Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a noninvasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). RESULTS: A total of 16 studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI: 3.71-10.58, P <0.001) and OS (HR=4.23; 95% CI: 2.72-6.57, P <0.001) regardless of metastatic status, ctDNA sampling time, treatment type, and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI: 0.17-0.41, P <0.001) and OS (HR=0.21, 95% CI: 0.11-0.38, P <0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. CONCLUSION: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.

Predicting abiraterone efficacy in advanced prostate cancer: Insights from marker of proliferation Ki67.

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.

Molecular complexity of intraductal carcinoma of the prostate.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.

Digital protractor as an intraoperative guide to cup anteversion in total hip arthroplasty.

INTRODUCTION: To explore if digital protractor could guide the anteversion of acetabular cup during primary THA and make it consistent with preoperative. METHODS: We retrospectively reviewed 172 cases of primary THA with direct anterior approach (DAA) over 2 years. The anteversion of acetabular cup were measured from computed tomography (CT) scan preoperative and de-identified plain radiographs postoperative by two blinded investigators who were not involved in the surgery. The effect of the digital protractor on the anteversion was determined using regression analysis. RESULTS: The mean anteversion for the THAs in digital protractor group was 15.5°and 21.4°in control group (P < 0.01). The mean anteversion bias for the THAs in digital protractor group was 1.59° and 6.63° in control group (P < 0.01).Regression analysis identified a 10.7% difference in anteversion due to the use of digital protractor (P < 0.01), and THAs performed without digital protractor were six times more likely to result in anteversion of > 25°. The correlation coefficient for the interobserver reliability of the measurement of the two investigators was 0.94. CONCLUSION: The digital protractor is a practical tool in the DAA for THA to determine the anteversion of the acetabular prosthesis.

Is Full-Endoscopic Transforaminal Lumbar Interbody Fusion Superior to Open Transforaminal Lumbar Interbody Fusion for Single-Level Degenerative Lumbar Spondylolisthesis? A Retrospective Study.

BACKGROUND: In this study, we evaluate the clinical efficacy and safety of full-endoscopic transforaminal lumbar interbody fusion (TLIF) for treatment of single-level lumbar degenerative spondylolisthesis. METHODS: Fifty-three patients were divided into two groups according to the surgical techniques: Full endoscopic (Endo)-TLIF (n = 25) and TLIF (n = 28). Clinical efficacy was evaluated pre- and postoperatively. The operation time, operative blood loss, postoperative amount of serum creatine phosphokinase (CPK), postoperative drainage volume, postoperative hospital stay time, total cost, and operative complications were also recorded. RESULTS: Compared with the TLIF group, the Endo-TLIF group had similar intraoperative blood loss, less postoperative increased CPK, less postoperative drainage volume, and shorter postoperative hospital stay, but longer operative time and higher total cost. The postoperative visual analog scale (VAS) scores of back and leg pain and Oswestry Disability Index (ODI) scores significantly improved compared with the preoperative scores in both two groups; more significant improvement of postoperative VAS scores of back pain and ODI scores were shown in the Endo-TLIF group at the 1-month follow-up (p < 0.05). No difference was found in the intervertebral fusion rate between the two groups. CONCLUSION: The Endo-TLIF has similar clinical effect compared with the TLIF for the treatment of lumbar degenerative spondylolisthesis. It also has many surgical advantages such as less muscle trauma, less postoperative back pain, and fast functional recovery of the patient. However, steep learning curve, longer operative time, and higher total cost may be the disadvantages that limit this technique. Also, the Endo-TLIF treatment of patients with bilateral lateral recess stenosis is considered a relative contraindication.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients.

