tbuckley/cabot-search huggingface dataset:
Principles of immunology and its nuances in the central nervous system: Fig. 1.
Authors: Gavin P. Dunn, Hideho Okada
Journal: Neuro-Oncology (2015)

Cancer immunotherapy represents the biggest change in the cancer treatment landscape in the last several years. Indeed, the clinical successes in several cancer types have generated widespread enthusiasm that immune-based treatments may influence the management of patients with malignant brain tumors as well. A number of promising clinical trials in this area are currently ongoing in neuro-oncology, and a wave of additional efforts are sure to follow. However, the basic immunology underlying immunotherapy—and the nuances unique to the immunobiology in the central nervous system—is often not in the daily lexicon of the practicing neuro-oncologist and neurosurgeon. To this end, here we provide a timely and working overview of key principles of fundamental immunology as a pragmatic context for understanding where therapeutic efforts may act in the cellular dynamics of the immune response. Moreover, we review the issues of lymphatic drainage, antigen presentation, and the blood–brain barrier as considerations that are germane to thinking about immunity to tumors arising in the brain. Together, these topics will provide a foundation for the exciting efforts in immune-based treatments that will hopefully provide real benefit to brain tumor patients.
“Pure” large cell neuroendocrine carcinoma of the gallbladder. Report of a case and review of the literature
Authors: Salvatore Buscemi, Elisabetta Orlando, Giuseppe Damiano, Francesca Portelli, Vincenzo Davide Palumbo, Alessandro Valentino, Antonio Marrazzo, Giuseppe Buscemi, Attilio Ignazio Lo Monte
Journal: International Journal of Surgery (2015)
Abstract 14905: Combined Assessment of Serum Neutrophil Gelatinase-Associated Lipocalin and N-Terminal Pro-B-Type Natriuretic Peptide Levels on Admission Improves the Prediction of Mortality in Patients Hospitalized to Coronary Care Units
Authors: Ryunosuke Okuyama, Junnichi Ishii, Hideki Kawai, Takashi Muramatsu, Hiroyuki Naruse, Sadako Motoyama, Sigeru Matsui, Hideo Izawa, Yukio Ozaki
Journal: Circulation (2014)

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is best known clinically as a novel and early marker of acute kidney injury. Renal dysfunction portends significant risk in patients admitted to coronary care units (CCUs). Thus, a sensitive marker of renal injury might also help to risk stratify patients hospitalized to CCUs. We prospectively investigated the prognostic value of a combination of serum NGAL and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels on admission for mortality in patients hospitalized to CCUs. Methods: We measured serum NGAL and NT-proBNP levels on admission in 974 consecutive patients hospitalized to CCUs. Among these patients, heart failure was present in 55%, and acute coronary syndrome in 40%. Results: Serum NGAL levels significantly correlated with NT-proBNP levels (r = 0.37, p &lt;0.0001) and estimated glomerular filtration rate (r = -0.68, p &lt; 0.0001). During a mean follow-up period of 829 days after admission, there were 178 (18%) all-cause deaths including 145 cardiovascular deaths. Comparably, patients who died were older (median, 78 vs. 72 yrs, p &lt; 0.0001), had higher levels of NGAL (102 vs. 55 ng/ml, p &lt; 0.0001), NT-proBNP (4043 vs. 1250 pg/ml, p &lt; 0.0001), D-dimer (2.6 vs. 1.1 μg/ml, p &lt; 0.0001), and high-sensitive C-reactive protein (6.0 vs.2.0 mg/l, p &lt; 0.0001), and displayed lower values of left ventricular ejection fraction (39 vs. 50 %, p &lt; 0.0001) and estimated glomerular filtration rate (43 vs. 65 ml/min/1.73m 2 , p &lt; 0.0001) than those who did not. In multivariate Cox regression analysis including 11 clinical and biochemical variables, tertiles of NGAL (p = 0.02) and NT-proBNP (p = 0.02) was independently associated with all-cause deaths. The combination of NGAL and NT-proBNP tertiles were associated with increased all-cause mortality rates ( Figure ). Conclusion: The combined assessment of NGAL and NT-proBNP levels on admission may be useful for evaluating the risk of mortality in patients admitted to CCUs.
Nodules in the Pouch of Douglas
Authors: Krishnamachar Harish, Girish Govindaiah
Journal: JAMA Surgery (2015)

