tbuckley/cabot-search huggingface dataset:
Time to brain metastasis (TTBM) from initial diagnosis of distant metastasis in breast cancer: Prediction of TTBM according to breast cancer subtypes and treatment effect.
Authors: Yeon Hee Park, Hee Kyung Ahn, Silvia Park, Chi Hoon Maeng, Su Jin Lee, Jin Seok Ahn, Young-Hyuck Im
Journal: Journal of Clinical Oncology (2012)

644 Background: Brain metastasis (BM) from breast cancer (BC) is a growing problem. About 10-15% patients with metastatic breast cancer (MBC) developed BM, with a 1 year survival of 20%. Currently, one-third of MBC patients with either HER2+ve tumors or triple negative BC (TNBC) tumors develop brain metastases. We hypothesized that MBC patients may predispose to BM differently during the disease courses according to BC subtype and treatment. We analyzed TTBM from initial diagnosis of distant metastasis how BC subtypes and treatment affect on TTBM. Methods: We retrospectively investigated 189 consecutive patients who were diagnosed with BM from BC between 2000 and 2009 at Samsung Medical Center. We analyzed TTBM according to BC subtypes and treatment effect. Results: The median age of 189 BM patients from BC was 48 (range 26-87) years. The numbers of patients with hormone receptor (HR)+ve and HER2-ve, HER2+ve irrespective of HR status, and TNBC were 43 (22.8%), 88 (46.6%), and 58 (30.7%), respectively. Median TTBM of all 189 patients was 10.4 (95% CI, 7.7-13.1) months. We analyzed TTBC into four groups considering BC subtypes and treatment; HR+ve/HER2-ve (n=43), HER2+ve with trastuzumab (T) (n=59), HER2+ve without T (n=29), and TNBC patients (n=58). The median TTBMs for each group were 17.7 months, 13.8 months, 4.3 months, and 2.9 months, respectively (p=0.002). BM as an initial site of distant metastasis was much more common in HER2+ve without T and TNBC patients than in the other patients’ groups (40.2% vs 20.6%, p= 0.003). Conclusions: TTBMs were much shorter in patients with HER2+ve without T and TNBCs than in other BC patients. Different approaches for evaluation and therapeutic strategy for BM at the time of distant metastasis may be considered for these populations.
Permanent 125I prostate brachytherapy outcome in patients younger than 60
Authors: D. E. Linstadt, M. Logsdon, D. Stickney, D. Chabra, M. Russo, S. Workman
Journal: Journal of Clinical Oncology (2006)

14553 Background: Permanent 125 I prostate brachytherapy (PB) has been shown to be an effective form of treatment for men with clinically localized prostate cancer. However, the efficacy of PB in younger men is not well established, and many urologists and oncologists have been reluctant to recommend PB to younger men, since most reported PB outcome has been based on men implanted in their late 60s and 70s. Methods: Between 1/1/98 and 6/30/01, 100 consecutive men aged 49–59 (median 56) underwent PB. All had either low- or intermediate-risk disease. PB was performed without combined external beam irradiation or post-PB androgen deprivation. The prescribed radiation dose=144–145Gy, the median implant activity=38mCi, median prostate volume=36 ml. Mean day-30 post-PB CT-based implant dosimetry values were V 100 =94%; V 150 =60%; D 90 =160 Gy. The primary endpoint for this analysis was the 5-year biochemical no evidence of disease rate (bNED) defined by the ASTRO consensus definition. Secondary endpoints were disease-specific survival (DSS); freedom from salvage therapy (FSRx), and overall survival (OS). Median PSA followup was 59 months (maximum 93 months). Actuarial results were calculated using the Kaplan-Meier method. Results: The 5-year bNED rate was 92%. 8 patients developed biochemical failure, and 6 went on to salvage treatment with hormonal therapy. There were 2 biopsy-proven local recurrences: one in a patient with previously diagnosed bony metastases, and one with isolated seminal vesicle recurrence (prostate biopsies negative). 3 other patients with biochemical failure had negative re-biopsies at 24, 64, and 66 months post-PB. No patient received local salvage therapy. One patient died from a second malignancy (colon CA diagnosed after PB). The 5-year DSS rate = 100%; FSRx = 93%, and OS = 99%. There were 2 Grade 3 GU complications (urethral strictures) (2%) and one Grade 4 GU complication (TURP) (1%). There were no Grade 3 or 4 GI complications. Conclusions: PB is an effective treatment modality for men younger than 60, with 5 year results comparable to those reported with prostatectomy and external beam irradiation. Given that most men who fail PB do so within 5 years of the implant, there appears to be no compelling scientific reason to advise against PB in men younger than 60 solely based on their age. No significant financial relationships to disclose.
Abstract P228: Genome-Wide Association Study of Lipid Response to Fenofibrate Treatment in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study
Authors: Donna K Arnett, Ingrid B Borecki, Marguerite R Irvin, Hemant K Tiwari, Robert J Straka, Jose M Ordovas
Journal: Circulation (2012)

