Does MIS-TLIF or TLIF result in better pedicle screw placement accuracy and clinical outcomes with navigation guidance?

BACKGROUND: Although previous studies have suggested that navigation can improve the accuracy of pedicle screw placement, few studies have compared navigation-assisted transforaminal lumbar interbody fusion (TLIF) and navigation-assisted minimally invasive TLIF (MIS-TLIF). The entry point of pedicle screw insertion in navigation-assisted MIS-TLIF (NM-TLIF) may deviate from the planned entry point due to an uneven bone surface, which may result in misplacement. The purpose of this study was to explore the pedicle screw accuracy and clinical consequences of MIS-TLIF and TLIF, both under O-arm navigation, to determine which surgical method is better. METHODS: A retrospective study of 54 patients who underwent single-segment NM-TLIF or navigation-assisted TLIF (N-TLIF) was conducted. In addition to the patients' demographic characteristics, intraoperative indicators and complications, the Oswestry Disability Index (ODI) and visual analog scale (VAS) score were recorded and analyzed preoperatively and at the 1-, 6-, and 12-month and final postoperative follow-ups. The clinical qualitative accuracy and absolute quantitative accuracy of pedicle screw placement were assessed by postoperative CT. Multifidus muscle injury was evaluated by T2-weighted MRI. RESULTS: Compared with N-TLIF, NM-TLIF was more advantageous in terms of the incision length, intraoperative blood loss, drainage volume, time to ambulation, length of hospital stay, blood transfusion rate and analgesia rate (P < 0.05). The ODI and VAS scores for low back pain were better than those of N-TLIF at 1 month and 6 months post-surgery (P < 0.05). There was no significant difference in the clinical qualitative screw placement accuracy (97.3% vs. 96.2%, P > 0.05). The absolute quantitative accuracy results showed that the axial translational error, sagittal translational error, and sagittal angle error in the NM-TLIF group were significantly greater than those in the N-TLIF group (P < 0.05). The mean T2-weighted signal intensity of the multifidus muscle in the NM-TLIF group was significantly lower than that in the N-TLIF group (P < 0.05). CONCLUSIONS: Compared with N-TLIF, NM-TLIF has the advantages of being less invasive, yielding similar or better screw placement accuracy and achieving better symptom relief in the midterm postoperative recovery period. However, more attention should be given to real-time adjustment for pedicle insertion in NM-TLIF rather than just following the entry point and trajectory of the intraoperative plan.

[Finite element analysis of anatomic plate fixation for proximal clavicular fractures].

OBJECTIVE: To explore establishment and finite element analysis of personalized proximal clavicular anatomical plate screw fixation model. METHODS: A 40-year-old male healthy volunteer was selected and the finite element analysis modules of 3D reconstruction software Mimics 15.01, Hypermesh 2019 and Abaqus 2020 were used. The finite element model of anatomic plate at the proximal clavicle was established, and a vertical load of 250 N was applied to the distal end of long axis of clavicle about 15 mm, then the overall structure, plate and screw displacement cloud image, Mises stress distribution were observed. RESULTS: The displacement distribution of the overall structure shows the maximum displacement was distributed on the distal clavicle. Under the four conditions of normal upper limb weight, longitudinal clavicle fracture, oblique fracture and shoulder impact violence during fall, longitudinal clavicle fracture and oblique fracture, the maximum displacement were 1.04 mm, 1.03 mm, 1.35 mm and 1.33 mm, respectively. The displacement cloud map of titanium alloy steel plate showed the largest displacement was distributed near the distal clavicular bone, and the maximum displacement were 0.89 mm, 0.88 mm, 1.10 mm and 1.09 mm, respectively. The displacement cloud map of titanium alloy screw showed the largest displacement was distributed at the root of the distal screw, and the maximum displacement were 0.88 mm, 0.87 mm, 1.08 mm and 1.06 mm, respectively. Mises stress distribution showed the maximum stress was mainly distributed on titanium alloy plates and screws, and the stress on the clavicle was very small. Mises stress distribution cloud showed the maximum Mises stress was distributed at the second row of screw holes near the clavicle, and the maximum Mises stress were 673.1, 678.1, 648.5, 654.4 MPa, respectively. The maximum stresses of titanium alloy screws were 414.5, 417.4, 415.8 and 419.7 MPa, respectively. CONCLUSION: The biomechanical changes of personalized proximal clavicular anatomical plates are demonstrated by using 3D finite element method to provide biomechanical data for personalized proximal clavicular anatomical plates.

