tbuckley/cabot-search huggingface dataset:
Management of refractory myeloma: a review.
Authors: A C Buzaid, B G Durie
Journal: Journal of Clinical Oncology (1988)

Management of refractory myeloma represents a common and challenging clinical problem. Approximately 30% to 50% of patients with multiple myeloma do not respond to first-line therapy, and those who initially achieve a remission will eventually relapse. Surprisingly, there is no routinely accepted approach to patients with refractory disease. Therefore, we review the literature in an attempt to provide an overview of the published results and outline our treatment recommendations for such patients. We suggest the following: (1) for truly resistant patients (ie, those who clearly progress with initial therapy), administration of high-dose or pulsed glucocorticosteroids is the best treatment, with an expected response of 40% (defined as a greater than or equal to 50% reduction in monoclonal [M]-protein concentration); (2) for patients who relapse during therapy or relapse within 6 months of stopping the initial treatment, the VAD regimen (vincristine, doxorubicin, and dexamethasone) is one of the most effective salvage therapies, resulting in an approximately 75% response rate (greater than or equal to 50% reduction in M-protein concentration); (3) for patients who relapse within more than 6 months of stopping therapy (unmaintained remission), reinitiation of the initial therapy represents an excellent alternative, leading to recontrol in 60% to 70% of patients (greater than or equal to 50% reduction in M-protein concentration). If progression is observed or if there is response and then relapse in this setting, VAD chemotherapy can be administered again. (4) Patients who fail second-line salvage therapies should enter well-designed clinical trials to evaluate new treatment modalities. If this is not feasible, alpha-interferon or "systemic" radiotherapy are recommended in selected cases.
CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants
Authors: Sándor Spisák, Kate Lawrenson, Yanfang Fu, István Csabai, Rebecca T Cottman, Ji-Heui Seo, Christopher Haiman, Ying Han, Romina Lenci, Qiyuan Li, Viktória Tisza, Zoltán Szállási, Zachery T Herbert, Matthew Chabot, Mark Pomerantz, Norbert Solymosi, Simon A Gayther, J Keith Joung, Matthew L Freedman
Journal: Nature Medicine (2015)
Guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association.
Authors: H P Adams, T G Brott, R M Crowell, A J Furlan, C R Gomez, J Grotta, C M Helgason, J R Marler, R F Woolson, J A Zivin
Journal: Circulation (1994)
Early Life Transepidermal Water Loss (TEWL) Values Can Predate Atopic Dermatitis At Six and Twelve Months in Asymptomatic Infants: Results From the Baseline Study
Authors: Maeve M. Kelleher, Audrey Dunn Galvin, Deirdre Murray, Alan David Irvine, Jonathan O. Hourihane, Baseline Team
Journal: Journal of Allergy and Clinical Immunology (2013)
World Health Assembly hears warnings over WHO's relationship with industry
Authors: A. Gulland
Journal: BMJ (2015)

Delegates at the World Health Assembly have failed to agree on how the World Health Organization should collaborate with industry and other bodies.

Member states spent the week discussing WHO’s draft framework of engagement with non-state actors, a document that spells out the ground rules for WHO’s relationship with bodies from industry, academia, and non-governmental and philanthropic organisations. However, delegates could not come up with a final draft and agreed that an intergovernmental meeting, taking place no later than October, should produce a final statement in time for WHO’s executive board meeting in January.

Many non-governmental organisations and member states see the framework as crucial in clarifying WHO’s relationship with industries and avoiding conflicts of interest. Some …
Cytologically negative pericardial effusion complicating combined modality therapy for localized small-cell carcinoma of the lung.
Authors: R W Carey, J M Sawicka, N C Choi
Journal: Journal of Clinical Oncology (1987)

A 17% frequency of cytologically negative pericardial effusion (CNPE), accompanied in some cases by tamponade, occurred a median of 12.6 months from the onset of treatment for localized small-cell carcinoma of the lung. CNPE was apparently caused by toxicity of radiation/chemotherapy treatment rather than recurrent cancer. The occurrence of CNPE does not appear to represent enhanced toxicity of immediate (as opposed to delayed) concurrent chemoradiotherapy, but may be a consequence of the superior survival status of patients treated in this way. The onset of chest pain and/or dyspnea associated with increase in cardiac silhouette and positive echocardiogram allowed accurate diagnosis. Each instance was relatively easily managed by catheter drainage, and, for some patients, with the addition of nonsteroidal antiinflammatory drugs. It is important to recognize the possibility that a radiation/chemotherapy-related syndrome of pericardial effusion/tamponade may occur so that early diagnosis can be made and the risk of fatal tamponade avoided.
A Man with Fever, Cough, and Rash
Authors: Ibiayi Dagogo-Jack, Anand Vaidya, Bram Geller, Lindsey R. Baden, Richard Stone
Journal: New England Journal of Medicine (2014)

