tbuckley/cabot-search huggingface dataset:
Surgical neuro-oncology patient’s hospital discharge: improving the experience
Authors: Hannah Lowe, Nichola Brown, Eileen Andrews
Journal: Neuro-Oncology (2018)

The national cancer hospital in-patient experience survey 2015 identified unmet information needs for neuro-oncology patients regarding hospital discharge following surgery. To further understand what were the patient’s specific concerns the neuro-oncology clinical nurse specialist (CNS) team at the National Hospital for Neurology and Neurosurgery (NHNN) undertook a short survey with the objective of introducing an intervention to improve patient experience. To identify the needs of brain tumour patients following hospital discharge from NHNN post-surgery. Telephone survey. Patients identified between February-March 2016. Participants must have been discharged home following a craniotomy or biopsy of their brain tumour. A seven question qualitative questionnaire was developed from prior patient feedback. Patients received a telephone call from a member of the CNS team two weeks after discharge. All identified concerns were recorded and explored using an open approach. Responses were collated and analysed for key words and recurring themes. 24 patients identified within the time period. 22 discharged home; 1 transferred to a Neuro-rehab unit and 1 repatriated to a local hospital. Four main themes identified- pain and analgesia, future treatments wound care, and timing of discharge. We achieved our aim in identifying the needs of brain tumour patients following hospital discharge. We recognise that some of the patient suggestions are unable to be met e.g. receiving a diagnosis and treatment plan before discharge- this is due to the histopathology processing. Identified the need for improved patient information. A neuro-oncology specific discharge leaflet which can be provided to all brain tumour patients post-surgery will be created. Amend the discharge summary to include a comprehensive instruction of how/when to remove surgical clips/sutures for the patients GP practice. A discharge checklist to be implemented which is a brain tumour patient specific; as discussed with the senior nursing and surgical teams.
Hypoxia related mRNA biomarker to predict biochemical failure and metastasis for prostate cancer.
Authors: Ananya Choudhury, Lingjian Yang, Darren Roberts, Mandeep Takhar, Bhandari Vinayak, Becky Bibby, Wei-chen Cheng, Syed Haider, Niluja Thiruthaneeswaran, Peter Hoskin, Darragh McArt, Suneil Jain, Francesca Meteora Buffa, Nicholas Erho, Robert G. Bristow, Paul Christopher Boutros, Elai Davicioni, Catharine West
Journal: Journal of Clinical Oncology (2018)

5 Background: Hypoxia is an important regulatory factor in tumorigenesis and is associated with a poor prognosis. Patients with high risk locally advanced disease account for 13-21% of prostate cancer cases and the ten year cancer specific survival rate for these patients is 62%. Patients with hypoxic tumours could benefit from hypoxia modifying therapeutics in addition to radiotherapy. Clinical companion biomarkers are needed to stratify patients who would benefit from hypoxia modifying therapy in addition to radiotherapy. Methods: RNA-seq analysis was performed on prostate cell lines (PNT2-C2, PC-3, LNCaP and DU145) exposed to 1% hypoxia for 24 hrs. A prostate cancer hypoxia gene signature was derived in silico using publicly available prostate gene expression data sets and the RNA-seq data. The biomarker was then independently validated in multiple cohorts of prostate cancer patients with localized diseases receiving prostatectomy alone, prostatectomy plus adjuvant radiotherapy, prostatectomy plus salvage radiotherapy, or definitive radiotherapy alone. Results: In vitro the hypoxia inducible expression of the hypoxia gene signature was tested at 1% and 0.1% oxygen of which 21 of the 28 genes were regulated by hypoxia. Patients stratified as high hypoxia were associated with significantly poorer 5-year biochemical recurrence free survival in patients undergoing prostatectomy alone, prostatectomy plus adjuvant radiotherapy and definitive radiotherapy alone. In multivariable analysis, the biomarker retained significance after correcting for confounding factors including Gleason group, PSA, a molecular classifier, etc. In another cohort of prostatectomy and salvage radiotherapy treated patients, the mRNA signature predicts metastasis free survival in both univariable and multivariable analyses. Conclusions: We derived a de novo mRNA signature based on hypoxia-regulated genes. The biomarker consistently predicts biochemical failure and metastasis for prostate cancer patients with localized disease.
What are the opportunities for doing an MD? I have done MRCP part 1 and want to do an MD in medicine
Authors: Brian Angus
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Review of the Neurological Implications of von Hippel–Lindau Disease
Authors: David Dornbos, H. Jeffrey Kim, John A. Butman, Russell R. Lonser
Journal: JAMA Neurology (2018)

