Successful ABO-Incompatible Living Donor Liver Transplantation in a Patient with an Anaphylactic Reaction to Fresh Frozen Plasma During Therapeutic Plasma Exchange: A Case Report.

BACKGROUND: ABO-incompatible living donor liver transplantation (ABOi LDLT) is a complex procedure involving the reduction of anti-A and anti-B antibodies by therapeutic plasma exchange (TPE) to prevent acute antibody-mediated rejection. Fresh frozen plasma (FFP) is often used as replacement fluid during TPE. CASE DESCRIPTION: We report an ABOi LDLT case in which the patient experienced an anaphylactic reaction to FFP during TPE. Additional TPE was performed using 5% albumin as replacement fluid. ABOi LDLT was successfully performed by adapting the transfusion strategy to avoid FFP and cryoprecipitate and to administer washed platelets. CONCLUSION: This case highlights the importance of careful preoperative assessment, multidisciplinary coordination, and individualized approaches in ABOi LDLT, especially when the patient has an anaphylactic reaction to FFP.

IL-4/IL-4 Ab complex enhances the accumulation of both antigen-specific and bystander CD8 T cells in mouse lungs infected with influenza A virus.

BACKGROUND: Unlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population. In this study, we investigated whether exogenous IL-4 could enhance the immune response to a viral infection. RESULTS: In vivo administration of IL-4 and an anti-IL-4 antibody complex (IL-4C) increased CXCR3 expression in both memory and naïve phenotype CD8 T cells in the absence of antigenic stimulation, and protected mice from lethal influenza infection. Flow cytometric analysis of lung-infiltrating immune cells on day 5 after virus infection revealed higher numbers of antigen-specific and bystander CD8 T cells in IL-4C-treated mice than in control mice. In particular, the bystander CD8 T cells were a naïve or evident memory phenotypes. Crucially, an anti-CXCR3 blocking antibody abrogated this IL-4C effect, reflecting that the increased accumulation of CD8 T cells in the lungs after IL-4C treatment is dependent on CXCR3. CONCLUSIONS: These data demonstrate that exogenous IL-4C plays a protective role by enhancing CXCR3-dependent migration of CD8 T cells into influenza-infected lungs.

Prevention of severe lung immunopathology associated with influenza infection through adeno-associated virus vector administration.

BACKGROUND: Influenza A viruses (IAVs) have long posed a threat to humans, occasionally causing significant morbidity and mortality. The initial immune response is triggered by infected epithelial cells, alveolar macrophages and dendritic cells. However, an exaggerated innate immune response can result in severe lung injury and even host mortality. One notable pathology observed in hosts succumbing to severe influenza is the excessive influx of neutrophils and monocytes into the lung. In this study, we investigated a strategy for controlling lung immunopathology following severe influenza infection. RESULTS: To evaluate the impact of innate immunity on influenza-associated lung injury, we employed CB17.SCID and NOD.SCID mice. NOD.SCID mice exhibited slower weight loss and longer survival than CB17.SCID mice following influenza infection. Lung inflammation was reduced in NOD.SCID mice compared to CB17.SCID mice. Bulk RNA sequencing analysis of lung tissue showed significant downregulation of 827 genes, and differentially expressed gene analysis indicated that the cytokine-cytokine receptor interaction pathway was predominantly downregulated in NOD.SCID mice. Interestingly, the expression of the Cxcl14 gene was higher in the lungs of influenza-infected NOD.SCID mice than in CB17.SCID mice. Therefore, we induced overexpression of the Cxcl14 gene in the lung using the adeno-associated virus 9 (AAV9)-vector system for target gene delivery. However, when we administered the AAV9 vector carrying the Cxcl14 gene or a control AAV9 vector to BALB/c mice from both groups, the morbidity and mortality rates remained similar. Both groups exhibited lower morbidity and mortality than the naive group that did not receive the AAV9 vector prior to IAV infection, suggesting that the pre-administration of the AAV9 vector conferred protection against lethal influenza infection, irrespective of Cxcl14 overexpression. Furthermore, we found that pre-inoculation of BALB/c mice with AAV9 attenuated the infiltration of trans-macrophages, neutrophils and monocytes in the lungs following IAV infection. Although there was no difference in lung viral titers between the naive group and the AAV9 pre-inoculated group, pre-inoculation with AAV9 conferred lung injury protection against lethal influenza infection in mice. CONCLUSIONS: Our study demonstrated that pre-inoculation with AAV9 prior to IAV infection protected mouse lungs from immunopathology by reducing the recruitment of inflammatory cells.

