tbuckley/cabot-search huggingface dataset:
Phase III Randomized Trial of Sunitinib (SU) vs. Capecitabine (C) in Patients (Pts) with Previously Treated HER2-Negative Advanced Breast Cancer (ABC).
Authors: C. Barrios, M. Liu, S. Lee, L. Vanlemmens, J. Ferrero, T. Tabei, X. Pivot, H. Iwata, K. Aogi, M. Brickman, K. Zhang, K. Kern, M. Martin
Journal: Cancer Research (2009)

Abstract BackgroundC monotherapy is approved for pts with ABC who progress after anthracycline (A) and taxane (T) therapies. SU is an oral, multitargeted tyrosine kinase inhibitor that has demonstrated a single-agent response rate of 11% in heavily pretreated ABC.MethodsTo test the hypothesis that SU is superior to C, we compared the 2 agents in a multicenter, randomized, open-label, phase III trial of 700 pts. Eligible pts (≥18 yrs, ECOG PS ≤2) had HER2-negative ABC that recurred after A and T therapy in the (neo)adjuvant, metastatic, or locally advanced disease settings. Pts were randomized (1:1) to continuous daily dosing of SU 37.5 mg or to C 1,250 mg/m2 (1,000 mg/m2 in pts &amp;gt;65 yrs) twice daily on days 1–14 q3wk. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR), patient-reported outcomes, and safety.ResultsAfter a pre-planned interim analysis showed that the primary endpoint would not be reached, the Independent Data Monitoring Committee recommended stopping trial enrollment for futility. Pts randomized to SU were offered alternative treatment (tx). As of March 2009, 464 pts were randomized to SU (n=231; mean age 52.7 yrs; 29 pts ≥65 yrs) or C (n=233; mean age 52.4 yrs; 44 pts ≥65 yrs). 22.9% vs. 35.6% of pts continued to receive SU and C, respectively. Tx was discontinued due to adverse events (AEs) in 10.8% of pts in the SU arm vs. 7.7% of pts in the C arm. Most common AEs leading to discontinuation of SU were neutropenia (3 pts) and hand–foot syndrome, congestive cardiac failure, epistaxis, and thrombocytopenia (2 pts each). C was discontinued due to neutropenia in 3 pts. Median PFS was 2.8 mos (95% CI: 2.4–3.9; 162 PFS events) vs. 4.2 mos (95% CI: 3.4–5.0; 135 PFS events) for SU vs. C, respectively (HR 1.473; 95% CI: 1.167–1.858; P&amp;lt;0.001). ORR for SU was 9.1% (95% CI: 5.7–13.6) vs. 12.9% (95% CI: 8.9–17.9) for C. CBR was 14.3% (95% CI: 10.0–19.5) for SU vs. 21.9% (95% CI: 16.8–27.8) for C. Other secondary endpoint analyses are ongoing.ConclusionsAlthough some pts continue to benefit from SU, these data suggest that SU is not superior to C given as monotherapy. The observed AE profiles were similar to those previously reported for SU and C. C was better tolerated than SU. SU cannot be recommended as monotherapy on this dosing schedule. Phase III studies with SU in combination with chemotherapy and other agents are ongoing in ABC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 46.
Irradiation of Food — Helping to Ensure Food Safety
Authors: Donald W. Thayer
Journal: New England Journal of Medicine (2004)

In this issue of the Journal, Osterholm and Norgan (pages 1898–1901) present a convincing argument that physicians and other health care professionals, as health advocates, should also be advocates for the irradiation of foods to prevent the transmission of infection. The recent approval of irradiated hamburgers for school lunch programs in the United States has been met with unfounded claims by groups opposed to food irradiation that children are being used as experimental animals. Unfortunately, this campaign has influenced some school boards to deny their students the increased safety of irradiated foods.Research on methods to control foodborne pathogens and . . .
A Single Session of Low-Intensity Exercise Is Sufficient to Enhance Insulin Sensitivity Into the Next Day in Obese Adults
Authors: Sean A. Newsom, Allison C. Everett, Alexander Hinko, Jeffrey F. Horowitz
Journal: Diabetes Care (2013)

