The application of different machine learning models based on PET/CT images and EGFR in predicting brain metastasis of adenocarcinoma of the lung.

OBJECTIVE: To explore the value of six machine learning models based on PET/CT radiomics combined with EGFR in predicting brain metastases of lung adenocarcinoma. METHODS: Retrospectively collected 204 patients with lung adenocarcinoma who underwent PET/CT examination and EGFR gene detection before treatment from Cancer Hospital Affiliated to Shandong First Medical University in 2020. Using univariate analysis and multivariate logistic regression analysis to find the independent risk factors for brain metastasis. Based on PET/CT imaging combined with EGFR and PET metabolic indexes, established six machine learning models to predict brain metastases of lung adenocarcinoma. Finally, using ten-fold cross-validation to evaluate the predictive effectiveness. RESULTS: In univariate analysis, patients with N2-3, EGFR mutation-positive, LYM%≤20, and elevated tumor markers(P<0.05) were more likely to develop brain metastases. In multivariate Logistic regression analysis, PET metabolic indices revealed that SUVmax, SUVpeak, Volume, and TLG were risk factors for lung adenocarcinoma brain metastasis(P<0.05). The SVM model was the most efficient predictor of brain metastasis with an AUC of 0.82 (PET/CT group),0.70 (CT group),0.76 (PET group). CONCLUSIONS: Radiomics combined with EGFR machine learning model as a new method have higher accuracy than EGFR mutation alone. SVM model is the most effective method for predicting brain metastases of lung adenocarcinoma, and the prediction efficiency of PET/CT group is better than PET group and CT group.

Estimated Pulse Wave Velocity Predicts All-Cause and Cardiovascular-Cause Mortality in Individuals With Hypertension　- Findings From a National Health and Nutrition Examination Study 1999-2018.

BACKGROUND: This study aimed to investigate the association between estimated pulse wave velocity (ePWV) and mortality outcomes among individuals with hypertension. METHODS AND RESULTS: Based on the National Health and Nutrition Examination Survey (NHANES) 1999-2018, a total of 14,396 eligible participants with hypertension were enrolled. The ePWV was calculated using the equation based on blood pressure and age. The mortality outcomes of included participants were directly acquired from the National Death Index database. The multivariable Cox regression analysis was used to examine the relationship between ePWV and mortality outcomes. Moreover, the restricted cubic spline (RCS) was also used to explore this relationship. Receiver operating characteristics curves (ROC) were adopted to evaluate the prognostic ability of ePWV for predicting mortality outcomes of patients with hypertension. The median follow-up duration was 10.8 years; individuals with higher an ePWV had higher risks of mortality from both all causes (HR: 2.79, 95% CI: 2.43-3.20) and cardiovascular diseases (HR: 3.41, 95% CI: 2.50-4.64). After adjusting for confounding factors, each 1 m/s increase in ePWV was associated with a 43% increase in all-cause mortality risk (HR: 1.43, 95% CI: 1.37-1.48) and a 54% increase in cardiovascular mortality risk (HR: 1.54, 95% CI: 1.43-1.66). CONCLUSIONS: This study indicates that ePWV is a novel prognostic indicator for predicting the risks of mortality among patients with hypertension.

Effect of vegetable consumption on risk of gastric cancer: a systematic review and multi-level meta-analysis of prospective studies.

Vegetables are known to be beneficial to human health, but the association between vegetable consumption and gastric cancer remains uncertain. To synthesise knowledge about the relationship between vegetable group consumption and gastric cancer risk, update present meta-analyses and estimate associations between vegetable consumption and gastric cancer risk based solely on prospective studies, we perform a PRISMA-compliant three-level meta-analysis. Systematic search identified thirteen prospective studies with fifty-two effect sizes that met all inclusion criteria and no exclusion criteria for our meta-analysis. Pooled risk ratios (RRs) showed a positive association between high vegetable consumption and low gastric cancer risk (pooled RR 0·93, 95% confidence interval 0·90-0·97, P = 0·06). In moderator analyses for indicators of gender, region and quantity of vegetable intake, there was no significant difference between subgroups. However, the effect became significant in populations with lower than the minimum risk exposure level (TMREL) of vegetable consumption (P < 0·05). Higher vegetable intake is associated with a decreased risk of gastric cancer. This effect may be limited to specific populations, such as ones with lower vegetable consumption. Evidence from our study has important public health implications for dietary recommendations.

