tbuckley/cabot-search huggingface dataset:
Ventilation in Extremely Preterm Infants and Respiratory Function at 8 Years
Authors: Lex W. Doyle, Elizabeth Carse, Anne-Marie Adams, Sarath Ranganathan, Gillian Opie, Jeanie L.Y. Cheong
Journal: New England Journal of Medicine (2017)

Assisted ventilation for extremely preterm infants (<28 weeks of gestation) has become less invasive, but it is unclear whether such developments in care are associated with improvements in short-term or long-term lung function. We compared changes over time in the use of assisted ventilation and oxygen therapy during the newborn period and in lung function at 8 years of age in children whose birth was extremely premature.We conducted longitudinal follow-up of all survivors of extremely preterm birth who were born in Victoria, Australia, in three periods - the years 1991 and 1992 (225 infants), 1997 (151 infants), and 2005 (170 infants). Perinatal data were collected prospectively, including data on the duration and type of assisted ventilation provided, the duration of oxygen therapy, and oxygen requirements at 36 weeks of age. Expiratory airflow was measured at 8 years of age, and values were converted to z scores for age, height, ethnic group, and sex.The duration of assisted ventilation rose substantially over time, with a large increase in the duration of nasal continuous positive airway pressure. Despite the increase in the use of less invasive ventilation over time, the duration of oxygen therapy and the rate of oxygen dependence at 36 weeks rose, and airflows at 8 years of age were worse in 2005 than in earlier periods. For instance, for 2005 versus 1991-1992, the mean difference in the z scores for the ratio of forced expiratory volume in 1 second to forced vital capacity was -0.75 (95% confidence interval [CI], -1.07 to -0.44; P<0.001), and for 2005 versus 1997 the mean difference was -0.53 (95% CI, -0.86 to -0.19; P=0.002).Despite substantial increases in the use of less invasive ventilation after birth, there was no significant decline in oxygen dependence at 36 weeks and no significant improvement in lung function in childhood over time. (Funded by the National Health and Medical Research Council of Australia and the Victorian Government's Operational Infrastructure Support Program.).
Final results of a dose escalation (DE), pharmacokinetic (PK), and pharmacodynamic (PD) study of two schedules of OSI-930 in patients (pts) with advanced solid tumors
Authors: S. George, R. Lal, D. R. Camidge, H. Arkenau, J. Chick, S. Poondru, T. A. Yap, S. G. Eckhardt, G. D. Demetri, M. Scurr
Journal: Journal of Clinical Oncology (2009)

3564 Background: OSI-930 is an oral TKI with potent activity against Kit, VEGFR2, and PDGFR. Preclinical studies demonstrate tumor regression with long-term remissions across multiple xenograft models. Methods: Sequential cohorts of pts with advanced solid tumors received continuous daily OSI-930 to determine the maximum tolerated dose (MTD) and to evaluate safety, PK/PD and efficacy of OSI-930 with both QD and BID dosing. An expansion cohort was enrolled for detailed PD analysis including sVEGFR2 plasma levels, PET imaging in GIST pts or DCE-MRI in selected pts. Results: A total of 58 pts were treated (20M/38F; median 60 years (range 19–83)). OSI-930 was dosed up to 1600 mg QD without reaching MTD. 46 pts received BID dosing [mg(# pts treated)]; 400(7), 500 (31) and 600(8). DLT's were seen in 3/8 pts at 600 mg BID; G3 rash (2 pts) and G4 GGT; and 3/31 at 500 mg BID; G3 myalgia, G3 fatigue and G3 lipase. G3 hypertension was noted in 3/46 pts but not dose-limiting. Common G1/2 toxicities were fatigue (37%), diarrhea (27%), nausea (31%), and rash (24%). Objective (CA125) responses were seen in platinum-resistant ovarian cancer (2 PR/8) while in heavily pretreated GIST (median 4 prior therapies including imatinib/sunitinib), 8/18 pts achieved SD ≥12 w. Median therapy duration in the BID arm was 9 w and 18/46 pts with SD ≥12 w. PK indicated that C ss were achieved after ∼7d with BID dosing. PET scans showed reduction in glycolytic activity in 4/9 pts and DCE-MRI response was seen in 4/6 pts. A trend in decreased sVEGFR levels was seen at higher doses. Conclusions: At the MTD level of 500 mg BID OSI-930 is an active, well-tolerated compound with clinically relevant antitumor activity and exposure levels consistent with antitumor activity in preclinical models. PD data indicate mechanistic proof of concept for OSI-930. OSI-930/erlotinib combination phase I study is currently enrolling. [Table: see text]
Metanephrines for Evaluating Palpitations and Flushing
Authors: Fady Hannah-Shmouni, Karel Pacak, Constantine A. Stratakis
Journal: JAMA (2017)

