tbuckley/cabot-search huggingface dataset:
Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report
Authors: Osamu Honjo, Terufumi Kubo, Fumiko Sugaya, Takahiro Nishizaka, Koji Kato, Yoshihiko Hirohashi, Hiroki Takahashi, Toshihiko Torigoe
Journal: Journal for ImmunoTherapy of Cancer (2019)

Immune checkpoint inhibitors (ICIs) have provided more options in the treatment of lung cancer. However, ICIs can cause several unfavorable reactions generally referred to as immune-related adverse effects.In this report, we present the case of a 52-year-old woman with successful regression of pleomorphic carcinoma of the lung following nivolumab therapy. She developed purpura fulminans (PF) ultimately resulting in amputation of both lower extremities. Blood tests revealed thrombocytopenia with increased serum soluble IL-2 receptor, ferritin, and triglyceride levels suggesting hemophagocytic lymphohistiocytosis (HLH). In addition, serum A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 activity was decreased, suggesting thrombotic thrombocytopenic purpura (TTP). Further detailed analysis revealed severe hypercytokinemia including increased levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, and G-CSF.The severe systemic inflammatory reaction and impaired peripheral circulation in this patient was attributed to excessive immunological effect induced by nivolumab resulting in cytokine release syndrome (CRS). This is the first report of a patient with multiple pathological conditions including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Further accumulating thoroughly investigated cases would lead to better understanding of the disease and development of reliable cancer immunotherapy.
Abstract P5-04-29: Efficacy and safety of low-dose everolimus in Chinese HR-positive, HER2-negative metastatic breast cancer patients
Authors: X Shao, X Wang, Z Chen, Y Zheng
Journal: Cancer Research (2019)

Abstract Background: Everolimus has been testified to be effective among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, everolimus at dose of 10mg was accompanied by a higher incidence of mTOR-inhibitor class-effect adverse events (AEs) which usually leading to dose reduction or interruption. Additionally, some studies suggested that there was no correlation between dose intensity (5 vs. 10 mg labeled dose) and efficacy. Consequently, we conducted the present study aiming to explore the efficacy and safety of everolimus at dose of 5 mg plus endocrine therapy in Chinese population. Methods: 68 HR+/HER2- MBC patients were included in this exploratory study who received everolimus at the dose of 5mg in Zhejiang Cancer Hospital between September 2014 and September 2017. Progression free survival(PFS) and overall survival(OS) were estimated by the Kaplan- Meier method, and the hazard ratios(HRs) and corresponding 95% confidence intervals(CIs) were estimated using the Cox proportional harzard model. Besides, objective response rate(ORR), clinical benefitrate(CBR) and safety profile were also evaluated. Results: After a median follow up of 14 months, PFS was 5.3 months (95%CI 4.2-6.4), and OS was immature. 16(23.5%) were at the first or second-line, 52(76.5%) were at third-line or later. PFS for the first and second-line is significantly longer than that for the third-line or later (12.9 months vs. 4.6 months, P=0.009, HR=0.395, 95% CI=0.192-0.811). 11(16.2%) achieved partial response (PR), 42(61.7%) had stable disease (SD), and 15(22.1%) reported progressive disease (PD). The ORR and CBR were 16.2%, 35.2%, respectively. Most common all grade adverse events were stomatitis(26.5%), fatigue(10.0%), infection(11.8%), thrombocytopenia(5.9%), anemia(4.4%), hyperglycemia(4.4%). The most common ≥3 grade adverse events were stomatitis(4.4 %), infection(2.2%) and thrombocytopenia(1.1%). Conclusions: The combination of low-dose everolimus and endocrine therapy was highly effective especially at the earlier line in Chinese population. And the safety profiles were similar to previous studies but the incidences were greatly lower. The combination of low-dose everolimus and endocrine therapy may become a proper option for HR+/HER2- MBC. Citation Format: Shao X, Wang X, Chen Z, Zheng Y. Efficacy and safety of low-dose everolimus in Chinese HR-positive, HER2-negative metastatic breast cancer patients [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 P5-04-29.
Abstract 4179: Promising clinical activity of a NAB paclitaxel plus gemcitabine combination in a disease-specific phase I trial in patients with advanced pancreatic cancer
Authors: Daniel D. Von Hoff, Mitesh Borad, Ramesh K. Ramanathan, Lon S. Smith, Ronald L. Drengler, Tina E. Wood, Daniel Laheru, Manuel Hidalgo
Journal: Cancer Research (2008)

