Long-Term Outcome of Time-Staged Gamma Knife Radiosurgery for Large Arteriovenous Malformations.

BACKGROUND: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs. METHODS: For patients with large AVMs treated by time-staged GKS over 10 years, time-staged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis. RESULTS: Ninety-six patients were analyzed. For AVMs in the 10-20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20-30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10-20 mL, 20-30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively. Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH. CONCLUSION: Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate.

How does the consecutive use of intraoral scanners affect musculoskeletal health? A preliminary clinical study.

BACKGROUND: Minimizing muscle strain and reducing the risk of musculoskeletal disorders associated with intraoral scanner (IOS) usage require ergonomic awareness, device selection, and workplace adjustments in dental practice. This preliminary clinical study aimed to simulate intraoral scanning tasks using wired and wireless IOSs and assess muscle activation and fatigue for both types. MATERIALS AND METHODS: Fourteen participants performed intraoral scanning tasks using wired and wireless IOSs (i700; MEDIT), with weights of 280 g and 328 g, respectively. The same computer system and software conditions were maintained for both groups (N = 14 per IOS group). Electrodes were placed on arm, neck, and shoulder muscles, and maximal voluntary contraction (MVC) was measured. Surface electromyography (EMG) was performed during the simulation, and EMG values were normalized using MVC. The root mean square EMG (%MVC) and muscle fatigue (%) values were calculated. Statistical comparisons were performed using the Mann-Whitney U and Friedman tests, with the Bonferroni adjustment for multiple comparisons (α = 0.05). RESULTS: Arm (flexor digitorum superficialis) and neck muscles (left sternocleidomastoid and left splenius capitis) showed significantly higher EMG values with wireless IOS (P < 0.05). The neck (left sternocleidomastoid and right levator scapulae) and shoulder muscles (right trapezius descendens) demonstrated significantly higher muscle fatigue with wireless IOS (P < 0.05). CONCLUSIONS: The consecutive use of heavier wireless IOS may increase the risk of muscle activation and fatigue in certain muscles, which may have clinical implications for dentists in terms of ergonomics and musculoskeletal health.

Selection of Convolutional Neural Network Model for Bladder Tumor Classification of Cystoscopy Images and Comparison with Humans.

Purpose: An investigation of various convolutional neural network (CNN)-based deep learning algorithms was conducted to select the appropriate artificial intelligence (AI) model for calculating the diagnostic performance of bladder tumor classification on cystoscopy images, with the performance of the selected model to be compared against that of medical students and urologists. Methods: A total of 3,731 cystoscopic images that contained 2,191 tumor images were obtained from 543 bladder tumor cases and 219 normal cases were evaluated. A total of 17 CNN models were trained for tumor classification with various hyperparameters. The diagnostic performance of the selected AI model was compared with the results obtained from urologists and medical students by using the receiver operating characteristic (ROC) curve graph and metrics. Results: EfficientNetB0 was selected as the appropriate AI model. In the test results, EfficientNetB0 achieved a balanced accuracy of 81%, sensitivity of 88%, specificity of 74%, and an area under the curve (AUC) of 92%. In contrast, human-derived diagnostic statistics for the test data showed an average balanced accuracy of 75%, sensitivity of 94%, and specificity of 55%. Specifically, urologists had an average balanced accuracy of 91%, sensitivity of 95%, and specificity of 88%, while medical students had an average balanced accuracy of 69%, sensitivity of 94%, and specificity of 44%. Conclusions: Among the various AI models, we suggest that EfficientNetB0 is an appropriate AI classification model for determining the presence of bladder tumors in cystoscopic images. EfficientNetB0 showed the highest performance among several models and showed high accuracy and specificity compared to medical students. This AI technology will be helpful for less experienced urologists or nonurologists in making diagnoses. Image-based deep learning classifies bladder cancer using cystoscopy images and shows promise for generalized applications in biomedical image analysis and clinical decision making.

Comparative analysis of recurrence rates between intravesical gemcitabine and bacillus Calmette-Guérin induction therapy following transurethral resection of bladder tumors in patients with intermediate- and high-risk bladder cancer: A retrospective multicenter study.

PURPOSE: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy. MATERIALS AND METHODS: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. RESULTS: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively; p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien-Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). CONCLUSIONS: Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.

Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression.

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Ethanol Extracts of Cornus alba Improve Benign Prostatic Hyperplasia by Inhibiting Prostate Cell Proliferation through Modulating 5 Alpha-Reductase/Androgen Receptor Axis-Mediated Signaling.

