Association between intraoperative tidal volume and postoperative acute kidney injury in non-cardiac surgical patients using a propensity score-weighted analysis.

Acute kidney injury (AKI) is related to adverse clinical outcomes. Therefore, identifying patients at increased risk of postoperative AKI and proactively providing appropriate care is crucial. However, only a limited number of modifiable risk factors have been recognized to mitigate AKI risk. We retrospectively analyzed adult patients who underwent endotracheal intubation and mechanical ventilation of more than 2 h during non-cardiac surgery at Seoul National University Hospital from January 2011 to November 2022. Patients were grouped into low- or high-tidal volume groups based on their intraoperative tidal volume relative to their predicted body weight (PBW) of 8 ml/kg. The association between intraoperative tidal volume and postoperative AKI was evaluated using inverse probability of treatment weighting (IPTW), adjusting for various preoperative confounders. Among the 37,726 patients included, the incidence of postoperative AKI was 4.1%. The odds of postoperative AKI risk were significantly higher in the high-tidal volume group than in the low-tidal volume group before and after IPTW (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08-1.32, P = 0.001 and OR: 1.10, 95% CI 1.02-1.19, P = 0.010, respectively). In the multivariable logistic regression analysis after IPTW, a high tidal volume was independently associated with an increased risk of postoperative AKI (OR: 1.21, 95% CI 1.12-1.30, P < 0.001). In this propensity score-weighted analysis, an intraoperative high tidal volume of more than 8 ml/kg PBW was significantly associated with an increased risk of postoperative AKI after IPTW in non-cardiac surgical patients. Intraoperative tidal volume showed potential as a modifiable risk factor for preventing postoperative AKI.

Primary surgery versus pharmacotherapy for newly diagnosed ileocecal Crohn's disease: a hospital-based cohort study.

Background/Aims: Limited knowledge exists regarding the optimal timing and relative advantages of primary surgery compared to medical treatment in ileocecal Crohn's disease (CD). This study aimed to compare long-term outcomes between medication-based treatment versus surgery in newly diagnosed ileocecal CD patients in an Asian population. Methods: Among the 885 patients diagnosed with CD and enrolled in the study site hospital cohort between 1980 and 2013, 93 (10.5%) had ileocecal CD. Patients were categorized into either the surgical or medical remission group based on their initial management strategy that led to remission. The rates of relapse, hospitalization, and surgery after achieving remission were compared using Kaplan-Meier curves. Results: The numbers of patients assigned to surgical and medical remission groups were 15 (17.0%) and 73 (83.0%), respectively. The surgical remission group exhibited a lower relapse rate and longer maintenance of remission (10.7 vs. 3.7 yr; p = 0.017) during a median follow-up of 6.6 years. Hospitalization after the first remission tended to be lower in the surgical remission group (p = 0.054). No cases required repeated intestinal resection after the initial surgical remission, whereas a 23% surgery rate was reported at 5 years after initial medical treatment (p = 0.037). In the multivariable analysis, the initial medication-based treatment was significantly associated with relapse (hazard ratio = 3.23, p = 0.039). Conclusions: In selected cases of localized ileocecal CD, ileocolic resection might be a favorable alternative to medication- based treatment, as it demonstrates a lower relapse rate and longer maintenance of remission.

The impact of preoperative coronavirus disease 19 infection on early postoperative mortality during the vaccination era: a nationwide retrospective cohort study.

