tbuckley/cabot-search huggingface dataset:
Nation-wide trends in mortality of patients with ocular and orbit melanoma: 2000 to 2014.
Authors: William Forehand, Swathi Gopishetty, Ashkan Shahbandi, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2019)

e21061 Background: Ocular and orbit melanoma is a rare subtype of melanoma for which outcomes have not been adequately reported. In this study we he have analyzed the incidence-based mortality trends of ocular and orbit melanoma over a 15 year period. Most ocular melanomas originate from the uvea and to a lesser extent from the conjunctiva. Primary orbital melanoma is exceedingly rare. The incidence of ocular melanoma has been stable for the past few decades but incidence-based mortality has not been studied over the past 15 years. Methods: The Surveillance, Epidemiology, and End Results (SEER) Database was utilized to query the incidence-based mortality for all patients diagnosed with ocular and orbit melanoma for the years 2000 to 2014. The results were grouped by gender and race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander). Paired T-test was used to determine statistically significance difference between various subgroups (p &lt; 0.05). Results: Incidence-based mortality has been the highest in Caucasian/White patients from 2000 to 2014 followed by African American/Black and Asian/Pacific Islander patients. American Indian/Alaskan native patients appear to have the least mortality. There was a statistically significant difference (p &lt; 0.05) in mortality between Caucasian/White patients from 2000 to 2014 followed by African American/Black and Asian/Pacific Islander patients. The sample size for African American/Black and American Indian/Alaskan native patients was too low for discerning a meaningful trend in mortality. Overall it appears that Caucasian males and females have a far higher and worsening incidence-based mortality compared to other races. Conclusions: Ocular melanoma and orbit melanoma are rare entities which are predominantly seen in Caucasian/White patients. This study shows that the incidence-based-mortality has been worsening for these patients in the past two decades. These entities have poor prognosis and have not been studied extensively in immunotherapy trials. This study highlights the need for new clinical trials to help improve the mortality rates.
Assessment of breast cancer risk in BRCA carriers with ovarian cancer: Evaluation of data from longitudinal observation.
Authors: Tamar Safra, Barliz Waissengrin, Deanna Gerber, Rinat Bernstein Molho, Amnon Amit, Lina Salman, Dana Josephy, Rakefet Chen-Shtoyerman, Ilan Bruchim, Melissa Kristen Frey, Bhavana Pothuri, Franco Muggia
Journal: Journal of Clinical Oncology (2019)

e13062 Background: To confirm data from older studies reporting reduced risks of breast cancer (BC) in BRCA mutated (BRCA+) ovarian cancer (OC) patients and to re-evaluate BC surveillance and/or prophylactic mastectomy in OC patients. Methods: Data on 430 BRCA+ mutation carriers diagnosed with OC between 2000 and 2017 in 6 medical centers (one in the USA and five in Israel) were analyzed. Data included demographics, breast surveillance type, family history, BRCA mutation types, timing of BC diagnosis (before or after OC diagnosis) and family history of cancer. Results: Median age at diagnosis of OC was 55.4 years (range, 31.3-90) and median follow-up was 4.6 years. Most patients were BRCA1 (66.6%), and 35.7% had 185delAG. Most patients (68.4%) were Ashkenazi Jews, 27.4% had a family history of BC and 16.5% were diagnosed with BC before OC. Five percent developed BC following OC diagnosis with a median time to BC diagnosis of 68 months (range, 11-210). Of those diagnosed with BC, 50% had triple-negative BC, 40% had luminal B ER+, PR-, Her2-neg and 10% had luminal A -ER+, PR+, her2-neg. There was a non-significant increase in BC after OC, and in BC prior to OC diagnosis; there was no correlation of BC with family history. No definite deaths from BC were recorded. Conclusions: The incidence of BC after OC diagnosis in the BRCA+ population at a median follow-up of 4.6 years is consistent with prior series. Prophylactic bilateral Surveillance measures should be re-evaluated in this population and may only be needed in long-term disease-free survivors and/or subpopulations to be identified. Clinical trial information: 07-146.
