ETHNOPHARMACOLOGICAL RELEVANCE: Erjingpill, a well-known prescription documented in the classic Chinese medical text "Shengji Zonglu," has been proven to have effective alleviating effects on neuroinflammation in Alzheimer's disease (AD). Although the alterations in microglial cell glycolysis are known to play a crucial role in the development of neuroinflammation, it remains unclear whether the anti-neuroinflammatory effects of Erjingpill are associated with its impact on microglial cell glycolysis. AIM OF THE STUDY: This study aims to determine whether Erjingpill exerts anti-neuroinflammatory effects by influencing microglial cell glycolysis. MATERIALS AND METHODS: Firstly, Erjingpill decoction was prepared into an Erjingpill bionic cerebrospinal fluid (EBCF) through a process of in vitro intestinal absorption, hepatocyte incubation, and blood-brain barrier (BBB) transcytosis. Subsequently, UPLC/Q-TOF-MS/MS technology was used to analyze the compounds in Erjingpill and EBCF. Next, an in vitro neuroinflammation model was established by LPS-induced BV2 cells. The impact of EBCF on BV2 cell proliferation activity was evaluated using the CCK-8 assay, while the NO release was assessed using the Griess assay. Additionally, mRNA levels of pro-inflammatory factors (IL-1ß, IL-6, TNF-α, and COX-2), anti-inflammatory factors (IL-10, IL-4, Arg-1, and TGF-ß), M1 microglial markers (iNOS, CD86), M2 microglial markers (CD36, CD206), and glycolytic enzymes (HK2, GLUT1, PKM, and LDHA) were measured using qPCR. Furthermore, protein expression of microglial activation marker Iba-1, M1 marker iNOS, and M2 marker CD206 were identified through immunofluorescence, while concentrations of pro-inflammatory cytokines IL-1ß and TNF-α were measured using ELISA. Enzymatic activity of glycolytic enzymes (HK, PK, and LDH) was assessed using assay kits, and the protein levels of pro-inflammatory factors (IL-1ß, iNOS, and COX-2), anti-inflammatory factors (IL-10 and Arg-1), and key glycolytic proteins GLUT1 and PI3K/AKT/mTOR were detected by Western blot. RESULTS: Through the analysis of Erjingpill and EBCF, 144 compounds were identified in Erjingpill and 40 compounds were identified in EBCF. The results demonstrated that EBCF effectively inhibited the elevation of inflammatory factors and glycolysis levels in LPS-induced BV2 cells, promoted polarization of M1 microglial cells towards the M2 phenotype, and suppressed the PI3K/AKT/mTOR inflammatory pathway. Moreover, EBCF alleviated LPS-induced BV2 cell inflammatory response by modulating mTOR to inhibit glycolysis. CONCLUSIONS: EBCF exhibits significant anti-neuroinflammatory effects, likely attributed to its modulation of mTOR to inhibit microglial cell glycolysis. This study furnishes experimental evidence supporting the clinical utilization of Erjingpill for preventing and treating AD.
BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. ERAS can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay (LOS) after surgery. RESULTS: A total of 245 patients (age of 79.8 ± 3.4 yr) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between non-frail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.
PURPOSE: To evaluate outcomes of choosing different Roussouly shapes and improving in Schwab modifiers for surgical Roussouly type 1 patients. METHODS: Baseline (BL) and 2-year (2Y) clinical data of adult spinal deformity (ASD) patients presenting with Roussouly type 1 sagittal spinal alignment were isolated in the single-center spine database. Patients were grouped into Roussouly type 1, 2 and 3 with anteverted pelvis (3a) postoperatively. Schwab modifiers at BL and 2Y were categorized as follows: no deformity (0), moderate deformity (+), and severe deformity (++) for pelvic tilt (PT), sagittal vertical axis (SVA), and pelvic incidence and lumbar lordosis mismatch (PI-LL). Improvement in SRS-Schwab was defined as a decrease in the severity of any modifier at 2Y. RESULTS: A total of 96 patients (69.9 years, 72.9% female, 25.2 kg/m2) were included. At 2Y, there were 34 type 1 backs, 60 type 2 backs and only 2 type 3a. Type 1 and type 2 did not differ in rates of reaching 2Y minimal clinically important difference (MCID) for health-related quality of life (HRQOL) scores (all P > 0.05). Two patients who presented with type 3a had poor HRQOL scores. Analysis of Schwab modifiers showed that 41.7% of patients improved in SVA, 45.8% in PI-LL, and 36.5% in PT. At 2Y, patients who improved in SRS-Schwab PT and SVA had lower Oswestry disability index (ODI) scores and significantly more of them reached MCID for ODI (all P < 0.001). Patients who improved in SRS-Schwab SVA and PI-LL had more changes of VAS Back and Short Form-36 (SF-36) outcomes questionnaire physical component summary (SF-36 PCS), and significantly more reached MCID (all P < 0.001). By 2Y, type 2 patients who improved in SRS-Schwab grades reached MCID for VAS back and ODI at the highest rate (P = 0.003, P = 0.001, respectively), and type 1 patients who improved in SRS-Schwab grades reached MCID for SF-36 PCS at the highest rate (P < 0.001). CONCLUSION: For ASD patients classified as Roussouly type 1, postoperative improvement in SRS-Schwab grades reflected superior patient-reported outcomes while type 1 and type 2 did not differ in clinical outcomes at 2Y. However, development of type 3a should be avoided at the risk of poor functional outcomes. Utilizing both classification systems in surgical decision-making can optimize postoperative outcomes.
STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the mini nutritional assessment-short form (MNA-SF), geriatric nutritional risk index, prognostic nutritional index (PNI), and preoperative serum albumin level as predictors of postoperative adverse events (AEs) in degenerative spine deformity (DSD) patients. SUMMARY OF BACKGROUND DATA: Although various nutritional screening tools have been well evaluated in patients undergoing spinal fusion surgery, the most suitable tool for the DSD population remains uncertain at present. PATIENTS AND METHODS: The authors reviewed consecutive patients who underwent thoracolumbar fusion surgery for DSD between August 2016 and May 2023. Four screening tools were used to assess preoperative nutritional status. Patients were divided into two categories according to each screening tool, and the four screening tools were compared regarding their predictive power for postoperative AEs, including the rates of extended length of hospital stays (LOS), complications, and readmission within three months. Physical functional indicators such as time to first ambulation, nonhome discharge, and postoperative LOS were assessed as secondary outcome measures. A multivariable logistic regression analysis was used to identify factors associated with postoperative AEs. RESULTS: A total of 228 patients were included. The demographic characteristics, underlying disease, and magnitude of correction were not significantly different between well-nourished and malnourished groups. The nutritional risks shown by MNA-SF and albumin level were significantly associated with infectious complications ( P <0.05). The nutritional risk shown by MNA-SF was significantly associated with nonhome discharge, prolonged postoperative LOS (12.5±8.2 vs. 10.3±6.1, P =0.039), and delayed ambulation (3.7±2.1 vs. 2.2±1.8, P =0.001). Multivariable logistic regression revealed that PNI <50 was significantly associated with total AEs and minor AEs after DSD surgery. CONCLUSIONS: PNI was significantly associated with the incidence of total AEs and minor AEs, while preoperative albumin level and MNA-SF were more effective in predicting postoperative infectious complications and delayed recovery of physical function, respectively. LEVEL OF EVIDENCE: Level III.
Malnutrition , Nutritional Status , Humans , Aged , Nutrition Assessment , Retrospective Studies , Malnutrition/diagnosis , Albumins , Postoperative Complications/epidemiology
PURPOSE: This study aimed to develop a predictive model for prolonged length of hospital stay (pLOS) in elderly patients undergoing lumbar fusion surgery, utilizing multivariate logistic regression, single classification and regression tree (hereafter, "classification tree") and random forest machine-learning algorithms. METHODS: This study was a retrospective review of a prospective Geriatric Lumbar Disease Database. The primary outcome measure was pLOS, which was defined as the LOS greater than the 75th percentile. All patients were grouped as pLOS group and non-pLOS. Three models (including logistic regression, single-classification tree and random forest algorithms) for predicting pLOS were developed using training dataset and internal validation using testing dataset. Finally, online tool based on our model was developed to assess its validity in the clinical setting (external validation). RESULTS: The development set included 1025 patients (mean [SD] age, 72.8 [5.6] years; 632 [61.7%] female), and the external validation set included 175 patients (73.2 [5.9] years; 97[55.4%] female). Multivariate logistic analyses revealed that older age (odds ratio [OR] 1.06, p < 0.001), higher BMI (OR 1.08, p = 0.002), number of fused segments (OR 1.41, p < 0.001), longer operative time (OR 1.02, p < 0.001), and diabetes (OR 1.05, p = 0.046) were independent risk factors for pLOS in elderly patients undergoing lumbar fusion surgery. The single-classification tree revealed that operative time ≥ 232 min, delayed ambulation, and BMI ≥ 30 kg/m2 as particularly influential predictors for pLOS. A random forest model was developed using the remaining 14 variables. Intraoperative EBL, operative time, delayed ambulation, age, number of fused segments, BMI, and RBC count were the most significant variables in the final model. The predictive ability of our three models was comparable, with no significant differences in AUC (0.73 vs. 0.71 vs. 0.70, respectively). The logistic regression model had a higher net benefit for clinical intervention than the other models. The nomogram was developed, and the C-index of external validation for PLOS was 0.69 (95% CI, 0.65-0.76). CONCLUSION: This investigation produced three predictive models for pLOS in elderly patients undergoing lumbar fusion surgery. The predictive ability of our three models was comparable. Logistic regression model had a higher net benefit for clinical intervention than the other models. Our predictive model could inform physicians about elderly patients with a high risk of pLOS after surgery.
