tbuckley/cabot-search huggingface dataset:
Sentinel node biopsy after neoadjuvant therapy: Relevance of sentinel node micrometastases, isolated tumor cells, and value of immunohistochemistry.
Authors: Jean-Francois Boileau, Brigitte Poirier, Mark Basik, Claire Holloway, Louis Gaboury, Lucas Sideris, Sarkis H. Meterissian, Angel Arnaout, Muriel Brackstone, David R. McCready, Stephen Eric Karp, Frances Catriona Wright, Rami Younan, Louise Provencher, Erika Patocskai, Atilla Omeroglu, Andre Robidoux
Journal: Journal of Clinical Oncology (2013)

52 Background: Sentinel node biopsy (SNB) is used in breast cancer patients that present with clinically negative nodes. In this setting, most guidelines do not support the use of immunohistochemistry (IHC) and recommend against completion node dissection (CND) when only isolated tumor cells (pN0(i+)) or micrometasases (pN1mi) are identified. When SNB is used after neoadjuvant therapy (NAT), the relevance of ypN0(i+) and ypN1mi sentinel nodes (SNs) and the value of IHC are not well established. The goals of this study are to determine if CND should be recommended in the presence of ypN0(i+) or ypN1mi SNs and if IHC should be used to evaluate SNs after NAT. Methods: From March 2009 to December 2012, 152 women with biopsy proven node positive breast cancer were accrued to the multicentric prospective SN FNAC trial. After NAT, SNB was followed by a CND in all participants. SNs were cut in serial slices no thicker than 2 mm. Hematoxylin and eosin stains (H and E) were done on all slices, and if negative, IHC was used. The size of the largest SN metastasis and the primary method of identification (H and E or IHC) were recorded. ypN0(i+), ypN1mi and ypN1 SNs were considered as positive. Pathology was centrally reviewed. Results: 145 women were eligible for the trial. Axillary pathologic complete response rate = 34% (49/145). SNB success rate = 88% (127/145). False negative rate = 8.4% (7/83). If ypN0(i+) SNs are classified as node negative, the false negative rate is increased to 13.3% (11/83). For patients with ypN0(i+) (n=7), ypN1mi (n=8) and ypN1 (n=61) SNs, the rates of non-SN involvement are 57%, 38% and 56% respectively (p=NS). 40% (27/68) of positive SNBs are primarily detected by IHC. This is increased to 64% (9/14) for the identification of SN metastases ≤ 2mm. Conclusions: After NAT, particularly when presenting with biopsy proven node positive breast cancer, patients with ypN0(i+) and ypN1mi SNs have a significant rate of non-SN involvement. In the absence of evidence to show that a CND can be safely avoided, efforts should be made to identify even minimal amounts of disease when SNBs are done following NAT. IHC is useful to increase the detection of small SN metastases in this setting. Clinical trial information: NCT00909441.
Food Allergy-Fact or Fiction: A Review
Authors: R Finn
Journal: Journal of the Royal Society of Medicine (1992)

Food sensitivity is a common condition presenting with various clinical syndromes including migraine, urticaria, gluten enteropathy, Crohn's disease and irritable bowel syndrome. It is a heterogeneous condition affecting different organ systems and is also aetiologically diverse with subgroups due to allergy, pharmacological reactions, enzyme deficiencies and psychological causes. Clinical acceptance of food sensitivity has been delayed by the use of dubious diagnostic techniques by a minority of practitioners and the lack of laboratory diagnostic tests, but several double blind studies have now fully validated the existence of food sensitivity syndromes. More wide-spread recognition of food sensitivity would be cost effective for the National Health Service.
Identifying Women With Dense Breasts at High Risk for Interval Cancer
Authors: Karla Kerlikowske, Weiwei Zhu, Anna N.A. Tosteson, Brian L. Sprague, Jeffrey A. Tice, Constance D. Lehman, Diana L. Miglioretti
Journal: Annals of Internal Medicine (2015)

