tbuckley/cabot-search huggingface dataset:
Three-year disease-free survival (DFS) as surrogate end-point for predicting five-year overall survival (OS) benefit in adjuvant taxane-based chemotherapy for breast cancer (BC): Analysis of 10 randomized clinical trials (RCTs)
Authors: D. Giannarelli, E. Bria, F. Cuppone, M. Ciccarese, C. Nisticò, P. Carlini, M. Milella, V. Lorusso, E. Terzoli, F. Cognetti
Journal: Journal of Clinical Oncology (2007)

584 Background: The issue regarding the eventual correlation between DFS at earlier follow-up (i.e. 3-yrs) with 5-yrs OS has not actually been explored in trials addressing the role of taxanes in BC. All RCTs in which patients were randomized to receive a standard or a taxane-based regimen for early BC were analyzed to evaluate this topic. Methods: All phase III trials with at least 60 month follow-up were considered eligible. The correlation has been explored according to a linear regression model considering both each single outcome pair (DFS/OS) for all arms (extracted by curves), their differences, and each outcome Hazard Ratio (HR) or calculated Relative Risk (RRs), following 2 steps: 1) correlation between 5-yrs DFS and OS (to confirm the evidence); 2) correlation between 3-yrs DFS and 5-yrs OS (predictive role). The correlation was estimated according to Pearson (r) and R 2 coefficients (parametric) and Spearman (Rho) coefficient (non- parametric). A model to calculate the target sample size to determine 5-yrs OS benefit of 3%, 5% and 7%, respectively, was calculated as well. Results: Ten RCTs (17,067 patients) with available data for outcomes were gathered. For 5-yrs DFS/OS, a linear correlation was found between rates (r=0.74, R 2 =0.55; p&lt;0.0001; Rho=0.83; p&lt;0.0001), and HRs (r=0.90, R 2 =0.81; p&lt;0.0001; Rho=0.91; p&lt;0.0001). Three-yrs DFS correlates with 5-yrs OS, with both rates (r=0.81, R 2 =0.66; p&lt;0.0001; Rho=0.92; p&lt;0.0001), and RRs (r=0.84, R 2 =0.71; p=0.002; Rho=0.85; p=0.002). Three-yrs DFS and 5-yrs OS absolute differences strongly correlate (r=0.86, R 2 =0.74; p=0.001; Rho=0.84; p=0.002). The sample size model (on the basis of the r-coefficient=0.81), calculates 2,733, 863, and 389 pts to improve 3-yrs DFS of 4%, 7% and 10%, which means to improve 5-yrs OS of 3.2%, 5.7% and 8.1%, respectively. Conclusions: By these data, 3-yrs DFS is a reliable surrogate end-point for OS when testing new drugs in early BC, and is able to predict a late survival benefit. Thanks to the smaller patient sample size, RCTs with this design will provide early results in a shorter time period, allowing a faster data transfer to clinical practice. No significant financial relationships to disclose.
Diabetic Nephropathy and Dyslipidaemia
Authors: Asim Afaq
Journal: Journal of the Royal Society of Medicine (2001)

In their review article on diabetic nephropathy (May 2001 JRSM, pp. 210-217), Dr Foggensteiner and his colleagues refer to ‘compelling reasons for the aggressive management of dyslipidaemia’ in this condition. They focus on the benefits of lipid-lowering to prevent cardiovascular disease in these patients, but the benefits specific to renal function also deserve consideration. In both diabetic and non-diabetic animal models, statin therapy has decreased glomerular injury and the rate of decline in glomerular filtration rate (GFR)1. These effects may be mediated by the action of statins on prosclerotic cytokines rather than their lipid-lowering properties2. However, among non-diabetic individuals, renal function declines more slowly in those with low ratios of low-density lipoprotein to high-density lipoprotein cholesterol3, and in diabetic patients normalization of hypercholesterolaemia may retard the progression of nephropathy4. A meta-analysis of thirteen prospective controlled trials supports the idea that lipid reduction preserves GFR and reduces proteinuria5.