Thinking through other minds: A variational approach to cognition and culture
Authors: Samuel P. L. Veissière, Axel Constant, Maxwell J. D. Ramstead, Karl J. Friston, Laurence J. Kirmayer
Journal: Behavioral and Brain Sciences (2019)

Abstract The processes underwriting the acquisition of culture remain unclear. How are shared habits, norms, and expectations learned and maintained with precision and reliability across large-scale sociocultural ensembles? Is there a unifying account of the mechanisms involved in the acquisition of culture? Notions such as “shared expectations,” the “selective patterning of attention and behaviour,” “cultural evolution,” “cultural inheritance,” and “implicit learning” are the main candidates to underpin a unifying account of cognition and the acquisition of culture; however, their interactions require greater specification and clarification. In this article, we integrate these candidates using the variational (free-energy) approach to human cognition and culture in theoretical neuroscience. We describe the construction by humans of social niches that afford epistemic resources called cultural affordances. We argue that human agents learn the shared habits, norms, and expectations of their culture through immersive participation in patterned cultural practices that selectively pattern attention and behaviour. We call this process “thinking through other minds” (TTOM) – in effect, the process of inferring other agents’ expectations about the world and how to behave in social context. We argue that for humans, information from and about other people's expectations constitutes the primary domain of statistical regularities that humans leverage to predict and organize behaviour. The integrative model we offer has implications that can advance theories of cognition, enculturation, adaptation, and psychopathology. Crucially, this formal (variational) treatment seeks to resolve key debates in current cognitive science, such as the distinction between internalist and externalist accounts of theory of mind abilities and the more fundamental distinction between dynamical and representational accounts of enactivism.
Endocrine therapy discontinuation rates in older women with early stage breast cancer who are candidates for omission of radiation.
Authors: Heidi Egloff, Leigh Klaus Swartz, Fang Fang, Kelley M. Kidwell, Anne F. Schott
Journal: Journal of Clinical Oncology (2019)

e23018 Background: As the treatment for early-stage breast cancer continually evolves, there has been a pragmatic shift with regard to standard treatment placing a high-value on multidisciplinary management. Recent studies have shown that sentinel lymph node biopsy (SLNB) and adjuvant radiation (RT) can be omitted in a subset of older women with early-stage hormone receptor positive breast cancer who plan to take adjuvant endocrine therapy (ET). Prior analyses estimate a wide range of discontinuation rates, with studies citing 31-73%. The primary aim of this analysis is to estimate the discontinuation rate of endocrine therapy in women ages 70 and older with early stage breast cancer who omit radiation therapy at our institution. Methods: We performed a retrospective review of institutional cancer registry and EMR data to identify all women with breast cancer, ages 70 or older, AJCC 7 stage I or II, hormone receptor positive, HER2 negative, who underwent lumpectomy at the University of Michigan inclusive of years 2014 through 2017. Multiple variables of interest were collected and analyzed. Results: 174 women met initial inclusion criteria for ER/PR positive, HER2 negative, Stage I/II disease, who underwent lumpectomy. Of these, N = 10 pursued adjuvant radiation therapy with omission of ET, and N = 19 declined both ET and RT upfront. The remaining 145 women chose to pursue ET alone (N = 78) or ET+RT (N = 67). 30/145 (21%) discontinued endocrine therapy, 22% (N = 15) in the ET+RT, 19% (N = 15) in the ET alone groups. There was no statistically significant difference between groups with regard to the discontinuation of ET upon comparison, log-rank p-value 0.4. The primary reason for ET discontinuation, N = 27 (90%) was secondary to side effects. Conclusions: This review demonstrated that a significant number (54%) of older women opt to omit radiation in favor of ET alone after multidisciplinary discussion, in accordance with NCCN guidelines. Endocrine therapy discontinuation rates among older women at our institution were comparable to rates in the literature for women of all ages, and the reason for discontinuation was attributed to side effects. The pivotal clinical trials (PRIME II and CALGB 9343) exploring ET alone versus ET+RT did not report on ET discontinuation rates. In our analysis, almost 20% of women receiving ET alone discontinued ET therapy, calling into question a missed radiation treatment opportunity in a curative setting.
Cell cycle progression score and PTEN as prognostic factors for metastasis in intermediate and high-risk prostate cancer.