Abstract Patients (pts) with pancreatic cancer have very poor survival. A substantial percentage of pancreatic cancers have increased expression of SPARC (Secreted Protein And Rich in Cysteine) (Guweidhi et al., Annals of Surgery, 2005; 242: 224-234,Von Hoff et al., J Clin Oncol 2006; 24(18s): 138, Infante et al., J Clin Oncol 2007; 25 (3): 319.) Increased SPARC expression has been correlated with improved response to nanoparticle albumin-bound paclitaxel(nab-paclitaxel) due to a SPARC-albumin interaction (Trieu et al., New Targets in Delivery System for Diagnosis and Treatment (SKCC), 2007; abstract 53). Based on this observation, SPARC may play a role in selectively concentrating nab-paclitaxel in pancreatic tumors. Therefore a disease specific modified phase I trial of nab-paclitaxel + gemcitabine in pts with advanced pancreatic cancer was performed. Tumor samples were obtained for SPARC evaluation and CA19-9 levels were monitored as a drop in CA19-9 has been correlated with improved survival. In this study, pts with advanced pancreatic cancer with no prior chemotherapy except as a radiation sensitizer received nab-paclitaxel + gemcitabine on days 1, 8, 15 every 28 days with a starting dose of 100 mg/m2 and 1000 mg/m2 respectively. Subsequent dose escalations of nab-paclitaxel were planned at 125 and 150mg/m2. To date, 20 pts have been recruited for this study. All of the pts received nab-paclitaxel 100mg/m2 + gemcitabine 1000 mg/m2. 18/20 patients completed at least one cycle of treatment and were considered evaluable. Independent review of the patient’s measurable disease on CAT and PET scans is ongoing with many of the patients continuing to have radiographic regression of disease. 17/18 evaluable subjects had paired CA19-9 levels available for analysis. Clinical activity has been demonstrated by CA19-9 reduction of greater than 20% from baseline in 82% (14/17pts) and more than 70% from baseline in 59% (10/17 pts). A decrease of CA19-9 of at least 20% has been associated with improvement in patient survival (AH Ko et al., BJC 2005; 93, 195-199, Park BB et al., Cancer Chemother Pharmacol 2007 Sep; 60 (4): 489-94, and Boeck S et al., Oncology 2006; 70 (4): 255-64). The most common Grade 3/4 adverse event (AE) was neutropenia (n=3, 2, respectively). Other grade 3 AEs include febrile neutropenia (1), fatigue (1) and hyperglycemia (1). In addition, 2 cases of grade 2 anemia and 2 cases of thrombocytopenia were observed. Based on these results, the combination of nab-paclitaxel and gemcitabine in pancreatic cancer warrants further study. Dose escalation to cohort 2 is proceeding. When the MTD is determined, that cohort will be expanded. The optimum dose as determined in this study will be used in a larger, randomized phase II/III study.
Abstract P6-17-29: Withdrawn
Authors: ZW Veitch, P Bedard, PA Tang, JL Conway, D Ribnikar, H Albaba, K King, S Lupichuk, D Cescon
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Veitch ZW, Bedard P, Tang PA, Conway JL, Ribnikar D, Albaba H, King K, Lupichuk S, Cescon D. 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 P6-17-29.
Abstract P1-07-14: Enabling biomarker validation in breast cancer molecular subtypes: sensitivity and specificity of array-based subtype classification in 983 patients
Authors: B Györffy, A Lanczky
Journal: Cancer Research (2012)

