tbuckley/cabot-search huggingface dataset:
The importance of rhesus status
Authors: Holly Morris, Bharati Yasmaras
Journal: BMJ (2010)

The history of haemolytic disease of the newborn, caused by incompatibility between the fetus and mother for the rhesus D (RhD) antigen, has been called one of the most brilliant successes achieved in medicine.1 Preventive treatment is so effective that it has decreased the number of intrauterine fetal deaths by more than 100 fold and the incidence of maternal alloimmunisation by more than 50 fold.2

The first dated case report of haemolytic disease of the newborn was in a set of twins born in the 1600s.3 However, it was not until 1940 that the link with the RhD antigen was made by Landsteiner and Weiner. They discovered an antibody that led to the agglutination of human erythrocytes after experiments in which rabbits were immunised with rhesus monkey erythrocytes.4

In 1969, a campaign of anti-D immunoglobulin prophylaxis was introduced. Deaths attributed to RhD alloimmunisation were reduced from 46 in 100 000 births to 1.6 in 100 000 births during the first 20 years of the campaign. However, haemolytic disease of the newborn and neonatal death continued to occur, and still do—owing in part to covert sensitising events during pregnancy, and in part to a lack of knowledge and compliance with guidelines.5

Erythrocytes carry many antigens on their surface. The most important are those belonging to the ABO system and to the rhesus system.

The rhesus system comprises antigens c, C, D, e, and E. Of these, the D antigen is the most important. It is inherited on one gene, located on chromosome 1. It has two alleles: the dominant RhD positive, where the individual expresses the D antigen, and the recessive RhD negative, where there is no expression.6

The incidence of the rhesus D antigen varies between different ethnic groups.6 It is estimated that the prevalence …
Unnecessarily conservative stance is unsupported by evidence
Authors: Michael Farrell
Journal: BMJ (2013)

Isted’s article provides us with the facts about the harms of shisha smoking, enabling students to make more informed decisions.1 However, it also works from the flawed assumption that medics are right to be utterly opposed to the idea of smoking.

If I saw a medic launch into a tirade of health warnings after being offered a cigarette …
James Ian Summers Robertson
Authors: Anna Dominiczak, Robert Fraser, John Connell, M Gary Nicholls
Journal: BMJ (2019)

James Ian Summers Robertson was born in Welbeck, Nottinghamshire, and educated at Queen Elizabeth’s Grammar School in Mansfield, Nottinghamshire, and then St Mary’s Hospital Medical School, University of London, Ian graduated bachelor of science with 1st class honours in human and comparative anatomy in 1949 and bachelor of medicine, bachelor of surgery with honours, and distinctions in medicine and pathology, in 1952. At St Mary’s he also found time to be captain of both cricket and soccer. He was admitted as a member of the Royal College of Physicians of London in 1954 and was subsequently elected as a fellow.

Ian did national service with the Royal Army Medical Corps from 1954 to 1956, during which time he represented the army at cricket and rugby union football. He later said that one of his most demanding military duties was batting at first wicket down against Yorkshire. He also played club cricket for Worksop in the Bassetlaw League in the north of England, and later for West of Scotland in the Western Union.

He then joined St Mary’s Hospital medical unit, initially as a lecturer in medicine from 1956 to 1964, and, thereafter, as a senior lecturer in therapeutics and honorary consultant physician from 1964 to 1967. From 1956 Stanley Peart led the unit. Peart had purified and sequenced angiotensin II, the product of the action of the renal enzyme renin and the most potent vasopressor …
Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders
Authors: Kate Downes, Karyn Megy, Daniel Duarte, Minka Vries, Johanna Gebhart, Stefanie Hofer, Olga Shamardina, Sri V. V. Deevi, Jonathan Stephens, Rutendo Mapeta, Salih Tuna, Namir Al Hasso, Martin W. Besser, Nichola Cooper, Louise Daugherty, Nick Gleadall, Daniel Greene, Matthias Haimel, Howard Martin, Sofia Papadia, Shoshana Revel-Vilk, Suthesh Sivapalaratnam, Emily Symington, Will Thomas, Chantal Thys, Alexander Tolios, Christopher J. Penkett, Willem H. Ouwehand, Stephen Abbs, Michael A. Laffan, Ernest Turro, Ilenia Simeoni, Andrew D. Mumford, Yvonne M. C. Henskens, Ingrid Pabinger, Keith Gomez, Kathleen Freson
Journal: Blood (2019)
Inside out: Art on the fringes
Authors: Toby Pitts-Tucker
Journal: BMJ (2012)

