tbuckley/cabot-search huggingface dataset:
Myeloid and plasmacytoid dendritic cell vaccinations for castration-resistant prostate cancer patients.
Authors: Harm Westdorp, Inge M. van Oort, Jeroen H.A. Creemers, Gerty Schreibelt, Niven Mehra, Anna L. de Goede, Christina Hulsbergen-Van De Kaa, Carl G. Figdor, Alfred Witjes, Erik H.J.G. Aarntzen, Roel D.M. Mus, Martin Gotthardt, Jelle O. Barentsz, Jolanda De Vries, Winald R. Gerritsen
Journal: Journal of Clinical Oncology (2018)

219 Background: Immunotherapy has limited applicability in the treatment for CRPC patients (pts). An advantageous effect of immune stimulation in CRPC pts was shown by sipuleucel-T, a dendritic cell (DC)-based vaccine. Vaccination (Vac) strategies using myeloid and plasmacytoid DC (mDC and pDC) may improve immunological and clinical outcome of CRPC pts. Methods: In this randomised phase II trial, 21 HLA-A*02.01 positive chemo-naive CRPC pts received maximally 3 cycles of 3 Vac consisting of mDC, pDC or combined mDC + pDC, loaded with tumour-associated antigens (MUC1, NY-ESO-1, and MAGE-C2). Radiological responses were assessed on 68Ga-PSMA PET-CT scan for RECIST 1.1, iron oxide-enhanced MRI scan of lymph nodes and MRI bones. Primary endpoint is the immunological response after DC Vac. Secondary endpoints are safety, feasibility, PSA responses, radiological PFS and OS. Results: All vaccine types were well tolerated, 14 out of 21 pts had grade 1-2 toxicity. There was no grade 3-4 toxicity observed. After 6 months, no radiological disease progression was observed in 62% (13 out of 21 pts). At 12 months follow-up, 45% of patients (5 out of 11) showed stable disease. Mean radiological PFS was 6.1 months (95% CI: 3.7-8.6). No difference between the groups was observed. One patient had a partial radiological response and a significant drop in PSA level from 120 ng/ml to 3.4 ng/ml. Radiological stable pts showed preVac a PSA doubling time of 6.9 months (95% CI: 3.8-10.1), at 6 months after randomisation this was 13.1 months (95% CI: 4.9-21.2). Over a median follow-up period of 12.0 months, median OS was not reached. Primary immunological outcome will be presented. Conclusions: Myeloid and plasmacytoid DC Vac is feasible and safe in early CRPC pts, with preliminary results hinting at possible clinical efficacy. This warrants further study. Clinical trial information: NCT02692976.
Focus assessed transthoracic echocardiography (FATE)
Authors: Tim Astles
Journal: BMJ (2011)

The course is aimed at any doctor involved in the care of critically ill patients, whether in the intensive care unit, operating theatre, emergency department, or other area. All the candidates on the 2010 course were anaesthetists, but the course is also suitable for emergency or acute medicine physicians or intensivists.

I was a specialty trainee year 4 in anaesthesia when I went on the course; the other participants were fellow registrars or consultants.

I was keen to start learning how to use echocardiography to assess the critically ill patient. This course was aimed at people with little or no previous skill in echocardiography; and as well as covering the basic foundations of echocardiography it quickly allowed me to gain the skills needed to use echocardiography to assess real patients, initially with supervision. Although …
NATIONAL TRENDS IN REVASCULARIZATION AND OUTCOMES OF ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION IN ADULTS AGED 60 YEARS OR OVER, 2005-2014
Authors: Bing Yue, Mariam Khandaker, Xin Wei, Shuyang Fang, Chayakrit Krittanawong, Ashish Correa, Abel Casso Dominguez, Matthew Tomey
Journal: Journal of the American College of Cardiology (2018)
LEFT VENTRICULAR MECHANICAL DISPERSION IN ISCHEMIC CARDIOMYOPATHY: ASSOCIATION WITH MYOCARDIAL SCAR BURDEN AND PROGNOSTIC IMPLICATIONS
Authors: Rachid Abou, Edgard Prihadi, Laurien Goedemans, Rob Van Der Geest, Martin Schalij, Nina Ajmone Marsan, Jeroen J. Bax, Victoria Delgado
Journal: Journal of the American College of Cardiology (2018)
Long-term follow-up of clinical presentation and outcomes of patients with urinary bladder paragangliomas.
Authors: Kareem Rayn, Michael Daniel Weintraub, Gustavo Pena-LaGrave, Samuel Gold, Graham R. Hale, Jonathan Bloom, Sam Joseph Brancato, Piyush K. Agarwal
Journal: Journal of Clinical Oncology (2018)

