tbuckley/cabot-search huggingface dataset:
Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression
Authors: Georgina V. Long, Jeffrey S. Weber, James Larkin, Victoria Atkinson, Jean-Jacques Grob, Dirk Schadendorf, Reinhard Dummer, Caroline Robert, Ivan Márquez-Rodas, Catriona McNeil, Henrik Schmidt, Karen Briscoe, Jean-François Baurain, F. Stephen Hodi, Jedd D. Wolchok
Journal: JAMA Oncology (2017)

Immune checkpoint inhibitors have demonstrated atypical response patterns, which may not be fully captured by conventional response criteria. There is a need to better understand the potential benefit of continued immune checkpoint inhibition beyond progression.To evaluate the safety and potential benefit of nivolumab (anti-programmed cell death receptor 1) monotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression.Pooled, retrospective analysis of data from phase 3 trials of nivolumab in treatment-naive patients with advanced melanoma (CheckMate 066 or CheckMate 067) conducted at academic and clinical cancer centers. Participants were patients treated beyond first disease progression, defined as those who received their last dose of nivolumab more than 6 weeks after progression (TBP group); and patients not treated beyond progression, who discontinued nivolumab therapy before or at progression (non-TBP group). Data analyses were conducted from November 6, 2015, to January 11, 2017.Nivolumab (3 mg/kg every 2 weeks) administered until progression or unacceptable toxic effects. Patients could be treated beyond progression if deriving apparent clinical benefit and tolerating study drug, at the investigator's discretion.Tumor response and safety in TBP and non-TBP patients.Among 526 randomized patients (39% [n = 203] female; median age, 62 years [range, 18-90 years]), 306 (58%) experienced disease progression, including 85 (28%) TBP patients and 221 (72%) non-TBP patients. Twenty-four (28%) of the TBP patients had a target lesion reduction of greater than 30% after progression compared with baseline (TBP>30% group). At the time of this analysis, 65 (76%) TBP patients and 21 (87%) TBP>30% patients were still alive; 27 (32%) and 11 (46%), respectively, continued to receive treatment. Median (range) time from progression to last dose of treatment was 4.7 (1.4-25.8) months for TBP patients and 7.6 (2.4-19.4) months for TBP>30% patients. Median (range) time from progression to greater than 30% tumor reduction was 1.4 (0.2-7.0) months. Treatment-related select grade 3 to 4 adverse events were similar in the TBP and non-TBP groups (5 [6%] and 9 [4%], respectively).A substantial proportion of selected patients treated with frontline nivolumab who were clinically stable and judged to be eligible for treatment beyond RECIST v1.1-defined progression by the treating investigators derived apparent clinical benefit without compromising safety. Further analysis will help define the potential benefit of continued nivolumab treatment beyond progression.clinicaltrials.gov Identifiers: NCT01721772 (CheckMate 066) and NCT01844505 (CheckMate 067).
The Use of Antibiotic Prophylaxis in Gastrointestinal Endoscopies at the Level of District General Hospital
Authors: RJ Aslam, S Aye, M Hawley, Z Mahmood
Journal: Endoscopy (2006)

Background: British Society of Gastroenterology (BSG) guidelines published in 2001, recommends antibiotic prophylaxis according to the underlying condition and the risk of the procedure.
Anticystinuric Effects of Glutamine and of Dietary Sodium Restriction
Authors: Philippe Jaeger, Luc Portmann, Alda Saunders, Leon E. Rosenberg, Samuel O. Thier
Journal: New England Journal of Medicine (1986)

We studied four patients with cystinuria to assess the effects of glutamine and dietary sodium on the urinary excretion of dibasic amino acids. In Patient 1, at an ad libitum dietary sodium intake of about 300 mmol per day, oral administration of glutamine led to reproducible and marked anticystinuria and antiornithinuria, whereas the excretion of lysine and arginine was not significantly affected. In Patient 2, at an ad libitum dietary sodium intake of about 150 mmol per day, no effect of glutamine could be demonstrated in studies lasting up to three weeks. Since the principal difference between Patients 1 and 2 was their dietary intake of sodium, Patient 3 was studied during dietary sodium intakes of 150 and 300 mmol per day. His cystine excretion was found to be higher at 300 than at 150 mmol per day. Glutamine suppressed his cystine excretion at a sodium intake of 300 mmol per day but had no effect at 150 mmol per day. When the effect of a further reduction in sodium intake alone was studied in a fourth patient, a decrease of 150 to 50 mmol per day was found to reduce cystine excretion markedly within 17 days. The low-sodium diet alone also reduced the excretion of lysine, arginine, and ornithine. We conclude that glutamine may reduce the excretion of dibasic amino acids at a high sodium intake but not at an intake of about 150 mmol per day. However, since a sodium-dependent excretion of the dibasic amino acids occurs at an intake down to about 50 mmol of sodium per day, dietary restriction of sodium can provide a safe approach to the treatment of cystinuria.
Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action
Authors: Teodora Wi, Monica M. Lahra, Francis Ndowa, Manju Bala, Jo-Anne R. Dillon, Pilar Ramon-Pardo, Sergey R. Eremin, Gail Bolan, Magnus Unemo
Journal: PLoS Medicine (2017)