Abstract Background: The diverse breast cancer molecular subtypes have different clinicopathological characteristics and outcomes. Here, we assessed the correlation between microarray-defined and author-reported molecular subtypes using publicly available breast cancer datasets. Methods: GEO was searched for datasets where the authors determined molecular subtypes. The molecular subtype was re-calculated for each patient using the StGallen guidelines by assessing the microarray-based expression of ER, HER2 and MKI67 (Basal: ER negative + HER2 negative, Luminal A: ER positive + HER2 negative + low MKI67, HER2 enriched: HER2 positive + ER negative, Luminal B: ER positive + HER2 positive and ER positive + HER2 negative + high MKI67). The thresholds used were 500 for ER (probe set 205225_at), 4800 for HER2 (216836_s_at) and 470 for MKI67 (212021_s_at). Sensitivity and specificity were calculated for each subtype separately. Results: Molecular subtype was published in all together six datasets (GSE1456, GSE21653, GSE25066, GSE20711, GSE31519 and GSE17907) for 983 patients. In these, 380, 306, 169 and 128 were Basal, Luminal A, Luminal B and HER2 enriched, respectively. The microarray-based molecular subtype determination resulted in a sensitivity of 0.70, 0.55, 0.63 and 0.38 and a specificity of 0.96, 0.87, 0.67 and 0.99 for Basal, Luminal A, Luminal B and HER2 enriched subtypes, respectively. Finally, the option to filter for molecular subtypes was implemented into our online biomarker validation platform at www.kmplot.com. Discussion. Microarray data provided highest sensitivity and specificity to independent subtype classification for Basal tumors, while the luminal B subtype displayed the highest discordance. Our registration-free online service enables the validation of gene expression based biomarkers in each subtype separately. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-14.
Abstract P1-16-07: Progression-free survival is a surrogate of survival in maintenance therapy for metastatic breast cancer: Randomized trial level analysis
Authors: E Song, H Yao, Y Yu, Q Ou, Y Wang
Journal: Cancer Research (2019)

Abstract Background:The validity of progression-free survival (PFS) as a surrogate end point for overall survival (OS) in maintenance therapy trials of metastatic breast cancer (MBC) is uncertain. We aimed to compare treatment effect sizes and the strength of associations between OS and PFS in trials of maintenance therapy for MBC. Methods: We searched for randomized trials investigating maintenance chemotherapy, endocrine therapy or immunotherapy after first-line chemotherapy in MBC and selected those reporting results for both OS and PFS. Treatment effect size differences between OS and PFS by a ratio of hazard ratios (rHRs) with 95% confidence intervals [CIs] were evaluated using random effects analysis. Surrogacy were analyzed using a weighted linear regression model, correlations were evaluated by squared correlation R2. Results: We analyzed data from 16 trials and 3,898 patients that received maintenance chemotherapy, endocrine therapy or immunotherapy for MBC. In the all trial-level analysis, treatment effect sizes were 28% greater for PFS than for OS (combined rHR, 0.72; 95% CI, 0.62 to 0.85, P &amp;lt; 0.001), and the correlation coefficient R2 between PFS and OS was 18% (95% CI, 12% to 26%). Differences were greater with PFS than OS for trials of maintenance chemotherapy compared with observation (rHR, 0.72; 95% CI, 0.59 to 0.80, P &amp;lt; 0.001), and the correlation coefficient R2between treatment effects on PFS and on OS ranged from 12% (95% CI, 8% to 16%) when all trials were considered to 40% (95%CI, 30% to 54%) after exclusion of one highly influential trial by sensitivity analysis. Differences were also great for trials of maintenance endocrine therapy vs. observation (rHR, 0.54; 95% CI, 0.44 to 0.66), and immunotherapy vs. observation (rHR, 0.85; 95% CI, 0.80 to 0.91). Conclusion: PFS was greater than OS in the treatment effect sizes, which is a valid surrogate end point for OS to assess treatment effect in MBC maintenance therapy trials. PROSPERO registry: No. CRD42017071858; Support: ChiCTR-IIR-17014036, SYS-C-201801. Citation Format: Song E, Yao H, Yu Y, Ou Q, Wang Y. Progression-free survival is a surrogate of survival in maintenance therapy for metastatic breast cancer: Randomized trial level analysis [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 P1-16-07.
The view from the other side
Authors: James Conlon
Journal: BMJ (2012)

As a junior doctor working in a busy teaching hospital, I have become accustomed to arriving at work in the morning and being greeted by a barrage of requests from the nursing staff. Last Thursday morning I noticed that the questions seemed slightly different: “When did you last have a drink?” “Who’s your next of kin?” “Can you provide a urine sample?” It was a day of surgery admissions and I, for a change, was a patient.

As I was escorted towards the operating theatre, a …
Trump introduces “religious freedom” rule allowing medical staff to refuse to provide treatments
Authors: Owen Dyer
Journal: BMJ (2019)

Donald Trump, speaking in the White House Rose Garden during a National Day of Prayer service on 2 May, announced a new final rule that expands the rights of medical professionals to refuse to provide treatments or services that they say infringe their religious beliefs, such as abortion, advance directives, and assisted suicide.

The 440 page final rule1 will apply to all healthcare providers that take federal money—essentially, all hospitals and their staff, as well as most doctors. It is effectively the health department’s summation of existing law and its guideline for enforcing it.

