tbuckley/cabot-search huggingface dataset:
End‐Stage Renal Disease in African Americans With Lupus Nephritis Is Associated With <i>APOL1</i>
Authors: Barry I. Freedman, Carl D. Langefeld, Kelly K. Andringa, Jennifer A. Croker, Adrienne H. Williams, Neva E. Garner, Daniel J. Birmingham, Lee A. Hebert, Pamela J. Hicks, Mark S. Segal, Jeffrey C. Edberg, Elizabeth E. Brown, Graciela S. Alarcón, Karen H. Costenbader, Mary E. Comeau, Lindsey A. Criswell, John B. Harley, Judith A. James, Diane L. Kamen, S. Sam Lim, Joan T. Merrill, Kathy L. Sivils, Timothy B. Niewold, Neha M. Patel, Michelle Petri, Rosalind Ramsey‐Goldman, John D. Reveille, Jane E. Salmon, Betty P. Tsao, Keisha L. Gibson, Joyce R. Byers, Anna K. Vinnikova, Janice P. Lea, Bruce A. Julian, Robert P. Kimberly
Journal: Arthritis & Rheumatology (2013)

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that exhibits familial aggregation and may progress to end-stage renal disease (ESRD). LN is more prevalent among African Americans than among European Americans. This study was undertaken to investigate the hypothesis that the apolipoprotein L1 gene (APOL1) nephropathy risk alleles G1/G2, common in African Americans and rare in European Americans, contribute to the ethnic disparity in risk.APOL1 G1 and G2 nephropathy alleles were genotyped in 855 African American SLE patients with LN-ESRD (cases) and 534 African American SLE patients without nephropathy (controls) and tested for association under a recessive genetic model, by logistic regression.Ninety percent of the SLE patients were female. The mean ± SD age at SLE diagnosis was significantly lower in LN-ESRD cases than in SLE non-nephropathy controls (27.3 ± 10.9 years versus 39.5 ± 12.2 years). The mean ± SD time from SLE diagnosis to development of LN-ESRD in cases was 7.3 ± 7.2 years. The G1/G2 risk alleles were strongly associated with SLE-ESRD, with 25% of cases and 12% of controls having 2 nephropathy alleles (odds ratio [OR] 2.57, recessive model P = 1.49 × 10(-9)), and after adjustment for age, sex, and ancestry admixture (OR 2.72, P = 6.23 × 10(-6)). The age-, sex-, and admixture-adjusted population attributable risk for ESRD among patients with G1/G2 polymorphisms was 0.26, compared to 0.003 among European American patients. The mean time from SLE diagnosis to ESRD development was ∼2 years earlier among individuals with APOL1 risk genotypes (P = 0.01).APOL1 G1/G2 alleles strongly impact the risk of LN-ESRD in African Americans, as well as the time to progression to ESRD. The high frequency of these alleles in African Americans with near absence in European Americans explains an important proportion of the increased risk of LN-ESRD in African Americans.
Effect of endoscopic lung volume reduction on established pulmonary hypertension in severe emphysema patients
Authors: Ralf Eberhardt, Vasiliki Gerovasili, Konstantina Kontogianni, Daniela Gompelmann, Nicola Ehlken, Felix J.F. Herth, Ekkehard Gruenig, Christian Nagel
Journal: European Respiratory Journal (2014)