Nestled in the grounds of Bethlem Royal Hospital, a psychiatric hospital in south east London, a small but lively museum displays a remarkable collection of artwork by psychiatric patients. The collection was started by two psychiatrists, Eric Guttmann and Walter Maclay, in the 1930s. It comprises art by past and present patients of Bethlem Royal Hospital and its sister hospitals in the South London and Maudsley NHS Foundation Trust. It includes work by established artists who became mentally ill, by those who used art to communicate mental distress, and by patients for whom art contributed to their recovery. The genre of art on display can be loosely described as “outsider art,” a term …
Abstract P4-04-11: A small amount of primary breast cancer shows high tumor mutation burden that may benefit from immune checkpoint inhibitor therapy
Authors: J Wang, W Chen, Z Jiang, X Lin, T Qin, X Yang, T Liu, H Hu, Z Li, D Xie, H Yao, E Song
Journal: Cancer Research (2019)

Abstract Background: Targeted therapy using immune checkpoint inhibitors (ICIs) is a major breakthrough in cancer treatment in the last decade. ICIs like PD1 or PD-L1 antibodies have been shown to be quite effective in cancer like melanoma. However, in most other tumor types including breast cancer, the situation is not as optimistic. Only a small percentage of those patients respond to ICIs therapy. This highlights the importance of identifying biomarkers to predict which patients may benefit from such treatment. Tumor Mutation Burden (TMB) has been shown to be a sensitive marker for ICI treatment. This study is to investigate whether TBM could be used as a biomarker for breast cancer treatment. Methods: We reviewed next generation sequencing studies of breast cancer. Two such studies with raw data provided were included in our analysis. One study entitled METABRIC performed targeted sequencing of 173 cancer-related genes in around 2500 primary breast cancer tissues. The other study was from TCGA breast cancer project, which performed Whole Exome Sequencing (WES) of around 1000 primary breast cancer samples. Mutation data were downloaded from public data deposit. The number of mutations per sample was calculated. TBM was calculated by divide the coverage in million base pair from that of the total mutation counts. Results: In METABRIC study, 17272 mutations were identified in 2369 samples, with a median of 7 mutations per sample (95% CI: 6 ˜ 7). The median TMB of METABRIC dataset was 5.8 SNVs/Mb (95% CI: 5 ˜ 5.8). Totally 30 out 2369 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb. In another cohort from TCGA breast cancer study using WES technology, 90172 mutations were identified in 977 samples, with a median of 44 mutations per sample (95% CI: 39 ˜ 50). The median TMB was 1 SNVs/Mb (95% CI: 0.9 ˜ 1.1). Totally 13 out 977 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb. Conclusions: Breast cancer shows middle to low mutation burden compared to other cancer types. Around 1.3% of breast cancer has quite high TMB of at least 20 SNVs/Mb, which may be qualified for immune checkpoint inhibitors therapy. Our study indicates that TMB may be incorporated as a standard test for late stage breast cancer patients in the clinical practice. Keywords: Breast cancer, Tumor Mutation Burden, Whole exome sequencing, Targeted sequencing, Immune checkpoint Citation Format: Wang J, Chen W, Jiang Z, Lin X, Qin T, Yang X, Liu T, Hu H, Li Z, Xie D, Yao H, Song E. A small amount of primary breast cancer shows high tumor mutation burden that may benefit from immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-04-11.
New healthcare checks for medical and dental students
Authors: Poonam Jani
Journal: BMJ (2014)

Medical students will require additional health clearance before being permitted to carry out medical procedures with a high risk of transmission of infection, after the publishing of new guidance by the Medical Schools Council, the Dental Schools Council, Public Health England and Health Protection Scotland.1

All students and healthcare employees already undergo standard health clearance, which assesses exposure to tuberculosis and offers immunisation …
Use of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Statin‐Associated Immune‐Mediated Necrotizing Myopathy: A Case Series
Authors: Eleni Tiniakou, Erika Rivera, Andrew L. Mammen, Lisa Christopher‐Stine
Journal: Arthritis & Rheumatology (2019)

