tbuckley/cabot-search huggingface dataset:
Abstract 4012: Mild Troponin Elevation In subjects Presenting With Atrial Fibrillation With Rapid Ventricular Rate Is Associated With Adverse Cardiovascular Outcomes
Authors: Mazda Biria, Tareq Abu-Salah, Micah Pescetto, Chandra Annapureddy, Jayasree Pillarisetti, Subbareddy Vanga, Akshar Patel, Lisa Watkins, Kay Ryschon, Dhanunjaya Lakkireddy, Kamal Gupta
Journal: Circulation (2008)

Introduction: Cardiac markers are frequently checked in patients presenting with atrial fibrillation (AF) and rapid ventricular rate (RVR). Clinical significance of mild troponin elevation in this setting and clinical value of this practice is not well known. It has been suggested that mild troponin elevation in this setting represents rate related demand ischemia and not ACS. Hypothesis: We hypothesized that measuring Troponin in AF/ RVR without signs/ symptoms of myocardial infarction has low yield and limited clinical value in predicting cardiovascular events. Method: Multi-center, retrospective cohort study of 452 subjects (age 67±14, M:F=4:1) presenting with AF/ RVR between 2000 and 2006. Occurrence of MI at one year after discharge was primary outcome. Results: Of all cases presenting with A fib/ RVR, Troponin was checked in 351 cases (77.7%). Of these 197 (age 70±11, M:F=7.1) had elevated Troponin(group-I) and 154 (age 61±16, M:F=1.1) had a normal Troponin (group-II) (1.4±5.3 vs 0.02±0.01 ng/ml, P=0.003). Group-I was older with more renal failure compared to group-II (P=0.0001, 0.0001, 0.0002 respectively). However, there was no difference in the rate of diabetes, anemia and symptom of chest pain at the time of presentation (P=0.9, 0.07 and 0.058 respectively). There was no significant difference in ventricular rate (123+31vs 123+33, P=0.3), duration of symptoms (61±186.6 vs 30.3±46.1 h , P=0.2), and ST-T changes (38(21%) vs 38 (28%) P=0.8) between two groups. During hospitalization, 76(38.6%) stress tests were performed on subjects in group-I vs. 48(31%) in group-II (p=0.17). These stress tests led to 37(48.7%) vs 12(25%) coronary angiographies (P=0.013). In group-I at one year follow up, 15 (7%) of subjects developed MI, but none in group-II. Based on these data, Troponin has sensitivity, specificity, positive and negative predictive values of 84.6%, 27.8%, 29.7% and 83.3% respectively for detecting coronary disease in A Fib weith RVR and 100%, 45.8%, 7.6% and 100% respectively for occurrence of MI in one year. Conclusion: Even mild troponin elevation in the setting of AFib with RVR predicts a significant increase in risk of MI at 1 yr. A normal Troponin in this setting is predictive of a favorable cardiovascular outcome at one year.
Directional Coronary Atherectomy and Implantation of Drug-Eluting Stents in Selected Bifurcation Lesions
Authors: Antonio Colombo
Journal: Journal of the American College of Cardiology (2007)

Plaque removal with directional coronary atherectomy (DCA) and stent implantation appears to be a very rational binomial because a stent implanted on a lesion with a lower plaque burden should expand to a larger lumen area ([1][1]). A larger final lumen has always been a major requirement for most
A phase II study of combined methotrexate and teniposide infusions prior to reinduction therapy in relapsed childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.
Authors: J Ochs, J Rodman, M Abromowitch, R Kavanagh, M Harris, J Yalowich, G K Rivera
Journal: Journal of Clinical Oncology (1991)

