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Jun Hyeong Song,1 Woo Yong Lee,2 Kyoung Rai Cho,3 Sang Hyun Nam,4 Ki Deok Park,5,&ast; Yongbum Park1,&ast; 1Department of Physical Medicine & Rehabilitation, Sanggye Paik Hospital, Inje UniversityCollege of Medicine, Seoul, Republic of Korea; 2Department of Anesthesiology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea; 3Department of Otorhinolaryngology Head and Neck Surgery, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea; 4Department of Plastic and Reconstructive Surgery, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea; 5Department of Rehabilitation Medicine, Gachon University, Gil Medical Center, Incheon, South Korea&ast;These authors contributed equally to this workCorrespondence: Yongbum ParkDepartment of Physical Medicine & Rehabilitation, Sanggye Paik Hospital, Inje University College of Medicine, Sanggye 7 Dong 761-7, Nowon-gu, Seoul, 139-707, KoreaEmail swc328@naver.comKi Deok ParkDepartment of Rehabilitation Medicine, Gachon University, Gil Medical Center, Namdong-Daero 774 Beon-gil, Namdong-gu, Incheon, Korea, 33 Tel +82-2-950-1145Fax +82-2-935-3076Email bduck@gilhospital.comIntroduction: This study is to compare advantages, safety and mid-term effects of fluoroscopy (FL)-guided transforaminal (TF) to caudal (CA) epidural steroid injection (ESI) for chronic pain after spinal surgery (CPSS) by assessing pain relief and improvement of functionality.Methods: Patients with radicular pain in CPSS who received FL-guided CA (n = 21) or TF (n = 28) ESI were included in this retrospective study. Complication frequencies, adverse events, treatment effects, and functional improvements for each procedure were compared at 1, 3, and 6 months following the last injection.Results: Both the Oswestry Disability Index (ODI) and verbal numeric pain scale scores (VNS) demonstrated improvement in both groups at all 1, 3, and 6 months following the last injection, without meaningful difference between groups (p < 0.05). Moreover, no meaningful difference was present between groups in terms of treatment success rate at every time point. The amount of time used for the injection procedure was shorter in CA group than in TF group (410.32 ± 25.73 seconds vs 640.65 ± 18.03 seconds, p < 0.05). Within 2 weeks of the injection treatment, the patient satisfactory scores were evaluated, with excellent being rated 85.7% (n = 18) among CA-ESI patients and 55.7% (n = 16) among TF-ESI patients (p < 0.05). Logistic regression analysis revealed that variables such as method of injection (CA or TF approach), sex, use of analgesics, pain duration, number of injections, and age were not significant variables for successful treatment results. There were no adverse complications after the procedure in both groups.Conclusion: The outcomes of FL-guided CA-ESI and TF-ESI for CPSS are similar in terms of pain reduction and functional improvements. CA-ESI is associated with lesser procedure time. In addition, compared with the TF-ESI, the patient experiences less discomfort during the injection, and the satisfaction with the injection treatment is confirmed to be better. Accordingly, both methods are effective; however, in the CA approach, patient satisfaction is higher and the procedure time is shorter.Keywords: epidural block, fluoroscopy, transforaminal, caudal, FL, CA, TF

A 2-year-old female child is reported with congenital cholesteatoma of the right external auditory canal. We describe the clinical features, computed tomography finding and surgical treatment. Congenital cholesteatomas can occur within the temporal bone. Congenital cholesteatoma of the external auditory canal is rare. Generally, it appears in the canal floor. Treatment consists of the resolution of granulation and removal of debris. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive., Methods: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities., Results: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy., Conclusions: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients., (© 2024. The Author(s).)

Objective: The lateral spread response (LSR) is an important electrophysiological sign that predicts successful decompression in patients undergoing microvascular decompression (MVD) for hemifacial spasm (HFS). However, LSRs do not consistently correlate with clinical outcomes, and there are cases in which LSRs are absent. In this study, the authors identified a unique pattern on facial nerve electromyography (EMG) when the root exit zone (REZ) is touched. This distinctive EMG pattern, which the authors coined the "Sang-ku sign" (SKS), could aid in identifying the offending vessel on the REZ, even in the absence of LSRs., Methods: Between November 2022 and August 2023, the authors analyzed EMG findings from 185 patients undergoing MVD for HFS. Bipolar stimulation electrodes were placed at the marginal mandibular branch, and recordings were obtained from the frontalis and orbicularis oris muscles. Additionally, stimulation electrodes were placed at the temporal branch, and recordings were obtained from the oris and mentalis muscles. The authors statistically analyzed the presence of SKS and its association with demographic, surgical, clinical outcomes, and anatomical factors., Results: The authors observed a brief, burst-like wave pattern arising from all recorded muscle branches when Teflon felt was placed between the REZ and the facial nerve. This EMG pattern, the SKS, was found in 164 patients (88.6%). Among the factors analyzed, only patient age showed a significant association with the presence of the SKS in univariate analysis (p = 0.007). The presence of the SKS was significantly associated with predicting the disappearance of LSRs (p = 0.045). Clinical outcomes were favorable (99% at the last follow-up) in all cases; thus, no positive correlation was observed in the existence of the SKS and LSRs., Conclusions: The SKS could serve as an excellent guide for the facial nerve REZ during surgery. Given that HFS results from abnormal vascular contact on the REZ, this finding plays a crucial role in ensuring surgical success. Alongside LSRs, the SKS could provide valuable insights for neurosurgeons.