Background: KMT2 (lysine methyltransferase) family enzymes are epigenetic regulators that activate gene transcription. KMT2C is mainly involved in enhancer-associated H3K4me1, and is also one of the top mutated genes in cancer (6.6% in pan-cancer). Currently, the clinical significance of KMT2C mutations in prostate cancer is understudied. Methods: We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study. We investigated the association between KMT2C mutations, other mutations, and pathways. Furthermore, we evaluated the prognostic value of KMT2C mutations, measured by overall survival (OS) and castration resistance-free survival (CRFS). Also, we explored the prognostic value of KMT2C mutations in different patient subgroups. Lastly, we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade (CAB) and abiraterone (ABI) as measured by PSA progression-free survival (PSA-PFS). Results: The KMT2C mutation rate in this cohort is 7.24% (16/221). KMT2C-mutated patients showed worse survival than KMT2C-wild type (WT) patients regarding both CRFS and OS (CRFS: mutated: 9.9 vs. WT: 22.0 months, p = 0.015; OS: mutated: 71.9 vs. WT 137.4 months, p = 0.012). KMT2C mutations were also an independent risk factor in OS [hazard ratio: 3.815 (1.461, 9.96), p = 0.006] in multivariate analyses. Additionally, we explored the association of KMT2C mutations with other genes. This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11 (STK11, p = 0.004) and Catenin Beta 1 (CTNNB1, p = 0.008) mutations. In the CAB treatment, KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients. (PSA-PFS: mutated: 9.9 vs. WT: 17.6 months, p = 0.014). Moreover, KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups. Conclusions: KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS, and KMT2C mutations were associated with STK11 and CTNNB1 mutations. Furthermore, KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.

Retraction to the prognostic value of the pretreatment lung immune prognostic index in patients with metastatic hormone-sensitive and castration-resistant prostate cancer.

[This retracts the article DOI: 10.21037/atm-22-4318.].

Decreased Synovial Fluid Ghrelin Level Is Associated With Acute Cartilage Injury in Patients With Anterior Cruciate Ligament Tear.

Background: Ghrelin, an amino acid hormone secreted primarily from the stomach, can regulate bone metabolism, regulate inflammation via suppressing proinflammatory cytokines, and suppress expression of matrix metalloproteinases (MMPs). Purpose: To measure synovial fluid levels of ghrelin in young patients with anterior cruciate ligament (ACL) tear to assess the role of ghrelin as a potential biomarker for cartilage injury. Study Design: Controlled laboratory study. Methods: This study included 120 patients who underwent ACL reconstructionbetween January 1, 2016, and May 31, 2021. We categorized 60 patients with acute cartilage injury (International Cartilage Regeneration & Joint Preservation Society grade 2 or 3) as the acute group and 60 patients with no acute cartilage injury as the nonacute group, with the healthy contralateral knee of each patient acting as the control group (n = 120). Synovial fluid samples were collected from the knees in the operating room before ACL reconstruction. We assessed the inflammatory biomarkers interleukin (IL)-6, MMP-1, MMP-9, and MMP-13, as well as serum ghrelin level and Mankin score, and results were compared between the 3 study groups with the Mann-Whitney U test. Results: Lower serum ghrelin levels in the synovial fluid were found in the acute group compared with the nonacute group and healthy controls (232.4 vs 434.4 vs 421.5 pg/mL, respectively; P < .001). Ghrelin level in the synovial fluid was significantly and positively correlated with IL-6 (r = 0.4223; P < .0001), MMP-13 (r = 0.3402; P < .0001), and Mankin score (r = 0.1453; P = .0244). Conclusion: In patients with ACL injury, ghrelin synovial fluid was significantly differently expressed in patients with cartilage injury and no cartilage injury. Clinical Relevance: Ghrelin synovial fluid has the potential to be a biomarker to predict acute cartilage injury in patients with ACL injury.

Percutaneous Curved Vertebroplasty and Bilateral-Pedicle-Approach Percutaneous Vertebroplasty in the Treatment of Osteoporotic Vertebral Compression Fracture: A Meta-Analysis.

