tbuckley/cabot-search huggingface dataset:
First-in-human phase 1 PET study of CTT1057, a novel <sup>18</sup>F-labeled imaging agent targeting prostate specific membrane antigen (PSMA) in prostate cancer.
Authors: Rahul Raj Aggarwal, Spencer Behr, Youngho Seo, Kenneth Gao, Vahid Rahanfar, Jim Slater, Joseph Blecha, Beatrice Langton-Webster, Clifford Berkman, Henry Vanbrocklin
Journal: Journal of Clinical Oncology (2017)

e16562 Background: Urea-based 68 Ga-PSMA PET is increasingly being utilized for diagnostic purposes in prostate cancer; however high tracer uptake within the salivary gland and kidney may be dose-limiting upon translation to radiotherapy. We developed a novel 18 F labeled agent, CTT1057, a PSMA inhibitor based on a phosphoramidate scaffold with nanomolar and irreversible binding affinity to PSMA and robust internalization, and performed a first-in-human imaging study. Methods: Patients (pts) with metastatic castration resistant prostate cancer (mCRPC) were eligible. 10 mCi (370 MBq) of CTT1057 was injected and whole body PET/MR imaging (SIGNA PET/MR, GE) was performed 60 min post-injection. SUV mean in normal organs was recorded by drawing a 1 cm 3 volume-of-interest. SUV max was determined for each PSMA-avid metastasis. 10 randomly selected, consecutive 68 Ga-PSMA PET scans from an independent cohort were used for descriptive comparison. Results: 5 pts with mCRPC were enrolled, with average age of 66 years (range 35–85) and median PSA of 12.2 (range 0.73 – 157.7). 55 PSMA-avid metastases were seen, including 37 osseous (average SUV max = 8.1 ± 4.4), 15 lymph node (SUV max = 11.0 ± 6.1), and 3 pulmonary (SUV max = 3.2 ± 0.6). 31 (83%) and 12 (32%) of the PSMA-avid osseous lesions were visible on CT and bone scan, respectively. The mean short axis diameter of PSMA-avid lymph nodes was 0.7 ± 0.4 cm. Tumor-to-background ratios (liver, muscle, blood pool) were 2.8 ± 2.3, 14.9 ± 11.6, and 3.2 ± 2.4, respectively. SUV mean in salivary gland and kidney were 3.6 ± 0.4 and 9.1 ± 0.8 for CTT1057 and 15.8 ± 2.7 and 35.9 ± 9.6 for 68 Ga-PSMA, respectively. No tracer-related adverse events were observed and radiation dose estimates for organs and whole-body effective dose were within acceptable limits. Conclusions: 18 F-labeled CTT1057 targeting PSMA, detected mCRPC lesions in the soft tissue and bone at greater sensitivity than conventional imaging. CTT1057 distribution of uptake was similar to urea-based PSMA imaging, with preliminary evidence of lower uptake in the salivary gland and kidney. Further clinical studies of the CTT1057 backbone as a diagnostic and therapeutic agent in mCRPC are warranted. Clinical trial information: NCT02916537.
Analysis of stroma and immune-related gene expression patterns during breast cancer (BC) progression
Authors: L. Molinero, J. Albanell, H. Koeppen, E. Martinez de Dueñas, D. Halligan, A. Guerrero, J.I. Chacón López-Muñiz, R. Perez, S. Antolin, I. Blancas, M. Muñoz, A. Oltra, M.H. LÓpez de Ceballos, M. Sánchez-Aragó, R. Caballero, E. Carrasco, A.M. González-Angulo, A. Lluch, E.A. Mittendorff, F. Rojo
Journal: Annals of Oncology (2017)
Pazopanib (p) or sorafenib (s) + radium-223 (rad) in metastatic renal cell carcinoma (mrcc) with bone metastases (bm)
Authors: D. Bossé, R.R. McKay, K.P. Gray, M.D. Michaelson, C. Sleeper, M. Walsh, K.M. Krajewski, H. Jacene, J. Bellmunt, M.M. Pomerantz, L.C. Harshman, T.K. Choueiri
Journal: Annals of Oncology (2017)
Coronary Computed Tomographic Angiography—The First Test for Evaluating Patients With Chest Pain?
Authors: Todd C. Villines, Leslee J. Shaw
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Evidence and context of use for contrast enhancement as a surrogate of disease burden and treatment response in malignant glioma
Authors: Benjamin M Ellingson, Patrick Y Wen, Timothy F Cloughesy
Journal: Neuro-Oncology (2017)