von Hippel-Lindau (VHL) disease-associated central nervous system (CNS) lesions include hemangioblastomas and endolymphatic sac tumors (ELSTs), which are associated with significant neurological morbidity and mortality. Recent studies provide critical new biological, diagnostic, and management insights into these tumors.Biological features, natural history, clinical findings, and management strategies of VHL disease-associated CNS tumors are reviewed. The VHL disease results from a germline mutation of the VHL gene (located on the short arm of chromosome 3), a tumor suppressor that encodes for the VHL protein. Whereas VHL disease is associated with visceral manifestations, CNS lesions are the most common source of morbidity and mortality. Craniospinal hemangioblastomas are almost entirely (99%) found in the cerebellum, brainstem, and spinal cord. These tumors arise from multipotent hemangioblasts. Peritumoral cysts frequently underlie the clinical findings associated with hemangioblastomas (>90% of symptomatic tumors). Prospective natural history studies demonstrate that CNS hemangioblastomas typically grow in a saltatory pattern. Due to this unpredictable growth pattern, surgical resection is reserved for symptomatic lesions, as many tumors do not become symptomatic. Recent studies indicate that VHL disease-associated ELSTs cause audiovestibular morbidity (hearing loss, tinnitus, and vertigo) via 3 mechanisms-otic capsule invasion, intralabyrinthine hemorrhage, and endolymphatic hydrops. Specialized magnetic resonance imaging techniques have been defined to elucidate each of these mechanisms, even when a tumor mass is not identified on imaging. Endolymphatic sac tumors cause audiovestibular morbidity unrelated to size or progression, and resection is now recommended at initial discovery of a tumor mass or a tumor-associated mechanism of morbidity.New insights into the development, pathobiological origin, natural history, and long-term outcomes of VHL disease-associated CNS tumors have redefined their management and treatment indications and potentially provide new targeted therapeutic strategies. Resection is reserved for symptomatic hemangioblastomas, but early resection of newly detected ELSTs is now recommended.
A First-in-Human Study of the New Oral Selective Estrogen Receptor Degrader AZD9496 for ER+/HER2− Advanced Breast Cancer
Authors: Erika P. Hamilton, Manish R. Patel, Anne C. Armstrong, Richard D. Baird, Komal Jhaveri, Matthias Hoch, Teresa Klinowska, Justin P.O. Lindemann, Shethah R. Morgan, Gaia Schiavon, Hazel M. Weir, Seock-Ah Im
Journal: Clinical Cancer Research (2018)

Purpose: AZD9496 is an oral nonsteroidal, small-molecule inhibitor of estrogen receptor alpha (ERα) and a potent and selective antagonist and degrader of ERα. This first-in-human phase I study determined the safety and tolerability of ascending doses of oral AZD9496 in women with estrogen receptor (ER)+/HER2- advanced breast cancer, characterized its pharmacokinetic (PK) profile, and made preliminary assessment of antitumor activity.Patients and Methods: Forty-five patients received AZD9496 [20 mg once daily (QD) to 600 mg twice daily (BID)] in a dose-escalation, dose-expansion "rolling 6" design. Safety, tolerability, and PK activity in each cohort were reviewed before escalating to the next dose. PK was determined by mass spectrometry. Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Objective tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.Results: Most common causally related AEs were diarrhea (35.6%), fatigue (31.1%), and nausea (22.2%), and seven patients had grade ≥3 AEs. Three patients experienced a dose-limiting toxicity: one each at 150 mg BID (abnormal hepatic function), 400 mg BID (diarrhea and elevated liver function tests), and 600 mg BID (diarrhea), and all were reversible. The maximum tolerated dose was not reached. Partial response was confirmed in one patient, who also had decreased tumor marker Ca15.3. Four patients had stable disease at 12 months' follow-up.Conclusions: AZD9496 is well tolerated with an acceptable safety profile, showing evidence of prolonged disease stabilization in heavily pretreated patients with ER+/HER2- advanced breast cancer. Clin Cancer Res; 24(15); 3510-8. ©2018 AACRSee related commentary by Jordan, p. 3480.
Many global health organisations fail to act on gender equality
Authors: Adrian O’Dowd
Journal: BMJ (2018)

Many of the world’s leading global health organisations do not follow gender balanced policies or have gender equality practices in place, a report1 from an independent research initiative has claimed.

Fewer than a third of the group define gender in a manner that is consistent with global norms—a prerequisite for effective and equitable programming, Global Health 50/50, an independent initiative that seeks to promote action and accountability for gender, said.

