tbuckley/cabot-search huggingface dataset:
Countdown to exams with a card
Authors: Maham Khan
Journal: BMJ (2012)

Fed up of rewriting textbooks? Can’t learn from a computer or phone screen? Whether it’s for your first or final year examinations, with a curriculum as broad as medicine, revision is daunting. Numerous textbooks are mandatory for learning different aspects of the same condition, from pathology to anatomy to clinical examination. Altogether, the revision process is long, tedious, and time consuming. So, for those who are fed up of wasting valuable revision time, and desperate to have all the basic principles in one place, the Oxford Handbooks Clinical Tutor Study Cards offer a solution and make an invaluable addition to any revision arsenal.

Reviewing the breadth of medicine, Oxford Handbooks Clinical Tutor Study Cards: …
The Aging Thyroid: A Reappraisal Within the Geroscience Integrated Perspective
Authors: Claudio Franceschi, Rita Ostan, Stefano Mariotti, Daniela Monti, Giovanni Vitale
Journal: Endocrine Reviews (2019)

The thyroid plays a crucial and pervasive role in physiology (metabolism, thermogenesis, and immunity, among others) and its aging and related changes in thyroid hormone production contribute to the common occurrence of thyroid diseases in elderly and to age-associated changes in other organs and systems. We address the complexity of thyroid aging following the basic suggestions of geroscience. This integrative new perspective identifies a few basic molecular mechanisms or "pillars" (inflammation, adaptation to stress, loss of proteostasis, stem cell exhaustion, metabolism derangement, macromolecular damage, and epigenetic modifications) as a unifying conceptual framework to understand the aging process and age-associated diseases. Within this scenario, we review available data on the presence and role in the thyroid of alterations of such mechanistic pillars, paying particular attention to (i) inflammation, focusing on cellular senescence and age-associated dysbiosis (alteration of gut microbiota); (ii) telomere shortening as an example of macromolecular damage; (iii) proteasomal function, including mitophagy and autophagy; (iv) stem cells and cell renewal; (v) energy metabolism and mitochondrial dysfunction; and (vi) age-related epigenetic changes, focusing on DNA methylation. Overall, the study of these topics in the thyroid is in its infancy and deserves much more attention. Finally, thyroid function in centenarians as a model of healthy aging is reviewed within the framework of possible adaptive mechanisms involving the thyroid to attain longevity. Accordingly, the concept of "thyroid biography" is proposed to grasp the complex combination of factors (including endocrine disruptors and lifestyle habits) impinging lifelong on thyroid function at the individual level.
Computed Tomography–Based Score Indicative of Lung Cancer Aggression (SILA) Predicts the Degree of Histologic Tissue Invasion and Patient Survival in Lung Adenocarcinoma Spectrum
Authors: Cyril Varghese, Srinivasan Rajagopalan, Ronald A. Karwoski, Brian J. Bartholmai, Fabien Maldonado, Jennifer M. Boland, Tobias Peikert
Journal: Journal of Thoracic Oncology (2019)
Abstract P6-01-01: Immunohistochemical staining and <i>in vitro</i> analysis of HER2-positive breast cancer using trastuzumab and pertuzumab to develop an appropriate tracer in image-guided surgery
Authors: R Otsubo, PJ Kuppen, S Bhairosingh, AL Vahrmeijer, VT Smit, T Nagayasu, CJ van de Velde, CF Sier
Journal: Cancer Research (2019)