Comprehensive geriatric assessment to predict adverse events in elderly patients undergoing posterior lumbar fusion surgery.

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.

Radiographic and surgery-related predictive factors for increased segmental lumbar lordosis following lumbar fusion surgery in patients with degenerative lumbar spondylolisthesis.

OBJECTIVE: This study aimed to evaluate preoperative (pre-op) radiographic characteristics and specific surgical interventions in patients with degenerative lumbar spondylolisthesis (DLS) who underwent lumbar fusion surgery (LFS), with a focus on analyzing predictors of postoperative restoration of segmental lumbar lordosis (SLL). METHODS: A retrospective review at a single center identified consecutive single-level DLS patients who underwent LFS between 2016 and 2022. Radiographic measures included disc angle (DA), SLL, lumbar lordosis (LL), anterior/posterior disc height (ADH/PDH), spondylolisthesis percentage (SP), intervertebral disc degeneration, and paraspinal muscle quality. Surgery-related measures included cage position, screw insertion depth, spondylolisthesis reduction rate, and disc height restoration rate. A change in SLL ≥ 4° indicated increased segmental lumbar lordosis (ISLL), and unincreased segmental lumbar lordosis (UISLL) < 4°. Propensity score matching was employed for a 1:1 match between ISLL and UISLL patients based on age, gender, body mass index, smoking status, and osteoporosis condition. RESULTS: A total of 192 patients with an average follow-up of 20.9 months were enrolled. Compared to UISLL patients, ISLL patients had significantly lower pre-op DA (6.78° vs. 11.84°), SLL (10.73° vs. 18.24°), LL (42.59° vs. 45.75°), and ADH (10.09 mm vs. 12.21 mm) (all, P < 0.05). ISLL patients were predisposed to more severe intervertebral disc degeneration (P = 0.047) and higher SP (21.30% vs. 19.39%, P = 0.019). The cage was positioned more anteriorly in ISLL patients (67.00% vs. 60.08%, P = 0.000), with more extensive reduction of spondylolisthesis (- 73.70% vs. - 56.16%, P = 0.000) and higher restoration of ADH (33.34% vs. 8.11%, P = 0.000). Multivariate regression showed that lower pre-op SLL (OR 0.750, P = 0.000), more anterior cage position (OR 1.269, P = 0.000), and a greater spondylolisthesis reduction rate (OR 0.965, P = 0.000) significantly impacted SLL restoration. CONCLUSIONS: Pre-op SLL, cage position, and spondylolisthesis reduction rate were identified as significant predictors of SLL restoration after LFS for DLS. Surgeons are advised to meticulously select patients based on pre-op SLL and strive to position the cage more anteriorly while minimizing spondylolisthesis to maximize SLL restoration.

Surgical treatment of Roussouly type 1 with realigning Roussouly spinal shape and improving SRS-Schwab modifier: effect on minimal clinically important difference.

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.

Development and external validation of a predictive model for prolonged length of hospital stay in elderly patients undergoing lumbar fusion surgery: comparison of three predictive models.

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.

The association between body mass index and bone mineral density in older adults: a cross-sectional study of community population in Beijing.

BACKGROUND: Older subjects have a higher risk for vertebral compression fracture. Maintaining a higher bone mineral density (BMD) at this age can protect individuals from osteoporosis-related events. Body mass index (BMI) has been found to have a robust association with BMD. However, excessive BMI is detrimental to bone health and may cause systemic disorders. Therefore, the present study aimed to determine the association between BMI and BMD, and identify a reasonable BMI range. METHODS: A total of 961 participants were recruited from community-dwelling residents between August 2021 and May 2022. A weighted multivariate linear regression model was applied to identify the relationship between BMI and BMD. Meanwhile, subgroup stratified analysis by BMI quartile and gender was also performed. A non-linear relationship and threshold value were determined based on the smooth curve fittings and threshold effects analysis model. RESULTS: A robust relationship was found between BMI and BMD, which remained significant in subgroups stratified by gender and BMI quartile. The BMI inflection point values in lumbar BMD and femoral neck BMD were 25.2 kg/m2 and 27.3 kg/m2, respectively. For individuals with BMI < 25.2 kg/m2, an increase in BMI was related to an increase in lumbar BMD. For BMI > 25.2 kg/m2, an increase in BMI was associated with a decrease in lumbar BMD. For subjects with BMI < 27.3 kg/m2, the femoral neck BMD rose by 0.008 kg/m2 for each unit rise in BMI. However, when BMI exceeded 27.3 kg/m2, the femoral neck BMD increased only by 0.005 kg/m2. Fracture risk assessment based on the spinal deformity index (SDI) failed to determine the optimal BMI range. CONCLUSIONS: This study found an inflection point between BMI and lumbar/ femoral neck BMD in older community-dwelling subjects. An appropriate BMI but not an excessive BMI may allow older adults to have a better BMD.