507 Background: Urinary bladder paragangliomas (UBPGLs) are extremely rare, accounting for less than 6% of paragangliomas (PGLs) and 0.06% of bladder tumors. The goal of this study is to examine the presentation, clinical characteristics and outcomes of patients with UBPGLs. Methods: We determined the presenting symptoms, clinical characteristics, and outcomes of patients who presented to a single institution with UBPGLs from 2000-2017. Results: 28 patients with an average age of 27 ± 15.6 at symptom onset presented to the NIH from 2000-2017. The majority had standard paraganglioma symptoms (n = 24, 85.7%) defined as headaches, palpitations, pallor and anxiety, and hypertension (n = 20, 71.4%) on presentation. 8 patients (29%) presented with hematuria; hematuria was the only presenting symptom in 1 of these patients. 3 (10.7%) of the patients were completely asymptomatic and were discovered to have bladder paragangliomas incidentally on imaging. Overall, 9 patients (32%) were under 18 (average age = 10.9 ± 3.9) at symptom onset. 14 (50%) patients developed metastasis, with bone (n = 9) and lung (n = 8) being the most common metastatic sites. All but 1 patient received surgical treatment, with 6 patients receiving transurethral resection of bladder tumor (TURBT), 3 receiving robotic-assisted partial cystectomy (RAPC) and the remaining patients undergoing open cystectomy. In total, 2 patients experienced bladder cancer recurrence, both of whom had undergone TURBT. Comparing patients with and without hematuria, metastasis and standard paraganglioma symptoms, we found no statistically significant difference in mean diameter of the largest lesion or plasma catecholamine values. Conclusions: Our experience reveals that most patients with UBPGLs present at an early age with characteristic paraganglioma symptoms. Despite the variety of surgical methods used to manage these patients, the only 2 recurrences were in patients who underwent TURBT. Further work is necessary to establish preoperative indicators of disease severity in patients with UBPGLs. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH and NIH Medical Research Scholars Program
Defining the number of lymph nodes needed to accurately stage small bowel neuroendocrine tumors: An 8-institution study from the US neuroendocrine tumor study group.
Authors: Mohammad Zaidi, Alexandra G Lopez-Aguiar, Mary Dillhoff, Eliza W Beal, George A. Poultsides, Eleftherios Makris, Flavio G. Rocha, Angelena Crown, Kamran Idrees, Paula Marincola Smith, Hari Nathan, Megan Beems, Daniel Abbott, James Barrett, Ryan C Fields, Jesse T Davidson, Kenneth Cardona, Shishir Maithel
Journal: Journal of Clinical Oncology (2018)

265 Background: Small bowel neuroendocrine tumors (SB-NETs) frequently involve regional lymph nodes (LNs). The prognostic value of LN positivity on recurrence of disease is not well defined. The number of LNs needed to accurately stage patients is unknown. Methods: All patients with primary SB-NETs who underwent curative-intent resection at 8 institutions in the US Neuroendocrine Tumor Study Group between 2000 and 2016 were identified. Patients with distant metastatic disease were excluded. The association of LN positivity with recurrence of disease and the extent of lymphadenectomy required were analyzed. Results: Of 2182 patients with resected NETs, 203 had SB-NETs. Median age was 60 yrs, 56% were male, and median follow-up was 39 months. 83.5% of patients (n = 157) had LN positive disease. There was no difference in 3-year recurrence free survival (3-yr RFS) among patients with 1 or 2 positive LNs compared to patients with negative LNs (p = 0.63). Patients who had 3 or more positive LNs had a worse 3-yr RFS compared to those with 0, 1, or 2 positive LNs (n = 92 vs n = 73; 3-yr RFS 82% vs 92%; p &lt; 0.001). Retrieval of 8 or more LNs was associated with a higher positive LN count compared to less than 8 LNs (4.6 vs. 1.6; p = 0.002). However, an increasing LN ratio was not associated with 3-yr RFS. When examining patients who had less than 8 lymph nodes retrieved, there was no difference in 3-yr RFS in those patients with 3 or more positive LNs compared to those with 0, 1, or 2 positive LNs (3-yr RFS: 100% vs 91%; p = 0.37). Retrieval of more than 8 lymph nodes, however, accurately discriminated patients with 3 or more positive LNs compared to those with 0, 1, or 2 positive LNs (3-yr RFS: 79.7% vs 93.5%; p = 0.005). Conclusions: For patients undergoing curative-intent resection of small bowel NETs, accurate lymph node staging requires a minimum of 8 lymph nodes for examination. 3 or more positive LNs is associated with decreased 3-yr RFS compared to 0, 1, or 2 positive lymph nodes. A thorough regional lymphadenectomy is critical for accurate staging and management of patients with small bowel neuroendocrine tumors.
Engaging Survivors of Human Trafficking: Complex Health Care Needs and Scarce Resources
Authors: Abigail M. Judge, Jennifer A. Murphy, Jose Hidalgo, Wendy Macias-Konstantopoulos
Journal: Annals of Internal Medicine (2018)

