tbuckley/cabot-search huggingface dataset:
Abstract 15795: Hydration Prior to CT-Pulmonary Angiography is Not Required for Prevention of Contrast Induced-Acute Kidney Injury: The Randomized Nefros Trial
Authors: Judith Kooiman, Yvo W Sijpkens, Marjolijn van Buren, Marc J Groeneveld, Soerindra Ramai, Aart J van der Molen, Nico J Aarts, Cees J van Rooden, Suzanne C Cannegieter, Hein Putter, Ton J Rabelink, Menno V Huisman
Journal: Circulation (2013)

Introduction: Hydration to prevent contrast induced-acute kidney injury (CI-AKI) results in a diagnostic delay when performing CT-pulmonary angiography (CTPA) in patients presenting with clinically...
Abstract P3-05-15: Divergent activation of AKT1 and AKT2 isoforms downstream of PI3K mutation impacts response of breast cancer cells to estradiol and PI3K inhibitors
Authors: Harikrishna Nakshatri, Chirayu Goswami, Sunil Badve, Luca Magnani, Mathieu Lupien, Poornima Bhat-Nakshatri
Journal: Cancer Research (2015)

Abstract Background: PI3K mutations are observed in 30% of breast cancers, which are more common in estrogen receptor (ERα) positive breast cancers compared to ERα-negative breast cancers. AKT, a the major kinase downstream of PI3K, modulates ERα activity. It is unknown whether PI3K mutation leads to preferential activation of specific AKT isoform with ability to modulate ERα function. Results: We report elevated AKT1 but not AKT2 mRNA in breast cancers with PI3K mutation. Breast epithelial cells with targeted substitution of PI3K with PI3K-E545K or PI3K-H1047R demonstrated elevated AKT1_pS473 compared to AKT2_pS474, distinct AKT substrate phosphorylation, and enhanced Estrogen Receptor (ERα) activity. AKT1 had a dominant role in ERα:estradiol (E2)-dependent gene expression and proliferation. We have identified an unique gene expression signature in ERα-positive breast cancers that is dependent on ERα, estradiol (E2), AKT1, and the pioneer factor FOXA1. Elevated expression of this signature in ERα-positive tumor was associated with better response to endocrine therapy and outcome. In addition, AKT1 determined the sensitivity to PI3α-specific inhibitor BYL719 and pan-PI3K inhibitor BKM120. In contrast, AKT2 controlled global gene expression and elevated levels of an AKT2-directed protein signature predicted poor outcome in breast cancer patients. Conclusions: PI3K mutation favors AKT1 activation leading to imbalance in AKT isoform-specific kinome/proteome and an effect on specific signaling pathways, particularly ERα:E2 signaling network. Knowledge gained from this functional dissection of AKT isoform activity downstream of PI3K mutation can be exploited for therapeutic stratification, particularly for anti-estrogen and PI3K inhibitor-based therapies. Citation Format: Harikrishna Nakshatri, Chirayu Goswami, Sunil Badve, Luca Magnani, Mathieu Lupien, Poornima Bhat-Nakshatri. Divergent activation of AKT1 and AKT2 isoforms downstream of PI3K mutation impacts response of breast cancer cells to estradiol and PI3K inhibitors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-15.
T1abN0M0 HER2+ invasive breast cancer recurrence: Population-based cohort of 17,000+ consecutive breast cancers 2000-2006 at Kaiser Permanente Northern California (KPNC).
Authors: L. Fehrenbacher, P. Shiraz, M. Sattavat, A. Capra, C. Quesenberry, R. Fulton, L. A. Habel
Journal: Journal of Clinical Oncology (2011)