Nomograms , Humans , Aged , Prospective Studies , Length of Stay , Retrospective Studies , Risk Factors
BACKGROUND: The burden of lumbar degenerative diseases (LDD) has increased substantially with the unprecedented aging population. Identifying elderly patients with high risk of postoperative adverse events (AEs) and establishing individualized perioperative management is critical to mitigate added costs and optimize cost-effectiveness to the healthcare system. We aimed to develop a predictive tool for AEs in elderly patients with transforaminal lumbar interbody fusion (TLIF), utilizing multivariate logistic regression, single classification and regression tree (hereafter, "classification tree"), and random forest machine learning algorithms. METHODS: This study was a retrospective review of a prospective Geriatric Lumbar Disease Database (age ≥ 65). Our outcome measure was postoperative AEs, including prolonged hospital stays, postoperative complications, readmission, and reoperation within 90 days. Patients were grouped as either having at least one adverse event (AEs group) or not (No-AEs group). Three models for predicting postoperative AEs were developed using training dataset and internal validation using testing dataset. Finally, online tool was developed to assess its validity in the clinical setting (external validation). RESULTS: The development set included 1025 patients (mean [SD] age, 72.8 [5.6] years; 632 [61.7%] female), and the external validation set included 175 patients (73.2 [5.9] years; 97 [55.4%] female). The predictive ability of our three models was comparable, with no significant differences in AUC (0.73 vs. 0.72 vs. 0.70, respectively). The logistic regression model had a higher net benefit for clinical intervention than the other models. A nomogram based on logistic regression was developed, and the C-index of external validation for AEs was 0.69 (95% CI 0.65-0.76). CONCLUSION: The predictive ability of our three models was comparable. Logistic regression model had a higher net benefit for clinical intervention than the other models. Our nomogram and online tool ( https://xuanwumodel.shinyapps.io/Model_for_AEs/ ) could inform physicians about elderly patients with a high risk of AEs within the 90 days after TLIF surgery.
Nomograms , Spinal Fusion , Humans , Aged , Lumbar Vertebrae/surgery , Prospective Studies , Spinal Fusion/adverse effects , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies
PURPOSE: Although comprehensive geriatric assessment (CGA) has been used widely, its impact on adverse events in elderly patients has not been fully examined. The present study aimed to investigate the relationships between subcomponents of CGA and adverse events (AEs) in elderly patients undergoing posterior lumbar fusion surgery. METHODS: A total of 242 eligible elderly patients enrolled. Our CGA included activities of daily living, instrumental activities of daily living, nutritional status, cardiac function, pulmonary function, renal function, frailty, cognition, anxiety, depression, delirium, chronic pain score, comorbidity and polypharmacy. Comprehensive complication index was used to summarize postoperative complications and its severity. Logistic regression was performed to determine the relationships between subcomponents of a CGA and postoperative AEs. RESULTS: Present study found that female were more vulnerable to have AEs. Postoperative major AEs were associated with delirium (odds ratio (OR): 4.302, 95% confidence interval (CI) 1.720-10.761, p = 0.002), nutritional status (OR: 3.030, 95%CI 1.218-7.541, p = 0.017), cognitive impairment (OR: 4.122, 95%CI 1.179-14.407, p = 0.027), Charlson comorbidity index (CCI) (OR: 4.800, 95%CI 1.852-12.440, p = 0.001) and severe dependent (OR: 3.772, 95%CI 1.116-9.841, p = 0.007). Further analysis showed that delirium (OR: 2.824, 95%CI 1.068-7.467, p = 0.036) and CCI (OR: 3.221, 95%CI 1.184-8.766, p = 0.022) were independently related to major AEs. CONCLUSIONS: These results indicate that preoperative screening preoperative delirium, cognitive, nutrition and CCI are essential to prevent postoperative major AEs of the surgical elderly.
