tbuckley/cabot-search huggingface dataset:
The Obama Administration's Cancer Moonshot: A Call for Proteomics
Authors: Thomas P. Conrads, Emanuel F. Petricoin
Journal: Clinical Cancer Research (2016)

Abstract The Cancer Moonshot Program has been launched and represents a potentially paradigm-shifting initiative with the goal to implement a focused national effort to double the rate of progress against cancer. The placement of precision medicine, immunotherapy, genomics, and combination therapies was placed at the central nexus of this initiative. Although we are extremely enthusiastic about the goals of the program, it is time we meet this revolutionary project with equally bold and cutting-edge ideas: it is time we move firmly into the postgenome era and provide the necessary resources to propel and seize on innovative recent gains in the field of proteomics required for it to stand on equal footing in this narrative as a combined, synergistic engine for molecular profiling. After all, although the genome is the information archive, it is the proteins that actually do the work of the cell and represent the structural cellular machinery. It is the proteins that comprise most of the biomarkers that are measured to detect cancers, constitute the antigens that drive immune response and inter- and intracellular communications, and it is the proteins that are the drug targets for nearly every targeted therapy that is being evaluated in cancer trials today. We believe that a combined systems biology view of the tumor microenvironment that orients cancer studies back to the functional proteome, phosphoproteome, and biochemistry of the cell will be essential to deliver on the promise of the Cancer Moonshot Program. Clin Cancer Res; 22(18); 4556–8. ©2016 AACR.
Surgery for Gastrinoma and Insulinoma in Multiple Endocrine Neoplasia Type 1
Authors: Jeffrey A. Norton, Tony D. Fang, Robert T. Jensen
Journal: Journal of the National Comprehensive Cancer Network (2006)

The surgical management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are the 2 most common functional pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid hypersecretion and peptic ulcer disease that are best managed using proton pump inhibitors. Surgery to remove the gastrinoma in patients with multiple endocrine neoplasia type 1 is seldom curative unless a more extensive Whipple pancreaticoduodenectomy is performed. Because the prognosis is excellent, aggressive resections such as a Whipple procedure are only indicated for large, locally metastatic, advanced tumors. Furthermore, surgery to remove imageable tumors that are 2 cm in diameter is associated with excellent outcomes and decreased probability of liver metastases. Because gastrinomas are commonly multiple and most originate in the duodenum and develop lymph node metastases, the duodenum should be opened and all tumors and lymph nodes excised. Insulinomas cause hypoglycemia that results in neuroglycopenic symptoms. Medical management of the hypoglycemia is less effective than that of the gastric acid hypersecretion. Fortunately, the insulinoma is usually clearly identified using routine pancreatic imaging studies. There is a high likelihood of cure when the insulinoma is excised surgically. However, recurrent hypoglycemia may occur, and careful follow-up is indicated.
Diet and Cancer — An Overview
Authors: Walter C. Willett, Brian MacMahon
Journal: New England Journal of Medicine (1984)

SeleniumSelenium is an essential trace element that has a key role in the activity of glutathione peroxidase, an enzyme that protects against oxidative tissue damage on a cellular level.85 Both internationally5 and within the United States86 geographic areas with low selenium levels in the soil or in pooled blood-bank serum samples generally have higher cancer rates than areas with higher selenium levels. In a study that examined selenium intake in relation to site-specific cancer rates, the strongest inverse correlations were with breast cancer (r = 0.8) and colon cancer (r = 0.7).5 Although these correlational studies are useful for . . .
Association of Pioneer Accountable Care Organizations vs Traditional Medicare Fee for Service With Spending, Utilization, and Patient Experience
Authors: David J. Nyweide, Woolton Lee, Timothy T. Cuerdon, Hoangmai H. Pham, Megan Cox, Rahul Rajkumar, Patrick H. Conway
Journal: JAMA (2015)