551 Background: T1abN0M0 BC has a low recurrence risk. In contrast, HER2+ BC has an increased risk of local/distant recurrence. In small case series of T1abN0M0 HER2+ BCs from tertiary referral centers, recurrence rates have ranged from 8-23%. Data on sites of recurrence have been limited. While adjuvant chemotherapy plus trastuzumab provides a relative reduction in recurrences of ~50% for HER2+ stage II patients, it remains unclear if women with small HER2+ tumors have sufficient risk to warrant such therapy. Methods: All invasive BC diagnosed from 2000 -2006 at KPNC had routine measurement of HER2, ER, PR at a single, high volume laboratory of excellence. A study physician reviewed the medical record of all T1abN0M0 BC to confirm HER2, ER status, stage, therapy, recurrence, and other outcomes. Kaplan-Meier methods were used to estimate recurrence-free (RFI) and distant recurrence-free intervals (DRFI) and 95% confidence intervals (CI). Results: We identified 237 cases of T1abN0M0 HER2+ BC: 116 T1a (including 18 < 0.1 cm) and 121 T1b. Median follow up was 5.8 years. 15 (6.3%) of all T1ab N0 patients had invasive cancer recurrence (ICR) with 7 (2.9%) local only and 8 (3.4%) distant. T1a patients had 3 (2.6%) ICR local only and 1 distant (0.9%) recurrence. 9.1% of T1b patients had ICR: 4 (3.3%) local only and 7 (5.8%) distant. 8 of 11 T1b recurrent patients had 1.0 cm tumors as did 6 of 7 distant T1b recurrences. 3 recurrences were DCIS only. For the T1a and T1b patients, the 5-year RFIs were 96.2% (95% CI 90.0, 98.6) and 91.1% (95% CI 83.4, 95.3); the DRFIs were 99.1% (95% CI 93.9, 99.9) and 94.0% (95% CI 87.1, 97.3) respectively. 24.9% of T1ab patients received adjuvant chemotherapy without a clear benefit. Overall, 8.9% received adjuvant trastuzumab: 3.3% during 2000-2004 and 18.6% during 2005-2006. Conclusions: Recurrence risk for T1a N0 HER2+ BC was too low to justify adjuvant therapy with chemotherapy or trastuzumab. T1b N0 tumors <1.0cm also had very low distant and local recurrence. Nearly half (7/15) of invasive recurrences in T1ab patients were local only and their prevention might be attained with more aggressive local therapy.
Comparison between patient's (pt) and doctor's (dr) expectation about the efficacy of cancer treatment (tx). A prospective blind mis-match analysis
Authors: E. L. Morgenfeld, E. Rivarola, C. Cataldi, E. Gil Deza, F. Tognelli, S. Polo, M. De Romedi, D. Santillan, S. Ares, F. G. Gercovich
Journal: Journal of Clinical Oncology (2004)

8248 Background: Few data about cancer pt's and clinical oncologist's expectations about the efficacy of a systemic treatment are available. Methods: A written self-report questionnaire was distributed within pts attending to our cancer clinic during a two-week period. Questions about satisfaction with medical care were included. Pts were asked about their expectations from cancer treatment i.e. cure, prolongation of life or improving quality of life. The doctors were blindly requested to provide their reason for the prescription of a given chemotherapy regimen.. The sign test was used to match drs' and pts' expectation from tx. Results: A total of 273 consecutive pts completed the questionnaire. Median age was 61 y.o. (range 15 to 86). Cancer diagnosis included: breast 114 (41.8%), colo-rectal 45 (16.5%), prostate 35 (12.8%), lung 11 (4%), ovary 9 (3.3%), lymphoma 8 (2.9%) head and neck 6 (2.2%), testes 6 (2.2%) and miscellaneous 39 (14.2%). One hundred and seventy four pts (63.7%) had stage III-IV disease while 99 (36.3%) had stage I-II disease. A high degree of satisfaction with medical care, the provided medical information and the willingness to follow their drs instructions, were reported by over 90% of the pts. One hundred and seventy six pts (72.7%) stated that they expected that treatment would cure them, while 53 pts (21.9%) felt that tx would help to prolong life. Five pts (2.1%) reported that tx was prescribed to improve quality of life and the remaining 5 pts (2.1%) quoted a combination of options. The dr's expectations for treatment outcome were comparable to that of their patients' in 49% of the cases. There was 90% agreement between pts and drs for stage I and II pts (p=0.001) and less than 30% agreement for stage III/IV pts (p=0.001). However, drs were more pesimistic than pts in 44.3% of stage III/IV while they have a more optimistic vision for 7% of stage I-II. Conclusions: In our setting, cancer patients are highly satisfied with the doctor-patient interaction, however their high expectations for cure may be unrealistic. No significant financial relationships to disclose.
Safety of bevacizumab-based therapy as first-line treatment of patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): MO19390 (SAiL)
Authors: E. Dansin, J. Mezger, D. Isla, F. Barlesi, A. Bearz, P. Garrido Lopez, J. J. Laskin, N. Pavlakis, N. Thatcher, L. Crinò
Journal: Journal of Clinical Oncology (2008)