One of the most common forms of pulmonary hypertension (PH) is the one associated with chronic obstructive pulmonary disease (COPD) and it is associated with worse prognosis. So far patients with severe emphysema and established PH have been excluded from endoscopic lung volume reduction (ELVR) therapy.   Objective : Whether ELVR achieved with one way endobronchial valve (EBV) placement influences in anyway the severity of PH in this specific group of patients.   Methods :Single-center case series study; 6 patients with severe heterogeneous emphysema and established PH were prospectively included. ELVR with unilateral EBV-placement was performed. Patients were assessed at baseline and 90 days post procedure.   Results :This pilot study was not powered to measure any statistical differences in endpoints. At 90 days post ELVR pulmonary function test (PFT) tended to improve and so did 6-minute walking distance +59±99meters; in right heart catheterization (RHC) mean haemodynamics also improved: mean pulmonary artery pressure -2.5±3.5mmHg, pulmonary arterial wedge pressure -4.4±8.3mmHg, pulmonary vascular resistance -61±158 dynes* s*cm -5 , cardiac index +0.3±0.6l/min/m 2 ; Right atrial (RA) size measured by echo decreased and right ventricular size and the tricuspid annular plane systolic excursion (TAPSE) remained the same. ELVR was performed without PH-related complications in all patients.   Conclusion : ELVR in this case series was safe and feasible in patients with PH. We did not observe a deterioration of the pulmonary and systemic circulation. Further larger-scaled invasive studies are encouraged to examine cardiopulmonary interaction in ELVR.
Abstract 3137: Long-term Outcomes Following Sirolimus-Eluting Stent Implantation for Off Label Indications
Authors: John Cosgrave, Tiziana Claudia Aranzulla, Asif Qasim, Azeem Mohamed Latib, Gloria Melzi, Flavio Airoldi, Alaide Chieffo, Giuseppe Massimo Sangiorgi, Matteo Montorfano, Iassen Michev, Mauro Carlino, Antonio Colombo
Journal: Circulation (2007)

Introduction: Only limited long term data exist following SES implantation and these primarily come from the randomized trials which enrolled highly selected patients. Due to the risk of stent thrombosis long term safety concerns exist particularly following off label SES implantation. Hypothesis: Off label implantation of SES has a favorable long term safety profile. Methods: All consecutive patients successfully treated with SES prior to March 2003 were considered for analysis. The endpoints analyzed were MACE, death, myocardial infarction (MI), target vessel revascularization (TVR) and target lesion revascularization (TLR) and late stent thrombosis. We considered the following as off-label indications: ostial lesions, chronic total occlusions, bifurcations, left main stem lesions, saphenous vein grafts, internal mammary artery, ejection fraction &lt; 30 %, restenotic lesions. Results: Our cohort comprised 445 patients with 954 lesions. At least one off label indication was present in 322 (72%) of patients and 161 (36.2%) had more than 1 off label indication (Table ). Median clinical follow-up was 4.4 years and 78% of patients had at least 4 years of follow-up. There was a trend towards a higher MACE rate in the off-label group due in the main to a significantly higher repeat revascularization rate. There were no differences in the incidence of death or myocardial infarction. The overall rate of late thrombosis was similar to that seen in the literature (1–2%) and while there was a slightly higher number in the off-label group this did not reach statistical significance. Conclusions: In our experience off label implantation of SES is associated with higher MACE rates due to the increased need for repeat revascularization. This can be explained by the complexity of this cohort with a large number of lesion types not included in randomized trials. Of note long term safety is acceptable with no difference in death or MI when compared to on-label indications. Follow-up clinical events in the two groups
Effect of Long-Acting Testosterone Treatment on Functional Exercise Capacity, Skeletal Muscle Performance, Insulin Resistance, and Baroreflex Sensitivity in Elderly Patients With Chronic Heart Failure
Authors: Giuseppe Caminiti, Maurizio Volterrani, Ferdinando Iellamo, Giuseppe Marazzi, Rosalba Massaro, Marco Miceli, Caterina Mammi, Massimo Piepoli, Massimo Fini, Giuseppe M.C. Rosano
Journal: Journal of the American College of Cardiology (2009)
Does ROSE really impacts in EBUS-TBNA results?
Authors: Ines Neves, Helena Barroca, Maria Sucena, Adriana Magalhaes, Gabriela Fernandes
Journal: European Respiratory Journal (2013)

Background : It is well established that rapid on site evaluation (ROSE) has the potential to increase ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) accuracy . From May 2009 until January 2012, our group performed 227 exams of EBUS-TBNA. ROSE was used till the first semester 2012 and later we continued without the collaboration of the cytopathologist.

Objective: To assess adequacy of the aspirated cellular material of EBUS-TBNA performed with or without ROSE in the diagnosis of hilar/mediastinal lesions and lung cancer staging.

Methods: During a one-year period (2012), seventy consecutive patients who underwent EBUS-TBNA were included. EBUS-TBNA adequate sampling was compared in two distinct time periods, with and without ROSE, respectively.

