tbuckley/cabot-search huggingface dataset:
Abstract MP003: Alpha-linolenic Acid Intake and Biomarker in Relation to Risk of Cardiovascular Disease: A Meta-analysis and Systematic Review
Authors: An Pan, Mu Chen, Rajiv Chowdhury, Jason Wu, Qi Sun, Dariush Mozaffarian, Frank B Hu
Journal: Circulation (2012)

Introduction: Several studies have investigated the association between the plant-based omega-3 alpha-linolenic acid (ALA) and risk of cardiovascular disease (CVD); however, results remain largely inconsistent. We have conducted a meta-analysis of all available epidemiological studies reporting on association between ALA consumption or its biomarker composition and risk of CVD. Methods: A search of MEDLINE, EMBASE, Web of Science, Cochrane Library and clinical trial registry databases (to February 2011) was supplemented by manual searches of bibliographies of retrieved articles and relevant reviews. Prospective cohort or case-control studies were included if they reported the association between ALA (assessed in dietary intake, and as circulating blood or adipose tissue biomarker) and CVD (including myocardial infarction [MI], sudden cardiac arrest, acute coronary syndrome, and stroke). Multivariate-adjusted risk estimate in each study was converted to relative risk (RR) comparing the top vs. bottom thirds of ALA, and were combined using fixed-effect models given that heterogeneity was not detected in most situations. A fixed-effect dose-response meta-analysis was conducted if data were available. Results: Fifteen prospective cohort and 12 case-control studies were identified with aggregate data on 188,896 individuals and 12,233 total CVD events. Comparing the top to bottom thirds, a higher ALA intake was associated with a lower risk of CVD death (RR=0.80; 95% CI 0.67–0.96; 6 cohort studies), but not non-fatal MI (RR=0.95; 95% CI 0.85–1.06; 1 cohort and 2 case-control studies), or total CVD (RR=0.93; 95% CI 0.85–1.02; 1 case-control and 6 cohort studies). Higher ALA biomarker levels in adipose tissues, plasma or serum (top vs. bottom thirds) were inversely associated with non-fatal MI (RR=0.75; 95% CI 0.62–0.92; 7 case-control studies), but not CVD death (RR=1.20; 95% CI 0.98–1.46; 1 case-control and 2 cohort studies) or total CVD (RR=0.89; 95% CI 0.75–1.04; 4 cohort and 3 case-control studies). In the dose-response meta-analyses, each 1 g/d increment of ALA intake was associated with a 10% lower risk of CVD death (RR=0.90; 95% CI 0.83–0.99; 5 cohort studies), and each 0.5% increment of adipose tissue ALA concentration was associated with a 21% (RR=0.79; 95% CI 0.70–0.89; 5 case-control studies) lower risk of non-fatal MI. Conclusion: Higher dietary ALA intakes are associated with a lower risk of CVD death, while higher ALA biomarker levels are associated with a lower risk of non-fatal MI. These findings highlight the need for additional well-designed observational studies as well as large randomized clinical trials to evaluate effects of ALA on CVD.
Standardize uptake value of 18F-FDG-PET-CT is in accordance with the 21-gene recurrence score (Oncotype Dx) in ER-positive and HER2-negative breast cancer patients
Authors: S.G. Ahn, J.-H. Lee, J.T. Park, H.M. Lee, T.J. Jeon, Y.H. Ryu, J. Sohn, M. Yun, J. Jeong
Journal: Annals of Oncology (2015)
Smallpox — 26 Years Ago
Authors: Charles Herron
Journal: New England Journal of Medicine (1996)