8085 Background: MO19390 (SAiL) is an open-label single-arm trial evaluating the safety of first-line bevacizumab (Bev) combined with standard chemotherapy regimens, in some 2000 patients (pts) with NSCLC. As baseline brain scans were not required, pts with asymptomatic brain metastases (mets) could be recruited allowing preliminary analysis of Bev safety in pts diagnosed with CNS mets during the course of the study. Methods: The primary endpoint is safety. Eligibility criteria include; untreated, locally advanced, metastatic or recurrent non-squamous NSCLC; performance status (ECOG PS) 0–2. Pts with history of gross hemoptysis or evidence of tumor invading major blood vessels are ineligible. Pts receive a standard first-line chemotherapy regimen for up to 6 cycles combined with Bev, followed by Bev until disease progression. Results: Here we present preliminary data as documented in the EDC system (November 2007). Analyses are based on the safety population (pts who received ≥1 cycle of therapy; n=1065). Patient characteristics are: median age 60 years (range 24–83); male/female (%) 61/39; ECOG PS 0/1/2 (%) 39.9/53.3/6.8; adenocarcinoma/other (%) 83.8/15.7 (no data 26 pts); stage IIIb/IV (%) 20.2/79.8 (no data 4 pts); chemotherapy regimen: carboplatin doublets/cisplatin-doublets/non-platinum doublets/monotherapy (%) 48.2/40.0/1.2/2.7. 396 serious adverse events (SAEs) were reported, 64 (16%) Bev related: 207 in the Bev and chemotherapy phase and 29 in the Bev maintenance phase. 299 of these 396 SAEs (75.5%) have resolved or improved. CNS progression was observed in 12 pts (1.1%). No CNS hemorrhage was observed during treatment. Grade 3–4 hypertension was seen in 29 pts (2.7%). One patient diagnosed with brain mets after cessation of Bev had a CNS hemorrhage 26 weeks after the last dose. Conclusions: Preliminary analyses in >1000 pts confirm the well-characterized safety profile of Bev based therapy in the treatment of NSCLC, using a range of chemotherapy partners in a large patient population. There have been no cases of CNS hemorrhage associated with metastases under therapy to date. Updated results will be discussed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly, Roche, sanofi-aventis Amgen, AstraZeneca Oncology, Eli Lilly, Roche, sanofi-aventis Roche Amgen, Eli Lilly, Roche, sanofi-aventis
Association of margin assessment method with reexcision rates in breast-conserving surgery (BCS).
Authors: L. Choi, C. K. Culpepper, J. I. Goldberg, A. S. Heerdt, T. A. King, L. Sclafani, A. S. Reiner, S. Patil, E. Brogi, K. J. Van Zee
Journal: Journal of Clinical Oncology (2010)

