[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To analyze postictal electroencephalographic(EEG) characteristics of patients with status epilepticus (SE) based on the score of grand total electroencephalography (GTE), and explore the relationship between electroencephalographic characteristics of SE and clinical prognosis.Methods:A total of 110 SE patients were enrolled in the Department of Neurology, the Affiliated Hospital of Yangzhou University from September 1, 2021 to September 1, 2023. EEG and GTE scores were performed in all patients after seizures (0-2 days after the cessation of SE). After one year of discharge, the medication and seizure status of patients were followed up by phone or outpatient visits. The seizure outcomes were recorded according to the international league against epilepsy (ILAE) seizure outcome classification, with favorable outcomes defined as good prognosis group ( n=54) and unfavorable outcomes defined as poor prognosis group ( n=56). SPSS 27.0 software was used for statistical analysis. Binary Logistic regression analysis was employed to screen impact variables of prognosis. The receiver operating characteristic(ROC) curve was plotted to determine the optimal cut-off point for predicting prognosis in epilepsy. Results:There were statistically significant differences in the total GTE score(2(1, 4), 8(5, 10); Z=-6.837, P<0.001), diffuse slow activity(0(0, 1), 2(0, 2); Z=-6.495, P<0.001), reactivity of the rhythmic background activity(0(0, 0), 0(0, 1); Z=-2.705, P=0.007), paroxysmal activity(0(0, 0), 1.5(0, 3.0); Z=-4.420, P<0.001), focal disturbances(0(0, 0), 0(0, 0); Z=-2.130, P=0.033), and sharp wave activity(0(0, 2), 2(2, 3); Z=-5.714, P<0.001)between the good prognosis group and poor prognosis group. The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity and total GTE score (all P<0.05). The differences in EEG results between SE patients with clear and unknown causes were statistically significant in terms of paroxysmal activity and focal disturbances(both P<0.05). The results of binary Logistic regression analysis showed that independent factors associated with the prognosis of SE included medication adherence ( B=-0.496, OR=0.609, 95% CI=0.395-0.940, P=0.025), diffuse slow activity( B=1.580, OR=4.854, 95% CI=1.586-14.855, P=0.006), sharp wave activity( B=0.824, OR=2.280, 95% CI=1.210-4.297, P=0.011), and total GTE score ( B=0.561, OR=1.753, 95% CI=1.360-2.259, P<0.001). In evaluating the prognosis of SE, the GTE score had a certain sensitivity (74.6%) and specificity (85.1%), with a optimal cut-off point of 6. Conclusions:The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity. The appearance of diffuse slow activity and sharp wave activity in the electroencephalogram of SE patients indicates poor prognosis, and the total GTE score≥6 may be a strong predictor of poor prognosis. However, good medication adherence is a protective factor for epilepsy recurrence.

Objective:To analyze postictal electroencephalographic(EEG) characteristics of patients with status epilepticus (SE) based on the score of grand total electroencephalography (GTE), and explore the relationship between electroencephalographic characteristics of SE and clinical prognosis.Methods:A total of 110 SE patients were enrolled in the Department of Neurology, the Affiliated Hospital of Yangzhou University from September 1, 2021 to September 1, 2023. EEG and GTE scores were performed in all patients after seizures (0-2 days after the cessation of SE). After one year of discharge, the medication and seizure status of patients were followed up by phone or outpatient visits. The seizure outcomes were recorded according to the international league against epilepsy (ILAE) seizure outcome classification, with favorable outcomes defined as good prognosis group ( n=54) and unfavorable outcomes defined as poor prognosis group ( n=56). SPSS 27.0 software was used for statistical analysis. Binary Logistic regression analysis was employed to screen impact variables of prognosis. The receiver operating characteristic(ROC) curve was plotted to determine the optimal cut-off point for predicting prognosis in epilepsy. Results:There were statistically significant differences in the total GTE score(2(1, 4), 8(5, 10); Z=-6.837, P<0.001), diffuse slow activity(0(0, 1), 2(0, 2); Z=-6.495, P<0.001), reactivity of the rhythmic background activity(0(0, 0), 0(0, 1); Z=-2.705, P=0.007), paroxysmal activity(0(0, 0), 1.5(0, 3.0); Z=-4.420, P<0.001), focal disturbances(0(0, 0), 0(0, 0); Z=-2.130, P=0.033), and sharp wave activity(0(0, 2), 2(2, 3); Z=-5.714, P<0.001)between the good prognosis group and poor prognosis group. The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity and total GTE score (all P<0.05). The differences in EEG results between SE patients with clear and unknown causes were statistically significant in terms of paroxysmal activity and focal disturbances(both P<0.05). The results of binary Logistic regression analysis showed that independent factors associated with the prognosis of SE included medication adherence ( B=-0.496, OR=0.609, 95% CI=0.395-0.940, P=0.025), diffuse slow activity( B=1.580, OR=4.854, 95% CI=1.586-14.855, P=0.006), sharp wave activity( B=0.824, OR=2.280, 95% CI=1.210-4.297, P=0.011), and total GTE score ( B=0.561, OR=1.753, 95% CI=1.360-2.259, P<0.001). In evaluating the prognosis of SE, the GTE score had a certain sensitivity (74.6%) and specificity (85.1%), with a optimal cut-off point of 6. Conclusions:The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity. The appearance of diffuse slow activity and sharp wave activity in the electroencephalogram of SE patients indicates poor prognosis, and the total GTE score≥6 may be a strong predictor of poor prognosis. However, good medication adherence is a protective factor for epilepsy recurrence.