Network meta-analysis of combination strategies in metastatic hormone-sensitive prostate cancer.

This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the Cochrane Library were comprehensively searched for eligible randomized controlled trials (RCTs) published from inception to October 2023. Interventions included abiraterone, apalutamide, enzalutamide, docetaxel, darolutamide, and androgen deprivation therapy (ADT), either as doublet or triplet therapies. The outcomes examined were overall survival (OS), progression-free survival (PFS), castration-resistant prostate cancer (CRPC)-free survival, time to symptomatic skeletal event (SSE), and toxicity. The surface under the cumulative ranking curve (SUCRA) was determined to identify the preferred treatments. Ten RCTs were included. The combination of darolutamide, docetaxel, and ADT had the highest SUCRA of 84.3 for OS, followed by combined abiraterone, docetaxel, and ADT (SUCRA = 71.6). The highest SUCRAs for PFS were observed for triplet therapies (abiraterone, docetaxel, and ADT [SUCRA = 74.9], followed by enzalutamide, docetaxel, and ADT [SUCRA = 74.3]) and other androgen receptor axis-targeted therapy-based doublet therapies (SUCRAs: 26.5-59.3). Darolutamide, docetaxel, and ADT had the highest SUCRAs, i.e ., 80.8 and 84.0 regarding CRPC-free survival and time to SSE, respectively. Regarding Grade >3 adverse events (AEs), the SUCRAs of triplet therapies (SUCRAs: 14.8-31.5) were similar to that of docetaxel and ADT (SUCRA = 39.5). Three studies had a low risk of bias in all categories; the remaining studies had at least an unclear risk of bias in at least one category. Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC, with acceptable safety concerns. Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT.

[Digital study on proximal clavicle anatomical plate based on 3D printing technology].

OBJECTIVE: To explore feasibility of 3D metal printing technology combined with virtual design proximal clavicle anatomical plate. METHODS: A 52-year-old male healthy volunteer was retrospectively selected to design proximal clavicle anatomical plate system by using Mimics15.01,NX12.0 and other software. STL data were input into 3D printer to print 1:1 clavicle model and proximal clavicle anatomical plate. The fit of the plate was tested in vitro and the accuracy of screw position was evaluated by imaging. Printing time of model,nail path design and fabrication time of the anatomical plate at proximal clavicle were recorded. RESULTS: The 3D metal printing proximal clavicle anatomical plate fitted well to clavicle model,orientation of proximal clavicle locking screw was accurate,and X-ray and CT scan showed the screw position was good. Printing time of model,the time of nail path design,and the time of making anatomical plate of proximal clavicle were 120,15 and 300 min respectively. CONCLUSION: The proximal clavicular anatomical plate system based on 3D metal printing technology could achieve good lamination of proximal clavicular fracture plate and precise screw placement,providing a new and accurate surgical method for the treatment of the proximal clavicular fracture.

Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy.

Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified, TCEB1 (3/18) and VHL (3/18) variants occurred at the highest frequencies. Germline mutation detection showed that nine variants associated with Fanconi anemia (VAFAs) pathway (FANCA, 6/18; FANCI, 3/18) were identified in 18 ccpRCC patients. Among ccpRCC patients with VAFAs, five out of eight patients had second primary malignancy or family history of cancer. Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.

[Preliminary development of guided template of middle and upper thoracic percutaneous vertebroplasty in thoracic pedicle approach due to three dimentional soft tissue print technique].