Results: In the 70 patients included (36 with ROSE and 34 without ROSE) no significant differences were found between groups concerning sex, age, exam indication (diagnosis or staging) and punctures location. The percentage of adequate sampling in the group with ROSE and without ROSE was 86.1% and 82.4%, respectively. This difference was not statistically significant (p=0.66). The mean number of transbronchial aspirates/per exam was statistical superior for EBUS-TBNA without ROSE (4.4 ±2.0) than with ROSE (3.2±1.5, p=0.002). There were no complications in both groups.

Conclusions: The adequacy of the aspirated cellular material of EBUS-TBNA was similar with or without the use of ROSE. EBUS-TBNA accuracy for the diagnosis of hilar/mediastinal lesions and lung cancer staging was not influenced by the availability of ROSE.
Combined use of genomic prognostic and treatment response predictors in breast cancer
Authors: L. Pusztai, C. Hatzis, F. Cardoso, C. Sotiriou, V. Lazar, M. Piccart-Gebhart, G. N. Hortobagyi, L. van't Veer, W. F. Symmans
Journal: Journal of Clinical Oncology (2008)

527 Background: An advantage of gene expression profiling-based diagnostic tests is that several different predictors can be applied to the same data and prognostic, as well as endocrine- and chemotherapy-sensitivity predictions can be generated from a single specimen. We tested this concept on two cohorts of breast cancers including a total of 427 cases. Methods: Gene expression profiling results generated with Affymetrix U133A gene chips were available on 198 stage I-II, lymph node-negative patients who received no systemic adjuvant therapy and on 229 stage I-III, HER-2 normal breast cancers who all received preoperative paclitaxel/FAC chemotherapy. We applied the Genomic Grade prognostic index (GGI) and 2 separate predictive signatures including a 200-gene endocrine sensitivity index and a 207-gene clinical phenotype-specific chemotherapy response predictor to each case. MammaPrint prognostic prediction results were also available on the 198 cases. The predictive accuracies of each of these tests were reported previously. Results: Sixty-four (32%) of the 198 cases from the prognostic data set were assigned to good prognosis by MammaPrint, among these low risk patients, 8 (12%) were predicted to be highly chemotherapy sensitive and 20 (31%) to be highly endocrine sensitive. Among the high risk patients, 69 (51%) were predicted to be highly sensitive to chemo- and 8 (6%) highly sensitive to endocrine-therapy while 57 (42%) showed low sensitivity to both modalities. In the neoadjuvant data, 82 patients (36%) were low risk for recurrence by the GGI (MammaPrint results were not available) and 10 of these (12%) were predicted to achieve excellent pathologic response (pCR or RCB-I). Sixty-one (41%) of the high-risk patients were predicted to have pCR/RCB-I response and 54% of the poor prognosis group was predicted to be insensitive to both endocrine- and chemotherapy. Conclusions: Patients predicted to be at low risk for recurrence are mainly sensitive to endocrine therapy but about 12% may also be sensitive to chemotherapy; 40–50% of high-risk patients are predicted to be insensitive to existing therapies. Simultaneous prediction of risk of recurrence and sensitivity to endocrine- and chemotherapies is currently possible and may allow more personalized treatment decisions in the future. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Agendia, Nuvera Biosciences Inc Nuvera Biosciences, Pfizer Inc, Roche Pharmaceuticals Agendia, Nuvera Biosciences, Nuvera Biosciences Inc Bristol-Myers Squibb, Genentech
Abstract 3208: Does Myocardial Fibrosis Differ Among Septal Morphologic Subtypes in Hypertrophic Cardiomyopathy?
Authors: Ahmed A Alsaileek, Steve R Ommen, Uma Valeti, Jamil Tajik, Philip A Araoz, Michael J Ackerman, Rick A Nishimura, James B Seward
Journal: Circulation (2006)
Dangers of rising indemnity insurance costs
Authors: N. Hawkes
Journal: BMJ (2015)

Soaring subscription fees could discourage new entrants to general practice



UK general practitioners reeling back in frank disbelief at their annual subscription renewal for indemnity insurance must be tempted to echo Oscar Wilde: when the gods wish to punish us, they answer our prayers. Many blamed the legal aid system for fomenting medical negligence claims: the BMA itself asserted in 1997 that, by funding worthless cases, legal aid was draining millions from patient care. The money, said Mac Armstrong, BMA secretary, “was going into lawyers’ pockets.”