The purpose of this study was to determine the effect of a relatively modest session of exercise on insulin sensitivity and fatty acid uptake the next day in obese adults.Eleven sedentary obese adults (male/female: 3/8; BMI 37 ± 1 kg/m(2); peak oxygen uptake [VO2peak] 20 ± 1 mL/kg/min) completed three experimental trials. On two of these occasions, subjects exercised to expend 350 kcal in the afternoon. These two exercise trials were identical except for the exercise intensity (50% VO2peak [EX50] and 65% VO2peak [EX65]) and the duration of exercise necessary to expend 350 kcal (EX50 = ≈ 70 min; EX65 = ≈ 55 min). Subjects also completed a control trial (CON), without exercise. The next morning, we measured insulin sensitivity (hyperinsulinemic-euglycemic clamp) and whole-body fatty acid uptake (palmitate rate of disappearance from plasma [Rd]).Exercise increased insulin sensitivity the next day, but whereas the 35% improvement after EX50 compared with CON was statistically significant (P = 0.01), the 20% improvement after EX65 was not (P = 0.17). Despite nearly identical values between CON and EX65 (P = 0.88), systemic fatty acid uptake was lower after EX50 compared with EX65 (P = 0.02), but not quite significant compared with CON (P = 0.07). Importantly, the change in fatty acid uptake after exercise compared with CON was negatively correlated with the change in insulin sensitivity for all trials (r = -0.60, P = 0.003).A relatively modest single session of exercise in obese adults improved insulin sensitivity the next day, and a reduction in systemic fatty acid uptake in the several hours after exercise may be important for this effect.
Anti–Factor Xa and Activated Partial Thromboplastin Time Measurements for Heparin Monitoring in Mechanical Circulatory Support
Authors: Sirtaz Adatya, Nir Uriel, Hirad Yarmohammadi, Christopher T Holley, Amy Feng, Samit S Roy, Mark T Reding, Ranjit John, Peter Eckman, Nicole D Zantek
Journal: JACC Heart Failure (2015)
Will medicine ever be able to halt the process of ageing?
Authors: G. Watts
Journal: BMJ (2011)

Geoff Watts reports on the elusive search for ways to keep us young

Anti-ageing medicine may not be the most well developed branch of healthcare and medical research, but one thing it doesn’t lack is self confidence. “Anti-aging medicine is the pinnacle of biotechnology joined with advanced clinical preventive medicine,” according to the website of the American Academy of Anti-Aging Medicine (A4M), one of the leading organisations in this endeavour.1 “It is scientific . . . It is evidence-based . . . It is well-documented in peer-reviewed journals.” The advances on offer to patients are the “most potent emerging biomedical technologies today.”

Some manifesto. And while A4M members and most other anti-ageists limit their ambitions to minimising age related disease and achieving a modest increase in longevity, a minority of true believers foresee much more: the indefinite postponement of death. Orthodox science may be irritated by what can be seen as ill founded over-optimism, but the notion of fending off the decrepitude of old age has always captured the public imagination. By 2015, according to one estimate, the global market in anti-ageing products will be worth nearly $300bn (£190bn; €210bn) annually.2

What, precisely, is encompassed by the term “anti-ageing”? A great deal of ordinary everyday medicine, be it the prevention of strokes or the removal of malignant tumours, is about prolonging life. But the full bloodied anti-ageing prospectus goes beyond this; it focuses not only on the diseases associated with age but on the process of ageing. Evidence of the benefits of disease interventions is overwhelming; those aimed at the ageing process are still characterised less by achievement than by theory, by extrapolation from laboratory experiments, and by a limited amount of animal work. The gulf separating the two remains wide if not unbridgeable.