The lipid-lowering drug fenofibrate (FF) is best known for its triglyceride (TG)-lowering properties, but it also reduces low-density lipoprotein (LDL), very low density lipoprotein (VLDL) and increases high-density lipoprotein concentrations (HDL). Response to FF varies considerably among individuals and may be under genetic influence. This study seeks to uncover genetic variants that underlie the interindividual response of TG, LDL, and VLDL to FF treatment. Methods: TG, LDL, and VLDL concentrations were measured as part of the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study before and after a 3-week FF treatment (160 mg/day). Genotyping was done using the Affymetrix 6.0 genome-wide array. Lipid response phenotypes were generated using growth curve models adjusted for age, agê2, sex, and center. Associations between single nucleotide polymorphisms (SNPs) and lipid phenotypes were assessed with mixed linear models including kinship correlation structure using the R package LMEKIN . Results: Genotype and TG, LDL, and VLDL response phenotype data were successfully collected from 769, 772, and 752 participants, respectively. The strongest evidence for association (P=3.80*10-7) was observed for LDL on chromosome 10 (133.7Mb) for SNP rs1646693. This lies near SLC35B4, a gene associated with obesity and glucose homeostasis. LDL also showed evidence of association (P=4.33*10-7) with rs6593376 on chromosome 10 (43.8Mb). The strongest evidence of association (P=5.54*10-7) with TG response was also on chromosome 10 (90.2Mb) at rs7917100 within RNLS, previously associated with cardiovascular function, cardiac hypertrophy, ischemia, and hypertension. Suggestive evidence of association (P=2.52*10-6) of rs11196872, with VLDL was also found on chromosome 10 (132Mb). Conclusions: We identified several novel loci suggestively associated with TG, LDL, and VLDL response to fenofibrate treatment.
Abstract 12004: Correction of Hyperphosphosphatemia by Dietary Phosphorus Restriction or Phosphorus Binder Similarly Ameliorates Vascular Complications and Mineral Disorders in CKD Rats
Authors: Yutaka Taketani, Haruka Ueda, Maerjanghan Abuduli, Hironori Yamamoto
Journal: Circulation (2014)