BACKGROUND: We aimed to investigate the optimal surgical timing in patients with preoperative coronavirus disease 2019 (COVID-19) infection to minimize postoperative morbidity and mortality during the COVID-19 vaccination era. METHODS: The Korean nationwide data on patients who underwent standard surgery under general anesthesia in 2021 were analyzed. Patients were categorized based on the time from COVID-19 diagnosis to surgery: 0-4, 5-8, > 8 weeks, and those without preoperative COVID-19 infection. Multivariable logistic regression analysis, considering preoperative COVID-19 vaccination status (fully vaccinated vs. unvaccinated or partially vaccinated), was performed to associate the preoperative COVID-19 infection timing with 30- and 90-day postoperative mortality and 30-day respiratory complications. RESULTS: Among the 750,175 included patients, 28.2% were preoperatively fully vaccinated. Compared with patients without prior COVID-19 infection, those who had surgery 0-4 weeks (adjusted odds ratio [OR]: 4.28, 95% CI [1.81, 10.13], P = 0.001) and 5-8 weeks (adjusted OR: 3.38, 95% CI [1.54, 7.44], P = 0.002) after COVID-19 infection had a significantly increased risk of 30-day mortality. Preoperative full vaccination was significantly associated with a decrease in 90-day mortality (adjusted OR: 0.93, 95% CI [0.89, 0.98], P = 0.007) and 30-day respiratory complications (adjusted OR: 0.85, 95% CI [0.82, 0.87], P < 0.001), but not with 30-day mortality (P = 0.916). CONCLUSIONS: COVID-19 infection eight weeks preoperatively was associated with an increased 30-day postoperative mortality. Preoperative full vaccination was not associated with 30-day mortality but was related to lower risk of 90-day mortality and 30-day respiratory complications.

Randomized controlled trial of the effect of general anesthetics on postoperative recovery after minimally invasive nephrectomy.

BACKGROUND: General anesthetic techniques can affect postoperative recovery. We compared the effect of propofol-based total intravenous anesthesia (TIVA) and desflurane anesthesia on postoperative recovery. METHODS: In this randomized trial, 150 patients undergoing robot-assisted or laparoscopic nephrectomy for renal cancer were randomly allocated to either the TIVA or desflurane anesthesia (DES) group. Postoperative recovery was evaluated using the Korean version of the Quality of Recovery-15 questionnaire (QoR-15K) at 24 h, 48 h, and 72 h postoperatively. A generalized estimating equation (GEE) was performed to analyze longitudinal QoR-15K data. Fentanyl consumption, pain severity, postoperative nausea and vomiting, and quality of life three weeks after discharge were also compared. RESULTS: Data were analyzed for 70 patients in each group. The TIVA group showed significantly higher QoR-15K scores at 24 and 48 h postoperatively (24 h: DES, 96 [77, 109] vs. TIVA, 104 [82, 117], median difference 8 [95% CI: 1, 15], P = 0.029; 48 h: 110 [95, 128] vs. 125 [109, 130], median difference 8 [95% CI: 1, 15], P = 0.022), however not at 72 h (P = 0.400). The GEE revealed significant effects of group (adjusted mean difference 6.2, 95% CI: 0.39, 12.1, P = 0.037) and time (P < 0.001) on postoperative QoR-15K scores without group-time interaction (P = 0.051). However, there were no significant differences in other outcomes, except for fentanyl consumption, within the first 24 h postoperatively. CONCLUSIONS: Propofol-based TIVA showed only a transient improvement in postoperative recovery than desflurane anesthesia, without significant differences in other outcomes.

IDF-11774 Induces Cell Cycle Arrest and Apoptosis by Inhibiting HIF-1α in Gastric Cancer.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a regulatory factor of intracellular oxygen supersession. The expression or increased activity of HIF-1α is closely related to various human cancers. Previously, IDF-11774 was demonstrated to inhibit HSP70 chaperone activity and suppress the accumulation of HIF-1α. In this study, we aimed to determine the effects of IDF-11774 on gastric cancer cell lines. Treatment with IDF-11774 was found to markedly decrease the proliferation, migration, and invasion of the gastric cancer cell lines. Furthermore, the phosphorylation levels of extracellular signal-regulated kinase 1/2, p38, and Jun N-terminal kinase in the mitogen-activated protein kinase signaling pathways were markedly increased in a dose-dependent manner, ultimately promoting apoptosis via the induction of cell cycle arrest. Our findings indicate that HIF-1α inhibitors are potent drugs for the treatment of gastric cancer.