e11018 Background: The need for reexcision after BCS is common, reported to be > 50% in some series. We examined reexcision rates using 3 different methods of margin assessment (METHODs) at our institution from 2003-2008. Methods: The study population consisted of all patients completing BCS and sentinel node biopsy after needle biopsy diagnosis of breast cancer from Jul-Dec 2003, 2004, and 2008. These 3 time periods corresponded to 3 METHODs: perpendicular (P) (pathologist-evaluated perpendicular margins in serial sections of the specimen, 2003), tangential shaved (T) (pathologist shaved margins from the specimen, 2004), and cavity shaved (C) (surgeon shaved margins from the cavity, 2008). The need for > 1 excision and the volume of tissue excised were examined for each METHOD. Kruskal-Wallis and Chi-squared tests were used for statistical analysis. Results: For each METHOD, the number of cases was as follows: P =174, T = 160, and C = 299. Overall, positive margin rates were higher for T than P or C (p < 0.0001) resulting in rates of > 1 excision in 35% (T), 28% (P) and 24% (C) (p = 0.05). Cases with extensive intraductal component (EIC) required > 1 excision in 38%, vs. 27% of non-EIC cases (p = 0.01). Among women with EIC, the proportion needing > 1 excision rose to 54% (T), 29% (P), and 36% (C) while cases without EIC underwent > 1 excision in 30% (T), 28% (P), and 24% (C). The initial excision volume was significantly lower for P than for the other methods (mean, 63 cc [P] vs. 78 cc [C], 70 cc [T], p = 0.003). Among surgeons, there was variability in initial volume excised (p < 0.0001) and need for > 1 excision (p = 0.02). However, for 6 of the 9 surgeons, the C METHOD resulted in the lowest reexcision rate. Conclusions: METHOD has a significant impact on reexcision rates; risks and benefits of each method must be weighed. T results in higher margin positivity and reexcision rates than P and C, while P has lower excision volumes. Although P and C have similar reexcision rates, C has an advantage in that it allows the surgeon to more accurately define margins of resection, thereby directing reexcision more precisely. Lower volume of excision in P, however, may translate to better cosmesis. No significant financial relationships to disclose.
The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote TH17 cell–dependent emphysema
Authors: Wen Lu, Ran You, Xiaoyi Yuan, Tianshu Yang, Errol L G Samuel, Daniela C Marcano, William K A Sikkema, James M Tour, Antony Rodriguez, Farrah Kheradmand, David B Corry
Journal: Nature Immunology (2015)
Cisplatin combination regimen in the second-line treatment of non-small cell lung cancer.
Authors: O. Altundag, H. Mertsoylu, Z. Akcali, H. Sakalli, O. Ozyilkan
Journal: Journal of Clinical Oncology (2010)

e18136 Background: In advanced NSCLC pts who experienced relapse or disease progression during or after first-line treatment, single agent docetaxel, pemetrexed or erlotinib are used. Platinum group agents are not preferred in second-line therapy due to possibility of platinum resistance or cumulative toxicity. However there is not enough data to justify not using cisplatin as a part of second-line regimens. Methods: In this study we compared two groups of patients who whether cisplatin or not as part of second-line regimen in terms of response rate, survival and toxicity. Results: 53 pts with progressive NSCLC (21 inoperable stage IIIB and 32 stage IV) who received platinum-based regimen in the first line therapy were enrolled. 26 pts received cisplatin combination therapy and 27 pts were treated with standard single agent chemotherapy (docetaxel) as second line therapy. Median OS in combination and Docetaxel groups were 6.3 and 7.8 mos. Median OS of pts who received second-line therapy before and after 5 mos from start of the first-line treatment due to disease progression were 5.6 and 9.8 mos respectively. In the subgroup analysis of the pts who received cisplatin combination as a second-line treatment, pts that received cisplatin before (14 pts) and after (12 pts) 5 months median OS was 7.6 and 5.6 mos respectively. Among 26 pts who received cisplatin, median OS of 10 who had > 9 cycles and 16 who had < 9 cycles of cisplatin containing combination therapy were 20.1 and 11.8 mos, respectively (p = 0.0001). Grade 3-4 toxicities and renal toxicity were rare in both groups and no toxic deaths were observed. Conclusions: For pts with good PS, using platinum based regimen beyond first-line chemotherapy may have a positive impact on OS in pts whom had early progression or resistant to the first-line treatment. Defining the criteria of platinum sensitivity in pts with NSCLC to support rechallenging them with platinum-based treatments may be important strategy as second-line therapy in advanced NSCLC. No significant financial relationships to disclose.
Correlation between immune-related adverse events and response to pembrolizumab in advanced melanoma patients
Authors: Antonio Grimaldi, Ester Simeone, Lucia Festino, Diana Giannarelli, Marco Palla, Corrado Caracò, Marcello Curvietto, Assunta Esposito, Maria Grimaldi, Nicola Mozzillo, Paolo A Ascierto
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immunomodulation with pembrolizumab (anti-PD-1) has been shown to reach significant objective response (RR) and extend overall survival (OS) both in ipilimumab pre-treated and naive patients with metastatic melanoma. While this immunotherapy gives OS and OR benefits, it can also
Reducing black neonatal mortality [letter]
Authors: Sepkowitz S
Journal: JAMA (1985)