A 67-year-old man presented to the emergency department with a 5-week history of recurrent daily fevers, with temperatures as high as 38.7°C, night sweats, dyspnea, and cough. He reported no dysuria, chills, diarrhea, or vomiting. During the preceding year, he had had no known contact with persons who were sick, and had not traveled outside the United States. In the preceding . . .
Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila
Authors: Subhash D. Katewa, Kazutaka Akagi, Neelanjan Bose, Kuntol Rakshit, Timothy Camarella, Xiangzhong Zheng, David Hall, Sonnet Davis, Christopher S. Nelson, Rachel B. Brem, Arvind Ramanathan, Amita Sehgal, Jadwiga M. Giebultowicz, Pankaj Kapahi
Journal: Cell Metabolism (2015)
Prostate-Specific Antigen Screening After 2012 US Preventive Services Task Force Recommendations
Authors: Jesse D. Sammon, Firas Abdollah, Toni K. Choueiri, Philip W. Kantoff, Paul L. Nguyen, Mani Menon, Quoc-Dien Trinh
Journal: JAMA (2015)

This observational study examines prostate-specific antigen screening data from the National Health Interview Survey from 2000-2013 to determine the prevalence and determinants of screening before and after the 2012 US Preventive Services Task Force recommendations against such screening.
Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone alone or with levamisole or with levamisole plus BCG for malignant lymphoma: a Southwest Oncology Group Study.
Authors: S E Jones, P N Grozea, T P Miller, E J Van Slyck, S P Balcerzak, J J Costanzi, F S Morrison, H J Eyre, C J Fabian, L Dabich
Journal: Journal of Clinical Oncology (1985)

Between 1977 and 1983 the Southwest Oncology Group (SWOG) evaluated chemotherapy alone (cyclophosphamide, doxorubicin, vincristine, prednisone; CHOP) or chemoimmunotherapy (CHOP-levamisole or CHOP-levamisole-BCG) in a randomized prospective clinical trial involving 715 eligible patients with all types of malignant lymphoma (ML). Of 281 evaluable patients with favorable histologic types of ML, 171 (61%) achieved complete remission (CR) and there was no difference in CR rate, CR duration, or survival according to the type of initial treatment. Of 388 evaluable patients with unfavorable histologic types of ML, 194 (50%) achieved CR. Levamisole appeared to adversely affect CR rates in nodular mixed and nodular large-cell lymphoma and CR duration in patients with unfavorable histology ML. Chemoimmunotherapy with levamisole or levamisole-BCG offers no advantage in terms of CR rates, CR duration, or survival compared to CHOP chemotherapy alone, and levamisole may have had an adverse impact on outcome in certain subtypes of ML.
Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma.
Authors: K M Kelly, R B Womer, P H Sorensen, Q B Xiong, F G Barr
Journal: Journal of Clinical Oncology (1997)

PURPOSE We evaluated the clinical features of the common PAX3-FKHR and variant PAX7-FKHR gene fusions observed in rhabdomyosarcoma. PATIENTS AND METHODS Reverse-transcriptase polymerase chain reaction (RT-PCR) assays were used to detect the gene fusions in 34 cases of rhabdomyosarcoma. Clinical data were obtained retrospectively and compared with the molecular results. RESULTS The PAX3-FKHR and PAX7-FKHR gene fusions were present in tumors from 18 and 16 patients, respectively. The group with a PAX7-FKHR fusion was younger (P = .01) and presented more often with an extremity lesion (82% v 22%; P = .001). PAX7-FKHR tumors were more often localized than PAX3-FKHR tumors (P = .03). In patients with metastatic disease at diagnosis, the patterns were different: PAX7-FKHR patients had metastatic disease that involved only bone (n = 2) and distant nodes (n = 2), while the PAX3-FKHR group had multiple sites involved, including bone (n = 7), marrow (n = 7), lungs (n = 3), distant nodes (n = 2), skin (n = 1), and brain (n = 1). No significant difference in relapse rate was observed. A trend toward improved overall survival in the PAX7-FKHR group was noted (P = .09). Event-free survival for this PAX7-FKHR group was significantly longer (P = .04). CONCLUSION Our results suggest that the common PAX3-FKHR and the variant PAX7-FKHR fusions are associated with distinct clinical phenotypes. Identification of fusion gene status may be a useful diagnostic tool in rhabdomyosarcoma.
The Pig as a Model for Human Nutrition
Authors: E. R. Miller, D. E. Ullrey
Journal: Annual Review of Nutrition (1987)