Pulmonary artery catheter monitoring versus arterial waveform-based monitoring during liver transplantation: a retrospective cohort study.

Although pulmonary artery catheter (PAC) has been used during liver transplantation surgery, the usefulness of PAC has rarely been investigated. We evaluated whether the use of PAC is associated with better clinical outcomes compared to arterial waveform-based monitoring after liver transplantation. A total of 1565 cases undergoing liver transplantation were reviewed. We determined whether patients received PAC or not and divided our cohort into the PAC with hemodynamic monitoring using PAC and the non-PAC with arterial waveform-based monitoring using FloTrac-Vigileo. Propensity score matching was performed. Acute kidney injury (AKI), early allograft dysfunction (EAD) and 1-year all-cause mortality or graft failure were compared in the matched cohorts. Logistic regression analysis was performed in the inverse probability of treatment-weighted (IPTW) cohort for postoperative EAD and AKI, respectively. Five-year overall survival was compared between the two groups. In the matched cohort, there was no significant difference in the incidence of AKI, EAD, length of hospital or ICU stay, and 1-year all-cause mortality between the groups. In the IPTW cohort, the use of PAC was not a significant predictor for AKI or EAD (AKI: odds ratio (95% confidence interval) of 1.20 (0.47-1.56), p = 0.229; EAD: 0.99 (0.38-1.14), p = 0.323). There was no significant difference in the survival between groups after propensity score matching (Log-rank test p = 0.578). In conclusion, posttransplant clinical outcomes were not significantly different between the groups with and without PAC. Anesthetic management without the use of PAC may be possible in low-risk patients during liver transplantation. The risk should be carefully assessed by considering MELD scores, ischemic time, surgical history, previous treatment of underlying liver disease, and degree of portal and pulmonary hypertension.Registration: https://clinicaltrials.gov/ct2/show/NCT05457114 (registration date: July 15, 2022).

Effect of driving pressure-guided positive end-expiratory pressure on postoperative pulmonary complications in patients undergoing laparoscopic or robotic surgery: a randomised controlled trial.

BACKGROUND: Individualised positive end-expiratory pressure (PEEP) improves respiratory mechanics. However, whether PEEP reduces postoperative pulmonary complications (PPCs) remains unclear. We investigated whether driving pressure-guided PEEP reduces PPCs after laparoscopic/robotic abdominal surgery. METHODS: This single-centre, randomised controlled trial enrolled patients at risk for PPCs undergoing laparoscopic or robotic lower abdominal surgery. The individualised group received driving pressure-guided PEEP, whereas the comparator group received 5 cm H2O fixed PEEP during surgery. Both groups received a tidal volume of 8 ml kg-1 ideal body weight. The primary outcome analysed per protocol was a composite of pulmonary complications (defined by pre-specified clinical and radiological criteria) within 7 postoperative days after surgery. RESULTS: Some 384 patients (median age: 67 yr [inter-quartile range: 61-73]; 66 [18%] female) were randomised. Mean (standard deviation) PEEP in patients randomised to individualised PEEP (n=178) was 13.6 cm H2O (2.1). Individualised PEEP resulted in lower mean driving pressures (14.7 cm H2O [2.6]), compared with 185 patients randomised to standard PEEP (18.4 cm H2O [3.2]; mean difference: -3.7 cm H2O [95% confidence interval (CI): -4.3 to -3.1 cm H2O]; P<0.001). There was no difference in the incidence of pulmonary complications between individualised (25/178 [14.0%]) vs standard PEEP (36/185 [19.5%]; risk ratio [95% CI], 0.72 [0.45-1.15]; P=0.215). Pulmonary complications as a result of desaturation were less frequent in patients randomised to individualised PEEP (8/178 [4.5%], compared with standard PEEP (30/185 [16.2%], risk ratio [95% CI], 0.28 [0.13-0.59]; P=0.001). CONCLUSIONS: Driving pressure-guided PEEP did not decrease the incidence of pulmonary complications within 7 days of laparoscopic or robotic lower abdominal surgery, although uncertainty remains given the lower than anticipated event rate for the primary outcome. CLINICAL TRIAL REGISTRATION: KCT0004888 (http://cris.nih.go.kr, registration date: April 6, 2020).

