Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy: A Randomized Clinical Trial.

Importance: Propofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events. Objective: To evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo). Interventions: After induction of sedation with 0.1 µg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration. Main Outcomes and Measures: The primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction. Results: Among the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, -12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P < .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q < .001) and reduced propofol requirements (difference, -58.9 mg; 95% CI, -65.7 to -52.2 mg; q < .001), without significant effects on other secondary outcomes. Conclusions and Relevance: In this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200055938.

Low-Dose Esketamine as an Adjuvant to Propofol Sedation for Same-Visit Bidirectional Endoscopy: Protocol for a Multicenter Randomized Controlled Trial.

Background: Same-visit bidirectional endoscopy (esophagogastroduodenoscopy and colonoscopy) is widely performed under sedation. At present, the optimal sedation regimen remains unclear. This study aims to test the hypothesis that a low-dose esketamine added to propofol sedation reduces hemodynamic and respiratory adverse events in these procedures. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 660 adult patients scheduled for same-visit bidirectional endoscopy under sedation from 3 teaching hospitals in China will be recruited. Patients will be randomly allocated, in a 1:1 ratio, to an esketamine group or a normal saline group (n = 330 in each group), stratified by study center. All patients will receive intravenous propofol 0.5 mg/kg and sufentanil 0.1 µg/mL for induction of sedation, followed by intravenous esketamine 0.15 mg/kg or the same volume of normal saline. Propofol will be titrated to the target sedation levels during the procedures. The primary endpoint is a composite of desaturation (peripheral oxygen saturation < 90%) and hypotension (systolic blood pressure <80 mmHg or decrease >30% of baseline). Secondary endpoints include desaturation, hypotension, total dose of propofol, pain scores and fatigue scores on the 0-10 numerical rating scale, dizziness or headache, hallucination or nightmare, nausea or vomiting, endoscopist satisfaction, and patient satisfaction. All analyses will be intention-to-treat. Discussion: We expect that a low-dose esketamine adjunct to propofol-based sedation will improve cardiorespiratory stability in patients undergoing same-visit bidirectional endoscopy, providing reference for clinical sedation practice during these procedures. Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR-ChiCTR2200055938).

Molecular characterization and functional analysis of IL-18 in snakehead (Channa argus) during Aeromonas schubertii and Nocardia seriolae infections.

As a proinflammatory cytokine of the interleukin-1 (IL-1) family, IL-18 plays important roles in host protection against bacterial, viral, and fungal infection. We cloned the open reading frame of snakehead (Channa argus) IL-18 (shIL-18) and found that it contained 609 base pairs and encoded 202 amino acid residues. The shIL-18 included a conserved IL-1-like family signature and two potential IL-1ß-converting enzyme cutting sites; one was conserved in all analyzed IL-18s, but the other was unique to shIL-18. Unlike other IL-18s, shIL-18 also contained a predicted signal peptide. In this study, shIL-18 was constitutively expressed in all tested tissues, and its expression was induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo and by lipoteichoic acid, lipopolysaccharides, and polyinosinic-polycytidylic acid in head kidney leukocytes in vitro. Moreover, recombinant shIL-18 upregulated the expression of interferon-γ, IL-1ß, and tumor necrosis factor-α1 and -α2 and promoted the proliferation of leukocytes. Taken together, these results showed that IL-18 played crucial roles in host defense against bacterial infection in fish, as it does in mammals.

Two types of TNF-α and their receptors in snakehead (Channa argus): Functions in antibacterial innate immunity.