��:�����:�: ���f;��'::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::: THE PIG AS MODEL   . Maternal and Fetal Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Infant Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Carbohydrate and Lipid Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Amino Acid Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vitamin and Mineral Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONCLUSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association
Authors: Caroline S. Fox, Sherita Hill Golden, Cheryl Anderson, George A. Bray, Lora E. Burke, Ian H. de Boer, Prakash Deedwania, Robert H. Eckel, Abby G. Ershow, Judith Fradkin, Silvio E. Inzucchi, Mikhail Kosiborod, Robert G. Nelson, Mahesh J. Patel, Michael Pignone, Laurie Quinn, Philip R. Schauer, Elizabeth Selvin, Dorothea K. Vafiadis
Journal: Diabetes Care (2015)

Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus.
Exercise and Coronary Heart Disease
Authors: N A Rigotti, G S Thomas, A Leaf
Journal: Annual Review of Medicine (1983)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Prostate Cancer Incidence and PSA Testing Patterns in Relation to USPSTF Screening Recommendations
Authors: Ahmedin Jemal, Stacey A. Fedewa, Jiemin Ma, Rebecca Siegel, Chun Chieh Lin, Otis Brawley, Elizabeth M. Ward
Journal: JAMA (2015)

<h3>Importance</h3> Prostate cancer incidence in men 75 years and older substantially decreased following the 2008 US Preventive Services Task Force (USPSTF) recommendation against prostate-specific antigen (PSA)–based screening for this age group. It is unknown whether incidence has changed since the USPSTF recommendation against screening for all men in May 2012. <h3>Objective</h3> To examine recent changes in stage-specific prostate cancer incidence and PSA screening rates following the 2008 and 2012 USPSTF recommendations. <h3>Design and Settings</h3> Ecologic study of age-standardized prostate cancer incidence (newly diagnosed cases/100 000 men aged ≥50 years) by stage from 2005 through 2012 using data from 18 population-based Surveillance, Epidemiology, and End Results (SEER) registries and PSA screening rate in the past year among men 50 years and older without a history of prostate cancer who responded to the 2005 (n = 4580), 2008 (n = 3476), 2010 (n = 4157), and 2013 (n = 6172) National Health Interview Survey (NHIS). <h3>Exposures</h3> The USPSTF recommendations to omit PSA-based screening for average-risk men. <h3>Main Outcomes and Measures</h3> Prostate cancer incidence and incidence ratios (IRs) comparing consecutive years from 2005 through 2012 by age (≥50, 50-74, and ≥75 years) and SEER summary stage categorized as local/regional or distant and PSA screening rate and rate ratios (SRRs) comparing successive survey years by age. <h3>Results</h3> Prostate cancer incidence per 100 000 in men 50 years and older (N = 446 009 in SEER areas) was 534.9 in 2005, 540.8 in 2008, 505.0 in 2010, and 416.2 in 2012; rates began decreasing in 2008 and the largest decrease occurred between 2011 and 2012, from 498.3 (99% CI, 492.8-503.9) to 416.2 (99% CI, 411.2-421.2). The number of men 50 years and older diagnosed with prostate cancer nationwide declined by 33 519, from 213 562 men in 2011 to 180 043 men in 2012. Declines in incidence since 2008 were confined to local/regional-stage disease and were similar across age and race/ethnicity groups. The percentage of men 50 years and older reporting PSA screening in the past 12 months was 36.9% in 2005, 40.6% in 2008, 37.8% in 2010, and 30.8% in 2013. In relative terms, screening rates increased by 10% (SRR, 1.10; 99% CI, 1.01-1.21) between 2005 and 2008 and then decreased by 18% (SRR, 0.82; 99% CI, 0.75-0.89) between 2010 and 2013. Similar screening patterns were found in age subgroups 50 to 74 years and 75 years and older. <h3>Conclusions and Relevance</h3> Both the incidence of early-stage prostate cancer and rates of PSA screening have declined and coincide with 2012 USPSTF recommendation to omit PSA screening from routine primary care for men. Longer follow-up is needed to see whether these decreases are associated with trends in mortality.
Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial
Authors: Martine Piccart-Gebhart, Eileen Holmes, José Baselga, Evandro de Azambuja, Amylou C. Dueck, Giuseppe Viale, Jo Anne Zujewski, Aron Goldhirsch, Alison Armour, Kathleen I. Pritchard, Ann E. McCullough, Stella Dolci, Eleanor McFadden, Andrew P. Holmes, Liu Tonghua, Holger Eidtmann, Phuong Dinh, Serena Di Cosimo, Nadia Harbeck, Sergei Tjulandin, Young-Hyuck Im, Chiun-Sheng Huang, Véronique Diéras, David W. Hillman, Antonio C. Wolff, Christian Jackisch, Istvan Lang, Michael Untch, Ian Smith, Frances Boyle, Binghe Xu, Henry Gomez, Thomas Suter, Richard D. Gelber, Edith A. Perez
Journal: Journal of Clinical Oncology (2015)

