Risk factors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: A multicenter retrospective study.

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.

Fospropofol disodium versus propofol for long-term sedation during invasive mechanical ventilation: A pilot randomized clinical trial.

STUDY OBJECTIVE: Fospropofol disodium is a propofol prodrug that is water-soluble and has a reduced risk of bacterial contamination and hypertriglyceridemia compared with propofol. Prior to implementing a large randomized trial, we investigated the feasibility, initial efficacy, and safety of fospropofol disodium compared with propofol in long-term mild-to-moderate sedation in intensive care units (ICUs). DESIGN: Single-centered, prospective, unblind, randomized, parallel-group clinical trial. SETTING: The general ICU of university-affiliated teaching hospital. PATIENTS: Adult patients (n = 60) expected to have mechanical ventilation for >24 h were enrolled and randomly assigned to the fospropofol or propofol group. INTERVENTIONS: The fospropofol group received continuous fospropofol disodium infusions and the propofol group received continuous propofol infusions. The sedation goal was a score of -3 to 0 on the Richmond Agitation and Sedation Scale (RASS). MEASUREMENTS: The primary outcome was the percentage of time spent in the target sedation range without rescue sedation. Safety outcomes were based on adverse events. Blood samples were collected to measure formate concentration in plasma. MAIN RESULTS: The median dose was 4.33 (IQR, 3.08-4.94) mg/kg/h in the fospropofol group and 1.96 (IQR, 1.44-2.94) mg/kg/h in the propofol group. The median percentage of time spent in the target RASS range without rescue sedation was identical in both groups, with 83.33% (IQR, 74.43%-100.00%) in the fospropofol group and 83.33% (IQR, 77.45%-100.00%) in the propofol group (p = 0.887). At least one adverse event was identifed in 23 (76.7%) fospropofol patients and 27 (90.0%) propofol patients. The most common adverse events were tachycardia and hypotension. No paresthesia, catheter-related bloodstream infection or propofol infusion syndrome in both groups was reported. Three patients in the fospropofol group had mild hypertriglyceridemia, and nine patients in propofol group had hypertriglyceridemia (mild in eight patients and moderate in one patient) (10% versus 30%, p = 0.104). The formate concentration in plasma was very low, and no significant difference was identified at any time point between the two groups. CONCLUSIONS: Fospropofol disodium appears to be a feasible, effective and safe sedative for patients receiving invasive mechanical ventilation with long-term sedation.

Mechanical Properties and Fatigue Life Analysis of Motion Cables in Sensors under Cyclic Loading.

Motion cables, which are widely used in aero-engine sensors, are critical components that determine sensor stability. Because motion cables have unique motion characteristics, the study of their mechanical properties and reliability is very important. In addition, motion cables are complex in structure and cannot be applied to conventional fixed cable research methods. In this study, a new approach is proposed to introduce the theory of anisotropic composites into a simplified cable model, so that the cable is both physically conditioned and has good mechanical properties. While applying the theory of anisotropic composites, the forces of tension and torsion are considered in a motion cable under the combined action. In this context, the reliability of the structure is the fatigue life of the cable. In this paper, the mechanical properties and fatigue life of motion cables are investigated using the finite element method at different inclination angles and fixation points. The simulation results show that there is a positive correlation between the inclination angle and the extreme stress in the motion cables, and the optimal inclination angle of 0° is determined. The number of fixing points should be reduced to minimize the additional moments generated during the movement and to ensure proper movement of the cables. The optimal configuration is a 0° inclination angle and two fixing points. Subsequently, the fatigue life under these optimal conditions is analyzed. The results show that the high-stress zone corresponds to the location of the short-fatigue life, which is the middle of the motion cables. Therefore, minimizing the inclination angle and the number of fixing points of the motion cables may increase their fatigue life and thus provide recommendations for optimizing their reliability.

Extracorporeal membrane oxygenation in adult patients with sepsis and septic shock: Why, how, when, and for whom.

