tbuckley/cabot-search huggingface dataset:
Living with neuroendocrine tumors: Assessing quality of life (QoL) through a mobile application.
Authors: Jared Adams, David Ray, Renee Willmon, Linda Kaleis, Anand Gautam, Sonia J. Pulgar, A. Dasari
Journal: Journal of Clinical Oncology (2018)

359 Background: The study aim was to understand neuroendocrine tumor (NET) patients’ (pts) QoL through PROMIS-29, symptom tracking and patient journaling via the Carcinoid Health Storylines mobile application (app). Methods: This 12-week prospective, observational study was conducted among US NET pts recruited through the Carcinoid Cancer Foundation on either Lanreotide depot (L) or octreotide LAR (O) via surveys at baseline, week (w) 6, and w 12 with PROMIS-29 and symptom questionnaires at baseline, w 4 &amp; w 8. Pts were asked to monitor symptoms, mood, bowel movement frequency, food, activity and sleep in their app 5x / week. Demographics and medical history were collected at baseline. Results: Of the 120 NET pts, 78% were female (mean age=57); 76% were gastroenteropancreatic NETs and 88% with metastases. L and O use was at 41% and 59% respectively. 82% completed ≥ 1 follow-up survey; the most common symptoms at baseline were fatigue (76.7%), diarrhea (62.5%), abdominal discomfort (64.1%) and trouble sleeping (57.5%). The baseline PROMIS-29 assessment revealed high proportions endorsing clinically significant depression (17.7%), anxiety (24.2%), fatigue (58.8%), dissatisfaction with social role (i.e. daily routine, 42.2%), difficulty with physical functioning (i.e. run errands, 16%) and insomnia (34.9%). Thus, 26.9% reported their QoL being poor and yet, a high percentage of patients were hopeful and reported their life as being meaningful (72.3%). Reported symptoms decreased significantly from initial to subsequent surveys (e.g. 59.3% to 33% for diarrhea; p=0.002). App tracking effectively captured day to day variations in reported symptoms and weekly averages correlated well with symptom surveys and PROMIS-29 scores. Seventy-seven pts journaled with 26 providing unsolicited injection experience (L =10; O =16). Conclusions: This study suggests that the use of apps for recording daily symptoms in NET pts, with decreased symptom reporting over time perhaps due to reduced recall bias from frequent tracking, or a potential therapeutic effect of journaling. Apps should be developed further to record the experiences and needs of NET pts.
Pre-operative chemotherapy (ctx) in plasmacytoid urothelial carcinoma (PUC).
Authors: Min Yuen Teo, Hikmat Al-Ahmadie, Kenneth Seier, Irina Ostrovnaya, Ashley Marie Regazzi, Guido Dalbagni, Bernard H. Bochner, Samuel Funt, Gopa Iyer, Dean F. Bajorin, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2018)