You don’t of course …
PROGNOSTIC VALUE OF THE ACCELERATED DOBUTAMINE STRESS ECHOCARDIOGRAPHY PROTOCOL
Authors: Ricardo Sanz, Jose R. Ortega, Matias Pérez-Paredes, María J. Rollán, Marta Pinedo, Roman Arnold, Jose M. Novoa, Diego Jimenez, Ana C. Muñoz, Francisco Fernández-Avilés, Jose A. San Román
Journal: Journal of the American College of Cardiology (2010)
Changes in serum‐free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis
Authors: Shaji K. Kumar, Angela Dispenzieri, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, Steven R. Zeldenrust, Tow Tan, Shirshendu Sinha, Nelson Leung, Robert A. Kyle, S. Vincent Rajkumar, Morie A. Gertz
Journal: American Journal of Hematology (2010)

Current response criteria for light-chain amyloidosis (AL) relegate FLC response to a subsidiary status relative to serum M-protein response. Given that light chains form the substrate for amyloid fibril formation, we hypothesized that changes in FLC might better predict outcome compared to changes in intact immunoglobulin levels. Two patient cohorts were studied, 347 patients who underwent an autologous stem-cell transplant (SCT) and 96 patients treated with melphalan/dexamethasone. We identified the lowest value following therapy for intact serum M-protein and the difference between involved and uninvolved FLC (FLC-diff). We first examined the relative contribution of M-protein and FLC-diff on the overall survival (OS), and found that FLC reduction, rather than M-protein reduction, significantly impacted OS. The median OS was not reached among those with a 50% decrease in FLC-diff compared to 20 months for the remainder. On regression analysis, a 90% reduction in FLC-diff following SCT best predicted being alive at 3 or 5 years. The median OS among those with a 90% decrease was not reached compared to 37.4 months for the rest P < 0.001. The current study supports the notion that FLC response is a more useful measure of hematological response than M-protein response. It also highlights the importance of achieving at least a 90% reduction in the FLC-diff to improve the outcome of patients with light-chain AL.
Endoscopic Observation of Squamous Metaplasia of the Stomach: A Report of Two Cases
Authors: None Takeda, None Nagashima, None Goto, None Shibata, None Shinzawa, None Takahashi
Journal: Endoscopy (2000)

Squamous metaplasia of the stomach is a rare clinical entity that occurs during healing of gastric ulcers or chronic inflammation. We have treated two patients with this condition, which has only occasionally been observed endoscopically. The first was a 60-year-old woman who initially presented with multiple gastric ulcers. Two months after treatment, a white patch about 4 cm in diameter was found in the lesser curvature of the cardiac region of stomach. The second patient was a 65-year-old woman, who also developed a white patch in the same region. Two months later, a small ulcer and inflamed mucosa were seen near the lesion. The white areas in both patients were stained with Lugol's iodine solution, and biopsy specimens confirmed squamous epithelium. The squamous metaplasia was observed as a white mucosal area in the stomach, and the metaplastic area stained positively with Lugol's iodine solution.
Abstract 1045: Enhancement of drug-induced apoptotic cell death in human hepatocellular carcinoma cells with knock-down of BNIP3
Authors: Pak Lun Yau, Tsun Yee Tsang, Ngai Na Co, Siu Cheong Choi, Chi Lam Au Yeung, Tim Tak Kwok
Journal: Cancer Research (2010)

Abstract Although BNIP3 is known for its pro-apoptotic function by forming dimer to help the release of cytochrome c in apoptosis, its role in the cell death pathways was not yet well-defined. To investigate the role of BNIP3 in drug-induced apoptosis, stable transfectants were established from human hepatocarcinoma HepG2 cells transfected with pSilencer inserted with scramble oligos or BNIP3 siRNA. By MTT assay, knock-down of BNIP3 in HepG2 stable transfectant decreased cell survival towards vincristine, Taxol and doxorubicin. By DNA fragmentation assay and Annexin V binding assay, the level of drug-induced apoptosis in BNIP3i cells was elevated as compared with the control cells. Further analyses on caspases activation and mitochondrial cytochrome c release were done by Western blot analysis while the mitochondrial membrane depolarization was monitored by flow cytometry of JC-1 dye staining. By comparing with the control cells, the presence of vincristine or Taxol induced less cytochrome c release, mitochondrial membrane depolarization and activation of caspases-3, −8 and −9 in HepG2 BNIP3i cells. The results from present study indicated that BNIP3 might induce apoptosis by therapeutic drugs in HepG2 cells through a non-classical apoptotic pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1045.
Interaction of serum ferritin and body mass index in patients with chronic hepatitis B: Improved prediction of cirrhosis
Authors: Sanjoy Paul, Kevin O'Regan, Andrew St John, Katherine Stuart, Darrell Crawford
Journal: Hepatology (2012)