Sepsis and septic shock remain the leading causes of death in intensive care units. Some patients with sepsis fail to respond to routine treatment and rapidly progress to refractory respiratory and circulatory failure, necessitating extracorporeal membrane oxygenation (ECMO). However, the role of ECMO in adult patients with sepsis has not been fully established. According to existing studies, ECMO may be a viable salvage therapy in carefully selected adult patients with sepsis. The choice of venovenous, venoarterial, or hybrid ECMO modes is primarily determined by the patient's oxygenation and hemodynamics (distributive shock with preserved cardiac output, septic cardiomyopathy (left, right, or biventricular heart failure), or right ventricular failure caused by acute respiratory distress syndrome). Veno-venous ECMO can be used in patients with sepsis and severe acute respiratory distress syndrome when conventional mechanical ventilation fails, and early application of veno-arterial ECMO in patients with sepsis-induced refractory cardiogenic shock may be critical in improving their chances of survival. When ECMO is indicated, the choice of an appropriate mode and determination of the optimal timing of initiation and weaning are critical, particularly in an experienced ECMO center. Furthermore, some special issues, such as ECMO flow, anticoagulation, and antibiotic therapy, should be noted during the management of ECMO support.

Remimazolam besylate versus propofol for deep sedation in critically ill patients: a randomized pilot study.

OBJECTIVE: To compare the efficacy and safety of remimazolam besylate and propofol for deep sedation in critically ill patients. METHODS: In this single-center, prospective, randomized, controlled pilot study, patients in the intensive care unit (ICU) requiring deep sedation were randomized to receive remimazolam besylate or propofol intravenously. Deep sedation was defined as a Richmond Agitation and Sedation Scale (RASS) score of - 4 or - 5. Sedation depth was monitored using RASS and Narcotrend Index (NI). The primary outcome was the percentage of time within the target sedation range without rescue sedation. The secondary outcomes included ventilator-free hours within 7 days, successful extubation, length of ICU stay, and 28-day mortality. Adverse events during the interventional period were also recorded. RESULTS: Thirty patients were assigned to each group. The median (IQR) RASS score was - 5.0 (- 5.0, - 4.0), and the median (IQR) NI value was 29.0 (21.0, 37.0) during the intervention period. Target RASS was reached a median of 100% of the sedation time in the two groups. No significant differences were observed in ventilator-free hours within 7 days, successful extubation, length of ICU stay, or 28-day mortality among groups. Hypotension occurred in 16 (53.3%) patients of remimazolam group and 18 (60.0%) patients of propofol group (p > 0.05). No patient experienced bradycardia. CONCLUSIONS: Remimazolam besylate appears to be an effective and safe agent for short-term deep sedation in critically ill patients. Our findings warrant large sample-sized randomized clinical trials.

Long-term sedation with remimazolam besylate versus propofol in critically ill patients during invasive mechanical ventilation: a study protocol for a multicenter randomized non-inferior trial.

Background: Remimazolam besylate is a novel ultra-short-acting benzodiazepine that can potentially be a safe and effective sedative in intensive care units. This study aims to assess whether remimazolam besylate is not inferior to propofol in maintaining mild-to-moderate sedation in critically ill patients receiving long-term mechanical ventilation. Methods and analysis: This is a multicenter, randomized, single-blind, propofol-controlled, non-inferiority study. Eligible patients are randomly assigned to receive remimazolam besylate or propofol in a 1:1 ratio to maintain a Richmond Agitation-Sedation Scale score between -3 and 0. When patients are under-sedated, rescue sedation of dexmedetomidine is added. The primary outcome is the percentage of time in the target sedation range. The secondary outcomes are hours free from the invasive ventilator in 7 days, successful extubation in 7 days, and weaning time, the length of intensive care unit stay, the length of hospital stay, and mortality in 28 days. Modified intention-to-treat and safety analysis is performed. Clinical trial registration number: https://clinicaltrials.gov/ct2/show/NCT05555667.

Impact of early enteral nutrition on ventilator associated pneumonia in intubated severe trauma patients: A propensity score-matched study.

