tbuckley/cabot-search huggingface dataset:
Effect of Wnt pathway inhibitor on ovarian cancer tumors.
Authors: M. V. Mindar, Anna S. Goncharova, A. V. Volkova, Ekaterina V. Verenikina, Anna P. Menshenina, Ekaterina V. Zaikina, D. V. Khodakova, Ekaterina A. Lukbanova, Anna Yu. Ardzha, L. Z. Kurbanova, M. L. Adamyan
Journal: Journal of Clinical Oncology (2021)

e15010 Background: Ovarian cancer (OC) is the fourth most common cancer in women aged 40-54 years. Despite advances in cancer research, no existing methods provide effective early diagnosis and treatment of OC, so the search for new medications is an urgent task. The effectiveness of the XAV-939 pharmacological substance, which inhibits the Wnt signaling pathway, was studied in an orthotopic patient-derived xenograft of human ovarian cancer. Methods: A PDX model was created in 20 female immunodeficient Balb/c Nude mice. A tumor fragment was implanted into the ovary, and the ovary was transposed under the skin to better visualize the xenograft growth. When the average tumor volume was 67.4 mm 3 , animals were divided into 4 groups: group 1 – controls (n = 5); group 2 – animals receiving paclitaxel (n = 5); group 3 – animals with XAV-939 (n = 5); group 4 – animals with combined paclitaxel+XAV-939 (n = 5). The control group received the carrier substance, and the test substances were administered at 10 mg/kg; the substances were administered intraperitoneally twice a week for 22 days. The tumor growth was assessed throughout the experiment by measuring its linear dimensions (length and width), and the volume and tumor growth index were calculated. The data were statistically processed using Microsoft Excel and STATISTICA 10. The Mann-Whitney nonparametric test was used to assess the differences between the control and experimental groups. Results: No statistically significant differences were observed in the indices of tumor growth between groups 2 (paclitaxel) and 1 (control), and groups 3 (XAV-939) and 1 (control). However, the difference was statistically significant between groups 4 (paclitaxel+XAV-939) and 1 (control). The tumor growth inhibition index was calculated at the end of the experiment. It was maximal in group 4 (paclitaxel+XAV-939) – 67.78%; in groups 2 (paclitaxel) and 3 (XAV-939), it was 21.39% and 30.33%, respectively. Conclusions: An orthotopic PDX model of ovarian cancer was generated, and the activity of XAV-939 towards the OC xenograft was studied; the greatest efficacy of the preparation was noted in combination with paclitaxel.
Adult Philadelphia-like B-cell acute lymphoblastic leukemia: Characteristics, outcomes, and role of allogeneic hematopoietic cell transplantation in comparison to Philadelphia-positive and Philadelphia-negative acute lymphoblastic leukemia.
Authors: Zaid Abdel Rahman, Michael Heckman, Theodora Anagnostou, Launia White, Sara M. Kloft-Nelson, Ryan A. Knudson, Hassan Alkhateeb, Lisa Ostrosky Sproat, Nandita Khera, Hemant S. Murthy, Ernesto Ayala, William J. Hogan, Vivek Roy, Jess Peterson, Mohamed Kharfan-Dabaja, Rhett P. Ketterling, Mark Robert Litzow, Mrinal Patnaik, James M. Foran, Patricia T. Greipp
Journal: Journal of Clinical Oncology (2021)

