tbuckley/cabot-search huggingface dataset:
Reproductive health assessment in women with cancer: A pilot study
Authors: M. Sreedevi, R. Sutaria, M. Schoenhage, A. R. Patel, E. K. Radeke, H. A. Zaren, A. Patel
Journal: Journal of Clinical Oncology (2007)

19660 Background: Many women in the reproductive age group are diagnosed with cancer. Reproductive health issues remain an important concern in caring for these women. Based on a case series in our institution and a review of the literature, we found a paucity of literature and clinical acumen regarding reproductive health issues. The purpose of this study was to pilot a survey instrument to develop descriptive data on the reproductive goals of reproductive aged women (15–44yrs) presenting with cancer. Methods: A cross- sectional pilot survey study of 20 selected women diagnosed with various types of cancers presenting to Hematology-Oncology clinic of John.H.Stroger Jr. Hospital of Cook County, Chicago, from January through July 2006. A survey instrument was developed and performed a reproductive health assessment. Patients were interviewed about their obstetric/menstrual history, contraceptive motivations and choices as well as future child bearing options. Results: Of the 20 patients with mean age of 36.6 years who were surveyed, 90 % had breast cancer. Child bearing was completed by 50%, 45% desired future childbearing, 5% were unsure. Contraception was used by 55 %( n=11) of patients out of which 55 %(n=6) were using abstinence, 45% denied the use of any contraception. Amongst the patients who received chemotherapy with radiation and chemotherapy without radiation, 75% and 72.7% respectively continued to menstruate. Ten percent would continue pregnancy, if they become pregnant while on treatment. Conclusions: The result of this pilot study demonstrates some insight into the reproductive health needs and concerns of women diagnosed with cancer. A reproductive health assessment should be performed on all cancer patients who are in the reproductive age group. We plan a large prospective study providing a larger database that may aid in developing treatment plan. No significant financial relationships to disclose.
Neoadjuvant pelvic perfusion may facilitate resection of pelvic recurrent rectal cancer.
Authors: Harold J. Wanebo, Giovanni Begossi, James Belliveau, Eric Gustafson
Journal: Journal of Clinical Oncology (2013)

e14599 Background: Pelvic recurrence of rectal cancer is a persisting therapeutic challenge in spite of wide spread use of adjuvant/neoadjuvant chemo radiation and wide resection isolated pelvic perfusion (IPP) may facilitate pelvic resection in selected high-risk patients.IPP was done in 42 patients with locally advanced previously irradiated rectal cancer, 26 as a preoperative therapy and 16 for palliation. A comparative larger non-perfused group included 63 patients with pelvic resection only for recurrent rectal cancer. Methods: Isolated pelvic perfusion (60 min) utilized pump oxygenation (Temp&gt;41°C)with chemo agents – 5 FU 1500mg/m 2 , Cisplatin/Oxaliplatin 100/ 150mg/m 2 , Mitomycin 10-20 mg/m 2 , which was done in 42 patients (26 as preoperative and 16 as palliative therapy). Results: Palliative IPP in 16 advanced rectal cancer patients (pts)resulted in significant relief (1-4 months) of narcotic resistant pain (in 70%). Preoperative IPP in 26 locally advanced rectal cancer pts achieved a clinical pathologic complete response (CR) in 2 patients, and significant regression in 11 patients rendering them resectable. Seven pts had R0 pelvic resections,(6 abdominal sacral resection (ABSR) and 1 extended APR).Of 8 other patients, 3 responders refused surgery, 5 were excluded.(medical or disease related ). Median survival was 22.5 months in 15 resectable and 32 mos in 7 resected pts (2 pts were 5 year survivors). This is compared to outcome in 63 patients amenable to having pelvic resection alone: 57% had R0 resection (median OS 36 mos), 28% had R1 resection (med OS = 15 mos) and 15% had R2 resection (med OS 21 mos). Conclusions: Neoadjuvant IPP may facilitate selection of recurrent rectal cancer by identifying therapeutic responders likely to benefit from major pelvic resection and excluding non-responders most likely to benefit from non-surgical therapy. The potential to induce regression and facilitate R0 resection merits further exploration.
Phase II study of dendritic cell vaccination combined with recombinant adenovirus-p53 in treatment for patients with advanced pancreatic carcinoma.
Authors: K Chai, Yq Ai, Lw Jiang
Journal: Journal of Clinical Oncology (2013)