Figure 1 The last case of smallpox within a 20-nation area of west and central Africa was found in Nigeria on May 21, 1970. This event marked the success of a five-year program to eradicate smallpox from a large area in which it was endemic. The 27-year-old patient was the last victim in an epidemic of about 86 documented cases. She had been vaccinated about 10 days before these photographs were taken, as part of activities to control the outbreak after the discovery of smallpox in one other resident of her village a week previously. These figures illustrate some classic features of smallpox: the patient appears weak or fatigued, the lesions have a peripheral distribution, there is facial edema, and the lesions are deep-seated, firm in appearance, and uniform in terms of stage of development (Panel A). The relatively small and variable size of the lesions on the left arm and the large pustule consistent with a successful primary vaccination (Panel B), as well as a relatively rapid course of illness (the photographs were taken on day 3 of the rash), suggest that this last case was modified (and almost prevented) by vaccination. This program's successful techniques were later used in the parts of the world where the disease was still endemic, ultimately leading to the complete cessation of natural transmission of smallpox in October 1977. Figure 1 The last case of smallpox within a 20-nation area of west and central Africa was found in Nigeria on May 21, 1970. This event marked the success of a five-year program to eradicate smallpox from a large area in which it was endemic. The 27-year-old patient was the last victim in an epidemic of about 86 documented cases. She had been vaccinated about 10 days before these photographs were taken, as part of activities to control the outbreak after the discovery of smallpox in one other resident of her village a week previously. These figures illustrate some classic features of smallpox: the patient appears weak or fatigued, the lesions have a peripheral distribution, there is facial edema, and the lesions are deep-seated, firm in appearance, and uniform in terms of stage of development (Panel A). The relatively small and variable size of the lesions on the left arm and the large pustule consistent with a successful primary vaccination (Panel B), as well as a relatively rapid course of illness (the photographs were taken on day 3 of the rash), suggest that this last case was modified (and almost prevented) by vaccination. This program's successful techniques were later used in the parts of the world where the disease was still endemic, ultimately leading to the complete cessation of natural transmission of smallpox in October 1977. Charles Herron, M.D.10014 Edgewater Dr., Cleveland, OH 44102
Hepatitis C Virus Infection in Chronic Kidney Disease
Authors: Marco Ladino, Fernando Pedraza, David Roth
Journal: Journal of the American Society of Nephrology (2016)

Soon after the hepatitis C virus (HCV) was identified in 1989, it was recognized that the prevalence of infection in patients with ESRD far exceeded that in the general population. Infection with HCV predisposes to the hepatic complications of cirrhosis and hepatocellular carcinoma. However, important extrahepatic manifestations include immune complex glomerular disease, accelerated progression of CKD, increases in cardiovascular event risk, and lymphoproliferative disorders. Advances in understanding the molecular biology of HCV have ushered in a new era in the treatment of this infection. Second generation direct–acting antiviral agents have revolutionized therapy, with sustained virologic response rates (undetectable viral load 12 weeks after completing therapy) of &gt;90% in most patients. Studies using direct-acting antivirals in patients with CKD and those on dialysis are showing excellent safety and efficacy as well. In this context, it is imperative that nephrologists become familiar with this literature, reviewed here, so that the important decisions, including which patients should be treated and the optimal timing to initiate therapy, are vetted in association with the compounding issues of CKD, ESRD, and kidney transplantation.
Psychotic depression: a separate entity?
Authors: A Frances, R P Brown, J H Kocsis, J J Mann
Journal: American Journal of Psychiatry (1981)

