tbuckley/cabot-search huggingface dataset:
A substantial change in breast cancer (BC) biology arises after 50 years old regardless of patient (pt) menopausal status
Authors: I. Veys, V. Durbecq, L. Ameye, C. Desmedt, M. Paesmans, N. Sirtaine, C. Sotiriou, J. Nogaret, M. Piccart, D. Larsimont
Journal: Journal of Clinical Oncology (2007)

21002 Background: To explore the hypothesis that ageing alters BC biology, we correlated pt age at diagnosis with biopathological data collected retrospectively from 2723 BC pts treated at the Bordet Institute between 2000 and 2003. Pt's characteristics: Median pts’ age was 56 years old [25–96] and 36% of pt had nodal invasion. Seventy-eight and 63% of the BC were ER+ and PR+ respectively, 33% were grade 3, 24% overexpressed Ki67 (&gt;25%) and 8% were Her2 FISH+. Results: Pts &lt;40 years old had the highest Her2 FISH+ (12%) and hormone-independent (39%) BC rates. More than 50% of the BC were undifferentiated (grade 3) and highly proliferative (Ki67&gt;25%). Moreover, lobular BC were almost absent in young pts (p&lt;.0001); in agreement with the fact that lobular BC were less aggressive than ductal ones (less grade 3, Her2 FISH+ and ER- BC; p&lt;.0001). Hence pts &lt;40 years had a statistically higher rate of “Her2” and “basal-like” BC subtypes. On the contrary, pts &gt;50 years had ‘better prognostic luminal-A” BC with 60% of hormone-dependent BC and a significant drastic decrease of Ki67 expression, tumor grading and Her2 FISH+ (all p=.002). No biological difference was observed between BC of pts &gt;50 years. However, in this group we observed that high ER scores (7–8 vs 3–6) were statistically associated with Her2 FISH- and PR+ characteristics (all p&lt;.0004). Interestingly, the 40–50 years old group which contains 16% of postmenopausal pts, appeared as a transition group according to its biology. Nevertheless, no statistically biological difference could be observed between the BC of pre- and postmenopausal pts. Additionally, when considering the postmenopausal pts from all ages, a clear difference was observed for the different parameters between tumors from pts &lt;50 years compared to older ones (ER, p=.046; grade, p=.0007; Ki67, p=.0001), suggesting that age, and not the menopausal status, is responsible for changes in BC biology Conclusions: BC biology is greatly different in pts before and after the age of 50 but after 50 years old, all pts have BC with similar characteristics. Nevertheless, menopausal status can not account by itself to all these differences and pt ageing appears to have a great impact on BC biology (i.e. Her2 FISH+). No significant financial relationships to disclose.
Thyrotoxic atrial fibrillation.
Authors: Malvinder S Parmar
Journal: BMJ (1982)

Atrial fibrillation is the most common cardiac complication of hyperthyroidism and occurs in 15% of patients with hyperthyroidism. It is associated with a higher risk of thromboembolism that often involves the central nervous system. Oral anticoagulation is important in the majority of these patients to prevent thromboembolic complications. These patients require adjustment in the dose of various rate-controlling agents because of increased clearance associated with hyperthyroidism and a decrease in warfarin dosage because of increased clearance of vitamin K-dependent clotting factors. The management of thyrotoxic atrial fibrillation is summarized in this clinical review.
Effect of treatment on the prognostic value of S-phase fraction in non-Hodgkin's lymphoma.
Authors: H Joensuu, R Ristamäki, K O Söderström, S Jalkanen
Journal: Journal of Clinical Oncology (1994)