Its wishes were in due course granted, with changes enacted that scrapped legal aid for almost all clinical negligence cases in England and Wales. In future, said the then justice secretary, Kenneth Clarke, all claimants would have to use the “no win, no fee” provisions that were already used by those too well off to qualify for legal aid. Lawyers warned that the removal of legal aid would make it harder for people to find advocates willing to launch complex negligence cases.

There’s little evidence of that. The medical protection organisations and the NHS Litigation Authority warn of a tsunami of claims funded by no win, no fee agreements …
Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients.
Authors: S L Goldberg, T R Klumpp, A J Magdalinski, K F Mangan
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the value of pretransplant studies in predicting day 100 nonrelapse toxic mortality following high-dose therapy. PATIENTS AND METHODS A retrospective review of 383 consecutive hematopoietic stem-cell transplants was performed with attention to toxic mortality and pretransplant factors. Univariate log-rank analysis was used to yield the most significant cut-off values for individual factors. Multivariate analysis using Cox proportional hazards regression determined factors independently predictive of early toxic death. RESULTS Nonrelapse toxic mortality before day 100 occurred in 23 of 383 (6.0%) transplant recipients. Factors associated with an increased risk of toxic death by univariate analysis included forced expiratory volume in 1 second (FEV1) less than 78% of predicted (P = .0002), allogeneic versus autologous transplant (P = .0003), diffusion capacity of carbon monoxide less than 52% of predicted (P = .002), serum creatinine concentration greater than 1.1 mg/dL (P = .003), Eastern Cooperative Oncology Group performance status greater than 0 (P = .006), preparative regimen containing total-body irradiation versus chemotherapy alone (P = .006), marrow versus blood stem cell (P = .01), serum ALT greater than 50 IU/L (P = .02), diagnosis of hematologic disorder versus solid tumor (P = .06), serum bilirubin level greater than 1.1 mg/dL (P = .08), left ventricular ejection fraction (P = .09), and growth factor use (P = .09). In the multivariate model, transplant type (relative risk, 4.2), FEV1 (relative risk, 4.5), performance status (relative risk, 3.7), serum creatinine (relative risk, 3.8), and serum bilirubin (relative risk, 3.7) were found to be independent predictors of early toxic mortality. CONCLUSION The pretransplant evaluation is a useful tool to identify patients at risk for early toxic mortality following high-dose therapy.
Survival Benefit of Exclusive Use of In Situ Arterial Conduits Over Combined Use of Arterial and Vein Grafts for Multiple Coronary Artery Bypass Grafting
Authors: Hiroshi Nishida, Yasuko Tomizawa, Masahiro Endo, Hiromi Kurosawa
Journal: Circulation (2005)

Background— The purpose of this study was to evaluate mortality after coronary artery bypass grafting (CABG) comparing the use of only in situ arterial grafts with the use of arterial and venous conduits. Methods and Results— From April 1985 to March 1999, 1159 patients with multivessel disease underwent elective, isolated, primary, multiple CABG with at least one in situ arterial conduit. Patients who were on chronic dialysis, had active malignant disease, or had free arterial conduits were excluded. The long-term results were compared between 532 patients who had CABG using only in situ arterial conduits (group A; mean follow-up, 7.8 years) and 627 patients who underwent CABG using in situ arterial conduits and saphenous vein grafts (group B; mean follow-up, 10.3 years). Actuarial survival and freedom from cardiac death were determined by the Kaplan-Meier method. Propensity score was included in the Cox multivariable regression model for adjustment of selection bias. Survival at 10 years after surgery was 81.4% in group A and 76.9% in group B ( P =0.11). Freedom from cardiac death at 10 years was 93.4% in group A and 90.4% in group B. Hazard ratio for cardiac death was significantly lower in group A (0.61; 95% confidence interval, 0.38 to 1.00; P =0.05). Conclusions— Our data suggest that the exclusive use of in situ arterial grafts in CABG achieves significantly better long-term survival compared with combined use of arterial and vein grafts.
Docetaxel: an active drug for squamous cell carcinoma of the head and neck.
Authors: A I Dreyfuss, J R Clark, C M Norris, R M Rossi, J W Lucarini, P M Busse, M D Poulin, L Thornhill, R Costello, M R Posner
Journal: Journal of Clinical Oncology (1996)