The Pioneer Accountable Care Organization (ACO) Model aims to drive health care organizations to reduce expenditures while improving quality for fee-for-service (FFS) Medicare beneficiaries.To determine whether FFS beneficiaries aligned with Pioneer ACOs had smaller increases in spending and utilization than other FFS beneficiaries while retaining similar levels of care satisfaction in the first 2 years of the Pioneer ACO Model.Participants were FFS Medicare beneficiaries aligned with 32 ACOs (n = 675,712 in 2012; n = 806,258 in 2013) and a comparison group of alignment-eligible beneficiaries in the same markets (n = 13,203,694 in 2012; n = 12,134,154 in 2013). Analyses comprised difference-in-differences multivariable regression with Oaxaca-Blinder reweighting to model expenditure and utilization outcomes over a 2-year performance period (2012-2013) and 2-year baseline period (2010-2011) as well as adjusted analyses of Consumer Assessment of Healthcare Providers & Systems (CAHPS) survey responses among random samples of beneficiaries in Pioneer ACOs (n = 13,097), FFS (n = 116,255), or Medicare Advantage (n = 203,736) for 2012 care.Beneficiary alignment with a Pioneer ACO in 2012 or 2013.Medicare spending, utilization, and CAHPS domain scores.Total spending for beneficiaries aligned with Pioneer ACOs in 2012 or 2013 increased from baseline to a lesser degree relative to comparison populations. Differential changes in spending were approximately -$35.62 (95% CI, -$40.12 to -$31.12) per-beneficiary-per-month (PBPM) in 2012 and -$11.18 (95% CI, -$15.84 to -$6.51) PBPM in 2013, which amounted to aggregate reductions in increases of approximately -$280 (95% CI, -$315 to -$244) million in 2012 and -$105 (95% CI, -$148 to -$61) million in 2013. Inpatient spending showed the largest differential change of any spending category (-$14.40 [95% CI, -$17.31 to -$11.49] PBPM in 2012; -$6.46 [95% CI, -$9.26 to -$3.66] PBPM in 2013). Changes in utilization of physician services, emergency department, and postacute care followed a similar pattern. Compared with other Medicare beneficiaries, ACO-aligned beneficiaries reported higher mean scores for timely care (77.2 [ACO] vs 71.2 [FFS] vs 72.7 [MA]) and for clinician communication (91.9 [ACO] vs 88.3 [FFS] vs 88.7 [MA]).In the first 2 years of the Pioneer ACO Model, beneficiaries aligned with Pioneer ACOs, as compared with general Medicare FFS beneficiaries, exhibited smaller increases in total Medicare expenditures and differential reductions in utilization of different health services, with little difference in patient experience.
Newborn minor physical anomalies and problem behavior at age three
Authors: C Burg, J L Rapoport, L S Bartley, P O Quinn, P Timmins
Journal: American Journal of Psychiatry (1980)

The authors followed up 136 three-year-olds who had high or low scores for minor physical anomalies of face, head, hands, and feet at birth. Interviews with parents revealed that high-anomaly infants were somewhat more likely to have problem behaviors at age three; this was particularly true for hyperactive-impulsive behavior for boys. Preschool teachers' ratings of hyperactivity, however, did not show a significant relationship to anomaly score. The results suggest some congenital contributors to behavior disorders of childhood, but the relationship between anomalies and problem behavior is weak and limits clinical usefulness of this measure when used alone for identifying a high-risk population.
Vitamin D
Authors: H. F. DeLuca
Journal: New England Journal of Medicine (1969)

ALTHOUGH vitamin D deficiency diseases have long ceased to be a problem to the physician, many related diseases such as familial hypophosphatemia, renal osteodystrophy, pseudo-vitamin D deficiency, corticoid-induced osteomalacia, vitamin-D-resistant hypoparathyroidism and others immediately suggest that much is left to be learned concerning the action of this fat-soluble vitamin. This has dramatically been borne out in the past decade, in which new and revolutionary concepts have emerged in our understanding of the metabolism and function of vitamin D.With highly radioactive vitamin D preparations it has been demonstrated that the vitamin is converted to at least three biologically active metabolites. . . .
Fiberoptic Intubation
Authors: Thomas Heidegger
Journal: New England Journal of Medicine (2011)

Fiberoptic intubation plays an important part in the management of a difficult airway and is recommended by many societies of anesthesia. It is primarily important for the management of the anticipated difficult airway, but can also be used to secure the airway in an unexpected situation. There are different techniques for both situations -- the nasal and oral approach in the awake and anesthetized status, respectively. The choice of the equipment and medication is primarily dependent on personal preference. This video will demonstrate a nasal approach in an awake patient with a difficult airway and will also demonstrate an oral technique in an anesthetized patient whose . . .
Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR).
Authors: Alexander I. Spira, Keunchil Park, Julien Mazières, Johan F. Vansteenkiste, Achim Rittmeyer, Marcus Ballinger, Daniel Waterkamp, Marcin Kowanetz, Ahmad Mokatrin, Louis Fehrenbacher
Journal: Journal of Clinical Oncology (2015)