Background: Early enteral nutrition (EN) is recommended for critically ill patients. However, the impact of early EN on intubated severe trauma patients remains unclear. Methods: Severely traumatized adult patients who received invasive mechanical ventilation (MV) for more than 48 h during intensive care unit (ICU) stay at our institution between 2017 and 2022 were retrospectively included. Early EN was defined as EN initiation ≤48 h from ICU admission and late EN >48 h. Propensity score matching (PSM) analysis was used to compare outcomes between the groups. The primary endpoint was the incidence of ventilator-associated pneumonia (VAP). Multivariable logistic regression analysis was performed to identify independent predictors of delayed EN. Results: For final analysis, 337 intubated severe trauma patients were available, including 204 (60.5%) in the early EN group and 133 (39.5%) in the late EN group. After PSM, early EN patients had a lower incidence of VAP (12.9 vs. 25.8%, p = 0.026) and a shorter length of hospital stay (21 vs. 24 days, p = 0.015) compared to late EN patients. There was no demonstrable difference in mortality between the two groups. Abdominal trauma, massive blood transfusion, and serum albumin were identified as independent risk factors for delayed EN. Conclusion: Early EN decreased the VAP rate and reduced the length of hospital stay in invasively ventilated patients with severe trauma. Abdominal injury, massive blood transfusion and low albumin were associated with delayed EN.

NLRC3 Participates in Inhibiting the Pulmonary Inflammatory Response of Sepsis-Induced Acute Lung Injury.

Acute lung injury (ALI) progresses rapidly, is difficult to treat, and has a high fatality rate. The excessive inflammatory response is an important pathological mechanism of ALI. NLRC3 (NLR family CARD domain-containing 3), a non-inflammasome member of the NLR family, has been found that it could negatively regulates various biological pathways associated with inflammatory response, such as NF-κB (nuclear factor kappa B), PI3K (Phosphatidylinositol 3'-kinase)-Akt (protein kinase B)-mTOR (mammalian target of the rapamycin), and STING (stimulator of interferon genes) pathways, which are responsible for the progression of pulmonary inflammation and participate in regulating the pathological progression of ALI. However, the effects of NLRC3 in sepsis-induced pathological injury of lung tissue remain unclear. In this study, we aimed to investigate the potential effects of NLRC3 in the sepsis-induced ALI. To investigate whether NLRC3 participates in inhibiting the pulmonary inflammatory response of sepsis-induced ALI. Sepsis-induced ALI mice models were established by intrabronchial injection of lipopolysaccharide (LPS) or cecum ligation and puncture (CLP). The lentivirus with overexpression of NLRC3 (LV-NLRC3) and downregulation of NLRC3 (LV-NLRC3-RNAi) were transfected to LPS-induced ALI mice. The expression of NLRC3 was upregulated or downregulated in the lung tissue of sepsis-induced ALI mice. Transfection with NLRC3-overexpression lentivirus significantly decreased inflammatory response in the lung of LPS-induced ALI mice in contrast to the control group. By transfection with NLRC3-silencing lentivirus, the inflammatory response in LPS-induced ALI mice was aggravated. Our study provides evidence of the protective effect of NLRC3 in sepsis-induced ALI by inhibiting excessive inflammatory response of the lung tissue.AbbreviationsAcute lung injury: ALI; intensive care units: ICU; lipopolysaccharide: LPS; acute respiratory distress syndrome: ARDS; bronchoalveolar lavage fluid: BALF; nucleotide-binding oligomerization domain-like receptors: NLRs; NLR family CARD domain containing 3: NLRC3; nuclear factor kappa B: NF-κB; tumor necrosis factor receptor-associated factor 6: TRAF6; Phosphatidylinositol 3'-kinase: PI3K; protein kinase B: Akt; mammalian target of the rapamycin: mTOR; stimulator of interferon genes: STING; TANK-binding kinase 1: TBK1; type I interferon: IFN-I; toll-like receptors: TLRs; tumor necrosis factor: TNF; interleukin: IL; NOD-like receptor protein 3: NLRP3; enhanced green fluorescent protein: EGFP; lentivirus: LV; phosphate-buffered saline: PBS; intrabronchial: i.t.; cecum ligation and puncture: CLP; wet/dry: W/D; Real time polymerase chain reaction: RT-PCR; enzyme-linked immunosorbent assay: ELISA; hematoxylin and eosin: H&E; radio immunoprecipitation assay: RIPA; sodium dodecyl sulfate polyacrylamide gel electrophoresis: SDS-PAGE; polyvinylidene fluoride: PVDF; glyceraldehyde 3-phosphate dehydrogenase: GAPDH; bovine serum albumin: BSA; Tris buffered saline containing Tween 20: TBST; standard deviation: SD; one-way analysis of variance: ANOVA; janus kinase 2: JAK2; activators of transcription 3: STAT3; pathogen associated molecular patterns: PAMPs; danger associated molecular patterns: DAMPs.

