Construction of a predictive nomogram for functional recovery after Bernese periacetabular osteotomy.

Background and purpose: Surgical indications for Bernese periacetabular osteotomy (PAO) are well-established. However, the extent of postoperative functional recovery varies widely, as observed in clinical follow-ups. Thus, preoperative evaluation is crucial. This study aims to identify factors that influence functional recovery post-PAO and to develop a predictive nomogram. Patients and methods: Retrospective data were collected between December 2016 and March 2022 at The First Affiliated Hospital of Shandong First Medical University. The dataset included demographic and imaging data of patients who underwent PAO. The least absolute shrinkage and selection operator (LASSO) regression was utilized to identify influencing factors, which were further analyzed using multivariate logistic regression to construct a predictive nomogram for post-PAO functional recovery. Result: The analysis identified critical factors affecting functional recovery post-PAO, namely, the preoperative distance from the innermost surface of the femoral head to the ilioischial line, the surgical approach, preoperative acetabular depth, and the continuity of the preoperative Calve line. A nomogram was developed using these significant predictors. The model's validity was demonstrated by the receiver operating characteristic curve, with an area under the curve of 0.864. Additionally, the calibration curve confirmed the nomogram's accuracy, showing a strong correlation between observed and predicted probabilities, indicating high predictive accuracy. Conclusion: This predictive nomogram effectively identifies patients most suitable for PAO, providing valuable guidance for selecting surgical candidates and determining the appropriate surgical approach.

Immune- and metabolism-related gene signature analysis uncovers the prognostic and immune microenvironments of hepatocellular carcinoma.

BACKGROUND: Metabolic reprogramming is an emerging hallmark that influences the tumour microenvironment (TME) by regulating the behavior of cancer cells and immune cells. The relationship between metabolism and immunity remains elusive. The purpose of this study was to explore the predictive value of immune- and metabolism-related genes in hepatocellular carcinoma (HCC) and their intricate interplay with TME. METHODS: We established the immune- and metabolism-related signature (IMRPS) based on the LIHC cohort from The Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis and Cox regression analysis confirmed the prognostic value of IMRPS. We investigated differences in immune cell infiltration, clinical features, and therapeutic response between risk groups. The quantitative real-time PCR (qPCR) was used to confirm the expression of signature genes. Immunohistochemical staining was performed to evaluate immune infiltration features in HCC tissue samples. We conducted cell experiments including gene knockout, cell counting kit-8 (CCK-8), and flow cytometry to explore the role of the IMRPS key gene UCK2 in HCC. RNA-seq was used to further investigate the potential underlying mechanism involved. RESULTS: The IMRPS, composed of four genes, SMS, UCK2, PFKFB4 and MAPT, exhibited significant correlations with survival, immune cell infiltration, clinical features, immune checkpoints and therapeutic response. The IMRPS was shown to be an excellent predictor of HCC prognosis. It could stratify patients appropriately and characterize the TME accurately. The high-risk HCC group exhibited an immunosuppressive microenvironment with abundant M2-like macrophage infiltration, which was confirmed by the immunohistochemistry results. The results of qPCR revealed that the expression of signature genes in 20 HCC tissues was significantly greater than that in adjacent normal tissues. After the key gene UCK2 was knocked out, the proliferation of the Huh7 cell line was significantly inhibited, and monocyte-derived macrophages polarized towards an M1-like phenotype in the coculture system. RNA-seq and GSEA suggested that the phenotypes were closely related to the negative regulation of growth and regulation of macrophage chemotaxis. CONCLUSIONS: This study established a new IMRS for the accurate prediction of patient prognosis and the TME, which is also helpful for identifying new targets for the treatment of HCC.

A novel nomogram to predict the recurrence of hepatocellular carcinoma after liver transplantation using extended selection criteria.

BACKGROUND: Liver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria. METHODS: Retrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram. RESULTS: A total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement. CONCLUSIONS: The nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.

The m6A-related gene signature stratifies poor prognosis patients and characterizes immunosuppressive microenvironment in hepatocellular carcinoma.

