tbuckley/cabot-search huggingface dataset:
Circulating tumor DNA to reveal mutation profiling in relation to treatment response in different subtypes of metastatic breast cancer.
Authors: Quchang Ouyang, Zheyu Hu, Liping Liu, Huawu Xiao, Jing Li, Ning Xie, Can Tian, Yu Tang, Lianpeng Chang, Xuefeng Xia, Qiongzhi He
Journal: Journal of Clinical Oncology (2018)

e12551 Background: Previous molecular studies has classed breast cancer into three subtypes. Corresponding treatment has improved outcome of subtypes of patients (pts) with metastatic breast cancer (mBC). Although liquid biopsy has been reported in detecting actionable mutations in mBC, the relationship between molecular characteristics in circulating tumor DNA (ctDNA) and treatment received by pts with different subtypes mBC remains unclear. Methods: This study enrolled 68 pts with different subtypes of mBC. Peripheral blood sample were collected at baseline and during targeted drugs or chemotherapy treatments. Capture-based sequencing was performed in all ctDNA using a panel covering 1021 genes related to solid tumors. Somatic mutations were analyzed. TMB in blood (bTMB) interrogated single nucleotide variants, small insertion and deletion, with variated allele frequency > 0.5%. Results: Among all pts, 22 cases were triple-negative breast cancer (TNBC), 23 cases were ER+/ PR+(HER2-), and 20 cases were HER2+. TP53, PIK3CA, ERBB2 and CDK12 were the top four mutated genes, with mutant frequency of 42.65% (29 pts), 32.35% (22 pts), 14.71% (10 pts) and 10.29% (7 pts), respectively. For missense mutations, the hotspot locus was p.C238F/Y in TP53 and the hotspot locus in PIK3CA gene was p.H1047L/R. PIK3CA mutation patients was significantly more frequent in HER2+ and HR+ groups (p=0.001). Wild TP53 tend to be associated with a better outcome in all pts (p=0.059). For 4 early progressed HER2+ pts, TP53, PIK3CA and ERBB2 increased after 3 months of anti-HER2 treatment. Furthermore, TNBC and HR+ groups showed significantly higher bTMB than HER2+ group (p<0.05), suggesting a potential better effect when received treatment of immune checkpoint inhibitors. Conclusions: Liquid biopsy based ctDNA uncovered genomic profiling of different subtypes of mBC. Molecular characteristics in serial ctDNA may be a potential biomarker in predicting treatment outcome of subtypes of mBC. Key words: metastatic breast cancer, subtypes, circulating tumor DNA (ctDNA), gene mutation pattern, treatment response
Visa cap is driving up salaries of overseas doctors
Authors: Ingrid Torjesen
Journal: BMJ (2018)

NHS trusts are being forced to pay overseas doctors 50% more than their UK counterparts so that they are eligible for visas, a recruitment agent has said.

The news comes after The BMJ launched its Scrap the Cap campaign to review current restrictions on overseas doctors working in the NHS (bmj.com/scrap-the-cap).1

For the past six months demand for tier 2 visas for doctors from countries outside the European Economic Area who have offers of jobs in the UK has exceeded the number available, and more than 1500 applications have been refused.2 When the monthly cap on visas is close to being reached, the Home Office takes salaries into account and will grant visas to …
At surgery for a core needle biopsy diagnosis of ductal carcinoma in situ with microinvasion: Is sentinel lymph node biopsy required?
Authors: Meghan Rose Flanagan, Michelle Stempel, Edi Brogi, Monica Morrow, Hiram S. Cody
Journal: Journal of Clinical Oncology (2018)