PURPOSE To investigate the prognostic value of cell proliferation rate in non-Hodgkin's lymphoma, study its association with histologic classification, and investigate whether its predictive value is influenced by the type of treatment given. PATIENTS AND METHODS The S-phase fraction (SPF) size was determined by DNA flow cytometry from paraffin-embedded tissue obtained at diagnosis from 490 patients with non-Hodgkin's lymphoma, diagnosed in a defined geographic area from 1970 to 1991. Clinical data were collected from hospital records and the files of the Finnish Cancer Registry. RESULTS SPF size correlated well with histologic grading performed either according to the Working Formulation or Kiel classification (P &lt; .0001 for both). The mean SPFs of low-, intermediate-, and high-grade malignant lymphomas were 4.9% (95% confidence interval [CI], 4.2% to 5.5%), 10.3% (95% CI, 9.3% to 11.4%), and 15.5% (95% CI, 14.0% to 16.9%), respectively. Lymphomas with an SPF lower than the median (7.9%) had a 58% 5-year and 44% 15-year survival rate, whereas those with an SPF larger than the median had a 44% 5-year and 40% 15-year survival rate (P &lt; .0001). SPF size was not significantly associated with prognosis in some subgroups, such as among patients treated primarily with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 114) or cyclophosphamide, vincristine, and prednisone (COP) (n = 124) with or without radiotherapy (P &gt; .05), whereas a stronger association was found among patients with stage I or II lymphoma treated with radiotherapy only (n = 100; P = .003) and among patients with stage III or IV lymphoma who did not receive chemotherapy (n = 44; P &lt; .0001). In multivariate analyses that included the factors used to construct the International Prognostic Index, SPF had independent prognostic value both in low-grade and intermediate- or high-grade lymphomas, but not in the subset of patients treated with combination chemotherapy with or without radiotherapy. CONCLUSION Cell proliferation rate measured as SPF is closely associated with histologic grading in non-Hodgkin's lymphoma, and it has independent prognostic value. The treatment given influences considerably the prognostic value of SPF.
EORTC liver metastases intergroup randomized phase III study 40983: Long-term survival results.
Authors: Bernard Nordlinger, Halfdan Sorbye, Bengt Glimelius, Graeme John Poston, Peter M. Schlag, Philippe Rougier, Wolf Bechstein, John Neil Primrose, Euan Thomas Walpole, Murielle E. Mauer, Thomas Gruenberger
Journal: Journal of Clinical Oncology (2012)

3508 Background: This study evaluates the benefit of combining peri-operative chemotherapy and surgery for patients with liver only metastases from colorectal cancer (LM) deemed resectable on pre-operative imaging. The PFS results, the primary endpoint, were reported (ASCO 2007). We now report on the secondary endpoint overall survival (OS) results, after a median follow-up of 8.5 years. Methods: Between September 2000 and July 2004, 364 patients (pts) with up to 4 LM were randomized between peri-operative FOLFOX4 (oxaliplatin 85mg/m² and LV5FU2), 6 cycles before and 6 cycles after surgery, (CT arm), and surgery alone (S arm). OS was compared between arms using a 2-sided non-stratified log-rank test at the 0.05 level of significance (intent-to-treat analysis). Results: 182 pts were randomized in each arm (CT arm and S arm) of which 171 were eligible (CT and S) and 152 underwent resection (CT and S). In the CT arm, 171 received preop CT and 115 received postop CT. At a median follow-up of 8.5 years, 221 deaths were reported (61 % of all randomized pts). Causes of death in CT arm were cancer relapse (85 pts), complication of surgery (2 pts), other causes (16 pts) and unknown cause (4 pts), and in S arm, cancer relapse (99 pts), complication of surgery (2 pts), other causes (11 pts) and unknown cause (2 pts). Observed median OS was higher in CT arm: 61 months (CT) vs. 54 months (S) in all randomized pts and 64 months (CT) vs. 55 months (S) in eligible pts. The 5 year OS rate was 51.2% (CT) vs. 47.8% (S) (all randomized) and 52.4% (CT) vs. 48.3% (S) (eligible pts). There was no significant difference in OS between arms (HR=0.88, 95% CI 0.68-1.14, p=0.34) (all randomized). After progression, second line treatment with chemotherapy was given in 59 % (CT) and 77% (S) of the pts with cancer progression and repeat surgery in 46% (CT) and 40% (S), respectively. Conclusions: Peri-operative chemotherapy with FOLFOX4 improves PFS but does not significantly improve OS over surgery alone. A potential benefit may have been diluted by second treatment lines and by more deaths unrelated to cancer in the CT arm.
Inflammation, immunological reaction and role of infection in pulmonary hypertension
Authors: S.S. Pullamsetti, R. Savai, W. Janssen, B.K. Dahal, W. Seeger, F. Grimminger, H.A. Ghofrani, N. Weissmann, R.T. Schermuly
Journal: Clinical Microbiology and Infection (2010)
Adding network approaches to a neurobiological framework of resilience
Authors: Nava Levit-Binnun, Yulia Golland
Journal: Behavioral and Brain Sciences (2015)

