tbuckley/cabot-search huggingface dataset:
Modified FOLFOXIRI (mFOLFOXIRI) plus cetuximab (cet), followed by cet or bevacizumab (bev) maintenance, in <i>RAS</i>/<i>BRAF</i> wild-type (wt) metastatic colorectal cancer (mCRC): Results of the phase II randomized MACBETH trial by GONO.
Authors: Carlotta Antoniotti, Chiara Cremolini, Fotios Loupakis, Francesca Bergamo, Roberta Grande, Giuseppe Tonini, Silvio Ken Garattini, Gianluca Masi, Francesca Battaglin, Sara Lucchesi, Lisa Salvatore, Domenico C. Corsi, Francesca Di Fabio, Maria Banzi, Elisa Sensi, Daniela Tomcikova, Gabriella Fontanini, Vittorina Zagonel, Luca Boni, Alfredo Falcone
Journal: Journal of Clinical Oncology (2016)

3543 Background: The combination of triple chemotherapy regimens with an anti-EGFR reported promising activity with some safety concerns in phase II trials. MACBETH trial aimed at evaluating the activity and safety of 1st-line mFOLFOXIRI plus cet and at exploring the role of maintenance with cet or bev in unresectable mCRC patients (pts). The study initially enrolled KRAS wt pts and, after an amendment in Oct 2013, only RAS/BRAF wt pts. Methods: Eligibility criteria included measurable, unresectable, RAS/BRAF wt disease (centrally screened), age 18-75 yrs, no prior therapy for advanced disease. Pts were randomized to receive up to 8 cycles of mFOLFOXIRI + cet (cet 500 mg/sqm, iri 130 mg/sqm, oxa 85 mg/sqm, I-LV 200 mg/sqm, 5FU 2400 mg/sqm over 48h q2w), followed by cet (arm A) or bev (arm B) until progression. The trial was a phase II randomized non-comparative study, with primary endpoint 10 months-Progression Free Rate (10m-PFR). Results: Between Nov 2011 and Feb 2015, 323 pts from 21 Italian centers were screened. Out of 143 randomized pts, 116 were RAS/BRAF wt and were therefore included in the modified ITT (mITT) population (arm A/B N = 59/57). Pts' characteristics were: median age 60 yrs, ECOG PS 0 89%, synchronous metastases 84%, liver-only disease 45%. At a median follow up of 25.5 months, 10m-PFR was 52% in arm A and 41% in arm B (primary endpoint not met), with median PFS of 11.2 and 9.3 months. Response rate was 76% in 106 evaluable pts and 70% (arm A/B 68%/72%) in the mITT population; only 2 pts per arm experienced PD as best response. Resection rate was 38% (arm A/B 46%/30%), 65% (arm A/B 71%/58%) in the liver-only subgroup. Main grade 3-4 toxicities during induction were neutropenia (33%), febrile neutropenia (3%), diarrhoea (19%), skin rash (18%), stomatitis (6%). Conclusions: Neither of the two arms met the primary endpoint. However, 4 months-induction with mFOLFOXIRI + cet was feasible and had relevant activity, leading to high conversion rate. This may positively affect OS results, still immature (an update will be presented). Clinical trial information: NCT02295930.
Glioproliferative Lesion of the Spinal Cord as a Complication of “Stem-Cell Tourism”
Authors: Aaron L Berkowitz, Michael B Miller, Saad A Mir, Daniel Cagney, Vamsidhar Chavakula, Indira Guleria, Ayal Aizer, Keith L Ligon, John H Chi
Journal: New England Journal of Medicine (2016)

A primitive neoplasm composed predominantly of nonhost cells was detected in the thoracic spinal cord and thecal sac of a 66-year-old man who had received experimental stem-cell treatment from commercial clinics.
Engraftment Syndrome Is Common in Patients with POEMS Syndrome Undergoing PBSCT.
Authors: Angela Dispenzieri, Martha Q. Lacy, Suzanne R. Hayman, Shaji K. Kumar, Francis Buadi, David Dingli, Mark R. Litzow, Dennis A. Gastineau, David J. Inwards, Michelle A. Elliott, Ivana N. Micallef, Stephen M. Ansell, William J. Hogan, Luis F. Porrata, Bekele Afessa, Alan Bryce, Robert A. Kyle, Morie A. Gertz
Journal: Blood (2007)
Bleeding from portal biliopathy in situs inversus totalis
Authors: Sundeep Lakhtakia, Rajesh Gupta, Domenico Galasso, Mohan Ramchandani, Palle Reddy, Guduru Rao, Nageshwar Reddy
Journal: Endoscopy (2015)