Apregnantwoman in her 30s in the first trimesterwas evaluated for incidentally detected anemia. At colonoscopy, she was found to have a 3 × 4-cm ulceroproliferative lesion in the rectum7 cm from the anal verge. A biopsy specimenwas reported asmoderately differentiatedadenocarcinoma.Noother lesionwasfoundintherestofcolon.Thepregnancywasmedically terminated. Further evaluation showed that the disease was limited to the rectal wall, withnonodal involvement, andtherewasno livermetastasis.Hercarcinoembryonicantigen level was 4.3 ng/mL (to convert to micrograms per liter, multiply by 1.0). A definitive resectionwasplanned.On laparotomy, no asciteswas observed.However, the pelvic peritoneum in the pouch of Douglas showed dark brown-black nodules (Figure, A). The rest of the peritoneal cavity was normal. The rectal growthwasmobile andwas palpable below the peritoneal reflection.Thenodulewasbiopsied,andthespecimenwassent for frozensectionanalysis. The histopathological findings are shown in Figure, B. Benign endometrial glands B Pouch of Douglas A
Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab
Authors: David I. Rosenthal, Paul M. Harari, Jordi Giralt, Diana Bell, David Raben, Joyce Liu, Jeltje Schulten, Kian K. Ang, James A. Bonner
Journal: Journal of Clinical Oncology (2015)

We conducted a retrospective evaluation of the IMCL-9815 study to examine the association of human papillomavirus (HPV) and p16 protein expression status with outcomes in patients with oropharyngeal carcinoma (OPC) receiving radiotherapy (RT) plus cetuximab or RT alone.In the IMCL-9815 study, patients were randomly allocated to receive RT plus weekly cetuximab or RT alone. A subpopulation of patients with p16-evaluable OPC was retrospectively evaluated on the basis of locoregional control (LRC), overall survival (OS), and progression-free survival (PFS). Evaluable samples from patients with p16-positive OPC were also tested for HPV DNA.Tumor p16 status was evaluable in 182 patients with OPC enrolled in the IMCL-9815 study; 41% were p16 positive. When treated with RT alone or RT plus cetuximab, p16-positive patients had a longer OS than p16-negative patients (hazard ratio, 0.40; 95% CI, 0.21 to 0.74 and hazard ratio, 0.16; 95% CI, 0.07 to 0.36, respectively). The addition of cetuximab to RT increased LRC, OS, and PFS in both patients with p16-positive OPC and those with p16-negative disease. Interaction tests for LRC, OS, and PFS did not demonstrate any significant interaction between p16 status and treatment effect (P = .087, .085, and .253, respectively). Similar trends were observed when patients with p16-positive/HPV-positive OPC (n = 49) and those with p16-positive/HPV-negative OPC (n = 14) were compared.p16 status was strongly prognostic for patients with OPC. The data suggest that the addition of cetuximab to RT improved clinical outcomes regardless of p16 or HPV status versus RT alone.
Interim Analysis of a Phase II Pilot Trial of Ruxolitinib Combined with Danazol for Patients with Primary Myelofibrosis (MF), Post Essential Thrombocythemia-Myelofibrosis (Post ET), and Post Polycythemia Vera Myelofibrosis (PV MF) Suffering from Anemia
Authors: Krisstina L. Gowin, Amylou C. Dueck, John O Mascarenhas, Ronald Hoffman, Craig B. Reeder, John Camoriano, Katherine Gano, Vineta Ghurye, Sravan Nagi Reddy, Patricia Koenig, Veena Fauble, Raoul Tibes, Ruben Mesa
Journal: Blood (2014)
Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance)
Authors: H.H. Yoon, N.R. Foster, J.P. Meyers, P.D. Steen, D.W. Visscher, R. Pillai, D.M. Prow, C.M. Reynolds, B.T. Marchello, R.B. Mowat, B.I. Mattar, C. Erlichman, M.P. Goetz
Journal: Annals of Oncology (2015)
An outbreak of severe respiratory tract infection caused by human metapneumovirus in a residential care facility for elderly in Utrecht, the Netherlands, January to March 2010
Authors: M J te Wierik, D T Nguyen, M F Beersma, S F Thijsen, K A Heemstra
Journal: Eurosurveillance (2012)