Introduction: The aim of this study was to evaluate the use of percutaneous curved vertebroplasty procedure (PCVP) and bilateral-pedicle-approach percutaneous vertebroplasty (bPVP) for the treatment of osteoporotic vertebral compression fractures (OVCFs) through a systematic review and meta-analysis of the scientific literature. Methods: A systematic review of the scientific literature in PubMed, China National Knowledge Infrastructure (CNKI), Wanfang and other databases was conducted in conjunction with different keywords. Nine studies were included; all but 3 were randomised controlled studies and all were prospective or retrospective cohort studies. Results: We observed statistically significant differences between the PCVP group and the bPCVP group in terms of postoperative visual analogue scale (VAS) scores (mean difference [MD]: -.08; 95% confidence intervals [CI]: -.15 to .00), bone cement leakage rates (OR = .33; 95%CI: .20 to .54), bone cement injection (MD: -1.52; 95%CI: -1.58 to 1.45), operative times (MD: -16.69; 95%CI: -17.40 to -15.99) and intraoperative fluoroscopies (MD: -8.16; 95%CI: -9.56 to -6.67), with the PCVP group being more dominant. There were no statistical differences in postoperative Oswestry Disability Index (ODI) scores (MD: -.72; 95%CI: -2.11 to .67) and overall bone cement distribution rates (MD: 2.14; 95%CI: .99 to 4.65) between the 2 groups. Conclusions: Meta-analysis showed more favourable outcomes in the PCVP group compared to the bPVP group. PCVP might be effective and safe in the treatment of OVCFs because it relieves postoperative patient pain, reduces operative time and cement injection, and decreases the risk of cement leakage and radiation exposure to the surgeon and patient.

Primary renal mucinous adenocarcinoma masquerading as a giant renal cyst: a case report.

Mucinous adenocarcinoma of the kidney is rarely reported in the literature. We present a previously unreported mucinous adenocarcinoma arising from the renal parenchyma. A 55-year-old male patient with no complaints showed a large cystic hypodense lesion in the upper left kidney on contrast-enhanced computed tomography (CT) scan. A left renal cyst was initially considered, and a partial nephrectomy (PN) was performed. During the operation, a large amount of jelly-like mucus and bean-curd-like necrotic tissue was found in the focus. The pathological diagnosis was mucinous adenocarcinoma, and further systemic examination revealed no clinical evidence of primary disease elsewhere. Then the patient underwent left radical nephrectomy (RN), and the cystic lesion was found in the renal parenchyma, while neither the collecting system nor the ureters were involved. Postoperative sequential chemotherapy and radiotherapy were administered, and no signs of disease recurrence were observed over 30 months of follow-up. Based on a literature review, we summarize the lesion with rarity and the associated dilemma in preoperative diagnosis and treatment. Given the high degree of malignancy, a careful history analysis accompanied by dynamic observation of imaging and tumor markers is recommended for the diagnosis of the disease. Comprehensive treatment based on surgery may improve its clinical outcomes.

Safety and efficacy associated with single-fraction high-dose-rate brachytherapy in localized prostate cancer: a systematic review and meta-analysis.

OBJECTIVE: Although single-fraction high-dose-rate brachytherapy (SFHDR) for localized prostate cancer has been tried in clinical trials, relevant medical evidence is currently lacking. It is necessary to systematically analyze the safety and efficacy of SFHDR. METHODS: Comprehensive and systematic searches for eligible studies were performed in PubMed, Embase, and the Cochrane Library databases. The primary endpoints included safety and efficacy, represented by toxic effects and biochemical recurrence-free survival (bRFS), respectively. The proportion rates were used as the effect measure for each study and were presented with corresponding 95% confidence intervals (CI) and related 95% prediction interval (PI). Restricted maximum-likelihood estimator (REML) and the Hartung-Knapp method were used in the meta-analysis. RESULTS: Twenty-five studies met the inclusion criteria for quantitative analysis, including 1440 patients. The median age of patients was 66.9 years old (62-73 years old) and the median follow-up was 47.5 months (12-75 months). The estimates of cumulative occurrence for severe gastrointestinal (GI) and genitourinary (GU) toxic effects were 0.1% (95% CI 0-0.2%) and 0.4% (95% CI 0-1.2%), and for grade 2 toxic effects were 1.6% (95% CI 0.1-4.7%) and 17.1% (95% CI 5.4-33.5%), respectively. The estimate of 3­year bRFS was 87.5% (95% CI 84.4-90.3%) and 71.0% (95% CI 63.0-78.3%) for 5­year bRFS. The pooled bRFS rates for low-risk patients were 99.0% (95% CI 85.2-100.0%) at 3 years and 80.9% (95% CI 75.4-85.9%) at 5 years, and the risk group was found to be statistically correlated with bRFS (3-year bRFS, P < 0.01; 5­year bRFS, P = 0.04). CONCLUSION: SFHDR is associated with favorable tolerability and suboptimal clinical benefit in patients with localized prostate cancer. Ongoing and planned high-quality prospective studies are necessary to verify its safety and efficacy.

