tbuckley/cabot-search huggingface dataset:
Combined use of two monoclonal antibodies in patients with systemic AL amyloidosis and cardiac involvement.
Authors: Amandeep Godara, Nauman Saleem Siddiqui, Lisa Lee, Denis Toskic, Teresa Fogaren, Cindy Varga, Ray Comenzo
Journal: Journal of Clinical Oncology (2019)

8009 Background: Systemic AL amyloidosis (AL) is a rare disease in which circulating immunoglobulin light chains misfold, are directly toxic to key organs and also cause organ failure by mass effect. Patients with cardiac involvement have a poor prognosis; 25% of them die within 6 months of diagnosis. Depth of hematologic and organ response has prognostic significance and as new therapies become available, combining targeted therapies might hold the key to improve survival and deepen responses. Methods: We report the outcomes of 9 patients with AL amyloidosis who simultaneously received dual monoclonal antibody therapy with daratumumab and the investigational anti-fibril antibody NEOD001 at our institution. We also provide a descriptive comparison of 10 other AL amyloidosis patients who received treatment with daratumumab alone. Results: Of these 9 patients, there were 4 men/5 women with a median age of 68 years (range, 52-75) and a median of 261 days from diagnosis (range, 51-2037). Median NT-proBNP was 3807 pg/ml (range, 1326-13193). These 9 patients did not respond to initial therapy with a bortezomib-based regimen. Infusions of both monoclonals were separated by 2 days and were well tolerated without any unexpected toxicity. 88% of patients achieved ≥VGPR with daratumumab+NEOD001 in a median of 33 days and cardiac responses were achieved in &lt; 90 days. In contrast, patients receiving daratumumab alone (n=10) achieved hematologic and cardiac responses at later times (Table). Conclusions: In conclusion, dual monoclonal antibodies targeting different epitopes can be safely combined in patients with systemic AL amyloidosis. Although this report features a small number of patients, high rates of hematologic and cardiac responses achieved suggest that this combination should be studied further, possibly in a prospective randomized trial. [Table: see text]
Risk factors for childhood and adult primary brain tumors
Authors: Quinn T Ostrom, Maral Adel Fahmideh, David J Cote, Ivo S Muskens, Jeremy M Schraw, Michael E Scheurer, Melissa L Bondy
Journal: Neuro-Oncology (2019)

Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurring solid tumors in children. These tumors are very heterogeneous and can be broadly classified into malignant and benign (or non-malignant), and specific histologies vary in frequency by age, sex, and race/ethnicity. Epidemiological studies have explored numerous potential risk factors, and thus far the only validated associations for brain tumors are ionizing radiation (which increases risk in both adults and children) and history of allergies (which decreases risk in adults). Studies of genetic risk factors have identified 32 germline variants associated with increased risk for these tumors in adults (25 in glioma, 2 in meningioma, 3 in pituitary adenoma, and 2 in primary CNS lymphoma), and further studies are currently under way for other histologic subtypes, as well as for various childhood brain tumors. While identifying risk factors for these tumors is difficult due to their rarity, many existing datasets can be leveraged for future discoveries in multi-institutional collaborations. Many institutions are continuing to develop large clinical databases including pre-diagnostic risk factor data, and developments in molecular characterization of tumor subtypes continue to allow for investigation of more refined phenotypes. Key Point 1. Brain tumors are a heterogeneous group of tumors that vary significantly in incidence by age, sex, and race/ethnicity.2. The only well-validated risk factors for brain tumors are ionizing radiation (which increases risk in adults and children) and history of allergies (which decreases risk).3. Genome-wide association studies have identified 32 histology-specific inherited genetic variants associated with increased risk of these tumors.
Perinatal care: mental health support expands but weight and smoking services “extremely disappointing”
Authors: Jacqui Wise
Journal: BMJ (2019)

There has been significant expansion in mental health support for women during pregnancy and postnatally, according to the latest snapshot survey of NHS maternity and neonatal services in England, Scotland, and Wales.1

There has been no improvement, however, in access to specialist services on weight management and smoking services—a situation which Lesley Regan, president of the Royal College of Obstetricians and Gynaecologists, described as “extremely disappointing.”

The second organisational survey of the National Maternity and Perinatal Audit gathered data from all 151 eligible trusts and health boards across Britain as of January 2019. It shows how maternity and neonatal services have changed since the last survey in January 2017.