A 29-year-old woman with chronic paroxysmal palpitations, flushing, paleness, and diaphoresis had a blood pressure of 112/74 mm Hg, a heart rate of 82 beats/min, normal physical examination, and normal plasma metanephrines with elevated normetanephrines. How do you interpret the results?
Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia
Authors: Marjet J.A.M. Braamskamp, Gisle Langslet, Brian W. McCrindle, David Cassiman, Gordon A. Francis, Claude Gagne, Daniel Gaudet, Katherine M. Morrison, Albert Wiegman, Traci Turner, Elinor Miller, D. Meeike Kusters, Joel S. Raichlen, Paul D. Martin, Evan A. Stein, John J.P. Kastelein, Barbara A. Hutten
Journal: Circulation (2017)

Background: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Children with HeFH exhibit early signs of atherosclerosis manifested by increased carotid intima-media thickness (IMT). In this study, we assessed the effect of 2-year treatment with rosuvastatin on carotid IMT in children with HeFH. Methods: Children with HeFH (age, 6–&lt;18 years) and low-density lipoprotein cholesterol &gt;4.9 mmol/L or &gt;4.1 mmol/L in combination with other risk factors received rosuvastatin for 2 years, starting at 5 mg once daily, with uptitration to 10 mg (age, 6–&lt;10 years) or 20 mg (age, 10–&lt;18 years). Carotid IMT was assessed by ultrasonography at baseline and 12 and 24 months in all patients and in age-matched unaffected siblings. Carotid IMT was measured at 3 locations (common carotid artery, carotid bulb, internal carotid artery) in both the left and right carotid arteries. A linear mixed-effects model was used to evaluate differences in carotid IMT between children with HeFH and the unaffected siblings. P values were adjusted for age, sex, carotid artery site, and family relations. Results: At baseline, mean±SD carotid IMT was significantly greater for the 197 children with HeFH compared with the 65 unaffected siblings (0.397±0.049 and 0.377±0.045 mm, respectively; P =0.001). During 2 years of follow-up, the change in carotid IMT was 0.0054 mm/y (95% confidence interval, 0.0030–0.0082) in children with HeFH and 0.0143 mm/y (95% confidence interval, 0.0095–0.0192) in unaffected siblings ( P =0.002). The end-of-study difference in mean carotid IMT between children with HeFH and unaffected siblings after 2 years was no longer significant (0.408±0.043 and 0.402±0.042 mm, respectively; P =0.2). Conclusions: In children with HeFH who were ≥6 years of age, carotid IMT was significantly greater at baseline compared with unaffected siblings. Rosuvastatin treatment for 2 years resulted in significantly less progression of increased carotid IMT in children with HeFH than untreated unaffected siblings. As a result, no difference in carotid IMT could be detected between the 2 groups after 2 years of rosuvastatin. These findings support the value of early initiation of statin treatment for low-density lipoprotein cholesterol reduction in children with HeFH. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01078675.
Implementation and outcomes of lung cancer screening in a community health care system.
Authors: Vita McCabe, Ruth Raleigh, Alice Pichan, Beth Irene Lavasseur, Rajeev Swarup, David Fugenschuh, Eric Ferguson, Philip J. Stella, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2017)

