marina as a basis for identifying a suitable depth range for successful restoration. To achieve these aims, Z. marina shoots were transplanted from a nearby donor site, Swan Lake, to an experimental site, Ailian Bay, and the temporal responses of Z. marina shoots to light availability at water depths ranging from 1 to 8 m were investigated using in situ suspended cultures. Four suspended shoot transplantation experiments were conducted in 4 years. The results showed that the transplanted Z. marina shoots could survive and branch during an annual growth cycle, permanently underwater, at a depth ≤3 m. Due to the local turbidity of the waters in Ailian Bay, a depth of 4 m led to sufficient light deprivation (reduced to 6.48-10.08% of surface irradiance) to negatively affect seagrass shoot density and clonal reproduction. In addition, reproductive shoot density also tended to decline with water depth and light deprivation. Our results indicated that Z. marina population recruitment, through sexual and asexual (clonal growth) reproduction, were negatively affected by increasing water depth and light deprivation. These findings may provide a suitable depth range for the successful restoration of Z. marina in local coastal waters. They may also be applied to the management and restoration of Z. marina globally.

New Insights into Different Reproductive Effort and Sexual Recruitment Contribution between Two Geographic Zostera marina L. Populations in Temperate China.

Seagrasses are important components of global coastal ecosystems, and the eelgrass Zostera marina L. is widely distributed along the Atlantic and Pacific coasts in the temperate northern hemisphere, but limited datum related to the contribution of sexual reproduction to population recruitment have been reported. This study aimed to understand eelgrass sexual reproduction and population recruitment in Swan Lake (SLL), and Huiquan Bay (HQB) was included for comparison. Random sampling, permanent quadrats or cores and laboratory seed germination-based experimental methods were employed. The flowering, seed production, seed banks, seed germination, seedling survival, and seedling growth of eelgrass were investigated from July 2014 to December 2015 to evaluate the contribution of sexual reproduction to population recruitment. Results indicated a dominant role of asexual reproduction in HQB, while sexual reproduction played a relatively important role in SLL. The highest flowering shoot density in SLL was 517.27 ± 504.29 shoots m-2 (June) and represented 53.34% of the total shoots at the center site. The potential seed output per reproductive shoot and per unit area in SLL were 103.67 ± 37.95 seeds shoot-1 and 53,623.66 ± 19,628.11 seeds m-2, respectively. The maximum seed bank density in SLL was 552.21 ± 204.94 seeds m-2 (October). Seed germination mainly occurred from the middle of March to the end of May, and the highest seedling density was 296.88 ± 274.27 seedlings m-2 in April. The recruitment from seedlings accounted for 41.36% of the Z. marina population recruitment at the center site, while the sexual recruitment contribution at the patch site (50.52%) was greater than that at the center site. Seeds in SLL were acclimated to spring germination, while in HQB, they were acclimated to autumn germination (early October-late November). Seed bank density in HQB was very low, with a value of 254.35 ± 613.34 seeds m-2 (early October). However, seeds in HQB were significantly larger and heavier than those in SLL (size: P = 0.004; weight: P < 0.001). The recruitment from seedlings accounted for as low as 2.53% of the Z. marina population recruitment in HQB. Our laboratory seed germination experiment, which was conducted in autumn, showed that the seed germination percent in HQB was significantly greater than in SLL at optimal germination temperatures (10 and 15°C; P < 0.001). A laboratory seed germination test at suitable temperature may be a potential novel approach to identify the ecological differences among different geographic populations. It is suggested that the Z. marina population recruitment may have different strategies and adapt to specific local conditions, such as in SLL and HQB, and the temperature regime may control morphological and phonological variations.

Trace element exposure of whooper swans (Cygnus cygnus) wintering in a marine lagoon (Swan Lake), northern China.