Twenty-one states have laws requiring that women be notified if they have dense breasts and that they be advised to discuss supplemental imaging with their provider.To better direct discussions of supplemental imaging by determining which combinations of breast cancer risk and Breast Imaging Reporting and Data System (BI-RADS) breast density categories are associated with high interval cancer rates.Prospective cohort.Breast Cancer Surveillance Consortium (BCSC) breast imaging facilities.365,426 women aged 40 to 74 years who had 831,455 digital screening mammography examinations.BI-RADS breast density, BCSC 5-year breast cancer risk, and interval cancer rate (invasive cancer ≤12 months after a normal mammography result) per 1000 mammography examinations. High interval cancer rate was defined as more than 1 case per 1000 examinations.High interval cancer rates were observed for women with 5-year risk of 1.67% or greater and extremely dense breasts or 5-year risk of 2.50% or greater and heterogeneously dense breasts (24% of all women with dense breasts). The interval rate of advanced-stage disease was highest (>0.4 case per 1000 examinations) among women with 5-year risk of 2.50% or greater and heterogeneously or extremely dense breasts (21% of all women with dense breasts). Five-year risk was low to average (0% to 1.66%) for 51.0% of women with heterogeneously dense breasts and 52.5% with extremely dense breasts, with interval cancer rates of 0.58 to 0.63 and 0.72 to 0.89 case per 1000 examinations, respectively.The benefit of supplemental imaging was not assessed.Breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient-provider discussions about alternative screening strategies.National Cancer Institute.
Sputum fluid endotoxin is associated with the FEV1 response to oral steroids in non-smokers with asthma
Authors: Charles McSharry, Mark Spears, Rekha Chaudhuri, Euan Cameron, Neil Thomson
Journal: European Respiratory Journal (2012)

Background   Asthma patients who smoke have a reduced sensitivity to corticosteroids. The mechanisms for this are not well understood. Increased bacterial endotoxin has been found in BAL fluid of non-smokers with steroid-resistant asthma and cigarette smoke is a rich source of endotoxin. We compared sputum endotoxin concentration in smokers and non-smokers with asthma, with the FEV 1  response to oral corticosteroids.   Methods   Sputum was induced from 31 non-smokers and 22 smokers with asthma. Endotoxin was quantified by ELISA (LAL-QCL®, Lonza Biologics plc), and cytokines by luminex (InVitrogen). Spirometry and exhaled nitric oxide measurements were recorded. The response to oral dexamethasone was the change in FEV 1  compared with baseline.   Results   Non-smokers had improved FEV 1  after steroids; p=0.015, but smokers were refractory; p=0.591. The steroid response decreased with increasing sputum endotoxin in non-smokers; r= -0.422, p=0.032, but not in smokers; r= -0.126, p=0.585.  The steroid response increased with pre-steroid FeNO in non-smokers; r=0.479, p=0.015, but not in smokers; r=0.310, p=0.226. The endotoxin and IL-1RA concentrations correlated in non-smokers; r=0.633, p   Conclusions   Higher endotoxin in sputum fluid was associated with an impaired FEV 1  improvement after steroids only in non-smokers; and was associated with decreased FeNO and increased sputum IL-1RA. We suggest that smoking establishes a chronic refractory state to both steroids and to endotoxin. Identifying intracellular signalling pathways common to both may help understand and potentially reverse these processes.
Microbial culturomics: paradigm shift in the human gut microbiome study
Authors: J.-C. Lagier, F. Armougom, M. Million, P. Hugon, I. Pagnier, C. Robert, F. Bittar, G. Fournous, G. Gimenez, M. Maraninchi, J.-F. Trape, E.V. Koonin, B. La Scola, D. Raoult
Journal: Clinical Microbiology and Infection (2012)
Social skills training for psychiatric patients, II: Clinical outcome studies
Authors: J P Brady
Journal: American Journal of Psychiatry (1984)

In this second paper on social skills training for psychiatric patients the author critically reviews the controlled clinical outcome studies of social skills training in a number of psychiatric populations: mentally retarded persons, depressed patients, psychiatric outpatients, and psychiatric inpatients. He points out that more research is needed to determine the effectiveness of social skills training, especially for patients with debilitating chronic mental illness.
Molecular Biological Events in the Selection of Chemotherapy Resistant-Cells in Human Malignant Gliomas
Authors: Joan Rankin Shapiro, Adrienne C. Scheck
Journal: Neuro-Oncology (1991)