Breast cancer is the most prevalent cancer among women worldwide. B-mode ultrasound (US) is essential for early detection, offering high sensitivity and specificity without radiation exposure. This study introduces a semi-automatic method to streamline breast US report generation, aiming to reduce the burden on radiologists. Our method synthesizes comprehensive breast US reports by combining the extracted information from radiologists' annotations during routine screenings with the analysis results from deep learning algorithms on multimodal US images. Key modules in our method include image classification using visual features (ICVF), type classification via deep learning (TCDL), and automatic report structuring and compilation (ARSC). Experiments showed that the proposed method reduced the average report generation time to 3.8 min compared to manual processes, even when using relatively low-spec hardware. Generated reports perfectly matched ground truth reports for suspicious masses without a single failure on our evaluation datasets. Additionally, the deep-learning-based algorithm, utilizing DenseNet-121 as its core model, achieved an overall accuracy of 0.865, precision of 0.868, recall of 0.847, F1-score of 0.856, and area under the receiver operating characteristics of 0.92 in classifying tissue stiffness in breast US shear-wave elastography (SWE-mode) images. These improvements not only streamline the report generation process but also allow radiologists to dedicate more time and focus on patient care, ultimately enhancing clinical outcomes and patient satisfaction.

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8 + T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4 + breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4 + cancer., Competing Interests: Declaration of interests W.Z. has served as a scientific advisor or consultant for Cstone, NextCure, and Hanchorbio. S. Wang is a co-founder and paid consultant of Ascentage Pharma Group International and owns stock in Ascentage. L.C. has been a scientific founder, consultant, and/or board observer for NextCure, Normunity, Tayu, Zai Lab, Tpioneer, Vcanbio, OncoC4, and GenomiCare and has sponsored research funds from NextCure, Normunity, and DynamiCure. This research is conducted independently and has not received resources from and is unrelated to the scientific and commercial pursuits of these industrial entities, including NextCure., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic Subdural Hemorrhage(cSDH) is often treated with surgical blood drainage, but concerns about recurrence and outcomes persist. Surgical techniques, including irrigation, vary. This study compares the outcomes of irrigation in cSDH surgery., Materials and Methods: From September 2020 to September 2022, 92 cSDH patients underwent surgery. Two different irrigation methods were used: extensive irrigation (IG) and non-irrigation (NIG). Method of irrigation was selected by each surgeon's preference. Parameters measured included volume of hematoma changes, midline shifting, complications, and basic demographics. Recurrence was defined as symptomatic or hematoma expansion more than double the volume before surgery. Factors predicting recurrence and irrigation method impact were analyzed., Results: Eleven patients were excluded because of bilateral or related to other disease. We analyzed 81 patients (44 NIG, 37 IG). Recurrence occurred in 6 IG cases (16.2%) and 1 NIG case (2.3%). Irrigation method significantly affected recurrence (P = 0.043). Age, gender, medication, medical history, and preoperative measurements had no major impact on recurrence. NIG had unexpected cases of intracerebral hemorrhage., Conclusion: Extensive irrigation may increase recurrence in cSDH drainage. Non-irrigation drainage had fewer recurrences, but unexpected complications arose. Careful drainage in non-irrigated cases is crucial., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

In situ AFM observations show that when PILP droplets contact a surface, their initial properties are either a liquid with a high interfacial tension (350 mJ m -2 ) or a soft gel-like material with a low modulus (less than 0.2 MPa). These findings suggest that PILP may initially be liquid-like to infiltrate collagen fibrils, enabling the production of interpenetrating composites, and/or become viscoelastic, to provide a means for moulding minerals.

Clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (ENOC) are ovarian carcinoma histotypes, which are both thought to arise from ectopic endometrial (or endometrial-like) cells through an endometriosis intermediate. How the same cell type of origin gives rise to two morphologically and biologically different histotypes has been perplexing, particularly given that recurrent genetic mutations are common to both and present in nonmalignant precursors. We used RNA transcription analysis to show that the expression profiles of CCOC and ENOC resemble those of normal endometrium at secretory and proliferative phases of the menstrual cycle, respectively. DNA methylation at the promoter of the estrogen receptor (ER) gene (ESR1) was enriched in CCOC, which could potentially lock the cells in the secretory state. Compared with normal secretory-type endometrium, CCOC was further defined by increased expression of cysteine and glutathione synthesis pathway genes and downregulation of the iron antiporter, suggesting iron addiction and highlighting ferroptosis as a potential therapeutic target. Overall, these findings suggest that while CCOC and ENOC arise from the same cell type, these histotypes likely originate from different cell states. This "cell state of origin" model may help to explain the presence of histologic and molecular cancer subtypes arising in other organs., Significance: Two cancer histotypes diverge from a common cell of origin epigenetically locked in different cell states, highlighting the importance of considering cell state to better understand the cell of origin of cancer., (©2023 The Authors; Published by the American Association for Cancer Research.)

In this study, we propose an optimal method for monitoring the key electrophysiological sign, the Lateral Spread Response (LSR), during microvascular decompression (MVD) surgery for hemifacial spasm (HFS). Current monitoring methods and interpretations of LSR remain unclear, leading to potential misinterpretations and undesirable outcomes." We prospectively collected data from patients undergoing MVD for HFS, including basic demographics, clinical characteristics, and surgical outcomes. Stimulation intensity was escalated by 1 mA increments to identify the optimal range for effective LSR. We designated the threshold at which we can observe LSR as THR1 and THR2 for when LSR disappears, with high-intensity stimulation (30 mA) designated as THR30. Subsequently, we compared abnormal muscle responses (AMR) between the optimal range (between THR1 and THR2) and THR30. Additionally, we conducted an analysis to identify and assess factors associated with artifacts and their potential impact on clinical outcomes. As stimulation intensity increases, the onset latency to detect AMR was shortened. The first finding of the study was high intensity stimulation caused artifact that mimic the wave of LSR. Those artifacts were observed even after decompression thus interfere interpretation of disappearance of LSR. Analyzing the factors related to the artifact, we found the AMR detected at onset latency below 9.6 ms would be the lateral spreading artifact (LSA) rather than true LSR. To avoid false positive LSR from LSA, we should stepwise increase stimulation intensity and not to surpass the intensity that cause LSR onset latency below 10 ms., (© 2023. The Author(s).)