Teniposide (VM-26) can increase intracellular methotrexate (MTX) and its polyglutamate derivatives in vitro and thus has the potential to improve the therapeutic index of regimens containing MTX. In this phase II study, children and adolescents with acute lymphoblastic leukemia (ALL) in first or second marrow relapse were randomly assigned to receive either simultaneous (n = 11) or sequential (n = 12) continuous infusions of MTX and VM-26 prior to reinduction. Infusions of VM-26 were begun 12 hours after completion of MTX infusion in the sequential group. Dosages were individually adjusted to maintain plasma concentration levels of 10 microns for MTX and 15 microns for VM-26; total infusion times were 24 and 72 hours, respectively. Significant toxicity in the first six patients who received the scheduled 72-hour VM-26 infusion (including one drug-related death) prompted a 50% reduction in infusion duration. The reduced dose was associated with similar but more manageable toxicity. Examination of bone marrow aspirates 10 days after therapy was begun showed one complete and two partial marrow remissions; a fourth patient who had an aplastic marrow on day 10 received no further chemotherapy and had a complete remission (CR) documented on day 31. There was no obvious clinical advantage associated with either infusion schedule, although small sample sizes preclude definitive conclusions. The 17% response rate to the MTX/VM-26 therapeutic window in patients with refractory disease suggests the need for further investigation to evaluate alternative schedules and concomitant therapy for this drug combination.
CRISPR-mediated Genome Editing Restores Dystrophin Expression and Function in mdx Mice
Authors: Li Xu, Ki Ho Park, Lixia Zhao, Jing Xu, Mona El Refaey, Yandi Gao, Hua Zhu, Jianjie Ma, Renzhi Han
Journal: Molecular Therapy (2015)

Duchenne muscular dystrophy (DMD) is a degenerative muscle disease caused by genetic mutations that lead to the disruption of dystrophin in muscle fibers. There is no curative treatment for this devastating disease. Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) has emerged as a powerful tool for genetic manipulation and potential therapy. Here we demonstrate that CRIPSR-mediated genome editing efficiently excised a 23-kb genomic region on the X-chromosome covering the mutant exon 23 in a mouse model of DMD, and restored dystrophin expression and the dystrophin-glycoprotein complex at the sarcolemma of skeletal muscles in live mdx mice. Electroporation-mediated transfection of the Cas9/gRNA constructs in the skeletal muscles of mdx mice normalized the calcium sparks in response to osmotic shock. Adenovirus-mediated transduction of Cas9/gRNA greatly reduced the Evans blue dye uptake of skeletal muscles at rest and after downhill treadmill running. This study provides proof evidence for permanent gene correction in DMD. Duchenne muscular dystrophy (DMD) is a degenerative muscle disease caused by genetic mutations that lead to the disruption of dystrophin in muscle fibers. There is no curative treatment for this devastating disease. Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) has emerged as a powerful tool for genetic manipulation and potential therapy. Here we demonstrate that CRIPSR-mediated genome editing efficiently excised a 23-kb genomic region on the X-chromosome covering the mutant exon 23 in a mouse model of DMD, and restored dystrophin expression and the dystrophin-glycoprotein complex at the sarcolemma of skeletal muscles in live mdx mice. Electroporation-mediated transfection of the Cas9/gRNA constructs in the skeletal muscles of mdx mice normalized the calcium sparks in response to osmotic shock. Adenovirus-mediated transduction of Cas9/gRNA greatly reduced the Evans blue dye uptake of skeletal muscles at rest and after downhill treadmill running. This study provides proof evidence for permanent gene correction in DMD.
Spotlight on measles 2010: Excretion of vaccine strain measles virus in urine and pharyngeal secretions of a child with vaccine associated febrile rash illness, Croatia, March 2010
Authors: B Kaic, I Gjenero-Margan, B Aleraj, T Vilibić-Čavlek, M Santak, A Cvitković, T Nemeth-Blazic, I Ivic Hofman
Journal: Eurosurveillance (2010)