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae seriously compromises the management and control of gonorrhea.• In vitro and clinical resistance in N. gonorrhoeae to the extended-spectrum cephalosporins (ESCs), the last-line treatment for gonorrhea, have been reported from many, particularly well-resourced, settings globally.• The World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Programme (GASP) is key to monitoring AMR trends, identifying emerging AMR, and informing regular refinements of treatment guidelines and public health policy globally.• Enhanced international collaborative actions are crucial for the control of gonorrhea, including improved prevention, early diagnosis (development of accurate, rapid, point-of-care tests), partner management, and enhanced surveillance (including population-based surveillance and surveillance of treatment failures and antimicrobial use).• Rapid, accurate, point-of-care diagnostic tests (which would ideally predict AMR and/or antimicrobial susceptibility), new therapeutic drugs, and a gonococcal vaccine-which will ultimately be the only sustainable way to achieve gonorrhea control-are needed.
Using Computational Psychiatry to Rule Out the Hidden Causes of Depression
Authors: Erdem Pulcu, Michael Browning
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
First-line gemcitabine versus treatment of physician’s choice in patients with metastatic and stage IV breast cancer: A prospective cohort study.
Authors: Kazutaka Narui, Takashi Ishikawa, Kazuhiro Shimada, Kumiko Kida, Daisuke Shimizu, Ikuko Ota, Kounosuke Kiuchi, Mikiko Tanabe, Mari Saito Oba, Satoshi Morita, Sadatoshi Sugae, Takako Doi, Satoshi Hasegawa, Tomoyuki Morita, Ayako Kito, Takashi Chishima, Yasushi Ichikawa, Itaru Endo
Journal: Journal of Clinical Oncology (2014)

e12013 Background: Treatment for metastatic and stage IV breast cancer demands both improving or maintaining quality of life and prolongation of life. Gemcitabine is one of the recommended cytotoxic agents with extremely well tolerance. This study is designed to clarify efficacy of gemcitabine evaluating health-related quality of life (HRQoL) by comparing with treatment of physician’s choice. Methods: This study was prospective cohort study. Patients with metastatic and stage IV breast cancer were registered and administered gemcitabine or treatment of physician’s choice for first-line chemotherapy. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. Primary endpoints were time to treatment failure (TTF) and FACT-B total score. Outcome measures included severe toxicity (grade 3 evaluated with Common Toxicity Criteria by National Cancer Institute version 3.0). Patients completed FACT-B at the screening visit every 4 weeks. Results: From June 2010 to January 2014, 100 patients were registered from 9 hospitals and 98 patients were eligible. The trial was accrued already and 13 patients continued to be treated. This is an interim analysis of 96 patients. 49 patients were gemcitabine group (GEM) and 47 were treatment of physician’s choice group (TPC). Median age was 62 years (30-79) in GEM and 60 years (31-77) in TPC. 42 (85.7%) in GEM and 34 (70.8%) in TPC had ER-positive disease. Two (4.1%) of GEM and 8 (16.7%) in TPC had Her2-positive disease. Median of TTF was 5.3 months in GEM and 4.6 months in TPC. TTF demonstrated no significant difference between the two groups (p=0.670). Mean QoL scores in GEM were 97.0 at baseline and 94.9, 97.8 and 96.7 at 1st, 2nd and 3rd questionnaires. The scores in TPC were 92.4 at baseline and 93.2, 89.1 and 90.3 at 1st, 2nd and 3rd. Grade 3 hematotoxicity was observed in 7 (16.7%) of GEM and 4 (9.3%) of TPC (p=0.31). Grade 3 non-hematologic toxicity was observed 2 (4.1%) in GEM and 4 (8.5%) in TPC (p=0.37). Conclusions: There were no significant differences in TTF and HRQoL scores between two groups. This is an interim report and we will present further analysis at the meeting. Clinical trial information: 000013002.
Optimising Culture for Helicobacter Pylori Sensitivity
Authors: R MacNicholas, A Hassan, M Healy, B O'Connell, S McKiernan
Journal: Endoscopy (2006)