Kowdley et al.1 recently explored the relationship between demographic, biochemical, clinical factors, and liver fibrosis in patients with nonalcoholic liver disease (NAFLD), and reported the independent association of serum ferritin (SF) with advanced hepatic fibrosis and disease severity. Although this study explored the association of body mass index (BMI) with disease severity by different levels of SF, it did not address the key issues of the relationship between SF and BMI, and the likely interaction effect of BMI and SF on the risk of fibrosis. Furthermore, they only described the importance of this relationship in NAFLD when increased BMI and elevated SF often coexist with other liver diseases, such as chronic viral hepatitis. We studied 498 patients with chronic hepatitis B (CHB) and explored the effect of BMI on SF, and evaluated the interaction effects of SF and BMI on liver fibrosis as determined by transient elastrography score (TES). The patients were 54% male, of mean age 44 ± 12 years, and BMI of 25 ± 4 kg/m2. The median SF (interquartile range [IQR]) was 205 (115, 324) μg/L and 88 (38, 202) μg/L, respectively, for males and females. The median TES (IQR) was 5.4 (4.4, 6.7). The average levels of SF and TES had a significantly increasing trend over higher categories of BMI, defined by the quartiles of observed BMI. To evaluate the association of BMI with SF, multivariate quantile regression models were used. Adjusting for sex and age, the median level of SF would be significantly higher by 20.4 μg/L (95% confidence interval [CI]: 4.5-36.7, P = 0.014) for every 3 kg/m2 increase in BMI. Male patients are likely to have a significantly higher level of SF by 87.3 μg/L (95% CI: 57.5-117.1, P ≤ 0.01). Additive regression models, adjusting for the effects of age, sex, and BMI, did not reveal any clinically meaningful effect of SF on TES. To evaluate the interaction effect of BMI and SF on continuously measured TES and the cirrhosis cutpoint (TE < or ≥13), we developed generalized interaction models. The TES increased exponentially with increasing level of SF in patients with higher BMI level (BMI ≥28 kg/m2; Fig. 1). In this group, TES is likely to increase exponentially above 13 as SF level increases above 650 μg/L (Fig. 1B). The probability of TE score ≥13 is significantly higher with increasing SF levels in patients with higher BMI (Fig. 1A). The TES is unlikely to be affected with increasing SF levels in patients with BMI <25 kg/m2. Our data support and extend the conclusions of Kowdley et al. and suggest that CHB patients with SF >650 μg/L and BMI >28 kg/m2 are at high risk of cirrhosis and clinicians should carefully assess the extent of fibrosis in patients with these characteristics. The interaction effect of BMI and SF on: (A) the probability of TES ≥13 and (B) the continuous measure of TES.
Measles in the Pribilof Islands
Authors: A. D. Migliore
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In the article "Rubella Epidemic on St. Paul Island in the Pribilofs, 1963," (<i>JAMA</i><b>191</b>:619-623 [Feb 22] 1965), a previous measles epidemic 22 years earlier was mentioned. I was the physician stationed at St. Paul Island during the measles epidemic which occurred during March, April, and May of 1941. The epidemic was introduced from Unalaska by a native woman, a boat passenger, who wore dark glasses and a face veil on debarking to conceal a measly rash on her face. The erythematous disease then ran like wildfire among the 300 native Aleuts who lived in the island village. The main complaints were rash, fever, and malaise. The throats resembled those with measles ( rubeola) in the United States, many having Koplik's spots. Adenopathy was usually absent or mild. Coryza and cough were usually absent. A rash was present in all patients seen. In about one third of
Massive Collapse of the Lungs
Authors: M. G. Baggot
Journal: JAMA (1961)

