tbuckley/cabot-search huggingface dataset:
P3-07-47: Validated Nomogram To Predict Sentinel Lymph Node Positivity in Breast Cancer Patients.
Authors: R Kaplan, Q Qiu, S Monni, T D'Alfonso, SJ Shin
Journal: Cancer Research (2011)

Abstract Background: Sentinel lymph node(SLN) biopsy is commonly used to assess axillary lymph node status in breast cancer patients. Intraoperative (frozen section) evaluation of SLN may lead to immediate axillary dissection if the lymph node is found to be positive. In light of the recent outcomes of the Z00011 trial, the use of intraoperative evaluation for SLN should diminish since only select patients appear to benefit from axillary dissection. We have previously reported that tumor size and lymphovascular invasion (LVI) strongly predict SLN positivity in a cohort of 350 breast cancer patients [Modern Pathology (2011) 24, 30A]. From this test cohort, we developed a nomogram which could help identify patients more likely to have sentinel lymph node positivity. The aim of this study was to validate the efficacy of this nomogram by applying a new, non-overlapping cohort of breast cancer patients who had undergone sentinel lymph node sampling. Materials and Methods: 93 breast cancer patients aged 29–82 (mean:59) who underwent excision (54, 58%) or mastectomy (39, 42%) with a SLN biopsy were studied. Patients who had undergone neoadjuvant chemotherapy were excluded. Clinicopathologic parameters such as number of sentinel lymph nodes removed and/or positive, number of non-sentinel lymph nodes removed and/or positive, tumor size, histologic type/grade, presence of lymphovascular invasion, biomarker expression (ER,PR, HER-2/neu) and multifocality were recorded. Statistical analysis was performed to identify which variables correlated with SLN positivity in this validation cohort. In addition, the probability of SLN positivity for each case was determined by using the nomogram and this value was then compared to the patient's true SLN status. Results: When analyzed separately, tumor size (p=0.03) and LVI (p=0.01) were variables that were significantly associated with SLN positivity in both the test and validation cohorts. Employment of the nomogram demonstrated that 60% of patients who were predicted to have a positive SLN with at least 0.8 probability were truly positive by histologic and immunohistochemical examination. Moreover, 89% of patients who were predicted to have a negative SLN with at least 0.8 probability were truly negative by histologic and immunohistochemical examination. Conclusions: We conclude that the utility of this nomogram prior to surgery can help predict SLN positivity. This can serve as a complimentary adjunctive tool to better select patients who will likely need intraoperative evaluation of their sentinel lymph node due to their higher risk of sentinel node positivity and thus, benefit from the option of immediate axillary dissection at that time. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-47.
Combination Therapy with Cyclosporine and Methotrexate in Severe Rheumatoid Arthritis
Authors: Peter Tugwell, Theodore Pincus, David Yocum, Michael Stein, Oscar Gluck, Gunnar Kraag, Robert McKendry, John Tesser, Philip Baker, George Wells
Journal: New England Journal of Medicine (1995)

Patients with severe rheumatoid arthritis who are treated with methotrexate frequently have only partial improvement.
The Influence of KRAS Mutation Analysis Before Primary Chemotherapy for Unresectable and Recurrent Colorectal Cancer
Authors: H. Satake, T. Kotake, Y. Ito, H. Kitamoto, K. Takashima, S. Ogawa, K. Masuo, M. Fujita, T. Inokuma, A. Tsuji
Journal: Annals of Oncology (2013)
Abstract 1394: Stable knockdown of osteoprotegerin increases cell proliferation and metastasis in breast cancer cells.
Authors: Michael Weichhaus, Prabu Segaran, Andrew Le, Dirk Geerts, Linda Connelly
Journal: Cancer Research (2013)