Trace element poisoning remains a great threat to various waterfowl and waterbirds throughout the world. In this study, we determined the trace element exposure of herbivorous whooper swans (Cygnus cygnus) wintering in Swan Lake (Rongcheng), an important swan protection area in northern China. A total of 70 samples including abiotic factors (seawater, sediments), food sources (seagrass, macroalgae), feathers and feces of whooper swans were collected from the marine lagoon during the winters of 2014/2015 and 2015/2016. Concentrations of Cu, Zn, Pb, Cr, Cd, Hg and As were determined to investigate the trace element exposure of whooper swans wintering in the area. Results showed that there was an increasing trend in sediment trace element concentrations, compared with historical data. The trace element concentrations in swan feces most closely resembled those of Zostera marina leaves, especially for Cd and Cr. The Zn and Hg concentrations in the swan feces (49.57 and 0.01mg/kg, respectively) were lower than the minimum values reported in the literature for other waterfowls, waterbirds and terrestrial birds. However, the concentrations of the other five trace elements fell within the lower and mediate range of values reported for birds across the world. These results suggest that the whooper swans wintering in Swan Lake, Rongcheng are not suffering severe trace element exposure; however, with the increasing input of trace elements to the lagoon, severe adverse impacts may occur in the future, and we therefore suggest that the input of trace elements to this area should be curbed.

Salinity and temperature significantly influence seed germination, seedling establishment, and seedling growth of eelgrass Zostera marina L.

Globally, seagrass beds have been recognized as critical yet declining coastal habitats. To mitigate seagrass losses, seagrass restorations have been conducted in worldwide over the past two decades. Seed utilization is considered to be an important approach in seagrass restoration efforts. In this study, we investigated the effects of salinity and temperature on seed germination, seedling establishment, and seedling growth of eelgrass Zostera marina L. (Swan Lake, northern China). We initially tested the effects of salinity (0, 5, 10, 15, 20, 25, 30, 35, and 40 ppt) and water temperature (5, 10, 15, and 20 °C) on seed germination to identify optimal levels. To identify levels of salinity that could potentially limit survival and growth, and, consequently, the spatial distribution of seedlings in temperate estuaries, we then examined the effect of freshwater and other salinity levels (10, 20, and 30 ppt) on seedling growth and establishment to confirm suitable conditions for seedling development. Finally, we examined the effect of transferring germinated seeds from freshwater or low salinity levels (1, 5, and 15 ppt) to natural seawater (32 ppt) on seedling establishment rate (SER) at 15 °C. In our research, we found that: (1) Mature seeds had a considerably lower moisture content than immature seeds; therefore, moisture content may be a potential indicator of Z. marina seed maturity; (2) Seed germination significantly increased at low salinity (p < 0.001) and high temperature (p < 0.001). Salinity had a much stronger influence on seed germination than temperature. Maximum seed germination (88.67 ± 5.77%) was recorded in freshwater at 15 °C; (3) Freshwater and low salinity levels (< 20 ppt) increased germination but had a strong negative effect on seedling morphology (number of leaves per seedling reduced from 2 to 0, and maximum seedling leaf length reduced from 4.48 to 0 cm) and growth (seedling biomass reduced by 46.15-66.67% and maximum seedling length reduced by 21.16-69.50%). However, Z. marina performed almost equally well at salinities of 20 and 30 ppt. Very few germinated seeds completed leaf differentiation and seedling establishment in freshwater or at low salinity, implying that freshwater and low salinity may potentially limit the distribution of this species in coastal and estuarine waters. Therefore, the optimum salinity for Z. marina seedling establishment and colonization appears to be above 20 ppt in natural beds; (4) Seeds germinated in freshwater or at low salinity levels could be transferred to natural seawater to accomplish seedling establishment and colonization. This may be the optimal method for the adoption of seed utilization in seagrass restoration. We also identified seven stages of seed germination and seedling metamorphosis in order to characterize growth and developmental characteristics. Our results may serve as useful information for Z. marina habitat establishment and restoration programs.