Effects of airway pressure release ventilation on lung physiology assessed by electrical impedance tomography in patients with early moderate-to-severe ARDS.

OBJECTIVE: The aim of this study was to investigate the physiological impact of airway pressure release ventilation (APRV) on patients with early moderate-to-severe acute respiratory distress syndrome (ARDS) by electrical impedance tomography (EIT). METHODS: In this single-center prospective physiological study, adult patients with early moderate-to-severe ARDS mechanically ventilated with APRV were assessed by EIT shortly after APRV (T0), and 6 h (T1), 12 h (T2), and 24 h (T3) after APRV initiation. Regional ventilation and perfusion distribution, dead space (%), shunt (%), and ventilation/perfusion matching (%) based on EIT measurement at different time points were compared. Additionally, clinical variables related to respiratory and hemodynamic condition were analyzed. RESULTS: Twelve patients were included in the study. After APRV, lung ventilation and perfusion were significantly redistributed to dorsal region. One indicator of ventilation distribution heterogeneity is the global inhomogeneity index, which decreased gradually [0.61 (0.55-0.62) to 0.50 (0.42-0.53), p < 0.001]. The other is the center of ventilation, which gradually shifted towards the dorsal region (43.31 ± 5.07 to 46.84 ± 4.96%, p = 0.048). The dorsal ventilation/perfusion matching increased significantly from T0 to T3 (25.72 ± 9.01 to 29.80 ± 7.19%, p = 0.007). Better dorsal ventilation (%) was significantly correlated with higher PaO2/FiO2 (r = 0.624, p = 0.001) and lower PaCO2 (r = -0.408, p = 0.048). CONCLUSIONS: APRV optimizes the distribution of ventilation and perfusion, reducing lung heterogeneity, which potentially reduces the risk of ventilator-induced lung injury.

Fine-grained Lesion Classification Framework for Early Auxiliary Diagnosis.

The deep neural networks are envisaged for the early disease diagnosis from medical images. However, in the early stage of the disease, the medical images of patients and healthy people have only subtle visual differences. Distinguishing the medical images for early diagnosis belongs to the Fine-Grained Visual Classification (FGVC) task. Many recent works are based on a standard FGVC learning paradigm: locate the discriminative regions first and then classify by fusing the information of these regions. However, it is still not enough for medical images. Because the shape and size of the lesions are variable, and the relationship between lesions and the background is complex. In order to solve these problems, we propose a fine-grained lesion classification framework for early auxiliary diagnosis. We first locate and extract multiple lesions with different sizes and shapes from the original image and then fuse the feature of lesion and background based on attention mechanism. As shown by experiment results in two real-world clinical data sets, our model can locate accurately and perform better.

NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.