Comparison of propofol vs. remimazolam on emergence profiles after general anesthesia: A randomized clinical trial.

STUDY OBJECTIVE: The emergence profiles in patients undergoing total intravenous anesthesia with either propofol or remimazolam with flumazenil reversal were compared. DESIGN: A prospective, double-blind, randomized trial. SETTING: An operating room and a post-anesthesia care unit (PACU). PATIENTS: Adult patients (n = 100) having American Society of Anesthesiologists (ASA) physical status of I-III undergoing general anesthesia were enrolled and randomly assigned to the propofol or the remimazolam group. INTERVENTIONS: The propofol group received target-controlled infusion of propofol, and the remimazolam group received continuous infusion of remimazolam. Continuous infusion of remifentanil was used in both groups. For emergence, flumazenil was used in increments of 0.2 mg in the remimazolam group. MEASUREMENTS: The primary outcome was the time required for the patient to obey verbal commands. The secondary outcomes included the time to bispectral index (BIS) over 80, the time to laryngeal mask airway (LMA) removal, the Richmond Agitation-Sedation Scale (RASS) scores in the PACU, and adverse events throughout the study period. MAIN RESULTS: The time taken to obey verbal commands was significantly longer in the propofol group than the remimazolam group (14 [9, 19]) vs. 5 [3, 7]) minutes, P < 0.001; median difference -9, 95% confidence interval -11 to -6). The times to BIS over 80 and to LMA removal were also significantly longer in the propofol group. In addition, the RASS score upon arrival to the PACU differed significantly between the two groups (P = 0.006). Re-sedation in the PACU was observed in 11 (22%) of the patients in the remimazolam group. CONCLUSIONS: Remimazolam-based total intravenous anesthesia with flumazenil reversal may be effective in reducing emergence time, but a significant incidence of re-sedation was observed in the PACU. Further studies are needed to determine adequate dose and timing of routine flumazenil use and minimize the risk of re-sedation.

Forced-air prewarming prevents hypothermia during living donor liver transplantation: a randomized controlled trial.

Despite various intraoperative thermal strategies, core heat loss is considerable during liver transplantation and hypothermia is common. We tested whether forced-air prewarming prevents hypothermia during liver transplantation. Adult patients undergoing living donor liver transplantation were randomly assigned to non-prewarming group (n = 20) or prewarming group (n = 20). Patients in prewarming group underwent 30-min forced-air warming before anesthetic induction. During surgery, core temperature was measured in the pulmonary artery. The primary outcome was intraoperative hypothermia (< 36.0 °C). The secondary outcomes included plasma lactate concentration. Intraoperative hypothermia risk was significantly lower in prewarming group than in non-prewarming group (60.0% vs. 95.0%, P = 0.020). The difference in hypothermia incidence between groups was greater in the post-induction phase (20.0% vs. 85.0%, P < 0.001) than in the anhepatic or post-reperfusion phase, suggesting that prewarming mainly acts on preventing post-induction core-to-peripheral heat redistribution. Hypothermia duration was significantly shorter in prewarming group (60 [0-221] min vs. 383 [108-426] min, P = 0.001). Lactate concentration decreased during 3 h after graft reperfusion in prewarming group, whereas it continuously increased in non-prewarming group (- 0.19 [- 0.48 to 0.13] mmol/L vs. 1.17 [3.31-0.77] mmol/L, P = 0.034). In conclusion, forced-air prewarming decreases the incidence and duration of intraoperative hypothermia with potential clinical benefit while mainly acting by preventing the core-to-peripheral heat redistribution.Clinical trial registration: Registered at the Clinical Research Information Service ( https://cris.nih.go.kr , [KCT0003230]) on 01/10/2018.

Evaluation of pre-induction dynamic arterial elastance as an adjustable predictor of post-induction hypotension: A prospective observational study.