The use of contrast enhancement within the brain on CT or MRI has been the gold standard for diagnosis and therapeutic response assessment in malignant gliomas for decades. The use of contrast enhancing tumor size, however, remains controversial as a tool for accurately diagnosing and assessing treatment efficacy in malignant gliomas, particularly in the current, quickly evolving therapeutic landscape. The current article consolidates overwhelming evidence from hundreds of studies in the field of neuro-oncology, providing the necessary evidence base and specific contexts of use for consideration of contrast enhancing tumor size as an appropriate surrogate biomarker for disease burden and as a tool for measuring treatment response in malignant glioma, including glioblastoma.
Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study
Authors: Janet Bee, Sharon Fuller, Suzanne Miller, Simon R Johnson
Journal: Thorax (2017)

Mechanistic target of rapamycin inhibitors reduce loss of lung function in lymphangioleiomyomatosis (LAM), although their benefit varies between individuals. We examined lung function response and side effects to rapamycin in a national cohort.Subjects were receiving rapamycin for progressive lung disease. Clinical evaluation, detailed phenotyping, serial lung function, rapamycin and safety monitoring were performed according to a clinical protocol. Lung function change, measured as FEV1 slope (ΔFEV1), was reported for those treated for 1 year or longer.Rapamycin was associated with improved ΔFEV1 in 21 individuals where pretreatment data were available (p<0.0001). In 47 treated for a mean duration of 35.8 months, mean ΔFEV1 was +11 (SD 75) mL/year, although it varied from +254 to -148 mL/year. The quartile with the highest positive ΔFEV1 had greater pretreatment FEV1 (p=0.02) and shorter disease durations (p=0.02) than the lowest quartile. Serum rapamycin level was positively associated with side effects (p=0.02) but not ΔFEV1 over 1 year. Within the first month of therapy, apthous ulcers, nausea and diarrhoea were associated with higher rapamycin levels. Acne, oedema and menstrual irregularities tended to increase over the first year of therapy. At the end of observation, the prevalence of side effects was 5% or less.Rapamycin reduces lung function loss in LAM, although in some, ΔFEV1 continues to fall at an accelerated rate. Poor response to rapamycin was associated with lower pretreatment lung function and longer disease duration but not serum level. Early intervention with low-dose rapamycin may preserve lung function and reduce side effects.
Quantification of CT bronchiectasis and its relationship to ventilation in cystic fibrosis
Authors: Tim Rosenow
Journal: Thorax (2017)

Structural lung abnormalities and impaired pulmonary function are key facets of respiratory disease in cystic fibrosis (CF). Over the last decade, CT and the multiple breath washout (MBW) technique have been extensively investigated and validated as clinical and research tools to measure their severity. However, little is known about the relationship between the structural and functional aspects of CF lung disease. This may in part be due to limitations inherent to visual CT scoring: in particular, …
Une épidémie de cryptosporidiose aux Pays-Bas
Authors: I. A. van Asperen, T Mank, G. J. Medema, C Stijnen, A S de Boer, J. F. Groot, P TenHam, J. F. Sluiters, M W Borgdorff
Journal: Eurosurveillance (1996)

Le 16 aout 1995, un microbiologiste de l'hopital de Spijkenisse, au sud ouest des Pays-Bas, qui avait recemment suivi un cours de parasitologie, identifiait des oocystes de cryptosporidium dans les selles d'un patient souffrant de diarrhee. Le re-examen de 89 echantillons de selles recus depuis le 10 aout et dans lesquels aucun agent bacterien pathogene n'avait ete identifie, revelait 15 cas de cryptosporidiose, tous confirmes au laboratoire de parasitologie de l'Universite de Leiden (Dr A.M. Polderman). La plupart des cas etaient des enfants de 0-5 ans et des femmes de 25-35 ans. Aucun ne presentait de signe de deficit immunitaire.
Efficacy of alternating-week fixed dose rate gemcitabine (FDR gem) plus capecitabine (CAP) in advanced pancreatic cancer (APC).
Authors: Claire Johns, Celso L. Diaz, William Kerridge, Jimmy Hwang, Andrew H. Ko, Margaret A. Tempero
Journal: Journal of Clinical Oncology (2017)