Introduction:  Hyperphosphatemia has been identified as an independent risk factor for cardiovascular disease (CVD) in chronic kidney disease patients. Higher serum phosphorus (P) concentration can cause both endothelial dysfunction and vascular calcification. Dietary P restriction and P binders are available for correction of hyperphosphatemia, however, it has not been clarified if both treatments can similarly ameliorate vascular complecations, especially endothelial dysfunction, as well as mineral disorders in CKD patients or not.   Hypothesis:  Here, we compared lanthanum carbonate as a P binder with dietary P restriction on the correction of hyperphosphatemia and endothelial dysfunction in adenine-induced chronic kidney disease rats.   Methods:  Adenine-induced CKD model rats were prepared by feeding 0.5% adenine containing diet for 35 days on male 7-wk-old Sprague-Dawley rats. Then, the adenine-induced CKD rats were divided 5 groups and treated with either control diet (CP; 1%P), low P diet (LP; 0.2%P), 1.5% lanthanum carbonate (La1.5; 1%P, 1.5%LaCO3), 3% lanthanum carbonate (La3; 1%P, 3%LaCO3), or 6% lanthanum carbonate (La6; 1%P, 6%LaCO3) for 14 days. After sacrifice, plasma P, intact-PTH, FGF23, and creatinine were measured. We evaluated acetylcholine-dependent vasodilation of aortic ring by isometric transducers, and F4/80 positive cells and MCP-1 expression on aortic arch by immunohistochemical analysis.   Results:  Hyperphosphatemia, high PTH and FGF23 levels were similarly and significantly corrected in LP and La6 groups compared with CP group. LP and La6 groups similarly and significantly ameliorated impaired vasodilation in response to acetylcholine. However, correction of hyperphosphatemia was not enough in La1.5 and La3 groups so that impaired vasodilation was not significantly ameliorated. LP and La6 groups also decreased F4/80 positive cells and MCP-1 expression on aortic arch.   Conclusions:  Correction of hyperphosphatemia by either dietary P restriction or lanthanum carbonate can similarly ameliorate vascular complecations and mineral disorders including abnormal PTH and FGF23 observed in adenine-induced CKD rats.
Ameliorated effects of Lactobacillus delbrueckii subsp. lactis DSM 20076 and Pediococcus acidilactici NNRL B-5627 on Fumonisin B1-induced Hepatotoxicity and Nephrotoxicity in rats
Authors: Amira A. Abdellatef, Ashraf A. Khalil
Journal: Asian Journal of Pharmaceutical Sciences (2016)

Oxidative stress has been implicated in a number of human regeneration and disease processes including atherosclerosis, pulmonary fibrosis, cancer, and different neurodegenerative diseases. The aim of this study was to evaluate the protective effects of Lactobacillus delbrueckii subsp. lactis DSM 20076 (LL-DSM) and Pediococcus acidilactici NNRL B-5627 (PA-NNRL) against the hepatic- and nephro-toxicity of fumonisin B1 (FB1) in FB1-treated rats for an experimental period of 4-weeks. Eighty mature male Sprague-Dawley rats were divided to 12 groups: 1 untreated group; 3 groups fed by a FB1-contaminated diet (50, 100 and 200 mg FB1/kg diet, respectively); 1 group fed orally by LL-DSM (1 ml/d); 1 group fed orally by PA-NNRL (1 ml/d); 3 groups co-administered by FB1-contaminated diet and LL-DSM (1 ml/d), and 3 groups co-administered by FB1-contaminated diet and PA-NNRL (1 ml/d). Malonaldehyde (MDA) nitric oxide, glutathione content, SOD activity, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined. DPA assay was used to assess apoptosis in liver and kidney tissues. The animals fed with FB1-contaminated diet showed a significant increase in oxidative stress markers and DNA fragmentation accompanied with significant decrease in GSH content, SOD activity, and TAC in liver and kidney tissues, especially at high-dosage of FB1 (T200). Probiotics antioxidant strains (LL-DSM and PA-NNRL) relatively succeeded to restore almost all parameters investigated as well as to reduce DNA fragmentation in liver and kidney tissues. As a conclusion, probiotics may induce its protective role via increasing the antioxidant capacity, inhibition of lipid peroxidation, scavenging of free radicals and decreasing DNA lesions in liver and kidney of experimental animals tested.
Role of prognostic factors in patients with metastatic renal cell carcinoma (MRCC) eligible for treatment with interleukin (IL2)
Authors: H. Muniswamy, J. P. Dutcher, P. Mannam, S. Malik, V. Rusciano, L. Paul, P. H. Wiernik
Journal: Journal of Clinical Oncology (2006)