To determine the safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with statin-associated anti-3-hydroxy-3-methlyglutaryl coenzyme A reductase (anti-HMGCR)-positive immune-mediated necrotizing myopathy (IMNM).Muscle strength was assessed in anti-HMGCR-positive patients at each visit before and after initiation of PCSK9 inhibitors. The trends in creatine kinase (CK) levels and serum anti-HMGCR antibody titers were monitored over time.Among 122 anti-HMGCR-positive patients, we identified 8 patients who were receiving PCSK9 inhibitors for hyperlipidemia. Patients were followed up for an average of 1.5 years (range 3-37 months), and none exhibited reduction in muscle strength. The mean ± SD CK level prior to the initiation of PCSK9 inhibitors was 956 ± 1,137 IU/liter, which was reduced to 419 ± 393 IU/liter at their last visit. Anti-HMGCR antibody titers followed a similar trend. Notably, in 2 patients, the initiation of the lipid-lowering medication was followed by unanticipated spontaneous clinical improvement and reduction in immunosuppression.PCSK9 inhibitors are safe for long-term use as a cholesterol-lowering agent in patients with statin-associated IMNM.
Abstract ES11-1: Lymphedema management in 2018: Are we making any progress?
Authors: B Mehrara
Journal: Cancer Research (2019)

Abstract Lymphedema is a common and morbid complication of cancer treatment. To date, lymphedema treatment has been palliative aiming to prevent disease progression and improve symptoms of swelling. Development of novel therapies for lymphedema has been limited by the fact that the pathophysiology of the disease remains unknown. While it is true that lymphatic injury during surgery is an important initiating event, the mechanisms that regulate the development of the disease in a subset of patients remain unknown. Recent studies in our lab have suggested that the pathophysiology of lymphedema is related to inflammatory changes that occur following surgery. We have shown that CD4+ T cells play a key role in the pathology of lymphedema by orchestrating a variety of changes including tissue fibrosis, lymphatic leakiness, impaired collecting vessel pumping, and changes in the lymphatic smooth muscle cells. More importantly, in preclinical models we have shown that inhibition of this response can prevent development of lymphedema following surgery or reverse it once it has been initiated. These findings have led to novel treatments for lymphedema that may be effective either as standalone therapies or used in conjunction with surgical treatments for lymphedema. Citation Format: Mehrara B. Lymphedema management in 2018: Are we making any progress? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES11-1.
Abstract P3-03-39: Sentinel lymph node biopsy after surgery with removal of the primary tumor
Authors: E Zhiltsova, P Krivorotko, G Dashayan, A Emelyanov, T Tabagua, A Bessonov, O Ivanova, S Kanaev, S Novikov, P Krzivickiyi, A Komayachov, K Nikolaev, L Gigolaeva, K Zernov, V Semiglazov
Journal: Cancer Research (2019)

Abstract Nowadays, sentinel lymph node biopsy (SLNB) is one of the basic methods for diagnosing the lesion of regional lymph nodes (LN) and it is recommended by experts as a standard method in determining the prevalence of the disease in breast cancer patients (BC). The aim of the study was the possibility of sentinel lymph node biopsy after surgery with removal of the primary tumor. Materials and methods The study was conducted in the N.N. Petrov's National Medical Center of Oncology from 2013 to 2018. SLNB was performed in patients who had a primary tumorectomy in another medical institution. The study included patients with the stage cN0. Radionuclide imaging of the sentinel lymph nodes (SLN) was performed in 37 patients with breast cancer. The injection of radiopharmaceuticals in postoperative scar was performed before the biopsy. Median of the period between the operations was 21 days (14 to 30 days). Results After injection, the image of SLN was obtained in 91.9% (34 of 37) of patients. During the operation, 1-5 sentinel lymph nodes were visualized. The lesion of the sentinel lymph nodes (N+) was detected in 21.6% (8) patients, N0 in 78.4% (29) patients, respectively. There is no data for locoregional relapse for the period of observation from 2014 to nowadays. Conclusions The obtained results are comparable with the results of sentinel lymph node biopsy in primary patients with breast cancer stage cN0. This indicates the possibility of biopsy after surgery with removal of the primary tumor. Citation Format: Zhiltsova E, Krivorotko P, Dashayan G, Emelyanov A, Tabagua T, Bessonov A, Ivanova O, Kanaev S, Novikov S, Krzivickiyi P, Komayachov A, Nikolaev K, Gigolaeva L, Zernov K, Semiglazov V. Sentinel lymph node biopsy after surgery with removal of the primary tumor [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-39.
Correction: An Acquired <i>HER2</i>T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant–Driven Breast Cancer
Authors: Ariella B. Hanker, Monica Red Brewer, Jonathan H. Sheehan, James P. Koch, Gregory R. Sliwoski, Rebecca Nagy, Richard Lanman, Michael F. Berger, David M. Hyman, David B. Solit, Jie He, Vincent Miller, Richard E. Cutler, Alshad S. Lalani, Darren Cross, Christine M. Lovly, Jens Meiler, Carlos L. Arteaga
Journal: Cancer Discovery (2019)
A cardiac mass in a breathless patient
Authors: Ayesha Ejaz, Geoffrey Berg
Journal: BMJ (2012)