The number of trusts and health boards that participate in a perinatal mental health network has increased from 70% to 93% in England, …
Uptake of 18F-Fluciclovine in Paget Disease
Authors: Oladunni O. Akin-Akintayo, Dacian Bonta, Bruce Barron
Journal: Clinical Nuclear Medicine (2019)

Abstract Since its recent approval by the United States Food and Drug Administration, fluciclovine PET-CT has gained widespread use for imaging of recurrent prostate cancer patients. As an amino acid–based radiotracer transported by LAT-1 and ASCT-2 transporters, fluciclovine exploits the up-regulation of amino acid transporters in malignant cells. We present a rare case of fluciclovine uptake in Paget disease in a 58-year-old man with suspected recurrent prostate cancer and asymmetric increased left hemipelvic uptake on imaging.
Abstract 16227: A Chemokine C-C motif receptor 2 Antagonist, INCB3344, Reverses Hypertension and Macrophage Accumulation in the Artery Wall in Angiotensin II-Treated Mice
Authors: Jeffrey P Moore, Christopher Chan, Samy Sakkal, Sharon L Ricardo, Christopher G Sobey, Grant R Drummond
Journal: Circulation (2012)

Macrophages accumulate in the artery wall during hypertension and contribute to the vascular inflammation, oxidative stress and endothelial dysfunction that are hallmarks of the condition. The aim ...
Unconventional diagnostic tests for Lyme borreliosis: a systematic review
Authors: A. Raffetin, A. Saunier, K. Bouiller, P. Caraux-Paz, C. Eldin, S. Gallien, R. Jouenne, A. Belkacem, J. Salomon, O. Patey, E. Talagrand-Reboul, B. Jaulhac, A. Grillon
Journal: Clinical Microbiology and Infection (2019)

Lyme borreliosis (LB) diagnosis currently relies mainly on serological tests and sometimes PCR or culture. However, other biological assays are being developed to try to improve Borrelia-infection diagnosis and/or monitoring.To analyse available data on these unconventional LB diagnostic assays through a systematic literature review.We searched PubMed and Cochrane Library databases according to the PRISMA-DTA method and the Cochrane Handbook for Systematic Reviews of Interventions. We analysed controlled and uncontrolled studies (published 1983-2018) on biological tests for adults to diagnose LB according to the European Study Group for Lyme Borreliosis or the Infectious Diseases Society of America definitions, or identify strongly suspected LB. Two independent readers evaluated study eligibility and extracted data from relevant study reports; a third reader analysed full texts of papers to resolve disagreements. The quality of each included study was assessed with the QUADAS-2 evaluation scale.Forty studies were included: two meta-analyses, 25 prospective controlled studies, five prospective uncontrolled studies, six retrospective controlled studies and two case reports. These biological tests assessed can be classified as: (i) proven to be effective at diagnosing LB and already in use (CXCL-13 for neuroborreliosis), but not enough to be standardized; (ii) not yet used routinely, requiring further clinical evaluation (CCL-19, OspA and interferon-α); (iii) uncertain LB diagnostic efficacy because of controversial results and/or poor methodological quality of studies evaluating them (lymphocyte transformation test, interferon-γ, ELISPOT); (iv) unacceptably low sensitivity and/or specificity (CD57+ natural killer cells and rapid diagnostic tests); and (v) possible only for research purposes (microscopy and xenodiagnoses).QUADAS-2 quality assessment demonstrated high risk of bias in 25/40 studies and uncertainty regarding applicability for 32/40, showing that in addition to PCR and serology, several other LB diagnostic assays have been developed but their sensitivities and specificities are heterogeneous and/or under-evaluated or unassessed. More studies are warranted to evaluate their performance parameters. The development of active infection biomarkers would greatly advance LB diagnosis and monitoring.
Doctor who worked consecutive 12 hour shifts without telling employers is suspended for four months
Authors: Clare Dyer
Journal: BMJ (2019)

A specialist doctor in an urgent treatment unit who worked back-to-back 12 hour shifts at different hospitals without telling his employers has been suspended from the UK medical register for four months.

Bevan Hyder, 47, left his job at Crawley Hospital early on four occasions in 2014 to work locum shifts elsewhere.