We describe excretion of measles vaccine strain Schwarz in a child who developed a febrile rash illness eight days after primary immunisation against measles, mumps and rubella. Throat swabs and urine specimens were collected on the fifth and sixth day of illness, respectively. Genotyping demonstrated measles vaccine strain Schwarz (genotype A). If measles and rubella were not under enhanced surveillance in Croatia, the case would have been either misreported as rubella or not recognised at all.
To the Editors:
Authors: J. D. Brain, W. Kreyling, P. Gehr
Journal: European Respiratory Journal (2009)

discussed in the study [1], the major reason for illness may be due to the powder in the coating, which contains nanoparticles.As for the rashes the patients experienced on their faces, these may show the physical damage caused by polyacrylate nanoparticles to skin.It is not appropriate to link them to pre-existing atopy or immunological impairment.The rashes on the face of patients, characterised by skin itching, pachylosis and breakage, varied greatly from the rashes experienced in patients with immune-related disorders, such as systemic lupus erythematosus, which were characterised by no inching but smooth and intact skin.Moreover, detailed clinical examinations and follow-up excluded the immune-related disorders or pre-existing atopy.
It is time for consensus on return to play after injury: five key questions
Authors: Clare L Ardern, Mario Bizzini, Roald Bahr
Journal: British Journal of Sports Medicine (2015)

“When will I be able to play again?” is usually the reflex thought when an athlete suffers an injury. When making return to play decisions, clinicians (including physiotherapists, athletic trainers and physicians) and athletes might engage in a risk–benefit analysis of sorts, consciously or unconsciously weighing up the risks associated with participation and the extent to which those risks can be tolerated.1 ,2 There are a number of questions to contemplate: How does the clinician determine when the athlete is ready to return to play? Is physical recovery alone enough for return to play? What is successful return to play? What are the sports medicine clinician's responsibilities within the team, and to the athlete? Should athletes even return to play?

But what evidence can be used to answer these questions? We highlight some of the complexities in making the return to play decision, and key areas that need to be addressed.

### How does the clinician determine when the athlete is ready to return to play?

In the traditional evidence-based practice model,3 the clinician integrates the best available evidence from research with individual clinical experience and the patient's preferences when making decisions. In the search for the best evidence, considering an ankle sprain, the clinician might consult a textbook, where the evidence says that the athlete should have no pain or swelling, full strength and range of motion, and a healed ligament before returning to full competition.4 The time taken for pain and swelling to subside and full range of motion to return might vary from a couple of weeks to a couple of months; it may take a year for ligament healing.5 But in real life the athlete may return to play within 1 or 2 weeks of …
Bone and soft tissue sarcomas during pregnancy
Authors: A. Al-Jubran, M. Abdel Salam, A. El-Weshi, M. Memon, A. Ezzat, I. Maghfoor
Journal: Journal of Clinical Oncology (2005)

9077 Background: Cancer may be diagnosed concurrently with pregnancy in approximately 0.1% of pregnancies. Sarcoma in pregnancy is even rarer. Most of the literature is in the form of case reports and literature reviews. With this background we decided to identify and review our experience with sarcomas diagnosed during pregnancy. Methods: We used our tumor registry records to identify patients who were either diagnosed or referred with a diagnosis of sarcoma during pregnancy. Data were collected on maternal age, gestational age at diagnosis of malignancy, management of pregnancy as well as sarcoma and maternal and fetal outcomes. Additional data on diagnostic work-up where done and available were also recorded. Results: We identified a total of 14 patients from 1991–2002. Median age of 14 patients included in this study was 27 years (range 15–39). The diagnoses included osteosarcoma (5), Rhabdomyosarcoma (2), Liposarcoma (2), Ewing’s Sarcoma (2), Chondrosarcoma (1), High Grade Sarcoma NOS (1), High Grade Spindle Cell Sarcoma (1). Five were diagnosed during first trimester, one during 3rd and 7 during 2nd trimester (data unknown in one patient). Only three patients underwent chemotherapy during pregnancy, 2-during 2nd trimester, and 1 during 3rd trimester. One received VAIA for Ewing’s Sarcoma and the other Adriamycin for rhabdomyosarcoma. Both developed intrauterine fetal distress and delivered either spontaneously or via cesarean section with immediate neonatal death. The fetus exposed to VAIA was malformed. Overall fetal loss was documented either as therapeutic decision or complication of therapy in 7 patients, while 5 delivered normal healthy babies and data was not known in 2. Six patients were alive at last follow-up without evidence of disease, 4 had died of sarcoma or complication of treatment, 3 were alive with disease and one was lost to follow-up. Conclusions: Prognosis for fetus as well as mother is adversely affected by diagnosis of sarcoma during pregnancy. Administration of chemotherapy generally considered safe during 2nd trimester may result in fetal distress and demise and should be undertaken cautiously. Since long-term survival may be achieved, management should be with a multi-disciplinary approach with involvement of mother in all decision making. No significant financial relationships to disclose.
Navigating uncertainty: a valuable cost-effectiveness analysis in the rapidly changing field of metastatic melanoma treatment
Authors: P.K. Curl
Journal: British Journal of Dermatology (2015)