Impairment of innate immune cell function and metabolism underlies immunosuppression in sepsis; however, a promising therapy to orchestrate this impairment is currently lacking. In this study, high levels of NOD-like receptor family CARD domain containing-3 (NLRC3) correlated with the glycolytic defects of monocytes/macrophages from septic patients and mice that developed immunosuppression. Myeloid-specific NLRC3 deletion improved macrophage glycolysis and sepsis-induced immunosuppression. Mechanistically, NLRC3 inhibits nuclear factor (NF)-κB p65 binding to nuclear factor of activated T cells 5 (NFAT5), which further controls the expression of glycolytic genes and proinflammatory cytokines of immunosuppressive macrophages. This is achieved by decreasing NF-κB activation-co-induced by TNF-receptor-associated factor 6 (TRAF6) or mammalian target of rapamycin (mTOR)-and decreasing transcriptional co-activator p300 activity by inducing NLRC3 sequestration of mTOR and p300. Genetic inhibition of NLRC3 disrupted the NLRC3-mTOR-p300 complex and enhanced NF-κB binding to the NFAT5 promoter in concert with p300. Furthermore, intrapulmonary delivery of recombinant adeno-associated virus harboring a macrophage-specific NLRC3 deletion vector significantly improved the defense of septic mice that developed immunosuppression upon secondary intratracheal bacterial challenge. Collectively, these findings indicate that NLRC3 mediates critical aspects of innate immunity that contribute to an immunocompromised state during sepsis and identify potential therapeutic targets.

[A child suffering from severe acute respiratory distress syndrome due to multiple trauma was treated with veno-veous extracorporeal membrane oxygenation with the dual lumen cannula: a case report].

Veno-veous extracorporeal membrane oxygenation (VV-ECMO) has been widely used in the treatment for severe acute respiratory distress syndrome (ARDS). Up to now, the routine access to establish VV-ECMO involves two-sites single lumen cannula via femoral vein and internal jugular venous in adult and children, while few studies about the dual lumen cannula (DLC) in VV-ECMO implemented in adult and children have been reported. On December 16, 2021, an unconscious child with severe ARDS due to multiple trauma caused by fatal falling from a height was admitted to Taihe Hospital. The initial diagnosis was hemorrhagic shock, bilateral hemopneumothorax, sternal fracture, cavity organ perforation, splenic rupture, and pelvic fracture and severe ARDS. Despite mechanical ventilation, he progressed to refractory hypoxemia and was treated with VV-ECMO after successful DLC placement in the right internal jugular vein by the mobile ECMO team of intensive care unit of the Union Hospital eventually. In addition, he received endoscopic sputum aspiration, prone position ventilation, anti-infection and nutritional treatment. His oxygenation gradually improved and he was successfully weaned from ECMO after 11 days. In this case, DLC simplified the process without any related complications, suggesting that it can be safely and effectively used in the treatment of Child's severe ARDS.

Prone positioning in ARDS patients supported with VV ECMO, what we should explore?

BACKGROUND: Acute respiratory distress syndrome (ARDS), a prevalent cause of admittance to intensive care units, is associated with high mortality. Prone positioning has been proven to improve the outcomes of moderate to severe ARDS patients owing to its physiological effects. Venovenous extracorporeal membrane oxygenation (VV ECMO) will be considered in patients with severe hypoxemia. However, for patients with severe hypoxemia supported with VV ECMO, the potential effects and optimal strategies of prone positioning remain unclear. This review aimed to present these controversial questions and highlight directions for future research. MAIN BODY: The clinically significant benefit of prone positioning and early VV ECMO alone was confirmed in patients with severe ARDS. However, a number of questions regarding the combination of VV ECMO and prone positioning remain unanswered. We discussed the potential effects of prone positioning on gas exchange, respiratory mechanics, hemodynamics, and outcomes. Strategies to achieve optimal outcomes, including indications, timing, duration, and frequency of prone positioning, as well as the management of respiratory drive during prone positioning sessions in ARDS patients receiving VV ECMO, are challenging and controversial. Additionally, whether and how to implement prone positioning according to ARDS phenotypes should be evaluated. Lung morphology monitored by computed tomography, lung ultrasound, or electrical impedance tomography might be a potential indication to make an individualized plan for prone positioning therapy in patients supported with VV ECMO. CONCLUSION: For patients with ARDS supported with VV ECMO, the potential effects of prone positioning have yet to be clarified. Ensuring an optimal strategy, especially an individualized plan for prone positioning therapy during VV ECMO, is particularly challenging and requires further research.