e15758 Background: Phase III trials support the use of FOLFIRINOX and gemcitabine plus albumin-bound paclitaxel as first-line treatment options in patients with APC. However, these treatments have significant side effects including cumulative neuropathy and cytopenias that limit their use. Our group previously reported results from a phase II trial evaluating a regimen of alternating-week FDR GEM/CAP showing promising efficacy as well as good tolerability. In the current analysis, we examined a larger retrospective cohort of APC patients treated using this strategy. Methods: Eligible patients received FDR GEM (1000 mg/m 2 ) infusion on days 1 and 15, along with CAP 1,000 mg/m 2 on days 1 to 7 and 15-22, in 28-day cycles. We evaluated OS, PFS, and objective radiologic response (ORR) by RECIST 1.1; as well as tabulated adverse events that necessitated dose or schedule modification. Results: 62 patients were treated at UCSF from 2008-2016 (52% male; and 48% female with a median age of 64.3 years. 49 had metastatic disease and 13 were locally advanced. Median OS was 10.3 and 12.0 months in the metastatic and locally advanced cohorts, respectively; median PFS was 5.4 and 5.6 months. ORR in evaluable patients with metastatic disease was 19% (all partial responses), with a disease control rate of 64%. In total, 37% of patients required dose modification at some point during therapy; the most common reason was hand-foot syndrome. Conclusions: FDR GEM/CAP represents an active and safe regimen for patients with APC, with OS and PFS rates comparable to those achieved with other first-line treatments. This regimen, based on its ease of administration and tolerability, may represent a suitable alternative option in select patients.
Exercise therapy is a beneficial intervention for chronic fatigue syndrome (PEDro synthesis)
Authors: Jasan Dannaway, Cameron C New, Charles H New, Chris G Maher
Journal: British Journal of Sports Medicine (2017)

Larun L, Brurberg KG, Odgaard-Jensen J  et al . Exercise therapy for chronicfatigue syndrome. Cochrane Database Syst Rev 2017;(4):CD003200.

Chronic fatigue syndrome (CFS) is a common, systemic condition that impairs function due to incapacitating fatigue, the cause of which is unknown.1 Typical symptoms include fatigue, sleep impairment, muscular pain, headaches and trouble concentrating. If left untreated, the prognosis is poor.2 Exercise has demonstrated promising positive effects for CFS3 possibly via reversing physical deconditioning1 or central desensitisation of the effort of activity.4 

To evaluate the effectiveness of exercise for CFS.

Three databases were searched up to May 2014. Additional searches were performed for ongoing and unpublished trials. Reference lists and topic experts were used to source further studies. Randomised controlled trials of exercise interventions were included.

Trials reporting all forms of exercise, defined as a ‘regimen or plan of physical activity designed and prescribed (and) intended to relieve or …
Anti-HER2 therapy efficacy in HER2-negative metastatic breast cancer with HER2-amplified circulating tumor cells: results of the CirCe T-DM1 trial
Authors: F-C. Bidard, P. cottu, C. Dubot, L. Venat-Bouvet, A. Lortholary, H. Bourgeois, M. Bollet, V. Servent Hanon, E. Luporsi-Gely, M. Espie, S. Guiu, V. D'Hondt, V. Diéras, M.P. Sablin, S. Neffati, F. Berger, J-Y. Pierga, W. Jacot
Journal: Annals of Oncology (2017)
Abstract 12519: Identification of Novel Atrial Fibrillation Risk Factors in The Women’s Health Initiative Database Utilizing the Random Generalized Linear Model
Authors: Justin Parizo, Marco Perez
Journal: Circulation (2016)