3049 Background: There are few choices of treatments for advanced pancreatic carcinoma (PC) due to the resistances to chemo- or radio-therapy. Immunotherapy based on dendritic cell (DC) vaccines and p53-based gene therapy are two promising therapeutic modalities. They also demonstrated favorable safety profiles. In this study, we compared the immunological and clinical response between DC vaccine therapy and DC vaccine combined with recombinant adenovirus-p53 (rAd-p53) gene therapy. Methods: Thirty-six patients with a stage IV pancreatic cancer, 21 men and 15 women with an average age of 56.2 years old, were included in this study and randomly assigned to two groups: 16 patients in DC group (DCG) and 20 in DC plus rAd-p53 group (DPG). The DCG patients received autologous antigen-loaded DC (antigen from isolated pancreatic cancer cells) and the DPG patients received both DC and rAd-p53. DC vaccines were injected intra-dermally once every week for 4 injections and rAd-p53 were given by intravenous injections once per 3 days for 5 times at a dose of 3 x 10 12 viral particles. The response, safety and peripheral blood lymphocyte subsets were investigated. Results: The post-treatment CD3+, CD3+CD4+, CD4+/CD8+ ratio of patients’ peripheral blood in both groups were increased. But the percent of CD4+CD25+ regulatory T cells were significantly decreases. In DPG, 5 patients had a partial response (PR) and 4 patients had stable disease (SD) according to the RECIST standard. The 3 and 3 DCG patients achieved a PR and SD, respectively. The disease control rates (PR+SD) were 45.0% and 37.5% for DPG and DCG, respectively. The 6-month overall survival rates were 50.0% and 43.8% for DPG and DCG, respectively. The median survival times were 6.8 and 5.5 months for DPG and DCG, respectively. Mild to medium grade fever was observed in most of the patients in the two groups. No serious adverse events were found. Conclusions: DC-based immunotherapy and p53 gene therapy are safe and appropriate treatments for patients with advanced pancreatic carcinoma. The combined treatments showed more beneficial results than the DC immunotherapy alone.
Medicine in Europe: The changing scene in general practice in Europe
Authors: P R Evans
Journal: BMJ (1994)

raised jugular venous pressure, as in this woman.Both conditions produce a pansystolic murmur at the left sternal edge.A high pulmonary artery oxygen satur- ation in a patient with a low cardiac output gives the diagnosis when echocardiography is not available.AJR: Is there ever any confusion between acquired and congenital ventricular septal defects when someone presents with an infarct?CMO: Patients with a congenital condition usually know their diagnosis and also would have a murmur at the outset, unlike people with an acquired ventricular septal defect.Most congenital ventricular septal defects in adults are perimembranous and have a different location in the echocardiogram.AJR: What causes ventricular septal rupture?CMO: The underlying pathological finding is transmural infarction.Coronary angiographic studies show that about 40-50% of patients have single vessel disease and seem to have fewer collateral vessels to the septum.This may explain the full thickness necrosis.'PKM: Whether treatment with streptokinase affects the incidence of septal rupture is unclear,'8 but rupture seems to occur earlier, at around 24 hours, in patients who have been given thrombolysis.19GJD: Elderly people, women, and those with hyper- tension seem to be at greatest risk.Many patients who die of myocardial infarction do so because of cardiac rupture; this just happens to be an internal rupture.The fact that mortality from infarction is higher in elderly people might be explained by the frailty of their tissues or the more advanced state of their coronary disease as they do not seem to have larger infarcts.
<i>BRN4</i> Is a Novel Driver of Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer and Is Selectively Released in Extracellular Vesicles with <i>BRN2</i>
Authors: Divya Bhagirath, Thao Ly Yang, Z. Laura Tabatabai, Shahana Majid, Rajvir Dahiya, Yuichiro Tanaka, Sharanjot Saini
Journal: Clinical Cancer Research (2019)