Abstract In their paper, Kalisch et al. make an important attempt to create a unifying theoretical framework for the neuroscientific study of general resilience mechanisms. We suggest that such attempts can benefit tremendously by incorporating the recently emerging network approaches that enable the characterization of complex brain network architecture and dynamics, in both health and disease.
Treatment of Solid P815X2 Murine Mastocytoma With Adriamycin (NSC-123127): Toxicity Limitations 2
Authors: Larry L. Schenken, Lawrence Poulakos, Ronald F. Hagemann, Dennis Burholt, S. Lesher
Journal: JNCI Journal of the National Cancer Institute (1976)

The efficacy of adriamycin (NSC-123127), given as weekly or as 5-day-per-week doses, on the control of solid P815X2 murine mastocytomas was severely limited by hematopoietic and gastrointestinal toxicity. Although daily or weekly drug schedules both elicited dose responsiveness in terms of tumor control, no dose level of drug increased the life-span of tumor-bearing animals.
Abstract 5137: Normalization of Visceral Adiposity is a Better Therapeutic Target Than Normalisation of Body Weight: Evidence From the Synergie Trial
Authors: Melanie Cote, Amelie Cartier, Paul Poirier, Pascale Mauriege, Jean Bergeron, Natalie Almeras, Angelo Tremblay, Isabelle Lemieux, Jean-Pierre Despres
Journal: Circulation (2008)

A moderate weight loss of 5 to 10% has been shown to induce several improvements in the cardiometabolic profile of high risk obese patients and is therefore generally recommended as a clinically meaningful therapeutic target. The SYNERGIE study is a lifestyle modification program which aims at reshaping the nutritional and physical activity habits of sedentary men with visceral obesity. In the present analyses, 101 healthy men aged 30 to 65 years without diabetes but characterized by visceral obesity and by the high triglyceride-low HDL cholesterol atherogenic dyslipidemia were assigned to a personalized nutritional and physical activity management program which included a monthly visit. In response to the intervention program, men of the study decreased their body weight, waist circumference (Δ=−9 cm, p&lt;0.0001) and their visceral adipose tissue (VAT) (Δ=−79 cm 2 , p&lt;0.0001). The intervention program also significantly improved several metabolic parameters such as HDL cholesterol (Δ=+0.13 mmol/l, p&lt;0.0001) and triglycerides levels (Δ =−0.6 mmol/l, p&lt;0.0001) as well as glucose and insulin homeostasis variables. However, when compared to a control group of healthy nonobese men (mean BMI=24 kg/m 2 , n=65), men of the intervention group did not fully normalize their cardiometabolic profile after 1-year. In order to further explore this issue, men of the intervention group were classified into quartiles of VAT accumulation achieved after 1-year. In comparison with men in the top VAT quartile, men in the lowest VAT quartile had markedly improved cardiometabolic profile. Moreover, when compared to nonobese controls, men who reached low levels of VAT were characterized by a lower VAT accumulation (100 cm vs. 124 cm) despite higher body weight (80 kg vs. 73 kg) and body mass index (27 kg/m 2 vs. 24 kg/m 2 ) than healthy nonobese controls. These men were also characterized by “normalized” HDL cholesterol (1.17 mmol/l), triglycerides (1.58 mmol/l), glucose (5.8 mmol/l), apolipoprotein B (0.97 mg/dl) and apolipoprotein AI (1.35 g/l) compared to nonobese controls. These results suggest that VAT may represent a better therapeutic target than the normalisation of body weight in the management of cardiometabolic risk in high risk abdominally obese men.
Sleep-disordered breathing and C-reactive protein in obese children and adolescents
Authors: Annelies Van Eyck, Kim Van Hoorenbeeck, Benedicte De Winter, Jose Ramet, Luc Van Gaal, Wilfried De Backer, Stijn Verhulst
Journal: European Respiratory Journal (2013)