Psoas attenuation is associated with early postoperative complications in geriatric patients undergoing multilevel lumbar fusion surgery for degenerative lumbar spinal stenosis.

BACKGROUND: Morphometric analysis of the psoas major muscle has shown utility in predicting postoperative morbidity in various surgical fields, but its usefulness in predicting complications in elderly patients undergoing multilevel lumbar fusion surgery has not been studied. The study aimed to investigate if psoas major parameters are independent risk factors of early postoperative complication among elderly patients. METHODS: Patients who underwent multilevel lumbar fusion for degenerative lumbar spinal stenosis (DLSS) were included. The psoas major was measured at the lumbar 3/4 intervertebral disc level in three ways on computed tomography image: psoas muscle mass index, mean muscle attenuation, and morphologic change of the psoas major. Early complications were graded using the Clavien-Dindo classification system and the Comprehensive complication index (CCI). A CCI ≥ 26.2 indicated severe complications. Logistic regression was performed to identify independent risk factors. RESULTS: This retrospective study reviewed 108 patients (mean age 70.9 years, female to male ratio 1.8:1). Complications were observed in 72.2% of patients, with allogeneic blood transfusion being the most frequent (66.7%), followed by wound infection, acute heart failure (2.8% each). Severe complications occurred in 13.9% of patients. After multivariable regression analysis, those in the lowest psoas muscle attenuation tertile had higher odds of experiencing early postoperative complications (OR: 3.327, 95% CI 1.134-9.763, p = 0.029) and severe complications (OR: 6.964, 95% CI 1.928-25.160, p = 0.003). CONCLUSION: The psoas muscle attenuation can be used as a predictor of early postoperative complications in elderly patients undergoing multilevel lumbar fusion surgery for DLSS.

Association between delayed ambulation and increased risk of adverse events after lumbar fusion surgery in elderly patients.

PURPOSE: The relationship between delayed ambulation (DA) and postoperative adverse events (AEs) following transforaminal lumbar interbody fusion (TLIF) in elderly patients remains elusive. The aim of our study was to evaluate the effects of DA on the postoperative AEs including complications, readmission and prolonged length of hospital stay (LOS). METHODS: This was a retrospective analysis of a prospectively established database of elderly patients (aged 65 years and older) who underwent TLIF surgery. The early ambulation (EA) group was defined as patients ambulated within 48 h after surgery, whereas the delayed ambulation (DA) group was patients ambulated at a minimum of 48 h postoperatively. The DA patients were 1:1 propensity-score matched to the EA patients based on age, gender and the number of fused segments. Univariate analysis was used to compare postoperative outcomes between the two groups, and multivariate logistic regression analysis was used to identify risk factors for adverse events and DA. RESULTS: After excluding 125 patients for various reasons, 1025 patients (≤ 48 h: N = 659 and > 48 h: N = 366) were included in the final analysis. After propensity score matching, there were 326 matched patients in each group. There were no significant differences in the baseline data and the surgery-related variables between the two groups (p > 0.05). The patients in the DA group had a significant higher incidence of postoperative AEs (46.0% vs. 34.0%, p = 0.002) and longer LOS (p = 0.001). Multivariate logistic regression identified that age, operative time, diabetes, and DA were independently associated with postoperative AEs, whereas greater age, higher international normalized ratio, and intraoperative estimated blood loss were identified as independent risk factors for DA. CONCLUSIONS: Delayed ambulation was an independent risk factor for postoperative AEs after TLIF in elderly patients. Older age, increased intraoperative blood loss and worse coagulation function were associated with delayed ambulation.