Neuroendocrine prostate cancer (NEPC), an aggressive variant of castration-resistant prostate cancer (CRPC), often emerges after androgen receptor-targeted therapies such as enzalutamide or de novo, via trans-differentiation process of neuroendocrine differentiation. The mechanistic basis of neuroendocrine differentiation is poorly understood, contributing to lack of effective predictive biomarkers and late disease recognition. The purpose of this study was to examine the role of novel proneural Pit-Oct-Unc-domain transcription factors (TF) in NEPC and examine their potential as noninvasive predictive biomarkers.Experimental Design: Prostate cancer patient-derived xenograft models, clinical samples, and cellular neuroendocrine differentiation models were employed to determine the expression of TFs BRN1 and BRN4. BRN4 levels were modulated in prostate cancer cell lines followed by functional assays. Furthermore, extracellular vesicles (EV) were isolated from patient samples and cell culture models, characterized by nanoparticle tracking analyses, Western blotting, and real-time PCR.We identify for the first time that: (i) BRN4 is amplified and overexpressed in NEPC clinical samples and that BRN4 overexpression drives neuroendocrine differentiation via its interplay with BRN2, a TF that was previously implicated in NEPC; (ii) BRN4 and BRN2 mRNA are actively released in prostate cancer EVs upon neuroendocrine differentiation induction; and (iii) enzalutamide treatment augments release of BRN4 and BRN2 in prostate cancer EVs, promoting neuroendocrine differentiation induction.Our study identifies a novel TF that drives NEPC and suggests that as adaptive mechanism to enzalutamide treatment, prostate cancer cells express and secrete BRN4 and BRN2 in EVs that drive oncogenic reprogramming of prostate cancer cells to NEPC. Importantly, EV-associated BRN4 and BRN2 are potential novel noninvasive biomarkers to predict neuroendocrine differentiation in CRPC.
A phase II clinical study of dendritoma vaccination combined with low dose interleukin-2 in advanced melanoma patients
Authors: Y. C. Wei, J. J. Stephenson, J. Li, K. E. Burgin, H. Bouton-Verville, S. Jakubchak, L. M. Holmes, K. Meyer, J. Martin, S. D. Trocha, T. E. Wagner
Journal: Journal of Clinical Oncology (2007)

3051 Background: The use of the fusion product of dendritic cells (DC) and tumor cells as a tumor vaccine represents one of the most promising approaches for cancer immunotherapy. We have developed a novel technology that instantly isolates the hybrids (Dendritomas) from the fusion mixture of DCs and tumor cells and thereby maintains tumor cellular diversity. Animal studies demonstrated that Dendritomas are superior activators of tumor cell specific antitumor immunity compared to fusion mixtures; and phase I clinical studies in advanced melanoma and renal cell carcinoma patients demonstrated that Dendritomas can be safely administered to cancer patients and are able to stimulate immunological and clinical responses in some of the patients. Methods: In order to determine the efficacy of Dendritoma vaccines, we designed a small phase II clinical trial in which individualized Dendritomas are manufactured from and injected into 15 stage IV melanoma patients. In order to boost the antitumor immune responses, a low dose interleukin-2 regime was followed only after the first Dendritoma vaccine. The patients received various numbers of vaccines (1 to 6) at six-week intervals. Clinical responses defined as complete response (CR), partial response (PR), stable disease (SD), mixed response (MR), progressive disease (PD), and no evidence of disease (NED) are monitored. The survival of the patients are monitored as well. Results: Twelve weeks after the first vaccine, three patients were NED; four patients were SD; two patients were PD/MR; and six patients were PD. At the time of the submission of this abstract, two patients were still NED and the median survival was 684 days with twelve of the fifteen patients (80%) surviving more than 431 days and eleven of fifteen patients (73%) surviving more than 519 days. Seven out of fifteen patients (47%) are still alive. Conclusions: The data from this small phase II study demonstrated that Dendritoma therapy combined with low dose IL-2 or other adjuvants may represent an effective therapy for melanoma patients and/or other cancer patients. No significant financial relationships to disclose.
Quality and Safety in Healthcare, Part LVI
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2019)

Abstract All members of the healthcare system should make positive contributions to improve the overall level of wellness. However, leaders should have certain specific responsibilities to prevent burnout and increase happiness and wellness at work. It has been proposed that a chief wellness officer direct the initiatives to improve wellness, in collaboration with many others including those in the executive suite. Part of improving joy in the workplace is improving efficiency, quality care for patients, safety for patients and workers, meaningful work for the workers, and respect and fairness for all.
Recent insights into apoptosis and toxic autophagy: The roles of MDA-7/IL-24, a multidimensional anti-cancer therapeutic
Authors: Luni Emdad, Praveen Bhoopathi, Sarmistha Talukdar, Anjan K. Pradhan, Devanand Sarkar, Xiang-Yang Wang, Swadesh K. Das, Paul B. Fisher
Journal: Seminars in Cancer Biology (2019)
Evaluation of radiologic diagnosis in peripheral clinical IA lung cancers—A prospective study for radiological diagnosis of peripheral early lung cancer (JCOG 0201)
Authors: K. Suzuki, T. Koike, T. Shibata, M. Kusumoto, H. Asamura, K. Nagai, H. Tada, T. Mitsudomi, M. Tsuboi, H. Kato
Journal: Journal of Clinical Oncology (2006)