14514 Background: Motzer (JCO1999) defined 5 factors that predict for poor survival of patients with MRCC: low Karnofsky scale (&lt;80%), high LDH (&gt;1.5 times upper limit), low Hb (&lt;lower limit of normal), elevated corrected calcium (10 mg/dl) and absence of nephrectomy. Method: We retrospectively evaluated 124 patients with MRCC (81 male/43 female, median age 54 years, range (R) 27 to 79 years) treated in our center from 10/98–12/05 with IL2 based therapy. Patients eligible for IL2 study were included. Patients were categorized into favorable (F - 0 risk factors), intermediate (I - 1–2 risk factors) and poor (P - 3 or more risk factors) groups. 89 patients had high dose (HD) IL2 (600,000 u/kg/dose every 8 hours up to 14 doses), and 35 patients had moderate dose (MD) IL2 (5 mu/m 2 /day for 5 days continuous infusion or 72,000 u/kg every 8h up to 14 doses). 26 patients had prior treatment. Prognostic factors were identified at the start of IL2 therapy. Primary endpoint was survival time defined as the time from initiation of IL2 treatment to time of death or December 2005 as the last follow up for all patients. Results: Analyzed using Kaplan-Meier method. Conclusions: 1. These prognostic factors apply to IL2 treated patients and separate them into prognostic groups. 2. HD IL2 treated patients have ≥ 6 months greater survival compared to MD IL2 treated patients or historical data. [Table: see text] No significant financial relationships to disclose.
Long term prognostic importance of primary Ki-1 (CD30) antigen expression and anaplastic morphology in adult patients with diffuse large-cell lymphoma
Authors: J.E. Romaguera, J.T. Manning, J. Rodriguez, T.E. Brooks, W.C. Pugh, N.G. Ordonez, A.M. Goodacre, E. Cabanillas, C.S. Tornos
Journal: Annals of Oncology (1994)
Frameless hypofractionated stereotactic radiosurgery to the tumor bed after resection of solitary brain metastases.
Authors: S. Lindsey, D. Stacy, B. Collett, A. Stroink, K. Kattner, E. Nardone, J. Seibly, M. Ali, L. Howard
Journal: Journal of Clinical Oncology (2010)

e12542 Background: Conventional tx of a solitary brain met consists of surgical resection followed by postop whole-brain radiotherapy (WBRT). For pts with controllable systemic dz this tx regimen has been shown to improve overall survival and functional independence. An alt tx modality for small, discrete mets is stereotactic radiosurgery (SRS). SRS, with or without WBRT, provides adequate local control (LC), preserves performance status, and improves length of survival (LOS). To date, no studies have looked at the role of post-op SRS. This study will analyze the role of SRS to the postop tumor bed following gross total surgical resection (GTR) of brain mets. Methods: Retrospective chart review on 23 pts (1 pt received similar tx to a separate brain lesion: 24 sites tx) who underwent hypofractionated frameless SRS following GTR of a newly diagnosed cerebral met. All pts underwent a craniotomy for GTR. Post op, each pts resection bed was tx using a frameless, image-guided 6 MV linear accelerator. Tx was divided into 5 fx in each case. Total delivered dose: 25 Gy to the 78-85% (median 81%) isodose line. Target vols were tx non- isocentrically, allowing conformality of RT to the tumor cavity. Variables analyzed were LOS, LC, regional control, and major post-RT complications. Results: Mean fu for 23 pts: 6.3 mos post SRS. Mean LOS: 9.5 mos. LC rate: 92% (22 of 24 tx sites). Local recurrence: 2 pts. 1 required add'l surgical resection, the other was tx with add'l SRS. Distant cerebral recurrence: 4 pts (2 pts developed lesions distant from the original site that were successfully tx with add'l SRS; 2 pts developed diffuse intracranial dz and received WBRT). No major complications as a result of SRS were noted. 8 of the 23 pts are still alive, mean LOS 15.3 mos. Conclusions: SRS is typically viewed as an alt to surgery in the mgmt of cerebral met dz, rather than an adjunct tx option. The isocentric, homogeneous dose delivery provided by frameless robotic SRS allows for the tx of GTR cavity beds. Unfortunately, no studies have investigated the role of post-GTR SRS to the tumor bed in place of WBRT. This data suggests that GTR followed by SRS to the residual cavity may be as efficacious as surgery followed by WBRT. A large prospective trial is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Central Illinois Neuro Health Sciences
Prognostic uncertainty drives GP antibiotic prescribing in children, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