Nitrosylation of ß2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice.

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of ß2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-ß2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-ß2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION: This is the first discovery of a new target molecule of NO, ß2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-ß2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

The effect of high perioperative inspiratory oxygen fraction for abdominal surgery on surgical site infection: a systematic review and meta-analysis.

Guidelines from the World Health Organization strongly recommend the use of a high fraction of inspired oxygen (FiO2) in adult patients undergoing general anesthesia to reduce surgical site infection (SSI). However, previous meta-analyses reported inconsistent results. We aimed to address this controversy by focusing specifically on abdominal surgery with relatively high risk of SSI. Medline, EMBASE, and Cochrane CENTRAL databases were searched. Randomized trials of abdominal surgery comparing high to low perioperative FiO2 were included, given that the incidence of SSI was reported as an outcome. Meta-analyses of risk ratios (RR) were performed using a fixed effects model. Subgroup analysis and meta-regression were employed to explore sources of heterogeneity. We included 27 trials involving 15977 patients. The use of high FiO2 significantly reduced the incidence of SSI (n = 27, risk ratio (RR): 0.87; 95% confidence interval (CI): 0.79, 0.95; I2 = 49%, Z = 3.05). Trial sequential analysis (TSA) revealed that z-curve crossed the trial sequential boundary and data are sufficient. This finding held true for the subgroup of emergency operations (n = 2, RR: 0.54; 95% CI: 0.35, 0.84; I2 = 0%, Z = 2.75), procedures using air as carrier gas (n = 9, RR: 0.79; 95% CI: 0.69, 0.91; I2 = 60%, Z = 3.26), and when a high level of FiO2 was maintained for a postoperative 6 h or more (n = 9, RR: 0.68; 95% CI: 0.56, 0.83; I2 = 46%, Z = 3.83). Meta-regression revealed no significant interaction between SSI with any covariates including age, sex, body-mass index, diabetes mellitus, duration of surgery, and smoking. Quality of evidence was assessed to be moderate to very low. Our pooled analysis revealed that the application of high FiO2 reduced the incidence of SSI after abdominal operations. Although TSA demonstrated sufficient data and cumulative analysis crossed the TSA boundary, our results should be interpreted cautiously given the low quality of evidence.Registration: https://www.crd.york.ac.uk/prospero (CRD42022369212) on October 2022.

Characteristics and Treatment Outcomes of Transition among Patients with Inflammatory Bowel Disease.

PURPOSE: This study aimed to assess disease characteristics and outcomes of transition in patient care among adolescent patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: Data from patients younger than 18 years who were diagnosed with IBD (Crohn's disease, ulcerative colitis, or intestinal Behçet's disease) were investigated. We categorized the patients into two groups: transition IBD group (Group A, diagnosed in pediatric care followed by transfer to/attendance in adult IBD care) and non-transition group (Group B, diagnosed and followed up in pediatric care or adult IBD care without transfer). RESULTS: Data from a total of 242 patients [Group A (n=29, 12.0%), Group B (n=213, 88.0%)] were analyzed. A significantly higher number of patients was diagnosed at an earlier age in Group A than in Group B (p<0.001). Group A patients had more severe disease in terms of number of disease flare ups (p=0.011) and frequency of bowel-related complications (p<0.001). Multiple linear regression analysis showed that Group B patients had more medical non-compliance than Group A patients (ß=2.31, p=0.018). After transition, IBD-related admission frequency, emergency admission frequency, disease flare frequency, and medical non-compliance were significantly improved. CONCLUSION: The transition IBD group had more severe disease. Medical non-compliance was lower in the transition IBD group. Clinical outcomes improved after transition.