The author of this letter asserts that the differences in weight-specific mortality between blacks and whites of low birthweight is even greater than that reported by Binkin et al.  In addition all mortality rates but particularly those in the 500-1499 gm birthweight group are higher than those reported by Binkin as a result of under-reporting of deaths in very low birthweight groups.  Binkin et al included 609191 white sigletons in their analysis and 75735 blacks--6.4% and 2.9% fewer respectively than registered in the vital records of California.  As a result black births are more completely reported.  A review of US natality statistics revealed that 3.6% of all white births lacked gestational age information compared to 4.4% of black births.  Thus gestational age underreporting is similar to birthweight underreporting in that both cluster among the smallest infants where mortality and failures of reporting are greatest.  The consistently lower mortality rates among blacks in the low birthweight groups suggests a need to separate white and black mortality rates in area studies as well as studies in which the mortality rate of low birthweight infants serves as an index of the quality of medical care.
Precise Longitudinal Tracking of Microscopic Structures in Melanocytic Nevi Using Reflectance Confocal Microscopy
Authors: Alon Scope, Limor Selinger, Margaret Oliviero, Francesca Farnetani, Elvira Moscarella, Caterina Longo, Harold S. Rabinovitz, Giovanni Pellacani
Journal: JAMA Dermatology (2016)

Reflectance confocal microscopy (RCM), a cellular-level, in vivo imaging technique, may be potentially used for monitoring melanocytic neoplasms for microscopic stability vs changes over time.To test feasibility of using RCM to track specific microscopic structures within nevi over 1 year.This was an observational study, a review of prospectively acquired RCM images, performed at a tertiary academic medical center. Seventeen patients were enrolled from adult patients presenting to pigmented lesion clinic; from each participant, 3 confirmed benign nevi were randomly selected from the upper and lower back and from the lower extremity.Nevi underwent standardized RCM imaging at baseline and after 1 year.We tested interobserver reproducibility in recognition of tissue anchors, RCM structures that can be identified at 2 time points. We used 2 tests to measure concordance between independent readers: (1) In the multiple choice matching test (n = 43 nevi), readers were shown a tissue anchor in a baseline RCM image (≤ 1 × 1-mm field-of-view) and asked to identify the same structure in 1 of 4 equally sized RCM images obtained from the same nevus at follow-up. (2) In the annotation test (n = 29 nevi), readers were shown a tissue anchor in a follow-up RCM image (≤ 1 × 1-mm field-of-view) and asked to annotate the corresponding location of this structure in the baseline RCM mosaic image (≤ 5 × 5-mm field-of-view) from the same nevus; good agreement was defined as annotations deviant by less than 10% of the mosaic's width.In total, 17 patients (mean age, 45 years [range, 28-70 years]; 10 [59%] were women) contributed a total of 51 nevi, of which 44 nevi (86%) were used for the study. Images from 7 nevi (14%) were suboptimal in quality. Tissue anchors were identified at both time points in all 44 nevi. Selected tissue anchors were located at a mean depth of 54.3 µm; the most commonly selected anchors (37 of 44 images [84.1%]) were dermal papillae. In the multiple choice matching test, compared with a reference reader, 2 readers correctly matched baseline to follow-up tissue anchors in 40 of 43 nevi (93%; P < .01) and 42 of 43 nevi (98%; P < .01), respectively. In the annotation test, there was good agreement between 2 readers in all 29 cases (100%); the mean deviation was 2% (range, 0%-7.5%).Precise longitudinal tracking of microscopic structures in melanocytic nevi using RCM is feasible.
DETOXICATION OF SODIUM BENZOATE IN NEUROPSYCHIATRIC DISORDERS
Authors: ISIDORE FINKELMAN, JERRY HORA, IRVING C. SHERMAN, M. K. HORWITT
Journal: American Journal of Psychiatry (1940)