Breast cancer is a heterogeneous disease, and computed tomography texture analysis (CTTA), which reflects the tumor heterogeneity, may predict the prognosis. We investigated the usefulness of CTTA for the prediction of disease-free survival (DFS) and prognostic factors in patients with invasive breast cancer. A total of 256 consecutive women who underwent preoperative chest CT and surgery in our institution were included. The Cox proportional hazards model was used to determine the relationship between textural features and DFS. Logistic regression analysis was used to reveal the relationship between textural features and prognostic factors. Of 256 patients, 21 (8.2%) had disease recurrence over a median follow-up of 60 months. For the prediction of shorter DFS, higher histological grade (hazard ratio [HR], 6.12; p < 0.001) and lymphovascular invasion (HR, 2.93; p = 0.029) showed significance, as well as textural features such as lower mean attenuation (HR, 4.71; p = 0.003) and higher entropy (HR, 2.77; p = 0.036). Lower mean attenuation showed a correlation with higher tumor size, and higher entropy showed correlations with higher tumor size and Ki-67. In conclusion, CTTA-derived textural features can be used as a noninvasive imaging biomarker to predict shorter DFS and prognostic factors in patients with invasive breast cancer.

Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aldehyde dehydrogenase (ALDH) enzymatic activity is a marker of cancer-initiating cells (CIC) in many tumor types. Our group and others have found that ALDH1A family inhibitors (ALDHi) can preferentially induce death of ovarian CIC in established ovarian cancer. We sought to determine if ALDHi, by targeting CIC at the time of tumor initiation, could function as a chemopreventive for ovarian cancer. As BRCA1/2 mutation carriers represent a population who could benefit from an ovarian cancer chemopreventive, we focused on BRCA mutation-associated tumor cell lines and murine tumor models. We found that, compared to BRCA wild-type cells, BRCA mutant ovarian cancer cells are more sensitive to the ALDHi673A. Similarly, while 673A treatment of wild-type fallopian tube epithelial (FTE) cells is non-toxic, 673A induces death in FTE cells with BRCA1 knockdown. Using a murine fallopian tube organoid model of ovarian carcinogenesis, we show that 673A reduced organoid complexity and significantly reduce colony formation of BRCA-mutant cells. Organoids that persisted after 673A treatment were predominantly BRCA1wt, but NF1 mutant, suggesting a resistance mechanism. Finally, using the BPRN (Brca1, Trp53, Rb1, Nf1 inactivated) mouse model of tubo-ovarian cancer, we evaluated the impact of intermittent 673A therapy on carcinogenesis. 673A treatment resulted in a significant reduction in serous tubal intraepithelial carcinoma (STIC) lesions and carcinomas. Collectively, the findings suggest that ALDHi, such as 673A, could serve as chemopreventive agents for BRCA1/2 mutation carriers., Competing Interests: Declaration of Competing Interest Dr. Buckanovich has patents related to the use of ALDH inhibitors in cancer therapies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rationale and Objectives: To investigate whether machine learning (ML) approaches using breast magnetic resonance imaging (MRI)-derived multiparametric and radiomic features could predict axillary lymph node metastasis (ALNM) in stage I-II triple-negative breast cancer (TNBC)., Materials and Methods: Between 2013 and 2019, 86 consecutive patients with TNBC who underwent preoperative MRI and surgery were enrolled and divided into ALNM (N = 27) and non-ALNM (n = 59) groups according to histopathologic results. For multiparametric features, kinetic features using computer-aided diagnosis (CAD), morphologic features, and apparent diffusion coefficient (ADC) values at diffusion-weighted images were evaluated. For extracting radiomic features, three-dimensional segmentation of tumors using T2-weighted images (T2WI) and T1-weighted subtraction images were respectively performed by two radiologists. Each predictive model using three ML algorithms was built using multiparametric features or radiomic features, or both. The diagnostic performances of models were compared using the DeLong method., Results: Among multiparametric features, non-circumscribed margin, peritumoral edema, larger tumor size, and larger angio-volume at CAD were associated with ALNM in univariate analysis. In multivariate analysis, larger angio-volume was the sole statistically significant predictor for ALNM (odds ratio = 1.33, P = 0.008). Regarding ADC values, there were no significant differences according to ALNM status. The area under the receiver operating characteristic curve for predicting ALNM was 0.74 using multiparametric features, 0.77 using radiomic features from T1-weighted subtraction images, 0.80 using radiomic features from T2WI, and 0.82 using all features., Conclusion: A predictive model incorporating breast MRI-derived multiparametric and radiomic features may be valuable in predicting ALNM preoperatively in patients with TNBC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sung Eun Song reports financial support was provided by Basic Science Research Program through the National Research Foundation of Korea (NRF) (NRF-2021R1F1A10), Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (HR22C1302), and Guerbet., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Long-term complications are becoming more important as the survival rate of breast cancer improves. Treatment-related myeloid neoplasm is an important long-term complication in breast cancer survivors as it has a poor prognosis., Objective: We evaluated the incidence and risk factors for the development of treatment-related acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) in patients treated with early breast cancer., Methods: We accessed the national Korean database to identify 153,565 patients diagnosed with breast cancer between January 2007 and October 2016 who underwent surgery for breast cancer. We estimated the cumulative incidence of AML/MDS and analysed the risk factors for developing AML/MDS., Results: Of 153,575 patients, 79,321 received anthracycline-based adjuvant therapy, 14,317 received adjuvant therapy without anthracyclines and 46,657 did not receive adjuvant chemotherapy. Overall, 120 developed AML (105 in the anthracycline group, 9 in the non-anthracycline group and 6 in the control group), and 128 developed MDS (96, 9 and 23 in each group). The 10-year cumulative incidence of AML/MDS was the highest in the anthracycline group (0.221% and 0.199%), followed by the non-anthracycline group (0.122% and 0.163%) and the control group (0.024% and 0.089%). The risk of developing AML/MDS was significantly higher in patients treated with anthracyclines (hazard ratio [HR] 9.531; p < 0.0001 for AML and HR 2.559; p < 0.0001 for MDS) compared to patients in the control group., Conclusion: This study found that anthracycline-based adjuvant therapy significantly increased the risk of AML/MDS in Korean breast cancer patients, with the risk persisting for at least 10 years. While the cumulative incidence was low, the long-term risks of AML/MDS should be taken into account considering the poor outcomes associated with these neoplasms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hemifacial spasm (HFS) is a rare disorder characterized by involuntary facial muscle contractions. The primary cause is mechanical compression of the facial nerve by nearby structures. Lateral spread response (LSR) is an abnormal muscle response observed during electromyogram (EMG) testing and is associated with HFS. Intraoperative monitoring of LSR is crucial during surgery to confirm successful decompression. Proper anesthesia and electrode positioning are important for accurate LSR monitoring. Stimulation parameters should be carefully adjusted to avoid artifacts. The disappearance of LSR during surgery is associated with short-term outcomes, but its persistence does not necessarily indicate poor long-term outcomes. LSR monitoring has both positive and negative prognostic value, and its predictive ability varies across studies. Early disappearance of LSR can occur before decompression and may indicate better clinical outcomes. Further research is needed to fully understand the implications of LSR monitoring in HFS surgery.