The prognostic value of the pretreatment lung immune prognostic index in patients with metastatic hormone-sensitive and castration-resistant prostate cancer.

Background: The lung immune prognostic index (LIPI) was first reported to predict the effectiveness of immune checkpoint inhibitors in patients with metastatic non-small cell lung cancer and there are no studies investigating the predictive value of LIPI for patients with PCa. This study explores the prognostic value of the LIPI in patients with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC). Methods: Data from 502 patients with mHSPC primarily treated with maximal androgen blockade (MAB; 89% of patients received MAB) and 158 patients with mCRPC who received abiraterone were retrospectively analyzed. All cases were classified into LIPI-good, LIPI-intermediate, and LIPI-poor groups based on their LIPI score as calculated with the derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase level. The potential for LIPI to be used in predicting mCRPC-free survival (CFS), prostate-specific antigen (PSA) response, PSA-progression-free survival (PSA-PFS), and overall survival (OS) was analyzed. A propensity score matching (PSM) methodology was performed to balance the baseline factors of the different groups. Results: In the mHSPC cohort, patients of the LIPI-good (mCFS: 25.7 months; mOS: 93.3 months), LIPI-intermediate (mCFS: 14.8 months; mOS: 51.9 months), and LIPI-poor group (mCFS: 6.8 months; mOS: 18.5 months) had sequentially worse clinical outcomes (P<0.001 for all pairwise comparisons). The results remained consistent after PSM. Multivariate Cox regression further confirmed that LIPI was an independent predictor of survival outcomes. Subgroup analysis verified that LIPI was associated with an unfavorable prognosis in all subgroups except for cases with visceral metastases or those receiving abiraterone or docetaxel. As for patients with mCRPC receiving abiraterone, LIPI was also an indicator of poor prognosis. Specifically, cases in the LIPI-good, LIPI-intermediate, and LIPI-poor groups had a ladder-shaped worse PSA response [71.4% (50/70) vs. 56.5% (39/69) vs. 36.8% (7/19); P=0.015], PSA-PFS (14.9 vs. 9.3 vs. 3.1 months; P<0.001), and OS (14.6 vs. 32.3 vs. 53.4 months; P<0.001). The results were robust even after PSM. Multivariate Cox regression confirmed that LIPI was an independent prognosticator of PSA-PFS and OS in patients with mCRPC treated with abiraterone. Conclusions: This study demonstrated that the baseline LIPI was a significant prognostic biomarker for patients with both mHSPC and mCRPC and could potentially facilitate risk classification and clinical decision-making.

Neuroendocrine differentiation predicts the therapeutic efficacy of abiraterone and docetaxel as first-line therapy in metastatic castration-resistant prostate cancer.