Neuromuscular blocking agent re-exposure in a retrospective cohort with neuromuscular blocking agent-associated anaphylaxis.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are one of the most common causes of perioperative anaphylaxis. Although skin test positivity may help identify reactive NMBAs, it is unclear whether skin test negativity can guarantee the safety of systemically administered NMBAs. OBJECTIVE: This study aimed to evaluate the real-world safety of alternative NMBAs screened using skin tests in patients with suspected NMBA-induced anaphylaxis. METHODS: A retrospective cohort of suspected NMBA-induced anaphylaxis were recruited among patients at Seoul National University Hospital from June 2009 to May 2021, and their characteristics and outcomes were assessed. RESULTS: A total of 47 cases (0.017%) of suspected anaphylaxis occurred in 282,707 patients who received NMBAs. Cardiovascular manifestations were observed in 95.7%, whereas cutaneous findings were observed in 59.6%. Whereas 83% had a history of undergoing general anesthesia, 17% had no history of NMBA use. In skin tests, the overall positivity to any NMBA was 94.6% (81.1% to culprit NMBAs) and the cross-reactivity was 75.7%, which is related to the chemical structural similarity among NMBAs; the cross-reactivity and chemical structure similarity of rocuronium were 85.3% and 0.814, respectively, with vecuronium; this is in contrast to 50% and 0.015 with cisatracurium and 12.5% and 0.208 with succinylcholine. There were 15 patients who underwent subsequent surgery with a skin test-negative NMBA; whereas 80.0% (12/15) safely completed surgery, 20.0% (3/15) experienced hypotension. CONCLUSION: Similarities in chemical structure may contribute to the cross-reactivity of NMBAs in skin tests. Despite the high negative predictability of skin tests for suspected NMBA-induced anaphylaxis, the potential risk of recurrent anaphylaxis has not been eliminated.

Impact of Enhanced in-Hospital Infection Prevention During the COVID-19 Pandemic on Postoperative Pneumonia in Older Surgical Patients.

Purpose: We aimed to investigate the impact of enhanced in-hospital infection prevention during the coronavirus disease 2019 (COVID-19) pandemic on postoperative pneumonia in older surgical patients. Patients and Methods: We retrospectively reviewed the electronic medical records of consecutive patients ≥70 years who underwent elective surgery between 2017 and 2021 at our institution. All perioperative variables were retrieved from the electronic medical records. The primary outcome was new-onset postoperative pneumonia during the hospitalization period. Since February 2020, our institution implemented a series of policies to enhance infection prevention, hence patients were divided into groups according to whether they underwent surgery before or during the COVID-19 pandemic. An interrupted time series analysis was performed to evaluate the difference between pre- and post-intervention slopes of the primary outcome. Results: Among the 29,387 patients included in the study, 10,547 patients underwent surgery during the COVID-19 pandemic. Although there was a decreasing trend of the monthly incidence rate of postoperative pneumonia compared to before the COVID-19 pandemic, there was no statistical significance in the trend (slope before COVID-19 period: ß-coefficient, -0.007; 95% CI, -0.022 to 0.007). Conclusion: Our study revealed that enhanced in-hospital infection prevention implemented to manage the COVID-19 pandemic did not significantly affect the decreasing trend of postoperative pneumonia at our institution.

Serum neutrophil gelatinase-associated lipocalin and lactate level during surgery predict acute kidney injury and early allograft dysfunction after liver transplantation.