How does cervical sagittal profile change after the spontaneous compensation of global sagittal imbalance following one- or two-level lumbar fusion.

PURPOSE: This study aimed to evaluate the cervical sagittal profile after the spontaneous compensation of global sagittal imbalance and analyze the associations between the changes in cervical sagittal alignment and spinopelvic parameters. METHODS: In this retrospective radiographic study, we analyzed 90 patients with degenerative lumbar stenosis (DLS) and sagittal imbalance who underwent short lumbar fusion (imbalance group). We used 60 patients with DLS and sagittal balance as the control group (balance group). Patients in the imbalance group were also divided into two groups according to the preoperative PI: low PI group (≤ 50°), high PI group (PI > 50°). We measured the spinal sagittal alignment parameters on the long-cassette standing lateral radiographs of the whole spine. We compared the changes of spinal sagittal parameters between pre-operation and post-operation. We observed the relationships between the changes in cervical profile and spinopelvic parameters. RESULTS: Sagittal vertical axis (SVA) occurred spontaneous compensation (p = 0.000) and significant changes were observed in cervical lordosis (CL) (p = 0.000) and cervical sagittal vertical axis (cSVA) (p = 0.023) after surgery in the imbalance group. However, there were no significant differences in the radiographic parameters from pre-operation to post-operation in the balance group. The variations in CL were correlated with the variations in SVA (R = 0.307, p = 0.041). The variations in cSVA were correlated with the variations in SVA (R=-0.470, p = 0.001). CONCLUSION: Cervical sagittal profile would have compensatory changes after short lumbar fusion. The spontaneous decrease in CL would occur in patients with DLS after the spontaneous compensation of global sagittal imbalance following one- or two-level lumbar fusion. The changes of cervical sagittal profile were related to the extent of the spontaneous compensation of SVA.

Predictors of achieving minimal clinically important difference in functional status for elderly patients with degenerative lumbar spinal stenosis undergoing lumbar decompression and fusion surgery.

OBJECTIVE: To identify the predictors for the achievement of minimal clinically important difference (MCID) in functional status among elderly patients with degenerative lumbar spinal stenosis (DLSS) undergoing lumbar decompression and fusion surgery. METHODS: Patients who underwent lumbar surgery for DLSS and had a minimum of 1-year follow-up were included. The MCID achievement threshold for the Oswestry Disability Index (ODI) was set at 12.8. General patient information and the morphology of lumbar paraspinal muscles were evaluated using comparative analysis to identify influencing factors. Multiple regression models were employed to identify predictors associated with MCID achievement. A receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for predicting functional recovery. RESULTS: A total of 126 patients (46 males, 80 females; mean age 73.0 ± 5.9 years) were included. The overall rate of MCID achievement was 74.6%. Patients who achieved MCID had significantly higher psoas major muscle attenuation (43.55 vs. 39.23, p < 0.001) and preoperative ODI (51.5 vs. 41.6, p < 0.001). Logistic regression showed that elevated psoas major muscle attenuation (p = 0.001) and high preoperative ODI scores (p = 0.001) were independent MCID predictors. The optimal cut-off values for predicting MCID achievement were found to be 40.46 Hounsfield Units for psoas major muscle attenuation and 48.14% for preoperative ODI. CONCLUSION: Preoperative psoas major muscle attenuation and preoperative ODI were reliable predictors of achieving MCID in geriatric patients undergoing lumbar decompression and fusion surgery. These findings offer valuable insights for predicting surgical outcomes and guiding clinical decision-making in elderly patients.

Prevalence and risk factors of osteoporotic fracture among the elderly population in China: a multicenter cross-sectional study.