Remimazolam besylate versus propofol for long-term sedation during invasive mechanical ventilation: a pilot study.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of remimazolam besylate compared with propofol in maintaining mild-to-moderate sedation in patients receiving long-term mechanical ventilation. METHODS: In this single-centered randomized pilot study, adult patients mechanically ventilated longer than 24 h were randomized to receive remimazolam besylate or propofol. The target sedation range was - 3 to 0 on the Richmond Agitation and Sedation Scale (RASS). The primary outcome was the percentage of time in the target sedation range without rescue sedation. The secondary outcomes were ventilator-free days at day 7, the length of ICU stay and 28-day mortality. RESULTS: Thirty patients were assigned to each group. No difference was identified between the remimazolam group and propofol group in median age [60.0 (IQR, 51.5-66.3) years vs. 64.0 (IQR, 55.0-69.3) years, respectively, p = 0.437] or the median duration of study drug infusion [55.0 (IQR, 28.3-102.0) hours vs. 41.0 (IQR, 24.8-74.3) hours, respectively, p = 0.255]. The median percentage of time in the target RASS range without rescue sedation was similar in remimazolam and propofol groups [73.2% (IQR, 41.5-97.3%) vs. 82.8% (IQR, 65.6-100%), p = 0.269]. No differences were identified between the two groups in terms of ventilator-free days at day 7, length of ICU stay, 28-day mortality or adverse events. CONCLUSIONS: This pilot study suggested that remimazolam besylate was effective and safe for long-term sedation in mechanically ventilated patients compared with propofol.

Clinical characteristics and risk factors associated with ICU-acquired infections in sepsis: A retrospective cohort study.

Intensive care unit (ICU)-acquired infection is a common cause of poor prognosis of sepsis in the ICU. However, sepsis-associated ICU-acquired infections have not been fully characterized. The study aims to assess the risk factors and develop a model that predicts the risk of ICU-acquired infections in patients with sepsis. Methods: We retrieved data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. A multivariable logistic regression model was used to identify independent risk factors that could predict ICU-acquired infection. We also assessed its discrimination and calibration abilities and compared them with classical score systems. Results: Of 16,808 included septic patients, 2,871 (17.1%) developed ICU-acquired infection. These patients with ICU-acquired infection had a 17.7% ICU mortality and 31.8% in-hospital mortality and showed a continued rise in mortality from 28 to 100 days after ICU admission. The classical Systemic Inflammatory Response Syndrome Score (SIRS), Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Charlson Comorbidity Index (CCI), and Acute Physiology Score III (APS III) scores were associated with ICU-acquired infection, and cerebrovascular insufficiency, Gram-negative bacteria, surgical ICU, tracheostomy, central venous catheter, urinary catheter, mechanical ventilation, red blood cell (RBC) transfusion, LODS score and anticoagulant therapy were independent predictors of developing ICU-acquired infection in septic patients. The nomogram on the basis of these independent predictors showed good calibration and discrimination in both the derivation (AUROC = 0.737; 95% CI, 0.725-0.749) and validation (AUROC = 0.751; 95% CI, 0.734-0.769) populations and was superior to that of SIRS, SOFA, OASIS, SAPS II, LODS, CCI, and APS III models. Conclusions: ICU-acquired infections increase the likelihood of septic mortality. The individualized prognostic model on the basis of the nomogram could accurately predict ICU-acquired infection and optimize management or tailored therapy.

Remimazolam versus traditional sedatives for procedural sedation: a systematic review and meta-analysis of efficacy and safety outcomes.