210.2.1, 210.2.3, 102.1, 102.2, 102.3, 102.4, 102.5, 102.6, 102.7, 102.8, 102.9, 102.10, 202.39.25 top

Uncertainty about prognosis is a major reason that GPs prescribe antibiotics for children with respiratory tract infections, a study of UK primary care has shown.1

Respiratory tract infection is the most common reason parents take their child to see a GP in the UK. Although antibiotics have only marginal benefits they are often prescribed—a situation that has previously been blamed on parental pressure.

“Consultations for respiratory tract infections are more complex than most guidelines assume,” said the authors of the new study, led by Jeremy Horwood, from the centre for academic primary care …
A phase I study of combined docetaxel and repeated high activity rhenium-186- HEDP in castration-resistant prostate cancer metastatic to bone (the TAXIUM trial).
Authors: J. M. van Dodewaard-de Jong, H. Bloemendal, J. M. de Klerk, B. P. van Bezooijen, M. J. de Haas, R. H. Wilson, J. M. O'sullivan
Journal: Journal of Clinical Oncology (2010)

4688 Background: Bone seeking radionuclides have proven palliative benefit in castration resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown an improvement of survival and quality of life when radiopharmaceuticals were given in repeated dosages or in combination with chemotherapy. Docetaxel is the only cytotoxic agent with a proven survival benefit. We designed a phase I study combining docetaxel, prednisolone and rhenium-186-HEDP (Re-186-HEDP) in men with CRPC and bone metastases in order to evaluate safety and feasibility of both combined chemo-radionuclide therapy and repeated treatment with the radionuclide. Methods: A dose escalation schedule was designed consisting of four different dose levels with a standard dosage of docetaxel (75mg/m2 IV on day 1 every 3 weeks) for 6 cycles and prednisolone 10mg PO BID continuously. Re-186-HEDP was given in increasing activities (1250MBq up to 2500MBq) after the third and sixth cycle of docetaxel. Men with histologically confirmed CRPC metastatic to bone, WHO performance score 0/1, normal renal and bone marrow function and no previous cytotoxic chemotherapy were eligible. Dose limiting toxicity (DLT) was defined as any grade 4 toxicity lasting more than 7 days or any grade 3 toxicity that did not recover within 10 days. Three patients were planned for each dose level expanding to 6 if a DLT occurred. Results: 14 patients were recruited to this study with an average age of 64 years. The median PSA at time of inclusion was 98ng/ml (range 26-15000). One DLT, grade 4 thrombocytopenia, was experienced at dose level 3 leading to expansion of this group to 6. One of these patients had an episode of unrelated acute renal failure which resolved. Conclusions: Combined therapy with docetaxel and Re-186-HEDP is safe and generally well tolerated in patients with CRPC metastatic to bone. DLT was thrombocytopenia. We will conduct a randomised phase II study using dose level three as the experimental arm: docetaxel 75mg/m2 3-weekly and prednisolone 10mg PO BID continuously for a maximum of 10 cycles with or without the addition of Re-186-HEDP, given as 2500MBq after cycle 3 and 1250MBq after cycle 6 of docetaxel. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Open-label, multicenter, phase Ib, dose-escalation study of oral lapatinib (L) in combination with docetaxel (D) and trastuzumab (T) in untreated HER2-overexpressing (HER+) metastatic breast cancer (MBC).
Authors: V. Dieras, M. J. Kennedy, P. Tresca, M. E. Marty, H. Burris, M. DeSilvio, N. O'Donovan, M. Lau, M. Ridderheim, J. Crown
Journal: Journal of Clinical Oncology (2010)