Although several studies on lipid-lowering in diabetic nephropathy have been inconclusive, possibly because of short follow-up time or small sample size, others have shown benefit from aggressive management. Primary prevention studies are necessary to determine the specific effects of lipid management on diabetic nephropathy.
What Comes First? Multitissue Involvement Leading to Radiographic Osteoarthritis: Magnetic Resonance Imaging–Based Trajectory Analysis Over Four Years in the Osteoarthritis Initiative
Authors: Frank W. Roemer, C. Kent Kwoh, Michael J. Hannon, David J. Hunter, Felix Eckstein, Tomoko Fujii, Robert M. Boudreau, Ali Guermazi
Journal: Arthritis & Rheumatology (2015)

Objective To assess whether the presence of structural osteoarthritis (OA) features over as many as 4 years prior to incident radiographic OA increases the risk of radiographic OA in a nested, case–control design. Methods We studied 355 knees from the Osteoarthritis Initiative cohort that developed radiographic OA before the 48‐month visit. They were matched one‐to‐one by sex, age, and contralateral knee radiographic status with a control knee. Magnetic resonance images (MRIs) were read for bone marrow lesions (BMLs), cartilage damage, meniscal damage (including tears and extrusion), Hoffa synovitis, and effusion synovitis. Conditional logistic regression was applied to assess the risk of radiographic OA with regard to the presence of BMLs (score ≥2), cartilage lesions (score ≥1.1), meniscal damage (any) and extrusion of ≥3 mm ± (score ≥2), and Hoffa and effusion synovitis (any). Time points were defined as incident radiographic OA visit (P0), 1 year prior to the detection of radiographic OA (P −1), 2 years prior to the detection of radiographic OA (P −2), etc. Results The presence of Hoffa synovitis (hazard ratio [HR] 1.76 [95% confidence interval (95% CI) 1.18–2.64]), effusion synovitis (HR 1.81 [95% CI 1.18–2.78]), and medial meniscal damage (HR 1.83 [95% CI 1.17–2.89]) at P −2 predicted radiographic OA incidence. At P −1, all features but meniscal extrusion predicted radiographic OA, with highest odds for medial BMLs (HR 6.50 [95% CI 2.27–18.62]) and effusion synovitis (HR 2.50 [95% CI 1.76–3.54]). The findings at P −3 and P −4 did not reach statistical significance. Conclusion Our findings indicate that the presence of specific structural features of MRI‐detected joint damage 2 years prior to incident radiographic OA increases the risk of incident radiographic OA. However, 1 year prior to radiographic OA, the presence of almost any abnormal morphologic feature increases the risk of radiographic OA in the subsequent year.
Phenotypic and molecular characterization of multidrug-resistant Salmonella enterica serovar Hadar in Greece, from 2007 to 2010
Authors: T Papadopoulos, E Petridou, A Zdragas, S Nair, T Peters, E de Pinna, G Mandilara, M Passiotou, A Vatopoulos
Journal: Clinical Microbiology and Infection (2014)
Clinical effectiveness of anti-IgE therapy in allergic severe asthma
Authors: Pai-Chien Chou, Chun-Hwa Wang, Han-Pin Kuo
Journal: European Respiratory Journal (2014)

Severe asthma patients remain symptomatic despite of high dose medication, and experience frequent exacerbations. Allergic severe asthmatics with high serum IgE levels may be responsive to anti-IgE treatment. Omalizumab was administered to 89 allergic severe asthmatics with serum IgE >70 IU/ml. Clinical effectiveness of omalizumab was assessed every 3 months. 92.1% (82/89) of allergic severe asthmatics responded to omalizumab in terms of improvement of asthma control, reduction of ER visit, hospitalization, dosage of steroids. 68.5% (n=61) and 23.6% (n=21) of patients achieved well control and partial control of asthma, respectively after 3 months of treatment. For patients with partial control, 52.4% (n=12) and 33.3% (n=7) attained well control after 3 months of additional itraconazole or rhinosinus surgery, respectively. The effectiveness of omalizumab persisted for 8.8+4.5 months after cessation of >1 year of treatment (n=62), but only 3.2+1.2 months in  12 months (78+14% predicted, n=21, P 1 year may preserve longer effectiveness.
Erb-B2 and P53 expression as predictive factors in high grade osteosarcoma
Authors: R. Khodabakhshi, R. Khodabakhshi, A. Moradi, S. Amini, H. Madani, M. Gohari
Journal: Journal of Clinical Oncology (2005)