Delirium , Frailty , Humans , Female , Aged , Geriatric Assessment/methods , Activities of Daily Living , Frailty/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Delirium/complications , Delirium/diagnosis
BACKGROUND CONTEXT: Elderly patients are less likely to recover from lumbar spine fusion (LSF) as rapidly compared with younger patients. However, there is still a lack of research on the effect of early ambulation on elderly patients undergoing LSF surgery for lumbar degenerative disorders. PURPOSE: To evaluate the safety and benefit of ambulation within 24 hours in elderly patients who underwent LSF. STUDY DESIGN: A retrospective study. PATIENT SAMPLE: Consecutive patients (aged 65 and older) who underwent elective transforaminal lumbar interbody fusion surgery for degenerative disorders from January 2019 to October 2022. OUTCOME MEASURES: Outcome measures included postoperative complications, postoperative drainage (mL), laboratory test data, length of hospital stay [LOS], readmission and reoperation within 3 months. METHODS: Early ambulation patients (ambulation within 24 hours after surgery) were propensity-score matched 1:1 to a delayed ambulation patients (ambulation at a minimum of 48 hours postoperatively) based on age, intraoperative blood loss, and number of fused segments. The incidence of postoperative adverse events (AEs, including rates of complications, readmission, and prolonged LOS) and the average LOS were used to assess the safety and benefit of early ambulation, respectively. Multivariable regression analysis was performed to assess the association between early ambulation and postoperative AEs. The risk factors for delayed ambulation were also determined using multivariable logistic analyses. RESULTS: A total of 998 patients with LSF surgery were reviewed in this study. After excluding 116 patients for various reasons, 882 patients (<24 hours: N=350, 24-48 hours: N=230, and >48 hours: N= 302) were included in the final analysis. After matching, sex, BMI, preoperative comorbidities, laboratory test data and surgery-related variables were comparable between the groups. The incidence of postoperative AEs was significantly lower in the EA group (44.3% vs. 64.0%, p<.001). The average postoperative LOS of the EA group was 2 days shorter than the DA group (6.5 days vs. 8.5 days, p<.001). Patients in the EA group had a significantly lower rate of prolonged LOS compared with the DA group (35.1% vs. 55.3%, p<.001). There was no significant difference in postoperative drainage volumes between the two groups. Multivariable analysis identified older age (odds ratio [OR] 1.07, p<.001), increased intraoperative EBL (OR 1.002, p=.001), and higher international normalization ratio (OR 10.57, p=.032) as significant independent risk factors for delayed ambulation. CONCLUSIONS: Ambulation within 24 hours after LSF surgery is independently associated fewer AEs and shorter hospital stays in elderly patients. Implementing the goal of ambulation within 24 hours after LSF surgery into enhanced recovery after surgery protocols for elderly patients seems appropriate. Older age, increased intraoperative blood loss and worse coagulation function are associated with delayed ambulation.
Gardenia, as a medicinal and edible herb, has the pharmacological activity of protecting the liver and cholagogue, but the hepatotoxicity induced by the chemical component genipin (GP) limits its application. The aim of this study was to evaluate the acute and subacute hepatotoxicity of genipin in normal mice and mice with α-naphthalene isothiocyanate (ANIT)-induced liver injury. The results of the acute study showed that the LD50 of genipin was 510 mg/kg. Genipin exhibited hepatotoxicity in normal and jaundiced mice at doses of 125 mg/kg, 250 mg/kg, and 500 mg/kg, which increased with dose. In a 28-day subacute study, the 50 mg/kg and 100 mg/kg dose groups showed some pharmacodynamic effects at 7 days but exhibited hepatotoxicity that increased with time and improved after drug withdrawal. In addition, based on proteomics, the mechanism of liver injury induced by genipin may be related to the disruption of the UDP-glucuronosyltransferase system and cytochrome P450 enzyme activity. In conclusion, this study showed that genipin hepatotoxicity was time- and dose dependent, but it is worth mentioning that hepatotoxicity was reversible. It is hoped that this study will provide a scientific basis for circumventing the adverse effects of genipin.
Background: Enhanced recovery after surgery (ERAS) is currently widely used in many surgical specialties, but there is still a lack of concern about the cervical ERAS program for old patients (>60 years old). We aimed to determine whether our ERAS program significantly improved satisfaction and outcomes in old patients (>60 years old) with anterior cervical discectomy and fusion (ACDF). Methods: This is a retrospective cohort study. The study enrolled patients if they were over the age of 60 years old underwent ACDF from July 2019 and June 2021 (ERAS group) and from January 2018 and June 2019 (non-ERAS group). Data including demographic, comorbidity, and surgical information were collected. We also evaluated ERAS process compliance, primary outcome, surgical complication, and length of stay (LOS). Results: There were 135 patients in the ERAS group, and 122 patients in the non-ERAS group were included. A comparison of the demographic data revealed that there were no statistically significant intergroup differences observed between the group. Overall, ERAS pathway compliance was 91.9%. There were no significant differences in the fusion levels, operative time, intraoperative blood loss, postoperative VAS score, and complications between the ERAS and non-ERAS groups. In addition, there was no significant difference in readmission and mortality at 30-day follow-up between the two groups. However, we observed a statistically significant decrease in the LOS in the ERAS group (8.68±2.34 of ERAS group versus 10.43±4.05 in non-ERAS group, p=0.013). Conclusion: This report describes the first ERAS protocol used in old patients with ACDF. Our ERAS program is safe and associated with incremental benefits with respect to LOS in old patients with ACDF.