Amina Mohammed, United Nations deputy secretary-general, said in the report’s foreword that the findings showed …
Selective bladder preservation with twice-daily radiation plus 5-flourouracil/cisplatin (FCT) or daily radiation plus gemcitabine (GD) for patients with muscle invasive bladder cancer: Primary results of NRG/RTOG 0712—A randomized phase 2 multicenter trial.
Authors: John J Coen, Peixin Zhang, Philip James Saylor, Cheryl T. Lee, Chin-Lee Wu, William Parker, Tim Lautenschlaeger, Anthony L. Zietman, Jason A. Efstathiou, Ashesh B. Jani, Omer Kucuk, Luis Souhami, Joseph P Rodgers, Howard M. Sandler, William U. Shipley
Journal: Journal of Clinical Oncology (2018)

408 Background: To assess GD or FCT as the chemoradiation (CRT) component of a bladder sparing regimen. Methods: Patients with T2-4a bladder cancer were randomized. Patients had a maximal transurethral resection and induction CRT to 40 Gy followed by cystoscopic assessment. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others were offered cystectomy and no further CRT. Adjuvant gemcitabine/cisplatin chemotherapy was subsequently administered. The primary endpoint was the rate of distant metastasis at 3 years (DM3). Toxicity and other efficacy related endpoints including CR and bladder intact distant metastasis free survival at 3 years (BI-DMFS3) were also assessed. Using the Clopper-Pearson method, the study required 32 patients per arm, with a benchmark DM3 of 25% and a 1-sided significance level of 0.1. If both arms meet this benchmark, toxicity will be used to select a regimen for future study. This study was not designed to compare arms. Results: From 12/2008 to 4/2014, 70 patients were enrolled; 66 were eligible for analysis (33 per arm). Median follow-up was 4.3 years. DM3 was 22% and 16% for FCT and GD, respectively. BI-DMFS3 was 67% and 72%, respectively. CR rates were 88% and 78%, respectively. Of 33 patients in the FCT group, 32 (97%) completed induction, 27 (93%) completed induction and consolidation, and 18 (55%) completed the entire protocol. Of 33 patients in the GD group, these figures were 31 (94%), 23 (92%), and 16 (49%), respectively. Of 33 patients in the FCT group, 21 (64%) had grade 3-4 toxicity during protocol treatment with 18 (55%), 2 (6%) and 2 (6%) experiencing hematologic, GI and GU toxicity, respectively. For 33 patients in the GD group, these figures were 18 (55%) overall and 14 (43%), 3 (9%) and 2 (6%), respectively. Conclusions: Both regimens are promising, given DM3 rates &lt; 25%. As there was less toxicity in the GD arm, it would be reasonable to consider a gemcitabine based option as well as a cisplatin based regimen for future trials. Daily radiation may be as effective as twice-daily radiation, which may broaden appeal. Clinical trial information: NCT00777491.
EARLY COMBINATION THERAPY WITH SIMVASTATIN AND FENOFIBRATE IN PATIENTS WITH RECENT ACUTE CORONARY SYNDROME AND DIABETES IS SAFE AND RELIABLY REDUCES LIPOPROTEIN (A) LEVEL ALONG WITH OTHER LIPID INDEXES
Authors: Olena Koval, Tetiana Pugach, Sergiy Romanenko, Pavlo Kaplan, Anastasiya Skoromna
Journal: Journal of the American College of Cardiology (2018)
MET-amplification (MET-amp) in relation to aggressive biology in esophagogastric cancer (EGC): An analysis of clinical outcomes of MET-amp vs non-MET-amp EGC.
Authors: Theodore S. Hong, Katie L. Hwang, Jeffrey W. Clark, Jochen K Lennerz, Amy Shui, Hui Zheng, Jackie Szymonifka, Ryan Bruce Corcoran, Rebecca Suk Heist, Andrea Lyn Russo, Aparna Raj Parikh, Darrell R. Borger, Lawrence Scott Blaszkowsky, Jason Edward Faris, Janet E. Murphy, Christopher G. Azzoli, John Thomas Mullen, David P. Ryan, A. John Iafrate, Eunice Lee Kwak
Journal: Journal of Clinical Oncology (2018)