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia and confers significant risk of morbidity and mortality. The etiology of AF remains incompletely understood. The Women’s Health Initiative (WHI) provides an opportunity to evaluate an extensive and diverse set of covariates in a large population to identify novel risk factors. Hypothesis: We hypothesized that we would validate existing predictors of AF and discover novel markers associated with AF using a random generalized linear model (RGLM). Methods: A training subset of women enrolled into the WHI without pre-existing AF were included. Women were followed for AF using self-report and medical records coding. 104 demographic, medical history and environmental exposure covariates were selected for analysis in a RGLM. RGLM is a bootstrapped aggregated generalized linear model (GLM) that combines the predictive accuracy of random forests, a machine-learning algorithm, with the interpretability of forward selected GLM’s. Variables that are most commonly found in the best-performing regression models with randomly generated covariates are determined the most influential. Results: Of the 60,000 women included in this training set, 5,047 developed AF over an average of 16.3 years. The women were on average 61.9 years old at enrollment, 1.7% were African American, 0.9% were Hispanic, 35.2% had hypertension and 4.2% had diabetes. The RGLM generated 100 sub-cohorts with 75 covariates through random sampling. The top 50 covariates, based on correlation with incident AF, were evaluated by forward selection to generate GLM’s. The variables identified by the RGLM as being the most influential predictors were history of leukemia, prior pregnancy, systolic blood pressure, waist circumference, history of DVT, depression, and vegetable consumption. Conclusions: Using RGLM, we validated several established risk factors for AF. We also, for the first time in a large population cohort, identified history of leukemia as an influential risk marker of AF. Additional study will be needed to determine if leukemia-specific chemotherapy mediates this association. Finally, these novel markers will need to be validated in additional cohorts.
Effects on 18F-FDG PET/CT Brain Glucose Metabolism in Rectal Cancer Patients Undergoing Neoadjuvant Chemotherapy
Authors: Alexei M. C. Machado, Theara C. Fagundes, Arnoldo Mafra, Rodrigo G. Silva, Ana Carolina G. Castro, Marcelo Mamede
Journal: Clinical Nuclear Medicine (2017)

Retrospective study of the effects of anticancer treatment on the brain metabolism of patients diagnosed with rectal cancer based on a large and homogeneous sample of 40 paired F-FDG PET/CT volumes taken from 20 patients. The results are compared to the ones presented by related works to help elucidating the mechanisms of neurotoxicity associated to a decrease in memory, learning and motor skills.Twenty patients with rectal adenocarcinoma were scanned before and after neoadjuvant chemoradiation based exclusively on 5-fluorouracil and leucovorin. The sample was non-rigidly registered to a common template to allow for the comparison of regional metabolism. Statistical analysis was based on adjusted paired t-tests.The analysis primarily revealed a statistically significant decrease in the metabolism after neoadjuvant chemotherapy at the hypothalamus, putamen, head of the caudate, globus pallidus, red nucleus, substantia nigra, amygdala, cerebellum and the parahippocampal gyrus. The analysis also revealed smaller regions of increased metabolic activity at the middle temporal gyrus, precuneus of the parietal lobe and cuneus of the occipital lobe.The regions of decreased metabolism detected in the study are related to memory, learning and voluntary movement which is consistent with previous findings based on clinical studies and neuropsychological tests that report impairments on neurocognitive and motor skills associated to these therapies.
Radiation-induced cognitive toxicity: pathophysiology and interventions to reduce toxicity in adults
Authors: Christopher Wilke, David Grosshans, Joseph Duman, Paul Brown, Jing Li
Journal: Neuro-Oncology (2017)

Radiotherapy is ubiquitous in the treatment of patients with both primary brain tumors as well as disease which is metastatic to the brain. This therapy is not without cost, however, as cognitive decline is frequently associated with cranial radiation, particularly with whole brain radiotherapy (WBRT). The precise mechanisms responsible for radiation-induced morbidity remain incompletely understood and continue to be an active area of ongoing research. In this article, we review the hypothetical means by which cranial radiation induces cognitive decline as well as potential therapeutic approaches to prevent, minimize, or reverse treatment-induced cognitive deterioration. We additionally review advances in imaging modalities that can potentially be used to identify site-specific radiation-induced anatomic or functional changes in the brain and their correlation with clinical outcomes.
M. tuberculosis-Induced Necrosis of Infected Neutrophils Promotes Bacterial Growth Following Phagocytosis by Macrophages
Authors: Tobias Dallenga, Urska Repnik, Björn Corleis, Jacqueline Eich, Rudolph Reimer, Gareth W. Griffiths, Ulrich E. Schaible
Journal: Cell Host & Microbe (2017)
The topoisomerase I inhibitor gimatecan exhibits anti-tumor activity against malignant glioma xenografts as single agent and in combination
Authors: G. Vassal, N. Hamelin, P. Opolon, R. Versace, B. Geoerger
Journal: Journal of Clinical Oncology (2007)