Background: There are increasing concerns about that sentinel lymph node biopsy (SLNB) could be omitted in patients with clinically T1-2 N0 breast cancers who has negative axillary ultrasound (AUS). This study aims to assess the false negative result (FNR) of AUS, the rate of high nodal burden (HNB) in clinically T1-2 N0 breast cancer patients, and the diagnostic performance of breast magnetic resonance imaging (MRI) and nomogram., Methods: We identified 948 consecutive patients with clinically T1-2 N0 cancers who had negative AUS, subsequent MRI, and breast conserving therapy between 2013 and 2020 from two tertiary medical centers. Patients from two centers were assigned to development and validation sets, respectively. Among 948 patients, 402 (mean age ± standard deviation, 57.61 ± 11.58) were within development cohort and 546 (54.43 ± 10.02) within validation cohort. Using logistic regression analyses, clinical-imaging factors associated with lymph node (LN) metastasis were analyzed in the development set from which nomogram was created. The performance of MRI and nomogram was assessed. HNB was defined as ≥ 3 positive LNs., Results: The FNR of AUS was 20.1% (81 of 402) and 19.2% (105 of 546) and the rates of HNB were 1.2% (5/402) and 2.2% (12/546), respectively. Clinical and imaging features associated with LN metastasis were progesterone receptor positivity, outer tumor location on mammography, breast imaging reporting and data system category 5 assessment of cancer on ultrasound, and positive axilla on MRI. In validation cohorts, the positive predictive value (PPV) and negative predictive value (NPV) of MRI and clinical-imaging nomogram was 58.5% and 86.5%, and 56.0% and 82.0%, respectively., Conclusion: The FNR of AUS was approximately 20% but the rate of HNB was low. The diagnostic performance of MRI was not satisfactory with low PPV but MRI had merit in reaffirming negative AUS with high NPV. Patients who had low probability scores from our clinical-imaging nomogram might be possible candidates for the omission of SLNB., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Brainstem auditory evoked potential (BAEP) testing during microvascular decompression (MVD) is very important in the treatment of hemifacial spasm (HFS). The reason for this is that the vestibulocochlear nerve is located immediately next to the facial nerve, so the vestibulocochlear nerve may be affected by manipulation during surgery. BAEP testing for detecting vestibulocochlear nerve damage has been further developed for use during surgery. In most HFS patients with normal vestibulocochlear nerves, the degree of vestibulocochlear nerve damage caused by surgery is well-reflected in the BAEP test waveforms. Therefore, real-time testing is the best way to minimize damage to the vestibulocochlear nerve. The purpose of this study was to review the most recently published BAEP test waveforms that were obtained during MVD surgery to determine the relationship between vestibulocochlear nerve damage and BAEP waveforms.

(1) Background: Cerebrospinal fluid (CSF) leakage is one of the most common complications of microvascular decompression (MVD) surgery. Before fatal complications, such as intracranial infection, occur, early recognition and prompt treatment are essential. (2) Methods: The clinical data of 475 patients who underwent MVD surgery from September 2020 to March 2023 were retrospectively analyzed. In these patients, if there were any symptoms of CSF leakage, and if CSF leakage was evident, a lumbar drainage catheter was inserted immediately. (3) Results: CSF leakage was suspected in 18 (3.8%) patients. Five of these patients (1.1%) showed signs of CSF leakage during conservative management and subsequently underwent catheter insertion for lumbar drainage. The lumbar drain was removed after an average of 5.2 days, resulting in an average hospitalization of 14.8 days. In all 5 patients, CSF leakage was resolved without reoperation. (4) Conclusions: Our treatment strategy prevented the development of fatal complications. Close observation of the symptoms and postoperative temporal bone computed tomography and audiometry are considered to be good evaluation methods for all patients. If CSF leakage is certain, it is important to perform lumbar drainage immediately.

Purpose: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters., Methods: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1β, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-β1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster., Results: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype., Conclusions: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: There are few prospective studies on the correlations between MRI features and whole RNA-sequencing data in breast cancer according to molecular subtypes. The purpose of our study was to explore the association between genetic profiles and MRI phenotypes of breast cancer and to identify imaging markers that influences the prognosis and treatment according to subtypes., Methods: From June 2017 to August 2018, MRIs of 95 women with invasive breast cancer were prospectively analyzed, using the breast imaging-reporting and data system and texture analysis. Whole RNA obtained from surgical specimens was analyzed using next-generation sequencing. The association between MRI features and gene expression profiles was analyzed in the entire tumor and subtypes. Gene networks, enriched functions, and canonical pathways were analyzed using Ingenuity Pathway Analysis. The P value for differential expression was obtained using a parametric F test comparing nested linear models and adjusted for multiple testing by reporting Q value., Results: In 95 participants (mean age, 53 years ± 11 [standard deviation]), mass lesion type was associated with upregulation of CCL3L1 (sevenfold) and irregular mass shape was associated with downregulation of MIR421 (sixfold). In estrogen receptor-positive cancer with mass lesion type, CCL3L1 (21-fold), SNHG12 (11-fold), and MIR206 (sevenfold) were upregulated, and MIR597 (265-fold), MIR126 (12-fold), and SOX17 (fivefold) were downregulated. In triple-negative breast cancer with increased standard deviation of texture analysis on precontrast T1-weighted imaging, CLEC3A (23-fold), SRGN (13-fold), HSPG2 (sevenfold), KMT2D (fivefold), and VMP1 (fivefold) were upregulated, and IGLC2 (73-fold) and PRDX4 (sevenfold) were downregulated (all, P < 0.05 and Q < 0.1). Gene network and functional analysis showed that mass type estrogen receptor-positive cancers were associated with cell growth, anti-estrogen resistance, and poor survival., Conclusion: MRI characteristics are associated with the different expressions of genes related to metastasis, anti-drug resistance, and prognosis, depending on the molecular subtypes of breast cancer., (© 2023. The Author(s).)