He did not tell his employers at Crawley about his other work or seek formal permission to leave early. Instead, he told the medical practitioners tribunal, he would message the nurse in charge on the day and ask to leave early without giving a reason. The earliest he left was 102 minutes before his shift was …
Single-cell MYD88 sequencing of isolated B cells from vitreous biopsies aids vitreoretinal lymphoma diagnosis
Authors: Wei Jian Tan, Mona Meng Wang, Paola Ricciardi-Castagnoli, Tiffany Tang, Soon Phaik Chee, Tong Seng Lim, Anita Sook Yee Chan
Journal: Blood (2019)
Association of TSR1 Variants and Spontaneous Coronary Artery Dissection
Authors: Yang Sun, Yanghui Chen, Yuanyuan Li, Zongzhe Li, Chenze Li, Ting Yu, Lei Xiao, Bo Yu, Hu Zhao, Min Tao, Jiangang Jiang, Jiangtao Yan, Yan Wang, Hesong Zeng, Xiaoqing Shen, Yiwu Zhou, Li Jin, Weihua Song, Kefei Dou, Dao Wen Wang
Journal: Journal of the American College of Cardiology (2019)
Pneumococcal vaccination coverages by age, sex and specific underlying risk conditions among middle-aged and older adults in Catalonia, Spain, 2017
Authors: Angel Vila-Córcoles, Olga Ochoa-Gondar, Cinta de Diego, Eva Satué, Angel Vila-Rovira, Maria Aragón
Journal: Eurosurveillance (2019)

BackgroundRecent published data on pneumococcal vaccination coverages among adults are scarce.AimTo update on pneumococcal vaccination uptakes among middle-aged and older adults in Catalonia.MethodsWe conducted a population-based retrospective observational study including 2,057,656 individuals ≥ 50 years old assigned to primary care centres managed by the Catalonian Health Institute on 1 January 2017 (date of data collection). An institutional clinical research database (SIDIAP) was used to classify persons by vaccination status for both 23-valent pneumococcal polysaccharide (PPsV23) and 13-valent pneumococcal conjugate (PCV13) vaccines, as well as to identify underlying risk conditions.ResultsOverall, 796,879 individuals (38.7%) had received PPsV23 and 13,607 (0.7%) PCV13. PPsV23 coverage increased with age: 9.2% (95,409/1,039,872) in 50-64 year olds, 63.1% (434,408/688,786) in 65-79 year olds and 81.2% (267,062/328,998) in ≥ 80 year olds (p < 0.001). PCV13 coverage also increased with age, although percentages were smaller in all age strata (4,250/1,039,872: 0.4%; 6,005/688,786: 0.9% and 3,352/328,998: 1.0%, respectively; p < 0.001). By sex, no substantial coverage differences were observed. Considering publically funded target groups for PPsV23 vaccination in Catalonia (i.e. < 65 year olds with at least one risk factor, plus all adults aged ≥ 65 years), PPsV23 coverage reached 52.8% (771,722/1,462,261) in our study population. Regarding PCV13 publicly funded targets (i.e. all-age immunocompromised persons), PCV13 coverage was 3.3% (6,617/202,348). By risk conditions, the highest PPsV23 coverage appeared in congestive heart failure (51,909/63,596; 81.6%), chronic renal disease (122,791/158,726; 77.4%) and chronic bronchitis/emphysema (96,453/132,306; 72.9%). Maximum PCV13 coverage appeared in cirrhosis (294/7,957; 3.7%), chronic renal disease (5,633/158,726; 3.5%) and chronic bronchitis/emphysema (2,859/132,306; 2.2%).ConclusionPneumococcal vaccination coverages in Catalonian adults are suboptimal, especially for PCV13.
Malignant Liver Tumors: Current and Emerging Therapies, Second Edition, Pierre Clavien, Yuman Fong, H Kim Lyerly, Michael A Morse, Alan P Venook (Eds.). Jones and Bartlett Publishers, Boston (2004), 482, $174.95, ISBN: 0 76371 857 2
Authors: Peter Hohenberger
Journal: The Lancet (2004)
Axillary lymph node ratio (LNR) versus pathologic nodal stage (pN) as a prognostic factor in breast cancer: Validation of Vinh-Hung's model in an Indian population.
Authors: Swati Batra, Manomoy Ganguly, Narayanan Kannan, Rajnish Talwar, Puneet Takkar, Dharmesh Soneji, Pranjal Kulshreshtha, Naveen Sanchety, Mani Kalaivani
Journal: Journal of Clinical Oncology (2013)