STUDY OBJECTIVE: Dynamic arterial elastance (Eadyn) has been suggested as a functional measure of arterial load. We aimed to evaluate whether pre-induction Eadyn can predict post-induction hypotension. DESIGN: Prospective observational study. PATIENTS: Adult patients undergoing general anesthesia with invasive and non-invasive arterial pressure monitoring systems. MEASUREMENTS: We collected invasive and non-invasive Eadyns (n = 38 in each), respectively. In both invasive and non-invasive Eadyns, pre-induction Eadyns were obtained during one-minute tidal and deep breathing in each patient before anesthetic induction. Post-induction hypotension was defined as a decrease of >30% in mean blood pressure from the baseline value or any absolute mean blood pressure value of <65 mmHg for 10 min after anesthetic induction. The predictabilities of Eadyns for the development of post-induction hypotension were tested using receiver-operating characteristic curve analysis. MAIN RESULTS: Invasive Eadyn during deep breathing showed significant predictability with an area under the curve (AUC) of 0.78 (95% Confidence interval [CI], 0.61-0.90, P = 0.001). But non-invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.49-0.81, P = 0.096) and deep breathing (AUC = 0.53, 95% CI, 0.36-0.70, P = 0.75), and invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.41-0.74, P = 0.095) failed to predict post-induction hypotension. CONCLUSION: In our study, invasive pre-induction Eadyn during deep breathing -could predict post-induction hypotension. Despite its invasiveness, future studies will be needed to evaluate the usefulness of Eadyn as a predictor of post-induction hypotension because it is an adjustable parameter.

Intraoperative Factors Modifying the Risk of Postoperative Pulmonary Complications After Living Donor Liver Transplantation.

BACKGROUND: The relationship between intraoperative anesthetic management and postoperative pulmonary complications (PPCs) after liver transplantation is not fully understood. We aimed to determine the intraoperative contributors to PPC. METHODS: The retrospectively collected cohort included 605 patients who underwent living donor liver transplantation. PPCs comprised respiratory failure, respiratory infection, pulmonary edema, atelectasis (at least moderate degree), pneumothorax, and pleural effusion (at least moderate degree). The presence and type of PPC were evaluated by 2 pulmonary physicians. Logistic regression analysis was performed to determine the association between perioperative variables and PPC risk. RESULTS: Of the 605 patients, 318 patients (52.6%) developed 486 PPCs. Multivariable analysis demonstrated that PPC risk decreased with low tidal volume ventilation (odds ratio [OR] 0.62 [0.41-0.94], P = 0.023) and increased with greater driving pressure at the end of surgery (OR 1.08 [1.01-1.14], P = 0.018), prolonged hypotension (OR 1.85 [1.27-2.70], P = 0.001), and blood albumin level ≤3.0 g/dL at the end of surgery (OR 2.43 [1.51-3.92], P < 0.001). Survival probability at 3, 6, and 12 mo after transplantation was 91.2%, 89.6%, and 86.5%, respectively, in patients with PPCs and 98.3%, 96.5%, and 93.4%, respectively, in patients without PPCs (hazard ratio 2.2 [1.3-3.6], P = 0.004). Graft survival probability at 3, 6, and 12 mo after transplantation was 89.3%, 87.1%, and 84.3%, respectively, in patients with PPCs and 97.6%, 95.8%, and 92.7%, respectively, in patients without PPCs (hazard ratio 2.3 [1.4-3.7], P = 0.001). CONCLUSIONS: We found that tidal volume, driving pressure, hypotension, and albumin level during living donor liver transplantation were significantly associated with PPC risk. These data may help determine patients at risk of PPC or develop an intraoperative lung-protective strategy for liver transplant recipients.

The impact of driving pressure on postoperative pulmonary complication in patients with different respiratory spirometry.

Risk factors for postoperative pulmonary complication (PPC) have not been determined according to preoperative respiratory spirometry. Thus, we aimed to find contributors for PPC in patients with restrictive or normal spirometric pattern. We analyzed 654 patients (379 with normal and 275 with restrictive spirometric pattern). PPCs comprised respiratory failure, pleural effusion, atelectasis, respiratory infection, and bronchospasm. We analyzed the association between perioperative factors and PPC using binary logistic regression. In particular, we conducted subgroup analysis on the patients stratified according to preoperative spirometry. Of 654 patients, 27/379 patients (7.1%) with normal spirometric pattern and 33/275 patients (12.0%) with restrictive spirometric pattern developed PPCs. Multivariable analysis demonstrated that high driving pressure was the only intraoperative modifiable factor increasing PPC risk (OR = 1.13 [1.02-1.25], p = 0.025). In the subgroup of patients with restrictive spirometric pattern, intraoperative driving pressure was significantly associated with PPC (OR = 1.21 [1.05-1.39], p = 0.009), whereas driving pressure was not associated with PPC in patients with normal spirometric pattern (OR = 1.04 [0.89-1.21], p = 0.639). In patients with restrictive spirometric pattern, greater intraoperative driving pressure is significantly associated with increased PPC risk. In contrast, intraoperative driving pressure is not associated with PPC in patients with normal spirometric pattern.