7022 Background: Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) is a high-risk subset of adult ALL. Until recently, there has not been a systematic platform to recognize this entity in clinical practice. Furthermore, data regarding the role of allogeneic hematopoietic cell transplantation (allo-HCT) is lacking. We conducted this study to identify patients with Ph-like ALL and describe their outcomes in comparison to Ph + and Ph - ALL with emphasis on the role of allo-HCT. Methods: To identify cases of Ph-like ALL, available diagnostic cytogenetic pellets for patients in the Mayo Clinic ALL cohort (N=365) were tested using a targeted fluorescence in situ hybridization (FISH) panel developed by the Mayo Clinic Genomics Laboratory and includes probes to detect Ph-like-specific rearrangements (i.e., ABL1, ABL2, PDGFRB, JAK2 and CRLF2). Results: Thirty-three (9%) patients with Ph-like ALL were identified, the remaining patients were classified as Ph + (N=132, 36%) or Ph - ALL (N=200, 55%). Patients with Ph-like ALL were younger (Median: 39 vs. 50 vs. 49 years, P=.01), had higher WBC (Median: 27.9 vs. 21.5 vs. 4.5 x10 9 /L, P&lt;.001), were less likely to achieve CR (91% vs. 99% vs. 96%, P=.02), more likely to be MRD+ (64% vs. 34% vs. 36%, P=.03), had a higher relapse rate (5-year: 39% vs. 24% vs. 38%, P=.01) and lower OS (5-year: 41% vs. 64% vs. 49%, P=.02), see Table. Patients who achieved MRD negativity had better OS (MRD+ vs MRD-, P=.01). Importantly, no statistically significant difference in OS, relapse or non-relapse mortality were noted between the 3 groups in patients who underwent allo-HCT in CR1. Conclusions: Ph-like ALL is a high risk subgroup with increased prevalence in younger adults. Allo-HCT appears to offset the poor prognosis associated with this entity. A targeted FISH panel offers timely recognition of this entity in a clinical setting.[Table: see text]
SARS-CoV2 infection rate in patients and health care personnel in a chemoradiotherapy unit: A prospective cohort in Mexico.
Authors: Mónica Isabel Meneses Medina, Jorge Humberto Hernandez-Felix, Vanessa Rosas Rosas Camargo, Ana Karen Valenzuela, Alberto Cedro-Tanda, Edgar Omar Martos Armendariz, Luis Guillermo Anaya Sánchez, Lucero Itzel Torres Valdiviezo, Arturo Galindo Fraga, Luis A. Herrera Montalvo, Alfredo Hidalgo, Fidel David Huitzil Melendez
Journal: Journal of Clinical Oncology (2021)

e22521 Background: Cancer treatment during the COVID-19 pandemic represents a challenge. Increased hospital visits to receive treatment as well as interaction with healthcare personnel (HCP), represent a potential risk factor for acquiring COVID-19. Our objective was to analyze the SARS-CoV-2 infection rate in patients (pts) with cancer and HCP of a chemoradiotherapy unit localized in a center designated as a COVID-19 priority facility in Mexico City. Methods: We invited HCP and pts with solid tumors attending the chemoradiotherapy unit to participate in a prospective follow-up cohort to early detect asymptomatic COVID-19 infection. Only participants who gave informed consent were included. A RT-PCR test for SARS-COV-2 from nasopharyngeal swab samples was performed every 2 weeks, and daily electronic clinical questionnaires were sent. Recruitment started on June 12, 2020. Participants entered the study in different moments and they were followed until a positive test for COVID-19 was found, or pts finished treatment or, HCP changed work area or, withdrawal of inform consent, or follow up completion, which ever occurred first. The last day of follow up was September 30, 2020. The general infection rate during all the period of follow-up was calculated, as well as the infection rate per month. Results: We included 130 asymptomatic participants, 44.6% (n = 58) were HCP and 55.4% (n = 72) were cancer pts, 45.9% (n = 61) were men, and 54.1% (n = 72) were women. During a median follow-up of 85 days (IQR 48-103) we performed 634 nasopharyngeal swabs for SARS-CoV-2 RT-PCR, with a median number per participant of 5 (IQR 3-7). Within this period, 18 (13.5%) participants tested positive for SARS-CoV-2 infection. 12 were asymptomatic and 6 developed symptoms. None of them had a severe form of COVID-19 and we did not register any death associated to COVID-19. Table shows the infection rate per month. Conclusions: In our center, during the time period of follow up, the overall rate of COVID-19 infection was higher than that reported in a study from asymptomatic HCP and office workers in Mexico City (13.5 vs 8.4%). We also observed a monthly variation that was consistent with the months with the highest number of cases detected in Mexico City during the first wave. With careful implementation, it is feasible to continue to safely deliver systemic oncologic treatments during the COVID-19 pandemic.[Table: see text]
Despite Improvements, COVID-19’s Health Care Disruptions Persist
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