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care.
Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa
Authors: Vassiliki Tzanetakou, Theodora Kanni, Sophia Giatrakou, Alexandros Katoulis, Evangelia Papadavid, Mihai G. Netea, Charles A. Dinarello, Jos W. M. van der Meer, Dimitrios Rigopoulos, Evangelos J. Giamarellos-Bourboulis
Journal: JAMA Dermatology (2015)

Hidradenitis suppurativa (HS) is a common skin disorder in which excessive inflammation is believed to have an important role. There is no specific therapy for HS.To investigate the safety and efficacy of the anti-inflammatory biological therapy anakinra in HS.Double-blind, randomized, placebo-controlled clinical trial with a 12-week treatment phase and a 12-week follow-up phase. The setting was Attikon University General Hospital, a tertiary care institution in Athens, Greece. Participants were 20 patients with Hurley stage II or III HS. The study and the analysis were conducted between March 1, 2012, and February 28, 2014.Patients were randomized to receive injections from identical syringes containing placebo or anakinra subcutaneously once daily for 12 weeks. Peripheral blood mononuclear cells were isolated and stimulated for cytokine production before the beginning of treatment and at week 12 (the end of treatment) and week 24.The primary end point was the effect of anakinra on HS disease severity. Secondary end points were the time to a new exacerbation and the production of cytokines.Among the 20 trial participants, 10 each were randomized to the group to receive anakinra or the placebo group. The mean (SD) ages were 42.8 (13.8) and 36 (11.3) years in the anakinra and placebo groups, respectively. The disease activity score was decreased at the end of treatment in 20% (2 of 10) of the placebo arm compared with 67% (6 of 9) of the anakinra arm (P = .04). Hidradenitis suppurativa clinical response at 12 weeks was achieved in 30% (3 of 10) of the placebo arm and in 78% (7 of 9) of the anakinra arm (P = .04). The production of interferon-γ by peripheral blood mononuclear cells in the anakinra arm was decreased, and the production of interleukin 22 was increased. The time to a new HS exacerbation was prolonged in the anakinra arm by log-rank test (log rank, 6.137; P = .01). No serious adverse events were reported.Anakinra has the potential to be an effective and well-tolerated treatment for HS. Inhibition of interleukin 1 is a promising treatment strategy.clinicaltrials.gov Identifier: NCT01558375.
Treatment of Idiopathic Thrombocytopenic Purpura (ITP)
Authors: Y S Ahn, W J Harrington
Journal: Annual Review of Medicine (1977)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
On the Causes of Evolutionary Transition:Transversion Bias
Authors: Arlin Stoltzfus, Ryan W. Norris
Journal: Molecular Biology and Evolution (2015)

A pattern in which nucleotide transitions are favored several fold over transversions is common in molecular evolution. When this pattern occurs among amino acid replacements, explanations often invoke an effect of selection, on the grounds that transitions are more conservative in their effects on proteins. However, the underlying hypothesis of conservative transitions has never been tested directly. Here we assess support for this hypothesis using direct evidence: the fitness effects of mutations in actual proteins measured via individual or paired growth experiments. We assembled data from 8 published studies, ranging in size from 24 to 757 single-nucleotide mutations that change an amino acid. Every study has the statistical power to reveal significant effects of amino acid exchangeability, and most studies have the power to discern a binary conservative-vs-radical distinction. However, only one study suggests that transitions are significantly more conservative than transversions. In the combined set of 1,239 replacements (544 transitions, 695 transversions), the chance that a transition is more conservative than a transversion is 53 % (95 % confidence interval 50 to 56) compared with the null expectation of 50 %. We show that this effect is not large compared with that of most biochemical factors, and is not large enough to explain the several-fold bias observed in evolution. In short, the available data have the power to verify the "conservative transitions" hypothesis if true, but suggest instead that selection on proteins plays at best a minor role in the observed bias.
Hepatitis C virus treatment in the real world: optimising treatment and access to therapies: Table 1
Authors: Fabien Zoulim, T Jake Liang, Alexander L Gerbes, Alessio Aghemo, Sylvie Deuffic-Burban, Geoffrey Dusheiko, Michael W Fried, Stanislas Pol, Jürgen Kurt Rockstroh, Norah A Terrault, Stefan Wiktor
Journal: Gut (2015)

Chronic HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. The treatment of HCV has undergone a rapid and spectacular revolution. In the past 5 years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective, well tolerated, allow for shorter treatment regimens and offer new opportunities for previously excluded groups. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication. This manuscript addresses the new challenges regarding treatment optimisation in the real world, improvement of antiviral efficacy in 'hard-to-treat' groups, the management of patients whose direct acting antiviral drug treatment was unsuccessful, and access to diagnosis and treatment in different parts of the world.