Early allograft dysfunction (EAD) and acute kidney injury (AKI) are common and clinically important complications after liver transplantation. Serum lactate level at the end of surgery could predict EAD and neutrophil gelatinase-associated lipocalin (NGAL) is known as a biomarker for AKI after liver transplantation. The authors investigated whether the combination of these two laboratory tests could be used as an early predictor of these two complications of EAD and AKI. We reviewed cases undergoing living donor liver transplantation (n = 353). Lactate-adjusted NGAL level, a combination of these two predictors, was calculated as the sum of each value multiplied by the odds ratio for EAD or AKI. We evaluated whether this combined predictor at the end of surgery is significantly associated with both postoperative AKI or EAD. We compared the area under the receiver operating characteristic curve (AUC) between our multivariable regression models with and without NGAL, lactate, or lactate-adjusted NGAL. NGAL, lactate and lactate-adjusted NGAL are significant predictors for EAD and AKI. The regression model for EAD or AKI including lactate-adjusted NGAL showed a greater AUC (for EAD: odds ratio [OR] 0.88, 95% confidence interval [CI] 0.84-0.91; for AKI: OR 0.89, 95% CI 0.85-0.92) compared to the AUC of the models including lactate (for EAD: OR 0.84, 95% CI 0.81-0.88; for AKI: OR 0.79, 95% CI 0.74-0.83) or NGAL alone (for EAD: OR 0.82, 95% CI 0.77-0.86; for AKI: OR 0.84, 95% CI 0.80-0.88) or the model without lactate or NGAL (for EAD: OR 0.64, 95% CI 0.58-0.69, for AKI: OR 0.75, 95% CI 0.70-0.79). In conclusion, lactate-adjusted NGAL level at the end of surgery could be a reliable combined laboratory predictor for postoperative EAD or AKI after liver transplantation with a greater discriminative ability than lactate or NGAL alone.

Postoperative NSAIDs use and the risk of anastomotic leakage after restorative resection for colorectal cancer.

BACKGROUND: Although non-steroidal anti-inflammatory drugs (NSAIDs) are useful options for multimodal opioid-sparing analgesia, their effect on anastomotic leakage (AL) after colorectal surgery remains unclear. We aimed to investigate the association between early postoperative NSAID use and AL occurrence in patients who underwent colorectal cancer surgery at a high-volume tertiary care center. METHODS: This retrospective observational study included all adult patients who underwent elective colorectal cancer resection surgery during 2011-2021 at a tertiary teaching hospital. Based on NSAID use within five postoperative days, patients were classified into either NSAID or no NSAID groups. We performed multivariable logistic regression analysis for the primary outcome, AL, within the first 30 postoperative days, before and after propensity score analysis using stabilized inverse probability of treatment weighting (sIPTW). RESULTS: Among the 7928 patients analyzed, 0.6% experienced AL after surgery. The occurrence rates of AL were 1.7% (12/714) and 0.5% (37/7214) in the NSAID and no NSAID groups, respectively. Multivariable logistic regression analysis revealed that early postoperative NSAID use was significantly associated with AL [odds ratio (OR), 3.41; 95% confidence interval (CI), 1.76-6.60; P < 0.001]. Significance was maintained after sIPTW (OR, 3.65; 95% CI, 1.86-6.72; P < 0.001). CONCLUSION: Early postoperative NSAID use was significantly associated with AL in patients undergoing colorectal cancer surgery at a high-volume tertiary care center. Further prospective studies are required to investigate NSAIDs' clinically meaningful unfavorable effects following colorectal cancer surgery.

T-cell specific antibody induction versus corticosteroid induction immunosuppression for liver transplant recipients: a meta-analysis.