OBJECTIVE: To investigate the feasibility of a drill template for the placement of guided template of middle and upper thoracic percutaneous vertebroplasty in thoracic pedicle approach on digital design and 3D printing technology. METHODS: The preoperative CT images of 20 patients with thoracic fracture were collected retrospectively. With the 3D soft tissue printing technology, the data was reconstructed by 3D imaging reconstruction software to produce 1∶1 three dimensional soft tissue model. The pedicle screw channel and the digital template were designed by the 3-matic module of Mimics15.0 software. After guide template was printed by 3D printer and three dimensional template was fixed on the model, 2.0 mm Kirschner was placed and the accuracy of a drill template was observed by CT scans, bone cement was injected through the puncture tube and verified with images. The time of nail guide design, guide template production and cost were recorded. RESULTS: The effectiveness of three dimensional thoracic model and digital guided template of middle and upper thoracic percutaneous vertebroplasty of thoracic fractures in thoracic pedicle approach was confirmed. Kirschner was placed and the accuracy of screw placement was confirmed with CT scanning. Template and the corresponding anatomical landmark fitted well, bone cement had showed good filling. The average printing time of upper thoracic spine model with soft tissue, the mean time of nail guide design, guide template production and cost were (719.00±3.03) min, (12.30±1.01) min, (55.50±10.30) min and RMB 3 150 yuan on average respectively. CONCLUSION: By means of individual design and 3D soft tissue printingtechnology, accurate placement of guided template of middle and upper thoracic percutaneous vertebroplasty could be realized.

[Meta-analysis of direct anterior approach and other approaches for hemiarthroplasty in elderly patients with femoral neck fracture].

OBJECTIVE: To systematically evaluate the clinical efficacy of high-quality direct anterior approach (DAA) and other approaches for the treatment of elderly patients with femoral neck fracture. METHODS: Literatures published in English or Chinese about the direct anterior approach and other approaches for hemiarthroplasty in femoral neck fracture were searched on Cochrane Library, PubMed, EMBASE, Web of science, Wanfang, CNKI databases from their establishment to May 2019. According to the inclusion and exclusion criteria, two researchers independently screened the literatures, and extracted the data. The quality of RCT were evaluated by Cochrane Risk of Bias Assessment Tool, and non-RCT were evaluated by the NOS scale. Meta-analysis was performed using the RevMan 5.3 software. RESULTS: A total of 9 articles were included with 901 cases, in which 429 cases used DAA, and 472 used other approaches. DAA had a significantly lower dislocation rate compared to subgroup of posterior and posterolateral approach [OR=0.19, 95%CI (0.06, 0.61), P=0.005]. No significant differences were found between DAA group and subgroup of direct lateral and anterolateral approach[OR=1.08, 95%CI(0.20, 5.76), P=0.93]. Also there were no relevant differences between the DAA group and control in infection rate[OR=1.07, 95%CI(0.47, 2.43), P=0.88], perioperative fracture rate[OR=0.95, 95%CI(0.36, 2.50), P=0.92], re operation rate[OR=0.76, 95%CI(0.30, 1.89), P=0.55], overall complication rate [OR=0.88, 95%CI (0.63, 1.22), P=0.44], mortality [OR=1.33, 95%CI (0.84, 2.11), P=0.23], operative time[MD=1.43, 95%CI(-5.85, 8.71), P=0.70]. CONCLUSION: The current evidenceindicates that the DAA was associated with a significantly lower dislocation rate compared to posterior capsular approaches for hemiarthroplasty. There was no significant difference in dislocation rate with the lateral and anterolateral approach.

Development and validation of a robust multigene signature as an aid to predict early relapse in stage I-III clear cell and papillary renal cell cancer.