A 73 year old woman, Mrs K, presented to her general practitioner with a one month history of increasing breathlessness and fatigue. She had no other symptoms and no medical history. Mrs K was a non-smoker and was not taking any drugs. On examination, Mrs K’s respiratory rate was 14 breaths per minute and her heart rate was 64 beats per minute. Her blood pressure was 125/73 mm Hg and she was clinically euvolaemic. She was found to have a new systolic murmur, loudest at the apex, with bibasal fine crackles. Her elecrocardiogram showed sinus rhythm. Her C reactive protein level was raised at 12 mg/L (<10 mg/L). Mrs K was referred to hospital because of her symptoms and the results of her examination. A transthoracic echocardiogram (figure⇓) showed a mobile mass in the left atrium, measuring 7 × 3.5cm . It was protruding through the mitral valve, resulting in moderate mitral regurgitation. Transthoracic echocardiogram of Mrs K
Fabrication of magnesium/zinc-metal organic framework on titanium implants to inhibit bacterial infection and promote bone regeneration
Authors: Xinkun Shen, Yangyang Zhang, Pingping Ma, Linawati Sutrisno, Zhong Luo, Yan Hu, Yonglin Yu, Bailong Tao, Chuanqiang Li, Kaiyong Cai
Journal: Biomaterials (2019)
TARA study: a new perspective on tapering drugs in RA
Authors: Debashish Mishra, Arghya Chattopadhyay, Sanjay Jain, Varun Dhir
Journal: Annals of the Rheumatic Diseases (2019)

We read with great interest the article on ‘Gradual tapering TNF inhibitors vs conventional synthetic DMARDs after achieving controlled disease in patients with rheumatoid arthritis: first-year results of the randomised controlled TARA study’1by van Mulligen et al . This was the first head-to-head comparison between two tapering strategies—biological versus conventional in rheumatoid arthritis. The final results favour tapering tumour necrosis factor inhibitors (TNFis) before conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). However, certain points need clarifications.

First, many patients in the …
High-Dose Folic Acid Supplement Use From Prepregnancy Through Midpregnancy Is Associated With Increased Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study
Authors: Qian Li, Yu Zhang, Li Huang, Chunrong Zhong, Renjuan Chen, Xuezhen Zhou, Xi Chen, Xiating Li, Wenli Cui, Ting Xiong, Qin Gao, Shangzhi Xu, Yuanjue Wu, Xiaoyi Wang, Guofu Zhang, Xu Zhang, Lixia Lin, Duan Gao, Mei Xiao, Guoping Xiong, Hongying Yang, Nianlan Yang, Xuefeng Yang, Liping Hao, Zhichun Jin, Nianhong Yang
Journal: Diabetes Care (2019)

Periconceptional folic acid (FA) supplementation is widely recommended for substantial benefits on preventing neural tube defects (1), but concerns regarding the potential side effects on both mothers and their infants have been raised recently (2,3). Higher plasma folate was found to be associated with higher risk of gestational diabetes mellitus (GDM) (4). A Chinese cohort had reported association between FA supplement use in early pregnancy and increased GDM risk (5). However, no details on FA doses and durations had been addressed. To further understand the safe dose and duration of FA supplement use regarding GDM risk, for the first time, we evaluated the impact of FA supplement use on GDM with consideration of both doses and durations.

Participants came from the Tongji Maternal and Child Health Cohort (TMCHC), a cohort investigating the role of maternal nutritional, environmental, and lifestyle influences on the outcomes of pregnant women and their offspring. Information on social-demographic status, reproductive factors, lifestyle factors, illnesses, and medical records was collected via questionnaire-based interviews at enrollment (<16 weeks of gestation) and follow-up visits. The study was approved by the ethics committee (Tongji Medical College of Huazhong University of Science and Technology, NO-201302).

Among 8,649 women in TMCHC, after excluding those with diabetes/glucose intolerance prepregnancy, multiple pregnancies, and abortions and without reliable FA information (unclear doses/durations or varying doses) and/or oral glucose tolerance test (OGTT), 4,353 women were eligible for final analysis. The incidence of GDM was 8.6%.