Authors: Bruce J. Trock, Saradha Rajamani, Igor Vidal, Stephanie Glavaris, Tracy Jones, Misop Han, Alan W. Partin, Todd Cohen, Steven Stone, Angelo M De Marzo
Journal: Journal of Clinical Oncology (2019)

e16575 Background: To evaluate the cell cycle progression (CCP) score and PTEN as prognostic markers for risk of metastasis in a radical prostatectomy (RP) cohort of NCCN intermediate and high risk prostate cancer. Methods: This IRB-approved case-cohort study included men treated with RP at Johns Hopkins from 2007-2015. Paraffin-embedded RP tissue was analyzed blind to study outcome at Myriad Genetics, for CCP score using qRT-PCR, and PTEN by immunohistochemistry. Metastasis-free survival (MFS) was analyzed with the Cox proportional hazards model, weighted for case-cohort design. CCP and PTEN were analyzed independently, and adjusted for CAPRA-S. The CCR score, which combines CCP and CAPRA-S, was also analyzed. Data were analyzed independently by Johns Hopkins and Myriad Genetics. Results: There were 209 patients, of whom 42 were cases (metastasis). Median age was 59 years, 47% had Gleason 4+3 or higher, 48% had non-organ confined tumor, and 18% had seminal vesicle or lymph node involvement. NCCN risk was intermediate in 77% and high in 23%. Median follow-up was 4 years. Both CCP and PTEN, as well as CCR score, were statistically significant in univariate analyses, but only CCP retained statistical significance in a multivariable model of CCP, PTEN, and CAPRA-S (Table). Conclusions: This is the first comparison of the CCP score and PTEN as risk factors for metastasis in a recent RP cohort of patients at NCCN intermediate or high risk. Both CCP score and PTEN were strongly associated with MFS in univariate analyses, but only CCP score retained significance in a multivariable analysis with both biomarkers adjusted for CAPRA-S. [Table: see text]
SP0174 ADVANCES IN THE DETECTION OF PATHOGENIC AUTOANTIBODIES IN SLE
Authors: Luis Munoz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The accumulation of late apoptotic or so-called Secondary NEcrotic Cells (SNEC) in germinal centers challenges B and T cell tolerance and leads to the development of autoimmunity and the production of autoantibodies. <h3>Objectives:</h3> Determine the test performance of immobilized SNEC autoantigens for the diagnosis of Systemic Lupus Erythematosus. <h3>Methods:</h3> SNEC ELISA of sera from patients with SLE and test performance statistics were deployed to evaluate the diagnostic potential SNEC-derived autoantigens. Functional assays confirmed its pathophysiological relevance. <h3>Results:</h3> SNEC contains nuclear autoantigens bearing apoptosis-associated modifications such as histone H3 K27me3, histone H2A/H4AcK8,12,16, and histone H2B-AcK12. The SNEC ELISA clearly discriminated patients with SLE from patients with Rheumatoid Arthritis (RA), Primary Anti-Phospholipid Syndrome (PAPS), Spondyloarthropathy (SpA), Psoriatic Arthritis (PsA), and Systemic Sclerosis (SSc). A positive test result in SNEC ELISA significantly correlated with serological variables and reflected the uptake of opsonized SNEC by neutrophils in the blood. <h3>Conclusion:</h3> SNEC ELISA allows for the sensitive detection of pathologically relevant autoantibodies in the serum of patients with SLE. The clearance of nuclear remnants by neutrophils enhances inflammatory responses supporting the role of clearance deficiency in the etiopathogenesis of SLE. <h3>Reference:</h3> [1] Biermann MHC, Boeltz S, Pieterse E, Knopf J, Rech J, Bilyy R, van der Vlag J, Tincani A, Distler JHW, Krönke G, Schett GA, Herrmann M and Muñoz LE (2018) Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and Identify Patients With Systemic Lupus Erythematosus. Front. Immunol. 9:989. doi: 10.3389/fimmu.2018.00989 <h3>Disclosure of Interests:</h3> None declared
Incidence and severity of postoperative complications following neoadjuvant therapy and full-thickness local excision for moderately advanced rectal cancer.