PURPOSE: The aim of this study was to investigate the efficacy of ethanol extracts of Cornus alba (ECA) against benign prostatic hyperplasia (BPH) in vitro and in vivo. MATERIALS AND METHODS: The prostate stromal cells (WPMY-1) and epithelial cells (RWPE-1) were used to examine the action mechanism of ECA in BPH in vitro. ECA efficacy was evaluated in vivo using a testosterone propionate (TP)-induced BPH rat model. RESULTS: Treatment with ECA inhibited the proliferation of prostate cells by inducing G1-phase cell cycle arrest through the regulation of positive and negative proteins. Treatment of prostate cells with ECA resulted in alterations in the mitogen-activated protein kinases and protein kinase B signaling pathways. The transcriptional binding activity of the NF-κB motif was suppressed in both ECA-treated prostate cells. In addition, treatment with ECA altered the level of BPH-associated axis markers (5α-reductase, fibroblast growth factor-2, androgen receptor, epidermal growth factor, Bcl-2, and Bax) in both cell lines. Finally, the administration of ECA attenuated the enlargement of prostatic tissues in the TP-induced BPH rat model, accompanied by histology, immunoblot, and serum dihydrotestosterone levels. CONCLUSIONS: These results demonstrated that ECA exerted beneficial effects on BPH both in vitro and in vivo and might provide valuable information in the development of preventive or therapeutic agents for improving BPH.

Corrigendum: Korean Ginseng Berry Extract Enhances the Male Steroidogenesis Enzymes In Vitro and In Vivo.

This corrects the article on p. 446 in vol. 41, PMID: 36649918.

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

BACKGROUND AND AIMS: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Difference of Microbial Community in the Stream Adjacent to the Mixed Antibiotic Effluent Source.

Released antibiotics from source to stream can influence bacterial communities and potentially alter the ecosystem. This research provides a comprehensive examination of the sources, distribution, and bacterial community dynamics associated with varied antibiotic release sources adjacent to the stream. The residual of antibiotics from different sources was determined, and the bacterial community structure was examined to reveal the differences in the bacteria community in the stream. The residual of antibiotics was quantified with liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the Illumina MiSeq platform was utilized to sequence bacterial 16S rRNA genes, providing comprehensive insights into the bacterial community structure in the sediment across five different sites. Results indicated that the presence and distribution of antibiotics were significantly influenced by released sources. In the case of the bacterial community, the Proteobacteria and Firmicutes were the most dominant phyla in the sediment, and especially, the Firmicutes showed higher abundance in sites mostly affected by livestock sources. Additionally, livestock gut bacteria such as Clostridium saudiense, Proteiniclasticum ruminis, and Turicibacter sanguinis were prevalent in antibiotic-contaminated sites adjacent to livestock facilities. Overall, this study provides critical insights into the effect of antibiotic contamination by verifying the relationship between the occurrence of antibiotic residuals and the alteration in the bacterial community in the stream.

Differential effect of cancer-associated fibroblast-derived extracellular vesicles on cisplatin resistance in oral squamous cell carcinoma via miR-876-3p.

Rationale: Platinum-based chemotherapy is commonly used for treating solid tumors, but drug resistance often limits its effectiveness. Cancer-associated fibroblast (CAF)-derived extracellular vesicle (EV), which carry various miRNAs, have been implicated in chemotherapy resistance. However, the molecular mechanism through which CAFs modulate cisplatin resistance in oral squamous cell carcinoma (OSCC) is not well understood. We employed two distinct primary CAF types with differential impacts on cancer progression: CAF-P, representing a more aggressive cancer-promoting category, and CAF-D, characterized by properties that moderately delay cancer progression. Consequently, we sought to investigate whether the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism. Methods: The secretion profile was examined by utilizing an antibody microarray with conditioned medium obtained from the co-culture of OSCC cells and two types of primary CAFs. The effect of CAF-dependent factors on cisplatin resistance was investigated by utilizing conditioned media (CM) and extracellular vesicle (EVs) derived from CAFs. The impacts of candidate genes were confirmed using gain- and loss-of-function analyses in spheroids and organoids, and a mouse xenograft. Lastly, we compared the expression pattern of the candidate genes in tissues from OSCC patients exhibiting different responses to cisplatin. Results: When OSCC cells were cultured with conditioned media (CM) from the two different CAF groups, cisplatin resistance increased only under CAF-P CM. OSCC cells specifically expressed insulin-like growth factor binding protein 3 (IGFBP3) after co-culture with CAF-D. Meanwhile, IGFBP3-knockdown OSCC cells acquired cisplatin resistance in CAF-D CM. IGFBP3 expression was promoted by GATA-binding protein 1 (GATA1), a transcription factor targeted by miR-876-3p, which was enriched only in CAF-P-derived EV. Treatment with CAF-P EV carrying miR-876-3p antagomir decreased cisplatin resistance compared to control miRNA-carrying CAF-P EV. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, there was a positive correlation between IGFBP3 and GATA1 expression and cisplatin sensitivity in OSCC tissues from patients. Conclusion: These results provide insights for overcoming cisplatin resistance, especially concerning EVs within the tumor microenvironment. Furthermore, it is anticipated that the expression levels of GATA1 and miR-876-3p, along with IGFBP3, could aid in the prediction of cisplatin resistance.