PURPOSE: We aim to explore the predictive value of neuroendocrine differentiation (NED) in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone or docetaxel as first-line therapy. METHODS: We retrospectively analyzed data of 262 mCRPC patients receiving abiraterone or docetaxel as first-line mCRPC treatment. NED was evaluated using prostate biopsy samples at the time of mCRPC by immunohistochemical staining. Kaplan-Meier curves and Cox regression were used to assess the association between NED and treatment outcomes including PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS). RESULTS: NED was confirmed in 100/262 (38.2%) mCRPC patients, with 76/100 (76.0%) and 24/100 (24.0%) men harboring NED < 10% and NED ≥ 10%, respectively. 203/262 (77.5%) and 59/262 (22.5%) patients received abiraterone and docetaxel, respectively. In abiraterone treatment, NED was associated with a significantly shorter median PSA-PFS (mPSA-PFS, 7.5 vs. 10.3-Mo, P < 0.001), median rPFS (mrPFS, 15.9 vs. 19.5-Mo, P = 0.010), and median OS (mOS, 23.2 vs. 34.3-Mo, P = 0.014)). Likewise, for mCRPC patients receiving docetaxel, the positive detection of NED also predicted shorter mPSA-PFS (3.8 vs. 5.9-Mo, P = 0.052), mrPFS (8.4 vs. 20.4-Mo, P = 0.016) and mOS (13.6 vs. 29.0-Mo, P = 0.033). The adverse prognostic trait of NED is consistent in most subgroups. Additionally, patients' survival outcomes deteriorated as the NED proportion grew in both therapies. After propensity score matching, NED-positive patients showed comparable prognosis in abiraterone and docetaxel therapy. CONCLUSION: For mCRPC patients receiving abiraterone or docetaxel, NED and its proportion were critical predictive factors. NED detection at mCRPC might aid in predicting patients' outcomes and optimizing treatment decisions.

The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (223Ra) combined with new-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapies remains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of 223Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bone mCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), five retrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the 223Ra+NHA combination group and the 223Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91-2.34, P = 0.66), but the incidences in both the 223Ra+NHA combination group (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01) and the 223Ra monotherapy group (OR: 2.24, 95% CI: 1.23-4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, in the meta-analysis involving only RCTs, there was no difference between the 223Ra monotherapy group and the NHA monotherapy group (OR: 1.14, 95% CI: 0.22-5.95, P = 0.88), while the difference between the 223Ra+NHA combination group and the NHA monotherapy group remained significant (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-free survival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significant difference. Our results indicate that the combination of 223Ra with NHAs was well tolerated in bone mCRPC patients compared to 223Ra monotherapy, even though the incidence of fracture was higher in patients who received 223Ra than that among those who received NHA monotherapy. More evidence is needed to explore the safety and efficiency of 223Ra combination therapies.

Effect of pharmacist intervention on antibiotic prophylaxis in orthopedic internal fixation: A retrospective study.

BACKGROUND: Despite the availability of guidelines and official policies, antibiotic prophylaxis in clean surgery remains suboptimal. OBJECTIVE: The aim of this study was to evaluate the clinical effects and cost-effectiveness of pharmacist-led intervention in the perioperative anti-infection prophylaxis of patients undergoing orthopedic internal fixation. METHODS: We performed a retrospective analysis based on the medical records of internal fixation surgery in a tertiary hospital from July 2019 to June 2020. Data were divided into two groups based on whether a full-time pharmacist participated in the treatment. The research parameters included use of antibiotics, rationality of medication, postoperative complications, and related cost. To deal with selection bias, propensity score matching method was employed at a ratio of 1:1. Meanwhile, a cost-effectiveness analysis was used to evaluate the impact of pharmacist intervention on antibiotic prevention in internal fixation surgery. RESULTS: A total of 537 participants were included in this study. After matching, 236 patients were comparable in each group. During the pharmacist intervention period, less pharmacologic prophylaxis (96.6% vs 100.0%, p = 0.007) and shorter prophylaxis duration (1.60 vs 2.28 days, p < 0.001) were observed. The reasonable rate increased dramatically in usage and dosage (96.6% vs 83.9%, p < 0.001), timing of administration (94.5% vs 78.4%, p < 0.001) and medication duration (64.4% vs 37.7%, p < 0.001). In addition, pharmacist intervention yielded net economic benefits. A remarkable reduction was observed in average length of stay (10.43 vs 11.14 days, p = 0.012), drug cost ($610.57 vs $706.60, p = 0.001) and defined daily doses (2.31 vs 3.27, p < 0.001). The cost-effectiveness ratios, divided drug cost savings by cost of pharmacist time, were 28:1 for drug and 2:1 for antibiotics, respectively. CONCLUSION: Pharmacist-driven antibiotic stewardship for orthopedic internal fixation patients improved compliance with peri-procedure antibiotic prophylaxis, and reduced the cost and utilization of antibiotics. This helped to bring significant clinical and economic benefits.