2081 Background: Gimatecan, a novel oral lipohilic camptotecan (ST1481; NVP-LBQ707), has shown to irinotecan and topotecan superior anti-tumor activity against several cell lines and human xenografts. We evaluated gimatecan in microemulsion in vivo alone and in combination with temozolomide and the EGFR and VEGF tyrosine kinase inhibitor AEE788 against subcutaneous malignant glioma xenografts derived from primary tumors. Results: Gimatecan exhibited dose-dependent activity against all three advanced tumor stage glioma models with IGRG93 being the most sensitive: 0.10 to 0.25 mg/kg gimatecan daily orally in a protracted schedule 5 days/week during 4 weeks resulted in 100% partial and complete tumor regressions, significant tumor growth delays (TGD; 48 to &gt;100 days), log cell kills of 4.3 to 9.1, and were thus considered as ++++ highly active according to the SRI activity criteria. Anti-tumor activity in the TP53 wild-type IGRG93 correlated with significant induction of apoptotic cell death, as measured by TUNEL and cell cycle analysis, and lack of induction of p21. Moreover, combination of gimatecan and temozolomide resulted in synergistic activity against the TP53 wild-type IGRG121 glioblastoma and gimatecan at the MTD could be combined with temozolomide without enhanced toxicity. Gimatecan 0.19 mg/kg q5/wx4w combined with AEE788 50 mg/kg q3/wx4w was evaluated against the TP53 mutant, EGFR gene amplified IGRG88 glioma. Both agents were highly active resulting in 100% tumor regression. Gimatecan treated tumors started to grow 2–3 weeks after treatment end, while tumors treated with AEE788 regrew directly after treatment stop resulting in less significant TGD. Gimatecan and AEE788 given simultaneously during 4 weeks yielded less significant TGD compared to gimatecan alone, thus antagonistic effects. AEE788 induced G1 cell growth arrest which may reduce sensitivity to gimatecan, necessitating S-phase to be most efficient. An alternative schedule with gimatecan followed by AEE788 may be more appropriate. Conclusions: Gimatecan is highly active against malignant glioma xenografts and has synergistic activity with temozolomide suggesting this new topoisomerase I inhibitor for the treatment of malignant glioma. No significant financial relationships to disclose.
Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial
Authors: Dorothy K. Sit, James McGowan, Christopher Wiltrout, Rasim Somer Diler, John (Jesse) Dills, James Luther, Amy Yang, Jody D. Ciolino, Howard Seltman, Stephen R. Wisniewski, Michael Terman, Katherine L. Wisner
Journal: American Journal of Psychiatry (2017)

Objective: Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality. Method: The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less. Results: At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4–6 and significantly lower depression scores (9.2 [SD=6.6] compared with 14.9 [SD=9.2]; adjusted β=–5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them. Conclusions: The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.
Blood first line ready screening trial (B-F1RST) and blood first assay screening trial (BFAST) enable clinical development of novel blood-based biomarker assays for tumor mutational burden (TMB) and somatic mutations in 1L advanced or metastatic NSCLC
Authors: T.S.K. Mok, S. Gadgeel, E.S. Kim, V. Velcheti, S. Hu, T. Riehl, E. Schleifman, S.M. Paul, S. Mocci, D.S. Shames, S. Phan, C. Yun, M. Mathisen, M. Kowanetz, U. Sweere, M.A. Socinski
Journal: Annals of Oncology (2017)
Sodium fluoride PET imaging as a quantitative pharmacodynamic biomarker for bone homeostasis during anti-DKK1 therapy for multiple myeloma
Authors: Y Wang, A J Yee, C Sirard, S Landau, N Raje, U Mahmood
Journal: Blood Cancer Journal (2017)

Sodium fluoride PET imaging as a quantitative pharmacodynamic biomarker for bone homeostasis during anti-DKK1 therapy for multiple myeloma