Many authors report that patients with psychotic and nonpsychotic major depressions differ in their response to somatic treatment. Psychotic depression is less responsive to tnicyclic antidepressants (1) and often requires a combined regimen of antipsychotics and antidepressants (2) on ECT (3). The nosological status of psychotic depression remains in question. Is psychotic depression best considered as a severe variant of major depression on as a separate entity with a characteristic pattern of demographic and symptom features, family history, course, biochemical profile, and response to treatment? There are limited and inconsistent data on this issue, but some differences between psychotic and nonpsychotic depression have been suggested. Nelson and Bowers (2) reported more psychomotor disturbance and previous episodes in psychotic depressive patients than in nonpsychotic depressive patients. In contrast Glassman and Roose (4) found more psychomotor retardation, less placebo responsiveness, and fewer previous episodes in psychotic depressive patients. Several preliminary biochemical and physiological findings seem to distinguish psychotic from nonpsychotic depressive patients. Meltzen and associates (5) reported that psychotic patients had increased serum creatinine phosphokinase and aldolase, skeletal musdc abnormalities, and lower serum dopamine 3-hydroxylase. Sweeney and associates (6) reported lower urine 3-methoxy-4-hydroxyphenethylene glycol and higher CSF homovanillic acid. These authors all used the Research Diagnostic Criteria (RDC) definition of psychotic major depressive disorder in defining their cohorts. Mendels and associates used a clinical judgment definition of psychotic depfession and found decreased CSF 5-hydnoxyindoleacetic acid (7) and decreased stage 4 and REM sleep (8). If psychotic depression is no more than a severe variant of nonpsychotic major depression, it should, aside from the presence of the psychotic symptoms, have similar clinical features. Guze and associates (9) studied 1 15 variables in 253 patients with primary and secondary affective disorder and found that delusional unipolan patients were distinguished only by more frequent psychiatric hospitalization. Most ofthe vania-
Soundings: Looking sideways
Authors: George Dunea
Journal: BMJ (2005)

Joseph Vissarionovich Stalin, the theology student turned dictator, once said that “a man's eyes ought to be torn out if he can only see the past.” I note, therefore, with some trepidation, that this is my 300th column in this journal. Many of my middle aged readers have retired—some enjoying the felicity of the Victorian novelist George Gissing's Henry Ryecroft, who was enabled, by an unexpected legacy, to escape from a life of drudgery; others getting under their spouses' feet and brooding that “I married you for better or worse but not for lunch.”

Now, as in 1975, we worry about high medical costs and the malpractice crisis, and argue about abortion and “death with dignity.” But there have also been dramatic changes: at the time we had no mobile phones, no email, no computers, not even fax machines. Manuscripts were typed interminably and sent off by snail mail, as were the galley proofs. And since my first “Letter from Chicago” this city has grown into a wonderful metropolis, with music, theatre, and flowers lining the streets, and Michigan Avenue with its Millennium Park attracting multitudes.

Stalin's regime survived almost a century. Nobody knows how long our infatuation with targets, audits, evidence, outcome studies, peer review, and meta-analyses will last. Margaret Thatcher thought that “nothing is more obstinate than a fashionable consensus”; Hughlings Jackson that it took 50 years to get a wrong idea out of medicine; and Albert Einstein that it was easier to split the atom than a prejudice.

One thing is certain: in diagnosis, as in other ways of life, mistakes are inevitable. Napoleon said he had been mistaken so often that he no longer blushed for it; and Ella Wheeler Wilcox once wrote a poem called “God sent us here to make mistakes.” But a recent US law allows doctors to report their mistakes without the risk of the information being used against them, so we can all learn from such mistakes.

The old extol the virtues of the past, the young those of the future, a difference in perspective that may only be relative. Einstein, at least, thought that the distinction between past, present, and future was only an illusion; and Saint Augustine that “time comes from the future, which does not yet exist, into the present, which has no duration, and which goes into the past, which has ceased to exist.”
Retinoic Acid Embryopathy
Authors: Edward J. Lammer, Diane T. Chen, Richard M. Hoar, Narsingh D. Agnish, Paul J. Benke, John T. Braun, Cynthia J. Curry, Paul M. Fernhoff, Art W. Grix, Ira T. Lott, James M. Richard, Shyan C. Sun
Journal: New England Journal of Medicine (1985)

Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5). Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.
Immunodetection of Estrogen Receptor and 52,000-Dalton Protein in Fine Needle Aspirates of Breast Cancer Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: V Cavailles, M Garcia, G Salazar, J Domergue, J Simony, H Pujol, H Rochefort
Journal: JNCI Journal of the National Cancer Institute (1987)