A 43-year-old male patient presented with obstructive jaundice. Blood samples showed total bilirubin 3.1 mg/dL, direct bilirubin 2.0 mg/dL, aspartate aminotransferase (AST) 261 U/L, alanine transaminase (ALT) 165 U/L, alkaline phosphatase 241 U/L. Coagulation, hemogram, albumin, and renal function test findings were within the normal range. Serological testing for hepatitis B and hepatitis C virus was negative. Abdominal ultrasonography and magnetic resonance imaging revealed situs inversus totalis, and a thrombosed portal vein with cavernoma, and common bile duct/common hepatic duct (CBD/CHD) obstruction.
Soil Ingestion: A Concern for Acute Toxicity in Children
Journal: Environmental Health Perspectives (1998)

Several soil ingestion studies have indicated that some children ingest substantial amounts of soil on given days. Although the EPA has assumed that 95% of children ingest 200 mg soil/day or less for exposure assessment purposes, some children have been observed to ingest up to 25-60 g soil during a single day. In light of the potential for children to ingest such large amounts of soil, an assessment was made of the possibility for soil pica episodes to result in acute intoxication from contaminant concentrations the EPA regards as representing conservative screening values (i.e., EPA soil screening levels and EPA Region III risk-based concentrations for residential soils). For a set of 13 chemicals included in the analysis, contaminant doses resulting from a one-time soil pica episode (5-50 g of soil ingested) were compared with acute dosages shown to produce toxicity in humans in clinical studies or case reports. For four of these chemicals, a soil pica episode was found to result in a contaminant dose approximating or exceeding the acute human lethal dose. For five of the remaining chemicals, the contaminant dose from a soil pica episode was well within the reported dose range in humans for toxicity other than lethality. Because both the exposure episodes and the toxicological response information are derived from observations in humans, these findings are regarded as particularly relevant for human health risk assessment. They suggest that, for some chemicals, ostensibly conservative soil criteria based on chronic exposure using current EPA methodology may not be protective of children during acute soil pica episodes.
Randomized phase III study of nedaplatin (N) plus docetaxel (D) versus cisplatin (C) plus D for advanced or relapsed squamous cell carcinoma of the lung (SqLC): WJOG5208L.
Authors: Takehito Shukuya, Takeharu Yamanaka, Takashi Seto, Haruko Daga, Koichi Goto, Hideo Saka, Shunichi Sugawara, Toshiaki Takahashi, Soichiro Yokota, Hiroyasu Kaneda, Tomoya Kawaguchi, Seisuke Nagase, Tetsuya Oguri, Yasuo Iwamoto, Takashi Nishimura, Yoshihiro Hattori, Kazuhiko Nakagawa, Yoichi Nakanishi, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2015)

8004 Background: N is a second-generation platinum compound with lower nausea/vomiting and nephrotoxicity than C. N plus D (ND) showed a promising efficacy with acceptable toxicity for advanced SqLC in the previous phase II study. Methods: Eligible patients (pts) were those with pathologically proven SqLC with stage IIIB/IV or postoperative recurrence, aged 20-74 and ECOG PS 0-1. Pts were randomized 1:1 to ND (N 100 mg/m2 and D 60mg/m2 intravenous, q3w, up to 6 cycles) or C plus D (CD) (C 80 mg/m2 and D 60mg/m2 intravenous, q3w, up to 6 cycles) according to stage, gender and institution. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate (RR) and adverse events (AEs). Target sample size of 350 provided 90% statistical power to detect a hazard ratio of 0.71 with one-sided type I error of 0.05. Results: Between July 2009 and July 2012, 355 pts were randomized. Of 349 for efficacy analysis (ND 177; CD 172), baseline characteristics were well-balanced between two arms. ND had a significantly longer OS (p = 0.037, one-sided stratified log-rank test). The OS HR was 0.81 (90%CI, 0.67-0.98) with a median OS of 13.6 months [m] for ND and 11.4 for CD. ND had a longer PFS (p = 0.050) with a HR of 0.83 (0.69-1.00) and a median PFS of 4.9 m in ND and 4.5 in CD. RR was 54.5% in ND vs 52.9% in CD (p = 0.829). Grade 3 or higher AEs of nausea (4.0% vs 14.3%), fatigue (3.4% vs 10.9%), hyponatremia (13.6% vs 30.3%) and hypokalemia (2.3% vs 8.6%) are more frequent in CD. Grade 3 or higher AEs of neutrophils (82.5% vs 70.3%) and platelets (9.0% vs 0.0%) are more frequent in ND, but there was no difference in grade 3 or higher febrile neutropenia (13.6% vs 15.4%). Treatment related deaths occurred in 4 and 3 pts in ND and CD, respectively. Conclusions: ND showed a significantly longer OS as compared to CD with different toxicity profile. ND will be considered as a new standard treatment for advanced or relapsed SqLC. Clinical trial information: UMIN000002015.
Human case of Onchocerca lupi infection, Germany, August 2014
Authors: A Bergua, B Hohberger, J Held, B Muntau, E Tannich, D Tappe
Journal: Eurosurveillance (2015)