8010 Background: MPDL3280A (anti-PDL1) has demonstrated promising response rates in NSCLC that correlated with PD-L1 expression on tumor-infiltrating immune cells (IC) and/or tumor cells (TC) (Horn et al, ASCO 2015). Methods: Previously treatedNSCLC patients (pts) were stratified by PD-L1 IC status, histology and prior lines of therapy and randomized to 1200 mg IV q3w MPDL3280A (M) or 75 mg/m2 IV q3w docetaxel (D). PD-L1 expression was centrally evaluated by IHC using the SP142 antibody assay. Pts were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3. The primary endpoint was OS (data cutoff, January 30, 2015; median follow-up, 12 mo). Results: 287 pts were randomized. In this interim analysis, improved efficacy was observed with increasing PD-L1 expression (e.g., OS HR, 0.47; PFS HR, 0.56 and ORR, 38% vs 13% in TC3 or IC3 pts), while pts with the lowest PD-L1 levels (TC0 and IC0) did not appear to benefit from M (OS HR, 1.22; see table). ITT OS HR was 0.78. Safety was evaluable for 277 pts. Despite a longer median treatment duration for M (3.6 vs 2.1 mo for D), fewer pts receiving M (43%) vs D (56%) experienced Gr ≥ 3 AEs. There were no unexpected toxicities. Conclusions: This is the first randomized study in non-squamous and squamous NSCLC to demonstrate that inhibition of the PD-L1/PD-1 pathway may lead to improved survival. Furthermore, these data showed that PD-L1 biomarker selection, using a highly sensitive and specific IHC assay measuring PD-L1 on both TC and IC, can identify both pts most likely to derive improved OS, PFS and ORR and pts unlikely to benefit vs standard of care (NCT01903993). A second randomized study in this pt population is ongoing. Clinical trial information: NCT01903993.Efficacy. n = TC3 or IC3 TC2/3 or IC2/3 TC1/2/3 or IC1/2/3 TC0 and IC0 ITT M 24 D 23 M 50 D 55 M 93 D 102 M 51 D 41 M 144 D 143 OS Median, mo NR 11.1 13 7.4 NR 9.1 9.7 9.7 11.4 9.5 HRa 95% CI 0.47 0.20-1.11 0.56 0.33-0.95 0.63 0.42-0.95 1.22 0.69-2.14 0.78 0.59-1.03 PFS Median, mo 9.7 3.9 4.0 2.8 3.3 3.0 1.9 4.1 2.8 3.4 HR 95% CI 0.56 0.28-1.11 0.70 0.45-1.08 0.87 0.63-1.20 1.15 0.72-1.82 0.96 0.76-1.20 ORR, % (confirmed) 38 13 22 15 18 18 8 10 15 15 NR, not reached. aStratified HR for ITT and unstratified HR for subgroups.
Stent-Retriever Thrombectomy for Stroke
Authors: Jeffrey L Saver, Mayank Goyal, Hans-Christoph Diener
Journal: New England Journal of Medicine (2015)

_To the Editor:_   
In their report on the Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) trial, Saver et al. provide additional evidence on the effectiveness of endovascular therapy for acute ischemic stroke. In phase 3 stroke trials, the functional outcome on the modified Rankin scale is typically regarded as an important and valid measure. In the SWIFT PRIME trial, the effect of treatment on this functional outcome was impressively large. However, the blinding of this partly subjective assessment is crucial to minimizing bias. In this study, patients and their proxies were aware of the treatment they received, and the blind may easily have been broken. In the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), we created masked structured reports, which were assessed by an independent committee. In the SWIFT PRIME trial, local investigators were responsible for the assessment of outcomes, even if they were not otherwise involved with the trial. This factor may have influenced the score on the modified Rankin scale.  
In this otherwise very well conducted trial, the treatment effect on secondary outcomes pointed in the desired direction, which corroborates the observed effect on the primary outcome. Nevertheless, we have to remain aware that any outcome assessment that is not properly blinded, particularly in stroke trials, may lead to an overestimation of the treatment effect.
Toxicity study of 6-aminonicotinamide (6-AN), 6-MMPR, and PALA in mice.
Authors: Vince R. Torti, James E. Heath, Ronna Fulton, David S. Weinberg, Karen Schweikart, Joseph E. Tomaszewski, Naiyer A. Rizvi, John G. Page
Journal: Cancer Research (2004)