Abstract Human breast cancer cells express and secrete osteoprotegerin (OPG, also called TNFRSF11B), a negative regulator for osteoclast differentiation. Previous in vitro data indicated that OPG expression promotes survival of breast cancer cells by inhibiting the apoptotic effect of TRAIL, through direct interaction of OPG with TRAIL. We generated stably transfected OPG-knockdown (KD) MDA-MB-231 breast cancer cells, using OPG shRNA clones, to examine the effect of OPG expression on primary tumor growth and metastasis in vivo. Positive selection of successfully transfected clones revealed that OPG KD cells expressed 60% less OPG (mRNA and protein) than control shRNA cells. OPG expression in control shRNA cells was not different from wild-type (wt) cells. Cell proliferation showed a small decrease after TRAIL challenge of KD cells compared to control and wt cells, assessed by MTT-assay, suggesting this was not a significant interaction. We decided to investigate the impact of OPG KD on tumor growth and metastasis using the chick embryo in vivo model. In brief, fertilized white leghorn chicken eggs were incubated for 10 days, after which the chorioallantoic membrane (CAM) was inoculated with 3 million KD or control cells. After an additional 7 days incubation, the primary tumor and a portion of the distant CAM were excised and measured for weight and the presence of human DNA, respectively. Primary tumor weight of KD cells was 31% higher than primary tumors from control cells. Moreover detection of human DNA in the distant CAM was 58% higher in eggs incubated with KD cells than in eggs incubated with control cells. Cell growth experiments in vitro showed that cell proliferation of KD cells was 40% higher compared to control and wt cells, as measured by trypan exclusion method. For validation in human cancer patients we mined a public microarray database, detailing gene expression in primary breast tumors. In agreement with our experimental data, high OPG gene expression in breast tumors was correlated with better prognosis. Contrary to the current understanding of OPG expression in breast cancer cells, our data indicates that OPG expression in breast cancer cells inhibits growth, the ability to metastasize and may promote survival in breast cancer patients. Citation Format: Michael Weichhaus, Prabu Segaran, Andrew Le, Dirk Geerts, Linda Connelly. Stable knockdown of osteoprotegerin increases cell proliferation and metastasis in breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1394. doi:10.1158/1538-7445.AM2013-1394
An Unusual Case of Haematuria
Authors: T. Oliver
Journal: BMJ (1888)

changes which, I think, take place when the abdominal cavity has been filled with fluid or an ovarian tumour.The result of my treatment in this case will encoutrage me to attempt, at some future date, a repetition of the operation.I may mention that I have under my care several patients who are troubled with symptoms of displaced cartilage or growth in the joint, which are constantly slipping or getting pinched between the ends of the bone, thus causing pain and crippling them.I intend, therefore, if I find no improvement after a fair trial, say six months, to open their joints, anid remove a fringe or fix a cartilage; and, by so doing, I shail hope to rid them of pain, discomfort, and inability to use the limb.P.S.-The patient wrote to me on April 16th, 1888 (seven months after the operation), snying lie continued quite well.
AB0738 Prevalence and incidence of systemic lupus eythematosus (SLE) in south korea
Authors: Y.-K. Sung, Y.B. Joo, J.S. Shim, J.-H. Lee, S.-Y. Park, C.-B. Choi, H.-S. Lee, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is one of the most common autoimmune disorders mainly affecting women of all ages. There are likely multiple genetic and environmental factors associated with differences in incidence and prevalence. These include ethnicity, gender, and geographic location. However, until now, most epidemiologic studies have been performed in the US and Europe, with less in Asia. <h3>Objectives</h3> We aimed to estimate the prevalence and incidence of SLE in South Korea using the Korean National Health Insurance (NHI) Claims Database which is the system of universal mandatory health insurance of South Korea. <h3>Methods</h3> On the basis of our previous validation study, the SLE patient was defined as the patient who had diagnostic code of SLE (M32) with any of history of hospitalization (1≤), simultaneous prescription of hydroxychloroquine and immunosuppressant (1≤), or had been taken complement test (C3&amp;C4) or anti-dsDNA antibody test (2≤). Prevalence of SLE during 2006-2010 was calculated. Age and sex-specific annual incidence rates of SLE per 100,000 general population for the year 2008 and 2009 and their CI were calculated for ten-year age intervals. <h3>Results</h3> The prevalence of SLE in South Korea was estimated to range from 20.6 in 2006 and 26.6 per 100,000 general population in 2010. Specifically, the prevalence of male was between 5.5 and 7.6 per 100,000 and that of female was between 35.9 and 45.6 per 100,000. The incidence rates of SLE in 2008 and 2009 were estimated as 2.6 and 2.8 per 100,000 in the general population of South Korea, respectively. The incidence of SLE peaks in the forth decade of life and female to male ratio during these years period is approximately 9:1. <h3>Conclusions</h3> Data gathered nationwide through the NHI yielded estimates of SLE prevalence and incidence in South Korea. They are comparable to values for other countries in Europe and US. <h3>Disclosure of Interest</h3> None Declared
The acute effect of lithium on renal renin and prostaglandin E synthesis in the dog.
Authors: J V Nally, G W Rutecki, T F Ferris
Journal: Circulation Research (1980)