More Comprehensive Care for Miscarriage Needed WorldwideAbout 1 in 10 women will have a miscarriage over a lifetime-a statistic that represents 23 million pregnancies lost annually, or 44 per minute worldwide, according to a series of articles in The Lancet.Despite the magnitude, the articles described miscarriage as a misunderstood phenomenon and called for more comprehensive care to prevent and treat miscarriage.The 15% of pregnancies that end in a miscarriage can be attributed to risk factors including age during pregnancy, smoking, stress, air pollution, and exposure to pesticides, 1 of the studies reported.For repeated miscarriages, which affect about 2% of women, another study indicated that progesterone could increase live-birth rates and that levothyroxine may decrease the risk of miscarriage for women with subclinical hypothyroidism.Repeated miscarriages can be emotionally devastating and pose a risk of future pregnancy complications, the authors noted.In some cultures, they added, women who are unable to have children and their partners may face discrimination, stigma, and ostracism.Another study in the series recommended using high-quality ultrasound for accurate miscarriage diagnoses and surgical management with vacuum suction aspiration as the preferred approach for missed miscarriages-those that occur without pain or bleeding.The authors noted that dedicated early pregnancy units are emerging as a model of care in the UK, Canada, Australia, and other countries.These units should be equipped with appropriate medications, ultrasound machines, efficient blood test processing, and staff who are properly trained in ultrasound scanning, giving bad news, and providing psychological support, the authors wrote.Co-lead author of the series, Siobhan Quenby, MD, of the University of Warwick in the UK, said in a statement that many women who've had a miscarriage are advised only to try again."That is not good enough, and we must ensure women are properly supported."
Variation of National and International Guidelines on Respiratory Protection for Health Care Professionals During the COVID-19 Pandemic
Authors: Gabriel Birgand, Nico T. Mutters, Jonathan Otter, Vanessa M. Eichel, Didier Lepelletier, Daniel J. Morgan, Jean-Christophe Lucet
Journal: JAMA Network Open (2021)

in respiratory protection guidelines between neighboring countries created confusion over optimal measures.Strong collaborations between national and international organizations are critical in such circumstances.
Impact of Palliative Care Involvement on End-of-Life Care Patterns Among Adolescents and Young Adults With Cancer: A Population-Based Cohort Study
Authors: Alisha Kassam, Abha Gupta, Adam Rapoport, Amirrtha Srikanthan, Rinku Sutradhar, Jin Luo, Kimberley Widger, Joanne Wolfe, Craig Earle, Sumit Gupta
Journal: Journal of Clinical Oncology (2021)

Evidence suggests that adolescents and young adults (AYAs) with cancer (defined as age 15-39 years) receive high-intensity (HI) medical care at the end-of-life (EOL). Previous population-level studies are limited and lack information on the impact of palliative care (PC) provision. We evaluated prevalence and predictors of HI-EOL care in AYAs with cancer in Ontario, Canada. A secondary aim was to evaluate the impact of PC physicians on the intensity of EOL care in AYAs.A retrospective decedent cohort of AYAs with cancer who died between 2000 and 2017 in Ontario, Canada, was assembled using a provincial registry and linked to population-based health care data. On the basis of previous studies, the primary composite measure HI-EOL care included any of the following: intravenous chemotherapy < 14 days from death, more than one emergency department visit, and more than one hospitalization or intensive care unit admission < 30 days from death. Secondary measures included the most invasive (MI) EOL care (eg, mechanical ventilation < 14 days from death) and PC physician involvement. We determined predictors of outcomes using appropriate regression models.Of 7,122 AYAs, 43.8% experienced HI-EOL care. PC physician involvement (odds ratio [OR], 0.57; 95% CI, 0.51 to 0.63) and older age at death (OR, 0.60; 95% CI, 0.48 to 0.74) were associated with a lower risk of HI-EOL care. AYAs with hematologic malignancies were at highest risk for HI and MI-EOL care. PC physician involvement substantially reduced the odds of mechanical ventilation at EOL (OR, 0.36; 95% CI, 0.30 to 0.43).A large proportion of AYAs with cancer experience HI-EOL care. Our study provides strong evidence that PC physician involvement can help mitigate the risk of HI and MI-EOL care in AYAs with cancer.
Association of Demographic Factors and Infantile Hemangioma Characteristics With Risk of PHACE Syndrome
Authors: Colleen H. Cotton, Jusleen Ahluwalia, Daniel M. Balkin, Ilona J. Frieden, Anita N. Haggstrom, Leslie A. Castelo-Soccio, Carmen Liy-Wong, Elena Pope, Jack E. Steiner, Dawn H. Siegel, Esteban Fernandez-Faith, Kimberly D. Morel, Christine T. Lauren, Maria C. Garzon, Anthony J. Mancini, Sarah L. Chamlin, Megha M. Tollefson, Marilyn G. Liang, Sophia Delano, Sharon A. Glick, Marcia Hogeling, Victoria R. Barrio
Journal: JAMA Dermatology (2021)