e13035 Background: Lung cancer screening using low dose computed tomography (LDCT) in patients meeting criteria is a covered preventative service under the Affordable Care Act and policies of CMS. The purpose of this study is to describe implementation and results of a lung cancer screening program in a community health care system. Methods: We prospectively collected data on all patients obtaining a baseline LDCT scan who enrolled beginning February 2015. Referring provider, smoking history, demographics, comorbidity, findings, and, in those found to have an abnormality, diagnosis were collected. The study was reviewed by the St Joseph Mercy Health System Institutional Review Board and was considered exempt. Results: Over the course of 18 months, 955 patients were referred for a baseline LDCT. 57% were current smokers, 53% were male, and 38% had no comorbid conditions. The mean number of pack-years was 50 (range 6 to 160). 76% of patients were referred by primary care providers. The number of new patients referred per month increased from 8 to 89, largely due to outreach and education directed at primary care physicians and office staff. Of the 955 patients screened, we identified cancer in 2% overall (small cell cancer in 0.2% patients and non-small cell lung cancer (NSCLC) in 1.6%). Among those with NSCLC, 60% had Stage I disease, 20% had Stage II, 13% had Stage III, and 7% had Stage IV disease. Compared to the stage distribution of lung cancer patients identified before the implementation of the screening program, there was significant down-staging in those with NSCLC. Barriers to implementation have included lack of clear smoking history documentation and billing code release delays which led to reimbursement difficulties. Conclusions: Successful implementation of a LDCT lung cancer screening program in a community setting. Improving patient/provider education and documentation of tobacco use in electronic medical records will streamline the referral process and increase screening among eligible patients. Outreach to practices that serve minority and other medically-underserved populations will require specific efforts to achieve health equity in the area of lung cancer screening.
Abstract #2300: Combined effect of silibinin with r-irradiation in colorectal cancer
Authors: Jung-Eun Lee, Seung-Sook Lee, Won Suk Jang, Nuri Kim, Sun-Joo Lee, Sunhoo Park
Journal: Cancer Research (2009)

Background: Colorectal cancer (CRC) is the forth most common malignancy and has steadily increased during the past decade in Korea. In the treatment of advanced CRC, irradiation with chemotherapy enhanced curative value. Silibinin, a naturally occurring polyphenolic flavonoid, constitutes a major biologically active portion of the plant extract from milk thistle (Silybum marianum) that has been clinically used to treat certain liver complications. Recently, silibinin is studied as a chemopreventive and chemotherapeutic agent which was shown to have a low toxicity in animal and human trial. In this study, we show the silibinin exerts antiproliferative effect in human colon cancer and enhances the therapeutic potential of the gamma-irradiation. Material and Methods: CRC cell lines (HCT-116 and HT-29) were utilized to assess the combined effects of silibinin and \#947;-irradiation. Cell death and proliferation inhibition were assessed by MTT, and clonogenic assay. Cell cycle progression was determined by PI staining and fluorescence-activated cell sorter (FACS) analysis. The expression of cell cycle and apoptosis-related molecules was detected by western blot. HT-29 tumor xenograft in nude mice randomized into four groups, and treated with vehicle (0.5% CMC), silibinin (200mg/kg), \#947;-irradiation(5Gy), and silibinin in combination with \#947;-irradiation. Tumors were analyzed for proliferation, apoptosis, and angiogenesis biomarkers and molecular alterations by immunohistochemistry and western blot. Results: Silibinin treatment revealed a dose-dependent cytotoxicity, however, irradiation exhibited the different sensitivity in two cell lines. HCT-116 cells were more sensitive to irradiation than HT-29 cells. Combination with silibinin and radiation showed increased cytotoxicity than either alone in HT-29 cells. Combination of two agents contributed to increase G2/M arrest through the reduction of cyclin B1, Cdc25c, cyclinA, cdc2 and phospho-cdc2. Moreover, silibinin enhanced irradiation-induced apoptosis, which was involved PARP-1 cleavage and caspase-3 activation. In vivo studies, Silibinin significantly enhanced the efficacy of irradiation therapy by prolonging the time to tumor re-growth and by reducing the Ki-67 proliferation index. Moreover, the combination silibinin with irradiation therapy decreased apoptosis by Tunnel staining and also suppressed angiogenesis, as indicated by a decrease in vascular endothelial growth factor and microvessel density. Conclusion: These results suggest a novel mechanism for silibinin-mediated radiosensitization involving increased cell cycle arrest and apoptosis and decreased angiogenesis in colorectal cancer. Silibinin application might be an effective radiation modifying modality in the treatment of colorectal cancer.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2300.
Nonsurgical premature menopause (NSPM) in the Childhood Cancer Survivor Study (CCSS): Prevalence, risk factors, and reproductive outcomes.
Authors: Jennifer Levine, John Whitton, Wendy M. Leisenring, Daniel M. Green, Jill P. Ginsberg, Marilyn Stovall, Gregory T. Armstrong, Leslie L. Robison, Charles A. Sklar
Journal: Journal of Clinical Oncology (2016)

