tbuckley/cabot-search huggingface dataset:
Hypomethylating Agents (HMAs) in Patients with Relapsed and Refractory Acute Myeloid Leukemia (RR-AML)— Transplant Outcomes Post HMA Therapy in a Large International Patient Cohort
Authors: Maximilian Stahl, Michelle Deveaux, Pau Montesinos, Raphael Itzykson, Ellen K Ritchie, Mikkael A. Sekeres, Navneet S. Majhail, Nikolai A. Podoltsev, Amir T. Fathi, Rami S. Komrokji, Vijaya R. Bhatt, Aref Al-Kali, Thomas Cluzeau, Valeria Santini, Andrew M. Brunner, Gail J. Roboz, Pierre Fenaux, Mark R. Litzow, Sera Perreault, Tae Kon Kim, Thomas Prebet, Norbert Vey, Vivek Verma, Guido Kobbe, Juan Bergua, Josefina Serrano, Steven D. Gore, Amer M. Zeidan
Journal: Blood (2017)
Trends in body mass index before and after diagnosis of hidradenitis suppurativa
Authors: S. Wright, A. Strunk, A. Garg
Journal: British Journal of Dermatology (2020)

Background A temporal relationship between hidradenitis suppurativa (HS) and obesity has not been established. Objectives To compare baseline body mass index (BMI) and change in BMI for patients with HS and controls before and after diagnosis. Methods We performed a retrospective case–control analysis of 1284 patients with HS and controls matched for age, sex, race and calendar year between 1 January 1999 and 9 September 2019. BMI 7 years prior to first HS diagnosis, and rate of BMI change, were compared for patients with HS and controls using linear mixed effects models. Results Baseline BMI was higher among patients with HS than controls [mean difference 3·03 kg m−2, 95% confidence interval (CI) 2·44–3·62; P < 0·001)]. This difference was larger for women [mean difference 3·37 kg m−2 (95% CI 2·73–4·01)] than men [mean difference 1·27 kg m−2 (95% CI − 0·20–2·73; interaction P = 0·01)], and for patients with HS diagnosed before age 40 years [mean difference 4·10 kg m−2 (95% CI 3·15–5·06)] than those diagnosed after age 40 years [mean difference 2·38 kg m−2 (95% CI 1·63–3·12; interaction P < 0·001)]. Prior to diagnosis, average annual increase in BMI among patients with HS was slightly higher than controls. There was no statistically significant change in annual BMI among patients with HS following diagnosis. Conclusions Baseline BMI and, to a lesser extent, rate of BMI change appear to be risk factors for developing HS. The influence of BMI may play a larger role among female patients and younger patients.
DIPG-84. COMPLEMENTARY AND ALTERNATIVE MEDICINE IN DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Fatma El-Khouly, Syed Adil, Harry Hendrikse, Gertjan Kaspers, Christof Kramm, Sophie Veldhuijzen van Zanten, Dannis van Vuurden
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Diffuse intrinsic pontine glioma (DIPG) is a rare and aggressive childhood brainstem malignancy with a two-year survival rate of ≤10%. In this international survey study we aim to evaluate the use of complementary and alternative medicine (CAM) in this patient population. METHODS Parents of-, and physicians treating DIPG patients were asked to participate in a retrospective online survey with questions regarding CAM use during time of illness. RESULTS 120 parents and 75 physicians contributed to the online survey between January and May 2020. Physicians estimated that &amp;lt;50% of their patients used CAM, whereas 69% of the parents reported to have used CAM to treat their child during time of illness. Cannabis was the most widely used form of CAM, followed by vitamins and minerals, melatonin, curcumin and boswellic acid. CAM was mainly used to actively treat the tumor. Other motivations were to treat side effects of chemotherapy, or to comfort the child. Children diagnosed ≥2016 were more likely to use CAM (χ2=6.08, p=0.014). No significant difference was found between CAM users and non-users based on ethnicity (χ2=4.18, p=0.382) and country of residence (χ2=9.37, p=0.154). Almost 50% of the physicians do not frequently ask their patients about possible CAM use. CONCLUSION This survey demonstrates that worldwide a considerable number of DIPG patients use CAM. Physicians should be more aware of potential CAM use and more actively discuss the topic. More research is needed to gain knowledge about possible anticancer effects of CAM and their interactions with conventional therapies.