The double immunohistochemical detection of estrogen receptor (ER) and the estrogen-regulated 52,000-dalton protein (52kDa-P) was performed on 35 fine needle aspirates of primary breast cancers. The nuclear ER, stained brown, was differentiated from the 52kDa-P, stained in red, in the cytoplasm of the same cells. The significant correlation obtained between the percentages of positive aspirated cells and the cytosolic concentrations of these two markers showed the validity of semiquantitative detection in fine needle aspirates, which appeared to be more representative of the content of these markers in tumors than was the detection in a single tissue section. Tumor heterogeneity also was defined by this double immunostaining, since among the tumors positive for both ER and 52kDa-P (18 of 35 cases), a heterogeneous group of 12 tumors contained the markers in two distinct cell populations, whereas a more homogeneous group of 6 tumors contained double-stained cells. The first information provided by this study is that the 52kDa-P is not correlated with the ER. This absence of correlation is in accordance with other studies and indicates that the 52kDa-P is associated with tumor proliferation and possibly invasion, rather than with hormone responsiveness or differentiation. The feasibility and validity of double immunostaining of these two markers in human breast cancer aspirates should stimulate larger studies--with clinical follow-up of the patients--aimed at establishing the clinical usefulness of this presurgical test.
Trends in the frequency of schizophrenia by different diagnostic criteria
Authors: J B Kuriansky, B J Gurland, R L Spitzer, J Endicott
Journal: American Journal of Psychiatry (1977)

The authors report results of rediagnoses of 128 cases from two decades (1932-1941 and 1947-1956) by clinicians using the Research Diagnostic Criteria as guidelines and compare these results to rediagnoses by clinicians in a previous study using more general guidelines. Although hospital records indicated an increased frequency of schizophrenia over the two decades, the rediagnosticians found no change or a decrease. Severity of symptoms did not change during the two decades, but patients in the second decade showed more borderline symptoms, leading to more diagnostic disagreement. The authors conclude that changes in diagnostic criteria and pateints' conditions influence admission trends for schizophrenia.
Mass spectroscopy-based cancer genotyping of 800 patients enrolled in a personalized cancer medicine registry.
Authors: C. Beadling, M. C. Heinrich, K. Schuff, B. J. Druker, C. L. Corless
Journal: Journal of Clinical Oncology (2010)

10503 Background: A challenge in delivering personalized cancer care to the clinic is identifying tumor genotypes that predict response to targeted therapeutics. Methods: In 2008, we established a Personalized Cancer Medicine Registry (PCMR) and began consenting patients for the following: 1) prospective genotyping of their cancer; 2) storing their tumor material for future research; and 3) permission to re-contact them if their tumor genotype fits the profile for a new therapeutic. As of the end of 2009, more than 800 patients were enrolled in the PCMR, including cases of colorectal carcinoma (CRC, n = 199), endometrioid carcinoma (EC, n = 95), thyroid carcinoma (TC, n = 276), bladder carcinoma (n = 80), and malignant melanoma (MM, n = 163 ). Tumor DNA from archival tissue was genotyped using a Sequenom MassArray system. Each sample was analyzed using a panel (320 assays) that detects known mutations in 29 genes. Clinical and genotyping data are stored in a web-interfaced, customized SQL database. Results: 95% of approached patients consented to registry enrollment. Archival tumor suitable for analysis was obtained in 95% of cases. Mutations in EC include PIK3CA (21%), CTNNB1 (13%), KRAS (11%), FBXW7 (5%), TP53 (5%), AKT1 (4%), FGFR2 (3%), NRAS (1%) and PDGFRA (1%); 14 cases harbor 2 or more mutations. Among cutaneous MM we found mutations in BRAF (47%; 10.8% other than V600E), NRAS (13%), CTNNB1 (3%), PIK3CA (2%), AKT1 (1%) and MEK2 (1%). In CRC we found mutations in KRAS (30%), TP53 (16%), PIK3CA (12%), NRAS / BRAF / FBXW7 (3% each), CTNNB1 (2%), and MEK1 / AKT1 / AKT2 / RET (1% each). Remarkably, 10 of 14 CRC tumors (71%) with a PIK3CA mutation also have a KRAS mutation. In TC, we found mutations of BRAF (63%), RET-PTC (7%), and PIK3CA/KRAS/NRAS/HRAS (1.5% each). Conclusions: Prospective tumor genotyping for PCMR patients reveals a remarkable diversity of potentially druggable mutations, knowledge of which will help in clinical trial enrollment. While rare in the examined tumors, mutations in FGFR2, MEK1/2, AKT1/2, PDGFRA and RET could be targeted as part of individualized cancer treatments. In CRC, the common overlap of PIK3CA mutations with KRAS mutations may negatively impact response to inhibitors of the PI3 kinase pathway. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Sequenom MolecularMD Novartis, Sequenom Novartis
S94 The role of oxidative stress and antioxidants in severe asthma; a case control study
Authors: A Bishopp, R Sathyamurthy, AH Mansur
Journal: Thorax (2015)