Comparison of Complications between Anterior Cervical Diskectomy and Fusion versus Anterior Cervical Corpectomy and Fusion in Two- and Three-Level Cervical Spondylotic Myelopathy: A Meta-analysis.

BACKGROUND: In this study, we systematically analyze the differences in complications between anterior cervical diskectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) in two- and three-level cervical spondylotic myelopathy (CSM). METHODS: We performed a systematic search in MEDLINE, EMBASE, PubMed, Web of Science, Cochrane databases, Chinese Biomedical Literature Database, CNKI, and Wan Fang Data for all relevant studies. All statistical analyses were performed using Review Manager version 5.3. RESULTS: A total of 11 articles with 849 study subjects were included, with 474 patients in the ACDF group and 375 patients in the ACCF group. The results of the meta-analysis showed that in C5 palsy (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.16-1.06), pseudarthrosis (OR: 1.07; 95% CI: 0.23-5.07), dysphagia (OR: 1.06; 95% CI: 0.60-1.86), infection (OR: 0.41; 95% CI: 0.16-1.09), cerebrospinal fluid leakage (OR: 1.21; 95% CI: 0.39-3.73), graft dislodgment (OR: 0.28; 95% CI: 0.06-1.37), and hematoma (OR: 0.32; 95% CI: 0.06-1.83), there are no significant differences between the ACDF and ACCF groups, whereas total complication (OR: 0.50; 95% CI: 0.31-0.80) showed that the ACDF group had a significantly lower morbidity than the ACCF group. Furthermore, the three-level subgroup of ACDF had significantly better results in C5 palsy (OR: 0.31; 95% CI: 0.11-0.88), infection (OR: 0.22; 95% CI: 0.05-0.94), graft dislodgment (OR: 0.07; 95% CI: 0.01-0.40), and total complication (OR: 0.37; 95% CI: 0.23-0.60) compared with the ACCF subgroup. CONCLUSION: In general, postoperative pseudarthrosis, dysphagia, cerebrospinal fluid leakage, hematoma, C5 palsy, infection, and graft dislodgment did not differ significantly between the two groups. Total complication was significantly less in the ACDF group compared to the ACCF group. In the three-level subgroup, the morbidity of C5 palsy, infection, and graft dislodgment was significantly lower in ACDF than in ACCF.

The therapeutic efficacy of radical prostatectomy and external beam radiation therapy in patients with different pathological patterns of prostate cancer.

BACKGROUND: We aim to investigate the prognostic value of different pathological patterns of non-adenocarcinoma prostate cancers (PCa) in radical prostatectomy (RP) and external beam radiation therapy (EBRT). METHODS: Data of 470,258 localized PCa patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance the baseline characteristics of patients in different groups. Kaplan-Meier curves and Cox regression were used for survival analysis. Overall survival (OS) and cancer-specific survival (CSS) were set as endpoints. RESULTS: Totally, 1044 patients with non-adenocarcinoma patterns of PCa were included. Patients with small cell neuroendocrine carcinoma (SCNC) and neuroendocrine differentiation (NED) harbored the worst prognosis in both RP and EBRT among all pathological groups. RP exhibited superior effects to EBRT for this group of cases. Ductal carcinoma (DA) was also related to poorer survival outcomes versus PAC in both local therapies. Yet, for men with DA, both RP and EBRT still improved patients' prognosis against no local therapy (NLT), with RP being the superior modality. Cases harboring mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) shared comparable clinical outcomes to men with PAC. However, for cases with MA, neither RP nor EBRT was related to better survival outcomes against NLT, while for patients with SRCC, both RP and EBRT prolonged patients' survival with similar effects. CONCLUSIONS: Our study provided a comprehensive view of the treatment effect of RP and EBRT in non-adenocarcinoma PCa patients. These findings could facilitate clinicians in making therapeutic decision-making for non-adenocarcinoma patients.