522 Background: PUC is characterized by E-cadherin loss, diffuse growth pattern and aggressive natural history. Management of this entity is controversial. This retrospective study aims to evaluate the impact of PUC histology on clinical outcomes with ctx compared to UC-NOS. Methods: Consecutive cases of nonmetastatic PUC were identified as either (1) localized disease (LD: cT2-3 cN0) or (2) locally-advanced (LA: fixed bladder or radiographic nodal disease). All cases were reviewed by a GU pathologist to confirm PUC histology per WHO classification (2016). A separate cohort of neoadjuvant(NAC)-treated UC-NOS (Tully et al, ASCO GU 2014) served as comparator for clinical outcomes. Kaplan-Meier estimates and logrank test were used for analysis of recurrence free (RFS) and overall survival (OS) defined from date of cystectomy (RC). Results: Between 2000 and 2017, eighty one PUC were identified, with median age of 65 years (range: 22 - 84) and 65% male. Thirty patients (pts) had up-front RC; 51 pts had ctx. In the former group, all pts had LD but upstaging was seen on post-op pathology: 63% pT3, 17% pT4 and 37% pN+. Among ctx pts, 33/51(65%) were LD and had NAC: 70% had ctx doublet and 24% triplet; 82% had 4 cycles and 18% had up to 6 cycles. Response ( &lt; pT2 pN0) was seen in 7/33(22%), four (12%) of which had no residual disease (pCR). Six RC were aborted after NAC for pT4b disease. NAC response was not associated superior RFS (NR vs. 17.3 months; HR 0.52 95% CI 0.18 – 1.47, p = .218) or OS (41.3 vs. 25.5 months; HR 0.65 95% CI 0.23 – 1.87, p = .428). Compared to UC-NOS, PUC responders had significantly inferior outcomes (table). In LA cohort, majority had triplet chemotherapy (72%) and up to 6 cycles (89%). Response was seen in 4/18(22%) pts, with two pCR (11%). Five RC were aborted for pT4b disease. Median RFS and OS were 5.8 and 10.5 months, respectively, with 19% alive at 2-years. Most common sites of recurrence/progression for PUC were peritoneal (42%) and locoregional invasion (26%). Conclusions: Outcomes for PUC are poor with conventional NAC-RC approach. [Table: see text]
Recurrent Medullary Thyroid Carcinoma on 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Saurabh Arora, Nishikant Avinash Damle, Girish Kumar Parida, Abhinav Singhal, Harish Nalli, Shreya Dattagupta, Chandrasekar Bal
Journal: Clinical Nuclear Medicine (2018)

The prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells. Few other malignancies have shown expression of PSMA. We present a case of 35-year-old man with medullary thyroid carcinoma, post total thyroidectomy and bilateral neck dissection, now presenting with rising calcitonin levels (doubling time 9 months) and local neck recurrence with negative I-MIBG scan. We decided to perform Ga-PSMA-HBED-CC PET/CT scan to assess PSMA expression and explore the therapeutic option in view of rising serum calcitonin. It revealed intense PSMA uptake in the soft tissue mass in left thyroid bed and cervical lymph nodes.
CORRELATION BETWEEN CIRCULATING MICRORNAS AND CHRONIC KIDNEY DISEASE IN PATIENTS WITH AND WITHOUT TYPE 2 DIABETES
Authors: Axel Muendlein, Kathrin Geiger, Andreas Leiherer, Christoph Saely, Janine Ebner, Eva-Maria Brandtner, Daniela Zanolin, Alexander Vonbank, Peter Fraunberger, Heinz Drexel
Journal: Journal of the American College of Cardiology (2018)
Early relapsed disease of multiple myeloma following up-front HDM-ASCT: a study based on the Danish Multiple Myeloma Registry in the period 2005 to 2014
Authors: Sissel Helm-Petersen, Rasmus Sørrig, Tobias W. Klausen, Birgitte Preiss, Ulf Christian Frølund, Carsten Helleberg, Marie Breinholt, Mette Klarskov Andersen, Niels Abildgaard, Peter Gimsing, Annette J. Vangsted
Journal: Leukemia (2018)
Abstract P6-07-08: Dual TGFβ/BMP inhibition allows in vitro expansion of multiple cell types from normal and cancerous breast
Authors: H Nakshatri, M Ananappa, MS Prasad, B Kumar, Y Liu, AM Storniolo, KD Miller, P Bhat-Nakshatri
Journal: Cancer Research (2018)

