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Epithelial ovarian cancer (EOC) has a low overall survival rate, largely due to frequent recurrence and acquiring resistance to platinum-based chemotherapy. EOC with homologous recombination (HR) deficiency has increased sensitivity to platinum-based chemotherapy because platinum-induced DNA damage cannot be repaired. Mutations in genes involved in the HR pathway are thought to be strongly correlated with favorable response to treatment. Patients with these mutations have better prognosis and an improved survival rate. On the other hand, mutations in non-HR genes in EOC are associated with increased chemoresistance and poorer prognosis. For this reason, accurate predictions in response to treatment and overall survival remain challenging. Thus, analyses of 360 EOC cases on NCI's The Cancer Genome Atlas (TCGA) program were conducted to identify novel gene mutation signatures that were strongly correlated with overall survival. We found that a considerable portion of EOC cases exhibited multiple and overlapping mutations in a panel of 31 genes. Using logistical regression modeling on mutational profiles and patient survival data from TCGA, we determined whether specific sets of deleterious gene mutations in EOC patients had impacts on patient survival. Our results showed that six genes that were strongly correlated with an increased survival time are BRCA1, NBN, BRIP1, RAD50, PTEN, and PMS2. In addition, our analysis shows that six genes that were strongly correlated with a decreased survival time are FANCE, FOXM1, KRAS, FANCD2, TTN, and CSMD3. Furthermore, Kaplan-Meier survival analysis of 360 patients stratified by these positive and negative gene mutation signatures corroborated that our regression model outperformed the conventional HR genes-based classification and prediction of survival outcomes. Collectively, our findings suggest that EOC exhibits unique mutation signatures beyond HR gene mutations. Our approach can identify a novel panel of gene mutations that helps improve the prediction of treatment outcomes and overall survival for EOC patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ovarian cancer is the deadliest gynecologic malignancy in women, with a 46% five-year overall survival rate. The objective of the study was to investigate the effects of non-homologous end-joining (NHEJ) genes on clinical outcomes of ovarian cancer patients. To determine if these genes act as prognostic biomarkers of mortality and disease progression, the expression profiles of 48 NHEJ-associated genes were analyzed using an array of statistical and machine learning techniques: logistic regression models, decision trees, naive-Bayes, two sample t-tests, support vector machines, hierarchical clustering, principal component analysis, and neural networks. In this process, the correlation of genes with patient survival and disease progression and recurrence was noted. Also, multiple features from the gene set were found to have significant predictive capabilities. APTX , BRCA1 , PAXX , LIG1 , and TP53 were identified as most important out of all the candidate genes for predicting clinical outcomes of ovarian cancer patients., Competing Interests: The authors declare that they have no competing interest., (© 2023 The Author(s).)

Stroke is a common cause of long-term disability and death, which leaves many patients with significant and unique palliative care (PC) needs. Shared decision-making for patients with stroke poses distinct challenges due to the sudden nature of stroke, the uncertainty inherent in prognostication around recovery, and the common necessity of relying on surrogates for decision-making. Patients with stroke suffer from frequently underrecognized symptoms, which PC clinicians should feel comfortable identifying and treating. This article provides 10 tips for palliative clinicians to increase their knowledge and comfort in caring for this important population.

Background: Given the growing prevalence of initial endovascular treatment for type 1 spinal dural arteriovenous fistulae (dAVF), there are an increasing number of patients presenting with progressive symptoms related to recurrent previously embolized spinal dAVF. This study's goal was to identify demographic, clinical, and radiographic variables among patients who have failed embolization of type I spinal dAVF., Methods: A retrospective review of 24 consecutive surgeries for type I spinal dAVF performed by the senior author (A.D.L.) identified 5 patients who underwent open surgery for failed embolization. These 5 cases were reviewed for location of fistula, time from embolization to recurrence, preoperative functional status, fistulous point encountered at surgery, and clinical outcome of the patient at 3-month follow-up. A representative example case is reviewed in detail., Results: The median age at time of recurrence was 63 years (range 51-73 years). The median timing of embolization to recurrence of neurologic symptoms was 5 months (range 1-54) and to surgery 7 months (range 2-60 months). The level of the spinal dAVF was most frequently at T12-L1 (n = 3). Spinal magnetic resonance arteriography led to localization of the spinal dAVF in 2 patients and spinal catheter angiogram in 3 cases. All patients had definitive radiographic cure of the dAVF at last clinical follow-up., Conclusions: The increased use of endovascular treatment of spinal dAVF has led to the treatment of refractory cases with a greater degree of surgical complexity. Open surgical ligation continues to provide the most definitive treatment outcomes for this complex spinal vascular entity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Poly ADP-ribose polymerase (PARP) inhibitors are promising targeted therapy for epithelial ovarian cancer (EOC) with BRCA mutations or defective homologous recombination (HR) repair. However, reversion of BRCA mutation and restoration of HR repair in EOC lead to PARP inhibitor resistance and reduced clinical efficacy of PARP inhibitors. We have previously shown that triapine, a small molecule inhibitor of ribonucleotide reductase (RNR), impaired HR repair and sensitized HR repair-proficient EOC to PARP inhibitors. In this study, we performed in silico screening of small molecule libraries to identify novel compounds that bind to the triapine-binding pocket on the R2 subunit of RNR and inhibit RNR in EOC cells. Following experimental validation of selected top-ranking in silico hits for inhibition of dNTP and DNA synthesis, we identified, DB4, a putative RNR pocket-binding inhibitor markedly abrogated HR repair and sensitized BRCA-wild-type EOC cells to the PARP inhibitor olaparib. Furthermore, we demonstrated that the combination of DB4 and olaparib deterred the progression of BRCA-wild type EOC xenografts and significantly prolonged the survival time of tumor-bearing mice. Herein we report the discovery of a putative small molecule inhibitor of RNR and HR repair for combination with PARP inhibitors to treat PARP inhibitor-resistant and HR repair-proficient EOC.