Tracheostomy is commonly performed on patients who require long-term ventilator support. As with all other airway managements, tracheostomy comes with risks: tracheal scarring, tracheal rupture, pneumothorax, and tracheoesophageal fistula. Although rare, free air leakage into the surrounding tissues of the tracheostomy site and consequent pneumomediastinum can also occur due to various reasons, such as tracheal rupture and mispositioning of the tracheal tube. Such conditions may require treatments including high flow oxygen, ventilator management, and occasionally surgical intervention. In our case of a 61-year-old female, emergent tracheostomy was performed and subsequent complications of massive pneumomediastinum and subcutaneous emphysema were treated with negative pressure wound therapy. The follow-up radiograph after negative pressure wound therapy showed resolution of pneumomediastinum and subcutaneous emphysema, and there were no additional complications. Negative pressure wound therapy is an effective treatment option for massive pneumomediastinum and subcutaneous emphysema after tracheostomy.

There are few radiogenomic studies to correlate ultrasound features of breast cancer with genomic changes. We investigated whether vascular ultrasound phenotypes are associated with breast cancer gene profiles for predicting angiogenesis and prognosis. We prospectively correlated quantitative and qualitative features of microvascular ultrasound (vascular index, vessel morphology, distribution, and penetrating vessel) and contrast-enhanced ultrasound (time-intensity curve parameters and enhancement pattern) with genomic characteristics in 31 breast cancers. DNA obtained from breast tumors and normal tissues were analyzed using targeted next-generation sequencing of 105 genes. The single-variant association test was used to identify correlations between vascular ultrasound features and genomic profiles. Chi-square analysis was used to detect single nucleotide polymorphisms (SNPs) associated with ultrasound features by estimating p values and odds ratios (ORs). Eight ultrasound features were significantly associated with 9 SNPs (p < 0.05). Among them, four ultrasound features were positively associated with 5 SNPs: high vascular index with rs1136201 in ERBB2 (p = 0.04, OR = 7.75); large area under the curve on contrast-enhanced ultrasound with rs35597368 in PDGFRA (p = 0.04, OR = 4.07); high peak intensity with rs35597368 in PDGFRA (p = 0.049, OR = 4.05) and rs2305948 in KDR (p = 0.04, OR = 5.10); and long mean transit time with rs2275237 in ARNT (p = 0.02, OR = 10.25) and rs755793 in FGFR2 (p = 0.02, OR = 10.25). We identified 198 non-silent SNPs in 71 various cancer-related genes. Vascular ultrasound features can reflect genomic changes associated with angiogenesis and prognosis in breast cancer., (© 2023. The Author(s).)