Sleep disordered breathing (SDB) is common among overweight and obese children. It is a risk factor for several health complications, including cardiovascular disease. Inflammatory processes leading to endothelial dysfunction are a possible mechanism linking SDB and cardiovascular disease. C-reactive protein (CRP) is a marker for cardiovascular risk and is independently correlated with obstructive sleep apnea syndrome (OSAS) in adults. Our goal is to evaluate the relationship between CRP and OSAS in overweight and obese children and adolescents. One hundred and twenty children were included in this study (85 controls, 20 mild OSAS, 15 moderate-to-severe OSAS). All subjects underwent polysomnography and a blood sample was taken to determine CRP levels. No significant differences were found in CRP between subjects with or without OSAS and no correlations were found between CRP and OSAS severity. On the other hand we did find a relationship between CRP and BMI (r=0.21; p=0.015) and between CRP en fat mass (r=0.31; p
Vascular endothelialgrowth factor of poor prognosis of a new form of bronchopulmonary dysplasia
Authors: Olga Logvinova, Ganna Senatorova
Journal: European Respiratory Journal (2014)

Study of the function and capacity of the lung interstitium is very important to determine the reasons for extrauterine lung ontogeny braking in order to prevent a decrease in lung volume and vital development of diffusion-perfusion disorders with a new form of bronchopulmonary displasia.  Purpose. Improving the efficiency of diagnosis of a new form of bronchopulmonary dysplasia by defining the role of cytokines and growth of the proteoglycans in the prognosis of the disease.  Patients and methods.Electrophoresis conducted with ELISA to determine the performance of vascular endothelialgrowth factor (VEGF) serum in 72 children with a new form of bronchopulmonary dysplasia corrected aged 1-36 months.   Results.  Found that children with a new form of bronchopulmonary dysplasia characterized by reduced levels VEGF (p    Conclusion.  Of great importance in assessing the state of the pulmonary interstitium in the alveolar lung ontogenetic stage in children with a new form of bronchopulmonary dysplasia is the level VEGF. The level of VEGF is possible to predict the absence of positive dynamics to reduce the severity of a new form of bronchopulmonary dysplasia within the first 3 years of life.
An educational programme for patients with psoriasis and atopic dermatitis: a prospective randomized controlled trial
Authors: J. Bostoen, S. Bracke, S. De Keyser, J. Lambert
Journal: British Journal of Dermatology (2012)