PURPOSE: Prevalence of osteoporotic fracture (OPF) is increasing with ageing, resulting in a significant financial burden for healthcare. However, research on the nationwide epidemiological data of OPF in Chinese elderly is still scarce. The aim of this study was to investigate the prevalence and risk factors of OPF in Chinese population aged 60 years or order. METHODS: A cross-sectional survey was conducted in an elderly Chinese population in five centres. Questionnaire investigation and imaging examination were taken in all participants to identify OPF prevalence and risk factors. Diagnosis of OPF was determined based on imaging of vertebral fractures or history of fall-related fractures. We then used multivariate logistic regression model to analyze the associations between the potential risk factors and OPF. RESULTS: The overall prevalence of OPF in population aged 60 years or older was 24.7% (1,071/4,331), showing an increasing trend with age (P < 0.001). The prevalence of OPF was geographically distinct (P < 0.001), but similar between men and women (P > 0.05). Up to 96.8% of OPFs consisted of vertebral fractures, especially involving T11, T12, and L1 segments. Advanced age (≥ 80), vision loss, severe hearing loss, multiple exercise forms, chronic kidney disease, osteoarthritis, and trauma-related vertebral fractures were significantly associated with risk factors, while education level and vitamin D supplementation were associated with protective factors of OPF. CONCLUSION: High prevalence of OPF is a serious threat to bone health among elderly people in China. There is an urgent need for effective strategies to diagnose, prevent, and treat OPF in elderly adults.

Clinical Effect of Dermatologic Trephination Combined With Radiotherapy in the Treatment of Keloids.

BACKGROUND: Keloids are excessive formations of scar tissue that develop at the site of a skin injury. Due to their invasive nature, they have a negative impact on the skin's appearance and are prone to recurrence, making them a challenging condition to treat in terms of skin aesthetics. OBJECTIVES: The objective of this article is to compare the long-term effects of dermatologic trephination with non-surgical treatments in scar repair and evaluate their clinical value. METHODS: A retrospective analysis was conducted on 48 patients who received keloids treatment in the Department of Dermatology and Thoracic Surgery of our hospital from January 2021 to October 2023, of which 24 patients received dermatologic trephination and 24 patients received non-surgical treatment. Outcome measures included scar appearance, scar healing time, pain and itching levels, and patient satisfaction. RESULTS: In the comparison of scar healing time, the healing time of patients using dermatologic trephination was significantly shorter than that of patients in the non-surgical group. In the evaluation of the degree of itching, the degree of itching in patients undergoing dermatologic trephination was significantly lower than that of patients in the non-surgical group. In the evaluation of satisfaction, the satisfaction of patients using dermatologic trephination was significantly higher than that of patients in the non-surgical group. CONCLUSIONS: This study demonstrates that trephination achieves more significant long-term results in keloid revision, including improved keloid appearance, itching and patient satisfaction.

Ampicillin exacerbates acetaminophen-induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction.

BACKGROUND AND AIMS: Antibiotics (ATBx) and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury (ALI) and might be used in combination with ATBx in clinics. However, the impact of ATBx on APAP-induced ALI has rarely been studied. METHODS: First, we compared the effects of seven ATBx on APAP-induced ALI. Then, we analysed faecal, serum and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short-chain fatty acids in this process. RESULTS: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin (Amp) instead of other ATBx. Amp exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP-induced ALF, which was proven by faecal microbiota transplantation from ATBx-treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in Amp-treated mice. Gavage with Lactobacillus, especially Lactobacillus rhamnosus, significantly reversed the severer ALF induced by APAP and Amp. Moreover, Lactobacillus supplementation increased butyrate-producing clostridia and lowered butyrate levels in Amp-treated mice. In accordance, butyrate supplementation could also alleviate Amp-aggravated ALI. In addition, inhibition of nuclear factor erythroid 2-related factor 2 counteracted the protective effect of butyrate on aggravated ALI induced by Amp and APAP. CONCLUSION: Together, this study revealed a potential health impact of Amp that may exacerbate liver damage when co-exposed to excess APAP.

Host ALDH2 deficiency aggravates nonalcoholic steatohepatitis through gut-liver axis.