9043 Background: Over-expression and gene amplification of P53 and erb-B2 have been shown to be associated with poor prognosis in many cancers. Studies have revealed that erb-B2 over-expression is associated with poor prognosis in osteosarcoma. The methodological used in these studies has been questioned as they were not quantitative and possibly not reliable. The current study aimed to assess the correlation of HER2 or P53 over-expression with histological response to preoperative chemotherapy and event-free survival. Patient and Methods: We performed immunohistochemical (IHC) staining (HER2 and P53) on paraffin-embedded tissue obtained from 17 patients with ostesarcoma treated in our department from 2000 to 2003. Patients were treated preoperatively with 3 cycles of cisplatin 75–100mg/m2 (day 1) + Adriamycin 25mg/m2 (days 1–3). Membranous and cytoplasmic staining for HER2 were separately done a more than 25% statining was considered positive. P53 was categorized as positive (>25%), weakly positive (10–25%) and negative (<10%).The patient were also categorized according to chemotherapy response (Huvos grading): good response (grade 3–4) and poor response (grade 1–2). Results: Mean age of patients was 19.2 year and median events-free survival was 481 days. No positive membranous HER2 staining was detected. 4 specimens were positive for cytoplasmic HER2, and 9 stained positive for P53. No relationship between cytoplasmic staining and chemotherapy response was found on Chi-square test (p=0.662). P53 expression did not correlate with histological response or patient’s event-free survival. Cox-proportional hazards regression analysis with forward selection of variable was performed to estimate possible risk factors (sex, age, HER2, P53, response) for event-free survival. Only histological response was a significant risk factor (p=0.024). Conclusion: Over-expression of HER2 and P53 (using IHC) in high grade osteosarcoma was not predictive of response to preoperative chemotherapy in our study. In relation to event-free survival, only good response to chemotherapy was found to be a statistically significant prognostic factor. Larger prospective studies using additional methods such as FISH or PCR are warranted. No significant financial relationships to disclose.
Hepatic subcapsular biloma complicating laparoscopic cholecystectomy
Authors: Evangelos Kalaitzakis, Håkan Weiber, Ervin Toth
Journal: Endoscopy (2015)

A 74-year-old woman presented with upper abdominal pain. An ultrasound scan showed signs of acute cholecystitis but the liver parenchyma and liver function tests were normal. She underwent laparoscopic cholecystectomy. An intraoperative cholangiogram was normal.
Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial.
Authors: P J Loehrer, D Johnson, P Elson, L H Einhorn, D Trump
Journal: Journal of Clinical Oncology (1995)