Background and objectives: Multi-gene signature can be used as prognostic indicator in many types of cancer, but the association with early-relapse in patients with stage I-III clear cell and papillary renal cell cancer (RCC) is unknown. We aim to establish a mRNAs signature for improving prediction of early-relapse in patients with stage I-III clear cell and papillary RCC. Methods: The data of 610 patients with stage I-III RCC from The Cancer Genome Atlas (TCGA) and 270 patients from Fudan University Shanghai Cancer Center (FUSCC) were extracted. Propensity score matching analysis, linear models for microarray data VOOM method, least absolute shrinkage and selection operation Cox regression modeling analysis was conducted in turn for selecting multi-mRNA signature. Survival differences were assessed by Kaplan-Meier estimate and compared using log-rank test. Multivariable Cox regression and time-dependent receiver operating characteristic curves were used to evaluate the association of mRNAs signature with relapse-free survival (RFS). Results: Seventeen mRNAs were identified to constitute the early-relapse signature. Among patients with stage I-III RCC, those with high-risk score calculated from 17 mRNAs signature showed shorter RFS than those with low-risk score, both in TCGA discovery and internal validation sets, and in FUSCC discovery and internal validation sets (all p < 0.05). In multivariable Cox regression analysis, the 17 mRNAs signature remained an independent prognostic factor both in TCGA discovery (HR 2.43, 95%CI 1.98-2.96) and internal validation sets (HR 1.66, 95%CI 1.19-2.30), and FUSCC discovery (HR 1.28, 95%CI 1.13-1.43) and internal validation sets (HR 1.65, 95%CI 1.11-2.48). Additionally, the 17 mRNAs signature achieved a higher accuracy for RFS estimation beyond clinical indicator. Conclusion: The 17 mRNAs signature could classify stage I-III RCC patients into low- or high-risk of early-relapse, and will help to guide interventions to optimize survival outcomes.

Prognostic value of primary tumor surgery in seminoma patients with distant metastasis at diagnosis: a population-based study.

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

Decreased CD4+CD25+CD127dim/- Regulatory T Cells and T Helper 17 Cell Responsiveness to Toll-Like Receptor 2 in Chronic Hepatitis C Patients with Daclatasvir Plus Asunaprevir Therapy.

Direct-acting antivirals (DAAs) not only rapidly inhibited hepatitis C virus (HCV) replication but also modulated innate and adaptive immune response in chronic hepatitis C patients. However, the regulatory activity of DAAs to Toll-like receptor 2 (TLR2) stimulation on CD4+CD25+CD127dim/- regulatory T cells (Tregs) and T helper (Th) 17 cells was not completely understood. In the present study, a total of 23 patients with chronic HCV genotype 1b infection were enrolled, and blood samples were collected at baseline (treatment naive), end of therapy (EOT), and 12 weeks after EOT (SVR12) with daclatasvir plus asunaprevir therapy. TLR2 expression on Tregs and Th17 cells was measured by flow cytometry. Cellular proliferation, cytokine production, and suppressive activity were also tested in purified CD4+CD25+CD127dim/- Tregs in response to the stimulation of Pam3Csk4, an agonist of TLR2. Inhibition of HCV RNA by daclatasvir and asunaprevir did not affect either percentage of Tregs/Th17 cells or TLR2 expression on Tregs/Th17 cells. Pam3Csk4 stimulation also did not influence either cellular proliferation or Tregs/Th17 proportion at each time point. Stimulation with Pam3Csk4 only enhanced the suppressive function and interleukin (IL)-35 production by Tregs purified from baseline, but not those from EOT or SVR12. Similarly, Pam3Csk4 stimulation only elevated Th17 cell frequency of CD4+ T cells from baseline, but not those from EOT or SVR12. Moreover, daclatasvir and asunaprevir therapy did not promote TLR2-induced shift of Tregs toward Th17-like phenotype and function. These data suggested that daclatasvir plus asunaprevir therapy resulted in the decreased responsiveness of Tregs/Th17 cells to TLR2 stimulation in chronic hepatitis C patients, which might provide a novel mechanism underlying DAA-induced immunoregulation.

External validation and newly development of a nomogram to predict overall survival of abiraterone-treated, castration-resistant patients with metastatic prostate cancer.