74 Background: c-MET gene amplified ( MET-amp) tumors have been identified as a rare but targetable subset of esophagogastric cancer (EGC). In a phase I study, patients with MET-amp EGC had a 50% response rate to the oral MET inhibitor AMG 337, with some responses exceeding a year (Kwak EL, GI ASCO 2015). We evaluate clinical characteristics and outcomes were evaluated in patients with MET amplified esophagogastric cancer to facilitate identification of patients and establishment of treatment paradigms. Methods: Patients with metastatic MET amplified EGC were identified. MET-amplification was identified by fluorescent in situ hybridization (FISH) on paraffin-embedded tissue, with a gene to control ratio of &gt; 2.2 defined as positive. Clinical characteristics, treatment factors, and survival were recorded. A group of metastatic non- MET amplified patients identified during the same time period who had undergone tumor genotyping and treatment at our institution was evaluated as a comparison group. Results: 21 patients were identified with metastatic MET amplified EGC and 65 patients with metastatic non- MET amplified EGC. The majority of MET amplified tumors occurred in the distal esophagus. 4 patients had co-amplification of HER2, 1 patient had PIK3CA mutation and 1 patient had a TP53 mutation. Compared to non- MET amplified tumors, MET-amplified tumors were more likely to have poorly differentiated tumors. There was no difference in initial sites of metastatic disease. Progression-free survival (PFS) for first line therapy was substantially shorter for patients with MET (6.5 mo vs 14.3 mo, p = 0.0033). MET amplified patients trended towards a shorter overall survival (OS) as well (12.3 mo vs. 20.1 mo, p = 0.0523). Conclusions: MET amplified EGC represents a distinct clinical entity characterized by rapid progression and short survival. Given the efficacy seen with MET inhibition, patients need to be tested and identified early and directed to appropriate MET-targeted clinical trials.
ACUTE CHANGE IN MYOCARDIAL DEFORMATION DOES NOT PREDICT HEART FAILURE READMISSION AFTER TAVR AMONG PATIENTS WITH A LOW FLOW LOW GRADIENT PHYSIOLOGY
Authors: Vasvi Singh, Vijay Iyer, Asma Mursleen, Rose Hansen, Stanley Fernandez, Saurabh Malhotra
Journal: Journal of the American College of Cardiology (2018)
INCREMENTAL VALUE OF SYSTEMIC EXTRACELLULAR WATER VOLUME ASSESSMENT BY BIOELECTRICAL IMPEDANCE ANALYSIS AND ECHOCARDIOGRAPHY IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE
Authors: Akiko Idemoto, Haruhiko Abe, Masayuki Nakamura, Yoshinori Iida, Chieko Toriyama, Tatsuhisa Ozaki, Kaori Yasumura, Hiroki Nishida, Taishi Kato, Kazuya Shinouchi, Tsuyoshi Mishima, Masaki Awata, Motoo Date, Yasunori Ueda, Masaaki Uematsu, Yukihiro Koretsune
Journal: Journal of the American College of Cardiology (2018)
Abstract P2-10-11: A microRNA signature associated with pathological complete response to a novel neoadjuvant therapy regimen in triple negative breast cancer
Authors: RG Vázquez, CL Camarillo, LM Marchau, ER García, AA Miranda, HM Martínez, AC Parra, HA De la Vega, AG Barrios, SR Cuevas
Journal: Cancer Research (2018)

