Diagnosis for autism spectrum disorder children using T1-based gray matter and arterial spin labeling-based cerebral blood flow network metrics.

Introduction: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in motor skills, communication, emotional expression, and social interaction. Accurate diagnosis of ASD remains challenging due to the reliance on subjective behavioral observations and assessment scales, lacking objective diagnostic indicators. Methods: In this study, we introduced a novel approach for diagnosing ASD, leveraging T1-based gray matter and ASL-based cerebral blood flow network metrics. Thirty preschool-aged patients with ASD and twenty-two typically developing (TD) individuals were enrolled. Brain network features, including gray matter and cerebral blood flow metrics, were extracted from both T1-weighted magnetic resonance imaging (MRI) and ASL images. Feature selection was performed using statistical t-tests and Minimum Redundancy Maximum Relevance (mRMR). A machine learning model based on random vector functional link network was constructed for diagnosis. Results: The proposed approach demonstrated a classification accuracy of 84.91% in distinguishing ASD from TD. Key discriminating network features were identified in the inferior frontal gyrus and superior occipital gyrus, regions critical for social and executive functions in ASD patients. Discussion: Our study presents an objective and effective approach to the clinical diagnosis of ASD, overcoming the limitations of subjective behavioral observations. The identified brain network features provide insights into the neurobiological mechanisms underlying ASD, potentially leading to more targeted interventions.

A Novel Mis-Seg-Focus Loss Function Based on a Two-Stage nnU-Net Framework for Accurate Brain Tissue Segmentation.

Brain tissue segmentation plays a critical role in the diagnosis, treatment, and study of brain diseases. Accurately identifying these boundaries is essential for improving segmentation accuracy. However, distinguishing boundaries between different brain tissues can be challenging, as they often overlap. Existing deep learning methods primarily calculate the overall segmentation results without adequately addressing local regions, leading to error propagation and mis-segmentation along boundaries. In this study, we propose a novel mis-segmentation-focused loss function based on a two-stage nnU-Net framework. Our approach aims to enhance the model's ability to handle ambiguous boundaries and overlapping anatomical structures, thereby achieving more accurate brain tissue segmentation results. Specifically, the first stage targets the identification of mis-segmentation regions using a global loss function, while the second stage involves defining a mis-segmentation loss function to adaptively adjust the model, thus improving its capability to handle ambiguous boundaries and overlapping anatomical structures. Experimental evaluations on two datasets demonstrate that our proposed method outperforms existing approaches both quantitatively and qualitatively.

Establishment and Validation of Nomograms and Web Calculators for Different Cement Leakage Risk Types in Pedicle Screw Augmentation for Degenerative Lumbar Stenosis in Osteoporotic Vertebrae.

BACKGROUND: The use of cement in pedicle screw augmentation (PSA) enhances the pullout force of pedicle screws in vertebrae affected by osteoporosis. Risks involved in the use of cement for PSA include nerve injury and vascular damage caused by cement leakage. METHODS: This study included all patients who received PSA for degenerative lumbar stenosis in osteoporotic vertebrae from January 2014 to May 2022. Postoperative computed tomography was used to assess cement leakage. Correlation analysis and logistic regression analyses were used to establish the associated clinical or radiological factors, which were then used to construct nomograms and web calculators. RESULTS: The study comprised 181 patients including 886 screws inserted into 443 vertebrae. Perivertebral cement leakage was significantly associated with female sex, decreased bone mineral density, solid screws, and scattered cement distribution. Cement leakage through segmental veins (type S, 72.1%), leakage through basivertebral veins (type B, 23.9%), and instrument-related leakage (type I, 13.9%) accounted for most cement leakage. Patients with lower bone mineral density and scattered cement distribution were more likely to experience type S or type B leakage. Our analysis data showed that cement augmentation with cannulated and fenestrated screws tended toward concentrated cement distribution. Creation and verification of each nomogram additionally showcased the prognostic capability and medical significance of the corresponding model. CONCLUSIONS: Nomograms and web-based calculators can accurately forecast the probability of cement leakage. PSA should be routinely performed using cannulated and fenestrated screws, along with a moderate amount of high-viscosity cement, with continuous monitoring using fluoroscopy.

Anatomic distribution of basivertebral foramen with a magistral form in vertebral bodies of T10~L5 and its clinical significance for extensive epidural cement leakage in cement-augmented pedicle screw fixation: a multicenter case-control study.