Human trafficking, also known as modern-day slavery, is an egregious human rights violation associated with wide-ranging medical and mental health consequences. Because of the extensive health problems related to trafficking, health care providers play a critical role in identifying survivors and engaging them in ongoing care. Although guidelines for recognizing affected patients and a framework for developing response protocols in health care settings have been described, survivors' ongoing engagement in health care services is very challenging. High rates of disengagement, lost contact, premature termination, and attrition are common outcomes. For interventions to be effective in this marginalized population, challenges in engaging survivors in long-term therapeutic primary and mental health care must be better understood and overcome. This article uses the socioecological model of public health to identify barriers to engagement; offers evidence- and practice-based recommendations for overcoming these barriers; and proposes an interdisciplinary call to action for developing more flexible, adaptable models of care.
Implementation of treatment pathways in a large integrated health care system.
Authors: James Leighton Weese, Levi Citrin, Corey J. Shamah, Marija Bjegovich-Weidman
Journal: Journal of Clinical Oncology (2016)

6613 Background: ASCO recently addressed the importance and role of treatment pathways in value based medicine. The 35 medical oncologists at QOPI certified Aurora Cancer Care (ACC) are developing its value-based care model around Via Pathways. VIA's decision support algorithms are evidence based, and updated quarterly by both academic and community oncologists. Regimens are based on efficacy, then toxicity, and finally cost. When available, a clinical trial is the first recommended option. In the 2 years prior to VIA, over 40 different treatment plans were used for first line treatment for Stage II breast cancer. Our initial goal was to determine if pathways would be accepted by a large, diverse and geographically separated group, decrease the number of treatment algorithms used, increase clinical trial enrollment, and reduce ED utilization. Methods: Stage IV non-small cell lung and stage II breast cancer patients who received first chemotherapy by ACC were selected for analysis. Patients were split into two cohorts: one diagnosed between 10/1/13 – 4/30/14 (prior to VIA) and another between 12/1/14 – 6/30/15 (post VIA). Data collected include demographics, diagnosis, treatments (pathway selected), and ED visits. The data were integrated together and filtered by disease site and treatment pathway. Protocol selection and ED visit rates for the two populations were analyzed. Results: ACC successfully integrated clinical, financial and quality data from its pathway tool with data from other primary systems and demonstrated reporting capabilities. VIA has been well received with a visit capture rate of 81% and on-pathway protocol selection of 82%. Post VIA, clinical trial participation increased 66%. The table below contains a select description of our initial data set. Conclusions: Adoption of VIA decision support has been high; the tool was used for 92% of patients in the data set. Although the data set didn't contain a sufficient number of patients to draw statistically significant conclusions, it will serve as a model for ongoing reporting supporting the development of a value-based care model. Number of patients with an ED visit within 7 days of chemotherapy. Pre VIA: Post VIA: n: PTs w/ ED: %: n: PTs w/ ED: % Lung: 72 18 25% 30 7 23% Breast: 76 13 17% 69 6 9%
HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis
Authors: Celine Hernandez, Peter Huebener, Jean-Philippe Pradere, Daniel J Antoine, Richard A Friedman, Robert F Schwabe
Journal: Journal of Clinical Investigation (2018)

Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive. Here, we tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in CLD. While liver-specific HMGB1 deficiency did not significantly affect chronic injury responses such as fibrosis, regeneration, and inflammation, it inhibited ductular/progenitor cell expansion and hepatocyte metaplasia. HMGB1 promoted ductular expansion independently of active secretion in a nonautonomous fashion, consistent with its role as a DAMP. Liver-specific HMGB1 deficiency reduced HCC development in 3 mouse models of chronic injury but not in a model lacking chronic liver injury. As with CLD, HMGB1 ablation reduced the expression of progenitor and oncofetal markers, a key determinant of HCC aggressiveness, in tumors. In summary, HMGB1 links hepatocyte death to ductular reaction, progenitor signature, and hepatocarcinogenesis in CLD.
Prognostic and predictive role of fumarate hydratase in metastatic clear cell renal cell carcinoma.
Authors: Claudio Vernieri, Giovanni Fucà, Simona Massa, Raffaele Ratta, Elena Verzoni, Paolo Grassi, Giuseppina Calareso, Giancarlo Pruneri, Saverio Minucci, Filippo de Braud, Maurizio Colecchia, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2018)