Abstract 13014: Gender Differences in the Incidence of Adverse Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors
Authors: Sheharyar Minhas, Ahmed Minhas, Maira Malik, Sunil Dhar
Journal: Circulation (2020)

Introduction: Immune checkpoint inhibitors (ICIs) are increasingly being used for cancer therapy. Cardiotoxicity from ICIs has largely been underestimated since cardiovascular monitoring is not routinely performed after initiating immunotherapy. Cardiotoxic side effects are uncommon but are serious complications of ICIs with a high morbidity and mortality. Hypothesis: Adverse cardiovascular events in cancer patients are associated with the number of immune checkpoint inhibitor injections and the gender. Methods: In this observational, retrospective, pharmacovigilance study, we used MarketScan Databases to compare cardiovascular adverse events reported in patients who received ICIs. The data used in this study was fully integrated and de-identified data. The study included 9,583 male and 6,991 female patients who had cancer and underwent ICI therapy between Jan 1, 2011 and Dec 31, 2018. ICI drugs in this study included nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and ipilimumab. The time to an event and the end of follow-up was counted from the time of first ICI injection. Our primary exposure variable was gender. Results: At least one cardiovascular IRAE was reported in 3,804 (23%) of 16,574 patients enrolled in the study. The hazard time to cardiovascular events (CVEs) between the male and female gender varied by age. There was no difference in CVEs between males and females at a younger age. The hazard time to CVEs increased with age above 60 years in males when compared to females. The hazard of time to CVE in males was 1.18 times the hazard in females at the mean study age of 60.5 years. Adjusted Kaplan-Meier survival curves for males and females stratified by ICI injection categories showed that those with fewer number of ICI injections had a shorter time to CVE. Conclusions: The number of ICI injections and the gender both impact adverse cardiovascular events in cancer patients. Managing and reducing cardiotoxicity is vital for safe delivery of this effective therapy. There needs to be multidisciplinary approach between primary care physicians, cardiologists, oncologists, and immunologists for better understanding and management of ICI associated cardiotoxicity.
SURG-32. DIFFERENCES IN SURGICAL OUTCOME BETWEEN VON HIPPEL-LINDAU DISEASE RELATED AND SPORADIC HEMANGIOBLASTOMAS IN THE CENTRAL NERVOUS SYSTEM
Authors: Shohei Nambu, Shunsaku Takayanagi, Hirokazu Takami, Taichi Kin, Shota Tanaka, Hirofumi Nakatomi, Nobuhito Saito
Journal: Neuro-Oncology (2020)

Abstract Central nervous system hemangioblastoma (CNS HB) is a benign but highly vascular tumor, which accounts for 1.7% of all intracranial tumors. CNS HBs predominantly arise in the cerebellum, brainstem, and spinal cord. Approximately 20% of CNS HB is related to von-Hippel-Lindau (VHL) disease and repeated surgical resections are often required in VHL patients due to the presence of multiple CNS HBs. To explore the differences of surgical effect between VHL disease related and sporadic CNS HBs, outcome analyses were performed based on the tumor locations. PATIENT AND METHODS: A total 83 cases that underwent surgical resections of CNS HBs at Tokyo University in 1996-2019 were included. Clinical information including age, sex, number of past surgical resections, pre- and post-operative modified Rankin Scale(mRS) were examined. RESULTS: Regarding the etiology, 46 VHL cases(cerebellum:30, medulla oblongata:6, spinal cord:10) and 37 sporadic cases (cerebellum: 28, medulla oblongata:4, spinal cord:5) were enrolled. The average changes in the postoperative mRS minus preoperative mRS were cerebellum -0.9/medulla oblongata -0.5/spinal cord -0.8 for VHL cases, and cerebellum -0.75/medulla oblongata -1/spinal cord -1 for sporadic cases. Fisher`s exact tests were used for between-group comparison. DISCUSSION: The study showed no statistically significant difference between cerebellar and spinal cord cases regarding the perioperative change in the patient capability. Because of multiple lesions and repeated surgeries, VHL patients have a possibility to present with worse neurology after surgery. Further analysis is needed to clarify differences in surgical outcome for VHL disease related and sporadic related CNS HBs.