Aims: Standard antibiotic regimens do not eradicate Helicobacter Pylori in 4–10% of patients necessitating gastroscopy to obtain biopsies for culture and sensitivity. We investigated the clinical parameters associated with successful culture as in our institution only 52% of these biopsies grew Helicobacter Pylori.
Local intracerebral delivery of endogenous inhibitors by osmotic minipumps effectively suppresses glioma growth in Vivo (Cancer Research (2003) (2499-2505))
Authors: Carlo Giussani, Giorgio Carrabba, Mauro Pluderi, Valeria Lucini, Marilou Pannacci, Dario Caronzolo, Francesco Costa, Matteo Minotti, Giustino Tomei, Roberto Villani, Rona S. Carroll, Andreas Bikfalvi, Lorenzo Bello
Journal: Cancer Research (2003)
KEYNOTE-029: Efficacy and safety of pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma.
Authors: Matteo S. Carlino, Victoria Atkinson, Jonathan S. Cebon, Michael B. Jameson, Bernie M. Fitzharris, Catriona M. McNeil, Andrew G Hill, Antoni Ribas, Michael B. Atkins, John A. Thompson, Wen-Jen Hwu, F. Stephen Hodi, Alexander M. Menzies, Alexander David Guminski, Richard Kefford, Xinxin Shu, Nageatte Ibrahim, Blanca Homet Moreno, Georgina V. Long
Journal: Journal of Clinical Oncology (2017)

9545 Background: We previously showed that standard-dose pembro plus reduced-dose ipi has manageable safety and robust antitumor activity in patients (pts) with advanced melanoma. Here, we present more mature data, including 1-y landmark PFS and OS estimates. Methods: In the phase 1 KEYNOTE-029 expansion cohort (NCT02089685), pts with advanced melanoma, ECOG PS 0-1, no active brain metastases, and no prior immune checkpoint inhibitor therapy received pembro 2 mg/kg Q3W + ipi 1 mg/kg Q3W for 4 doses, then pembro alone for up to 2 y. Primary end point was safety. Efficacy end points were ORR, PFS, and DOR per RECIST v1.1 by independent central review and OS. Results: 153 pts were enrolled between Jan 13, 2015, and Sep 17, 2015. Median age was 60 y, 66% were male, 25% had elevated LDH, 56% had stage M1c disease, 36% were BRAF V600 mutant, and 13% received ≥1 prior therapy. As of Oct 17, 2016, median follow-up was 17 mo, and 64 (42%) pts remained on pembro. 110 (72%) pts received all 4 ipi doses. There were no treatment-related (TR) deaths. TRAEs occurred in all pts, were grade 3/4 in 69 (45%), and led to discontinuation of pembro and ipi in 17 (11%), ipi alone in 11 (7%), and pembro alone after ipi completion or discontinuation in 19 (12%). PD occurred in 1/11 pts who discontinued ipi alone and 4/17 pts who discontinued ipi and pembro. Of the 11 pts who discontinued ipi alone for a TRAE, 0 experienced recurrence of the same TRAE during pembro monotherapy and 2 discontinued pembro for a different TRAE (both elevated lipase). Immune-mediated AEs occurred in 90 (59%) pts and were grade 3/4 in 39 (25%). With 7 mo additional follow-up, there were 6 additional responses for an ORR of 61% (95% CI, 53%-69%); the CR rate increased from 10% to 15%. Median DOR was not reached (range, 1.6+ to 18.1+ mo), with 86/93 responders (92%), including 23/23 (100%) with CR, alive and without subsequent PD at cutoff. Median PFS and OS were not reached; 1-y estimates were 69% for PFS and 89% for OS. Conclusions: Pembro 2 mg/kg plus 4 doses of ipi 1 mg/kg has a manageable toxicity profile and provides robust, durable antitumor activity in pts with advanced melanoma. Clinical trial information: NCT02089685.
Accessible Chromatin Landscape Reveals a Proliferative Osteoprogenitor Transcriptional Program in Bone Marrow Mesenchymal Stromal Cells from Patients with Primary Myelofibrosis
Authors: Christophe Desterke, Nadira Ruzehaji, Bernadette Guerton, Johanna Konopacki, Solene-Florence Kammerer-Jacquet, Alessandro M. Vannucchi, Lisa Pieri, Christophe Martinaud, Marie-Caroline Le Bousse-Kerdiles
Journal: Blood (2016)
Glial contributions to neurodegeneration in tauopathies
Authors: Cheryl E. G. Leyns, David M. Holtzman
Journal: Molecular Neurodegeneration (2017)