1099 Background: The axillary lymph node ratio (LNR), i.e., the ratio of positive over excised lymph nodes offers potentially improved prognostication, selection for adjuvant therapy and inter-institutional comparability compared to conventional pathological nodal staging (pN). A consensus on appropriate cut-offs however, remains to be achieved. Values of 0.20 and 0.65 to classify patients into low, intermediate and high-risk groups were proposed by Vinh-Hung et al, in the largest study on the subject till date. We perform a validation of the LNR concept for the first time in an independent patient population from the Indian subcontinent. Methods: 225 patients with a median follow-up of 42 months (range: 2 – 246 months) who underwent upfront surgery for breast cancer at a tertiary care hospital in Delhi, India, were retrospectively analysed, using Cox multivariate regression. Results: Using the above cut-off points, 10-year disease-free survival (DFS) rates of 83%, 74% and 28% and adjusted hazard ratios (HR) of 1.19 (95% CI 0.33 to 4.37), 2.21 (95% CI 0.75 to 6.51) and 6.88 (95% CI 1.58 – 29.92; P = 0.01) were obtained for the low-, intermediate- and high-risk groups respectively. The corresponding risks for the pN1, pN2 and pN3 categories were 1.74, 1.74, and 1.35, representing inadequate, even reversed prognostic separation. When both the LNR and pN were included as continuous variables, the nodal ratio remained prognostically significant with an adjusted HR of 12.33 (95% CI 1.1 – 142.5, P = 0.04) in contrast to the number of positive nodes which were not found to be significantly associated with DFS (HR = 0.97, 95% CI 0.9 – 1.1, P = 0.41). Conclusions: The LNR outperformed the pN staging in predicting DFS in our cohort of patients, irrespective of whether it was modeled as a categorical or a continuous variable. Simultaneous analysis with pN only increased its prognostic weight and resulted in exclusion of pN from the multivariate model. Our study thus provides independent external validation of Vinh-Hung’s proposed cut-offs and contributes to the growing body of literature supporting the incorporation of a ratio-based system into breast cancer staging.
Are there disparities in adjuvant treatment of HER2 positive breast cancer patients by age, race/ethnicity, and socioeconomic status?
Authors: Carol Parise, Vincent Caggiano
Journal: Journal of Clinical Oncology (2013)

e12512 Background: Standard adjuvant therapy for HER2-positive female breast cancer patients who are estrogen receptor (ER) positive is chemotherapy, trastuzumab, and endocrine therapy. Some studies report disparities in receipt of adjuvant treatment based on race/ethnicity, age, and socioeconomic status (SES). This study assessed the likelihood of receipt of adjuvant chemotherapy and endocrine therapy (C+E) versus endocrine therapy (E) alone by race/ethnicity, age, and SES in the ER+/PR+/HER- and ER+/PR+/HER+ subtypes. These subtypes differ only by HER2 status. Methods: We identified 86,666 cases of stages 1-3 ER+/PR+/HER- (n=74,422) and ER+/PR+/HER+ (n=12,244) breast cancer diagnosed between January, 2000 and December, 2010 from the California Cancer Registry. Logistic regression evaluating the odds of receipt of C+E versus E alone adjusting for age, race/ethnicity, SES, grade, and year of diagnosis was conducted separately for each stage and subtype. Odds Ratios (OR) and 95% confidence intervals were reported. Results: For both subtypes in all stages, patients over age 70 were less likely to receive C+E. Stage 1 ER+/PR+/HER-: Blacks were less likely to receive C+E (OR=0.77;0.59,0.99). The opposite was true for Hispanics (OR=1.31;1.15, 1.50) and Asians (API) (OR=1.25; 1.10;1.43). Stage 1 ER+/PR+/HER+:Hispanics were more likely (OR=1.67;1.24,2.24) to receive C+E while patients in the lowest SES category were less likely to receive C+E. Stage 2: ER+/PR+/HER-:Hispanics were more likely to receive C+E (OR=1.40;1.22,1.59) Stage 2: ER+/PR+/HER+:There were no treatment differences among race or SES. Stage 3: ER+/PR+/HER-:APIs were more likely (OR=1.87;1.19,2.94) to receive C+E. Stage 3: ER+/PR+/HER+:Patients in the lowest SES category were more likely to receive C+E (OR=2.97;1.29,6.87). Conclusions: Based on this investigation of a racially diverse population, there is no striking disparity in receipt of adjuvant treatment by race/ethnicity or SES. However there are some differences among the stages and subtypes. Patients over 70 are less likely to receive chemo and endocrine therapy for the subtypes studied.
Low-dose IL-12 preconditions the tumor microenvironment to enhance the efficacy of PD-1 blockade.
Authors: C. Marcela Diaz-Montero, Sairekha Ravichandran, Paul G. Pavicic, Patricia A. Rayman, Charles Tannenbaum, James Finke, Jennifer S. Ko, Pauline Funchain, Ahmad A. Tarhini
Journal: Journal of Clinical Oncology (2019)