Availability of ChatGPT to provide medical information for patients with kidney cancer.

ChatGPT is an advanced natural language processing technology that closely resembles human language. We evaluated whether ChatGPT could help patients understand kidney cancer and replace consultations with urologists. Two urologists developed ten questions commonly asked by patients with kidney cancer. The answers to these questions were produced using ChatGPT. The five-dimension SERVQUAL model was used to assess the service quality of ChatGPT. The survey was distributed to 103 urologists via email, and twenty-four urological oncologists specializing in kidney cancer were included as experts with more than 20 kidney cancer cases in clinic per month. All respondents were physicians. We received 24 responses to the email survey (response rate: 23.3%). The appropriateness rate for all ten answers exceeded 60%. The answer to Q2 received the highest agreement (91.7%, etiology of kidney cancer), whereas the answer to Q8 had the lowest (62.5%, comparison with other cancers). The experts gave low assessment ratings (44.4% vs. 93.3%, p = 0.028) in the SERVQUAL assurance (certainty of total answers) dimension. Positive scores for the overall understandability of ChatGPT answers were assigned by 54.2% of responders, and 70.8% said that ChatGPT could not replace explanations provided by urologists. Our findings affirm that although ChatGPT answers to kidney cancer questions are generally accessible, they should not supplant the counseling of a urologist.

Multiregional analysis of combined hepatocellular-cholangiocarcinoma reveals histologic diversity and molecular clonality.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare type of liver tumour that exhibits both hepatocytic and biliary differentiation within the same tumour. The histology and genomic alterations of recurrent/metastatic cHCC-CC are poorly understood. We selected six patients with cHCC-CC whose recurrent or metastatic tumours were histologically confirmed. Four patients with classic cHCC-CCs and two with intermediate cell carcinomas (ICs) were included. The clinicopathological features were evaluated, and next-generation sequencing was performed in 17 multiregional and longitudinal tumour samples. The histology of recurrent/metastatic lesions of classic cHCC-CCs was variable: hepatocellular carcinoma (HCC) was observed in one (25.0%) patient, cHCC-CC in one (25.0%) patient, and cholangiocarcinoma (CC) in two (50.0%) patients. Among 13 samples from four classic cHCC-CC patients, the most frequent pathological variants were TP53 (46.2%), TERT promoter (38.5%), ARID1A mutations (23.1%), and MET amplification (30.8%). In the sequencing analysis of each HCC and CC component, three (75.0%) of the four classic cHCC-CCs shared pathogenic variants. A large proportion of mutations, both pathogenic and those of undetermined significance, were shared by each HCC and CC component. Regarding ICs, the ATM mutation was detected in one patient. In conclusion, the histology of recurrent/metastatic cHCC-CCs was heterogeneous. Genomic profiling of classic cHCC-CCs revealed similar genomic alterations to those of HCC. Considerable overlapping genomic alterations in each HCC and CC component were observed, suggesting a monoclonal origin. Genetic alterations in ICs were different from those in either HCC or CC, suggesting the distinct nature of this tumour.

Validation of real-time inside-out tracking and depth realization technologies for augmented reality-based neuronavigation.