Abstract Functional modeling of breast epithelial hierarchy and stromal-epithelial cell interactions has been difficult due to inability to obtain sufficient stem-progenitor-mature epithelial cells and stromal cells. The recently developed epithelial reprogramming assay has partially overcome this limitation, allowing propagation of epithelial cells with stem, luminal progenitor and mature cell features. However, characterizing stromal cells using this assay is difficult because irradiated fibroblasts which can be difficult to distinguish from stromal cells are needed as feeder layer. A recent study demonstrated expansion of airway basal stem cells without a feeder layer through pharmacologic inhibition of TGFβ/BMP/SMAD signaling. We sought to develop this method for culture and expansion of cells from normal and cancerous breast samples. With appropriate modifications to growth media, we were able to obtain normal and stromal cells from breast biopsies of healthy women. The expanded cell population included CD10+/EpCAM- basal/myoepithelial cells, CD49f+/EpCAM+ luminal progenitor cells, CD49f-/EpCAM+ mature luminal cells, CD73+/EpCAM+/CD90- rare endogenous pluripotent somatic stem cells, CD73+/CD90+/EpCAM- mesenchymal stem cells, ALCAM (CD166)+/EpCAM+ cells, CD44+/CD24- cells, CD44+/CD24+ cells and ALDFLUOR+ stem/luminal progenitor cells. Epithelial cells were KRT14+, KRT19+ or both further documenting heterogeneity within epithelial cell population. We have extended this technique to grow breast epithelial cells from high-risk patients including BRCA1 mutant-carriers, tumor-adjacent normal and tumor cells from the same patient, pleural effusions and liver metastasis from breast cancer patients. Phenotypic characterization showed differences in the differentiation state of adjacent-normal and tumor cells. Tumor cells from pleural effusions showed remarkable phenotypic heterogeneity with a fraction of these cells expressing estrogen receptor. The assay described here, therefore, is versatile and provides resources to model epithelial-stromal interactions under normal and cancerous conditions as well as for genomics and screening of drugs to target metastasis on an individual level. Susan G. Komen for the Cure and Department of Defense supported this work. Citation Format: Nakshatri H, Ananappa M, Prasad MS, Kumar B, Liu Y, Storniolo AM, Miller KD, Bhat-Nakshatri P. Dual TGFβ/BMP inhibition allows in vitro expansion of multiple cell types from normal and cancerous breast [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 P6-07-08.
CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages
Authors: Lydia Meziani, Michele Mondini, Benoît Petit, Alexandre Boissonnas, Vincent Thomas de Montpreville, Olaf Mercier, Marie-Catherine Vozenin, Eric Deutsch
Journal: European Respiratory Journal (2018)

Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration. We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation. High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveolar lavage demonstrated upregulation of both types of cytokines. At steady state, tissue-infiltrating macrophages (IMs) expressed 10-fold more arginase (Arg)-1 than alveolar macrophages (AMs), and a 40-fold upregulation of Arg-1 was found in IMs isolated from RIF. IMs, but not AMs, were able to induce myofibroblast activation in vitro . In addition, whereas depletion of AMs using Clodrosome didn't affect RIF score, depletion of IMs using a clinically available colony-stimulating factor receptor-1 (CSF1R) neutralising antibody was antifibrotic. These findings suggest differential contributions of alveolar versus interstitial macrophages in RIF, highlighting the fibrogenic role of IMs. The CSF1/CSF1R pathway was identified as a new therapeutic target to inhibit RIF.
Association of liquid biopsy and gastric cancer patients' prognosis: Comprehensive synopsis and a meta-analysis.
Authors: Lin Chen, Yunhe Gao, Hongqing Xi, Jianxin Cui, Aizhen Cai, Weisong Shen, Kecheng Zhang, Jiyang Li, Zheng Peng, Bo Wei
Journal: Journal of Clinical Oncology (2018)