Onchocerca lupi, a nematode parasite infecting dogs and cats with a hitherto unknown arthropod vector, is also being recognised as a parasite also responsible for human eye infections. Here we describe a case of human eye infection diagnosed molecularly by nematode 12S rDNA PCR in a German patient who had travelled to Tunisia and Turkey. The patient recovered after treatment with antibiotic and anti-inflammatory therapy.
Association Between Hyperhemolysis and Vascular Complications in Sickle Cell Disease Sub-Saharan African Patients
Authors: Marie Dubert, Dapa Aly Diallo, Aissata Tollo, Saliou Diop, Suzanne Belinga, Ibrahima Sanogo, Odette Guifo, Guillaume Wamba, Ibrahima Diagne, Indou Deme LY, Kouakou Boidy, Gustave Koffi, Ismael Kamara, Youssouf Traore, Lucile Offredo, Aymeric Menet, Xavier Jouven, Brigitte Ranque
Journal: Blood (2015)
Everolimus versus placebo in Japanese patients with advanced pancreatic neuroendocrine tumors (pNET): Japanese subgroup analysis of RADIANT-3.
Authors: T. Ito, T. Okusaka, M. Ikeda, T. Tajima, A. Kasuga, Y. Fujita, J. Furuse
Journal: Journal of Clinical Oncology (2011)

289 Background: Everolimus demonstrated a statistically and clinically significant improvement in PFS over placebo in a multi-national, randomized, placebo-controlled, phase III trial in patients with advanced low- or intermediate-grade pNET with disease progression within the prior 12 months (RADIANT-3) (Ann Oncol [2010] 21[suppl 6]: NP doi:10.1093/annonc/mdq340). Forty patients were enrolled from Japanese sites and randomized (n=23: everolimus; n=17: placebo) in that study. The purpose of this report is to investigate the efficacy and safety in the Japanese subgroup. Methods: Subgroup analysis for the Japanese patients was performed comparing the efficacy and safety between everolimus 10mg/d orally plus best supportive care (BSC) and matching placebo plus BSC. The primary efficacy endpoint was progression-free survival (PFS). The safety was evaluated based on the incidence of adverse events (AEs). Results: Treatment with everolimus resulted in a significant prolongation by 16.62 months in median PFS (19.45 months for everolimus, 2.83 months for placebo), with 81% reduction in the hazard ratio of progression/death (HR 0.19 [95% CI: 0.08, 0.48]; one-sided unstratified log-rank test: p&lt;.001). The most common AE was stomatitis (73.9% everolimus vs 23.5% placebo); mostly grade 1/2. Grade 3/4 AEs occurred in 69.5% of the everolimus arm and 29.4% of the placebo arm, and amongst the most frequent included (% in everolimus vs % in placebo): neutropenia (17.4% vs 3%); anemia (8.7% vs 0%); pneumonitis (8.7% vs 0%); leukopenia (8.7% vs 0%). The remainder of grade 3/4 AEs was less than 3%. Median duration of exposure to everolimus was 57 weeks vs 47 weeks on placebo. Treatment discontinuation for AEs was 17% in the everolimus arm vs 0% in the placebo arm. Conclusions: Everolimus demonstrated a clinically meaningful improvement in PFS over placebo in Japanese patients. Everolimus was well tolerated in Japanese patients, and no new safety concerns were noted. This result suggests that everolimus can be a standard treatment for Japanese patients with advanced pNET. [Table: see text]
Urinary MHPG excretion in minimal brain dysfunction and its modification by d-amphetamine
Authors: W O Shekim, H Dekirmenjian, J L Chapel
Journal: American Journal of Psychiatry (1979)