A 2010 prospective study of 108 infants estimated the incidence of PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome to be 31% in children with facial infantile hemangiomas (IHs) of at least 22 cm2. There is little evidence regarding the associations among IH characteristics, demographic characteristics, and risk of PHACE syndrome.
無視できる皮膚光毒性を有する癌光化学療法のための光熱-pH-低酸素応答性多機能ナノプラットフォーム【JST・京大機械翻訳】
Authors: Chen Dapeng, Tang Yunyun, Zhu Jiawei, Zhang Jiaojiao, Song Xuejiao, Wang Wenjun, Shao Jinjun, Huang Wei, Chen Peng, Dong Xiaochen
Journal: Biomaterials (2019)
Evaluation of cohort diversity in development and validation studies of hereditary cancer genetic risk assessment models.
Authors: Amanda Gammon, Ambreen Khan, Joanne M. Jeter
Journal: Journal of Clinical Oncology (2021)

10600 Background: Multiple models estimate a person’s chance of harboring a pathogenic variant increasing cancer risk. Some pathogenic variants are more common in individuals from specific ancestries, such as the BRCA1 and BRCA2 founder variants in Ashkenazi Jews. Yet data remains limited on the larger variant spectrum seen among people of different ancestral backgrounds and whether or not the pathogenic variant frequency differs in many populations. Due to this, it is important that genetic risk assessment models be validated in a diverse cohort including Black, Indigenous, People of Color (BIPOC). Methods: A literature search was conducted to identify published development and validation studies for the following genetic risk assessment models: BRCAPRO, MMRPRO, CanRisk/BOADICEA, Tyrer-Cuzick, and PREMM. Validation studies that only evaluated the cancer risk prediction capabilities of the models (and not the genetic variant risk prediction) were excluded. The following participant information was abstracted from each study: total number of participants, gender, race, and ethnicity. Authors were contacted to obtain missing information (if available). Results: 12 development and 12 validation studies of the genetic risk assessment models BRCAPRO, MMRPRO, CanRisk/BOADICEA, Tyrer-Cuzick, and PREMM were abstracted. Of the validation studies, five were internal validation studies conducted by the model developers, and seven were external validation studies. Four external validation studies compared multiple models. 75% (18/24) of papers did not include reporting of participant race or ethnicity information in their published reports. External validation studies (4/7, 57%) more often reported participant race/ethnicity than development (0/12, 0%) or internal validation (2/5, 40%) studies. The external validation studies for BRCAPRO reporting race/ethnicity information involved cohorts that ranged from 50-51% non-Ashkenazi Jewish white, 28% African American, 1% Asian, 2-49% Hispanic, and 19-42% Ashkenazi Jewish. The external validation studies for MMRPRO and PREMM reporting race/ethnicity information involved cohort that ranged from 0-82% white, 4-100% Asian, 7% Black, and 7% Hispanic. Conclusions: Increased reporting of participant ancestry and ethnicity is needed in the development and validation studies of genetic risk assessment models. BRCAPRO’s validation cohorts have included a higher percentage of Hispanic and Black/African American participants, while MMRPRO and PREMM have been validated in a higher percentage of Asian participants. As debate continues about the utility of currently used racial categories in genetics research, it will be important to determine how best to report on participant diversity. These findings highlight the continued need for genetics researchers to engage BIPOC and identify ways to diversify their participant cohorts.
Abstract 216: Renal Failure After Cardiac Arrest and the role of Targeted Temperature Management
Authors: Abhishek Bhardwaj, Steve Balian, David G Buckler, Benjamin S Abella
Journal: Circulation (2018)