BACKGROUND: There are no reports discussing anatomic distribution of basivertebral foramen (BVF) in the osteoporotic vertebral body, which is critical in the analysis of the risk of epidural cement leakage (ECL) after cement-augmented pedicle screw fixation (CAPSF). METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was used to determine the frequency, width, height, and depth of magistral BVF in T10~L5. Additionally, we measured the distance between BVF and the left/right borders of vertebral body as well as the distance between BVF and upper/lower endplates. Following CAPSF, the severity of ECL and the position of pedicle screws were determined by postoperative CT. Finally, significant risk factors for extensive ECL were identified through binary logistic regression analysis. RESULTS: Of 2968 vertebral bodies ranging from T10 to L5, 801 (42.2%) had a magistral BVF. From T10 to L5, the frequency of magistral BVF appeared to gradually increase. The magistral BVF was much closer to the upper endplate and the depth accounted for about a quarter of anteroposterior diameter of vertebral body. Overall, there were 19 patients (5.1%) and 32 screws (1.7%) with extensive ECL, nine of whom had neurological symptoms. The independent risk factors for extensive ECL were the magistral BVF (OR = 8.62, P < 0.001), more volume of cement injected (OR = 1.57, P = 0.031), reduced distance from screw tip to vertebral midline (OR = 0.76, P = 0.003) and vertebral posterior wall (OR = 0.77, P < 0.001) respectively. CONCLUSION: When planning a CAPSF procedure, it is important to consider anatomical distribution of BVF and improve screw implantation methods.

What is the Preferable Method for the C3 and C7 Segments in Unilateral Open-Door Laminoplasty for Patients Diagnosed with Cervical Spondylotic Myelopathy?

BACKGROUND: Traditional C3-C7 unilateral open-door laminoplasty (UOLP) often leads to various postoperative complications as a result of damage of cervical posterior muscles and nuchal ligaments. We aimed to thoroughly evaluate postoperative outcomes after our modified UOLP versus traditional UOLP in treating multilevel cervical spondylotic myelopathy (MCSM). METHODS: Seventy-six patients with MCSM who underwent the modified UOLP with C3 laminectomy and C7 upper hemilaminectomy (40 patients) or traditional C3-C7 UOLP (36 patients) were included. Preoperative and postoperative cervical radiologic parameters, as well as clinical and surgical outcomes, were evaluated. RESULTS: Postoperatively, Japanese Orthopaedic Association scores improved significantly more in the modified UOLP group than in the traditional UOLP group (P = 0.028), whereas visual analog scale scores and Neck Disability Index improved similarly in both groups. Follow-up scores for Japanese Orthopaedic Association, Neck Disability Index, and visual analog scale were not significantly different between the 2 groups. At the final follow-up, the C2-C7 sagittal vertical axis and T1 slope increased in the traditional UOLP group and did not change in the modified UOLP group and were unchanged in the modified UOLP group. The C2-C7 Cobb angle decreased significantly in the traditional UOLP group and did not change in the modified UOLP group. The modified UOLP group lost less cervical posterior muscle area compared with the traditional UOLP group (3.72% ± 3.54% vs. 6.67% ± 2.81%; P < 0.001). The range of motion in the modified UOLP group was significantly greater than in the traditional UOLP group at the final follow-up (P < 0.001). Also, the modified UOLP group experienced a notable reduction in operative time, blood loss volume, and postoperative hospital stay. CONCLUSIONS: We recommend performing our modified UOLP with C3 laminectomy and C7 upper hemilaminectomy instead of traditional C3-C7 UOLP.

The incidence and risk factors for extensive epidural cement leakage in cement-augmented pedicle screw fixation: a multicenter retrospective study.