PURPOSE We conducted a phase II study designed to evaluate the activity, safety, and tolerability of docetaxel (Taxotere: Rhône-Poulenc Rorer Pharmaceuticals Inc, Collegeville, PA) in patients with advanced, incurable, or recurrent squamous cell carcinoma of the head and neck (SCCHN) who had not received prior palliative chemotherapy. PATIENTS AND METHODS Thirty-one patients with measurable, locoregional, or metastatic SCCHN were treated with docetaxel, administered at a dose of 100 mg/m2 as a 1-hour intravenous (i.v.) infusion once every 21 days on an outpatient basis. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic administration of growth factors or antiemetics was not permitted. RESULTS Thirty-one patients were treated. Twenty-nine patients were assessable for response and 30 for toxicity. Four of 31 patients (13%) achieved complete response (CR), nine (29%) achieved partial response had stable disease (SD) and seven (23%) experienced progression of disease (PD). The major response rate was 42% (95% confidence interval [CI], 24% to 60%). The median duration of responses was 5 months (range, 2 to 14). The principal toxicity was leukopenia, which occurred with rapid onset and brief duration. Sixteen patients (53%) experienced nadir fever, and 13 required dose reduction. Hypersensitivity reactions occurred in four patients. Grade 3 peripheral neuropathy occurred in two patients; grade 2 or 3 fatigue occurred in six (20%) and 10 (33%), respectively. Minimal edema (grade 1) occurred in five patients (17%). Clinically significant mucositis, diarrhea, or dermatitis were not observed. CONCLUSION Docetaxel has major activity against SCCHN. It appears to be well tolerated in this group of patients and can be safely administered on an outpatient basis. Premedication with dexamethasone, cimetidine, and diphenhydramine is associated with a reduced incidence of significant edema, hypersensitivity reactions, and dermatologic toxicities.
Influence Of Acute and Chronic Graft-Versus-Host Disease On Outcome After Allogeneic Hematopoietic Stem Cell Transplantation For Chronic Myelomonocytic Leukemia
Authors: Hidehiro Itonaga, Masako Iwanaga, Kazunari Aoki, Jun Aoki, Ken Ishiyama, Takeshi Kobayashi, Toru Sakura, Takahiro Fukuda, Toshiaki Yujiri, Makoto Hirokawa, Yasuo Morishima, Tokiko Nagamura-Inoue, Yoshiko Atsuta, Takayuki Ishikawa, Yasushi Miyazaki
Journal: Blood (2013)
QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES
Authors: A. Bruce MacDonald, Alfred Nisonoff
Journal: The Journal of Experimental Medicine (1970)

Changes and persistence of idiotypic specificities of specifically purified rabbit anti-p-azobenzoate antibodies were studied by quantitative methods. In each rabbit idiotypes identified 2 months after the start of immunization were still present in comparable concentrations 2 months later. After month 4, they were replaced by new and unrelated specificities; the changes were abrupt in two rabbits and gradual in the third, and were associated with an increase in the average affinity for specific hapten. In two surviving rabbits the new sets of specificities persisted in part for at least 1 yr. Quantitative changes occurred during this period, and the antibody preparation used as immunogen reacted most effectively with the homologous anti-D serum. The antibody population present at month 17 (D(17)) in one rabbit was deficient in idiotypic specificities present in D(8) and lacked specificities present in D(2), indicating the presence in D(17) of a third group of specificities. The percentage of the antibody population from each rabbit reactive with homologous anti-idiotypic serum was greater at month 8 than at month 2, suggesting a decrease in heterogeneity. Since the donor rabbits were challenged repeatedly with antigen, it appears that, after month 8, a portion of the antigen was utilized to stimulate existing cell lines and a portion to initiate new clones. Precipitation of anti-p-azobenzoate antibodies removed idiotypic specificities, indicating that they were not present on the anti-bovine gamma-globulin antibodies in the same sera.