Acute administration of lithium chloride (Li) to hydropenic anesthetized dogs significantly increased mean arterial pressure (MAP), plasma renin activity (PRA), and urinary prostaglandin E (UPGE) excretion with an increase in urinary volume, osmolar clearance, and sodium excretion.Solute-free water reabsorption increased during Li administration which argues against antagonism to ADH induced by increased PGE synthesis being a factor in the diuresis.The increase in renin secretion during Li administration was not caused by variation in sodium delivery to the macula densa, activation of the adrenergic nervous system, or change in renal resistance.Indomethacin, 5 mg/kg, prevented the rise in PRA and UPGE, abolished the natriuresis and diuresis, but did not prevent hypertension, whereas the angiotensin I-converting enzyme inhibitor, SQ20881, prevented both the rise in MAP and UPGE excretion.The fall in renal blood flow, rather than the inhibition of prostaglandin synthesis following indomethacin administration, probably accounted for the prevention of the natriuresis and diuresis since the converting enzyme inhibitor prevented the increase in UPGE excretion without effect on the natriuresis or diuresis.These studies demonstrate that Li increases renin and PGE synthesis.The increased renin secretion appears to be a direct effect of lithium on the juxtaglomerular apparatus, and the increase in PGE synthesis, which is secondary to angiotensin II generation, is not the cause of the diuresis or natriuresis.Circ Res 46: [739][740][741][742][743][744] 1980 THE effect of lithium on renal function has received increasing attention because of its use in the treatment of manic-depressive states.Both a primary polydipsia and a concentrating defect have been described in patients receiving lithium (Forrest et al., 1974;Singer et al., 1972).In animals, a natriuresis and diuresis occur with acute infusion of Li, and in vitro studies using the toad bladder have demonstrated that lithium antagonizes the hydroosmotic effect of ADH, as well as the aldosteroneinduced increase in sodium transport (Singer and Franko, 1973;Cox and Singer, 1978).Since PGE 2 is known to antagonize the hydro-osmotic effect of ADH in the isolated collecting tubule (Grantham and Orloff, 1968) and to cause a natriuresis when infused into the renal artery (Vander, 1968), we determined the acute effects of lithium chloride on urinary prostaglandin E (UPGE) excretion and renal function in the hydropenic dog.The results indicate that lithium significantly increases renal renin and PGE synthesis, but the accompanying diuresis and
HOSPITAL-LEVEL VARIATION IN THE USE OF EARLY CATHETERIZATION FOR PATIENTS WITH NON-ST ELEVATION MYOCARDIAL INFARCTION: INSIGHTS FROM THE NCDR ACTION REGISTRY-GWTG
Authors: Carolina Malta Hansen, Tracy Wang, Anita Chen, Karen Chiswell, Deepak Bhatt, Jonathan Enriquez, Timothy Henry, Matthew Roe
Journal: Journal of the American College of Cardiology (2016)
FRI0363 Children have a longer delay in diagnosis of takayasu arteritis than adolescents: lack of awareness about the disease?
Authors: G. Clemente, C. Len, C. A. Silva, S. Sachetti, V. Ferriani, F. Sztajnbok, S. Oliveira, B. Bica, A. Cavalcanti, T. Robazzi, M. Bandeira, M. O. Hilário, M. T. Terreri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Takayasu’s arteritis (TA) is a chronic granulomatous vasculitis affecting the large and medium arteries and can result in end organ damage. The disease is rare and there are few reports about the clinical features in the pediatric population. <h3>Objectives</h3> To evaluate and to compare the clinical features of TA in Brazilian children and adolescents. <h3>Methods</h3> In this Brazilian multicenter retrospective study including 10 pediatric rheumatology centers we identified 71 children and adolescents with TA diagnosed before the age of 18 years according to the validated classification criteria for pediatric age<sup>1</sup>. Patients’ demographic, clinical, laboratory and angiographic data were collected. The angiographic type was classified according to the 1994 International Conference of Takayasu arteritis in Tokyo<sup>2</sup>. Patients were divided in 2 groups: children, younger than 10 years – group 1, and adolescents, older than or equal to 10 years – group 2 and their disease characteristics at initial presentation were compared. <h3>Results</h3> Thirty-six (50.7%) patients were in group 1 and 35 (49.3%) were in group 2. Twenty-one (58.3%) patients in group 1 and 30 (85.7%) patients in group 2 were girls (p=0.010). The mean onset age was 5.7 and 12.7 in groups 1 and 2 (p&lt;0.001); the mean time to diagnosis was 1.8 and 0.7 in groups 1 and 2 (p= 0.001) and the mean follow-up time was 7.2 and 3.6 in groups 1 and 2 (p &lt;0.001). The predominant clinical symptoms at onset were decreased pulses (85.9%), followed by arterial hypertension (84.5%), constitutional (77.5%) and neurological symptoms (70.4%), however without statistical differences between the two groups. The main laboratory finding was an increased erythrocyte sedimentation rate followed by leukocytosis. Anemia and thrombocytosis were significantly more frequent in group 1 (p = 0.031; p= 0.001). Angiographic data were similar in both groups. <h3>Conclusions</h3> Children under the age of 10 had more laboratory abnormalities, but similar clinical and angiographic features when compared to adolescents with TA. A delay in diagnosis is more common in younger patients and clinicians must be aware about this disease in this age group. <h3>References</h3> Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R et al. EULAR/PRINTO/PRES criteria for Henoch-Schoenlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu’s arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010;69:798-806. Hata A, Noda M, Moriwaki R, Numano F. Angiographic findings of Takayasu arteritis: New classification. Int J Cardiol.1996;54(suppl):S155-S163. <b>Disclosure of Interest</b>: None Declared
Intractable Ventricular Fibrillation Associated with Profound Accidental Hypothermia — Successful Treatment with Partial Cardiopulmonary Bypass
Authors: William D. Towne, W. Peter Geiss, Hector O. Yanes, Shahbudin H. Rahimtoola
Journal: New England Journal of Medicine (1972)