Background: Tumor heterogeneity and vascularity can be noninvasively quantified using histogram and perfusion analyses on computed tomography (CT) and magnetic resonance imaging (MRI). We compared the association of histogram and perfusion features with histological prognostic factors and progression-free survival (PFS) in breast cancer patients on low-dose CT and MRI., Methods: This prospective study enrolled 147 women diagnosed with invasive breast cancer who simultaneously underwent contrast-enhanced MRI and CT before treatment. We extracted histogram and perfusion parameters from each tumor on MRI and CT, assessed associations between imaging features and histological biomarkers, and estimated PFS using the Kaplan-Meier analysis., Results: Out of 54 histogram and perfusion parameters, entropy on T2- and postcontrast T1-weighted MRI and postcontrast CT, and perfusion (blood flow) on CT were significantly associated with the status of subtypes, hormone receptors, and human epidermal growth factor receptor 2 ( p < 0.05). Patients with high entropy on postcontrast CT showed worse PFS than patients with low entropy ( p = 0.053) and high entropy on postcontrast CT negatively affected PFS in the Ki67-positive group ( p = 0.046)., Conclusions: Low-dose CT histogram and perfusion analysis were comparable to MRI, and the entropy of postcontrast CT could be a feasible parameter to predict PFS in breast cancer patients.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future., Methods: The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations., Results: All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient's prognosis unless immediate intervention is given within 24-48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4-6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic., Conclusion: It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Purpose: Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer., Materials and Methods: We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment., Results: Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors., Conclusion: Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period., Methods: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed., Results: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase ( IDH )-mutant and oligodendroglioma with IDH -mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count., Conclusion: It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Background/aim: Bevacizumab-containing chemotherapy constitutes an important salvage treatment for recurrent/refractory glioblastoma(r/rGBM)., Patients and Methods: We retrospectively collected the data of r/rGBM patients treated with the combination of bevacizumab and irinotecan (BEV+IRI) as their salvage treatment from July 2013 and December 2021 in Konkuk Medical Center of Korea. Patients with available results from molecular diagnostic tests were eligible, and markers of interest were examined including the presence of MGMT methylation, IDH1/2 mutation, or 1p/19q co-deletion. Efficacy of BEV+IRI and its potential biomarker was explored., Results: Among 21 patients, 38.1% demonstrated European Cooperative Oncology Group-Performance scale (ECOG-PS) ≥3. The majority (71.4%) received BEV+IRI as their second-line chemotherapies, and the median dose was 5 (range=1-25). Objective response rate (ORR) was 33.3% and disease-control rate (DCR) was 85.7%. Irrespective of objective response, early clinical response was achieved in 14(66.7%) patients. During the median follow-up of 16.4 months for survivors, median progression-free survival (PFS) and overall survival (OS) were 3.6 and 6.8 months, respectively. ECOG PS≥3 and TP53 loss were independent predictors of an unfavorable OS, while prompt clinical improvement could predict favorable OS. Any molecular aberration was associated with OS or PFS in the study., Conclusion: Salvage BEV+IRI treatment in r/rGBM conferred comparable clinical benefit. ECOG PS ≥3, TP53 loss, and lack of prompt clinical improvement after the treatment were significantly associated with an unfavorable OS., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To evaluate the diagnostic performance of digital breast tomosynthesis (DBT) with the two-dimensional synthesized mammogram (2DSM), compared to full-field digital mammography (FFDM), for suspicious microcalcifications in the breast ahead of stereotactic biopsy and to assess the diagnostic image visibility of the images., Materials and Methods: This retrospective study involved 189 patients with microcalcifications, which were histopathologically verified by stereotactic breast biopsy, who underwent DBT with 2DSM and FFDM between January 8, 2015, and January 20, 2020. Two radiologists assessed all cases of microcalcifications based on Breast Imaging Reporting and Data System (BI-RADS) independently. They were blinded to the histopathologic outcome and additionally evaluated lesion visibility using a five-point scoring scale., Results: Overall, the inter-observer agreement was excellent (0.9559). Under the setting of category 4A as negative due to the low possibility of malignancy and to avoid the dilution of malignancy criteria in our study, McNemar tests confirmed no significant difference between the performances of the two modalities in detecting microcalcifications with a high potential for malignancy (4B, 4C, or 5; p = 0.1573); however, the tests showed a significant difference between their performances in detecting microcalcifications with a high potential for benignancy (4A; p = 0.0009). DBT with 2DSM demonstrated superior visibility and diagnostic performance than FFDM in dense breasts., Conclusion: DBT with 2DSM is superior to FFDM in terms of total diagnostic accuracy and lesion visibility for benign microcalcifications in dense breasts. This study suggests a promising role for DBT with 2DSM as an accommodating tool for stereotactic biopsy in female with dense breasts and suspicious breast microcalcifications., Competing Interests: Conflicts of Interest: Kyu Ran Cho has been a Editorial Board Member of the Journal of the Korean Society of Radiology since 2013; however, she was not involved in the peer reviewer selection, evaluation, or decision process of this article. Otherwise, no other potential conflicts of interest relevant to this article were reported., (Copyrights © 2022 The Korean Society of Radiology.)

Recurrent loss-of-function deletions cause frequent inactivation of tumour suppressor genes but often also involve the collateral deletion of essential genes in chromosomal proximity, engendering dependence on paralogues that maintain similar function. Although these paralogues are attractive anticancer targets, no methodology exists to uncover such collateral lethal genes. Here we report a framework for collateral lethal gene identification via metabolic fluxes, CLIM, and use it to reveal MTHFD2 as a collateral lethal gene in UQCR11-deleted ovarian tumours. We show that MTHFD2 has a non-canonical oxidative function to provide mitochondrial NAD + , and demonstrate the regulation of systemic metabolic activity by the paralogue metabolic pathway maintaining metabolic flux compensation. This UQCR11-MTHFD2 collateral lethality is confirmed in vivo, with MTHFD2 inhibition leading to complete remission of UQCR11-deleted ovarian tumours. Using CLIM's machine learning and genome-scale metabolic flux analysis, we elucidate the broad efficacy of targeting MTHFD2 despite distinct cancer genetic profiles co-occurring with UQCR11 deletion and irrespective of stromal compositions of tumours., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The erosion of tooth enamel is a common oral disease. The erosion pattern and location and the effects of nanoscale chemical composition on the erosion susceptibility of enamel have been well documented. However, the enamel remineralization accompanied by erosion and its underlying physicochemical mechanisms still remain poorly understood. Here, using rat molars selected for its good relevancy to human teeth, we investigated the remineralization behavior of the outermost enamel surface at the nanoscale level during erosion in diluted hydrochloric acid solutions. While particles on the outermost enamel surface that represent the termination of crystallites protruding to the surface from the near-surface core eroded by acid-attack, the lateral-growth of the particles (i.e., the main remineralization picture of the surface enamel) occurred concurrently. Ionic analyses indicate that the particle growth is driven by the local increase in pH near the eroding enamel surface as a result of the combination of the PO 4 3- and CO 3 2- released from the enamel surface with H + . As the pH increases eventually to the equilibrium pH level (∼5.5), a local supersaturation of solute ions is induced, resulting in particle growth. A simple growth model based on the experimental results together with an assumption that the particle growth is a diffusional process suggests that the particle growth rate is controlled by the degree of supersaturation and accommodation site for solute ions, which are affected by the pH of solution eroding the enamel surface. The remineralization mechanism presented by our study can explain how the enamel on being acid-exposed or tooth decay progress by beverage or food can naturally remineralize in the oral cavity and how remineralization can foster different surface topology at the nanoscale, depending on the pH value of etchant before the dental filling material is applied.