Abstract Background: Pre- and intraoperative visualization of cancer cells using monoclonal antibody-based multimodal tracers can demarcate tumor margins in breast-conserving surgery. We focused on trastuzumab (Tmab) to develop a tracer for HER2-positive breast cancer by conjugation with a fluorescent dye. However, whether Tmab can be used as an imaging tracer for patients who receive Tmab as neoadjuvant therapy (NAD) is unclear, because tumor-cell HER2 could be bound by NAD Tmab at the time of surgery. This study evaluated immunohistochemical (IHC) staining and in vitro experiments with Tmab and pertuzumab (Pmab) as primary antibodies to find a suitable tracer. Pmab has a different antigen epitope than Tmab. Methods: We included 43 patients with HER2-positive breast cancer, who were treated between 2010 and 2016. The NAD cohort (n=10, with 26 lesions) received chemotherapy and Tmab before surgery. The Tmab-naïve cohort (n=33, with 95 lesions) did not receive chemotherapy or Tmab before surgery. We excluded NAD patients with pathological complete responses. We evaluated the lesions, using IHC with Tmab and Pmab. We also performed flow cytometry and fluorescent microscopic analysis (FMA) using Tmab and Pmab conjugated with a fluorescent agent for the HER2-negative MCF7 and HER2-positive HCC1954 cell lines, which were pre-treated with Tmab to model NAD conditions. Results: IHC with anti-HER2 antibody showed positive staining in all patients. Tmab staining was less intense, but positive Tmab IHC reactions were detected on tumor cell membranes in 77.8% of lesions in the naïve cohort and 70.8% in the NAD cohort. Pmab staining was seen in 46.3% of naïve cohort lesions and 22.2% of NAD lesions. Notably, we observed cytoplasmic staining in 87.8% of Pmab-negative cases in the NAD cohort. Flow cytometry showed less Tmab binding than Pmab binding in HCC1954 cells. After 24 hours' pretreatment incubation with Tmab, FMA showed a clear decrease in Tmab binding from 73.3% (without pretreatment) to 5.7%(after pretreatment), and a smaller decrease in Pmab binding from 72.7% (without pretreatment) to 66.4% (after pretreatment) in HCC1954 cells. Conclusions:Pmab might be a suitable tracer for image-guided surgery after NAD, but identifying a suitable tracer for HER2-positive breast cancer will require further study. Citation Format: Otsubo R, Kuppen PJ, Bhairosingh S, Vahrmeijer AL, Smit VT, Nagayasu T, van de Velde CJ, Sier CF. Immunohistochemical staining and in vitro analysis of HER2-positive breast cancer using trastuzumab and pertuzumab to develop an appropriate tracer in image-guided surgery [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 P6-01-01.
Development of resistance to FAK inhibition in pancreatic cancer is linked to stromal depletion
Authors: Hong Jiang, Xiuting Liu, Brett L Knolhoff, Samarth Hegde, Kyung Bae Lee, Hongmei Jiang, Ryan C Fields, Jonathan A Pachter, Kian-Huat Lim, David G DeNardo
Journal: Gut (2019)

Objective We investigated how pancreatic cancer developed resistance to focal adhesion kinase (FAK) inhibition over time. Design Pancreatic ductal adenocarcinoma (PDAC) tumours from KPC mice (p48-CRE; LSL-KRas G12D/wt ; p53 flox/wt ) treated with FAK inhibitor were analysed for the activation of a compensatory survival pathway in resistant tumours. We identified pathways involved in the regulation of signal transducer and activator of transcription 3 (STAT3) signalling on FAK inhibition by gene set enrichment analysis and verified these outcomes by RNA interference studies. We also tested combinatorial approaches targeting FAK and STAT3 in syngeneic transplantable mouse models of PDAC and KPC mice. Results In KPC mice, the expression levels of phosphorylated STAT3 (pSTAT3) were increased in PDAC cells as they progressed on FAK inhibitor therapy. This progression corresponded to decreased collagen density, lowered numbers of SMA + fibroblasts and downregulation of the transforming growth factor beta (TGF-β)/SMAD signalling pathway in FAK inhibitor-treated PDAC tumours. Furthermore, TGF-β production by fibroblasts in vitro drives repression of STAT3 signalling and enhanced responsiveness to FAK inhibitor therapy. Knockdown of SMAD3 in pancreatic cancer cells abolished the inhibitory effects of TGF-β on pSTAT3. We further found that tumour-intrinsic STAT3 regulates the durability of the antiproliferative activity of FAK inhibitor, and combinatorial targeting of FAK and Janus kinase/STAT3 act synergistically to suppress pancreatic cancer progression in mouse models. Conclusion Stromal depletion by FAK inhibitor therapy leads to eventual treatment resistance through the activation of STAT3 signalling. These data suggest that, similar to tumour-targeted therapies, resistance mechanisms to therapies targeting stromal desmoplasia may be critical to treatment durability.
As good as new
Authors: Neil Chanchlani
Journal: BMJ (2012)