Tumor necrosis factor-α (TNF-α) is a pluripotent mediator of pro-inflammatory and antimicrobial defense mechanisms and a regulator of lymphoid organ development. Although two types of TNF-α have been identified in several teleost species, their functions in pathogen infection remain largely unexplored, especially in pathogen clearance. Herein, we cloned and characterized two types of TNF-α, termed shTNF-α1 and shTNF-α2, and their receptors, shTNFR1 and shTNFR2, from snakehead (Channa argus). These genes were constitutively expressed in all tested tissues, and were induced by Aeromonas schubertii and Nocardia seriolae in head kidney and spleen in vivo, and by lipoteichoic acid (LTA), lipopolysaccharides (LPS), and Polyinosinic-polycytidylic acid [Poly (I:C)] in head kidney leukocytes (HKLs) in vitro. Moreover, recombinant shTNF-α1 and shTNF-α2 upregulated the expression of endogenous shTNF-α1, shTNF-α2, shTNFR1, and shTNFR2, and enhanced intracellular bactericidal activity, with shTNF-α1 having a greater effect than shTNF-α2. These findings suggest important roles of fish TNFα1, TNFα2, and their receptors in bacterial infection and pathogen clearance, and provide a new insight into their function in antibacterial innate immunity.

Bacteria-induced IL-1ß and its receptors in snakehead (Channa argus): Evidence for their involvement in antibacterial innate immunity.

As a central pro-inflammatory cytokine, interleukin-1ß (IL-1ß) plays critical roles in the inflammatory response, pathogen infection, and immunological challenges in mammals. Although fish IL-1ß has been confirmed to participate in inflammatory response to pathogen infection, few studies have been performed to characterize the antibacterial and bactericidal functions of fish IL-1ß. In this study, snakehead (Channa argus) IL-1ß (shIL-1ß) and its receptors, shIL-1R1 and shIL-1R2, were cloned and functionally characterized. ShIL-1ß contained the IL-1 family signature domain, and a potential cutting site at Asp96 that presented in all vertebrate IL-1ß sequences. ShIL-1R1 had three extracellular IG-like domains and one intracellular signal TIR domain, while shIL-1R2 had three extracellular IG-like domain but lacked the intracellular signal TIR domain. ShIL-1ß, shIL-1R1, and shIL-1R2 were constitutively expressed in all tested tissues, and their expressions could be induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo, and by LTA, LPS, and Poly (I:C) in head kidney leukocytes (HKLs) in vitro. Moreover, recombinant shIL-1ß upregulated the expression of endogenous shIL-1ß, shIL-R1, and shIL-R2 in snakehead HKLs, and enhanced intracellular bactericidal activity. Taken together, this study found that, like IL-1ß and its receptors in mammals, shIL-1ß and its receptors play crucial roles in antibacterial innate immunity. This provides new insight into the evolution of IL-1ß function in vertebrates.

Isolation, identification and character analysis of Streptococcus dysgalactiae from Megalobrama terminalis.

Pure bacterial cultures were isolated from different tissues of moribund Megalobrama terminalis from a high mortality event that occurred at a farm in Foshan, China. Two isolates (F2 and F3) were identified as Streptococcus dysgalactiae subsp. dysgalactiae based on morphological and biochemical detection as well as molecular analysis. In brain heart infusion broth, the best growth conditions of isolate F3 were 35ºC, salinity 5‰ and pH 7. Furthermore, infection with isolate F3 (1.2 × 106  CFU/fish) led to the death of M. terminalis and zebrafish (Danio rerio). However, isolate F3 had no obvious pathogenicity to tilapia (GIFT, Oreochromis niloticus). When the water temperature was 29ºC, the corresponding mortality rates for zebrafish infected by isolate F3 were higher than those at 23ºC. Culture for 24 and 72 hr with isolate F3 resulted in the same mortality rates for zebrafish. The antimicrobial susceptibility assay revealed that isolate F3 was susceptible to ampicillin, florfenicol and several other antibiotics but resistant to nalidixic acid, streptomycin, sulfamethoxazole/trimethoprim, neomycin and amikacin. To our knowledge, this is the first report that S. dysgalactiae infected the subtropical freshwater fish M. terminalis, which indicates that this bacterium is a potential threat to subtropical freshwater fish.