Patient education in addition to standard treatment, with the aim of affecting care through courses, is a relatively new concept in dermatology. Here we introduce a randomized controlled trial (RCT) regarding a previously described 12-week educational programme for chronic skin diseases.The primary objective of the RCT was to measure the effect of an educational programme on disease severity and quality of life in patients with psoriasis or atopic dermatitis.We recruited 50 patients from Ghent University Hospital. Patients with diagnosed psoriasis or atopic dermatitis were randomized (1 : 1) to the intervention or control group. The clinical outcome was measured by two blinded observers using the Psoriasis Area and Severity Index (PASI), Scoring Atopic Dermatitis or the Eczema Area and Severity Index. Quality of life was measured by dermatology-specific quality-of-life questionnaires. There was a follow-up period of 9 months.We found that disease severity and quality of life improved significantly for patients with psoriasis (n = 29) but not for patients with atopic dermatitis (n = 21) at 3 months. Patients in the intervention group showed a significant reduction in mean PASI (P = 0·036), mean Dermatology Life Quality Index (P = 0·019) and mean Psoriasis Disability Index (P = 0·015), compared with the control group at 3 months. This improvement continued for at least 6 months, i.e. 3 months after the intervention, but was lost at follow-up after 9 months.Evaluating this form of educational programme, by means of a single-centre RCT, indicates its added value in the longer term management of psoriasis.
Long-term treatment with monoclonal antibodies anti-IgE in severe asthma: Follow-up of ten patients
Authors: Marco Brunori, Roberto Pierro, Francesca Serena Pignataro, Giulio Onelli
Journal: European Respiratory Journal (2011)

Omalizumab is a monoclonal anti-IgE antibody suggested for the treatment of very severe asthma. Duration of therapy remains an open question.  We tried to evaluate the long-term response to omalizumab in a population of patients who extended the treatment beyond the 12 months period suggested by EMEA, with the aim of contributing to establish the ideal duration of the therapy.  10 patients (8 females, 2 males, mean age:45 yrs), with severe allergic asthma, uncontrolled despite GINA Step 4 therapy, received optimized asthma therapy and omalizumab up to 36 months. They underwent complete clinical evaluation, spirometry tests and Asthma Control Test questionnaire every month.  Patients showed, after 24 months of treatment, persistency of good clinical and functional response: medium ACT score was 20, with a 19,2% improvement compared to basal value, FEV1 and MMEF showed an increase of 21% and 26%, with best values registered after 18 months. No side-effects were reported.  Long-term therapy with omalizumab in our patients was well tolerated with significant improvement of both symptoms and function, and absence of side-effects, suggesting that administration of omalizumab for longer than 12 months could be beneficial for some responders patients, despite costs.
Mania following head trauma
Authors: Sashi Shukla, Brian L. Cook, Sukdeb Mukherjee, Charles Godwin, Morton G. Miller
Journal: American Journal of Psychiatry (1987)

The authors present psychiatric and neurologic data on 20 patients who developed mania after closed head trauma. An association was seen between severity of head trauma (based on length of posttraumatic amnesia), posttraumatic seizure disorder, and type of bipolar disorder. The manic episodes were characterized by irritable mood rather than euphoria and by assaultiveness. Psychosis occurred in only 15% of the sample, and 70% had no depressive episodes. Bipolar disorders were absent among 85 first-degree relatives. The authors suggest that posttraumatic seizures may be a predisposing factor in posttraumatic mania.
Abstract 15125: Calculated Plasma Volume Status Predicts Survival in Aortic Valve Replacement
Authors: Suneil K Aggarwal, Alistair Connell, Nay Aung, Francesco Papalia, Julia Flint, Susanne Weissert, Hua Zen Ling, Toby Richards, Darlington O Okonko
Journal: Circulation (2011)

Background: Plasma volume (PV) expansion underlies systemic congestion in patients (pts) awaiting aortic valve replacement (AVR) and can be significant despite clinical euvolemia. Although PV statu...
Perforated Duodenal Ulcer and Cigarette Smoking
Authors: F Smedley, T Hickish, M Taube, C Yale, R Leach, C Wastell
Journal: Journal of the Royal Society of Medicine (1988)