Background: The predictive value of intraoperative disappearance of the lateral spread response (LSR) during microvascular decompression surgery for hemifacial spasm treatment is unclear. Studies evaluating the clinical implications of the LSR recorded during the postoperative period are also limited., Objective: To analyze the LSR 1 month postoperatively and to evaluate its prognostic value until 1 year postsurgery., Methods: In total, 883 patients who underwent microvascular decompression between 2016 and 2018 were included. LSR was recorded preoperatively, intraoperatively before decompression, intraoperatively after decompression, and 1 month postoperatively. The outcomes were evaluated at 1 week, 1 month, and 1 year postoperatively., Results: The presence of preoperative and intraoperative LSR after decompression did not predict the postoperative outcome at 1 year. In 246 patients (27.9%), the postoperative LSR at 1 month was not identical to that recorded intraoperatively after decompression. Postoperative LSR at 1 month was associated with a worse outcome at 1 month (P < .0001) and 1 year (P = .0002) postoperatively. Patients with residual symptoms and a LSR 1 month postoperatively were more likely to show residual symptoms 1 year postoperatively, with a positive predictive value of 50.7%., Conclusion: Unlike the intraoperative LSR, the LSR at 1 month postoperatively showed prognostic value in predicting 1-year postoperative outcomes and was useful for identifying patients with a high risk of unfavorable outcomes. Thus, confirming the presence of postoperative LSR is necessary., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

One of the most widely used electric field sensors for low-frequency electric field detection (LFEFD) in seawater uses the Ag/AgCl electrode. The surface structure of the electrode including AgCl layers plays a critical role in the electrode's electrochemical performance required for the sensor. In this study, the sequential AgCl formation process under the constant current was examined on the Ag wire in an electrode size for actual applications, and an optimal electrode surface structure was suggested for the LFEFD Ag/AgCl sensor. Upon mild anodization (0.2 mA/cm 2 ) in 3.3 M KCl solution that permits us to follow the AgCl formation process manageably, Ag dissolution from the wire surface begins leaving cavities on the surface, with the accompanied growth of initial Ag grains. During this period, AgCl deposits in sizes of about several micrometers to 10 μm with crystal planes also form primarily along scratch lines on the wire surface, but in a partial scale. Then, with further anodization, the assumed thin AgCl deposits start to form, covering a large portion of the wire surface. They grow to become deposits in sizes of about several micrometers to 10 μm with no clear facet planes next to one another and are connected to form the network structure, representing the main developing mode of the AgCl deposits. While they cover all the surface, AgCl deposits also form on the surface of the already formed ones, making multiple AgCl layers. All these deposits develop through the nucleation process with a relatively high surface energy barrier, and their formation rate is solely controlled by the release rate of Ag + from the wire, thus by the applied current magnitude. The Ag/AgCl electrode with a thick AgCl layer and many holes in the AgCl surface structure like microchannels is considered to work effectively for the LFEFD sensor in terms of both detection sensitivity and service lifetime., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objectives: The "incessant ovulation" hypothesis links increased risk for tubo-ovarian high-grade serous carcinoma (HGSC) due to more ovulations and reduced risk conferred by pre-menopausal exposures like oral contraceptive use, multiparity, and breastfeeding. However, most women diagnosed with HGSC are postmenopausal, implying age is a major risk factor for HGSC. Our mouse model for HGSC, based on tamoxifen (TAM)-induced somatic inactivation of the Brca1, Trp53, Rb1, and Nf1 (BPRN) tumor suppressor genes in oviductal epithelium, recapitulates key genetic, histopathologic, and biological features of human HGSCs. We aimed to credential the model for future efforts to define biological and risk modification factors in HGSC pathogenesis., Methods: BPRN mice were treated with TAM to induce tumors at defined ages and parity status., Results: BPRN mice aged 9-months prior to tumor induction had markedly shorter survival than 6-8 week old mice induced to form tumors (median 46.5 weeks versus 61.5 weeks, log-rank test P = 0.0006). No significant differences in cancer phenotypes were observed between multiparous versus nulliparous BPRN mice. However, using a modified tumor model with one wild-type Nf1 allele (BPRN fl/+ ), nulliparous mice had more advanced tumors than multiparous mice (Mantel-Haenszel Chi-square test of association, P = 0.01)., Conclusions: Our findings show aging is associated with significantly shortened survival post tumor induction in the BRPN model and multiparity delays development and/or progression of HGSC in certain genetic contexts. The findings support relevance of our mouse model to gain mechanistic insights into how known factors exert their protective effects and to test novel approaches for HGSC prevention., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: We compared the 10-year graft occlusion rates and long-term clinical outcomes of right gastroepiploic artery (RGEA) composite grafts with those of right internal thoracic artery (RITA) composite grafts., Methods: From 2000 to 2008, 548 patients had undergone total arterial revascularization for multivessel coronary artery disease using the RGEA (RGEA group; n = 389) or RITA (RITA group; n = 159) as a second-limb Y-composite graft based on the in situ left ITA. A propensity score-matched analysis was used to match the RGEA group (n = 152) with the RITA group (n = 152). The 10-year angiographic occlusion rates and long-term clinical outcomes were compared. The follow-up data were complete for all 304 patients (100%) with a median follow-up of 143.7 months., Results: The early clinical outcomes were similar between the matched groups. The overall graft occlusion rate was 9.5% at 10 years in the matched group patients (matched RGEA and RITA groups, 10.3% and 8.4%, respectively; P = .639). The 10-year occlusion rates of the second-limb conduits showed no differences between the matched RGEA and RITA groups (14.1% and 10.2%, respectively; P = .487). No statistically significant differences were found at 15 years postoperatively in the overall survival (52.9% vs 49.4%; P = .470), cardiac mortality-free survival (92.1% vs 90.9%; P = .560), freedom from target vessel revascularization (83.0% vs 91.4%; P = .230), freedom from reintervention (68.8% vs 76.2%; P = .731), or freedom from major adverse cardiac and cerebrovascular events (56.4% vs 64.6%; P = .364) rates between the matched groups., Conclusions: Total arterial revascularization using RGEA composite grafts showed comparable results to those using RITA composite grafts in terms of the 10-year occlusion rates and long-term clinical outcomes., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate whether machine learning-based prediction models using 3-T multiparametric MRI (mpMRI) can predict Ki-67 and histologic grade in stage I-II luminal cancer., Methods: Between 2013 and 2019, consecutive women with luminal cancers who underwent preoperative MRI with diffusion-weighted imaging (DWI) and surgery were included. For prediction models, morphology, kinetic features using computer-aided diagnosis (CAD), and apparent diffusion coefficient (ADC) at DWI were evaluated by two radiologists. Logistic regression analysis was used to identify mpMRI features for predicting Ki-67 and grade. Diagnostic performance was assessed using eight machine learning algorithms incorporating mpMRI features and compared using the DeLong method., Results: Of 300 women, 203 (67.7%) had low Ki-67 and 97 (32.3%) had high Ki-67; 242 (80.7%) had low grade and 58 (19.3%) had high grade. In multivariate analysis, independent predictors for higher Ki-67 were washout component > 13.5% (odds ratio [OR] = 4.16; p < 0.001) and intratumoral high SI on T2-weighted image (OR = 1.89; p = 0.022). Those for higher grade were washout component > 15.5% (OR = 7.22; p < 0.001), rim enhancement (OR = 2.59; p = 0.022), and ADC value < 0.945 × 10 -3 mm 2 /s (OR = 2.47; p = 0.015). Among eight models using these predictors, six models showed the equivalent performance for Ki-67 (area under the receiver operating characteristic curve [AUC]: 0.70) and Naive Bayes classifier showed the highest performance for grade (AUC: 0.79)., Conclusions: A prediction model incorporating mpMRI features shows good diagnostic performance for predicting Ki-67 and histologic grade in patients with luminal breast cancers., Key Points: • Among multiparametric MRI features, kinetic feature of washout component >13.5% and intratumoral high signal intensity on T2-weighted image were associated with higher Ki-67. • Washout component >15.5%, rim enhancement, and mean apparent diffusion coefficient value < 0.945 × 10 -3 mm 2 /s were associated with higher histologic grade. • Machine learning-based prediction models incorporating multiparametric MRI features showed good diagnostic performance for Ki-67 and histologic grade in luminal breast cancers., (© 2021. European Society of Radiology.)