Corticosteroids remain the mainstay of immunosuppression for liver transplant recipients despite several serious complications including infection, hepatitis C virus (HCV) recurrence, diabetes mellitus (DM), and hypertension. We attempted to compare the safety and efficacy of T-cell specific antibody induction with complete corticosteroid avoidance. We searched MEDLINE, EMBASE, and Cochrane central library. Randomized controlled trials comparing T-cell specific antibody induction with corticosteroid induction immunosuppression were included. Our primary outcome was the incidence of biopsy-proven acute rejection. Eleven trials involving 1683 patients were included. The incidence of acute rejection was not significantly different between the antibody and steroid induction groups (risk ratio [RR] 0.85, 95% confidence interval [CI] 0.72, 1.01, P = 0.06, I2 = 0%). However, T-cell specific antibody induction significantly reduced the risk of cytomegalovirus infection (RR 0.48, 95% CI 0.33, 0.70, P = 0.0002, I2 = 3%), HCV recurrence (RR 0.89, 95% CI 0.80, 0.99, P = 0.03, I2 = 0%), DM (RR 0.41, 95% CI 0.32, 0.54, P < 0.0001, I2 = 0%) and hypertension (RR 0.71, 95% CI 0.55, 0.90, P = 0.005, I2 = 35%). Trial sequential analysis for acute rejection showed that the cumulative z-curve did not cross the Trial sequential boundary and the required information size was not reached. T-cell specific antibody induction compared to corticosteroid induction seems to significantly reduce opportunistic infections including cytomegalovirus infection and HCV recurrence and metabolic complications including DM and hypertension. However, given the insufficient study power, low quality of evidence, and heterogeneous immunosuppressive regimens, our results should be cautiously appreciated.

Effects of sugammadex versus neostigmine on postoperative nausea and vomiting after general anesthesia in adult patients:a single-center retrospective study.

We aimed to compare the effect of sugammadex to that of neostigmine with respect to the occurrence of postoperative nausea and vomiting (PONV) during the first 24 h following general anesthesia. This retrospective cohort study included patients who underwent elective surgery under general anesthesia in 2020 at an academic medical center in Seoul, South Korea. The exposure groups were determined according to whether the patient received sugammadex or neostigmine as a reversal agent. The primary outcome was PONV occurrence during the first 24 h postoperatively (overall). The association between the type of reversal agent and primary outcome was investigated using logistic regression while adjusting for confounding variables using stabilized inverse probability of treatment weighting (sIPTW). Of the 10,912 patients included in this study, 5,918 (54.2%) received sugammadex. Sugammadex was associated with a significantly lower incidence of overall PONV (15.8% vs. 17.7%; odds ratio, 0.87; 95% confidence interval [CI], 0.79-0.97; P = 0.010) after sIPTW. In conclusion, compared with neostigmine/glycopyrrolate, sugammadex use has a lower risk of PONV during the first 24 h following general anesthesia.

Fulminant Eosinophilic Myocarditis Without Peripheral Eosinophilia.

Eosinophilic myocarditis is a rare form of myocarditis characterized by eosinophilic infiltration and usually associated with peripheral hypereosinophilia. The clinical spectrum of eosinophilic myocarditis ranges widely, from mildly symptomatic to fulminant disease. When patients have fulminant eosinophilic myocarditis, high-dose corticosteroids can lead to dramatic improvement and peripheral eosinophil counts are used as an indicator of response to treatment. However, in some patients, peripheral eosinophilia is absent at initial presentation; reaching a diagnosis and determining treatment response can be challenging in this situation. This report describes a patient with fulminant eosinophilic myocarditis who initially presented with a normal peripheral eosinophil count, was diagnosed through an early endomyocardial biopsy, and was successfully treated with corticosteroids. Endomyocardial biopsy should be performed to confirm the presence of myocardial eosinophilic infiltration, especially for patients who present with fulminant myocarditis, even when peripheral eosinophilia is absent.

Risk Factors for Surgery in Patients with Intestinal Behçet's Disease During Anti-Tumor Necrosis Factor-Alpha Therapy.