Journal Article Navigating uncertainty: a valuable cost‐effectiveness analysis in the rapidly changing field of metastatic melanoma treatment Get access P.K. Curl P.K. Curl Department of Medicine Alameda Health System Highland Hospital Oakland CA U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 6, 1 December 2015, Pages 1365–1366, https://doi.org/10.1111/bjd.14306 Published: 01 December 2015
Charity says NHS must deal with “woeful lack of support” for colorectal cancer survivors
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

The charity Macmillan Cancer Support has called for the UK government to improve the support the NHS in England offers people who have survived colorectal cancer or else face increasing costs of emergency care and welfare benefits.

A study reported in the Journal of Clinical Oncology in August found that just under one in six people (15%) in England who survived one year to three years after a colorectal cancer diagnosis—an estimated 7000 people—experienced “social distress,” perceiving their daily social interactions to …
Central pain processing is altered in people with Achilles tendinopathy
Authors: Nefeli Tompra, Jaap H van Dieën, Michel W Coppieters
Journal: British Journal of Sports Medicine (2015)

Tendinopathy is often a chronic condition. The mechanisms behind persistent tendon pain are not yet fully understood. It is unknown whether, similar to other persistent pain states, central pain mechanisms contribute to ongoing tendon pain.We investigated the presence of altered central pain processing in Achilles tendinopathy by assessing the conditioned pain modulation (CPM) effect in people with and without Achilles tendinopathy.20 people with Achilles tendinopathy and 23 healthy volunteers participated in this cross-sectional study. CPM was assessed by the cold pressor test. The pressure pain threshold (PPT) was recorded over the Achilles tendon before and during immersion of the participant's hand into cold water. The CPM effect was quantified as the absolute difference in PPT before and during the cold pressor test.An increase in PPT was observed in the Achilles tendinopathy and control group during the cold pressor test (p<0.001). However, the CPM effect was stronger in the control group (mean difference=160.5 kPa, SD=84.9 kPa) compared to the Achilles tendinopathy group (mean difference=36.4 kPa, SD=68.1 kPa; p<0.001).We report a reduced conditioned pain modulation effect in people with Achilles tendinopathy compared to people without Achilles tendinopathy. A reduced conditioned pain modulation effect reflects altered central pain processing which is believed to contribute to the persistence of pain in other conditions. Altered central pain processing may also be an important factor in persistent tendon pain that has traditionally been regarded to be dominated by peripheral mechanisms.
Androgen receptor splice variant, AR-V7, and resistance to enzalutamide and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Emmanuel S. Antonarakis, Changxue Lu, Hao Wang, Brandon Luber, Mary Nakazawa, Yan Chen, Jeffrey C. Roeser, Helen L. Fedor, Tamara L. Lotan, Qizhi Zheng, Angelo M. De Marzo, John T. Isaacs, William B. Isaacs, Rosa Nadal, Channing Judith Paller, Samuel R. Denmeade, Michael Anthony Carducci, Mario A. Eisenberger, Jun Luo
Journal: Journal of Clinical Oncology (2014)