INTRODUCTION: Remimazolam is a novel and ultra-short-acting benzodiazepine currently approved for procedural sedation and induction of general anaesthesia, with a possible indication for ICU sedation. This study aimed to evaluate the efficacy and safety of remimazolam and traditional sedatives for patients undergoing procedural sedation. EVIDENCE ACQUISITION: We systematically searched Cochrane Library, Embase, PubMed, Web of Science and ClinicalTrials.gov for randomized controlled trials of procedural sedation performed with remimazolam versus traditional sedatives. Data from the eligible studies were combined to calculate pooled risk ratio or standardized mean difference. EVIDENCE SYNTHESIS: Eleven studies of 2356 patients met the inclusion criteria. The results showed that remimazolam was associated with a higher procedure success rate (RR: 1.28, 95% CI: 1.07 to 1.52, P=0.006; I2=99%), a shorter duration of recovery after procedure (SMD: -0.56, 95% CI: -0.98, -0.14, P=0.009; I2=89%), and an earlier patient discharge after procedure (SMD: -0.37, 95% CI: -0.49, -0.25, P<0.00001; I2=0%) in comparison with traditional sedatives. There were no statistically significant differences in onset time, procedure time, and cognitive recovery between remimazolam and traditional sedatives groups. Remimazolam significantly decreased the rate of bradycardia (RR: 0.65, 95% CI: 0.43, 0.97, P=0.04; I2=0%), hypotension (RR: 0.57, 95% CI: 0.40, 0.80, P=0.001; I2=80%), and respiratory depression/hypoxia (RR: 0.46, 95% CI: 0.25, 0.83, P=0.01; I2=61%) compared to traditional sedatives. CONCLUSIONS: Remimazolam is a safe and effective sedative for procedural sedation on account of a higher success procedure rate, a faster recovery, a shorter discharge time, and a superior safety profile in comparison with traditional sedatives. Larger sample-sized and well-designed clinical trials are needed to verify our finding.

Subacute liver and respiratory failure after segmental hepatectomy for complicated hepatolithiasis with secondary biliary cirrhosis: A case report.

BACKGROUND: Despite being a benign disease, hepatolithiasis has a poor prognosis because of its intractable nature and frequent recurrence. Nonsurgical treatment is associated with high incidences of residual and recurrent stones. Consequently, surgery via hepatic lobectomy or segmental hepatectomy has become the main treatment modality. Clinical management and resolution of complicated hepatolithiasis with bilateral or diffuse intrahepatic stones remain very difficult and challenging. Repeated cholangitis and calculous obstruction may result in secondary biliary cirrhosis, a limiting factor in the treatment of hepatolithiasis. CASE SUMMARY: A 53-year-old woman with a 5-year history of intermittent abdominal pain and fever was admitted to the hepatopancreatobiliary surgery department following worsening symptoms over a 3-d period. Blood tests revealed elevated transaminases, alkaline phosphatase, γ-glutamyl transpeptidase, and total bilirubin, as well as anemia. Magnetic resonance cholangiopancreatography showed dilatation of the intrahepatic, left and right hepatic, common hepatic, and common bile ducts, and multiple short T2 signals in the intrahepatic and common bile ducts. Abdominal computed tomography showed splenomegaly and splenic varices. The diagnosis was bilateral hepatolithiasis and choledocholithiasis with cholangitis. Surgical treatment included hepatectomy of segments II and III, cholangioplasty, left hepaticolithotomy, second biliary duct exploration, choledocholithotomy, T-tube drainage, and accretion lysis. Surgical and pathological findings confirmed secondary biliary cirrhosis. Liver-protective therapy and anti-infectives were administered. The patient developed liver and respiratory failure, severe abdominal infection, and septicemia. Eventually, her family elected to discontinue treatment. CONCLUSION: Liver transplantation, rather than hepatectomy, might be a treatment option for complicated bilateral hepatolithiasis with secondary liver cirrhosis.

(-)-Epicatechin Reduces Neuroinflammation, Protects Mitochondria Function, and Prevents Cognitive Impairment in Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy is a common neurological complication of sepsis. Despite advances in pathological and diagnostic investigations, its treatment remains a major challenge. In sepsis-associated encephalopathy, neuroinflammatory overactivation and mitochondrial damage are thought to contribute to cognitive and behavioral impairments. In this study, we found that administration of (-)-Epicatechin, a dietary flavonoid of the flavan-3-ol subgroup, improves memory deficits and behavior performance by ameliorating neuroinflammation, regulating mitochondria function, enhancing synaptic plasticity, and reducing neuronal loss in a mouse model of lipopolysaccharide-induced sepsis. We further show that the AMPK signaling pathway might be among the mechanisms involved in the beneficial memory effects. Our data demonstrated the potential of (-)-Epicatechin as a new drug candidate for the treatment of sepsis-associated cognitive impairment by targeting AMPK.