Trump said, “Just today we finalised new protections of conscience rights for physicians, pharmacists, nurses, teachers, students, and faith based charities. They’ve been wanting to do that a long time.”

The Obama era rule did not offer enough protections to religious people and failed to reflect some laws …
Sleep on the wards: an ongoing battle
Authors: Luke Staveley-Wadham
Journal: BMJ (2013)

As a junior doctor, aside from the predictable daily tasks, I found an all too familiar request from many patients. “Doctor, I had a terrible night’s sleep, you couldn’t prescribe me something could you?” My colleagues were surprised at the frequency of this request—patients’ sleep not being a subject covered in detail when we were medical students. But, whether it’s a nurse thrusting a drug chart in front of us to request sleeping tablets or a …
Looking at the medical couple
Authors: Katherine Bettany
Journal: BMJ (2014)

They distract you in lectures with their displays of affection; leave you “third wheeling” at lunch; and never turn up anywhere without the other. The medical couple is practically a medical school institution—every cohort has at least one. This month we take a look at what it’s like to be in a couple with another medical student today, and ask three pairs about the ins and outs of their relationship ( p 12 ).

Some medical students forgo flesh and blood relationships, instead forming an obsession with their choice of specialty. Medical lore says that some …
Tips on how to prepare as a junior doctor
Authors: Lisa Sabir
Journal: BMJ (2015)

Junior doctors advise on how to prepare for your foundation years Every doctor will remember his or her first days as a junior doctor. Excitement is tempered by the fear that you have no idea what you are doing . . . “What was the code for that door again? How do I bleep? How do I spell para-ce-ta-mol?” I remember being casually handed an electrocardiogram with broad complex tachycardia, running to assess the patient, and being so grateful that my registrar was on the ward as I put out the crash call. I have collected some advice from junior doctors on how you can prepare and make the most of your foundation years. #### Preparation for the job ##### Lisa Sabir, foundation year 1 doctor, Oxford University Hospitals NHS Trust ###### Ward rounds Ward rounds vary with specialty, and surgeons generally have a much speedier round than others. Here are a few things you can do to make sure you are well prepared.
Abstract 11830: Increased Coronary Perivascular Adipose Tissue Volume on Cardiac Computed Tomography in Patients With Vasospastic Angina -Possible Correlation With Adventitial Vasa Vasorum Formation
Authors: Kazuma Ohyama, Yasuharu Matsumoto, Hirokazu Amamizu, Hironori Uzuka, Kensuke Nishimiya, Kiyotaka Hao, Ryuji Tsuburaya, Jun Takahashi, Kenta Ito, Hiroaki Shimokawa
Journal: Circulation (2015)

Background: The adventitial components, such as perivascular adipose tissue (PVAT) and vasa vasorum (VV), play important roles in the pathogenesis of cardiovascular disease. However, the roles of epicardial adipose tissue (EAT) and VV in the pathogenesis of vasospastic angina (VSA) remain to be examined. In this study, we thus examined whether coronary PVAT volume is increased at the spastic coronary segment, and if so, whether the volume is correlated with the extent of VV formation in VSA patients. Methods and Results: We measured the volume of EAT and coronary PVAT of the left anterior descending coronary arteries (LAD) on cardiac computed tomography (CT) in 48 consecutive patients with documented spasm in LAD and 18 control subjects without the spasm. We further examined the extent of VV formation of LAD in 26 VSA patients by using optical frequency domain imaging (OFDI). Patient characteristics were comparable between the 2 groups in terms of sex, age, body weight, body mass index and cardiovascular risks. Although the EAT volume was comparable between the 2 groups, the PVAT volume of LAD was significantly increased in VSA group as compared with control group (VSA, 29.8±15.2 vs. control, 18.8±9.2 cm3, P&lt;0.01) (Figure). Furthermore, there was a significant positive correlation between the PVAT volume of LAD and the VV area (R=0.43, P&lt;0.05) (Figure). Conclusions: These results indicate that the coronary PVAT volume, but not the EAT volume, is increased at the spastic coronary segments associated with enhanced adventitial VV formation in VSA patients, suggesting the pathophysiological correlation between the 2 changes.
How do students prepare for the SJT?
Authors: Aaron Koshy
Journal: BMJ (2013)

For an exam as important as the SJT, students were advised that little could be done to prepare for this “unrevisable” test. The most reliable resource is the practice test offered on the UKFPO website, and General Medical Council guidance. There are many unofficial books, courses, and assessment websites that sprung up prior to the exam. After purchasing a few of these products I have little doubt that some were hastily prepared, containing an array of spelling mistakes and contradictions.