563 Background: Surgical excision upstages approximately 20% of patients with a core needle biopsy (CNB) diagnosis of ductal carcinoma in situ (DCIS) to invasive cancer, a rate insufficient to recommend routine sentinel lymph node biopsy (SLNB) at the initial procedure. The rate of upstaging for patients with a CNB diagnosis of DCIS with suspected or definite microinvasion (DCISM) is unknown, as is the role of SLNB. Methods: We identified consecutive patients with a CNB diagnosis of DCISM, suspected or definite, who underwent surgical excision between 2007 and 2017. The extent of DCISM was stratified as suspicious focus (n = 106), single focus (n = 187), multiple foci in a single biopsy (n = 69) or multiple foci in multiple biopsies (n = 24) (Table). SLNB was performed in 77%, 94%, 96% and 100%, respectively. CNB strata were correlated with imaging characteristics and final pathology in the breast and SLN. Results: Across CNB strata there were no clear differences in imaging characteristics. Although there was a trend toward higher final T and N stage with increasing extent of DCISM, the median extent of invasive cancer on final pathology was 0.2 cm for all strata. Among patients with CNB suspicious for DCISM, 28% were upstaged to T1a or greater but the SLNB was positive in only 1 patient (1%). In the definite DCISM strata, 37-46% were upstaged to T1a or greater, and 1-12% were at least pN1. Conclusions: In patients with suspicion of DCISM on CNB, 28% were upstaged to invasive cancer but the frequency of SLN metastasis is low, suggesting that SLNB may be deferred to final pathology in this setting. For patients with definite DCISM on CNB, the frequency of clinically significant lymph node metastasis supports SLNB at initial surgery. Focus suspicious (N = 106) N (%) Single focus (N = 187) N (%) Multiple foci (N = 69) N (%) Multiple biopsies (N = 24) N (%) P value Final pathology 0.01 No cancer 2 (1.9) 5 (2.7) 0 (0.0) 0 (0.0) In situ only 53 (50.0) 60 (32.1) 12 (22.9) 5 (20.8) Microinvasive 21 (19.8) 53 (28.3) 22 (31.4) 9 (37.5) Invasive 30 (28.3) 69 (36.9) 32 (45.7) 10 (41.7) pNa 0.02 N0 81 (98.8) 161 (92.5) 62 (93.9) 20 (83.4) N1 1 (1.2) 12 (6.9) 3 (4.6) 3 (12.5) N2 or N3 0 (0.0) 1 (0.6) 1 (1.5) 1 (4.2) aTotal is among 351 women with SLNB
On-orbit sleep problems of astronauts and countermeasures
Authors: Bin Wu, Yue Wang, Xiaorui Wu, Dong Liu, Dong Xu, Fei Wang
Journal: Military Medical Research (2018)

Sufficient sleep duration and good sleep quality are crucial to ensure normal physical and mental health, cognition and work performance for the common people, as well as astronauts. On-orbit sleep problem is very common among astronauts and has potential detrimental influences on the health of crewmembers and the safety of flight missions. Sleep in space is becoming a new medical research frontier. In this review we summarized on-orbit sleep problems of astronauts and six kinds of causes, and we presented the effects of lack of sleep on performance as well as mental and physical health, then we proposed seven kinds of countermeasures for sleep disturbance in spaceflight, including pharmacologic interventions, light treatment, crew selection and training, Traditional Chinese Medicine and so on. Furthermore, we discussed and oriented the prospect of researches on sleep in space.
GMC reply to letter by Harris, “Five new medical schools: a decline in standards is inevitable”
Authors: Colin Melville
Journal: BMJ (2018)

While the matter of employment and increasing the number of home grown doctors is not for the GMC, we decide which organisations can award UK primary medical qualifications, and we will not allow the increase in student numbers or additional medical schools to lead to any decline in the high standards that UK medical education offers.1

Our standards are there to ensure that patients …
Ultrasound assessment as predictor of disease relapse in children and adults with arthritis in clinical stable remission: new findings but still unmet needs
Authors: Elisa Gremese, Anna Laura Fedele, Stefano Alivernini, Gianfranco Ferraccioli
Journal: Annals of the Rheumatic Diseases (2018)

Several lines of evidence suggest that imaging plays an important role in the diagnosis and monitoring of patients with juvenile idiopathic arthritis (JIA) leading the European League against Rheumatism (EULAR)–Paediatric Rheumatology European Society (PReS) to develop as point to consider the use of imaging within the JIA assessment in clinical practice.1 The use of ultrasound (US) may increase the sensitivity of clinical examination through its ability to detect joint inflammation (in terms of synovial hypertrophy, joint effusion and power Doppler (PDUS) activity) in case of clinically inactive disease.2–4 In particular, it has been shown that the majority of patients with JIA in clinical remission may exhibit greyscale (GSUS) abnormalities and in half of them the presence of PDUS signal can be found,4 without any significant difference on the basis of the pharmacological treatment scheme through which the remission was achieved2–4 and even in case of drug-free remission (DFR).