Background: N6-methyladenosine (m6A) is the most abundant epitranscriptomic modification of RNA, which can affect RNA metabolism and protein translation. The m6A modification plays a critical role in cancer development, including hepatocellular carcinoma (HCC). Despite several m6A-related signatures in HCC, most of them lack the necessary validation and the reliability is still elusive. Methods: Differentially expressed genes (DEGs) in the Cancer Genome Atlas were comprehensively analyzed to identify m6A signature associated with HCC prognosis. Gene set enrichment analysis, tumor mutation burden (TMB), immune infiltration, and therapeutic response were evaluated. Importantly, mass spectrometry proteomics and multiplex immunofluorescence assays were performed for validation. Results: The m6A-related protein-coding gene signature was established, which can divide HCC into high-/low-risk subgroups with markedly different overall survival (OS) and clinical stages. Furthermore, we validated its reliability and robustness in our 101 independent HCC specimens using proteomic detection and confirmed that our signature readily identified high-risk HCC patients with 3-year survival rates of 44.1% vs. 71.8% in the low-risk group. Functional analysis indicated that the high-risk group might stimulate the cell cycle and activate oncogenic pathways such as MAPK, mTOR, and VEGF, whereas the low-risk group mainly regulated amino acid, fatty acid, and drug metabolism. Additionally, the high-risk group had more TMB, upregulated immune checkpoint molecule expression, including PD-1, CTLA4, TIM3, and LAG3, and preferentially formed an immunosuppressive microenvironment. Accordingly, potential therapeutic responses showed that high-risk patients were potentially sensitive to inhibitors targeting the cell cycle and MAPK signaling, with patients possibly benefiting from immunotherapy. Moreover, multiplex immunofluorescence assays indicated that high-risk HCC samples displayed distinct immunosuppressive features, with abundant M2-polarized macrophages and T-regulatory cell infiltration. Conclusion: The m6A signature had a prominent capacity to evaluate OS and characterize the tumor immune microenvironment of HCC, which may serve as a useful approach for risk stratification management and provide a valuable clue to choosing rational therapeutic strategies.

Early surgical outcomes and influencing factors of high tibial osteotomy.

Objective: To investigate the influencing factors of functional recovery after high tibial osteotomy (HTO). Methods: A retrospective research was carried on 98 patients who underwent HTO between January 2018 and December 2020. In each case, the medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), femoral tibial angle (FTA), hip-knee-ankle (HKA), weight bearing line (WBL) ratio of the knee joint, opening gap, opening angle, American knee society knee score (KSS), US Hospital for Special Surgery (HSS) score, Lysholm score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were measured to determine postoperative function and influential factors of pain through logistic regression analysis. Results: The follow-up time was between 18 and 42 months after operation with an average of 27.66 ± 12.9 per month. Overall functional scores were significantly improved. The influencing factors that may affect the postoperative effect of HTO include age and preoperative WBL ratio of the knee joint (WBL%). After incorporating these two factors into the multivariate logistic regression analysis, for every 1 unit increase in the preoperative WBL%, the probability of postoperative HSS being superior is 1.06 times higher than before [Exp(ß): 1.062, 95% CI: 1.01-1.1, p = 0.018]. For every year increase in age, the probability of an excellent HSS score after surgery was 0.84 times higher than that before surgery [Exp(ß): 0.843, 95% CI: 0.718-0.989, p = 0.036]. Preoperative WBL% ≥ 14.37 was 17.4 times more likely to be rated as excellent postoperative HSS than that <14.37 [Exp(ß): 17.406, 95% CI: 1.621-186.927, p = 0.018]. Conclusion: The postoperative functional scores of the patients significantly improved. Patients with preoperative WBL% ≥ 14.37% had better function after surgery.

The effectiveness and influencing factors of the "Y" line technique in reducing the leg length discrepancy after total hip arthroplasty.

Objective: To introduce a surgical technique (the "Y" line technique) that will control leg length discrepancy (LLD) after total hip arthroplasty and to observe its effectiveness and influencing factors. Methods: According to the inclusion and exclusion criteria, a total of 350 patients were selected in this study; 134 patients in whom used the "Y" line technique was used to control lower limb length were included in Group A and 166 patients treated with freehand methods to control lower limb length were included in Group B. A total of 50 patients in whom the standard anteroposterior x-ray of bilateral hips was taken preoperatively and in whom the "Y" line technique was used during the operation were included in Group C. Results: The postoperative LLD of Group A was 4.74 mm (3.93), that of Group B was 5.85 mm (4.60), and that of Group C was 2 mm (1.00)-the difference was statistically significant (p < 0.001). There were significant statistical differences when comparisons were made between any two groups (p < 0.01). The distribution of postoperative LLD in Group A was better than that in Group B, and this factor was better in Group C than in Group A-the difference was statistically significant (p < 0.001). Severe unequal length rates of the lower extremities (LLD > 10 mm) were 5.97% (8/134) in Group A, 14.3% (24/166) in Group B, and 0% (0/50) in Group C-the difference was statistically significant (p < 0.001). There were significant differences between Group A and Group B and between Group B and Group C (p < 0.05), but there was no significant difference between Group A and Group C (p = 0.078). Conclusion: The "Y" line technique, which does not increase the operating time and patient cost, can effectively reduce postoperative LLD. Insufficient internal rotation of the healthy lower extremity and the low projection position in the preoperative anteroposterior x-ray of the bilateral hips were important factors affecting the accuracy of the "Y" line technique.