1049 Background: While most patients with HER+ MBC respond to treatment with D+T, the majority ultimately develop and die from progressive MBC. L produces responses in patients with T-pretreated HER+ MBC, and the combination of T+L is synergistic in vitro and superior to L in a trial in T-failed MBC. There is thus a rationale for the study of D+L+T in HER+ MBC. We performed a phase Ib study to determine the recommended optimally-tolerated, first-line regimen for phase II trials (ROTR) of these drugs in patients with untreated HER+ MBC. Methods: Eligibility criteria included HER+ MBC (3+ immunochemistry and/or FISH positive). T was given weekly at a fixed dose of 2mg/kg IV following a loading dose of 4mg/kg. D was given IV every 3 weeks at increasing doses (60, 75, and 100mg/m2). L was given orally once daily at increasing fixed doses (500, 750, 1,000, 1,250, and 1,500mg). Dose escalation followed a classical 3+3 design. Dose-limiting toxicities (DLT) were assessed during the first treatment cycle. The ROTR was defined as the dose level that produced a rate of DLT <33%. The protocol was amended to include growth-stimulating factor (GSF) support because of a high rate of febrile neutropenia at the first 2 dose levels. Results: Fifty patients with locally advanced or metastatic breast cancers were enrolled. Median age was 51 years (range: 22-67). Most patients had an ECOG performance status of 0 or 1. Sites of metastatic disease included bone (52%), lung (36%), liver (34%), and brain (4%). Twenty-six (52%) patients received prior adjuvant chemotherapy, including T in 23 (46%) patients. DLTs consisted mainly of myelosuppression, rash, diarrhea, and peripheral neuropathy. Two ROTR have been determined, including T in combination with L 1,250 mg daily and D with GSF support 75 mg/m2; IV every 3 weeks, or L 1,000 mg and D 100 mg/m2;. Efficacy data will be presented. Conclusions: L in combination with D and T is tolerable with 2 ROTR: either L 1,250 mg-D 75 mg/m2; or L 1,000 mg-D 100 mg/m2; with T. The first regimen is 1 of the study arms of the adjuvant ALTTO trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline Celgene, Debiopharm, GlaxoSmithKline, Pierre Fabre Oncologie, sanofi-aventis
Perforated and embedded intrauterine devices [letter]
Authors: Wright Ch
Journal: JAMA (1983)

Zakin et al (1982; 247:2144) in their article entitled Perforated and Embedded Intrauterine Devices failed to mention a method of managing its complication that has served me well.  The following case illustrates its use.  A 39-year old woman para 2 reappeared 15 years after the insertion of an IUD demanding its removal.  Since the string was not visible an ultrasound study confirmed that it was still present.  Efforts to remove it in the office failed.  The patient was hospitalized a few days later with a temperature of 38 degrees Celsius and pelvic pain but no pelvic mass.  She was taken to the operating room.  While probing for the IUD I opened a posterior myometrial abscess from which 10-15 mL of pus escaped.  Further surgery was abandoned for fear of perforating the uterine wall.  A drain was left in the cavity and she was treated with antibiotics.  Meanwhile anteroposterior and lateral roentgenograms were made for better localization of the device.  5 days later the patient was taken again to the operating room.  Again I was unable to locate the IUD even while looking at the roentgenogram.  The cervix was split at the 6-oclock position through the internal os allowing the index finger to reach the fundus.  The device was located higher in the posterior wall than was suggested by ultrasound or roentgenogram.  The lower end of the object was grasped with the polyp forceps and extracted with ease.  The uterine wound was closed with a running Vicryl suture 0.  She had a normal recovery.  The menses have been normal and the wound healed by primary intention.  (full text)