INTRODUCTION: In cement-augmented pedicle screw fixation (CAPSF), epidural cement leakage (CL) is a frequently reported complication with the potential for neural injury, especially when it is extensive. To date, there has been no reports discussing basivertebral foramen morphology and pedicle screw placement, which is critical in the analysis of the risk of extensive epidural CL. Thus, this study aimed to identify the incidence and risk factors for extensive epidural CL in osteoporotic patients with CAPSF. MATERIALS AND METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was utilized to characterize basivertebral foramen morphology. Following CAPSF, the severity of epidural CL, the implantation position of pedicle screw and cement extension within the vertebral body were determined by postoperative CT. In this study, significant risk factors for extensive epidural CL were identified through logistic regression analysis. RESULTS: There were 19 patients (5.1%) and 32 screws (1.7%) with extensive epidural CL. Nine patients (involving 19 screws) had neurological symptoms. The independent risk factors for patients with extensive epidural CL were decreased BMD and increased number of augmented screws. Significant predictors for extensive epidural CL were a magistral type of basivertebral foramen, more volume of cement injected, solid screw, a shallower screw implantation, and the smaller distance between the tip of the screw and the midline of vertebral body. CONCLUSION: Extensive epidural CL risk was significant in CAPSF when a magistral basivertebral foramen was present; solid screws and more volume of cement were used; and screw tip was implanted shallower or closer to the midline.

Lower ratio of adjacent to injured vertebral bone quality scores can predict augmented vertebrae recompression following percutaneous kyphoplasty for osteoporotic vertebral fractures with intravertebral clefts.

BACKGROUND: Despite the favorable clinical outcome of percutaneous kyphoplasty (PKP) in symptomatic osteoporotic vertebral fractures (OVFs) patients with intravertebral clefts (IVCs), previous studies have demonstrated a high incidence of augmented vertebrae recompression (AVR). We aim to evaluate the usefulness of the adjacent and injured vertebral bone quality scores (VBQS) based on T1-weighted MRI images in AVR after PKP for OVFs with IVCs. METHODS: Patients who underwent PKP for single OVFs with IVCs between January 2014 and September 2020 were reviewed and met the inclusion criteria. The follow-up period was at least 2 years. Relevant data affecting AVR were collected. Pearson and Spearman correlation coefficients were used to calculate the correlation between the injured and adjacent VBQS and BMD T-score. We determined independent risk factors and critical values using binary logistic regression analysis and receiver operating characteristic curves (ROC). RESULTS: A total of 165 patients were included. Recompression group was found in 42 (25.5%) patients. The independent risk factors for AVR were lumbar BMD T-score (OR = 2.53, p = 0.003), the adjacent VBQS (OR = 0.79, p = 0.016), the injured VBQS (OR = 1.27, p = 0.048), the ratio of adjacent to injured VBQS (OR = 0.32, p < 0.001), and cement distribution pattern. Among these independent significant risk factors, the prediction accuracy of the ratio of adjacent to injured VBQS was the highest (Cutoff = 1.41, AUC = 0.753). Additionally, adjacent and injured VBQS were negatively correlated with lumbar BMD T-scores. CONCLUSION: For the patients after PKP treatment for OVFs with IVCs, the ratio of adjacent to injured VBQS had the best prediction accuracy in predicting recompression and when the ratio of adjacent to injured VBQS was <1.41, the augmented vertebrae were more likely to have recompression in the future.

Clinical Outcomes and Radiologic Parameters of Endoscopic Lumbar Interbody Fusion Using a Novel Nerve Baffle with a Minimum 1-year Follow-up.

OBJECTIVE: Since endoscopic lumbar interbody fusion procedure has established, the insertion of cage requires a large working tube, which may lead to nerve root irritation. A novel nerve baffle was used for endoscopic lumbar interbody fusion (ELIF) and its short-term outcomes were analyzed. METHODS: A total of 62 patients (32 cases in tube group, 30 cases in baffle group) with lumbar degenerative diseases who underwent endoscopic lumbar fusion surgery from July 2017 to September 2021 were retrospectively analyzed. Clinical outcomes were measured using pain visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedic Association Scores (JOA), and complications. Perioperative blood loss was calculated using the Gross formula. Radiologic parameters included lumbar lordosis, surgical segmental lordosis, cage position, and fusion rate. RESULTS: There were significant differences in VAS, ODI, and JOA scores postoperatively, 6 months after operation, and at the last follow-up (P < 0.05) within the 2 groups. The VAS and ODI score and hidden blood loss were significantly lower (P < 0.05) for the baffle group. There was no significant difference in lumbar lordosis and segmental lordosis (P > 0.05). Postoperative disc height was significantly higher than preoperative and follow-up disc heights (P < 0.05) for both groups. There was no statistical difference in fusion rate and cage position parameters or subsidence rate. CONCLUSIONS: Endoscopic lumbar interbody fusion using the novel baffle has more advantages in nerve protection and hidden blood loss reduction than traditional ELIF with working tube. Compared with the working tube procedure, it has similar or even better short-term clinical outcomes.