editor, Student BMJ 

More than 7000 people are on a renal transplantation waiting list in the UK. Although this number has declined with the implementation of living donor transplantation, many people still die while waiting for kidneys ( BMJ 2011;343:d7300). One suggestion to tackle the problem is that doctors should get more actively involved. Our head to head this month is “Is it unethical for doctors to encourage healthy adults to donate …
Writing about your work experience in your personal statement—case examples
Authors: Alison Walker
Journal: BMJ (2015)

All applicants need to write about their work experience in their personal statement to demonstrate why they are a good candidate not only for a place at medical school but also as a future doctor. How have successful medical students done this? I asked four students at different medical schools to tell me how they got their work experience, what they did, and, most importantly, how they put into words what they learnt from it all.

My main work experience placement during sixth form was volunteering at a care home for elderly people for almost a year. The application process was straightforward: I called the care home, was sent an application pack in the post, and was then interviewed by the manager a few weeks later. The placement involved visiting once a week for a few hours to provide company for some of the residents. Although this was not work experience in a hospital, I was able to reflect on how it highlighted the difficulties of being a doctor in my personal statement. I wrote:

“I have experienced both sadness and frustration with regards to a resident who suffers from Alzheimer’s, because she learns to trust me, only to forget who I am later on. Despite this I visit her regularly because a few kind words on my part, grants her a sense of security. This, amongst other experiences, has allowed me to begin to appreciate the intensity of the emotional stress doctors face daily.”

Out of all the work experience I did (including shadowing consultants at various hospitals) I now know that it was …
Abstract 20526: Bleeding Episode Predicts the Occurrence of Dyspnea During Ticagrelor Treatment in Patients With Acute Coronary Syndrome
Authors: Min Gyu Kang, Kyehwan Kim, Jae Seok Bae, Jong-Hwa Ahn, Jeong Yoon Jang, Hyun Woong Park, Jin-Sin Koh, Yongwhi Park, Seok-Jae Hwang, Choong Hwan Kwak, Jin-Yong Hwang, Young-Hoon Jeong
Journal: Circulation (2017)

Background & Objective: Compared with thienopyridine, ticagrelor increases the rate of dyspnea that has contributed to the drug discontinuation. We sought to determine which factors determine the d...
Transient respiratory distress and difficulty passing a nasogastric tube in a newborn baby
Authors: Emma Vittery (née Firth),, Keren Sloan, Mark Powis
Journal: BMJ (2016)

A baby was born at 30 weeks and 5 days’ gestation, by emergency caesarean section after onset of labour. It was a twin pregnancy, with an antenatal history of polyhydramnios, but no risk factors for sepsis. Polyhydramnios is excess amniotic fluid in the amniotic sac during a pregnancy. The baby was the second twin and weighed 1160 g.

On delivery the baby had irregular respirations, low saturations, and excessive secretions necessitating intermittent positive pressure ventilation. Ten minutes after the delivery she was intubated and given surfactant through an endotracheal tube. Soon after, her respiratory effort improved and she was extubated and managed with short term nasal continuous positive airway pressure (CPAP) before stepping down to self ventilation within hours.

On examination the baby had a left pre-auricular skin tag, but was not dysmorphic. No limb abnormalities were found. Examination of the abdomen was unremarkable except for a single umbilical artery. Perineal examination showed a urethra and vagina and no patent anus.

Three attempts at passing a nasogastric tube were unsuccessful and a radiograph showed it coiling in the upper oesophagus. A Replogle tube—used to suction excess saliva from the oesophagus—was placed before the baby was transferred to a surgical unit. A radiograph of the chest and abdomen was obtained (fig 1).