COVD-12. THE LONGITUDINAL IMPACT OF COVID-19 PANDEMIC ON NEUROSURGICAL PRACTICE
Authors: Abdullah Alatar, Khalid Bajunaid, Ashwag Alqurashi, Abdulrazag Ajlan
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE This observational cross-sectional multicenter study aimed to evaluate the longitudinal impact of the coronavirus disease 2019 (COVID-19) pandemic on neurosurgical practice. METHODS We included 29 participating neurosurgeons in centers from all geographical regions in the Kingdom of Saudi Arabia. The study period, which was between March 5, 2020 and May 20, 2020, was divided into three equal periods to determine the longitudinal effect of COVID-19 measures on neurosurgical practice over time. RESULTS During the 11-week study period, 474 neurosurgical interventions were performed. The median number of neurosurgical procedures per day was 5.5 (interquartile range [IQR]: 3.5–8). The number of cases declined from 72 in the first week and plateaued at the 30’s range in subsequent weeks. The most and least number of performed procedures were oncology (129 [27.2%]) and functional procedures (6 [1.3%]), respectively. Emergency (Priority 1) cases were more frequent than non-urgent (Priority 4) cases (178 [37.6%] vs. 74 [15.6%], respectively). In our series, there were three positive COVID-19 cases. There was a significant among-period difference in the length of hospital stay, which dropped from a median stay of 7 days (IQR: 4 – 18) to 6 (IQR: 3 - 13) to 5 days (IQR: 2 - 8). There was no significant among-period difference with respect to institution type, complications, or mortality. CONCLUSION Our study demonstrated that the COVID-19 pandemic decreased the number of procedures performed in neurosurgery practice. The load of emergency neurosurgery procedures did not change throughout the three periods, which reflects the need to designate ample resources to cover emergencies. Notably, with strict screening for COVID -19 infections, neurosurgical procedures could be safely performed during the early pandemic phase. We recommend to restart performing neurosurgical procedures once the pandemic gets stabilized to avoid possible post-pandemic health-care system intolerable overload.
Abnormal FDG Biodistribution in a Patient With Gitelman Syndrome
Authors: Yuka Yamamoto, Katsuya Mitamura, Takashi Norikane, Kengo Fujimoto, Yasukage Takami, Yoshihiro Nishiyama
Journal: Clinical Nuclear Medicine (2020)

Gitelman syndrome is an autosomal recessive renal tubulopathy. A 38-year-old woman was diagnosed with Gitelman syndrome. Eight years later, 18F-FDG PET/CT was performed to evaluate recurrence of endometrial cancer. FDG PET images showed an extremely abnormal FDG biodistribution. They showed decreased brain uptake, increased cardiac muscle uptake, and diffuse increased muscle and adipose tissue uptake. This pattern is similar to high insulin state; however, her glucose level was normal, and insulin level was very low.
MBRS-24. FUNCTIONAL CHARACTERIZATION OF IKBKAP/ELP1 AS A NOVEL SHH MEDULLOBLASTOMA PREDISPOSITION GENE
Authors: Jesus Garcia Lopez, Lena Kutscher, Marija Kojic, Brian Gudenas, Kyle Smith, Jennifer Hadley, Amar Gajjar, Giles W Robinson, Stefan M Pfister, Brandon J Wainwright, Daisuke Kawauchi, Paul A Northcott
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma (MB), a common malignant pediatric brain tumor, comprises at least four distinct molecular entities: WNT, SHH, Group 3, and Group 4. SHH-MB is driven by aberrant activation of the Sonic hedgehog (SHH) pathway in granule neuron progenitors (GNPs) and is associated with hereditary cancer predisposition syndromes including Li Fraumeni and Gorlin. We recently identified germline loss of function (LoF) mutations affecting IKBKAP/ELP1, the primary scaffolding subunit of the Elongator complex in a subset of SHH-MB patients. Germline ELP1 mutations account for ~15% of all pediatric SHH-MBs and position ELP1 as the most prevalent hereditary predisposition gene in MB. We genetically engineered Elp1 LoF in mouse GNPs to determine Elp1 function in cerebellar development and SHH-MB. Results of both mechanistic and phenotypic experiments demonstrate that GNPs harboring Elp1 loss exhibit ribosome pausing and protein aggregation, reinforcing the critical role of Elp1 in translational elongation and protein homeostasis. Further, we generated new transgenic mouse models mimicking germline ELP1 LoF mutations observed in SHH-MB patients. Elp1+/- transgenic mice exhibit purkinje cell degeneration and an increased DNA damage response. These mice are currently being evaluated for their capacity to recapitulate ELP1-associated SHH-MB. Additional analyses carried out on SHH-MB patient-derived xenografts showed that ELP1-mutant tumor cells specifically exhibit defects in tRNA biogenesis. Therefore, the function of ELP1 as a translational regulator is severely impaired in ELP1-mutant SHH-MBs. Our ongoing molecular and functional studies will provide important insights into the most common MB predisposition gene and will lay the foundation for future preclinical studies.