The authors studied the excretion of 3-methoxy-4-hydroxyphenlyglycol (MHPG) in 15 hyperactive boys and 13 controls. They further examined soft neurologic signs and clinical drug response to d-amphetamine administration for two weeks in the hyperactive boys. MHPG excretion was significantly lower in the hyperactive boys than in the controls. d-Amphetamine decreased MHPG excretion significantly in the drug responders only. Pretreatment MHPG excretion did not predict clinical drug response. The responders had more soft neurologic signs than the nonresponders. Furthermore, soft neurologic signs were not related to pretreatment MHPG levels.
Rareté des polypes adénomateux dans la recto-colite hémorragique et ses conséquences en terme de carcinogenèse colique
Authors: S Lecleire
Journal: Endoscopy (2016)

La survenue d’adénomes colorectaux sporadiques chez les patients atteints de rectocolite hémorragique (RCH) est assez peu étudiée. Chez ces malades, le cancer colorectal se développe préférentiellement à partir d’une dysplasie plane (DALM) et ne passe pas par la séquence habituelle de développement de l’adénome sporadique que l’on rencontre dans la population générale. Il existe très peu de données concernant le risque de survenue d’adénomes sporadiques classiques chez des malades atteints de RCH.
D5-03: Prognostic implications of cell cycle-related proteins in primary resectable pn2 non-small cell lung cancer
Authors: Sherif Mohamed, Kazuhiro Yasufuku, Takahiro Nakajima, Shigetoshi Yoshida, Makoto Suzuki, Yasuo Sekine, Kiyoshi Shibuya, Kenzo Hiroshima, Atef Farouk, Takehiko Fujisawa
Journal: Journal of Thoracic Oncology (2007)
Separation of Cells Exhibiting Acid Phosphatase Activity From Disaggregated Hamster Prostate Cells in an Isokinetic Gradient of Ficoll in Tissue Culture Medium 2
Authors: Sherron H. Dow, Thomas G. Pretlow
Journal: JNCI Journal of the National Cancer Institute (1975)

Cells exhibiting histochemically demonstrable acid phosphatase were separated from suspensions of hamster prostate cells with velocity and isopyknic sedimentation. Unseparated suspensions of hamster prostate cells contained 57.l ± 11.3% cells with histochemically apparent acid phosphatase. After the cells were separated by velocity sedimentation in a previously described isokinetic gradient, the purest fractions from the gradient contained 97.2 ± 0.8% cells with histochemically evident acid phosphatase. More than 99% of these separated cells excluded trypan blue. These cells were thought to be the acinar cells of the prostate. Isopyknic sedimentation was not as effective as velocity sedimentation for the purification of these cells.
FDG PET/CT Imaging of Calcified Sister Mary Joseph Nodule
Authors: Sabahat Inanir, Kevser Oksuzoglu
Journal: Clinical Nuclear Medicine (2016)

Sister Mary Joseph nodule (SMJN) refers to any metastatic deposit in the periumbilical region. Herein, we report a very rare case of calcified SMJN from ovarian papillary serous adenocarcinoma showing intense FDG uptake.
Attenuated Poliovirus Infection in Infants Fed Colostrum From Poliomyelitis Immune Cows
Authors: A J GONZAGA, R J WARREN, F C ROBBINS
Journal: JAMA (1963)

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RM-024 Survival analysis of post-operatively treated cancer gall bladder patients with Adjuvant Chemo-radiotherapy: an institutional study
Authors: S. Saugat, H. Kumar, N. Sharma, M. Singhal, S. Beniwal, P. Kumari, S. Narayan, A. Kapoor, S. Jakhar, S. Maharia, R. Nirban
Journal: Annals of Oncology (2016)
Set a low bar for starting palliative care
Authors: Scott A Murray
Journal: BMJ (2016)

Dying patients and their families most need support early on

About two years ago, death tapped me on the shoulder. I’d been coughing on and off for a year but didn’t want to think about a danse macabre .1 Eventually I went to my GP. The x ray report could not be ignored. Neither could the computed tomography scan, which confirmed lung cancer.