In ARD , De Lucia et al analysed the predictive power of US assessment to foresee disease flare in patients with JIA in clinical remission.5 The authors included 88 consecutive patients with JIA, stratified based on the joint involvement, undergoing US assessment (including GSUS and PDUS) of 44 joints, finding that nearly one-fourth of them showed US abnormal findings despite clinically inactive disease, mainly in patients with extended joint involvement and with shorter period of time from remission achievement (less than 6 months). Interestingly, during the 4 years of follow-up, almost half of patients with JIA experienced a disease flare with the higher rate of relapse in patients with JIA with residual PDUS synovitis at the time of remission achievement. These can be considered relevant findings since previous studies failed to confirm the predictive value of US assessment in foreseeing the chance of disease flare in JIA.6 …
Respiratory Syncytial Virus–induced Acute Disease Severity and Long-Term Wheezing. Uncovering the Unexpected
Authors: Octavio Ramilo, Asuncion Mejias
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

has already started to address this issue, taking the steps to better serve the Hispanic population by not only making available educational materials in Spanish but also, and as important, exploring the needs of this community through a recent national survey.We look forward to their findings and plans to improve the health of all patients with CF.These efforts in aggregate to scientific investigations will permit the clearer identification of factors amenable to intervention and achieve a goal of eliminating problematic differentials in outcomes.
Questioning the Associations of ω-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks—Reply
Authors: Robert J. Clarke, Theingi Aung, Jane Armitage
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
GM-CSF therapy in human caspase recruitment domain–containing protein 9 deficiency
Authors: Rebecca A. Drummond, Fatema Tuz Zahra, Mukil Natarajan, Muthulekha Swamydas, Amy P. Hsu, L. Joseph Wheat, Christina Gavino, Donald C. Vinh, Steven M. Holland, Constantinos M. Mikelis, Michail S. Lionakis
Journal: Journal of Allergy and Clinical Immunology (2018)
Clearance of carbapenemase-producing Enterobacteriaceae (CPE) carriage: a comparative study of NDM-1 and KPC CPE
Authors: Y.J. Lim, H.Y. Park, J.Y. Lee, S.H. Kwak, M.N. Kim, H. Sung, S.-H. Kim, S.H. Choi
Journal: Clinical Microbiology and Infection (2018)
Human CD30+ B cells represent a unique subset related to Hodgkin lymphoma cells
Authors: Marc A. Weniger, Enrico Tiacci, Stefanie Schneider, Judith Arnolds, Sabrina Rüschenbaum, Janine Duppach, Marc Seifert, Claudia Döring, Martin-Leo Hansmann, Ralf Küppers
Journal: Journal of Clinical Investigation (2018)

Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human CD30+ B cells. Phenotypic and IgV gene analyses indicated that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ EF B cells are mostly post-GC B cells. The transcriptomes of CD30+ GC and EF B cells largely overlapped, sharing a strong MYC signature, but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. CD30+ GC B cells represent MYC+ centrocytes redifferentiating into centroblasts; CD30+ EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with CD30+ B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal CD30+ B cells we redefined aberrant and disease-specific features of HRS cells. A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity.
Impact of high deductible insurance on out-of-pocket cost burden in breast cancer.
Authors: Christine Lu, Fang Zhang, Anita K. Wagner, Larissa Nekhlyudov, Craig Earle, Matthew Callahan, Robert LeCates, Xin Xu, Jamie Wallace, Stephen Soumerai, Dennis Ross-Degnan, James Frank Wharam
Journal: Journal of Clinical Oncology (2018)