Recognition of infections with human metapneumovirus (HMPV) among institutionalised elderly is rising. When HMPV was found to be the causative agent of an outbreak of pneumonia in a residential care facility for elderly in the Netherlands, an elaborate outbreak investigation was set up, including active surveillance for new cases. From clinical cases, defined by fever (> 38°C) and symptoms of respiratory tract infections, respiratory samples for analyses of viral pathogens by real-time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) and blood samples for determination of HMPV-specific IgM and IgG antibody titres were taken. Five staff members and 18 residents fulfilled the clinical case definition. Of those, five residents tested positive for HMPV by rRT-PCR. The combination of rRTPCR and serology identified nine confirmed cases, six probable cases, six possible cases and ruled out two persons as cases. Among residents, the outbreak of HMPV had an attack rate, ranging from 5% for laboratory- confirmed cases, to 13% for clinical cases. This outbreak investigation shows that HMPV is a potential serious pathogen for institutionalised elderly.
Neo-adjuvant chemotherapy in advanced epithelial ovarian cancer (EOC): A prospective, randomized study
Authors: D. Janga, L. Kumar, S. Kumar, N. K. Shukla, S. Thulkar, R. Singh
Journal: Journal of Clinical Oncology (2004)

5123 Background: To determine the impact of NACT on surgical debulking rate, overall and disease-free survival and quality of life. Methods: Between Oct 2001 and Dec 2003, 43 previously untreated patients (median age- 50 years, range 30–65) with FIGO stage III C & IV were randomized into two arms; Arm A (n=22) upfront debulking Sx followed by 6 cycles of paclitaxel & carboplatin (TC). In Arm B (n=21) patients received upfront 3 cycles of TC followed by debulking Sx followed by 3 more cycles. Eligibility criteria included –age 18 to 65 years, biopsy / cytological proven diagnosis of EOC, adequate hematological, renal, liver & cardiac functions, normal upper & lower GI endoscopy & CEA levels. Both groups were compared with respect to tumor debulking rate, duration of Sx, blood loss, intra & postoperative morbidity & mortality, overall response to treatment and quality of life, using FACT-O questionnaire. Results: A total of 174 CT cycles were administered with grade III-IV GI toxicity (3% vs 4%) & myelosuppression (10% Vs 8%, p=ns) in arm A & B, respectively. Patients receiving NACT had higher optimum debulking rate, 78% Vs 9%, p<. 001. There was good correlation between CAT scan findings and sub-optimal debulking (p<.001). Mean operative time (69.5 vs 79.2 minutes, p=0.5), mean blood loss (461 vs 327 ml, p=0.430), PO infection rate 29.4% vs 10%, p=0.35 and hospital stay (14.2 Vs 11 days, p=0.52) ) were not significantly different. Mean survival is similar in both arms (22.3 vs 18.6 months). The physical & functional wellbeing were similar in both groups. 23 have completed treatment; of these 16 are alive & disease-free (arm A-9, arm B-7), 7 relapsed, 3 in arm A & 4 in B. 8 patients are currently on treatment. 11 patients have died; 4 of PO complications (3 in arm A), CT toxicity-2, 5 of progressive disease, 1 lost to follow up . Conclusion: Primary NACT followed by debulking surgery is associated with higher resection rates & lower morbidity with outcome similar to standard approach. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dabur India Limited
O077 : Use of direct oral anticoagulants (DOACs) in patients with splanchnic vein thrombosis and/or cirrhosis
Authors: A. De Gottardi, S. Seijo, A. Plessier, J. Schouten, J. Trebicka, B. Terziroli, L. Magenta, D. Semela, P. Langlet, F. Turon, R. Arya, M. Peck-Radosavljevic, D. Valla, J.C. Garcia-Pagan
Journal: Journal of Hepatology (2015)
Transient Acute Kidney Injury in the Postoperative Period
Authors: Christian de Virgilio, Dennis Yong Kim
Journal: JAMA Surgery (2015)