PURPOSE This prospective, randomized trial was designed to determine if three cycles of cisplatin plus etoposide (PVP16) can produce therapeutic results comparable to three cycles of cisplatin, etoposide, and bleomycin (PVP16B) in patients with disseminated germ cell tumors. PATIENTS AND METHODS One hundred seventy-eight patients with minimal- or moderate-stage disease (Indiana staging system) were randomized to receive cisplatin (20 mg/m2 on days 1 to 5) plus etoposide (100 mg/m2 on days 1 to 5) with or without weekly bleomycin (30 IU/wk for 9 consecutive weeks). Following three cycles of chemotherapy over 9 weeks, patients with residual radiographic disease underwent surgical resection. If persistent carcinoma was noted, two additional 3-week courses of chemotherapy were administered. RESULTS One hundred seventy-one patients were fully assessable for response and survival. The two treatment groups were similar with respect to patient characteristics. The toxicities were comparable between the two arms. No clinically significant incidence of pulmonary toxicity occurred with PVP16B. Overall, 81 of 86 patients (94%) who received PVP16B and 75 of 85 patients (88%) who received PVP16 achieved a disease-free status with chemotherapy and/or surgery. However, greater numbers of treatment failures, including persistent carcinoma in postchemotherapy resected residual disease and relapses from complete remission, occurred on the arm without bleomycin (overall adverse outcome, P = .004). The failure-free (86% v 69%; P = .01) and overall survival (95% v 86%; P = .01) rates were inferior on the PVP16 arm. CONCLUSION Bleomycin is an essential component of PVP16B therapy in patients who receive three cycles of treatment for minimal- or moderate-stage disseminated germ cell tumors.
LBA-02 High Response Rate and PFS with PEGPH20 added to Nab-Paclitaxel/Gemcitabine in Stage IV Previously Untreated Pancreatic Cancer Patients with High-HA Tumors: Interim Results of a Randomized Phase 2 Study
Authors: A. Hendifar, S. Hingorani, W. Harris, T. Seery, D. Sigal, W. Wu, S. Dychter, P. Jiang
Journal: Annals of Oncology (2015)
Incidence of Tardive Dyskinesia in Early Stages of Low-Dose Treatment With Typical Neuroleptics in Older Patients
Authors: Dilip V. Jeste, Jonathan P. Lacro, Barton Palmer, Enid Rockwell, M. Jackuelyn Harris, Michael P. Caligiuri
Journal: American Journal of Psychiatry (1999)

The authors studied the risk of tardive dyskinesia for older patients in the early stages of treatment with typical neuroleptics.They examined the cumulative incidence of tardive dyskinesia 1, 3, 6, 9, and 12 months after the institution of neuroleptic therapy among 307 psychiatric outpatients over age 45. The patients' median dose was 68.4 mg/day of chlorpromazine equivalent.In the patients who had never received neuroleptics at baseline (N = 87), the mean cumulative incidence of tardive dyskinesia was 3.4% and 5.9% at 1 and 3 months, respectively. There was no significant difference in the 12-month cumulative incidence of tardive dyskinesia among patients who had been neuroleptic-naive at baseline (22.3%) and the 89 patients who had received neuroleptics before baseline for 1-30 days (24.6%); however, the 131 patients who had received neuroleptics before baseline for more than 30 days tended to have a greater cumulative 12-month incidence of tardive dyskinesia (36.9%).The risk of tardive dyskinesia in older outpatients is high, even with relatively short treatment with low doses of conventional neuroleptics.
Experiments in ecology: Their logical design and interpretation using analysis of variance By A.J. Underwood Cambridge University Press, 1997. £65.00/$85.00 hbk, £22.95/$34.95 pbk (xviii + 504 pages) ISBN 0 521 55329 6 / 0 521 55696 1
Authors: T Floyd
Journal: Trends in Ecology & Evolution (1997)
Paroxetine and Study 329: what we already knew and when
Authors: Larry D Sasich
Journal: BMJ (2015)