Nonalcoholic steatohepatitis (NASH) is the major cause of liver dysfunction. Animal and population studies have shown that mitochondrial aldehyde dehydrogenase (ALDH2) is implicated in fatty liver disease. However, the role of ALDH2 in NASH and the underlying mechanisms remains unclear. To address this issue, ALDH2 knockout (ALDH2-/-) mice and wild-type littermate mice were fed a methionine-and choline-deficient (MCD) diet to induce a NASH model. Fecal, serum, and liver samples were collected and analyzed to investigate the impact of the gut microbiota and bile acids on this process. We found that MCD-fed ALDH2-/- mice exhibited increased serum pro-inflammation cytokines, hepatic inflammation and fat accumulation than their wild-type littermates. MCD-fed ALDH2-/- mice exhibited worsened MCD-induced intestinal inflammation and barrier damage, and gut microbiota disorder. Furthermore, mice receiving microbiota from MCD-fed ALDH2-/- mice had increased severity of NASH compared to those receiving microbiota from MCD-fed wild-type mice. Notably, the intestinal Lactobacillus was significantly reduced in MCD-fed ALDH2-/- mice, and gavage with Lactobacillus cocktail significantly improved MCD-induced NASH. Finally, we found that ALDH2-/- mice had reduced levels of bile salt hydrolase and specific bile acids, especially lithocholic acid (LCA), accompanied by downregulated expression of the intestinal FXR-FGF15 pathway. Supplementation of LCA in ALDH2-/- mice upregulated intestinal FXR-FGF15 pathway and alleviated NASH. In summary, ALDH2 plays a critical role in the development of NASH through modulation of gut microbiota and bile acid. The findings suggest that supplementing with Lactobacillus or LCA could be a promising therapeutic approach for treating NASH exacerbated by ALDH2 deficiency.

Radiographic predictors of reaching minimal clinically important difference following lumbar fusion surgery in patients with degenerative lumbar spondylolisthesis.

PURPOSE: The present study aimed to (1) compare sagittal alignment between patients with degenerative lumbar spondylolisthesis (DLS) who reached or missed the minimal clinically important difference (MCID) for clinical outcomes following lumbar fusion surgery (LFS) and (2) identify radiographic predictors associated with MCID achievement in DLS patients. METHODS: A total of 91 single-level DLS patients who underwent LFS and had a minimum of 1-year follow-up were enrolled in this study. The assessed radiographic parameters included thoracic kyphosis, lumbar lordosis (LL), segmental lumbar lordosis (SLL), slip percentage, sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and sagittal vertical axis. Changes in radiographic parameters were determined by subtracting the preoperative value from the final follow-up measurement. Clinical outcomes were assessed using the Oswestry Disability Index (ODI) and the visual analog scale (VAS) for both back and leg pain. MCID values were set at 10 points for ODI, 2.1 points for VAS back pain, and 2.8 points for VAS leg pain. Patients were assigned to the reached MCID (rMCID) and missed MCID (mMCID) groups based on the postoperative (post-op) recovery of clinical outcomes. RESULTS: At the last follow-up, 68.1% (62/91), 72.5% (66/91), and 76.9% (70/91) of patients reached MCID for ODI, VAS back pain, and VAS leg pain, respectively. Concerning ODI, the rMCID group exhibited higher post-op LL (47.93° vs. 42.95°, P = 0.044), higher post-op SLL (17.08° vs. 14.41°, P = 0.032), higher post-op SS (34.46° vs. 30.63°, P = 0.027), higher ∆LL (5.90° vs. 2.44°, P = 0.017), higher ∆SLL (4.63° vs. - 1.03°, P < 0.001), higher ∆SS (4.76° vs. 1.23°, P = 0.002), lower post-op PT/PI (36.95% vs. 42.01%, P = 0.049), lower ∆PT (- 3.71° vs. 1.05°, P < 0.001), lower ∆PT/PI (- 7.45% vs. 1.97%, P < 0.001), and lower ∆PI-LL (- 5.43° vs. - 3.71°, P = 0.011) than the mMCID group. Regarding VAS back pain, the rMCID group showed higher post-op SLL (17.06° vs. 14.05°, P = 0.021), higher post-op SS (34.34° vs. 30.33°, P = 0.027), higher ∆SLL (3.93° vs. - 0.09°, P < 0.001), and lower ∆PT (- 2.91° vs. - 0.30°, P = 0.039) than the mMCID group. For VAS leg pain, higher ∆SLL (3.55° vs. 0.41°, P = 0.003) was observed in the rMCID group than in the mMCID group. Multivariate logistic regression analysis revealed that higher ∆SLL, higher ∆SS, and higher post-op SS were independent predictors for the achievement of MCID in patients with DLS. CONCLUSION: DLS patients who reached MCID following LFS demonstrated improved post-op spinopelvic alignment. Higher ∆SLL, higher ∆SS, and higher post-op SS were the critical parameters associated with MCID achievement in patients with DLS.

Preoperative Zung depression scale predicts outcomes in older patients undergoing short-segment fusion surgery for degenerative lumbar spinal disease.