Objective:This study aims to explore the changes in brain surface morphology and their association with psychological characteristics in adolescents experiencing their first episode of major depressive disorder.Methods:This study included 48 adolescents with first-episode major depressive disorder (depression group) admitted to the Department of Psychiatry of the First Affiliated Hospital of Chongqing Medical University from October 2021 to July 2022. At the same period,35 healthy controls (control group) were also enrolled,from communities of Chongqing. All participants underwent assessments for depressive symptoms, emotion regulation capacity, impulsiveness, and psychological resilience using the 17-item Hamilton Depression Scale (HAMD 17), the Patient Health Questionnaire-9 (PHQ-9), the Emotion Regulation Questionnaire (ERQ), the Barratt Impulsiveness Scale-11 (BIS-11), and the Connor-Davidson Resilience Scale (CD-RISC). Structure magnetic resonance imaging (sMRI) was utilized to evaluate brain surface morphology. The values of cortical thickness, fractal dimension, sulcus depth, and cortical gyrification index were calculated. The index of brain surface morphology between the two groups was compared using the two-sample t-test, chi-square test, and non-parametric statistical tests with multiple comparisons correction using threshold-free cluster enhancement (TFCE) and false discovery rate (FDR). Pearson correlation analyses were used to analyze the correlation between the scores of each scale (HAMD 17, PHQ-9, ERQ, BIS-11, and CD-RISC) and the cortical thickness values and fractal dimension in the depression group. In addition, multiple linear regression was used to analyze the impact of clinical symptoms on the cortical thickness values in the depression group. Results:Compared with the control group, the depression group exhibited a significant reduction in the cortical thickness of the left occidental (FDR corrected, P<0.05) and an increase of the fractal dimension in the right insula, right superior temporal gyrus, and right transverse temporal gyrus (TFCE uncorrected, P<0.001). Correlation analyses showed that left occipital cortical thickness was positively correlated with the cognitive reappraisal scores of ERQ ( r=0.315, P=0.029), the total score of CD-RISC ( r=0.366, P=0.016), and the unplanned impulsiveness scores of BIS-11 (reverse scoring for this dimension) ( r=0.354, P=0.014). The partial correlation analysis revealed a positive linear correlation between cortical thickness and unplanned impulsiveness scores after controlling for age ( r=0.467, P=0.001). However, after Bonferroni correction, these correlations were not statistically significant. Conclusions:Compared with healthy individuals, adolescents with first-episode depressive disorders demonstrated increased fractal dimension in the right insula, right superior temporal gyrus, and right transverse temporal gyrus and decreased cortical thickness in the left occipital lobe. The decreased cortical thickness in the left occipital lobe was associated with impaired emotion regulation ability and impulse control ability during periods of stress.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective To investigate the effects of intraoperative intravenous administration of dexmedetomidine(DEX)on the recovery quality of donors undergoing pure laparoscopic donor hepatectomy.Methods A total of 56 liver donors who were going to undergo scheduled pure laparoscopic donor hepatectomy were enrolled and randomly assigned to two groups,a DEX group(n=28)and a control group(n=28).Donors in the DEX group received DEX infusion at a dose of 1 μg/kg over 15 minutes through a continuous pump,which was followed by DEX at 0.4 μg/(kg·h)until the disconnection of the portal branch.Donors in the control group were given an equal volume of 0.9% normal saline at the same infusion rate and over the same period of time as those of the dex infusion in the DEX group.The primary outcome was the incidence of emergence agitation(EA).The Aono's Four-point Scale(AFPS)score was used to assess EA.The secondary observation indicators included intraoperative anesthesia and surgery conditions,spontaneous respiration recovery time,recovery time,extubation time,scores for the Ramsay Sedation Scale,the incidence of chills,numeric rating scale(NRS)score for pain,and blood pressure and heart rate after extubation.Results The incidence of EA was 10.7% and 39.3% in the DEX group and the control group,respectively,and the incidence of EA was significantly lower in the DEX group than that in the control group(P=0.014).The APFS scores after extubation in the DEX group were lower than those in the control group(1[1,1]vs.2[1,3],P=0.005).Compared to the control group,the dosages of intraoperative propofol and remifentanil were significantly reduced in the DEX group(P<0.05).During the recovery period,the number of donors requiring additional boluses of analgesia,the blood pressure,and the heart rate were all lower in the DEX group than those in the control group(P<0.05).No significant differences between the two groups were observed in the spontaneous respiration recovery time,recovery time,extubation time,the incidence of chills,NRS score,scores for the Ramsay Sedation Scale,and the length-of-stay in postanesthesia care unit(PACU)(P>0.05).Conclusion DEX can reduce the incidence of EA after pure laparoscopic donor hepatectomy and improve the quality of recovery without prolonging postoperative recovery time or extubation time.