Abiraterone acetate is approved for the treatment of castration-resistant prostate cancer (CRPC); however, its effects vary. An accurate prediction model to identify patient groups that will benefit from abiraterone treatment is therefore urgently required. The Chi model exhibits a good profile for risk classification, although its utility for the chemotherapy-naive group is unclear. This study aimed to externally validate the Chi model and develop a new nomogram to predict overall survival (OS). We retrospectively analyzed a cohort of 110 patients. Patients were distributed among good-, intermediate-, and poor-risk groups, according to the Chi model. The good-, intermediate-, and poor-risk groups had a sample size of 59 (53.6%), 34 (30.9%), and 17 (15.5%) in our dataset, and a median OS of 48.4, 29.1, and 10.5 months, respectively. The C-index of external validation of Chi model was 0.726. Univariate and multivariate analyses identified low hemoglobin concentrations (<110 g l-1), liver metastasis, and a short time interval from androgen deprivation therapy to abiraterone initiation (<36 months) as predictors of OS. Accordingly, a new nomogram was developed with a C-index equal to 0.757 (95% CI, 0.678-0.836). In conclusion, the Chi model predicted the prognosis of abiraterone-treated, chemotherapy-naive patients with mCRPC, and we developed a new nomogram to predict the overall survival of this group of patients with less parameters.

Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells.

BACKGROUND: The stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell-cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells. METHODS: The exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively. RESULTS: Both the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs. CONCLUSION: Our study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.

Mitochondrial tRNA mutations in patients with myelodysplastic syndromes.

Increasing evidence showed that mitochondria play an important role in the development of myelodysplastic syndromes (MDS). Mitochondrial dysfunctions caused by mitochondrial DNA mutations, especially mitochondrial tRNA mutations, were found to be associated with MDS in many studies. However, the link between a candidate mitochondrial tRNA mutation and MDS was not clear. In this study, we investigated the role of some mitochondrial tRNA mutations, and their deleterious roles were further discussed.

MTHFR c.677C>T Inhibits Cell Proliferation and Decreases Prostate Cancer Susceptibility in the Han Chinese Population in Shanghai.

Methylenetetrahydrofolate reductase (MTHFR) c.677C>T and c.1298A>C variants were known to be associated with prostate cancer (PCa) risk with conflicting results, because of MTHFR and nutrient status interaction in the prostate development. In this large-scale, hospital-based, case-control study of 1817 PCa cases and 2026 cancer-free controls, we aimed to clarify the association between these two MTHFR variants and PCa risk in Shanghai and to explore the underlying molecular mechanisms. We found that both the heterozygous CT (adjusted OR = 0.78, 95% CI: 0.67-0.92) and the homozygous TT genotypes (adjusted OR = 0.68, 95% CI: 0.55-0.83) of c.677C>T were associated with a significantly decreased risk of PCa compared with homozygous wild-type CC genotype, respectively, using multivariate logistic regression. Furthermore, we confirmed that MTHFR c.677T allele was related to an increased serum homocysteine level in the Han Chinese population in Shanghai. In the cultured PCa cell lines, we observed that MTHFR c.677T could elevate the cellular homocysteine level and cause DNA damage, thus increasing cell apoptosis and finally inhibiting cell proliferation. In conclusion, MTHFR c.677T was a protective factor of PCa risk in ethnic Han Chinese males by inducing DNA damage and cell apoptosis.

P15 gene methylation in hepatocellular carcinomas: a systematic review and meta-analysis.

OBJECTIVE: This study was performed to investigate the correlation between P15 methylation and hepatocellular carcinoma (HCC) and hepatocirrhosis using a meta-analysis of available case control studies. METHODS: Previous studies have primarily evaluated the incidence of P15 methylation in HCC and corresponding control groups, and compared the incidence of P15 methylation in liver cirrhosis and control groups. Data regarding publication information, study characteristics, and incidence of P15 methylation in both groups were collected from these studies and summarized. RESULTS: Ten studies that assessed P15 gene methylation in 824 HCC tumour tissues and five studies analyzing P15 methylation in 155 liver cirrhosis tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P15 methylation was significantly higher in HCCs than in adjacent non-tumour tissues (OR 9.04, 95% CI 5.80-14.09, P < 0.00001). Moreover, P15 methylation was significantly higher in liver cirrhosis tissues than in control tissues (OR 7.82, 95% CI 3.58-17.07, P < 0.00001). CONCLUSIONS: we found that P15 methylation was associated with an increased risk of HCC and liver cirrhosis. P15 hypermethylation induced the inactivation of the P15 gene, which played an important role in hepatocarcinogenesis.