Hidden Blood Loss and Its Possible Risk Factors in Full Endoscopic Lumbar Interbody Fusion.

BACKGROUND: Full endoscopic lumbar interbody fusion (Endo-LIF) is a representative recent emerging minimally invasive operation. The hidden blood loss (HBL) in an Endo-LIF procedure and its possible risk factors are still unclear. METHODS: The blood loss (TBL) was calculated by Gross formula. Sex, age, BMI, hypertension, diabetes, ASA classification, fusion levels, surgical approach type, surgery time, preoperative RBC, HGB, Hct, PT, INR, APTT, Fg, postoperative mean arterial pressure, postoperative heart rate, Intraoperative blood loss (IBL), patient blood volume were included to investigate the possible risk factors by correlation analysis and multiple linear regression between variables and HBL. RESULTS: Ninety-six patients (23 males, 73 females) who underwent Endo-LIF were retrospective analyzed in this study. The HBL was 240.11 (65.51, 460.31) mL (median [interquartile range]). Fusion levels (p = 0.002), age (p = 0.003), hypertension (p = 0.000), IBL (p = 0.012), PT (p = 0.016), preoperative HBG (p = 0.037) were the possible risk factors. CONCLUSION: Fusion levels, younger age, hypertension, prolonged PT, preoperative HBG are possible risk factors of HBL in an Endo-LIF procedure. More attention should be paid especially in multi-level minimally invasive surgery. The increase of fusion levels will lead to a considerable HBL.

Prediction of subsequent vertebral compression fractures after thoracolumbar kyphoplasty: a multicenter retrospective analysis.

OBJECTIVE: Second fractures at the cemented vertebrae (SFCV) are often seen after percutaneous kyphoplasty, especially at the thoracolumbar junction. Our study aimed to develop and validate a preoperative clinical prediction model for predicting SFCV. METHODS: A cohort of 224 patients with single-level thoracolumbar osteoporotic vertebral fractures (T11-L2) from 3 medical centers was analyzed between January 2017 and June 2020 to derive a preoperative clinical prediction model for SFCV. Backward-stepwise selection was used to select preoperative predictors. We assigned a score to each selected variable and developed the SFCV scoring system. Internal validation and calibration were conducted for the SFCV score. RESULTS: Among the 224 patients included, 58 had postoperative SFCV (25.9%). The following preoperative measures on multivariable analysis were summarized in the 5-point SFCV score: bone mineral density (≤-3.05), serum 25-hydroxy vitamin D3 (≤17.55 ng/mL), standardized signal intensity of fractured vertebra on T1-weighted images (≤59.52%), C7-S1 sagittal vertical axis (≥3.25 cm), and intravertebral cleft. Internal validation showed a corrected area under the curve of 0.794. A cutoff of ≤1 point was chosen to classify a low risk of SFCV, for which only 6 of 100 patients (6%) had SFCV. A cutoff of ≥4 points was chosen to classify a high risk of SFCV, for which 28 of 41 (68.3%) had SFCV. CONCLUSION: The SFCV score was found to be a simple preoperative method for identification of patients at low and high risk of postoperative SFCV. This model could be applied to individual patients and aid in the decision-making before percutaneous kyphoplasty.

Establishment of a novel risk prediction model for recompression of augmented vertebrae at the thoracolumbar junction and modified puncture technique for prevention: a multicenter retrospective study.