Within the cellular heterogeneity of freshly resected human gliomas we have observed cells with a specific non-random karyotypic deviation to be intrinsically chemoresistant to the chemotherapeutic agent, BCNU (1,3 bis-(2 chloroethyl)-1-nitrosourea). The BCNU-resistant cells were near-diploid (2n± with chromosome complements of 35–57 chromosomes/metaphase) and resistant to concentrations of ≥7.5 μg/ml BCNU. In contrast, the hyperdiploid populations from the same tumor (3n± and 4n± with 58 or more chromosomes/metaphase) were sensitive. Cytogenetic analysis of the BCNU-resistant cells demonstrated that more than 90% of the karyotypes depicted cells with an over-representation of chromosomes 7 and 22, the chromosomes to which platelet-derived growth factor (PDGF) chains A and B were mapped. Further analyses determined that these cells secreted a factor(s) that stimulated 3H-thymidine incorporation in PDGF receptor-positive cells, and that this factor competed with 125I-PDGF in receptor binding experiments. Southern, northern and western blot analyses demonstrated amplification and over-expression of the genes encoding both the A and B chains, as well as aberrant forms of PDGF. Phosphorylation analyses demonstrated that these cells were autocrine. To determine if this same cell persisted in vivo following a patient's treatment with BCNU, we analyzed recurrent tumors from 5 patients whose original tumors were known to have this cell as a minor subpopulation and who required a second surgical resection. The cytogenetic and bioassay analyses demonstrated that in all 5 patients this BCNU-resistant cell was the dominant cell type in the recurrent tumor. In situ hybridization studies of paraffin-embedded sections from primary and recurrent samples of one tumor further substantiated that there is an increase in the proportion of cells that were producing PDGF-A chain mRNA. These data suggest that intrinsically resistant cells can survive currently available chemotherapeutic treatments and repopulate the tumor mass.
Left ventricular function assessment in patients with obstructive sleep apnea syndrome
Authors: Rabab El Wahsh, Ramadan Bakr, Mahmoud Ahmed, Rehab Yaseen
Journal: European Respiratory Journal (2012)

Background: There are conflicting data on the effect of obstructive sleep apnea syndrome (OSAS) on the cardiac structure and function in human subjects.

Aim: To assess the left ventricular functions and document prevalence of left ventricular dysfunction in patients with OSAS, and its relation to OSAS severity.

Patients and Methods: Forty patients with OSAS, diagnosed by complete polysomnography, underwent ECG and echocardiography using conventional mode and doppler tissue imaging to assess the function of the left ventricle.

Results: 11 patients had mild OSAS, 11 patients had moderate OSAS and 18 patients had severe OSAS. The three groups were matched in age, gender, BMI and incidence of systemic hypertension. Severe OSAS had significantly higher AHI, lowest oxygen saturation, average oxygen saturation, and desaturation time % of total sleep time (<90%). Pulmonary hypertension and left ventricular diastolic dysfunction were significantly higher in moderate and severe OSAS groups. No difference between groups was found in LV systolic function. Diastolic dysfunction parameters were better correlated with AHI and lowest oxygen saturation during sleep.

Conclusion: Assessment of left ventricular function is mandatory in OSAS patients even if they have no cardiac symptoms. Severer obstructive sleep apnoea syndrome may result in left ventricular diastolic dysfunction. Doppler tissue imaging is a better echocardiographic tool for assessment of left ventricular diastolic dysfunction. Severity of left ventricular diastolic dysfunction is correlated with AHI and lowest O2 saturation during sleep.
Abstract 1183: Longitudinal Assessment of Dyslipidemia in a Representative Sample of US Adults: Prevalence and Attainment of Goal/Recommended Levels
Authors: Baishali M Ambegaonkar, Jaewhan Kim, Joseph Biskupiak, Vasilisa Sazonov
Journal: Circulation (2008)