Medical Intelligence from The New England Journal of Medicine — Intractable Ventricular Fibrillation Associated with Profound Accidental Hypothermia — Successful Treatment with Partial Cardiopulmonary Bypass
A Continuous Infusion of Acyclovir for Severe Hemorrhagic Varicella
Authors: Hiroshi Kakinuma, Eisuke Itoh
Journal: New England Journal of Medicine (1997)

To the Editor: Severe infections with varicella–zoster virus are common in immunocompromised hosts.1 Hemorrhagic varicella is serious and frequently fatal. We describe a case of hemorrhagic varicella that was resistant to a conventional regimen of acyclovir but was successfully treated by a continuous infusion of acyclovir. A 40-year-old woman with leukemia treated with various chemotherapies was admitted with fever, general fatigue, and generalized hemorrhagic bullae without a dermatomic distribution (Figure 1A and Figure 1B). A Tzanck smear of the bullae was positive. The patient had had varicella in childhood. An intravenous infusion of 250 mg of acyclovir over a one-hour period every . . .
Saved by a Test Result
Authors: Eldad Ben-Chetrit, Galia Rahav
Journal: New England Journal of Medicine (1994)

A 38-year-old man came to the outpatient clinic complaining of symmetrical swelling and pain in his hands. Two months earlier he had been in Moscow as a tourist. One month later he contracted a flu-like illness, followed by generalized malaise, fatigue, diffuse myalgia, arthralgia, and morning stiffness. These symptoms improved somewhat during treatment with oral diclofenac.At this point it seems that the patient has arthritis, which could be related to a previous infection. Arthritis may accompany illnesses caused by a number of viruses, including rubella, parvoviruses, enteroviruses, and adenoviruses. Usually rheumatic symptoms first become apparent as a . . .
Abstract 4333: Self-stabilizing ADCs: antibody-drug conjugates prepared with maleimido drug-linkers that catalyze their own thiosuccinimide ring hydrolysis.
Authors: Robert P. Lyon, Jocelyn R. Setter, Tim D. Bovee, Svetlana O. Doronina, Martha E. Anderson, Chris L. Leiske, Peter D. Senter
Journal: Cancer Research (2013)

Abstract Many antibody-drug conjugates (ADCs) currently in clinical trials employ maleimide-containing drug-linkers which are conjugated to antibody cysteine residues to form thiosuccinimide linkages. It is now known that these thiosuccinimide linkages can undergo two competing reactions while in plasma: elimination of the maleimide resulting in undesirable loss of drug from the ADC, and hydrolysis of the thiosuccinimide ring resulting in a succinic acid derivative which cannot undergo elimination. Thus, thiosuccinimide ring hydrolysis is a reaction which stabilizes the chemical linkage of the drug to the antibody. We have engineered a new class of drug-linkers which incorporate a basic amino group adjacent to the maleimide, providing intramolecular base catalysis of the ring hydrolysis. This basic group induces the thiosuccinimide to undergo rapid self-catalyzed hydrolysis at neutral pH and room temperature, with complete hydrolysis achieved in less than 2 hours. Once hydrolyzed, the drug-linker is no longer subject to maleimide elimination reactions, preventing loss of drug from the antibody by this mechanism and forming a highly stable ADC. To compare these new drug-linkers to traditional maleimido drug-linkers, a number of in vitro and in vivo studies have been conducted. Results of these studies will be presented to demonstrate a robust improvement in drug-linker stability compared to traditional drug-linker formats. Citation Format: Robert P. Lyon, Jocelyn R. Setter, Tim D. Bovee, Svetlana O. Doronina, Martha E. Anderson, Chris L. Leiske, Peter D. Senter. Self-stabilizing ADCs: antibody-drug conjugates prepared with maleimido drug-linkers that catalyze their own thiosuccinimide ring hydrolysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4333. doi:10.1158/1538-7445.AM2013-4333
Myelofibrosis with Myeloid Metaplasia
Authors: Ayalew Tefferi
Journal: New England Journal of Medicine (2000)