Authors: Ahmed Abdalla, Amr Aref, Amer Alame, Mohammed Barawi, Abdelkader Hawasl, Adli Yakan
Journal: Journal of Clinical Oncology (2019)

e15167 Background: Trans-anal full-thickness local excision (LE) for patients with moderately advanced rectal cancer (MARC) whose tumors respond well to neoadjuvant therapy, is one approach for organ preservation. Some authors call for abandoning this procedure because it causes frequent and severe complications. We aim to report our post-operative complications rate and severity following this procedure. Methods: This is a retrospective review of the complications observed in 10 patients who underwent LE at our center between May 2017-January 2019. Primary outcomes were the presence and nature of complications associated with the treatment course. Results: Five patients were treated according to Phase II trial and received three months of FOLFOX chemotherapy followed by concurrent chemo-RT. Five additional patients received only concurrent chemo-radiotherapy as they were treated off protocol. Radiation therapy (RT) dose ranged between 45-54 Gy and the interval between completion of RT and LE ranged between 6-15 weeks; median 11.5 weeks. Gross residual disease was resected with no margin in nine patients. The size of removed specimens ranged between 6.8-1.4cm; median 2.2 cm with a depth of resection of 1.5-0.4 cm; median .6 cm. Two patients had a very low residual gross abnormality and the surgical resection extended to the dentate line. Both patients experienced grade III complications of severe pain, infection and fistula formation. Of the remaining 8 patients with tumors located between 3-8 cm from the anal verge, two patients developed grade II complications requiring a short course of antibiotics and symptomatic treatment. In both cases, symptoms resolved within one week. Conclusions: Post-operative complications in this setting are not prohibitive if LE doesn’t extend to the dentate line and the resection is limited to only residual abnormality with no mucosal margin. A complete pathological response, confirmed by LE after neoadjuvant therapy provides valuable prognostic information and can influence the intensity and burden of future follow up. The risk of surgical complications is acceptable in view of these advantages. LE remains a viable option in pursuing organ preservation for MARC when complete remission is achieved by neoadjuvant therapy.
Osteopontin Promotes Left Ventricular Diastolic Dysfunction Through a Mitochondrial Pathway
Authors: Keyvan Yousefi, Camila I. Irion, Lauro M. Takeuchi, Wen Ding, Guerline Lambert, Trevor Eisenberg, Sarah Sukkar, Henk L. Granzier, Mei Methawasin, Dong I. Lee, Virginia S. Hahn, David A. Kass, Konstantinos E. Hatzistergos, Joshua M. Hare, Keith A. Webster, Lina A. Shehadeh
Journal: Journal of the American College of Cardiology (2019)
The Ongoing Ebola Epidemic in the Democratic Republic of Congo, 2018–2019
Authors: Oly Ilunga Kalenga, Matshidiso Moeti, Annie Sparrow, Vinh-Kim Nguyen, Daniel Lucey, Tedros A. Ghebreyesus
Journal: New England Journal of Medicine (2019)

The international response to the evolving Ebola epidemic in eastern Democratic Republic of Congo (DRC) has had interim successes while facing ongoing difficulties. The outbreak has occurred in an area of intractable conflict among multiple armed groups at a time of contentious national elections. Despite porous international borders and considerable population movement, however, transmission has been confined to North Kivu and Ituri provinces. Factors potentially contributing to this containment include conduct of about 55 million screenings, surveillance of contacts (12,591 under surveillance currently), testing of 280 samples per day, provision of safe and dignified burials for most deaths, vaccination of high-risk people (112,485 vaccinated as of May 7, 2019), and medical treatment including four investigational therapies. Major challenges remain. Since late February 2019, a sharp rise in cases and increased transmission have been observed. These coincide with organized attacks by armed groups targeting response teams, deteriorating security, and the population's increasing distrust of the response effort. The risk of local and regional spread remains high given the high proportion of deaths occurring outside treatment facilities, relatively low proportions of new patients who were known contacts, ongoing nosocomial transmission, and persistent delays in detection and reporting. Stopping this epidemic will require the alignment of the principal political and armed groups in eastern DRC in support of the response.
Association of geographic clustering of cutaneous T-cell lymphoma in the state of Georgia with environmental exposure to benzene and trichloroethylene.