OBJECTIVE: Recompression of augmented vertebrae (RCAV) is often seen after percutaneous kyphoplasty (PKP), especially at the thoracolumbar junction. The authors aimed to develop and validate a risk prediction model (nomogram) for RCAV and to evaluate the efficacy of a modified puncture technique for RCAV prevention after PKP for thoracolumbar osteoporotic vertebral fractures (OVFs). METHODS: Patients who underwent PKP for single thoracolumbar OVFs (T10-L2) between January 2016 and October 2020 were reviewed and followed up for at least 2 years. All patients were randomly divided into a training group (70%) and a validation group (30%). Relevant potential data affecting recompression were collected. Predictors were screened by using binary logistic regression analysis to construct the nomogram. Calibration and receiver operating characteristic curves were used to evaluate the consistency of the prediction models. Finally, the efficacy of the modified puncture technique for prevention of RCAV in OVF patients with a preoperative intravertebral cleft (IVC) was further demonstrated through binary logistic regression analysis. RESULTS: Overall, 394 patients were included and 116 of them (29.4%) sustained RCAV. The independent risk factors included decreased bone mineral density, lower level of serum 25-hydroxy vitamin D3, larger C7-S1 sagittal vertical axis (SVA), preoperative IVC, and solid-lump cement distribution. The area under the curve (AUC) of the prediction model was 0.824 in the training group and 0.875 in the validation group patients. The calibration curve indicated the predictive power of this nomogram, with the preoperative IVC having the highest prediction accuracy (AUC 0.705). The modified puncture technique significantly reduced the incidence of RCAV by enhancing bone cement distribution into a sufficiently diffused distribution in OVF patients with preoperative IVC. CONCLUSIONS: The nomogram prediction model had satisfactory accuracy and clinical utility for identification of patients at low and high risk of postoperative RCAV. Patients at high risk of postoperative RCAV might benefit from the target puncture technique and vitamin D supplementation as well as effective antiosteoporotic therapies.

Artificial Intelligence-Driven Morphology-Based Enrichment of Malignant Cells from Body Fluid.

Cell morphology is a fundamental feature used to evaluate patient specimens in pathologic analysis. However, traditional cytopathology analysis of patient effusion samples is limited by low tumor cell abundance coupled with the high background of nonmalignant cells, restricting the ability of downstream molecular and functional analyses to identify actionable therapeutic targets. We applied the Deepcell platform that combines microfluidic sorting, brightfield imaging, and real-time deep learning interpretations based on multidimensional morphology to enrich carcinoma cells from malignant effusions without cell staining or labels. Carcinoma cell enrichment was validated with whole genome sequencing and targeted mutation analysis, which showed a higher sensitivity for detection of tumor fractions and critical somatic variant mutations that were initially at low levels or undetectable in presort patient samples. Our study demonstrates the feasibility and added value of supplementing traditional morphology-based cytology with deep learning, multidimensional morphology analysis, and microfluidic sorting.

The Potential Impact of Basivertebral Foramen Morphology and Pedicle Screw Placement on Epidural Cement Leakage With Cement-Augmented Fenestrated Pedicle Screw Fixation: A Multicenter Retrospective Study of 282 Patients and 1404 Augmented Screws.

BACKGROUND: Epidural cement leakage (CL) is a common complication in cement-augmented fenestrated pedicle screw fixation (CAFPSF) with the potential for neural injury. However, there are no reports discussing basivertebral vein morphology and pedicle screw placement, which are critical in the analysis of the risk of epidural CL after CAFPSF. OBJECTIVE: To identify the incidence and risk factors of epidural CL in osteoporotic patients during CAFPSF. METHODS: Two hundred and eighty-two osteoporotic patients using 1404 cement-augmented fenestrated screws were included. Preoperative computed tomography (CT) was used to characterize the morphology of posterior cortical basivertebral foramen. After CAFPSF, the severity of epidural CL, the implantation position of the screw tip, and cement extension within the vertebral body were determined by postoperative CT scans. In this study, significant risk factors for epidural CL were identified through logistic regression analysis. RESULTS: In total, 28 patients (18.8%) and 108 screws (7.7%) had epidural CL and 7 patients (13 screws) experienced neurological symptoms. Although local epidural CL was generally not clinically significant, extensive epidural leakage posed a higher risk of neurological symptoms. Significant predictors for extensive epidural CL were a magistral type of basivertebral foramen and the smaller distance between the tip of the screw and the posterior wall of the vertebral body. CONCLUSION: In osteoporotic patients receiving CAFPSF, epidural CL is relatively common. The morphology of basivertebral foramen should be taken into account when planning a CAFPSF procedure. It is important to try and achieve a deeper screw implantation, especially when a magistral type of basivertebral foramen is present.

The role of intraoperative electron radiotherapy in centrally located hepatocellular carcinomas treated with narrow-margin (<1 cm) hepatectomy: a prospective, phase 2 study.