The rate of detoxication of benzoic acid was determined in patients with various neuropsychiatric diseases. About one half of the patients with catatonia showed a defect in hippuric acid synthesis. This may be due to the state of muscular rigidity and immobility of these patients. Deteriorated patients with epilepsy showed a defect in the synthesis of hippuric acid, whereas extramural patients with epilepsy showed a normal excretion of the equivalent benzoic acid. This may indicate a defect in glycine synthesis in deteriorated patients with epilepsy. Normal average values were found in post-encephalitic Parkinsonism and multiple sclerosis. A patient with progressive muscular dystrophy was able to synthesize glycine at a normal rate.
A phase II trial of RAD001 in patients (Pts) with metastatic renal cell carcinoma (MRCC)
Authors: R. J. Amato, A. Misellati, M. Khan, S. Chiang
Journal: Journal of Clinical Oncology (2006)

4530 Background: RAD001 an oral serine-threonine kinase inhibitor of mTOR, blocks progression from the GI to the S phase of the cell cycle by a mechanism of action that is unique for an anticancer drug. Mechanistically, it is thought that RAD001 may play a role in VEGF inhibition. Main endpoints were to evaluate: time to progression (TTP), response rate, toxicity and to assess changes in metabolic imaging utilizing CT-PET. Methods: Eligibility included: progressive measurable MRCC, adequate organ/marrow function, zubrod performance status (ZPS) ≤ 2, no more than 1 prior therapy, and no active CNS involvement. RAD001 is given orally at a dose of 10mg daily without an interruption (28-day cycle), with dose modifications for toxicity. Re-evaluation was assessed every 3 cycles (12 weeks). RECIST criteria is utilized to determine response rate. TTP is determined from entry into the study. Results: 25 pts have been enrolled as of this review. 19 male/6 female, range 43–80 (median 60) years. All pts had predominant clear cell elements with progressive MRCC. 17 pts received prior immunotherapy, targeted agents, or chemotherapy. 22 pts had a ZPS of 0, 2/1 and 1/2. Sites of disease included: lung, nodal, bone, adrenal, kidney and liver. 7 pts had 1 metastatic site, 10 pts/2 metastatic sites and 8 pts/3 or more metastatic sites. 22 pts continue to receive RAD001 therapy. 7 pts had partial responses, 11 pts were stable for 3+ months, (5 pts/6+ months). 4 pts too early. Median duration of therapy is 7+ months (range 1+ to 9+). Treatment related adverse events to date include: mucositis, skin rash, pneumonitis, hypophosphatemia, hyperglycemia, thrombocytopenia, anemia and elevated LFTs. Conclusion: RAD001 has promising anti-tumor activity in pts with MRCC as demonstrated by a 33% partial response rate. Anti-tumor activity was further suggested by prolonged TTP ≥ 3 months for 86% of pts. The tumor effect was also demonstrated as a second line therapy. Independent radiology review is planned. Anti-tumor activity, toxicity and metabolic imaging correlation will be presented. [Table: see text]