Bridged combined fixation system versus locking plate in the treatment of patients with implant periprosthetic refracture following proximal femoral fracture surgery: A retrospective observational study.

Locking plate (LP) re-fixation is mainly used to treat postoperative implant periprosthetic refractures; however, the extensive trauma and the fixation form of LP make the operation difficult. The bridge combined fixation system (BCFS) is a new clip-rod internal fixation system, and its clinical application is in its infancy. To compare the clinical effect of BCFS and LP in the treatment of geriatric postoperative implant periprosthetic refracture following proximal femoral fracture surgery. Thirty-two patients (14 with BCFS and 18 with LP) with postoperative implant periprosthetic refracture following proximal femoral fracture surgery, who underwent surgery in our hospital, were analyzed retrospectively. The incision length, operation time, intraoperative bleeding volume, postoperative drainage volume, postoperative hospital stay, fracture healing time and complications of each patient were recorded. Regular radiographs were taken after the operation to evaluate the fracture reduction and fixation. All the patients were followed for 12 months to evaluate their limb function by Johner-Wruhs scoring criteria. The patients were followed for an average of 24.1 months, and all achieved bony union, with no complications such as infection, nonunion, and internal fixation instrument falling off and loosening after the operation. Delayed healing occurred in two cases in the LP group. The average value of surgical incision length, operation time, postoperative hospitalization time and fracture healing time in the BCFS group were significantly smaller than those in the LP group, accompanied by a decrease in intraoperative bleeding and postoperative drainage volumes (P < .05). The rate of limb function in the BCFS group (85.7%) was higher than that in the LP group (83.3%), with no significance (P > .05). The BCFS in the refracture around the implant of the proximal femoral fracture exhibited many advantages such as simple operation, strong plasticity, effective reduction of surgical trauma, promotion of fracture healing and early functional rehabilitation, etc, making it an advantageous clinical application.

Theaflavin-3,3'-Digallate Inhibits Erastin-Induced Chondrocytes Ferroptosis via the Nrf2/GPX4 Signaling Pathway in Osteoarthritis.

There is evidence that osteoarthritis (OA) is associated with ferroptosis which is a kind of lipid peroxidation-related cell death. Theaflavin-3,3'-digallate(TF3), a polyphenol compound extracted from black tea, possesses antioxidative and anti-inflammatory properties, but its effects on chondrocyte ferroptosis in osteoarthritis (OA) remain unclear. Our present study aims at exploring the protective role and underlying mechanisms of TF3 against erastin-induced chondrocyte ferroptosis in OA. In human primary chondrocytes treated with erastin alone or combined with different doses of TF3, cell viability was assessed by MTS. Ferroptosis-related proteins, including Gpx4, HO-1, and FTH1, were detected by western blot. The levels of lipid peroxidation and Fe2+ were determined by fluorescence staining. Meanwhile, the change of related proteins in the Nrf2/Gpx4 signaling pathway was determined by western blot. siRNA-mediated Nrf2 knockdown and the Gpx4 inhibitor RSL3 were used to explore molecular mechanisms for TF3-induced ferroptosis in OA chondrocyte. The magnetic resonance imaging (MRI), HE staining, Masson's staining, and immunohistochemistry were used to evaluate articular cartilage damages in the rat OA model. The results showed that Gpx4 expression was markedly downregulated in the chondrocytes of OA patients. TF3 reversed erastin-induced ferroptosis of human cultured chondrocytes, lipid ROS, and Fe2+ production in mitochondria. Moreover, the expression of Gpx4, HO-1, FTH1, and Nrf2 was markedly induced by TF3 in the erastin-treated chondrocytes. The antiferroptotic effect of TF3 was related to enhance Nrf2/Gpx4 signaling pathway. Finally, TF3 inhibited OA progression by alleviating in vivo cartilage damage related to chondrocyte ferroptosis. Thus, TF3 significantly inhibits chondrocyte ferroptosis by activating the Nrf2/Gpx4 signaling pathway, suggesting that TF3 serves as a potential therapeutic supplement for OA treatment.