Erdheim-Chester disease (ECD) is a rare disorder characterized by accumulation of non-Langerhans cell histiocytes in multiple organs. The clinical manifestations are protean and vary from asymptomatic focal disease to potentially fatal multisystem disorder. The commonest presentation is symmetric osterosclerotic lesions of lower extremity long bones; other organs, including cardiovascular, nervous, and endocrine system may be affected. Central nervous system involvement can occur in up to 50% cases and is associated with poor prognosis. The disease pathogenesis involves organ involvement secondary to histiocytic infiltration and systemic inflammation driven by Th1 cytokine activation. The recent discovery of activating mutations in proto-oncogene B-rapidly accelerated fibrosarcoma (BRAF) V600E and other genes involved in mitogen-activated protein kinase (MAPK) pathways has led to redefinition of ECD as a myeloid neoplastic disorder. The diagnosis requires histochemical and molecular analysis of histiocytes in tissue biopsies in patients with compatible clinical and imaging features. The treatment options include interferon-alpha, anakinra, and immunosuppressive therapies. Better understanding of disease pathogenesis has led to development of novel targeted and effective therapies including BRAF and MEK inhibitors. The rarity of the disease and variable clinical features and course often results in diagnostic errors and delays. Rare primary neurological presentation can occur mimicking CNS inflammatory, neoplastic, or demyelinating disorders. We report an unusual case of ECD presenting with progressive encephalopathy and ataxia along with multifocal brainstem and cerebellar lesions. A comprehensive review of clinical and neuroimaging features and immunohistochemical and molecular characteristic of ECD are presented along with review of neuroimaging findings in two previously reported cases., (© 2020 American Society of Neuroimaging.)

Over the last 2 decades, the proliferation of magnetic resonance imaging (MRI) availability and continuous improvements in acquisition speeds have led to significantly increased MRI utilization across the health care system, and MRI studies are increasingly ordered in the emergent setting. Depending on the clinical presentation, MRI can yield vital diagnostic information not detectable with other imaging modalities. The aim of this text is to report on the up-to-date indications for MRI of the spine in the ED, and review the various MRI appearances of commonly encountered acute spine pathology, including traumatic injuries, acute non traumatic myelopathy, infection, neoplasia, degenerative disc disease, and postoperative complications. Imaging review will focus on the aspects of the disease process that are not readily resolved with other modalities.

Spinal emergencies and urgent conditions must be recognized early so that the diagnosis can be quickly confirmed and treatment can be instituted to possibly prevent permanent loss of function. The American College of Radiology provides guidelines for recognition of patients presenting with myelopathy or acute low back pain who require further evaluation for suspicion of more serious problems and contribute to appropriate imaging utilization. Spinal emergencies include spinal cord compression secondary to vertebral fracture or space occupying lesion, spinal infection or abscess, vascular or hematologic damage, severe disc herniation, and spinal stenosis., (Copyright © 2018. Published by Elsevier Inc.)

The case of a 61-year-old woman who presented with herpes labialis, subclinical meningitis, and sudden onset of bilateral sensorineural hearing loss is presented. Contrast-enhanced MR imaging showed marked bilateral enhancement of the intracanalicular portion of the eighth cranial nerve, right cochlea, and left vestibule. Polymerase chain reaction was positive for human herpesvirus 1 obtained from the cerebral spinal fluid, which suggested the diagnosis of viral neuritis.