Authors: Pamela Blair Allen, Lindsay Clough, A. Rana Bayakly, Kevin C. Ward, Mohammad Khurram Khan, Suephy Chen, Christopher Flowers, Jeffrey M. Switchenko
Journal: Journal of Clinical Oncology (2019)

1551 Background: Geographic clustering of CTCL has been recently reported in large registries, but its association with environment factors is unknown. Benzene and trichloroethylene (TCE) are two common carcinogenic environmental toxins associated with hematological cancers. We investigated associations between geographic clustering of CTCL incidence in the state of Georgia with benzene and TCE exposure. Methods: We obtained county-level incidence of CTCL within Georgia from the Georgia Cancer Registry between 1999-2015. To account for the demographic structure in each county, standardized incidence ratios (SIR) were calculated by dividing the observed number of cases of CTCL in Georgia by the expected number of cases using national incidence rates by age, sex, and race. Using spatial analyses, we assessed for population-adjusted county-level clustering of SIRs. We also recorded county-level exposure concentration of benzene and TCE between 1996-2014 from the EPA’s National Air Toxics Assessment database. Linear regression analyses on CTCL incidence were performed comparing SIRs to exposure levels of benzene and TCE by county. Results: Our analyses demonstrated significant geographic clustering of CTCL in Georgia (Moran’s I statistic 0.0991, p-value = 0.022). Local spatial tests revealed several statistically significant hot spots throughout Georgia, particularly around Atlanta. This clustering was strongly correlated with benzene (R 2 0.0824, p-value 0.0006) and TCE (R 2 0.0614, p-value 0.0016) exposure concentration. Among the four most populous counties in Georgia (Cobb, Dekalb, Fulton, and Gwinnett) CTCL incidence was 1.7 to 2.7 times higher than the average county, and benzene and TCE exposure concentration was 3.0 to 6.3 times higher. Conclusions: These results demonstrate non-random geographic clustering of CTCL incidence in Georgia. This is the first analysis to correlate geographic clustering of CTCL with environmental toxic exposures, demonstrating a statistically significant correlation between environmental exposure to benzene and TCE and CTCL incidence within Georgia. [Table: see text]
AB0928 CORONARY ARTERY LESIONS AT PRESENTATION IN KAWASAKI DISEASE: A MARKER OF IVIG RESISTANCE?A RETROSPECTIVE STUDY FROM NORTH INDIA
Authors: MANJARI AGARWAL, Sumidha Mittal, Anju Singh, Sujata Sawhney
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Kawasaki disease has been well described from all around the world.This has been well described from our country. We recently changed our practice with regards to addition of corticosteroids and undertook this study. <h3>Objectives</h3> To study the clinical profile of children with Kawasaki disease presenting to our unit. To study the response of therapy in children with Kawasaki disease To study the efficacy of addition of upfront steroids in children with coronary artery lesions (z score&gt;2.5) <h3>Methods</h3> All children with Kawasaki disease seen in the last 5 years were included and data collected on prefilled proforma. IVIG 2gm/kg as a single dose over 18-24 hours was given to all children. Aspirin in dose of 30-80mg/kg/day was given to all children along with IVIG. Response was defined as defervescence within 36 hours of completion of IVIG. Fever beyond 36 hours of completion of IVIG was considered as no response/resistance to 1st dose of IVIG. <h3>Results</h3> 60 children diagnosed with Kawasaki disease were included. Median age at diagnosis of disease was 3.12 years(0.3-15 years).33 children had complete Kawasaki disease, 26 children had incomplete disease and one child had atypical Kawasaki disease36 children were diagnosed within first 10 days of disease onset and 24 children were diagnosed after day 10 of illness.18 children had history of infections prior to onset of Kawasaki disease.29 children(48%) had coronary artery lesions at the time of presentation.48 children(80%) were given1st dose of IVIG without any corticosteroids.36 children (75%)responded to first dose of IVIG, one child was not given IVIG as he was diagnosed retrospectively and had self limiting disease. 14 children(29%) did not respond to 1st dose of IVIG. 9 children were given intravenous methylprednisolone 2mg/kg/day in four divided doses along with IVIG. All of these responded to the first dose of IVIG. The size of coronary artery lesion also plays an important role. In children with z score &gt;2.5 the response to 1st dose of IVIG was 61.5% whereas it was 94%in those who had z scores&lt;2.5(p value 0.03) Response rate was significantly higher in patients with no coronary artery lesions (p value0.007).In children with coronary artery lesions at presentation, the response rate was significantly higher in children who were given steroids upfront (p value 0.027). <h3>Conclusion</h3> We see many children with coronary artery lesions at presentation. This seems to be an indicator of resistance to IVIG. It is beneficial to add steroids upfront along with IVIG to children with coronary artery lesions more than 2.5 z score. <h3>Reference</h3> [1] Dallaire F, Dahdah N. New equations and a critical appraisal of coronary artery Z scores in healthy children. J Am Soc Echocardiogr. 2011Jan;24(1):60-74. <h3>Disclosure of Interests</h3> None declared