What are the significant factors affecting pain in patients with Hartofilakidis type Ι developmental dysplasia of the hip?

OBJECTIVE: To explore the influencing factors of age at onset of pain and severe pain in patients with Hartofilakidis type I developmental dysplasia of the hip (DDH). METHODS: A retrospective study of 83 patients with DDH treated at our hospital from January 2017 to June 2021 was conducted. The age at onset of pain, patients' demographic data, and radiographic parameters were collected. Multiple linear regression was used to determine the influencing factors of age at onset of pain. Cox regression analysis was used to determine the influencing factors of severe pain attacks. RESULTS: According to the results of multiple linear regression analysis, when the distance between the medial femoral head and the ilioischial line increased by one millimetre, the age at onset of pain decreased by 1.7 years (ß = - 1.738, 95% CI - 1.914-[- 1.561], p < 0.001). When the sharp angle increases by one degree, the age at onset of pain decreases by 0.3 years (ß = - 0.334, 95% CI - 0.496-[- 0.171], p < 0.001). According to the results of the Cox regression analysis, for each additional degree of the lateral centre-edge angle (LCEA), the probability of severe pain was reduced by 5% (Exp [ß]: = 0.947, 95% CI 0.898-0.999, p = 0.044). For each additional millimetre in the distance between the medial femoral head and the ilioischial line, the likelihood of severe pain increased by 2.4 times (Exp [ß]: 2.417, 95% CI 1.653-3.533, p < 0.001). CONCLUSION: Larger distances between the medial femoral head and the ilioischial line and sharp angle can lead to an earlier age at onset of pain in patients with DDH. Small LCEA and excessive distance between the medial femoral head and the ilioischial line are risk factors for severe pain.

Analysis of Factors Affecting Early Functional Recovery of Bernese Periacetabular Osteotomy.

OBJECTIVES: To explore factors affecting the efficacy of Bernese periacetabular osteotomy for the treatment of hip dysplasia. METHODS: A retrospective study was conducted on 44 patients with hip dysplasia who underwent Bernese periacetabular osteotomy with a modified Smith-Peterson approach between January 2017 and November 2019. Among them, 40 were women and four were men. The average age was 31.2 ± 9.4. Preoperative and postoperative imaging parameters were measured. The acetabular top tilt angle, lateral central edge angle, acetabular abduction angle, femoral head extrusion index, sphericity index of femoral head, Shenton line, Tonnis grade of osteoarthritis, joint congruency, p/a ratio, acetabular anteversion angle, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale scores, and modified Harris hip score (MHHS) were observed. MHHS were divided into three clinically relevant categories: poor (<70 points), good (70-85 points), and excellent (86-91 points). Patient demographic data, as well as preoperative and postoperative radiographic parameters, were subjected to univariate logistic regression analysis. Multiple regression analysis was used to determine factors influencing postoperative MHHS. RESULTS: The follow-up time was 1.0-3.9 years after surgery, with an average of 1.6 years. By the last follow-up, MHHS increased from 70 points before surgery to 91 points after surgery (P < 0.001), WOMAC pain score decreased from 4 points before surgery to 0 points after surgery (P < 0.001). WOMAC functional score decreased (Preoperative: 18.0 [4.0]; Postoperative: 4.0 [0], P = 0.004). Six patients had sensory disturbance of the lateral femoral cutaneous nerve, four of which recovered completely during follow-up. No other complications related to surgical approach, osteotomy, acetabular displacement, acetabular fixation, and postoperative stage were found. There was no significant vascular, nerve, or visceral injuries in any of the patients. On multiple regression analysis, the probability of the postoperative modified Harris hip score of a hip joint with a preoperative lateral center edge angle ≥4.5° being classified as excellent was six times that of angles <4.5° (Exp[ß]: 6.249, 95% CI: 1.03-37.85, P = 0.046). Regression analysis of other factors found no significant correlation with postoperative functional scores. CONCLUSION: Overall functional scores post-PAO significantly improved, and pain symptoms were significantly reduced. Patients with a preoperative lateral center edge angle ≥4.5° had better joint function after surgery.