617 Background: Metabolic disruption is frequent in renal cell carcinoma (RCC). Loss of the mitochondrial fumarate hydratase (FH) enzyme is associated with enhanced glycolytic metabolism, angiogenesis and clinical aggressiveness in type 2 papillary RCC. However, FH expression has never been evaluated in clear cell RCC (ccRCC). In this study, we investigated the impact of FH expression on the outcomes of patients (pts) with metastatic ccRCC (mccRCC). Methods: We included pts with mccRCC, for whom formalin-fixed, paraffin embedded (FFPE) tissue from the primary tumor had been obtained before initiation of systemic treatment. FH levels were evaluated by immunohistochemistry (IHC), and were defined as “normal” if FH expression in most cancer cells was comparable to the adjacent normal tubular cells and “low” in the opposite case. We evaluated the association between FH levels and clinico-pathological characteristics through the chi-squared or Fisher’s exact test. The log-rank test was used to compare survival between patient subgroups. Results: We evaluated 49 mccRCC pts, of whom 36 (73.5%) had synchronous metastases. FH levels were normal in 29 (59.2%) pts and low in 20 (40.8%) pts. FH expression was not associated with patient age (p = 0.5), sex (p = 0.34), tumor grade (p = 0.66), T stage (p = 0.38), N stage (p = 0.88), metastatic disease at the time of diagnosis (p = 0.4), number of metastatic sites (p = 1) or sarcomatoid morphology (p = 0.36). 44 pts received first-line therapy with tyrosine kinase inhibitors (TKIs). In pts with low as compared to normal FH levels, median progression free survival (mPFS) during any first-line treatment was 34 and 10.1 months, respectively (HR 0.39, 95% CI 0.18-0.85; p = 0.014), while mPFS during first-line TKI therapy was 34 and 8.42 months, respectively (HR 0.4, 95% CI 0.17-0.94; p = 0.03). Median overall survival (OS) was not reached in pts with FH-low tumors, while it was 22.9 months in normally expressing ones (HR 0.14, 95% CI 0.032-0.63; p = 0.028). Conclusions: In mccRCC pts, low FH expression in primary tumors is associated with longer PFS during any first-line or TKI treatment, and also with better OS. This is the first study to reveal a prognostic and predictive role of FH levels in mccRCC.
Department of Health looks into junior doctors' concerns about morale review
Authors: Abi Rimmer
Journal: BMJ (2016)

The Department of Health is examining concerns raised by junior doctors about a review it has commissioned into their morale.

The department said that it was working with the Academy of Medical Royal Colleges to answer questions that had been raised by junior doctors about the remit of the review.

Last week the Independent reported that a leaked document from the academy’s Trainee Doctors’ Group showed that the …
GPs leaving clinical practice
Authors: Abi Rimmer
Journal: BMJ (2017)

The career intentions of 2177 GPs in the south-west of England were examined in a study by researchers from the University of Exeter, published in BMJ Open .1

Of the GPs who responded, 20% (473) said that there was a high likelihood that they would quit direct patient care within the next two years, and 38% (863) said that they would quit direct patient care within the next five years. Over half (57%, 1252) said that they were likely to reduce their hours.

Over a third (36%, …
Effect of a tumor staging template on consistency and clarity of prostate cancer staging.
Authors: Ryan Nasseri, Susan S Levy, Edward Cohen, Paul Dato, Hillary Prime, Uchey Dijeh, James Filicko, Catherine E Ball, Franklin Gaylis
Journal: Journal of Clinical Oncology (2018)