Fig 1 Neonatal chest and abdominal radiograph



1.  Describe the findings in the radiograph.

2.  Which diagnoses are evident or suspected?

3.  What further investigations should be performed and why?

4.  How should this baby be managed …
Abstract P1-06-09: Withdrawn
Authors: Y Yu, Y Zhen, Y Zhang
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Yu Y, Zhen Y, Zhang Y. Withdrawn [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 P1-06-09.
Use of caffeinated substances and risk of crashes in long distance drivers of commercial vehicles: case-control study
Authors: Joris C Verster
Journal: BMJ (2013)

The paper

“Use of caffeinated substances and risk of crashes in long distance drivers of commercial vehicles: case-control study” by Lisa Sharwood and colleagues ( BMJ 2013;346:f1140, doi:10.1136/bmj.f1140).

Abstract

Objective To determine whether there is an association between use of substances that contain caffeine and the risk of crash in long distance commercial vehicle drivers.

Design Case-control study.

Setting New South Wales (NSW) and Western Australia (WA), Australia.

Participants 530 long distance drivers of commercial vehicles who were recently involved in a crash attended by police (cases) and 517 control drivers who had not had a crash while driving a commercial vehicle in the past 12 months.

Main outcome measure The likelihood of a crash associated with the use of substances containing caffeine after adjustment for factors including age, health disorders, sleep patterns, and symptoms of sleep disorders as well as exposures such as kilometres driven, hours slept, breaks taken, and night driving schedules.

Results 43% of drivers reported consuming substances containing caffeine, such as tea, coffee, caffeine tablets, or energy drinks for the express purpose of staying awake. Only 3% reported using illegal stimulants such as amfetamine (“speed”); 3,4 methylenedioxymethamfetamine (ecstasy); and cocaine. After adjustment for potential confounders, drivers who consumed caffeinated substances for this purpose had a 63% reduced likelihood of crashing (odds ratio 0.37, 95% confidence interval 0.27 to 0.50) compared with drivers who did not take caffeinated substances.

Conclusions Caffeinated substances are associated with a reduced risk of crashing for long distance commercial motor vehicle drivers. While comprehensive mandated strategies for fatigue management remain a priority, the use of caffeinated substances could be a useful adjunct strategy in the maintenance of alertness while driving.

Sleepiness at the wheel and reduced arousal are a common cause of road …
Noise-driven attractor landscapes for perception by mesoscopic brain dynamics
Authors: Walter J. Freeman
Journal: Behavioral and Brain Sciences (2001)

Tsuda offers advanced concepts to model brain functions, includ-ing “chaotic itinerancy,” “attractor ruins,” “singular-continuous nowhere-differentiable attractors,” “Cantor coding,” “multi-Milnor attractor systems,” and “dynamically generated noise.” References to physiological descriptions of attractor landscapes governing activity over cortical fields maintained by millions of action potentials may facilitate their application in future experimental designs and data analyses.
Cases in Precision Medicine: Concerns About Privacy and Discrimination After Genomic Sequencing
Authors: Deborah Stiles, Paul S. Appelbaum
Journal: Annals of Internal Medicine (2019)

Patients and research participants have indicated that privacy of their genetic test results is an important concern, particularly with respect to insurance coverage. Internists and other physicians whose patients ask about legal protections for information generated by genome sequencing for clinical purposes can provide both reassurance and caution. Protections for medical information in general, as well as laws in some states that provide additional safeguards for genetic data, should reassure patients that this information will remain private. Patients themselves will need to weigh the risks versus the benefits of generating genomic data in deciding whether to undergo exome sequencing.
The correct answer is . . .
Authors: Moayed Alawami
Journal: BMJ (2011)

The purpose of this app is to work through case based scenarios and decide appropriate investigations and management for the patient. In each case, a succinct history and physical examination findings are presented and then the user is required to choose the relevant investigations. Results of the investigations are then provided and a decision is needed to decide which management option is best.