Enhanced Recovery After Surgery , Spinal Fusion , Humans , Retrospective Studies , Cervical Vertebrae/surgery , Spinal Fusion/methods , Diskectomy/methods , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Treatment Outcome
Genipin has been the focus of research as a multifunctional compound for the treatment of pathogenic diseases. However, hepatotoxicity caused by oral genipin raises concerns about its safety. To obtain novel derivatives with low toxicity and efficacy, we synthesized methylgenipin (MG), a new compound, using structural modification, and investigated the safety of MG administration. The results showed that the LD50 of oral MG was higher than 1000 mg/kg, no mice died or were poisoned during the experiment in the treatment group, and there was no significant difference in biochemical parameters and liver pathological sections compared with the control. Importantly, MG (100 mg/kg/d) treatment for 7 days reduced alpha-naphthylisothiocyanate (ANIT)-induced increases in liver index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and total bilirubin (TBIL) levels. Histopathology demonstrated that MG could treat ANIT-induced cholestasis. In addition, using proteomics to investigate the molecular mechanism of MG in the treatment of a liver injury may be related to enhancing antioxidant function. Kit validation showed that ANIT induced an increase in malondialdehyde (MDA) and a decrease in superoxide dismutase (SOD) and glutathione (GSH) levels, while the MG pretreatments, both of which were significantly reversed to some extent, suggested that MG may alleviate ANIT-induced hepatotoxicity by enhancing endogenous antioxidant enzymes and inhibiting oxidative stress injury. In this study, we demonstrate that the treatment of mice with MG does not cause impaired liver function and provide an investigation of the efficacy of MG against ANIT-induced hepatotoxicity, laying the foundation for the safety evaluation and clinical application of MG.
Chemical and Drug Induced Liver Injury , Cholestasis , Mice , Animals , Liver , Iridoids/therapeutic use , Cholestasis/pathology , Antioxidants/therapeutic use , Glutathione , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology
In this paper, we propose and experimentally verify a phase-modulated radio-over-fiber (RoF) link capable of transmitting the radio frequency (RF) signal linearly. By executing the Kramers-Kronig (KK) algorithm at the receiver, the proposed link can accomplish linear optical phase demodulation with a single photodetector rather than a coherent receiver. In the 16-quadrature amplitude modulation (16-QAM) and 64-QAM microwave vector signal transmission experiments, measured error vector magnitudes (EVMs) are 4.14% and 4.38%, respectively, after 25-km fiber transmission, and the measured spurious-free dynamic range (SFDR) is 114.5â dB·Hz2/3, which shows a good performance in linearity.
Background: Primary central nervous system lymphoma (PCNSL) is a highly aggressive non-Hodgkin's B-cell lymphoma which normally treated by high-dose methotrexate (HD-MTX)-based chemotherapy. However, such treatment cannot always guarantee a good prognosis (GP) outcome while suffering several side effects. Thus, biomarkers or biomarker-based models that can predict PCNSL patient prognosis would be beneficial. Methods: We first collected 48 patients with PCNSL and applied HPLC-MS/MS-based metabolomic analysis on such retrospective PCNSL patient samples. We then selected the highly dysregulated metabolites to build a logical regression model that can distinguish the survival time length by a scoring standard. Finally, we validated the logical regression model on a 33-patient prospective PCNSL cohort. Results: Six metabolic features were selected from the cerebrospinal fluid (CSF) that can form a logical regression model to distinguish the patients with relatively GP (Z score ≤0.06) from the discovery cohort. We applied the metabolic marker-based model to a prospective recruited PCNSL patient cohort for further validation, and the model preformed nicely on such a validation cohort (AUC = 0.745). Conclusions: We developed a logical regression model based on metabolic markers in CSF that can effectively predict PCNSL patient prognosis before the HD-MTX-based chemotherapy treatments.