Background: There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects., Methods: This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. The prediagnosis inflammation-related exposures of interest included alcohol use; aspirin use; other nonsteroidal anti-inflammatory drug use; body mass index; environmental tobacco smoke exposure; history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis; menopausal hormone therapy use; physical inactivity; smoking status; and talc use. Using Cox proportional hazards models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed, and its association with survival was assessed using Cox proportional hazards models in the remaining 50% of the data., Results: There was a statistically significant trend of increasing risk of death per quartile of the IRRS [HR = 1.09; 95% confidence interval (CI), 1.03-1.14]. Women in the upper quartile of the IRRS had a 31% higher death rate compared with the lowest quartile (95% CI, 1.11-1.54)., Conclusions: A higher prediagnosis IRRS was associated with an increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether postdiagnosis exposures are also associated with survival., Impact: Given that pre- and postdiagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among patients with ovarian cancer., (©2021 American Association for Cancer Research.)

Backgrounds: Although the short-term efficacy of bilateral subthalamic deep brain stimulation (DBS) has been reported in a limited number of Parkinson's disease (PD) patients with SNCA mutations, there are no data for long-term outcome., Methods: This multicenter retrospective study investigated previously reported PD patients with SNCA mutations, implanted with bilateral subthalamic DBS. We compared demographic and clinical data at baseline and last follow-up. Clinical data of motor and nonmotor symptoms and motor fluctuation were collected up to 10 years from DBS surgery., Results: Among four subjects, three had SNCA duplication and one had c.158C.A (p.A53E) mutation. The mean post-implantation follow-up duration was 5.4 ± 3.7 years. All patients with SNCA duplication showed favorable outcome, although one died from breast cancer 1.5 years after DBS. The patient with the missense mutation became wheelchair-bound due to progressed axial, cognitive and psychiatric symptoms after 3.5 years from DBS despite the benefit on motor fluctuation., Conclusion: Based on findings in our small cohort, subthalamic DBS could be beneficial for motor fluctuation in PD patients with SNCA mutations, especially those with SNCA duplication, and cognitive and psychiatric symptoms are important for the long-term outcome of subthalamic DBS., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objectives: To investigate machine learning approaches for radiomics-based prediction of prognostic biomarkers and molecular subtypes of breast cancer using quantification of tumor heterogeneity and angiogenesis properties on magnetic resonance imaging (MRI)., Methods: This prospective study examined 291 invasive cancers in 288 patients who underwent breast MRI at 3 T before treatment between May 2017 and July 2019. Texture and perfusion analyses were performed and a total of 160 parameters for each cancer were extracted. Relationships between MRI parameters and prognostic biomarkers were analyzed using five machine learning algorithms. Each model was built using only texture features, only perfusion features, or both. Model performance was compared using the area under the receiver-operating characteristic curve (AUC) and the DeLong method, and the importance of MRI parameters in prediction was derived., Results: Texture parameters were associated with the status of hormone receptors, human epidermal growth factor receptor 2, and Ki67, tumor size, grade, and molecular subtypes (p < 0.002). Perfusion parameters were associated with the status of hormone receptors and Ki67, grade, and molecular subtypes (p < 0.003). The random forest model integrating texture and perfusion parameters showed the highest performance (AUC = 0.75). The performance of the random forest model was the best with a special scale filter of 0 (AUC = 0.80). The important parameters for prediction were texture irregularity (entropy) and relative extracellular extravascular space (V e )., Conclusions: Radiomic machine learning that integrates tumor heterogeneity and angiogenesis properties on MRI has the potential to noninvasively predict prognostic factors of breast cancer., Key Points: • Machine learning, integrating tumor heterogeneity and angiogenesis properties on MRI, can be applied to predict prognostic biomarkers and molecular subtypes in breast cancer. • The random forest model showed the best predictive performance among the five machine learning models (logistic regression, decision tree, naïve Bayes, random forest, and artificial neural network). • The most important MRI parameters for predicting prognostic factors in breast cancer were texture irregularity (entropy) among texture parameters and relative extracellular extravascular space (V e ) among perfusion parameters., (© 2021. European Society of Radiology.)