Elevated low density lipoprotein cholesterol (LDL-C), low high density lipoprotein cholesterol (HDL-C) and elevated triglycerides (TG) are cardiovascular (CV) risk factors. The objective of this study was to evaluate attainment of goal/recommended lipid levels and predictors thereof post initiation of lipid modifying therapy (LMT) in a representative sample of US adults with commercial and government health insurance. Among 111,623 patients age &gt;35 from GE Centricity Electronic Medical Records with ≥1 abnormal lipid value (before June 2004), we extracted 51,891 patients who initiated LMT between June 2004 and December 2006 (index date), continued therapy for 1 year, and had full lipid panels (LDL-C, HDL-C and TG) pre and post index date. LDL-C goals were defined according to NCEP ATP III guidelines. Recommended level for TG was &lt;200 mg/dL, and for HDL-C &gt;40mg/dL for men and &gt;50mg/dL for women. Patients with history of coronary heart disease (CHD), diabetes and 10 year CHD risk&gt;20% were classified as high CV risk. Multiple logistic regressions evaluated predictors of lipid level attainment (individual and ≥2). Among 51,891 patients, 53% had elevated LDL-C, 60% had low HDL-C, 37% had elevated TG and 73% had low HDL-C and/or elevated TG prior to LMT initiation. Despite 1 year therapy - with over 80% initiating statin therapy - 34% had elevated LDL-C (29% for high risk), 56% had low HDL-C (67% for high risk), 30% had elevated TG (32% for high risk) and 65% had low HDL-C and/or elevated TG (75% for high risk). CHD and diabetes were associated with better attainment of LDL-C goal and TG recommended levels. Females (Odds Ratio=0.24, 95% Confidence Interval [0.16 – 0.34]), patients with 10 year CHD risk&gt;20% (OR=0.22, 95% CI [0.12– 0.40]) and those with higher baseline total cholesterol (OR=0.98, 95% CI [0.97– 0.99]) were less likely to attain ≥2 recommended lipid levels. In this cohort of insured US adults, additional 19% attained LDL-C goal following LMT for 1 year but few improved in terms of HDL-C (4%), TG (7%) and HDL-C and/or TG (8%). Additionally, dyslipidemia persisted among high risk patients despite higher likelihood of reaching LDL-C goal with presence of CHD or diabetes. Control of multiple lipid parameters remained poor.
Recovery from Pneumocystis carinii pneumonia in dexamethasone-treated Wistar rats
Authors: A Sukura, YT Konttinen, R Sepper, LA Lindberg
Journal: European Respiratory Journal (1995)

Our aim was to study histopathological changes in lung tissue at the light microscopic and ultrastructural level during recovery from immunosuppression and Pneumocystis carinii pneumonia. Male Wistar rats were immunosuppressed by per oral dexamethasone for 12 weeks to induce P. carinii pneumonia, after which dexamethasone was stopped. Recovery was monitored 1, 2 and 4 weeks after cessation of the immunosuppression. In immunosuppressed animals, CD4+ and CD8+ lymphocytes were both decreased in situ. CD8+ lymphocytes increased above control level at week one. Like CD8+ cells, the ED1+ macrophages increased rapidly in situ. This was accompanied by a progressively increasing migration (more transient for lymphocytes) of macrophages into bronchoalveolar fluid, associated with morphological signs of activation and phagocytosis and proliferation of type II pneumocytes. Bronchoalveolar lavage (BAL) fluid tumour necrosis factor-alpha (TNF-alpha) increased from subnormal levels to a 4 week peak, with an inverse correlation between TNF-alpha and cyst count (r = -0.626). Our observations suggest a sequence of changes characterized by an increase in CD4+ cells, accompanied by a more rapid and prolonged recruitment/activation of CD8+ cells, macrophages and type II pneumocytes.
Effect of NO2 on inflammatory response in subjects with asthma
Authors: Michel Aubier, Véronique Ezratty, Gaëlle Guillossou, Monique Dehoux, Catherine Neukirch
Journal: European Respiratory Journal (2012)

Patients with asthma may be more susceptible to NO2. Our aim was to investigate whether repeated exposure to realistic indoor concentrations of NO2 enhances inflammatory response in the airways of subjects with asthma. Participating were 19 nonsmoking subjects with intermittent asthma and airway hyperresponsiveness during methacholine-challenge. The study had a double-blinded, crossover design. On day 1, the subjects were exposed to either 200 ppb NO2, 600 ppb NO2, or purified air for 30 min, and on day 2, to the same pollutant, for 2 x 30 min. The order of exposure to the two concentrations of NO2 and air-only was randomized and exposures were separated by 2 weeks. Markers of inflammation were measured in sputum daily, 6 hours after the first (on Day 1) and the third exposure (on Day 2) and 48 h after the first exposure (Day 3) and compared to baseline. The effect of NO2 on bronchial responsiveness to methacholine was tested at baseline and on Day 3. Exposure at rest to 200 ppb or 600 ppb of NO2 had no direct effect on respiratory function either during or after the exposure sessions. Compared to baseline, the variation in the percentage of eosinophils in induced sputum after exposure to NO2 was -2% after air, +16% after 200 ppb NO2, and +78% after 600 ppb NO2. The linear association between the variation and the level of exposure was significant (p=0.01). Exposure to NO2 did not cause any change in lung function and no NO2-related effect on responsiveness to methacholine was found. NO2 exposure had a significant and dose-related effect on the eosinophilic inflammatory response of patients. These data suggest that exposure to NO2 might enhance the eosinophilic activity in sputum in subjects with intermittent asthma.
Abstract 66: The Duration of Asystole Before Return of an Organized Rhythm or Spontaneous Circulation After Defibrillation
Authors: Ava Pierce, Pamela Owens, Ahamed H Idris
Journal: Circulation (2011)