Background: Postoperative radiotherapy (RT) is known to play an important role in the treatment of hepatocellular carcinomas (HCCs), but the specific role of intraoperative electron radiotherapy (IOERT) in HCCs remains unclear. The aim of this study was to investigate the safety and efficacy of IOERT in centrally located HCCs treated with narrow-margin (<1 cm) hepatectomy. Methods: This was a single-center, phase 2, prospective non-randomized controlled study, including 268 patients with centrally located HCCs who underwent narrow-margin hepatectomy. The patients were subsequently allocated to the IOERT group (n=59) or to the control group (n=65). The primary outcome of the study was to compare recurrence-free survival (RFS) between the IOERT group and the control group, and the secondary outcome was to compare overall survival (OS) rate between the two groups. Results: Of 268 patients enrolled, a total of 124 were included in the study: 59 in IOERT group, 65 in control group. The 1-, 2-, 3-year RFS rates were 79.3%, 62.1% and 45.8% for patients in the IOERT group, and 47.6%, 28.6%, and 22.9% for patients in the control group, respectively (P=0.025). The 1-, 2-, and 3-year OS rates were 100.0%, 94.9%, and 83.7% for patients in the IOERT group, and 92.3%, 87.5%, and 79.4% for patients in the control group, respectively (P=0.314). Subgroup analysis of MVI (+) patients revealed that RFS and OS are significantly prolonged in the IOERT subgroup as compared to the control, whereas there was no significant difference of RFS and OS between the two groups in MVI (-) patients. Conclusions: IOERT for centrally located HCCs with concurrent narrow-margin hepatectomy was feasible and safe. Statistically better RFS rate was observed in the IOERT group compared to the control group. Subgroup analysis revealed that IOERT was more beneficial for postoperative survival of HCC patients with MVI. Trial Registration: ChiCTR-TRC-12002802; www.who.int/ictrp.

Effect of long-term ageing on graphene oxide: structure and thermal decomposition.

After long-term ageing, the structure of graphene oxide prepared by the modified Hummers method changed. Because of the desorption of oxygen-containing functional groups, the C/O ratio of graphene oxide increased from 1.96 to 2.76. However, the average interlayer distance decreased from 0.660 to 0.567 nm. The content of -CH- and -CH2- decreased; however, the type of oxygen-containing functional groups did not change. Moreover, I D/I G increased from 0.87 to 0.92, indicating that the defect density decreased because of desorbing oxygen functional groups after ageing. When the temperature exceeded 60°C, CO2 produced by decomposing graphene oxide was detected. The thermal decomposition changed after ageing. The decomposition peak temperature decreased from 216°C to 195°C. The CO2 amount produced remained almost unchanged; however, the amount of CO, SO2 and H2O decreased. After ageing, the apparent activation energy of graphene oxide decreased from 150 to 134 kJ mol-1.

A Preliminary Study of Deep-Learning Algorithm for Analyzing Multiplex Immunofluorescence Biomarkers in Body Fluid Cytology Specimens.

INTRODUCTION: Multiplex biomarker analysis of cytological body fluid specimens is often used to assist cytologists in distiguishing metastatic cancer cells from reactive mesothelial cells. However, evaluating biomarker expression visually may be challenging, especially when the cells of interest are scant. Deep-learning algorithms (DLAs) may be able to assist cytologists in analyzing multiple biomarker expression at the single cell level in the multiplex fluorescence imaging (MFI) setting. This preliminary study was performed to test the feasibility of using DLAs to identify immunofluorescence-stained metastatic adenocarcinoma cells in body fluid cytology samples. METHODS: A DLA was developed to analyze MFI-stained cells in body fluid cytological samples. A total of 41 pleural fluid samples, comprising of 20 positives and 21 negatives, were retrospectively collected. Multiplex immunofluorescence labeling for MOC31, BerEP4, and calretinin, were performed on cell block sections, and results were analyzed by manual analysis (manual MFI) and DLA analysis (MFI-DLA) independently. RESULTS: All cases with positive original cytological diagnoses showed positive results either by manual MFI or MFI-DLA, but 2 of the 14 (14.3%) original cytologically negative cases had rare cells with positive MOC31 and/or BerEP4 staining in addition to calretinin. Manual MFI analysis and MFI-DLA showed 100% concordance. CONCLUSION: MFI combined with DLA provides a potential tool to assist in cytological diagnosis of metastatic malignancy in body fluid samples. Larger studies are warranted to test the clinical validity of the approach.

Single Cell Mechanotype and Associated Molecular Changes in Urothelial Cell Transformation and Progression.