PURPOSE: The prevalence of degenerative spinal deformity (DSD) and the increased cost of correction surgery impose substantial burdens on the health care and insurance system. The aim of our study was to investigate the effects of the implementation of Enhanced Recovery After Surgery (ERAS) protocol on postoperative outcomes after complex spinal surgery. METHODS: A retrospective analysis of prospectively established database of DSD was performed. The consecutive patients who underwent open correction surgery for degenerative spinal deformity between August 2016 and February 2022 were reviewed. We extracted demographic data, preoperative radiographic parameters, and surgery-related variables. The ERAS patients were 1:1 propensity-score matched to a historical cohort by the same surgical team based on age, gender, BMI, and number of levels fused. We then compared the length of hospital stay (LOS), physiological functional recovery, and the rates of complications and readmissions within 90 days after surgery between the groups. RESULTS: There were 108 patients included, 54 patients in the ERAS cohort, and 54 patients matched control patients in the historical cohort. The historical and ERAS cohorts were not significantly different regarding demographic characteristics, comorbidities, preoperative parameters, operative time, and reoperation rate (P > 0.05). Patients in the ERAS group had significantly shorter postoperative LOS (12.0 days vs. 15.1 days, P = 0.001), average days of drain and urinary catheters placement (3.5 days vs. 4.4 days and 1.9 days vs 4.8 days, respectively), and lower 90-day readmission rate (1.8% vs. 12.9%, P = 0.027). The first day of assisted-walking and bowel movement occurred on average 1.9 days (2.5 days vs. 4.4 days, P = 0.001) and 1.7 days (1.9 days vs. 3.6 days, P = 0.001) earlier respectively in the ERAS group. Moreover, the rate of postoperative urinary retention (3.7% vs. 16.7%, P = 0.026) and surgical site infection (0% vs. 7.4%, P = 0.046) were significantly lower with ERAS protocol applied. CONCLUSIONS: Our study confirmed that the ERAS protocol was safe and essential for patients undergoing thoracolumbar deformity surgery for DSD. The ERAS protocol was associated with a shorter postoperative LOS, a lower rate of 90-day readmission, less rehabilitation discharge, and less postoperative complications.
Enhanced Recovery After Surgery , Spinal Fusion , Humans , Retrospective Studies , Spine , Surgical Wound Infection , Recovery of Function , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Spinal Fusion/adverse effects , Spinal Fusion/methods
PURPOSE: To identify the relationship between depression measured by Zung depression rating scale (ZDRS) and postoperative outcomes (including the patients reported outcomes [PRO] and clinical outcomes) two years after short-segment fusion surgery for degenerative lumbar spinal disease in older patients (aged 75 years and older). METHODS: We enrolled patients who underwent short-segment fusion surgery for lumbar degenerative disease from May 2018 to June 2020. All patients were assessed for depression using the ZDRS. Patients were included in the depression group and not-depressed group based on their scores. Preoperative baseline data were collected on characteristics, comorbidities, laboratory data, pain levels (visual analogue scale [VAS]), functional status (Oswestry Disability Index [ODI]), and surgery-related variables. The primary outcomes were PRO measures, including VAS, ODI and satisfaction two years after lumbar fusion surgery. Other outcomes included postoperative complications, the length of stay, and reoperation. Univariate and multivariate analyses were performed to identify the risk factors for poor satisfaction. RESULTS: A total of 231 patients (201 in not-depressed and 30 in depressed group) were enrolled in this study. There were no significant differences between the two groups for baseline data. Depressed group had higher rates of choices for dissatisfaction (36.7% vs. 14.0%, p = 0.015), higher VAS scores of low back pain (2.8 ± 2.3 vs. 1.6 ± 1.7, p = 0.012), and worse functional status (31.5 ± 22.5 vs 21.8 ± 19.9, p = 0.015) than the not-depressed group. Depressed patients reported significantly higher rates of postoperative complications and readmissions. Multivariate regression analysis revealed that depression (p = 0.001) was independently associated with postoperative dissatisfaction. CONCLUSION: Preoperative depression was a risk factor for postoperative dissatisfaction, worse functional status, readmission, and complications in older patients undergoing lumbar fusion surgery. Preoperative screening using the Zung depression scale helps inform decision-making when considering fusion surgery for patients aged 75 and older.