To find out what students thought of their SJT preparation and how confident they felt about their performance, I conducted a questionnaire of students who had recently sat the SJT.

The questionnaire was created using an online survey site and sent via email to final …
Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission
Authors: Majid Arefi, Valerie Wilson, Siobhan Muthiah, Simon Zwolinski, Dalvir Bajwa, Paul Brennan, Katie Blasdale, David Bourn, John Burn, Mauro Santibanez-Koref, Neil Rajan
Journal: Journal of the American Academy of Dermatology (2019)

BackgroundClusters of rare cylindroma or spiradenoma tumors are a recurrent clinical presentation, yet conventional genetic testing results in individuals with these tumors are frequently normal.ObjectiveTo determine if genetic mosaicism accounts for such cases.MethodsA study of 6 cases from a series of 55 patients who met criteria for diagnostic gene testing for pathogenic CYLD variants over a 5-year period (2012-2017) was performed. A novel genetic assay was used to study DNA from peripheral blood leukocytes and, where possible, matched skin and tumor tissue.ResultsTwo patients had mosaic pathogenic CYLD variants in both the blood and skin. One of these patients transmitted a pathogenic variant to her daughter, and we report the novel phenotype of a contiguous gene deletion syndrome involving CYLD. Two patients had recurrent pathogenic variants in skin tumors from a single cluster but none detectable in the blood.LimitationsThe remaining 2 patients had clinical features of mosaicism, but these cases were not solved with the assays used because of a lack of access of fresh tumor tissue.ConclusionGenetic mosaicism should be considered in patients presenting with clustered cylindromas, because this may inform genetic testing and counseling of these patients.Graphical abstract
Development and Validation of Machine Learning Models in Prediction of Remission in Patients With Moderate to Severe Crohn Disease
Authors: Akbar K. Waljee, Beth I. Wallace, Shirley Cohen-Mekelburg, Yumu Liu, Boang Liu, Kay Sauder, Ryan W. Stidham, Ji Zhu, Peter D. R. Higgins
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Biological therapies have revolutionized inflammatory bowel disease management, but many patients do not respond to biological monotherapy. Identification of likely responders could reduce costs and delays in remission. <h3>Objective</h3> To identify patients with Crohn disease likely to be durable responders to ustekinumab before committing to long-term treatment. <h3>Design, Setting, and Participants</h3> This cohort study analyzed data from 3 phase 3 randomized clinical trials (UNITI-1, UNITI-2, and IM-UNITI) conducted from 2011 to 2015. Participants (n = 401) were individuals with active (C-reactive protein [CRP] measurement of ≥5 mg/L at enrollment) Crohn disease who received ustekinumab therapy. Data analysis was performed from November 1, 2017, to June 1, 2018. <h3>Exposures</h3> All included patients were exposed to 1 or more dose of ustekinumab for 8 weeks or more. <h3>Main Outcomes and Measures</h3> Random forest methods were used in building 2 models for predicting Crohn disease remission, with a CRP level lower than 5 mg/dL as a proxy for biological remission, beyond week 42 of ustekinumab treatment. The first model used only baseline data, and the second used data through week 8. <h3>Results</h3> In total, 401 participants, with a mean (SD) age of 36.3 (12.6) years and 170 male (42.4%), were included. The week-8 model had a mean area under the receiver operating characteristic curve (AUROC) of 0.78 (95% CI, 0.69-0.87). In the testing data set, 27 of 55 participants (49.1%) classified as likely to have treatment success achieved success with a CRP level lower than 5 mg/L after week 42, and 7 of 65 participants (10.8%) classified as likely to have treatment failure achieved this outcome. In the full cohort, 87 patients (21.7%) attained remission after week 42. A prediction model using the week-6 albumin to CRP ratio had an AUROC of 0.76 (95% CI, 0.71-0.82). Baseline ustekinumab serum levels did not improve the model's prediction performance. <h3>Conclusions and Relevance</h3> In patients with active Crohn disease, demographic and laboratory data before week 8 of treatment appeared to allow the prompt identification of likely nonresponders to ustekinumab without the need for costly drug-level monitoring.