2109  This study examined the effect of three compounds: 6-Aminonicotinamide (6-AN, NSC-21206), methylmercaptopurine riboside (6-MMPR), and L-aspartic acid-N-(phosphonoacetyl)-disodium salt (PALA) in CD2F1 mice. Single ip doses of 6-AN (10, 20, or 40 mg/kg) were administered in combination with single ip doses of 75 mg/kg 6-MMPR and 83 mg/kg PALA. PALA was administered 17 hours prior to ip doses of 6-AN and/or 6-MMPR. Treated mice were monitored for alterations in clinical observations, body weight, clinical pathology parameters, and histopathology. Lethality was noted in 7/20 male mice and 3/20 female mice (40 mg/kg 6-AN) and in 2/20 male mice and 1/20 female mice (20 mg/kg 6-AN) in the combination dose groups. Hunched posture, hypoactivity, prostration, and head tilt, ataxia, circling, cold-to-touch, eye discharge, splayed hindlimbs, and tremors were noted in mice given 6-AN (20 or 40 mg/kg) in combination with 6-MMPR and PALA. For mice that received doses of all 3 drugs, there appeared to be a reversible decrease in body weight gain proportional to the dose of 6-AN. Administration of 6-AN in combination with 6-MMPR and PALA was associated with decreases in group mean WBC, RBC, HGB, HCT, reticulocyte, lymphocyte and neutrophil values and increases in MCV and platelet counts. Administration of 6-MMPR and PALA resulted in decreases in serum glucose concentrations and mild to moderate increases in AST and ALT activity that were also observed in mice in the combination group with 40 mg/kg 6-AN. Microscopic pathology examination revealed status spongiosis in the brains and spinal cords of mice treated with 10, 20 or 40 mg/kg 6-AN in combination with 6-MMPR and PALA. These lesions were noted in some of the animals that survived to Day 29. Additional lesions found in combination treatment groups included splenic, thymic, and bone marrow atrophy, hyperplasia of the non-glandular stomach, and liver necrosis, mineralization, and fibrous adhesions. Doses of 75 mg/kg 6-MMPR and 83 mg/kg PALA treatment appear to induce the hematopoeitic toxicity, while 20 or 40 mg/kg of 6-AN appears responsible for the neurotoxicity and lethality. The induction of neuropathic lesions by 6-AN is consistent with previously published studies. Toxicity appeared more pronounced in the male mice than in female mice. A NOAEL was not achieved in this study. Supported by NCI Contract No. N01-CM-87100.
Erratum. A Randomized Controlled Trial of Cognitive Behavioral Therapy for Adherence and Depression (CBT-AD) in Patients With Uncontrolled Type 2 Diabetes. Diabetes Care 2014;37:625–633
Authors: Steven A. Safren, Jeffrey S. Gonzalez, Deborah J. Wexler, Christina Psaros, Linda M. Delahanty, Aaron J. Blashill, Aleksandra I. Margolina, Enrico Cagliero
Journal: Diabetes Care (2016)

In the results section of the article cited above, the sentence “For medication adherence, a significant main effect for study arm indicated that the CBT-AD arm maintained 24.3 percentage points higher medication adherence than the ETAU arm during the follow-up period (95% CI –38.2 to –10.3, P = 0.001) (Table 3)” should have read, “For medication adherence, a significant main effect for study arm indicated that the CBT-AD arm maintained 16.3 percentage points higher medication …
<i>Staphylococcus aureus</i>Infections
Authors: S Blot, K Vandewoude, F Colardyn
Journal: New England Journal of Medicine (1998)