Introduction: While Acute Kidney Injury (AKI) is a common complication of cardiac arrest (CA), the incidence of AKI and Chronic Kidney Disease (CKD) following resuscitation are not well studied. Further, the association of Targeted Temperature Management (TTM) with AKI and CKD incidence has not been extensively studied. Aim: We compared the incidence of post-arrest AKI and CKD among patients who received TTM and those who did not receive TTM. Methods: In this retrospective cohort study, we studied adult patients following resuscitation from out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). Serum creatinine (Cr) data for post-arrest patients were extracted from the electronic medical record. Baseline serum Cr was defined as the most recent pre-arrest Cr value or the lowest Cr value within 6 hrs of arrest. Using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, AKI was defined as an increase in Cr by &gt; 0.3 mg/dL within 48 hrs or an increase in serum Cr by 1.5x the baseline value within a one-week period. CKD was defined as a GFR of &lt; 60 mL/min per 1.73 m 2 3 months post-arrest. Results: From 1/2005 to 12/2017, 1099 patients had serial post-arrest creatinine values available. Median age at arrest was 63 (IQR 25), 58% were male, survival to discharge was 20%, with a 17 % favorable CPC score of 1 or 2. Of these, 240 patients had documented TTM status (89 received TTM and 151 did not). Of the patients who received TTM, 31% developed AKI compared to 40 % who did not receive TTM (P=NS). The incidence of CKD was 56% in the TTM group and 45% in the non-TTM group. McNemar’s test for CKD at baseline and at 3 months post-arrest showed a significant increase in the incidence of CKD post arrest (45% vs. 49%, p = 0.031). Conclusions: Post cardiac arrest, AKI and CKD are common complications. The use of TTM was not associated with the incidence of AKI or CKD. Further research is needed to study factors that affect AKI and CKD in CA.
Characteristics of local inflammation in patients with uterine fibroids and endometrial cancer.
Authors: Tatiana A. Zykova, Elena Yu. Zlatnik, Vera P. Nikitina, Elena A. Shevyakova, Oksana E. Zhenilo, Ekaterina V. Verenikina, Viktoria A. Ivanova, Polina A. Kruze, Anna Yu. Ardzha
Journal: Journal of Clinical Oncology (2021)

e17561 Background: Contribution of local inflammation to the course of endometrial cancer (EC) is of interest since it may aggravate the disease. Methods: The study included 25 women aged 62+1.6 years with histologically verified EC (group 1a), 29 women aged 48+8.4 years with uterine fibroids (UF) (group 1b) and 13 non-cancer women aged 42+2.3 years (group 2, controls). Vaginal swabs were taken prior to antitumor treatment. Relative expression of genes encoding the synthesis of IL1B, IL10, IL18, TNFA, TLR4, GATA3, and CD68 in comparison with the reference gene B2M was determined by Real-time PCR using the ImmunoQuantex kit (Russia). An integral parameter of an inflammation index was calculated using binary logistics, and the ratios of the listed indicators were also calculated. 12 parameters were analyzed in total. Groups Ia and Ib were compared with healthy people (p 1 ) and with each other (p 2 ). Results: 4 of 12 studied parameters in EC patients differed from control; no differences were found in UF patients. 7 statistically significant differences were registered between EC and UF. Relative expression of the gene encoding the synthesis of IL10 was maximal in EC (2.8+0.2 vs. 1.8+0.3 in healthy women (p 1 = 0.006) and 1.8+0.2 in UF (p 2 = 0.002)). The IL10/IL18 ratio in EC statistically significantly exceeded the ratios in UF patients and in healthy women (61.4+21.7 (p 1 = 0.003), 46.3+32.2 (p 2 &lt; 0.001) and 53.7+47.1 respectively). The TNFA/IL18 ratio in EC patients was also higher than in UF patients (1.1+0.7 vs. 0.5+0.2 (p 2 = 0.035)) due to higher TNFA levels (3.7+0.1 vs. 3.3+0.1 (p 2 = 0.006)), one of which effects includes stimulation of neoangiogenesis. The ratio of TLR4/GATA3, on the contrary, was lower in EC than in UF (0.7+0.3 and 1.5+0.9 respectively (p 2 = 0.001). Apparently, it characterized antimicrobial immunity because both of these genes are involved in the response to PAMP (TLR4) and in the genesis of intraepithelial lymphocytes related to innate immunity, as well as in the development of a humoral response via stimulation of Th2 (GATA3). The latter, in addition, is involved in the ontogenesis some organs, including the vagina and uterus. The highest TLR4/GATA3 ratio was found in UF, which, in our opinion, indicated the predominance of the inflammatory process in UF and local immunosuppression in EC. The inflammation index determined with the ImmunoQuantex test system did not differ between the studied groups of women. Conclusions: Some differences were observed in local reactions of immunity and inflammation in benign and malignant uterine tumors, involving the prevalence of immunosuppressive and angiogenic factors in EC and inflammatory factors in UF.