10504 Background: Female survivors of childhood cancers are at increased risk for NSPM, cessation of menses prior to age 40 not secondary to resection of reproductive organs. Our aims were to assess prevalence of and risk factors for NSPM and to examine the implications of NSPM on reproductive outcomes. Methods: Participants included 2930 female survivors diagnosed between 1970 and 1986 and enrolled in the original CCSS cohort (median age at diagnosis 6 years, range 0-20; median age at follow-up 34 years; range 18-59) who were older than age 18 at last follow-up without prior acute ovarian failure. They were compared to 1399 siblings (median age 38 years, range 19-63). Among survivors, multivariable logistic regression identified risk factors for NSPM. Pregnancy and live birth rates were compared between survivors with and without NSPM. Results: 110 survivors developed NSPM [median age 32, range 16-40, prevalence of 9.1 % at age 40 (95% CI 4.9-17.2), relative risk 10.5 (95% CI 4.2-26.3) compared to siblings (0.9% at age 40, 95% CI 0.4-2.3)]. The prevalence was highest among survivors who received cyclophosphamide equivalent dose (CED) > 6000 mg/m2 (18.7% at age 40) or ≥ 5Gy RT to the ovaries (24.1%). Among survivors, independent risk factors included age > 14 at diagnosis (odds ratio [OR] 2.3, 95% Confidence Interval [CI] 1.4-3.8), CED ≥ 6,000 mg/m2(OR 3.6, 95% CI 2.1-6.3; referent group: CED=0), and any dose of RT to the ovaries (<5Gy, OR 4.0, 95% CI 1.9-8.5; ≥5Gy, OR 20.4, 95% CI 7.8-53.5). Compared to survivors without NSPM, those who developed NSPM were less likely to ever be pregnant (OR 0.41, 95% CI 0.22-0.68) or have a live birth (OR 0.35, 95% CI = 0.16-0.66) between the ages of 31-40. The same comparisons were not significant between the ages of 21-30. Conclusions: Ongoing follow-up of the original CCSS cohort enabled us to identify a threshold exposure to alkylating agents and older age at diagnosis as increasing the risk for NSPM among survivors. The development of NSPM is associated with lower rates of pregnancy and live birth after age 31. This information will assist clinicians counseling patients about their risk for early menopause and need for alternative reproductive options.
Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology
Authors: Philippe E. Spiess, Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Peter E. Clark, Tracy M. Downs, Jason A. Efstathiou, Thomas W. Flaig, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Noah Hahn, Harry W. Herr, Christopher Hoimes, Brant A. Inman, Masahito Jimbo, A. Karim Kader, Subodh M. Lele, Joshua J. Meeks, Jeff Michalski, Jeffrey S. Montgomery, Lance C. Pagliaro, Sumanta K. Pal, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Michael P. Porter, Mark A. Preston, Wade J. Sexton, Arlene O. Siefker-Radtke, Guru Sonpavde, Jonathan Tward, Geoffrey Wile, Mary A. Dwyer, Lisa A. Gurski
Journal: Journal of the National Comprehensive Cancer Network (2017)

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.
All That Wheezes...
Authors: Sanjay Divakaran, Anand Vaidya, Lester Kobzik, Paul Dellaripa
Journal: New England Journal of Medicine (2017)

A 20-year-old woman with a history of allergic rhinitis presented to her physician in the autumn with persistent cough and shortness of breath. She had been seen 6 weeks earlier for nasal congestion, rhinorrhea, postnasal drip, and cough that had bothered her on and off throughout the summer. Her symptoms occurred at home and at work. Just recently she had begun to have shortness of breath . . .
Correction: Vitamin B12 deficiency
Authors: Ralph Green, Lindsay H. Allen, Anne-Lise Bjørke-Monsen, Alex Brito, Jean-Louis Guéant, Joshua W. Miller, Anne M. Molloy, Ebba Nexo, Sally Stabler, Ban-Hock Toh, Per Magne Ueland, Chittaranjan Yajnik
Journal: Nature Reviews Disease Primers (2017)
Adjuvant irradiation to prevent keloidal fibroproliferative growth should be standard of care
Authors: M.K. Ramirez-Fort, B. Meier, A. Feily, S. L. Cooper, C.S. Lange
Journal: British Journal of Dermatology (2017)