All participants were instructed to report at enrollment whether they used any FA or other supplements prepregnancy and in early pregnancy, and if so, the brand, dose, timing, and frequency …
A rubbish day out
Authors: Katherine Ngo
Journal: BMJ (2010)

It was like a scene from Spider Man. We were standing atop a 20 metre feeding shoot as Doctor Octopus-type claws picked up, pivoted across, and dropped countless yellow and black bags in front of us. Breathing in the smell of accumulated rubbish, I found myself asking, “How did an Australian medical student end up at LondonWaste?”

I had been in the middle of my elective at the Royal London Hospital when a senior house officer who I had been relentlessly shadowing suggested the tour. I was intrigued: where do gloves, needles, and other waste go after we …
Correction: MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences
Authors: Alberto L’Abbate, Doron Tolomeo, Ingrid Cifola, Marco Severgnini, Antonella Turchiano, Bartolomeo Augello, Gabriella Squeo, Pietro D’Addabbo, Debora Traversa, Giulia Daniele, Angelo Lonoce, Mariella Pafundi, Massimo Carella, Orazio Palumbo, Anna Dolnik, Dominique Muehlematter, Jacqueline Schoumans, Nadine Van Roy, Gianluca De Bellis, Giovanni Martinelli, Giuseppe Merla, Lars Bullinger, Claudia Haferlach, Clelia Tiziana Storlazzi
Journal: Leukemia (2018)
Heterogeneity of 68Ga-PSMA PET/CT Uptake in Fibrous Dysplasia
Authors: Nicolas Plouznikoff, Camilo Garcia, Carlos Artigas, Kim Entezari, Patrick Flamen
Journal: Clinical Nuclear Medicine (2019)

Abstract Fibrous dysplasia is an uncommon benign bone pathology with only rare potential for malignant transformation. We describe the heterogeneous uptake of fibrous dysplasia of a whole rib on 68 Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT. 68 Ga-PSMA binds to PSMA-expressing prostate cancer cells, but it can also bind to the neovasculature of various solid tumors, as well as to some benign lesions. 68 Ga-PSMA expression in fibrous dysplasia should not automatically be equated with malignant transformation or confused with prostate cancer metastases.
Abstract P4-04-08: Genomic profiling of 304 treatment-naïve Chinese breast cancer patients: A comparison of Chinese and TCGA cohorts
Authors: N Liao, G Zhang, Y Wang, L Guo, L Cao, Z Zhang, CM Balch, F Meric-Bernstam
Journal: Cancer Research (2019)

Abstract Background: The complexity of BC at the clinical, morphological and molecular level has been well recognized. Molecular profiling, which reveals the intrinsic biology among subtypes, has significantly advanced the management of this disease. However, previous studies have provided very limited molecular data on Chinese breast cancer patients. Methods: We performed targeted sequencing using a panel consisting of 36 BC related genes to interrogate the genomic landscape of 304 consecutive treatment-naïve Chinese BC patients and compared our results to the TCGA data set. Results: Comparing to TCGA, our cohort had significantly fewer patients with triple negative breast cancer (8.2% vs 15.5% p=0.002). The most prominent genomic difference was our cohort had significantly higher TP53mutation frequency in HR+/HER2- and HR+/HER2+ groups. The composition of TP53 mutations also differed significantly between two cohorts in HR+/HER2- group, with TCGA cohort having missense mutation as the predominant mutation; whereas, in our cohort, nonsense and frameshift mutations were predominant. We classified the most populated and diverse group of HR+/HER2- cancer into 4 subgroups based on molecular signature. The clinical significance of this proposed classification was confirmed by differences in overall survival using data from the TCGA. Conclusions:We identified distinctive genomic patterns associated with Chinese breast cancer patients compared to TCGA data, suggesting the importance of mutation-based stratification according to ethnic status. To the best of our knowledge, this is one of the largest study of Chinese BC patients that interrogated the spectrum of mutational events and correlated these molecular signatures with clinical outcomes. This study was supported by funding from National Natural Science Foundation of China (Grant No. 81602645), Guangdong Provincial Natural Science Foundation (Grant No. 2016A030313768) and Research Funds from Guangzhou Science and Technology Bureau (Grant No. 201707010418 and 201804010430). Citation Format: Liao N, Zhang G, Wang Y, Guo L, Cao L, Zhang Z, Balch CM, Meric-Bernstam F. Genomic profiling of 304 treatment-naïve Chinese breast cancer patients: A comparison of Chinese and TCGA cohorts [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-04-08.