Cancer cell mechanotype changes are newly recognized cancer phenotypic events, whereas metastatic cancer cells show decreased cell stiffness and increased deformability relative to normal cells. To further examine how cell mechanotype changes in early stages of cancer transformation and progression, an in vitro multi-step human urothelial cell carcinogenic model was used to measure cellular Young's modulus, deformability, and transit time using single-cell atomic force microscopy, microfluidic-based deformability cytometry, and quantitative deformability cytometry, respectively. Measurable cell mechanotype changes of stiffness, deformability, and cell transit time occur early in the transformation process. As cells progress from normal, to preinvasive, to invasive cells, Young's modulus of stiffness decreases and deformability increases gradually. These changes were confirmed in three-dimensional cultured microtumor masses and urine exfoliated cells directly from patients. Using gene screening and proteomics approaches, we found that the main molecular pathway implicated in cell mechanotype changes appears to be epithelial to mesenchymal transition.

Adjuvant radiotherapy in central hepatocellular carcinoma after narrow-margin hepatectomy: A 10-year real-world evidence.

OBJECTIVE: A prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma (HCC) after narrow-margin hepatectomy (<1 cm). This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy. METHODS: Patients with central HCC after narrow-margin hepatectomy (<1 cm) were prospectively assigned to adjuvant radiotherapy group and control group. Patients' outcome, adverse events, long-term recurrence and survival rates were investigated. RESULTS: The 1-, 5-, and 10-year recurrence-free survival (RFS) rates were 81.0%, 43.9%, and 38.7%, respectively in adjuvant radiotherapy group and 71.7%, 35.8%, and 24.2%, respectively in control group (log-rank test, P=0.09). The 1-, 5-, and 10-year overall survival (OS) rates were 96.6%, 54.7%, and 42.8%, respectively in adjuvant radiotherapy group and 90.2%, 55.1%, and 30.0%, respectively in control group (log-rank test, P=0.20). The 1-, 5-, and 10-year RFS rates for patients with small HCC (≤5 cm) were 91.1%, 51.6%, and 48.4%, respectively in adjuvant radiotherapy group and 80.0%, 36.6%, and 26.6%, respectively in control group (log-rank test, P=0.03). Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group (log-rank test, P=0.05). CONCLUSIONS: Our updated results showed a sustained clinical benefit on reducing recurrence, improving long-term survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy. Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC.

Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma.

After two decades of unchanged paradigms, the treatment strategies for advanced urothelial bladder cancer have been revolutionized by emerging programmed death ligand-1 (PD-L1)/programmed death-1 (PD1) inhibition therapy. Increased evidence is demonstrating the efficacy of PD-L1/PD1 inhibition therapy in both second-line and first-line settings. However, the percentage of patients who benefit from anti-PD-L1/anti-PD1 therapy is still low. Many questions have been raised in the development of biomarker-driven approaches for disease classification and patient selection. In this perspective, we discuss PD-L1/PD1 expression in urothelial bladder carcinoma, review approved anti-PD-L1/anti-PD1 agents for bladder cancer treatment and current ongoing studies investigating combination treatment strategies, and explore PD-L1 expression status for the evaluation of bladder cancer immunotherapy.

Regional Ischemic Preconditioning Has Clinical Value in Cirrhotic HCC Through MAPK Pathways.

BACKGROUND: This study assessed the clinical value of regional ischemic preconditioning (RIP) and the role of the mitogen-activated protein kinase (MAPK) pathways in the protective mechanism of RIP in cirrhotic hepatocellular carcinoma (HCC) patients undergoing hepatectomy. METHODS: Liver resection was performed with hemi-hepatic vascular inflow occlusion (HHV) under RIP (RIP group) or with HHV alone (HHV group). Clinical data, surgical outcomes, and the levels of phosphorylated MAPKs before occlusion and 30 min after reperfusion were estimated. RESULTS: HHV under RIP was associated with less intraoperative blood loss (300 vs. 400 ml; P = 0.042), postoperative plasma transfused (400 vs. 800 ml; P = 0.019), and a higher level of prothrombin activity at postoperative days 3, 5, and 7 compared to HHV alone. The level of phosphorylated ERK protein was significantly increased and the levels of phosphorylated p38 and JNK proteins were significantly decreased 30 min after reperfusion compared to HHV group in the RIP group. CONCLUSIONS: HHV under RIP may have clinical value in cirrhotic HCC patients requiring resection and the protective mechanism of RIP may be associated with changes in the protein phosphorylation level of MAPK pathways.