Beta-Blockers after Myocardial InfarctionTo the Editor: In their report on an observational study of beta-blockade after myocardial infarction, Gottlieb et al. (Aug.20 issue) 1 firmly conclude that beta-blockers should be used for high-risk patients after acute myocardial infarction, including patients with congestive heart failure.This conclusion is not supported by the data presented.The randomized studies of beta-blockers excluded patients with severe heart failure -and all physicians are trained in such contraindications.Therefore, we know that physicians will be reluctant to use beta-blockers in high-risk patients, and we can readily anticipate that the willingness to use a beta-blocker is a marker of low risk, both overall and in subgroups of patients.The authors' demonstration that beta-blockers are associated with a dramatic reduction in risk confirms a self-evident truth, regardless of the huge sample.The authors could have confirmed this explanation by demonstrating that beta-blockers are a marker of good exercise performance, a short hospital stay, and higher social status -other unspecific indicators of low risk.The value of beta-blockers in high-risk patients must be considered uncertain until proper randomized trials have proved otherwise.Such studies are under way in our country and elsewhere, and their completion must be awaited before firm conclusions are drawn.
A comparative trial of pharmacologic strategies in schizophrenia
Authors: W T Carpenter, D W Heinrichs, T E Hanlon
Journal: American Journal of Psychiatry (1987)

An open comparative trial was conducted involving 42 schizophrenic outpatients randomly assigned to one of two methods of drug administration: continuous medication (N = 21) and targeted medication plus psychosocial intervention (N = 21). The results, which suggest an extensive similarity with respect to outcome for the two treatments over a 2-year period, argue for the continuation of research on the relative effectiveness of the targeted drug approach, particularly in cases judged suitable for drug reduction strategies.
Understanding and Utilizing Patient Preferences in Cancer Treatment Decisions
Authors: Peter A. Ubel
Journal: Journal of the National Comprehensive Cancer Network (2016)

Shared decision-making is a complex endeavor that should take into account the patient's personal preferences regarding treatment options. To truly empower patients to be partners in decision-making, especially in situations in which their preferences are important, physicians must learn to communicate better and to distinguish between what is “medical fact” versus a “value judgement.” Knowing what are, when to ask, and how to ask the right questions will help physicians be effective in guiding patients toward the right treatments.
Self-portrait
Authors: Thomas B. Cole
Journal: JAMA (2012)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Corrigendum to “Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells”
Authors: Jun Yan, Abhisek Mitra, Jiemiao Hu, Jeffery J. Cutrera, Xueqing Xia, Thomas Doetschman, Mihai Gagea, Lopa Mishra, Shulin Li
Journal: Journal of Hepatology (2016)
Doxil and gemcitabine combination therapy for recurrent ovarian cancer: Results of a phase II trial
Authors: R. W. Holloway, N. J. Finkler, L. P. Nye, G. E. Bigsby, B. H. Ortiz
Journal: Journal of Clinical Oncology (2004)

5090 Background: Phase I trials have established the combination of pegylated liposomal doxorubicin (Doxil [D]) and gemcitabine as a tolerable regimen for patients (pts) with recurrent malignancies. Response rates and durations to single agent therapies in recurrent ovarian cancer are disappointingly low enough to warrant investigation of combination therapies. Methods: Twenty-five pts with recurrent ovarian cancer were enrolled in a phase II trial of D 25mg/m2 day 1 with gemcitabine 650mg/m2 day 1 and 8. All pts were previously treated with carboplatin and taxol, and 11 pts had received a second platinum regimen for relapsed disease. Four pts were platinum refractory, four were platinum resistant, and 17(68%) were platinum sensitive with a mean of 14.5 (range 7 to 29) months since the last platinum therapy. The median number of prior chemotherapy regimens was 2 (range 1 to 4). All pts had measurable disease and radiographic responses were determined with CAT scans every three cycles. Results: Twenty-four pts completed 3 to 12 (mean 6) cycles of therapy, and one pt was lost to followup after cycle four. Objective responses were demonstrated in 16 (64%) pts. Seven pts achieved a complete response (CR) with a mean progression free interval (PFI) of 7 (range 6 to 18) months. Nine (36%) pts had a partial response (PR) and six (24%) pts demonstrated stable disease (SD). The PFI for both PR and SD pts was 5.4 (range 3 to 10) months. Three (12%) pts showed progression at cycle 3. Overall 22/25 (88%) pts demonstrated a clinical benefit with disease response or stabilization (17/17 platinum sensitive vs. 5/8 platinum resistant/refractory). Two pts with PR withdrew secondary to toxicity at 4 and 5 cycles (recurrent grade 4 (G 4) thrombocytopenia, palmar plantar erythrodysesthesia). There were no episodes of febrile neutropenia. Transient G 4 neutropenia was observed in 6 (24%) pts and G 4 thrombocytopenia in one. Conclusions: The combination of D and gemcitabine is an active regimen for recurrent ovarian cancer, with response rates that exceed those reported for either single agent. No significant financial relationships to disclose.