545 Background: High-deductible health plans (HDHP) requiring out-of-pocket (OOP) costs for most services may place heavy economic burden on patients. This study examined the impact of modern HDHPs on OOP costs among women with early-stage breast cancer. Methods: We included 886 women with incident early-stage breast cancer, age 25 to 64 years, who were insured by employers that mandated a transition from low-deductible ( < = $500/year) to high deductible ( > = $1000/year) coverage, and 3099 exact matched contemporaneous patients whose employers offered only low-deductible plans. Measures were pharmacy and medical OOP costs per person-year. Medical services were categorized as inpatient, emergency room (ER), primary care visits, and outpatient care which included specialist visits, radiology, lab tests, and chemotherapy. We calculated OOP costs as the sum of deductibles, copays, and coinsurance. Effect estimates of changes between study groups were established using difference-in-differences analyses. Results: HDHP members faced an absolute baseline-to-follow-up increase in total OOP costs of $1067 per person-year compared to controls (p = < 0.001). The absolute change in medical OOP costs per person-year among HDHP members compared to controls from baseline to follow-up was significant ($1004, 95% CI: [$580, $1429]) and the relative change was also significant (41.2%, 95% CI: [17.8%, 64.5%]). The increase in medical OOP costs was driven by increases in outpatient care OOP costs. The absolute change in outpatient care OOP costs per person-year among HDHP members compared to controls from baseline to follow-up was $919 (95% CI: [$506, $1332]; relative change: 43.7%, 95% CI: [17.0%, 70.5%]). Changes in OOP costs for pharmacy, inpatient, ER, and primary care visits were not significant. Conclusions: In this rigorous, natural experimental study, women with incident breast cancer experienced increases in total OOP costs after employer-mandated HDHP switches, a change driven by a 44% increase in outpatient care OOP costs. Further research should examine which outpatient services contributed to this substantial economic burden, when the differences occur and the proportion of women reaching their annual deductible.
Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies
Authors: Ajay Prakash, Catherine S. Diefenbach
Journal: Clinical Cancer Research (2018)

The activity of T-cell-mediated immunotherapies in B-cell lymphoma has been limited to date. The novel bispecific antibody CD20-TCB has a 2:1 antibody design to maximize T-cell engagement and demonstrates activity in preclinical models. This may represent a novel therapeutic approach for patients with relapsed/refractory non-Hodgkin lymphoma (NHL). Clin Cancer Res; 24(19); 4631-2. ©2018 AACRSee related article by Bacac et al., p. 4785.
Benefit of CDK 4/6 inhibition in less common breast cancer subsets: A U.S. Food and Drug Administration pooled analysis.
Authors: Jennifer J Gao, Joyce Cheng, Erik Bloomquist, Robert Schroeder, Laleh Amiri-Kordestani, Rajeshwari Sridhara, Gideon Michael Blumenthal, Richard Pazdur, Julia A. Beaver, Tatiana Michelle Prowell
Journal: Journal of Clinical Oncology (2018)

1024 Background: Cyclin dependent kinase 4/6 inhibitors (CDKIs) are approved for 1st and 2nd line endocrine-based therapy in hormone-receptor positive, HER2-negative advanced breast cancer. There is limited clinical data on the benefit and value of adding CDKIs to endocrine therapy in less common subtypes, such as progesterone receptor negative (PR-), de novo metastatic, and lobular breast cancer, which may have differing degrees of endocrine sensitivity. Methods: We pooled data from 5 phase 3 randomized registration trials of CDKI with an aromatase inhibitor (AI) in the 1st or fulvestrant in the 2nd-line setting. Exploratory subset analyses focused on patients with de novo metastatic, PR-, and lobular cancer. Progression free survival (PFS) was examined in the ITT populations using Kaplan Meier plots and hazard ratios (HR) with 95% confidence intervals (CI). Results: We estimated median PFS differences between the CDKI and control arms (Table 1). In patients with PR- tumors (n = 490), the estimated median PFS difference with the additional CDKI to endocrine therapy was 9.1 mo (HR 0.50, 95% CI 0.40-0.64). In patients with de novo metastatic disease (n = 877), the estimated median PFS difference was 9.6 mo (HR 0.59, 0.48-0.71). In patients with lobular cancer(n = 264), the estimated median PFS difference was 6.9 mo (HR 0.58, 0.42-0.80). Analyses of studies limited to the 1st line setting with an AI and studies in the 2nd line setting with fulvestrant showed similar results. These results are considered hypothesis generating. Conclusions: Addition of CDKIs to endocrine-based therapy appears to confer a similar benefit in the relative risk of disease progression or death for the studied subsets of patients compared to the broad population in the labeled indication. Further research is needed to help clinicians identify which patients benefit most from addition of CDKI to endocrine therapy and which should receive CDKI in the 1st-line, 2nd-line, or both settings. Results. Subset N Median PFS (mo), CDKI Median PFS (mo), Placebo PFS Difference (mo) HR (95% CI) PR Negative 490 16.5 7.4 9.1 0.50 (0.40-0.64) De Novo Metastatic 877 24.3 14.7 9.6 0.59 (0.48-0.71) Lobular Histology 264 16.1 9.2 6.9 0.58 (0.42-0.80)
Single center experience of dermatologic and oncologic surveillance patterns for late stage melanomas that progressed from early stage melanoma.
Authors: Jung Min Song, Joel Daniel Marcus, Carolyn Stanek, Michael J. McNamara, Brian Gastman, Ahmad A. Tarhini, Pauline Funchain
Journal: Journal of Clinical Oncology (2018)