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.

Description of age-related changes in cervical sagittal alignment based on pelvic incidence classification in asymptomatic Chinese population.

PURPOSE: To investigate the pelvic incidence (PI)- and age-related cervical alignment changes of Chinese healthy population. METHODS: Six hundred and twenty-five asymptomatic adult subjects, who underwent the standing whole spinal radiograph, were recruited in this work. The sagittal parameters were measured, including Occipito-C2 angle (O-C2), C2-7 angle (C2-7), cranial arch, caudal arch, T1-slope (T1S), C2-7 sagittal vertical axis (C2-7 SVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), sacral slope (SS), PI, and sagittal vertical axis (SVA). All subjects were stratified into 5 age groups, namely 40-59 years, 60-64 years, 65-69 years, 70-74 years, and 75 years and above, with each age group further divided into 2 subgroups based on PI (deeming PI < 50° as low PI, and PI ≥ 50° as high PI). The correlations between PI or age, and other sagittal parameters were assessed. The age-related changes of sagittal parameters in each PI subgroup were also assessed, followed by one-way analysis of variance analysis for change comparison between age groups. RESULTS: The average cervical sagittal parameters were as below: 18.2 ± 6.8° for O-C2, 10.4 ± 10.2° for C2-7, 3.9 ± 7.5° for cranial arch, 6.5 ± 7.1° for caudal arch, 23.6 ± 7.3° for T1S, and 21.0 ± 9.7 mm for C2-7 SVA. There was no obvious difference observed between PI and cervical sagittal parameters, excepting for caudal arch. While, C2-7, cranial arch, caudal arch, T1S, and C2-7 SVA increased remarkably with the age. Thereof, C2-7 exhibited great increases at the age of 60-64 years and 70-74 years, respectively, cranial arch increased notably at 60-64 years of age, and caudal arch developed obviously at 70-74 years of age, regardless of PI. CONCLUSION: This study showed the PI- and age-related cervical alignment changes of Chinese healthy population. Based on the classification in our study, high or low PI apparently did not correlate with the occurrence of cervical degenerative disease.

Age-related changes in cervical sagittal alignment: based on 625 Chinese asymptomatic subjects.

PURPOSE: This work aimed to provide a comprehensive description of cervical alignment including cranial arch and caudal arch according to age, thus offering a reference database for cervical deformity treatment. METHODS: Total 150 males and 475 females aged at 48-88 were enrolled from August 2021 to May 2022. Radiographic parameters were measured, including Occipito-C2 angle (O-C2), C2-7 angle (C2-7), cranial arch, caudal arch, T1-slope (T1s), and C2-7 sagittal vertical axis (C2-7 SVA). Pearson correlation coefficient was employed in analyzing associations among sagittal parameters and between age and each parameter. Five groups were set according to different age stages, namely group with age 40-59 (N = 77), group with age 60-64 (N = 189), group with age 65-69 (N = 214), group with age 70-74 (N = 97), and group with age exceeding 75 (N = 48). An analysis of variance (ANOVA) test was applied to compare multi-sets of cervical sagittal parameters (CSPs). Chi-square test or Fisher's exact test was used in assessing the relationships of various cervical alignment patterns with age groups. RESULTS: T1s exhibited the strongest correlation with C2-7 (r = 0.655) and caudal arch (r = 0.561), and moderately correlated with cranial arch (r = 0.355). The positive correlations between age and C2-7 angle (r = 0.189, P < 0.001), cranial arch (r = 0.150, P < 0.001), caudal arch (r = 0.112, P = 0.005), T1s (r = 0.250, P < 0.001), as well as C2-7 SVA (r = 0.090, P = 0.024) were observed. Moreover, two progressive growths of C2-7 were shown after 60-64 and 70-74 years old, respectively. Thereof, cranial arch increased greatly after the age of 60-64, followed by a relative stability in the degeneration. The notable growth of caudal arch was observed after the age of 70-74, and the growth remained stable when exceeding the age of 75. The difference between cervical alignment patterns and age groups was obvious (Fisher's exact test P < 0.001). CONCLUSION: This work explored in detail the normal reference values of cervical sagittal alignment including cranial arch and caudal arch under different age groups. Age-related changes in cervical alignment depended on the increase in the cranial and caudal arches in different proportions with age.