Whilst the association between smoking and peptic ulceration has been reported previously, the relationship between smoking and the complications of ulcers, such as perforation, bleeding or acute painful exacerbation, has not been examined. In a retrospective study comparing 275 emergency admissions for peptic ulcer with 275 controls, cigarette smoking was significantly more common only in those with a perforated duodenal ulcer. Of 128 patients with perforated duodenal ulcers, 110 (86%) were cigarette smokers compared with 65 (51%) of the 128 matched controls (X2, P less than 0.01). Cigarette smoking in patients with bleeding or acutely exacerbated ulcers was not significantly more common than in controls. These findings strongly suggest a particular association between smoking and perforated duodenal ulcer.
Afatinib plus Cetuximab Delays Resistance Compared to Single-Agent Erlotinib or Afatinib in Mouse Models of TKI-Naïve EGFR L858R-Induced Lung Adenocarcinoma
Authors: Valentina Pirazzoli, Deborah Ayeni, Catherine B. Meador, Basavaraju G. Sanganahalli, Fahmeed Hyder, Elisa de Stanchina, Sarah B. Goldberg, William Pao, Katerina Politi
Journal: Clinical Cancer Research (2015)

The EGFR tyrosine kinase inhibitors (TKIs), erlotinib and afatinib, have transformed the treatment of advanced EGFR-mutant lung adenocarcinoma. However, almost all patients who respond develop acquired resistance on average approximately 1 year after starting therapy. Resistance is commonly due to a secondary mutation in EGFR (EGFR(T790M)). We previously found that the combination of the EGFR TKI afatinib and the EGFR antibody cetuximab could overcome EGFR(T790M)-mediated resistance in preclinical models. This combination has shown a 29% response rate in a clinical trial in patients with acquired resistance to first-generation TKIs. An outstanding question is whether this regimen is beneficial when used as first-line therapy.
Glucose-induced alkalosis in fasting subjects
Authors: Bobby J. Stinebaugh, Francis X. Schloeder
Journal: Journal of Clinical Investigation (1972)

This study documents the development of alkalosis in patients returning to caloric intake after a period of starvation and investigates the mechanisms responsible for this metabolic alteration. We studied the acid-base status, bicarbonate reabsorption, acid excretion, and sodium metabolism during fasting and glucose refeeding in 19 patients receiving sodium supplements. Metabolic alkalosis developed promptly in all of the subjects who terminated an 18 day fast with 300 g of glucose daily for 4 days. Tubular maximum reabsorptive capacity for bicarbonate and renal bicarbonate threshold determinations were performed at varying intervals in six and seven subjects, respectively, who had fasted for 3-18 days. The results demonstrated that bicarbonate reabsorptive capacity was normal or low during early fasting, markedly elevated during the 2nd wk; and moderately elevated during the 3rd wk of fasting. Glucose administration at all stages of fasting caused a further increase in bicarbonate threshold. Sodium balance during fasting with sodium supplements was found to follow a triphasic pattern, with the occurrence of a natriuresis during the 1st wk followed by a period of sodium retention after which neutral daily sodium balance was reestablished. Correlation of bicarbonate reabsorption with sodium homeostasis indicated a slight decrease in renal bicarbonate threshold during the natriuretic phase, a marked increase in bicarbonate reabsorption during the period of sodium retention, and a continued moderate elevation of threshold after sodium balance was reestablished. This relationship was interpreted to indicate that changes in bicarbonate reabsorption during fasting and refeeding may be secondary to alterations in the renal reabsorption of sodium.
Food Consumption and its Impact on Cardiovascular Disease: Importance of Solutions Focused on the Globalized Food System
Authors: Sonia S. Anand, Corinna Hawkes, Russell J. de Souza, Andrew Mente, Mahshid Dehghan, Rachel Nugent, Michael A. Zulyniak, Tony Weis, Adam M. Bernstein, Ronald M. Krauss, Daan Kromhout, David J.A. Jenkins, Vasanti Malik, Miguel A. Martinez-Gonzalez, Dariush Mozaffarian, Salim Yusuf, Walter C. Willett, Barry M. Popkin
Journal: Journal of the American College of Cardiology (2015)