Tauopathies are a broad set of neurodegenerative dementias characterized by aggregation of the tau protein into filamentous inclusions that can be found in neurons and glial cells. Activated microglia, astrocytes and elevated levels of proinflammatory molecules are also pathological hallmarks that are found in brain regions affected by tau pathology. There has been abundant research in recent years to understand the role of gliosis and neuroinflammation in neurodegenerative diseases, particularly in Alzheimer's disease (AD) which is the most common form of dementia. AD is a tauopathy characterized by both extracellular amyloid-β plaques in addition to intracellular neurofibrillary tangles and neuropil threads containing aggregated tau protein. Accumulating evidence suggests that neuroinflammation offers a possible mechanistic link between these pathologies. Additionally, there appears to be a role for neuroinflammation in aggravating tau pathology and neurodegeneration in tauopathies featuring tau deposits as the predominant pathological signature. In this review, we survey the literature regarding inflammatory mechanisms that may impact neurodegeneration in AD and related tauopathies. We consider a physical role for microglia in the spread of tau pathology as well as the non-cell autonomous effects of secreted proinflammatory cytokines, specifically interleukin 1 beta, interleukin 6, tumor necrosis factor alpha and complement proteins. These molecules appear to have direct effects on tau pathophysiology and overall neuronal health. They also indirectly impact neuronal homeostasis by altering glial function. We conclude by proposing a complex role for gliosis and neuroinflammation in accelerating the progression of AD and other tauopathies.
Le roi est mort, vive le roi?
Authors: Joachim Heinrich
Journal: European Respiratory Journal (2017)

Barker's or Doerner's hypothesis on early programming factors during perinatal life leading to common chronic diseases [1, 2] is the scientific background for a massive amount of research on the potential impact of perinatal nutrition on the development of chronic diseases in later life. Pregnant women are extremely interested in what professionals state is the best nutritional care for a healthy baby. Journal editors and public media representatives are also very much engaged in the topic of perinatal nutrition, as it guarantees substantial attention from the scientific community and media customers. However, nutritional epidemiology has often been strongly attacked due to the observational nature of most of its studies and small randomised trials; but it has been particularly criticised for the limitations regarding dietary assessment, inconsistent findings and short-lived naive-driven recommendations [3]. Indeed, dietary recommendations for pregnant women have changed over the past decades, with the exception of folic acid and iodine intake, iron (in case of suboptimal iron stores) and gestational weight gain [4–8]. While the evidence of these recommendations in the prevention of neural tube defects or obesity-related disorders is sufficiently strong, there is only little evidence to support that specific dietary recommendations during pregnancy can prevent asthma and other allergic disorders. These recommendations include pre- or probiotics [9], as well as prenatal macronutrient and micronutrient intake. Historically, preventive recommendations focused on allergen avoidance in early life, but recent findings do not support this strategy or at least discuss the weaknesses of this approach [10], in particular for food allergies [11, 12]. Recent publications even reported that extended breastfeeding has no or only very little impact on the onset of asthma and other allergic diseases in childhood, although there are many other good reasons to recommend breastfeeding [13, 14]. Thus, there is a strong need to understand the role of dietary intake during pregnancy with regard to developing allergies, specifically asthma, later in life. So far, observational studies in pregnant women explored the impact of allergenic foods, "healthy" food intake such as vegetables and fruit, the Mediterranean diet, and fatty acids, with mixed results. Dietary interventions in randomised control trials (RCTs) during pregnancy involving vitamin C supplementation, probiotics use, or avoidance of egg and cow's milk did not show any protective effects on allergies [15], whilst more recent RCTs showed borderline reduction of asthma for vitamin D supplementation during last trimester [16, 17], and a preventive potential of high fish oil supplementation during third trimester [18]. Free sugar intake during pregnancy increases the risk of atopy in offspring, but replication is suggested <http://ow.ly/TKIF30cy4Qo>
A prospective, proteomics study identified potential biomarkers of encapsulating peritoneal sclerosis in peritoneal effluent
Authors: Vasileios Zavvos, Anthony T. Buxton, Caroline Evans, Mark Lambie, Simon J. Davies, Nicholas Topley, Martin Wilkie, Angela Summers, Paul Brenchley, Dimitrios S. Goumenos, Timothy S. Johnson
Journal: Kidney International (2017)
Case 20-2017 — A 48-Year-Old Man with Weight Loss, Confusion, Skin Lesions, and Pancytopenia
Authors: Shibani S. Mukerji, R. Gilberto Gonzalez, Rajesh T. Gandhi, Stefan Kraft
Journal: New England Journal of Medicine (2017)