7220 Background: The spread of computed tomography (CT) screening for lung cancer (LC) leads to the increased detection of small sized LC. Performance and accuracy of radiological diagnosis had not been evaluated and indication of limited surgery for CT detected LC remains unknown. Methods: Between Dec/2002 and May/2004, a prospective study was performed. Patients (pts) having peripheral lung adenocarcinoma (AD) of T1N0M0 were eligible. Radiologic findings of LC were evaluated as to ground-glass opacity (GGO) with thin-section CT (TSCT). A radiological non-invasive cancer (NIC) was defined as a tumor having consolidation less than half of the maximum tumor dimension. A pathological NIC, which is future candidate for limited surgery, was defined as a tumor with no lymph node mets, lymphatic, nor vascular invasion. A validity of radiological diagnosis by above criteria was investigated. Primary endpoint is specificity as the proportion of pts with radiologically diagnosed invasive LC in pts with pathologically diagnosed invasive LC. Planned sample size was 450 with precision-base. We expected that lower limit of 95% CI of specificity is over 97%. Results: Totally 811 pts were enrolled onto the study at 31 institutions, including 357 men. Age ranged 27 to 75 (median 61). Primary endpoint was evaluated on central-reviewed 545 AD resected by lobectomy. Specificity and sensitivity for the diagnosis of pathological NIC were 96.4% (161/167 95% CI 92.3% to 98.7%) and 30.4% (115/378 95% CI 25.8% to 35.3%), respectively. As to relationship between radiologic NIC and pathological nodal involvement, specificity and sensitivity for the diagnosis were 98.3% (59/60 95% CI 91.1% to 100%) and 24.7% (120/485 95% CI 21.0% to 28.8%), respectively. Conclusions: Our pre-determined criterion for the specificity was not confirmed, and candidates for limited surgical resection can not be selected based on our criteria. However, radiological diagnosis of node-negative LC with TSCT was well coincide, and the criterion might be used for selecting node negative peripheral LC. A phase II study of limited surgical resection for peripheral LC 2.0 cm or less in size is now planned based on the results of exploratory analysis of this study. No significant financial relationships to disclose.
Interim Safety Analysis of a Phase 2 Randomized Study of Daratumumab (Dara), Lenalidomide (R), Bortezomib (V), and Dexamethasone (d; Dara-Rvd) Vs. Rvd in Patients (Pts) with Newly Diagnosed Multiple Myeloma (MM) Eligible for High‐Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT)
Authors: Peter M. Voorhees, Luciano J. Costa, Brandi Reeves, Nitya Nathwani, Cesar Rodriguez, Yana Lutska, Laura Hydutsky, Huiling Pei, Jon Ukropec, Ming Qi, Thomas Lin, Paul G Richardson
Journal: Blood (2017)
Abstract 1002: Effect of Atrial Natriuretic Peptide on Myocardial Infarct Size and 30 Day Survival.
Authors: Rachel McNamee, Pallavi Sharma, Attila Kerner, Jonathan Tronolone, Almois Mohamad, William Maddox, Aiilyan Houng, Guy L Reed
Journal: Circulation (2007)

Acute coronary artery occlusion triggers the activation of molecular pathways (inflammatory, vasoactive, endocrine, reparative, etc.) that lead to myocardial ischemia and infarction. Atrial natriur...
Outcomes of Endovascular Thrombectomy vs Medical Management Alone in Patients With Large Ischemic Cores
Authors: Amrou Sarraj, Ameer E. Hassan, Sean Savitz, Clark Sitton, James Grotta, Peng Chen, Chunyan Cai, Gary Cutter, Bita Imam, Sujan Reddy, Kaushik Parsha, Deep Pujara, Roy Riascos, Nirav Vora, Michael Abraham, Haris Kamal, Diogo C. Haussen, Andrew D. Barreto, Maarten Lansberg, Rishi Gupta, Gregory W. Albers
Journal: JAMA Neurology (2019)