Proteomic signatures of 16 major types of human cancer reveal universal and cancer-type-specific proteins for the identification of potential therapeutic targets
Authors: Yangying Zhou, T. Mamie Lih, Jianbo Pan, Naseruddin Höti, Mingming Dong, Liwei Cao, Yingwei Hu, Kyung-Cho Cho, Shao-Yung Chen, Rodrigo Vargas Eguez, Edward Gabrielson, Daniel W. Chan, Hui Zhang, Qing Kay Li
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Proteomic characterization of cancers is essential for a comprehensive understanding of key molecular aberrations. However, proteomic profiling of a large cohort of cancer tissues is often limited by the conventional approaches. Methods We present a proteomic landscape of 16 major types of human cancer, based on the analysis of 126 treatment-naïve primary tumor tissues, 94 tumor-matched normal adjacent tissues, and 12 normal tissues, using mass spectrometry-based data-independent acquisition approach. Results In our study, a total of 8527 proteins were mapped to brain, head and neck, breast, lung (both small cell and non-small cell lung cancers), esophagus, stomach, pancreas, liver, colon, kidney, bladder, prostate, uterus and ovary cancers, including 2458 tissue-enriched proteins. Our DIA-based proteomic approach has characterized major human cancers and identified universally expressed proteins as well as tissue-type-specific and cancer-type-specific proteins. In addition, 1139 therapeutic targetable proteins and 21 cancer/testis (CT) antigens were observed. Conclusions Our discoveries not only advance our understanding of human cancers, but also have implications for the design of future large-scale cancer proteomic studies to assist the development of diagnostic and/or therapeutic targets in multiple cancers.
Single-session endoscopic fundoplication after peroral endoscopic myotomy (POEM+F) for prevention of post gastroesophageal reflux – 1-year follow-up study
Authors: Amol Bapaye, Parag Dashatwar, Siddharth Dharamsi, Rajendra Pujari, Harshal Gadhikar
Journal: Endoscopy (2020)

Peroral endoscopic myotomy (POEM) is an established treatment for achalasia cardia; however, post-POEM gastroesophageal reflux (GER) remains a significant problem. Concomitant endoscopic fundoplication following POEM (POEM + F) was recently described to reduce post-POEM GER. This single-center study reports short-term outcomes of POEM + F.This was a retrospective analysis of a prospectively maintained database of patients undergoing POEM + F. Abstracted data included demographics, achalasia type, pre-POEM Eckardt score, prior therapy, follow-up. Follow-up assessment was 3-monthly for 1 year and included post-POEM Eckardt score, GerdQ score, wrap integrity and esophagitis on esophagogastroduodenoscopy, and pH studies. GER was defined according to Lyon Consensus.25 patients underwent POEM + F (mean age 40.1 years [standard deviation (SD) 13.7]; 12 females). POEM + F was technically successful in 23/25 (92.0 %). Significant dysphagia improvement was seen in all 25 patients (mean pre- and post-POEM Eckardt scores 8.21 [SD 1.08] and 0.1 [SD 0.3], respectively; P = 0.001). Mean total procedure and fundoplication times were 115.6 (SD 27.2) minutes and 46.7 (SD 12.4) minutes, respectively; times reduced significantly after the initial five cases. Median follow-up was 12 months (interquartile range [IQR] 9-13). Intact wrap was seen in 19/23 (82.6 %). GER (abnormal esophageal acid exposure time [EAET]) was seen in 2/18 (11.1 %) and there was one reported GerdQ > 8. Borderline GER (asymptomatic grade A esophagitis, normal EAET) was identified in 4/22 (18.2 %). Three (12.0 %) minor delayed adverse events occurred but required no intervention. CONCLUSIONS : POEM + F was safe and reproducible. At 12 months' follow-up, incidence of post-POEM + F GER was low and acceptable.