Simultaneous determination of plant growth regulator and pesticides in bean sprouts by liquid chromatography-tandem mass spectrometry.

A simple and sensitive analytical method based on QuEChERS approach using liquid chromatography tandem mass spectrometry was developed and validated for the determination of 6-benzylaminopurine, carbendazim and thiabendazole in bean sprouts. Sodium chloride and sodium acetate were used for salting-out step and magnesium sulfate for clean-up. The validation of optimized method was satisfactory with recoveries, between 89.5% and 103.2% for the three compounds, and relative standard deviation (RSD) values less than 3.3% at 20 and 40ng/g fortification levels (n=5). Limit of detection (LOD) and limit of quantification (LOQ) was 2.1-3.7ng/g and 6.3-11.1ng/g, respectively. Monitoring of 126 bean sprout samples collected from local markets was performed to verify the adaptability in real samples. No pesticides were detected but 6-benzylaminopurine was found in 3 samples at the level of 15-20ng/g. The optimized method should be applicable for monitoring of 6-benzylaminopurine, carbendazim and thiabendazole in bean sprouts in short time.

Pesticide residues in leafy vegetables, stalk and stem vegetables from South Korea: a long-term study on safety and health risk assessment.

South Korea has a unique food culture. South Koreans enjoy wrapping meat and eating or making kimchi (traditionally fermented Korean food) and eating using raw leafy vegetables, stalk and stem vegetables. Therefore, there is a high chance of being exposed to pesticide residues of vegetables. The objective of this study was to investigate pesticide residues in leafy vegetables, stalk and stem vegetables from South Korea. A total of 8496 samples were mainly collected from Gwangju and Jeonnam area (the largest production region of leafy vegetables, stalk and stem vegetables) in South Korea from 2010 to 2014. A total of 230 pesticides were used for multi-residue analysis of pesticides. Among 8496 samples, 61 different pesticides (1029 times) were detected in 890 samples, of which 118 samples (1.4%) exceeded the Korea maximum residue limits (MRLs). Samples exceeding the MRLs were mostly found in leafy vegetables (brassica lee ssp. namai, leafy lettuce, spinach, perilla leaves, crown daisy, marsh mallow, aster scaber, pimpinella brachycarpa) and Chinese chive. Procymidone, dimethomorph and azoxystrobin were the most frequently found pesticides. A risk assessment of pesticides exceeding the MRLs was evaluated by calculating the estimated daily intake (EDI) and the acceptable daily intake (ADI). The ratio of EDI to ADI was 0.003-30.4%.

Immunohistochemical and quantitative competitive PCR analyses of midkine and pleiotrophin expression in cervical cancer.

OBJECTIVE: The aim of this study was to determine midkine (MK) and pleiotrophin (PTN) expression in cervical cancer. METHODS: Prospective study in tertiary teaching hospital. Normal and cancerous cervical tissues were obtained from healthy women (n = 19) and from patients with cervical cancer (n = 42). The expressions of MK and PTN mRNA and protein were examined by quantitative competitive PCR and by immunohistochemistry. MK and PTN mRNA and protein expressions were examined with respect to tumor stage and size. RESULTS: The expressions of midkine and pleiotrophin mRNA in cervical cancer were higher than those in the normal cervix (MK, 175.59 +/- 63.3 vs 1.00 +/- 0.18 fmol, respectively; PTN, 3.18 +/- 1.25 vs. 0.86 +/- 0.12 fmol, respectively, P < 0.05), and their expressions were not correlated with cervical cancer stage or size of the tumor. The expressions of MK and PTN protein in cancerous tissue were higher than those in the normal cervix (P < 0.05). Moreover, the protein expression of MK, but not of PTN, correlated with tumor stage and size. The expressions of MK and PTN were not correlated with vascular density. CONCLUSIONS: Our results suggest that increased midkine mRNA and protein expressions are associated with the carcinogenesis of cervical cancer.