PURPOSE: Concomitant with the significant advances in computing technology, the utilization of augmented reality-based navigation in clinical applications is being actively researched. In this light, we developed novel object tracking and depth realization technologies to apply augmented reality-based neuronavigation to brain surgery. METHODS: We developed real-time inside-out tracking based on visual inertial odometry and a visual inertial simultaneous localization and mapping algorithm. The cube quick response marker and depth data obtained from light detection and ranging sensors are used for continuous tracking. For depth realization, order-independent transparency, clipping, and annotation and measurement functions were developed. In this study, the augmented reality model of a brain tumor patient was applied to its life-size three-dimensional (3D) printed model. RESULTS: Using real-time inside-out tracking, we confirmed that the augmented reality model remained consistent with the 3D printed patient model without flutter, regardless of the movement of the visualization device. The coordination accuracy during real-time inside-out tracking was also validated. The average movement error of the X and Y axes was 0.34 ± 0.21 and 0.04 ± 0.08 mm, respectively. Further, the application of order-independent transparency with multilayer alpha blending and filtered alpha compositing improved the perception of overlapping internal brain structures. Clipping, and annotation and measurement functions were also developed to aid depth perception and worked perfectly during real-time coordination. We named this system METAMEDIP navigation. CONCLUSIONS: The results validate the efficacy of the real-time inside-out tracking and depth realization technology. With these novel technologies developed for continuous tracking and depth perception in augmented reality environments, we are able to overcome the critical obstacles in the development of clinically applicable augmented reality neuronavigation.

Hepatic hemangioma: proportion and predictor of surgical treatment with emphasis on its growth rate.

BACKGROUND/AIMS: There are limited studies on the management of hepatic hemangiomas (HHs). We investigated the proportion and predictors of surgical resection and analyzed HH growth rates in addition to associated factors. METHODS: A retrospective case-control study of patients treated in 2 centers was conducted. Thirty-six patients who underwent surgical resection were assigned to the case group. Patients who did not undergo surgical treatment were randomly sigselected at a 1:10 ratio and assigned to the control group (n = 360). Baseline characteristics, clinical course and surgical outcomes were analyzed. RESULTS: The proportion of surgically treated HH patients was 0.3% (36 per 11,049). The longest diameter at diagnosis (mean ± standard deviation) was 7.7 ± 5.2 cm in the case group and 2.4 ± 1.8 cm in the control group (p < 0.001). In the multivariate analysis, the presence of more than 2 HHs (odds ratio [OR] 7.64, 95% confidence interval [CI] 1.40-41.72) and a growth rate of more than 4.8%/year (OR 30.73, 95% CI 4.86-194.51) were independently associated with surgical treatment. Symptom development during follow-up was related to HH size > 10 cm (OR 10.50, 95% CI 1.06-103.77, p = 0.04). The subgroup analysis showed substantial growth in 41.3% with an overall mean annual growth rate of 0.14 cm. CONCLUSION: Approximately one in 300 patients with an HH underwent surgical treatment. Multiple HHs and a growth rate of more than 4.8%/year were indications for surgical treatment. Nearly half of the HHs showed growing pattern in our study.

Changes in patient perceptions regarding ChatGPT-written explanations on lifestyle modifications for preventing urolithiasis recurrence.

Purpose: Artificial Intelligence (AI) imitating human-like language, such as ChatGPT, has impacted lives throughout various multidisciplinary fields. However, despite these innovations, it is unclear how well its implementation will assist patients in clinical situations. We evaluated changes in patient perceptions regarding AI before and after reading a ChatGPT-written explanation. Materials and methods: In total, 24 South Korean patients receiving urolithiasis treatment were surveyed through questionnaires. The ChatGPT explanatory note was provided between the first and second questionnaires, detailing lifestyle modifications for preventing urolithiasis recurrence. The study questionnaire was the Korean version of the General Attitudes toward Artificial Intelligence Scale, including positive and negative attitude items. Wilcoxon signed-rank tests were accomplished to compare questionnaire scores before and after receiving the explanatory note. A linear regression analysis with stepwise elimination was used to assess variable (demographic data) accuracy in predicting outcomes. Results: There were significant differences between total negative questionnaire scores pre- and post-surveys of ChatGPT, but not in the positive scores. Among variables, only education level significantly influenced mean score differences in the negative questionnaires. Conclusions: The negative perception change among urolithiasis patients after receiving the explanatory note provided by the AI chatbot program was observed, evidencing that patients with lower education levels expressed a more negative response. The explanatory note provided by the AI chatbot program could provoke an adverse change in AI perception. Negative human responses must be considered to improve and adapt new technology in health care. Only through changing patient perspectives will upgraded AI technology integrate into medical healthcare.

Long-Term Outcome of Unilateral Acoustic Neuromas With or Without Hearing Loss: Over 10 Years and Beyond After Gamma Knife Radiosurgery.

BACKGROUND: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. METHODS: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm3 (range, 0.10-23.30 cm3). The median marginal tumor dose was 12.5 Gy (range, 8.0-15.0 Gy) and the median follow-up duration was 153 months (range, 120-216 months). RESULTS: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively. The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). CONCLUSION: GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.