The effects of acetylcholine on both pyramidal neurons and interneurons in the area CA1 of the rat hippocampus were examined, using intracellular recording techniques in an <i>in vitro</i>slice preparation. In current-clamp mode, fast local application of acetylcholine (ACh) to the soma of inhibitory interneurons in stratum radiatum resulted in depolarization and rapid firing of action potentials. Under voltage-clamp, ACh produced fast, rapidly desensitizing inward currents that were insensitive to atropine but that were blocked by nanomolar concentrations of the nicotinic α7 receptor-selective antagonists α-bungarotoxin (αBgTx) and methyllycaconitine. Nicotinic receptor antagonists that are not selective for α7-containing receptors had little (mecamylamine) or no effect (dihydro-β-erythroidine) on the ACh-induced currents. Glutamate receptor antagonists had no effect on the ACh-evoked response, indicating that the current was not mediated by presynaptic facilitation of glutamate release. However, the current could be desensitized almost completely by bath superfusion with 100 nm nicotine. In contrast to those actions on interneurons, application of ACh to the soma of CA1 pyramidal cells did not produce a detectable current. Radioligand-binding experiments with [<sup>125</sup>I]-αBgTx demonstrated that stratum radiatum interneurons express α7-containing nAChRs, and <i>in situ</i>hybridization revealed significant amounts of α7 mRNA. CA1 pyramidal cells did not show specific binding of [<sup>125</sup>I]-αBgTx and only low levels of α7 mRNA. These results suggest that, in addition to their proposed presynaptic role in modulating transmitter release, α7-containing nAChRs also may play a postsynaptic role in the excitation of hippocampal interneurons. By desensitizing these receptors, nicotine may disrupt this action and indirectly excite pyramidal neurons by reducing GABAergic inhibition.
Effect of nanoparticle and NO2 exposure on thoracic gas volume in Brown Norway rat
Authors: Skander Layachi, Françoise Rogerieux, Christelle Gamez, Kelly Blazy, Franck Robidel, Anthony Lecomte, Ghislaine Lacroix, Sam Bayat
Journal: European Respiratory Journal (2011)

Rationale:  Air pollutant exposure, has been associated with increased asthma morbidity in children. The aim of the present study was to determine whether exposure to NO 2  and carbon nanoparticles (CNP) affect the rate of Thoracic gas volume (TGV) change with growth in 7-week old Brown-Norway (BN) rats.   Methods:  Animals were anesthetized and tracheally intubated. TGV was measured using whole-body plethysmography at age 49 days, and following a 4-wk exposure to air, NO 2  (10 ppm) 5h/d, 5d/wk, CNP (FW2, O13 nm; 3 instillations at 7-day intervals), or CNP+NO 2 . Serum cytokines were quantified using multi-array immunoassay.   Results:  TGV significantly increased after 4 weeks in all groups. When normalized to body weight, TGV increased significantly only in the air-exposed group.   Conclusions:  These data show that a 4-wk exposure to either NO 2  or CNP significantly decreases TGV and the rate of TGV increase with age in BN rat, suggesting a reduced lung growth rate. CNP, NO 2  and combined exposure produced distinct lung inflammatory cytokine profiles.
Gain study: A phase III trial to compare ETC versus EC-TX and ibandronate versus observation in patients with node-positive primary breast cancer
Authors: V. Möbus, B. Conrad, A. Schneeweis, R. Kreienberg, E. F. Solomayer, M. R. Clemens, H. Tesch, S. Loibl, V. Nekljudova, G. von Minckwitz
Journal: Journal of Clinical Oncology (2009)