The efficacy and safety of endovascular thrombectomy (EVT) in patients with large ischemic cores remains unknown, to our knowledge.To compare outcomes in patients with large ischemic cores treated with EVT and medical management vs medical management alone.This prespecified analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) trial, a prospective cohort study of imaging selection that was conducted in 9 US comprehensive stroke centers, enrolled patients between January 2016 and February 2018, and followed them up for 90 days. Patients with moderate to severe stroke and anterior circulation large-vessel occlusion presenting up to 24 hours from the time they were last known to be well were eligible for the cohort. Of these, patients with large ischemic cores on computed tomography (CT) (Alberta Stroke Program Early CT Score <6) or CT perfusion scanning (a volume with a relative cerebral blood flow <30% of ≥50 cm3) were included in analyses.Endovascular thrombectomy with medical management (MM) or MM only.Functional outcomes at 90 days per modified Rankin scale; safety outcomes (mortality, symptomatic intracerebral hemorrhage, and neurological worsening).A total of 105 patients with large ischemic cores on either CT or CT perfusion images were included: 71 with Alberta Stroke Program Early CT Scores of 5 or less (EVT, 37; MM, 34), 74 with cores of 50 cm3 or greater on CT perfusion images (EVT, 39; MM, 35), and 40 who had large cores on both CT and CT perfusion images (EVT, 14; MM, 26). The median (interquartile range) age was 66 (60-75) years; 45 patients (43%) were female. Nineteen of 62 patients (31%) who were treated with EVT achieved functional independence (modified Rankin Scale scores, 0-2) vs 6 of 43 patients (14%) treated with MM only (odds ratio [OR], 3.27 [95% CI, 1.11-9.62]; P = .03). Also, EVT was associated with better functional outcomes (common OR, 2.12 [95% CI, 1.05-4.31]; P = .04), less infarct growth (44 vs 98 mL; P = .006), and smaller final infarct volume (97 vs 190 mL; P = .001) than MM. In the odds of functional independence, there was a 42% reduction per 10-cm3 increase in core volume (adjusted OR, 0.58 [95% CI, 0.39-0.87]; P = .007) and a 40% reduction per hour of treatment delay (adjusted OR, 0.60 [95% CI, 0.36-0.99]; P = .045). Of 10 patients who had EVT with core volumes greater than 100 cm3, none had a favorable outcome.Although the odds of good outcomes for patients with large cores who receive EVT markedly decline with increasing core size and time to treatment, these data suggest potential benefits. Randomized clinical trials are needed.
Variation in a Left Ventricle–Specific <i>Hand1</i> Enhancer Impairs GATA Transcription Factor Binding and Disrupts Conduction System Development and Function
Authors: Joshua W. Vincentz, Beth A. Firulli, Kevin P. Toolan, Dan E. Arking, Nona Sotoodehnia, Juyi Wan, Peng-Sheng Chen, Corrie de Gier-de Vries, Vincent M. Christoffels, Michael Rubart-von der Lohe, Anthony B. Firulli
Journal: Circulation Research (2019)

Rationale: The ventricular conduction system (VCS) rapidly propagates electrical impulses through the working myocardium of the ventricles to coordinate chamber contraction. GWAS (Genome-wide association studies) have associated nucleotide polymorphisms, most are located within regulatory intergenic or intronic sequences, with variation in VCS function. Two highly correlated polymorphisms (r 2 &gt;0.99) associated with VCS functional variation (rs13165478 and rs13185595) occur 5′ to the gene encoding the basic helix–loop–helix transcription factor HAND1 (heart- and neural crest derivatives-expressed protein 1). Objective: Here, we test the hypothesis that these polymorphisms influence HAND1 transcription thereby influencing VCS development and function. Methods and Results: We employed transgenic mouse models to identify an enhancer that is sufficient for left ventricle (LV) cis -regulatory activity. Two evolutionarily conserved GATA transcription factor cis -binding elements within this enhancer are bound by GATA4 and are necessary for cis -regulatory activity, as shown by in vitro DNA binding assays. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9-mediated deletion of this enhancer dramatically reduces Hand1 expression solely within the LV but does not phenocopy previously published mouse models of cardiac Hand1 loss-of-function. Electrophysiological and morphological analyses reveals that mice homozygous for this deleted enhancer display a morphologically abnormal VCS and a conduction system phenotype consistent with right bundle branch block. Using 1000 Genomes Project data, we identify 3 additional single nucleotide polymorphisms (SNPs), located within the Hand1 LV enhancer, that compose a haplotype with rs13165478 and rs13185595. One of these SNPs, rs10054375, overlaps with a critical GATA cis -regulatory element within the Hand1 LV enhancer. This SNP, when tested in electrophoretic mobility shift assays, disrupts GATA4 DNA-binding. Modeling 2 of these SNPs in mice causes diminished Hand1 expression and mice present with abnormal VCS function. Conclusions: Together, these findings reveal that SNP rs10054375, which is located within a necessary and sufficient LV-specific Hand1 enhancer, exhibits reduces GATA DNA-binding in electrophoretic mobility shift assay, and this enhancer in total, is required for VCS development and function in mice and perhaps humans.