Spinal Diseases , Spinal Fusion , Humans , Aged , Depression/diagnosis , Depression/epidemiology , Depression/complications , Lumbar Vertebrae/surgery , Comorbidity , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Spinal Fusion/adverse effects , Treatment Outcome , Retrospective Studies
BACKGROUND: It has been shown that Kudzu root has significant pharmacological effects such as improving microcirculation, dilating coronary arteries, and increasing cerebral and coronary blood flow, but its material basis and mechanism of action are not clear. OBJECTIVE: The aim of this study was to investigate the mechanism of action of Kudzu root in the prevention and treatment of cerebral ischemia (CI) through network pharmacology combined with animal experiments. METHODS: The components of kudzu root were screened by using the Chemistry Database, Chinese Academy of Science. Linpinski's five rules were used to perform pharmacophore-like analysis to obtain the active ingredients of Kudzu root. The Swiss Target Prediction Service database was used to predict the potential protein targets of kudzu root components associated with CI. An active ingredient-target network was constructed by using Cytoscape 3.6.0. A rat model of middle cerebral artery occlusion (MCAO) was established, then the main targets and signaling pathways predicted were verified by observing the area of cerebral infarction and Western blot experiments. RESULTS: In total, 84 major active compounds and 34 targets included gerberoside, belonging to the isoflavone class, gallic acid, amino acid class, 4-Methylphenol, phenolic class, and quercetin, and flavonoid class (Flavonoids). The targets covered were proteins related to excitatory amino acids and calcium overload, including Excitatory amino acid transporter 2 (SLC1A2), Glutamate receptor ionotropic, kainate 1 (GRIK1), Glutamate receptor ionotropic, NMDA 1 (GRIN1), Glutamate receptor 2(GRIA2), Calcium/calmodulin-dependent protein kinase II (CaMKII), Neuronal nitric oxide synthase(nNOS). Glutamatergic energy is prominent, and calcium transport across the membrane is central to the network and occupies an important position. CONCLUSION: Kudzu root can significantly reduce neurological damage in rats with CI, and also significantly reduce the rate of cerebral infarction. It is worth noting that Kudzu root can prevent and treat CI by reducing excitatory amino acid toxicity and improving calcium overload.
Brain Ischemia , Drugs, Chinese Herbal , Pueraria , Rats , Animals , Pueraria/chemistry , Network Pharmacology , Calcium , Brain Ischemia/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Flavonoids , Cerebral Infarction/drug therapy , Receptors, Glutamate/therapeutic use , Molecular Docking Simulation
Objective: To identify the risk factors associated with prolonged length of stay (LOS) despite an enhanced recovery after surgery (ERAS) protocol in short-level lumbar fusion surgery. Methods: We gathered data for all patients undergoing short-level lumbar fusion surgery from January to November 2021. Given the discharge criteria, a threshold was set according to mean LOS, and two groups were spontaneously formed: LOS shorter than the threshold for discharge (control group, n = 114) and LOS longer or equal to the threshold for discharge (delayed group, n = 72). Preoperative metrics were compared to identify risk factors associated with prolonged LOS. Results: A total consecutive 186 patients with complete medical records were enrolled (77 males and 109 females; mean age 71.08 ± 5.70 years). After dichotomization according to the threshold for discharge, there were 114 patients in control group and 72 in delayed group. Statistical analysis demonstrated that age ≥75 years (P = .002), female sex (P < .001), American Society of Anesthesiologists grade ≥ 3 (P = .035), operation time (P < .001), anesthesia time (P < .001), ambulation time >1 day (P = .027), removal of urinary catheter time >1 day (P = .019), fusion levels (P < .001), Clavien-Dindo grade > 1 (P <.001) and allogeneic transfusion (P = .009) were significantly related to prolonged LOS. Binary logistic regression revealed that age (odds ratio (OR) 5.149; 95% confidence interval (CI) 2.045-12.966, P = .001), sex (OR 5.185, 95% CI 2.183-12.317, P < .001) and Clavien-Dindo grade > 1(OR 15.936, 95% CI 5.220-48.652, P < .001) were independent risk factors of prolonged LOS. Conclusions: In this retrospective study, we analyzed the potential risk factors associated with delayed LOS despite implementing ERAS, further, binary logistic regression exhibited that age ≥75 years old, female sex and Clavien-Dindo grade >1 were independently correlated with prolonged LOS.
Liposarcoma (LPS) is a rare and heterogeneous malignancy of adipocytic origin. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes, showing similar genetic characterizations but distinct biological behaviors and clinical prognosis. Compared to WDLPS, DDLPS is more aggressive and has the potential of metastasis, as the malignant adipocytic tumor's metabolic changes may have taken place during the tumorigenesis of LPSs. Therefore, to investigate the lipid alterations between the two subtypes, high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) based untargeted lipidomic analysis was performed onto LPS tissues from 6 WDLPS and 7 DDLPS patients. The lipidomic analysis showed the upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and the upregulated triglycerides and diglycerides in WDLPS, which might be due to the uncompleted adipocytic dedifferentiation leading to such tumorigenesis. Such a finding was also confirmed by the similarity comparison of two LPS subtypes to the transcriptome of stromal vascular fraction at different differentiation stages. Transcriptomic analysis also demonstrated that metabolic pathways including the pentose phosphate pathway (PPP) were upregulated in WDLPS compared to DDLPS. Therefore, the cell line LPS853 was treated with the PPP inhibitor 6-aminonicotinamide ex vivo and the proliferation and invasion of LPS853 was significantly promoted by PPP inhibition, suggesting the potential role of PPP in the development and differentiation of LPS. In conclusion, this study described the altered lipid profiles of WDLPS and DDLPS for the first time, revealing the different differentiation stages of the two subtypes and providing a potential metabolic target for LPS treatment.