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Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection
Authors: Rebecca M. Lynch, Eli Boritz, Emily E. Coates, Adam DeZure, Patrick Madden, Pamela Costner, Mary E. Enama, Sarah Plummer, Lasonji Holman, Cynthia S. Hendel, Ingelise Gordon, Joseph Casazza, Michelle Conan-Cibotti, Stephen A. Migueles, Randall Tressler, Robert T. Bailer, Adrian McDermott, Sandeep Narpala, Sijy O’Dell, Gideon Wolf, Jeffrey D. Lifson, Brandie A. Freemire, Robert J. Gorelick, Janardan P. Pandey, Sarumathi Mohan, Nicolas Chomont, Remi Fromentin, Tae-Wook Chun, Anthony S. Fauci, Richard M. Schwartz, Richard A. Koup, Daniel C. Douek, Zonghui Hu, Edmund Capparelli, Barney S. Graham, John R. Mascola, Julie E. Ledgerwood
Journal: Science Translational Medicine (2015)

Passive immunization with HIV-1-neutralizing monoclonal antibodies (mAbs) is being considered for prevention and treatment of HIV-1 infection. As therapeutic agents, mAbs could be used to suppress active virus replication, maintain suppression induced by antiretroviral therapy (ART), and/or decrease the size of the persistent virus reservoir. We assessed the impact of VRC01, a potent human mAb targeting the HIV-1 CD4 binding site, on ART-treated and untreated HIV-1-infected subjects. Among six ART-treated individuals with undetectable plasma viremia, two infusions of VRC01 did not reduce the peripheral blood cell-associated virus reservoir measured 4 weeks after the second infusion. In contrast, six of eight ART-untreated, viremic subjects infused with a single dose of VRC01 experienced a 1.1 to 1.8 log10 reduction in plasma viremia. The two subjects with minimal responses to VRC01 were found to have predominantly VRC01-resistant virus before treatment. Notably, two subjects with plasma virus load <1000 copies/ml demonstrated virus suppression to undetectable levels for over 20 days until VRC01 levels declined. Among the remaining four subjects with baseline virus loads between 3000 and 30,000 copies, viremia was only partially suppressed by mAb infusion, and we observed strong selection pressure for the outgrowth of less neutralization-sensitive viruses. In summary, a single infusion of mAb VRC01 significantly decreased plasma viremia and preferentially suppressed neutralization-sensitive virus strains. These data demonstrate the virological effect of this neutralizing antibody and highlight the need for combination strategies to maintain virus suppression.
Ruthenium‐Containing Block Copolymer Assemblies: Red‐Light‐Responsive Metallopolymers with Tunable Nanostructures for Enhanced Cellular Uptake and Anticancer Phototherapy
Authors: Wen Sun, Maria Parowatkin, Werner Steffen, Hans‐Jürgen Butt, Volker Mailänder, Si Wu
Journal: Advanced Healthcare Materials (2015)

The use of self‐assembled nanostructures consisting of red‐light‐responsive Ru(II)‐containing block copolymers (BCPs) for anticancer phototherapy is demonstrated. Three Ru‐containing BCPs with different molecular weights are synthesized. Each BCP contains a hydrophilic poly(ethylene glycol) block and an Ru‐containing block. In the Ru‐containing block, more than half of the side chains are coordinated with [Ru(2,2′:6′,2′′‐terpyridine)(2,2′‐biquinoline)] 2+ , resulting in more than 40 wt% Ru complex in the BCPs. The Ru complex acts as both a red‐light‐cleavable moiety and a photoactivated prodrug. Depending on their molecular weights, the BCPs assemble into micelles, vesicles, and large compound micelles. All of the BCP assemblies are taken up by cancer cells. Red‐light irradiation releases the Ru complex and generates singlet oxygen ( 1 O 2 ) in cancer cells. The released Ru complex and 1 O 2 inhibit the growth of cancer cells. Among the three BCP assemblies, the BCP micelle exhibits the most efficient cellular uptake and best anticancer performance.
Validation of quality of life questionnaire St George's for patients with respiratory diseases in Colombia, Latin America
Authors: Ana Catalina Vanegas, Victor Calvo
Journal: European Respiratory Journal (2012)