Myelofibrosis with myeloid metaplasia is classified broadly as a chronic myeloid disorder and, more specifically, as a chronic myeloproliferative disease1 (Figure 1). The primary pathogenetic mechanism is a clonal stem-cell disorder that leads to ineffective erythropoiesis, dysplastic-megakaryocyte hyperplasia, and an increase in the ratio of immature granulocytes to total granulocytes. This clonal myeloproliferation is characteristically accompanied by reactive myelofibrosis (bone marrow fibrosis) and by extramedullary hematopoiesis in the spleen or in multiple organs. The diagnosis is often suspected when teardrop-shaped red cells and myeloid precursors are detected in the peripheral blood. The typical clinical features include marked splenomegaly, progressive anemia, . . .
Pharmacokinetics and assessment of renal toxicity of a clofarabine (Clo), melphalan (Mel), and alemtuzumab (Alm) conditioning regimen.
Authors: K. Van Besien, J. P. Kline, M. Hardj, L. A. Godley, R. A. Larson, V. H. Nguyen, O. Odenike, W. Stock, S. Horowitz, A. S. Artz
Journal: Journal of Clinical Oncology (2010)

6541 Background: In a phase I-II study of allo transplant in advanced heme malignancy we gave Clo daily over 60 min for 5 doses (d -7 to d -3), Alm 20 mg daily for 5 doses (d-7 to d-2) and Mel on d -2. Level 1 was clo 10 mg/m2/d and mel 100 mg/m2. Clo was increased by 10 mg/m2/d per cohort until 40 mg/m2/d. Then, Mel was increased by 20 mg/m2 until 140 mg/m2. Because of grade III renal toxicity in 4 of 24 pts at Clo 40 mg/m2, 20 later pts were given 30 mg/m2. Pts also receive trimethoprim-sulfamethoxazole from d-7 to d-2 and ganciclovir or acyclovir IV from d -7 to d -2. Tacrolimus IV is started on d -2. Tacrolimus target level is 5-15 ng/ml. Methods: Clo pharmacokinetics were analyzed in 42 pts (clo dose range 10-40 mg/m2). Baseline GFR was estimated by Cockroft-Gault. Renal toxicity was assessed by Creatinine Increments (Cr Incr) (i.e., the difference between the highest Cr from d-7 to d12, and the Cr on d-7). Clo levels were drawn, at 1, 1.5, 2, 3, 5, 7, 9 and 24 hrs following the first and third (or fourth) dose. Results: Mean (95% CI) Cmax, CL and AUC were 481 ng/mL (95% CI 414-549), 36,894 mL/min (95% CI 29,149-44,639) and 1721 ng*hr/mL (95% CI 1,455-1,986), respectively. Mean AUC per dose 21.0 ng*hr/mL/mg (95% CI18- 23). Systemic exposure was similar between d1 and 3. Further analyses used d1 exposure, except for 3 pts with missing d1. 7 of 42 had Cr Incr of 0.5-1 mg/dL. 5 had Cr Incr 1-2mg/dL. 4 had Cr Incr > 2 mg/dL. 8 of 9 pts with Cr Inc > 1 mg/dL had severe comorbidities. There was a correlation between Clo Cmax and Cr Incr (r = 0.43, p = 0.004) and a correlation between Clo AUC and Cr Incr (r = 0.28, p = 0.06). In multivariate analysis only Clo Cmax was correlated with Cr Incr. Conclusions: CloMelAlm can cause renal impairment, often transient. Since Clo is renally excreted, and a strong correlation exists between Cr Incr and Clo Cmax, we hypothesize that prolonged Clo infusion schedules might avoid renal toxicity with this conditioning regimen. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genzyme Genzyme Genzyme Genzyme Genzyme