35 Background: Risk stratification (RS) is central in assessment and treatment of Prostate cancer (PCa). Accurate clinical staging (cT-Stage) based on AJCC criteria is a key component of RS and certain quality measures (PQRS #102). We assessed the potential of a tumor staging template (TST) embedded into an electronic medical record (EMR) to improve consistency and clarity of clinical tumor staging based on digital rectal examination (DRE) near the time of prostate needle biopsy (PNB). Methods: Retrospective analysis before TST implementation followed by prospective analysis after implementation of the TST was performed at Genesis Health Care Partners. Study period was January 1, 2017 through August 23, 2017. TST was implemented into the EMR and physicians were trained in its use on April 1, 2017. CT-Stage was independently categorized based on physicians’ notations. Descriptions of DRE included; confident-explicit (CE) (cT-Stage documented), confident-implicit (CI) (cT-Stage not documented, DRE amply detailed to interpret cT-Stage), and unconfident- inability to discern T-stage (UI). Classification categories prior to and after TST implementation were compared and analyzed using a chi-square test. Two cohorts were evaluated; men at risk for PCa undergoing PNB, and men with diagnosed PCa. Results: 573 PNBs were analyzed: 234/573 before TST (40.2%) and 339/573 after TST (59.8%). 305/573 (53.2%) PNBs were positive for PCa: 118 before TST and 187 after TST. In men at risk of PCa, CE staging increased from 15.8% to 57.8% (p &lt; 0.001) after TST use. Overall staging (CE+CI) increased from 73.5% to 89.1% (p &lt; 0.001), while UI staging decreased from 26.5% to 10.9% (p &lt; 0.001) after TST use. In men with positive PNBs, CE staging increased from 28.8% to 62.6% (p &lt; 0.001) after TST use. Overall staging (CE+CI) increased from 75.4% to 88.8% (p = 0.004), while UI staging decreased from 24.6% to 11.2% (p = 0.003) after TST use. Conclusions: In an era of precision-oriented medicine, accurate clinical tumor assessment, description, and staging is of great importance in RS and treatment recommendation. Our study demonstrates the ability of a standardized EMR-embedded, AJCC based template to improve the consistency and clarity of clinical staging of PCa.
Inspiring real life stories could encourage doctors into medical leadership
Authors: Matthew Limb
Journal: BMJ (2015)

Inspiring accounts of medical leadership could be used to encourage more doctors to move into leadership roles, a team of management consultants has said.

A report by Hay Group global management consulting1 found that “inspiring accounts” could help spur more doctors into leadership and pursue roles “out of their comfort zone.” Such accounts can present a “more positive picture” of roles that deter many doctors, it added. The report is the fourth in a series on aspects of medical leadership; an earlier survey by the group found that the unattractiveness of medical leadership roles was a key barrier …
T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities
Authors: B.C. Melnik, S.M. John, W. Chen, G. Plewig
Journal: British Journal of Dermatology (2018)

Disintegration of the infundibula of terminal hair follicles (HFs) in intertriginous skin areas exhibits the histological hallmark of hidradenitis suppurativa (HS)/acne inversa, featuring a dissecting terminal hair folliculitis. Elevated serum levels of interleukin (IL)-17 and local increase in the ratio of proinflammatory T helper (Th)17 cells and anti-inflammatory regulatory T cells (Tregs) have been reported. Perifollicular Tregs play a key role in HF stem cell homeostasis and infundibular integrity.In this review, we evaluate the Th17/Treg ratio in HS, its aggravating conditions and associated comorbidities. Furthermore, we intended to clarify whether drugs with reported beneficial effects in the treatment of HS readjust the deviated Th17/Treg axis.PubMed-listed, peer-reviewed original research articles characterizing Th17/Treg regulation in HS/acne inversa and associated comorbidities were selected for this review.This review presents HS as a disease that exhibits an increased Th17/Treg ratio. Perifollicular deficiencies in Treg numbers or function may disturb HF stem cell homeostasis, initiating infundibular dissection of terminal HFs and perifollicular inflammation. The Th17/Treg imbalance is aggravated by obesity, smoking and decreased Notch signalling. In addition, HS-associated autoimmune diseases exhibit a disturbed Th17/Treg axis resulting in a Th17-dominant state. All drugs that have beneficial effects in the treatment of HS normalize the Th17/Treg ratio.HS immunopathogenesis is closely related to deviations of the Th17/Treg balance, which may negatively affect Treg-controlled HF stem cell homeostasis and infundibular integrity. Pharmacological intervention should not only attenuate Th17/IL-17 signalling, but should also improve Treg function in order to stabilize HF stem cell homeostasis and infundibular integrity.
DERIVATION AND COMPARISON OF TAVR MORTALITY RISK SCORE WITH STS RISK SCORE FOR PREDICTING 30-DAY MORTALITY AFTER TAVR
Authors: Erica Flores, Ashish Pershad, Brian Whisenant, Kenith Fang, Ligita Cetorino, Michael Morris, George Gellert, Timothy Byrne, Divya Ratan Verma
Journal: Journal of the American College of Cardiology (2018)