Background : The SGRQ a self-administered questionnaire specific for pulmonary diseases, validated in different cultures and countries.The objective of this study was to adapt one specific scale of quality of life in patients with acute and chronic pulmonary diseases in Colombia, Latin America.   Materials and methods : The Spanish version of the SGRQ was applied to 277 patients with COPD and asthma; the different components and overall scores of SGRQ were described; the forced expiratory volume in one second (FEV 1 ), % predicted FEV 1 , 6-minute walk test (6MWT) and SF36 were used in the assessment battery.   Results:  The SGRQ showed Chronbach9s alpha coefficient internal consistence was 0.94 for the overall total scale, 0.89 for symptoms, 0.93 for activity and 0.89 for impact. Correlations of coefficient inter-reliability were 0.82 and intra-reliability 0.65 for the overall scores. The contents validity of the three factor structure was established; in construct validity met a slight difference between acute and chronic patients in activity with statistically and clinically significant (p   Conclutions:  SGRQ version for acute and chronic patients in Colombia is psycometrically equivalent to the original version, reliable, valid and could be used in our country and Spanish speaking countries with similar etnic, cultural and social conditions.
P-252 The effectiveness of colonoscopy in early gastric cancer patients who received endoscopic submucosal dissection
Authors: J.H. Jeon, W.C. Kim, D.G. Yu, H.S. Nam, D.H. Kang, H.W. Kim, C.W. Choi, S.B. Park, S.J. Kim
Journal: Annals of Oncology (2015)
A phase I study evaluating a novel schedule of oral eniluracil (EU) combined with escalating doses of oral 5-fluorouracil (5- FU)
Authors: J. R. Infante, S. F. Jones, M. Lawton, P. Wing, R. K. Malik, W. P. Peters, H. A. Burris
Journal: Journal of Clinical Oncology (2007)

2560 Background: 5-FU, a commonly utilized cytotoxic, is rapidly catabolized by dihydropyrimidine dehydrogenase (DPD), and requires anabolic conversion for anti-tumor activity. It has poor oral bioavailability due to DPD in the GI tract and liver, and toxicities such as hand-foot skin reaction. In addition, high levels of DPD are associated with 5-FU resistance. EU is a mechanism-based irreversible inactivator of DPD. Early studies in combination with oral 5-FU demonstrated activity; however, 3 Phase 3 studies were negative, due to an unrecognized inhibition of 5-FU anabolic activation by EU (Fourie et al; 2006 ASCO Proceedings; a 2058). Lower doses of eniluracil given 12–20 hrs prior to 5- FU preserves the desired DPD inhibition, without inhibiting these anabolic enzymes. Methods: The objectives are to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK), and DPD activity in peripheral blood mononuclear cells (PBMCs) following administration of a fixed dose of EU in combination with escalating doses of 5-FU. The combination of oral 5.0 mg EU 12 to 20 hours prior to oral 5-FU, is given qW for 3 weeks in 28 day cycles. Results: Twenty subjects have been enrolled, at 5-FU doses of 30, 40, 50, 60, and 70 mg. A total of 39 cycles have been administered, with 4 patients currently on study. The oral combination of EU and 5-FU has been well tolerated. All toxicities have been grade 1 or 2 with the exception of two grade 3 toxicities reported at the 50mg dose (anemia and neutropenia). The grade 3 neutropenia is the only observed DLT and resulted in a 1 week delay in initiation of cycle 2. No CR or PR noted, but 4 patients (2 previously treated with 5-FU) with 4 cycles of SD. 95–100% of DPD inhibition achieved at the time of 5-FU dosing and PK results demonstrate a dose proportional increase in 5-FU C max and AUC, and a half life of ∼3.5 hours. Conclusions: The oral combination of 5mg of EU given 12–20 hrs prior to 5-FU has been well tolerated and achieves full functional inhibition of DPD in all patients. The MTD is not yet defined and the next cohort is enrolling at the 80mg dose. EU in combination with 5-FU may provide a promising therapeutic option for patients with tumors known to be resistant to 5-FU due to high levels of DPD. No significant financial relationships to disclose.