20 Background: The immunomodulatory effects of IL-12 are well known to result in potent anti-tumor responses. However its therapeutic development has been hindered by its potential toxicity. Here we explored the impact of systemic low dose IL-12 administration as a strategy to enhance the efficacy of PD-1 blockade. Methods: Mice bearing D4M melanoma tumors were treated with anti PD-1 antibody alone or in combination with low dose IL-12 (100ng twice a week). Tumor progression was monitored, and characterization of immune cell types was performed by flow cytometry and gene expression analysis. Results: A significant reduction in tumor progression after combinatorial treatment with low dose IL-12 and anti PD-1 was observed. This synergistic effect was associated with elevated levels of intratumoral IFN-γ, iNOS, CXCL9, CXCL10, CXCL11, and perforin. Single treatment with low dose IL-12 induced a decrease in the levels of circulating neutrophils and an increase in the levels of circulating CD8 + T cells. Within the TME, low dose IL-12 treatment was associated with an increase in the frequencies of tumor infiltrating M-MDSCs expressing high levels of CXCL9. Elevated levels of CD8 + TILs were also found, which were characterized by their increased expression of PD-1 and PD-L1, as well as CD107a, CXCR3 and CD103. No signs of toxicity were noted. Conclusions: Low dose IL-12 synergizes with anti PD-1 to induce superior regression of D4M melanoma tumors. This effect was associated with an increase in the levels of molecules involved in the recruitment and effector function of CD8 + T cells. Analysis of tissues from animals treated with low dose IL-12 alone showed significant changes in the composition and phenotype of myeloid and T cells in both the tumor and blood. Expression of CXCL9 on tumor infiltrating MDSCs suggested a reversal of their immunosuppressive function to an immunopromoting one, and could explain the elevated accumulation of CD8 + TILs via enhanced CXCR3-dependent recruitment. These findings suggest that low dose IL-12 is sufficient to induce changes in the TME, with minimal toxicity,that enhance the anti-tumor effects of PD-1 blockade. A clinical study testing the safety of this combination is currently underway.
Patient-Perceived Lack of Choice in Receipt of Radioactive Iodine for Treatment of Differentiated Thyroid Cancer
Authors: Lauren P. Wallner, David Reyes-Gastelum, Ann S. Hamilton, Kevin C. Ward, Sarah T. Hawley, Megan R. Haymart
Journal: Journal of Clinical Oncology (2019)

For many patients with differentiated thyroid cancer, use of radioactive iodine (RAI) does not improve survival or reduce recurrence risk. Yet there is wide variation in RAI use, emphasizing the importance of understanding patient perspectives regarding RAI decision making.
Retrospective Next Generation DNA Sequencing Analysis in Patients with Hemophagocytic Lymphohistiocytosis (HLH) Highlights Genetic Variants Associated with Secondary/Late-Onset Disease
Authors: Meeta Sunil, Chirantan Bose, Coral Karunakaran, Sunil Bhat, Nita Radhakrishnan, Srisha Rani, Sakthivel Murugan Sm, Sharat Damodar, Ravi Gupta, Rohit Gupta, Mukesh Manharlal Desai, Arati Khanna-Gupta
Journal: Blood (2017)
Genetic Affinities among Southern Africa Hunter-Gatherers and the Impact of Admixing Farmer and Herder Populations
Authors: Mário Vicente, Mattias Jakobsson, Peter Ebbesen, Carina M Schlebusch
Journal: Molecular Biology and Evolution (2019)

Southern African indigenous groups, traditionally hunter-gatherers (San) and herders (Khoekhoe), are commonly referred to as "Khoe-San" populations and have a long history in southern Africa. Their ancestors were largely isolated up until ∼2,000 years ago before the arrival of pastoralists and farmers in southern Africa. Assessing relationships among regional Khoe-San groups has been challenging due to admixture with immigrant populations that obscure past population affinities and gene flow among these autochthonous communities. We re-evaluate a combined genome-wide data set of previously published southern Africa Khoe-San populations in conjunction with novel data from Khoe-San individuals collected in Xade (Central Kalahari Game Reserve, Botswana) prior to their resettlement outside the reserve. After excluding regions in the genome that trace their ancestry to recent migrant groups, the genetic diversity of 20 Khoe-San groups fitted an isolation-by-distance model. Even though isolation-by-distance explained most genetic affinities between the different autochthonous groups, additional signals of contact between Khoe-San groups could be detected. For instance, we found stronger genetic affinities, than what would be explained by isolation-by-distance gene flow, between the two geographically separated Khoe-San groups, who speak branches of the Kx'a-language family (ǂHoan and Ju). We also scanned the genome-wide data for signals of adaptive gene flow from farmers/herders into Khoe-San groups and identified a number of genomic regions potentially introduced by the arrival of the new groups. This study provides a comprehensive picture of affinities among Khoe-San groups, prior to the arrival of recent migrants, and found that these affinities are primarily determined by the geographic landscape.