<h3>Background</h3> A number of antioxidant defences counteract potentially damaging oxidising species within the respiratory tract. Many enzymes, such as the superoxide dismutases and glutathione peroxidases, require essential elements to maintain function. Vitamins A, C and E also have antioxidant properties. It has been suggested that asthmatic patients are deficient in antioxidants. This study assessed levels of serum antioxidants, markers of airways inflammation and resultant oxidative stress burden with increasing severity of asthma. <h3>Method</h3> This is a case control study comparing patients with severe asthma (BTS steps 4/5) to mild corticosteroids-naïve asthmatics and normal healthy controls. Participants were assessed in terms of asthma diagnosis, severity, exhaled breath condensate (EBC) nitrite, fractional exhaled nitric oxide (feNO), spirometry, and serum copper, zinc, selenium, vitamin A and vitamin E measurements. Analyses were conducted using Kruskal-Wallis, one way analysis of variance. <h3>Results</h3> The severe asthma group was comprised of 30 patients (23 females, mean age 41.4 years [range 19 to 56], mean FEV1 2.2 litres [% predicted 72.2%], mean FEV1/FVC ratio 72.7%, mean daily inhaled corticosteroid equivalent to 2,390 µg BDP, with 17/30 [57%] on maintenance oral corticosteroids). Fifteen mild and corticosteroid naïve patients were recruited (9 females, mean age 34.6 years [range 19–57], mean FEV1 3.48l [% predicted 100.5%], FEV1/FVC ratio 82.2%). All 15 were treated with salbutamol only. The control group was comprised of 15 patients (12 females, mean age 37.6 years [range 25–52], mean FEV1 3.53 [%predicted 111.7%], and FEV1/FVC ratio 81.9%). FeNO increased significantly with increasing severity (p = 0.001), but EBC nitrite did not (p = 0.9). Vitamin A and E levels increased significantly with increased disease severity (p = 0.04 and 0.0008 respectively). There was no significant difference between groups with copper (p = 0.98), zinc (p = 0.8) or selenium (p = 0.9). <h3>Conclusion</h3> We observed no evidence of deficiency in the serum minerals or vitamins in the severe asthmatics with increased FeNO but not EBC nitrite. We conclude that impaired oxidative stress defences in severe asthma may be driven by factors other than vitamin or mineral deficiency.
Pulmonary Arterial Enlargement and COPD Exacerbations
Authors: Andrew R Medford
Journal: New England Journal of Medicine (2012)

2253This trial was conceived in 1996 and opened to accrual in 1999, a time when we were not yet asking when, or for whom, to initiate treatment. In fact, during the accrual period the threshold PSA level for entry was reduced in order to facili-tate accrual. Patients and their doctors were un-willing to wait for the PSA level to rise.We agree that the timing of androgen-depri-vation therapy remains an open question. Two recent trials comparing early versus deferred an-drogen ablation have closed early owing to poor accrual.