5001 Background: Androgen receptor splice variant-7 (AR-V7) is a truncated form of the androgen receptor that lacks the ligand-binding domain, the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of AR-V7 in circulating tumor cells (CTCs) from men with mCRPC may be associated with primary resistance to enzalutamide and abiraterone. Methods: We used quantitative reverse-transcription PCR (qRT-PCR) to interrogate CTCs for the presence or absence of AR-V7 from prospectively enrolled patients with mCRPC initiating treatment with enzalutamide or abiraterone. We examined associations between AR-V7 status and PSA response rates, PSA progression-free survival (PSA-PFS), and clinical/radiographic progression-free survival (PFS). Multivariable Cox regression analyses were performed to determine the independent effect of AR-V7 status on these clinical outcomes. 30 men (per cohort) were required to detect a difference in PSA response rates from 10% (in AR-V7–positive men) to 60% (in AR-V7–negative men), using a 2-sided α=0.10 and β=0.15. Results: 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled, of which 38.7% and 19.4% had detectable AR-V7 from CTCs, respectively. Among men receiving enzalutamide, AR-V7–positive patients had inferior PSA response rates (0% vs 52.6%, P=0.004), PSA-PFS (median 1.4 vs 5.9 months, P<0.001), and PFS (median 2.1 vs 6.1 months, P<0.001) compared to AR-V7–negative patients. Similarly, among men receiving abiraterone, AR-V7–positive patients had inferior PSA response rates (0% vs 68.0%, P=0.004), PSA-PFS (median 1.3 months vs not reached, P<0.001), and PFS (median 2.3 months vs not reached, P<0.001). The negative prognostic impact of AR-V7 was maintained after adjusting for full-length AR expression levels. Conclusions: Detection of AR-V7 in CTCs from men with mCRPC is associated with resistance to enzalutamide and abiraterone. AR-V7 status may be used as a biomarker to predict resistance to AR-targeting agents, facilitate treatment selection, and fuel the development AR N-terminal domain inhibitors.
Abstract 13444: Complete Left-Sided Reverse Remodeling in Cardiac Resynchronization Therapy and Clinical Implications: a MADIT-CRT Long-term Follow-up Sub-study
Authors: Andrew M Mathias, Scott D Solomon, Arthur J Moss, Dorit Knappe, Anne-Catherine Pouleur, Wojciech Zareba, Helmut Klein, Rafael Kuperstein, Robert Klempfner, Ilan Goldenberg, Valentina Kutyifa
Journal: Circulation (2014)

Background: Left ventricular and left atrial remodeling (defined as a reduction in left ventricular end-systolic volume [LVESV] and left atrial volume [LAV] respectively) have both been shown to be associated with better clinical outcome in patients with cardiac resynchronization therapy (CRT). However, a portion of CRT patients exhibit discordant remodeling (e.g. improvement in LVESV but not in LAV or vice versa). Whether combined assessment of LA and LV remodeling predicts clinical outcome is unknown. Objectives: We aimed to evaluate the predictive value of a combined assessment of LAV and LVESV change in CRT patients with left bundle branch block (LBBB) enrolled in MADIT-CRT. We hypothesized that combined assessment better predicts outcome than LAV or LVESV reduction alone. Methods: The study population comprised 533 CRT-D LBBB patients assigned to lesser remodeling (below median LAV and LVESV change), discordant remodeling (above median change in only LAV or LVESV), or complete left-sided remodeling (above median change in both LAV and LVESV). The end point was heart failure (HF) during follow-up. Results: At 1-year follow-up, 206 patients had lesser remodeling, 115 had discordant remodeling and 212 had complete left-sided remodeling. Patients with complete left-sided remodeling had less HF than those with discordant remodeling or lesser remodeling (Figure, p=0.002). Multivariate analysis confirmed that complete left-sided remodeling is associated with lower risk of HF than discordant remodeling and discordant remodeling is better than lesser remodeling (HR=0.62 per each group, 95% CI: 0.44-0.86, p = 0.004). Conclusions: A combined assessment of LAV and LVESV reduction predicts HF in CRT patients with LBBB. Patients with complete left-sided remodeling had a significantly lower risk of HF during long-term follow-up.