568 Background: Möbus et al. showed that dd epirubicin (E), paclitaxel (T), cyclophosphamide (C) results in a superior DFS compared to conventionally dosed EC-T in pts with primary breast cancer (PBC) and ≥3 involved lymph nodes (LN). In this study, the dd, dose intensified strategy has been further investigated as well as the use of ibandronate (I) adjuvant and ESF. Methods: A prospective, multi-center, controlled, non-blinded, randomized phase III trial investigating ETC (E: 150 mg/m 2 , T: 225 mg/m 2 , C: 2,000 mg/m 2 , i.v. day 1, q15 for 3 cycles each: A1; or EC→TX (E: 112.5 mg/m 2 + C: 600 mg/m 2 , i.v. day 1 q 15 for 4 cycles → T: 67.5 mg/m 2 i.v. day 1, q 8 for 10 weeks + X: 2000 mg/m 2 p. o. day 1–14, q 22 for 4 cycles: A2). Pts were further randomized in a 2:1 ratio to receive I: 50 mg/day p.o. for 2 years (B1) or observation (B2). Pts received a primary prophylaxis with either epoetin β or darbepoetin α and during ETC/EC with pegfilgrastim. After recruitment of 1500 pts prophylactic ciprofloxacin was implemented. Eligible: Females ≥18 and &lt;65 years, histologically confirmed LN positive uni- or bilateral PBC; adequate surgery, ≥1 pos. LN out of ≥ 10; no previous/concurrent therapy; ECOG ≤2; written informed consent. Primary objective: compare DFS A1 vs. A2 and B1 vs. B2. Secondary objectives: OS, safety, incidence of secondary primaries, and EFS in subgroups of hormone sensitivity and pos. LN between arms; assessment of compliance and responders to ESF; determine prognostic factors. 3,000 pts with 801 events are needed to show an increase of 5-year DFS from 75% to 79% for pts receiving EC→TX and 728 events to show an increase of 5-year DFS from 75% to 79.5% for pts receiving I, assuming a drop-out rate of 5%. A clinically relevant difference between the arms is to be detected at α = 0.05 (two-sided) with 80% power. Results: 3024 patients were recruited between June 2004 and August 2008. The trial was amended several times implementing an oral antibiotic prophylaxis, reducing the dose of C; reducing the dose of dexamethasone in the group receiving weekly T, and using an Hb adapted dosing of ESF. Conclusions: The therapy in the two regimen seems feasible if precautions are taken. Final safety data will be presented at the Meeting. [Table: see text]
Abstract 3073: Metabolic Syndrome, Inflammation and Risk of Symptomatic Peripheral Artery Disease in Women: A Prospective Study
Authors: David Conen, Kathryn M Rexrode, Paul M Ridker, Aruna D Pradhan
Journal: Circulation (2008)

Background Metabolic syndrome (MetS) includes a number of cardiovascular risk factors known to predict vascular disease. Little is known, however, about the interrelationships between MetS, inflammation and the risk of incident peripheral artery disease (PAD). Methods We conducted a prospective cohort study among 27111 women participating in the Women’s Health Study. Subjects were free of cardiovascular disease at baseline and followed for the incidence of symptomatic PAD (n=114) over a follow-up period of 13.3 years. We used Cox proportional-hazards models to compare the risk of PAD among women with and without the MetS. We also evaluated relationships between MetS and markers of subclinical inflammation including high sensitivity C-reactive protein (hsCRP) and soluble intercellular adhesion molecule-1 (sICAM-1) and adjusted for these biomarker levels in multivariable models. Results At study entry, 25.5% of participants had the MetS. Women with the MetS had a 62% increased risk of incident PAD (HR 1.62; 95% CI 1.10 –2.38). After multivariable adjustment, MetS remained significantly associated with incident PAD (Table ). Similar results were obtained when we assessed the risk of PAD according to the number of MetS defining traits (21% risk increase per additional trait) (Table ). Median plasma levels of hsCRP and sICAM-1 were 4.0 mg/L versus 1.53 mg/L (p&lt;0.0001) and 374 ng/mL versus 333 ng/mL (p&lt;0.0001) in women with and without MetS, respectively. From 0 to 5 MetS defining traits, median hsCRP levels gradually increased from 1.0 to 5.9 mg/L (p&lt;0.0001) and median sICAM-1 levels increased from 321 to 413 ng/mL (p&lt;0.0001). When hsCRP and sICAM-1 were added to multivariable models for incident PAD, risk estimates for the MetS were substantially attenuated and became non-significant (Table ). Conclusion Women with the MetS have an increased risk of incident PAD. This increased risk may be largely mediated by the effects of inflammation and/or endothelial activation. Metabolic Syndrome and Risk of PAD
Dilatation and curettage procedure raises risk of premature birth in subsequent pregnancies, study finds
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Use of dilatation and curettage in cases of miscarriage or for termination increases the risk of preterm birth and very preterm birth (under 32 weeks) in a subsequent pregnancy, a large analysis has found. The study’s lead author has called for a more “restrained use” of the procedure in favour of medical interventions.

The analysis of 21 cohort studies included almost two million women and was presented at the annual meeting of the European Society of Human Reproduction and Embryology in Lisbon on 14-17 June. It found that use of dilatation and curettage in cases of miscarriage …