PURPOSE: Behçet's disease (BD) is a chronic inflammatory immune-mediated disease involving multiorgan systems. Gastrointestinal (GI) manifestations of BD include abdominal pain, vomiting, GI bleeding, fistula formation, obstruction, and perforation that might require surgery. Recently, anti-tumor necrosis factor-alpha (anti-TNF-α) therapy has been shown to have favorable outcomes in patients with intestinal BD who are refractory to conventional therapy. This study sought to figure out the risk factors for undergoing surgery during anti-TNF-α therapy in patients with intestinal BD. MATERIALS AND METHODS: In this retrospective analysis of intestinal BD patients who were treated with anti-TNF-α, we collected the baseline patient data including comorbidities, clinical, endoscopic, and radiologic characteristics, and the Disease Activity Index for Intestinal Behçet's Disease at the time of anti-TNF-α initiation. Each potential risk factor was compared. For multivariate analysis, Cox regression was used. RESULTS: A total of 62 patients were considered eligible for analysis, and 15 of them (24.1%) underwent surgery. In univariate analysis, the presence of extraintestinal manifestation, such as joint symptoms and erythrocyte sedimentation rate (ESR), were significantly associated with surgery during therapy. In multivariate analysis, drug response within 4 weeks [hazard ratio (HR), 64.59], skin and joint manifestation (HR, 10.23 and HR, 6.22), geographic ulcer (HR, 743.97), and ESR >42.5 mm/h (HR, 9.16) were found to be factors predictive of undergoing surgery during anti-TNF-α therapy. CONCLUSION: We found five risk factors predictive of surgery in patients with intestinal BD receiving anti-TNF-α therapy, which can guide physicians in selecting appropriate patients between anti-TNF-α therapy and early surgery.

Lipocalin-2 activates hepatic stellate cells and promotes nonalcoholic steatohepatitis in high-fat diet-fed Ob/Ob mice.

BACKGROUND AND AIMS: In obesity and type 2 diabetes mellitus, leptin promotes insulin resistance and contributes to the progression of NASH via activation of hepatic stellate cells (HSCs). However, the pathogenic mechanisms that trigger HSC activation in leptin-deficient obesity are still unknown. This study aimed to determine how HSC-targeting lipocalin-2 (LCN2) mediates the transition from simple steatosis to NASH. APPROACH AND RESULTS: Male wild-type (WT) and ob/ob mice were fed a high-fat diet (HFD) for 20 weeks to establish an animal model of NASH with fibrosis. Ob/ob mice were subject to caloric restriction or recombinant leptin treatment. Double knockout (DKO) mice lacking both leptin and lcn2 were also fed an HFD for 20 weeks. In addition, HFD-fed ob/ob mice were treated with gadolinium trichloride to deplete Kupffer cells. The LX-2 human HSCs and primary HSCs from ob/ob mice were used to investigate the effects of LCN2 on HSC activation. Serum and hepatic LCN2 expression levels were prominently increased in HFD-fed ob/ob mice compared with normal diet-fed ob/ob mice or HFD-fed WT mice, and these changes were closely linked to liver fibrosis and increased hepatic α-SMA/matrix metalloproteinase 9 (MMP9)/signal transducer and activator of transcription 3 (STAT3) protein levels. HFD-fed DKO mice showed a marked reduction of α-SMA protein compared with HFD-fed ob/ob mice. In particular, the colocalization of LCN2 and α-SMA was increased in HSCs from HFD-fed ob/ob mice. In primary HSCs from ob/ob mice, exogenous LCN2 treatment induced HSC activation and MMP9 secretion. By contrast, LCN2 receptor 24p3R deficiency or a STAT3 inhibitor reduced the activation and migration of primary HSCs. CONCLUSIONS: LCN2 acts as a key mediator of HSC activation in leptin-deficient obesity via α-SMA/MMP9/STAT3 signaling, thereby exacerbating NASH.

Efficacy and Safety of Infliximab in Intestinal Behçet's Disease: A Multicenter, Phase 3 Study (BEGIN).

Background/Aims: To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet's disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. Methods: This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. Results: A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies. Conclusions: This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568).