Background: Enhanced recovery after surgery (ERAS) is an evidence-based multimodal perioperative management designed to reduce the length of stay (LOS) and complications. The purpose of the present study is to evaluate the recovery of physiological function, LOS, complications, pain score, and clinical efficacy in frail elderly patients undergoing multisegment fusion surgery after the implementation of the ERAS protocol. Methods: Frail patients older than 75 years undergoing multilevel lumbar fusion surgery for degenerative discogenic conditions, lumbar spinal stenosis, and lumbar spondylolisthesis from January 2017 to December 2018 (non-ERAS frail group) and from January 2020 to December 2021 (ERAS frail group) were enrolled in the present study. Propensity score matching for age, sex, body mass index, and smoking status was performed to keep comparable characteristics between the two groups. Further recovery of physiological function, LOS, complications, pain score, and clinical efficacy were compared between the groups. Results: There were 64 pairs of well-balanced patients, and the clinical baseline data were comparable between the two groups. There was significant improvement in terms of recovery of physiological function (10.65 ± 3.51 days vs. 8.31 ± 3.98 days, p = 0.011) and LOS (12.18 ± 4.69 days vs. 10.44 ± 4.60 days, p = 0.035), while no statistical discrepancy was observed with regard to complications between the groups, which indicated favorable outcomes after the implementation of the ERAS protocol. Further analysis indicated that more patients were meeting a minimally clinical important difference for the visual analog score for the legs and the Oswestry Disability Index in the ERAS frail group. With regard to postoperative pain, the score was higher in the ERAS frail group than in the non-ERAS frail group on postoperative day (POD) 1 (4.88 ± 1.90 in the ERAS frail group vs. 4.27 ± 1.42 in the non-ERAS frail group, p = 0.042), while there was no significant discrepancy on POD 2 (3.77 ± 0.88 in the ERAS frail group vs. 3.64 ± 1.07 in the non-ERAS frail group, p = 0.470) and POD 3 (3.83 ± 1.89 in the ERAS frail group vs. 3.47 ± 1.75 in the non-ERAS frail group, p = 0.266). Conclusions: In this retrospective cohort study, we found a significant improvement in terms of LOS, recovery of physiological function, and clinical efficacy after the implementation of the ERAS protocol in elderly and frail patients undergoing multilevel lumbar fusion surgery, while there was no significant discrepancy with regard to complications, 90-day readmission, and postoperative pain.
STUDY DESIGN: Retrospective case-control study. OBJECTIVES: Proximal junctional kyphosis (PJK) is a postoperative complication involving the proximal segments which is commonly seen in patients with degenerative spine diseases (DSD). The purpose of the present study was to identify predictive factors for postoperative PJK in elderly patients with DSD. METHODS: We reviewed elderly patients with DSD who underwent thoracolumbar fusion involving no less than 3 levels. Patients who developed PJK were propensity score-matched with patients with DSD who received the same procedure but did not develop PJK. Demographic characteristics, sagittal vertical axis (SVA), computed tomography (CT) value (Hounsfield unit), and paraspinal muscle parameters were compared between PJK and non-PJK groups. RESULTS: Eighty-three PJK and non-PJK patients were selected by propensity score matching for age, sex, history of smoking, body mass index, number of fused segments, and upper instrumented vertebra (UIV) location. SVA showed no significant difference between the two groups. In PJK group, fatty infiltration (FI) in erector spinae and multifidus was significantly greater, while the relative cross-sectional area (rCSA) of erector spinae was significantly smaller than that in non-PJK group. CT value was significantly lower in PJK group. Lower erector spinae rCSA and CT value of the UIV, higher erector spinae FI and multifidus FI were identified as predictors of postoperative PJK. CONCLUSIONS: PJK is a common complication in older patients with DSD. Paraspinal muscle degeneration and low bone mineral density of the UIV are predictors of PJK. Protective measures targeting paraspinal muscles and the UIV may help prevent postoperative PJK.
Kyphosis , Musculoskeletal Abnormalities , Spinal Fusion , Aged , Humans , Bone Density , Case-Control Studies , Kyphosis/diagnostic imaging , Kyphosis/surgery , Kyphosis/etiology , Paraspinal Muscles/diagnostic imaging , Propensity Score , Retrospective Studies , Spinal Fusion/adverse effects , Spinal Fusion/methods , Spine