25 Background: Liquid biopsy including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) has offered a minimally invasive approach for detection and measurement of gastric cancer (GC). Reports regarding associations between liquid biopsy and gastric cancer have been emerging rapidly in recent decades, yet their prognostic value still remains paradoxical. Methods: We searched Medline, Embase, Cochrane Central Register of Controlled Trials database for relevant studies that assessed the prognosis significance of CTCs and cfNAs in gastric cancer from peripheral blood(PB). Newcastle-Ottawa Scale (NOS) was used to assess the quality of evidence. Stata 12.0 was used for pooled analysis and subgroup analysis was performed to determine the association of CTCs or cfNAs’ presence and major clinical characteristics. Pooled results were displayed as hazard ratios (HRs) with their 95% confidence intervals (95% CI) with random effect models. Results: We identified 1258 studies, and then 43 were finally eligible for analysis. A total of 3792 patients were included for final evaluation. Pooled analysis showed that detection of certain CTCs, ctDNA or circulating miRNA was associated with poorer overall survival (OS) (CTCs, HR=2.05, 95%CI 1.65-2.55, p &lt; 0.001; circulating miRNA HR=1.74, 95%CI 1.13-2.69, p=0.013; ctDNA, HR=1.77, 95%CI 1.28-2.44, p=0.001) and disease-free survival(DFS) (CTCs, HR=2.92, 95%CI 1.93-4.40, p &lt; 0.001; circulating miRNA, HR=3.30, 95%CI 2.39-4.55, p &lt; 0.001; ctDNA, HR=4.69, 95%CI 2.23-9.86, p &lt; 0.001) of gastric cancer patients, regardless of the disease’s early or late stage. Conclusions: Several high-quality circulating biomarkers or detection methods for gastric cancer prognosis prediction were identified by subgroup analysis, including the Cellsearch system, cytokeratins, miR-20a, miR-200c, etc. Detection of these certain dysregulation circulating markers in patients’ PB indicates poor prognosis with advanced GC patients.
Human-to-human transmissions of severe fever with thrombocytopenia syndrome virus in Anhui province, 2010–2017
Authors: L. Gong, D.D. Song, J.B. Wu, M.H. Cao, B. Su, Y. Sun, Y. Lyu, L. Zhang, F. Wang, Y.X. He, J.S. Wang
Journal: Clinical Microbiology and Infection (2018)
All doctors on foundation reserve list are now placed
Authors: Caroline White
Journal: BMJ (2013)

The last group of newly qualified doctors on the reserve list for the start of this year’s foundation year training programme have been allocated a place, the UK Foundation Programme Office has announced.

In October last year it emerged that there were more applicants for this year’s foundation programme than places available at that time, prompting 295 applicants to be placed on a reserve list on 8 March this year.1

A total of 236 reserve list applicants were allocated in the first three batch allocations between May …
MANAGEMENT OF RESISTANT HYPERTENSION AND IMPLICATIONS OF PATHWAY-2 TRIAL IN US CARDIOLOGY PRACTICE: INSIGHTS FROM THE NCDR PINNACLE REGISTRY
Authors: Lauren Thompson, Kevin Kennedy, Thomas M. Maddox, P. Michael Ho, Javier Valle, Amneet Sandhu, Frederick A. Masoudi, Franz Messerli, Stacie L. Daugherty
Journal: Journal of the American College of Cardiology (2018)
Review: DOACs reduce intracranial hemorrhage more than warfarin in AF with CKD
Authors: Tejas Patel, Vihas Patel
Journal: Annals of Internal Medicine (2018)

Source Citation Kimachi M, Furukawa TA, Kimachi K, et al. Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease. Cochrane Database Syst Rev. 2017;11:CD011373. 29105079
Margaret McCartney: The NHS shouldn’t have to pick up the bill for private screening tests
Authors: Margaret McCartney
Journal: BMJ (2018)

It had to happen eventually: Bluecrest Health Screening has sent me my very own invitation for one of its private health assessments.

The invitation included a venue, a date, and a request that I call them to organise a time. The company takes out full page advertisements in national newspapers, claiming that you can “Help avoid a stroke with your New Year Health MOT” and asking, “Why leave your health to chance when you can be in control?”