182 Background: Recent data suggests a greater proportion and greater absolute number of thin (T1) melanomas contribute to melanoma death than thicker melanomas (Whiteman et al., J Invest Dermatol 2015). NCCN guidelines for early stage melanoma, defined as stages IA-IIA, suggest at least yearly skin check and H&amp;P, but do not specify if dermatologic and/or oncologic surveillance should be pursued. Methods: We reviewed internal and external records of 16 consecutive patients with new, non-de novo diagnoses of unresectable stage III or IV melanoma undergoing active cancer treatment, i.e. late stage melanoma, from 2016-2017 that had progressed from a preceding primary early stage (IA-IIA) melanoma. Results: Primary early stage melanomas were diagnosed a median of 10.5 years (range, 4 to 29) prior to advanced disease progression. Two of 16 patients (13%) had oncologic follow up. Seven (44%) had continuous dermatology follow-up, of which 6 (38%) were followed only by dermatology. Only one patient had both dermatology and oncology follow-up at the time of progression. Follow up could not be determined for 8 patients due to lack of sufficient records, it is notable however that these 8 (50%) were not following dermatology or oncology at the time of progression. Conclusions: Only a small minority of patients who progressed from early stage melanoma to advanced stage melanoma requiring treatment were followed regularly by medical oncology, despite half having at least regular dermatology follow-up. We conclude that survivorship plans are important for early stage melanomas, and there is a need to effectively educate a larger early stage melanoma population about the infrequent but real oncologic issue of progressing to late stage melanoma.
Does depression affect illness beliefs in cancer survivors?
Authors: Sarah Prieto, Kimberly A. Muellers, Juan P. Wisnivesky, Lin J. Jenny
Journal: Journal of Clinical Oncology (2018)

156 Background: As cancer survivors live longer and many die from their comorbidities rather than from cancer, it is important to understand how a cancer diagnosis may impact survivors’ perception of their other comorbidities. In addition, cancer is associated with increased risk for depression. We aim to assess the relationship between depressive symptoms and illness beliefs in cancer survivors with diabetes (DM). Methods: We recruited 75 patients with DM who were newly diagnosed with early-stage breast, prostate, lung or colon cancer. Depressive symptoms were assessed with the Center for Epidemiological Studies Depression Scale; illness beliefs were assessed with the Brief Illness Perception Questionnaire. Illness belief questions were dichotomized at the median, and non-parametric analyses were used to assess the relationship between depressive symptom scores and presence of illness beliefs. Results: Seventy-five patients with DM and a new diagnosis of cancer were enrolled. The average age was 61.8 years, 47% were male, 45% had breast cancer, 42% prostate cancer, 8% colon cancer, and 4% had lung cancer. Patients who perceived having more control over their DM had lower depression scores (median 26 vs. 20, p = 0.01). Furthermore, those who did not feel their health depended on their DM medications at present (median score 21 vs. 26, p = 0.007) had lower depression scores. Regarding beliefs about cancer, those who reported being less concerned about cancer had lower depression scores (median 21 vs. 25, p = 0.01). Additionally, patients who did not feel that cancer affected their lives much (median 19 vs. 26, p = 0.001) or who did not report that cancer affected them emotionally (median 19 vs. 26, p = 0.001) had lower depression scores. Patients’ perception of their control over their cancer was not associated with depression scores. Conclusions: Cancer survivors with higher depression scores report being more affected by cancer and simultaneously feel they have less control over DM. It is important to support survivors emotionally while increasing their self-efficacy over their comorbidity management to improve survivors’ health outcomes.