The answers are submitted, marked, and overall feedback of “Well,” “OK,” and “Poor” is given in …
Abstract P6-17-05: Independent validation of a combined biomarker based on the PAM50 HER2-enriched subtype and ERBB2 mRNA levels following HER2 blockade without chemotherapy in the PerELISA phase II trial
Authors: A Prat, G Griguolo, MV Dieci, G Bisagni, A Frassoldati, GV Bianchi, T Pascual, L Pare, P Galvan, L Urso, P Conte, V Guarneri
Journal: Cancer Research (2019)

Abstract Background: A combined biomarker based on HER2-enriched subtype (HER2-E) and ERBB2 mRNA predicts response and survival in HER2+ breast cancer following trastuzumab +/- lapatinib in the absence of chemotherapy (Prat et al. ASCO 2018). Here, we tested the ability of the combined biomarker to predict pathological complete response (pCR) following neoadjuvant trastuzumab, pertuzumab and endocrine therapy. Methods: RNA from 40 baseline tumor samples from the phase II PerELISA trial were evaluated. PerELISA evaluated the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen based on dual HER2 blockade with trastuzumab and pertuzumab in combination with letrozole in HER2+/hormone receptor-positive breast cancer selected on the basis of Ki67 response after short course letrozole-alone (Guarneri ASCO 2018). Ki67 response was defined by protocol as relative Ki67 reduction ≥20% from baseline at day 14. Gene-expression was measured using the nCounter platform. Intrinsic subtypes and ERBB2 levels were determined by the PAM50 gene expression predictor. A pre-specified ERBB2 cutoff was determined to define ERBB2-high. Univariate and multivariable logistic regression analyses were performed. Results: The proportion of HER2-E disease within the ERBB2-high and ERBB2-low groups was 46.2% (6/13) and 18.5% (5/27), respectively. The discordance rate at the individual level was 30% (12/40). A total of 6 (15%) and 34 (85%) samples were HER2-E/ERBB2-high and others, respectively. The magnitude of Ki67 reduction of the HER2-E/ERBB2-high and others groups was 64.8% and 63.2%, respectively (p=0.88). The pCR rate of HER2-E/ERBB2-high was 66.7%. The pCR rate of the others group was 14.7%. The univariate odds ratio between HER2-E/ERBB2-high tumors and the others groups was 11.60 (95% CI 1.66-81.10; p=0.014). No other clinical-pathological variable was significantly associated with pCR. Conclusion: The combined HER2-E/ERBB2-high biomarker can identify patients who might be good candidates to receive dual HER2 blockade alone without chemotherapy. Citation Format: Prat A, Griguolo G, Dieci MV, Bisagni G, Frassoldati A, Bianchi GV, Pascual T, Pare L, Galvan P, Urso L, Conte P, Guarneri V. Independent validation of a combined biomarker based on the PAM50 HER2-enriched subtype and ERBB2 mRNA levels following HER2 blockade without chemotherapy in the PerELISA phase II trial [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 P6-17-05.
Ear discharge and hearing loss in an elderly woman
Authors: Paul McLean, Andy Chin, Paul Cullis
Journal: BMJ (2013)

A 78 year old woman was referred by her general practitioner to the outpatient ear, nose, and throat clinic with a three week history of a discharging right ear (otorrhoea). She had difficulty hearing in both ears and normally used a hearing aid in her “better,” right ear. On further questioning she denied experiencing any pain in her ear or tinnitus in either ear. She had no other relevant symptoms.

(1) What are the findings on otoscopy?

(2) What should you look for on otoscopy?

(3) What is the differential diagnosis of otorrhoea?

(4) How would you treat this patient and what advice could be given?

(5) Are there any other investigations you would organise?

(1) The figure⇓ shows the otoscopic view of the right tympanic membrane. There is a large, infective, central perforation. Additionally, mucopurulent discharge is present and the surrounding skin appears erythematous and wet.



Otoscopic view of right ear



(2) To make an accurate assessment of the tympanic membrane clinicians need to be competent in their ability to use an otoscope (also known as an auriscope). Before carrying out the examination, the procedure should be explained to the patient. It is good practice to ensure that the patient is comfortable, lighting is adequate in the room, and the light on the otoscope is fully functional. Look for any scars around the ear that might denote previous surgery. Check for tenderness in and around the ear before inserting the otoscope. To …