The company offers “Five free tests when you accept in the next 28 days.” Its tests include body fat percentage; “hydration levels”; height, weight, and body mass index percentages; and …
Fatal Yellow Fever in Travelers to Brazil, 2018
Authors: Davidson H. Hamer, Kristina Angelo, Eric Caumes, Perry J.J. van Genderen, Simin A. Florescu, Corneliu P. Popescu, Cecilia Perret, Angela McBride, Anna Checkley, Jenny Ryan, Martin Cetron, Patricia Schlagenhauf
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Yellow fever virus is a mosquito-borne flavivirus that causes yellow fever, an acute infectious disease that occurs in South America and sub-Saharan Africa. Most patients with yellow fever are asymptomatic, but among the 15% who develop severe illness, the case fatality rate is 20%-60%. Effective live-attenuated virus vaccines are available that protect against yellow fever (1). An outbreak of yellow fever began in Brazil in December 2016; since July 2017, cases in both humans and nonhuman primates have been reported from the states of São Paulo, Minas Gerais, and Rio de Janeiro, including cases occurring near large urban centers in these states (2). On January 16, 2018, the World Health Organization updated yellow fever vaccination recommendations for Brazil to include all persons traveling to or living in Espírito Santo, São Paulo, and Rio de Janeiro states, and certain cities in Bahia state, in addition to areas where vaccination had been recommended before the recent outbreak (3). Since January 2018, 10 travel-related cases of yellow fever, including four deaths, have been reported in international travelers returning from Brazil. None of the 10 travelers had received yellow fever vaccination.
Case 7-2018: A 25-Year-Old Man with New-Onset Seizures
Authors: Erica C. Camargo, Susie Y. Huang, Amel Karaa, Matthew W. Rosenbaum
Journal: New England Journal of Medicine (2018)

A 25-year-old man with marfanoid habitus was admitted to the hospital because of new-onset seizures. Imaging studies revealed thrombosis of the cerebral venous sinus and internal jugular vein. A diagnostic test was performed.
Surgical trainees will be taught about communication and teamwork
Authors: Abi Rimmer
Journal: BMJ (2014)

Surgical trainees across the United Kingdom are to be taught non-technical skills, such as communication and teamwork, after changes to the surgical training programme.

The Intercollegiate Surgical Curriculum Programme, which provides the UK syllabus for training in each of the 10 surgical specialties, has now adopted the Non-Technical Skills for Surgeons (NOTSS) training programme. The programme was developed by the Royal College of …
I am a final year medical student, but owing to academic problems my graduation is being delayed. I have secured a job for February 2006 but wish to use the intervening time beneficially. Do you have any advice on how to do this or what I should be thinking of doing?
Authors: Mark Wilson
Journal: BMJ (2005)

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>
THE CHA2DS2VASC SCORE CAN PREDICT MORTALITY IN PATIENTS WITH ATRIAL FIBRILLATION FOLLOWING HOSPITALIZATION FOR AN ACUTE MYOCARDIAL INFARCTION: INSIGHTS FROM THE WORCESTER HEART ATTACK STUDY
Authors: Amartya Kundu, Kevin O’Day, Darleen Lessard, Joel Gore, Robert Goldberg, David McManus
Journal: Journal of the American College of Cardiology (2018)
GPs call for better funded occupational health services, as stress levels soar
Authors: Helen Jaques
Journal: BMJ (2013)

GPs have condemned the patchy occupational health services across the UK and the poor support offered to the rising number of GPs who are reporting work related stress.

A survey by the BMA earlier this year found that 97% of GPs expected work related stress levels to rise once the new general medical services (GMS) contract came into place this …
DECLINING IN-HOSPITAL MORTALITY RATES IN WOMEN AND MEN WITH DIABETES MELLITUS PRESENTING WITH OUT-OF-HOSPITAL CARDIAC ARREST: A 22-YEAR OBSERVATIONAL STUDY FROM THE MIDDLE EAST
Authors: Ayobami Omosola, Abdulrahman Arabi, Jassim Al Suwaidi, Rajvir Singh, Awad Alqahtani
Journal: Journal of the American College of Cardiology (2018)
Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration
Authors: Lin Weng, Sunil Kumar Boda, Hongjun Wang, Matthew J. Teusink, Franklin D. Shuler, Jingwei Xie
Journal: Advanced Healthcare Materials (2018)