<h3>To the Editor:—</h3> I do not agree that massive collapse of the<i>lungs</i>occurred in the cases described by Raffensperger and others inThe Journal, Nov. 12, 1960, page 1386. Many apparently forget that the air chambers do not constitute the lungs but merely a part thereof. If the thorax is normal, massive collapse of the lungs, by absorption of their gaseous content, is impossible, insofar as it would create a vacuum in the chest. Again, if the thorax is normal, only when an abnormal mass arises within the chest, e.g., pleural effusion, can the lungs collapse. In such a case, the alveoli empty readily not into the already saturated circulation but through the larynx (the only way residual air can suddenly vanish). What obviously did happen, in the cases described, may be summarized as follows. The patients endured prolonged surgery of heroic proportions, after which they went into shock
Glucose-Insulin-Potassium for Acute Myocardial Infarction
Authors: Carl S. Apstein
Journal: Circulation (1998)

landmark study is reported in this issue of Circulation, 1 continuing the rediscovery of glucose-insulin-potassium (GIK) treatment of acute myocardial infarction (AMI) that began in this journal last year with a meta-analysis and editorial. 2,3That meta-analysis considered all prior randomized trials of GIK for AMI (these were all done in the prethrombolytic era) and concluded that GIK had the potential to reduce AMI mortality by 28% to 48% depending on dosage and timing of therapy initiation relative to symptom onset.An accompanying editorial called for a modern large-scale trial of GIK in combination with thrombolysis for AMI.Such a prospective trial is now reported by the ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group, and the results are dramatic. GIK-Reperfusion InteractionAn important interaction between GIK and reperfusion therapy for AMI was observed in the ECLA study, but this result was not consistent with the meta-analysis. 2 In the ECLA study, the reduction of AMI mortality by GIK was
EVIDENCE OF MOTOR EFFERENT PATHWAY ACTIVATION IN NORMAL VOLUNTEERS IN RESPONSE TO TRANSCRANIAL MAGNETIC STIMULATION AS SHOWN BY HMPAOSPECT
Authors: M. W. Graves, M. Stecker, A. Alavi, D. Duncan, P. Veloso, B. Zukerberg
Journal: Clinical Nuclear Medicine (1996)

Graves, M.; Stecker, M.; Alavi, A.; Duncan, D.; Veloso, P.; Zukerberg, B. Author Information
The leukemogenic AF4–MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures
Authors: A Benedikt, S Baltruschat, B Scholz, A Bursen, T N Arrey, B Meyer, L Varagnolo, A M Müller, M Karas, T Dingermann, R Marschalek
Journal: Leukemia (2010)
Fighting Antibiotic Resistance
Authors: Rebecca Voelker
Journal: JAMA (2000)

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Additional Steps for Cardiovascular Health
Authors: Paul D. Thompson
Journal: New England Journal of Medicine (2002)

“Lucy” is a fossilized female australopithecus, a member of an advanced genus of hominids who walked upright approximately 4 million years ago.1 Today, walking remains a major form of physical activity for women. We have witnessed, however, a recent decline in the use of bipedal motion — to the point where the Segway Human Transporter, a self-balancing personal-transportation device, is being evaluated by the U.S. Postal Service as a means for permitting letter carriers to make their appointed rounds without walking.2 Two articles in this issue of the Journal demonstrate that such developments are likely to accelerate the decline in . . .
CONGENITAL TOTAL HEMIHYPERTROPHY
Authors: Hans Lisser
Journal: JAMA (1924)

Stanton and Tuft carefully surveyed the literature and compiled only forty-one cases of this queer congenital deformity. These they reported,<sup>1</sup>together with a case of their own. Reed<sup>2</sup>recorded another instance in October, 1923. Because of the exceeding rarity of this peculiar malady, a case that I observed is noted, which, together with those referred to above, makes a sum total of forty-four published instances of congenital total hemihypertrophy. The table of measurements suffices for the diagnosis. Theories of etiology would be entirely speculative. The reader interested in further details is referred to the article of Stanton and Tuft and to the references in their bibliography. <h3>REPORT OF CASE</h3> M. M., aged 45, a married woman of Greek nationality, came to the outpatient department of the University of California, Oct. 18, 1923. She was seen first in the neurology clinic, because her complaints were nervousness and depression. She
IMPACT OF PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR VERY ELDERLY PATIENTS WITH NON-ST ELEVATED-ACUTE CORONARY SYNDROME
Authors: Yoshio Maeno, Naoyuki Yokoyama, Yoshitaka Shiratori, Hirosada Yamamoto, Syuichi Ishikawa, Akiyoshi Miyazawa, Ken Kozuma, Takaaki Isshiki
Journal: Journal of the American College of Cardiology (2011)