After cutaneous injury, cytokine mediators recruit an inflammatory infiltrate that stimulates migration of keratinocytes and fibroblasts; subsequent proliferation of fibroblasts and keratinocytes begins 4 to 5 days later [1]. The formation of a keloid is dependent upon fibroblast migration, proliferation and type III collagen production [1].

First{\hyphen}line treatment of keloids involves topical or intralesional steroids. Recurrent or resistant keloids are managed by surgical excision or cryotherapy, followed by steroidal application, that presumably limits inflammation and cellular migration. Adjuvant irradiation to surgical excision is an alternative but underutilized modality that has demonstrated superior patient satisfaction and local control compared to post{\hyphen}cryotherapy or resection intralesional steroids, respectively [2, 3].

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Effect of treating glioblastoma with a cytokine inhibitor, ibudilast, in combination with temozolomide on survival in a patient-derived xenograft model.
Authors: Kerrie Leanne McDonald, Wendy Ha, Hatice Sevim, Kazuko Matsuda, Mustafa Khasraw
Journal: Journal of Clinical Oncology (2017)

2062 Background: Recurrence in patients with glioblastoma (GBM) is inevitable, even in patients with O-6-Methylguanine-DNA Methyl Transferase ( MGMT) methylation. We identified increased expression of the inflammatory cytokine, Macrophage Inhibitory Factor (MIF) and its receptor CD74 in patients with recurrent tumors. High levels of MIF and CD74 were associated with poor overall survival in GBM patients. This study aims to determine efficacy of Ibudliast (MN-166; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) to block MIF expression and decrease tumor burden. Ibudilast is an anti-inflammatory drug that was developed for the treatment of bronchial asthma. Methods: The patient derived cell lines (PDCLs) RN1 ( MGMT unmethylated), BAH1 ( MGMT methylated), and HW1 ( MGMT methylated) were treated in vitrowith different concentrations of ibudilast in combination with temozolomide (TMZ). Patient derived xenograft (PDX) models of GBM were developed and treated with the combination of ibudilast and TMZ. Overall survival was calculated. Results: Regardless of MGMT status, significant synergism between ibudilast and TMZ was observed in the PDCLs. Efficacy was associated with significantly decreased expression of its targets, MIF and CD74. Downstream proteins such as Src and Akt were also significantly inhibited. The combination induced apoptosis. RN1 tumors were established intracranially in Balb/c nude mice. Significant increases in survival times of the mice were recorded when treated with the combination. Conclusions: Ibudilast in combination with TMZ resulted in significant blockage of MIF expression, increased apoptosis and longer survival in vivo. A human pilot study for recurrent GBM patients is underway.
Dose-Intensified Combined Modality Treatment with 2 Cycles of BEACOPP Escalated Followed by 2 Cycles of ABVD and IF-RT in Patients with Early Unfavourable Hodgkin Lymphoma (HL): An Analysis of the German Hodgkin Study Group (GHSG) HD14 Trial
Authors: P. Borchmann, A. Engert, A. Pluetschow, M. Fluchs, J. Markova, A. Lohri, Zdeněk Král, R. Greil, M. Topp, M. Villalobos, J. Zijlstra, M. Soekler, H. Stein, H. Eich, R. Mueller, V. Diehl
Journal: Blood (2008)
Successful two-sided sponge pull-through treatment of anastomotic leakage following pancreaticoduodenectomy with pancreaticogastrostomy
Authors: Richard Knoop, Robert Thimme, Andreas Fischer
Journal: Endoscopy (2017)

A 66-year-old man with pancreatic cancer developed an anastomotic leakage of the pancreaticogastrostomy 15 days after pylorus-preserving pancreaticoduodenectomy. An easy-flow drain was identified endoscopically in the extraluminal cavity.