Tough luck, I thought, because I’ve never smoked. And, how ironic: I teach palliative care to medical students and routinely ask them what they’d wish to die from. The smart choice is cancer, because end of life services are much better developed for that. I’d also led the Making a Difference campaign in The BMJ to extend palliative care to all conditions.2 But …
P-132 The impact of obesity on complete pathologic response to neoadjuvant chemoradiotherapy in rectal cancer patients
Authors: C. Diaz, G. Calderillo, H. Marytere, E. Ruiz-Garcia, F. Manuel, E. Trejo, L. Horacio, A. J Luis, A. Herrera, A. Meneses, P. Alejandro
Journal: Annals of Oncology (2016)
ATPS-13AROMATASE EXPRESSION IN HIGH GRADE GLIOMAS: A POTENTIAL NEW TARGET FOR THERAPY
Authors: Nimita Dave, Vidula Sengaonkar, Lionel M.L. Chow, Ady Kendler, Kathleen LaSance, Pankaj B. Desai
Journal: Neuro-Oncology (2015)

The prognosis for patients with malignant gliomas remains dismal and novel therapeutic agents are urgently needed. We investigated the potential role of aromatase (CYP19A1), an enzyme that catalyzes the conversion of androgens to estrogens in peripheral tissues, as a target for the treatment of CNS malignancies, as well as brain disposition and anti-tumor efficacy of letrozole, an aromatase inhibitor. Two recent discoveries from our lab have immediate clinical import. First, we analyzed the expression of aromatase in 67 human biopsy samples obtained from the University of Cincinnati Cancer Institute Tumor bank. De-identified frozen tissue samples (containing at least 50 % tumor cells, confirmed by HE i.p. injections) had long term suppression with overall survival exceeding 65 days and no signs of overt toxicity. In contrast, control untreated rats (N = 6, 2ml/kg vehicle i.p. injections) developed significant morbidity/mortality in 15-20 days. Overall, our studies strongly suggest that aromatase is a new “druggable target” for treatment of HGGs and that letrozole can potentially be readily used for this purpose.
Cardiac Amyloidosis Presenting as Severe Mitral Regurgitation
Authors: Khawaja Afzal Ammar, Bijoy K. Khandheria, Tanvir Bajwa, Steven C. Port, Suhail Allaqaband, Renuka Jain, Gary Neitzel, A. Jamil Tajik
Journal: JACC. Cardiovascular imaging (2016)
Emerging high-level mupirocin resistance among MRSA isolates in Ireland
Authors: Angela Rossney, S O'Connell
Journal: Eurosurveillance (2008)

High-level mupirocin resistance was detected among 37 of 2,586 (1.4%) methicillin-resistant Staphylococcus aureus (MRSA) blood-stream isolates sent to the Ireland's National MRSA Reference Laboratory between 1 January 1999 and 31 December 2005, compared with 29 of 997 isolates (2.9%) sent between 1 January 2006 and 31 December 2007.
Flow‐Through Electroporation of HL‐60 White Blood Cell Suspensions using Nanoporous Membrane Electrodes
Authors: Zhiqiang Chen, Michael A. Akenhead, Xinghua Sun, Harrison Sapper, Hainsworth Y. Shin, Bruce. J. Hinds
Journal: Advanced Healthcare Materials (2016)

A flow‐through electroporation system, based on a novel nanoporous membrane/electrode design, for the delivery of cell wall‐impermeant molecules into model leukocytes, HL‐60 promyelocytes, was demonstrated. The ability to apply low voltages to cell populations, with nm‐scale concentrated electric field in a periodic array, contributes to high cell viability. With applied biases of 1–4V, delivery of target molecules was achieved with 90% viability and up to 65% transfection efficiency. More importantly, the system allowed electrophoretic pumping of molecules from a microscale reservoir across the membrane/electrode system into a microfluidic flow channel for transfection of cells, a design that can reduce reagent amount by eightfold compared to current strategies. The flow‐through system, which forces intimate membrane/electrode contact by using a 10μm channel height, can be easily scaled‐up by adjusting the microfluidic channel geometry and/or the applied voltage pulse frequency to control cell residence times at the cell membrane/electrode interface. The demonstrated system shows promise in clinical applications where low‐cost, high cell viability and high volume transfection methods are needed without the risk of viral vectors. In particular genetic modification of freely mobile white blood cells to either target disease cells or to express desired protein/enzyme biomolecules is an important target platform enabled by this device system.
A reconsideration of the relation of ventricular enlargement to duration of illness in schizophrenia
Authors: B T Woods, J Wolf
Journal: American Journal of Psychiatry (1983)

The size of the ventricles of 19 young hospitalized patients with chronic schizophrenia was compared with that of 29 same-age control subjects. The patients had a slightly but significantly larger bicaudate ratio. Analysis of these results in the context of previous studies of ventricular size and schizophrenia suggests that, contrary to current views, there is a direct relationship between size of ventricles and duration of schizophrenic illness. The authors argue that the conflicting results of different studies of ventricular size and schizophrenia can be reconciled by postulating that both clinical schizophrenia and ventricular enlargement are overt signs of an underlying neuronal degeneration that is hereditary and progressive.