GCT-22. PROTEIN DEUBIQUITINATION PATHWAY IS A NOVEL THERAPEUTIC TARGET AGAINST MALIGNANT NON-GERMINOMATOUS CNS GERM CELL TUMORS
Authors: Arata Tomiyama, Eita Uchida, Kojiro Wada, Koichi Ichimura
Journal: Neuro-Oncology (2020)

Abstract Central nervous system germ cell tumors (CNSGCTs) are rare intracranial neoplasm usually developed in adolescents and young adults. However, in East Asia including Japan, incidence of CNSGCTs is considerably higher compare with other regions of the world. Whereas germinomas generally respond to chemo-radiotherapy well, malignant subtypes of non-germinomatous germ cell tumors (NGGCT) are refractory, and development of novel therapy against NGGCTs is urgently needed. To develop a new therapeutic strategy against aggressive NGGCTs, we have investigated novel molecular targets for NGGCT treatment. We screened a total of 120 CNSGCT tumor tissues (including 55 NGGCT), which were registered to the Intracranial Germ Cell Tumor Consortium (iGCT), and discovered multiple mutations of a molecule that regulates protein ubiquitination and degradation specifically in NGGCT cases (5 of 55 cases; 1 immature teratoma, 3 mixed gem cell tumors, and 1 embryonal carcinoma). An in vitro ubiquitination assay revealed the mutations of this molecule discovered in NGGCT cases were loss of function mutations. Reduced expression of this molecule by knockdown in an established human seminoma cell line Tcam2 or a human yolk sac tumor cell line YST1, which was recently established in our institute, resulted in enhanced proliferation as well as upregulation of MEK-ERK activation. Importantly, treatment of these two GCT cell lines with reduced expression of this molecule by MEK inhibitor trametinib suppressed augmented proliferation of these cells. Taken together, these results suggest that protein ubiquitination-related pathways as well as MEK-ERK cascade may serve as a novel therapeutic target against NGGCTs.
QOLP-19. INSOMNIA IN BRAIN TUMOR PATIENTS: ASSESSING NEEDS IN NEURO-ONCOLOGY
Authors: Kelcie Willis, Scott Ravyts, Autumn Lanoye, Ashlee Loughan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Insomnia is a prevalent consequence of cancer diagnosis and treatment. In primary brain tumor (PBT) patients specifically, insomnia has been rated as one of the most severe symptoms and linked with other negative side effects, such as increased fatigue and emotional distress. Despite these findings, research has consistently omitted PBT patients in understanding the detailed effects and treatment for insomnia. METHODS Adult PBT patients (N=74) completed anonymous surveys at routine neuro-oncology appointments at an NCI-designated academic medical center. The surveys included validated measures of insomnia (ISI &amp; PSQI), fatigue (BFI), and other original items (e.g., How would you describe your feelings towards medication treatment for insomnia?). The current investigation aimed to assess: 1) the prevalence of clinically elevated symptoms of insomnia, 2) the relationship between sleep disturbance and daytime fatigue and distress, and 3) patients’ preferences for pharmacological and non-pharmacological treatment for insomnia in PBT patients. RESULTS Of the sampled PBT patients, 38% reported significant sleep disturbance as measured by the PSQI. Moreover, 23% endorsed clinically elevated, moderate-severe symptoms of insomnia as measured by the ISI. Excessive worrying (r =.31) and bad dreams (r =.29, p&amp;lt; .05) were both associated, though not predictive of insomnia severity (p &amp;gt;.05). Insomnia symptoms predicted increased fatigue severity, F(1,72) =52.60, β=.65, p&amp;lt; .001, R2 =.42. Of the patients with clinical insomnia, 59% felt that their symptoms were not well-managed by their medical team; 53% expressed interest in pharmacological treatment and 47% in non-pharmacological treatment. CONCLUSIONS The prevalence and consequences of insomnia identified in PBT patients are similar to that of other cancers, yet the majority of PBT patients with insomnia reported their symptoms were poorly managed. Though there was slight preference for pharmacological treatment, the sizeable proportion of those interested in non-pharmacological treatments warrants investigations into such therapies (e.g., CBT-I) in medical settings
68Ga–Prostate-Specific Membrane Antigen PET/CT in Sinonasal Glomangiopericytoma—Exploring Theranostic Avenues!
Authors: Pirabu Sakthivel, Arunav Kumar, Sreedharan Thankarajan Arunraj, Kuldeep Thakur, Avinash Shekhar Jaiswal, Chirom Amit Singh, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2020)

Prostate-specific membrane antigen (PSMA) is expressed in the tumor-associated endothelial neovasculature of various nonprostatic benign and malignant neoplasms. A 25-year-old man with recurrent sinonasal glomangiopericytoma underwent whole-body 68Ga PSMA PET/CT to explore its theranostic role. There was intense PSMA uptake (SUVmax = 23.9) noted in the tumor. The uptake was more than that of the salivary glands, lacrimal glands, aorta, spleen, and the liver. Performance of PSMA PET/CT in sinonasal glomangiopericytoma opens up new frontiers concerning radiological imaging, early recurrence identification, and perhaps even radioligand therapy of residual/recurrent tumors.