Abstract Background: Locally advanced triple negative breast cancer (laTNBC) patient's exhibits resistance to neoadjuvant chemotherapy (NC) and poor survival. Distinct therapeutic combinations have been used to reduce high mortality. Recently, novel regimens of NC for laTNBC have achieved pathological complete response (pCR) rates of 10-50%. Evaluation of pCR during oncologic treatment is decisive to identify those patients that response or not response to NC. MicroRNAs (miRNAs) are small non-coding RNAs that represent novel and potential predictive biomarkers useful to identify the patients who will get pCR in cancer. Methods: Thirty-five patients diagnosed with laTNBC, were invited to participate in this study and enrolled after they signed an informed consent. The 22 patients with pCR and 13 patients without pCR received the experimental NC fluorouracil, adriamycin, cyclophosphamide, cisplatin, paclitaxel (FAC--CDDP/paclitaxel). MiRNA expression profiling was evaluated for 754 miRNAs. A discovery cohort (n=10 pCR and n=8 no-pCR) and a validation cohort (n=12 pCR and n=5 no-pCR). Bioinformatics analysis revealed the affected cellular pathways in pCR group. After a median clinical follow-up of 60 months, statistical analysis was performed to identify miRNAs that could discriminate pCR from no-pCR by using FAC--CDDP/paclitaxel. Results: MiRNAs expression profiling identified 11 miRNAs that showed significant differences between pCR and no-pCR (p&amp;lt;0.05 and fold change &amp;gt;1.5) groups. Eight miRNAs (miR-9-3p, -30a-3p, -135b, -135b*, -380-5p, -941, -652 and miR-181c*) were upregulated and three miRNAs (miR-770-5p, -584 and miR-143) were downregulated in pCR patients. The altered cellular pathways for the set of miRNAs were PI3K/AKT, FoxO, Ras and ERBB (p&amp;lt;0.05). Four differentially expressed miRNAs (miR-770-5p, miR-143-5p, miR-30a-3p, miR-9-3p) were confirmed in the validation phase. Expression of these miRNAs above the median level was a significant predictor of pCR to experimental NC in laTNBC patients (p&amp;lt;0.001). Conclusions: These four validated miRNAs could be used as predictors of pCR in response to FAC---CDDP/Paclitaxel treatment in laTNBC patients. Citation Format: Vázquez RG, Camarillo CL, Marchau LM, García ER, Miranda AA, Martínez HM, Parra AC, De la Vega HA, Barrios AG, Cuevas SR. A microRNA signature associated with pathological complete response to a novel neoadjuvant therapy regimen in triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-11.
Vaccine-Derived Poliovirus Outbreaks and Events — Three Provinces, Democratic Republic of the Congo, 2017
Authors: Mary M. Alleman, Rohit Chitale, Cara C. Burns, Jane Iber, Naomi Dybdahl-Sissoko, Qi Chen, Djo-Roy Van Koko, Raimi Ewetola, Yogolelo Riziki, Hugo Kavunga-Membo, Cheikh Dah, Rija Andriamihantanirina
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The last confirmed wild poliovirus (WPV) case in Democratic Republic of the Congo (DRC) had paralysis onset in December 2011 (1). DRC has had cases of vaccine-derived polioviruses (VDPVs) documented since 2004 (Table 1) (1-6). After an outbreak of 30 circulating VDPV type 2 (cVDPV2) cases during 2011-2012, only five VDPV2 cases were reported during 2013-2016 (Table 1) (1-6). VDPVs can emerge from oral poliovirus vaccine (OPV types 1, 2, or 3; Sabin) polioviruses that have genetically mutated resulting in reversion to neurovirulence. This process occurs during extensive person-to-person transmission in populations with low immunity or after extended replication in the intestines of immune-deficient persons following vaccination (1-6). During 2017 (as of March 8, 2018), 25 VDPV cases were reported in three provinces in DRC: in Tanganyika province, an emergence with one VDPV2 case (pending final classification) in Kabalo health zone and an emergence with one ambiguous VDPV type 1 (aVDPV1) case in Ankoro health zone; in Maniema province, an emergence with two cVDPV2 cases; and in Haut Lomami province, an emergence with 20 cVDPV2 cases that originated in Haut Lomami province and later spread to Tanganyika province (hereafter referred to as the Haut Lomami outbreak area) and an emergence with one aVDPV type 2 (aVDPV2) case in Lwamba health zone (Table 1) (Figure) (6). Outbreak response supplementary immunization activities (SIAs) were conducted during June-December 2017 (Table 2) (6). Because of limitations in surveillance and suboptimal SIA quality and geographic scope, cVDPV2 circulation is likely continuing in 2018, requiring additional SIAs. DRC health officials and Global Polio Eradication Initiative (GPEI) partners are increasing human and financial resources to improve all aspects of outbreak response.
Evaluation of the eighth TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands and the importance of additional HPV DNA testing
Authors: I.H. Nauta, M.M. Rietbergen, A.A.J.D. van Bokhoven, E. Bloemena, B.I. Lissenberg-Witte, D.A.M. Heideman, R.J. Baatenburg de Jong, R.H. Brakenhoff, C.R. Leemans
Journal: Annals of Oncology (2018)
Cyclophosphamide in steroid refractory unclassifiable idiopathic interstitial pneumonia and interstitial pneumonia with autoimmune features (IPAF)
Authors: Ivo A. Wiertz, Coline H.M. van Moorsel, Adriane D.M. Vorselaars, Marian J.R. Quanjel, Jan C. Grutters
Journal: European Respiratory Journal (2018)

Unclassifiable idiopathic interstitial pneumonia (IIP) accounts for ∼15% of interstitial pneumonia diagnoses [1–3], and is therefore an important category in the daily practice of hospitals specialised in interstitial lung disease (ILDs). In unclassifiable IIP patients a confident diagnosis is not established despite a thorough diagnostic work-up and multidisciplinary discussion. Analysis of FVC shows that steroid refractory unclassifiable idiopathic interstitial pneumonia patients can benefit from cyclophosphamide treatment <http://ow.ly/e5D630iXt3p>