Background: Defibrillation success has been traditionally defined as termination of ventricular fibrillation five seconds after the shock. The current American Heart Association guidelines for Cardiopulmonary Resuscitation (CPR) recommend that chest compressions resume immediately after defibrillation and to perform rhythm and pulse checks after 5 cycles of CPR. Few studies have reported the duration of asystole after defibrillation before return of an organized rhythm or return of spontaneous circulation (ROSC). Objective: To describe the duration of asystole before return of an organized rhythm or ROSC after defibrillation during out-of-hospital (OOH) non-traumatic cardiac arrest. Methods: This observational study analyzed Dallas-Fort Worth ROC site data collected in the Resuscitation Outcomes Consortium (ROC) Epistry database. We reviewed monitor-defibrillator recordings of patients who were defibrillated for ventricular fibrillation or pulseless ventricular tachycardia during OOH cardiac arrest. We analyzed the duration of asystole after defibrillation before return of an organized rhythm or ROSC. An organized rhythm was defined as similar QRS complexes that produce a consistent rhythm without a palpable pulse. Results: A total of 176 patients were defibrillated after OOH cardiac arrest from November 2009 to April 2011. Mean age was 61 ± 17 years and 66.6% were male. The mean interval of asystole after defibrillation was 56 ± 144 sec (0 - 1098 sec), median 6 sec (IQR 29). The mean time to return of an organized rhythm after defibrillation was 64 ± 157 sec, median 7 sec (IQR 26). The mean time to ROSC after defibrillation was 280 ± 320 sec, median 136 sec (IQR 445). ROSC occurred in 51 (29%) patients and 16% survived to hospital discharge. The defibrillation energy that resulted in ROSC were as follows: twenty-nine at 200 Joules, eight at 300 Joules, nine at 360 Joules, one at 70 Joules, and 4 in the Emergency Department. Conclusion: The post-shock duration of asystole before return of an organized rhythm or ROSC is longer than 30 seconds in 25% of patients. Our findings support the recommendation to immediately resume chest compressions following attempted defibrillation and to continue CPR for two more minutes before checking the rhythm.
The first case of Lassa fever imported from Mali to the United Kingdom, February 2009
Authors: S Atkin, S Anaraki, P Gothard, A Walsh, D Brown, R Gopal, J Hand, D Morgan
Journal: Eurosurveillance (2009)

This is the first case of Lassa fever to be imported from Mali to the United Kingdom. This paper discusses the investigations, the virological analysis, the surveillance and management of contacts undertaken following a case of Lassa fever.
Using community pharmacy to identify patients at risk of poor asthma control and potential contributory factors
Authors: Helen Reddel, Kate LeMay, Bandana Saini, Sinthia Bosnic-Anticevich, Lorraine Smith, Deborah Burton, Jun Ju Christine Song, M. Chehani Alles, Kay Stewart, Lynne Emmerton, Ines Krass, Carol Armour
Journal: European Respiratory Journal (2011)

Aim: To describe a population identified by trained community pharmacists as being at risk for poor asthma outcomes, and to identify factors associated with poor asthma control.

Methods: A cross-sectional study was conducted in 96 metropolitan and regional Australian pharmacies. Community pharmacists with specialised asthma training enrolled 570 patients aged ≥18 years with doctor-diagnosed asthma who were considered at risk based on suboptimal asthma control or lack of recent GP asthma review, and conducted a comprehensive asthma assessment. Assessment of asthma control was based on self-reported frequency of symptoms and activity limitation during the previous month. Asthma history, spirometry and inhaler technique were documented. Medication use was recorded from pharmacy records and self-report.

Results: 570 patients were recruited, of whom 437 (77%) had poor asthma control. 21% smoked, 28% had an action plan, 69% used combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) medications, and only 17-28% used their inhaler correctly. In terms of adherence, 90% had their ICS or ICS/LABA dispensed <6 times in the previous 6 months, which is inconsistent with regular use. A logistic regression model showed that patients who smoked, had incorrect inhaler technique or low adherence were more likely to have poor control.

Conclusions: Community pharmacists identified patients with asthma at risk of suboptimal control, and factors that contribute to this were identified. There is an opportunity within pharmacies to target poorly-controlled asthma and provide timely and tailored interventions.