Abstract An ideal synthetic bone graft is a combination of the porous and nanofibrous structure presented by natural bone tissue as well as osteoinductive biochemical factors such as bone morphogenetic protein 2 (BMP‐2). In this work, ultralight 3D hybrid nanofiber aerogels composed of electrospun PLGA‐collagen‐gelatin and Sr–Cu codoped bioactive glass fibers with incorporation of heptaglutamate E7 domain specific BMP‐2 peptides have been developed and evaluated for their potential in cranial bone defect healing. The nanofiber aerogels are surgically implanted into 8 mm × 1 mm (diameter × thickness) critical‐sized defects created in rat calvariae. A sustained release of E7‐BMP‐2 peptide from the degradable hybrid aerogels significantly enhances bone healing and defect closure over 8 weeks in comparison to unfilled defects. Histomorphometry and X‐ray microcomputed tomography (µ‐CT) analysis reveal greater bone volume and bone formation area in case of the E7‐BMP‐2 peptide loaded hybrid nanofiber aerogels. Further, histopathology data divulged a near complete nanofiber aerogel degradation along with enhanced vascularization of the regenerated tissue. Together, this study for the first time demonstrates the fabrication of 3D hybrid nanofiber aerogels from 2D electrospun fibers and their loading with therapeutic osteoinductive BMP‐2 mimicking peptide for cranial bone tissue regeneration.
Effect of andecaliximab (anti-MMP9) on proteolysis of IL-7 in vitro, TCR diversity in mice, and serum IL-7 in gastric cancer patients in combination with chemotherapy.
Authors: Andrew E. Greenstein, Marianna Zavodovskaya, Maile Velasquez, Perry Weissburg, Vladi Juric, Amanda Mikels-Vigdal, Carrie Brachmann
Journal: Journal of Clinical Oncology (2018)

101 Background: Andecaliximab (andeca) is a monoclonal antibody that selectively inhibits matrix metalloproteinase 9 (MMP9). IL-7 selectively enhances the proliferation and survival of naïve, memory, and effector T-cells (but not regulatory T-cells) in the periphery. Previous clinical trials with systemic recombinant IL-7 therapy increased TCR diversity. In the disease setting, elevated circulating IL-7 may be due to a compensatory increase in IL-7 production as demonstrated in mice upon inhibition of IL-7 signaling. Methods: An in vitro screen, in which recombinant active human MMP9 was incubated with &gt; 140 human recombinant folded proteins, identified IL-7 as the most efficient substrate of MMP9. Results: IL-7 proteolysis occurred between A128:L129. IL-7 proteolysis altered the global protein structure, evidenced by a loss of cooperative unfolding observed with intact IL-7 (intrinsic fluorescence, T m = 59.3o C). Mouse MMP9 proteolyzed mouse IL-7 in vitro. In the orthotopic syngeneic NeuT mouse model, MMP9 inhibition reduced tumor growth (p = 0.0005). In a 7-day NeuT study, anti-MMP9 alone improved TCR diversity (decreased clonality) within tumor-infiltrating T-cells (Dunnett’s p = 0.0083). Further, anti-MMP9 and anti-PDL1 co-treatment promoted an increase in CD3+ cells (p = 0.01), CD4+ T cells (p = 0.006), and CD8+ T cells (p = 0.013) concomitant with a decrease in tumor-associated CD25+ FoxP3+ regulatory T cells (p = 0.04) in the tumor. In gastric cancer patient serum, pro-MMP9 (p &lt; 0.0001), active MMP9 (p &lt; 0.0001), and IL-7 (p &lt; 0.0001) were higher than healthy controls. Serum IL-7 levels were normalized upon treatment with andeca plus mFOLFOX6 (N = 40; FDR-corrected p &lt; 0.001) in a Phase I gastric cancer study. Conclusions: MMP9 proteolyzed IL-7 in vitro. Specific MMP9 inhibition in a mouse tumor model improved TCR diversity. Andeca +mFOLFOX6 therapy normalized serum IL-7 levels, which could be due to andeca, chemotherapy, or disease resolution. The functional implications of IL-7 proteolysis by MMP9 in gastric cancer are currently under investigation.