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective:This study aims to explore the changes in brain surface morphology and their association with psychological characteristics in adolescents experiencing their first episode of major depressive disorder.Methods:This study included 48 adolescents with first-episode major depressive disorder (depression group) admitted to the Department of Psychiatry of the First Affiliated Hospital of Chongqing Medical University from October 2021 to July 2022. At the same period,35 healthy controls (control group) were also enrolled,from communities of Chongqing. All participants underwent assessments for depressive symptoms, emotion regulation capacity, impulsiveness, and psychological resilience using the 17-item Hamilton Depression Scale (HAMD 17), the Patient Health Questionnaire-9 (PHQ-9), the Emotion Regulation Questionnaire (ERQ), the Barratt Impulsiveness Scale-11 (BIS-11), and the Connor-Davidson Resilience Scale (CD-RISC). Structure magnetic resonance imaging (sMRI) was utilized to evaluate brain surface morphology. The values of cortical thickness, fractal dimension, sulcus depth, and cortical gyrification index were calculated. The index of brain surface morphology between the two groups was compared using the two-sample t-test, chi-square test, and non-parametric statistical tests with multiple comparisons correction using threshold-free cluster enhancement (TFCE) and false discovery rate (FDR). Pearson correlation analyses were used to analyze the correlation between the scores of each scale (HAMD 17, PHQ-9, ERQ, BIS-11, and CD-RISC) and the cortical thickness values and fractal dimension in the depression group. In addition, multiple linear regression was used to analyze the impact of clinical symptoms on the cortical thickness values in the depression group. Results:Compared with the control group, the depression group exhibited a significant reduction in the cortical thickness of the left occidental (FDR corrected, P<0.05) and an increase of the fractal dimension in the right insula, right superior temporal gyrus, and right transverse temporal gyrus (TFCE uncorrected, P<0.001). Correlation analyses showed that left occipital cortical thickness was positively correlated with the cognitive reappraisal scores of ERQ ( r=0.315, P=0.029), the total score of CD-RISC ( r=0.366, P=0.016), and the unplanned impulsiveness scores of BIS-11 (reverse scoring for this dimension) ( r=0.354, P=0.014). The partial correlation analysis revealed a positive linear correlation between cortical thickness and unplanned impulsiveness scores after controlling for age ( r=0.467, P=0.001). However, after Bonferroni correction, these correlations were not statistically significant. Conclusions:Compared with healthy individuals, adolescents with first-episode depressive disorders demonstrated increased fractal dimension in the right insula, right superior temporal gyrus, and right transverse temporal gyrus and decreased cortical thickness in the left occipital lobe. The decreased cortical thickness in the left occipital lobe was associated with impaired emotion regulation ability and impulse control ability during periods of stress.

ObjectiveTo explore factors related to dysphagia early after surgery for head-and-neck squamous cell carcinoma (HNSCC). MethodsA total of 80 HNSCC inpatients in Department of Oral and Maxillofacial Surgery, the Frist Affiliated Hospital of Chongqing Medical University, from October, 2019 to April, 2021, were reviewed swallowing function with Kubota water drinking test, Functional Oral Intake Scale (FOIs) and M.D. Anderson Dysphagia Inventory (MDADI), two weeks after radical surgery for the first time; while the related data were collected and analyzed. ResultsThe incidence of early post-operative dysphagia was 91.25%. The T stages of the tumor, the location of the primary tumor, simultaneous flap repairment and neck dissection were the factors related to dysphagia (P < 0.05), and T stages of the tumor was the independent factor (B = -5.092, t = -6.770, P < 0.001). ConclusionIt's necessary to evaluate the swallowing function of HNSCC patients after surgery, especially for those in worse stages, for early intervention.