A 48-year-old man was evaluated for confusion that had developed while he was traveling in Mexico. He had purplish skin lesions, pancytopenia, and pleocytosis and an elevated protein level in the cerebrospinal fluid. Diagnostic tests were performed.
A phase 2 study of investigational TORC1/2 inhibitor TAK-228 with fulvestrant in women with ER+/HER2–advanced or metastatic breast cancer (mBC) that has progressed during or after aromatase inhibitor (AI) therapy.
Authors: Jose Angel Garcia Saenz, Manuel Ramos Vazquez, Miguel Martin, Amparo Ruiz, Serafin Morales, Begona Bermejo, Isabel Ruiz, Ricardo Cubedo, Luis De la Cruz Merino, Antonio Anton, Eva Maria Carrasco, Michelle Kneissl, Fabian Zohren, Noelia Martinez
Journal: Journal of Clinical Oncology (2017)

TPS1118 Background: Antiestrogen therapy, including AI, is standard for ER+ tumors in the adjuvant and metastatic setting; however, resistance is common. These tumors may respond to alternative second-line anti-estrogen therapies such as fulvestrant but response durations are often short. Preclinical and clinical studies suggest that simultaneous inhibition of ER and PI3K/mTOR could prevent/delay the emergence of hormone-independent cancer cells, thereby improving patient (pt) outcomes. This study will test whether fulvestrant plus TAK-228, a dual TORC1/2 inhibitor, can overcome endocrine therapy resistance in ER+ mBC. This is an open-label, randomized, phase 2 study of continuous once-daily TAK-228 (4 mg) or once-weekly TAK-228 (30 mg) plus fulvestrant (per label), vs fulvestrant alone, in pts with ER+/HER2– advanced or mBC that has progressed during/after AI therapy (EudraCT 2015-003612-20). Methods: 153 pts will be randomized 1:1:1 and stratified (presence or absence of visceral metastasis, prior hormonal therapy sensitivity, and prior exposure to CDK 4/6 inhibitors). Pts will receive study drug(s) until progressive disease (PD), unacceptable toxicity, or consent withdrawal. Pts with histological confirmation of ER+/HER2– advanced or mBC with measureable disease, ECOG 0–1, PD during/after prior AI therapy (progression ≤12 mos after discontinuation of adjuvant therapy or ≤1 mo after discontinuation in the metastatic setting) and adequate organ function, but not prior therapy with mTOR, PI3K, dual PI3K-mTOR or AKT inhibitors, or fulvestrant, &gt; 1 prior line of chemotherapy for mBC or recurrent or progressive disease on &gt; 2 endocrine therapies for mBC are eligible. This study aims to determine the efficacy (primary endpoint: PFS; secondary endpoints: OS, TTP, ORR), safety and tolerability of TAK-228 plus fulvestrant vs fulvestrant alone. The primary hypothesis (TAK-228 plus fulvestrant can improve median PFS to 8 mos [hazard ratio, HR 0.5] vs fulvestrant-alone median PFS of 4 mos) is to be tested at the 0.10 significance level (2-sided; dropout rate 10%). To date, 24 pts have been enrolled. Clinical trial information: EudraCT 2015-003612-20.
A strategy for actualization of active targeting nanomedicine practically functioning in a living body
Authors: Kyoung Jin Lee, Seol Hwa Shin, Jae Hee Lee, Eun Jin Ju, Yun-Yong Park, Jung Jin Hwang, Young-Ah Suh, Seung-Mo Hong, Se Jin Jang, Jung Shin Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi
Journal: Biomaterials (2017)